Getting to the heart of the matter: diagnostic tools and therapeutic approach to cardiac involvement in Behçet syndrome A Tunisian case series.

The aim was to investigate the frequency and spectrum of cardiac involvement (CI) in patients with Behçet syndrome (BS) in the Tunisian context, and to assess the clinical and imaging features, treatment, and outcomes. We retrospectively retrieved the medical records of patients with CI among 220 BS patients admitted to the hospital internal medicine department between February 2006 and April 2019, who fulfilled the International Study Group diagnostic criteria for BS. Ten patients (8 men, 2 women) were eligible for the study. Mean age was 37.3 years. Three patients had 2 isolated episodes of cardiac BS. The different types of CI were coronary artery disease (5/10), intracardiac thrombus (4/10), pericarditis (1/10), myocarditis (1/10), and myocardial fibrosis (1/10). Five patients had associated vascular involvement (50%). Medical treatment was based on corticosteroids and colchicine in all patients (100%), anticoagulants in 8 (80%), and cyclophosphamide followed by azathioprine in 9 (90%). The clinical course was favorable in 9 patients; 1 patient died. CI remains an important feature of BS because of its association with increased risk of mortality and morbidity. Therefore, early screening and detection with imaging methods are paramount. Also, better cooperation between rheumatologists and cardiologists could improve outcomes.

Outcomes of a primary care mental health implementation program in rural Rwanda: A quasi-experimental implementation-effectiveness study.

INTRODUCTION: To address the know-do gap in the integration of mental health care into primary care in resource-limited settings, a multi-faceted implementation program initially designed to integrate HIV/AIDS care into primary care was adapted for severe mental disorders and epilepsy in Burera District, Rwanda. The Mentoring and Enhanced Supervision at Health Centers (MESH MH) program supported primary care-delivered mental health service delivery scale-up from 6 to 19 government-run health centers over two years. This quasi-experimental study assessed implementation reach, fidelity, and clinical outcomes at health centers supported by MESH MH during the scale up period. METHODS: MESH MH consisted of four strategies to ensure the delivery of the priority care packages at health centers: training; supervision and mentorship; audit and feedback; and systems-based quality improvement (QI). Implementation reach (service use) across the 19 health centers supported by MESH MH during the two year scale-up period was described using routine service data. Implementation fidelity was measured at four select health centers by comparing total clinical supervisory visits and checklists to target goals, and by tracking clinical observation checklist item completion rates over a nine month period. A prospective before and after evaluation measured clinical outcomes in consecutive adults presenting to four select health centers over a nine month period. Primary outcome assessments at baseline, 2 and 6 months included symptoms and functioning, measured by the General Health Questionnaire (GHQ-12) and the World Health Organization Disability Assessment Scale (WHO-DAS Brief), respectively. Secondary outcome assessments included engagement in income generating work and caregiver burden using a quantitative scale adapted to context. RESULTS: A total of 2239 mental health service users completed 15,744 visits during the scale up period. MESH MH facilitated 70% and 76% of supervisory visit and clinical checklist utilization target goals, respectively. Checklist item completion rates significantly improved overall, and for three of five checklist item subgroups examined. 121 of 146 consecutive service users completed outcome measurements six months after entry into care. Scores improved significantly over six months on both the GHQ-12, with median score improving from 26 to 10 (mean within-person change 12.5 [95% CI: 10.9-14.0] p< 0.0001), and the WHO-DAS Brief, with median score improving from 26.5 to 7 (mean within-person change 16.9 [95% CI: 14.9-18.8] p< 0.0001). Over the same period, the percentage of surveyed service users reporting an inability to work decreased significantly (51% to 6% (p < 0.001)), and the proportion of households reporting that a caregiver had left income-generating work decreased significantly (41% to 4% (p < 0.001)). CONCLUSION: MESH MH was associated with high service use, improvements in mental health care delivery by primary care nurses, and significant improvements in clinical symptoms and functional disability of service users receiving care at health centers supported by the program. Multifaceted implementation programs such as MESH MH can reduce the evidence to practice gap for mental health care delivery by nonspecialists in resource-limited settings. The primary limitation of this study is the lack of a control condition, consistent with the implementation science approach of the study. STUDY REGISTRATION: ISRCTN #37231.

Short- and long-term follow-up of living kidney donors.

Living-donor kidney transplantation is a well-established treatment of end-stage renal disease in Tunisia. Over the years, concerns have increased about the harmlessness of kidney donation. This longitudinal single center study was carried out to evaluate the safety of nephrectomy as well as further medical and surgical outcomes among donors. We collected and analyzed clinical, biological, biochemical and kidney size data at the time of nephrectomy and at M1, M3, M6, Y1, Y2, and Y4 after donation measured by ultrasound. All donor nephrectomies performed in the nephrology and transplantation unit of Sahloul Hospital of Sousse since October 2006 were included. Criteria of exclusion were lost to follow-up or lack of complete data. Of the 106 donors (66 females and 40 males), 92 donors were included in the follow-up analysis after following exclusion criteria. The mean age at the time of nephrectomy was 42.8 ± 10 years with the sex ratio 0.6. and 27% of our donors were mothers. Twenty-two percent of the donors were obese and 4% were hypertensive. The median initial glomerular filtration rate (GFR) was 105 mL/min/1.73 m2. The surgical approach was costal lumbotomy in 96% of cases and laparoscopy for four cases. The kidneys were removed from the left side in 93% of cases. Postoperative mortality was zero and early postoperative morbidity was low. The median duration of hospital stay was nine days. During follow-up, 14% attended all recommended visits. The median follow-up duration was 26 months. After two years post donation, the prevalence of HTN was 28% and obesity was 26%. The prevalence of GFR decline (50-59 mL/min) was 14% using formula by modification of diet in renal disease. None of our donors reached stage 4 or 5 CKD. Twelve had proteinuria and one donor had diabetes, a comparable prevalence of morbidities to the general population.

Recombinant human erythropoietin prevents etoposide- and methotrexate-induced toxicity in kidney and liver tissues via the regulation of oxidative damage and genotoxicity in Wistar rats.

Etoposide (ETO) and methotrexate (MTX) are two effective chemotherapeutic drugs. However, the clinical use of these drugs is limited by its toxicity in normal tissues, especially in kidney and in liver tissues. Recombinant human erythropoietin (rhEPO), erythropoietin hormone, has also been shown to exert tissue protective effects. The purpose of this study was to explore the protective effect of rhEPO against oxidative stress and genotoxicity induced by ETO and MTX in vivo. Adult male Wistar rats were divided into 10 groups (6 animals each): control group, rhEPO alone group, ETO alone group, MTX alone group and rhEPO + ETO/MTX groups. In rhEPO + ETO/MTX groups, three doses of pretreatment with rhEPO were performed: 1000, 3000 and 6000 IU/kg. Our results showed that rhEPO pretreatment protects liver and kidney tissues against oxidative stress induced by the anticancer drugs. The glycoprotein decreased malondialdehyde (MDA) levels, reduced catalase activity and ameliorated glutathione depletion. Furthermore, we showed that rhEPO administration prevented drug-induced DNA damage accessed by comet test. Altogether, our results suggested a protective role of rhEPO, especially at 3000 IU/kg, against ETO- and MTX-induced oxidative stress and genotoxicity in vivo.

Clinical impact of NK-cell reconstitution after reduced intensity conditioned unrelated cord blood transplantation in patients with acute myeloid leukemia: analysis of a prospective phase II multicenter trial on behalf of the Société Française de Greffe de Moelle Osseuse et Thérapie Cellulaire and Eurocord.

Unrelated cord blood transplantation (UCBT) after a reduced intensity conditioning regimen (RIC) has extended the use of UCB in elderly patients and those with co-morbidities without an HLA-identical donor, although post-transplant relapse remains a concern in high-risk acute myeloid leukemia (AML) patients. HLA incompatibilities between donor and recipient might enhance the alloreactivity of natural killer (NK) cells after allogeneic hematopoietic stem-cell transplantation (HSCT). We studied the reconstitution of NK cells and KIR-L mismatch in 54 patients who underwent a RIC-UCBT for AML in CR in a prospective phase II clinical trial. After RIC-UCBT, NK cells displayed phenotypic features of both activation and immaturity. Restoration of their polyfunctional capacities depended on the timing of their acquisition of phenotypic markers of maturity. The incidence of treatment-related mortality (TRM) was correlated with low CD16 expression (P=0.043) and high HLA-DR expression (P=0.0008), whereas overall survival was associated with increased frequency of NK-cell degranulation (P=0.001). These features reflect a general impairment of the NK licensing process in HLA-mismatched HSCT and may aid the development of future strategies for selecting optimal UCB units and enhancing immune recovery.

Evaluating process and clinical outcomes of a primary care mental health integration project in rural Rwanda: a prospective mixed-methods protocol.

INTRODUCTION: Integrating mental healthcare into primary care can reduce the global burden of mental disorders. Yet data on the effective implementation of real-world task-shared mental health programmes are limited. In 2012, the Rwandan Ministry of Health and the international healthcare organisation Partners in Health collaboratively adapted the Mentoring and Enhanced Supervision at Health Centers (MESH) programme, a successful programme of supported supervision based on task-sharing for HIV/AIDS care, to include care of neuropsychiatric disorders within primary care settings (MESH Mental Health). We propose 1 of the first studies in a rural low-income country to assess the implementation and clinical outcomes of a programme integrating neuropsychiatric care into a public primary care system. METHODS AND ANALYSIS: A mixed-methods evaluation will be conducted. First, we will conduct a quantitative outcomes evaluation using a pretest and post-test design at 4 purposively selected MESH MH participating health centres. At least 112 consecutive adults with schizophrenia, bipolar disorder, depression or epilepsy will be enrolled. Primary outcomes are symptoms and functioning measured at baseline, 8 weeks and 6 months using clinician-administered scales: the General Health Questionnaire and the brief WHO Disability Assessment Scale. We hypothesise that service users will experience at least a 25% improvement in symptoms and functioning from baseline after MESH MH programme participation. To understand any outcome improvements under the intervention, we will evaluate programme processes using (1) quantitative analyses of routine service utilisation data and supervision checklist data and (2) qualitative semistructured interviews with primary care nurses, service users and family members. ETHICS AND DISSEMINATION: This evaluation was approved by the Rwanda National Ethics Committee (Protocol #736/RNEC/2016) and deemed exempt by the Harvard University Institutional Review Board. Results will be submitted for peer-reviewed journal publication, presented at conferences and disseminated to communities served by the programme.

Effect of recombinant human erythropoietin on mitomycin C-induced oxidative stress and genotoxicity in rat kidney and heart tissues.

Mitomycin C (MMC) is an antineoplastic agent used for the treatment of several human malignancies. Nevertheless, the prolonged use of the drug may result in a serious heart and kidney injuries. Recombinant human erythropoietin (rhEPO) has recently been shown to exert an important cytoprotective effect in experimental brain injury and ischemic acute renal failure. The aim of the present work is to investigate the cardioprotective and renoprotective effects of rhEPO against MMC-induced oxidative damage and genotoxicity. Our results showed that MMC induced oxidative stress and DNA damage. rhEPO administration in any treatment conditions decreased oxidative damage induced by MMC. It reduced malondialdehyde and protein carbonyl levels. rhEPO ameliorated reduced glutathione plus oxidized glutathione modulation and the increased catalase activity after MMC treatment. Furthermore, rhEPO restored DNA damage caused by MMC. We concluded that rhEPO administration especially in pretreatment condition protected rats against MMC-induced heart and renal oxidative stress and genotoxicity.

[A multicenter study on profile of hypertension in focal segmental glomerulosclerosis in Tunisia]. / Profil de l'hypertension artérielle dans la hyalinose segmentaire et focale (HSF). Étude multicentrique de 116 cas en Tunisie.

UNLABELLED: Hypertension in focal segmental glomerulosclerosis is frequent and responsible for the progression of the disease. It could be a circumstance of the diagnosis of FSG or a complication of the nephrotic syndrome. PURPOSE: To determine the prevalence of hypertension among patients with FSG diagnosed in Tunisia and to describe the profile of patients with FSG having hypertension in contrast with who do not. PATIENTS AND METHODS: It was a retrospective multicentric study based on 116 patient files having FSG located in 5 specialized centers in Tunisia. RESULTS: The prevalence of hypertension among our patients was 41%, with a feminine predominance, their mean age was 36.34 ± 15.71 years. The systolic blood pressure among the patients with hypertension was 153.18 mmHg. The nephrotic syndrome was impure due to hypertension in 14.5% of the cases. The patients affected by hypertension were more obese. Proteinuria was higher among those not having hypertension than those with it, who score an average value of 5.67 ± 4.51 g/24h, with an insignificant difference. Serum creatinine at presentation was significantly higher among patients with hypertension. Vascular lesions were present at the renal biopsy among 39.45% of patients affected by hypertension, associated with renal failure in 58.50% of patients. The etiopathogenic treatment of FSG was essentially based on steroids full dose. CONCLUSION: Hypertension is often present in FSG and its' treatment must be as soon as possible in order to slow the progression of kidney chronic disease.

Tacrolimus and mycophenolate mofetil associations: Induction of oxidative stress or antioxidant effect?

Gastrointestinal risk factors after organ transplantation are prevalent, due to the chronic use of immunosuppressant. The immunosuppressive drugs such as tacrolimus/mycophenolate mofetil (TAC/MMF) association are the most commonly used therapy. TAC and MMF have been implicated in gastrotoxicity, but their direct effects, alone and combined, on intestinal cells are not completely elucidated. This study investigated the effect of TAC and MMF alone and combined on human colon carcinoma cells. Our results demonstrated that TAC and MMF individually inhibit clearly cells proliferation, enhanced free radicals, lipid peroxidation production, induced DNA lesions and reduced mitochondrial membrane potential. In this study, we also showed that the two molecules TAC and MMF combined at high concentrations amplified the cell damage. Furthermore, the TAC (5 µM) prevented cell death induced by MMF (half maximal inhibitory concentration (IC(50))). Also, MMF (50 µM) induced cytoprotection in HCT116 cells against TAC (IC(50)) toxicity. Our findings provide additional evidence that oxidative damage is the major contribution of TAC and MMF combined toxicities. In fact, MMF and TAC exert a gastroprotective effect by modulating reactive oxygen species production. These data underscore the pleiotropic effect of TAC and MMF on HCT116 cells that play a preventive and critical role on intestinal function.

Role of recombinant human erythropoietin against mitomycin C-induced cardiac, hepatic and renal dysfunction in Wistar rats.

Mitomycin C (MMC) is one of the most effective chemotherapeutic drugs. However, the dose of MMC is greatly limited by its toxicity in normal tissues. Recombinant human erythropoietin (rhEPO), an erythropoietic hormone, has also been shown to exert tissue protective effects. The purpose of this study was to explore the protective effect of rhEPO against MMC-induced heart, liver, and renal dysfunction. Adult male Wistar rats were divided into six groups (with six animals each), namely control, rhEPO alone group, MMC alone group, and rhEPO + MMC group (pre-, co-, and posttreatment conditions). The results showed that MMC induced a marked cardiac, renal, and liver failure characterized by a significant decrease in body weight, organs weight, and organs ratio and a significant increase in creatinine, blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transferase, and conjugated and total bilirubin levels in serum. Histological examination showed that MMC caused liver alterations. rhEPO treatment restored body weight, organs weight, and organs ratio as well as serum biochemical parameters and histological damage caused by MMC exposure.

The protective effect of recombinant human erythropoietin against cisplatin-induced renal and hepatic dysfunctions in Wistar rats.

Cisplatin (Cisp) is one of the most effective chemotherapeutic drugs. However, the dose of Cisp is greatly limited by its toxicity. Recombinant human erythropoietin (rhEPO), a hormone that regulates hematopoiesis, has also been shown to exert tissue-protective effects. The purpose of this study was to explore the protective effect of rhEPO against Cisp-induced renal and liver dysfunctions. Adult male Wistar rats were divided into six groups of six each: control, rhEPO-alone group, Cisp-alone group and rhEPO + Cisp group (pretreatment, cotreatment and posttreatment conditions). Our results showed that Cisp-induced a marked renal and liver failure characterized by a significant decrease in body weight, organ weight and organ ratio and a significant increase in creatinine, blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, G-glutamyl transferase, alkaline phosphatase, bilirubin conjugated and bilirubin total levels in serum. Histological examination showed that Cisp caused kidney alterations. rhEPO treatments restored body weight, organ weight and organ ratio as well as serum biochemical parameters changed due to Cisp exposure.

Anti-cardiolipin and anti-beta 2-glycoprotein I antibodies in celiac disease.

AIMS: To determine the frequency of anti-cardiolipin (aCL) and anti-ß2-glycoprotein I antibodies (aß2GPI) in celiac disease (CD) patients. PATIENTS AND METHODS: Sixty-three untreated CD patients and 40 healthy blood donors (HBD) were studied. IgG, IgA and IgM aCL and aß2GPI were detected by Elisa. RESULTS: The frequency of antiphospholipid antibodies (aPL) (aCL and/or aß2GPI) was significantly higher in CD patients (12 out of 63) than in HBD (two out of 40) (19% vs 5%, P=0.04). Six CD patients out of 63 (9.5%) and one HBD out of 40 (2.5%) had aCL. Ten CD patients (15.9%) and two HBD (5%) had aß2GPI. Only aß2GPI-IgA was significantly more frequent in CD patients than in HBD (14.3% vs 2.5%, P=0.048). In CD patients, aß2GPI-IgA (nine out of 63) was significantly more frequent (14.3%) than aß2GPI-IgG (1.6%) and IgM (1.6%) (P=0.008). In CD patients, the frequency of aCL-IgA and IgM was 6.3% (four out of 63) and aCL-IgG were not detected. Simultaneous presence of positive antibodies was found in four CD patients: one patient had four aPL, one had three aPL and two had two aPL. The four patients who had aCL-IgA had also aß2GPI-IgA and three of them had a titer higher than 50 units. Among nine patients with aß2GPI-IgA, four had a titer higher than 100 units. The highest titers were found in adults. CONCLUSIONS: aPL and particularly aß2GPI-IgA are frequent in CD. The significance of these antibodies has to be determined.

[Study of cardiovascular risk factors in Tunisian patients with recent type 2 diabetes]. / Étude des facteurs de risque cardiovasculaire chez le diabétique de type 2 Tunisien récemment découvert.

OBJECTIVE: To study the frequency of silent myocardial ischemia (SMI) in Tunisian patients with recent type 2 diabetes and identify cardiovascular risk factors directly in relation with SMI. PATIENTS AND METHODS: One hundred and twenty diabetics and sixty healthy people have benefited from blood sampling, electrocardiogram and exercise test. RESULTS: The frequency of SMI was 21% in diabetics and 3% in healthy people (P=0.01). Obesity and hypertension were higher in diabetics than in healthy people (P=0.001 and P<10(-4)). Using unvaried analysis for risk factors with the presence of SMI in diabetics, we found that age greater than 60 yrs, male sex, sedentary and smoking were significantly correlated with SMI; respectively P=0.004, 0.01, 0.009 and 0.03. The SMI was found in 37% of diabetics with high blood pressure vs 8% in diabetics with normal blood pressure and was correlated with hypertriglyceridemia, hypoHDLemia and microalbuminuria. Patients with SMI had at least two cardiovascular risk factors apart from diabetes among those: age greater or equal to 60 yrs, male sex, smoking, hypertension, dyslipidemia and family history of early coronaropathy. Chronic inflammation and hyperhomocysteinemia were significantly correlated to SMI; OR=4.2 and 3.8. In addition, SMI was found in one diabetic over three who had bad glycemic control. Using multivariate analysis, only age greater or equal to 60 yrs, smoking, hypertension, hyperhomocysteinemia and hypertriglyceridemia were risk factors directly in relation with SMI in type 2 diabetes. CONCLUSION: The assessment of global cardiovascular risk from the moment of discovering type 2 diabetes and the early screening of SMI should be necessary.

Hierarchical carbon nanostructure design: ultra-long carbon nanofibers decorated with carbon nanotubes.

Hierarchical carbon nanostructures based on ultra-long carbon nanofibers (CNF) decorated with carbon nanotubes (CNT) have been prepared using plasma processes. The nickel/carbon composite nanofibers, used as a support for the growth of CNT, were deposited on nanopatterned silicon substrate by a hybrid plasma process, combining magnetron sputtering and plasma-enhanced chemical vapor deposition (PECVD). Transmission electron microscopy revealed the presence of spherical nanoparticles randomly dispersed within the carbon nanofibers. The nickel nanoparticles have been used as a catalyst to initiate the growth of CNT by PECVD at 600°C. After the growth of CNT onto the ultra-long CNF, SEM imaging revealed the formation of hierarchical carbon nanostructures which consist of CNF sheathed with CNTs. Furthermore, we demonstrate that reducing the growth temperature of CNT to less than 500°C leads to the formation of carbon nanowalls on the CNF instead of CNT. This simple fabrication method allows an easy preparation of hierarchical carbon nanostructures over a large surface area, as well as a simple manipulation of such material in order to integrate it into nanodevices.