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[This corrects the article DOI: 10.1155/2014/859090.].
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Macrophages play crucial roles in organ-specific functions and homeostasis. In the adrenal gland, macrophages closely associate with sinusoidal capillaries in the aldosterone-producing zona glomerulosa. We demonstrate that macrophages preserve capillary specialization and modulate aldosterone secretion. Using macrophage-specific deletion of VEGF-A, single-cell transcriptomics, and functional phenotyping, we found that the loss of VEGF-A depletes PLVAP+ fenestrated endothelial cells in the zona glomerulosa, leading to increased basement membrane collagen IV deposition and subendothelial fibrosis. This results in increased aldosterone secretion, called "haptosecretagogue" signaling. Human aldosterone-producing adenomas also show capillary rarefaction and basement membrane thickening. Mice with myeloid cell-specific VEGF-A deletion exhibit elevated serum aldosterone, hypokalemia, and hypertension, mimicking primary aldosteronism. These findings underscore macrophage-to-endothelial cell signaling as essential for endothelial cell specialization, adrenal gland function, and blood pressure regulation, with broader implications for other endocrine organs.
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Glándulas Suprarrenales , Aldosterona , Presión Sanguínea , Células Endoteliales , Macrófagos , Animales , Macrófagos/metabolismo , Aldosterona/metabolismo , Células Endoteliales/metabolismo , Ratones , Humanos , Glándulas Suprarrenales/metabolismo , Glándulas Suprarrenales/patología , Factor A de Crecimiento Endotelial Vascular/metabolismo , Zona Glomerular/metabolismo , Zona Glomerular/patología , Masculino , Hiperaldosteronismo/metabolismo , Hiperaldosteronismo/patología , Hiperaldosteronismo/genética , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: The method of transecting the pancreatic parenchyma during pancreatic resection may influence the rate of complications, including pancreatic fistula and bleeding. The objective of this study was to compare the transection of the pancreatic parenchyma during pancreatoduodenectomy with monopolar electrocautery versus scalpel in terms of postoperative complications. METHODS: A retrospective analysis of patients with open pancreatoduodenectomy from the German DGAV StuDoQ|Pancreas registry (January 2013 to December 2021) was performed. Transection of the pancreatic parenchyma with a scalpel versus monopolar electrocautery was compared regarding postoperative pancreatic fistula B/C, post-pancreatectomy hemorrhage B/C, and major complications (Clavien-Dindo classification ≥3) rates. Multivariable analysis with adjustment for potential confounders and surgical center cluster effect was performed. RESULTS: Overall, 6,752 patients were included in the study. In 4,072 (60.3%), transection was performed with a scalpel and, in 2,680 (39.7%), with electrocautery. Transection with electrocautery was associated with higher postoperative pancreatic fistula B/C (15.4% vs 12.8%; P = .003), post-pancreatectomy hemorrhage B/C (11% vs 7.4%; P < .001), and major complications (33.4% vs 29.6%; P = .001) rates. In the multivariable analysis, after adjustment for potential confounders and surgical center, the association of the transection method with postoperative pancreatic fistula B/C (odds ratio = 1.01; 95% CI, 0.79-1.2; P = .962), post-pancreatectomy hemorrhage B/C (odds ratio = 1.23; 95% CI, 0.94-1.6; P = .127), and major complications (odds ratio = 1.09; 95% CI, 0.93-1.27; P = .297) was not significant. CONCLUSION: The study found no significant association between transection of the pancreatic parenchyma during open pancreatoduodenectomy with a scalpel compared with monopolar electrocautery regarding pancreatic fistula, postoperative bleeding, or overall major complication rates.
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Electrocoagulación , Páncreas , Fístula Pancreática , Pancreaticoduodenectomía , Complicaciones Posoperatorias , Sistema de Registros , Humanos , Pancreaticoduodenectomía/efectos adversos , Pancreaticoduodenectomía/métodos , Estudios Retrospectivos , Masculino , Femenino , Electrocoagulación/efectos adversos , Electrocoagulación/instrumentación , Electrocoagulación/métodos , Persona de Mediana Edad , Anciano , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Fístula Pancreática/etiología , Fístula Pancreática/epidemiología , Páncreas/cirugía , Hemorragia Posoperatoria/etiología , Hemorragia Posoperatoria/epidemiología , Neoplasias Pancreáticas/cirugía , Instrumentos Quirúrgicos/efectos adversosRESUMEN
PURPOSE: The presence of an aberrant right hepatic artery (aRHA), arising from the superior mesenteric artery, is a common variant of the liver vascular anatomy. Considering that tumor spread occurs along vessels, the question arises, whether the presence of an aRHA influences the oncologic outcome after resection for cancer of the pancreatic head. METHODS: Patients with ductal adenocarcinoma of the pancreatic head, who underwent resection from 2011 to 2020 at the Frankfurt University Hospital, Germany, were analyzed retrospectively. Surgical records and computed tomography imaging were reviewed for the presence of aRHA. Overall and disease-free survival as well as hepatic recurrence were analyzed according to the presence of aRHA. RESULTS: aRHA was detected in 21 out of 145 patients (14.5%). The median overall survival was 26 months (95%CI 20.8-34.4), median disease-free survival was 12.1 months (95%CI 8.1-17.3). There was no significant difference in overall survival (26.1 versus 21.4 months, adjusted hazard ratio 1.31, 95%CI 0.7-2.46, p = 0.401) or disease-free survival (14.5 months versus 12 months, adjusted hazard ratio 0.98, 95%CI 0.57-1.71, p = 0.957) without and with aRHA. The hepatic recurrence rate was 24.4.% with conventional anatomy versus 30.8% with aRHA (adjusted odds ratio 1.36, 95%CI 0.3-5.38, p = 0.669). In the multivariable analysis, only lymphatic vessel invasion was an independent prognostic factor for hepatic recurrence. CONCLUSIONS: The presence of an aRHA does not seem to influence the long-term survival and hepatic recurrence after resection for ductal adenocarcinoma of the pancreatic head.
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Adenocarcinoma , Arteria Hepática , Humanos , Arteria Hepática/cirugía , Estudios Retrospectivos , Páncreas , PancreatectomíaRESUMEN
Importance: Surgical site infections frequently occur after open abdominal surgery. Intraoperative wound irrigation as a preventive measure is a common practice worldwide, although evidence supporting this practice is lacking. Objective: To evaluate the preventive effect of intraoperative wound irrigation with polyhexanide solution. Design, Setting, and Participants: The Intraoperative Wound Irrigation to Prevent Surgical Site Infection After Laparotomy (IOWISI) trial was a multicenter, 3-armed, randomized clinical trial. Patients and outcome assessors were blinded to the intervention. The clinical trial was conducted in 12 university and general hospitals in Germany from September 2017 to December 2021 with 30-day follow-up. Adult patients undergoing laparotomy were eligible for inclusion. The main exclusion criteria were clean laparoscopic procedures and the inability to provide consent. Of 11â¯700 screened, 689 were included and 557 completed the trial; 689 were included in the intention-to-treat and safety analysis. Interventions: Randomization was performed online (3:3:1 allocation) to polyhexanide 0.04%, saline, or no irrigation (control) of the operative wound before closure. Main Outcome and Measures: The primary end point was surgical site infection within 30 postoperative days according to the US Centers for Disease Control and Prevention definition. Results: Among the 689 patients included, 402 were male and 287 were female. The median (range) age was 65.9 (18.5-94.9) years. Participants were randomized to either wound irrigation with polyhexanide (n = 292), saline (n = 295), or no irrigation (n = 102). The procedures were classified as clean contaminated in 92 cases (8%). The surgical site infection incidence was 11.8% overall (81 of 689), 10.6% in the polyhexanide arm (31 of 292), 12.5% in the saline arm (37 of 295), and 12.8% in the no irrigation arm (13 of 102). Irrigation with polyhexanide was not statistically superior to no irrigation or saline irrigation (hazard ratio [HR], 1.23; 95% CI, 0.64-2.36 vs HR, 1.19; 95% CI, 0.74-1.94; P = .47). The incidence of serious adverse events did not differ among the 3 groups. Conclusions and Relevance: In this study, intraoperative wound irrigation with polyhexanide solution did not reduce surgical site infection incidence in clean-contaminated open abdominal surgical procedures compared to saline or no irrigation. More clinical trials are warranted to evaluate the potential benefit in contaminated and septic procedures, including the emergency setting. Trial Registration: drks.de Identifier: DRKS00012251.
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Biguanidas , Laparotomía , Infección de la Herida Quirúrgica , Irrigación Terapéutica , Humanos , Infección de la Herida Quirúrgica/prevención & control , Masculino , Femenino , Laparotomía/efectos adversos , Persona de Mediana Edad , Biguanidas/uso terapéutico , Biguanidas/administración & dosificación , Anciano , Cuidados Intraoperatorios/métodos , AdultoRESUMEN
Respiratory syncytial virus (RSV) is the most common cause of upper and lower respiratory tract infections in infants and young children. Virus-specific monoclonal antibodies (mAbs) can be used for diagnosis, prophylaxis, and research of RSV pathogenesis. A panel of 16 anti-RSV mAbs was obtained from mice immunized by RSV strain Long. Half of them had virus-neutralizing activity. According to Western blot all of these mAbs effectively bound native oligomeric (homodimeric and homotrimeric) forms of the RSV fusion (F) protein. Only five of the mAbs interacted with the monomeric form, and only one of these possessed neutralizing activity. None of these mAbs, nor the commercial humanized neutralizing mAb palivizumab, reacted with the denaturated F protein. Thus, interaction of all these mAbs with F protein had clear conformational dependence. Competitive ELISA and neutralization assays allowed the identification of nine antigenic target sites for the interaction of mAb with the F protein. Five partially overlapping sites may represent a complex spatial structure of one antigenic determinant, including one neutralizing and four non-neutralizing epitopes. Four sites (three neutralizing and one non-neutralizing) were found to be distinct. As a result of virus cultivation RSV-A, strain Long, in the presence of a large amount of one of the neutralizing mAbs, an escape mutant with a substitution, N240S, in the F protein, was obtained. Thus, it was shown for the first time that position 240 is critical for the protective effect of an anti-RSV antibody. To assess the ability of these mAbs to interact with modern RSV strains circulating in St. Petersburg (Russia) between 2014 and 2022, 73 RSV-A and 22 RSV-B isolates were analyzed. Six mAbs were directed to conserved epitopes of the F protein as they interacted most efficiently with both RSV subtypes in a fixed cell-ELISA and could be used for diagnostic assays detecting RSV.