Guava Leaf Extract Diminishes Hyperglycemia and Oxidative Stress, Prevents β-Cell Death, Inhibits Inflammation, and Regulates NF-kB Signaling Pathway in STZ Induced Diabetic Rats

Traditional Chinese medication has been utilized by Chinese medical practitioners to treat the varied symptoms of diabetes mellitus (DM). Notably, guava leaf has been used to treat diabetes in Asia. Our present study has been designed to analyze the action of guava leaf extract (GLE) at the molecular level in treating DM. A low dose of streptozotocin (STZ) was used to induce experimental diabetes in animals. Rats were treated with GLE at different concentrations (100, 200, and 400 mg/kg b.w.). The standard drug glibenclamide (GB) (600 μg/kg b.w.) was used for comparison. The diabetic rats showed a reduced level of insulin, accompanied by exaggerated levels of blood glucose, lipid peroxidation product, and augmented expressions of inflammatory cytokines, and showed reduced levels of antioxidants compared to the control rats. Supplementation with GLE counteracted the consequences of STZ. It suppresses the oxidative stress and inhibits the state of inflammation and the results are almost similar to that of standard drug group (GB group 5). Our present research, therefore, provides useful data concerning guava leaf extract by a thorough assessment in diabetes management. Being a natural product, additional analysis on GLE can shed light on finding effective phytochemicals within the field of diabetes mellitus.

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Readiness of US General Surgery Residents for Independent Practice: Erratum

No abstract available

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Homelessness and Emergency Medicine: Where Do We Go From Here?

Abstract

In many emergency departments (EDs) around the country, providers care for patients experiencing homelessness on every single shift. Despite its proven impact on health, housing status is not a routine part of the history taken by most emergency providers, and in many cases providers are unaware that they are caring for someone who has no stable home. Patients experiencing homelessness have unique needs spanning acute and chronic illness, injury, behavioral health diagnoses, and material deprivation.

This article is protected by copyright. All rights reserved.

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Kawasaki Disease After Streptococcal Pneumonia

A 4.5-year-old girl presented to the emergency department with a 5-day history of high fever, fatigue, and rash. Because of pneumonia with pleural empyema and sepsis caused by Streptococcus pyogenes, she was admitted to the pediatric intensive care unit. After initial improvement and on the eighth day, she became febrile again and also developed conjunctivitis, rash, cervical lymphadenopathy, periungual desquamation, and elevated inflammatory markers. A cardiac echo revealed a limited dilatation of the left main coronary artery. Because of suspicion of secondary Kawasaki disease, she received intravenous immunoglobulin and acetylsalicylic acid. There was an immediate clinical response with improvement of all clinical manifestations and laboratory findings. During follow-up examination 1 month later, the diameter of the left main coronary artery was within normal limits. A high index of suspicion of Kawasaki disease in children is required upon development of fever and compatible signs and symptoms in patients with serious streptococcal disease. Correspondence to: Ioanna Argyri, PhD, 2nd Pediatric Department, "P. & A. Kyriakou" Children's Hospital, National and Kapodistrian University of Athens, Thivon & Levadeias, 11527 Athens, Greece. E-mail: ioarg@yahoo.gr. The authors have no funding or conflicts of interest to disclose. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Emphysematous Gastritis is a Severe Infectious Disease: Case Report and Review

Purpose Emphysematous gastritis (EG) is a rare form of infectious gastritis reported in many immunocompromised patient with extreme severity and many potential comorbidities. However, despite lots of critically ill case reports, there is a trend towards conservative management. Furthermore, it has never been described in refractory septic intensive care unit patient treated successfully with a sleeve gastrectomy. We wanted to focus on the progress made in diagnosis and treatments since the early 2000s and to report a case. Methods We report the case of a critically ill and immunocompromised 45-year-old women, who presented an EG secondary to an ileus due to a high dose of barbiturates for a refractory epilepticus status. Then, we conducted a literature search for reported adult cases of EG since 2000. Results Study cohort included 53 new cases of EG since 2000. Mean age was 54, and mean (SD) length of stay was 23 ± 36 days. Diabetes mellitus is still the main predisposing factor identified. Causative pathogen was found in only 40% of the cases, mostly Enterobacteriaceae, Enterococcus spp, and Streptococcus. An emergent surgery was required in only 6 cases of refractory septic shock or gastric necrosis. The global mortality rate reached 34%. Conclusions Emphysematous gastritis remains a severe disease, which can evolve quickly in septic shock or in gastric necrosis. Early diagnosis and management are warranted to favor a conservative management, even for severe forms and prevent further complications. Cases refractory to supportive measures can be successfully managed with minimally invasive surgery. Correspondence to: Melanie Fromentin, MD, Department of Anesthesia and Intensive Care, Cochin University Hospital, 27 rue du faubourg Saint Jacques, 75014 Paris, France. E-mail: melanie.fromentin@aphp.fr. The authors have no funding or conflicts of interest to disclose. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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A Fatal Case of Hemophagocytic Lymphohistiocytosis in a Patient With Ehrlichiosis

We present a case of Ehrlichia-induced hemophagocytic lymphohistiocytosis (HLH), which resulted in a fatal outcome. Hemophagocytic lymphohistiocytosis is a rare syndrome of abnormal activation of the cellular immune system, which can be potentially fatal. Infections are a common trigger of the secondary form of the syndrome. We review the literature for published reports of Ehrlichia-induced HLH, all of which have resulted in a favorable outcome. We try to analyze the reasons for the poor outcome in our case including the possibility of central nervous system involvement with HLH. Early recognition and treatment of HLH and its associated central nervous system involvement may improve outcome. Correspondence to: Jad A. Khoury, MD, 621 S New Ballas Rd, Suite 7018-B, St Louis. MO 63141. E-mail: jad.khoury@mercy.net. The authors have no funding or conflicts of interest to disclose. All authors have contributed equally to this article. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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A Case of Pyelonephritis With Bacteremia Caused by Gardnerella Vaginalis in a Man

Gardnerella vaginalis is known to be associated with bacterial vaginosis and has less frequently been reported to contribute to polymicrobial gynecologic and postsurgical infections in women. It is not considered to be a common cause of disease in men. We now report a case of pyelonephritis with G. vaginalis bacteremia in a male patient with nephrolithiasis. We found 10 other cases of Gardnerella infection in men and reviewed the predisposing factors, case descriptions, treatments, and outcomes. Infection due to G. vaginalis in men is rare, but it should be considered to be a potential pathogen men, especially in those with urogenital tract abnormalities. Correspondence to: Haley Pritchard, MD, Department of Infectious Diseases, Baylor College of Medicine, BCM 901, 7200 Cambridge St, Houston, TX 77030. E-mail: haley.pritchard@bcm.edu. The author has no funding or conflicts of interest to disclose. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Epidemiology and the Changing Face of HIV Infection in Qatar

Background The aim of the study was to study the demographics, modes of transmission, clinical features, and outcome of human immunodeficiency virus (HIV) infection in Qatar and the change in epidemiology over time before and after 2000. Method Review of the records of all cases of HIV infection diagnosed in Qatar between 1984 and October 2014 was conducted. Results During the study period, 306 cases of HIV infection were diagnosed in Qatar. Files were available for review for only 148 patients. Males were more than females with a ratio of 2.5:1. The male to female ratio in those diagnosed after 2000 (group 2) was significantly more than in those diagnosed before 2000 (group 1). Almost half of the cases were Qatari. The most common mode of transmission was sexual (72%); however, in a significant proportion (43%) of those in group 1, the mode of transmission was blood transfusion. Fifty-four percent of patients had a late presentation with an acquired immunodeficiency syndrome defining condition or with CD+4 less than 350 cells/mm3. The mean CD+4 cell count at presentation was 359 cells/mm3, and there was no significant difference between the two groups. Evidence of previous infection with hepatitis B virus, hepatitis C virus, syphilis, and toxoplasmosis was low (10%, 4%, 2.5%, and 11%, respectively); however, the difference between the two groups was significant only for HCV infection. One hundred four patients (70%) are still alive despite some of them were diagnosed early in HIV epidemic. Conclusions Qatar remains a low prevalence country for HIV infection. The disease affects mainly young male adults with many of them presenting late in the disease. The epidemiology of HIV infection in Qatar has changed over time with infection being mostly sexually transmitted in later years. More non-Qataris are being diagnosed compared with earlier years, and this reflects the change in population that occurred in Qatar in recent years. More efforts are needed to educate the public especially the young in prevention measures and to improve early diagnosis. Correspondence to: Hussam Al Soub, MD, CABM, FACP, Hamad Medical Corporation, PO Box 3050, Doha, Qatar. E-mail: hussamalsoub@yahoo.com. The authors have no funding or conflicts of interest to disclose. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Long-Term Safety of Tedizolid in a Patient With Spondilodiscitis After Switch From Linezolid Due to Toxicity

The patient is a 57-year-old man with liver cirrhosis, Bricker anastomosis after a radical cystoprostatectomy and, a history of bacteremias caused by extended-spectrum β-lactamase–positive Escherichia coli, Enterococcus faecium, and Candida albicans. He presented with persistent low back pain and was diagnosed with vertebral osteomyelitis, for which he received ertapenem-linezolid treatment. However, after 20 days, linezolid had to be discontinued because of myelotoxicity and metabolic acidosis. The patient was switched to tedizolid, which, in combination with ertapenem, was successfully given for 114 days until biopsy showed no growth of gram-positive cocci. We conclude that tedizolid can be an alternative to linezolid in case of toxicity, especially in long-term treatments. Correspondence to: Rosa Maria Martínez Álvarez, MD, PhD, Infectious Diseases Unit, Antimicrobial Stewardship, Internal Medicine Department, Miguel Servet University Hospital, Avenida Isabel La Católica 1-3, 50009 Zaragoza, Spain. E-mail: rmartineza@salud.aragon.es. The authors have no conflicts of interest to disclose. Editorial assistance was provided by Content Ed Net, Madrid, Spain. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Recurrent Idiopathic Anaphylaxis in a Woman After Suspected Food Poisoning

Rationale Recurrent idiopathic anaphylaxis represents a vexing clinical problem associated with stress for patients and allergists. The cause is often not identified despite exhaustive testing. Methods The history of a 54-year old woman with repeated bouts of unexplained anaphylaxis is reviewed. The relationship between preceding or active infection (emphasis on gastrointestinal infections) and chronic idiopathic urticaria and anaphylaxis was explored by electronic media search (PubMed, Google) and review of reference lists of published articles. The literature on the relationship of Campylobacter jejuni infection and urticaria is reviewed. Gastrointestinal infections (Giardia, Anisakis) have been better documented in such patients. Results The patient had persistent flatulence, and looser and more frequent bowel movements for months after recovery from a bout of food poisoning. A diagnosis of "postinfectious irritable bowel syndrome" was made by a gastroenterologist. These symptoms were not related to her simultaneous diagnosis of chronic idiopathic urticaria and idiopathic anaphylaxis. After treatment with azithromycin (positive stool culture for C. jejuni), she had a systemic allergic reaction. Subsequently, the diarrhea and urticaria/anaphylaxis cleared. C. jejuni has been reported to cause chronic urticaria, but predominantly in children. A related organism, Helicobacter pylori, has been associated with chronic idiopathic urticaria. Anaphylaxis has not been related to Campylobacter infection in the past. Conclusions Urticaria and recurrent bouts of mild unexplained anaphylaxis were triggered by C. jejuni infection. The allergic and gastrointestinal symptoms resolved after antibiotic treatment. Gastrointestinal (and other) infections should be looked for in patients with urticaria or anaphylaxis Correspondence to: Shalini Koppisetty, MBBS, 3535 W 13 Mile Rd, Royal Oak, MI, 48073. E-mail: shalini.k.amc@gmail.com. The authors have no funding or conflicts of interest to disclose. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Extravaginal Gardnerella vaginalis Infection—An Uncommon Variable: A Case of Gardnerella vaginalis Pyelonephritis With Bacteremia

Extravaginal infections due to Gardnerella vaginalis are rare and likely underappreciated. We present a case of G. vaginalis pyelonephritis and bacteremia due to an obstructing nephrolith. It is important for healthcare providers to be aware of such infections, including genitourinary or bloodstream infections, which may follow local anatomic disruption. Correspondence to: Katelyn J. Booher, DO, Department of Internal Medicine, School of Medicine, Wright State University Boonshoft, Weber CHE Bldg, 2nd Floor, 128 E Apple St, Dayton, OH 45409. E-mail: katebooher@gmail.com. The authors have no funding or conflicts of interest to disclose. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Moraxella Species Bacteremia in Cancer Patients: A Case Series and Review of the Literature

Moraxella is a genus of gram-negative diplococci considered to be an important cause of upper respiratory tract disease in humans. Bacteremia caused by Moraxella species, however, remains rare and tends to occur in individuals with a compromised immune system. We reviewed all cultures positive for Moraxella species at an academic cancer hospital between the years of 2011 and 2016. We also performed a literature review of Moraxella species bacteremia in cancer patients in the decade between 2006 and 2016. At the H. Lee Moffitt Cancer Center, between 2011 and 2016, there were 41 positive cultures (from all sites) for Moraxella species. Of these 41 cultures, only 3 were positive blood cultures. Our findings indicate that bacteremia caused by Moraxella species can range in severity from fever and chills to frank sepsis. As has been noted in other publications, the source of the bacteremia is not always clinically apparent, but upper and lower respiratory sources seem to predominate. None of the patients presented in this case series died of their bacteremia. The 2 publications discovered in our literature review similarly describe 2 nonfatal cases of Moraxella osloensis bacteremia: 1 case in a patient with a recent diagnosis of acute myeloid leukemia and 1 case in a patient with an unspecified lung cancer. Correspondence to: John N. Greene, MD, Infectious Diseases and Hospital Epidemiologist, Moffitt Cancer Center and Research Institute, 12902 Magnolia Dr, FOB-3, Tampa, FL 33612-9497. E-mail: john.greene@moffitt.org. The authors have no conflicts of interest to disclose. None of the authors are affiliated with, or have financial involvement in any organization or entity with direct financial involvement in the subject matter or materials of the research discussed in this article. All authors have participated significantly in writing of this article and approve of its content. There is no material that is under the copyright of another party or appearing in another unpublished manuscript. The final manuscript has been seen and approved by all authors. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Autoimmune Manifestations of Acute Q Fever Infection

Q fever is nearly a worldwide zoonotic infection caused by the intracellular bacterium Coxiella burnetii, which is endemic in Israel. Acute infection mostly presents as a self-limited febrile illness, and occasionally involves respiratory or hepatic disease. Immune reactivation in the setting of acute illness was previously reported as well as various infectious positive cross-reactive serologic tests during the course of disease. Other autoimmune manifestation is infectious-type antiphospholipid syndrome linked to acute Q fever. Herein, we report a case of acute Q fever–related antiphospholipid syndrome with features resembling systemic lupus erythematosus treated successfully with corticosteroids. We review the literature and discuss the present state of knowledge on the link between Q fever and autoimmunity, aiming to raise clinicians' awareness of this possible rare presentation of the disease. Correspondence to: Nasreen Hassoun-Kheir, MD, Infectious Diseases Institute, Rambam Health Care Campus, Ha'aliya ha sheneia St 8, Haifa 3109601, Israel. E-mail: n_hassoun@rambam.health.gov.il. The authors have no funding or conflicts of interest to disclose. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Clostridium Perfringens Infection With Massive Hemolysis: A Rare Survivor. Case Report and Literature Review

Clostridium perfringens infection is rarely complicated by severe hemolysis caused by the microbial alpha-toxin, a phospholipase. Patients with this complication usually have a hepatobiliary or colonic source of infection. The mortality rate is extremely high when massive hemolysis supervenes, and the duration of illness from symptom onset to death is often only hours. We describe a patient with a liver abscess, C perfringens bacteremia, and massive hemolysis with severe multiorgan failure. He survived with supportive treatment including aggressive transfusion of packed red cells, systemic antibiotics, and surgical intervention. A literature review disclosed 45 cases of arbitrarily defined massive hemolysis, with 41/45 (91.1%) mortality and a median survival time of 6 hours from symptom onset in those patients who died. There were no reported survivors in cases of hemolysis due to C perfringens septicemia of the severity seen in our patient. A search of the area pathology service database identified 132 cases of C perfringens bacteremia during the period January 2001 to December 2016. Although there were no well-confirmed (by laboratory testing) cases of massive hemolysis in these patients, 4 of 132 patients (3%) died suddenly with blood samples that were not analyzed because of marked visual hemolysis. Correspondence to: Paul A Wilson, BMed, Department of Medicine, Calvary Mater Newcastle, Edith Street, Waratah, New South Wales, Australia. E-mail: paul.wilson@calvarymater.org.au. The authors have no conflicts of interest to disclose. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Insulin-like growth factor 2: a poor prognostic biomarker linked to racial disparity in women with uterine carcinosarcoma

Abstract

The objective of this study was to investigate the relationship of insulin-like growth factor 2 (IGF2) expression and survival in women with uterine carcinosarcoma (UCS). Insulin-like growth factor 2 protein expression was determined by immunohistochemical staining of tumor tissues from 103 patients with UCS. The H-score (product of staining intensity and percentage positive cells) was quantified for the epithelial cytoplasmic (EC), epithelial nuclear (EN), and malignant stromal compartments. Multivariable Cox proportional hazard regression models were used to examine the relationship of IGF2 levels with progression-free survival (PFS) and overall survival (OS). Adjusting for stage, race, and adjuvant therapy, PFS and OS were reduced in patients with high IGF2 (H-score ≥ median) in the EC and EN compartments. Black race was independently associated with reduced PFS and OS in patients with early-stage disease, and IGF2 levels in the EC were higher in black than in white patients (P = 0.02, Wilcoxon test). In a race-stratified multivariable analysis, high IGF2 in the epithelial compartments more than doubled the risk of death in black women; HR = 2.43 (95% CI: 1.18–5.01, P = 0.02) for high IGF2 in the EC; and HR = 2.34 (95% CI: 1.25–4.39, P = 0.008) for high IGF2 in the EN. In conclusion, high tumor IGF2 expression is an independent risk factor for reduced PFS and OS in UCS. Black women have elevated tumor IGF2 compared with white women, and decreased survival associated with high IGF2. These findings identify IGF2 as a candidate biomarker for survival linked to racial disparity in women with UCS.

This study shows that IGF2 protein expression is an independent poor prognostic biomarker in uterine carcinosarcoma, a lethal uterine cancer that disproportionately impacts black women. These novel findings suggest that IGF2 is a biological mediator of an aggressive cancer phenotype and a potential therapeutic target in this disease. Moreover, we have uncovered an intriguing association of IGF2 with racial disparity in uterine carcinosarcoma survival.

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Comparative Study of Different Classification Models in Renal-Cell Carcinoma

Abstract

The aim of this study was to compare the Memorial Sloan-Kettering Cancer Center (MSKCC) and the Cleveland Clinic Foundation (CCF) models of classification of aRCC patients. In addition, the model developed from the pivotal trial of temsirolimus and those proposed by Motzer et al. in 2004, Escudier et al., Heng et al., Choueiri et al. and Bamias et al. were examined. An observational, retrospective study of patients starting first-line systemic therapy was conducted between 2008 and 2011. The variables used to evaluate the classification models were median overall survival (mOS) and median progression-free survival (mPFS). The comparison of different classification models was performed by comparing the area under the ROC (Receiver Operating Characteristic) curve (AUC) for time-dependent variables proposed by Heagerty. Eighty-eight patients were included. When the different models were compared, it was found that although based on the mOS, the Escudier model had better short-term (1-year) prognostic value, followed by the Heng model; in the long term, the models that presented a higher prognosis capacity were the Hudes and CCF models, closely followed by the Heng model. In addition, the Heng model had a slightly higher predictive ability than the other models. Based on the results, and in line with the European society for medical oncology (ESMO) guidelines, it appears that the model of Heng could be the best model to classify patients with aRCC and combines good short- and long-term prognostics while possessing better predictive ability and a more equal distribution of patients.

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Age-Related Hearing Impairment Associated NAT2 , GRM7 , GRHL2 Susceptibility Gene Polymorphisms and Haplotypes in Roma and Hungarian Populations

Abstract

Age-related hearing impairment (ARHI) is the most frequent sensory disease in the elderly, which is caused by an interaction between genetic and environmental factors. Here we examined the ethnic differences, allele and genotype frequencies of the NAT2, GRM7, and GRHL2 genes pooled samples of healthy Hungarian and healthy and hearing impaired Roma people. Study populations of healthy Hungarian and Roma subjects were characterized for the rs1799930 NAT2, rs11928865 GRM7, rs10955255, rs13263539, and rs1981361 GRHL2 polymorphisms and deaf Roma subjects were characterized for the rs1799930 NAT2, rs13263539, and rs1981361 GRHL2 using a PCR-RFLP method. We found significant differences in minor allele frequencies for GRHL2 rs13263539 and rs1981361 polymorphism between healthy Roma and Hungarian samples (37.9% vs. 51.0% and 43.6% vs. 56.2%, respectively; p < 0.05). The differences of homozygous genotype of GRHL2 rs13263539 and rs1981361 variants, values were also significantly different (13.0% vs. 25.3% and 16.5 vs. 32.3%; p < 0.05). The NAT2 rs1799930 homozygous genotype was 14.0% in healthy Romas and 7.7% in Hungarians, while the minor A allele frequency was 38.0% and 26.7% in Roma and Hungarian population, respectively (p < 0.05). Furthermore, the frequency of GGT, GAC and GAT haplotypes was significantly higher in the Hungarian population than in healthy Roma (1.87 vs. 4.47%, 0.91 vs. 2.07% and 1.15 vs. 5.51%, respectively; p < 0.008). Present study revealed significant interethnic differences in allele polymorphisms of NAT2, GRM7 and GRHL2 exhibit quite marked ethnic differences in Roma populations that might have important implications for the preventive and therapeutic treatments in this population.

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Dual-Stained Cervical Cytology and Histology with Claudin-1 and Ki67

Abstract

Several biomarkers are in use to improve the sensitivity and specificity of cervical cancer screening. Previously, increased expression of tight junction protein claudin-1 (CLDN1) was detected in premalignant and malignant cervical lesions and applied for cytology screening. To improve the specificity, a double immunoreaction with CLDN1/Ki67 was developed in the recent study. Parallel p16/Ki67 (CINtec® PLUS) and CLDN1/Ki67 dual-stained cytology and histology were performed and compared. p16/Ki67 immunoreaction showed positivity in 317 out of 1596 smears with negativity in 1072 and unacceptable reactions in 207 samples. CLDN1/Ki67 dual staining was positive in 200 of 1358 samples, negative in 962, whereas 196 smears could not be evaluated due to technical reasons. Considering the high-grade squamous intraepithelial lesion cytology as gold standard, sensitivity of CLDN1/Ki67 reaction was 76%, specificity was 85.67%, while for p16/Ki67 sensitivity was 74% and specificity was 81.38%. Comparison of CLDN1/Ki67 and p16/Ki67 dual stainings showed the results of the two tests not to be significantly different. Analysing histological slides from 63 cases, the results of the two tests agreed perfectly. As conclusion the sensitivity and specificity proved to be similar using p16/Ki67 and CLDN1/Ki67 double immunoreactions both on LBC samples and on histological slides.

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Miki (Mitotic Kinetics Regulator) Immunoexpression in Normal Liver, Cirrhotic Areas and Hepatocellular Carcinomas: a Preliminary Study with Clinical Relevance

Abstract

Hepatocellular carcinoma (HCC) is the most common type of primary malignant tumor in the liver. One of the main features of cancer survival is the generalized loss of growth control exhibited by cancer cells, and Miki is a protein related to the immunoglobulin superfamily that plays an important role in mitosis. We aim to study protein expression levels of Miki in non-tumoral liver and 20 HCCs recruited from a Pathology Department. Clinical information was also obtained. A tissue microarray was performed, and immunohistochemical techniques applied to study protein expression levels of Miki. In normal liver, Miki was weakly expressed, showing nuclear staining in the hepatocytes. Cirrhotic areas and HCCs showed a variety of staining patterns. Most HCC samples showed positive expression, with three different staining patterns being discernible: nuclear, cytoplasmic and mixed. Statistical analysis showed a significant association between grade of differentiation, Ki-67 proliferative index, survival rates and staining patterns. This study has revealed the positive expression of Miki in normal liver, cirrhotic areas and HCCs. Three different staining patterns of Miki expression with clinical relevance were noted in HCCs.

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Diabetes and obesity are the main metabolic drivers of peripheral neuropathy

Abstract

Objective

To determine the associations between individual metabolic syndrome (MetS) components and peripheral neuropathy in a large population-based cohort from Pinggu, China.

Methods

A cross-sectional, randomly selected, population-based survey of participants from Pinggu, China was performed. Metabolic phenotyping and neuropathy outcomes were performed by trained personnel. Glycemic status was defined according to the American Diabetes Association criteria, and the MetS using modified consensus criteria (body mass index instead of waist circumference). The primary peripheral neuropathy outcome was the Michigan Neuropathy Screening Instrument (MNSI) examination. Secondary outcomes were the MNSI questionnaire and monofilament testing. Multivariable models were used to assess for associations between individual MetS components and peripheral neuropathy. Tree-based methods were used to construct a classifier for peripheral neuropathy using demographics and MetS components.

Results

The mean (SD) age of the 4002 participants was 51.6 (11.8) and 51.0% were male; 37.2% of the population had normoglycemia, 44.0% prediabetes, and 18.9% diabetes. The prevalence of peripheral neuropathy increased with worsening glycemic status (3.25% in normoglycemia, 6.29% in prediabetes, and 15.12% in diabetes, P < 0.0001). Diabetes (odds ratio [OR] 2.60, 95% CI 1.77–3.80) and weight (OR 1.09, 95% CI 1.02–1.18) were significantly associated with peripheral neuropathy. Age, diabetes, and weight were the primary splitters in the classification tree for peripheral neuropathy.

Interpretation

Similar to previous studies, diabetes and obesity are the main metabolic drivers of peripheral neuropathy. The consistency of these results reinforces the urgent need for effective interventions that target these metabolic factors to prevent and/or treat peripheral neuropathy.

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Phenotypic heterogeneity in m.3243A>G mitochondrial disease: The role of nuclear factors

Abstract

Objective

The pathogenic mitochondrial DNA m.3243A>G mutation is associated with a wide range of clinical features, making disease prognosis extremely difficult to predict. We aimed to understand the cause of this heterogeneity.

Methods

We examined the phenotypic profile of 238 adult m.3243A>G carriers (patients and asymptomatic carriers) from the UK MRC Mitochondrial Disease Patient Cohort using the Newcastle Mitochondrial Disease Adult Scale. We modeled the role of risk factors for the development of specific phenotypes using proportional odds logistic regression. As mitochondria are under the dual control of their own and the nuclear genome, we examined the role of additive nuclear genetic factors in the development of these phenotypes within 46 pedigrees from the cohort.

Results

Seizures and stroke-like episodes affect 25% and 17% of patients, respectively; more common features include hearing impairment, gastrointestinal disturbance, psychiatric involvement, and ataxia. Age, age-adjusted blood heteroplasmy levels, and sex are poor predictors of phenotypic severity. Hearing impairment, diabetes, and encephalopathy show the strongest associations, but pseudo-R² values are low (0.14–0.17). We found a high heritability estimate for psychiatric involvement (h²=0.76, P = 0.0003) and moderate estimates for cognition (h²=0.46, P = 0.0021), ataxia (h² = 0.45, P = 0.0011), migraine (h² = 0.41, P = 0.0138), and hearing impairment (h² = 0.40, P = 0.0050).

Interpretation

Our results provide good evidence for the presence of nuclear genetic factors influencing clinical outcomes in m.3234A>G-related disease, paving the way for future work identifying these through large-scale genetic linkage and association studies, increasing our understanding of the pathogenicity of m.3243A>G and providing improved estimates of prognosis.

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Nucleocytoplasmic transport defect in a North American patient with ALS8

Abstract

Amyotrophic lateral sclerosis 8 (ALS8) is a rare progressive neurodegenerative disease resulting from mutation in the gene for vesicle-associated membrane protein-associated protein B. We evaluated a North American patient using exome sequencing, and identified a P56S mutation. The disease protein had similar subcellular localization and expression levels in the patient and control fibroblasts. Patient fibroblasts showed increased basal endoplasmic reticulum stress and dysfunction of nucleocytoplasmic transport as evidenced by impaired Ran trafficking. This finding extends the identification of ALS8 into North America, and indicates a cellular defect similar to other forms of hereditary motor neuron disease.

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Placebo-controlled crossover assessment of mecasermin for the treatment of Rett syndrome

Abstract

Objective

To measure the efficacy of mecasermin (recombinant human insulin-like growth factor 1, rhIGF-1), for treating symptoms of Rett syndrome (RTT) in a pediatric population using a double-blind crossover study design.

Methods

Thirty girls with classic RTT in postregression stage were randomly assigned to placebo or rhIGF-1 in treatment period 1 and crossed over to the opposite assignment for period 2 (both 20 weeks), separated by a 28-week washout period. The primary endpoints were as follows: Anxiety Depression and Mood Scale (ADAMS) Social Avoidance subscale, Rett Syndrome Behaviour Questionnaire (RSBQ) Fear/Anxiety subscale, Parent Target Symptom Visual Analog Scale (PTSVAS) top three concerns, Clinical Global Impression (CGI), Parent Global Impression (PGI), and the Kerr severity scale. Cardiorespiratory- and electroencephalography (EEG)-based biomarkers were also analyzed.

Results

There were no significant differences between randomization groups. The majority of AEs were mild to moderate, although 12 episodes of serious AEs occurred. The Kerr severity scale, ADAMS Depressed Mood subscale, Visual Analog Scale Hyperventilation, and delta average power change scores significantly increased, implying worsening of symptoms. Electroencephalography (EEG) parameters also deteriorated. A secondary analysis of subjects who were not involved in a placebo recall confirmed most of these findings. However, it also revealed improvements on a measure of stereotypic behavior and another of social communication.

Interpretation

As in the phase 1 trial, rhIGF-1 was safe; however, the drug did not reveal significant improvement, and some parameters worsened.

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Reflection impulsivity perceptual decision-making in patients with restless legs syndrome

Abstract

Objectives

The objective of this study was to investigate perceptual decision-making and reflection impulsivity in drug naïve patients with restless legs syndrome (RLS) and patients with dopaminergic therapy.

Methods

A total of 35 RLS patients (20 who were drug naïve regarding dopaminergic medication and 15 patients treated with dopaminergic therapy without augmentation or impulse control disorders) were included in this study. We used the Beads task and the Pixel task which assess reflection impulsivity and perceptual decision-making, respectively. Results were compared to 20 healthy controls.

Results

Both RLS patient groups gathered less evidence than healthy controls in the Beads task before making a decision (P < 0.001), but patients with dopaminergic treatment gathered less information than drug naïve patients (P = 0.026). Moreover, both patient groups made more choices against the evidence than healthy controls (both P < 0.01), but there was no difference between the two patient groups. In the Pixel task, we found an effect of task difficulty on reaction times with patients and controls responding faster with reduced task difficulty. There was neither an effect of group on reaction times nor an effect of group on error rates.

Conclusions

Reflection impulsivity is common in RLS patients, regardless whether they are drug naïve or treated with dopaminergic therapy. Thus, RLS patients tend to gather less information compared to healthy controls which could have a negative effect on decision-making in daily life and should be investigated further.

http://ift.tt/2C8Rr1o

Brain atrophy and disability worsening in primary progressive multiple sclerosis: insights from the INFORMS study

Abstract

Objective

To investigate the relationship between brain volume and disability worsening over ≥3 years in the natural history of primary progressive multiple sclerosis using data from the placebo group of the INFORMS trial (n = 487; clinicaltrials.gov NCT00731692).

Methods

Magnetic resonance imaging scans were collected annually. Brain volume loss was determined using SIENA. Patients were stratified by baseline normalized brain volume after adjusting for demographic and disease-burden covariates.

Results

Baseline normalized brain volume was predictive of disability worsening: Risk of 3-month confirmed disability progression was reduced by 36% for high versus low baseline normalized brain volume (Cox's model hazard ratio 0.64, P = 0.0339; log-rank test: P = 0.0297). Moreover, on-study brain volume loss was significantly associated with disability worsening (P = 0.012) and was evident in patients with or without new lesions or relapses. Brain volume loss depended significantly on baseline T2 lesion volume (P < 0.0001). Despite low inflammatory activity at baseline (13% of patients had gadolinium-enhancing lesions) and throughout the study (mean 0.5 new/enlarging T2 lesions and 172 mm³ T2 lesion volume increase per year), baseline T2 lesion volume was substantial (mean 10 cm³). Lower normalized brain volume at baseline correlated with higher baseline T2 volume and older age (both P < 0.0001).

Interpretation

Baseline brain volume and the rate of ongoing brain atrophy are significantly associated with disability worsening in primary progressive multiple sclerosis. Brain volume loss is significantly related to baseline T2 lesion volume, but partially independent of new lesion activity, which might explain the limited efficacy of anti-inflammatory treatment.

http://ift.tt/2sB41CN

Impact of stroke mechanism in acute basilar occlusion with reperfusion therapy

Abstract

Objective

We aimed to evaluate the impact of underlying mechanism of basilar artery (BA) occlusion on the outcomes after endovascular therapy (EVT) for reperfusion and the outcome factors associated with each mechanism, and to identify radiologic parameters enabling to distinguish the underlying mechanism.

Methods

From a registry database, 194 consecutive patients with acute BA occlusion who underwent EVT were analyzed. Stroke mechanism, classified into in situ atherosclerotic thrombosis (ISAT) and embolism, clot sign location profiles in pre-angiography magnetic resonance image (MRI), parameters of angiography and EVT, and reperfusion were assessed. Poor outcome was defined as a modified Rankin-Scale score at 90 days of 3–6.

Results

The mean age was 68.8±11.8 years (range 21–92 years) and seventy-eight (40.2%) were female patients. 102 (52.6%) patients were classified into an embolism mechanism and 92 (47.4%) into an ISAT mechanism. Overall, ISAT mechanism compared with embolism was significantly associated with poor outcomes (P = 0.002), along with the NIHSS scores, reperfusion status, and collateral status. In the embolism group, reperfusion (P = 0.001), NIHSS scores (P < 0.001), and onset-to-treatment time (P = 0.030) were significant outcome factors. However, in the ISAT group, baseline collateral status (P = 0.001) and NIHSS scores (P < 0.001) were significant outcome factors. A clot sign at the distal BA segment on pre-angiography MRI was strongly associated with embolism mechanism (P < 0.001).

Interpretation

Stroke mechanism has a major influence on outcomes, and outcome predictors differ according to the underlying mechanism in acute BA occlusion with EVT. Clot sign profile on pre-angiography MRI might be useful to determine the underlying mechanism.

http://ift.tt/2EO2Ww9

De novo variants in CAMK2A and CAMK2B cause neurodevelopmental disorders

Abstract

Objective

α (CAMK2A) and β (CAMK2B) isoforms of Calcium/calmodulin-dependent protein kinase II (CaMKII) play a pivotal role in neuronal plasticity and in learning and memory processes in the brain. Here, we explore the possible involvement of α- and β-CaMKII variants in neurodevelopmental disorders.

Methods

Whole-exome sequencing was performed for 976 individuals with intellectual disability, developmental delay, and epilepsy. The effect of CAMK2A and CAMK2B variants on CaMKII structure and firing of neurons was evaluated by computational structural analysis, immunoblotting, and electrophysiological analysis.

Results

We identified a total of five de novo CAMK2A and CAMK2B variants in three and two individuals, respectively. Seizures were common to three individuals with CAMK2A variants. Using a minigene splicing assay, we demonstrated that a splice site variant caused skipping of exon 11 leading to an in-frame deletion of the regulatory segment of CaMKIIα. By structural analysis, four missense variants are predicted to impair the interaction between the kinase domain and the regulatory segment responsible for the autoinhibition of its kinase activity. The Thr286/Thr287 phosphorylation as a result of release from autoinhibition was increased in three mutants when the mutants were stably expressed in Neuro-2a neuroblastoma cells. Expression of a CaMKIIα mutant in primary hippocampal neurons significantly increased A-type K⁺ currents, which facilitated spike repolarization of single action potentials.

Interpretation

Our data highlight the importance of CaMKIIα and CaMKIIβ and their autoinhibitory regulation in human brain function, and suggest the enhancement of A-type K⁺ currents as a possible pathophysiological basis.

http://ift.tt/2sENQUG

Magnetic resonance spectroscopy reveals abnormalities of glucose metabolism in the Alzheimer's brain

Abstract

Objective

Brain glucose hypometabolism is a prominent feature of Alzheimer's disease (AD), and in this case–control study we used Magnetic Resonance Spectroscopy (MRS) to assess AD-related differences in the posterior cingulate/precuneal ratio of glucose, lactate, and other metabolites.

Methods

J-modulated Point-Resolved Spectroscopy (J-PRESS) and Prior-Knowledge Fitting (ProFit) software was used to measure glucose and other metabolites in the posterior cingulate/precuneus of 25 AD, 27 older controls, and 27 younger control participants. Clinical assessments for AD participants included cognitive performance measures, insulin resistance metrics and CSF biomarkers.

Results

AD participants showed substantially elevated glucose, lactate, and ascorbate levels compared to older (and younger) controls. In addition, the precuneal glucose elevation discriminated well between AD participants and older controls. Myo-inositol correlated with CSF p-Tau_181P, total Tau, and the Clinical Dementia Rating (CDR) sum-of-boxes score within the AD group.

Interpretation

Higher glucose to creatine ratios in the AD brain likely reflect lower glucose utilization. Our findings reveal pronounced metabolic abnormalities in the AD brain and strongly suggest that brain glucose merits further investigation as a candidate AD biomarker.

http://ift.tt/2C5l1VA

ESMO 2017—my personal highlights

Summary

This article is not intended to be a comprehensive review of all highlights presented at the recent ESMO Annual Meeting, but rather a summary from a personal point of view in three very different fields of oncology. Breast cancer and lung cancer are traditionally in the focus of interest, and again, relevant new data were presented. The third part of this overview is focused on novel treatment strategies in malignant lymphoma, a field that is also quickly evolving and traditionally underrepresented at meetings dealing with solid cancers.

http://ift.tt/2C8Q030

Anti-angiogenic therapies in brain metastases

Summary

Brain metastases are a major challenge in modern oncology, as treatment options upon the diagnosis of symptomatic brain metastases are limited. Neo-angiogenesis was identified as a hallmark of brain metastasis development and inhibition using anti-angiogenic therapy might therefore be an experimental promising preventive as well as therapeutic approach. The current review will summarize the current available data on the efficacy of neo-angiogenic therapies in patients with brain metastases.

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Functional Gastrointestinal Disorders: All Roads Lead to Prevention

In this issue of Clinical Gastroenterology and Hepatology, Scarpato et al1 from the Mediterranean-European Area Project describe the findings of the largest epidemiologic study of functional gastrointestinal disorders (FGIDs) in children. In this school-based, cross-sectional study of 13,750 children, more than 1 in 5 children who were 4–10 years of age and 1 in 4 children who were 11–18 years of age met Rome III criteria for an FGID. Functional constipation was the most common FGID in both age groups, followed by a functional abdominal pain disorder, irritable bowel syndrome in children and abdominal migraine in adolescents.

http://ift.tt/2o763pd

The Infection Returns: A Case of Pulmonary Sporotrichosis Relapse after Chemotherapy

Background. Pulmonary sporotrichosis is a rare disease caused by a dimorphic fungus, Sporothrix schenckii. It is rarely found in association with malignancy. We present a case of pulmonary sporotrichosis recurrence after chemotherapy. Case Presentation. A 44-year-old man, treated for pulmonary sporotrichosis in the past, presented with dysphagia and was found to have squamous cell carcinoma of the esophagus. After undergoing chemotherapy, extensive cavitary lesions were observed on thoracic computed tomography scan. A bronchoalveolar lavage revealed the presence of Sporothrix schenckii sensu lato. Despite treatment with itraconazole, he eventually required a left pneumonectomy for progressive destructive cavitary lesions involving the left lung. Conclusion. This case highlights the importance of considering past fungal infections, albeit cured, in patients initiating immunosuppressive therapy.

http://ift.tt/2EQqAIu

Analytic validity of DecisionDx-Melanoma, a gene expression profile test for determining metastatic risk in melanoma patients

The DecisionDx-Melanoma test provides prognostic information for patients with cutaneous melanoma (CM). Using formalin-fixed paraffin-embedded primary tumor tissue, the RT-PCR-based test classifies patients in...

http://ift.tt/2o7fJ3i

PD-L1 diagnostic tests: a systematic literature review of scoring algorithms and test-validation metrics

The programmed death receptor 1 (PD-1) protein is a cell-surface receptor on certain lymphocytes that, with its ligand programmed death ligand 1 (PD-L1), helps to down-regulate immune responses. Many cancer ty...

http://ift.tt/2oewCZb

Differences in the expression profiles of claudin proteins in human nasopharyngeal carcinoma compared with non-neoplastic mucosa

Several studies have suggested that claudin proteins, which are the main components of tight junction structures, are related to the regulation of cell polarity and cell differentiation.

http://ift.tt/2o6ZzGZ

Treponema pallidum Immunohistochemistry is positive in human intestinal Spirochetosis

Human intestinal spirochetosis (IS) has been recognized for decades, but whether it represents commensalism or a pathogenic process remains controversial. IS is diagnosed on routine stains with confirmation by...

http://ift.tt/2oi6VXJ

How Older Adults Experience an Emergency Department Visit: Development and Validation of Measures

This study aims to develop and validate measures of experiences of an emergency department (ED) visit suitable for use by older adults or their family members.

http://ift.tt/2o7LqJU

Aromatherapy Versus Oral Ondansetron for Antiemetic Therapy Among Adult Emergency Department Patients: A Randomized Controlled Trial

We compare aromatherapy with inhaled isopropyl alcohol versus oral ondansetron for treating nausea among emergency department (ED) patients not requiring immediate intravenous access.

http://ift.tt/2of8sxE

The Evolving Landscape of HIV Screening in the Emergency Department

SEE RELATED ARTICLES, P. ■■■.

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Is Procalcitonin Useful in the Diagnosis and Treatment of Acute Respiratory Infections in the Emergency Department?

A total of 32 randomized controlled trials (9,909 patients) met inclusion criteria. However, individual participant data were available from only 26 trials (6,708 patients), which were used in the individual participant data meta-analysis displayed in the Table. A sensitivity aggregate analysis was performed on all 32 trials, and in this analysis, mortality was not significantly different in the procalcitonin group compared with the control group.

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Looking Ahead: The Role of Emergency Physicians in the Opioid Epidemic

SEE RELATED ARTICLES, P. ■■■.

http://ift.tt/2o7LmKa

Predictors of activity and participation across neurodegenerative conditions: a comparison of people with motor neurone disease, multiple sclerosis and Parkinson’s disease

Comparisons between neurological conditions have the potential to inform service providers by identifying particular areas of difficulty experienced by affected individuals. This study aimed to identify predic...

http://ift.tt/2C5w555

Tachycardia-Induced Cardiomyopathy As a Chronic Heart Failure Model in Swine

Here, we present a protocol to produce tachycardia-induced cardiomyopathy in swine. This model represents a potent way to study the hemodynamics of progressive chronic heart failure and the effects of applied treatment.

http://ift.tt/2C8ylZg

Construction and Evaluation of a Murine Calvarial Osteolysis Model by Exposure to CoCrMo Particles in Aseptic Loosening

This manuscript describes a murine calvarial osteolysis model by exposure to CoCrMo particles, which constitutes an ideal animal model for assessing the interactions between wear particles and various cells in aseptic loosening.

http://ift.tt/2o9wrig

Fluid therapy and outcome: a prospective observational study in 65 German intensive care units between 2010 and 2011

Outcome data on fluid therapy in critically ill patients from randomised controlled trials may be different from data obtained by observational studies under "real-life" conditions. We conducted this prospecti...

http://ift.tt/2Gnp7Gz

High expression of NPRL2 is linked to poor prognosis in patients with prostate cancer

As a tumor suppressor candidate gene, NPRL2 has anti-cancer effects against several cancers, but its potential role in prostate cancer (PCa) has not been reported. The present study aimed to explore the expression of NPRL2 in PCa and its potential clinical significance. Our results showed that expression of NPRL2 in PCa tissues was significantly higher than in non-PCa tissues (P<.001). High NPRL2 expression in PCa tissue was significantly correlated with a high Gleason grade group (P<.001), high pT stage (P<.001), and lymph node metastasis (P=.003).

http://ift.tt/2C6RgU8

Ovarian microcystic stromal tumor with undetermined potential: Case study with molecular analysis and literature review

Ovarian microcystic stromal tumor is a relatively rare tumor type. This tumor is characterized by a unique microcyst structure and essentially all tumors show benign biological behavior. Here, we report a case with a primary ovarian microcystic stromal tumor that experienced recurrence. Pathological findings showed that the original tumor, relapsed tumor in the ovary, and the recurrent tumor in the iliac fossa presented similar histological features. The tumor mainly consisted of microcysts, solid cellular regions, and a fibrous stroma.

http://ift.tt/2swxD3S

An Anatomical Study of Nerves at Risk During Minimally Invasive Hallux Valgus Surgery

Minimally invasive surgical (MIS) procedures rely on anatomical references to localize structures not directly visible to the surgeon. This manuscript describes a combined method of plane-by-plane dissection and sectional anatomy of fresh-frozen specimens to locate the structures at risk during MIS procedures.

http://ift.tt/2EzApag

Quantifying X-Ray Fluorescence Data Using MAPS

Here, we demonstrate the use of the X-ray fluorescence fitting software, MAPS, created by Argonne National Laboratory for the quantification of fluorescence microscopy data. The quantified data that results is useful for understanding the elemental distribution and stoichiometric ratios within a sample of interest.

http://ift.tt/2EMDK9f

EMCrit RACC Wee – State of the Crit

what's going on with the EMCrit Project

EMCrit Project by Scott Weingart.

http://ift.tt/2FbD4rT

Evidence of reduced treatment adherence among HIV infected paediatric and adolescent populations in Nairobi at the onset of the UNAIDS Universal Test and Treat Program

We conducted a retrospective cohort study to evaluate the efficacy of the World Health Organization (WHO) "Universal Test and Treat" (UTT) policy, initiated in Kenya in September 2016. Under this policy, every...

http://ift.tt/2C8pCGu

The transcriptome response of the ruminal methanogen Methanobrevibacter ruminantium strain M1 to the inhibitor lauric acid

Lauric acid (C12) is a medium-chain fatty acid that inhibits growth and production of the greenhouse gas methane by rumen methanogens such as Methanobrevibacter ruminantium. To understand the inhibitory mechanism...

http://ift.tt/2sCCX5W

Beyond Pain: Nurses’ Assessment of Patient Suffering, Dignity, and Dying in the Intensive Care Unit

Deaths in the Intensive Care Unit (ICU) are increasingly common in the United States, yet little is known about patients' experiences at the end-of-life in the ICU.

http://ift.tt/2HmLNrI

Organisation of lymphocytic infiltrates inANCA-associated glomerulonephritis

Abstract

Aims

Renal involvement in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis contributes to significant morbidity and mortality in patients. In chronic inflammation, B cells are recruited to the inflamed tissue and organised lymphoid structures have been described in several autoimmune diseases. Aim of this study was to correlate the lymphoid organisation in renal biopsies with renal outcome in ANCA-associated glomerulonephritis (GN).

Methods and results

We investigated 112 renal biopsies from patients with newly diagnosed ANCA-associated necrotizing GN. We identified four different levels of the intrarenal organisation of lymphocytes: T cells without B cells, scattered B and T cells, clustered lymphocytic infiltrates, and nodular compartmentally arranged B and T cell aggregates. Almost half of patients showed clusters of B and T lymphocytes in their biopsies. In 15 of these biopsies, a higher degree of organisation with lymphocytic compartments was detected. Inflammatory cell organisation was associated with renal failure, but not with tubular atrophy and interstitial fibrosis. Patients with organised lymphocytic infiltrates in their biopsy had worse renal function during follow-up and were more likely to develop end stage renal disease.

Conclusions

In the present study, we show that the renal lymphocytic organisation is associated with renal outcome in ANCA-associated GN. The organisation of the lymphocytic infiltrate may be a morphologic correlate of a perpetual and exaggerated inflammation in renal ANCA disease. Classifying the lymphocytic infiltrate could help predict renal outcome, and might therefore be used for individualised adjustments in the intensity and duration of immunosuppressive therapy.

This article is protected by copyright. All rights reserved.

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The anti-malarial mefloquine inhibits NF-κB signaling and induces apoptosis in colorectal cancer cells

Abstract

The NF-κB signaling pathway is activated in many colorectal cancer (CRC) cells and in the tumor microenvironment, which plays a critical role in cancer initiation, development, and response to therapies. We found in the present study that the widely used antimalarial drug mefloquine was a NF-κB inhibitor that blocked the activation of IκBα kinase, leading to the reduction of IκBα degradation, decrease of p65 phosphorylation, and suppressed expression of NF-κB target genes in colorectal cancer cells. We also found that mefloquine induced growth arrest and apoptosis of colorectal cancer cells harboring phosphorylated p65 in culture and mice. Furthermore, expression of constitutive active IKKβ kinase significantly attenuated the cytotoxic effect of the compound. These results demonstrated that mefloquine could exert anti-tumor action through inhibiting the NF-κB signaling pathway, and indicated that the antimalaria drug might be re-purposed for anti-CRC therapy in clinic as a single agent or in combination with other anti-cancer drugs.

This article is protected by copyright. All rights reserved.

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Downregulation of reticulocalbin-1 differentially facilitates apoptosis and necroptosis in human prostate cancer cells

Abstract

Reticulocalbin 1 (RCN1), an endoplasmic reticulum (ER)-resident Ca²⁺-binding protein, is dysregulated in cancers, but its pathophysiological roles are largely unclear. Here, we demonstrate that RCN1 is overexpressed in clinical prostate cancer (PCa) samples, associated with Cyclin B, not Cyclin D1 expression, compared to that of benign tissues in a Chinese Han population. Downregulation of endogenous RCN1 significantly suppresses PCa cell viability and arrests the cell cycles of DU145 and LNCaP cells at the S and G2/M phases, respectively. RCN1 depletion causes ER stress, which is evidenced by induction of GRP78, activation of PERK, and phosphorylation of eIF2α in PCa cells. Remarkably, RCN1 loss triggers DU145 cell apoptosis in a caspase-dependent manner but mainly causes necroptosis in LNCaP cells. An animal based analysis confirms that RCN1 depletion suppresses cell proliferation and promotes cell death. Further investigations reveal that RCN1 depletion leads to elevation of PTEN and inactivation of AKT in DU145 cells. Silencing of PTEN partially restores apoptotic cells upon RCN1 loss. In LNCaP cells, predominant activation of CaMKII is important for necroptosis in response to RCN1 depletion. Thus, RCN1 may promote cell survival and serve as a useful target for cancer therapy.

This article is protected by copyright. All rights reserved.

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Lymphatic Microsurgical Preventing Healing Approach (LYMPHA) for Prevention of Breast Cancer-Related Lymphedema—a Preliminary Report

Abstract

Lymphatic microsurgical preventing healing approach (LYMPHA) for prevention of breast cancer-related lymphedema (BCRL)—a preliminary report BCRL—is a chronic debilitating condition which impairs quality of life of breast cancer survivors. The aim is to study the feasibility of preventing lymphedema by performing "Lymphatic Microsurgical Preventive Healing Approach (LYMPHA)." Patients undergoing breast cancer surgery with complete nodal dissection were taken up for the study. After the standard axillary nodal dissection, lymphatics were identified by the help of blue dye and were anastomosed with a tributary to the axillary vein. Post-operatively, patients were followed up clinically for development of lymphedema and lymphoscintigraphy was performed after treatment completion. A total of 35 patients were enrolled for the study. The average BMI was 29.5. LYMPHA was feasible in all cases. The number of lymphatics identified was 1 to 5 per axilla. Two patients developed transient lymphedema which resolved with conservative therapy and patients were able to discontinue the compression garment. Follow-up lymphoscintigraphy is performed in two patients, which showed normal lymphatic flow. LYMPHA is a feasible technique, not difficult to perform, takes a short time, is accomplished in same general anesthesia as for axillary dissection, and gives no extra scar. The early results are promising and long-term follow-up may make the procedure as a routine.

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Cancers, Vol. 10, Pages 54: Advanced EUS Guided Tissue Acquisition Methods for Pancreatic Cancer

Cancers, Vol. 10, Pages 54: Advanced EUS Guided Tissue Acquisition Methods for Pancreatic Cancer

Cancers doi: 10.3390/cancers10020054

Authors: Pujan Kandel Michael B. Wallace

Pancreas cancer is a lethal cancer as the majority patients are diagnosed at an advanced incurable stage. Despite improvements in diagnostic modalities and management strategies, including surgery and chemotherapies, the outcome of pancreas cancer remains poor. Endoscopic ultrasound (EUS) is an important imaging tool for pancreas cancer. For decades, resected pancreas cancer and other cancer specimens have been used to identify tissue biomarkers or genomics for precision therapy; however, only 20% of patients undergo surgery, and thus, this framework is not useful for unresectable pancreas cancer. With advancements in needle technologies, tumor specimens can be obtained at the time of tissue diagnosis. Tumor tissue can be used for development of personalized cancer treatment, such as performing whole exome sequencing and global genomic profiling of pancreas cancer, development of tissue biomarkers, and targeted mutational assays for precise chemotherapy treatment. In this review, we discuss the recent advances in tissue acquisition of pancreas cancer.

http://ift.tt/2GoWIjh

Using eHealth to engage and retain priority populations in the HIV treatment and care cascade in the Asia-Pacific region: a systematic review of literature

The exponential growth in the reach and development of new technologies over the past decade means that mobile technologies and social media play an increasingly important role in service delivery models to ma...

http://ift.tt/2sBewWG

Long-term outcomes of the aphakic snap-on Boston type I keratoprosthesis at the Bascom Palmer Eye Institute

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Takotsubo syndrome in a premenopausal patient

Takotsubo syndrome is a rare clinical condition, with a pathophysiology that is not fully understood. Characterised by an acute and usually reversible heart failure, the condition is often preceded by a stressful event. For the diagnosis of Takotsubo syndrome to be possible, the absence of coronary artery disease as a cause is required. We report a case of Takotsubo syndrome in a 47-year-old woman of fertile age. Electrical and echocardiographic presentations were classical in the patient. However, abnormally elevated cardiac biomarkers were registered. The patient showed signs of clinical improvement, with a follow-up angiography excluding coronary artery disease and therefore leading to a diagnosis of Takotsubo syndrome.

http://ift.tt/2EyjngW

Bladder necrosis: 'A man without a bladder

Since the use of antibiotics, bladder necrosis has become a rare condition. We report a case of bladder necrosis in a 90-year-old man following urinary retention. After insertion of a transurethral catheter (TUC), 2 L of urine was evacuated. In the following days, the TUC became intermittently blocked. Adequate bladder drainage could not be obtained despite intensive rinsing and placement of a suprapubic catheter. On surgical exploration necrosis of almost the entire bladder wall, except for the trigone, was encountered. Surgical debridement of the non-viable bladder wall without opening the abdominal cavity was conducted, and a TUC was placed in the Retzius cavity to ensure evacuation of urine. Since the patient was haemodynamically unstable, construction of a urinary diversion was waived and urinary drainage of the Retzius cavity by the TUC was accepted, resulting in adequate urinary drainage without compromising renal function.

http://ift.tt/2BzEFb4

Disabling pansclerotic morphoea of childhood

Disabling pansclerotic morphoea (DPM) of childhood is a severe and often fatal variant of deep morphoea. It usually starts in childhood and rarely seen in adults. The course of the disease is progressive with lifelong morbidity in the form of joint contractures and immobility. The causes of mortality include complications such as sepsis, gangrene and cardiopulmonary involvement. Herein, we discuss the case of a 15-year-old girl with limb deformity and finger contractures, that is, bone involvement. The diagnosis of DPM of childhood was fortuitously made after the correction of limb deformity, when the patient was seen in the dermatology department for evaluation of skin discolouration on the thighs.

http://ift.tt/2EyjiKa

When a polyp is not a polyp: incidental finding of a sigmoid schwannoma at first colonoscopic screening

Schwannomas, peripheral nerve sheath tumours arising from Schwann cells, are often associated with inherited disorders such as neurofibromatosis. Gastrointestinal schwannomas, while rare, have been reported in those without personal or family history of neurofibromatosis. Diagnoses of these lesions, however, typically follow evaluations prompted by symptomatic presentations associated with abdominal pain, rectal bleeding, change in bowel habits or positive results on faecal occult blood tests performed for colorectal cancer screening. Further, management of these predominantly benign lesions commonly incorporates surgical resection. We present the case of a sigmoid schwannoma found in an asymptomatic individual on first screening colonoscopy and treated with complete endoscopic polypectomy with anticipated surveillance colonoscopy.

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Pulmonary inflammatory myofibroblastic tumour misdiagnosed as a round pneumonia

Description

A 9-year-old male patient, previously healthy, presented with acute-onset chest pain. The pain was on the right lateral chest, 10/10 in severity and non-reproducible. The patient had 1-week history of cough that had been improving; no fever, weight loss, dyspnoea, palpitations or night sweats were reported. He had positive sick contacts. Examination was remarkable for slight decrease in breath sounds at the right lower lung field posteriorly. Initial chest radiograph showed a well-circumscribed opacity in the right lower lobe posteriorly with adjacent consolidation seen on the lateral view. The lesion appeared to be distinct from the cardiomediastinal silhouette (figure 1). Sonography was performed to characterise the nature of the lesion; however, it was difficult to visualise and only revealed mixed echotexture (figure 2). Contrast-enhanced CT scan of the thorax was then obtained. CT showed a right posterior basal segment consolidation with hypo-enhancing components...

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Late diagnosis: a case of rapidly progressive extranodal NK/T cell lymphoma, nasal type

Extranodal natural killer (NK)/T cell lymphoma, nasal type is a condition that has poor prognosis. Accurate diagnosis of lymphoma is made by pathological findings. We report a case of extranodal NK/T cell lymphoma, nasal type affecting the lung and liver and which was difficult to diagnose because of negative biopsy results from multiple sites. A 39-year-old man who had dry cough and fever for 1 month was referred to our hospital. He had pancytopenia and elevated serum levels of lactate dehydrogenase and soluble interleukin-2 receptor. Hepatosplenomegaly and multiple lung nodules were found on imaging study. Specimens of bronchoscopic lung, percutaneous liver, bone marrow and random skin biopsies were all negative. Open lung biopsy was not definitive. Unfortunately, disease progression was rapid and fatal before results of pleural fluid cytology and a second liver biopsy showed extranodal NK/T cell lymphoma, nasal type. This report focused on diagnostic planning for rapidly progressive extranodal NK/T-cell lymphoma, nasal type.

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A quintessential syndrome with a rare marvelling aetiology: Rosai-Dorfman disease presenting as Conus-Cauda syndrome

A 19-year-old woman presented with a history of severe lower backache and asymmetric proximal lower limb weakness during the past 3 months. In addition, she also suffered from lower motor neuron-type bladder and bowel symptoms. On examination, paraparesis was noted. Further, sensory examination suggested patchy asymmetric sensory loss in both lower limbs with saddle anaesthesia and areflexia. A clinical diagnosis of Conus-Cauda syndrome was made and contrast-enhanced MRI of the lumbar and sacral spine was done, which confirmed the presence of a mass lesion within the spinal canal involving the cauda equina extending up to the sacral level. She underwent partial resection of the lesion following which the neurological deficits and lower backache resolved. Histopathological evaluation and immunohistochemical analyses uncovered Rosai-Dorfman disease. There was no evidence of disease elsewhere in the body. Since the patient improved significantly following surgery and exhibited no further neurological worsening, she remains under close follow-up.

http://ift.tt/2C3CL3M

NMDAR (N-methyl-D-aspartate receptor) encephalitis in a patient with MS (multiple sclerosis): a rare and challenging case

We present a rare case of N-methyl-D-aspartate receptor (NMDAR) encephalitis in a 41-year-old Caucasian woman, who initially presented with prominent neuropsychiatric symptoms on the background of pre-existing multiple sclerosis. Here, the authors navigate the muddy water between neurology and psychiatry, describing the caveats of antibody testing with a misdiagnosed case of acute and transient psychotic episode. NMDAR encephalitis in MS is a rare condition, which can be easily confused with a new onset psychotic episode. This case report can be helpful in recognition and diagnosis of this rare condition. Making the right diagnosis is important since it can prevent an unnecessary radical treatment and long-term neuropsychiatric complications.

http://ift.tt/2BBjuFR

2017 Thank you to our reviewers

The Editor would like to publicly acknowledge the people listed below who served as reviewers on the journal during 2017. Without their efforts, the quality of the journal could not be sustained.

A-Cienfuegos, Javier

A.C, Jyothi

Aaronson, Nicole

Abba-Aji, Adam

Abbas, Ossama

Abbas, Syed Hussain

Abbey-Mensah, Geraldine

Abbott, Iain

Abd El-Latif, Amani N

Abdalla, Ahmed

Abdallah, Hassane

Abdel Hay, Sameh

Abdel Razek, Ahmed

Abdeldayem, Hussein

Abdelgadir, Ibtihal

Abdul Haium, Abdul Alim

Abduljabbar, Fahad

Abdullah, Ibrahim

Abdullah, Nurul

Abdussalam, Abdullah

Abe, Kazuo

Abe, Tomomi

Abegunde, Ayokunle

Abeygunasekara, Anuruddha

Abid, Noina

Abou Dargham, Hanadi

Abourazzak, Sana

Abreo, Kenneth

Abreo, Mohini

Abu Amna, Fatima

Abu Bakar, Mohd Zulkiflee

Abu Freha, Naim

Abu Saadeh, Feras

Abu-Arafeh, I

Abu-Zaid, Ahmed

Abuomara, Hossamaldin

Acar, Fahrettin

Aceto, P

Acheampong, Derrick

Acien, Pedro

Adachi, Masanori

Adam, D.N

Adam, Ervin

Adam, Ishag

Adams, Daniel

Adams, Derick

Adams, G. G. W

Adams, Nicholas

Adams, Phil

Adamski, Jill

Adebajo, Ade

...

http://ift.tt/2EAGB63

A child with tubulointerstitial nephritis and uveitis (TINU) syndrome

Tubulointerstitial nephritis and uveitis syndrome is an uncommon disease, probably underdiagnosed in clinical practice. Its aetiology and pathogenesis remain unknown. This syndrome is defined by an association of uveitis and tubulointerstitial nephritis, with no evidence of systemic disease or infection that might cause both ocular and renal inflammation. Renal and ocular manifestations may not occur simultaneously, making the diagnosis even more challenging. Treatment includes topical and oral corticosteroids. Renal involvement usually resolves spontaneously with full recovery of kidney function, however uveitis can persist or recur years after its initial presentation. We report a case of a 13-year-old girl with tubulointerstitial nephritis and uveitis syndrome.

http://ift.tt/2BBjupl

Early discontinuation of empirical antibacterial therapy in febrile neutropenia: the ANTIBIOSTOP study

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http://ift.tt/2EzhufX

PD1 protein expression in tumor infiltrated lymphocytes rather than PDL1 in tumor cells predicts survival in triple-negative breast cancer

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http://ift.tt/2sFtz1y

Body mass index in HER2-negative metastatic breast cancer treated with first-line paclitaxel and bevacizumab

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http://ift.tt/2EMIonB

Expression analysis of liver-specific circulating microRNAs in HCV-induced hepatocellular Carcinoma in Egyptian patients

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http://ift.tt/2sC44hp

Experiences of Australian men diagnosed with advanced prostate cancer: a qualitative study

Objective

To explore men's lived experience of advanced prostate cancer (PCa) and preferences for support.

Design

Cross-sectional qualitative study applying open-ended surveys and interviews conducted between June and November 2016. Interviews audio-recorded and transcribed verbatim and analysed from an interpretive phenomenological perspective.

Setting

Australia, nation-wide.

Participants

39 men diagnosed with advanced PCa (metastatic or castration-resistant biochemical regression) were surveyed with 28 men subsequently completing a semistructured in depth telephone interview.

Results

Thematic analysis of interviews identified two organising themes: lived experience and supportive care. Lived experience included six superordinate themes: regret about late diagnosis and treatment decisions, being discounted in the health system, fear/uncertainty about the future, acceptance of their situation, masculinity and treatment effects. Supportive care included five superordinate themes: communication, care coordination, accessible care, shared experience/peer support and involvement of their partner/family.

Conclusions

Life course and the health and social context of PCa influence men's experiences of advanced disease. Multimodal interventions integrating peer support and specialist nurses are needed that more closely articulate with men's expressed needs.

http://ift.tt/2EM53Ax

Evaluation of learning from Practical Obstetric Multi-Professional Training and its impact on patient outcomes in Australia using Kirkpatricks framework: a mixed methods study

Objectives

The aim of this study was to evaluate the implementation of the Practical Obstetric Multi-Professional Training (PROMPT) simulation using the Kirkpatrick's framework. We explored participants' acquisition of knowledge and skills, its impact on clinical outcomes and organisational change to integrate the PROMPT programme as a credentialing tool. We also aimed to assess participants' perception of usefulness of PROMPT in their clinical practice.

Study design

Mixed methods approach with a pre-test/post-test design.

Setting

Healthcare network providing obstetric care in Victoria, Australia.

Participants

Medical and midwifery staff attending PROMPT between 2013 and 2015 (n=508); clinical outcomes were evaluated in two cohorts: 2011–2012 (n=15 361 births) and 2014–2015 (n=12 388 births).

Intervention

Attendance of the PROMPT programme, a simulation programme taught in multidisciplinary teams to facilitate teaching emergency obstetric skills.

Main outcome measure

Clinical outcomes compared before and after embedding PROMPT in educational practice.

Secondary outcome measure

Assessment of knowledge gained by participants through a qualitative analysis and description of process of embedding PROMPT in educational practice.

Results

There was a change in the management of postpartum haemorrhage by early recognition and intervention. The key learning themes described by participants were being prepared with a prior understanding of procedures and equipment, communication, leadership and learning in a safe, supportive environment. Participants reported a positive learning experience and increase in confidence in managing emergency obstetric situations through the PROMPT programme, which was perceived as a realistic demonstration of the emergencies.

Conclusion

Participants reported an improvement of both clinical and non-technical skills highlighting principles of teamwork, communication, leadership and prioritisation in an emergency situation. An improvement was observed in management of postpartum haemorrhage, but no significant change was noted in clinical outcomes over a 2-year period after PROMPT. However, the skills acquired by medical and midwifery staff justify embedding PROMPT in educational programmes.

http://ift.tt/2sCp87p

The development of an online intervention (Care Assist) to support male caregivers of women with breast cancer: a protocol for a mixed methods study

Introduction

It is projected that 17 730 women will be diagnosed with breast cancer in Australia in 2017, with 3114 of these predicted to be fatal. Caregiving for a person with cancer can significantly impact caregivers' physical and mental health. Many caregivers feel ill-prepared for this role, especially when care involves complex medical needs accompanied by the psychological challenges experienced following a cancer diagnosis.

Methods and analysis

This study employs a convergent, parallel, mixed methods design combining an online survey with an optional interview. Eligible, consenting participants will be invited to participate in a survey to examine (1) participants' unmet needs, (2) challenges experienced throughout the cancer journey, (3) perceived self-efficacy to determine participants' level of confidence in undertaking caregiver tasks, (4) views regarding suitable content to include in a caregiver training intervention, (5) preferred method of intervention delivery (ie, website, smartphone application and/or interactive video), and (6) preferences for the timing of delivery of the intervention content (ie, ability to choose a module, access to the entire content or have a set order in which they receive the information). Caregivers will be eligible to participate if they (1) are male, (2) have previously cared for or are currently caring for a woman with breast cancer, (3) are aged over 18 years, and (4) do not currently suffer from a cognitive impairment or mental health condition (ie, depression, anxiety). Data analysis will include examination of differences in psychological outcomes and needs based on demographic variables, and mediation analysis to explore whether self-efficacy mediates the relationship between challenges, unmet needs and distress. Qualitative data will be analysed using thematic analysis.

Ethics and dissemination

The study was reviewed and approved by two human research ethics committees within Australia. We anticipate two to three publications may be developed from the study.

http://ift.tt/2C4vgcK

Theory of change for the delivery of talking therapies by lay workers to survivors of humanitarian crises in low-income and middle-income countries: protocol of a systematic review

Introduction

There is a severe shortage of specialist mental healthcare providers in low-income and middle-income countries (LMICs) affected by humanitarian crises. In these settings, talking therapies may be delivered by non-specialists, including lay workers with no tertiary education or formal certification in mental health. This systematic review will synthesise the literature on the implementation and effectiveness of talking therapies delivered by lay workers in LMICs affected by humanitarian crises, in order to develop a Theory of Change (ToC).

Methods and analysis

Qualitative, quantitative and mixed-methods studies assessing the implementation or effectiveness of lay-delivered talking therapies for common mental disorders provided to adult survivors of humanitarian crises in LMICs will be eligible for inclusion. Studies set in high-income countries will be excluded. No restrictions will be applied to language or year of publication. Unpublished studies will be excluded. Seven electronic databases will be searched: MEDLINE, Embase, PsycINFO, PsycEXTRA, Global Health, Cochrane Library and ClinicalTrials.gov. Contents pages of three peer-reviewed journals will be hand-searched. Sources of grey literature will include resource directories of two online mental health networks (MHPSS.net and MHInnovation.net) and expert consultation. Forward and backward citation searches of included studies will be performed. Two reviewers will independently screen studies for inclusion, extract data and assess study quality. A narrative synthesis will be conducted, following established guidelines. A ToC map will be amended iteratively to take into account the review results and guide the synthesis.

Ethics and dissemination

Findings will be presented in a manuscript for publication in a peer-reviewed journal and disseminated through a coordinated communications strategy targeting knowledge generators, enablers and users.

PROSPERO registration number

CRD42017058287.

http://ift.tt/2sDWByi

Comparison and validation of screening tools for substance use in pregnancy: a cross-sectional study conducted in Maryland prenatal clinics

Introduction

Prescription-drug use in the USA has increased by more than 60% in the last three decades. Prevalence of prescription-drug use among pregnant women is currently estimated around 50%. Prevalence of illicit drug use in the USA is 14.6% among pregnant adolescents, 8.6% among pregnant young adults and 3.2% among pregnant adults. The first step in identifying problematic drug use during pregnancy is screening; however, no specific substance-use screener has been universally recommended for use with pregnant women to identify illicit or prescription-drug use. This study compares and validates three existing substance-use screeners for pregnancy—4 P's Plus, National Institute on Drug Abuse (NIDA) Quick Screen/Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST) and the Substance Use Risk Profile-Pregnancy (SURP-P) scale.

Methods and analysis

This is a cross-sectional study designed to evaluate the sensitivity, specificity and usability of existing substance-use screeners. Recruitment occurs at two obstetrics clinics in Baltimore, Maryland, USA. We are recruiting 500 participants to complete a demographic questionnaire, NIDA Quick Screen/ASSIST, 4 P's Plus and SURP-P (ordered randomly) during their regularly scheduled prenatal appointment, then again 1 week later by telephone. Participants consent to multidrug urine testing, hair drug testing and allowing access to prescription drug and birth outcome data from electronic medical records. For each screener, reliability and validity will be assessed. Test–retest reliability analysis will be conducted by examining the results of repeated screener administrations within 1 week of original screener administrations for consistency via correlation analysis. Furthermore, we will assess if there are differences in the validity of each screener by age, race and trimester.

Ethics and dissemination

This study is approved by the Institutional Review Board of the University of Maryland (HP-00072042), Baltimore, and Battelle Memorial Institute (0619–100106433). All participants are required to give their informed consent prior to any study procedure.

http://ift.tt/2C5jM8L

Surgical efficiency in femtosecond laser cataract surgery compared with phacoemulsification cataract surgery: a case-control study

Objectives

To investigate differences in surgical time, the distance the surgical instrument travelled and number of movements required to complete manual phacoemulsification cataract surgery versus femtosecond laser cataract surgery.

Design

Non-randomised comparative case series.

Setting

Single surgery site, Moorfields Eye Hospital, UK.

Participants

40 cataract surgeries of 40 patients.

Interventions

Laser-assisted and manual phacoemulsification cataract surgery. Laser-assisted surgery cases were performed using the AMO Catalys platform.

Primary and secondary outcome measures

Computer vision tracking software PhacoTracking were applied to the recordings to establish the distance the instrument travelled, total number of movements (the number of times an instrument stops and starts moving) and time taken for surgery steps including phacoemulsification, irrigation–aspiration (IA) and overall surgery time. The time taken for laser docking and delivery was not included in the analyses.

Results

Data on 19 laser-assisted and 19 manual phacoemulsification surgeries were analysed (two cases were excluded due to insufficient video-recording quality). There were no differences in the number of instrument moves, the distance the instrument travelled or time taken to complete the phacoemulsification stage. However for IA, the number of instrument moves (manual: mean 20 (SD 15) vs laser: mean 38 (SD 22), P=0.008) and time taken (manual: mean 75 s (SD 24) vs laser: mean 108 s (SD 36), P=0.003) were significantly greater for laser cases. For laser versus manual cases overall, there was no difference in number of moves or the distance the instrument travelled, but laser cases took longer (mean 88 s, P=0.049).

Conclusions

Laser cataract surgery cases took longer to complete without accounting for the time taken to complete the laser procedure itself. This appears to be in part due to IA requiring more instrument manoeuvres and taking longer to complete. Data from a large randomised series would better elucidate this relationship.

http://ift.tt/2sAwJU7

Pulmonary metastasis in rectal cancer: a retrospective study of clinicopathological characteristics of 404 patients in Chinese cohort

Objectives

This study aim to investigate the incidence, timing and risk factors of metachronous pulmonary recurrence after curative resection in patients with rectal cancer.

Design

A retrospective cohort study.

Setting

This study was conducted at a tertiary referral cancer hospital.

Participants

A total of 404 patients with rectal cancer who underwent curative resection from 2007 to 2012 at Beijing Hospital were enrolled in this study.

Interventions

The pattern of recurrence was observed and evaluated.

Primary and secondary outcome measures

The incidence and timing of recurrences by site were calculated, and the risk factors of pulmonary recurrence were analysed.

Results

The 5-year disease-free survival for the entire cohort was 77.0%. The most common site of recurrence was the lungs, with an incidence of 11.4%, followed by liver. Median interval from rectal surgery to diagnosis of pulmonary recurrence was much longer than that of hepatic recurrence (20 months vs 10 months, P=0.022). Tumour location, pathological tumor-node-metastasis (TNM) stage and positive circumferential resection margin were identified as independent risk factors for pulmonary recurrence. A predictive model based on the number of risk factors identified on multivariate analysis was developed, 5-year pulmonary recurrence-free survival for patients with 0, 1, 2 and 3 risk factors was 100%, 90.4%, 77.3% and 70.0%, respectively (P<0.001).

Conclusions

This study emphasised that the lung was the most common site of metachronous metastasis in patients with rectal cancer who underwent curative surgery. For patients with unfavourable risk profiles, a more intensive surveillance programme that could lead to the early detection of recurrence is strongly needed.

http://ift.tt/2EJtAGD

Community-deliverable exercise and anxiety in adults with arthritis and other rheumatic diseases: a systematic review with meta-analysis of randomised controlled trials

Background/purpose

Given conflicting findings, the purpose of this study was to use the meta-analytic approach to examine the effects of exercise (aerobic, strength training or both) on anxiety in adults with arthritis and other rheumatic diseases (AORD).

Methods

Randomised controlled exercise intervention trials ≥4weeks in adults ≥18 years of age with osteoarthritis, rheumatoid arthritis or fibromyalgia were included. Studies were located by searching eight electronic databases, cross-referencing and expert review. Dual selection and data abstraction of studies were performed. Hedge's standardised effect size (ES) was calculated for each result and pooled using the recently developed inverse heterogeneity model. Two-tailed z-alpha values ≤0.05 and non-overlapping 95% CI were considered statistically significant. Heterogeneity was estimated using Q and I² with alpha values ≤0.10 for Q considered statistically significant. Small-study effects were examined using funnel plots and Egger's regression test. In addition, the number needed to treat (NNT), percentile improvement and meta-regression were conducted.

Results

Of the 639 citations screened, 14 studies representing 926 initially enrolled participants (539 exercise, 387 control) met the criteria for inclusion. Length of training (mean±SD) averaged 15.8±6.7 weeks, frequency 3.3±1.3 times per week and duration 28.8±14.3 min per session. Overall, statistically significant reductions in anxiety were found (exercise minus control changes ES=–0.40, 95% CI –0.65 to –0.15, tau²=0.14; Q=40.3, P=0.0004; I²=62.8%). The NNT was 6 with a percentile improvement of 15.5% and an estimated 5.3 million inactive US adults with AORD improving their anxiety if they started exercising regularly. Statistically significant small-study effects were observed (P<0.0001).

Conclusions

Exercise is associated with reductions in anxiety among adults with selected types of AORD. However, a need exists for additional, well-designed, randomised controlled trials on this topic.

PROSPERO registration number

CRD42016048728.

http://ift.tt/2sCoQNR

Positron emission tomography (PET) for prediction of glioma histology: protocol for an individual-level data meta-analysis of test performance

Introduction

Gliomas, the most commonly diagnosed primary brain tumours, are associated with varied survivals based, in part, on their histological subtype. Therefore, accurate pretreatment tumour grading is essential for patient care and clinical trial design.

Methods and analysis

We will perform an individual-level data meta-analysis of published studies to evaluate the ability of different types of positron emission tomography (PET) to differentiate high from low-grade gliomas. We will search PubMed and Scopus from inception through 30 July 2017 with no language restriction and full-text evaluation of potentially relevant articles. We will choose studies that assess PET using 18-Fludeoxyglucose (18F-FDG), l-[Methyl-()11C]Methionine (11C-MET), 18F-Fluoro-Ethyl-Tyrosine (18F-FET) or (18)F-Fluorothymidine (18F-FLT)for grading, verified with histological confirmation. We will include both prospective and retrospective studies. Bias will be assessed by two reviewers with the Quality Assessment of Diagnostic Accuracy Studies-2 tool and as per method described by Deeks et al.

Ethics and dissemination

Ethics approval was not applicable, as this is a meta-analytic study. Results of the analysis will be submitted for publication in a peer-reviewed journal.

PROSPERO registration number

CRD42017078649.

http://ift.tt/2C24Lo8

Visual-motor integration and fine motor skills at 61/2 years of age and associations with neonatal brain volumes in children born extremely preterm in Sweden: a population-based cohort study

Objectives

This exploratory study aimed to investigate associations between neonatal brain volumes and visual–motor integration (VMI) and fine motor skills in children born extremely preterm (EPT) when they reached 61/2 years of age.

Setting

Prospective population-based cohort study in Stockholm, Sweden, during 3 years.

Participants

All children born before gestational age, 27 weeks, during 2004–2007 in Stockholm, without major morbidities and impairments, and who underwent MRI at term-equivalent age.

Main outcome measures

Brain volumes were calculated using morphometric analyses in regions known to be involved in VMI and fine motor functions. VMI was assessed with The Beery-Buktenica Developmental Test of Visual–Motor Integration—sixth edition and fine motor skills were assessed with the manual dexterity subtest from the Movement Assessment Battery for Children—second edition, at 61/2 years. Associations between the brain volumes and VMI and fine motor skills were evaluated using partial correlation, adjusted for total cerebral parenchyma and sex.

Results

Out of 107 children born at gestational age <27 weeks, 83 were assessed at 61/2 years and 66/83 were without major brain lesions or cerebral palsy and included in the analyses. A representative subsample underwent morphometric analyses: automatic segmentation (n=34) and atlas-based segmentation (n=26). The precentral gyrus was associated with both VMI (r=0.54, P=0.007) and fine motor skills (r=0.54, P=0.01). Associations were also seen between fine motor skills and the volume of the cerebellum (r=0.42, P=0.02), brainstem (r=0.47, P=0.008) and grey matter (r=–0.38, P=0.04).

Conclusions

Neonatal brain volumes in areas known to be involved in VMI and fine motor skills were associated with scores for these two functions when children born EPT without major brain lesions or cerebral palsy were evaluated at 61/2 years of age. Establishing clear associations between early brain volume alterations and later VMI and/or fine motor skills could make early interventions possible.

http://ift.tt/2sCbyB3

Assessing factors associated with long-term work disability after cancer in Belgium: a population-based cohort study using competing risks analysis with a 7-year follow-up

Objectives

The number of workers with cancer has dramatically increasing worldwide. One of the main priorities is to preserve their quality of life and the sustainability of social security systems. We have carried out this study to assess factors associated with the ability to work after cancer. Such insight should help with the planning of rehabilitation needs and tailored programmes.

Participants

We conducted this register-based cohort study using individual data from the Belgian Disability Insurance. Data on 15 543 socially insured Belgian people who entered into the long-term work disability between 2007 and 2011 due to cancer were used.

Primary and secondary outcome measures

We estimated the duration of work disability using Kaplan-Meier and the cause-specific cumulative incidence of ability to work stratified by age, gender, occupational class and year of entering the work disability system for 11 cancer sites using the Fine and Gray model allowing for competing risks.

Results

The overall median time of work disability was 1.59 years (95% CI 1.52 to 1.66), ranging from 0.75 to 4.98 years. By the end of follow-up, more than one-third of the disabled cancer survivors were able to work (35%). While a large proportion of the women were able to work at the end of follow-up, the men who were able to work could do so sooner. Being women, white collar, young and having haematological, male genital or breast cancers were factors with the bestlikelihood to be able to return to work.

Conclusion

Good prognostic factors for the ability to work were youth, woman, white collar and having breast, male genital or haematological cancers. Reviewing our results together with the cancer incidence predictions up to 2025 offers a high value for social security and rehabilitation planning and for ascertaining patients' perspectives.

http://ift.tt/2EJtoqT

Transmission of ESBL-producing Enterobacteriaceae and their mobile genetic elements--identification of sources by whole genome sequencing: study protocol for an observational study in Switzerland

Introduction

Extended-spectrum beta-lactamases (ESBL)-producing Enterobacteriaceae were first described in relation with hospital-acquired infections. In the 2000s, the epidemiology of ESBL-producing organisms changed as especially ESBL-producing Escherichia coli was increasingly described as an important cause of community-acquired infections, supporting the hypothesis that in more recent years ESBL-producing Enterobacteriaceae have probably been imported into hospitals rather than vice versa. Transmission of ESBL-producing Enterobacteriaceae is complicated by ESBL genes being encoded on self-transmissible plasmids, which can be exchanged among the same and different bacterial species. The aim of this research project is to quantify hospital-wide transmission of ESBL-producing Enterobacteriaceae on both the level of bacterial species and the mobile genetic elements and to determine if hospital-acquired infections caused by ESBL producers are related to strains and mobile genetic elements predominantly circulating in the community or in the healthcare setting. This distinction is critical in prevention since the former emphasises the urgent need to establish or reinforce antibiotic stewardship programmes, and the latter would call for more rigorous infection control.

Methods and analysis

This protocol presents an observational study that will be performed at the University Hospital Basel and in the city of Basel, Switzerland. ESBL-producing Enterobacteriaceae will be collected from any specimens obtained by routine clinical practice or by active screening in both inpatient and outpatient settings, as well as from wastewater samples and foodstuffs, both collected monthly over a 12-month period for analyses by whole genome sequencing. Bacterial chromosomal, plasmid and ESBL-gene sequences will be compared within the cohort to determine genetic relatedness and migration between humans and their environment.

Ethics and dissemination

This study has been approved by the local ethics committee (Ethikkommission Nordwest-und Zentralschweiz) as a quality control project (Project-ID 2017–00100). The results of this study will be published in peer-reviewed medical journals, communicated to participants, the general public and all relevant stakeholders.

http://ift.tt/2sDk42I

Information for Readers

http://ift.tt/2HnZAyl

Calendar

▮ Advanced Wilderness Life Support. March 1–12, 2018. Cape Town, Cape Town. Contact: Anne Bole. Email: info@awls.org. Url: www.awls.org. (20.5)

http://ift.tt/2CremAR

Man With Rash

A 58-year-old man presented with a 1-day history of an asymptomatic rash preceded by intermittent fevers, headaches, myalgias, nausea, and mild abdominal pain for the previous 2 weeks. The patient denied exposure to new medications or herbal remedies. He reported hiking in Upstate New York 2 weeks before, at which time he noted "bug bites" on his left posterior thigh.

http://ift.tt/2EB4nip

Managers Are Necessary; Leaders Are Essential

In 1943, the Allied Forces teetered on the verge of a historic military collapse in the Burmese Theater of World War II. The weapon that was devastating the British Fourteenth Army was not battleships or bombers but the tiny Anopheles mosquitoes that carried malarial parasites. For every man wounded in action, another 124 were evacuated for disease; at the peak, 84% of His Majesty's fighting force was infected. New pesticides, new malarial medications, and the best efforts of highly trained sanitation officers and front-line physicians failed to solve this seemingly intractable problem—intractable until Commander Field Marshall William Slim realized that it was not a medical problem, but a leadership problem.

http://ift.tt/2Cs9ACS

Bougie Use and First-Pass Intubation Success in the Emergency Department

With great interest, we read the recent article by Driver et al1 assessing the association of bougie use with first-pass intubation success in the emergency department. They showed that bougie use was associated with increased first-pass intubation success, but with prolonged median first-attempt duration. In addition to the limitations described in the "Discussion" section of their article, we noted other issues in this study that were not well addressed.

http://ift.tt/2Hr0LNG

Classified

FLORIDA, Port Charlotte: Stable, 22 year old, progressive independent group seeking residency trained, board certified EM physicians for expansion to second facility. 27k and 22k volume EDs. Full specialty backup. Excellent compensation based on productivity with full time income potential exceeding 350k. Flexible scheduling. Documentation by EMR. Malpractice, Health Insurance, Dental provided. Located on Charlotte Harbor with saltwater access to the Gulf. Short drive to Tampa, Sarasota, Fort Myers, Naples.

http://ift.tt/2CsQyfD