Background: Severe acute malnutrition (SAM) contributes to nearly 1 million deaths annually worldwide, with diarrhea and pneumonia being the common morbidity associated with mortality. Objectives: To assess the effect of probiotics on diarrhea, pneumonia, and nutritional recovery in children with uncomplicated SAM.Methods: A randomized, double-blind, placebo-controlled study was conducted involving 400 children with uncomplicated SAM randomly assigned to ready-to-use therapeutic food (RUTF) either with (n = 200) or without (n = 200) probiotics. Patients received 1 mL daily dose of a blend of Lacti-casebacillus rhamnosus GG and Limosilactobacillus reuteri DSM 17938 (dosage, 2 billion colony-forming units; 50:50) or placebo during 1 mo. They were simultaneously fed with the RUTF for 6 to 12 wk, depending on patients' recovery rates. The primary outcome was the duration of diarrhea. Secondary outcomes included diarrheal and pneumonic incidence, nutritional recovery, and transfer to inpatient care rate.Results: For children with diarrhea, the number of days of disease was lower in the probiotic group (4.11; 95% CI: 3.37, 4.51) than that in the placebo group (6.68; 95% CI: 6.26, 7.13; P < 0.001). For children aged 16 mo or older, the risk of diarrhea was lower in the probiotic group (75.6%; 95% CI: 66.2, 82.9) than that in the placebo group (95.0%; 95% CI: 88.2, 97.9; P < 0.001), but no significant difference of the risk for the youngest. In the probiotic group, nutritional recovery happened earlier: at the 6th wk, 40.6% of the infants were waiting for nutritional recovery, contrasting with 68.7% of infants in the placebo group; but the nutritional recovery rate at the 12th wk was similar between the groups. Probiotics had no effect on pneumonic incidence and transfer to inpatient care.Conclusions: This trial supports using probiotics for the treatment of children with uncomplicated SAM. Its effect on diarrhea could positively affect nutritional programs in resource-limited settings.

Background: The management of surgical site infection (SSI) after craniotomy remains challenging with few existing recommendations. Patients and Methods: We reviewed the medical files of patients who underwent surgery between 2009 and 2018 to manage infection after craniotomy at our tertiary hospital. The Cox proportional hazards model and the Renyi test were used to investigate the association between relapse or all-cause mortality and selected variables. We compared infections with and without intra-cranial involvement using the Fisher test and the Wilcoxon rank sum test. Results: Seventy-seven episodes of infection were identified in 58 patients. The proportion of relapse was estimated to be 32.2% (± standard deviation [SD] 6.9) at five years. Intra-cranial infection was present in 15.6% of the cases (n = 12). Bone flap was removed in the majority of cases (93.5%) and the overall median duration of antibiotic therapy was six weeks (interquartile range [IQR] 6-12 weeks). Staphylococcus aureus was associated with a higher risk of relapse (p = 0.037). The administration of parenteral antibiotic agents (p = 0.012) and bone flap removal (p = 0.0051) were correlated with less relapse. In contrast, immunosuppressive drug use and radiotherapy were correlated with a higher risk of relapse (p = 0.014 and p = 0.031, respectively) and a higher all-cause mortality (p = 0.0093 and p < 0.0001, respectively). We found no difference between infections with and without intra-cranial involvement. Conclusions: Bone flap removal and parenteral antibiotic agents remain important in the management of SSI after craniotomy and were associated with less relapse in our study. More studies are needed to better determine the optimal treatment of this infection.

BACKGROUND AND AIMS:Cystic fibrosis liver disease (CFLD) is the third leading cause of death in patients with cystic fibrosis (CF). We aim to determine the prevalence of CFLD in a cohort of adult patients with CF and to characterise liver involvement in this population highlighting the importance of histological diagnosis.METHODS:We retrospectively studied a cohort of patients with CF. Inclusion criteria were age ≥ 18 and minimum 1 year of follow-up. We excluded lung transplant patients. CFLD was defined as having 2 out of 3 criteria: persistent elevation of transaminases and/or gamma-glutamyltransferase; abnormal ultrasound; and abnormal transient elastography. Non-invasive fibrosis biomarkers were calculated in CFLD patients. Adult-onset CFLD (Ad-CFLD) was defined as CFLD ≥18 years. Severe CFLD (s-CFLD) was defined as CFLD with cirrhosis and/or portal hypertension.RESULTS:We included 113 patients. Median age was 29 years, 58 were male. Forty patients had CFLD. Median age at CFLD diagnosis was 10 years. Twenty-one patients had s-CFLD. Two s-CFLD patients had nodular regenerative hyperplasia, 1 had hepatocellular carcinoma and 4 underwent liver transplantation. Six patients had ad-CFLD. Both CFLD and s-CFLD groups were compared to a non-CFLD group. The CFLD group had significantly more males (p = 0.034). S-CFLD group had worse pulmonary function (p = 0.015).CONCLUSION:Thirty five percent of adult patients with CF, mainly males, had CFLD. Nineteen percent had s-CFLD and had worse pulmonary function. With recent reports unravelling different pathophysiological mechanisms in CFLD, we believe it is important to better characterise liver involvement using liver biopsy.

Background: ABO-incompatible (ABOi) living donor liver transplantation (LDLT) has been proposed to compensate for donor shortage. To date, few studies have reported detailed ABOi LDLT results in large series of pediatric patients. C4d complement deposition in graft capillaries has been reported to be associated with antibody-mediated rejection in solid organ transplantation. Methods: A retrospective case–control study was conducted, comparing clinical outcomes of each of 34 consecutive pediatric ABOi LDLT recipients with those of 2 non-ABOi pairs (n = 68), matched according to pre-transplant diagnostic criteria, age, and date of transplantation. In addition, we studied the C4d immunostaining pattern in 22 ABOi and in 36 non-ABOi recipients whose liver biopsy was performed within the first 4 post-transplant weeks for suspected acute rejection. Results: The incidence of biliary complications was higher in ABOi recipients (p < 0.05), as were the incidence of acute humoral rejection (p < 0.01) and the incidence of retransplantation (p < 0.05). All children who required retransplantation were older than 1 year at the time of ABOi LDLT. Positive C4d immunostaining was observed in 13/22 (59%) ABOi recipients versus 3/36 (8.3%) non-ABOi recipients (p < 0.0001). Conclusions: ABOi LDLT is a feasible option for pediatric end-stage liver disease but carries increased risks for the recipient, especially for children older than 1 year, even with a specific preparation protocol. C4d immunostaining may be a hallmark of acute humoral rejection in ABOi liver transplantation.

The kinetics of IgG antibodies after coronavirus disease 2019 (COVID-19) remain poorly understood. We investigated factors influencing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG antibody levels and time to seronegativation during the follow-up of severe and critically ill patients. We retrospectively reviewed serological evaluations drawn during the follow-up of severe or critical laboratory-proven COVID-19 patients hospitalized at a large academic hospital. Specific IgG titers were measured using a chemiluminescent assay targeting anti-spike and anti-nucleocapsid protein IgG. The influence of time, demographic factors, clinical and paraclinical characteristics, and COVID-19 therapeutics on IgG levels were assessed through linear regression using a mixed-effect model, and delay until IgG negativation through a Weibull regression model. The cohort included 116 patients with a total of 154 IgG measurements drawn at a median of 79 days after diagnosis. IgG antibodies were increased with age (p = 0.005) and decreased significantly over time (p = 0.0002). Using elapsed time and age as covariates, we demonstrated higher IgG levels in patients with a higher body mass index (BMI) (p = 0.0026) and lower IgG levels in immunocompromised patients (p = 0.032). A high BMI was further found to delay and immunodeficiency to hasten significantly seronegativation, whereas no significant effect was observed with corticosteroids. These data highlight the waning over time of IgG antibodies after severe or critical COVID-19. Age, BMI, and immunosuppression also appear to influence the IgG kinetics, while short-term corticotherapy does not. Those data improve the understanding of SARS-CoV-2 serology while further research should determine the determinants of long-term seroprotection.

Background Living donor liver transplantation is a treatment option for unresectable hepatic tumors in children. Methods We enrolled 45 living donor transplantations performed between 1993 and 2018 for liver malignacies, which included hepatoblastoma (n = 33), hepatocellular carcinoma (n = 10), hepatic angiosarcoma (n = 1), and rhabdomyosarcoma (n = 1). Results No mortality or major morbidities were encountered in any donor, and the complication rate was 9%. In the hepatoblastoma group, 5-year overall and event-free survival rate in recipients was 87.4% and 75.8%, respectively, and mortality was significantly higher in patients after rescue transplantation (p = .001). Inferior vena cava replacement in these recipients appeared to be associated with reduced mortality (p = .034), but this was not confirmed when rescue patients were excluded (p = .629). In hepatocellular carcinoma group, both 5-year overall and event-free survival rates were 75.4% each, and invasion of hepatic veins was significantly associated with increased risk of recurrence and death (p = .028). The patient with rhabdomyosarcoma died from EBV-induced lymphoma 2 months after transplantation. The patient with angiosarcoma was in complete remission at the last follow-up. Overall, 5-year graft survival rate was 81.3%, and one patient underwent re-transplantation due to chronic rejection. Conclusions Pediatric oncological liver transplantation has become a key player in the management of malignancies with cancer cure in 84% of patients in this series. Living donor liver transplantation for pediatric recipients with unresectable tumors might be a beneficial surgical option, which is technically safe for donors and recipients, thus, allowing timely planning according to chemotherapy protocols.

Background In the era of fast-track surgery, because pancreaticoduodenectomy (PD) carries a significant morbidity, surgeons hesitate to begin early oral feeding and achieve early discharge. We compared the outcome of two different approaches to the postoperative management of PD in two tertiary centers. Methods Of patients having undergone PD for malignancy from 2008 to 2017, 100 patients who received early postoperative oral feeding (group A) were compared to 100 patients from another center who received early enteral feeding and a delayed oral diet (group B). Surgical indication and approach and type of pancreatic anastomosis were similar between both groups. Postoperative outcomes were retrospectively reviewed. Results Patient characteristics were similar between both groups, except significantly more neoadjuvant treatment in group A (A = 20% vs. B = 9%,p < 0.01). Mortality rates were 3% and 4% in groups A and B, respectively (p = 0.71). The rate of severe postoperative morbidity was significantly lower in group A (13% vs. 26%,p = 0.02), resulting in a lower reoperation rate (p < 0.01). Delayed gastric emptying and clinically relevant pancreatic fistula were similar between both groups but chyle leaks were more frequent in group A (10% vs. 3%,p = 0.04). The median hospital stay was shorter in group A (16 vs. 20 days,p < 0.01). Conclusion In the present study, early postoperative oral feeding after PD was associated with a shorter hospital stay and did not increase severe postoperative morbidity or the rate of pancreatic fistula. However, it resulted in more chyle leaks and did not prevent delayed gastric emptying.

Background: Management of bile duct injury (BDI) after cholecystectomy is challenging. The authors analyzed their center's 49-year experience.Methods: From 1968 to 2016, 120 consecutive patients were managed in a tertiary HBP center, 105 referred from other centers (Group A), 15 from our center (Group B). Surgical strategies and long-term outcomes were retrospectively reviewed.Results: Primary cholecystectomy approach was open in 35% and laparoscopic in 65%. In Group A, intraoperative BDI diagnosis was made in 25/105 patients, including 13 via intraoperative cholangiography (IOC) which was used in 21% of cases. Median time from BDI to referral was 148 days (range 0-10,758), and 3 patients had BDI-related secondary cirrhosis. Ninety-four patients underwent secondary surgical repair, mostly a complex biliary procedure (97%). Postoperative overall and severe morbidity rates were 26% and 6%, respectively. One patient with biliary cirrhosis at referral died postoperatively from hepatic failure. Nine patients (9.6%) developed a secondary biliary stricture after a median of 54 months from repair (6-228 months). In Group B, IOC was performed in 14/15 in whom BDI were intraoperatively detected and immediately repaired. There were 13 minor and 2 major BDIs, all repaired by uncomplex procedures with uneventful postoperative course. One patient had a secondary biliary stricture after 5 months, successfully treated by temporary endoprosthesis.Conclusion: Late follow-up after primary or secondary repair of BDI is recommended to detect recurrent biliary stricture. Bile duct injuries may occur in a tertiary center, but are intraoperatively detected with routine IOC and immediately repaired resulting in satisfactory outcome.

Objectives: The Pierre Robin sequence (PRS) is defined by retromicrognathia, glossoptosis, and sleep apnea and can also be associated with cleft palate. Diagnosis, management and mandibular catch-up growth are still controversial issues in PRS patients. The aim of our retrospective study was to evaluate in three dimensions (3D) the airway space and mandibular morphology in PRS compared to a normal control group patients in the pre-orthodontic period of life. The null hypothesis was that we would not find a significant difference between the PRS and control group patients in oropharyngeal airway volume measurements. Material and methods: We analyzed 9 PRS patients (mean age: 8 years-old) who underwent cleft palate surgery in the first four months of life, performed by the same surgeon using the same technique. Cone-beam computed tomography (CBCT) was performed in these patients after local ethical committee approval. The control group consisted of 15 patients (mean age: 9 years-old) with CBCT already performed for other reasons. 3D Slicer was used in both groups for semi-automatic segmentation of the airway space. Two independent observers performed semi-automatic segmentations twice in each patient with a one- week interval between the two series of measurements. Airway volume was automatically measured using 3D Slicer. We also developed a 3D cephalometric analysis with Maxilim software in order to define a 3D mandibular morphology which consisted of 25 landmarks, 4 planes, and 23 distances. Two independent observers performed the 3D cephalometric analysis twice for each patient, with a one- week interval between the two series of measurements. Results: There was no significant difference in the intra- and inter-observer measurements between the PRS and control groups for airway space volume (p<0.05). However, there was a significant difference in the shape of the mandible between the PRS group and the control group (p<0.05). Conclusions: Vertical ramus width and mandibular global anteroposterior length were significantly lower in the PRS group. Mandibular hypoplasia could be found in PRS patients not only in the horizontal dimension. Nemesis relevance: the null hypothesis was confirmed. Moreover we failed to find exactly the same control group under 9 years-old due to radioprotection restrictions of application of cone beam CT in children.

Background: Mucin-producing hepatic cystic neoplasms (MHCN) are uncommon and potentially malignant.Methods: Nine MHCN were encountered in our centre for over 32 years. Patients' clinical, biological, radiological and pathological features were reviewed. Lesions were classified into Mucinous Cystic Neoplasms (MCN) and Intraductal Papillary Neoplasms of the Bile duct (IPNB) (WHO 2010 classification).Results: Five MCN and 4 IPNB were reviewed. Serum and intracystic tumour markers were insufficient to diagnose malignancy. Complications were encountered in five out of nine patients (56%), mean symptom duration was 26 months (range: 1-132). Three patients were mismanaged pre-referral. Radiological features enabled preoperative diagnosis in eight out of nine patients (89%). Greater tumour size, unilocular lesion and mural nodularity indicated malignancy. Radical tumour excision was achieved in eight patients. One IPNB patient was misdiagnosed and underwent unroofing. For 103 months median follow-up, five out of six patients with benign tumours were alive and disease-free, whereas the misdiagnosed IPNB recurred with fatal malignant transformation seven years later. Among the three patients with malignancies (median follow-up: 77 months), two IPNB died, one from cancer recurrence and one from unrelated causes, whereas the malignant MCN was alive and disease-free.Conclusions: Appropriate MHCN diagnosis is crucial, yet it is often misdiagnosed and mismanaged. The prognosis after complete excision is favourable.

Objective To investigate the effect of using volunteer screeners in active tuberculosis case-finding in South Kivu, the Democratic Republic of the Congo, especially among groups at high risk of tuberculosis infection. Methods To identify and screen high-risk groups in remote communities, we trained volunteer screeners, mainly those who had themselves received treatment for tuberculosis or had a family history of the disease. A non-profit organization was created and screeners received training on the disease and its transmission at 3-day workshops. Screeners recorded the number of people screened, reporting a prolonged cough and who attended a clinic for testing, as well as test results. Data were evaluated every quarter during the 3-year period of the intervention (2014-2016). Findings Acceptability of the intervention was high.Volunteers screened 650434 individuals in their communities, 73418 of whom reported a prolonged cough; 50 368 subsequently attended a clinic for tuberculosis testing.Tuberculosis was diagnosed in 1 in 151 people screened, costing 0.29 United States dollars (US$) per person screened and US$ 44 per person diagnosed. Although members of high-risk groups with poorer access to health care represented only 5.1% (33002/650 434) of those screened, they contributed 19.7% (845/4300) of tuberculosis diagnoses (1 diagnosis per 39 screened). The intervention resulted in an additional 4300 sputum-smear-positive pulmonary tuberculosis diagnoses, 42% (4 300/10 247) of the provincial total for that period. Conclusion Patient-led active tuberculosis case-finding represents a valuable complement to traditional case-finding, and should be used to assist health systems in the elimination of tuberculosis.

Cirrhosis in adults is associated with modifications of systemic and liver hemodynamics, whereas little is known about the pediatric population. The aim of this work was to investigate whether alterations of hepatic and systemic hemodynamics were correlated with cirrhosis severity in children. The impact of hemodynamic findings on surgical management in pediatric living donor liver transplantation (LT) was evaluated. Liver and systemic hemodynamics were studied prospectively in 52 children (median age, 1 year; 33 with biliary atresia [BA]). The hemodynamics of native liver were studied preoperatively by Doppler ultrasound and intraoperatively using invasive flowmetry. Portosystemic gradient was invasively measured. Systemic hemodynamics were studied preoperatively by Doppler transthoracic echocardiography and intraoperatively by using transpulmonary thermodilution. Hemodynamic parameters were correlated with Pediatric End-Stage Liver Disease (PELD) score and the histological degree of fibrosis (collagen proportionate area [CPA]). Cirrhosis was associated with a 60% reduction of pretransplant total liver flow (n = 46; median, 36 mL/minute/100 g of liver) compared with noncirrhotic livers (n = 6; median, 86 mL/minute/100 g; P = 0.002). Total blood flow into the native liver was negatively correlated with PELD (P < 0.001) and liver CPA (P = 0.005). Median portosystemic gradient was 14.5 mm Hg in children with cirrhosis and positively correlated with PELD (P < 0.001). Portal vein (PV) hypoplasia was observed mainly in children with BA (P = 0.02). Systemic hemodynamics were not altered in our children with cirrhosis. Twenty-one children met the intraoperative criteria for PV reconstruction using a portoplasty technique during the LT procedure and had a smaller PV diameter at pretransplant Doppler ultrasound (median = 3.4 mm; P < 0.001). Cirrhosis in children appears also as a hemodynamic disease of the liver, correlated with cirrhosis severity. Surgical technique for PV reconstruction during LT was adapted accordingly. Liver Transplantation 23 1440-1450 2017 AASLD.

INTRODUCTION:In the field of tuberculosis (TB), and particularly in regard to paediatric TB (PedTB), clinical skills of health professionals play an important role in determining quality of care. In an era where novel diagnostic technologies and efficient treatment regimens are being made available for the poorest, we must not divert our attention from the importance of clinical skills, as this deliverable remains the cornerstone of individualized patient care and ultimately the best assurance for optimal use of resources. The aim of our work was to study the epidemiology of PedTB and the determinants of PedTB under-detection in the South-Kivu Province of the Democratic Republic of Congo (DRC), a setting with nearly no technical resources allowing to support the clinical diagnosis of PedTB, i.e. chest X-rays, rapid molecular tests or culture laboratories.METHODS:We collected TB notification data from 2010 to 2015 and analysed the space-time variations in notification for the different forms of TB among the 113 health facilities (HF) the South-Kivu Province, a region with a low HIV incidence. The different forms of TB notified were: smear positive pulmonary TB (SS+PTB), smear negative pulmonary TB (SS-PTB) and extra-pulmonary TB (EPTB). We further analysed the distribution of these different forms of the disease per age group and explored the possibility to predict the detection of PedTB.RESULTS:Significant differences were observed between HF in regard to the proportion of paediatric TB and the proportion of SS-TB among adults. We found a strong correlation between the proportion of PedTB and three major factors: the proportion of TB cases with no bacteriological confirmation (SS-TB) among adults, the number of TB cases notified by the HF and the fact that the HF was supported or not by Médecins Sans Frontières (MSF). The proportion of SS-TB among adults was found to be a valid indicator for predicting the level of detection of PedTB at the same HF.CONCLUSION:Our observations strongly suggest that under-detection of PedTB is associated with insufficient clinical skills and technical resources at the HF level which similarly affects other forms of the disease, in particular SS-TB. We demonstrated that, in the specific context of South-Kivu, under-detection of PedTB can be predicted by a low SS-TB/SS+PTB ratio in the adult population. In the context of severely under-resourced settings, this ratio could be used to rapidly identify HF that should benefit in priority from deeper evaluation, and eventually targeted interventions.

One of the key aspects of three-dimensional (3D) craniofacial cephalometry is the measurement of posterior cranial base angle as this area is deeply involved in craniofacial development. The purpose of our retrospective study was to define the best reproducible 3D posterior cranial base angles among five 3D angles transposed from 2D cephalometry (Cousin, BL1 of Ross and Ravosa, Bjork, Delaire, CBA4 of Liberman) and seven 3D angles based on physical anthropology studies and on new concepts (R1 to R7). The null hypothesis was that all 3D posterior cranial base angles were equally reproducible.

Chemotherapeutic advances have enabled successful cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) expansion in treating metastatic colorectal cancer.

Our objective was to compare mortality, epidemiology, and morbidity in hospitalized patients with candidemia which was both related and unrelated to the central venous catheter (CVC). This was a monocentric, retrospective cohort study of candidemia. The sample consisted of 103 patients with laboratory-confirmed nosocomial candidemia hospitalized between 2006 and 2013 in a tertiary care public hospital. We included 65 (63.1 %) patients (24 in the CVC-positive group, 41 in the CVC-negative group). Demographic data and risk factors were recorded using a structured case report form. In the group of candidemia associated to the CVC, survival at day 50 was 58.6 ± 11.9 %, compared to 26.5 ± 8.9 % for the CVC-negative group (p-value = 0.012); the hazard ratio of death was 0.38 (95 % confidence interval 0.17–0.85, p-value = 0.019). Compared with the CVC-positive patients, CVC-negative patients were often colonized with yeast (41.5 % vs. 16.7 %, p-value = 0.041), had a shorter previous in-hospital stay (20 days vs. 34 days, p-value = 0.023), and were more severely ill (severe sepsis 85.4 % vs. 58.3 %, p-value = 0.016). In this study, when the origin of candidemia was not the CVC, patients were more seriously ill, had a higher mortality rate, and the removal of the catheter seemed to lead to disappointing results. It would be useful to explore the impact of retention of the CVC on survival in the CVC-negative patients, where the CVCs are essential to treating these patients.

Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental disorder with different nutritional phases from suckling deficit with failure to thrive to early onset of obesity. Hyperghrelinemia has been described in PWS long before the development of obesity. Ghrelin is found in both acylated (AG) and unacylated (UAG) forms in the circulation. In contrast to AG, UAG has been shown to inhibit food intake and to be elevated in anorexia nervosa. The present project is aiming to determine the underlying mechanisms driving the different nutritional phases in PWS.