Elucidating the non-genetic risk factors for celiac disease: an umbrella review of meta-analyses.

OBJECTIVE: The breadth and validity of the associations of nongenetic risk factors with celiac disease (CeD) are elusive in the literature. We aimed to evaluate which of these associations have strong epidemiological credibility and assessed presence and extent of potential literature biases. METHODS: We systematically searched PubMed until April 2024 for systematic reviews and meta-analyses of studies examining associations between putative risk factors and CeD. Each association was categorized in five evidence grades (convincing, highly suggestive, suggestive, weak, and not statistically significant) based on broadly used criteria for evaluating quality of evidence in observational studies. RESULTS: Five eligible publications were included, describing 15 meta-analytic associations on seven nongenetic risk factors, three of which were nominally significant (P < 0.05). None of the associations received a strοng or highly suggestive evidence. One meta-analytic association received suggestive evidence, namely any infections during childhood and adulthood for a higher risk of CeD (OR, 1.37; 95% CI, 1.2-1.56; P=3.77 × 10-6). Two meta-analyses reported weak evidence, pertaining to current smoking for a lower risk of CeD (OR, 0.52; 95% CI, 0.32-0.84; P=7.84 × 10-3) and use of antibiotics for a higher risk (OR, 1.2; 95% CI, 1.04-1.38; P 14.8 × 10-3). The rest of the meta-analyses did not report statistically significant results, and pertained to breastfeeding, time of gluten introduction, rotavirus vaccination, and cesarean section. CONCLUSION: No association of nongenetic risk factors for CeD received high levels of evidence. The evidence was suggestive for the association of any infections during childhood and adulthood with higher risk of CeD. More and prospective future research is warranted.

Systematic Review and Network Meta-analysis of Vessel Preparation Techniques With Plain Balloon Angioplasty, Atherectomy, or Intravascular Lithotripsy Before Application of a Drug Coated Balloon to Treat Atherosclerotic Femoropopliteal Disease.

OBJECTIVE: To compare one year outcomes after atherectomy, intravascular lithotripsy vs. plain balloon angioplasty before application of drug coated balloons for treating femoropopliteal atherosclerotic disease. DATA SOURCES: MEDLINE, EMBASE, and Cochrane Library were screened until May 2023 for randomised controlled trials. REVIEW METHODS: This was a systematic review and network meta-analysis. The inclusion criteria were patients with claudication and those with critical limb threatening ischaemia with lesion characteristics of all lengths, stenosis, calcification, and occlusions. Primary outcome was freedom from target lesion re-intervention at one year. Secondary outcomes were rate of bailout stenting, major amputation, and all-cause mortality at one year. Pooled point estimates were calculated with a standard random effects model. Further sensitivity analyses were completed with a mixed treatment Bayesian model. Risk of bias was assessed by the Revised Cochrane Risk of Bias tool 2 (RoB2) and certainty of evidence assessed via the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework. RESULTS: Four RCTs comprising 549 patients (two studies evaluating directional atherectomy, one evaluating rotational atherectomy, one evaluating intravascular lithotripsy against plain balloon angioplasty) were included. Weighted mean length of femoropopliteal lesions was 103.4 ± 6.67 mm. Results of the mixed treatment Bayesian analysis were consistent with pooled analysis for all outcomes. There were no significant differences in freedom from target lesion revascularisation (GRADE, high) (RoB2, low), major amputation (GRADE, low), or mortality (GRADE, moderate). Bailout stenting rates were significantly reduced with intravascular lithotripsy and atherectomy compared with plain balloon angioplasty (RR 0.25, 95% CI 0.07 - 0.89) (GRADE, moderate) (RoB2, low). CONCLUSION: This review found that intravascular lithotripsy or atherectomy did not appear to incur a statistically significant advantage in freedom from target lesion revascularisation, major amputation, or mortality at one year. There was moderate certainty of evidence that bailout stenting is significantly reduced after vessel preparation with intravascular lithotripsy and atherectomy.

Nephrology Partnership for Advancing Technology in Healthcare (N-PATH) Erasmus+ project: The Renal Expert in Vascular Access (REVAC) module.

The Renal Expert in Vascular Access (REVAC) is one of the four modules of the Nephrology Partnership for Advancing Technology in Healthcare (N-PATH) project, the first European-wide advanced training course in diagnostics and interventional nephrology, funded by Erasmus+ Knowledge Alliance, a European Commission program. The N-PATH primary goal was to train 40 young European nephrologists in both theoretical knowledge and practical skills related to interventional nephrology. The REVAC module focused on the crucial aspects of vascular access (VA) care in nephrology practice, as a complementary training path to the actual residency program. The aim was to provide nephrology fellows with comprehensive knowledge and skills related to VA management. The methodology was based on face-to-face meetings and online learning, modern facilities, experienced tutors, cutting edge simulators, augmented reality tools by means of a multidisciplinary international faculty and hands-on-courses. A feedback survey reported the experience of fellows who attended the REVAC module, confirming the positive impact on their ongoing nephrology training. We are confident that this project will revitalize their nephrology careers and will help training the next generation of nephrologists; they will be able to manage VA needs with the help of multi-disciplinary teams to safely optimize the care of hemodialysis patients.

Rapid and Precise Computation of Fractional Flow Reserve from Routine Two-Dimensional Coronary Angiograms Based on Fluid Mechanics: The Pilot FFR2D Study.

Objective: To present a novel pipeline for rapid and precise computation of fractional flow reserve from an analysis of routine two-dimensional coronary angiograms based on fluid mechanics equations (FFR2D). Material and methods: This was a pilot analytical study that was designed to assess the diagnostic performance of FFR2D versus the gold standard of FFR (threshold ≤ 0.80) measured with a pressure wire for the physiological assessment of intermediate coronary artery stenoses. In a single academic center, consecutive patients referred for diagnostic coronary angiography and potential revascularization between 1 September 2020 and 1 September 2022 were screened for eligibility. Routine two-dimensional angiograms at optimal viewing angles with minimal overlap and/or foreshortening were segmented semi-automatically to derive the vascular geometry of intermediate coronary lesions, and nonlinear pressure-flow mathematical relationships were applied to compute FFR2D. Results: Some 88 consecutive patients with a single intermediate coronary artery lesion were analyzed (LAD n = 74, RCA n = 9 and LCX n = 5; percent diameter stenosis of 45.7 ± 11.0%). The computed FFR2D was on average 0.821 ± 0.048 and correlated well with invasive FFR (r = 0.68, p < 0.001). There was very good agreement between FFR2D and invasive-wire FFR with minimal measurement bias (mean difference: 0.000 ± 0.048). The overall accuracy of FFR2D for diagnosing a critical epicardial artery stenosis was 90.9% (80 cases classified correctly out of 88 in total). FFR2D identified 24 true positives, 56 true negatives, 4 false positives, and 4 false negatives and predicted FFR ≤ 0.80 with a sensitivity of 85.7%, specificity of 93.3%, positive likelihood ratio of 13.0, and negative likelihood ratio of 0.15. FFR2D had a significantly better discriminatory capacity (area under the ROC curve: 0.95 [95% CI: 0.91-0.99]) compared to 50%DS on 2D-QCA (area under the ROC curve: 0.70 [95% CI: 0.59-0.82]; p = 0.0001) in predicting wire FFR ≤ 0.80. The median time of image analysis was 2 min and the median time of computation of the FFR2D results was 0.1 s. Conclusion: FFR2D may rapidly derive a precise image-based metric of fractional flow reserve with high diagnostic accuracy based on a single two-dimensional coronary angiogram.

Vacuum-Assisted Thrombo-Aspiration for Paradoxical Embolism in Left Renal Artery: A Case Report and Literature Review.

Paradoxical embolism through the foramen ovale is a rare and devastating event requiring urgent treatment. Herein, we present the case of a 23-year-old male who presented with a pulmonary embolism complicated by a left renal artery paradoxical embolism. Urgent vacuum-assisted thrombo-aspiration restored normal perfusion of the left kidney within 5 hours. The patient had a patent foramen ovale and heterozygous thrombophilia. However, a radioisotopic scan performed 2 years later revealed an unexpected decrease in left renal perfusion. Therefore, despite the angiographic success, functional evaluation using a renal scan should be performed to assess renal function.

Can Hypnotherapy Be Considered a Valuable Component in the Management of Inflammatory Bowel Disease? Insights from a Comprehensive Review.

Despite advancements in medication,managing inflammatory bowel disease (IBD) remains challenging, necessitatingalternative control methods. Gut-directed hypnotherapy, known for alleviating irritable bowel syndrome (IBS), is debated as an IBD management method. Anextensive search across PubMed, Cochrane Library, and Clinicaltrials.govuncovered five randomized trials and two case series involving IBD patients undergoing hypnotherapy. A small trial reported statistically significant remission at one year (p = .04), but larger trials, including one with 63 patients, showed no significant gastrointestinal improvements. The first case series noted post-intervention reduction in the mediators of inflammation in rectal mucosal, without long-term monitoring. The second case series observed the absence of flare episodes in 12 of 13 ulcerative colitis patients during follow-up, possibly influenced by the simultaneous use of two drugs alongside hypnotherapy. Psychological outcomes, demonstrated no significant differences between hypnotherapy and control groups. While current literature doesn't decisively support hypnotherapy for managing IBD symptoms, it underscores the importance of further research, including randomized clinical trials, to thoroughly assess its effectiveness in this context.

Evaluation of arteriovenous fistula maturation and early prediction of clinical eligibility, using ultrasound: The Fistula Maturation Evaluation (FAME) Study.

INTRODUCTION: The study of time-related alterations of ultrasound-determined parameters during maturation, and the assessment of time to hemodynamic maturation, enabling early prediction of clinical eligibility, of hemodialysis autologous arteriovenous fistulae (AVF). METHODS: This is an observational, prospective, study of only AVF-eligible patients referred for access creation, from 02/2019 to 02/2022 (ClinicalTrials.gov identifier: NCT0473687). Brachial artery diameter (dBA), access flow volume (FV), non-augmented efferent vein diameter (dEV), resistivity index (RI), and efferent vein total wall thickness (tEV), were assessed by ultrasound. Measurements were conducted daily in the first week and repeated on days 14, 21, 30, 60, and 90, postoperatively. The primary endpoint included the documentation of serial changes of flow and structural parameters related to AVF maturation in the first 90 days of the post-operative period and maturation early prediction. Secondary endpoints included the determination of factors affecting maturation. RESULTS: One hundred one participants (mean age, 67 ± 6 years; 76 males) were enrolled. Average dBA and FV reached maximum on day 60 (5.64 ± 0.85 mm) and 90 (1.172 ± 617 mL/min), respectively. Day 7 values of dBA (5.48 ± 0.73 mm) and FV (1.039 ± 531 mL/min) did not alter significantly during the follow-up period. Parameters indicative of clinical functionality, dEV (5.82 ± 0.90 mm) and tEV (0.493 ± 0.10 mm), reached approximately 90% of maximum (6.66 ± 1.42 mm and 0.526 ± 0.11 mm), by day 14. RI reached minimum on day 30 (0.46 ± 0.09), without significant changes after day 2 (0.48 ± 0.09, p = 0.284). A significant correlation was identified, between day 7 FV and day 60 dEV (r = 0.40, p = 0.0002). A FV cut-off value ⩾657.51 mL/min, on day 7, predicted successful fistula maturation with 85% sensitivity and 100% specificity. Multivariate analysis identified female gender, age >75, diabetes, and wrist access as independent predictors of decreased values of maturation parameters. CONCLUSION: Hemodynamic maturation is completed by the first postoperative week, while AVF is clinically functional, by the second. FV can be used for early prediction of maturation.

Ablative Radioembolization (SIRT) of a Large Inoperable Renal Cell Carcinoma Invading the Liver That Resulted in Hematuria Control and Complete Necrosis by mRECIST Criteria.

ABSTRACT: We report the successful application of radioembolization (SIRT) in a 77-year-old man with end-stage renal disease on hemodialysis and repeated episodes of macroscopic hematuria due to a large renal cell carcinoma of the right kidney extending to liver segment VI. A compassionate SIRT therapy was performed with resin microspheres through the upper pole renal artery and the feeding segmental artery of liver segment VI. Hematuria was resolved after treatment, and 4 months later, a follow-up CT scan revealed tumor size reduction and complete tumor necrosis (Response Evaluation Criteria in Solid Tumors criteria). Ablative SIRT therapy could be a safe and efficient option in a large inoperable RCC.

Comparison between tofacitinib and ustekinumab as a third-line therapy in refractory ulcerative colitis: A multicenter international study.

BACKGROUND: Ustekinumab and tofacitinib have recently been approved for the management of moderate to severe ulcerative colitis (UC). However, there is no evidence on how they should be positioned in the therapeutic algorithm. The aim of this study was to compare tofacitinib and ustekinumab as third-line therapies in UC patients in whom anti-TNF and vedolizumab had failed. METHODS: This was a multicenter retrospective observational study. The primary outcome was disease progression, defined as the need for steroids, therapy escalation, UC-related hospitalization and/or surgery. Secondary outcomes were clinical remission, normalization of C-reactive protein, endoscopic remission, treatment withdrawal, and adverse events. RESULTS: One-hundred seventeen UC patients were included in the study and followed for a median time of 11.6 months (q1-q3, 5.5-18.7). Overall, 65% of patients were treated with tofacitinib and 35% with ustekinumab. In the entire study cohort, 63 patients (54%) had disease progression during the follow-up period. Treatment with ustekinumab predicted increased risk of disease progression compared to treatment with tofacitinib in Cox regression analysis (HR: 1.93 [95% CI: 1.06-3.50] p = 0.030). Twenty-eight (68%) patients in the ustekinumab group and 35 (46%) in the tofacitinib group had disease progression over the follow-up period (log-rank test, p < 0.054). No significant differences were observed for the secondary outcomes. Six and 22 adverse events occurred in the ustekinumab and tofacitinib groups, respectively (15% vs. 31%, p = 0.11). CONCLUSIONS: Tofacitinib was more efficacious in reducing disease progression than ustekinumab in this cohort of refractory UC patients. However, prospective head-to-head clinical trials are needed as to confirm these data.

Effectiveness and safety of darvadstrocel in patients with complex perianal fistulizing Crohn's disease: a systematic review.

Background: Managing complex perianal fistulizing Crohn's disease (CD) remains challenging, despite current medical and surgical treatment approaches. Darvadstrocel, a therapy utilizing adipose-derived stem cells, shows promise in promoting tissue regeneration and healing, offering a novel and effective treatment for fistula management. Method: A systematic literature search was conducted on PubMed and Scopus to identify studies involving patients with complex perianal fistulizing CD treated with darvadstrocel. Results: In total, 2 randomized controlled trials (RCT), 5 observational studies with retrospective data collection and 2 observational studies with prospective design were included in the final review. Data from the European ADMIRE-CD RCT demonstrated that darvadstrocel is superior to placebo in terms of clinical and imaging improvement over both the short and long term. These findings align with the prospective studies analyzed in this systematic review. The rate of treatment-emergent adverse events in the ADMIRE-CD trial's RCTs was similar in both the darvadstrocel and control groups, with perianal abscess being the most common adverse event up to 52 weeks after drug administration. Retrospective studies indicated no side-effects beyond 52 weeks. Conclusions: Darvadstrocel appears to be a new, potentially effective and safe treatment option for the management of complex perianal fistulas. However, more randomized clinical trials are needed to evaluate the efficacy and safety profile of the drug.

TAMs and PD-1 Networking in Gastric Cancer: A Review of the Literature.

BACKGROUND: Gastric cancer (GC) is one of the most common and aggressive types of cancer. Immune checkpoint inhibitors (ICIs) have proven effective in treating various types of cancer. The use of ICIs in GC patients is currently an area of ongoing research. The tumor microenvironment (TME) also seems to play a crucial role in cancer progression. Tumor-associated macrophages (TAMs) are the most abundant population in the TME. TAMs are capable of displaying programmed cell death protein 1 (PD-1) on their surface and can form a ligand with programmed death ligand 1 (PD-L1), which is found on the surface of cancer cells. Therefore, it is expected that TAMs may significantly influence the immune response related to immune checkpoint inhibitors (ICIs). AIM OF THE STUDY: Understanding the role of TAMs and PD-1/PD-L1 networking in GC. METHODS: A systematic review of published data was performed using MEDLINE (PubMed), Embase, and Cochrane databases. We retrieved articles investigating the co-existence of TAMs and PD-1 in GC and the prognosis of patients expressing high levels of PD-1+ TAMs. RESULTS: Ten articles with a total of 2277 patients were included in the systematic review. The examined data suggest that the expression of PD-L1 has a positive correlation with the infiltration of TAMs and that patients who express high levels of PD-1+ TAMs may have a worse prognosis than those who express low levels of PD-1+ TAMs. CONCLUSIONS: TAMs play a pivotal role in the regulation of PD-1/PD-L1 networking and the progression of GC cells. Nevertheless, additional studies are needed to better define the role of TAMs and PD-1/PD-L1 networking in GC.

Unusual abscess masquerading as poorly differentiated adenocarcinoma of the colon showing characteristics of choriocarcinoma

Extragonadal non-gestational choriocarcinoma (ENC) is an uncommon malignant tumor occasionally found in the gastrointestinal tract. ENC is characterized by a biphasic tumor growth with distinct areas of adenocarcinoma and choriocarcinoma differentiation. Primary choriocarcinoma of the colon is extremely rare, with only 21 cases reported in the literature. Most of the perforation of colorectal cancers occurs in the abdominal cavity, while abdominal wall abscess is rare; the psoas abscess associated with colon carcinoma is even less observed. Herein, we report the case of a 61-year-old female with poorly differentiated adenocarcinoma of the ascending colon and sigmoid, with choriocarcinomatous differentiation, masquerading a psoas abscess formation. Unfortunately, despite the aggressive therapy, the patient's disease rapidly progressed, and she died within 2 months after the diagnosis. The typical morphological pattern, immunohistochemistry, and its correlation with serum β-human chorionic gonadotropin enabled a correct diagnosis.