A congenital CSF3R mutation in chronic neutropenia reveals a vital role for a cytokine receptor extracellular hinge motif in the response to granulocyte colony‐stimulating factor

alexandrossfakianakis shared this article with you from Inoreader A congenital CSF3R mutation in chronic neutropenia reveals a vital role for a cytokine receptor extracellular hinge motif in the response to granulocyte colony‐stimulating factor via Pediatric Blood & Cancer Abstract We describe a patient with congenital neutropenia (CN) with a homozygous germline mutation in the colony-stimulating factor 3 receptor gene (CSF3R). The patient's bone marrow shows lagging neutrophil development with subtle left shift and unresponsiveness to CSF3 in in vitro colony assays. This patient illustrates that the di-proline hinge motif in the extracellular cytokine receptor homology domain of CSF3R is critical for adequate neutrophil production, but dispensable for in vivo terminal neutrophil maturation. This report underscores that CN patients with inherited CSF3R mutations should be marked as a separate clinical entity, characterized by a failure to respond to CSF3. View on Web

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Transcriptome reveals the dysfunction of pancreatic islets after wound healing in severely burned mice

alexandrossfakianakis shared this article with you from Inoreader Transcriptome reveals the dysfunction of pancreatic islets after wound healing in severely burned mice via Journal of Trauma and Acute Care Surgery - Current Issue BACKGROUND Severely burned patients have a higher risk of diabetes mellitus after healing, but its mechanism remains unclear. Therefore, the purpose of the study was to explore the influence of burns on pancreatic islets of mice after wound healing. METHODS Forty-two male C57BL/6 mice were randomized into a sham group and a burn group and subjected to sham treatment or a third-degree burn model of 30% total body surface area. Fasting blood glucose was detected weekly for 8 weeks after severe burns. Glucose-stimulated insulin secretion was measured 8 weeks post severe burns. Islets of the two groups were isolated and mRNA libraries were sequenced by the Illumina sequencing platform. The expressions of differentially expressed genes (DEGs) related to the cell cycle and the amounts of mitochondrial DNA were detected by quantitative real-time polymerase chain reaction after gene ontology, gene set enrichment analysis, and protein-protein network analysis. Hematoxylin-eosin staining of pancreatic tail tissue and adenosine triphosphate (ATP) assay of islets were performed. RESULTS The levels of fasting blood glucose were significantly higher within 8 weeks post severe burns. Glucose-stimulated insulin secretion was impaired at the eighth week post severe burns. Totally 128 DEGs were selected. Gene ontology and gene set enrichment analysis indicated that the pathways related to the cell cycle, protein processing, and oxidative phosphorylation were downregulated. The expressions of DEGs related to the cell cycle showed a consistent trend with mRNA sequencing data, and most of them were downregulated post severe burns. The cell mass of the burn group was less than that of the sham group. Also, the concentration of ATP and the amount of mitochondrial DNA were lower in the burn group. CONCLUSION In the model of severe-burned mice, disorders in glucose metabolism persist for 8 weeks after burns, which may be related to low islet cell proliferation, downregulation of protein processing, and less ATP production. View on Web

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Prospective evaluation of the selective nonoperative management of abdominal stab wounds: When is it safe to discharge?

alexandrossfakianakis shared this article with you from Inoreader Prospective evaluation of the selective nonoperative management of abdominal stab wounds: When is it safe to discharge? via Journal of Trauma and Acute Care Surgery - Current Issue BACKGROUND The optimal observation time required to exclude hollow viscus injury in patients undergoing selective nonoperative management (SNOM) for abdominal stab wounds (SWs) remains unclear. The aim of this study was to determine the safe period of observation required before discharge. METHODS In this prospective observational study, all patients who sustained an abdominal SW were screened for study inclusion (July 2018 to May 2021). The primary study outcome was time to SNOM failure, defined as the need for surgical intervention after an initial period of observation. RESULTS During the study period, 256 consecutive patients with an abdominal SW met the study criteria. The mean age was 33 (26–46) years, and 89% were male. Of all patients, 77% had single SW, and 154 (60%) had an anterior abdominal SW (most common site right upper quadrant, 31%). Forty-six (18%) underwent immediate laparotomy because of evisceration (59%), hemodynamic instability (33%), or peritonitis (24%). The remaining 210 patients (82%) were taken for computed tomography scan (n = 208 [99%]) or underwent clinical observation only (n = 2 [ View on Web

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A comparison of management and outcomes following blunt versus penetrating pancreatic trauma: A secondary analysis from the Western Trauma Association Multicenter Trials Group on Pancreatic Injuries

alexandrossfakianakis shared this article with you from Inoreader A comparison of management and outcomes following blunt versus penetrating pancreatic trauma: A secondary analysis from the Western Trauma Association Multicenter Trials Group on Pancreatic Injuries via Journal of Trauma and Acute Care Surgery - Current Issue BACKGROUND The impact of injury mechanism on outcomes of pancreatic trauma has not been well studied, and current guidelines do not differentiate recommendations for blunt and penetrating injuries. The purpose of this study was to analyze interventions and outcomes as they relate to mechanism. We hypothesized that penetrating pancreatic trauma results in greater morbidity than blunt trauma because of more frequent operative exploration without imaging and thus more aggressive surgical management. METHODS Secondary analysis of a multicenter retrospective review of pancreatic injuries in patients 15 years and older from 2010 to 2018 was performed. Deaths within 24 hours of admission were excluded from analysis of the primary outcome, pancreas-related complications (PRCs). Data were analyzed by injury mechanism using various statistical tests where appropriate. RESULTS Thirty-three centers reported on 1,240 patients (44% penetrating). Penetrating trauma patients were twice as likely to undergo resection (45% vs. 23%) and suffer PRCs (39% vs. 20%). However, differences varied widely based on injury grade and management. There were fewer resections and more nonoperative management in blunt grades I to III injury. Pancreas-related complications occurred in 40% of high-grade injuries with no difference between mechanisms and in 40% of patients after resection, regardless of mechanism or injury grade. High-grade pancreatic injury (odds ratio [OR], 2.39; 95% confidence interval [CI], 1.55–3.67), penetrating injury (OR, 1.99; 95% CI, 1.31–3.05), and management in a low-volume center (i.e., five or fewer cases/year) (OR, 1.65; 95% CI, 1.16–2.35) were independent predictors of PRCs. CONCLUSION Management of grades I to III, but not grades IV/V, pancreatic injuries varies based on mechanism. Penetrating injury is an independent risk factor for PRCs, but main pancreatic duct injury and resection are associated with high rates of PRCs regardless of the injury mechanism. Resection appears to offer better outcomes for grade IV/V injuries, and grade I and II injuries should be managed nonoperatively. LEVEL OF EVIDENCE Therapeutic/Care Management; Level III. View on Web

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New perspectives for prosthetic valve endocarditis - impact of molecular imaging by FISHseq diagnostics

alexandrossfakianakis shared this article with you from Inoreader New perspectives for prosthetic valve endocarditis - impact of molecular imaging by FISHseq diagnostics via Clinical Infectious Diseases Advance Access Abstract BackgroundThe causative microbial etiology of prosthetic valve infective endocarditis (PVE) can be difficult to identify. Our aim was to investigate the benefit of the molecular imaging technique fluorescence in situ hybridization (FISH) combined with 16S rRNA-gene PCR and sequencing (FISHseq) for the analysis of infected prosthetic heart valves. Methods We retrospectively evaluated the diagnostic outcome of 113 prosthetic valves from 105 patients with suspected PVE, treated in the years 2003-2013 in the Department of Cardiac Surgery, Charité University Medicine Berlin. Each prosthetic valve underwent cultural diagnostics and was routinely examined by FISH combined with 16S rRNA-gene PCR and sequencing. We compared classical microbiological culture outcomes (blood and valve cultures) with FISHseq results and evaluated the diagnostic impact of the molecular imaging technique. Results Conventional microbiological diagnostic alone turned out to be insufficient, as 67% of p reoperative blood cultures were non-informative (negative, inconclusive or not obtained) and 67% valve cultures remained negative. FISHseq improved the conventional cultural diagnostic methods in PVE in 30% of the cases and increased diagnostic accuracy. Out of the valve culture-negative PVE cases, FISHseq succeeded to identify the causative pathogen in 35%. Conclusions FISHseq improves PVE diagnostics, complementing the conventional cultural methods. In addition to species identification, FISH provides information about the severity of PVE and state of the pathogens, e.g. stage of biofilm formation, activity and localization on and within the prosthetic material. As a molecular imaging technique, FISHseq enables the unambiguous discrimination of skin flora as contaminant or infectious agent. View on Web

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