Citations

Background and Objective: This study aimed to investigate glaucoma progression following secondary intraocular lens (SIOL) implantation by surgical approach. Patients and Methods: This was a single-center retrospective study of 440 eyes that received SIOL implantation, including scleral-sutured, scleral-fixated, anterior chamber, and sulcus-fixated. Glaucoma progression was defined as new diagnosis, procedure for intraocular pressure (IOP) control, or IOP elevation ≥ 24 mmHg or ≥ 5 mmHg above baseline requiring additional medications. Risk factors were assessed using multivariable analysis. Results: Mean age at surgery was 71.3 years and 29.3% of patients had prior glaucoma. Overall, 33.2% developed glaucoma progression. Prior glaucoma (hazard ratio 2.08 [95% CI 1.47–2.94], P < .001) and cystoid macular edema (1.63 [1.06–2.52], P = .026) were associated with glaucoma progression on multivariable analysis. There was no difference in glaucoma progression between scleral-sutured, scleral-fixated, anterior chamber, or sulcus-fixated implantation techniques. Conclusion: Our results suggest that surgeons should use their preferred SIOL implantation technique but closely monitor postoperative IOP.

Abstract Background Regorafenib and anti-EGFR monoclonal antibodies are standard therapies for RAS/BRAF wild-type (WT) metastatic colorectal cancer (mCRC) in the refractory setting, but the optimal sequencing remains unknown. Herein, we report results from REVERCE II, a randomized phase II trial evaluating the efficacy and safety of sequencing these therapies. Methods Patients with RAS WT mCRC previously treated with fluoropyrimidine, oxaliplatin, and irinotecan were randomized to receive (R-E) regorafenib followed by anti-EGFR therapy ± irinotecan or (E-R) anti-EGFR therapy ± irinotecan, followed by regorafenib sequentially. The primary endpoint was overall survival (OS). Key secondary endpoints included progression-free survival (PFS) with initial (PFS1) and second treatment (PFS2), sequential treatment PFS (stPFS), objective response rate (ORR), and safety. Exploratory endpoints included serial biomarker analyses. Unfortunately, the trial was closed prematurely due to slow enrollment and lack of funding. Results Twenty-two patients were enrolled (R-E: n = 12; E-R: n = 10) with sequential treatment initiated in 33% (4/12) and 80% (8/10) of patients in R-E and E-R, respectively. Median OS for R-E and E-R was 21.9 and 13.3 months, respectively (one-sided P = .114). PFS1 was 2.5 (R-E) vs 5.6 months (E-R) (one-sided P = .998), while PFS2 was 3.7 vs 2.0 months (one-sided P = .086). stPFS was similar (9.3 vs 9.6 months; one-sided P = .358). ORR for initial treatment was 0% in R-E and 20% (2/8) in E-R. Sequential treatment ORR was 25% (n = 1/4) in R-E and 0% in E-R. No significant differences were observed adverse effects between arms. Conclusion While the study was closed prematurely prior to completion, the sequence of regorafenib before to anti-EGFR therapy suggested a possible survival benefit. Further studies may help better determine the optimal treatment sequencing strategy in refractory mCRC.

ABSTRACT Coeliac disease (CeD) and immunoglobulin A deficiency (IgAD) frequently co‐occur and share a genetic background within the HLA‐DQ2 region. Although this has been known for decades, the underlying mechanisms linking the two conditions remain unclear. We conducted a scoping review to evaluate the prevalence, clinical characteristics, diagnostic challenges and histopathological features of IgAD in patients with CeD. Thirty‐one studies published between 1985 and 2024 were included. IgAD was more prevalent among individuals with CeD, 1.4%–4.8% than in the general population, and CeD occurred in 5.9%–14.1% of patients with IgAD. Most patients presented with gastrointestinal symptoms, although selection bias was common. IgG‐based serology remains essential for diagnosis and monitoring, but its reliability during follow‐up is limited by the slow decline of antibodies. Histological findings indicate compensatory IgM and IgG responses and persistent mucosal immune activation. Improved strategies for diagnosis and long‐term monitoring of patients with both conditions are warranted.

Background: While tobacco use is a well-known risk factor for adverse outcomes after carpal tunnel release (CTR), the impact of non-tobacco nicotine products remains unclear. This study evaluated complications in CTR patients with non-tobacco nicotine dependence (NTND) compared with tobacco users and controls. Methods: Patients who underwent CTR with ≥2-year follow-up were identified using a large national database. After 1:1 propensity score matching, patients with NTND (n = 6319) were matched to controls, tobacco users (n = 86 430) were matched to controls, and patients with NTND (n = 6325) were matched to tobacco users. Matching was based on age, gender, Charlson comorbidity index, and comorbidities. Outcomes including 90-day medical complications, infection, emergency department (ED) visits, readmissions, and 2-year revision rates were compared using multivariable logistic regression. Results: Compared with controls, patients with NTND demonstrated higher 90-day medical complication rates (2.4% vs 1.7%; odds ratio [OR], 1.35; 95% CI, 1.04-1.77) and ED visits (10.3% vs 8.1%; OR, 1.16; 95% CI, 1.02-1.32). Compared with tobacco users, patients with NTND had decreased ED visits (10.4% vs 14.2%; OR, 0.74; 95% CI, 0.66-0.83) and revision surgery (1.9% vs 2.5%; OR, 0.78; 95% CI, 0.62-0.99), with no significant differences in medical complications, infection, or readmissions. Conclusions: Non-tobacco nicotine dependence was associated with increased medical complications and ED visits compared with controls, but decreased ED visits and revision surgery compared with tobacco users. There were no significant differences in medical complications, infections, or readmissions between tobacco users and patients with NTND. These findings underscore the importance of screening for non-tobacco nicotine use during preoperative evaluations for CTR.

ABSTRACT Right ventricular (RV) failure after left ventricular assist device (LVAD) implantation is a serious complication which may necessitate temporary mechanical support in refractory cases. Here we describe a 63‐year‐old man with end‐stage ischemic cardiomyopathy and severe combined pre‐ and post‐capillary pulmonary hypertension who developed persistent RV failure post‐LVAD. He was intolerant to speed optimization secondary to preload mismatch, and invasive hemodynamics confirmed LV underfilling. An Impella RP Flex was placed for RV support, and biventricular (BiV) pressure‐volume (PV) loops were utilized to ascertain hemodynamic response. With increasing Impella RP Flex support, left ventricular end‐diastolic volume increased with subsequent improvement in left ventricular performance. This case represents the first reported use of BiV PV loop analysis to characterize the physiological effects of Impella RP Flex in a patient with LVAD support, underscoring its utility in understanding device‐ventricular interactions.

Background Loss of finger motion after zone II flexor tendon repair remains common and is largely caused by adhesion formation. Although intrinsic vascular and cellular contributions to tendon healing have been examined in canine, avian, and primate models, prior studies have emphasized biochemical or perfusion-based endpoints without comprehensive assessment of functional and mechanical outcomes after clinically relevant repair. Consequently, the influence of intrinsic healing elements on early postoperative function remains unclear. In this study, we employed a novel avian model of intrasynovial (zone II) tendon injury, which enables clinically relevant operative repair, postoperative rehabilitation, and quantitative assessment of tendon function and biomechanics, to investigate the contribution of intrinsic healing elements to tendon repair. Questions/purposes (1) Does operative ablation of intrinsic healing elements worsen early ROM after zone II flexor tendon repair? (2) Does disruption of intrinsic pathways increase adhesion formation, as measured by normalized work of flexion and gross adhesion scores? (3) Does intrinsic tendon component ablation compromise mechanical properties, including ultimate load to failure and stiffness? (4) Does removal of intrinsic elements alter the expression of fibrotic and matrix-related genes during early healing? Methods Using a clinically relevant, large-animal avian ( Meleagris gallopavo ) model of zone II flexor tendon repair, flexor digitorum longus (FDL) tendons underwent sharp transection and primary repair and were assigned to one of four groups: (1) control repair with intact intrinsic elements (3 weeks postinjury, n = 11; 6 weeks postinjury, n = 18), (2) vincular ligation and transection (3 weeks postinjury, n = 12; 6 weeks postinjury, n = 16), (3) tenocyte cryoablation via intraoperative freeze-thaw devitalization (3 weeks postinjury, n = 13; 6 weeks postinjury, n = 13), or (4) complete tendon devitalization (3 weeks postinjury, n = 13; 6 weeks postinjury, n = 16). A total of 112 male and female birds were used for this study. Harvested tendons were evaluated at 3 and 6 weeks postoperatively. Outcomes included interphalangeal ROM, normalized work of flexion, semiquantitative gross adhesion scoring, ultimate load to failure, stiffness, qualitative histologic assessment, qualitative immunofluorescence, and quantitative PCR for fibrotic and matrix-related genes. Results Operative ablation of the intrinsic healing elements did not worsen total ROM and/or increase normalized work of flexion. All experimental groups demonstrated reduced total ROM of the operative digit at 3 weeks postoperatively compared with the contralateral nonoperative digit: mean ± SD control repair with intact intrinsic healing elements (50° ± 10° versus 14° ± 6°, mean difference 36.41° [95% confidence interval (CI) 26.87° to 45.94°]; p < 0.001), vincular disruption group (50° ± 10° versus 14° ± 7°, mean difference 35.97° [95% CI 21.44° to 45.51°]; p < 0.001), tenocyte cryoablation group (50° ± 10° versus 15° ± 8°, mean difference 35.27° [95% CI 25.99° to 44.55°]; p < 0.001), and complete tendon devitalization group (50° ± 10° versus 11° ± 4°, mean difference 38.97° [95% CI 29.44° to 48.50°]; p < 0.001). However, no differences between the groups were detected. Similarly, the total ROM was impaired at 6 weeks postinjury compared with the nonoperative digit in all groups. We did not detect any differences between the groups, and results did not demonstrate time-dependent differences between the two time points. Furthermore, normalized work of flexion, a proxy for peritendinous adhesion severity, was increased in all experimental groups at 3 weeks postinjury: mean ± SD control repair with intact intrinsic healing elements (0 ± 0 N mm/° versus 4 ± 3 N mm/°, mean difference -3.33 [95% CI -5.73 to -0.93]; p = 0.003), vincular disruption group (0 ± 0 N mm/° versus 4 ± 2 N mm/°, mean difference -3.09 [95% CI -5.49 to -0.69]; p = 0.006), tenocyte cryoablation group (0 ± 0 N mm/° versus 3 ± 2 N mm/°, mean difference -2.99 [95% CI -5.33 to -0.66]; p = 0.006), and complete tendon devitalization group (0 ± 0 N mm/° versus 4 ± 2 N mm/°, mean difference -3.31 [95% CI -5.70 to -0.91]; p = 0.003). However, no group differences were detected. At the 6-week follow-up, the normalized work of flexion was also elevated in all groups without any differences between the treatments. Furthermore, the integrity of the tendon intrinsic components has been presumed to be a major determinant of flexor tendon healing strength after zone II tendon repair. However, our results do not support this assumption. At both time points, there were no differences in ultimate load and stiffness between the experimental groups, and there were no group × time interaction effects. Additionally, structural removal of the intrinsic healing elements did not result in meaningful qualitative histologic differences in extrinsic fibrosis, neovascularization, or collagen fiber organization. The profibrotic gene, transforming growth factor beta induced (TGFBI), was upregulated in all experimental groups compared with the normal FDL tendon. Matrix remodeling, measured by matrix metalloproteinase 7 (MMP7) activity, was also activated in all groups relative to the normal FDL tendon. However, no differences were detected between the groups. Conclusion Operative ablation of intrinsic healing elements, including the flexor vincular system and resident tenocytes, did not worsen early ROM, adhesion formation, or mechanical properties after zone II flexor tendon repair in a clinically relevant large-animal model. Early healing was characterized by a robust fibrovascular response across all groups, indicating that extrinsic mechanisms predominate during the early reparative phase. Paradigms that modulate the extrinsic tendon healing mechanisms could represent a more viable approach to flexor tendon healing outcomes than focusing on bolstering the intrinsic components. Clinical Relevance Our findings suggest that early functional recovery in this model may depend more on modulation of the extrinsic fibrotic response than on preservation of intrinsic vascular or cellular elements, supporting the development of antiadhesion therapies. Additional preclinical studies are needed to identify the cellular niches that drive extrinsic fibrosis and adhesion formation, determine whether they can be selectively modulated without impairing tendon healing, and establish the translational relevance of these mechanisms across species before clinical application.