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BACKGROUND: Repeat open hepatectomy (ROH) for recurrent liver tumors is the preferred approach especially after initial open hepatectomy (OH). The aim of this study is to assess feasibility and safety of repeat laparoscopic hepatectomy (RLH) after initial OH in 2 high volume hepato-biliary hospitals. METHODS: Patients were retrieved from prospective data bases from 2012 to 2020. The patients were divided into two groups according to the approach used for repeat hepatectomy, ROH and RLH groups. RESULTS: Sixty-seven patients matched the criteria, 20 in RLH and 47 in ROH. Diagnoses were hepatocellular carcinoma in 52.3%, intrahepatic cholangiocarcinoma in 7.7% and colorectal liver metastases in 40%. Median operative time and blood loss were lower in RLH (199 vs 260 min, and 100 vs 400 ml respectively), as well as overall postoperative complications (20% vs 49%). There were 2 conversions (10%) due to adhesions and one died of postoperative pancreatitis in RLH. Median hospital stay was lower in RLH (5 vs 9 days). CONCLUSION: RLH is a feasible, safe technique and a realistic option to be considered in selected patients after previous OH. Early conversion should be considered when adhesions are more severe than expected.
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OBJECTIVE: To investigate in patients treated for a resectable pancreatic ductal adenocarcinoma (PA), the prognostic value of baseline CA19-9 and circulating tumour DNA (ctDNA) for overall survival (OS), to improve death risk stratification, based on a planned ancillary study from PANACHE01-PRODIGE 48 trial. SUMMARY BACKGROUND DATA: Biological borderline situation that was first used by the MD Anderson, became a standard practice following the international consensus conference in 2016 to manage PA. Regarding the risk of systemic disease especially in the setting of "markedly elevated" CA19-9, neoadjuvant therapy is advised to avoid unnecessary surgery, with risk of early recurrence. To best define biological borderline situations, new biomarkers are needed. METHODS: Characteristics at diagnosis and OS were compared between patients with or without ctDNA status available. OS was estimated with Kaplan Meier method and compared with log-rank test. Restricted cubic spline approach was used to identify optimal threshold for biological parameters for death risk stratification. Univariate and multivariate Cox proportional hazard models were estimated to assess the association of ctDNA status and other parameters with OS. RESULTS: Among the 132 patients from the primary population for analysis in the PANACHE01 -PRODIGE 48 trial, 92(71%) were available for ctDNA status at diagnosis. No selection bias was identified between patients with or without ctDNA status. 14 patients (15%) were ctDNA+ and exhibited a higher risk for death (P=0,0188; HR95% CI: 2.28 (1.12-4.63). In the 92 patients with ctDNA status available among the others parameter analysed only CA19-9 was statically associated with OS in univariate analysis. Patients with log of CA19-9 equal or superior to 4.4 that corresponds to a CA19-9 of 80 UI/mL were identified at higher risk for death (P=0,0143; HR95% CI: 2.2 (1.15-4.19). In multivariate analysis CA19-19 remained independently associated with OS (p-value=0.0323). When combining the two biomarkers, median OS was of 19.4 (IC 95% 3.8-Not reached) months, 30.2 (IC 95% 17.1-NR) months and not reached (IC 95% 39.3-NR) for "CA19-9 high and ctDNA+ group", "CA19-9 high or ctDNA+ group", and "CA19-9 low and ctDNA- group", respectively (logrank P=0,0069). DISCUSSION: Progress in the management of potentially operable PA remains limited, relying solely on strategies to optimize the sequence of complete treatment, based on modern multidrug chemotherapy (FOLFIRINOX, GemNabPaclitaxel) and surgical resection. The identification of risk criteria, such as the existence of systemic disease, is an important issue, currently referred to as "biologic borderline disease". Few data, particularly from prospective studies, allow us to identify biomarkers other than CA19-9. CONCLUSION: Combining ctDNA to CA19-9 could be of interest to best define biological borderline situations in PA.
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BACKGROUND: Despite advances in surgical techniques and care, pancreatoduodenectomy (PD) continues to have high morbidity and mortality rates. Complications such as sepsis, hemorrhage, pulmonary issues, shock, and pancreatic fistula are common postoperative challenges. A key concern in PD outcomes is the high incidence of infectious complications, especially surgical site infections (SSI) and postoperative pancreatic fistula (POPF). Bacteriobilia, or bile contamination with microorganisms, significantly contributes to these infections, increasing the risk of early postoperative complications. The occurrence of SSI in patients who undergo hepatobiliary and pancreatic (HPB) surgeries such as PD is notably higher than that in patients who undergo other surgeries, with rates ranging from 20 to 55%. Recent research by D'Angelica et al. revealed that, compared to cefoxitin, piperacillin/tazobactam considerably lowers the rate of postoperative SSI. However, these findings do not indicate whether extending the duration of antibiotic treatment is beneficial for patients at high risk of bacterial biliary contamination. In scenarios with a high risk of SSI, the specific agents, doses and length of antibiotic therapy remain unexplored. The advantage of prolonged antibiotic prophylaxis following PD has not been established through prospective studies in PD patients following biliary drainage. METHODS: This is an intergroup FRENCH-ACHBT-SFAR multicenter, open-labelled randomized, controlled, superiority trial comparing 2 broad-spectrum antibiotic (piperacillin/tazobactam) treatment modalities to demonstrate the superiority of 5-day postoperative antibiotic therapy to antibiotic prophylaxis against the occurrence of surgical site infections (SSI) following pancreaticoduodenectomy in patients with preoperative biliary stents. The primary endpoint of this study is the overall SSI rate, defined according to the ACS NSQIP, as a composite of superficial SSI, deep incisional SSI, and organ/space SSI. In addition, we will analyze overall morbidity, antibiotic resistance profiles, the pathogenicity of bacteriological and fungal cocontamination, the impact of complications after bile drainage and neoadjuvant treatment on the bacteriological and fungal profile of biliculture and cost-effectiveness. CONCLUSION: This FRENCH24-ANIS study aims to evaluate 5-day post-operative antibiotic therapy combined with antibiotic prophylaxis on the occurrence of surgical site infections (SSI) following pancreaticoduodenectomy in patients with preoperative biliary stents. TRIAL REGISTRATION: ClinicaTrials.gov number, NCT06123169 (Registration Date 08-11-2023); EudraCT number 2021-006991-18; EUCT Number: 2024-515181-14-00.
Subject(s)
Antibiotic Prophylaxis , Pancreaticoduodenectomy , Stents , Surgical Wound Infection , Pancreaticoduodenectomy/adverse effects , Humans , Surgical Wound Infection/prevention & control , Surgical Wound Infection/epidemiology , Antibiotic Prophylaxis/methods , Prospective Studies , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/administration & dosage , France/epidemiology , Randomized Controlled Trials as Topic , Postoperative Complications/prevention & control , Postoperative Complications/epidemiology , Male , Preoperative Care/methodsABSTRACT
CONTEXT: This work analyzes the isomerization effects and solvent contributions to the stability, electronic excitations, reactivity, and non-linear optical properties (NLO) of resveratrol molecules within the formalism of the Density Functional Theory. The findings suggest that resveratrol solvatochromism is significantly influenced by solvent polarization. The electronic and free energies (E and G) indicate that trans is the most stable conformer. The system is classified as a strong nucleophile. However, the analysis of the Fukui functions and the Mulliken charges indicate that cis-trans isomerization jointly affects the reactive indices of the carbon and hydrogen atoms. The results also suggest that solvent is relevant to solvatochromism and the NLO response. Both cis and trans conformers present strong π - π ∗ excitations that undergo a visible hypsochromic change when the polarity of the solvent increases. Once the absorption spectra are connected to the first hyperpolarization ( ß ) by the Oudar and Chemla relation, the hypsochromism of resveratrol is the reason for the drop in the generation of the second harmonic when the ambient polarity decreases. The CAM-B3LYP DFT results suggest that resveratrol is interesting for NLO applications. Depending on the choice of solvent, values â¼ 50 times those observed for urea ( ß = 0.34 × 10 - 34 esu), which is a standard NLO material. METHODS: The optimized geometries of cis and trans isomers of resveratrol in vacuum were obtained using Density Functional Theory (DFT) with the hybrid exchange-correlation function (CAM-B3LYP) and Pople basis set functions, specifically 6-311++G(d,p). The solvent effect on the geometries of both isomers was included using the polarizable continuum model (PCM) with the same level of QM calculation. Vibrational analysis was conducted to confirm that all optimized geometries correspond to the minimum energy. Various electronic properties, including dipole moments, molecular orbitals, transition energy, dipole polarizabilities, and global reactivity parameters, were calculated using both continuum and discrete solvation models based on the sequential QM/MM methodology. All QM calculations were performed with the Gaussian 09 program and the MC simulations with the DICE program. All NLO analysis was carried out using the Multiwfn code.
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Abstract Objective: To evaluate exclusive breastfeeding at discharge and hospital length-of-stay in pre-term infants undergoing or not the Kangaroo-Mother Care Method (KMC). Methods: A retrospective cohort study was conducted including preterm infants < 1800 g admitted to the neonatal unit of a KMC reference center. The infants were grouped into the KMC group and the non-KMC group. Multiple logistic and Poisson regressions were performed to evaluate the association between the KMC and two outcomes, exclusive breastfeeding at discharge, and hospital length-of-stay, adjusted for potential confounders. Results: 115 mother-infant dyads were included, 78 in the KMC group and 37 in the non-KMC group. In the bivariate analysis, the KMC group had a lower prevalence of maternal adverse conditions (6% vs. 32%, p < 0.001), a higher number of prenatal visits (median 6 vs. 3.5, p < 0.001), higher gestational ages (median 32 vs. 31 weeks, p < 0.05), higher birth weights (median 1530 vs. 1365 g, p < 0.01), a lower prevalence of necrotizing enterocolitis (3.8% vs. 16.2%, p < 0.05), parenteral nutrition (50% vs. 73%, p < 0.05), and deep vascular access (49.7% vs. 78.4%, p < 0.01), a higher prevalence of exclusive breastfeeding (65% vs. 8%, p < 0.001) and a shorter length of hospital stay (median 28 vs. 42 days, p < 0.001). In the multiple regression analysis, the KMC group was 23 times more likely to be exclusively breastfed at discharge (OR = 23.1; 95% CI = 4,85-109,93) and had a 19% reduction in the hospital length-of-stay (IDR = 0.81; 95% CI = 0.76-0.86) compared to the non-KMC group. Conclusions: The KMC is associated with better short-term neonatal outcomes and should be encouraged in all Brazilian maternity hospitals.
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Abstract Objective: To evaluate the effect of high-fidelity simulation of pediatric emergencies compared to case-based discussion on the development of self-confidence, theoretical knowledge, clinical reasoning, communication, attitude, and leadership in undergraduate medical students. Methods: 33 medical students were allocated to two teaching methods: high-fidelity simulation (HFS, n = 18) or case-based discussion (CBD, n = 15). Self-confidence and knowledge tests were applied before and after the interventions and the effect of HFS on both outcomes was estimated with mixed-effect models. An Objective Structured Clinical Examination activity was conducted after the interventions, while two independent raters used specific simulation checklists to assess clinical reasoning, communication, attitude, and leadership. The effect of HFS on these outcomes was estimated with linear and logistic regressions. The effect size was estimated with the Hedge'sg. Results: Both groups had an increase in self-confidence (HFS 59.1 × 93.6, p < 0.001; CDB 50.5 × 88.2, p < 0.001) and knowledge scores over time (HFS 45.1 × 63.2, p = 0.001; CDB 43.5 × 56.7, p-value < 0.01), but no difference was observed between groups (group*time effect in the mixed effect models adjusted for the student ranking) for both tests (p = 0.6565 and p = 0.3331, respectively). The simulation checklist scores of the HFS group were higher than those of the CBD group, with large effect sizes in all domains (Hedges g 1.15 to 2.20). Conclusion: HFS performed better than CBD in developing clinical reasoning, communication, attitude, and leadership in undergraduate medical students in pediatric emergency care, but no significant difference was observed in self-confidence and theoretical knowledge.
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OBJECTIVE: To analyse outcomes after adult right ex-situ split graft liver transplantations (RSLT) and compare with available outcome benchmarks from whole liver transplantation (WLT). SUMMARY BACKGROUND DATA: Ex-situ SLT may be a valuable strategy to tackle the increasing graft shortage. Recently established outcome benchmarks in WLT offer a novel reference to perform a comprehensive analysis of results after ex-situ RSLT. METHODS: This retrospective multicenter cohort study analyzes all consecutive adult SLT performed using right ex-situ split grafts from 01.01.2014 to 01.06.2022. Study endpoints included 1 year graft and recipient survival, overall morbidity expressed by the comprehensive complication index (CCI©) and specific post-LT complications. Results were compared to the published benchmark outcomes in low-risk adult WLT scenarii. RESULTS: In 224 adult right ex-situ SLT, 1y recipient and graft survival rates were 96% and 91.5%, within the WLT benchmarks. The 1y overall morbidity was also within the WLT benchmark (41.8 CCI points vs. <42.1). Detailed analysis, revealed cut surface bile leaks (17%, 65.8% Grade IIIa) as a specific complication without a negative impact on graft survival. There was a higher rate of early hepatic artery thrombosis (HAT) after SLT, above the WLT benchmark (4.9% vs. ≤4.1%), with a significant impact on early graft but not patient survival. CONCLUSION: In this multicentric study of right ex-situ split graft LT, we report 1-year overall morbidity and mortality rates within the published benchmarks for low-risk WLT. Cut surface bile leaks and early HAT are specific complications of SLT and should be acknowledged when expanding the use of ex-situ SLT.
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The nutritional composition of bovine liver, particularly in terms of vitamins E, ß-carotene, and cholesterol concentration, is significantly influenced by the cattle-rearing system and diet. This study aimed to elucidate the impact of four predominant cattle-rearing systems in the Eastern Amazon region on the vitamin E, ß-carotene content, and cholesterol levels in bovine liver during the rainy season. Liver-tissue samples were collected from 48 cattle, with twelve specimens representing each rearing system. The systems encompassed two native pastures located in flood-prone areas, cultivated pastures on upland terrain and a confinement-rearing system. Our findings indicate that, when considering all rearing systems collectively, there were no significant differences in the levels of vitamins and cholesterol in the liver tissues (p > 0.05). However, a marked disparity in cholesterol levels emerged when comparing intensive rearing systems to extensive ones, with the former demonstrating notably higher concentrations (p = 0.01). Additionally, the intensive rearing system was associated with elevated levels of ß-carotene (p < 0.01), α-tocopherol (p = 0.01), and ß-tocopherol (p = 0.01) relative to the extensive systems. No significant variations were observed amongst the different extensive systems (p > 0.05). These results suggest that, while all rearing systems yielded liver tissues with typical concentrations of vitamins and cholesterol, the intensive rearing system led to a higher accumulation of certain vitamin compounds. This study highlights the substantial nutritional implications of different cattle-rearing systems in the Eastern Amazon and provides valuable insights for developing dietary strategies to optimize the nutritional quality of bovine liver. Therefore, the generated results are groundbreaking in the Eastern Amazon, Brazil, and inspire the development of new research projects to address other demands in this field and achieve additional outcomes.
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Pancreatic diabetes is associated with glycemic variability, poor metabolic control, and reduced quality of life. Though hybrid closed-loop (HCL) insulin delivery systems were not originally developed for these types of diabetes, they could address the therapeutic challenge. We aimed to evaluate long-term metabolic control in ten adult patients (mean ± SD age: 59 ± 12) treated with HCL insulin delivery systems for pancreatitis or pancreatectomy-induced diabetes. After a median of 346 days (range 64 - 631) with HCL insulin delivery, continuous glucose monitoring showed 59±19 % time-in-range [70-180 mg/dl] (versus 49±24 % before HCL insulin delivery, P = 0. 049) and 0.8 ± 1.0 % time-below-range [< 70 mg/dl] (versus 2.2 ± 2.6 %, P = 0.142), with the coefficient of glucose variability at 35.4 ± 7.6 (versus 37.8 ± 7.1, P = 0.047). HbA1c decreased from 8.5 ± 1.7 % to 7.7 ± 1.3 % [69±18 to 60±14 mmol/mol] (P = 0.076). No patient experienced an acute adverse metabolic event.
Subject(s)
Insulin Infusion Systems , Insulin , Pancreatectomy , Pancreatitis , Humans , Middle Aged , Male , Female , Insulin/administration & dosage , Insulin/therapeutic use , Aged , Pancreatitis/etiology , Blood Glucose/analysis , Blood Glucose/drug effects , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/therapeutic use , Adult , Glycated Hemoglobin/analysis , Glycemic Control/methods , Diabetes Mellitus/drug therapy , Blood Glucose Self-MonitoringABSTRACT
Introduction: The quality of meat, with a focus on compounds important for human health, is directly related to the rearing systems in which the animals are produced. The search for a balanced diet, with an emphasis on low cholesterol and adequate levels of vitamins, aligns with society's emphasis on healthy eating, directly correlated with the importance of the offer made by producers for the cattle's diet. Objective and methodology: The objective was to verify the impact of different rearing systems, in the Eastern Amazon, during the rainy season, on the concentrations of vitamins (A, E) and cholesterol in the muscle (Longissimus lumborum) of crossbred Nelore cattle, castrated, aged between 24 and 36 months, and weighing between 410 and 628 kg. Twelve animals, from each of the three pasture rearing systems: native pasture in flooded areas of Monte Alegre; native pasture in a flooded area of Santa Cruz do Arari; and pasture cultivated on dry land in São Miguel do Guamá, all located in Pará, Brazil-were sampled in commercial slaughterhouses. Results: A notable influence was observed in the concentrations of ß-carotene (p < 0.01), α-Tocopherol (p = 0.02), ß-Tocopherol (p < 0.01) and the combined sum of ß-Tocotrienol and γ-Tocopherol (p < 0.01), as well as δ-Tocopherol (p < 0.01) when contrasting extensive with intensive systems (confinement). However, there was a difference in the content of vitamins and cholesterol between the isolated extensive systems, or between the four rearing systems (p > 0.05). Extensive systems, mainly in Monte Alegre, demonstrated greater amounts of α-Tocopherol and δ-Tocopherol. Conclusion: On the other hand, the intensive system exhibited higher levels of other investigated compounds, clarifying the nutritional variations generated by different livestock rearing practices in the region. Therefore, the results obtained are innovative in the Eastern Amazon, Brazil, in addition to inspiring the development of new research to meet other demands in this field, and achieve additional results, such as determining which meat, coming from cattle in production systems in the country, presents the better compositional quality of vitamins and lipids.
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BACKGROUND: The current version of the Fetal Medicine Foundation competing risks model for preeclampsia prediction has not been previously validated in Brazil. OBJECTIVE: This study aimed (1) to validate the Fetal Medicine Foundation combined algorithm for the prediction of preterm preeclampsia in the Brazilian population and (2) to describe the accuracy and calibration of the Fetal Medicine Foundation algorithm when considering the prophylactic use of aspirin by clinical criteria. STUDY DESIGN: This was a cohort study, including consecutive singleton pregnancies undergoing preeclampsia screening at 11 to 14 weeks of gestation, examining maternal characteristics, medical history, and biophysical markers between October 2010 and December 2018 in a university hospital in Brazil. Risks were calculated using the 2018 version of the algorithm available on the Fetal Medicine Foundation website, and cases were classified as low or high risk using a cutoff of 1/100 to evaluate predictive performance. Expected and observed cases with preeclampsia according to the Fetal Medicine Foundation-estimated risk range (≥1 in 10; 1 in 11 to 1 in 50; 1 in 51 to 1 in 100; 1 in 101 to 1 in 150; and <1 in 150) were compared. After identifying high-risk pregnant women who used aspirin, the treatment effect of 62% reduction in preterm preeclampsia identified in the Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence-Based Preeclampsia Prevention trial was used to evaluate the predictive performance adjusted for the effect of aspirin. The number of potentially unpreventable cases in the group without aspirin use was estimated. RESULTS: Among 2749 pregnancies, preterm preeclampsia occurred in 84 (3.1%). With a risk cutoff of 1/100, the screen-positive rate was 25.8%. The detection rate was 71.4%, with a false positive rate of 24.4%. The area under the curve was 0.818 (95% confidence interval, 0.773-0.863). In the risk range ≥1/10, there is an agreement between the number of expected cases and the number of observed cases, and in the other ranges, the predicted risk was lower than the observed rates. Accounting for the effect of aspirin resulted in an increase in detection rate and positive predictive values and a slight decrease in the false positive rate. With 27 cases of preterm preeclampsia in the high-risk group without aspirin use, we estimated that 16 of these cases of preterm preeclampsia would have been avoided if this group had received prophylaxis. CONCLUSION: In a high-prevalence setting, the Fetal Medicine Foundation algorithm can identify women who are more likely to develop preterm preeclampsia. Not accounting for the effect of aspirin underestimates the screening performance.
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BACKGROUND: Despite the ongoing trend of increasing donor ages in liver transplantation (LT) setting, a notable gap persists in the availability of comprehensive guidelines for the utilization of organs from elderly donors. This study aimed to evaluate the viability of livers grafts from donors aged ≥85 years and report the post-LT outcomes compared with those from "ideal" donors under 40 years old. METHODS: Conducted retrospectively at a single center from 2005 to 2023, this study compared outcomes of LTs from donors aged ≥85 y/o and ≤40 y/o, with the propensity score matching to the recipient's gender, age, BMI, MELD score, redo-LT, LT indication, and cause of donor death. RESULTS: A total of 76 patients received grafts from donors ≥85 y/o and were compared to 349 liver grafts from donors ≤40 y/o. Prior to PSM, the 5-year overall survival was 63% for the elderly group and 77% for the young group (p = 0.002). After PSM, the 5-year overall survival was 63% and 73% (p = 0.1). A nomogram, developed at the time of graft acceptance and including HCC features, predicted 10-year survival after LT using a graft from a donor aged ≥85. CONCLUSIONS: In the context of organ scarcity, elderly donors emerge as a partial solution. Nonetheless, without proper selection, LT using very elderly donors yields inferior long-term outcomes compared to transplantation from very young donors ≤40 y/o. The resulting nomogram based on pre-transplant criteria allows for the optimization of elderly donor/recipient matching to achieve satisfactory long-term results, in addition to traditional matching methods.
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Trachoma is the world-leading infectious cause of preventable blindness and is caused by the bacteria Chlamydia trachomatis. In developing countries, diagnosis is usually based on clinical evaluation. Serological-based tests are cheaper than molecular-based ones, but the latter are more sensitive and specific. The present study developed a new duplex qPCR which concomitantly detects the C. trachomatis cryptic plasmid and the human 18S rRNA gene, with an LOD95% for C. trachomatis DNA of 13.04 genome equivalents per reaction. The new qPCR was tested using 50 samples from an endemic area and 12 from a non-endemic area that were previously characterized using direct immunofluorescence assay (DFA) and clinical evaluation. Among the 50 endemic samples, 3 were found to be positive by clinical evaluation (6%), 18 were found to be positive by DFA (36%), and 48 were found to be positive by qPCR (96%). Next, the new duplex qPCR was validated using 50 samples previously characterized by qPCR. Validation was carried out on a benchtop instrument (ABI7500) or on a portable point-of-care instrument (Q3-Plus), showing 95% specificity and 100% sensitivity. The ubiquitous presence of C. trachomatis DNA in samples from the endemic region confirms that constant monitoring is of paramount importance for the effective measurement of the elimination of trachoma. The newly developed duplex qPCR presented in this study, along with its validation in a portable qPCR system, constitutes important tools toward achieving this goal.
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OBJECTIVE: Pharmacological prevention of postoperative pancreatic fistula (POPF) after pancreatectomy is open to debate. The present study compares clinically significant POPF rates in patients randomized between somatostatin versus octreotide as prophylactic treatment. METHODS: Multicentric randomized controlled open study in patient's candidate for pancreaticoduodenectomy (PD) or distal pancreatectomy (DP) comparing somatostatin continuous intravenous infusion for 7 days versus octreotid 100 µg, every 8 hours subcutaneous injection for 7 days, stratified by procedure (PD vs DP) and size of the main pancreatic duct (>4 mm) on grade B/C POPF rates at 90 days based on an intention-to-treat analysis. RESULTS: Of 763 eligible patients, 651 were randomized: 327 in the octreotide arm and 324 in the somatostatin arm, with comparable the stratification criteria - type of surgery and main pancreatic duct dilatation. Most patients had PD (n=480; 73.8%), on soft/normal pancreas (n=367; 63.2%) with a nondilated main pancreatic duct (n=472; 72.5%), most often for pancreatic adenocarcinoma (n=311; 47.8%). Almost all patients had abdominal drainage (n=621; 96.1%) and 121 (19.5%) left the hospital with the drain in place (median length of stay=16 days). A total of 153 patients (23.5%) developed a grade B/C POPF with no difference between both groups: 24.1%: somatostatin arm and 22.9%: octreotide arm (χ 2 test, P =0.73, ITT analysis). Absence of statistically significant difference persisted after adjustment for stratification variables and in per-protocol analysis. CONCLUSION: Continuous intravenous somatostatin is not statistically different from subcutaneous octreotide in the prevention of grade B/C POPF after pancreatectomy. FINDINGS: In the PREFIPS Randomized Clinical Trial including 651 patients, a total of 153 patients (23.5%) developed a grade B/C POPF with no significant difference between both groups: 24.1%: somatostatin arm and 22.9%: octreotide arm (χ 2 test, P =0.73, ITT analysis). Absence of statistically significant difference persisted after adjustment for stratification variables and in per-protocol analysis.
Subject(s)
Octreotide , Pancreatectomy , Pancreatic Fistula , Pancreaticoduodenectomy , Postoperative Complications , Somatostatin , Humans , Pancreatic Fistula/prevention & control , Pancreatic Fistula/etiology , Pancreatic Fistula/epidemiology , Octreotide/therapeutic use , Octreotide/administration & dosage , Male , Female , Somatostatin/administration & dosage , Somatostatin/therapeutic use , Pancreatectomy/adverse effects , Pancreaticoduodenectomy/adverse effects , Middle Aged , Postoperative Complications/prevention & control , Aged , Infusions, Intravenous , Gastrointestinal Agents/administration & dosage , Gastrointestinal Agents/therapeutic use , Treatment Outcome , France/epidemiology , Adult , Injections, SubcutaneousABSTRACT
Iron catalyses the oxidation of lipids in biological membranes and promotes a form of cell death referred to as ferroptosis1-3. Identifying where this chemistry takes place in the cell can inform the design of drugs capable of inducing or inhibiting ferroptosis in various disease-relevant settings. Whereas genetic approaches have revealed underlying mechanisms of lipid peroxide detoxification1,4,5, small molecules can provide unparalleled spatiotemporal control of the chemistry at work6. Here, we show that the ferroptosis inhibitor liproxstatin-1 (Lip-1) exerts a protective activity by inactivating iron in lysosomes. Based on this, we designed the bifunctional compound fentomycin that targets phospholipids at the plasma membrane and activates iron in lysosomes upon endocytosis, promoting oxidative degradation of phospholipids and ferroptosis. Fentomycin effectively kills primary sarcoma and pancreatic ductal adenocarcinoma cells. It acts as a lipolysis-targeting chimera (LIPTAC), preferentially targeting iron-rich CD44high cell-subpopulations7,8 associated with the metastatic disease and drug resistance9,10. Furthermore, we demonstrate that fentomycin also depletes CD44high cells in vivo and reduces intranodal tumour growth in an immunocompetent murine model of breast cancer metastasis. These data demonstrate that lysosomal iron triggers ferroptosis and that lysosomal iron redox chemistry can be exploited for therapeutic benefits.
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OBJECTIVE: To evaluate the effect of high-fidelity simulation of pediatric emergencies compared to case-based discussion on the development of self-confidence, theoretical knowledge, clinical reasoning, communication, attitude, and leadership in undergraduate medical students. METHODS: 33 medical students were allocated to two teaching methods: high-fidelity simulation (HFS, n = 18) or case-based discussion (CBD, n = 15). Self-confidence and knowledge tests were applied before and after the interventions and the effect of HFS on both outcomes was estimated with mixed-effect models. An Objective Structured Clinical Examination activity was conducted after the interventions, while two independent raters used specific simulation checklists to assess clinical reasoning, communication, attitude, and leadership. The effect of HFS on these outcomes was estimated with linear and logistic regressions. The effect size was estimated with the Hedge's g. RESULTS: Both groups had an increase in self-confidence (HFS 59.1 × 93.6, p < 0.001; CDB 50.5 × 88.2, p < 0.001) and knowledge scores over time (HFS 45.1 × 63.2, p = 0.001; CDB 43.5 × 56.7, p-value < 0.01), but no difference was observed between groups (group*time effect in the mixed effect models adjusted for the student ranking) for both tests (p = 0.6565 and p = 0.3331, respectively). The simulation checklist scores of the HFS group were higher than those of the CBD group, with large effect sizes in all domains (Hedges g 1.15 to 2.20). CONCLUSION: HFS performed better than CBD in developing clinical reasoning, communication, attitude, and leadership in undergraduate medical students in pediatric emergency care, but no significant difference was observed in self-confidence and theoretical knowledge.
Subject(s)
Clinical Competence , Education, Medical, Undergraduate , Students, Medical , Humans , Education, Medical, Undergraduate/methods , Female , Male , Emergencies , Pediatrics/education , High Fidelity Simulation Training/methods , Communication , Educational Measurement , Young Adult , Self Concept , Clinical ReasoningABSTRACT
Emodin is a natural anthraquinone derivative found in nature, widely known as an herbal medicine. Here, the partition, location, and interaction of emodin with lipid membranes of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) are experimentally investigated with different techniques. Our studies have considered the neutral form of emodin (EMH) and its anionic/deprotonated form (EM-), and their interaction with a more and less packed lipid membrane, DMPC at the gel and fluid phases, respectively. Though DSC results indicate that the two species, EMH and EM-, similarly disrupt the packing of DMPC bilayers, spin labels clearly show that EMH causes a stronger bilayer disruption, both in gel and fluid DMPC. Fluorescence spectroscopy shows that both EMH and EM- have a high affinity for DMPC: the binding of EM- to both gel and fluid DMPC bilayers was found to be quite similar, and similar to that of EMH to gel DMPC, Kp = (1.4 ± 0.3)x103. However, EMH was found to bind twice more strongly to fluid DMPC bilayers, Kp = (3.2 ± 0.3)x103. Spin labels and optical absorption spectroscopy indicate that emodin is located close to the lipid bilayer surface, and suggest that EM- is closer to the lipid/water interface than EMH, as expected. The present studies present a relevant contribution to the current understanding of the effect the two species of emodin, EMH and EM-, present on different microregions of an organism, as local pH values can vary significantly, can cause in a neutral lipid membrane, either more or less packed, liked gel and fluid DMPC, respectively, and could be extended to lipid domains of biological membranes.
Subject(s)
Emodin , Dimyristoylphosphatidylcholine/chemistry , Lipid Bilayers/chemistry , Spin LabelsABSTRACT
The purpose of this study was to propose an innovative intraoperative criterion in a liver transplantation setting that would judge arterial flow abnormality that may lead to early hepatic arterial occlusion, that is, thrombosis or stenosis, when left untreated and to carry out reanastomosis. After liver graft implantation, and after ensuring that there is no abnormality on the Doppler ultrasound (qualitative and quantitative assessment), we intraoperatively injected indocyanine green dye (0.01 mg/Kg), and we quantified the fluorescence signal at the graft pedicle using ImageJ software. From the obtained images of 89 adult patients transplanted in our center between September 2017 and April 2019, we constructed fluorescence intensity curves of the hepatic arterial signal and examined their relationship with the occurrence of early hepatic arterial occlusion (thrombosis or stenosis). Early hepatic arterial occlusion occurred in 7 patients (7.8%), including 3 thrombosis and 4 stenosis. Among various parameters of the flow intensity curve analyzed, the ratio of peak to plateau fluorescence intensity and the jagged wave pattern at the plateau phase were closely associated with this dreaded event. By combining the ratio of peak to plateau at 0.275 and a jagged wave, we best predicted the occurrence of early hepatic arterial occlusion and thrombosis, with sensitivity/specificity of 0.86/0.98 and 1.00/0.94, respectively. Through a simple composite parameter, the indocyanine green fluorescence imaging system is an additional and promising intraoperative modality for identifying recipients of transplant at high risk of developing early hepatic arterial occlusion. This tool could assist the surgeon in the decision to redo the anastomosis despite normal Doppler ultrasonography.
Subject(s)
Hepatic Artery , Indocyanine Green , Liver Transplantation , Optical Imaging , Thrombosis , Humans , Liver Transplantation/adverse effects , Liver Transplantation/methods , Indocyanine Green/administration & dosage , Hepatic Artery/diagnostic imaging , Male , Female , Middle Aged , Optical Imaging/methods , Thrombosis/etiology , Thrombosis/diagnostic imaging , Aged , Adult , Postoperative Complications/etiology , Postoperative Complications/diagnostic imaging , Postoperative Complications/epidemiology , Postoperative Complications/diagnosis , Ultrasonography, Doppler/methods , Predictive Value of Tests , Arterial Occlusive Diseases/etiology , Arterial Occlusive Diseases/diagnostic imaging , Arterial Occlusive Diseases/diagnosis , Arterial Occlusive Diseases/surgery , Liver/diagnostic imaging , Liver/blood supply , Liver/surgery , Coloring Agents/administration & dosage , Constriction, Pathologic/etiology , Monitoring, Intraoperative/methods , Retrospective Studies , Intraoperative Care/methodsABSTRACT
OBJECTIVE: To evaluate exclusive breastfeeding at discharge and hospital length-of-stay in preterm infants undergoing or not the Kangaroo-Mother Care Method (KMC). METHODS: A retrospective cohort study was conducted including preterm infants < 1800 g admitted to the neonatal unit of a KMC reference center. The infants were grouped into the KMC group and the non-KMC group. Multiple logistic and Poisson regressions were performed to evaluate the association between the KMC and two outcomes, exclusive breastfeeding at discharge, and hospital length-of-stay, adjusted for potential confounders. RESULTS: 115 mother-infant dyads were included, 78 in the KMC group and 37 in the non-KMC group. In the bivariate analysis, the KMC group had a lower prevalence of maternal adverse conditions (6% vs. 32%, p < 0.001), a higher number of prenatal visits (median 6 vs. 3.5, p < 0.001), higher gestational ages (median 32 vs. 31 weeks, p < 0.05), higher birth weights (median 1530 vs. 1365 g, p < 0.01), a lower prevalence of necrotizing enterocolitis (3.8% vs. 16.2%, p < 0.05), parenteral nutrition (50% vs. 73%, p < 0.05), and deep vascular access (49.7% vs. 78.4%, p < 0.01), a higher prevalence of exclusive breastfeeding (65% vs. 8%, p < 0.001) and a shorter length of hospital stay (median 28 vs. 42 days, p < 0.001). In the multiple regression analysis, the KMC group was 23 times more likely to be exclusively breastfed at discharge (OR = 23.1; 95% CI = 4,85-109,93) and had a 19% reduction in the hospital length-of-stay (IDR = 0.81; 95% CI = 0.76-0.86) compared to the non-KMC group. CONCLUSIONS: The KMC is associated with better short-term neonatal outcomes and should be encouraged in all Brazilian maternity hospitals.