Epidemiology, Clinical Features and Antifungal Resistance Profile of Candida auris in Africa: Systematic Review

Candida auris since it discovery in 2009 is becoming a severe threat to human health due to its very quickly spread, its worldwide high resistance to systemic antifungal drugs. In resource-constrained settings where several conditions are met for its emergence and spread, this worrisome fungus could cause large hospital and/or community-based outbreaks. This review aimed to summarize the available data on C. auris in Africa focusing on its epidemiology and antifungal resistance profile. Major databases were searched for articles on the epidemiology and antifungal resistance profile of C. auris in Africa. Out of 2,521 articles identified 22 met the inclusion criteria. In Africa, nearly 89% of African countries have no published data on C. auris. The prevalence of C. auris in Africa was 8.74%. The case fatality rate of C. auris infection in Africa was 39.46%. The main C. auris risk factors reported in Africa were cardiovascular disease, renal failure, diabetes, HIV, recent intake of antimicrobial drugs, ICU admissions, surgery, hemodialysis, parenteral nutrition and indwelling devices. Four phylogenetic clades were reported in Africa, namely clades I, II, III and IV. Candida auris showed a pan-African very high resistance rate to fluconazole, moderate resistance to amphotericin B, and high susceptibility to echinocandins. Finally, C. auris clade-specific mutations were observed within the ERG2, ERG3, ERG9, ERG11, FKS1, TAC1b and MRR1 genes in Africa. This systematic review showed the presence of C. auris in the African continent and a worrying unavailability of data on this resilient fungus in most African countries.

Specific alterations of regional myocardial work in strength-trained athletes using anabolic androgenic steroids compared to athletes with genetic hypertrophic cardiomyopathy

Background:Strength-trained athletes using anabolic androgenic steroids(AAS)have left ventricular(LV)hypertrophy and myocardial fibrosis that can lead to sudden cardiac death.A similar feature was described in athletes with hypertrophic cardiomyopathy(HCM),which complicates the diagnosis for clinicians.In this context,we aimed to compare the LV function of the 2 populations by measuring global and regional strain and myocardial work using speckle-tracking imaging.Methods:Twenty-four strength-trained asymptomatic athletes using AAS(AAS-Athletes),22 athletes diagnosed with HCM(HCM-Athletes),and 20 healthy control athletes(Ctrl-Athletes)underwent a resting echocardiography to assess LV function.We evaluated LV global and regional strains and myocardial work,with an evaluation of the constructive work(CW),wasted work,and work efficiency(WE).Results:Compared to Ctrl-Athletes,both AAS-Athletes and HCM-Athletes had a thicker interventricular septum,with maj ored values in HCM-Athletes.LV strain was reduced in AAS-Athletes and even more in HCM-Athletes.Consequently,global WE was significantly diminished in both AAS and HCM-Athletes(93%±2%in Ctrl-Athletes,90%±4%in AAS-Athletes,and 90%±5%in HCM-Athletes(mean±SD);p<0.05).Constructive work and WE regional analysis showed specific alterations,with the basal septal segments preferentially affected in AAS-Athletes,and both septal and apical segments affected in HCM-Athletes.Conclusion:The regional evaluation of myocardial work reported specific alterations of the major LV hypertrophy induced by the regular use of AAS compared to the LV hypertrophy due to HCM.This finding could help clinicians to differentiate between these 2 forms of pathological hypertrophy.

Major gastrointestinal bleeding and antithrombotics: Characteristics and management

BACKGROUND There are few reports on major gastrointestinal(GI)bleeding among patients receiving an antithrombotic.AIM To describe clinical characteristics,bleeding locations,management and inhospital mortality related to these events.METHODS Over a three-year period,we prospectively identified 1080 consecutive adult patients admitted in two tertiary care hospitals between January 1,2013 and December 31,2015 for major GI bleeding while receiving an antithrombotic.The bleeding events were medically validated.Clinical characteristics,causative lesions,management and fatalities were described.The distribution of antithrombotics prescribed was compared across the bleeding lesions identified.RESULTS Of 576 patients had symptoms of upper GI bleeding and 504 symptoms of lower GI bleeding.No cause was identified for 383(35.5%)patients.Gastro-duodenal ulcer was the first causative lesion in the upper tract(209 out of 408)and colonic diverticulum the first causative lesion in the lower tract(120 out of 289).There was a larger proportion of direct oral anticoagulant use among patients with lower GI than among those with upper GI lesion locations(P=0.03).There was an independent association between gastro-duodenal ulcer and antithrombotic use(P=0.03),taking account of confounders and proton pump inhibitor coprescription.Pair wise comparisons pointed to a difference between vitamin K antagonist,direct oral anticoagulants,and antiplatelet agents in monotherapy vs dual antiplatelet agents.CONCLUSION We showed a higher rate of bleeding lesion identification and suggested a different pattern of antithrombotic exposure between upper and lower GI lesion locations and between gastro-duodenal ulcer and other identified upper GI causes of bleeding.Management was similar across antithrombotics and in-hospital mortality was low(5.95%).

Iron metabolism imbalance at the time of listing increases overall and infectious mortality after liver transplantation

BACKGROUND Liver transplantation(LT)is the best treatment for patients with liver cancer or end stage cirrhosis,but it is still associated with a significant mortality.Therefore identifying factors associated with mortality could help improve patient management.The impact of iron metabolism,which could be a relevant therapeutic target,yield discrepant results in this setting.Previous studies suggest that increased serum ferritin is associated with higher mortality.Surprisingly iron deficiency which is a well described risk factor in critically ill patients has not been considered.AIM To assess the impact of pre-transplant iron metabolism parameters on posttransplant survival.METHODS From 2001 to 2011,553 patients who underwent LT with iron metabolism parameters available at LT evaluation were included.Data were prospectively recorded at the time of evaluation and at the time of LT regarding donor and recipient.Serum ferritin(SF)and transferrin saturation(TS)were studied as continuous and categorical variable.Cox regression analysis was used to determine mortality risks factors.Follow-up data were obtained from the local and national database regarding causes of death.RESULTS At the end of a 95-mo median follow-up,196 patients were dead,38 of them because of infections.In multivariate analysis,overall mortality was significantly associated with TS>75%[HR:1.73(1.14;2.63)],SF<100μg/L[HR:1.62(1.12;2.35)],hepatocellular carcinoma[HR:1.58(1.15;2.26)],estimated glomerular filtration rate(CKD EPI Cystatin C)[HR:0.99(0.98;0.99)],and packed red blood cell transfusion[HR:1.05(1.03;1.08)].Kaplan Meier curves show that patients with low SF(<100μg/L)or high SF(>400μg/L)have lower survival rates at 36 mo than patients with normal SF(P=0.008 and P=0.016 respectively).Patients with TS higher than 75%had higher mortality at 12 mo(91.4%±1.4%vs 84.6%±3.1%,P=0.039).TS>75%was significantly associated with infection related death[HR:3.06(1.13;8.23)].CONCLUSION Our results show that iron metabolism imbalance(either deficiency or overload)is associated with post-transplant overall and infectious mortality.Impact of iron supplementation or depletion should be assessed in prospective study.

Outcomes of nonresected main-duct intraductal papillary mucinous neoplasms of the pancreas

AIM:To compare characteristics and outcomes of resected and nonresected main-duct and mixed intraductal papillary mucinous neoplasms of the pancreas(IPMN).METHODS:Over a 14-year period,50 patients who did not undergo surgery for resectable main-duct or mixed IPMN,for reasons of precluding comorbidities,age and/or refusal,were compared with 74 patients who underwent resection to assess differences in rates of survival,recurrence/occurrence of malignancy,and prognostic factors.All study participants had dilatation of the main pancreatic duct by ≥ 5 mm,with or without dilatation of the branch ducts.Some of the nonsurgical patients showed evidence of mucus upon perendoscopic retrograde cholangiopancreatography or endoscopic ultrasound and/or after fine needle aspiration.For the surgical patients,pathologic analysis of resected specimens confirmed a diagnosis of IPMN with involvement of the main pancreatic duct or of both branch ducts as well as the main pancreatic duct.Clinical and biologic follow-ups were conducted for all patients at least annually,through hospitalization or consultation every six months during the first year of follow-up,together with abdominal imaging analysis(magnetic resonance cholangiopancreatography or computed tomography) and,if necessary,endoscopic ultrasound with or without fine needle aspiration.RESULTS:The overall five-year survival rate of patients who underwent resection was significantly greater than that for the nonsurgical patients(74% vs 58%; P =0.019).The parameters of age(< 70 years) and absence of a nodule were associated with better survival(P < 0.05); however,the parameters of main pancreatic duct diameter > 10 mm,branch ductdiameter > 30 mm,or presence of extra pancreatic cancers did not significantly influence the prognosis.In the nonsurgical patients,pancreatic malignancy occurred in 36% of cases within a mean time of 33 mo(median:29 mo; range:8-141 mo).Comparison of the nonsurgical patients who experienced disease progression with those who did not progress showed no significant differences in age,sex,symptoms,subtype of IPMN,or follow-up period; only the size of the main pancreatic duct was significantly different between these two sub-groups,with the nonsurgical patients who experienced progression showing a greater diameter at the time of diagnosis(> 10 mm).CONCLUSION:Patients unfit for surgery have a 36% greater risk of developing pancreatic malignancy of the main-duct or mixed IPMN within a median of 2.5 years.

Combined evaluation of biomarkers as predictor of maintained remission in Crohn's disease

BACKGROUND The individual performances and the complementarity of Crohn's disease(CD)activity index(CDAI), C-reactive protein(CRP) and faecal calprotectin(Fcal) to monitor patients with CD remain poorly inves-tigated in the era of "tight control"and "treat to target" strategies.AIM To assess CDAI, CRP and Fcal variation, alone or combined, after 12 wk(W12) of anti-tumor necrosis factor(TNF) therapy to predict corticosteroids-free remission(CFREM = CDAI < 150, CRP < 2.9 mg/L and Fcal < 250 μg/g with no therapeutic intensification and no surgery) at W52.METHODS CD adult patients needing anti-TNF therapy with CDAI > 150 and either CRP >2.9 mg/L or Fcal > 250 μg/g were prospectively enrolled.RESULTS Among the 40 included patients, 13 patients(32.5%) achieved CFREM at W52. In univariable analysis, CDAI < 150 at W12(P = 0.012), CRP level < 2.9 mg/L at W12(P = 0.001) and Fcal improvement at W12(Fcal < 300 μg/g; or, for patients with initial Fcal < 300 μg/g, at least 50% decrease of Fcal or normalization of Fcal(< 100 μg/g)(P = 0.001) were predictive of CFREM at W52. Combined endpoint(CDAI < 150 and CRP ≤ 2.9 mg/L and FCal improvement) at W12 was the best predictor of CFREM at W52 with positive predictive value = 100.0%(100.0-100.0)and negative predictive value = 87.1%(75.3-98.9). In multivariable analysis, Fcal improvement at W12 [odd ratio(OR) = 45.1(2.96-687.9); P = 0.03] was a better predictor of CFREM at W52 than CDAI < 150 [OR = 9.3(0.36-237.1); P = 0.145]and CRP < 2.9 mg/L(0.77-278.0; P = 0.073).CONCLUSION The combined monitoring of CDAI, CRP and Fcal after anti-TNF induction therapy is able to predict favorable outcome within one year in patients with CD.

Influence of teeth on the smile and physical attractiveness.A new internet based assessing method

Objectives: Traditional methods for evaluating aesthetic perceptions of the teeth have involved panels of people observing photographs, and the person commenting on the appearance of the teeth generally is aware that his opinion of the dental appearance is being sought. The situation is artificial and may involve bias. We propose a novel method for evaluating the effect of dental imperfections on perceptions in which the participant is unaware of participating in a survey and in which his or her opinion is not sought. Rather, involvement in the study betrays the importance of dental aesthetics for the observer. Methods: Starting with a digitally manipulated photograph of a smiling young woman, two portrait photographs A and B were produced in which the only differences were in the dentition revealed by the smile. The two photographs were anonymously posted on an online dating service site covering two large cities in southwestern France. During a period of one month, all “hits” on each of the photographs and all attempts to make contact were counted. Results: There was no significant difference between the number of hits on each of the portraits A and B. On the other hand, the ratio of attempts to contact to hits showed a clear difference: the ratio was 4.8 times greater for Portrait A than for Portrait B

AB047.Quebec database of clinical data and biological material for research on uveal melanoma

Background:Sharing biological material and clinical data from patients with uveal melanoma.Methods:Uveal melanoma is the most common intraocular malignancy in the adult population.Because uveal melanoma is primarily a sporadic cancer and familial cases are rare,it is difficult to prevent or detect it.Despite effective treatment of ocular tumors,more than 50%of patients develop incurable liver metastases mainly in the 5-10 years following the detection of the primary tumor.This cancer is relatively rare and the obtained biopsies are very small.About 20 samples are taken each year in Quebec.This provincial infrastructure is made of biological material from donors with uveal melanoma and a large clinical database.Collected tumor biopsies are used for culturing cell lines and the creation of a DNA/RNA library used for genomic and genetic studies.Results:This infrastructure plays an important role in the achievement of various research programs for a better understanding of genetic and environmental factors involved in the development of melanoma and the spread of metastasis.It allows collaboration with other researchers at a provincial,national and international level in order to make progress in basic and clinical research on uveal melanoma.Conclusions:The biological material and clinical data of this infrastructure are available upon request to VHRN members whose research project was approved by the ethics committee of the institution.

EGFR Expression Is Unreliable to Decide for Cetuximab Treatment in Patients with Metastatic Colorectal Cancer: Results from “ERBITUX-OUEST”

Purpose: Although controversial, assessment of epidermal growth factor receptor (EGFR) expression is required for the approved indications of Cetuximab in metastatic colorectal cancer (mCRC). With the objective of improving patient selection, “ERBITUX-OUEST” study aimed at analyzing EGFR status in a large cohort of mCRC patients who received cetuximab without preliminary EGFR screening, and assessing the correlation between EGFR status and response to treatment retrospectively. Patients and methods: 332 patients treated with Irinotecan Cetuximab based regimen after progression on irinotecan or oxaliplatin therapy were included. EGFR status was assessed using three available immunohistochemistry (IHC) tests and in situ hybridization in case of negativity. Clinical outcomes of EGFR-positive and EGFR-non-detected (or considered as negative with at least one test) patients were compared. Results: Of the 332 samples centrally screened, 194 were classified as full-positive (i.e., EGFR-positive for all three tests), 86 as full-negative, and 52 as discordant. One third of the 131 negative samples with FDA approved test should be reclassified as positive with at least one of the two others tests. Regarding results from FDA approved test only, neither objective response rate (ORR), progression-free survival (PFS) nor overall survival (OS) differed significantly between EGFR-negative and EGFR-positive patients (P = 0.788, 0.326 and 0.888, respectively). Similarly, comparison of full-negative to other groups did not show any significant difference in terms of ORR (P = 0.507), PFS (P = 0.222) or OS (P = 0.686). Conclusion: These data strongly argue against mCRC patients selection for Cetuximab treatment based on EGFR expression as measured by currently available IHC technics.

IMPACT de la déprivation sociale sur les difficultés psychosociales au décours d’un cancer pédiatrique:uneétude prospective IMPACT of the Social Deprivation on Psychosocial Difficulties of Pediatric Cancer Survivors:A Prospective Study

The posttreatment period is a key part of the management of pediatric cancer.During this time,school and psychological difficulties have been described in childhood cancer survivors(CCS)and can be prognostic for the success of social reintegration.This study estimated the influence of the household’s socioeconomic status(SES)on these psychosocial difficulties.This study is based on a prospective multicentric database and focused on children who received a psychosocial evaluation during their follow-up from 2013 to 2020.We retrieved data on school and psychological difficulties.Household SES was estimated by a social deprivation score.Data from1003 patients were analyzed.School difficulties were noted in 22%of CCS.A greater social deprivation was significantly associated with school difficulty.Tumor relapse,treatment with hematopoietic stem cell transplantation,and central nervous system(CNS)tumors remained significant risk factors.In the subgroup of CNS tumors,school difficulties were increased and associated with greater social deprivation.Psychological difficulties were not associated with the deprivation score.There is a link between SES and school difficulties in CCS.Further investigations should be carried out for children with CNS tumors,which is the population of the greatest concern.

Liver transplantation for perihilar cholangiocarcinoma is not a provocative idea

This is a multicenter benchmarking study on liver transplantation(LT)for perihilar cholangiocarcinoma(PHC)after neoadjuvant chemoradiotherapy(1).The study comprises of 134 patients from 2014 to 2018 among whom the majority had underlying primary sclerosing cholangitis(PSC).Dropout rate was available from 4 out of 17 centers and was 28%,primarily for oncological reasons(tumor progression and lymph node invasion).All patients followed neo-adjuvant chemoradiotherapy according to the Mayo(88%)or Mayo-like protocol.Liver grafts originated from brain-dead donors in 61.3%of cases and from living donors in 29.7%of cases.

Comparison of alternative arterial anastomosis site during liver transplantation when the recipient’s hepatic artery is unusable

Background:Few studies have analyzed outcomes of liver transplantation(LT)when the recipient hepatic artery(HA)was not usable.Methods:We retrospectively evaluated the outcomes of LT performed using the different alternative sites to HA.Results:Between 2002 and 2017,1,677 LT were performed in our institution among which 141(8.4%)with unusable recipient HA were analyzed.Four groups were defined according to the site of anastomosis:the splenic artery(SA group,n=26),coeliac trunk(CT group,n=12),aorta using or not the donor’s vessel(Ao group,n=91)and aorta using a vascular prosthesis(Ao-P group,n=12)as conduit.The median number of intraoperative red blood cell transfusions was significantly increased in the Ao and Ao-P groups(5,5,8.5 and 16 for SA,CT,Ao and Ao-P group respectively,P=0.002),as well as fresh frozen plasma(4.5,2.5,10,17 for the SA,CT,Ao and Ao-P groups respectively,P=0.001).Hospitalization duration was also significantly increased in the Ao and Ao-P groups(15,16,24,26.5 days for the SA,CT,Ao and Ao-P groups respectively,P<0.001).The occurrence of early allograft dysfunction(EAD)(P=0.07)or arterial complications(P=0.26)was not statistically different.Level of factor V,INR,bilirubin and creatinine during the 7th postoperative days(POD)was significantly improved in the SA group.No difference was observed regarding graft(P=0.18)and patient(P=0.16)survival.Conclusions:In case of unusable HA,intraoperative and postoperative outcomes are improved when using the SA or CT compared to aorta.

Autophagy is increased in cryptorchid testis resulting in abnormal spermatozoa

Autophagy is invoIved in spermatogenesis by regulating germ cell maturation.This catabolic process increases with hyperthermic conditions to prevent the accumulation of damaged organelles.Cryptorchidism is associated with impairment of germ cell maturation revealed by the presence of immature forms of sperm cells in ejaculates.The aim of the present study was to evaluate the status of autophagy in sperm cells from cryptorchid patients.Semen samples of cryptorchid patients and normozoospermic controls were analyzed by immuno cytochemistry and electron microscopy.Autophagy protei ns,autophagy-related protein 9(ATG9)and microtubule-associated protein,lA/lB-light chain 3(LC3)were localized by immunocytochemistry on the acrosome and on the equatorial segment of sperm cells.LC3 was also detected in the midpiece of cryptorchid sperm tail.Autophagy substrate p62 protein was present in the acrosome and in the postequatorial segment of sperm in control samples,but not in the cryptorchid ones.Transmission electron microscopy revealed double-membrane-limited autophagosomes in postequatorial part of spermatozoa head and midpiece in cryptorchid samples.Partly degraded mitochondria were frequently discerned in autophagic vacuoles.In conclusion,autophagy is increased in sperm cells from patients with cryptorchid history comparatively to control.Our work provides insights into the role of autophagy in the maturation and survival of human male gametes in pathological conditions.Thus,regulating autophagy could represent a potential way to improve sperm quality in cryptorchid men.

French Editorials from the Association de Chirurgie Hépato-Bilio-Pancréatique et Transplantation-France(ACHBPT)

The international journal Hepatobiliary Surgery and Nutrition(HBSN)offers a great opportunity to the French Association of Hepato-Biliary Surgery and Liver Transplantation(ACHBPT).Indeed,each of the monthly“analyzed articles”written by our colleagues will be submitted for publication as an editorial in HBSN.Of course,it has to be written in English and edited by one of our expert members(Video 1,Figures 1,2).

Dosage individualization in children:integration of pharmacometrics in clinical practice

Background:Children are in a continuous and dynamically changing state of growth and development.A thorough understanding of developmental pharmacokinetics(PK)and pharmacodynamics(PD)is required to optimize drug therapy in children.Data sources:Based on recent publications and the experience of our group,we present an outline on integrating pharmacometrics in pediatric clinical practice to develop evidence-based personalized pharmacotherapy.Results:Antibiotics in septic neonates and immunosuppressants in pediatric transplant recipients are provided as proof-of-concept to demonstrate the utility of pharmacometrics in clinical practice.Dosage individualization based on developmental PK-PD model has potential benefits of improving the efficacy and safety of drug therapy in children.Conclusion:The pharmacometric technique should be better developed and used in clinical practice to personalize drug therapy in children in order to decrease variability of drug exposure and associated risks of overdose or underdose.

How to identify better candidate to radioembolization in case of hepatocellular carcinoma and portal vein tumoral thrombosis

Hepatocellular carcinoma(HCC)is the most common primary liver cancer and the fifth most common malignant tumor worldwide.Liver resection is a curative treatment for HCC and can be safety performed by a minimally invasive procedure in all liver segments without size limitations(1,2).Nevertheless,some patients are diagnosed with HCC and portal vein tumor thrombosis(PVTT).According to the staging system of the Barcelona Clinic Liver Cancer(BCLC),patients with macrovascular invasion are staged as BCLC-C.For those patients,the prognosis is generally poor.However,the management of HCC with macrovascular invasion is still controversial.Indeed,recent studies proposed different surgical procedure such as one-stage resection or associating liver partition and portal vein ligation,with promising results(3-5).