Predicting Severity of Acute Pain After Cesarean Delivery: A Narrative Review

Cesarean delivery is one of the most common surgical procedures in the United States, with over 1.3 million performed annually. One-fifth of women who undergo cesarean delivery will experience severe pain in the acute postoperative period, increasing their risk of developing chronic pain and postpartum depression, and negatively impacting breastfeeding and newborn care. A growing body of research has investigated tools to predict which patients will experience more severe pain and have increased analgesic consumption after cesarean delivery. These include quantitative sensory testing, assessment of wound hyperalgesia, response to local anesthetic infiltration, and preoperative psychometric evaluations such as validated psychological questionnaires and simple screening tools. For this review, we searched MEDLINE, the Cochrane database, and Google Scholar to identify articles that evaluated the utility of various tools to predict severe pain and/or opioid consumption in the first 48 hours after cesarean delivery. Thirteen articles were included in the final review: 5 utilizing quantitative sensory testing, including patient responses to pressure, electrical, and thermal stimuli; 1 utilizing hyperalgesia testing; 1 using response to local anesthetic wound infiltration; 4 utilizing preoperative psychometric evaluations including the State-Trait Anxiety Inventory, the Pain Catastrophizing Scale, the Pittsburgh Sleep Quality Index, the Hospital Anxiety and Depression Scale, and simple questionnaires; and 2 utilizing a combination of quantitative sensory tests and psychometric evaluations. A number of modalities demonstrated statistically significant correlations with pain outcomes after cesarean delivery, but most correlations were weak to modest, and many modalities might not be clinically feasible. Response to local anesthetic infiltration and a tool using 3 simple questions enquiring about anxiety and anticipated pain and analgesic needs show potential for clinical use, but further studies are needed to evaluate the utility of these predictive tests in clinical practice.

https://ift.tt/2HhZPul

A Pain in the Abs: Predicting Post-Cesarean Analgesia

No abstract available

https://ift.tt/2HgOACh

Physiology and Role of Intraocular Pressure in Contemporary Anesthesia

More than 26 million Americans suffer with cataracts, and with 3.6 million cataract extractions performed annually in the United States, it is the most common surgical procedure. The integrity of the delicate structures of the eye that mediate vision is dependent on the intraocular pressure (IOP). Yet, IOP acts to compress the vessels within the globe—akin to a Starling resistor—and is a key component that determines the ocular perfusion pressure, defined as the difference between arterial pressure and IOP. The retina is one of the most metabolically active tissues in the body, and its functional integrity is dependent on an adequate blood supply, with retinal function linearly related to the ocular perfusion pressure. Retinal cell death has been demonstrated at low perfusion pressures (below 50 mm Hg). Modern ophthalmic surgery involves globe irrigation, manipulation, and instrumentation, resulting in dynamic pressure fluxes within the eye. Marked elevations of IOP (up to 4–5 times the normal value) with consequent borderline retinal and optic disk perfusion pressures occur for prolonged periods during many ophthalmic procedures. General surgeries, including laparoscopic, spinal, and cardiac procedures, especially, with their demand for steep Trendelenburg or prolonged prone positioning and/or hypotensive anesthesia, can induce IOP changes and ocular perfusion imbalance. These rapid fluctuations in IOP, and so in perfusion, play a role in the pathogenesis of the visual field defects and associated ocular morbidity that frequently complicate otherwise uneventful surgeries. The exact etiology of such outcomes is multifactorial, but ocular hypoperfusion plays a significant and frequently avoidable role. Those with preexisting compromised ocular blood flow are especially vulnerable to intraoperative ischemia, including those with hypertension, diabetes, atherosclerosis, or glaucoma. However, overly aggressive management of arterial pressure and IOP may not be possible given a patient's comorbidity status, and it potentially exposes the patient to risk of catastrophic choroidal hemorrhage. Anesthetic management significantly influences the pressure changes in the eye throughout the perioperative period. Strategies to safeguard retinal perfusion, reduce the ischemic risk, and minimize the potential for expulsive bleeding must be central to the anesthetic techniques selected. This review outlines: important physiological principles; ophthalmic and general procedures most likely to develop damaging IOP levels and their causative factors; the effect of anesthetic agents and techniques on IOP; recent scientific evidence highlighting the significance of perfusion changes during surgery; and key aspects of postoperative visual loss and management approaches for high-risk patients presenting for surgery.

https://ift.tt/2F21gep

The Eyes Have It: Factors that Influence Intraocular Pressure (IOP)

No abstract available

https://ift.tt/2HG69iP

Patient Harm in Cataract Surgery: A Series of Adverse Events in Massachusetts

Massachusetts state agencies received reports of 37 adverse events (AEs) involving cataract surgery from 2011 to 2015. Fifteen were anesthesia related, including 5 wrong eye blocks, 3 cases of hemodynamic instability, 2 retrobulbar hematoma/hemorrhages, and 5 globe perforations resulting in permanent loss of vision. While Massachusetts' reported AEs likely underrepresent the true number of AEs that occur during cataract surgery, they do offer useful signal data to indicate the types of patient harm occurring during these procedures.

https://ift.tt/2qO2vtA

Preventing Adverse Events in Cataract Surgery: Recommendations From a Massachusetts Expert Panel

Massachusetts health care facilities reported a series of cataract surgery–related adverse events (AEs) to the state in recent years, including 5 globe perforations during eye blocks performed by 1 anesthesiologist in a single day. The Betsy Lehman Center for Patient Safety, a nonregulatory Massachusetts state agency, responded by convening an expert panel of frontline providers, patient safety experts, and patients to recommend strategies for mitigating patient harm during cataract surgery. The purpose of this article is to identify contributing factors to the cataract surgery AEs reported in Massachusetts and present the panel's recommended strategies to prevent them. Data from state-mandated serious reportable event reports were supplemented by online surveys of Massachusetts cataract surgery providers and semistructured interviews with key stakeholders and frontline staff. The panel identified 2 principal categories of contributing factors to the state's cataract surgery–related AEs: systems failures and choice of anesthesia technique. Systems failures included inadequate safety protocols (48.7% of contributing factors), communication challenges (18.4%), insufficient provider training (17.1%), and lack of standardization (15.8%). Choice of anesthesia technique involved the increased relative risk of needle-based eye blocks. The panel's surveys of Massachusetts cataract surgery providers show wide variation in anesthesia practices. While 45.5% of surgeons and 69.6% of facilities reported increased use of topical anesthesia compared to 10 years earlier, needle-based blocks were still used in 47.0% of cataract surgeries performed by surgeon respondents and 40.9% of those performed at respondent facilities. Using a modified Delphi approach, the panel recommended several strategies to prevent AEs during cataract surgery, including performing a distinct time-out with at least 2 care-team members before block administration; implementing standardized, facility-wide safety protocols, including a uniform site-marking policy; strengthening the credentialing and orientation of new, contracted and locum tenens anesthesia staff; ensuring adequate and documented training in block administration for any provider who is new to a facility, including at least 10 supervised blocks before practicing independently; using the least invasive form of anesthesia appropriate to the patient; and finally, adjusting anesthesia practices, including preferred techniques, as evidence-based best practices evolve. Future research should focus on evaluating the impact of these recommendations on patient outcomes.

https://ift.tt/2F69YZ4

Forgetting the new locations of one’s keys: spatial-memory interference in Korsakoff’s amnesia

Abstract

The present study focused on interference in a group of patients with amnesia due to Korsakoff's syndrome (KS) within the domain of spatial memory. An object–location memory task was used in which participants first learned an array of objects on a computer screen, followed by a reconstruction of the object positions. Next a trial was given in which the same objects were presented only now in different locations. Participants had to place the objects a second time but at the new locations. This was repeated for seven pairs of baseline/interference trials. Both Korsakoff patients and matched controls did worse on the interference trials than on the baseline trials, indicating that it is difficult to relearn new spatial locations for objects that previously were remembered in other locations. When computing relative interference effects (that is the percentage change from baseline in the interference trials), Korsakoff patients were less affected than controls. It is discussed in how far interference depends on the strength of the original memories, which are markedly lower in KS patients.

https://ift.tt/2HHMOOp

Cancers, Vol. 10, Pages 125: Selective Inhibition of Histone Deacetylation in Melanoma Increases Targeted Gene Delivery by a Bacteriophage Viral Vector

Cancers, Vol. 10, Pages 125: Selective Inhibition of Histone Deacetylation in Melanoma Increases Targeted Gene Delivery by a Bacteriophage Viral Vector

Cancers doi: 10.3390/cancers10040125

Authors: Samuel Campbell Keittisak Suwan Sajee Waramit Eric Ofori Aboagye Amin Hajitou

The previously developed adeno-associated virus/phage (AAVP) vector, a hybrid between M13 bacteriophage (phage) viruses that infect bacteria only and human Adeno-Associated Virus (AAV), is a promising tool in targeted gene therapy against cancer. AAVP can be administered systemically and made tissue specific through the use of ligand-directed targeting. Cancer cells and tumor-associated blood vessels overexpress the αν integrin receptors, which are involved in tumor angiogenesis and tumor invasion. AAVP is targeted to these integrins via a double cyclic RGD4C ligand displayed on the phage capsid. Nevertheless, there remain significant host-defense hurdles to the use of AAVP in targeted gene delivery and subsequently in gene therapy. We previously reported that histone deacetylation in cancer constitutes a barrier to AAVP. Herein, to improve AAVP-mediated gene delivery to cancer cells, we combined the vector with selective adjuvant chemicals that inhibit specific histone deacetylases (HDAC). We examined the effects of the HDAC inhibitor C1A that mainly targets HDAC6 and compared this to sodium butyrate, a pan-HDAC inhibitor with broad spectrum HDAC inhibition. We tested the effects on melanoma, known for HDAC6 up-regulation, and compared this side by side with a normal human kidney HEK293 cell line. Varying concentrations were tested to determine cytotoxic levels as well as effects on AAVP gene delivery. We report that the HDAC inhibitor C1A increased AAVP-mediated transgene expression by up to ~9-fold. These findings indicate that selective HDAC inhibition is a promising adjuvant treatment for increasing the therapeutic value of AAVP.

https://ift.tt/2HjhT7i

Diagnosis and Novel Approaches to the Treatment of Hypereosinophilic Syndromes

Abstract

Purpose of Review

Hypereosinophilic syndrome (HES) is characterized by persistent hypereosinophilia associated with end-organ damage. As our understanding of the pathogenesis of various forms of HES broadens, so does our ability to tailor steroid-sparing therapies for each subtype. The purpose of this review is to summarize recent literature related to the etiology, diagnosis, and management of HES.

Recent Findings

Mutations involved in subsets of HES can guide the choice of tyrosine kinase inhibitors beyond just imatinib. Several biologics that target interleukin-5 or its receptor have shown beneficial and selective eosinophil-reducing effects in clinical trials for asthma and other disorders including HES. Early clinical data with emerging therapies such as dexpramipexole and anti-Siglec-8 antibody show promise, but need to be confirmed in randomized trials.

Summary

Several new biologics and tyrosine kinase inhibitors have been shown to lower eosinophil numbers, but more randomized trials are needed to confirm efficacy in HES.

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Diagnostic role of serum tryptase in anaphylactic deaths in forensic medicine: a systematic review and meta-analysis

Abstract

Postmortem diagnosis of sudden death due to anaphylaxis can be very difficult due to the non-specific pathological findings in forensic practice. Postmortem serum tryptase has been used as an indicator of possible ante-mortem anaphylaxis. Though many previous studies have been conducted to explore the diagnostic significance of serum tryptase for lethal anaphylaxis, inconsistent results were documented. In this study, we made a retrospective study and presented a systematic review and meta-analysis that aims to summarize the diagnostic significance of postmortem serum tryptase in the deceased with and without anaphylactic shock and to calculate a cutoff value for future reference in the identification of deaths due to anaphylactic shock. A complete literature search in the PubMed, Cochrane Library, CNKI and Embase databases (published prior to March 1st, 2017) was performed. The quality of the eligible literature was evaluated according to the Newcastle-Ottawa Quality Assessment Scale (NOS), and the relevant data was extracted. The procedure of meta-analysis was performed by RevMan 5.3 software. Subgroup analysis was performed according to different causes of death. A total of nine studies with 296 patients were identified. The NOS of each included study was equal to 7. The results indicated that high concentrations of tryptase were significantly associated with anaphylactic shock when compared to the other causes of death. The weighted mean difference (WMD) was 29.53 (95% CI = 7.58–51.47, p = 0.008). Similar results were detected in the subgroup analysis when compared to deaths due to cardiovascular disease (CVD). However, no obvious elevation of tryptase in decedents with CVD compared to the other cause of death was observed (WMD = 4.42, 95% CI = −0.94–9.79). We concluded that high serum tryptase is a promising diagnostic biomarker for deaths due to anaphylactic shock, especially when it is higher than 30.4 μg/L.

https://ift.tt/2qP5Esm

In Response

No abstract available

https://ift.tt/2HNm64k

Differential Effects of Anesthetics and Opioid Receptor Activation on Cardioprotection Elicited by Reactive Oxygen Species–Mediated Postconditioning in Sprague-Dawley Rat Hearts

BACKGROUND: Despite an array of cardioprotective interventions identified in preclinical models of ischemia–reperfusion (IR) injury, successful clinical translation has not been achieved. This study investigated whether drugs routinely used in clinical anesthesia influence cardioprotective effectiveness by reducing effects of reactive oxygen species (ROS), upstream triggers of cardioprotective signaling. Effects of propofol, sevoflurane, or remifentanil were compared on postischemic functional recovery induced by ROS-mediated postconditioning with Intralipid. METHODS: Recovery of left ventricular (LV) work, an index of IR injury, was measured in isolated Sprague-Dawley rat hearts subjected to global ischemia (20 minutes) and reperfusion (30 minutes). Hearts were either untreated or were treated with postconditioning with Intralipid (1%, throughout reperfusion). Propofol (10 μM), sevoflurane (2 vol%), remifentanil (3 nM), or combinations thereof were administered peri-ischemically (before and during IR). The effects of anesthetics on ROS production were measured in LV cardiac fibers by Amplex Red assay under phosphorylating and nonphosphorylating conditions. RESULTS: Recovery of LV work (expressed as percentage of the preischemic value ± standard deviation) in untreated hearts was poor (20% ± 7%) and was improved by Intralipid postconditioning (58% ± 8%, P = .001). In the absence of Intralipid postconditioning, recovery of LV work was enhanced by propofol (28% ± 9%, P = .049), sevoflurane (49% ± 5%, P

https://ift.tt/2vvwA63

A Pain in the Abs: Predicting Post-Cesarean Analgesia

No abstract available

https://ift.tt/2HgOACh

Delineating the Trajectory of Cognitive Recovery From General Anesthesia in Older Adults: Design and Rationale of the TORIE (Trajectory of Recovery in the Elderly) Project

BACKGROUND: Mechanistic aspects of cognitive recovery after anesthesia and surgery are not yet well characterized, but may be vital to distinguishing the contributions of anesthesia and surgery in cognitive complications common in the elderly such as delirium and postoperative cognitive dysfunction. This article describes the aims and methodological approach to the ongoing study, Trajectory of Recovery in the Elderly (TORIE), which focuses on the trajectory of cognitive recovery from general anesthesia. METHODS: The study design employs cognitive testing coupled with neuroimaging techniques such as functional magnetic resonance imaging, diffusion tensor imaging, and arterial spin labeling to characterize cognitive recovery from anesthesia and its biological correlates. Applying these techniques to a cohort of age-specified healthy volunteers 40–80 years of age, who are exposed to general anesthesia alone, in the absence of surgery, will assess cognitive and functional neural network recovery after anesthesia. Imaging data are acquired before, during, and immediately after anesthesia, as well as 1 and 7 days after. Detailed cognitive data are captured at the same time points as well as 30 days after anesthesia, and brief cognitive assessments are repeated at 6 and 12 months after anesthesia. RESULTS: The study is underway. Our primary hypothesis is that older adults may require significantly longer to achieve cognitive recovery, measured by Postoperative Quality of Recovery Scale cognitive domain, than younger adults in the immediate postanesthesia period, but all will fully recover to baseline levels within 30 days of anesthesia exposure. Imaging data will address systems neuroscience correlates of cognitive recovery from general anesthesia. CONCLUSIONS: The data acquired in this project will have both clinical and theoretical relevance regardless of the outcome by delineating the mechanism behind short-term recovery across the adult age lifespan, which will have major implications for our understanding of the effects of anesthetic drugs.

https://ift.tt/2HNo8kQ

Auditing Intraoperative Transfusions to Promote High-Value Perioperative Care

No abstract available

https://ift.tt/2HBP3CJ

Postoperative Troponin Elevation, Myocardial Injury, and Pulmonary Embolism

No abstract available

https://ift.tt/2F4Zj0P

In Response

No abstract available

https://ift.tt/2HRAlFu

The American College of Surgeons Children’s Surgery Verification and Quality Improvement Program: Be Careful What You Wish For!

No abstract available

https://ift.tt/2HCqbup

Effect of Stellate Ganglion Block on the Regional Hemodynamics of the Upper Extremity: A Randomized Controlled Trial

BACKGROUND: The success of stellate ganglion block (SGB) is traditionally determined on the basis of findings such as Horner's syndrome, temperature rise in the face, hyperemia of the tympanic membrane, and nasal congestion. However, decreases in vascular resistance and increases in blood flow in the arm may be more meaningful findings. To date, the effect of SGB on the regional hemodynamics of the arm has not been evaluated using pulsed-wave Doppler ultrasound. METHODS: A total of 52 patients who were to undergo orthopedic surgery of the forearm were randomly assigned to either the mepivacaine group (SGB with 5 mL of 0.5% mepivacaine) or the saline group (SGB with 5 mL of normal saline). Before surgery, a single anesthesiologist performed a SGB under ultrasound guidance. The temperature of the upper extremity and the resistance index and blood flow in the brachial artery were measured before SGB, 15 and 30 minutes after SGB, and 1 hour after surgery. The severity of pain, requirement for rescue analgesics, and side effects of the local anesthetic agent were all documented. RESULTS: After SGB, the resistance index decreased significantly and the blood flow increased significantly in the brachial artery of members of the mepivacaine group (15 minutes: P = .004 and P

https://ift.tt/2vwQD3R

The Pros of Publishing Standalone Clinical Trial Protocols in Anesthesiology Journals

No abstract available

https://ift.tt/2F4ZitN

Can Lung Ultrasound Be the First-Line Tool for Evaluation of Intraoperative Hypoxemia?

No abstract available

https://ift.tt/2HNYrR9

Publishing Methods Without Results: A First That Hopefully Will Not Last

No abstract available

https://ift.tt/2HDY7XC

Pain Medicine: An Essential Review

No abstract available

https://ift.tt/2vvuJ0O

The Eye: What You Don’t Know Can Hurt Your Patient

No abstract available

https://ift.tt/2HjlwKL

Renal Interstitial Exhaustion and SGLT2 Blockers

No abstract available

https://ift.tt/2HNo5FG

Looking Beyond the Pain: Can Effective Labor Analgesia Prevent the Development of Postpartum Depression?

No abstract available

https://ift.tt/2qMY6Hd

Perioperative Cardiac Arrest: Focus on Local Anesthetic Systemic Toxicity (LAST) Erratum

No abstract available

https://ift.tt/2F3ThOb

Testing Times: Routine to Indicated!

No abstract available

https://ift.tt/2HfCyJt

Teaching Medical Students Clinical Anesthesia

There are many reasons for evaluating our approach and improving our teaching of America's future doctors, whether they become anesthesiologists (recruitment) or participate in patient management in the perioperative period (general patient care). Teaching medical students the seminal aspects of any medical specialty is a continual challenge. Although no definitive curricula or single clinical approach has been defined, certain key features can be ascertained from clinical experience and the literature. A survey was conducted among US anesthesiology teaching programs regarding the teaching content and approaches currently used to teach US medical students clinical anesthesia. Using the Accreditation Council for Graduate Medical Education website that lists 133 accredited anesthesiology programs, residency directors were contacted via e-mail. Based on those responses and follow-up phone calls, teaching representatives from 125 anesthesiology departments were identified and asked via e-mail to complete a survey. The survey was returned by 85 programs, yielding a response rate of 68% of individuals contacted and 63% of all departments. Ninety-one percent of the responding departments teach medical students, most in the final 2 years of medical school. Medical student exposure to clinical anesthesia occurred as elective only at 42% of the institutions, was requirement only at 16% of responding institutions, and the remainder had both elective and required courses. Anesthesiology faculty at 43% of the responding institutions reported teaching in the preclinical years of medical school, primarily in the departments of pharmacology and physiology. Forty-five percent of programs reported interdisciplinary teaching with other departments teaching classes such as gross anatomy. There is little exposure of anesthesiology faculty to medical students in other general courses. Teaching in the operating room is the primary teaching method in the clinical years. Students are allowed full access to patient care, including performing history and physical examinations, participating in the insertion of IVs and airway management. Simulation-based teaching was used by 82% of programs during medical student anesthesia clerkships. Sixty-eight percent of respondents reported that they have no formal training for their anesthesiology faculty teachers, 51% stated that they do not receive nonclinical time to teach, and 38% of respondents stated that they received some form of remuneration for teaching medical students, primarily nonclinical time. This article presents a summary of these survey results, provides a historical review of previous evaluations of teaching medical students clinical anesthesia, and discusses the contributions of anesthesiologists to medical student education.

https://ift.tt/2HP7amj

Implementing Obstetric Early Warning Systems

AJP Rep 2018; 08: e79-e84
DOI: 10.1055/s-0038-1641569

Severe maternal morbidity and mortality are often preventable and obstetric early warning systems that alert care providers of potential impending critical illness may improve maternal safety. While literature on outcomes and test characteristics of maternal early warning systems is evolving, there is limited guidance on implementation. Given current interest in early warning systems and their potential role in care, the 2017 Society for Maternal-Fetal Medicine (SMFM) Annual Meeting dedicated a session to exploring early warning implementation across a wide range of hospital settings. This manuscript reports on key points from this session. While implementation experiences varied based on factors specific to individual sites, common themes relevant to all hospitals presenting were identified. Successful implementation of early warnings systems requires administrative and leadership support, dedication of resources, improved coordination between nurses, providers, and ancillary staff, optimization of information technology, effective education, evaluation of and change in hospital culture and practices, and support in provider decision-making. Evolving data on outcomes on early warning systems suggest that maternal risk may be reduced. To effectively reduce maternal, risk early warning systems that capture deterioration from a broad range of conditions may be required in addition to bundles tailored to specific conditions such as hemorrhage, thromboembolism, and hypertension.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  open access Full text

https://ift.tt/2F49bIt

Prevalence and antifungal susceptibility of mycotic agents isolated from skin lesions of horses in Enugu State, Nigeria

Abstract

The study was conducted at Obollo-Afor horse market to determine the occurrence and the antifungal susceptibility profile of mycotic agents in skin lesions of trade horses. The samples were collected by plucking the hair and scraping the epidermal scales using sterile scapel blades. Each sample was planted onto the surface of Sabouraud dextrose agar (SDA) media plate. Inoculated plates was incubated at 25–30 °C and examined daily for fungal growth for 4 weeks. After obtaining pure cultures, they were subcultured on the Potato dextrose agar (PDA) for proper sporulation. Identification of each of the fungal isolates were based on cultural characteristics, microscopic examinations, slide culture technique and biochemical tests. 150 (30.18%) of the examined horses had skin lesions, 97 (64.7%) of which were males while 53 (35.3%) were females. In the wet season, 140 (93.3%) of the horses with skin lesions were observed and 10 (6.6%) were observed to have lesions during the dry season. The overall isolation rates were as follows the genera Aspergillus (24.5%), Trichophyton (14.3%), Microsporum (6.1%), Penicillium (8.2%), Curvularia (6.1%) and Fusarium (4.1%) from skin lesions of horses. All the isolates apart of those of Penicillium spp. were resistant to fluconazole while none of the respective isolates were resistant to voriconazole and nystatin. This study has provided baseline information which includes sex and seasonal distributions of the fungal agents associated with skin lesions in trade horses in Obollo-Afor area of Enugu State. Antifungal susceptibility results shows that voriconazole and nystatin are the drugs of choice in the treatment of dermatomycoses of horses in Nigeria.

https://ift.tt/2Hgb4U6

Hematological and plasm biochemical values for Rhinogobio ventralis in the Yangtze River, China

Abstract

Fish blood parameters can be used as potential indicators for identification of stress caused by environmental factors. This study aimed to establish a "normal" hematological profile for the Rhinogobio ventralis and to provide the basis for future comparative surveys. The hematological and plasma biochemical parameters were measured in the cyprinid species, R. ventralis, collected from the upper reaches of the Yangtze River. The concentrations of red blood cell count, white blood cell count, hematocrit, hemoglobin, mean corpuscle volume, mean corpuscle hemoglobin, Cl⁻, Ca²⁺, creatinine, urea, glucose, plasma total protein, plasma albumin, globulins, triglyceride, cholesterol, alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase were obtained. The results revealed that no significant differences were found in the hematological and plasma parameters between different sexes when they were analyzed with the independent samples t test. Compared with other fish species, it is hard to find hematological and plasma parameters that can be used as a species-specific physiological indication, and there were no sex-dependent blood parameters in the present study.

https://ift.tt/2HELKup

Effects of atorvastatin on myocardial oxidative and nitrosative stress in diabetic rats

Abstract

Free radicals play a pivotal role in many pathophysiological states, such as myopathies. Atorvastatin is a known cholesterol-lowering agent with many pleiotropic actions including antioxidant properties. However, the impact of atorvastatin on myocardial oxidative stress is not well known. The aim of this study was to evaluate the role of atorvastatin in improving diabetes-induced oxidative stress in the myocardium. Male Wistar rats weighing 20–25 g were randomly divided into four groups as normal, normal-treated, diabetes, and diabetes-treated. Induction of diabetes was performed by a single dose of streptozotocin (40 mg/kg, i.v.). Treated animals received atorvastatin for 8 weeks orally (40 mg/kg/day). After 8 weeks, animals were sacrificed and myocardial tissues were removed. Then, nitrate, glutathione (GSH), and malondialdehyde (MDA) contents as well as enzymatic activities of catalase (CAT) and superoxide dismutase (SOD) in the myocardial tissues were determined. Diabetes-induced oxidative stress by increasing nitrous free radicals (nitrate) (p ≤ 0.001) and MDA content (p ≤ 0.001), but had no significant effects on SOD, CAT, and GSH activities. Atorvastatin treatment in diabetic animals decreased free radical-induced damages by decreasing nitrate and MDA content and increasing GSH and SOD activities compared to control non-diabetic animals. Uncontrolled hyperglycemia induces oxidative burden in myocardium. Treatment by atorvastatin decreases oxidative and nitrosative stress in the myocardium of diabetic animals.

https://ift.tt/2Hi0k7T

Molecular detection of Leishmania species in northeast of Iran

Abstract

Two known types of cutaneous leishmaniasis (CL) including zoonotic CL due to Leishmania major and anthroponotic CL due to Leishmania tropica are prevalent in 14 of 22 countries located in the Eastern Mediterranean region including Iran. According to existing data, CL is endemic in Sabzevar City (northeast of Iran) and, because of the climatic conditions in this semi-desert region, is suitable for living vector/reservoir hosts of infection. The aim of our study was to identify the recent status of CL causative species in rural areas of Sabzevar County. Suspected patients of CL who were referred to health centers in suburban areas of Sabzevar and confirmed via microscopic observation of amastigotes were included in the study. Molecular identification of Leishmania species was done via nested PCR assay, based on amplification of kinetoplast minicircle fragments of L. major and L. tropica. In total, 153 patients including 89 males and 64 females were enrolled in this study. A high infection rate was reported in the autumn season (with a peak in October). Our findings revealed that L. major is responsible for 100% of infections. In addition, there was no association between CL and risk factors after statistical analysis. It seems that the infection pattern of CL is changing predominantly to L. major in most regions of Iran, which may be due to environmental changes, or ecological amendment and their effects on (vector/reservoir) host distribution in rural parts. Finally, controlling programs as well as promotion in public health systems should be considered in this area.

https://ift.tt/2HgDHAt

Chronic immune thrombocytopenia. Egyptian experience

Abstract

Pathogenesis of thrombocytopenia is heterogeneous and resistance to treatment is a great challenge. In this study, we reviewed the demographic features of thrombocytopenic Egyptian patients. We also analyzed the role of T cell in chronic immune cases. IL-12, IL-35, IL-17, and TGF-β were measured by ELISA. The median age at the time of diagnosis was 30 years and its range was 14–70. The median platelet count at the time of diagnosis was 15 × 10⁹/L. Regarding treatment and follow-up, there was an indication for treatment in 96% of patients. Of the 150 ITP patients who were given first-line therapy (corticosteroid 1 mg/kg/day PO), there was a complete response (CR) in 40.3% while 59.7% patients were nonresponsive to therapy. Forty-five chronic cases fulfilled the criteria for cytokine assay. Comparison between the case group and the control group revealed statistically significant lower platelet count in cases, while the four measured cytokines were statistically significant higher in cases rather than the control. Correlation between the platelet count and the level of cytokines was statistically insignificant. The remission rate in ITP on steroid as first-line therapy is less than 50%. The higher expression of IL-12 and IL-35in chronic ITP is due to the persistently higher Th1 activity which explains the continuity of the disease, while the higher expression of Treg cytokines (IL-17 and TGF-β) may be explained by effect of immunosuppression or upregulation of the receptors on Treg cells.

https://ift.tt/2HDHmM4

Effect of powdered seed of Nigella sativa administration on sub-chronic and chronic lead acetate induced hemato-biochemical and histopathological changes in Sprague Dawley rats

Abstract

Lead acetate (PbAC) toxicity can occur by either ingestion or inhalation from contaminated surfaces or from the environment. Nigella sativa is a natural product with immense pharmacological properties, which include antioxidant, antibacterial, and antianemia properties. It has been showed to counter the effect of PbAC-induced hematological and biochemical changes in short-term studies. This study hypothesized that the N. sativa (NS) administration will ameliorate the deleterious effects of chronic PbAC toxicity in rats. A total of 75 Sprague Dawley rats were divided into three groups of 25 rats, and each group was further sub-divided into five groups of five rats each. Group 1 rats (negative control) were given distilled water, group 2 (positive control; PC) were given 10 mg/kg of lead acetate (PbAC) daily, and groups 3 (T1), 4 (T2), and 5 (T3) were each given 10 mg/kg of PbAC followed by graded concentrations of powdered seeds of NS; 100, 150, and 200 mg/kg, respectively. Five rats in each group were euthanized at 30, 60, and 90 days for collection of whole blood and selected organs. Whole blood was collected after euthanized via cardio puncture and used to evaluate the complete blood profile, while plasma was used for biochemical analysis. Tissue samples of the liver and kidney were fixed with 10% buffered formalin, processed, and stained with H&E and periodic acid–Schiff (PAS) for the liver. Aggression and fear were increased in the PbAC-exposed group and absent in the T3 group. There was a lower (p < 0.05) red blood cell count (RBC), packed cell volume (PCV), mean corpuscular hemoglobin concentration (MCHC), and lymphocyte count in the PC and T1 groups only. Biochemical analysis revealed elevated (p < 0.05) liver enzyme and creatinine levels in the PC and T1 groups on day 90 for AST and day 30 for ALT and creatinine. The level of alkaline phosphatase (ALP) was higher (p < 0.05) in the PC at 30 and 60 days of sampling. Other parameters, such as WBCs, prothrombin, urea, and cholesterol, were not significant in all groups. Histopathological lesions in the liver and kidneys were more severe in the PC and T1 groups, while the T2 and T3 groups showed mild lesions resulting from N. sativa administration. There was a decrease (p < 0.05) in the total PAS-stained area signifying glycogen depletion in the PC, T1, and T2 groups at 60 days and a higher distribution of the PAS-stained areas (p < 0.05) in the T3 group. At 90 days, the PC group had a lower (p < 0.05) distribution of PAS-stained areas in comparison to the other groups. The results showed the therapeutic potential of N. sativa extract in modulating both hematological and biochemical alterations induced by chronic lead acetate administration in rats.

https://ift.tt/2qMWYDt

Quercetin, rutin, and their combinations modulate penile phosphodiesterase-5′, arginase, acetylcholinesterase, and angiotensin-I-converting enzyme activities: a comparative study

Abstract

This study demonstrates the effects of rutin and quercetin and their various combinations on phosphodiesterase-5 (PDE-5), arginase, acetylcholinesterase (AChE), and angiotensin-I-converting enzyme (ACE) activities in vitro. The effects of the flavonoids against Fe²⁺- and sodium nitroprusside (SNP)-induced lipid peroxidation in rats' corpus cavernosum tissues were also investigated. Quercetin and rutin were dissolved in dimethylsulfoxide (DMSO) to a final concentration of 1 mM each. Thereafter, their combinations (50% quercetin + 50% rutin [Q1:R1]; 75% quercetin + 25% rutin [Q3:R1]; 25% quercetin + 75% rutin [Q1:R3]) were prepared. Our findings revealed that both flavonoids inhibited PDE-5, arginase, AChE, and ACE activities. Rutin exhibited significantly higher inhibitory effects on PDE-5, AChE, and ACE activities compared to quercetin. Considering the combinations, Q1:R3 was more potent compared to Q1:R1 and Q3:R1. Both flavonoids inhibited Fe²⁺- and SNP-induced lipid peroxidation in rat's corpus cavernosa tissues. Rutin also showed higher inhibitory effects on Fe- and SNP-induced lipid peroxidation. Similarly, the combinatorial effects of the flavonoids revealed that Q1:R3 significantly inhibited malondialdehyde (MDA) production compared to Q1:R1 and Q3:R1. In conclusion, our findings suggest that the combination of quercetin and rutin is more potent than their individual effect.

https://ift.tt/2F1Tn8Z

Potential pharmaceutic effect of Shilajit (mumie) on experimental osteoarthritis in rat

Abstract

Osteoarthritis (OA) is a worldwide joint disease with clinically loss of motion and pain in human. The conventional treatments are associated with essential side effects. In folk medicine, Shilajit is applied for treatment of arthritis and bone fractures. The present study evaluated effect of Shilajit on the osteoarthritis in rat model. Thirty-six adult male rats were randomly divided into two groups including OA and treated with Shilajit groups. OA was induced by injection of monosodium iodoacetate in the articular space of femorotibial joint. Aqueous extract of Shilajit was given to the treatment group by gavage as daily during experimental course until 21 days. The joint samples were investigated 7, 14, and 21 days post induction. The main macroscopic changes in the affected joints were swelling and congestion at early stages. Histopathologic study showed surface irregularity, erosion and fissures, necrotic chondrocytes, depletion of toluidine blue staining, and lysis of subchondral bone in both OA and Shilajit groups after 7 and 14 days. Synovium revealed synovial cells hyperplasia and inflammatory cells infiltration. Moderate to advanced OA was seen in both groups without significant difference. After 21 days, histopathologic scores of destructive damages and synovitis were reduced in the Shilajit group and showed significant difference in compare to OA group. The present study shows that aqueous extract of Shilajit decreased cartilage degenerative changes in knee osteoarthritis. Also, it reduced inflammatory reactions in synovial membrane.

https://ift.tt/2HDHgEc

The study on rate of morbidity of fungal infections exiting in educational hospitals: Iran

Abstract

Whereas hospitals have been assumed as the sites for spreading infection at level of world health, therefore, the current descriptive study has been conducted on 248 inpatients and outpatients who were suspected to fungal infection or disease. Samples were collected from several wards along with radiographic and endoscopic analyses in three hospitals, including urine, blood, skin, nail, wound (burning, surgery, eye and injury), lung, phlegm, ascites, bronchoaveolar lavage, (cerebrospinal, abdominal, and knee) fluids, peritoneum, fistula, ear tests and biopsy and sent to reference mycological center. The fungal species were identified by studying their macroscopic and microscopic and using PCR-RFLP technique. Among total studied patients, 180 cases had fungal elements; among which, there were 53 (29%) nosocomial infection and 127 (71%) community-acquired infection cases out of which inpatients and outpatients suffered from fungal diseases. The highest incidence of nosocomial infection belongs to intensive care units (ICU) ward in 16% of patients. The most common isolated fungi were Candida spp. The statistical results of this study suggest nosocomial fungal infections as the most important problems in the course of treatment among hospitalized patients who are more likely to be infected.

https://ift.tt/2HEs5dX

Adjuvant therapy for colon cancer: genes, genes... and the patient in the center

Although molecular subtype-based stratification and genomic signatures of increasing complexity are becoming a new strategy to guide therapeutic decisions in stage II/III colon cancer, several prognostic factors that can be easily obtained from FFPE specimens should be considered in order to create combined models that better define individual patients needs

https://ift.tt/2HPPwPm

An RNAi Screen Identifies New Genes Required for Normal Morphogenesis of Larval Chordotonal Organs

The proprioceptive chordotonal organs (ChO) of a fly larva respond to mechanical stimuli generated by muscle contractions and consequent deformations of the cuticle. The ability of the ChO to sense the relative displacement of its epidermal attachment sites likely depends on the correct mechanical properties of the accessory (cap and ligament) and attachment cells that connect the sensory unit (neuron and scolopale cell) to the cuticle. The genetic programs dictating the development of ChO cells with unique morphologies and mechanical properties are largely unknown. Here we describe an RNAi screen that focused on the ChO's accessory and attachment cells and was performed in 2^nd instar larvae to allow for phenotypic analysis of ChOs that had already experienced mechanical stresses during larval growth. Nearly one thousand strains carrying RNAi constructs targeting more than 500 candidate genes were screened for their effects on ChO morphogenesis. The screen identified 31 candidate genes whose knockdown within the ChO lineage disrupted various aspects of cell fate determination, cell differentiation, cellular morphogenesis and cell-cell attachment. Most interestingly, one phenotypic group consisted of genes that affected the response of specific ChO cell types to developmental organ stretching, leading to abnormal pattern of cell elongation. The 'cell elongation' group included the transcription factors Delilah and Stripe, implicating them for the first time in regulating the response of ChO cells to developmental stretching forces. Other genes found to affect the pattern of ChO cell elongation, such as α-tub85E, β1-tub, TBCE, CG8258, mys, rac and shortstop, represent putative effectors that link between cell-fate determinants and the realization of cell-specific mechanical properties.

https://ift.tt/2Jbq4TO

The EZH2 Inhibitor Tazemetostat Is Well Tolerated in a Phase I Trial [Research Watch]

Tazemetostat has antitumor activity in B-cell non-Hodgkin lymphoma and advanced solid tumors.

https://ift.tt/2HgegDj

Dual Targeting of MDMX and MDM2 Has Antileukemic Activity [Research Watch]

A p53-stapled peptide, ALRN-6924, blocks binding to MDMX and MDM2 to activate p53.

https://ift.tt/2qP8GNj

From Pluripotent Stem to CAR T Cells [News in Brief]

Preclinical efficacy seen with FT819, a candidate off-the-shelf CAR T-cell therapy.

https://ift.tt/2HgebiZ

A Cancer-Germline Antigen Signature Predicts Anti-CTLA4 Resistance [Research Watch]

High expression of the MAGE-A subcluster III is associated with anti-CTLA4 resistance in melanoma.

https://ift.tt/2qP8AVX

Loss of p62 in Adipocytes Promotes Aggressive Prostate Cancer [Research Watch]

OPN released from p62-deficient adipocytes enhances fatty-acid oxidation in tumor cells.

https://ift.tt/2Hge5YF

FDA Approves First Drug for Rare Form of Rickets

FRIDAY, April 20, 2018 -- Ultragenyx Pharmaceutical Inc.'s Crysvita (burosumab-twza) has been approved by the U.S. Food and Drug Administration to treat adults and children ages 1 year and older with x-linked hypophosphatemia (XLH). A clinical trial...

https://ift.tt/2HEmggB

Questions Surround Concept of Internet Gaming Disorder

FRIDAY, April 20, 2018 -- The concept of internet gaming disorder (IGD) and the pathways leading to it are unclear, according to a review published online April 6 in Developmental Medicine & Child Neurology. Frank W. Paulus, Ph.D., from Saarland...

https://ift.tt/2JbO9tD

Annual Visits May Not Increase Cognitive Impairment Detection

FRIDAY, April 20, 2018 -- Medicare Annual Wellness Visits (AWVs) do not appear to substantially increase the detection of cognitive impairment in older adults, according to a study published online April 2 in the Journal of the American Geriatrics...

https://ift.tt/2HAOzwJ

High FGF-23 Linked to Recurrent Cardiac Events After ACS

FRIDAY, April 20, 2018 -- Elevated fibroblast growth factor 23 (FGF-23) is associated with increased risk of recurrent major cardiovascular (CV) events in patients after an acute coronary syndrome (ACS), according to a study published online April...

https://ift.tt/2JdDL4J

Medical Cannabis Not Recommended for Sleep Apnea

FRIDAY, April 20, 2018 -- Medical cannabis and/or its synthetic extracts should not be used for treating patients with obstructive sleep apnea (OSA), according to an American Academy of Sleep Medicine position statement published in the April 15...

https://ift.tt/2qMFnLU

A window into extreme longevity; the circulating metabolomic signature of the naked mole-rat, a mammal that shows negligible senescence

Abstract

Mouse-sized naked mole-rats (Heterocephalus glaber), unlike other mammals, do not conform to Gompertzian laws of age-related mortality; adults show no age-related change in mortality risk. Moreover, we observe negligible hallmarks of aging with well-maintained physiological and molecular functions, commonly altered with age in other species. We questioned whether naked mole-rats, living an order of magnitude longer than laboratory mice, exhibit different plasma metabolite profiles, which could then highlight novel mechanisms or targets involved in disease and longevity. Using a comprehensive, unbiased metabolomics screen, we observe striking inter-species differences in amino acid, peptide, and lipid metabolites. Low circulating levels of specific amino acids, particularly those linked to the methionine pathway, resemble those observed during the fasting period at late torpor in hibernating ground squirrels and those seen in longer-lived methionine-restricted rats. These data also concur with metabolome reports on long-lived mutant mice, including the Ames dwarf mice and calorically restricted mice, as well as fruit flies, and even show similarities to circulating metabolite differences observed in young human adults when compared to older humans. During evolution, some of these beneficial nutrient/stress response pathways may have been positively selected in the naked mole-rat. These observations suggest that interventions that modify the aging metabolomic profile to a more youthful one may enable people to lead healthier and longer lives.

https://ift.tt/2JfJOpd

Ameliorating effect of edible bird’s nest against lead acetate toxicity on the rat hypothalamic–pituitary–ovarian axis and expressions of epidermal growth factor and vascular endothelial growth factor in ovaries

Abstract

Lead acetate (LA) alters ovarian histology, size and function, as well as decreases oestrogen production. LA is also toxic to rat ovary and pituitary gland. Edible bird's nest (EBN) can reportedly alleviate these damages. This study aimed to evaluate the protective effect of EBN supplement on the ovaries and pituitary glands of rats exposed to LA toxicity. Five treatment groups were established as follows: group 1 (C), which was given distilled water; group 2 (T0), which was administered with LA (10 mg/kg body weight (BW); and groups 3 (T1), 4 (T2) and 5 (T3), which were given LA (10 mg/kg BW) plus graded concentrations of 30, 60 and 120 mg/kg BW of EBN, respectively. Rats were euthanised at day 35 to collect ovary and pituitary gland for histomorphological study and the expression analysis of epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF). Plasma was used to determine concentrations of E₂, progesterone (P₄), growth hormone (GH) and prolactin (P). E₂, P₄, GH and P levels were lower (p < 0.05) in T0, whereas T3 had the highest E₂ concentration. All EBN-treated groups had increased number of survival follicles, as well as significant proliferation of gonadotrophic cells in the pituitary gland and decreased degenerative changes. All immunohistochemistry results showed significantly higher EGF and VEGF expression levels (p < 0.05) in T3. Overall, results showed the detrimental effects of LA on the ovary and pituitary gland and revealed the ameliorating effect of oral EBN supplementation against LA toxicity.

https://ift.tt/2K1MjwQ

Surgical Management of Head and Neck Soft Tissue Sarcoma: 11-Year Experience at a Tertiary Care Centre in South India

Abstract

Head and neck soft tissue sarcoma (HNSTS) is a rare neoplasm accounting for 1% of all head and neck tumours. Because of rarity and varied biological behaviour among various subtypes, knowledge about these tumours is limited. This study aimed at analysing clinicopathological, recurrence and survival pattern of surgically treated HNSTS. Case records of 28 patients of HNSTS who underwent surgery at the Regional Cancer Centre (RCC), Trivandrum (India) between 2002 and 2012 were analysed retrospectively for demographic profile, clinical features, treatment given, recurrence pattern and outcome. The median age of patients was 37 years (range, 3–79) with male:female ratio of 3:2. Majority of patients presented with painless lump in the neck as the most common subsite affected followed by scalp and face. One patient had nodal disease, while none had distant metastasis at presentation. The most frequent histological subtypes were synovial sarcoma and fibrosarcoma followed by malignant fibrous histiocytoma, angiosarcoma and rhabdomyosarcoma. Majority (78.5%) of patients received adjuvant therapy in the form of radiation, chemotherapy or chemo-radiation. After mean follow-up of 49 months, four patients had died, and six developed local recurrence and four distant metastasis. The overall 5-year survival was 82.7% while 5-year disease-free survival was 55.3%. HNSTS is a rare entity that requires multimodality treatment to achieve optimum locoregional control and survival.

https://ift.tt/2HjzTCD

Duodenoscope reprocessing practice patterns in U.S. endoscopy centers: a survey study

After recent outbreaks of duodenoscope-related infections from multidrug-resistant organisms (MDRO), the United States Food and Drug Administration (FDA) recommended implementing one or more of four enhanced reprocessing measures in addition to updated manual cleaning methods and high-level disinfection (HLD). The implementation of these techniques in endoscopy facilities and provider opinions regarding reprocessing priorities remain unknown.

https://ift.tt/2K1Vz3X

Valuing innovative endoscopic techniques: per-oral endoscopic myotomy for the management of achalasia

Unclear reimbursement for new and innovative endoscopic procedures can limit adoption in clinical practice despite effectiveness in clinical trials. The aim of this study was to determine maximum cost-effective reimbursement for per-oral endoscopic myotomy (POEM) in treating achalasia.

https://ift.tt/2HkvMSV

When should we stop treatment with Terlipressin and Albumin for Patients with Hepatorenal Syndrome?

https://ift.tt/2qM8wa8

“Pancreatic mass” on computed tomography

https://ift.tt/2vwi4uL

Diagnotic Yield During Endoscopic Ultrasound-Guided Tissue Acquisition – Are We Ready to Abandon Fine Needle Aspiration Needles?

https://ift.tt/2HzG7hd

Treatment of Dyslipidemia in Common Liver Diseases

https://ift.tt/2JeJsPP

Evaluation of the efficacy of the four tests (p16 immunochemistry, PCR, DNA and RNA In situ Hybridization) to evaluate a Human Papillomavirus infection in head and neck cancers: a cohort of 348 French squamous cell carcinomas

It is now established that HPV plays a role in the development of a subset of head and neck squamous cell carcinomas (HNSCCs), notably oropharyngeal squamous cell carcinomas (SCCs). However, it is not clear which test one should use to detect HPV in oropharyngeal (OP) and non-OP SCCs. In this study, using 348 HNSCCs (126 OP SCCs and 222 non-OP SCCs), we evaluated diagnostic performances of different HPV tests in OP and non-OP SCCs: PCR, p16 immunostaining, in situ hybridization targeting DNA (DNA-CISH) and RNA (RNA-CISH), combined p16 + DNA-CISH, and combined p16 + RNA-CISH.

https://ift.tt/2HfQCXy

The clinicopathological comparison among nodal cases of idiopathic multicentric Castleman disease with and without TAFRO syndrome

Multicentric Castleman disease (MCD) is a systemic inflammatory disease potentially caused by an increase in the serum interleukin-6 (IL-6) level. Idiopathic MCD (iMCD) is histopathologically classified into three types: plasmacytic (PC), mixed, and hypervascular (hyperV) types. Recently, a unique clinical phenotype with a poor prognosis overlap with iMCD, thrombocytopenia, anasarca, fever, renal failure or reticulin fibrosis, and organomegaly (TAFRO syndrome), has been reported from Japan, but its detailed clinicopathological features remain unclear.

https://ift.tt/2qPEh11

Medical Management of a Prolactinoma in a 15-Year-Old Girl

A 15-year-old girl presented to her primary care physician for evaluation of recurrent headaches with occasional blurry vision, periodic white discharge from the left nipple, and primary amenorrhea. Family history was notable for maternal breast cancer. On physical examination, patient was Tanner stage 5 for both pubic hair and breast development and all cranial nerves were grossly intact. Initial laboratory results were as follows: prolactin 1070.0 ng/mL (reference, 3.2-20.0 ng/mL), testosterone 31 ng/dL (reference, < 40 ng/dL), thyroid-stimulating hormone 1.16 mIU/L (reference, 0.50-4.30 mIU/L), and free thyroxine 0.79 ng/mL (reference, 0.9-1.4 ng/mL).

https://ift.tt/2F3jCfi

Neurodevelopment of Infants with and without Craniofacial Microsomia

To determine whether infant cases with craniofacial microsomia (CFM) evidence poorer neurodevelopmental status than demographically similar infants without craniofacial diagnoses ("controls"), and to examine cases' neurodevelopmental outcomes by facial phenotype and hearing status.

https://ift.tt/2qOGISo

Validation of Transient Elastography Cut Points to Assess Advanced Liver Fibrosis in Children and Young Adults: The Boston Children's Hospital Experience

To derive an optimal liver stiffness measurement cut point to discriminate METAVIR fibrosis stage F4 and to validate both METAVIR fibrosis stage F3-F4 and F4 cut points in a separate cohort.

https://ift.tt/2qMax63

Ureterocele Causing Bladder Outlet Obstruction

A 1-month-old boy presented to the pediatric urologist with antenatally detected hydronephrosis. He was born at 39 weeks via cesarean delivery with no history of oligo or polyhydramnios. His parents described some straining and grunting with urination. Renal ultrasound showed bilateral duplicated collecting systems with grade 4 hydronephrosis of the right upper and lower poles. The patient was receiving antibiotic prophylaxis with amoxicillin and had not had any urinary tract infections. MAG3 nuclear medicine renal scan showed minimal function in the right upper pole.

https://ift.tt/2F3mokH

Interactions of HP1 Bound to H3K9me3 Dinucleosome by Molecular Simulations and Biochemical Assays

Heterochromatin protein 1 (HP1), associated with heterochromatin formation, recognizes an epigenetically repressive marker, trimethylated lysine 9 in histone H3 (H3K9me3), and generally contributes to long-term silencing. How HP1 induces heterochromatin is not fully understood. Recent experiments suggested that not one, but two nucleosomes provide a platform for this recognition. Integrating previous and new biochemical assays with computational modeling, we provide near-atomic structural models for HP1 binding to the dinucleosomes.

https://ift.tt/2F3fDzl

Are qSOFA Criteria Better Than the Systemic Inflammatory Response Syndrome Criteria for Diagnosing Sepsis and Predicting Inhospital Mortality?

Authors included 10 studies with 229,480 patients from 4,022 citations retrieved from their initial literature search. One study conducted among ICU patients accounted for 80.6% of included patients (184,875).2 Eight studies evaluated patients in the emergency department, whereas 2 studies evaluated patients at ICU admission. Studies used different criteria for diagnosis of infection in sepsis: 4 used clinically presumed or suspected infection; 1 considered suspicion of infection resulting in antibiotics; 2 considered clinical suspicion resulting in cultures and antibiotics; 1 used diagnosis of sepsis at admission; 1 considered at least 2 criteria of systemic inflammatory response syndrome criteria, SOFA, or qSOFA; and 1 used the International Classification of Diseases, Ninth Revision coding for infection.

https://ift.tt/2K5aoD0

Quality Through Coopetition: An Empiric Approach to Measure Population Outcomes for Emergency Care–Sensitive Conditions

We develop a novel approach for measuring regional outcomes for emergency care–sensitive conditions.

https://ift.tt/2JeBm9T

Resuscitative Endovascular Balloon Occlusion of the Aorta Improves Cardiac Compression Fraction Versus Resuscitative Thoracotomy in Patients in Traumatic Arrest

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is emerging as an alternative to resuscitative thoracotomy for proximal aortic control in select patients with exsanguinating hemorrhage below the diaphragm. The purpose of this study is to compare interruptions in closed chest compression or open chest cardiac massage during REBOA versus resuscitative thoracotomy.

https://ift.tt/2K2Lfc7

Emergency Physician Risk Estimates and Admission Decisions for Chest Pain: A Web-Based Scenario Study

We conducted this study to better understand how emergency physicians estimate risk and make admission decisions for patients with low-risk chest pain.

https://ift.tt/2Hiw0dd

The Dantastic Mr. Tox & Howard Episode 11 – In the Weeds with the Full Monte

https://ift.tt/2vwkF7V Legalization, edible issues and airport amnesty dumpster diving with Dr. Andrew Monte Join Dan (@drusyniak) &howard (@heshiegreshie) as they discuss all things marijuana with Dr. Andrew Monte (@PreciseMDMonte) on this very special day. Learn about the interaction between marijuana and ERs in Colorado before and after legalization, the influence of Big Green, and why […]

EMCrit Project by Tox & Hound.

https://ift.tt/2qK4XBq

Ex Utero Electroporation and Organotypic Slice Cultures of Embryonic Mouse Brains for Live-Imaging of Migrating GABAergic Interneurons

Here, we provide a low-cost and reliable method to generate electroporated brain organotypic slice cultures from mouse embryos suitable for confocal microscopy and live-imaging techniques.

https://ift.tt/2qPy8SL

Split-BioID — Proteomic Analysis of Context-specific Protein Complexes in Their Native Cellular Environment

We provide a step-by-step protocol for split-BioID, a protein fragments-complementation assay based on the proximity-labeling technique BioID. Activated on the interaction of two given proteins, it allows the proteomics analysis of context-dependent protein complexes in their native cellular environment. The method is simple, cost-effective and only requires standard laboratory equipment.

https://ift.tt/2Hf8u4I

Method for High Speed Stretch Injury of Human Induced Pluripotent Stem Cell-derived Neurons in a 96-well Format

Here we present a method for a human in vitro model of stretch injury in a 96-well format on a timescale relevant to impact trauma. This includes methods for fabricating stretchable plates, quantifying the mechanical insult, culturing and injuring cells, imaging, and high content analysis to quantify injury.

https://ift.tt/2qPy05J

Comments on ‘Comments on “Modeling Cell Survival after Photon Irradiation Based on Double-Strand Break Clustering in Megabase Pair Chromatin Loops” by Thomas Friedrich, Marco Durante and Michael Scholz (Radiat Res 2012; 178:385–94)’

Radiation Research, Volume 189, Issue 5, Page 549-549, May 2018.


https://ift.tt/2HDnuZC

NCI Expands Repository of Cancer Research Models: A Conversation with Drs. Doroshow and Evrard

NCI is expanding its Patient-Derived Models Repository (PDMR), which provides cancer research models made directly from human tumor tissue. In this Q&A, Drs. Yvonne Evrard and James Doroshow explain how the new models can help cancer researchers make more rapid progress.

https://ift.tt/2Hfn7oL

Study Finds 31 Percent Use No Opioids After Surgery

FRIDAY, April 20, 2018 -- Almost 63 percent of patients did not use opioids after having an elective procedure, according to a study presented at the annual meeting of the American Surgical Association, held from April 19 to 21 in Phoenix. Cornelius...

https://ift.tt/2HOD8Pn

Colon Cancer Survival Varies by Insurance Type

FRIDAY, April 20, 2018 -- Compared to patients with private insurance, colon cancer survival is lower for patients with no insurance or with Medicaid, according to a study published in the May issue of Diseases of the Colon & Rectum. Dianne...

https://ift.tt/2vuFctF

In LVSD, Diabetes Tied to Higher Risk of Heart Failure

FRIDAY, April 20, 2018 -- In patients with asymptomatic left ventricular systolic dysfunction, diabetes is associated with an increased risk of developing heart failure, according to a study published online April 6 in Diabetes Care. Rasmus Rørth,...

https://ift.tt/2HP9Sbz

Systolic BP Increases at Rapid Rate Above 120 to 125 mm Hg

FRIDAY, April 20, 2018 -- After systolic blood pressure (BP) reaches 120 to 125 mm Hg, it increases at a relatively rapid rate toward overt hypertension, according to a study published online March 21 in JAMA Cardiology. Teemu J. Niiranen, M.D.,...

https://ift.tt/2HOD81P

Newly Designed Pulsed-Dye Laser Found Effective for Rosacea

FRIDAY, April 20, 2018 -- A pulsed-dye laser with a novel 15-mm diameter treatment beam improves the appearance of rosacea, according to a study published online April 10 in Lasers in Surgery and Medicine. Eric F. Bernstein, M.D., from the Mainline...

https://ift.tt/2vC09CG

AAN: Neuromodulation Therapy Gives Relief From Hand Tremor

FRIDAY, April 20, 2018 -- Non-invasive neuromodulation therapy using a custom stimulation pattern provides symptomatic relief from hand tremor in essential tremor, according to a study presented at the annual meeting of the American Academy of...

https://ift.tt/2HN726G

PAs May Have Lower Diagnostic Accuracy for Melanoma

FRIDAY, April 20, 2018 -- Physician assistants (PAs) perform more skin biopsies per case of skin cancer diagnosed and diagnose fewer melanomas in situ than dermatologists, according to a study published online April 18 in JAMA Dermatology. Alyce M....

https://ift.tt/2vrDn0m

Eight Factors Predict Pain After Spine Surgery

FRIDAY, April 20, 2018 -- Eight factors contribute to postoperative pain after spine surgery, according to a study presented at the 2018 World Congress on Regional Anesthesia and Pain Medicine, held from April 19 to 21 in New York City. Quentin...

https://ift.tt/2HPRXS7

Mechanism in Non-Contact ACL Tears Similar in Men, Women

FRIDAY, April 20, 2018 -- Males and females have similar knee positions at the time of non-contact anterior cruciate ligament (ACL) rupture, according to a study published online April 18 in the American Journal of Sports Medicine. Kwadwo A....

https://ift.tt/2F48FtI

Efficient production of secretory Streptomyces clavuligerus β-lactamase inhibitory protein (BLIP) in Pichia pastoris

β-Lactamase inhibitory protein (BLIP), a low molecular weight protein from Streptomyces clavuligerus, has a wide range of potential applications in the fields of biotechnology and pharmaceutical industry because ...

https://ift.tt/2Hf4p0u

Evolution of deceased organ donation activity vs. efficiency over a 15 year period: an international comparison

Background The donation rate (DR) per million population is not ideal for an efficiency comparison of national deceased organ donation programs. The DR does not account for variabilities in the potential for deceased donation which mainly depends on fatalities from causes leading to brain death. In this study, the donation activity was put into relation to the mortality from selected causes. Based on that metric, this study assesses the efficiency of different donation programs. Methods This is a retrospective analysis of 2001–2015 deceased organ donation and mortality registry data. Included are 27 Council of Europe countries, as well as the USA. A donor conversion index (DCI) was calculated for assessing donation program efficiency over time and in international comparisons. Results According to the DCI and of the countries included in the study, Spain, France, and the USA had the most efficient donation programs in 2015. Even though mortality from the selected causes decreased in most countries during the study period, differences in international comparisons persist. This indicates that the potential for deceased organ donation and its conversion into actual donation is far from being similar internationally. Conclusions Compared with the DR, the DCI takes into account the potential for deceased organ donation, and therefore is a more accurate metric of performance. National donation programs could optimize performance by identifying the areas where most potential is lost, and by implementing measures to tackle these issues. Correspondence to: Franz F. Immer, MD, consultant cardiovascular surgeon FMH, Swisstransplant, Effingerstrasse 1/Postfach, CH-3011 Bern, Switzerland., franz.immer@swisstransplant.org **Please refer to Appendix 1, SDC, https://ift.tt/2HDeOT2 for information about Council of Europe European Committee on Organ Transplantation (CD-P-TO) membership Authors' contributions JW: acquired and analyzed data, reviewed the literature, wrote the manuscript; AE acquired and analyzed data, contributed to the writing of the manuscript; BM, provided the donation data from the Newsletter Transplant database; BDG, DA, ANC, BHK, KL: members of the Council of Europe's project TO077 CD-P-TO working group, participated in the study design, revised the manuscript critically; FFI conceived the study, advised on its design and revised the manuscript critically, member of the TO077 CD-P-TO working group. Conflict of interest: The authors declare no conflicts of interest. Funding: This study received no external funding. Supplemental digital content (SDC) is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (https://ift.tt/2EZJQTY). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2HDNzYp

Heavy Alcohol Use Among Deceased Donors Does Not Impact Recipient Outcomes After Liver Transplantation

Background Data on liver transplant (LT) outcomes using deceased donors with heavy drinking (HD) (>2 drinks/day) are scanty. Methods Using the United Network for Organ Sharing database (2002-2014), we examined outcomes after LT in adults comparing deceased HD donors with not heavy drinking (ND) donors. Results Of 56 182 first LTs performed in the US for 10 common indications using deceased donors, 47 882 with available information on alcohol use were analyzed. Of these 47 882 LT recipients, 7 298 (15%) were from HD donors, with similar proportion over time (2002-2014, Armitage trend test P=0.75) and for recipient liver disease etiology (Chi square P=0.42). Proportion of liver organ used for LT was lower for HD donors compared to ND donors (63 vs. 78%, P

https://ift.tt/2HgJCFK

Dendritic Cell Therapy in Transplantation, Phenotype Governs Destination and Function

No abstract available

https://ift.tt/2qMd7sV

State of the Art: Role of the Dendritic Cell in Induction of Allograft Tolerance

Despite decades of research, the induction and maintenance of long-term allograft tolerance without immunosuppression remains an elusive goal in the field of solid organ and cell transplantation. Immunosuppressive medications frequently prevent or minimize acute cellular rejection but have failed to halt anti-donor antibody production and chronic organ rejection. Past efforts aimed at promoting lasting allograft tolerance have focused primarily on peripheral T cell depletion,1 augmentation of regulatory T cells,2 or induction via simultaneous hematopoietic stem cell transplantation and facilitation of donor chimerism.3 So far, none of these methods have led to consistently safe, feasible and long lasting donor organ acceptance. Over the course of the past 4 decades, the study of a unique population of antigen-presenting cells known as dendritic cells (DCs) has shown promise for breaking new ground in achieving indefinite allograft survival without immunosuppression and its associated adverse effects. In this review, we discuss the discovery and early investigations of DCs and chronicle some of the key studies demonstrating their role in transplantation, particularly in indirect allorecognition, the immunologic pathway thought to drive chronic rejection and perhaps tolerance induction. Sarah J. Rosen, M.D., 630 W. 168th St., Rm. 10-502, New York, NY 10032. sr2490@cumc.columbia.edu Sarah J. Rosen participated in the writing of the paper. Paul E. Harris participated in the writing of the paper. Mark A. Hardy participated in the writing of the paper. The authors declare no conflicts of interest. Funding for this work was provided by the National Institutes for Health 2T32HL007854-21. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2F4Lvn8

Health care costs for the evaluation, surgery, and follow-up care of living kidney donors

Background The health care costs to evaluate, perform surgery, and follow a living kidney donor for the year after donation are poorly described. Methods We obtained information on the health care costs of 1099 living kidney donors between April 1, 2004 and March 31, 2014 from Ontario, Canada using comprehensive health care administrative databases. We estimated the cost of 3 periods of the living donation process: the predonation evaluation period (start of evaluation until the day before donation), perioperative period (day of donation until 30-days postdonation), and 1 year of follow-up period (after perioperative period until 1-year postdonation). We analyzed data for donors and healthy matched nondonor controls using regression-based methods to estimate the incremental cost of living donation. Costs are presented from the perspective of the Canadian health care payer (2017 $CAD). Results The incremental health care costs (compared with controls) for the evaluation, perioperative, and follow-up periods were $3,596 (95% confidence interval (CI) $3,350-$3,842), $11,694 ($11,415-$11,973), and $1,011 ($793-$1,230), respectively, totalling $16,290 ($15,814-$16,767). The evaluation cost was higher if the intended recipient started dialysis part-way through the donor evaluation [$886 ($19, $1,752)]. The perioperative cost varied across transplant centers (p

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Outcomes after Cardiac Transplant for Wild Type Transthyretin Amyloidosis

Background The true prevalence of heart failure (HF) due to wild type transthyretin amyloidosis (ATTRwt) is likely underestimated. There is a paucity of data with regard to the management of ATTRwt-related advanced HF and the natural history of extracardiac ATTRwt. Methods We conducted a retrospective cohort study of patients undergoing cardiac transplant (HTx) for ATTRwt at a single institution. Comprehensive clinical data, including baseline hemodynamic and echocardiographic characteristics, and posttransplant outcomes were obtained. Results Seven patients with ATTRwt underwent HTx between 2007 and 2015. All patients were male with a mean age of 66 ± 9. Patients had a reduced ejection fraction (mean 37 ± 14%) and elevated filling pressures pre-HTx (mean pulmonary capillary wedge pressure 22 ± 7 mmHg) prior to HTx. Three year survival was 100%; 1 patient died of pancreatic cancer 45 months post-HTx (1 death per 30.8 patient-years). Oxygen consumption (Δ +6.8 ± 4.9 ml/kg/min) and 6-minute walk distances (Δ +189 ± 60 m) improved. Symptomatic gastrointestinal involvement (n=2) and peripheral nerve involvement (n=4) by ATTRwt developed late. Conclusions This is the first report of a series of ATTRwt patients receiving HTx in which excellent outcomes are demonstrated. Although cardiac death is averted, systemic manifestations of ATTRwt may develop posttransplantation. REPRINTS AND CORRESPONDENCE: Andrew N. Rosenbaum, M.D., Mayo Clinic Rochester, 200 1st St. SW, Rochester, MN 55905. Phone#: +15072842511. Fax#: +1 5072840161. Email: Rosenbaum.Andrew@mayo.edu PI: Brooks S. Edwards: Phone#: +15072663841 Email: Edwards.Brooks@mayo.edu AUTHORSHIP: Andrew N Rosenbaum: Participated in research design, writing of the paper, performance of the research, and data analysis Omar F. Abou Ezzeddine: Participated in writing of the paper and data analysis Martha Grogan: Participated in research design, writing of the paper, and data analysis Angela Dispenzieri: Participated in writing of the paper and data analysis Sudhir Kushwaha: Participated in writing of the paper and data analysis Alfredo Clavell: Participated in writing of the paper and data analysis Richard C. Daly: Participated in writing of the paper and data analysis Brooks S Edwards: Participated in research design, writing of the paper, and data analysis DISCLOSURES: The authors declare no conflicts of interest SOURCES OF FUNDING: No funding was provided for the current study Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Frailty, Inflammatory Markers, and Waitlist Mortality Among Patients with End-Stage Renal Disease in a Prospective Cohort Study

Background Among community-dwelling older adults, frailty is associated with heightened markers of inflammation and subsequent mortality. Although frailty is common among ESRD patients, the role of frailty and markers of inflammation in this population remains unclear. We quantified these associations in patients on the kidney transplant (KT) waitlist and tested whether frailty and/or markers of inflammation improve waitlist mortality risk prediction. Methods We studied 1,975 ESRD patients on the KT waitlist (11/1/09-2/28/17) in a multi-center cohort study of frailty. Serum inflammatory markers (interleukin-6 [IL-6], soluble tumor necrosis factor-α receptor-1 [sTNFR1], and C-reactive protein [CRP]) were analyzed in 605 of these participants; we calculated the inflammatory index score using IL-6 and sTNFR1. We compared the C-statistic of an established registry-based prediction model for waitlist mortality adding frailty and/or inflammatory markers (1SD change in log IL-6, sTNFR1, CRP, or inflammatory index). Results The registry-based model had moderate predictive ability (c-statistic=0.655). Frailty was associated with increased mortality (2.19, 95%CI:1.26-3.79) but did not improve risk prediction (c-statistic=0.646; P=0.65). Like frailty, IL-6 (2.13, 95%CI:1.41-3.22), sTNFR1 (1.70, 95%CI:1.12-2.59), CRP (1.68, 95%CI:1.06-2.67), and the inflammatory index (2.09, 95%CI:1.38-3.16) were associated with increased mortality risk; unlike frailty, adding IL-6 (c-statistic=0.777; P=0.02), CRP (c-statistic=0.728; P=0.02), or inflammatory index (c-statistic=0.777; P=0.02) substantially improved mortality risk prediction. Conclusion Frailty and markers of inflammation were associated with increased waitlist mortality risk, but only markers of inflammation significantly improved ESRD risk prediction. These findings help clarify the accelerated aging physiology of ESRD and highlight easy to measure markers of increased waitlist mortality risk. Contact Information: Mara McAdams-DeMarco, Ph.D. Department of Epidemiology, 615, N. Wolfe St, W6033, Baltimore, MD 21205 (410) 502-1950 email: mara@jhu.edu Authorship Mara A. McAdams-DeMarco: Research design, data analysis, writing of the paper and review of the paper Hao Ying: Performance of the research, data analysis, writing of the paper and review of the paper Alvin Thomas: Writing of the paper and review of the paper Fatima Warsame: Performance of the research, writing of the paper and review of the paper Ashton A. Shaffer: Writing of the paper and review of the paper Christine E. Haugen: Performance of the research, writing of the paper and review of the paper Jacqueline M. Garonzik-Wang: Performance of the research, writing of the paper and review of the paper Niraj M. Desai: Performance of the research, writing of the paper and review of the paper Ravi Varadhan: Performance of the research, writing of the paper and review of the paper Jeremy D. Walston: Writing of the paper and review of the paper Silas P. Norman: Performance of the research, writing of the paper and review of the paper Dorry L. Segev: Research design, writing of the paper and review of the paper Disclosure The authors declare no conflicts of interest. Funding This study was supported by NIH grant R01AG042504 (PI: Dorry Segev), R01AG055781 (PI: McAdams-DeMarco) and K24DK101828 (PI: Dorry Segev). Mara McAdams-DeMarco was also supported by the Johns Hopkins University Claude D. Pepper Older Americans Independence Center (P30AG021334), National Institute on Aging (K01AG043501). Christine Haugen was supported by the National Institute on Aging (F32AG053025). Ashton Shaffer was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (F30DK116658). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Measured Glomerular Filtration Rate After Kidney Donation: No Evidence of Accelerated Decay

Background The rate of measured GFR change in kidney donors years after donation has not been adequately addressed. Whether this change is accelerated in the setting of 1 kidney is also understudied. Methods 214 randomly selected donors underwent serial GFR measurements of nonradioactive iohexol. eGFR at each visit was calculated using the CKD EPI and MDRD study equations. Results GFR visits were 4.8 ±1.3 years apart and the second occurring 16.9±9.1 years after donation. The majority (97.7%) were White; 60.8% female and 78.5% were related to their recipient. Most, 84.6%, had a GFR ≥60 ml/min/1.73m2, 14.0% had a GFR between 45-60 ml/min/1.73m2 and 1.4% had a GFR

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Gearing Up for Stem Cell-Derived Beta Cells – Are We Ready?

No abstract available

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Measured vs estimated glomerular filtration (eGFR) rate in the assessment of living kidney donors: eGFR has its limitations

No abstract available

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Therapeutic outcomes of haploidentical allogeneic hematopoietic stem cell transplantation in patients with severe aplastic anemia: a multicenter study

Background Haploidentical donor allogeneic hematopoietic stem cell transplantation (HID-HSCT) is an alternative curative treatment for patients with severe aplastic anemia (SAA) who do not have suitable matched related donors (MRD). The aim of this study was to compare the therapeutic outcomes of HID-HSCT with those of MRD-HSCT for SAA. Methods A total of 235 SAA patients who underwent HID-HSCT (116) or MRD-HSCT (119) at 11 transplantation centers from January 2007 to January 2016 were included. Complications and survival outcomes were evaluated and compared between the 2 groups. Results The HID group had a lower incidence of secondary graft failure (GF) but higher incidences of acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD). However, the incidence of severe aGVHD (grade III-IV), poor graft function (PGF), and infections was comparable between groups. Patients in the HID group had a significantly lower survival and overall survival rates than those in the MRD group. The estimated 3-year survival rates for the MRD and HID groups were 82.82% and 75.00%, respectively. Ferritin levels, GF, PGF, severe aGVHD, and infections were the significant risk factors for survival. Conclusion The overall survival rate is acceptable for patients who underwent HID-HSCT, making it a feasible treatment choice for SAA patients. Corresponding author: Professor Yang Xiao, Stem Cell Translational Medicine Center, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China & Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, China. Email: jdxiao111@163.com Yonghua Li, Fengqi Duan and Haowen Xiao contributed equally to this work. Author contributions Yonghua Li and Yang Xiao designed the research. Yonghua Li and Fengqi Duan analyzed the data and wrote the manuscript. All authors conducted the research, collected the clinical data, and approved the submitted and final versions of the manuscript. Conflicts of interest The authors declare that there are no conflicts of interest. Funding This work was partly supported by the State Natural Sciences Fund (Project number 81570107), Natural Science Foundation of Guangdong Province (Project number 2014A030311006) and Guangzhou Pearl River Scientific and Technological New Star Capitals (grant no. 2012 J2200008). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Cytomegalovirus: a Guide for the Perplexed

No abstract available

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CORM-401 reduces ischemia reperfusion injury in an ex vivo renal porcine model of the donation after cardiac death

Background Carbon monoxide (CO) inhalation protects organ by reducing inflammation and cell death during transplantation processes in animal model. However, using CO in clinical transplantation is difficult due to its delivery in a controlled manner. A manganese-containing CORM-401 has recently been synthesized which can efficiently deliver 3 molar equivalents of CO. We report the ability of this anti-inflammatory CORM-401 to reduce ischemia reperfusion injury associated with prolonged cold storage of renal allografts obtained from donation after cardiac death in a porcine model of transplantation. Methods To stimulate DCD condition, kidneys from large male Landrace pig were retrieved after 1h warm ischemia in situ by cross-clamping the renal pedicle. Procured kidneys, after a brief flushing with HTK solution were subjected to pulsatile perfusion at 4°C with UW solution for 4h and both kidneys were treated with either 200μM CORM-401 or inactive CORM-401 (iCORM-401) respectively. Kidneys were then reperfused with normothermic isogeneic porcine blood through oxygenated pulsatile perfusion for 10h. Urine was collected, vascular flow was assessed during reperfusion and histopathology was assessed after 10h of reperfusion. Results We have found that CORM-401 administration reduced urinary protein excretion, attenuated kidney damage markers (KIM-1 and NGAL), and reduced ATN and TUNEL staining in histopathologic sections. CORM-401 also prevented intrarenal hemorrhage and vascular clotting during reperfusion. Mechanistically, CORM-401 appeared to exert anti-inflammatory actions by suppressing Toll-like receptors 2, 4 and 6. Conclusions CORM-401 provides renal protection following cold storage of kidneys and provides a novel clinically relevant ex vivo organ preservation strategy. Correspondence: Patrick P.W. Luke, London Health Sciences, 339 Windermere Road, London, Ontario, Canada N6A 5A5. Email: patrick.luke@lhsc.on.ca Authorship R.N.B. participated in the performance of the research, data analysis, construction of figures and article writing. M.R.M participated in kidney perfusion and preparation of perfusion circuit. A.H participated in data analysis and pathological evaluation of tissue sections. G.A. participated in surgical procedures. P.B participated in kidney perfusion and urine collection. R.M. participated in kidney perfusion and blood collection. I.A. participated in surgical procedures. K.P.S participated in surgical procedures. Q. S., H.A and L.J. participated in data analysis. M.S. participated in performing RT-PCR experiments of TLR data. E.P. participated in measuring CO from CORM-401. A.S. participated in article editing. G.C participated in technical support regarding CORM-401 release. A.M.J. participated in intellectual conception of project, article editing and approval of the article. P.P.L participated in the intellectual conception of project, extensive literature review, partial article writing, editing and final approval of the article. Conflicts of Interest. All the authors declared no competing interests. Funding We would like to thank the Canadian National Transplantation Research Program sponsored by Canadian Institutes for Health Research (PPL), Physicians Services Incorporated Foundation (PSIF) (PPL, RNB), Academic Medical Organization of Southwestern Ontario (PPL, RNB), HSFO grant (G-17-0018622) to GC and Internal Research Fund (RNB, PPL), Department of Surgery at LHSC for financial support. HTK and UW solutions were provided by Methapharm Inc. and Bridge to life respectively. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Changes in pediatric heart transplant hospitalization costs over time

Background Despite significant changes in the past decade for children undergoing heart-transplantation, including the evolution of mechanical circulatory support and increasing patient complexity, costs and resource utilization have not been reassessed. We sought to utilize a novel linkage of clinical-registry and administrative data to examine changes in hospitalization costs over time in this population. Methods We identified all pediatric heart transplant recipients in a unique linked PHIS/SRTR dataset (2002-2016). Hospital costs were estimated from charges using cost-to-charge ratios, inflated to 2016 dollars. Severity-adjusted costs were calculated using generalized linear mixed-effects models. Costs were compared across 3 eras (Era-1:2002-2006; Era-2:2007-2011; and Era-3:2012-2016). Results A total of 2896 pediatric heart transplant recipients were included; Era-1:649 (22.4%), Era-2:1028 (35.5%), and Era-3:1219 (42.1%). ECMO support at transplant decreased over time, concurrent with an increase in VAD-supported patients. Between Era-1 and Era-2 there was an increase in pretransplant hospitalization costs ($343,692 vs. $435,554; p

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Isolation and In Vitro Culture of Murine and Human Alveolar Macrophages

This communication describes methodologies for isolation and culture of alveolar macrophages from humans and murine models for experimental purposes.

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A Fast Silver Staining Protocol Enabling Simple and Efficient Detection of SSR Markers using a Non-denaturing Polyacrylamide Gel

Here, we report a simple and low-cost silver staining protocol which requires only three reagents and 7 min of processing, and is suitable for fast generation of high-quality SSR data in the genetic analysis.

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Evolution of Acute Kidney Injury and Its Association With Systemic Hemodynamics in Children With Fluid-Refractory Septic Shock

Objectives: There are no studies in pediatrics evaluating the progression of acute kidney injury in septic shock. We investigated the evolution of sepsis-associated acute kidney injury and its association with systemic hemodynamics in children with fluid-refractory septic shock. Design: Prospective cohort study. Setting: PICU of a tertiary care hospital. Patients: All patients with fluid-refractory septic shock (n = 61) between September 2010 and February 2014. Interventions: Hemodynamic variables using noninvasive ultrasound cardiac output monitor were measured at admission and 6 hourly thereafter till 48 hours. We used the Kidney Disease: Improving Global Outcomes criteria to define and stage acute kidney injury. Associations between various hemodynamic variables and development of acute kidney injury were evaluated. Severe acute kidney injury was defined as stage 2 or 3 acute kidney injury and was compared with no acute kidney injury or stage 1 acute kidney injury. Measurements and Main Results: Severe acute kidney injury developed in 29.5% (n = 18) of the 61 children with fluid-refractory septic shock, whereas 43 patients (70.49%) had either no or stage 1 acute kidney injury. Most patients who developed acute kidney injury did so within the first 48 hours of PICU admission. Severe acute kidney injury conferred a three-fold increased risk of death by day 28 (hazard ratio, 3.23; 95% CI, 1.52–6.67; p = 0.002), longer ICU stay, and increased duration of mechanical ventilation. Central venous pressure at presentation was higher in severe acute kidney injury by 5 cm H2O. Highest lactate in the first 24 hours of PICU admission, low diastolic blood pressure, low systemic vascular resistance index at admission were associated with severe acute kidney injury. This model reliably predicted stage 2/3 acute kidney injury by day 3 with area under the curve equals to 94%; 95% CI, 88.3–99.99. None of the other hemodynamic variables showed any association with severe acute kidney injury. Conclusions: Manifestations of sepsis-associated acute kidney injury often occur early after PICU admission and is associated with increased morbidity and mortality. There is a need to develop a predictive model in septic shock which could facilitate early detection of acute kidney injury. This work was performed at King's College Hospital, Denmark Hill, London SE5 9RS, United Kingdom. Ethical Statement: This was an observational study of routinely monitored hemodynamic and biochemical variables in the clinical management of children in septic shock in PICU and their outcomes. All children received standard therapies. Therefore, according to local guidelines, Ethics Committee review was not required. However, this study was registered as a service evaluation project at King's College Hospital (Clinical Audit Support System project no. 2902). Dr. Deep is the supervisor who conceptualized the project and supervised data collection, interpretation and has reviewed and edited the article. He is the corresponding author. Drs. Sagar and Karthikeyan collected the data and contributed to the initial article. Drs. Goonasekera and Brierley helped edit the article. Dr. Douiri is senior lecturer of Biostatistics and Epidemiology in the department of primary care and public health sciences at King's College London who advised the statistical design and analysis of the data. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/29S62lw). Dr. Douiri acknowledges financial support from the National Institute for Health Research (NIHR) Biomedical Research and from the NIHR Collaboration for Leadership in Applied Health Research and Care South London at King's College Hospital NHS Foundation Trust. The remaining authors have disclosed that they do not have any potential conflicts of interest. Address requests for reprints to: Akash Deep, MD, FRCPCH, PICU, King's College Hospital, Denmark Hill, London SE5 9RS, United Kingdom. E-mail: akash.deep@nhs.net Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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Near-Continuous Glucose Monitoring Makes Glycemic Control Safer in ICU Patients

Objectives: Tight glycemic control using intermittent blood glucose measurements is associated with a risk of hypoglycemia. Glucose concentrations can now be measured near continuously (every 5–15 min). We assessed the quality and safety of glycemic control guided by a near-continuous glucose monitoring system in ICU patients. Design: Prospective, cluster-randomized, crossover study. Setting: Thirty-five–bed medico-surgical department of intensive care with four separate ICUs. Patients: Adult patients admitted to the department and expected to stay for at least 3 days were considered for inclusion if they had persistent hyperglycemia (blood glucose > 150 mg/dL) up to 6 hours after admission and/or were receiving insulin therapy. Interventions: A peripheral venous catheter was inserted in all patients and connected to a continuous glucose monitoring sensor (GlucoClear; Edwards Lifesciences, Irvine, CA). The four ICUs were randomized in pairs in a crossover design to glycemic control using unblinded or blinded continuous glucose monitoring monitors. The insulin infusion rate was adjusted to keep blood glucose between 90 and 150 mg/dL using the blood glucose values displayed on the continuous glucose monitor (continuous glucose monitoring group—unblinded units) or according to intermittent blood glucose readings (intermittent glucose monitoring group—blinded units). Measurements and Main Results: The quality and safety of glycemic control were assessed using the proportion of time in range, the frequency of blood glucose less than 70 mg/dL, and the time spent with blood glucose less than 70 mg/dL (TB70), using blood glucose values measured by the continuous glucose monitoring device. Seventy-seven patients were enrolled: 39 in the continuous glucose monitoring group and 38 in the intermittent glucose monitoring group. A total of 43,107 blood glucose values were recorded. The time in range was similar in the two groups. The incidence of hypoglycemia (8/39 [20.5%] vs 15/38 [39.5%]) and the TB70 (0.4% ± 0.9% vs 1.6% ± 3.4%; p

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Ky. fire dept. seeking grant for firefighter, EMS body armor

The department is asking for a $44,600 Homeland Security grant to purchase body armor responders can wear during incidents where responders might be in danger

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Severe bleeding is a rare event in patients receiving lumen-apposing metal stents for the drainage of pancreatic fluid collections

Pancreatic fluid collections (PFCs) including pancreatic pseudocysts (PPCs) and walled-off necrosis (WON) frequently develop in the context of pancreatitis. Lumen-apposing self-expanding metal stents (LAMS) are increasingly used for the endoscopic management of infected and symptomatic PFCs since they facilitate direct endoscopic inspection and necrosectomy of WONs.1–3 However, two reports recently published in Gut4 5 demonstrated high rates of haemorrhage associated with LAMS that were observed in up to 25% of patients and often occurred in a delayed manner with serious and fatal bleeding episodes reported. These data raised important concerns about the safety of LAMS and the optimal management of patients with infected or symptomatic PFCs.

As a limitation, the reports by Bang et al4 and Stecher et al5 were based on relatively small group sizes of 12 and 46 LAMS-treated patients, respectively. To investigate whether the...

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Sedation in GI endoscopy: a paradigm shift has taken place

We can agree to the letter of Braden and Walsh without any limitation.1

In consideration of the positive security data for the application of propofol by non-anaesthetists in the GI endoscopy, not least also by the ProSed2 study documented, specialised political interests should not have an influence on national guidelines any more.2

While there are extensive positive data for endoscopist/Nurse Administered Propofol Sedation (NAPS)-controlled sedation, this is not valid for the anaesthesia-controlled sedation in GI endoscopy. Hence, no claim or, in particular, none exclusivity on propofol-based sedation for GI endoscopy can be rose by anaesthetists. In addition, in countries in which propofol-based sedation is in the hands of gastroenterologists, the problem insists that the anaesthetist has no or few experiences with the sedation in GI endoscopy.

Undoubtedly also in future every gastroenterologist will examine patients with anatomical conspicuities without sedation or a priori by an anaesthetist escorted. Same is valid for...

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