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Sarcoidosis is a systemic granulomatous disease predominantly affecting the lungs. The mechanisms promoting disease pathogenesis and progression are unknown, although interleukin-15 (IL-15) has been associated with the immune-mediated inflammation of sarcoidosis. Because the identification of a mechanistically based, clinically relevant biomarker for sarcoidosis remains elusive, we hypothesized this role for IL-15. Pulmonary sarcoidosis granuloma formation was modeled using trehalose 6,6'-dimicolate (TDM), which was administered into wild-type and three lineages of mice those overexpressing IL-15, deficient in IL-15, and deficient in IL-15 receptor α. The number of granulomas per lung was counted and normalized to the wild type. IL-15 concentrations were measured in the bronchoalveolar lavage (BAL) from healthy controls and subjects with sarcoidosis in our cohort, where associations between IL-15 levels and clinical manifestations were sought. Findings were validated in another independent sarcoidosis cohort. TDM administration resulted in similar granuloma numbers across all lineages of mice. IL-15 concentrations were elevated in the BAL of both human cohorts, irrespective of disease phenotypes. In exploratory analysis, an association with obesity was observed, and various other soluble mediators were identified in the BAL of both cohorts. Although IL-15 is enriched in the sarcoidosis lung, it was independent of disease pathogenesis or clinical manifestations in our mouse model and human cohorts of sarcoidosis. An association with obesity perhaps reflects the ongoing inflammatory processes of these comorbid conditions. Our findings showed that IL-15 is redundant for disease pathogenesis and clinical progression of sarcoidosis.Introduction Over the past decades, a large amount of both adult and pediatric data has shown relationship between Nonalcoholic Fatty Liver Disease (NAFLD) and chronic kidney disease (CKD), resulting in an overall increased cardiometabolic burden. In view of the remarkable role of the genetic background in the NAFLD pathophysiology, a potential influence of the major NAFLD polymorphisms (e.g. the I148M variant of the Patatin-like phospholipase containing domain 3 (PNPLA3) gene, the E167K allele of the Transmembrane 6 superfamily member 2 (TM6SF2), the hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13), and the Membrane bound O-acyltransferase domain containing 7-transmembrane channel-like 4 (MBOAT7-TMC4) genes) on renal function has been supposed. A shared metabolic and proinflammatory pathogenesis has been hypothesized, but the exact mechanism is still unknown.Areas covered We provide a comprehensive review of the potential genetic link between NAFLD and CKD in children. Convincing both adult and pediatric evidence supports this association, but there is some dispute especially in childhood.Expert opinion Evidence supporting a potential genetic link between NAFLD and CKD represents an intriguing aspect with a major clinical implication because of its putative role in improving strategy programs to counteract the higher cardiometabolic risk of these patients.
As surgical education has evolved, most curricula have favoured a competency-based approach over traditional apprenticeship models. Surgical simulation can be a useful aide in the training of both oncological and reconstructive breast surgery trainees. This review investigates the extent to which simulation of breast surgery procedures has been validated as a training tool.
A comprehensive literature search for studies evaluating the objective validity of breast surgery simulators was performed, using MEDLINE, EMBASE and the Cochrane Library databases. Studies assessing construct, concurrent or predictive validity were included, as well as those demonstrating skill acquisition.
The initial literature search returned 1,625 hits, with only five articles meeting the inclusion criteria. Simulators were designed to train procedures such as breast augmentation, lesion biopsy and excision. Of these, breast biopsy was the most simulated procedure (three studies). Two studies evaluated animal models, two evaluatated synthetic models and one study assessed both a synthetic and animal model. Construct validity was confirmed in two studies, concurrent validity in one study and a learning curve demonstrated in another study. No association between experience and performance was seen in the remaining study. The quality of the evidence presented in each article was low due to numerous limitations. Despite the abundance of breast surgery simulators created for trainees, few have been objectively validated and they only cover a narrow range of breast procedures. Although early results are promising, further studies are required before routine use of simulators is considered in breast surgery curricula.
Two group and save (G&S) samples are routinely collected from patients undergoing diagnostic laparoscopy and/or emergency appendicectomy. We aimed to identify the necessity of this practice by looking at the perioperative transfusion rates.
Data were obtained from our electronic theatre system for all patients who underwent emergency laparoscopic surgery (specifically diagnostic laparoscopy and/or laparoscopic appendicectomy) between January 2017 and December 2018. Selleckchem AZD9291 Records were reviewed for the number of G&S samples sent and perioperative transfusion rates.
A total of 451 patients were included in the study. The numbers of procedures performed in 2017 and 2018 were 202 (44.8%) and 249 (55.2%), respectively. The total number of samples sent was 930. Only 786 (84.5%) samples were processed and the rest were rejected for various reasons. Of the 451 patients included in the study, 308 (68.3%) had two G&S samples sent, whereas 41 patients (9.1%) had only one G&S sample sent. Fifty-six (12.4%) and 20 (4.4%) patients had three and four G&S samples sent, respectively. Only two patients required transfusion perioperatively (0.4%), and the indication in both was irrelevant to the primary operation.
These results demonstrate a near-zero transfusion rate in this patient cohort. Omitting G&S is safe and potentially saves time and resources.
These results demonstrate a near-zero transfusion rate in this patient cohort. Omitting G&S is safe and potentially saves time and resources.Osteoclast-like giant cell tumours of the kidney are extremely rare and usually accompanied by a conventional urothelial neoplasm such as papillary, transitional renal cell, or sarcomatoid carcinoma. Although they have morphological features similar to those of the giant cell tumours in the skeletal system, their counterparts in the urinary system show highly malignant features. Our case is the third primer malignant giant cell tumour of the kidney in the literature. The patient was a 50-year-old male and underwent nephroureterectomy for a mass of 18×14×13cm in his left kidney. However, the patient died in the second month postoperatively as a result of local recurrences and multiple distant metastases. The general condition of the patient deteriorated progressively; hence, he could not have any adjuvant therapy. Having more information about the pathological and clinical findings of these exceedingly rare tumours can help inform treatment steps.The procedures undertaken to investigate a research misconduct are usually dictated by research ethics and integrity policy, prescribed either by the institute or by the national agency overseeing research. This policy would typically contain information on how an investigation should be conducted, as well as a non-exhaustive list of what constitutes research misconduct. Typically lacking from these policies would be a precise prescription of how the degree of severity of research misconduct could be determined. Adjudication of severity may often be left to the discretion of individual research integrity officers, or a committee of enquiry. Owing to the subjectivity of this process, the conclusion reached could vary between investigating officers/committees, even when adjudicating based on similar evidence. This variation would likely have an impact on the sanctions delivered. We hereby propose a research misconduct severity matrix, which considers eight independent ethical elements with different weightage, each assigned a numerical score by factoring against five different shades of severity (from minor to major). The sum of the scores associated with these elements returns the research misconduct severity score, a numerical value which would aid investigating officers/committees in reaching a consensus on misconduct severity, and better standardize sanctions meted out.
Diverticular disease is one of the most frequent reasons for attending emergency departments and surgical causes of hospital admission. In the past decade, many surgical and gastroenterological societies have published guidelines for the management of diverticular disease. The aim of the present study was to appraise the methodological quality of these guidelines using the Appraisal of Guidelines Research and Evaluation II (AGREE II) tool.
PubMed, Embase, Cochrane Library and Google Scholar databases were searched systematically. The methodological quality of the guidelines was appraised independently by five appraisers using the AGREE II instrument.
A systematic search of the literature identified 12 guidelines. The median overall score of all guidelines was 68%. Across all guidelines, the highest score of 85% was demonstrated in the domain 'Scope and purpose'. The domains 'Clarity and presentation' and 'Editorial independence' both scored a median of 72%. The lowest scores were demonstrated in the domlity of guidelines and their future updates.
Six of twelve guidelines (NICE, American Society of Colon & Rectal Surgeons (ASCRS), European Society of Coloproctology (ESCP), American Gastroenterological Association, German Society of Gastroenterology/German Society for General and Visceral Surgery (German), Netherlands Society of Surgery) scored above 70%. Only three, NICE, ASCRS and ESCP, scored above 75% and were voted unanimously by the appraisers for use as they are. Therefore, use of AGREE II may help improve the methodological quality of guidelines and their future updates.
Diagnostic work-up of acute appendicitis remains challenging. While some guidelines advise to use a risk stratification based on clinical parameters, others use standard imaging in all patients. As non-operative management of uncomplicated appendicitis has been identified as feasible and safe, differentiation between uncomplicated and complicated appendicitis is of paramount importance. We reviewed the literature to describe the optimal strategy for diagnosis of acute appendicitis.
A narrative review about the diagnosis of acute appendicitis in adult patients was conducted. Both diagnostic strategies and goals were analyzed.
For diagnosing acute appendicitis, both ruling in and ruling out the disease are important. Clinical and laboratory findings individually do not suffice, but when combined in a diagnostic score, a better risk prediction can be made for having acute appendicitis. However, for accurate diagnosis imaging seems obligatory in patients suspected for acute appendicitis. Scoring systems combining clinical and imaging features may differentiate between uncomplicated and complicated appendicitis and may enable ruling out complicated appendicitis.
