Endoscopic transmural necrosectomy for walled-off pancreatic necrosis: A systematic review and meta-analysis

BACKGROUND:

Endoscopic transmural necrosectomy (ETN) is emerging as a viable treatment option for walled-off pancreatic necrosis. This NOTES-type procedure is significantly less invasive than an extensive surgical debridement; however, published data regarding the success of ETN in treating pancreatic necrosis have varied.

OBJECTIVE:

To evaluate the published medical literature to determine the success of treating walled-off pancreatic necrosis with ETN.

METHODS:

Studies using ETN as a primary mode of therapy to treat organized pancreatic necrosis were selected. Success was defined as resolution of the necrotic cavity proven by radiology. Articles were searched in Medline, PubMed, Ovid journals, CINAH, old Medline, Medline nonindexed citations and the Cochrane controlled trials registry. The summary estimates were expressed as pooled proportions. First, the individual study proportions were transformed into a quantity using Freeman-Tukey variant of the arcsine square root transformed proportion. The pooled proportion was calculated as the back-transform of the weighted mean of the transformed proportions, using inverse arcsine variance weights for the fixed-effects model and DerSimonian-Laird weights for the random-effects model. Publication bias was calculated using the Begg-Mazumdar and Harbord bias estimators.

RESULTS:

The initial search identified 920 reference articles, of which 129 relevant articles were selected and reviewed. Data were extracted from eight studies (n=233) that met the inclusion criteria. Organization of pancreatic necrosis was determined by computed tomography scan in all of the studies. The mean time of ETN after onset of acute pancreatitis/abdominal pain was seven weeks. The weighted mean size of the necrotic cavity was 12.87 cm (95% CI 10.54 cm to 15.20 cm). The weighted mean number of endoscopic procedures needed to resolve the necrotic cavity was 4.09 (95% CI 2.31 to 5.87). Pooled proportion of successful resolution of pancreatic necrosis using ETN was 81.84% (95% CI 76.73% to 86.44%). The pooled proportion of recurrence in the form of necrotic cavity or pseudocyst after ETN was 10.88% (95% CI 7.27% to 15.11%). Complications were noted in 21.33% (95% CI 16.40% to 26.72%) of patients and included bleeding, sepsis and perforation. The weighted mean number of days in hospital after ETN was 32.85 days (95% CI 10.50 to 55.20 days). For pancreatic necrosis that did not resolve, surgery had to be performed in 12.98% (95% CI 9.05% to 17.51%) of patients. The fixed-effect model was used to report all of the pooled proportions. Estimates calculated using fixedand random-effects models were similar. Test of heterogeneity yielded P>0.10, indicating that the studies could be combined. The publication bias calculated using Begg-Mazumdar bias indicator yielded a Kendall’s tau b value of −0.07 (P=0.72) and the same using Harbord bias indicator gave a value of 0.33 (95% CI −1.35 to 2.01; P=0.60). Both of these indicators show that there was no publication bias.

CONCLUSION:

The present meta-analysis showed that ETN is safe and effective at treating patients with symptomatic walled-off necrosis. ETN offers the advantage of minimally invasive endoscopic treatment without transabdominal surgery; however, better techniques and equipment are still needed to improve procedural efficiency. Decisions to perform ETN should be made by advanced endoscopists in collaboration with a multidisciplinary team with the facilities and personnel to manage these complex patients.     

IL-25 and type 2 innate lymphoid cells induce pulmonary fibrosis

Disease conditions associated with pulmonary fibrosis are progressive and have a poor long-term prognosis with irreversible changes in airway architecture leading to marked morbidity and mortalities. Using murine models we demonstrate a role for interleukin (IL)-25 in the generation of pulmonary fibrosis. Mechanistically, we identify IL-13 release from type 2 innate lymphoid cells (ILC2) as sufficient to drive collagen deposition in the lungs of challenged mice and suggest this as a potential mechanism through which IL-25 is acting. Additionally, we demonstrate that in human idiopathic pulmonary fibrosis there is increased pulmonary expression of IL-25 and also observe a population ILC2 in the lungs of idiopathic pulmonary fibrosis patients. Collectively, we present an innate mechanism for the generation of pulmonary fibrosis, via IL-25 and ILC2, that occurs independently of T-cell–mediated antigen-specific immune responses. These results suggest the potential of therapeutically targeting IL-25 and ILC2 for the treatment of human fibrotic diseases.Disease conditions associated with pulmonary fibrosis are often progressive and have a poor long-term prognosis (1). In the context of developing new treatments for pulmonary fibrosis, the cytokines associated with the pathogenic milieu that can lead to aberrant extracellular matrix deposition are key targets, in particular interleukin (IL)-13, TGF-β, and, more recently, IL-17A (2). However, to develop more effective therapeutics for fibrotic lung diseases a greater understanding of the pathogenesis and the underlying mechanisms that lead to pulmonary fibrosis is needed (3, 4).The cytokine IL-13 was first implicated in fibrosis using profibrotic eggs from the type 2 cytokine-inducing pathogen Schistosoma mansoni, in the presence of a soluble IL-13Rα2-Fc fusion protein (5) and in Il13^−/− mice (6). IL-13 is now widely linked to a range of fibrotic conditions (7) including asthma, where IL-13 is being targeted as a therapy (8). In the context of the cellular source of IL-13 in the generation of fibrosis, CD4⁺ T helper (h) 2 cells are implicated (9). However, more recently innate lymphoid cells (ILC) are emerging as an important source of IL-13 (10, 11). In this context, the type 2 cytokine IL-25 is implicated in the generation of the recently identified IL-13–expressing ILC, termed ILC2 (11–14).Recent studies have implicated IL-25 and ILC2 in the pathogenesis of pulmonary conditions in both murine models and human conditions such as allergic asthma (12, 13, 15, 16). In murine studies intranasal administration of IL-25 results in evidence of pulmonary tissue remodeling including development of perivascular fibrosis, and intratracheal administration results in increased pulmonary Th2 cytokines and airways hyper-reactivity (AHR) (17, 18), whereas blocking IL-25 reduces AHR severity (19). Herein we describe a potential role for IL-25 in the generation of pulmonary fibrosis in experimental mouse models, via the activation of IL-13–producing ILC2. We also observe increases in both IL-25 and ILC2 in the lung of patients with idiopathic pulmonary fibrosis (IPF). These data suggest unique mechanisms for the generation of pulmonary fibrosis and identify an interesting area for further research on the role of IL-25 and ILC2 in the treatment of pulmonary fibrosis.     

Diagnostic accuracy and clinical utility of biopsy in musculoskeletal lesions: A comparison of fine‐needle aspiration,core, and open biopsy techniques

Selection of biopsy technique for musculoskeletal lesions is complex. Fine‐needle aspiration (FNA) is uncommonly used due to concerns regarding accuracy. We compared diagnostic accuracy of FNA, core, and open biopsy in a series of musculoskeletal lesions. Records of the University of Utah were searched for biopsy and resection specimens of musculoskeletal lesions. Results of corresponding imaging studies were obtained. Biopsy and FNA diagnoses were correlated with resection diagnoses. For each technique, diagnostic accuracy, utility, and frequency of subsequent biopsy were calculated. Open biopsy had the highest diagnostic accuracy (89%) followed by FNA (82%) and core biopsy (78%). Clinically significant errors occurred with all methods. The likelihood of an open biopsy being performed was affected by prior performance of an FNA or core biopsy and by diagnostic imaging and FNA results. Diagn. Cytopathol. 2014;42:476–486. © 2014 Wiley Periodicals, Inc.     

Selfie fundus imaging for diabetic retinopathy screening

BackgroundRegular screening for retinopathy and timely intervention reduces blindness from diabetes by 90%. Screening is currently dependent on the interpretation of images captured by trained technicians. Inherent barriers of accessibility and affordability with this approach impede widespread success of retinopathy screening programs. Herein, we report our observations on the potential of a novel approach, Selfie Fundus Imaging (SFI), to enhance diabetic retinopathy screening.MethodsThe study was undertaken over a two-month period during COVID 19 lockdown. 60 diabetic patients participated in the study. Retinal images were captured using three different approaches, handheld smartphone-based photographs captured by patients themselves after a short video-assisted training session (SFI group), and smartphone-based photographs captured by a trained technician and photographs taken on desktop conventional digital fundus camera (Gold standard). Sensitivity and kappa statistics was determined for retinopathy and macular oedema grading.FindingsMean age of the study participants was 52.4 years ± 9.8 years and 78% were men. Of 120 images captured using SFI, 90% were centred-gradable, 8% were decentred-gradable and 2% were ungradable. 82% patients captured the image within a minute (majority by 31–45 s). The sensitivity of SFI to detect diabetic retinopathy was 88.39%. Agreement between SFI grading and standard fundus photograph grading was 85.86% with substantial kappa (0.77). For the detection of diabetic macular oedema, the agreement between SFI images and standard images was 93.67, with almost perfect kappa (0.91).ConclusionFundus images were captured by patients using SFI without major difficulty and were comparable to images taken by trained specialist. With greater penetrance, advances, and availability of mobile photographic technology, we believe that SFI would positively impact the success of diabetic retinopathy screening programs by breaking the barriers of availability, accessibility, and affordability. SFI could ensure continuation of screening schedules for diabetic retinopathy, even in the face a highly contagious pandemic.Subject terms: Outcomes research, Retinal diseases, Physical examination     

Does Risk Mitigation Reduce 90-Day Complications in Patients Undergoing Total Knee Arthroplasty?: A Cohort Study

BackgroundWith ever-increasing demand for total knee arthroplasty (TKA), most healthcare systems around the world are concerned about its socioeconomic burden. Most centers have universally adopted well-defined clinical care pathways to minimize adverse outcomes, maximize volume, and limit costs. However, there are no prospective comparative trials reporting benefits of these risk mitigation (RM) strategies.MethodsThis is a prospective cohort study comparing post-TKA 90-day complications between patients undergoing RM before surgery and those following a standard protocol (SP). In the RM group, we used a 20-point checklist to screen for modifiable risk factors and evaluate the need for optimizing non-modifiable comorbidities. Only when optimization goals were achieved, patients were offered TKA.ResultsTKA was performed in 811 patients in the SP group and in 829 in the RM group, 40% of which were simultaneous bilateral TKA. In both groups, hypertension was the most prevalent comorbidity (48%), followed by diabetes (20%). A total of 43 (5.3%) procedure-related complications were seen over the 90-day postoperative period in the SP group, which was significantly greater than 26 (3.1%) seen in the RM group (p = 0.039). The commonest complication was pulmonary thromboembolic, 6 in each group. Blood transfusion rate was higher in the SP group (6%) than in the RM group (< 1%).ConclusionsScreening and RM can reduce 90-day complications in patients undergoing TKA.     

Over expression of brain and acute leukemia,cytoplasmic and ETS-related gene is associated with poor outcome in acute myeloid leukemia

The high expression of brain and acute leukemia, cytoplasmic (BAALC) and ETS-related gene (ERG) has been reported to influence the outcome in acute myeloid leukemia (AML), but due to limited prospective studies, their role as prognostic factors is unclear. At diagnosis, the prognostic value of BAALC and ERG expression with respect to other cytogenetic and molecular markers was analyzed in 149 AML patients. Patients were divided into quartiles which resulted in the formation of four groups (G1–G4) based on expression values of BAALC and ERG and clinical response defined across groups. Groups with similar survival probabilities were merged together and categorized subsequently as high versus low expressers. Patients with high BAALC and ERG expression had significantly lower overall survival (OS; BAALC: p = 0.001 at 5 years 29.4% vs. 69.8%; ERG: p < 0.0001 at 5 years 4% vs. 50.4%) and disease-free survival (BAALC: p = 0.001 at 5 years 19.5% vs. 69.8%; ERG: p < 0.0001 at 5 years 4.2% vs. 47%). Patients were further stratified combining BAALC and ERG expression in an integrative prognostic risk score (IPRS). After a median follow-up of 54 months (95% CI 45–63 months) among survivors, IPRS for high versus low expressers was a significant predictor for OS (BAALC + ERG: 4% vs. 71.6%, p < 0.0001) and DFS (BAALC + ERG: 4.5% vs. 74.1%, p < 0.0001). In a multivariate model, IPRS of BAALC + ERG expression retained prognostic significance for OS (hazard ratio [HR] 2.96, 95%CI 1.91–4.59, p < 0.001) and DFS (HR 3.61, 95%CI 2.26–5.76, p < 0.001).