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Context: Breast cancer is the most common cause of cancer mortality among women worldwide. It is a heterogeneous disease partly responsible for treatment failure in luminal B patients. Deregulation of fibroblast growth factor signaling has been found and its therapeutic/prognostic value is explored. Aims: Most of the research has studied the FGFR1 gene while our study explored its protein expression by immunohistochemestry and examined the association with clinicopathological features, different molecular subtypes and survival. Subjects and Methods: Formalin-fixed and paraffin-embedded samples of invasive breast carcinomas were used to analyze FGFR1 expression. FGFR 1 was scored by percentage and intensity of cell cytoplasm staining, correlations were investigated and survival curves were constructed. Statistical Analysis Used: Chi-square test was used to assess the relationship between the marker expression and the clinicopathological characteristics. Overall specific survival curves were estimated using the Kaplan-Meier method and statistical significance was assessed using the log-rank test. Results: FGFR1 was associated at different staining threshold cut-offs with tumor size (P = 0.002), infiltrating lymph node (P = 0.022), distant metastasis (P = 0.003), positive estrogen receptor (P = 0.000), HER2 overexpression (P = 0.044) and luminal phenotypes (P = 0.026). The results also emphasize FGFR1 correlation expression with distant metastasis in luminal B tumors (P = 0.035) but not with luminal A and with overexpressed HER2 protein in both luminal tumors. FGFR1 expression affect luminal B patients survival with poor outcome. Conclusions: FGFR1 expression may serve as a prognostic and predictive factor in luminal breast cancers, it can also be considered as a potential therapeutic target in luminal B cases.

Bortezomib, lenalidomide, and dexamethasone plus transplant is a standard of care for eligible patients with multiple myeloma. Because responses can deepen with time, regimens with longer and more potent induction/consolidation phases are needed. In this phase 2 study, patients received eight 28-day cycles of carfilzomib (K) 20/36 mg/m2 (days 1-2, 8-9, 15-16), lenalidomide (R) 25 mg (days 1–21), and dexamethasone (d) 20 mg (days 1-2, 8-9, 15-16, 22-23). All patients proceeded to transplant after 4 cycles and received 1 year of lenalidomide maintenance (10 mg, days 1-21). The primary objective was stringent complete response at the completion of consolidation. Overall, 48 patients were screened and 46 enrolled; 21% had adverse cytogenetics. Among 42 evaluable patients after consolidation, 26 were in stringent complete response (CR; 61.9%), 27 were at least in CR (64.3%): 92.6% had undetectable minimal residual disease according to flow cytometry (≥2.5 × 10−5) and 63.0% according to next-generation sequencing (10−6). Median time to CR was 10.6 months. According to multiparametric flow cytometry and next-generation sequencing, 69.0% and 66.7% of patients, respectively, had undetectable minimal residual disease at some point. With a median follow-up of 60.5 months, 21 patients progressed, and 10 died (7 of multiple myeloma). Median progression-free survival was 56.4 months. There were no KRd-related deaths. Four patients discontinued the program due to toxicities; 56 serious adverse events were reported in 31 patients, including 8 cardiovascular events (2 heart failures, 5 pulmonary embolisms or deep vein thrombosis). Common grade 3/4 adverse events were hematologic (74%) and infectious (22%). In summary, 8 cycles of KRd produce fast and deep responses in transplant-eligible patients with newly diagnosed multiple myeloma. The safety profile is acceptable, but cardiovascular adverse events should be closely monitored. This clinical trial is registered at www.clinicaltrials.gov as #NCT02405364.

Introduction Rituximab is a standard treatment for gastric mucosa-associated lymphoid tissue (MALT) lymphoma (GML). We sought to compare the effectiveness and safety of subcutaneous and intravenous rituximab in a retrospective case–control study. Patients and Methods All consecutive patients with GML treated with subcutaneous rituximab between January 2017 and December 2018 were included and compared to 3 matched control patients (based on Ann Arbor classification, presence of t(11;18) translocation, history of treatment, and type of current treatment) treated with intravenous rituximab between January 2000 and December 2018. Patients with t(11;18) translocation were treated with rituximab in combination with chlorambucil; the other patients were treated with rituximab alone. Effectiveness was assessed at week 52, and safety was assessed through weeks 0 to 52 and compared by the chi-square test. Results Twenty-five patients were included in the subcutaneous rituximab group and 75 in the intravenous group. There was no difference between the groups in complete remission (78% vs. 76%, P = .99) or overall response rates (91% vs. 89%, P = .99) at week 52. Safety profiles were similar in both groups, with a significant decrease in postinduction grade 2 injection-related reactions and outpatient hospital length of stay in the subcutaneous rituximab group. Conclusion In a small case–control study, we did not find any difference in the effectiveness or safety profiles between subcutaneously and intravenously delivered rituximab for the treatment of patients with GML. We found a decrease in postinduction grade 2 injection-related reactions and outpatient hospital length of stay in the subcutaneous rituximab group.

Objective To evaluate the impact that type 1 diabetes mellitus (T1DM) in children has on parents’ mental health and parents’ coping with this condition. Methods A cross-sectional study involving, at the outpatient examination, 41 caregivers of T1DM patients who had been diagnosed for at least 6 months. We evaluated the parents’ coping strategies with the Brief COPE and their depressive and anxiety symptoms with the Hospital Anxiety and Depression Scale (HADS). Glycemic control of patients was assessed using the last glycated hemoglobin (HbA1c) values. Results The average total score at HADS was 17.62 (SD = 6.98). Half of the parents had an anxious score over the cut-off. The more parents were depressed or anxious, the more they used emotion-focused coping (P = 0.002 and P = 0.00, respectively). The more parents were anxious or depressed, the more they used maladaptive coping strategies such as avoidance and distraction. Conclusion These findings emphasise the key role of healthcare providers in assessing parents’ difficulties and taking special care of those who have the most problems.

Background and aim The aim of this study is to evaluate the clinical, biological and hematological profiles of autoimmune hemolytic anemia (AIHA) in children and to specify its etiologies, therapeutic modalities, and treatment responses. Methods This is a 14-year retrospective study of AIHA cases collected at the department of pediatric emergency and reanimation of Hedi Chaker University Hospital in Sfax. We included patients under 14 years old with clinical and biological features of hemolysis and a positive direct antiglobulin test (DAT). The selected patients’ demographic characteristics, physical signs, laboratory findings, and treatment responses were recorded. Results Thirteen cases of AIHA were collected, including 8 girls and 5 boys. The median age at diagnosis was 4 years and 6 months (range: 8 months to 13 years). Consanguinity was reported in 6 cases and 4 patients had a previous infection history. The onset of AIHA was progressive in 9 cases, marked by an anemic syndrome and hemolysis symptoms in 6 and 8 cases, respectively. The clinical triad (pallor, jaundice and splenomegaly) was found in only 4 cases. At the time of diagnosis, the median hemoglobin (Hb) level was 6 g/dL (range: 4.2 to 9.2 g/dL), anemia was non-regenerative in 2 patients. Thrombocytopenia and neutropenia were noted in 5 and 1 patient, respectively. Peripheral smear examination showed spherocytosis in 2 cases. All the patients had a positive DAT. Of these, 10 were positive with IgG and 3 with both IgG and C3d. AIHA was secondary to other conditions in 9 patients: infection (3 cases), autoimmune disease (4 cases), and immunodeficiency (2 cases). All the patients received first-line corticosteroid therapy but only 8 of them required blood transfusions due to severe anemia. Complete remission was obtained in 7 cases. Corticosteroid resistance and dependence were noted in 1 and 2 cases, respectively. During evolution, additional therapy was indicated in 4 patients and it included cyclosporine A, azathioprine, and mycophenolate mofetil (MMF). After a median follow-up of 4.5 years, the cure rate was 80% and only 1 patient (a boy) died due to his underlying pathology. Conclusion Our study highlights the rarity, severity, and heterogeneity of etiological contexts of AIHA in children. The therapeutic difficulties justify specific expertise in pediatric hematology.

BackgroundInborn errors of immunity (IEI) predispose patients to various infectious and non-infectious complications. Thanks to the development and expanding use of flow cytometry and increased awareness, the diagnostic rate of IEI has markedly increased in Algeria the last decade.AimThis study aimed to describe a large cohort of Algerian patients with probable IEI and to determine their clinical characteristics and outcomes.MethodsWe collected and analyzed retrospectively the demographic data, clinical manifestations, immunologic, genetic data, and outcome of Algerian IEI patients - diagnosed in the department of medical immunology of Beni Messous university hospital center, Algiers, from 2008 to 2021.ResultsEight hundred and seven patients with IEI (482 males and 325 females) were enrolled, 9.7% of whom were adults. Consanguinity was reported in 50.3% of the cases and a positive family history in 32.34%. The medium age at disease onset was 8 months and at diagnosis was 36 months. The median delay in diagnosis was 16 months. Combined immunodeficiencies were the most frequent (33.8%), followed by antibody deficiencies (24.5%) and well-defined syndromes with immunodeficiency (24%). Among 287 patients tested for genetic disorders, 129 patients carried pathogenic mutations; 102 having biallelic variants mostly in a homozygous state (autosomal recessive disorders). The highest mortality rate was observed in patients with combined immunodeficiency (70.1%), especially in patients with severe combined immunodeficiency (SCID), Omenn syndrome, or Major Histocompatibility Complex (MHC) class II deficiency.ConclusionThe spectrum of IEI in Algeria is similar to that seen in most countries of the Middle East and North Africa (MENA) region, notably regarding the frequency of autosomal recessive and/or combined immunodeficiencies.

Background There is a growing literature showing that critically ill COVID-19 patients have an increased risk of pulmonary co-infections and superinfections. However, studies in developing countries, especially African countries, are lacking. The objective was to describe the prevalence of bacterial co-infections and superinfections in critically ill adults with severe COVID-19 pneumonia in Morocco, the micro-organisms involved, and the impact of these infections on survival. Methods This retrospective study included severe COVID-19 patients admitted to the intensive care unit (ICU) between April 2020 and April 2021. The diagnosis of pulmonary co-infections and superinfections was based on the identification of pathogens from lower respiratory tract samples. Co-infection was defined as the identification of a respiratory pathogen, diagnosed concurrently with SARS-Cov2 pneumonia. Superinfections include hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). A multivariate regression analysis was performed to identify factors independently associated with mortality. Results Data from 155 patients were analyzed. The median age was 68 years [62–72] with 87% of patients being male. A large proportion of patients (68%) received antibiotics before ICU admission. Regarding ventilatory management, the majority of patients (88%) underwent non-invasive ventilation (NIV). Sixty-five patients (42%) were placed under invasive mechanical ventilation, mostly after failure of NIV. The prevalence of co-infections, HAP and VAP was respectively 4%, 12% and 40% (64 VAP/1000 ventilation days). The most isolated pathogens were Enterobacterales for HAP and Acinetobacter sp. for VAP. The proportion of extra-drug resistant (XDR) bacteria was 78% for Acinetobacter sp. and 24% for Enterobacterales. Overall ICU mortality in this cohort was 64.5%. Patients with superinfection showed a higher risk of death (OR = 6.4, 95% CI: 1.8–22; p = 0.004). Conclusions In this single-ICU Moroccan COVID-19 cohort, bacterial co-infections were relatively uncommon. Conversely, high rates of superinfections were observed, with an increased frequency of antimicrobial resistance. Patients with superinfections showed a higher risk of death.

Introduction:breast cancer is related to age. The young age remains a controversial issue as a prognostic factor and have more aggressive clinical behavior with poor outcome. We aimed for the first time in Algeria to explore on a large cohort of patients the prevalence of the molecular phenotypes and to describe their clinical characteristics and survival. Methods:medical record of 1140 Algerian patients were analysed and categorized into three age groups: "young" when women were aged below 40 years; "middle-age" when women were aged from 41 to 54 years old and "elder" when women were over 54 years. Baseline categorical variables were analysed using the Chi-square test and survival curves were constructed using Kaplan Meir method. Results:the distribution of the various prognostic factors did not differ significativelly by age groups except for histological types, hormone receptors status and molecular phenotypes. Most patients were luminal A, indeed, young and intermediate age patients were most likely to be luminal A whereas the aged patients were triple negative with the highest mean DFS. Elsewhere young women are considered as human epidermal growth factor receptor 2 (HER2+) or triple negative molecular subtypes involving more rigorous therapeutic monitoring. The high rate of triple negative breast cancer in aged patients may due to genetic predispositions. Conclusion:this study sheds light on the histoclinical and molecular characteristics of breast cancer in young patients, which has a good prognosis than their older counterparts. Our results are therefore surprisingly different from what the literature suggests. A further study should understand this uncommon finding.

Onychomycosis is a fungal infection of nails caused by dermatophytes, yeasts or non-dermatophyte molds. The aim of our study was to describe the epidemiological features of onychomycoses encountered in the Tunis region. A retrospective study concerned 3458 cases of onychomycosis, confirmed by direct examination and/or a positive culture, was conducted in Parasitology - Mycology Laboratory, Rabta hospital, over a five-year period (2012-2016). Our patients were aged 1 to 85; more than half of the patients were aged over 60 years with a female predominance (67%). Toenail infections were most common, observed in 2702 cases (78%). Direct examination was positive in 3284 cases (95%), culture in 2409 cases (69.6%); these two examinations were positive simultaneously in 2235 cases (64.6%). The causative agents of these onychomycoses were dominated by the genus Candida in fingernails: Candida albicans (55.6%), Candida tropicalis (8.5%) and Candida parapsilosis (8.2%) were the most frequently incriminated species; while in toenail lesions, Trichophyton rubrum was by far the most frequently isolated species (96.8%). Our results join the literature; onychomycosis is a pathology of the adult, mainly candidosic etiology in hands and dermatophytic in feet.

Background: CASSIOPEIA part 1 showed superior depth of response and significantly improved progression-free survival with daratumumab, bortezomib, thalidomide, and dexamethasone (D-VTd) versus bortezomib, thalidomide, and dexamethasone (VTd) as induction and consolidation in patients with autologous stem-cell transplant (ASCT)-eligible newly diagnosed multiple myeloma. In part 2, we compared daratumumab maintenance versus observation only. Methods: CASSIOPEIA is a two-part, open-label, randomised, phase 3 trial of patients aged 18–65 years with newly diagnosed multiple myeloma and Eastern Cooperative Oncology Group performance status 0–2, done in 111 European academic and community practice centres. In part 1, patients were randomly assigned (1:1) to induction and consolidation with D-VTd or VTd. Patients still on study who had a partial response or better were randomly assigned (1:1) by an interactive web-response system to daratumumab 16 mg/kg intravenously every 8 weeks (a reduced frequency compared with standard daratumumab long-term dosing) or observation only for up to 2 years. Stratification factors were induction treatment and depth of response in part 1. The part 2 primary endpoint was progression-free survival from second randomisation. This preplanned interim analysis of progression-free survival was done after 281 events and shall be considered the primary analysis of progression-free survival. Sponsor personnel and designees who were involved in the analysis were masked to treatment group until the independent data monitoring committee recommended that the preplanned interim analysis be considered the main analysis of progression-free survival in part 2. Otherwise, treatment assignments were unmasked. The interaction between induction and consolidation and maintenance was tested at a two-sided significance level of 0·05 by a stratified Cox regression model that included the interaction term between maintenance treatment and induction and consolidation treatment. Efficacy analyses were done in the maintenance-specific intention-to-treat population, which comprised all patients who underwent second randomisation. Safety was analysed in all patients in the daratumumab group who received at least one dose and all patients randomly assigned to observation only. This trial is registered with ClinicalTrials.gov, NCT02541383. Long-term follow-up is ongoing and the trial is closed to new participants. Findings: Between May 30, 2016, and June 18, 2018, 886 patients (458 [84%] of 543 in the D-VTd group and 428 [79%] of 542 in the VTd group) were randomly assigned to daratumumab maintenance (n=442) or observation only (n=444). At a median follow-up of 35·4 months (IQR 30·2–39·9) from second randomisation, median progression-free survival was not reached (95% CI not evaluable [NE]–NE) with daratumumab versus 46·7 months (40·0–NE) with observation only (hazard ratio 0·53, 95% CI 0·42–0·68, p

Hematopoietic stem cell transplantation (HSCT) has evolved from an experimental to a successful treatment modality reaching worldwide 80.000 HSCT/year. Distribution and trends of HSCT, however, remain heterogeneous. Activities range from none to more than 511/10 million population between countries and regions. Here, we report on a successful autologous and allogeneic HSCT program for adult and pediatric patients started two decades ago in Northern Africa. From 1998 to December 2017, a total of 2828 HSCT was performed of which 2059 were allo-HSCT (1474 adults and 585 children). The activities were analyzed according to indication, donor type, stem cell source, and trends over time. There was a significant difference in indications according to age. Adult patients were transplanted more often for hematological malignancies. In children, the indications were distributed equally between malignant and non-malignant diseases. Overall activities increased substantially in AML and to a lower extent in ALL and CLL despite sharp reduction of activity in CML after 2005. Finally, a higher transplantation rate (33/10 million population) was reached as compared to most regions of the world except Europe and USA/Canada. Overall survival in children with AML was 56.0% at 15 years, in adults 61.3% at 5 years, and in patients with CML 55.5% at 15 years without difference between reduced intensity condition (RIC) and myeloablative conditioning (MAC). Patients with Ph+ ALL had the lowest survival reaching 26.7% at 5 years. Highest survival was observed in patients with aplastic anemia, Fanconi anemia, and thalassemia reaching 77.3%, 73.5%, and 75.7% at 15 years respectively. Long distances and late referral remain a challenge for this large country.

Autosomal recessive agammaglobulinemia (ARA) is a primary immunodeficiency characterized by absent peripheral B cells, severe hypogammaglobulinemia, and absent BTK gene mutations. In ARA, mutations occur in genes encoding the pre-B cell receptor (pre-BCR) or downstream signaling proteins. In this work, we used candidate gene and whole-exome sequencing to investigate the molecular basis of ARA in 6 patients from 4 consanguineous North-African families. Sanger sequencing of candidate genes encoding the pre-BCR components (ΙGΗΜ, CD79A, CD79B, IGLL1, and VPREB1) was initially performed and determined the genetic defect in five patients. Two novel mutations in IGHM (p.Val378Alafs*1 and p.Ile184Serfs*21) were identified in three patients from two unrelated kindred and a novel nonsense mutation was identified in CD79A (p.Trp66*) in two siblings from a third kindred. Whole-exome sequencing (WES) was performed on the sixth patient who harbored a homozygous stop mutation at position 407 in the RAG2 gene (p.Glu407*). We concluded that conventional gene sequencing, especially when multiple genes are involved in the defect as is the case in ARA, is costly and time-consuming, resulting in delayed diagnosis that contributes to increased morbidity and mortality. In addition, it fails to identify the involvement of novel and unsuspected gene defects when the phenotype of the patients is atypical. WES has the potential to provide a rapid and more accurate genetic diagnosis in ARA, which is crucial for the treatment of the patients.

The discovery of a hydatid cyst at autopsy poses the problem of its involvement in the mechanism of death. The aim of this study is to analyse the epidemiological and etiopathogenic characteristics of death attributed to hydatid disease, to discuss the mechanism of death and to propose preventive measures. This is a retrospective descriptive study of 26 cases of death with hydatid cyst autopsic discovered, collected at the forensic department of Fattouma Bourguiba University Hospital of Monastir (Tunisia) over a period of 27 years (from 1990 until 2017). In 26 cases, hydatid cyst was observed during autopsy of sudden death cases, which corresponds to 0.33% of the total of autopsies in this period. Of the 26 victims, 13 (50%) were men; the mean age was 43 years. Most victims were from rural zones (18 cases). In 20 cases, the complicated cyst was hepatic. It was cardiac in two cases. Of all cases, three cysts were cracked, and nine were broken. Of the 26 cases, only 15 were implicated in the death mechanism. Death was attributed to anaphylaxis in 12 cases, hydatid pulmonary embolism in 1 case, cardiac arythmia in one case and hemothorax in one case. Sudden death is the most dangerous complication of the hydatid cyst which can be discovered at autopsy. Several causes may explain its occurrence, the most common of which is anaphylactic shock.

The risk of venous thromboembolism (VTE) is higher in myeloma patients receiving immunomodulatory compounds. A VTE prophylaxis using low-molecular-weight heparin or aspirin is therefore proposed. Apixaban is an oral direct anti-Xa. Several studies have shown the efficacy and safety of apixaban in VTE prophylaxis compared to enoxaparin. The objective of this prospective phase 2 pilot study was to assess the risk of VTE and bleeding in patients with myeloma treated with immunomodulatory compounds lenalidomide (len) or thalidomide (thal), using apixaban in a preventive scheme. Myeloma patients requiring Melphalan-Prednisone-Thalidomide in the first line, or Lenalidomide-Dexamethasone in the relapse setting received apixaban, 2.5 mg x 2/day for 6 months. Venous (pulmonary embolism-PE, or symptomatic proximal or distal deep vein thrombosis-DVT, or all proximal asymptomatic events detected by systematic proximal bilateral compression ultrasound) or arterial thrombotic events, and bleeding events (ISTH 2005) were registered. One hundred and four patients were enrolled (mean age 69.8 ± 7.8 years), 11 in first line and 93 in relapse. Two venous thrombotic events were observed, for example, an asymptomatic proximal DVT and a symptomatic distal DVT, in the context of apixaban stopped 14 days before, due to lenalidomide-induced thrombocytopenia. No PE or arterial cardiovascular events were reported. Only one major and 11 CRNM hemorrhages were reported. These data must now be confirmed on a randomized large study.

Individuals with Lynch syndrome (LS), have an increased risk of developing cancer. Common genetic variants of telomerase reverse transcriptase (TERT) have been associated with a wide range of cancers, including colorectal cancer (CRC) in LS. We combined genotype data from 1881 LS patients, carrying pathogenic variants in MLH1, MSH2 or MSH6, for rs2075786 (G>A, intronic variant), 1207 LS patients for rs2736108 (C>T, upstream variant) and 1201 LS patients for rs7705526 (C>A, intronic variant). The risk of cancer was estimated by heterozygous/homozygous odds ratio (OR) with mixed-effects logistic regression to adjust for gene/gender/country of sample origin considering family identity. The AA genotype of SNP rs2075786 is associated with 85% higher odds at developing cancer compared to GG genotype in MSH2 pathogenic variant carriers (p = 0.0160). Kaplan–Meier analysis also shows an association for rs2075786; the AA allele for MSH2 variant carriers confers risk for earlier diagnosis of LS cancer (log-rank p = 0.0011). We report a polymorphism in TERT to be a possible modifier of disease risk in MSH2 pathogenic variant carriers. The rs2075786 SNP in TERT is associated with a differential risk of developing cancer for MSH2 pathogenic variant carriers. Use of this information has the potential to personalise screening protocols for LS patients.

ObjectivesTo evaluate the diagnostic and predictive contribution of autoantibodies screening in patients with primary immunodeficiencies (PIDs).MethodsIn the present study, PID patients and healthy controls have been screened for 54 different autoantibodies. The results of autoantibodies screening in PID patients were correlated to the presence of autoimmune diseases.ResultsA total of 299 PID patients were included in this study with a predominance of antibody deficiencies (27.8%) followed by immunodeficiencies affecting cellular and humoral immunity (26.1%) and complement deficiencies (22.7%). Autoimmune manifestations were present in 82 (27.4%) patients. Autoimmune cytopenia (10.4%) was the most common autoimmune disease followed by gastrointestinal disorders (10.0%), rheumatologic diseases (3.7%), and endocrine disorders (3.3%). Autoantibodies were found in 32.4% of PID patients and 15.8% of healthy controls (P < 0.0005). Anti-nuclear antibodies (ANA) (10.0%), transglutaminase antibody (TGA) (8.4%), RBC antibodies (6.7%), anti-smooth muscle antibody (ASMA) (5.4%), and ASCA (5.0%) were the most common autoantibodies in our series. Sixty-seven out of the 82 patients with autoimmune manifestations (81.7%) were positive for one or more autoantibodies. Eleven out of the 14 patients (78.6%) with immune thrombocytopenia had positive platelet-bound IgM. The frequencies of ASCA and ANCA among patients with IBD were 47.4% and 21.0% respectively. All patients with celiac disease had TGA-IgA, while six out of the 11 patients with rheumatologic diseases had ANA (54.5%). Almost one third of patients (30/97) with positive autoantibodies had no autoimmune manifestations. ANA, rheumatoid factor, ASMA, anti-phospholipid antibodies and ANCA were often detected while specific AID was absent. Despite the low positive predictive value of TGA-IgA and ASCA for celiac disease and inflammatory bowel disease respectively, screening for these antibodies identified undiagnosed disease in four patients with positive TGA-IgA and two others with positive ASCA.ConclusionThe present study provides valuable information about the frequency and the diagnostic/predictive value of a large panel of autoantibodies in PIDs. Given the frequent association of some AIDs with certain PIDs, screening for corresponding autoantibodies would be recommended. However, positivity for autoantibodies should be interpreted with caution in patients with PIDs due to their low positive predictive value.

The preterm birth represents a stressful situation that can lead to questions about the survival of the child and the possible consequences.To examine the interactions between mothers and premature babies in the neonatal care unit (NCU) and assess the psychological state of the mothers.Cross-sectional study conducted from March to May 2017 in the Department of Pediatrics and Neonatology of the Mongi Slim Hospital (Tunis, Tunisia). Ten mothers of premature babies hospitalized in NCU were involved and responded to the Postpartum Bonding Questionnaire (PBQ), the Edinburgh Postnatal Depression Scale (EPDS) (cut off≥10) and the Hospital Anxiety and Depression Scale (HADS).The mean age of the mothers was 31 years. A personal history of depression was found in two mothers. The current pregnancy was not desired in three cases, two corresponded to mothers with a history of depression. According to interactions, the median PBQ score was 11. The EPDS median score was six; four mothers had a score greater than 10. A high level on the anxiety sub-scale of the HADS was found in the two mothers who had a personal psychiatric history. The more depressed or anxious the mothers were, the higher the interaction scores (p = 0.012 and p = 0.032, respectively).Preterm birth seems to affect the psychological state of mothers and their interactions with their baby.

The aim of this study was to estimate the incidence of COVID-19 disease in the French national population of dialysis patients, their course of illness and to identify the risk factors associated with mortality. Our study included all patients on dialysis recorded in the French REIN Registry in April 2020. Clinical characteristics at last follow-up and the evolution of COVID-19 illness severity over time were recorded for diagnosed cases (either suspicious clinical symptoms, characteristic signs on the chest scan or a positive reverse transcription polymerase chain reaction) for SARS-CoV-2. A total of 1,621 infected patients were reported on the REIN registry from March 16th, 2020 to May 4th, 2020. Of these, 344 died. The prevalence of COVID-19 patients varied from less than 1% to 10% between regions. The probability of being a case was higher in males, patients with diabetes, those in need of assistance for transfer or treated at a self-care unit. Dialysis at home was associated with a lower probability of being infected as was being a smoker, a former smoker, having an active malignancy, or peripheral vascular disease. Mortality in diagnosed cases (21%) was associated with the same causes as in the general population. Higher age, hypoalbuminemia and the presence of an ischemic heart disease were statistically independently associated with a higher risk of death. Being treated at a selfcare unit was associated with a lower risk. Thus, our study showed a relatively low frequency of COVID-19 among dialysis patients contrary to what might have been assumed., Graphical abstract

Objective To review the relevant literature on abortion and summarize interviews with key stakeholders to assess the role of midwives in the evolution of abortion‐related care in Tunisia. Methods Interviews with eight stakeholders from different organizations based on a guide developed for the study, focusing on policies, strategies used for implementation, capacities used for expansion, user opinions and experience, obstacles and facilitators, and control and evaluation. Results Task‐sharing for midwifes was encouraged in the family planning program from the beginning and when medical abortion was introduced. It allows midwifes to contribute widely, develop good skills and performance for several tasks, and helps reduce regional disparities in human resource allocation. Success and safety of home use of medical abortion confirms the ability of women to manage their own abortion. Yet, obstacles to accessing abortion still exist for several reasons. Conclusion This study, based on interviews with personnel with significant experience and solid knowledge of sexual and reproductive health services, allowed us to consider proposals for a future strategy to integrate task‐sharing into abortion care and address the barriers to legal and safe abortion access for all women in Tunisia., Synopsis Task‐sharing of abortion care with midwives has a positive impact on quality of services and addresses barriers to accessing abortion in Tunisia.

Algeria is the largest country in Africa, located close to the Mediterranean coastal area, where nutrients consumption varies widely. Local data on selenium composition of foods are not available. We postulated a close correlation between selenium status predictions from food consumption analysis with a quantitative analysis of circulating biomarkers of selenium status. Population characteristics were recorded from 158 participants and dietary selenium intake was calculated by 24-h recall. The average total plasma selenium was 92.4 &plusmn, 18.5 &micro, g/L and the mean of selenium intake was 62.7 &micro, g/day. The selenoprotein P concentration was 5.5 &plusmn, 2.0 mg/L and glutathione peroxidase 3 activity was 247.3 &plusmn, 41.5 U/L. A direct comparison of the dietary-derived selenium status to the circulating selenium biomarkers showed no significant interrelation. Based on absolute intakes of meat, potato and eggs, a model was deduced that outperforms the intake composition-based prediction from all food components significantly (DeLong&rsquo, s test, p = 0.029), yielding an area under the curve of 82%. Selenium status prediction from food intake remains a challenge. Imprecision of survey method or information on nutrient composition makes extrapolating selenium intake from food data providing incorrect insights into the nutritional status of a given population, and laboratory analyses are needed for reliable information.

Background: Healthcare workers are at a high risk of developing Occupational Dermatitis (OD). Affected workers often experience severe impairment of their Quality of Life (QoL). This study aimed to assess the skin-related QoL of healthcare workers with OD and to explore its related factors. Methods: A cross-sectional and exhaustive study was conducted among healthcare personnel of four public hospitals in the central region of Tunisia. All the cases of OD declared were included. Skin-related QoL was assessed using the validated Tunisian version of the “Dermatology Life Quality Index” (DLQI). Some related patents have also been discussed. Results: A total of 37 cases of OD were collected with an annual incidence of 4.2 cases per 10000 workers. The population was predominantly female (73%) and the mean age was 44.7±9.4 years. Nurses were the most represented occupational category (38%). Allergic contact dermatitis was the most frequent diagnosis (96%). The use of gloves was the most frequently reported occupational hazard (86%). The most frequently affected sites were hands (97%). The median score of DLQI was five. Multivariate analysis showed an association between the impairment of skin-related QoL and female gender (p = 0.04; OR = 19.3,84), exposure to disinfecting chemicals in the workplace (p = 0.01; OR = 17,306) and the absence of occupational reclassification (p = 0.01; OR = 21,567). Conclusion: About one-third of the population had an impaired quality of life. The score impairment was significantly related to the female gender, exposure to disinfecting chemicals and the absence of occupational reclassification.

Despite tremendous improvements in the outcome of patients with multiple myeloma in the past decade, high-risk patients have not benefited from the approval of novel drugs. The most important prognostic factor is the loss of parts of the short arm of chromosome 17, known as deletion 17p (del(17p)). A recent publication (on a small number of patients) suggested that these patients are at very high-risk only if del(17p) is associated with TP53 mutations, the so-called “double-hit” population. To validate this finding, we designed a much larger study on 121 patients presenting del(17p) in > 55% of their plasma cells, and homogeneously treated by an intensive approach. For these 121 patients, we performed deep next generation sequencing targeted on TP53. The outcome was then compared with a large control population (2505 patients lacking del(17p)). Our results confirmed that the “double hit” situation is the worst (median survival = 36 months), but that del(17p) alone also confers a poor outcome compared with the control cohort (median survival = 52.8 months vs 152.2 months, respectively). In conclusion, our study clearly confirms the extremely poor outcome of patients displaying “double hit," but also that del(17p) alone is still a very high-risk feature, confirming its value as a prognostic indicator for poor outcome.

PURPOSE We report a multicenter controlled trial comparing renal recovery and tolerance profile of doublet versus triplet bortezomib-based regimens in patients with initial myeloma cast nephropathy (CN) and acute kidney injury (AKI) without need for dialysis. METHODS After symptomatic measures and high-dose dexamethasone, patients were randomly assigned to receive bortezomib plus dexamethasone (BD), or BD plus cyclophosphamide (C-BD). In patients with < 50% reduction of serum free light chains (sFLCs) after 3 cycles, chemotherapy was reinforced with either cyclophosphamide (BD group) or thalidomide (C-BD group). RESULTS Ninety-two patients were enrolled in each group. At random assignment, characteristics of the 2 groups were similar, including median age (68 years) and serum creatinine level (305.5 and 273.5 µmol/L in BD and C-BD group, respectively). At 3 months, renal response rate (primary end point) was not different (41 v 47 responders in the BD and C-BD groups, respectively; relative risk [RR], 0.87; P = .46). Very good partial response (free light chain reduction ≥ 90%) or more was achieved in 36 and 47 patients, respectively (RR, 0.76; P = .10). After 1 cycle of chemotherapy, 69 in the BD group and 67 patients in the C-BD group had achieved sFLC level ≤ 500 mg/L. Serious adverse events were recorded in 30 and 40 patients, respectively. At 12 months, 19 patients had died (9 in the BD group v 10 in the C-BD group), including 10 (6 in the BD group and 4 in the C-BD group) from myeloma progression and 3 (0 in the BD group and 3 in the C-BD group) from infection. Within median follow-up of 27 months, 43 and 42 patients switched to new therapy, respectively. Overall, 50 patients (24 in the BD group and 26 in the C-BD group) had died. CONCLUSION This randomized study did not show any benefit of C-BD compared with BD on renal recovery of patients with initial CN not requiring dialysis. Adding cyclophosphamide did not sufficiently improve the efficacy-toxicity balance. Patients with myeloma with AKI are fragile, and indication for doublet or triplet regimen should be adapted to frailty.

Objectives To assess the location of intravesical recurrence (IVR) after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC), to determine the main predictive factors for IVR in the bladder-cuff area (BCA), and to assess the effect of BCA recurrence (BCAR) on prognosis. Patients and methods This was a multicentre, retrospective study using the French collaborative database on UTUC, which includes data for all patients treated in 24 referral uro-oncology centres across the country. All patients who underwent RNU with bladder-cuff excision and who developed IVR between 1995 and 2010 were selected. Patients were divided into two groups: Group A: BCAR; and Group B: recurrence elsewhere in the bladder. The Kaplan-Meier method was used to estimate the probability of BCAR-free survival. Groups were compared using the log-rank test. Independent risk factors for BCAR were identified using a Cox proportional hazard regression model, with univariate and multivariate analyses. Results Overall, 163 patients were included in the final analysis: Group A, 87 patients (53.4%) and Group B, 76 (46.6%). The clinicopathological characteristics were similar in the groups. The median (interquartile range [IQR]) follow-up was 36 (31.7-40.39) months. The median (IQR) time to IVR was 10.0 (8.6-13.39) months [Group A: 11.0 (8.8-13.2) months vs Group B: 10.0 (8.5-11.5) months; P = 0.35]. The probability of BCAR at 1, 2, and 3 years was 45.5% (95% confidence interval [CI] 40.1-50.9), 17.9% (95% CI 13.7-22.1), and 10.8% (95% CI 7.4-14.2) respectively, whereas the probability of recurrence elsewhere in the bladder was 42.1% (95% CI 36.4-47.8), 14.7% (95% CI 10.6-18.8), and 4.4% (95% CI 1.9-6.9), respectively (P = 0.35). Pathological tumour stage (≥pT3) was significantly related to the risk of BCAR (P = 0.03). Conclusion There were more BCARs after RNU in advanced UTUC. However, no preferred site for recurrence was detected.

Explore the relationship between the recalled bond of pregnant women to their own mothers and the development of prenatal attachment.Women with a single-fetal pregnancy who consulted the outpatient service of the maternity "C" ward of the center of maternity and neonatology of Tunis and had perceived fetal movements were included. Maternal-fetal attachment was assessed by the Prenatal Attachment Inventory (PAI), and the Parental Bonding Instrument (PBI) was used to evaluate experienced bond to mother. Socio demographic and clinical data were collected on a pre-established form.Eighty respondents were retained from 95 recruited pregnant women. Their ages ranged from 19 to 44 with an average of 32 years. The rate of primiparity was of 28.7 % and half of pregnancies were identified at risk. The mean score of PAI was 55.3 (ET=10.79). Means scores of PBI "care" dimension and "overprotection" dimension were respectively of 26.26 (ET=5.82) and 17 (ET=6.38). The four types of maternal bonding according to the PBI scores were distributed as follow: affectionate constraint (31.3 %), affectionless control (35 %), optimal bonding (21.3 %) and weak bonding (12.5 %). The two PBI dimensions "care" and "overprotection" were significantly and negatively correlated (P0.05). The PAI scores were not correlated with the PBI "care" dimension scores but were significantly and negatively correlated with the "overprotection" dimension scores (P0.,01). In order to better explore this association, the "overprotection" dimension scores were studied according to the 21 items of the PAI. A negative and significant correlation was found only with three of the PAI items: item 12 (P0;01), 15, and 20 (P0;05).Our findings suggest that pregnant women whose mothers showed more overprotective and controlling behaviors could be at risk of developing a weak maternofetal attachment. Further research is needed.

IF 15.132 (2017); International audience; The introduction of novel agents has led to major improvements in clinical outcomes for patients with multiple myeloma. To shorten evaluation times for new treatments, health agencies are currently examining minimal residual disease (MRD) as a surrogate end point in clinical trials. We assessed the prognostic value of MRD, measured during maintenance therapy by next-generation sequencing (NGS). MRD negativity was defined as the absence of tumor plasma cell within 1 000 000 bone marrow cells (

Purpose To analyze the frequency and distribution of low-signal-intensity regions (LSIRs) in lymphoma lesions and to compare these to fluorodeoxyglucose (FDG) uptake and biologic markers of inflammation. Materials and Methods The authors analyzed 61 untreated patients with a bulky lymphoma (at least one tumor mass ≥7 cm in diameter). When a LSIR within tumor lesions was detected on diffusion-weighted images obtained with a b value of 50 sec/mm

Summary Objective To determine epidemiological, clinical and mycological characteristics of vulvovaginal candidiasis (VVC) in Tunisian population and to evaluate predisposing factors. Patients and methods In this retrospective study, 2160 vaginal swabs were performed over 2 years (January 2014–December 2015). It was carried out at the laboratory of Parasitology and Mycology, Rabta Hospital in Tunisia. After swab collecting, direct examination and culture on Sabouraud Chloramphenicol and Sabouraud Chloramphenicol Actidione media were implemented to research yeasts. Then identifying of yeast species was through chlamydosporulation test and auxanogram. For each patient, a questionnaire was filled noting age, medical and surgical history, symptoms and risk factors. Statistical analysis of data was performed on SPSS 16 using Khi 2 test, P Results Direct examination was positive showed spore and/or pseudohypha in 24.72%. Candida albicans was isolated most frequently (76.61%) followed by Candida glabrata (17.18%). The maximum frequency of Candida-positive cultures was in 25–34 years old age group. Leucorrhea was the most common symptom (72.25%) followed by vulvar prurits (63.23%), dyspareunia (32.25%) and urinary burning (24.92%). Only pregnancy was correlated positively with VVC. Conclusion It appears from our study that VVC is relatively common in Tunisia. His diagnosis results from confrontation of anamnestic, clinical and mycological data. The knowledge of risk factors and their correction would be necessary to prevent the occurrence of VVC, especially in its recurrent form.

Chemotherapy combining cyclophosphamide, bortezomib and dexamethasone is widely used in light-chain amyloidosis. The benefit is limited in patients with cardiac amyloidosis mainly because of adverse cardiac events. Retrospective analysis of our cohort showed that 39 patients died with 42% during the first month. A new escalation-sequential regimen was set to improve the outcomes. Nine newly-diagnosed patients were prospectively treated with close monitoring of serum N-terminal pro-brain natriuretic peptide, troponin-T and free light chains. The results show that corticoids may destabilise the heart through fluid retention. Thus, a sequential protocol may be a promising approach to treat these patients.

International audience; Measurable residual disease (MRD) status is widely adopted in clinical trials in patients with chronic lymphocytic leukemia (CLL). Findings from FILO group trials (CLL2007FMP, CLL2007SA, CLL2010FMP) enabled investigation of the prognostic value of high-sensitivity (0.7 × 10-5) MRD assessment using flow cytometry, in blood (N = 401) and bone marrow (N = 339), after fludarabine, cyclophosphamide, and rituximab (FCR)-based chemoimmunotherapy in a homogeneous population with long follow-up (median 49.5 months). Addition of low-level positive MRD

Child sexual abuse is a major health problem that remains under-declared and under-reported worldwide. In this paper we have taken an interest in establishing the profile of the victims in a clinical population of children consulting for sexual abuse.We conducted a descriptive retrospective study in the child and teenager psychiatry department of the Mongi-Slim hospital (Tunis, Tunisia). We included all patients referred for treatment or medical expertise during the period from January 2013 to June 2019 and recorded sociodemographic data and clinical characteristics on pre-established charts from patient files.The total number of consultants was 150 patients with 61,33 % of female subjects (n=92). The average age was 9,9 years old with extremes ranging from 2 to 18 years old. The assault was unique in 62,7 % and happened in a place known by the victim in 47,33 %. Sexual abuse with non-penetrating contact was the most frequent (48 %). The average age at which the first sexual abuse happened was 9 years old. In the vast majority of cases, the abuser was a male. Concerning the identity of the abuser, he was someone of the family in 37,3 % of the cases and in half of these cases, he was the father. In the other cases where the abuser wasn't a family member, the identity was known by the child and/or his family in 48,66 %. A psychiatric diagnosis was made in 58 % of the cases with a percentage of 52,1 % among girls and 60,3 % among boys. Main diagnoses were acute stress disorder in 10,6 %, post trauma stress disorder in 19,3 %, adjustment disorder in14,6 % and a major depressive disorder in 8 %.Knowing the profile of victims of child sexual abuse and taking into consideration the social and psychiatric impact can help in adapting the means to intervene properly in order to take care of the victims and prevent such abuse.

Background & Aims A significant proportion of colorectal cancer (CRC) cases have familial aggregation but little is known about the genetic factors that contribute to these cases. We performed an exhaustive functional characterization of genetic variants associated with familial CRC. Methods We performed whole-exome sequencing analyses of 75 patients from 40 families with a history of CRC (including early-onset cases) of an unknown germline basis (discovery cohort). We also sequenced specific genes in DNA from an external replication cohort of 473 families, including 488 patients with colorectal tumors that had normal expression of mismatch repair proteins (validation cohort). We disrupted the Fas-associated factor 1 gene (FAF1) in DLD-1 CRC cells using CRISPR/Cas9 gene editing; some cells were transfected with plasmids that express FAF1 missense variants. Cells were analyzed by immunoblots, quantitative real-time polymerase chain reaction, and functional assays monitoring apoptosis, proliferation, and assays for Wnt signaling or nuclear factor (NF)-kappa-B activity. Results We identified predicted pathogenic variant in the FAF1 gene (c.1111G>A; p.Asp371Asn) in the discovery cohort; it was present in 4 patients of the same family. We identified a second variant in FAF1 in the validation cohort (c.254G>C; p.Arg85Pro). Both variants encoded unstable FAF1 proteins. Expression of these variants in CRC cells caused them to become resistant to apoptosis, accumulate beta-catenin in the cytoplasm, and translocate NF-kappa-B to the nucleus. Conclusions In whole-exome sequencing analyses of patients from families with a history of CRC, we identified variants in FAF1 that associate with development of CRC. These variants encode unstable forms of FAF1 that increase resistance of CRC cells to apoptosis and increase activity of beta-catenin and NF-kappa-B.

Sudden cardiac death in young is seen as a dramatic phenomenon requiring knowledge of its impact. We aim to study the epidemiological characteristics of sudden cardiac ischemic death in young, and to discuss his involvement in the occurrence of death. We performed a retrospective cohort study using autopsy data from the department of forensic medicine of the University Hospital of Fattouma Bourguiba, Monastir-Tunisia. A review of all autopsies performed during 23 years was done. In each case, clinical information and circumstances of death were obtained. We have included all sudden death in persons aged between 1 year and 35 years for the male and from one year to 45 years for female. We collected 312 cases of sudden death during the studied period. The collected data were processed using SPSS 20. The significance level was set at 0.05. Thirty-two cases of cardiac ischemic sudden death have been collected. Myocardial infarction was the second cause of sudden death in young patients. There was a male predominance. The most affected subjects were aged between 25-45 years. The death occurred more frequently at rest. Coronary artery disease has been discovered in twenty-four cases (75%). The myocardial infarction occurred on healthy coronary arteries in eight cases. An anomalous course of coronary arteries, in particular myocardial bridging, was found in eight cases (25%). Toxicological screening was negative in all cases. Identifying epidemiological characteristics of sudden cardiac ischemic death in this population is important for guiding approaches to prevention that must be based on dietary hygienic measures and the control of cardiovascular risk factors.

Luminal B breast cancer is associated with a poor prognosis and resistance to hormone therapy. Studies have suggested that Ras-related protein 25 (RAB25), a member of Rab small GTPase family, is involved in breast cancer pathogenesis. Our aim in the present study is to analyze the association between RAB25 protein expression and clinical and pathological characteristics, and to investigate whether the expression of RAB25 was associated with a specific molecular subtype of breast cancer.A retrospective study was conducted regarding female patients diagnosed with breast cancer; clinicopathologic data was obtained from medical reports. RAB25 expression was evaluated by immunohistochemistry in 57 primary breast cancer samples. The results were correlated with clinicopathologic variables and different breast cancer molecular subtypes.RAB25 expression was significantly associated with tumors expressing oestrogen receptor (P=0.03). A high significant difference was observed by analyzing RAB25 expression in various breast cancer subtypes (P=0.01). RAB25 expression was found in 66.7% of Luminal B breast tumors, considered as the most aggressive hormone dependent mammary tumors and was strongly associated with luminal breast cancer subtypes (p=0.004) but not with age, tumor size, SBR grade, axillary lymph node, or tumor stage.RAB25 deregulated expression is most common in luminal B breast cancer tumors suggesting that RAB25 could be a potential therapeutic target for this molecular subtype.

Carfilzomib is a novel generation proteasome inhibitor. The Carmysap trial demonstrated that twice-weekly KMP (carfilzomib, melphalan, prednisone) might challenge the MPV (melphalan, prednisone, bortezomib) standard. We sought to study KMP weekly, allowing to increase carfilzomib's dose with maintained efficacy and improved safety profile., info:eu-repo/semantics/published

PURPOSE The wide heterogeneity in multiple myeloma (MM) outcome is driven mainly by cytogenetic abnormalities. The current definition of high-risk profile is restrictive and oversimplified. To adapt MM treatment to risk, we need to better define a cytogenetic risk classification. To address this issue, we simultaneously examined the prognostic impact of del(17p); t(4;14); del(1p32); 1q21 gain; and trisomies 3, 5, and 21 in a cohort of newly diagnosed patients with MM. METHODS Data were obtained from 1,635 patients enrolled in four trials implemented by the Intergroupe Francophone du Myélome. The oldest collection of data were used for model development and internal validation. For external validation, one of the two independent data sets was used to assess the performance of the model in patients treated with more current regimens. Six cytogenetic abnormalities were identified as clinically relevant, and a prognostic index (PI) that was based on the parameter estimates of the multivariable Cox model was computed for all patients. RESULTS In all data sets, a higher PI was consistently associated with a poor survival outcome. Dependent on the validation cohorts used, hazard ratios for patients in the high-risk category for death were between six and 15 times higher than those of patients in the low-risk category. Among patients with t(4;14) or del(17p), we observed a worse survival in those classified in the high-risk category than in those in the intermediate-risk category. The PI showed good performance for discriminating between patients who died and those who survived (Harrell’s concordance index greater than 70%). CONCLUSION The cytogenetic PI improves the classification of newly diagnosed patients with MM in the high-risk group compared with current classifications. These findings may facilitate the development of risk-adapted treatment strategies.

Objective Our study aimed to measure the health-related quality of life (QoL) of Tunisian children and adolescents with type 1 diabetes mellitus (T1MD). Methods This cross-sectional study included 48 patients aged 3–18 years with T1MD, diagnosed for at least 6 months, and their parents, who underwent outpatient examinations from September to December 2018. The children's QoL was assessed using the PedQL 3.0 Diabetes Module exploring five dimensions: diabetes symptoms, treatment barriers, treatment adherence, worry, and communication problems. Parents shared their perception of their children's QoL through the PedQL 4.0 parents’ report (general health and emotional, social, and scholar functioning). Glycemic control was assessed using the last glycated haemoglobin (HbA1c) values. Results The patients’ average QoL score was 80.52 (± 13.61) without significant differences between gender and age. The longer the duration of the disease, the worse the glycemic control. Girls and adolescents seemed to have poorer glycemic control. Boys and adolescents had more difficulties in all aspects of QoL. Parents perceived a worse QoL than that reported by their sons/daughters (72.34 ± 16.42; P = 0.006). Conclusion These findings emphasize the importance of an interdisciplinary, biopsychosocial, and family-centered care approach to patients with T1MD.

Although psychopathy and its predictive factors are well documented in clinical samples, studies in non-clinical populations are relatively rare. We proposed to assess psychopathy traits in a population of Tunisian university students and to analyze their predictive factors.This was a cross-sectional study of 516 university students enrolled at three major Tunisian universities (Faculty of Humanities and Social Sciences of Tunis, National Engineering School of Tunis, Faculty of Medicine of Tunis). Participants responded to a survey sheet containing sociodemographic data and the Levenson Self-Report Psychopathy Scale.The students were female in 63.2 % of the cases, with a mean age of 22.7years. The socio-economic level was middle class in 62.4% of the cases. More than one-quarter of students (26.7%) consumed tobacco. The majority of students (81.4%) spent their free time on the Internet, while 11.8% participated in associative work. Psychopathy scores were relatively high (mean LSRPS scores=64.8) with no noticeable gender differences. Psychopathic traits were significantly associated with university (P=0.017), maternal occupational status (P=0.038), and tobacco use (P=0.029). In addition, the total psychopathy score was significantly lower among students sharing activities with their families (P=0.044) and among students participating in associational work (P=0.025). The multivariate multiple regression has retained as predictive factors of psychopathic traits the fact of being the eldest of his siblings and the associative work.Prevention strategies should be put in place to prevent psychopathy and its individual and social impacts in young adults in general, and in university students in particular, especially promoting associative activity in the university environment which is currently lacking in our context.

Introduction: les conduites suicidaires sont en augmentation en Tunisie et touchent une population de plus en plus jeune. Le but de notre etude etait de decrire le profil sociodemographique et clinique des tentatives de suicide chez l'enfant et l'adolescent. Methodes: cette etude etait transversale et descriptive, incluant 50 suicidants, recrutes au service de pedopsychiatrie de l'Hopital Razi de la Manouba et dans deux services de reanimation et de pediatrie de Tunis, entre juillet 2012 et juin 2013. Ont ete releves les facteurs sociodemographiques et cliniques, les antecedents de maltraitance, la scolarite, les caracteristiques de la TS, l'intentionnalite suicidaire evaluee par le Suicide Intent Scale, et les troubles psychopathologiques a l'aide du Mini-International Neuropsychiatric Interview. Resultats: le sex-ratio etait de 0,56, la moyenne d'âge etait de 12,4 ans avec des extremes de 7 a 16 ans. Un echec ou un flechissement scolaire a concerne 86% des suicidants. Dans 38% des cas il s'agissait de recidive; des antecedents d'automutilations ont ete retrouves dans les memes proportions. Un contexte de maltraitance a ete signale dans 46% des cas. L'ingestion medicamenteuse etait le moyen le plus frequent, les psychotropes etant les plus representes. Une difference significative entre le genre a ete retrouvee dans le recours aux moyens suicidaires, ainsi les garcons ont eu davantage recours aux moyens physiques (p=0,04) et les filles aux intoxications (p=0,001). L'intentionnalite suicidaire etait elevee dans 44%. Un episode depressif majeur et le trouble de l'adaptation etaient les troubles les plus frequemment retrouves dans respectivement 58% et 24% des cas. Conclusion: les troubles depressifs et la maltraitance se degagent comme des facteurs de risque des TS chez les enfants et les adolescents, ces facteurs doivent etre pris en consideration dans les strategies de prevention du suicide dans cette population.

Summary Mechanical signals from the tumor microenvironment modulate cell mechanics and influence cell metabolism to promote cancer aggressiveness. Cells withstand external forces by adjusting the stiffness of their cytoskeleton. Microtubules (MTs) act as compression-bearing elements. Yet how cancer cells regulate MT dynamic in response to the locally constrained environment has remained unclear. Using breast cancer as a model of a disease in which mechanical signaling promotes disease progression, we show that matrix stiffening rewires glutamine metabolism to promote MT glutamylation and force MT stabilization, thereby promoting cell invasion. Pharmacologic inhibition of glutamine metabolism decreased MT glutamylation and affected their mechanical stabilization. Similarly, decreased MT glutamylation by overexpressing tubulin mutants lacking glutamylation site(s) decreased MT stability, thereby hampering cancer aggressiveness in vitro and in vivo. Together, our results decipher part of the enigmatic tubulin code that coordinates the fine-tunable properties of MT and link cell metabolism to MT dynamics and cancer aggressiveness.

Acinetobacter baumannii is an emerging threat in healthcare facilities owing to its ability to be multidrug-resistant (MDR) and to be involved in outbreaks. GES-type extended-spectrum β-lactamases (ESBLs) have been increasingly identified in A. baumannii. In this study, clinical A. baumannii isolates were characterised using standard biochemical methods and antibiotic susceptibility testing. Antibiotic resistance genes were sought by PCR and sequencing. Genetic support was characterised using S1 nuclease pulsed-field gel electrophoresis (PFGE) mapping, conjugation and electroporation assays. The genetic environment was investigated by PCR, and genetic relatedness was investigated by PFGE. Two MDR A. baumannii clinical isolates susceptible only to colistin and rifampicin were isolated from a tracheal aspirate of a 49-year-old woman hospitalised in 2006 at the Military Hospital of Tunis, Tunisia, and from a tracheal aspirate of a 53-year-old man hospitalised in 2010 at the Institut Orthopédique Mohamed El Kassab of Tunis, Tunisia. PCR revealed that the two isolates harboured the acquired carbapenemase blaOXA-23 and ESBL blaGES-11 genes along with chromosomally-encoded blaOXA-51 and blaADC-like genes. PFGE revealed that these A. baumannii isolates were unrelated; nevertheless, plasmid analysis revealed a similar sized plasmid following electrophoresis of the isolates. In addition, A. baumannii CIP70.10 transformants displayed similar resistance patterns. blaGES-11 was integron-borne and the ISAbaI element was identified upstream of blaOXA-23 and blaADC-like. Here we described two unrelated clinical A. baumannii isolates producing GES-11 ESBL and OXA-23 carbapenemase from two Tunisian hospitals. This work further illustrates the emergence of GES-type β-lactamases in A. baumannii in North Africa as early as 2006.

The purpose of this study was to develop a model system for targeted drug delivery. This system should enable targeted drug release at a certain tissue in the body. In conventional drug delivery systems, drugs are often delivered unspecifically resulting in unwarranted adverse effects. To circumvent this problem, there is an increasing demand for the development of intelligent drug delivery systems allowing a tissue-specific mode of delivery. Within this study, nanoparticles consisting of two biocompatible polymers are used. Because of their small size, nanoparticles are well-suited for effective drug delivery. The small size affects their movement through cell and tissue barriers. Their cellular uptake is easier when compared to larger drug delivery systems. Paclitaxel was encapsulated into the nanoparticles as a model drug, and to achieve specific targeting an aptamer directed against lung cancer cells was coupled to the nanoparticles surface. Nanoparticles were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), fourier transform infrared spectroscopy (FTIR), and nanotracking analysis (NTA). Also their surface charge was characterized from ζ-potential measurements. Their preparation was optimized and subsequently specificity of drug-loaded and aptamer-functionalized nanoparticles was investigated using lung cancer cells.

Background and study aims Colonoscopy remains the gold standard for the examination of the colon. However, its use in the elderly is not well tolerated, and there is often a need for general anaesthesia , thus increasing the risk, especially if there are co-morbidities. Water enema computed tomography has been suggested to be a satisfactory alternative as a non-invasive, fast and effective means for the diagnosis of colorectal supra-centimetric lesions. The aim of our study was to assess the performance of water enema computed tomography as first-line examination by calculating its negative predictive value (NPV) for the diagnosis of supra-centimetric lesions in symptomatic elderly referred to colonoscopy. Patients and methods This was a prospective study including 57 symptomatic patients older than 65 years. All patients were explored by water enema computed tomography at first, followed by colonoscopy, and responded to a questionnaire on the tolerance to the preparation and both procedures. Results The mean age of patients was 73 years. The M:F sex ratio was 1.59. The most frequent indication for colonoscopy was bowel disorders associated with abdominal pain (30%). Water enema computed tomography allowed the diagnosis of tumours (n = 2), polyps (n = 6), diverticulosis (n = 7), inflammatory wall thickening (n = 1) and extra-colic lesions (n = 28). NPV of water enema computed tomography for supra-centimetric lesions was 96.5%. Sensitivity and specificity were 87.3% and 98%, respectively. However, for sub-centimetric lesions, water enema computed tomography had a low sensitivity estimated at 6%, specificity at 89.9%, positive predictive value at 91.9% and NPV at 27.7%. Conclusion Water enema computed tomography has proven to be a valuable and non-invasive method indicated as a first-line examination in case of colonic symptoms in the elderly to diagnose supra-centimetric lesions.

Evaluate the effectiveness of the Eyes Movement Desensitization and Reprocessing psychotherapy for children with Post-Traumatic Stress Disorder.A retrospective study was conducted in the Child Psychiatry Department of CHU Mongi Slim, Marsa (Tunis, Tunisia). All Outpatients with a Post-Traumatic Stress Disorder diagnosis and who had Eyes Movement Desensitization and Reprocessing psychotherapy during the period from July 2016 to May 2018 were included. They were evaluated according to DSM 5 criteria in pre and post therapy.The sample consisted of sixteen children with a sex-ratio of 1.6. Their age ranged from 3 to 17 years old with a mean age of 9.5±4.6 years. Five patients were less than six years old. Our patients were exposed to a sexual assault (4 cases), a death of a family member (3 cases), a road accident (3 cases), a physical assault (4 cases), an arrest of the father (1 case) and burglary of the house (1 case). In 15 cases, the traumatic event was unique while it was repeated in one sexual assault case. The total number of follow-up sessions ranged from one to seven sessions with an average of 3±2.4 sessions. The average number of sessions for preschool children was 2.6±0.5 sessions. Bilateral tactile stimulations were used with thirteen children in our population, including the five children younger than six years old. At the end of the therapy all patients no longer met the criteria for Post-Traumatic Stress Disorder diagnosis. All the preschool patients and eight children older than 6 years did not respond to any of the four Post-Traumatic Stress Disorder criteria. The difference between the scores of the DSM 5 criteria in pre and post EMDR was statistically significant. We found P=10-3 for children over six years and P0.05 for children under six years old.Eyes Movement Desensitization and Reprocessing is a therapy that has several advantages. First, it is effective in Post Traumatic Stress Disorder in children. Second, its protocol is flexible and adaptable to all ages and developmental level of the child. Third, the number of sessions is usually reduced, which is a great advantage over other trauma-focused psychotherapies.

This study aimed to assess the seroprevalence, viraemia and genotype distribution of hepatitis C virus (HCV) in a region in Central-West Tunisia. A door-to-door cross-sectional study was conducted on a randomly selected sample. A total of 3178 individuals aged 5 to 74 years and members of 935 families were investigated. Seroprevalence of HCV was assessed using ELISA tests. The viral load was determined by real-time RT-PCR, and HCV genotyping was conducted by amplification and sequencing in the NS5b genomic region. The global prevalence of HCV antibodies was 3.32% (95% confidence interval [CI]: 2.72-4.00). It was significantly higher in women: 4.47% vs. 2.16% in men, p = 0.001. Seroprevalence increased with age, and the highest rates were found in the 50- to 59-year-old age group (12.90%, 95% CI: 9.45-16.86), suggesting a cohort effect with very low contribution of intrafamilial transmission. Genotyping showed a predominance of subtype 1b (84.6%), with cocirculation of subtypes 2c (9.6%), 1a (1.9%), 1d (1.9%) and 2k (1.9%), similar to the previously reported genotype distribution in Tunisia and with no genetic clusters specific to the study region. These results indicate a higher endemicity of HCV infection when compared to the previously reported nationwide surveillance data. This study provides valuable data that can contribute to current strategies to eliminate hepatitis C.

The cancer-predisposing syndrome caused by biallelic mutations in NTHL1 may not be a solely colorectal cancer (CRC) and polyposis syndrome but rather a multi-tumor recessive disease. The presence of ≤10 adenomas in several mutation carriers suggests a possible causal role of NTHL1 in hereditary or early-onset nonpolyposis CRC. The involvement of NTHL1 in serrated/hyperplastic polyposis remains unexplored. The aim of our study is to elucidate the role of NTHL1 in the predisposition to personal or familial history of multiple tumor types, familial/early-onset nonpolyposis CRC, and serrated polyposis. NTHL1 mutational screening was performed in 312 cancer patients with personal or family history of multiple tumor types, 488 with hereditary nonpolyposis CRC, and 96 with serrated/hyperplastic polyposis. While no biallelic mutation carriers were identified in patients with personal and/or family history of multiple tumor types or with serrated polyposis, one was identified among the 488 nonpolyposis CRC patients. The carrier of c.268C>T (p.Q90*) and 550-1G>A was diagnosed with CRC and meningioma at ages 37 and 45 respectively, being reclassified as attenuated adenomatous polyposis after the cumulative detection of 26 adenomas. Our findings suggest that biallelic mutations in NTHL1 rarely cause CRC, a personal/familial multi-tumor history, or serrated polyposis, in absence of adenomas Tis study was funded by the Spanish Ministry of Science, Innovation and Universities, co-funded by FEDER funds- a way to build Europe, [SAF2016-80888-R (LV), SAF2015-68016-R (GC), Formación de Personal Investigador (IQ)]; Instituto de Salud Carlos III [CIBERONC CB16/12/00234, PI16/00563 (CL), Sara Borrell postdoctoral contract (PM)], the Government of Catalonia [Department of Health PERIS SLT002/16/0037, SLT002/16/00164 “Acció instrumental d’incorporació de científcs i tecnòlegs” (MT)], AGAUR 2017SGR1282 and CERCA Program] and Fundación Olga Torres. Tis study has been enabled by COST Action CA17118

International audience; Importance: Professional use of pesticides is a risk factor for non-Hodgkin lymphoma. The main biological mechanisms of pesticides and chemotherapy are genotoxicity and reactive oxygen species generation. Cellular adaptation among patients exposed to low doses of genotoxic and oxidative compounds might hinder chemotherapy efficiency in patients with lymphoma. Objective: To examine the association of occupational exposure to pesticides with immunochemotherapy response and survival among patients treated for diffuse large B-cell lymphoma. Design, setting, and participants: This retrospective cohort study assessed patients treated from July 1, 2010, to May 31, 2015, for diffuse large B-cell lymphoma, with a 2-year follow-up. The study took place at 6 university and nonuniversity hospitals in Languedoc-Roussillon, France. A total of 404 patients with newly diagnosed diffuse large B-cell lymphoma treated with anthracycline-based immunochemotherapy were included before the study began. Occupational history was reconstructed for 244 patients and analyzed with the PESTIPOP French job-exposure matrix to determine likelihood of occupational exposure to pesticides. Analysis of the data was performed from July 15, 2017, to July 15, 2018. Main outcomes and measures: Treatment failure (ie, partial response, stable disease, disease progression, or interruption for toxic effects) rate, 2-year event-free survival, and overall survival between exposed and nonexposed patients after adjustment for confounding factors. Results: A total of 244 patients (mean [SD] age, 61.3 [15.2] years; 153 [62.7%] male) had complete occupational data. Of these patients, 67 (27.4%) had occupational exposure to pesticides, with 38 exposed through agricultural occupations. Occupational exposure was not associated with clinical and biological characteristics at diagnosis. Occupationally exposed patients had a significantly higher treatment failure rate (22.4% vs 11.3%; P = .03; adjusted odds ratio [AOR] for confounding factors, 3.0; 95% CI, 1.3-6.9); this difference was higher among patients with exposing agricultural occupations compared with other patients (29.0% vs 11.7%; AOR, 5.1; 95% CI, 2.0-12.8). Two-year event-free survival was 70% in the occupationally exposed group vs 82% in the unexposed group (adjusted hazard ratio [AHR] for confounding factors, 2.2; 95% CI, 1.3-3.9). Among patients with exposing agricultural occupations compared with other patients, the difference was more pronounced (2-year event-free survival, 56% vs 83%; AHR, 3.5; 95% CI, 1.9-6.5). Similarly, 2-year overall survival was lower in the group of patients with exposing agricultural occupations compared with other patients (81% vs 92%; AHR, 3.9; 95% CI, 1.5-10.0). Conclusions and relevance: This retrospective study showed that agricultural occupational exposure to pesticides was associated with treatment failure, event-free survival, and overall survival among patients with diffuse large B-cell lymphoma.