Postdepletion Lymphocyte Reconstitution During Belatacept and Rapamycin Treatment in Kidney Transplant Recipients.

Belatacept is used to prevent allograft rejection but fails to do so in a sizable minority of patients due to inadequate control of costimulation-resistant T cells. In this study, we report control of costimulation-resistant rejection when belatacept was combined with perioperative alemtuzumab-mediated lymphocyte depletion and rapamycin. To assess the means by which the alemtuzumab, belatacept and rapamycin (ABR) regimen controls belatacept-resistant rejection, we studied 20 ABR-treated patients and characterized peripheral lymphocyte phenotype and functional responses to donor, third-party and viral antigens using flow cytometry, intracellular cytokine staining and carboxyfluorescein succinimidyl ester-based lymphocyte proliferation. Compared with conventional immunosuppression in 10 patients, lymphocyte depletion evoked substantial homeostatic lymphocyte activation balanced by regulatory T and B cell phenotypes. The reconstituted T cell repertoire was enriched for CD28(+) naïve cells, notably diminished in belatacept-resistant CD28(-) memory subsets and depleted of polyfunctional donor-specific T cells but able to respond to third-party and latent herpes viruses. B cell responses were similarly favorable, without alloantibody development and a reduction in memory subsets-changes not seen in conventionally treated patients. The ABR regimen uniquely altered the immune profile, producing a repertoire enriched for CD28(+) T cells, hyporesponsive to donor alloantigen and competent in its protective immune capabilities. The resulting repertoire was permissive for control of rejection with belatacept monotherapy.

Renal transplantation using belatacept without maintenance steroids or calcineurin inhibitors.

Kidney transplantation remains limited by toxicities of calcineurin inhibitors (CNIs) and steroids. Belatacept is a less toxic CNI alternative, but existing regimens rely on steroids and have higher rejection rates. Experimentally, donor bone marrow and sirolimus promote belatacept's efficacy. To investigate a belatacept-based regimen without CNIs or steroids, we transplanted recipients of live donor kidneys using alemtuzumab induction, monthly belatacept and daily sirolimus. Patients were randomized 1:1 to receive unfractionated donor bone marrow. After 1 year, patients were allowed to wean from sirolimus. Patients were followed clinically and with surveillance biopsies. Twenty patients were transplanted, all successfully. Mean creatinine (estimated GFR) was 1.10 ± 0.07 mg/dL (89 ± 3.56 mL/min) and 1.13 ± 0.07 mg/dL (and 88 ± 3.48 mL/min) at 12 and 36 months, respectively. Excellent results were achieved irrespective of bone marrow infusion. Ten patients elected oral immunosuppressant weaning, seven of whom were maintained rejection-free on monotherapy belatacept. Those failing to wean were successfully maintained on belatacept-based regimens supplemented by oral immunosuppression. Seven patients declined immunosuppressant weaning and three patients were denied weaning for associated medical conditions; all remained rejection-free. Belatacept and sirolimus effectively prevent kidney allograft rejection without CNIs or steroids when used following alemtuzumab induction. Selected, immunologically low-risk patients can be maintained solely on once monthly intravenous belatacept.

The effect on outcome of peribulbar anaesthesia in conjunction with general anesthesia for vitreoretinal surgery.

The purpose of this study was to evaluate peri-operative outcome after vitreoretinal surgery when peribulbar anaesthesia is combined with general anaesthesia. Sixty adult patients undergoing elective primary retinal detachment surgery with scleral buckling or an encircling procedure received either peribulbar anaesthesia in conjunction with general anaesthesia or general anaesthesia alone. For peribulbar anaesthesia a single percutaneous injection of 5-7 ml of local anaesthetic solution (0.75% ropivacaine with hyaluronidase 15 iu.ml(-1)) was used. The incidence of intra-operative oculocardiac reflex and surgical bleeding interfering with the surgical field, postoperative pain and analgesia requirements, and postoperative nausea and vomiting were recorded. In the block group there was a lower incidence of oculocardiac reflex and surgical bleeding intra-operatively. Patients in the block group also had better postoperative analgesia and a lower incidence of postoperative nausea and vomiting compared with the group without a block. The use of peribulbar anaesthesia in conjunction with general anesthesia was superior to general anaesthesia alone for vitreoretinal surgery with scleral buckling.

Predicting Coronavirus Disease 2019 Infection Risk and Related Risk Drivers in Nursing Homes: A Machine Learning Approach.

OBJECTIVE: Inform coronavirus disease 2019 (COVID-19) infection prevention measures by identifying and assessing risk and possible vectors of infection in nursing homes (NHs) using a machine-learning approach. DESIGN: This retrospective cohort study used a gradient boosting algorithm to evaluate risk of COVID-19 infection (ie, presence of at least 1 confirmed COVID-19 resident) in NHs. SETTING AND PARTICIPANTS: The model was trained on outcomes from 1146 NHs in Massachusetts, Georgia, and New Jersey, reporting COVID-19 case data on April 20, 2020. Risk indices generated from the model using data from May 4 were prospectively validated against outcomes reported on May 11 from 1021 NHs in California. METHODS: Model features, pertaining to facility and community characteristics, were obtained from a self-constructed dataset based on multiple public and private sources. The model was assessed via out-of-sample area under the receiver operating characteristic curve (AUC), sensitivity, and specificity in the training (via 10-fold cross-validation) and validation datasets. RESULTS: The mean AUC, sensitivity, and specificity of the model over 10-fold cross-validation were 0.729 [95% confidence interval (CI) 0.690‒0.767], 0.670 (95% CI 0.477‒0.862), and 0.611 (95% CI 0.412‒0.809), respectively. Prospective out-of-sample validation yielded similar performance measures (AUC 0.721; sensitivity 0.622; specificity 0.713). The strongest predictors of COVID-19 infection were identified as the NH's county's infection rate and the number of separate units in the NH; other predictors included the county's population density, historical Centers of Medicare and Medicaid Services cited health deficiencies, and the NH's resident density (in persons per 1000 square feet). In addition, the NH's historical percentage of non-Hispanic white residents was identified as a protective factor. CONCLUSIONS AND IMPLICATIONS: A machine-learning model can help quantify and predict NH infection risk. The identified risk factors support the early identification and management of presymptomatic and asymptomatic individuals (eg, staff) entering the NH from the surrounding community and the development of financially sustainable staff testing initiatives in preventing COVID-19 infection.

An intraventricular clear cell meningioma revealed by an inflammatory syndrome in a male adult: a case report.

Intraventricular meningiomas are infrequent intracranial tumors. Clinical symptoms are mainly due to an increased intracranial pressure or a direct pressure on the surrounding brain structures. Inflammatory syndrome was described in some patients with chordoid meningiomas. Here we report a case of right intraventricular clear cell meningioma in a 50-year-old man who presented with fever, headache, and inflammatory syndrome. Clinical and biological normalization was rapidly obtained after tumor removal. Immunohistochemical examination showed tumor cells and lymphocytes positivity for the pyrogenic cytokine interleukin-6, with a same intensity. To our knowledge, this is the first case described in the literature concerning an adult man with an intraventricular clear cell meningioma associated with a systemic inflammatory syndrome.

Outcome of living donor liver transplantation for Egyptian patients with hepatitis C (genotype 4)-related cirrhosis.

BACKGROUND: Hepatitis C virus (HCV) recurrence after living donor liver transplantation (LDLT) represents a challenging issue due to universal viral recurrence and invasion into the graft, although the incidence of histological recurrence, risk factors, and survival rates are still controversial. PATIENTS AND METHODS: Recurrence of HCV was studied in 38 of 53 adult patients who underwent LDLT. RESULTS: Recipient and graft survivals were 86.6% at the end of the follow-up which was comparable to literature reports for deceased donor liver transplantation (DDLT). Clinical HCV recurrence was observed in 10/38 patients (26.3%). Four patients developed mild fibrosis with a mean fibrosis score of 0.6 and mean grade of histological activity index (HAI) of 7.1. None of the recipients developed allograft cirrhosis during the mean follow-up period of 16 +/- 8.18 months (range, 4-35 months). Estimated and actual graft volumes were negatively correlated with the incidence and early clinical HCV recurrence. None of the other risk factors were significantly correlated with clinical HCV recurrence: gender, donor and recipient ages, pretransplantation Child-Pugh or model for end-stage liver disease (MELD) scores, pre- and postoperative viremia, immunosuppressive drugs, pulse steroid therapy, and preoperative anti-HBc status. CONCLUSIONS: Postoperative patient and graft survival rates for HCV (genotype 4)-related cirrhosis were more or less comparable to DDLT reported in the literature. Clinical HCV recurrence after LDLT in our study was low. Small graft volume was a significant risk factor for HCV recurrence. A longer follow-up and a larger number of patients are required to clarify these issues.

The effect of environmental factors on the incidence of perforated appendicitis.

BACKGROUND: Acute appendicitis is the most common abdominal emergency. Its etiopathogenesis appears to be multifactorial. Several studies suggested a relationship between the development of acute appendicitis and some environmental factors. Air pollution predisposes some people to develop perforated appendicitis. However, data are relatively scarce and the results still controversial. AIM: Determine the seasonal variation of acute appendicitis and study the association between perforated appendicitis and short-term exposure to climatic factors and to air pollutants. METHODS: A cross-sectional study was conducted including patients hospitalized in the general surgery department of Farhat Hached University Hospital in Sousse for acute appendicitis between January 1st and December 31st, 2014. Climatic conditions were collected from the National Institute of Meteorology. Data on air pollution were given by the National Agency for the Protection of the Environment and obtained by the modeling of the atmospheric pollution. For statistical analysis, we used mean concentrations of each environmental factor corresponding to the day of hospital admission and lagged by the 7 previous days. These factors were compared between the group of patients with perforated appendicitis and patients with nonperforated appendicitis. RESULTS: We collected 246 cases of acute appendicitis. Perforated appendicitis was reported in 15.2% of the cases. The incidence of acute appendicitis was higher during summer. Compared to nonperforated appendicitis, perforated appendicitis was significantly associated with the mean relative humidity of the 5 day lag (p = 0.046), rainfall of the 7 day lag (p = 0.043), and consultation delay (p <10-3). Furthermore, perforated appendicitis was significantly associated with the daily mean concentration of carbon dioxide (p = 0.042), the 2- day lag mean concentration of particulate matter less than 10 µ (PM10 ) (p = 0.016), and the 2-day lag mean concentration of ozone (p = 0.048). After multivariate statistical analysis, predictive factors for perforated appendicitis were the consultation delay (OR: 1.621, 95% CI [1.288 - 2.039]; p<10-3) and the 2 day lag mean concentration of PM10 (OR: 1.066, 95% CI [1.007- 1.130]; p = 0.029). CONCLUSION: Short-term exposure to particulate matter was associated with perforated appendicitis. Further large-scale studies are needed to support this conclusion. KEY WORDS: Air pollution, Appendicitis, perforated appendicitis, Climateparticulate matter.

Plasma met-enkephalin, beta-endorphin and leu-enkephalin levels in human hepatic encephalopathy.

To address the role of the opioid system in the pathogenesis of hepatic encephalopathy (HE) we measured plasma met-enkephalin, beta-endorphin and leu-enkephalin in patients with different grades of HE compared to control subjects and patients with cirrhosis. Plasma met-enkephalin levels were significantly higher in patients with cirrhosis and all grades of HE than controls. Plasma beta-endorphin levels were similar in the 3 groups. Plasma leu-enkephalin levels were significantly higher in HE grades II, III and IV than in controls, patients with cirrhosis and HE grade I patients. Our results support data on the involvement of met-enkephalin and leu-enkephalin in the pathogenesis of HE and provide a rationale for the use of opioid receptor antagonists in the treatment of HE.

Serum levels of astroglial S100-beta and neuron-specific enolase in hepatic encephalopathy patients.

To find a reliable, noninvasive method for the diagnosis of cognitive impairment in patients with hepatic cirrhosis we measured serum levels of astroglial S100beta and neuron-specific enolase in cirrhotic patients with and without hepatic encephalopathy (HE). S100beta levels showed a significant increase in groups with HE stage 1 and 2 compared to both control and cirrhosis patients. However serum neuron-specific enolase levels were not significantly different between the studied groups. S100beta levels had a specificity of 91.3% and sensitivity of 51.7% for detection of HE from cirrhosis. Serum S100beta may be a useful surrogate marker for the diagnosis of mild cognitive impairment in cirrhotic patients before they progress to more advanced stages of HE.

Immunohistochemical expression of CD95 (Fas), c-myc and epidermal growth factor receptor in hepatitis C virus infection, cirrhotic liver disease and hepatocellular carcinoma.

Gene product expression in normal and chronic hepatitis C virus infection was determined in an attempt to improve our understanding of the molecular events leading to the development of cirrhosis and liver carcinoma. Activation of CD95 (Fas) causes apoptosis of cells and liver failure in mice and has been associated with human liver disorders. c-myc is involved in cell proliferation and EGFR in regeneration of cells. The material of the current study included 50 cases of chronic hepatitis C (CHC) (and negative hepatitis B virus infection), 29 cases of liver cirrhosis and HCV (LC), and 19 cases of hepatocellular carcinoma and HCV (HCC) admitted to the Theodor Bilharz Research Institute (TBRI) during the years 2003-2004. Ten wedge liver biopsies - taken during laparoscopic cholecystectomy - were included in the study as normal controls. Laboratory investigations, including liver function tests, serological markers for viral hepatitis and serum alpha fetoprotein level (alpha-FP), were determined for all cases. Histopathological study and immunohistochemistry using monoclonal antibodies for CD95, c-myc and EGFR were also done. In CHC cases, the histological activity index (HAI) revealed more expression of Fas antigen in liver tissues with active inflammation than in those without active inflammation (p < 0.01). EGFR and c-myc act synergistically in liver tumorigenesis. Upregulation of Fas in chronic hepatitis C infection and of c-myc & EGFR in malignant transformation was concluded from this study. c-myc expression may obstruct the induction of apoptosis of HCC cells and lead to uncontrolled cell growth.

[Chronic fatigue syndrome: A new disorder?] / Le syndrome de fatigue chronique : une nouvelle maladie ?

More than 30 years after its individualization, chronic fatigue syndrome (CFS) remains a debilitating condition for the patient and a confusing one to the physicians, both because of diagnostic difficulties and poorly codified management. Despite the numerous work carried out, its pathophysiology remains unclear, but a multifactorial origin is suggested with triggering (infections) and maintenance (psychological) factors as well as the persistence of inflammatory (low grade inflammation, microglial activation…), immunologic (decrease of NK cells, abnormal cytokine production, reactivity to a variety of allergens, role of estrogens…) and muscular (mitochondrial dysfunction and failure of bioenergetic performance) abnormalities at the origin of multiple dysfunctions (endocrine, neuromuscular, cardiovascular, digestive…). The complexity of the problem and the sometimes contradictory results of available studies performed so far are at the origin of different pathophysiological and diagnostic concepts. Based on a rigorous analysis of scientific data, the new American concept of Systemic Disease Exertion Intolerance proposed in 2015 simplifies the diagnostic approach and breaks with the past and terminologies (CFS and myalgic encephalomyelitis). It is still too early to distinguish a new disease, but this initiative is a strong signal to intensify the recognition and management of patients with CFS and stimulate research.

[Prevention of infections in adults and adolescents with systemic lupus erythematosus: Guidelines for the clinical practice based on the literature and expert opinion]. / Prévention des infections au cours du lupus systémique chez l'adulte et l'adolescent : élaboration de recommandations pour la pratique clinique, à partir d'une analyse de la littérature et de l'avis d'experts.

PURPOSE: To develop French recommendations about the management of vaccinations, the screening of cervical cancer and the prevention of pneumocystis pneumonia in systemic lupus erythematosus (SLE). METHODS: Thirty-seven experts qualified in internal medicine, rheumatology, dermatology, nephrology and pediatrics have selected recommendations from a list of proposition based on available data from the literature. For each recommendation, the level of evidence and the level of agreement among the experts were specified. RESULTS: Inactivated vaccines do not cause significant harm in SLE patients. Experts recommend that lupus patient should receive vaccinations accordingly to the recommendations and the schedules for the general public. Pneumococcal vaccination is recommended for all SLE patients. Influenza vaccination is recommended for immunosuppressed SLE patients. Live attenuated vaccines should be avoided in immunosuppressed patients. Yet, recent works suggest that they can be considered in mildly immunosuppressed patients. Experts have recommended a cervical cytology every year for immunosuppressed patients. No consensus was obtained for the prevention of pneumocystis pneumonia. CONCLUSION: These recommendations can be expected to improve clinical practice uniformity and, in the longer term, to optimize the management of SLE patients.

Donor outcomes in right lobe adult living donor liver transplantation: single-center experience in Egypt.

INTRODUCTION AND OBJECTIVES: Living donor liver transplantation (LDLT) is an alternative source of organs for patients with end-stage liver disease (ESLD) in absence of deceased donor LT. In LDLT the greatest concern is donor safety. Our objective was to evaluate the outcome of donors after right lobe liver donation in a single LT center in Egypt. PATIENTS AND METHODS: Fifty LDL resections were performed from 2001 to 2004. The mean donor age was 29.2 +/- 6.4 years. Residual liver volume was 41.1 +/- 4.5%. Mean operative time was 560 +/- 62.2 minutes; mean ICU stay, less than 24 hours; mean hospital stay, 15.4 +/- 7.7 days; and mean follow-up period, 6 months. RESULTS: There was no mortality. The overall complication rate was 68% (34 donors). Major complications included intraoperative bleeding in one, biliary leak in two, and pneumonia in three donors. Minor complications included mild pleural effusion in 13 donors, transient ascites in 10, mild depression in 7, intra-abdominal collections in 3, and wound infections in 1 donor. Residual liver volume did not affect the complication rate. None required reoperation. Return to predonation activity occurred within 6 to 8 weeks. No liver impairment occurred during follow-up. CONCLUSION: Right lobe adult LDLT is a safe procedure with regard to donor outcome. Major complications occurred in only 10% of our series.

[Screening and management of cardiovascular risk factors in systemic lupus erythematosus: Recommendations for clinical practice based on the literature and expert opinion]. / Dépistage et prise en charge du risque cardiovasculaire au cours du lupus systémique : élaboration de recommandations pour la pratique clinique, à partir d'une analyse de la littérature et de l'avis d'experts.

PURPOSE: To develop French recommendations about screening and management of cardiovascular risk factors in systemic lupus erythematosus (SLE). METHODS: Thirty-nine experts qualified in internal medicine, rheumatology and nephrology have selected recommendations from a list developed based on evidence from the literature. For each recommendation, the level of evidence and the level of agreement among the experts were specified. RESULTS: Experts recommended an annual screening of cardiovascular risk factors in SLE. Statins should be prescribed for primary prevention in SLE patients based on the level of LDL-cholesterol and the number of cardiovascular risk factors, considering SLE as an additional risk factor. For secondary prevention, experts have agreed on an LDL-cholesterol target of <0.7 g/L. Hypertension should be managed according to the 2013 European guidelines, using renin-angiotensin system blockers as first line agents in case of renal involvement. Aspirin can be prescribed in patients with high cardiovascular risk or with antiphospholipid antibodies. CONCLUSION: These recommendations about the screening and management of cardiovascular risk factors in SLE can be expected to improve clinical practice uniformity and, in the longer term, to optimize the management of SLE patients.

Does gland histopathology correlate with mode of presentation and surgical complications in benign prostatic hyperplasia?

The histopathology specimens from 256 consecutive prostatectomies were retrospectively analysed and classified into three categories namely BPH alone, BPH and an inflammatory lesion and adenocarcinoma. Mode of presentation (acute urine retention versus prostatism) as well as short term post-operative complications, namely, haemorrhage and genitourinary infection were compared in the three histological categories to study the impact of histology on clinical presentation and complications. There were no significant differences between the three categories neither in presentation nor in complications. We conclude that prostate gland histology neither correlates with the onset of acute urine retention nor with the surgical complications studied in this report.

[A common mutation C677T in the 5,10-methyltetrahydrofolate reductase gene is associated to idiopathic deep venous thrombosis]. / La mutation C677T du gène de la 5,10-méthyltétrahydrofolate réductase est associée aux thromboses veineuses idiopathiques.

PURPOSE: Moderate hyperhomocysteinemia is a risk factor for deep venous thrombosis. The homozygous C677T methylenetetrahydrofolate reductase (MTHFR) mutation is associated with increased level of total plasma homocysteine. The association between homozygous C677T mutation and deep venous thrombosis is still controversial. METHOD: In order to evaluate this association, we studied the prevalence of C677T mutation in 168 patients with confirmed deep venous thrombosis; 31 with an idiopathic deep venous thrombosis (group A) and 137 with thromboembolic event explained by one or more clinical and/or biological risk factors (group B). RESULTS: The distribution of genotypes was different between group A and B [++/+ -/- -(n(%))] : 9(29)/10(32)/12(39) vs 16(12)/57(42)/64(46) (chi(2) : 6.03; P: 0.049). The comparison between homozygotes and the two other genotypes showed significant statistical relationship between homozygous genotype and idiopathic character of deep venous thrombosis (chi(2) : 6.01; P : 0.014; OR : 3.09 [IC 95% : 1.06-8.53]). CONCLUSION: These results suggest that homozygous C677T methylenetetrahydrofolate reductase mutation could be considered as a genetic risk factor for venous thrombosis.

Clinical features and surgical outcome of benign prostatic hyperplasia.

The clinical features and outcome of surgery for benign prostatic hyperplasia (BPH) were studied retrospectively in Asir during the period between 1987 and 1993. Two hundred and fifty-three patients were included. The mean and median ages were both 70 years. The main presentation were acute retention (54%), prostatism (39%), and chronic retention (6.8%). Thirty-five and five-tenths percent of the patients had one or more pre-existing medical problems. Two hundred and forty-eight patients underwent prostatectomy. Open surgery constituted 26.6%, while transurethral resection of the prostate (TURP) was carried out in 73.4%. There was neither intraoperative death nor postoperative failure of voiding. The perioperative mortality rate was 0.8%. The main perioperative complications were bacteriuria in 48%, and significant bleeding requiring blood transfusion of three units or more in 20.6%. Histopathology revealed benign disease in 93.2% of the specimens and adenocarcinoma in 6.8%. It is concluded that the Saudi BPH patient in Asir presents late with acute retention of urine more often than in other places and so noninvasive therapeutic modalities may be less helpful.

The management of confidentiality in Egypt.

Patient confidentiality is an important issue for treating clinician regardless of the cultural background. Though cultural and religious issues may have an impact on the confidentiality standards. This article discusses the confidentiality standards in Egypt citing the laws and ethical codes governing them. This is followed by a research study in which a questionnaire containing ten vignettes representing different common themes confronted by the practicing clinician was completed by forty-one Egyptian psychiatrists. They checked off categories representing alternatives they might choose dealing with the themes. Each respondent received a score. The scores were compared with those of American and Israeli psychiatrists who participated in a similar study. There were no statistically significant differences though Egyptian and Israeli psychiatrists appear to be somewhat more inclined to break confidentiality. However, significant differences were found to exist for some of the vignettes between the three groups.

Patterns of cocaine abuse in an inner city emergency psychiatric service setting.

The reported study identifies the socio-demographic profile of the patient who presents himself to the emergency room of an inner city hospital with a history of recent cocaine use; and investigates the patterns of cocaine abuse.

Prognosis of vasculitis associated myelodysplasia.

Systemic and immune manifestations have been reported in patients with MDS. The correlation between immunological abnormalities and prognosis in myelodysplastic syndrome patients remains controversial. Most of the authors agree that the median survival in myelodysplastic syndrome is not related to the presence of systemic and immune manifestations, but only with the existence of a systemic vasculitis.