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Background: In islet transplantation, the use of dynamic hypothermic preservation techniques is a current challenge. This study compares the efficacy of 3 pancreas preservation methods: static cold storage, hypothermic machine perfusion (HMP), and oxygenated HMP. Methods: A standardized human pancreas split model was employed using discarded organs from both donation after brain death (nâ =â 15) and donation after circulatory death (DCD) (nâ =â 9) donors. The pancreas head was preserved using static cold storage (control group), whereas the tail was preserved using the 3 different methods (study group). Data on donor characteristics, pancreas histology, isolation outcomes, and functional tests of isolated islets were collected. Results: Insulin secretory function evaluated by calculating stimulation indices and total amount of secreted insulin during high glucose stimulation (area under the curve) through dynamic perifusion experiments was similar across all paired groups from both DCD and donation after brain death donors. In our hands, islet yield (IEQ/g) from the pancreas tails used as study groups was higher than that of the pancreas heads as expected although this difference did not always reach statistical significance because of great variability probably due to suboptimal quality of organs released for research purposes. Moreover, islets from DCD organs had greater purity than controls (P ≤ 0.01) in the HMP study group. Furthermore, our investigation revealed no significant differences in pancreas histology, oxidative stress markers, and apoptosis indicators. Conclusions: For the first time, a comparative analysis was conducted, using a split model, to assess the effects of various preservation methods on islets derived from pancreas donors. Nevertheless, no discernible variances were observed in terms of islet functionality, histological attributes, or isolation efficacy. Further investigations are needed to validate these findings for clinical application.
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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 Lacticasebacillus 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. This trial was registered https://pactr.samrc.ac.za as PACTR202108842939734.
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Probióticos , Desnutrição Aguda Grave , Lactente , Humanos , Criança , República Democrática do Congo , Probióticos/uso terapêutico , Diarreia/terapia , Diarreia/etiologia , Desnutrição Aguda Grave/terapia , Desnutrição Aguda Grave/complicações , Método Duplo-CegoRESUMO
BACKGROUND: The aim of this study was to evaluate the effect of a recipient's obesity on posttransplant complications and patient and graft survival. METHODS: A single-institution, retrospective study was performed on obese renal transplant recipients (BMI ≥ 30 kg/m2, n = 102) from January 2010 to December 2018, matched with non-obese recipients (BMI < 30 kg/m2, n = 204). For comparison, for every obese patient we selected 2 nonobese patients with a similar age, sex, and period of transplantation. The comparative analysis included patient and graft survival as primary outcomes and graft function and postoperative complications as a secondary outcome. RESULTS: Recipient demographics were comparable in both groups except for diabetic nephropathy in obese patients (P = .0006). Obesity was strongly related to a poorer patient survival (risk ratio [RR] = 2.83 confidence interval [CI] 95% 1.14-7.04; P = .020) but there was no observed difference in graft survival (P = .6). While early graft function was inferior in the obese population (RR = 2.41; CI 95% 1.53-3.79; P = .00016), during late follow-up, no statistically significant differences were observed between both groups (P = .36). Obese recipients had a significantly higher risk of delayed graft function (RR = 1.93; CI 95% (1.19-3.1), P = .0077), heart infarction (RR = 7; CI 95% 1.68-29.26; P = .0042), wound infections (RR = 8; CI 95% 1.96-32.87; P = .0015), diabetes aggravation (RR = 3.13; CI 95% 1.29-7.6; P = .011), and surgical revision for eventration (RR = 8; CI 95% 1.22-52.82; P = .026) when compared with nonobese recipients. CONCLUSIONS: Despite the inferior early kidney graft function in obese recipients, there was no difference observed at the long-term follow-up. However, recipient obesity demonstrated a negative effect on patient survival and postoperative complications.
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Nefropatias Diabéticas , Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Sobrevivência de Enxerto , Obesidade/complicações , Nefropatias Diabéticas/complicações , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Índice de Massa Corporal , Fatores de RiscoRESUMO
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.
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Fibrose Cística , Técnicas de Imagem por Elasticidade , Hipertensão Portal , Hepatopatias , Adulto , Humanos , Masculino , Criança , Feminino , Fibrose Cística/complicações , Fibrose Cística/epidemiologia , Fibrose Cística/diagnóstico , Estudos Retrospectivos , Prevalência , Hepatopatias/diagnóstico , Hipertensão Portal/etiologia , Hipertensão Portal/complicaçõesRESUMO
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.
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Craniotomia , Infecção da Ferida Cirúrgica , Antibacterianos/uso terapêutico , Craniotomia/efeitos adversos , Humanos , Recidiva , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/tratamento farmacológicoRESUMO
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.
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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.
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Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Doadores Vivos , Adolescente , Carcinoma Hepatocelular/cirurgia , Criança , Pré-Escolar , Feminino , Hemangiossarcoma/cirurgia , Hepatoblastoma/cirurgia , Humanos , Lactente , Masculino , Rabdomiossarcoma/cirurgiaRESUMO
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.
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Anticorpos Antivirais/sangue , COVID-19/imunologia , Hospedeiro Imunocomprometido , Imunoglobulina G/sangue , Insuficiência Respiratória/imunologia , SARS-CoV-2/imunologia , Corticosteroides/uso terapêutico , Idoso , Índice de Massa Corporal , COVID-19/sangue , COVID-19/diagnóstico , Teste Sorológico para COVID-19 , Convalescença , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Insuficiência Respiratória/sangue , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/tratamento farmacológico , Estudos Retrospectivos , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Fatores de Tempo , Tratamento Farmacológico da COVID-19RESUMO
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.
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Ductos Biliares/lesões , Doenças Biliares/cirurgia , Colecistectomia/efeitos adversos , Complicações Intraoperatórias/etiologia , Complicações Intraoperatórias/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Colangiografia , Feminino , Humanos , Complicações Intraoperatórias/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
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.
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Neoplasias , Pancreaticoduodenectomia , Anastomose Cirúrgica , Bélgica/epidemiologia , Humanos , Tempo de Internação , Fístula Pancreática , Pancreaticoduodenectomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos RetrospectivosRESUMO
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 650 434 individuals in their communities, 73 418 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% (33 002/650 434) 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.
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Serviços de Saúde Comunitária/métodos , Programas de Rastreamento/organização & administração , Escarro/microbiologia , Tuberculose Pulmonar/diagnóstico , Voluntários , Antituberculosos/uso terapêutico , República Democrática do Congo/epidemiologia , Feminino , Humanos , Masculino , Áreas de Pobreza , População Rural , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/prevenção & controleRESUMO
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.
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Atresia Biliar/fisiopatologia , Doença Hepática Terminal/fisiopatologia , Hemodinâmica , Cirrose Hepática/fisiopatologia , Transplante de Fígado/efeitos adversos , Fígado/irrigação sanguínea , Atresia Biliar/cirurgia , Circulação Sanguínea , Criança , Pré-Escolar , Ecocardiografia Doppler , Doença Hepática Terminal/cirurgia , Coração/fisiopatologia , Artéria Hepática/diagnóstico por imagem , Artéria Hepática/fisiopatologia , Humanos , Lactente , Fígado/diagnóstico por imagem , Fígado/cirurgia , Cirrose Hepática/cirurgia , Transplante de Fígado/métodos , Doadores Vivos , Veia Porta/diagnóstico por imagem , Veia Porta/fisiopatologia , Veia Porta/cirurgia , Período Pré-Operatório , Estudos Prospectivos , Índice de Gravidade de Doença , Ultrassonografia Doppler , Procedimentos Cirúrgicos VascularesRESUMO
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.
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Mycobacterium tuberculosis , Vigilância da População , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Adolescente , Fatores Etários , Criança , Pré-Escolar , República Democrática do Congo/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Modelos Estatísticos , Técnicas de Diagnóstico Molecular , Reprodutibilidade dos TestesRESUMO
OBJECTIVES: To assess the impact of the loss-of-function CYP3A5*3 allele (rs776746, 6986A>G SNP) on darunavir (DRV) plasma concentrations. METHODS: 135 HIV-1 infected patients treated with DRV-based therapy were included in the study and plasma samples were obtained immediately before drug intake in order to determine DRV trough concentrations using an ultra performance liquid chromatography method (UPLC) with diode-array detection (DAD). Noteworthy is the fact that in 16 (11.9%) patients, etravirine (ETR) was combined with DRV. CYP3A5 genotypes were determined using real time PCR method (TaqMan® genotyping assay). The patients were then classified into CYP3A5 expressors (CYP3A5*1 allele carriers) and non-expressors (CYP3A5*3 homozygous). Subsequently, the association between DRV plasma trough concentration ([DRV]plasma) and CYP3A5 genotype-based expression status was analyzed. RESULTS: 45% of the patients were classified as CYP3A5 expressors. In the whole cohort, mean [DRV]plasma was not different between CYP3A5 expressors and non-expressors (1894ng/ml [CI95%: 1566-2290] versus 1737ng/ml [CI95%: 1468-2057], p = 0.43). However, in the subgroup of the 16 patients receiving DRV combined with ETR, a significantly lower [DRV]plasma was observed for CYP3A5 expressors when compared to non-expressors (1385ng/ml [CI95%:886.3-2165] versus 3141ng/ml [CI95%:2042-4831], p = 0.007). CONCLUSIONS: Interaction between DRV and ETR is partly mediated by CYP3A5 polymorphism with lower DRV plasma trough concentrations in CYP3A5 expressors suggesting a specific ETR-driven CYP3A5 activation only in CYP3A5 expressors. Consequently, these patients might be more at risk of infra-therapeutic [DRV]plasma. This potentially important observation is a good illustration of a genotype-based drug interaction, which could also have considerable consequences if translated to other CYP3A5-metabolized drugs. Further investigations are thus needed to confirm this association and to explore its clinical impact, mainly in the African population among whom CYP3A5 expressors are more frequent, before recommending systematic CYP3A5 pre-emptive genotyping for DRV-ETR co-administration.
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Citocromo P-450 CYP3A/genética , Darunavir/farmacologia , Inibidores da Protease de HIV/farmacologia , Polimorfismo Genético , Piridazinas/farmacologia , Inibidores da Transcriptase Reversa/farmacologia , Adulto , Darunavir/administração & dosagem , Darunavir/uso terapêutico , Interações Medicamentosas , Feminino , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/administração & dosagem , Inibidores da Protease de HIV/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Nitrilas , Piridazinas/administração & dosagem , Piridazinas/uso terapêutico , Pirimidinas , Inibidores da Transcriptase Reversa/administração & dosagem , Inibidores da Transcriptase Reversa/uso terapêuticoRESUMO
BACKGROUND: Chemotherapeutic advances have enabled successful cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) expansion in treating metastatic colorectal cancer. OBJECTIVES: The aims of this study were to evaluate the safety of combining liver surgery (LS) with HIPEC and CRS (which remains controversial) and its impact on overall survival (OS) rates. METHODS: From 2007 to 2015, a total of 77 patients underwent CRS/HIPEC for peritoneal carcinomatosis (PC) of colorectal cancer. Twenty-five of these patients underwent concomitant LS for suspicion of liver metastases (LM; group 2), and were compared with patients who underwent CRS/HIPEC only (group 1). Demographic and clinical data were reviewed retrospectively. RESULTS: Among the group 2 patients, two underwent major hepatectomies, six underwent multiple wedge resections, 16 underwent single wedge resections (one with radiofrequency ablation), and one underwent radiofrequency ablation alone. For groups 1 and 2, median peritoneal cancer index was 6 and 10 (range 0-26; p = 0.08), complication rates were 15.4 and 32.0 % (Dindo-Clavien ≥3; p = 0.15), and median follow-up was 34.2 and 25.5 months (range 0-75 and 3-97), respectively. One group 2 patient died of septic shock after 66 days. Pathology confirmed LM in 21 patients in group 2 (four with benign hepatic lesions were excluded from long-term outcome analysis). Two-year OS rates were 89.5 and 70.2 % (p = 0.04), and 2-year recurrence-free survival rates were 38.3 and 13.4 % (p = 0.01) in groups 1 and 2, respectively. CONCLUSIONS: Simultaneous surgery for colorectal LM and PC is both feasible and safe, with low postoperative morbidity. Further longer-term studies would help determine its impact on patient survival.
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Neoplasias Colorretais/patologia , Hipertermia Induzida , Neoplasias Hepáticas/cirurgia , Neoplasias Peritoneais/terapia , Adolescente , Adulto , Idoso , Antibióticos Antineoplásicos/administração & dosagem , Antineoplásicos/administração & dosagem , Ablação por Cateter/efeitos adversos , Terapia Combinada/efeitos adversos , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Intervalo Livre de Doença , Feminino , Seguimentos , Hepatectomia/efeitos adversos , Humanos , Hipertermia Induzida/efeitos adversos , Infusões Parenterais , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Neoplasias Peritoneais/secundário , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Taxa de Sobrevida , Adulto JovemRESUMO
BACKGROUND: Venous thromboembolism has been reported in association with cytomegalovirus (CMV) infection both in immunocompromised and immunocompetent patients. In this population, it is yet undetermined whether CMV alone provokes VTE or other predisposing conditions are involved. MATERIALS AND METHODS: 1007 VTE patients consecutively recruited in one academic hospital were analyzed retrospectively in order to identify acute CMV infection. Acquired and inherited risk factors were screened. Only adults and immunocompetent patients were included. RESULTS: Among 1007 consecutive VTE patients, we identified 10 patients with synchronous acute CMV infection. Patients with coexistent VTE and acute CMV infection were younger (37.5 years vs. 56.6 years; p = 0.0088) and exhibited a female predominance (90% vs. 56%; p = 0.026), in comparison to the whole cohort. Hereditary thrombophilia was identified in 9 out of 10 patients. Acquired risk factors for VTE like estrogens administration and pregnancy were equally prevalent in patients with and without CMV infection. CONCLUSION: Acute CMV infection is a potential contributor to VTE whenever other prothrombotic conditions are required. This should help clinicians to privilege a limited duration of anticoagulant treatment like in other provoked VTE.
Assuntos
Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/epidemiologia , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: 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. METHODS: Measurement of at least 4 h-fasting plasma acylated and unacylated ghrelin in 37 infants with a genetic diagnosis of PWS aged from 1 month to 4 years and in 100 age-matched controls without endocrine disorder recruited prior to minor surgery. One blood sampling was analysed for each patient/control and clinical data were recorded. Eleven PWS infants underwent repetitive blood samples at 3 or 6-month intervals during routine visits. RESULTS: In infants with PWS, AG is not elevated (p = 0.45), UAG is significantly higher (p = 0.0044; confidence interval 1.06;1.33) resulting in a low AG/UAG ratio (p = 0.0056; confidence interval 0.76;0.95) compared to controls. CONCLUSION: Unlike children and adults with PWS that have high AG and AG/UAG ratio, infants with PWS have elevated UAG that supports the concept of anorexia in the early phases of the disease. The change in AG/UAG ratio possibly drives the switch from failure to thrive to obesity. CLINICAL TRIAL REGISTRATION: NCT02529085 .
Assuntos
Anorexia/sangue , Anorexia/metabolismo , Grelina/sangue , Grelina/metabolismo , Síndrome de Prader-Willi/sangue , Síndrome de Prader-Willi/metabolismo , Acilação , Feminino , Humanos , Lactente , Masculino , Obesidade/sangue , Obesidade/metabolismoRESUMO
OBJECTIVES: To describe the validation of a sensitive high performance liquid chromatography tandem mass spectrometry (LC-MS/MS) method allowing the simultaneous quantification of darunavir (DRV) and etravirine (ETR) in peripheral blood mononuclear cells (PBMCs) and its application in a cohort of HIV-1 infected patients. METHODS: Blood samples were obtained from 110 patients. PMBCs were isolated using density gradient centrifugation. Drug extraction from PBMCs was performed with a 60:40 methanol-water (MeOH-H2O) solution containing deuterated IS (DRV-d9 and ETR-d8). The chromatographic separation was performed on a RP18 XBridge™ column. RESULTS: The geometric mean (GM) of cell associated concentration ([DRV]CC) and plasmatic concentration ([DRV]plasma) were 360.5ng/mL (CI95%:294.5-441.2) and 1733ng/mL (CI95%:1486-2021), respectively. A geometric mean intracellular (IC)/plasma ratio (GMR) of 0.21 (CI95%:0.18-0.24) was calculated. Adjusted for dose/body surface area and post-intake time, a statistically significant correlation was observed between [DRV]Plasma and the eGFR (p=0.002) and between [DRV]Plasma and the concomitant use of ETR (p=0.038). For the 10 patients receiving ETR in addition to DRV, the GM of [ETR]Plasma (available for 8 out of 10 patients) and [ETR]CC were 492.3ng/mL and 2951ng/mL respectively. The GMR of ETR was 7.6 (CI95%: 3.61-13.83). CONCLUSIONS: A handy and sensitive high performance LC-MS/MS method allowing the simultaneous quantification of DRV and ETR in PBMCs has been described and successfully applied in the largest cohort of DRV-treated patients reported to date. ETR accumulates more efficiently in PBMCs compared to DRV. We have also highlighted a possible impact of ETR on DRV plasma concentrations requiring further investigations.
Assuntos
Biomarcadores/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Darunavir/sangue , Infecções por HIV/sangue , Leucócitos Mononucleares/metabolismo , Piridazinas/sangue , Espectrometria de Massas em Tandem/métodos , Estudos de Coortes , Darunavir/uso terapêutico , Interações Medicamentosas , Monitoramento de Medicamentos/métodos , Feminino , Seguimentos , HIV/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/sangue , Inibidores da Protease de HIV/uso terapêutico , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Limite de Detecção , Masculino , Pessoa de Meia-Idade , Nitrilas , Prognóstico , Piridazinas/uso terapêutico , Pirimidinas , Inibidores da Transcriptase Reversa/sangue , Inibidores da Transcriptase Reversa/uso terapêuticoRESUMO
AIMS: To assess the clinical performance of pro-B-type natriuretic peptide 1-108 (proBNP) for the prognosis of acute pulmonary embolism. METHODS: This study was ancillary to a recently published multicentre study including 570 patients with acute pulmonary embolism. ProBNP values were analysed using a new sandwich immunoassay proBNP1-108, Bioplex2200 (Bio-Rade Laboratories). Data was compared with BNP and N-terminal (NT) proBNP values. Adverse outcomes at 30 days were defined as death, secondary cardiogenic shock, or recurrent venous thromboembolism. RESULTS: ProBNP values were analysed in 549 patients, with 39 (7.1%) presenting adverse outcomes. All three natriuretic peptides were significantly elevated in these 39 patients compared with the group without adverse outcomes (BNP: p < 0.001; NT-proBNP: p < 0.001; proBNP: 0.044), with median proBNP values being 605 pg/ml (113-1437) and 109 pg/ml (30-444), respectively. Multivariate analyses revealed that proBNP significantly depended on patient age (p < 0.001) and renal failure (p=0.001), with proBNP values increasing with both factors. The areas under the receiver operating curve were 0.74 (95% CI 0.69-0.79) for BNP, 0.76 (95% CI 0.72-0.80) for NT-proBNP, and 0.70 (95% CI 0.65-0.75) for proBNP, meaning that the performance of proBNP was significantly lower than that of the two other peptides (p = 0.017). CONCLUSION: ProBNP, BNP, and NT-proBNP values were significantly increased in patients with adverse outcomes after acute pulmonary embolism. However, the prognostic performance of proBNP for predicting adverse versus favourable outcomes was lower than that of the other natriuretic peptides, thus limiting the clinical relevance of proBNP as a prognostic marker in pulmonary embolism.
Assuntos
Peptídeo Natriurético Encefálico/sangue , Embolia Pulmonar/diagnóstico , Doença Aguda , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Embolia Pulmonar/sangue , Curva ROCRESUMO
OBJECTIVES: The most frequent presentation of chemotherapy-related toxicity in colorectal liver metastases (CRLM) is sinusoidal obstruction syndrome (SOS). The purpose of the present study was to identify preoperative factors predictive of SOS and to establish associations between type of chemotherapy and severity of SOS. METHODS: A retrospective study was carried out in a tertiary academic referral hospital. Patients suffering from CRLM who had undergone resection of at least one liver segment were included. Grading of SOS on the non-tumoral liver parenchyma was accomplished according to the Rubbia-Brandt criteria. A total of 151 patients were enrolled and divided into four groups according to the severity of SOS (grades 0-3). RESULTS: Multivariate analysis identified oxaliplatin and 5-fluorouracil as chemotherapeutic agents responsible for severe SOS lesions (P < 0.001 and P = 0.005, respectively). Bevacizumab was identified as having a protective effect against the occurrence of SOS lesions (P = 0.005). Univariate analysis identified the score on the aspartate aminotransferase : platelets ratio index (APRI) as the most significant biological factor predictive of severe SOS lesions. Splenomegaly is also significantly associated with the occurrence of severe SOS lesions. CONCLUSIONS: The APRI score and splenomegaly are effective as factors predictive of SOS. Bevacizumab has a protective effect against SOS.