Miracle-dz/UniFAR-FTUs huggingface dataset:
Posttraumatic Mucormycosis

AbstractData on clinical, mycologic characteristics, and outcome of posttraumatic mucormycosis are scarce and often limited to case reports. From the French nationwide “RetroZygo” study, we compared posttraumatic mucormycosis cases with other forms of mucormycosis. We also reviewed reports of posttraumatic mucormycosis in the English-language literature from 1993 to 2013. We included all proven or probable cases for which underlying condition, route of infection, surgical and antifungal treatments, and outcome were detailed. From our cohort, posttraumatic mucormycosis (n = 16) differed significantly from other forms (n = 85) by rarity of underlying disease (31.2% vs 81%, p < 0.0001), frequency of cutaneous localization (87% vs 7%, p < 0.0001), short time before diagnosis (4.5 vs 21 d, p = 0.0002), species involved (Apophysomyces elegans complex and Saksenaea vasiformis), surgical requirement (93.7% vs 47%, p = 0.0006) and better survival (87.5% vs 47.6% at day 90, p = 0.03). We studied 122 cases of posttraumatic mucormycosis through our literature review. Most frequently reported traumas were traffic (37%), domestic accidents (15.1%), or natural disasters (13.4%). Mucormycosis occurred after extensive soft-tissue damage in 47.5% cases, with symptoms occurring a median of 9.5 days after trauma with necrosis being reported in 76.2% cases. Dissemination was found in 9% of patients, and bacterial coinfection in 41%. Nineteen percent of cases occurred in the Middle East or in India where Apophysomyces elegans complex was the predominant species recovered. Awareness of mucormycosis as a cause of posttrauma soft-tissue infection is warranted, especially in cases of soil-contaminated wounds. Survival is higher than in other forms of mucormycosis, but morbidity remains high.
The effect of allogeneic in vitro stimulation and in vivo immunization on memory CD4+ T‐cell APOBEC3G expression and HIV‐1 infectivity

Allogeneic immunity is one of the most potent natural immune responses. APOBEC3G (A3G) is an intracellular anti‐viral factor that deaminates cytidine to uridine. Allogeneic stimulation of human CD4+ T cells in vitro upregulated A3G mRNA and a significant correlation was found between the mixed leukocyte reaction and A3G mRNA. The mechanism of upregulation of A3G mRNA involves interaction between HLA on DC and TCR of CD4+ T cells, which is ZAP70 and downstream ERK phosphokinase signalling dependent and induces CD40L and A3G mRNA expression in CD4+ T cells. Alloimmune‐induced A3G was found to be significantly increased in CD45RA−, CCR5+ and CD45RA−CCR7− subsets of effector memory T cells. In vivo studies of women alloimmunized with their partners' PBMC also showed a significant increase in A3G protein in CD4+ T cells, CD45RO+ memory and CCR7− effector memory T cells. The functional effect of allostimulation upregulating A3G mRNA was demonstrated by a significant decrease in in vitro infectivity, using GFP‐labelled pseudovirus and confirmed by a decrease in HIV‐1 (BaL) infection of primary CD4+ T cells. The results suggest that alloimmunization offers an alternative or complementary strategy in inducing an innate anti‐viral factor that inhibits HIV‐1 infection.
Nonalcoholic Fatty Liver Disease

AbstractNonalcoholic fatty liver disease (NAFLD) is known to be associated with an increased risk of colorectal cancer (CRC). However, the relationship between NAFLD and the prognosis of CRC remains unclear. The primary objective of this study was to evaluate the overall survival (OS) and disease-free survival (DFS) rates in patients with CRC and the secondary objective was to compare clinicopathologic variables which were stratified by NAFLD.We performed a large cohort study of 1314 patients who were first diagnosed with CRC between January 2006 and April 2011. Postoperative follow-up data were collected from out-patient medical records, telephone consultations, and social security death indices. The Kaplan–Meier method was used to calculate the cumulative survival rate. Clinicopathologic variables were analyzed by univariate analysis and multivariate analysis through a Cox proportional hazard regression model.The mean follow-up time was 52.7 ± 25.3 months. Upon baseline comparison, the NAFLD group had significantly higher values of body mass index, triglycerides, and uric acid and significantly lower values of high-density lipoprotein, compared with the non-NAFLD group (P < 0.05 for all). There were no significant differences between the 2 groups with regard to tumor location, TNM staging, tumor differentiation, carcinoembryonic antigen, and vascular invasion. The cumulative 1-, 3-, and 5-year OS rates were 96.1%, 85.2%, and 80.6%, respectively, in the NAFLD group, which were statistically significantly higher than the OS rates of 91.6%, 76.2%, and 67.8%, respectively, in the non-NAFLD group (P = 0.075, P = 0.002, P = 0.030, respectively). There was no difference in DFS rates between the CRC patients with and without NAFLD (P = 0.267). Multivariate analysis showed that the presence of NAFLD was an independent negative risk factor for OS after adjusting for clinicopathologic covariates (hazard ratio = 0.593; 95% confidence interval 0.442, 0.921; P = 0.020), but not for DFS (P = 0.270). NAFLD may play a protective role in OS for CRC patients. Further studies are needed to elucidate the molecular mechanisms of putative protective effects in CRC patients with NAFLD.
Diagnosis and Management of Fecal Incontinence

Fecal incontinence is defined as either the involuntary passage or the inability to control the discharge of fecal matter through the anus. Clinically there are three subtypes (a) passive incontinence—the involuntary discharge of stool or gas without awareness; (b) urge incontinence—the discharge of fecal matter in spite of active attempts to retain bowel contents, and (c) fecal seepage—the leakage of stool following otherwise normal evacuation. The severity of incontinence can range from the unintentional elimination of flatus to the seepage of liquid fecal matter or sometimes the complete evacuation of bowel contents. Not surprisingly, these events cause considerable embarrassment, which in turn can lead to a loss of self-esteem, social isolation, and a diminished quality of life (1).
The Management of Complicated Diverticulitis and the Role of Computed Tomography

PURPOSE:Acute diverticulitis is a disease with a wide clinical spectrum, ranging from a phlegmon (stage Ia), to localized abscesses (stages Ib and II), to free perforation with purulent (stage III) or feculent peritonitis (stage IV). While there is little debate about the best treatment for mild episodes and/or very severe episodes, uncertainty persists about the optimal management for intermediate stages (Ib and II). The aim of our study was therefore to define the role of computed tomography (CT) and to analyze its impact on the management of acute diverticulitis.METHODS:We retrospectively analyzed 511 patients (296 males, 215 females) admitted for acute diverticulitis between January 1994 and December 2003. Excluded were patients with stoma reversal only, “diverticulitis” mimicked by cancer, or significantly deficient patient records. Patients were analyzed either as a whole or subgrouped according to age (<40 yr, >40 yr). A modified Hinchey classification was used to stage the severity of acute diverticulitis.RESULTS:In 99 patients (19.4%), an abscess was found (74 pericolic, 25 pelvic, median diameter: 4.0 cm). CT-guided drainage was performed in 16 patients, one failure requiring a two-stage operation. Whereas conservative treatment failed in 6.8% in patients without abscess or perforation, 22.2% of patients with an abscess required an urgent resection (68.2%, one-stage, 31.8%, two-stage). Recurrence rates were 13% for mild cases, as compared to 41.2% in patients with a pelvic abscess (stage II) treated conservatively with/without CT-guided drainage. Of all surgical cases, resection/primary anastomosis was achieved in 73.6% with perioperative mortality of 1.1% and leak rate was 2.1%. CONCLUSIONS:CT evidence of a diverticular abscess has a prognostic impact as it correlates with a high risk of failure from nonoperative management regardless of the patient's age. After treatment of diverticulitis with CT evidence of an abscess, physicians should strongly consider elective surgery in order to prevent recurrent diverticulitis.
Implementing a hospital based injury surveillance system in Africa: lessons learned

A multinational injury surveillance pilot project was carried out in five African countries in the first half of 2007 (Democratic Republic of the Congo, Kenya, Nigeria, Uganda and Zambia). Hospitals were selected in each country and a uniform methodology was applied in all sites, including an injury surveillance questionnaire designed by a joint programme of the Pan American Health Organization and the United States Centres for Disease Control and Prevention. A total of 4207 injury cases were registered in all hospitals. More than half of all injury cases were due to road traffic accidents (58.3%) and 40% were due to interpersonal violence. Self-inflicted injuries were minimal (1.2% of all cases). This report provides an assessment of the implementation of the project and a preliminary comparison between the five African countries on the context in which inter-personal injury cases occurred. Strengths and weaknesses of the project as well as opportunities and threats identified by medical personnel are summarized and discussed. A call is made to transform this pilot project into a sustainable public health strategy.
Transforming growth factor‐β1, Th1 responses, and autoimmune liver disease

Transforming growth factor‐β1 (TGF‐β1) is released during the storage of blood components, particularly platelet concentrates, and transfusion recipients are exposed to high levels of TGF‐β1. Because TGF‐β1 is one of the most potent immunosuppressive cytokines known, understanding the immunobiologic functions of TGF‐β1 may be relevant for understanding the immunobiologic effects of transfusion. Our laboratory studies the biologic effects of TGF‐β1 in the immune system. Mice deficient in TGF‐β1 spontaneously develop autoimmunity, confirming the important role of this cytokinean an immune regulator. A few years ago, my laboratory made the observation that genetic background strongly affects the phenotype of TGF‐β1–/– mice. TGF‐β1–/– mice on the BALB/c background rapidly develop an aggressive T‐cell–mediated hepatitis, whereas TGF‐β1–/– mice on the 129/CF‐1 background do not. In this review, I summarize findings published or in press from our laboratory on disease pathogenesis in TGF‐β1–/– mice and then discuss some of the exciting (as‐yet‐unpublished) directions our laboratory is currently taking.
The Diagnostic Value of Endoscopic Terminal Ileum Biopsies

OBJECTIVES:Biopsy of the terminal ileum (TI) is commonly performed during colonoscopy. The primary utility of this is to diagnose or rule out Crohn's disease in patients with symptoms and/or radiographic findings suggesting this diagnosis. We see many such biopsies in our gastrointestinal pathology service and have been impressed by the subjectively low yield of TI biopsies. Therefore, we studied this to obtain objective data.METHODS:We retrospectively reviewed 414 consecutive patients with terminal ileal biopsies. Histologic parameters evaluated were primarily those changes diagnostic of chronic inflammation or its sequelae. Histologic findings were then compared with the indication(s) and endoscopic findings.RESULTS:The TI was histologically normal in 82% and endoscopically normal in 81% with most endoscopic abnormals having “ileitis” (13%). Known or strongly suspected inflammatory bowel disease was the most common indication (38%) with Crohn's disease accounting for 20% and ulcerative colitis 16% followed by diarrhea (33%), anemia/hematochezia (15%), abdominal pain (6%), and abnormal imaging (5%). Diagnostic yield varied, with indication and endoscopic findings being highest with known suspected Crohn's disease (40%), abnormal imaging (32%), and with endoscopic “ileitis” (84%) or ulcers/erosions (69%). CONCLUSIONS:Diagnostic yield of TI biopsy varied with indication and endoscopic findings. Our study indicates that biopsy is of greatest value in patients undergoing endoscopy for known or strongly suspected Crohn's disease, or with an abnormal imaging study of the TI. Biopsy of endoscopically normal mucosa is unlikely to yield diagnostically useful information, and is not encouraged as routine. However, when “ileitis,” ulcers, or erosions are identified, biopsies can be very helpful.
The MyD88 protein 88 pathway is differently involved in immune responses induced by distinct substrains of Leishmania major

Host resistance to Leishmania major is highly dependent on the development of a Th1 immune response. The TLR adaptator myeloid differentiation protein 88 (MyD88) has been implicated in the Th1 immune response associated with the resistant phenotype observed in C57BL/6 mice after infection with L. major. To investigate whether the MyD88 pathway is differentially used by distinct substrains of parasites, MyD88−/− C57BL/6 mice were infected with two substrains of L. major, namely L. major LV39 and L. major IR75. MyD88−/− mice were susceptible to both substrains of L. major, although with different kinetics of infection. The mechanisms involved during the immune response associated with susceptibility of MyD88−/− mice to L. major is however, parasite substrain‐dependent. Susceptibility of MyD88−/− mice infected with L. major IR75 is a consequence of Th2 immune‐deviation, whereas susceptibility of MyD88−/− mice to infection with L. major LV39 resulted from an impaired Th1 response. Depletion of regulatory T cells (Treg) partially restored IFN‐γ secretion and the Th1 immune response in MyD88−/− mice infected with L. major LV39, demonstrating a role of Treg activity in the development of an impaired Th1 response in these mice.
Tolerability and clinical safety of Implanon®

Objectives To evaluate the tolerability and clinical safety of the subdermal, long-acting hormonal contraceptive Implanon®. Methods This integrated safety analysis included 11 international studies concerning Implanon® (68 mg etonogestrel) of which 10 had a duration of at least two years. Assessments included reports of adverse events (AEs), reasons and rates of discontinuation, insertion/removal complications, and the condition of the implant site. Metabolic and coagulation parameters are briefly discussed to fully describe the clinical safety profile. Results In total 942 women were exposed to Implanon® for 24,679 cycles over the course of one to five years. The overall discontinuation rate was 32.7%; the most frequently reported reasons for discontinuation were adverse events (13.9%), bleeding irregularities (10.4%), and planning pregnancy (4.1%). The most commonly reported drug-related AE was headache (15.3%); however, headache was reported in only 1.6% of women as a reason for discontinuation. Insertion and removal times for Implanon® were short with few complications, none of which were major. From earlier studies it is known that treatment with Implanon® has little effect on metabolic and coagulation parameters. Conclusions Implanon® is a well-tolerated and safe method of long-acting hormonal contraception for women.
Human mucosal leishmaniasis: Neutrophils infiltrate areas of tissue damage that express high levels of Th17‐related cytokines

Mucosal leishmaniasis (ML) is characterised by severe tissue destruction. Herein, we evaluated the involvement of the IL‐17‐type response in the inflammatory infiltrate of biopsy specimens from 17 ML patients. IL‐17 and IL‐17‐inducing cytokines (IL‐1β, IL‐23, IL‐6 and TGF‐β) were detected by immunohistochemistry in ML patients. IL‐17+ cells exhibited CD4+, CD8+ or CD14+ phenotypes, and numerous IL‐17+ cells co‐expressed the CC chemokine receptor 6 (CCR6). Neutrophils, a hallmark of Th17‐mediated inflammation, were regularly detected in necrotic and perinecrotic areas and stained positive for neutrophil elastase, myeloperoxidase and MMP‐9. Taken together, these observations demonstrate the existence of Th17 cells in ML lesions associated with neutrophils in areas of tissue injury and suggest that IL‐17 is involved in ML pathogenesis.
Altered Functional Connectivity in Essential Tremor

AbstractEssential tremor (ET) has been associated with a spectrum of clinical features, with both motor and nonmotor elements, including cognitive deficits. We employed resting-state functional magnetic resonance imaging (fMRI) to assess whether brain networks that might be involved in the pathogenesis of nonmotor manifestations associated with ET are altered, and the relationship between abnormal connectivity and ET severity and neuropsychological function.Resting-state fMRI data in 23 ET patients (12 women and 11 men) and 22 healthy controls (HC) (12 women and 10 men) were analyzed using independent component analysis, in combination with a “dual-regression” technique, to identify the group differences of resting-state networks (RSNs) (default mode network [DMN] and executive, frontoparietal, sensorimotor, cerebellar, auditory/language, and visual networks). All participants underwent a neuropsychological and neuroimaging session, where resting-state data were collected.Relative to HC, ET patients showed increased connectivity in RSNs involved in cognitive processes (DMN and frontoparietal networks) and decreased connectivity in the cerebellum and visual networks. Changes in network integrity were associated not only with ET severity (DMN) and ET duration (DMN and left frontoparietal network), but also with cognitive ability. Moreover, in at least 3 networks (DMN and frontoparietal networks), increased connectivity was associated with worse performance on different cognitive domains (attention, executive function, visuospatial ability, verbal memory, visual memory, and language) and depressive symptoms. Further, in the visual network, decreased connectivity was associated with worse performance on visuospatial ability.ET was associated with abnormal brain connectivity in major RSNs that might be involved in both motor and nonmotor symptoms. Our findings underscore the importance of examining RSNs in this population as a biomarker of disease.
Risk of Proximal and Distal Colorectal Cancer Following Flexible Sigmoidoscopy: A Population-Based Cohort Study

OBJECTIVES:Little is known about the risk of proximal and distal colorectal cancer (CRC) following flexible sigmoidoscopy (FS) in usual clinical practice. Our objective was to estimate the annual incidence of CRC within 7 yr following FS and to identify factors associated with incident CRC in those with a negative FS.METHODS:In this population-based retrospective cohort study, we included men and women 50–80 yr of age who had a negative or positive FS during 1996–1998 in Ontario. We followed each individual through December 31, 2005 and calculated the age- and sex-standardized incidence rates (SIRs) and 95% confidence intervals (CIs) for distal and proximal CRC. We compared the relative rate (RR) and 95% CIs of incident CRC between the negative and positive FS cohorts and the remaining Ontario population. Cox models were used to evaluate factors associated with incident cancers.RESULTS:The RR for distal CRC was significantly lower among those with a negative FS than in the Ontario population during each year of follow-up except the first year. For example, at 7 yr, the SIR for distal CRC following negative FS was 0.74 cancers/1,000 persons (95% CI 0.46–1.13) compared with 1.07/1,000 (95% CI 1.02–1.11) in the Ontario population (RR = 0.69, 95% CI 0.40–0.99). The RR for proximal CRC, except for year 2, did not differ between the negative FS cohort and the Ontario population during follow-up. In the positive FS cohort, the RR for distal CRC was significantly higher in the first year of follow-up compared with the Ontario population, but not thereafter. The results were similar for the RR for proximal CRC in the positive FS cohort. Only age was significantly associated with incident CRC following negative FS.CONCLUSIONS:Following negative FS, the incidence of distal but not proximal CRC was reduced for up to 7 yr. Following a positive FS, the incidence of distal and proximal cancer after the first year of follow-up did not differ from the Ontario population. The benefit of FS was confined to the distal colon, emphasizing the potential limitation of FS in practice.
A comparison between the risks of childhood leukaemia from parental exposure to radiation in the Sellafield workforce and those displayed among the Japanese bomb survivors

The cases of childhood leukaemia found near the Sellafield plant and those observed in the offspring of the Japanese bomb survivors are analysed using a relative risk model. The leukaemia relative risk coefficients for total paternal (whole-body) pre-conception exposure for the Sellafield children are found to be about 50 to 80 times higher than the (gonadal) coefficients applying to the offspring of the bomb survivors. This difference is statistically significant, and in particular the risk coefficients for the Sellafield cohort are significantly positive, unlike those for the Japanese. If the assumption is made that the excess relative risk estimated from the Sellafield data lasts for the whole of the life of the offspring, the apparent population leukaemia risk to the first-generation offspring (for an England and Wales population) would be between 4% Sv-1 and 5% Sv-1. On the more likely assumption that the relative risk falls off in the same way as has been observed for leukaemias in children directly exposed to radiation, the risk would then be reduced to about 0.5%-1.5% Sv-1. Such data as exist on the degree of heritability of susceptibility to cancer suggest that the risk to all generations could be about double this figure. The differences between the apparent pre-conception exposure risks in these two groups are discussed and several possible explanations for the findings near the Sellafield plant, other than pre-conception radiation exposure, are presented.
A Multicenter, Randomized, Double-Blind Trial of Everolimus Versus Azathioprine and Placebo to Maintain Steroid-Induced Remission in Patients With Moderate-to-Severe Active Crohn's Disease

OBJECTIVES:A prospective study was undertaken to compare the efficacy of everolimus versus azathioprine or placebo in maintaining steroid-induced remission in active Crohn's disease (CD) and assess the safety and pharmacokinetics of everolimus.METHODS:This was a randomized, double-blind, placebo-controlled, proof-of-concept study in adults with moderate-to-severe active CD. The patients received oral steroids for a rapid induction of remission plus everolimus 6 mg/day, azathioprine 2.5 mg/kg/day, or placebo as maintenance treatment. The main outcome measure was the treatment success, defined as a steroid-free remission by the end of month 3 and maintained until study cutoff without the use of prohibited efficacy treatments.RESULTS:Following an interim analysis, the study was terminated before enrollment was completed due to the lack of efficacy. The full intent-to-treat population comprised 138 patients. Only 96 patients who entered the study ≥7 months prior to data cutoff were included in the primary efficacy population. The treatment success was achieved in 13 of 38 everolimus patients, 22 of 36 azathioprine patients, and 8 of 22 placebo patients. Using the Kaplan–Meier estimates at month 7, the incidence of treatment success was 22.0% with everolimus group (95% confidence interval [CI] 6.7–37.3%, P = 0.610 vs placebo), 38.3% with azathioprine group (95% CI 20.6–55.9%, P = 0.500 vs placebo), and 28.8% with placebo group (95% CI 7.7–49.9%). The type and incidence of adverse events in the everolimus cohort were similar to those reported in the approved transplantation indications.CONCLUSIONS:The safety and tolerability of everolimus (6 mg/day) in patients with active CD were comparable to azathioprine. At this dose, everolimus is not more efficacious in achieving a steroid-free remission in active CD than the comparators.