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1.
Ann Surg Oncol ; 31(6): 4073-4083, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38459418

RESUMO

BACKGROUND: Although addition of adjuvant chemotherapy is the current standard, the prognosis of pancreatic cancers still remains poor. The NEPAFOX trial evaluated perioperative treatment with FOLFIRINOX in resectable pancreatic cancer. PATIENTS AND METHODS: This multicenter phase II trial randomized patients with resectable or borderline resectable pancreatic cancer without metastases into arm (A,) upfront surgery plus adjuvant gemcitabine, or arm (B,) perioperative FOLFIRINOX. The primary endpoint was overall survival (OS). RESULTS: Owing to poor accrual, recruitment was prematurely stopped after randomization of 40 of the planned 126 patients (A: 21, B: 19). Overall, approximately three-quarters were classified as primarily resectable (A: 16, B: 15), and the remaining patients were classified as borderline resectable (A: 5, B: 4). Of the 12 evaluable patients, 3 achieved partial response under neoadjuvant FOLFIRINOX. Of the 21 patients in arm A and 19 patients in arm B, 17 and 7 underwent curative surgery, and R0-resection was achieved in 77% and 71%, respectively. Perioperative morbidity occurred in 72% in arm A and 46% in arm B, whereas non-surgical toxicity was comparable in both arms. Median RFS/PFS was almost doubled in arm B (14.1 months) compared with arm A (8.4 months) in the population with surgical resection, whereas median OS was comparable between both arms. CONCLUSIONS: Although the analysis was only descriptive owing to small patient numbers, no safety issues regarding surgical complications were observed in the perioperative FOLFIRINOX arm. Thus, considering the small number of patients, perioperative treatment approach appears feasible and potentially effective in well-selected cohorts of patients. In pancreatic cancer, patient selection before initiation of neoadjuvant therapy appears to be critical.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Desoxicitidina , Fluoruracila , Gencitabina , Irinotecano , Leucovorina , Terapia Neoadjuvante , Oxaliplatina , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/análogos & derivados , Desoxicitidina/administração & dosagem , Masculino , Feminino , Leucovorina/administração & dosagem , Leucovorina/uso terapêutico , Irinotecano/administração & dosagem , Irinotecano/uso terapêutico , Fluoruracila/administração & dosagem , Oxaliplatina/administração & dosagem , Oxaliplatina/uso terapêutico , Pessoa de Meia-Idade , Idoso , Quimioterapia Adjuvante , Taxa de Sobrevida , Seguimentos , Prognóstico , Pancreatectomia , Adulto , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adenocarcinoma/mortalidade
2.
Int J Cancer ; 153(1): 153-163, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-36883420

RESUMO

This multicenter, randomized phase II/III study evaluated the addition of the vascular endothelial growth factor receptor-2 inhibitor ramucirumab to FLOT as perioperative treatment for resectable esophagogastric adenocarcinoma. Patients received either FLOT alone (Arm A) or combined with ramucirumab followed by ramucirumab monotherapy (Arm B). The primary endpoint for the phase II portion was the pathological complete or subtotal response (pCR/pSR) rate. Baseline characteristics were comparable between both arms with a high rate of tumors signet-ring cell component (A:47% B:43%). No between-arm difference in pCR/pSR rate was seen (A:29% B:26%), therefore the transition to phase III was not pursued. Nevertheless, the combination was associated with a significantly increased R0-resection rate compared with FLOT alone (A:82% B:96%; P = .009). In addition, the median disease-free survival was numerically improved in Arm B (A:21 months B:32 months, HR 0.75, P = 0.218), while the median overall survival was similar in both treatment arms (A:45 months B:46 months, HR 0.94, P = 0.803). Patients with Siewert type I tumors receiving transthoracic esophagectomy with intrathoracic anastomosis showed an increased risk of serious postoperative complications after ramucirumab treatment, therefore recruitment of those patients was stopped after the first-third of the study. Overall, surgical morbidity and mortality was comparable, whereas more non-surgical grade ≥ 3 adverse events were observed with the combination, especially anorexia (A:1% B:11%), hypertension (A:4% B:13%) and infections (A:19% B:33%). The combination of ramucirumab and FLOT as perioperative treatment shows efficacy signals, particularly in terms of R0 resection rates, for a study population with a high proportion of prognostically poor histological subtypes, and further evaluation in this subgroup seems warranted.


Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgia , Adenocarcinoma/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/cirurgia , Junção Esofagogástrica/patologia , Fluoruracila , Leucovorina , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Fator A de Crescimento do Endotélio Vascular , Ramucirumab
3.
Qatar Med J ; 2023(4): 29, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37920783

RESUMO

BACKGROUND: Critical illness-associated cerebral microbleeds and leukoencephalopathy connected to coronavirus disease 2019 (COVID-19) infection are emerging areas of concern in current medical literature. METHODS: We reviewed cases of patients with COVID-19-associated neurological manifestations to study the prevalence and outcome of such conditions. Case Series Findings: Our review yielded seven distinct patients. Six exhibited cerebral microbleeds, primarily localized in the juxtacortical white matter and the corpus callosum. In contrast, one individual presented with leukoencephalopathy. Tragically, of these patients, five succumbed to their ailments. One was discharged with mild cognitive impairments, while another underwent a tracheostomy and was subsequently moved to a long-term care establishment. CONCLUSION: Our findings underscore the significance of neuro-radiological observations in those grappling with severe manifestations of COVID-19, drawing attention to the possible neurological repercussions of the virus.

4.
BMC Cancer ; 21(1): 1158, 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34715810

RESUMO

BACKGROUND: The main reason for treatment failure after curative surgical resection of gastric cancer is intra-abdominal spread, with 40-50% peritoneal seeding as primary localization of recurrence. Peritoneal relapse is seen in 60-70% of tumors of diffuse type, compared to only 20-30% of intestinal type. Hyperthermic IntraPEritoneal Chemoperfusion (HIPEC) is an increasingly used therapy method for patients with peritoneal metastases. The preventive use of HIPEC could represent an elegant approach for patients (pts) before macroscopic peritoneal seeding, since pts. with operable disease are fit and may have potential risk of microscopic involvement, thus having a theoretical chance of cure with HIPEC even without the need for cytoreduction. No results from a PCRT from the Western hemisphere have yet been published. METHODS: This is a multicenter, randomized, controlled, open-label study including a total of 200 pts. with localized and locally advanced diffuse or mixed type (Laurens's classification) adenocarcinoma of the stomach and Type II/III GEJ. All enrolled pts. will have received 3-6 pre-operative cycles of biweekly FLOT (Docetaxel 50 mg/m2; Oxaliplatin 85 mg/m2; Leucovorin 200 mg/m2; 5-FU 2600 mg/m2, q2wk). Pts will be randomized 1:1 to receive surgery only and postoperative FLOT (control arm) or surgery + intraoperative HIPEC (cisplatin 75 mg/m2 solution administered at a temperature of 42 °C for 90 min) and postoperative FLOT (experimental arm). Surgery is carried out as gastrectomy or transhiatal extended gastrectomy. Primary endpoint is PFS/DFS, major secondary endpoints are OS, rate of pts. with peritoneal relapse at 2 and 3 years, perioperative morbidity/mortality and quality of life. The trial starts with a safety run-in phase. After 20 pts. had curatively intended resection in Arm B, an interim safety analysis is performed. Recruitment has already started and first patient in was on January 18th, 2021. DISCUSSION: If the PREVENT concept proves to be effective, this could potentially lead to a new standard of therapy. On the contrary, if the outcome is negative, pts. with gastric cancer and no peritoneal involvement will not be treated with HIPEC during surgery. TRIAL REGISTRATION: The study is registered on June 25th, 2020 under ClinicalTrials.gov Identifier: NCT04447352 ; EudraCT: 2017-003832-35 .


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Junção Esofagogástrica , Quimioterapia Intraperitoneal Hipertérmica/métodos , Neoplasias Peritoneais/prevenção & controle , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Cisplatino/administração & dosagem , Docetaxel , Esquema de Medicação , Fluoruracila/administração & dosagem , Gastrectomia/métodos , Humanos , Leucovorina/administração & dosagem , Terapia Neoadjuvante/métodos , Inoculação de Neoplasia , Oxaliplatina , Neoplasias Peritoneais/secundário , Cuidados Pré-Operatórios/métodos , Intervalo Livre de Progressão , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia
5.
BMC Pulm Med ; 21(1): 354, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34743710

RESUMO

BACKGROUND: Intravenous immunoglobulin (IVIG) has been used as an immunomodulatory therapy to counteract severe systemic inflammation in coronavirus disease 2019 (COVID-19). But its use in COVID-19 related acute respiratory distress syndrome (ARDS) is not well established. METHODS: We conducted a retrospective analysis of electronic health records of COVID-19 patients admitted to intensive care units (ICUs) at Hazm Mebaireek General Hospital, Qatar, between March 7, 2020 and September 9, 2020. Patients receiving invasive mechanical ventilation for moderate-to-severe ARDS were divided into two groups based on whether they received IVIG therapy or not. The primary outcome was all-cause ICU mortality. Secondary outcomes studied were ventilator-free days and ICU-free days at day-28, and incidence of acute kidney injury (AKI). Propensity score matching was used to adjust for confounders, and the primary outcome was compared using competing-risks survival analysis. RESULTS: Among 590 patients included in the study, 400 received routine care, and 190 received IVIG therapy in addition to routine care. One hundred eighteen pairs were created after propensity score matching with no statistically significant differences between the groups. Overall ICU mortality in the study population was 27.1%, and in the matched cohort, it was 25.8%. Mortality was higher among IVIG-treated patients (36.4% vs. 15.3%; sHR 3.5; 95% CI 1.98-6.19; P < 0.001). Ventilator-free days and ICU-free days at day-28 were lower (P < 0.001 for both), and incidence of AKI was significantly higher (85.6% vs. 67.8%; P = 0.001) in the IVIG group. CONCLUSION: IVIG therapy in mechanically ventilated patients with COVID-19 related moderate-to-severe ARDS was associated with higher ICU mortality. A randomized clinical trial is needed to confirm this observation further.


Assuntos
Tratamento Farmacológico da COVID-19 , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Síndrome do Desconforto Respiratório/tratamento farmacológico , Administração Intravenosa , Adulto , Idoso , COVID-19/complicações , COVID-19/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Síndrome do Desconforto Respiratório/mortalidade , Síndrome do Desconforto Respiratório/virologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Análise de Sobrevida , Resultado do Tratamento
7.
BMC Surg ; 19(1): 108, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31409334

RESUMO

OBJECTIVE: We aimed to determine the impact of surgical experience and frequency of practice on perioperative morbidity and mortality in pancreatic surgery. METHODS: 1281 patients that underwent pancreatic resections from 1993 to 2013 were retrospectively analyzed using logistic regression models. All cases were stratified according to the surgeon's level of experience, which was based on the number of previously performed pancreatic resections and the extent of received supervision (novice: n <  20 / intensive; intermediate: n = 21-90 / decreasing; and experienced surgeon: n > 90 / none). Additional stratification was based on the frequency of practice (sporadic: 3 resections > 6 weeks, frequent: 3 resections ≤6 weeks). RESULTS: The novice and experienced categories were related to a decreased risk of postoperative pancreatic fistulas (odds ratio [OR] 0.46, 95% confidence interval [CI] 0.26-0.82 and 0.54, 95% CI 0.36-0.82) and in-hospital mortality (OR 0.45, 95% CI 0.17-1.16 and 0.42, 95% CI 0.21-0.83) compared to the intermediate category. Frequent practice was associated with a significantly lower risk of delayed gastric emptying (OR 0.56, 95% CI 0.38-0.83), postpancreatectomy hemorrhage (OR 0.64, 95% CI 0.42-0.98) and in-hospital mortality (OR 0.45, 95% CI 0.24-0.87). CONCLUSIONS: Our results emphasize the importance of supervision within a pancreatic surgery training program. In addition, our data underline the need of a sufficient patient caseload to ensure frequent practice.


Assuntos
Competência Clínica , Pancreatectomia/efeitos adversos , Idoso , Feminino , Gastroparesia/etiologia , Mortalidade Hospitalar , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Pancreatectomia/métodos , Pancreatectomia/mortalidade , Fístula Pancreática/etiologia , Hemorragia Pós-Operatória/etiologia , Estudos Retrospectivos
8.
Sensors (Basel) ; 14(9): 17567-85, 2014 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-25244585

RESUMO

Changing the position of the Center of Gravity (CoG) for an aerial vehicle is a challenging part in navigation, and control of such vehicles. In this paper, an all-accelerometers-based inertial measurement unit is presented, with a proposed method for on-line estimation of the position of the CoG. The accelerometers' readings are used to find and correct the vehicle's angular velocity and acceleration using an Extended Kalman Filter. Next, the accelerometers' readings along with the estimated angular velocity and acceleration are used in an identification scheme to estimate the position of the CoG and the vehicle's linear acceleration. The estimated position of the CoG and motion measurements can then be used to update the control rules to achieve better trim conditions for the air vehicle.

9.
J Minim Invasive Surg ; 27(1): 33-39, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38494184

RESUMO

Purpose: This study aims to explore the feasibility and implications of Ramadan fasting for patients who have undergone laparoscopic sleeve gastrectomy (LSG), assessing impacts on hydration, nutrient intake, weight management, and gastrointestinal symptoms. Methods: A prospective online survey was conducted among 218 LSG patients and 83 control individuals with obesity who had not undergone surgery. Participants were surveyed before and after Ramadan, providing data on fasting practices, hunger and satiety levels, fluid and nutrient intake, and the occurrence of gastrointestinal symptoms. Statistical analysis was used to compare outcomes between fasting and non-fasting periods and between LSG patients and control participants. Results: A total of 70.2% of LSG patients completed the entire month of Ramadan fasting, with a significant correlation found between the duration post-surgery and the ability to fast. Fasting LSG patients reported decreased hunger, increased satiety, and significant reductions in fluid and nutrient intake during Ramadan. Weight loss was reported in 90.8% of fasting patients, with an average total weight loss of 7.2%. Gastrointestinal symptoms were mild and manageable. Conclusion: The majority of LSG patients can successfully fast during Ramadan with appropriate precautions, including adequate fluid and protein intake. The study highlights the need for patient education and tailored nutritional guidance to ensure safe and effective fasting post-LSG. In order to fast for the entire month, patients may be advised to consider postponing surgery for a few months after Ramadan, avoid overeating during non-fasting hours, and ensure sufficient fluid consumption and protein intake during fasting.

10.
Sci Rep ; 14(1): 12059, 2024 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802394

RESUMO

COVID-19 is a global pandemic that caused a dramatic loss of human life worldwide, leading to accelerated research for antiviral drug discovery. Herbal medicine is one of the most commonly used alternative medicine for the prevention and treatment of many conditions including respiratory system diseases. In this study, a computational pipeline was employed, including network pharmacology, molecular docking simulations, and molecular dynamics simulations, to analyze the common phytochemicals of ginger rhizomes and identify candidate constituents as viral inhibitors. Furthermore, experimental assays were performed to analyze the volatile and non-volatile compounds of ginger and to assess the antiviral activity of ginger oil and hydroalcoholic extract. Network pharmacology analysis showed that ginger compounds target human genes that are involved in related cellular processes to the viral infection. Docking analysis highlighted five pungent compounds and zingiberenol as potential inhibitors for the main protease (Mpro), spike receptor-binding domain (RBD), and human angiotensin-converting enzyme 2 (ACE2). Then, (6)-gingerdiacetate was selected for molecular dynamics (MD) simulations as it exhibited the best binding interactions and free energies over the three target proteins. Trajectories analysis of the three complexes showed that RBD and ACE2 complexes with the ligand preserved similar patterns of root mean square deviation (RMSD) and radius of gyration (Rg) values to their respective native structures. Finally, experimental validation of the ginger hydroalcoholic extract confirmed the existence of (6)-gingerdiacetate and revealed the strong antiviral activity of the hydroalcoholic extract with IC 50 of 2.727 µ g / ml . Our study provides insights into the potential antiviral activity of (6)-gingerdiacetate that may enhance the host immune response and block RBD binding to ACE2, thereby, inhibiting SARS-CoV-2 infection.


Assuntos
Antivirais , Tratamento Farmacológico da COVID-19 , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Extratos Vegetais , SARS-CoV-2 , Zingiber officinale , Zingiber officinale/química , Antivirais/farmacologia , Antivirais/química , Humanos , SARS-CoV-2/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Farmacologia em Rede , Enzima de Conversão de Angiotensina 2/metabolismo , Enzima de Conversão de Angiotensina 2/química , Proteases 3C de Coronavírus/antagonistas & inibidores , Proteases 3C de Coronavírus/metabolismo , Proteases 3C de Coronavírus/química , COVID-19/virologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Glicoproteína da Espícula de Coronavírus/química
11.
J Clin Med ; 13(10)2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38792391

RESUMO

Background: Thoracic duct ligation (TDL) during esophagectomy has been proposed to reduce the risk of postoperative chylothorax. Because of its role in immunoregulation, some authors argued that it had an unfavorable TDL effect on survival. The aim of this study was to analyze the effect of TDL on overall survival (OS). Methods: PubMed, MEDLINE, Scopus, and Web of Science were searched through December 2023. The primary outcome was 5-year OS. The restricted mean survival time difference (RMSTD), hazard ratios (HRs), and 95% confidence intervals (CI) were used as pooled effect size measures. The GRADE methodology was used to summarize the certainty of the evidence. Results: Five studies (3291 patients) were included. TDL was reported in 54% patients. The patients' age ranged from 49 to 69, 76% were males, and BMI ranged from 18 to 26. At the 5-year follow-up, the combined effect from the multivariate meta-analysis is -3.5 months (95% CI -6.1, -0.8) indicating that patients undergoing TDL lived 3.5 months less compared to those without TDL. TDL was associated with a significantly higher hazard for mortality at 12 months (HR 1.54, 95% CI 1.38-1.73), 24 months (HR 1.21, 95% CI 1.12-1.35), and 28 months (HR 1.14, 95% CI 1.02-1.28). TDL and noTDL seem comparable in terms of the postoperative risk for chylothorax (RR = 0.66; p = 0.35). Conclusions: In this study, concurrent TDL was associated with reduced 5-year OS after esophagectomy. This may suggest the need of a rigorous follow-up within the first two years of follow-up.

12.
J Clin Oncol ; 42(4): 410-420, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37963317

RESUMO

PURPOSE: This trial evaluates the addition of the PD-L1 antibody atezolizumab (ATZ) to standard-of-care fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) as a perioperative treatment for patients with resectable esophagogastric adenocarcinoma (EGA). METHODS: DANTE started as multicenter, randomized phase II trial, which was subsequently converted to a phase III trial. Here, we present the results of the phase II proportion, focusing on surgical pathology and safety outcomes on an exploratory basis. Patients with resectable EGA (≥cT2 or cN+) were assigned to either four preoperative and postoperative cycles of FLOT combined with ATZ, followed by eight cycles of ATZ maintenance (arm A) or FLOT alone (arm B). RESULTS: Two hundred ninety-five patients were randomly assigned (A, 146; B, 149) with balanced baseline characteristics between arms. Twenty-three patients (8%) had tumors with microsatellite instability (MSI), and 58% patients had tumors with a PD-L1 combined positive score (CPS) of ≥1. Surgical morbidity (A, 45%; B, 42%) and 60-day mortality (A, 3%; B, 2%) were comparable between arms. Downstaging favored arm A versus arm B (ypT0, 23% v 15% [one-sided P = .044]; ypT0-T2, 61% v 48% [one-sided P = .015]; ypN0, 68% v 54% [one-sided P = .012]). Histopathologic complete regression rates (pathologic complete response or TRG1a) were higher after FLOT plus ATZ (A, 24%; B, 15%; one-sided P = .032), and the difference was more pronounced in the PD-L1 CPS ≥10 (A, 33%; B, 12%) and MSI (A, 63%; B, 27%) subpopulations. Complete margin-free (R0) resection rates were relatively high in both arms (A, 96%; B, 95%). The incidence and severity of adverse events were similar in both groups. CONCLUSION: Within the limitations of the exploratory nature of the data, the addition of ATZ to perioperative FLOT is safe and improved postoperative stage and histopathologic regression.


Assuntos
Adenocarcinoma , Anticorpos Monoclonais Humanizados , Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgia , Adenocarcinoma/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Antígeno B7-H1/uso terapêutico , Docetaxel/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/cirurgia , Junção Esofagogástrica/patologia , Fluoruracila/efeitos adversos , Leucovorina/efeitos adversos , Terapia Neoadjuvante/métodos , Oxaliplatina/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia
13.
Int J Artif Organs ; 46(12): 629-635, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37926985

RESUMO

INTRODUCTION: Severe COVID-19 is associated with a dysregulated immune response that usually leads to cytokine release syndrome. This study aimed to compare the use of extracorporeal blood purification therapy (Oxiris®) versus standard continuous renal replacement therapy (CRRT) in critically-ill patients with severe COVID-19. METHODS: This was a national, multicenter, retrospective study of patients with COVID-19 admitted to the intensive care unit (ICU) between March and October 2020 who required CRRT. Patients were categorized into two groups: Oxiris® CRRT and standard CRRT. The primary outcome was the number of patients alive and ventilator-free at 30-days post-CRRT treatment. Key secondary endpoints included change in inflammatory markers, Sequential Organ Failure Assessment (SOFA) scores, and PaO2/FiO2 ratio at 24- and 72-h post Oxiris® initiation. RESULTS: Thirty-five patients received Oxiris® CRRT and 23 patients received standard CRRT. The primary outcome was 31.4% in the Oxiris® group versus 4.3% in the standard CRRT group (adjusted odds ratio 5.97, 95% confidence interval [CI], 0.64-55.6; p = 0.117). In the Oxiris® group, interleukin-6 (IL-6) concentrations significantly decreased at 24 and 72-h (p = 0.033) and PaO2/FiO2 ratio significantly increased at 24 and 72 h after Oxiris® initiation (p = 0.001). There was no significant change in SOFA scores at 24- and 72-h after Oxiris® initiation. CONCLUSION: The number of patients alive and ventilator-free at 30-days was higher in the Oxiris® group than that in the standard CRRT group; however, the difference did not reach statistical significance after adjusting for the baseline severity of illness. There was a significant reduction in IL-6 and significant improvement in PaO2/FiO2 ratio after Oxiris® CRRT initiation.


Assuntos
Injúria Renal Aguda , COVID-19 , Terapia de Substituição Renal Contínua , Humanos , Terapia de Substituição Renal Contínua/efeitos adversos , Estado Terminal , COVID-19/terapia , Estudos Retrospectivos , Interleucina-6 , Terapia de Substituição Renal , Injúria Renal Aguda/terapia
14.
Ann Surg Open ; 3(3): e195, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37601147

RESUMO

Background: Anastomotic leakage (AL) and stenosis (AS) are two of the most severe postoperative complications after total gastrectomy with esophagojejunostomy. The stapler diameter can be chosen by the surgeon. Therefore, this study aims to assess the correlation between the stapler size as main independent variable as well as other different risk factors and AL and AS. Methods: We conducted a retrospective analysis of data from 356 patients who underwent open total gastrectomy between 2000 and 2018, mostly due to gastric cancer (96.9%). After propensity score matching the outcome parameters AL and AS were compared between the two stapler size groups. We also assessed different risk factors for AL and AS in cancer patients using multivariate analysis. Results: Small circular stapler diameter (21/25 mm; n = 147 vs 28/29/31 mm; n = 209) was identified as a significant risk factor for the occurrence of AL (10% vs 4% for smaller vs larger staplers; P = 0.042). In multivariate analysis for the occurrence of AL an ASA score ≥ 3 could be identified as a risk factor (OR 2.85; 95% CI = 1.13-7.15; P = 0.026). Additionally, smaller stapler size could be identified as a risk factor for AS (OR small 1.00, OR large 0.24; 95% CI: 0.06-0.97; P = 0.045). AL was associated with lower survival (18.1 vs 38.16 months; P = 0.0119). Conclusion: The application of a larger circular stapler for esophagojejunostomy in open total gastrectomy shows significantly lower rates of AL and stenosis. Therefore, the largest possible stapler diameter should be applied.

15.
Sci Transl Med ; 14(635): eabj6879, 2022 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-35263149

RESUMO

Obesity has become a major health problem in the industrialized world. Immune regulation plays an important role in adipose tissue homeostasis; however, the initial events that shift the balance from a noninflammatory homeostatic environment toward inflammation leading to obesity are poorly understood. Here, we report a role for the costimulatory molecule programmed death-ligand 1 (PD-L1) in the limitation of diet-induced obesity. Functional ablation of PD-L1 on dendritic cells (DCs) using conditional knockout mice increased weight gain and metabolic syndrome during diet-induced obesity, whereas PD-L1 expression on type 2 innate lymphoid cells (ILC2s), T cells, and macrophages was dispensable for obesity control. Using in vitro cocultures, DCs interacted with T cells and ILC2s via the PD-L1:PD-1 axis to inhibit T helper type 1 proliferation and promote type 2 polarization, respectively. A role for PD-L1 in adipose tissue regulation was also shown in humans, with a positive correlation between PD-L1 expression in visceral fat of people with obesity and elevated body weight. Thus, we define a mechanism of adipose tissue homeostasis controlled by the expression of PD-L1 by DCs, which may be a clinically relevant finding with regard to immune-related adverse events during immune checkpoint inhibitor therapy.


Assuntos
Antígeno B7-H1 , Dieta , Obesidade , Linfócitos T , Tecido Adiposo/metabolismo , Animais , Antígeno B7-H1/metabolismo , Imunidade Inata , Inflamação , Linfócitos/metabolismo , Camundongos , Obesidade/metabolismo
16.
Health Sci Rep ; 5(3): e542, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35601034

RESUMO

Background and Aims: Clinical characteristics and factors associated with mortality in patients admitted to the intensive care unit (ICU) in countries with low case fatality rates (CFR) are unknown. We sought to determine these in a large cohort of critically ill COVID-19 patients in Qatar and explore the early mortality predictors. Methods: We retrospectively studied the clinical characteristics and outcomes in patients admitted to the ICU at the national referral hospital for COVID-19 patients in Qatar. Logistic regression analysis was used to determine factors associated with mortality. Results: Between March 7 and July 16, 2020, a total of 1079 patients with COVID-19 were admitted to the ICU. The median (IQR) age of patients was 50 (41-59) years. Diabetes (47.3%) and hypertension (42.6%) were the most common comorbidities. In-hospital mortality was 12.6% overall and 25.9% among those requiring mechanical ventilation. Factors independently associated with mortality included older age ([OR]; 2.3 [95% CI; 1.92-2.75] for each 10-year increase in age, p < 0.001), chronic kidney disease (OR; 1.9 [95% CI; 1.02-3.54], p = 0.04), active malignancy (OR; 6.15 [95% CI; 1.79-21.12], p = 0.004), lower platelet count at ICU admission (OR; 1.41 [95% CI; 1.13-1.75] for each 100 × 103/µl decrease, p = 0.002), higher neutrophil-to-lymphocyte ratio at admission (OR; 1.01 [95% CI; 1-1.02] for each 1- point increase, p = 0.016), higher serum ferritin level at admission (OR; 1.05 [(95% CI; 1.02-1.08] for each 500 µg/L increase, p = 0.002), and higher serum bilirubin level at admission (OR; 1.19 [95% CI; 1.04-1.36] for each 10 µmol/L increase, p = 0.01). Conclusions: The mortality rate among critically ill COVID-19 patients is low in Qatar compared to other countries. Older age, chronic kidney disease, active malignancy, higher neutrophil-to-lymphocyte ratios, lower platelet counts, higher serum ferritin levels, and higher serum bilirubin levels are independent predictors of in-hospital mortality.

17.
Int J Surg Case Rep ; 79: 394-397, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33517211

RESUMO

INTRODUCTION: Postsleeve gastrectomy fistula is a serious complication, and its management remains quite challenging. The clinical presentation of chronic fistula after sleeve gastrectomy (SG) varies widely and depends on the type of fistula. Management requires a multidisciplinary approach and patient cooperation. CASE PRESENTATION: We present a case of a 41-year-old woman with a body mass index (BMI) of 46 kg/m2 who initially underwent laparoscopic sleeve gastrectomy in our hospital. Later, she developed a gastro-colo-diaphragmatic fistula (GCD), which was successfully treated using an endolaparoscopic approach. Follow-up imaging and endoscopy showed complete healing of the fistula, as well as a marked clinical improvement of the patient. DISCUSSION: Gastro-colo-diaphragmatic fistula following sleeve gastrectomy is an extremely rare complication. This is the first case of a GCD fistula after sleeve gastrectomy that has been reported in the literature. CONCLUSION: One staged endolaparoscopic management was successful approach in our case and can be considered for complex gastric fistula following sleeve gastrectomy.

18.
J Surg Case Rep ; 2021(4): rjab136, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33927870

RESUMO

This article presents an alternative technique to the common Toupet fundoplication. It is a modern combination of the standard Toupet procedure and an additional fundophrenicopexie of the gastric wrap. In 1963 Toupet first described his technique of a fundoplication for reflux surgery. Over the past years this procedure has been modified and expanded many times. We have learned that the short gastric vessels need to be divided to get the wrap closer and easier around the esophagus. Furthermore, it is likely necessary to perform a balanced hiatoplasty to avoid slippage of the wrap. Our procedure is a modification of the standard Toupet fundoplication, but is extended by fixing the wrap to the anterior wall of the diaphragm. We consider our modification successful and safe in treating gastroesophageal reflux disease in patients with type I/II hiatal hernia and prevent postoperative complications such as dysphagia or slippage of the wrap.

19.
J Surg Case Rep ; 2021(4): rjab089, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33897996

RESUMO

Post-thyroidectomy bleeding is a fortunately rare but potentially life-threatening complication that may increase postoperative morbidity and hospital stay. In this case series, we demonstrate the relation between the measurement of neck circumference and haemorrhage following thyroid surgery and the value of this measurement in predicting post-thyroidectomy haemorrhage. Currently, there is no simple and reliable method available for the early detection of post-thyroidectomy bleeding. Continuous pressure measurement could be a potential tool for the early detection of haemorrhage but is invasive, and more data are required to recommend threshold values for revision surgery. Early recognition and prompt surgical intervention are key to the management of cervical haematoma. Measurement of the neck circumference is a valuable adjunct tool in the early recognition of post-thyroidectomy bleeding. In this case series, we concluded that a 4-cm increase in neck circumference may trigger the clinical decision for cervical exploration.

20.
Ann Med Surg (Lond) ; 65: 102370, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34026103

RESUMO

INTRODUCTION AND IMPORTANCE: Low molecular weight heparins are rarely associated with thrombocytosis. However, the safety of transitioning to unfractionated heparin is unknown. CASE PRESENTATION: We report a case of a 47-year-old South Asian male who presented to the hospital after ingestion of a caustic liquid. He received subcutaneous enoxaparin 40 mg once daily for prophylaxis against venous thromboembolism. His platelet count increased from the baseline of 748 × 109/L to a peak of 1213 × 109/L, after which enoxaparin was changed to unfractionated heparin. His platelet count returned to normal within seven days. The modified Naranjo scale with thrombocytosis-specific criteria was 6, indicating a probable association with enoxaparin. CLINICAL DISCUSSION: In this case, the patient developed thrombocytosis after initiation of low-molecular weight heparin and platelet count normalized after shifting to unfractionated heparin. CONCLUSION: Clinicians should suspect LMWH-induced thrombocytosis when platelet count elevation cannot be explained by other causes. Unfractionated heparin might be a safe alternative in case of low molecular weight heparin-induced thrombocytosis.

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