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Objectives: To evaluate a new tool for the early diagnosis of tuberculosis., Methods: A total of 374 smear-negative clinical specimens from patients with suspected tuberculosis were evaluated using a new procedure consisting of a preliminary step of culture in broth bottles followed by the detection of Mycobacterium tuberculosis complex (Mtb) and rifampicin resistance by the Xpert MTB/RIF assay (XMTB-RIF)., Results: A total of 30 Mtb strains were isolated, all susceptible to rifampicin. When broth cultures were subjected to XMTB-RIF analysis after 15 days of incubation, sensitivity, specificity, PPV, and NPV were each 100% when compared with liquid culture., Conclusion: The XMTB-RIF assay used in 15-day broth cultures may provide a final culture result for smear-negative specimens. This process, combined with clinical signs, may contribute to rapidly diagnosing tuberculosis and also to the early reevaluation of empirical antituberculosis treatment., (Copyright © 2018. Published by Elsevier Masson SAS.)

Background: Multiple quantitative trait loci for blood pressure (BP) have been localized throughout human and rodent genomes. Few of them have been functionally identified especially in humans, and little is known about their pathogenic directionality when identified. We focused on Chrm3 encoding the muscarinic cholinergic receptor 3 (M3R) as the causal gene for C17QTL1 in the Dahl salt-sensitive rat model., Methods and Results: Congenic knock-ins, gene-specific knockout, and ex vivo and in vivo function studies were applied in the Dahl salt-sensitive rat model of polygenic hypertension. A Chrm3 missense T1667C mutation in the last intracellular domain functionally correlated with a rise in BP increased the M3R signalling and resensitization, and adrenal epinephrogenesis. Gene targeting that abolished the M3R function without affecting any of noncoding Chrm3 variants caused a decrease in BP, indicating that the M3R-mediated signalling promotes hypertension. In contrast, removing 8 amino acids from the M3R first extracellular loop had no effect on BP., Conclusions: The M3R-specialized signalling constitutes a new pathway of hypertension pathogenesis within the context of a polygenic and quantitative trait. Increased epinephrine in the circulation and secreted from the adrenal glands are suggestive of a molecular mechanism partially mediating M3R to promote hypertension. The structure-function relationships for various M3R domains in their effects on BP pave the way for identifying missense mutations that impact functions on BP as potential diagnostic targets., (Copyright © 2018 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Almost 40% of cancers are attributable to preventable cancer risk factors related to behavior. Health professionals must take into account the respective weight of the different causes of cancer to enforce effective cancer prevention. Their involvement is needed on several levels. In primary prevention, not only for vaccinations, detection and support the withdrawal of addiction, but also by a greater consideration in their patients of all cancer risk behavioral factors. This involvement is essential in the care and monitoring of patients with cancer. Thus, enhancing patient compliance with cancer prevention tips (stopping smoking, reducing alcohol consumption, practice physical activity, physical inactivity reduction, reduction of overweight, adopting a diversified and balanced diet) appears as a new challenge of personalized care in oncology that not only aims to reduce the incidence of cancer but also to reduce the risks of morbidity and long-term mortality., (Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Background: Absence of outcome data is a barrier to quality improvement in resource poor settings. To address this challenge, we set out to determine whether follow up for surgical site infections (SSIs) using community health workers (CHWs) and smartphones is feasible in rural Haiti., Methods: In this pilot study, all patients from a specific mountain region who received an operation between March 10, and July 1, 2014, at Hôpital Albert Schweitzer in rural Haiti were eligible for inclusion. Patients or guardians of minors were approached for consent. We designed a smartphone application to enable CHWs to screen for SSIs during home visits by administering a questionnaire, obtaining GPS data, and submitting a photograph of an incision. We selected and trained CHWs to use the smartphone application and compensated them based on performance. CHWs completed home visits for 30 days after an operation for all participants. Surgeons examined all participants within 24 h after the second CHW home visit. Primary outcomes included the number of participants completing 30-day follow-up and home visits made on time. Secondary outcomes included the quality of the photographs and the agreement between surgeons and CHWs on the diagnosis of SSI. The Partners Healthcare institutional review board and the Ethics Committee at Hôpital Albert Schweitzer approved the study protocol., Findings: Five CHWs completed 30-day follow up for 37 of 39 participants (94·9%) and completed 107 of 117 home visits on time (91·5%). High quality photographs were submitted for 101 of 117 visits (86·3%). Surgeons and CHWs agreed on the diagnosis of SSI in 28 of 33 cases (84·8%)., Interpretation: Outpatient follow up for SSIs with CHWs and smartphones is feasible in rural Haiti. Further validation of the programme needs to be done before widespread adoption or advocating for task shifting post-operative follow up to CHWs., Funding: Partners Healthcare, Children's Hospital Boston, and Swiss Bündner Partnerschaft Hôpital Albert Schweitzer Haiti., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Diastolic dysfunction often precedes the onset of diastolic heart failure. We previously demonstrated that diastolic dysfunction and left ventricular hypertrophy (LVH) in Dahl salt-sensitive rats can be ameliorated by quantitative trait loci (QTLs)., Methods: We analyzed cardiac phenotypes of 2 "single" congenic strains, C10S.L33 and C10S.L28, by echocardiography, in which a specific Dahl salt-sensitive rat chromosome segment was replaced by its Lewis homologue. C10S.L33 improves diastolic function (DF) and LVH only in rats aged 10 weeks, not aged 15 weeks. C10S.L28 alleviated LVH, but not diastolic dysfunction. Thus, the QTLs captured by C10S.L33 and C10S.L28 are designated as DF/LVH C10QTL7 and LVH C10QTL4, respectively. We then combined multiple single strains to form 2 congenic combinations. One of the 2 congenic combinations included the chromosome segments covered by C10S.L33 and C10S.L28., Results: Diastolic dysfunction was either completely or partially reversed by 15 weeks in the 2 congenic combinations. LVH was permanently improved from 10 to 15 weeks., Conclusions: Distinct QTLs exist that regulate diastolic function and/or LVH in the short term when acting alone, but durably when combined. The Ccl2 chemokine (C-C motif) ligand 1 (Ccl2) gene is the prime candidate for DF/LVH C10QTL7, owing to a nonconserved coding mutation. Schlafen genes are candidates for LVH C10QTL4. Since CCL2 and Schlafens are not known for influencing diastolic function and left ventricular mass, novel long-term strategies of prognosis, diagnosis, and therapy for diastolic heart failure and LVH appear from this work., (Copyright © 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Adrenal insufficiency is a rare but life-threatening disease. Replacement therapy sometimes fails to prevent an acute adrenal crisis and most often does not lead to restoration of well-being. We report here the 1-year outcome of the first simultaneous kidney-adrenal gland-pancreas transplantation in a 33-year-old patient with type 1 diabetes and concomitant autoimmune adrenal insufficiency. En bloc left adrenal gland and kidney grafts were anastomosed on the left iliac vessels in normal vascular conditions and the pancreas graft was anastomosed on the right iliac vessels. The immunosuppressive regimen was not modified by the addition of the adrenal gland. We observed no additional morbidity due to the adrenal gland transplantation, as there were no surgical complications. One-year kidney and pancreas graft functions were satisfactory (estimated glomerular filtration rate: 55 mL/min/1.73 m(2) and HbA1c: 4.8%). The adrenal graft functioned well at 12 months with a normalization of cortisol and aldosterone baseline levels. Functional imaging at 3 months showed good uptake of [(123) I]-metaiodobenzylguanidine by the adrenal graft. Transplantation of the adrenal gland en bloc with the left kidney appears to be a good therapeutic option in patients with adrenal insufficiency awaiting kidney or kidney-pancreas transplantation., (© Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: It is unknown whether kidney transplant patients who receive rabbit antithymocyte globulin (rATG) become immunized against rabbit antibodies, leading to reduced efficacy, or are at higher risk of cytomegalovirus infection or post-transplant lymphoproliferative disorder (PTLD) on retreatment. The efficacy and tolerance of rATG when used as induction for the second time in patients undergoing retransplantation have not been evaluated., Methods: In a retrospective case-control study, 54 retransplanted patients who received rATG (Thymoglobulin) induction for the second time during 2004-2010 were compared to a matched cohort of 108 patients receiving rATG induction for a first kidney transplantation during the same period. Maintenance treatment was similar in both groups., Results: Median follow-up was 45.8 months and 47.3 months in the second and first treatment groups, respectively. No differences were observed between the two groups in terms of leukocyte, lymphocyte or platelet depletion. Dose and duration of rATG treatment were similar in both groups, suggesting a similar tolerance profile. Cytomegalovirus infection (including primoinfection and reactivation) occurred in 4/54 retreated patients versus 22/108 controls (p=0.108). Use of cytomegalovirus prophylaxis was similar between groups. PTLD occurred in one control patient and no retreated patients., Conclusion: A second course of rATG induction results in similar lymphocyte depletion and is as well tolerated as a first course. The incidence of cytomegalovirus infection and post-transplant lymphoproliferative disease was not increased during retreatment. Further studies are required to evaluate specific T cell subpopulation depletion and compare long-term outcome in patients receiving a second induction with rATG., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The use of uncontrolled deceased donors after cardiac arrest (uDDCA) has been developed in France to compensate for organ shortage. The quality of these kidneys remains unclear. We analyzed kidney graft function and histology from 27 uDDCA and compared them with kidneys from 30 extended criteria donors (ECD) and from 24 simultaneous pancreas kidney (SPK) donors as a control group of optimal deceased donors. Kidneys from ECD and SPK donors were preserved by static cold storage while kidneys from uDDCA were preserved by pulsatile perfusion. The uDDCA graft function at 3 years posttransplantation (estimated with MDRD and measured with inulin clearance) did not differ from that of the ECD group (eGFR 44.1 vs. 37.4 mL/min/1.73 m(2) , p = 0.13; mGFR 44.6 vs. 36.1 mL/min/1.73 m(2) , p = 0.07 in the uDDCA and ECD groups, respectively). The histological assessment of 3-month and 1-year protocol biopsies did not show differences for interstitial lesions between the uDDCA and ECD grafts (IF score at M3 was 30 vs. 28% and at M12 36 vs. 33%, p = NS). In conclusion, the results at 3 years with carefully selected and machine-perfused uDDCA kidneys have been comparable to ECD kidneys and encourage continuation of this program and development of similar programs., (© Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.)

We report 10 cases of intestinal microsporidiosis due to Enterocytozoon bieneusi in renal transplant (RT) recipients who were treated with fumagillin. All patients presented with afebrile subacute diarrhea (median of 2 weeks), associated with abdominal cramps (n = 5), and weight loss (n = 6), a mean of 68 months after RT. The diagnosis was made by the identification of microsporidial spores in stools with the use of appropriate staining and confirmed by a specific polymerase chain reaction assay for E. bieneusi in 7 patients. Median CD4 cell count was 292 cells/mm(3). All patients received a median of 14 days of oral fumagillin (20 mg tid), and four patients also discontinued or tapered their immunosuppressive regimen (mycophenolate mofetil in 3, and azathioprine in 2). Clinical symptoms resolved rapidly with the clearance of microsporidial spores from stools in all patients. A severe but reversible thrombocytopenia was observed in one patient during fumagillin therapy, and another patient presented with abdominal cramps. Trough levels of tacrolimus measured in seven patients dropped below 5 ng/mL in six of them after 7-14 days of fumagillin. Intestinal microsporidiosis can cause subacute diarrhea in RT recipients. Fumagillin is an effective treatment with an acceptable safety profile, but monitoring of tacrolimus levels is warranted.

We report the case of a renal transplanted patient, in whom the detection of a unique anti HLA-DP antibody response preceded the development of chronic humoral rejection. In addition to donor-specific anti-DP alloantibodies, the patient displayed reactions against several non-donor-specific DP antigens (NDSA). Interestingly, we found that all the DP molecules recognized by the alloantibodies displayed the same amino-acid sequence suggesting that epitope sharing between unrelated HLA molecules was the mechanism underlying NDSA generation. This case highlights the pathogenicity of anti-DP alloantibodies and suggests that it could be more meaningful to match the epitopes than the HLA antigens for the prevention of rejection.