BACKGROUND AND AIMS:An irregular Z-line is characterized by a squamocolumnar junction (SCJ) that extends proximally above the gastroesophageal junction by <1 cm, whereas Barrett's esophagus is defined as a columnar-lined esophagus (CLE) that extends proximally by ≥1 cm with the presence of specialized intestinal metaplasia on biopsy sampling. Measurement of the CLE is most accurate for lengths ≥1 cm, and, as such, guidelines do not recommend biopsy sampling of an irregular Z-line when seen on endoscopy. However, a CLE is often estimated by visual inspection rather than direct measurement, making this characterization imprecise. In this study, we present methodology to standardize the characterization of the SCJ, hypothesizing that the shape of the Z-line can be used as a surrogate classifier. We present a computer-generated algorithm capable of automated segmentation and shape complexity quantification of the Z-line. METHODS:We selected and manually segmented 849 images of the Z-line. We used the nnUNet framework (Nature Methods, Heidelberg, Germany) to train a model to segment the Z-line. An additional dataset of 58 videos containing the Z-line were obtained from the Mayo Clinic Endoscopy video library. A high-quality image containing the Z-line was selected from each video. Ten gastroenterologists (5 esophageal experts) rated each of the 58 video-image pairs containing the Z-line as "regular" or "irregular," including their degree of confidence. Fleiss κ statistics were used to determine interobserver variability. The "ground truth" classification was determined by the esophageal expert majority vote. A wavelet decomposition model was then used to determine the threshold of irregularity based on the ground truth. Heat maps were generated for each Z-line to determine localized areas of complexity. RESULTS:Fair agreement, with a Fleiss κ of .39, was observed among the 10 endoscopists when rating the Z-line as regular versus irregular using this dataset. Moderate agreement was observed among the 5 esophageal experts with a Fleiss κ statistic of .42, and fair agreement was observed among the 5 nonesophageal experts with a Fleiss κ statistic of .31. The wavelet energy coefficient optimal threshold to classify an SCJ as irregular was determined to be 1.53 × 107 with an accuracy of 78%. CONCLUSIONS:Our computer-generated model was capable of automatic segmentation and classification of the Z-line. We established a threshold of complexity using the wavelet energy coefficient to standardize the classification of the SCJ.
The diagnosis and management of small bowel bleeding (SBB) can be a clinical challenge. Advances in video capsule endoscopy, balloon-assisted enteroscopy, and multiphasic computed tomography allow for localization and therapeutic intervention. Etiologies of SBB including vascular, neoplastic, and inflammatory conditions are associated with age and comorbidities. The present review highlights terminologies that describe SBB, provides a differential diagnosis for bleeding etiologies, and summarizes a clinical approach to managing this condition.
Thrombosis is a common complication of Essential Thrombocythemia (ET) and is responsible for significant morbidity and mortality in affected individuals. The JAK2 V617F mutation is a well-established risk factor for thrombosis in ET, with a reported prevalence of approximately 50% in patients with ET. However, there is increasing evidence that other mutations, including CALR mutations, also independently confer increased thrombotic risk in ET. CALR functions as a chaperone protein that screens misfolded proteins in the endoplasmic reticulum and prevents transition to the Golgi apparatus and, ultimately, to the cell surface. CALR mutations are exon 9 frameshift mutations due to 52-base pair deletion in type 1 or 5-base pair insertion in type 2. JAK2 and CALR mutations have been proposed to represent two distinct subtypes of ET due to their significant differences in thrombosis risk and disease progression. Therefore, we conducted a systematic review and meta-analysis comparing the cumulative thrombotic risk between different CALR mutation types (type 1 and type 2), and JAK2 V617F mutation in ET. We searched PubMed, Google Scholar, MEDLINE OVID, Cochrane Library, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases to identify relevant peer-reviewed studies published from database inception to January 2023 without any language restrictions. The overall odds ratio (OR) was computed using the random-effects model to account for the expected heterogeneity among included studies. The meta-analysis included a total of 15 studies.1-15 There were 795 included patients with CALR1 mutations, 561 included patients with CALR2 mutations, and 3538 included patients with JAK2 mutations. Most of the studies were retrospective in design and conducted in different countries. The quality of studies was assessed by the JBI risk assessment tool. Most of the studies (10 out of 15) had a low risk of bias, while others had a moderate risk of bias. The rank correlation test for funnel plot asymmetry did not reveal publication bias. The pooled odds ratios for thrombosis in CALR1 versus JAK2, CALR2 versus JAK2, and CALR1 versus CALR2 were 0.65 (95% confidence interval [CI], 0.46–0.91), 0.45 (95% CI, 0.32–0.62), and 1.50 (95% CI, 1.00–2.24), respectively (Figure 1). Sensitivity analysis was conducted among 8 studies after excluding the medium and high risk of bias studies, which showed pooled odds ratio in CALR1 versus CALR2 and CALR1 versus JAK2 were 1.81 (95% CI of 1.04 to 3.13, p = .03) and 0.6 (95% CI of 0.44 to 0.82), respectively. Subgroup analysis based on the site of thrombosis did not show any statistically significant results except for a lower venous thrombotic risk with CALR2 compared to JAK2. This could be because our analysis was underpowered to detect the differential risk of arterial thrombosis between these patients. Our results suggest that ET patients with CALR1 or CALR2 mutations have a lower risk of thrombosis than those with JAK2 mutations. Moreover, ET patients with CALR1 were found to have a higher risk of thrombosis than those with CALR2. The pathophysiology for the difference is unknown, although it can be speculated that CALR2 mutation will lead to less activation of the thrombopoietin receptors and less ADP-induced platelet activation in light of its lower net positive charge.16 More recently, function of mutant CALR protein as rogue cytokine which functions in a way similar to thrombopoietin has been discovered. However, the association between CALR mutations and thrombotic risk requires further investigation, as the included studies varied in patient populations, study designs, and follow-up periods. In addition, we were unable to stratify the thrombotic events based on their severity or recurrence due to the lack of available data and we could not obtain adequate data on thrombosis-free survival. Our study highlights the need for personalized risk assessment and management strategies for ET patients based on their specific mutation status. The authors received no financial support for the research, authorship, and/or publication of this article. The authors have no conflicts of interest to declare. All the required information is in the manuscript itself.
This systematic review and meta-analysis aimed to investigate whether percutaneous mitral valve repair (PMVr) using MitraClip was more effective than surgery or medical therapy for long-term morbidity and mortality. We searched MEDLINE, EMBASE, and CENTRAL (Cochrane Library) databases to identify relevant studies that recruited adult patients with functional or secondary mitral valve regurgitation who underwent PMVr with MitraClip implantation using appropriate search terms and Boolean operators. The odds ratios (ORs) were pooled using the random-effects model. A total of 14 studies recruiting 2,593 patients were included. Within 12 months of follow-up, patients who underwent PMVr did not maintain mitral valve regurgitation grade 2+ (OR 0.22, 95% confidence interval [CI] 0.12 to 0.41, p <0.0001, I-2 = 0.0%, p = 0.52) or symptom-free heart failure (OR 0.47, 95% CI 0.29 to 0.77, p = 0.0028, I-2 = 0.0%, p = 0.66) compared with their surgical counterparts. Patients were more likely to be rehospitalized for heart failure (OR 2.79, 95% CI 1.54 to 5.05, p = 0.0007, I-2 = 0.0%, p = 0.51). However, there was no difference between the groups in terms of all-cause or cardiovascular mortality. Whereas, in comparison with medical therapy, PMVr significantly reduced all-cause mortality at 12 and >= 24 months of follow-up (OR 0.41, 95% CI 0.24, 0.69, p = 0.0009, I-2 = 32%, p = 0.23 and OR 0.55, 95% CI 0.40, 0.75, p = 0.0002, I-2 = 0.0%, p = 0.45, respectively). In conclusion, there was no difference in all-cause death at 12 or 24 months of follow-up between PMVr and the surgical approach, but the durability of valvular repair was inferior with PMVr. In comparison with medical therapy, there was a significant reduction in mortality with PMVr.(c) 2023 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) (Am J Car-diol 2023;207:159-169)
Introduction Solitary plasmacytoma refers to a rare form of mature B-cell malignancy that can present either extraosseous i.e., solitary extramedullary plasmacytoma (SEP), or the more common type, intraosseous i.e., solitary bone plasmacytoma (SBP). According to the National Comprehensive Care Network, the primary treatment of solitary plasmacytoma is radiotherapy with 40-50 Gy to the involved field +/- surgery (if the patient is unstable or has symptoms indicative of neurological compression), or chemotherapy (if the patient has bulky disease defined as ≥5 cm or unresponsive to radiotherapy). This systematic review aimed to assess relapse predictors of solitary plasmacytoma following definitive treatment. Methods A systematic review was conducted in adherence to the PRISMA guidelines with a pre-specified study protocol registered on PROSPERO (CRD42023432422). A literature search was performed utilizing Medline, ScienceDirect, Google Scholar, Cochrane, and Clinicaltrials.gov, on April 15, 2023. The MeSH terms “plasmacytoma”, “recurrence”, “relapse”, “prognosis”, and “treatment” were used. The inclusion criteria were defined as retrospective, randomized, or non-randomized controlled studies published in English that include patients with solitary plasmacytomas of any site, who received radiotherapy, chemotherapy, and/or surgery, and have outcomes of overall survival, progression-free/relapsed-free survival (PFS/RFS), and time to progression to multiple myeloma. Results After meeting the inclusion criteria, twenty-seven studies were included. Among 1412 patients,1034 (73%) SBP, 427 (30%) SEP, and 844 (60%) males were studied. Most articles were published in the USA (15%), followed by Italy (11%) and France (11%). Several overlapping predictors of relapse were observed (Table 1), with younger age (age <60) and tumor size <5 cm the most common significant better prognostic factors; mentioned in 10 (37%) and 7 (26%) studies, respectively. Interestingly, SBP tumor type was associated with worse prognosis in 3 (11%) studies, while SEP tumor type had mixed prognostic association; worse prognostic association in 4 (15%), and better in 3 (11%) studies. Less common negative prognostic indicators included immunoparesis at diagnosis, occult marrow disease, positive serum M protein, persistent M spike, positive serum B2 microglobulin, positive Bence Jones protein, and positive urinary monoclonal light chains. Radiotherapy exhibited a better prognosis alone, with surgery, and with chemotherapy. In addition, a higher radiation dose (>40 Gy) was associated with better prognosis, supported by another study that showed a worse prognosis with a lower radiation dose (<50 Gy). Four studies did not demonstrate a statistically significant prognostic factor. Conclusion Tumor size and age appear to be the most common significant prognostic indicators for solitary plasmacytoma when indexed to outcomes of OS, PFS, MMFS, and median time to MM progression. Several other prognostic indicators have been reported but require further research to ascertain their strength of association and possibly direct future screening and management.