Studies Find Much to Measure in Dog Faces

Dog facial expressions can be measured, and there's more than one way to do it

-- Read more on ScientificAmerican.com

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[Seminar] Polymyalgia rheumatica

Polymyalgia rheumatica is an inflammatory disease that affects the shoulder, the pelvic girdles, and the neck, usually in individuals older than 50 years. Increases in acute phase reactants are typical of polymyalgia rheumatica. The disorder might present as an isolated condition or in association with giant cell arteritis. Several diseases, including inflammatory rheumatic and autoimmune diseases, infections, and malignancies can mimic polymyalgia rheumatica. Imaging techniques have identified the presence of bursitis in more than half of patients with active disease.

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[Comment] Recovery from serious fungal infections should be realisable for everyone

Fungal infections are neglected by social and political communities. However, they affect more than a billion people, resulting in approximately 11·5 million life-threatening infections and more than 1·5 million deaths annually.1,2 There have been enormous advances in fungal diagnostics and antifungal drug development over the past 20 years, but most of the world's population has not yet benefited from these advances. The Lancet Infectious Diseases Fungal Infections Series brings readers up to date on fungal infections and addresses how fungal infection management can be integrated into health systems in low-income and middle-income countries (LMICs).

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[Series] Emerging issues, challenges, and changing epidemiology of fungal disease outbreaks

Several high-profile outbreaks have drawn attention to invasive fungal infections (IFIs) as an increasingly important public health problem. IFI outbreaks are caused by many different fungal pathogens and are associated with numerous settings and sources. In the community, IFI outbreaks often occur among people without predisposing medical conditions and are frequently precipitated by environmental disruption. Health-care-associated IFI outbreaks have been linked to suboptimal hospital environmental conditions, transmission via health-care workers' hands, contaminated medical products, and transplantation of infected organs.

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[Series] Immunotherapeutic approaches to treatment of fungal diseases

Fungal infections cause morbidity worldwide and are associated with an unacceptably high mortality despite the availability of antifungal drugs. The incidence of mycoses is rising because of the HIV pandemic and because immunomodulatory drugs are increasingly used to treat autoimmune diseases and cancer. New classes of antifungal drugs have only been partly successful in improving the prognosis for patients with fungal infection. Adjunctive host-directed therapy is therefore believed to be the only option to further improve patient outcomes.

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[Series] Improvement of fungal disease identification and management: combined health systems and public health approaches

More than 1·6 million people are estimated to die of fungal diseases each year, and about a billion people have cutaneous fungal infections. Fungal disease diagnosis requires a high level of clinical suspicion and specialised laboratory testing, in addition to culture, histopathology, and imaging expertise. Physicians with varied specialist training might see patients with fungal disease, yet it might remain unrecognised. Antifungal treatment is more complex than treatment for bacterial or most viral infections, and drug interactions are particularly problematic.

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[Series] Neglected endemic mycoses

Fungi often infect mammalian hosts via the respiratory route, but traumatic transcutaneous implantation is also an important source of infections. Environmental exposure to spores of pathogenic fungi can result in subclinical and unrecognised syndromes, allergic manifestations, and even overt disease. After traumatic cutaneous inoculation, several fungi can cause neglected mycoses such as sporotrichosis, chromoblastomycosis, mycetoma, entomophthoramycosis, and lacaziosis. Most of these diseases have a subacute to chronic course and they can become recalcitrant to therapy and lead to physical disabilities, including inability to work, physical deformities, and amputations.

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[Series] Pulmonary and sinus fungal diseases in non-immunocompromised patients

The human respiratory tract is exposed daily to airborne fungi, fungal enzymes, and secondary metabolites. The endemic fungi Histoplasma capsulatum, Coccidioides spp, Blastomyces dermatitidis, and Paracoccidioides brasiliensis, and occasionally Aspergillus fumigatus, are primary pulmonary pathogens of otherwise healthy people. Such infections resolve in most people, and only a few infections lead to disease. However, many fungi are directly allergenic by colonising the respiratory tract or indirectly through contact with cell wall constituents and proteases, causing or exacerbating allergic disease.

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[Series] Candida and invasive mould diseases in non-neutropenic critically ill patients and patients with haematological cancer

Critically ill patients and patients with haematological cancer are HIV-negative populations at high risk of invasive fungal infections. In intensive-care units, candidaemia and intra-abdominal candidiasis predominate, but aspergillosis has emerged as a lethal, under-recognised cause of pneumonia. In patients with haematological malignancies or who have undergone stem-cell transplantations, pulmonary disease due to aspergillus and other mould diseases predominate. In this Series paper, we provide an update on risk assessment, new diagnostic strategies, and therapeutic approaches.

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0.9 Percent Sodium Chloride Injection by ICU Medical: Recall - Presence of Particulate Matter

Audience: Pharmacy [Posted 07/31/2017] ISSUE: ICU Medical, Inc. is voluntarily recalling one lot of 0.9% Sodium Chloride Injection, USP 1000 mL to the hospital/user level due to a confirmed customer complaint of particulate matter identified as...

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The Scientific Basis of Guideline Recommendations on Sugar Intake

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Increasing Incidence of Multiply Recurrent Clostridium difficile Infection in the United States A Cohort Study

Background:

Clostridium difficile infection (CDI), the most common health care–associated infection, often recurs. Fecal microbiota transplantation is increasingly used to treat multiply recurrent CDI (mrCDI).

Objective:

To determine whether the incidence of mrCDI is increasing in proportion to CDI and to identify risk factors for mrCDI.

Design:

Retrospective cohort study.

Setting:

United States.

Participants:

38 911 718 commercially insured patients in the OptumInsight Clinformatics Database, of whom 45 341 developed CDI.

Measurements:

Age- and sex-standardized incidence rates for CDI and mrCDI.

Results:

From 2001 to 2012, the annual incidence of CDI and mrCDI per 1000 person-years increased by 42.7% (from 0.4408 to 0.6289 case) and 188.8% (from 0.0107 to 0.0309 case), respectively. The increase in mrCDI incidence was independent of known risk factors for CDI. Those who developed mrCDI were older (median age, 56.0 vs. 49.0 years; adjusted odds ratio [aOR] per 10-year increase in age, 1.25 [95% CI, 1.21 to 1.29]) and were more likely to be female (63.8% vs. 58.7%; aOR, 1.24 [CI, 1.11 to 1.38]) and to have used antibiotics (72.3% vs. 58.8%; aOR, 1.79 [CI, 1.59 to 2.01]), proton-pump inhibitors (24.6% vs. 18.2%; aOR, 1.14 [CI, 1.01 to 1.29]), or corticosteroids (18.3% vs. 13.7%; aOR, 1.15 [CI, 1.00 to 1.32]) within 90 days of CDI diagnosis. Chronic kidney disease (10.4% vs. 5.6%; aOR, 1.49 [CI, 1.24 to 1.80]) and diagnosis in a nursing home (2.1% vs. 0.6%; aOR, 1.99 [CI, 1.34 to 2.93]) were also associated with increased risk for mrCDI.

Limitation:

The primary analyses included only commercially insured patients in the United States.

Conclusion:

Relative to CDI, mrCDI incidence has disproportionately increased, indicating a rising demand for mrCDI therapies.

Primary Funding Source:

National Institute of Diabetes and Digestive and Kidney Diseases and National Institute of Allergy and Infectious Diseases.

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The Impact of Whole-Genome Sequencing on the Primary Care and Outcomes of Healthy Adult Patients A Pilot Randomized Trial

Background:

Whole-genome sequencing (WGS) in asymptomatic adults might prevent disease but increase health care use without clinical value.

Objective:

To describe the effect on clinical care and outcomes of adding WGS to standardized family history assessment in primary care.

Design:

Pilot randomized trial. (ClinicalTrials.gov: NCT01736566)

Setting:

Academic primary care practices.

Participants:

9 primary care physicians (PCPs) and 100 generally healthy patients recruited at ages 40 to 65 years.

Intervention:

Patients were randomly assigned to receive a family history report alone (FH group) or in combination with an interpreted WGS report (FH + WGS group), which included monogenic disease risk (MDR) results (associated with Mendelian disorders), carrier variants, pharmacogenomic associations, and polygenic risk estimates for cardiometabolic traits. Each patient met with his or her PCP to discuss the report.

Measurements:

Clinical outcomes and health care use through 6 months were obtained from medical records and audio-recorded discussions between PCPs and patients. Patients' health behavior changes were surveyed 6 months after receiving results. A panel of clinician-geneticists rated the appropriateness of how PCPs managed MDR results.

Results:

Mean age was 55 years; 58% of patients were female. Eleven FH + WGS patients (22% [95% CI, 12% to 36%]) had new MDR results. Only 2 (4% [CI, 0.01% to 15%]) had evidence of the phenotypes predicted by an MDR result (fundus albipunctatus due to RDH5 and variegate porphyria due to PPOX). Primary care physicians recommended new clinical actions for 16% (CI, 8% to 30%) of FH patients and 34% (CI, 22% to 49%) of FH + WGS patients. Thirty percent (CI, 17% to 45%) and 41% (CI, 27% to 56%) of FH and FH + WGS patients, respectively, reported making a health behavior change after 6 months. Geneticists rated PCP management of 8 MDR results (73% [CI, 39% to 99%]) as appropriate and 2 results (18% [CI, 3% to 52%]) as inappropriate.

Limitation:

Limited sample size and ancestral and socioeconomic diversity.

Conclusion:

Adding WGS to primary care reveals new molecular findings of uncertain clinical utility. Nongeneticist providers may be able to manage WGS results appropriately, but WGS may prompt additional clinical actions of unclear value.

Primary Funding Source:

National Institutes of Health.

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Osteoporosis

Osteoporosis is a common systemic skeletal disorder resulting in bone fragility and increased fracture risk. However, management of osteoporosis and fracture prevention strategies are often not addressed by primary care clinicians, even in older patients with recent fractures. Evidence-based screening strategies will improve identification of patients who are most likely to benefit from drug treatment to prevent fracture. In addition, careful consideration of when pharmacotherapy should be started and choice of medication and duration of treatment will maximize the benefits of fracture prevention while minimizing potential harms of long-term drug exposure.

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Benefits and Risks of Antithrombotic Therapy in Essential Thrombocythemia A Systematic Review

Background:

Patients with essential thrombocythemia (ET) are at high risk for both thrombosis and hemorrhage.

Purpose:

To evaluate the risks and benefits of antithrombotic therapy in adults with ET.

Data Sources:

Multiple databases, including MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials, through 4 March 2017.

Study Selection:

Randomized and observational studies of antiplatelet or anticoagulant therapy, published in any language and reporting thrombotic or hemorrhagic events.

Data Extraction:

Two reviewers independently extracted data, assessed risk of bias, and graded certainty of evidence.

Data Synthesis:

No relevant randomized trials were identified. Twenty-four observational studies (18 comparative and 6 single-group) involving 6153 patients followed for 31 711 patient-years were reviewed; most were deemed to have high risk of bias. Most patients receiving antiplatelet therapy (3613 of 4527 [80%]) received low-dose aspirin (50 to 150 mg/d); 914 (20%) received high-dose aspirin (300 to 600 mg/d), dipyridamole, or other agents. Overall, findings were inconsistent and imprecise. The reported incidence rates of thrombosis, any bleeding, and major bleeding without antiplatelet therapy ranged from 5 to 110 (median, 20), from 3 to 39 (median, 8), and from 2 to 53 (median, 6) cases per 1000 patient-years, respectively. The reported relative risks for thrombosis, any bleeding, and major bleeding with antiplatelet therapy compared with none ranged from 0.26 to 3.48 (median, 0.74), from 0.48 to 11.04 (median, 1.95), and from 0.48 to 5.17 (median, 1.30), respectively. Certainty of evidence was rated low or very low for all outcomes.

Limitation:

No randomized trials, no extractable data on anticoagulants, lack of uniform bleeding definitions, and systematic reporting of outcomes.

Conclusion:

Available evidence about the risk–benefit ratio of antiplatelet therapy in adults with ET is highly uncertain.

Primary Funding Source:

Regional Medical Associates. (PROSPERO: CRD42015027051)

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The Scientific Basis of Guideline Recommendations on Sugar Intake

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Patient Outcomes in Dose Reduction or Discontinuation of Long-Term Opioid Therapy A Systematic Review

Background:

Expert guidelines recommend reducing or discontinuing long-term opioid therapy (LTOT) when risks outweigh benefits, but evidence on the effect of dose reduction on patient outcomes has not been systematically reviewed.

Purpose:

To synthesize studies of the effectiveness of strategies to reduce or discontinue LTOT and patient outcomes after dose reduction among adults prescribed LTOT for chronic pain.

Data Sources:

MEDLINE, EMBASE, PsycINFO, CINAHL, and the Cochrane Library from inception through April 2017; reference lists; and expert contacts.

Study Selection:

Original research published in English that addressed dose reduction or discontinuation of LTOT for chronic pain.

Data Extraction:

Two independent reviewers extracted data and assessed study quality using the U.S. Preventive Services Task Force quality rating criteria. All authors assessed evidence quality using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. Prespecified patient outcomes were pain severity, function, quality of life, opioid withdrawal symptoms, substance use, and adverse events.

Data Synthesis:

Sixty-seven studies (11 randomized trials and 56 observational studies) examining 8 intervention categories, including interdisciplinary pain programs, buprenorphine-assisted dose reduction, and behavioral interventions, were found. Study quality was good for 3 studies, fair for 13 studies, and poor for 51 studies. Many studies reported dose reduction, but rates of opioid discontinuation ranged widely across interventions and the overall quality of evidence was very low. Among 40 studies examining patient outcomes after dose reduction (very low overall quality of evidence), improvement was reported in pain severity (8 of 8 fair-quality studies), function (5 of 5 fair-quality studies), and quality of life (3 of 3 fair-quality studies).

Limitation:

Heterogeneous interventions and outcome measures; poor-quality studies with uncontrolled designs.

Conclusion:

Very low quality evidence suggests that several types of interventions may be effective to reduce or discontinue LTOT and that pain, function, and quality of life may improve with opioid dose reduction.

Primary Funding Source:

Veterans Health Administration. (PROSPERO: CRD42015020347)

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Guidelines to Limit Added Sugar Intake

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Optimization of Collaborative Photo-Fenton Oxidation and Coagulation for the Treatment of Petroleum Refinery Wastewater with Scrap Iron

Abstract

The photo-Fenton oxidation treatment combined with a coagulation/flocculation process was investigated for removal of chemical oxygen demand (COD) from a refractory petroleum refinery wastewater. Scrap iron shavings were used as the catalyst source. A response surface methodology (RSM) with a cubic IV optimal design was employed for optimizing the treatment process. Kinetic studies showed that the proposed process could be described by a two-stage, second-order reaction model. Experiments showed that precipitation of iron ions can be utilized as a post-oxidation coagulation stage to improve the overall treatment efficiency. More than 96.9% of the COD removal was achieved under optimal conditions, with a post-oxidation coagulation stage accounting for about 30% of the removal, thus confirming the collaborative role of oxidation and coagulation in the overall treatment. A low-velocity gradient of 8.0 s⁻¹ for a short mixing time of 10 min resulted in optimum post-oxidation coagulation. Comparison of photo-Fenton oxidation to a standard Fenton reaction in the same wastewater showed more rapid COD removal for photo-Fenton, with an initial second-order rate constant of 4.0 × 10⁻⁴ L mg⁻¹ min⁻¹ compared to the Fenton reaction's overall second-order rate constant of 7.0 × 10⁻⁵ L mg⁻¹ min⁻¹.

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An Estimated 2 Million U.S. Adults Have an Opioid Use Disorder (FREE)

By Kelly Young Edited by David G. Fairchild, MD, MPH, and Jaye Elizabeth Hefner, MD Roughly one in three U.S. adults reported recent use of prescription opioids on the 2015 National Survey on Drug Use and Health, according to a study in Annals …

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Suicide-Related Internet Searches Elevated After Debut of "13 Reasons Why" (FREE)

By Kelly Young Edited by David G. Fairchild, MD, MPH, and Jaye Elizabeth Hefner, MD Internet searches for suicide-related terms were elevated following the release of the Netflix series "13 Reasons Why," according to a research letter in JAMA Internal Medicine. The …

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Occipital headaches and neuroimaging in children

Objective:

To investigate the common thinking, as reinforced by the International Classification of Headache Disorders, 3rd edition (beta), that occipital headaches in children are rare and suggestive of serious intracranial pathology.

Methods:

We performed a retrospective chart review cohort study of all patients ≤18 years of age referred to a university child neurology clinic for headache in 2009. Patients were stratified by headache location: solely occipital, occipital plus other area(s) of head pain, or no occipital involvement. Children with abnormal neurologic examinations were excluded. We assessed location as a predictor of whether neuroimaging was ordered and whether intracranial pathology was found. Analyses were performed with cohort study tools in Stata/SE 13.0 (StataCorp, College Station, TX).

Results:

A total of 308 patients were included. Median age was 12 years (32 months–18 years), and 57% were female. Headaches were solely occipital in 7% and occipital-plus in 14%. Patients with occipital head pain were more likely to undergo neuroimaging than those without occipital involvement (solely occipital: 95%, relative risk [RR] 10.5, 95% confidence interval [CI] 1.4–77.3; occipital-plus: 88%, RR 3.7, 95% CI 1.5–9.2; no occipital pain: 63%, referent). Occipital pain alone or with other locations was not significantly associated with radiographic evidence of clinically significant intracranial pathology.

Conclusions:

Children with occipital headache are more likely to undergo neuroimaging. In the absence of concerning features on the history and in the setting of a normal neurologic examination, neuroimaging can be deferred in most pediatric patients when occipital pain is present.

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Letter re: Evolving use of seizure medications after intracerebral hemorrhage: A multicenter study

Naidech et al.¹ concluded that increased prophylactic antiseizure drug (ASD) use in intracranial hemorrhage (ICH) between 2007 and 2012 was due to clinicians' hesitation to abandon a longstanding practice despite an established guideline.² We offer an additional interpretation.

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When sleep-related hypermotor epilepsy (SHE) met Charles Darwin and Francis Galton

Sleep-related hypermotor epilepsy (SHE) is characterized by short-lasting seizures patterned by repetitive and stereotyped motor events in the same person. In autosomal dominant SHE, genetic factors play a well-known key role. In The Expression of Emotions in Man and Animals, Charles Darwin quotes a plausible example of SHE illustrated by his cousin Sir Francis Galton: "the gentleman...lay fast asleep on his back in bed, raising his right arm slowly in front of his face, up to his forehead, and then dropping it with a jerk, so that the wrist fell heavily on the bridge of his nose. The trick did not occur every night, but occasionally, and was independent of any ascertained cause. Sometimes it was repeated incessantly for an hour or more." Similar manifestations during sleep occurred also in the patient's son and granddaughter, suggesting an autosomal inheritance without sex relationship. Differential diagnosis with REM behavior disorder and other parasomnias is discussed. To our knowledge, this could be the first description of a stereotyped SHE pattern with genetic transmission.

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Myoclonic dystonia (DYT11) responsive to insulin therapy: A case report

A 44-year-old man has been longitudinally followed for myoclonic dystonia (DYT11) due to a previously described heterozygous loss-of-function mutation involving a conserved residue in the epsilon-sarcoglycan gene (SGCE, NM_003919.2:c.1114C>T, p.Arg372Ter).¹

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Letter re: Neurologists and the economics of MS treatment: Lighting candles, not cursing the darkness

In their editorial, Drs. Bourdette and Whitham¹ mentioned "avoiding use of repository corticotropin (Acthar gel) to treat MS relapses." Objectively considering H.P. Acthar Gel, the only Food and Drug Administration–approved noncorticosteroid therapy option for multiple sclerosis (MS) relapse, as a treatment option is in the best interest of patients.

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Physical activity, but not body mass index, predicts less disability before and after stroke

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Serial changes in lymphocyte subsets in patients with newly diagnosed high grade astrocytomas treated with standard radiation and temozolomide

This study was performed to quantify serial changes in lymphocyte subsets in HGA following standard radiation (RT) and temozolomide (TMZ). Adults (KPS  >60, HIV negative) with newly diagnosed HGA scheduled to receive concurrent RT and TMZ and adjuvant TMZ were eligible. Blood was collected before beginning concurrent RT/TMZ and at weeks 6, 10, 18, and 26, and 3 months after completing adjuvant TMZ. Lymphocyte subsets were analyzed by flow cytometry. Twenty patients (70% glioblastoma, median age 53, 50% male, 80% Caucasian) who enrolled from January 2014 to August 2014 were followed until April 2016. Baseline dexamethasone dose was 0.5  mg/day and 15% had absolute lymphocyte counts (ALC) <1000 cells/mm3 before starting RT/TMZ. However, 75% developed lymphopenia with ALC  <10...

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Therapeutic efficacy of a respiratory syncytial virus fusion inhibitor

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Charge carrier localised in zero-dimensional (CH3NH3)3Bi2I9 clusters

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Seismological evidence for a localized mushy zone at the Earth’s inner core boundary

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A dsRNA virus with filamentous viral particles

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B Cell Tetramer Development for Veterinary Vaccinology

Viral Immunology , Vol. 0, No. 0. (Source: Viral Immunology)

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Determinants of Infection Outcome in HCV-Genotype 4

Viral Immunology , Vol. 0, No. 0. (Source: Viral Immunology)

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GBM radiosensitizers: dead in the water …or just the beginning?

AbstractThe finding that most GBMs recur either near or within the primary site after radiotherapy has fueled great interest in the development of radiosensitizers to enhance local control. Unfortunately, decades of clinical trials testing a wide range of novel therapeutic approaches have failed to yield any clinically viable radiosensitizers. However, many of  the previous radiosensitizing strategies were not based on clear pre-clinical evidence, and in many cases blood-barrier penetration was not considered. Furthermore, DNA repair inhibitors have only recenly arrived in the clinic, and likely represent potent agents for glioma radiosensitization. Here , we present recent progress in the use of small molecule DNA damage response inhibitors as GBM radiosensitizers. In addition, we discus...

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Factors of Pelvic Infection and Death in Patients with Open Pelvic Fractures and Rectal Injuries

Surgical Infections , Vol. 0, No. 0.


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Tubercular Abdominal Cocoon: Systematic Review of an Uncommon Form of Tuberculosis

Surgical Infections , Vol. 0, No. 0.


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Availability of adequately iodized in Northwest Ethiopia: a cross-sectional study

Universal salt iodization is the most cost-effective, safe and sustainable strategy to eliminate iodine deficiency disorders. However, little is known about the availability of adequately iodized salt in the n...

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Pulmonary fibrosis in connective tissue disease (CTD): urgent challenges and opportunities

Connective tissue disease associated interstitial lung disease (CTD-ILD) remains the poor cousin, with regards to specific disease modifying therapies. CTD in general and rheumatoid arthritis (RA) in particular has seen a surge of investment by industry and the provision of a range of therapies that significantly improve the quality of life for these patients.¹ More recently, two novel anti-fibrotic therapies for idiopathic pulmonary fibrosis (IPF) have been shown to significantly modify disease and improve survival.^2–4 Yet, for pulmonary fibrosis arising in those with CTD, there remains a desperate need to identify effective therapies.

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Challenges for Zika prevention in Myanmar

Myanmar reported its first case of Zika in a pregnant woman who returned from a country with active Zika transmission.¹ After coming back, she visited rural townships and health officials have confined her to prevent further transmission. So far, now new cases have been reported in Myanmar. It is a fledgling democracy, which endured decades of military rule that neglected the health care sector. The per capita health expenditure is only $20 and it is one of the lowest in South East Asia.² Myanmar is located in South East Asia, one of the regions that are highly suitable for Zika transmission (Figure 1).

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Ramsay Hunt syndrome following middle ear surgery

We present a 59-year-old woman with facial palsy 3 weeks after a right-sided tympanoplasty surgery via the endaural approach. Physical examination showed a House–Brackman grade III right-sided facial palsy. Two days after facial palsy, swelling and vesicles over the right auricle were noted (Figure 1A). Under the impression of Ramsay Hunt syndrome characterized by acute facial palsy associated with a herpetic eruption on the auricle, the patient was treated with a 2-week oral Famvir (250 mg/tid) and tapered dose of oral prednisolone (1 mg/kg). One week after treatment, the vesicles formed a herpetic crust over the auricle (Figure 1B). The patient's facial palsy abated within 2 weeks of treatment. The appearance of the auricle and external auditory canal completely subsided after 2 months (Figure 1C). The perforated eardrum of the right ear was successfully reconstructed and the patient's hearing acuity improved after 6 months of follow-up.

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Panda sign: sarcoidosis

A 54-year-old woman presented to our outpatient ophthalmology clinic complaining of eye redness, severe pain and photophobia that had persisted for 1 day. Slit lamp examination revealed she was found to have large greasy-white mutton-fat keratic precipitates on the endothelial surface of her both eyes. Physical examination showed bilateral cervical lymphadenopathy and multiple tender erythematous nodular skin swellings on both shins. The patient's previous medical history did not suggest trauma, insect bite, diabetes mellitus or tuberculosis. The patient had previously received the Bacille Calmette Guérin vaccination, but tuberculin skin testing was negative. Histopathological examination of skin lesion and lymph node biopsies revealed non-caseating sarcoidal granuloma, and a chest radiograph revealed bilateral hilar lymphadenopathy. Furthermore, gallium-67 scanning showed symmetrical uptake of gallium-67 into the nasopharynx, lacrimal glands, parotid glands (i.e. panda sign, Figure 1A) and lower extremities (Figure 1B). On the basis of the clinical and histopathological findings, the patient diagnosed as having sarcoidosis. Sarcoidosis is a chronic granulomatous disease that can involve almost any organ in the body. The cause of this disease remains uncertain. However, a recent study showed that Propionibacterium acnes is highly associated with sarcoidosis¹. The signs and symptoms of sarcoidosis can vary depending on which organs are affected. Clinical and radiographic manifestations also vary widely among individual patients. The panda sign indicates lacrimal and salivary gland gallium-67 uptake and is generally associated with other disorders, including Sjögren's syndrome, tuberculosis, post-irradiation lymphoma and acquired immunodeficiency syndrome². Therefore, when the panda sign is present, clinicians should consider sarcoidosis as a possible differential diagnosis.

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Papillon Lefevre syndrome

A 12-year-old female patient presented with chief complaint of severe bleeding of gingiva and foul breath. Medical history was noncontributory with normal physical and mental development. She lost all her deciduous teeth by 5 years of age and the permanent teeth started loosening at 8 years of age, till date there is no loss of any permanent teeth. Intraoral clinical examination revealed presence of severe destructive periodontitis of all the teeth (Figure 1A). Panoramic view showed severe generalized loss of alveolar bone around all the present teeth. Dermatological examination revealed well-demarcated, brownish, hyperkeratotic areas with crustations and fissuring affecting the skin on the palmar surface of her hands and on plantar surface of her feet (Figure 1B). Severe bone loss at such a young age was found to be abnormal so a genetic analysis was carried out utilizing peripheral blood sample and subjecting it to polymerase chain reaction which revealed a mutation in CTSC gene which encodes cathepsin C. Differential diagnosis consisted of Haim-Munk syndrome and Papillon Lefevre syndrome. Haim-Munk syndrome shows symptoms such as arachnodactyly, acroosteolysis and onychogryphosis and absent in our patient which lead us to final diagnosis of Papillon Lefevre syndrome. Dental treatment consisted of systemic amoxicillin (500 mg, thrice daily) and metronidazole (400 mg, thrice daily) for 1 week along with patient education for oral hygiene followed by full mouth periodontal flap surgery. Dermatological treatment consisted of systemic acetretin (25 mg) every alternate day for 4 months and intermittent Psoralen and Ultraviolet A therapy (8-methoxypsoralen taken by oral cavity followed 45–60 min later by exposure of the skin to ultraviolet A), 20 treatments were given 3 days apart. Patient is asymptomatic at 1 year of follow-up.

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Sonographic barcode sign of pneumothorax

A 16-year-old female presented with dyspnea and left chest pain after a severe motor vehicle accident. Upon arrival, her vital signs were temperature: 36.2°C, pulse rate: 86/min, respiratory rate: 17/min and blood pressure: 126/78 mmHg. Physical examinations revealed decreasing breath sound over left lung field. Thoracic ultrasound showed barcode sign over left lung (Figure 1A) in M-mode and indicated the presence of pneumothorax. Chest radiograph and computed tomography confirmed the diagnosis of pneumothorax (Figure 1B and C). Because the amount of pneumothorax is small, the patient received oxygenation therapy and supportive care. Several days later, follow-up of chest radiograph showed the re-expansion of left lung, and the patient's condition gradually improved.

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Sugar and artificially sweetened beverages linked to obesity: a systematic review and meta-analysis

Abstract

Background/Objectives

Artificial sweeteners are used widely to replace caloric sugar as one of the strategies to lessen caloric intake. However, the association between the risk of obesity and artificially sweetened soda consumption is controversial. The objective of this meta-analysis aimed to assess the association between consumption of sugar and artificially sweetened soda and obesity.

Methods

A literature search was performed using MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials from inception through May 2015. Studies that reported relative risks, odd ratios, or hazard ratios comparing the risk of obesity in patients consuming either sugar or artificially sweetened soda vs. those who did not consume soda were included. Pooled risk ratios (RRs) and 95% CI were calculated using a random-effect, generic inverse variance method.

Results

Eleven studies were included in our analysis to assess the association between consumption of sugar-sweetened soda and obesity. The pooled RR of obesity in patients consuming sugar-sweetened soda was 1.18 (95% CI, 1.10–1.27). Three studies were included to assess the association between consumption of artificially sweetened soda and obesity. The pooled RR of obesity in patients consuming artificially sweetened soda was 1.59 (95% CI, 1.22–2.08).

Conclusions

Our study demonstrated a significant association between sugar and artificially sweetened soda consumption and obesity. This finding raises awareness and question of negative clinical impact on both sugar and artificially sweetened soda and the risk of obesity.

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Laryngeal tuberculosis: a forgotten disease

A 93-year-old woman presented with a 2-month history of hoarseness and cough. The patient had never received immunosuppressive treatment, was serologically negative for HIV and hepatitis, and did not have a family history of tuberculosis. Laryngoscopy showed an ulcerated and granular lesion in the ventricular folds, larynx vestibule and bilateral vocal cords (Figure 1A). Histological analysis of the biopsy specimen revealed granulomas with caseating necrotic centers and Langhans giant cells without carcinoma. Ziehl-Neelsen staining of the bronchoalveolar lavage fluid revealed acid-fast bacilli and PCR using the fluid revealed Mycobacterium tuberculosis. High-resolution chest computed tomography showed micronodular lesions in the right lung and a lesion suggestive of tuberculosis in the apex (Figure 1B). The patient received a standard 6-month anti-tuberculous treatment (rifampicin, isoniazid, pyrazinamide, and ethambutol). Tuberculosis is an infectious disease that is caused by M.tuberculosis. Although laryngeal tuberculosis only accounts for ∼1% of all tuberculosis cases, laryngeal tuberculosis is terrific contagious.¹ Laryngeal tuberculosis has been considered to be the result of extra-pulmonary manifestations, and has often been associated with pulmonary tuberculosis. Thus, laryngeal tuberculosis should be suspected in all patients with chronic cough, hoarseness and significant dysphagia. The symptoms are often limited, although the diagnosis can be confirmed using adequate diagnostic and radiographic examinations. Tuberculosis has become a rare disease in the developed countries, but tuberculosis infections began increasing in 1985, partly because of the HIV/AIDS emerging. Also, the rise in drug-resistant tuberculosis and the outbreaks of multidrug resistant tuberculosis are serious underlying problems in the health-care infrastructure all over the world.² Early identification can facilitate appropriate management and treatment, which can reduce the prevalence of tuberculosis and improve public health.

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Response: Russell’s viper envenomation: acute hypopituitarism or acute primary adrenal insufficiency

We read with interest the points raised by Dr Krishnamurthy and Dr Vishnu about the distinction between acute hypopituitarism (AHP) and adrenal insufficiency related to Russell's viper envenomation (RVE). We strongly encourage them to read the supplementary materialsupplementary material provided with our manuscript.¹ Firstly, autopsy was performed on two of the four patients that died and it showed pituitary necrosis in both (Supplementary Table 2Supplementary Table 2). In the survivors (2, 3, 5), there was demonstrable hyposecretion of at least one other pituitary hormone apart from TSH and low cortisol in the acute setting (Supplementary Table 2Supplementary Table 2). In all the survivors, including the two cases without acute hormonal results (Cases 8 and 9) follow up showed persisting low cortisol, Thyroid-stimulating hormone (TSH) and Prolactin or testosterone at 3 months. Prednisolone and thyroxine replacement has been continued in all, including GH replacement for Case 9. Secondly, abnormalities in imaging are neither needed nor enough to support a diagnosis of AHP; pituitary imaging has been described to be normal in published cases of RVE-HP.² Thirdly, we do not agree with the statement that the combination of hypotension and hypoglycemia in the setting of RVE occurs with isolated capillary leak, major bleeding, renal or hepatic dysfunction; these are probably cases of AHP that are being missed by the authors. Fourthly, the aim of our manuscript was to describe a series of well-characterized patients of RVE-AHP so that a diagnosis of AHP is suspected prospectively in this setting thereby triggering steroidal replacement therapy. As we have pointed out in our manuscript, several cases of de-novo chronic HP related to RVE continue to be reported suggesting significant under-recognition of AHP with associated mortality. We believe, and it is our practice, to make the final diagnosis of AHP retrospectively with repeat biochemical testing at follow-up after withdrawing replacement under supervision. Finally, we agree that availability of ACTH results in the acute setting could have made our manuscript more robust but funding for this test was unavailable at the time of writing this manuscript and results are usually unavailable for weeks in our institution.

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Meta-analysis of statins in chronic kidney disease: who benefits?

Abstract

Background

Attempts to reduce the burden of vascular disease in advanced chronic kidney disease (CKD) by control of lipids have not been as successful as predicted.

Aim

To determine the extent to which the effectiveness of statins varies by kidney class.

Design

Meta-analysis.

Methods

We selected randomized trials of statin vs. placebo that gave outcomes for CKD3 (eGFR 30–59 ml/min), CKD4 (eGFR 15–29 ml/min), CKD5 (eGFR < 15 ml/min)/5D(dialysis) and transplant patients separately. Data sources were the Cholesterol Triallists' Treatment Collaboration and previously published meta-analyses. Main outcome measures were major cardiovascular events (MACE), cardiovascular death and all-cause mortality (ACM).

Results

A total of 13 studies provided 19 386 participants with CKD3, 2565 with CKD4, 7051 with CKD5/5D and 2102 with a functioning renal transplant. Statins reduced MACE (pooled HR 0.72, 95% CI 0.67–0.78) and ACM (0.82, 0.73–0.91) in CKD3; probably reduced MACE (0.78, 0.62–0.99) in CKD4; and probably reduced cardiovascular death (0.62, 0.40–0.96) in renal transplants. There were no cardiovascular or ACM data in CKD4; there was no convincing evidence of benefit for any outcome in CKD5/5D; and no significant reduction in MACE or ACM in patients with a functioning transplant.

Conclusions

Statins are indicated in CKD3, probably indicated in CKD4, not indicated in CKD5/5D and probably indicated in patients with a functioning transplant. Too few patients with CKD4 and renal transplants have been included in lipid lowering trials for confident conclusions to be drawn.

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Cardiac troponin-I as a predictor of mortality in patients with first episode acute atrial fibrillation

Abstract

Background

Recent-onset atrial fibrillation (AF) is a frequent cause for presentation to the emergency department. Recent studies proposed that the addition of biomarker information might improve the prediction of clinical outcomes by enabling identification of patients at high risk.

Aim

We aimed to examine the role of cardiac troponin I as a predictor of clinical outcome in patients with first episode acute AF.

Design

Patients, 18 years or older, presenting to our hospital with a primary diagnosis of first episode acute AF were included in this retrospective study.

Methods

The association between elevated cTnI with mortality or the composite endpoint (mortality, stroke or heart failure) was examined in a univariate Cox regression model.

Results

Of the 274 study patients, 111 had elevated cTnI levels (41%). Increased cTnI was associated with older age, history of myocardial infarction, higher creatinine levels and higher heart rate (All P < 0.01). Elevated cTn was associated with an adjusted hazard ratio of 1.86 [95% confidence interval (CI) 1.17–2.96; P = 0.009] for mortality and 1.89 (95% CI 1.27–2.84; P = 0.002) for the combined endpoint.

Conclusions

Elevated cardiac Troponin I is a significant predictor of mortality and a composite endpoint of mortality, stroke or heart failure in patients presenting with first episode acute AF.

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Impaired ability to grow colonies of endothelial stem cells could be the mechanism explaining the high cardiovascular morbidity and mortality of patients with depression

Abstract

Background

Subjects with depression are more prone to develop cardiovascular complications. Severity of depression is associated with higher rates of cardiovascular mortality and morbidity. Several mechanisms were suggested including accelerated atherosclerosis, alteration of the cardiac autonomic response with a decrease in heart rate variability. There is evidence that circulating endothelial progenitor cells (EPCs) are decreased in patients with major depression. Our hypothesis was that patients with depression would have an impaired ability to build colonies of EPCs.

Methods

A prospective study enrolled twenty women with a diagnosis of major. All were not treated before for depression. Thirteen healthy age-matched women served as controls. All signed a consent form before recruitment to the study. Peripheral blood was drawn to build colonies of EPCs within 5 days. ELISA methods were used to measure levels of vascular cell adhesion molecule-1 (VCAM-1) and vascular endothelial growth factor (VEGF).

Results

Twenty female patients with depression were recruited. The mean age was 43 ± 14 years (vs. controls 41 ± 11 years, P = 0.682), patients' average CFU-EPCs was 7 ± 8 colonies per well (controls 31 ± 11, P = 0.0001), VCAM-1 level was 121.7 ± 3.0 ng/ml (controls 119.3 ± 3.1 pg/ml, P = 0.037), VEGF level was 6.4 ± 0.2 pg/ml (controls 5.2 ± 0.5 pg/ml, P = 0.0001). An inverse correlation was found between VEGF level and EPCs' colonies (r  = −0.547, P < 0.001) and between age and CFU-EPCs (r = −0.576, P = 0.008).

Conclusions

We found that patients with major depression had high levels of VCAM-1 and VEGF. They also had a significant inhibition of EPCs' colonies. An inverse correlation was found between levels of VEGF and the ability to grow colonies of EPCs in culture.

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Predictors of failure to respond to fluid restriction in SIAD in clinical practice; time to re-evaluate clinical guidelines?

Abstract

Background

Fluid restriction is recommended as first line therapy for Syndrome of Inappropriate Antidiuresis (SIAD), despite of lack of good evidence base to support its use, and poor efficacy in clinical practice and in the literature.

Aim

We set out to determine how many patients with well-defined SIAD had pre-treatment criteria which would predict failure to fluid restriction.

Design and methods

This was a consecutive, prospective evaluation of 183 patients with a diagnosis of SIAD in two different hospitals. Full ascertainment of the diagnostic criteria for SIAD was obtained in all patients.

Results

About 47% of patients had a urine volume <1500 ml in 24 h, 41% had initial urine osmolality > 500 mOsm/kg, 26% a Furst-equation ratio > 1. About 59% had one criterion predicting failure to respond to fluid restriction, 37% two criteria, and 3% three criteria.

Conclusions

Our data suggest that up to 60% of patients with SIAD had criteria which recent clinical guidelines suggest would predict nonresponse to fluid restriction. This may explain why the recommended first line therapy for SIAD has been shown to be ineffective.

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Russell’s viper envenomation: acute hypopituitarism or acute primary adrenal insufficiency

Sir,

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Dilemmas in management of suspected venous thromboembolism in the obese patient

The incidence of obesity is increasing with an estimate of over 300 million people in the world currently categorized as obese by the World Health Organization. Obesity affects all age and socioeconomic groups and is a problem in both developed and developing countries. One of the well-recognized complications of obesity is venous thromboembolism (VTE) to include both deep vein thrombosis (DVT) and pulmonary embolism (PE). Although, increased awareness of VTE has improved the outcome in most patients, the diagnosis and treatment of obese patients defined as body mass index (BMI) ≥30 kg/m², suspected to have a VTE can present some unique challenges.

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Chemo Plus Hyperthermia Active in Advanced Pancreatic Cancer

Systemic and intraperitoneal chemotherapy + hyperthermia well tolerated and active (Source: The Doctors Lounge - Oncology)

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Review: Positive Link for Alcohol, Nonmelanoma Skin Cancer

For every 10 - g increase in ethanol intake per day, positive correlation seen for BCC, cutaneous SCC (Source: The Doctors Lounge - Oncology)

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Clinical Reasoning: A 22-year-old man with diplopia

A 22-year-old previously healthy man presented to an ophthalmology clinic with binocular horizontal diplopia. He had recently traveled to the main island of Hawaii. About 2 weeks after returning home, he developed a severe headache with associated fever, emesis, photophobia, phonophobia, and neck stiffness. He also reported a sensation of pressure in his left eye and both ears but denied any pulsatile tinnitus or transient vision loss. Over the next 2 weeks, his headaches worsened, causing him to wake up frequently in the night. He then developed horizontal diplopia that was worse at a distance and was referred to the neuro-ophthalmology clinic.

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Editors' Note

Editors' Note: In response to "Evolving use of seizure medications after intracerebral hemorrhage: A multicenter study," Srinivasan et al. suggest that newer antiseizure drugs (ASD) (e.g., levetiracetam) are safer, influencing drug prescription behavior. They also report their own experience that initiation of ASD in patients with intracerebral hemorrhage has not changed in 2 cohorts 10 years apart; ASDs were more frequently discontinued prior to discharge in the recent cohort.

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Pearls & Oy-sters: Transient neurologic events in a patient with leptomeningeal metastases

Patients with leptomeningeal metastases (LM) may develop transient neurologic events in the setting of temporary elevations of intracranial pressure (ICP).

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Author response: Neurologists and the economics of MS treatment: Lighting candles, not cursing the darkness

Dr. Otulana, Chief Medical Officer for Mallinckrodt Pharmaceuticals, which produces H.P. Acthar Gel, claims that Acthar is cost-effective in a response to our editorial.¹ To support this statement, Dr. Otulana references a study paid for by Mallinckrodt that is not a cost-effectiveness analysis.² The cited study compares costs of health care services delivered to patients who received Acthar compared with a group that received either plasmapheresis or IV immunoglobulins (IVIg) for multiple sclerosis (MS) relapse.³ While there was a modest difference in total cost of care over 12 and 24 months after treatment between the 2 groups, the article by Gold et al.² revealed that those receiving Acthar had much higher medication costs over 12 months compared with the plasmapheresis/IVIg group (mean cost of $87,200 vs $12,300). The high medication costs may reflect the expense of Acthar. The current average acquisition price of a 5-mL vial of Acthar containing 80 IU/mL of repository corticotropin is $34,000.³ Patients receive 80 IU of Acthar once a day for 5–15 days,⁴ costing a stunning and unjustified $34,000–$102,000. I stand by our editorial, in which we state that neurologists "should not be using repository corticotropin to treat MS relapses given its high cost."¹

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Teaching Video NeuroImages: Running into a "useless" hand

A 68-year-old woman presented with an insidious onset of strictly asymmetric left arm clumsiness (video at Neurology.org) in absence of any brain lesion but mild right hemisphere hypotrophy (figure). The presence of limb apraxia and bradykinesia fostered the clinical diagnosis of possible corticobasal syndrome, in the context of suspected corticobasal degeneration.¹ Bradykinesia and apraxia are 2 possible different faces of hypokinesia; their correct discrimination is not a diagnostic problem if a higher-level disturbance of praxis is present. An isolated limb apraxia is a confounder, and its early recognition allows clinicians to suspect parkinsonism with apraxia as a prominent feature.²

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Max-ICH score: Can it prevent self-fulfilling prophecy in ICH?

Prediction of outcomes of patients with spontaneous intracerebral hemorrhage (ICH) can be helpful for patients, their families, and physicians when deciding on treatment strategies, including consideration of withdrawal of care. The most recent American Heart Association guideline for the management of spontaneous ICH recommends the routine use of a standardized severity score to "help streamline assessment and communication between providers."¹ However, it warns that "severity scales should not be used as a singular indicator of prognosis."

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Self-reported sleep and Alzheimer disease CSF biomarkers: A wake-up call

Alzheimer disease (AD) is the most prevalent cause of dementia, and numerous studies have described sleep disturbances and circadian abnormalities in persons with symptomatic AD.¹ A rapidly accumulating body of research suggests that disturbed sleep is not only a consequence of pathologic brain changes of AD, but may also contribute to AD pathophysiologic mechanisms, even in the preclinical stages of AD.² Sleep disturbances are associated with amyloid deposition, the first known stage of preclinical AD. Poorer sleep quality, as measured by wrist actigraphy, and more frequent napping were tied to CSF evidence of amyloid deposition,³ and self-report of poorer sleep quality and shorter sleep duration were associated with greater amyloid burden, measured by amyloid PET imaging.^4,5 The hypothesized underlying mechanism is sleep-related decreases in soluble β-amyloid (Aβ) levels: sleep disturbance acutely increases soluble Aβ in humans and mice,⁶ and chronically increases deposition of Aβ into plaques in mouse models.⁷ Insufficient sleep is therefore a plausible promoter of amyloid deposition.

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Occipital headaches and neuroimaging in children

Objective:

To investigate the common thinking, as reinforced by the International Classification of Headache Disorders, 3rd edition (beta), that occipital headaches in children are rare and suggestive of serious intracranial pathology.

Methods:

We performed a retrospective chart review cohort study of all patients ≤18 years of age referred to a university child neurology clinic for headache in 2009. Patients were stratified by headache location: solely occipital, occipital plus other area(s) of head pain, or no occipital involvement. Children with abnormal neurologic examinations were excluded. We assessed location as a predictor of whether neuroimaging was ordered and whether intracranial pathology was found. Analyses were performed with cohort study tools in Stata/SE 13.0 (StataCorp, College Station, TX).

Results:

A total of 308 patients were included. Median age was 12 years (32 months–18 years), and 57% were female. Headaches were solely occipital in 7% and occipital-plus in 14%. Patients with occipital head pain were more likely to undergo neuroimaging than those without occipital involvement (solely occipital: 95%, relative risk [RR] 10.5, 95% confidence interval [CI] 1.4–77.3; occipital-plus: 88%, RR 3.7, 95% CI 1.5–9.2; no occipital pain: 63%, referent). Occipital pain alone or with other locations was not significantly associated with radiographic evidence of clinically significant intracranial pathology.

Conclusions:

Children with occipital headache are more likely to undergo neuroimaging. In the absence of concerning features on the history and in the setting of a normal neurologic examination, neuroimaging can be deferred in most pediatric patients when occipital pain is present.

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Residents don't just look miserable... they really are

Is the rite of passage of residency and fellowship a process of learning and maturing, or an exhausting and demoralizing experience that sets the stage for burnout? What factors can influence the start of burnout or help to promote wellness? It has become abundantly clear that physicians face a crisis not only of regulatory burdens, but also of a lack of well-being or burnout. This is especially true for neurologists. This does not begin with the graduation certificate from residency or fellowship, but instead the indicators for burnout are very much present early in their training—during residency. More than 50% of physicians in the United States meet the criteria for burnout, a well-recognized threat to the profession. Burnout disproportionately affects neurologists, and in this issue of Neurology®, Levin et al.¹ reveal that our next generation of colleagues are equally at risk.

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18F-FDG PET/CT Findings Following Repeated Intramuscular Injections of "Site Enhancement Oil" in the Upper Extremities.

We present the findings on 18F-FDG PET/CT in a 50-year-old man known to self-administer intramuscular injections with site enhancement oil in the upper extremities. PET images show diffuse pathological high FDG uptake in soft tissue of the upper arms and in scanned portions of the forearms. On the CT images, the muscles in the upper arm are swollen with a moth-eaten appearance and surrounding edema. Interspersed in the muscle tissue are several "cystic" lesions interpreted as oil deposits termed oleomas. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Thyroid Metastasis as First Manifestation of a Colon Adenocarcinoma With KRAS Mutation: Usefulness of 18F-FDG PET/CT.

The synchronous diagnosis of a thyroid metastasis and of the primary colon adenocarcinoma that produces it is very rare, with only 5 cases reported to date, all of them treated with thyroid surgery showing a mean survival of 7 months. An 18F-FDG PET/CT in an asymptomatic 74-year-old woman with a thyroid cytology suggestive of malignancy but uncertain about the origin of the tumor revealed an stage IV colon adenocarcinoma with KRAS mutation and multiple metastasis (thyroid, lung, and liver). A prompt therapeutic planning with chemotherapy allowed 21 months of survival. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Adrenocorticotropic Hormone-Secreting Neuroendocrine Tumor of the Rectum Demonstrated on 68Ga-DOTATATE and 18F-FDG PET Imaging.

An 81-year-old man with Cushing syndrome was referred for a 68Ga-DOTATATE PET/CT study to investigate for an ectopic source of adrenocorticotropic hormone. The scan demonstrated mildly increased octreopeptide uptake at a rectal mass and focal uptake at multiple regions throughout the bone marrow of the axial skeleton, consistent with metastases. A subsequent 18F-FDG PET/CT study was performed for further evaluation and demonstrated markedly increased metabolism at the previously identified rectal mass, in addition to the liver and multiple regions throughout the skeleton. Histopathology from biopsy of the rectal mass confirmed a small cell neuroendocrine carcinoma. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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18F-FDG Uptake in Parsonage-Turner Syndrome.

A 55-year-old man with large B-cell lymphoma developed atraumatic left shoulder pain. 18F-FDG PET/CT revealed new left supraspinatus and infraspinatus muscle uptake while the initial disease resolved. Given the discrepancy between initial disease treatment response and new left shoulder findings, an MRI scan was performed. This demonstrated diffuse supraspinatus and infraspinatus muscle edema and enhancement with no focal lesion. Muscle biopsy was negative for lymphoma, but features of muscle denervation were seen. Overall, clinical and imaging findings were compatible with Parsonage-Turner syndrome (acute brachial neuritis), an uncommon condition that presented as a false-positive finding on PET/CT. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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18F-FDG PET/CT Demonstrating Chorioadenoma Destruens After Evacuation of Complete Hydatidiform Mole.

Gestational trophoblastic neoplasias (GTNs) are a group of pregnancy-related neoplasms, which include chorioadenoma destruens (invasive mole), placental site trophoblastic tumor, and choriocarcinoma. Although the role of 18F-FDG PET/CT is still undefined in GTN, in selected cases, it can have significant impact on patient management. Here, we present the case of a 29-year-old woman with hydatidiform mole suggestive of GTN 3 months after evacuation. 18F-FDG PET/CT demonstrated chorioadenoma destruens (invasive mole) and ruled out metastasis in this case. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Quality and Safety in Health Care, Part XXIX: The Transcatheter Valve Therapy Registry.

The American College of Cardiology, the Society of Thoracic Surgeons, and other organizations cooperated to form the Transcatheter Valve Therapy Registry. This registry studies information on the outcome of valve therapy device placement with a transcatheter approach. The companies that manufacture these devices can use the registry to meet the post-product sale surveillance requirements of the US Food and Drug Administration. There will also be linkage to the registry information from the Society of Thoracic Surgeons Adult Cardiac Surgery Database, which has information on open cardiac valve surgery. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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08/01/17 PHD comic: 'Nice try'

Piled Higher & Deeper by Jorge Cham		www.phdcomics.com
title: "Nice try" - originally published 8/1/2017 For the latest news in PHD Comics, CLICK HERE!

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Second-Order Peer Reviews of Clinically Relevant Articles for the Physiatrist: Additional Weekend Therapy May Reduce Length of Rehabilitation Stay After Stroke: A Meta-analysis of Individual Patient Data.

No abstract available

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Aquatic Exercises in the Treatment of Low Back Pain: A Systematic Review of the Literature and Meta-Analysis of Eight Studies.

Objective: Low back pain is the most common musculoskeletal condition with a high prevalence. There was no sufficient evidence to recommend that aquatic exercise was potentially beneficial to patients with low back pain. The aim of this study was to systematically analyze all evidence available in the literature about effectiveness of the aquatic exercise. Design: A comprehensive search of PubMed, the Cochrane Library, Embase, and Cumulative Index to Nursing and Allied Health was conducted from their inceptions to November 2016 for randomized controlled trials, which concerned the therapeutic aquatic exercise for low back pain. The results were expressed in terms of standardized mean difference and the corresponding 95% confidence interval. Results: Eight trials involving 331 patients were included in the meta-analysis, and the results showed a relief of pain (standardized mean difference = -0.65, 95% confidence interval = -1.16 to -0.14) and physical function (standardized mean difference = 0.63, 95% confidence interval = 0.17 to 1.09) after aquatic exercise. However, there was no significant effectiveness with regard to general mental health in aquatic group (standardized mean difference = 0.46; 95% confidence interval = -0.22 to 1.15). Conclusions: Aquatic exercise can statistically significantly reduce pain and increase physical function in patients with low back pain. Further high-quality investigations on a larger scale are required to confirm the results. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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GSE80746 Gene regulation of candidate cancer gene DIP2C

Contributors : Chatarina Larsson ; Tobias Sjöblom
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

Purpose: The disco-interacting protein 2 homolog C (DIP2C) gene is an uncharacterized gene found mutated in breast and lung cancers. We want to understand the role of DIP2C in tumor development.
Methods: We engineered human DIP2C knockout cell systems by genome editing, and then use next-generation sequencing to identify the genes affected by the loss of DIP2C.
Results: Inactivation of DIP2C triggers substantial gene expression changes, cellular senescence and epithelial to mesenchymal transition in cancer cells.

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GSE90087 LMO1 Synergizes with MYCN to Promotes Neuroblastoma Initiation and Metastasis

Contributors : Shizhen Zhu ; Hu Li
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

High levels of LMO1 expression synergizes with MYCN to accelerate neuroblastomagenesis, enhance disease penetrance and promote widespread metastasis in zebrafish. Transcriptomic analysis of human neuroblasotma cells with programed expression of LMO1 vs vector control or neuroblastoma cells with differential endogenous LMO1 expression revealed that gene signitures affecting tumor cell-extracellular matrix interaction are significantly associated with high levels of LMO1 expression. Our findings provide compelling evidence for a major pathogenic role of LMO1 in MYCN-driven neuroblastoma.

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2017 Dave and Dan Classic raises more than $1.273 million for children's hospitals including UC Davis Children's Hospital

SACRAMENTO, Calif. (July 31, 2017) - This year's fifth annual Dave and Dan Classic, presented by First Tech Federal Credit Union, raised more than $1.273 million to support Credit Unions for Kids, benefiting six Children's Miracle Network Hospitals in California, Colorado, Oregon and Washington, including UC Davis Children's Hospital.

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Erythropoietin Receptor-Mediated Molecular Crosstalk Promotes T Cell Immunoregulation and Transplant Survival

Although spontaneous kidney transplant acceptance/tolerance occurs in mice and occasionally in humans, mechanisms remain unclear. Herein we test the hypothesis that EPO, a hormone predominantly produced by the adult kidney, has immunomodulating properties that are required for spontaneous kidney graft acceptance. In vitro, in a manner dependent on the EPO receptor and CD131 on antigen-presenting cells, EPO induced the secretion of active TGFβ by antigen-presenting cells, which in turn converted naïve CD4⁺ T cells into functional Foxp3⁺ regulatory T cells (Treg). In murine transplant models, pharmacologic downregulation of kidney-derived EPO prevented spontaneous Treg generation. In a controlled, prospective cohort clinical study, EPO administration at doses used to correct anemia augmented the frequency of peripheral CD4⁺CD25⁺CD127^lo T cells in humans with CKD. Furthermore, EPO directly inhibited conventional T cell proliferation in vitro via tyrosine phosphatase SHP-1–dependent uncoupling of IL-2Rβ signaling. Conversely, EPO-initiated signals facilitated Treg proliferation by augmenting IL-2R signaling and maintaining constitutively quenched IL-2Rβ signaling. In additional murine transplant models, recombinant EPO administration prolonged heart allograft survival, whereas pharmacologic downregulation of kidney-derived EPO reduced the expression of TGFβ mRNA and abrogated kidney allograft acceptance. Together, our findings delineate the protolerogenic properties of EPO in inhibiting conventional T cells while simultaneously promoting Treg induction, and suggest that manipulating the EPO/EPO receptor signaling axis could be exploited to prevent and/or treat T cell-mediated pathologies, including transplant rejection.

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Clinical and Genetic Spectrum of Bartter Syndrome Type 3

Bartter syndrome type 3 is a clinically heterogeneous hereditary salt-losing tubulopathy caused by mutations of the chloride voltage-gated channel Kb gene (CLCNKB), which encodes the ClC-Kb chloride channel involved in NaCl reabsorption in the renal tubule. To study phenotype/genotype correlations, we performed genetic analyses by direct sequencing and multiplex ligation-dependent probe amplification and retrospectively analyzed medical charts for 115 patients with CLCNKB mutations. Functional analyses were performed in Xenopus laevis oocytes for eight missense and two nonsense mutations. We detected 60 mutations, including 27 previously unreported mutations. Among patients, 29.5% had a phenotype of ante/neonatal Bartter syndrome (polyhydramnios or diagnosis in the first month of life), 44.5% had classic Bartter syndrome (diagnosis during childhood, hypercalciuria, and/or polyuria), and 26.0% had Gitelman-like syndrome (fortuitous discovery of hypokalemia with hypomagnesemia and/or hypocalciuria in childhood or adulthood). Nine of the ten mutations expressed in vitro decreased or abolished chloride conductance. Severe (large deletions, frameshift, nonsense, and essential splicing) and missense mutations resulting in poor residual conductance were associated with younger age at diagnosis. Electrolyte supplements and indomethacin were used frequently to induce catch-up growth, with few adverse effects. After a median follow-up of 8 (range, 1–41) years in 77 patients, chronic renal failure was detected in 19 patients (25%): one required hemodialysis and four underwent renal transplant. In summary, we report a genotype/phenotype correlation for Bartter syndrome type 3: complete loss-of-function mutations associated with younger age at diagnosis, and CKD was observed in all phenotypes.

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Relationship between Hypotension and Cerebral Ischemia during Hemodialysis

The relationship between BP and downstream ischemia during hemodialysis has not been characterized. We studied the dynamic relationship between BP, real-time symptoms, and cerebral oxygenation during hemodialysis, using continuous BP and cerebral oxygenation measurements prospectively gathered from 635 real-world hemodialysis sessions in 58 prevalent patients. We examined the relationship between BP and cerebral ischemia (relative drop in cerebral saturation >15%) and explored the lower limit of cerebral autoregulation at patient and population levels. Furthermore, we estimated intradialytic exposure to cerebral ischemia and hypotension for each patient, and entered these values into multivariate models predicting change in cognitive function. In all, 23.5% of hemodialysis sessions featured cerebral ischemia; 31.9% of these events were symptomatic. Episodes of hypotension were common, with mean arterial pressure falling by a median of 22 mmHg (interquartile range, 14.3–31.9 mmHg) and dropping below 60 mmHg in 24% of sessions. Every 10 mmHg drop from baseline in mean arterial pressure associated with a 3% increase in ischemic events (P<0.001), and the incidence of ischemic events rose rapidly below an absolute mean arterial pressure of 60 mmHg. Overall, however, BP poorly predicted downstream ischemia. The lower limit of cerebral autoregulation varied substantially (mean 74.1 mmHg, SD 17.6 mmHg). Intradialytic cerebral ischemia, but not hypotension, correlated with decreased executive cognitive function at 12 months (P=0.03). This pilot study demonstrates that intradialytic cerebral ischemia occurs frequently, is not easily predicted from BP, and may be clinically significant.

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Understanding Trends in Kidney Function 1 Year after Kidney Transplant in the United States

Lower eGFR 1 year after kidney transplant is associated with shorter allograft and patient survival. We examined how practice changes in the past decade correlated with time trends in average eGFR at 1 year after kidney transplant in the United States in a cohort of 189,944 patients who received a kidney transplant between 2001 and 2013. We calculated the average eGFR at 1 year after transplant for the recipient cohort of each year using the appropriate Modification of Diet in Renal Disease equation depending on the prevailing methodology of creatinine measurement, and used linear regression to model the effects of practice changes on the national post-transplant eGFR trend. Between the 2001–2005 period and the 2011–2013 period, average 1-year post-transplant eGFR remained essentially unchanged, with differences of 1.34 (95% confidence interval, 1.03 to 1.65) ml/min per 1.73 m² and 0.66 (95% confidence interval, 0.32 to 1.01) ml/min per 1.73 m² among deceased and living donor kidney transplant recipients, respectively. Over time, the mean age of recipients increased and more marginal organs were used; adjusting for these trends unmasked a larger temporal improvement in post-transplant eGFR. However, changes in immunosuppression practice had a positive effect on average post-transplant eGFR and balanced out the negative effect of recipient/donor characteristics. In conclusion, average 1-year post-transplant eGFR remained stable, despite increasingly unfavorable attributes in recipients and donors. With an aging ESRD population and continued organ shortage, preservation of average post-transplant eGFR will require sustained improvement in immunosuppression and other aspects of post-transplant care.

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Colon Cancer Screening among Patients Receiving Dialysis in the United States: Are We Choosing Wisely?

The American Society of Nephrology recommends against routine cancer screening among asymptomatic patients receiving maintenance dialysis on the basis of limited survival benefit. To determine the frequency of colorectal cancer screening among patients on dialysis and the extent to which screening tests were targeted toward patients at lower risk of death and higher likelihood of receiving a kidney transplant, we performed a cohort study of 469,574 Medicare beneficiaries ages ≥50 years old who received dialysis between January 1, 2007 and September 30, 2012. We examined colorectal cancer screening tests according to quartiles of risk of mortality and kidney transplant on the basis of multivariable Cox modeling. Over a median follow-up of 1.5 years, 11.6% of patients received a colon cancer screening test (57.9 tests per 1000 person-years). Incidence rates of colonoscopy, flexible sigmoidoscopy, and fecal occult blood test were 27.9, 0.6, and 29.5 per 1000 person-years, respectively. Patients in the lowest quartile of mortality risk were more likely to be screened than those in the highest quartile (hazard ratio, 1.53; 95% confidence interval, 1.49 to 1.57; 65.1 versus 46.4 tests per 1000 person-years, respectively), amounting to a 33% higher rate of testing. Additionally, compared with patients least likely to receive a transplant, patients most likely to receive a transplant were more likely to be screened (hazard ratio, 1.68; 95% confidence interval, 1.64 to 1.73). Colon cancer screening is being targeted toward patients on dialysis at lowest risk of mortality and highest likelihood of transplantation, but absolute rates are high, suggesting overscreening.

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Urine Ammonium Predicts Clinical Outcomes in Hypertensive Kidney Disease

Metabolic acidosis is associated with poor outcomes in CKD. Because impaired renal ammonium excretion is important in the pathogenesis of acidosis, urine ammonium excretion might be a better and perhaps earlier acid–base indicator of risk than serum bicarbonate, particularly in patients without acidosis. We evaluated the association between baseline ammonium excretion and clinical outcomes in African American Study of Kidney Disease and Hypertension participants (n=1044). Median daily ammonium excretion was 19.5 (95% confidence interval [95% CI], 6.5 to 43.2) mEq. In Cox regression models (adjusted for demographics, measured GFR, proteinuria, body mass index, net endogenous acid production, and serum potassium and bicarbonate), hazard ratios of the composite outcome of death or dialysis were 1.46 (95% CI, 1.13 to 1.87) in the low tertile and 1.14 (95% CI, 0.89 to 1.46) in the middle tertile of daily ammonium excretion compared with the high tertile. Among participants without acidosis at baseline, the adjusted hazard ratio for those with ammonium excretion <20 mEq/d was 1.36 (95% CI, 1.09 to 1.71) compared with those with ammonium excretion ≥20 mEq/d. Additionally, compared with participants in the high ammonium tertile, those in the low ammonium tertile had higher adjusted odds of incident acidosis at 1 year (adjusted odds ratio, 2.56; 95% CI, 1.04 to 6.27). In conclusion, low ammonium excretion is associated with death and renal failure in hypertensive kidney disease, even among those without acidosis. Low ammonium excretion could identify patients with CKD and normal bicarbonate levels who might benefit from alkali before acidosis develops.

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C1-Inhibitor Decreases the Release of Vasculitis-Like Chemotactic Endothelial Microvesicles

The kinin system is activated during vasculitis and may contribute to chronic inflammation. C1-inhibitor is the main inhibitor of the kinin system. In this study, we investigated the presence of the kinin B1 receptor on endothelial microvesicles and its contribution to the inflammatory process. Compared with controls (n=15), patients with acute vasculitis (n=12) had markedly higher levels of circulating endothelial microvesicles, identified by flow cytometry analysis, and significantly more microvesicles that were positive for the kinin B1 receptor (P<0.001). Compared with microvesicles from wild-type cells, B1 receptor-positive microvesicles derived from transfected human embryonic kidney cells induced a significant neutrophil chemotactic effect, and a B1 receptor antagonist blocked this effect. Likewise, patient plasma induced neutrophil chemotaxis, an effect decreased by reduction of microvesicle levels and by blocking the B1 receptor. We used a perfusion system to study the effect of patient plasma (n=6) and control plasma (n=6) on the release of microvesicles from glomerular endothelial cells. Patient samples induced the release of significantly more B1 receptor-positive endothelial microvesicles than control samples, an effect abrogated by reduction of the microvesicles in the perfused samples. Perfusion of C1-inhibitor–depleted plasma over glomerular endothelial cells promoted excessive release of B1 receptor-positive endothelial microvesicles compared with normal plasma, an effect significantly decreased by addition of C1-inhibitor or B1 receptor-antagonist. Thus, B1 receptor-positive endothelial microvesicles may contribute to chronic inflammation by inducing neutrophil chemotaxis, and the reduction of these microvesicles by C1-inhibitor should be explored as a potential treatment for neutrophil-induced inflammation.

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Chronic Fluid Overload and Mortality in ESRD

Sustained fluid overload (FO) is considered a major cause of hypertension, heart failure, and mortality in patients with ESRD on maintenance hemodialysis. However, there has not been a cohort study investigating the relationship between chronic exposure to FO and mortality in this population. We studied the relationship of baseline and cumulative FO exposure over 1 year with mortality in 39,566 patients with incident ESRD in a large dialysis network in 26 countries using whole-body bioimpedance spectroscopy to assess fluid status. Analyses were applied across three discrete systolic BP (syst-BP) categories (<130, 130–160, and >160 mmHg), with nonoverhydrated patients with syst-BP=130–160 mmHg as the reference category; >200,000 FO measurements were performed over follow-up. Baseline FO value predicted excess risk of mortality across syst-BP categories (<130 mmHg: hazard ratio [HR], 1.51; 95% confidence interval [95% CI], 1.38 to 1.65; 130–160 mmHg: HR, 1.25; 95% CI, 1.16 to 1.36; >160 mmHg: HR, 1.30; 95% CI, 1.19 to 1.42; all P<0.001). However, cumulative 1-year FO exposure predicted a higher death risk (P<0.001) across all syst-BP categories (<130 mmHg: HR, 1.94; 95% CI, 1.68 to 2.23; 130–160 mmHg: HR, 1.51; 95% CI, 1.35 to 1.69; >160 mmHg: HR, 1.62; 95% CI, 1.39 to 1.90). In conclusion, chronic exposure to FO in ESRD is a strong risk factor for death across discrete BP categories. Whether treatment policies that account for fluid status monitoring are preferable to policies that account solely for predialysis BP measurements remains to be tested in a clinical trial.

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Long-Term Endothelin-A Receptor Antagonism Provides Robust Renal Protection in Humanized Sickle Cell Disease Mice

Sickle cell disease (SCD)–associated nephropathy is a major source of morbidity and mortality in patients because of the lack of efficacious treatments targeting renal manifestations of the disease. Here, we describe a long-term treatment strategy with the selective endothelin-A receptor (ET_A) antagonist, ambrisentan, designed to interfere with the development of nephropathy in a humanized mouse model of SCD. Ambrisentan preserved GFR at the level of nondisease controls and prevented the development of proteinuria, albuminuria, and nephrinuria. Microscopy studies demonstrated prevention of podocyte loss and structural alterations, the absence of vascular congestion, and attenuation of glomerulosclerosis in treated mice. Studies in isolated glomeruli showed that treatment reduced inflammation and oxidative stress. At the level of renal tubules, ambrisentan treatment prevented the increased excretion of urinary tubular injury biomarkers. Additionally, the treatment strategy prevented tubular brush border loss, diminished tubular iron deposition, blocked the development of interstitial fibrosis, and prevented immune cell infiltration. Furthermore, the prevention of albuminuria in treated mice was associated with preservation of cortical megalin expression. In a separate series of identical experiments, combined ET_A and ET_B receptor antagonism provided only some of the protection observed with ambrisentan, highlighting the importance of exclusively targeting the ET_A receptor in SCD. Our results demonstrate that ambrisentan treatment provides robust protection from diverse renal pathologies in SCD mice, and suggest that long-term ET_A receptor antagonism may provide a strategy for the prevention of renal complications of SCD.

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Renal Tubular Ubiquitin-Protein Ligase NEDD4-2 Is Required for Renal Adaptation during Long-Term Potassium Depletion

Adaptation of the organism to potassium (K⁺) deficiency requires precise coordination among organs involved in K⁺ homeostasis, including muscle, liver, and kidney. How the latter performs functional and molecular changes to ensure K⁺ retention is not well understood. Here, we investigated the role of ubiquitin-protein ligase NEDD4-2, which negatively regulates the epithelial sodium channel (ENaC), Na⁺/Cl^– cotransporter (NCC), and with no-lysine-kinase 1 (WNK1). After dietary K⁺ restriction for 2 weeks, compared with control littermates, inducible renal tubular NEDD4-2 knockout (Nedd4L^Pax8/LC1) mice exhibited severe hypokalemia and urinary K⁺ wasting. Notably, expression of the ROMK K⁺ channel did not change in the distal convoluted tubule and decreased slightly in the cortical/medullary collecting duct, whereas BK channel abundance increased in principal cells of the connecting tubule/collecting ducts. However, K⁺ restriction also enhanced ENaC expression in Nedd4L^Pax8/LC1 mice, and treatment with the ENaC inhibitor, benzamil, reversed excessive K⁺ wasting. Moreover, K⁺ restriction increased WNK1 and WNK4 expression and enhanced SPAK-mediated NCC phosphorylation in Nedd4L^Pax8/LC1 mice, with no change in total NCC. We propose a mechanism in which NEDD4-2 deficiency exacerbates hypokalemia during dietary K⁺ restriction primarily through direct upregulation of ENaC, whereas increased BK channel expression has a less significant role. These changes outweigh the compensatory antikaliuretic effects of diminished ROMK expression, increased NCC phosphorylation, and enhanced WNK pathway activity in the distal convoluted tubule. Thus, NEDD4-2 has a crucial role in K⁺ conservation through direct and indirect effects on ENaC, distal nephron K⁺ channels, and WNK signaling.

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The MicroRNA-199a/214 Cluster Targets E-Cadherin and Claudin-2 and Promotes High Glucose-Induced Peritoneal Fibrosis

Serum response factor (SRF) was found to be involved in the phenotypic transition and fibrosis of the peritoneal membrane during treatment with peritoneal dialysis (PD), but the exact mechanism remains unclear. SRF regulates microRNAs (miRNAs) that contain the SRF-binding consensus (CArG) element in the promoter region. Therefore, we investigated whether the miR-199a/214 gene cluster, which contains a CArG element in its promoter, is directly regulated by SRF. High-glucose (HG) treatment significantly unregulated the expression of the miR-199a-5p/214–3p gene cluster in human peritoneal mesothelial cells (HPMCs). By chromatin immunoprecipitation and reporter assays, we found that SRF binds to the miR-199a-5p/214–3p gene cluster promoter after HG stimulation. In vitro, in HPMCs, silencing of miR-199a-5p or miR-214–3p inhibited the HG-induced phenotypic transition and cell migration but enhanced cell adhesion, whereas ectopic expression of mimic oligonucleotides had the opposite effects. Both miR-199a-5p and miR-214–3p targeted claudin-2 and E-cadherin mRNAs. In a PD rat model, treatment with an SRF inhibitor silenced miR-199a-5p and miR-214–3p and alleviated HG-PD fluid–induced damage and fibrosis. Overall, this study reveals a novel SRF–miR-199a/miR-214–E-cadherin/claudin-2 axis that mediates damage and fibrosis in PD.

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Na+/HCO3- Cotransporter NBCn2 Mediates HCO3- Reclamation in the Apical Membrane of Renal Proximal Tubules

The kidney maintains systemic acid-base balance by reclaiming from the renal tubule lumen virtually all HCO₃^– filtered in glomeruli and by secreting additional H⁺ to titrate luminal buffers. For proximal tubules, which are responsible for about 80% of this activity, it is believed that HCO₃^– reclamation depends solely on H⁺ secretion, mediated by the apical Na⁺/H⁺ exchanger NHE₃ and the vacuolar proton pump. However, _NHE3 and the proton pump cannot account for all HCO₃^– reclamation. Here, we investigated the potential contribution of two variants of the electroneutral Na⁺/HCO₃^– cotransporter NBCn2, the amino termini of which start with the amino acids MCDL (MCDL-NBCn2) and MEIK (MEIK-NBCn2). Western blot analysis and immunocytochemistry revealed that MEIK-NBCn2 predominantly localizes at the basolateral membrane of medullary thick ascending limbs in the rat kidney, whereas MCDL-NBCn2 localizes at the apical membrane of proximal tubules. Notably, NH₄Cl-induced systemic metabolic acidosis or hypokalemic alkalosis downregulated the abundance of MCDL-NBCn2 and reciprocally upregulated NHE₃. Conversely, NaHCO₃-induced metabolic alkalosis upregulated MCDL-NBCn2 and reciprocally downregulated NHE₃. We propose that the apical membrane of the proximal tubules has two distinct strategies for HCO₃^– reclamation: the conventional indirect pathway, in which NHE₃ and the proton pump secrete H⁺ to titrate luminal HCO₃^–, and the novel direct pathway, in which NBCn2 removes HCO₃^– from the lumen. The reciprocal regulation of NBCn2 and NHE₃ under different physiologic conditions is consistent with our mathematical simulations, which suggest that HCO₃^– uptake and H⁺ secretion have reciprocal efficiencies for HCO₃^– reclamation versus titration of luminal buffers.

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Two-Photon Intravital Fluorescence Lifetime Imaging of the Kidney Reveals Cell-Type Specific Metabolic Signatures

In the live animal, tissue autofluorescence arises from a number of biologically important metabolites, such as the reduced form of nicotinamide adenine dinucleotide. Because autofluorescence changes with metabolic state, it can be harnessed as a label-free imaging tool with which to study metabolism in vivo. Here, we used the combination of intravital two-photon microscopy and frequency-domain fluorescence lifetime imaging microscopy (FLIM) to map cell-specific metabolic signatures in the kidneys of live animals. The FLIM images are analyzed using the phasor approach, which requires no prior knowledge of metabolite species and can provide unbiased metabolic fingerprints for each pixel of the lifetime image. Intravital FLIM revealed the metabolic signatures of S1 and S2 proximal tubules to be distinct and resolvable at the subcellular level. Notably, S1 and distal tubules exhibited similar metabolic profiles despite apparent differences in morphology and autofluorescence emission with traditional two-photon microscopy. Time-lapse imaging revealed dynamic changes in the metabolic profiles of the interstitium, urinary lumen, and glomerulus—areas that are not resolved by traditional intensity-based two-photon microscopy. Finally, using a model of endotoxemia, we present examples of the way in which intravital FLIM can be applied to study kidney diseases and metabolism. In conclusion, intravital FLIM of intrinsic metabolites is a bias-free approach with which to characterize and monitor metabolism in vivo, and offers the unique opportunity to uncover dynamic metabolic changes in living animals with subcellular resolution.

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Quick Sequential Organ Failure Assessment and Systemic Inflammatory Response Syndrome Criteria as Predictors of Critical Care Intervention Among Patients With Suspected Infection.

Objectives: The Sepsis III clinical criteria for the diagnosis of sepsis rely on scores derived to predict inhospital mortality. In this study, we introduce the novel outcome of "received critical care intervention" and investigate the related predictive performance of both the quick Sequential Organ Failure Assessment and the Systemic Inflammatory Response Syndrome criteria. Design: This was a single-center, retrospective analysis of electronic health records. Setting: Tertiary care hospital in the United States. Patients: Patients with suspected infection who presented to the emergency department and were admitted to the hospital between January 2010 and December 2014. Interventions: Systemic Inflammatory Response Syndrome and quick Sequential Organ Failure Assessment scores were calculated, and their relationships to the receipt of critical care intervention and inhospital mortality were determined. Measurement and Main Results: A total of 24,164 patients were included of whom 6,693 (27.7%) were admitted to an ICU within 48 hours; 4,453 (66.5%) patients admitted to the ICU received a critical care intervention. Among those with quick Sequential Organ Failure Assessment less than 2, 13.4% received a critical care intervention and 3.5% died compared with 48.2% and 13.4%, respectively, for quick Sequential Organ Failure Assessment greater than or equal to 2. The area under the receiver operating characteristic was similar whether quick Sequential Organ Failure Assessment was used to predict receipt of critical care intervention or inhospital mortality (0.74 [95% CI, 0.73-0.74] vs 0.71 [0.69-0.72]). The area under the receiver operating characteristic of Systemic Inflammatory Response Syndrome for critical care intervention (0.69) and mortality (0.66) was lower than that for quick Sequential Organ Failure Assessment (p

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Adsorption-Desorption Characteristics of Nonylphenol on Two Different Origins of Black Carbon

Abstract

Black carbon (BC) is considered to be a promising novel material for controlling organic contaminants due to its strong adsorption property, low production cost, and less secondary pollution. However, seldom systemic research was conducted to investigate adsorption-desorption characteristics and interaction mechanism between BC and nonylphenol (NP), one kind of endocrine-disrupting contaminants (EDCs) and persistent organic pollutants (POPs). Therefore, in the present study, adsorption characteristics of NP on two BCs (rice straw black carbon (RC) and fly ash carbon (FC)) involving adsorption isotherm, kinetics, effect of pH, as well as desorption kinetics, were investigated to explore the feasibility of BC for remediation of NP pollution in a water environment. Adsorption isotherm data showed that Q _max was 61,889.21 ± 2777.68 and 6538.99 ± 606.72 mg/kg and n was 0.39 ± 0.037 and 0.55 ± 0.043 for RC and FC, respectively, suggesting the sorption capacity and nonlinearity of RC to NP is far higher than FC and indicating BC was an effective sorbent for NP pollution control, especially RC. The pH affected BC sorption capacity to NP by influencing the surface properties of BC and the NP speciation together. Desorption kinetics data indicated that more than 80% NP could not be released from both BCs, suggesting that BC could reduce NP releasing risk in a water environment evidently when BC is applied for NP pollution remediation.

Graphical Abstract

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