Accurate size estimation of large (≥ 20 mm) colorectal laterally spreading tumors (LSTs) is essential for procedural planning, risk stratification, and predicting technical difficulty. Yet, the reliability of visual LST size assessment among endoscopists has not been systematically evaluated. 46 LSTs were recorded during colonoscopy. Twenty-four international expert endoscopists independently reviewed de-identified videos and provided visual estimates for (1) maximal diameter, (2) oral–anal axis, (3) left–right axis, and (4) percentage of colonic circumference involved. Each lesion was assessed twice in randomized order. Fleiss’s kappa, Krippendorff’s alpha, and intraclass correlation coefficients (ICC) were used to evaluate inter- and intra-rater agreement. A total of 1104 measurements were collected. Inter-endoscopist kappa agreement for maximal diameter was poor (κ = 0.16), with similarly poor agreement for the oral–anal (κ = 0.15) and left–right axes (κ = 0.14). The percentage of circumferential involvement demonstrated moderate reproducibility (ICC 0.74 and 0.70 across rounds). Subgroup analyses showed consistently poor agreement for larger lesions for diameter-based methods, whereas circumferential percentage estimation ranged from poor to good depending on LST size and morphology. Intra-endoscopist agreement for diameter- and axis-based approaches showed wide variability (κ range 0.01–0.67), while circumferential estimates achieved good to excellent agreement for most endoscopists. Visual estimation of large colorectal LST size is highly variable among expert endoscopists. Maximal diameter and axial lengths demonstrate poor inter- and intra-observer reliability. Circumferential extent is the most reproducible descriptor and may be the preferred approach for reporting LST size in clinical practice and research.
Importance The injections of platelet-rich plasma (PRP) in the olfactory clefts of patients with olfactory dysfunction (OD) is an emerging treatment. To date, no study investigated the effectiveness of multiple PRP injections. Objective To evaluate the effectiveness and usefulness of multiple injections of PRP in the olfactory clefts of patients with OD. Design Prospective controlled study. Setting Monocentric medical center. Participants Patients with long-lasting OD treated with PRP injections and controls who underwent olfactory training with multiple psychophysical olfactory assessments. Intervention Two PRP injections into the olfactory clefts at 4- to 6-month intervals. Main Outcomes Outcomes included adverse events, dose-effect relationships, and olfactory function changes measured by threshold, discrimination, and identification (TDI) testing with minimal clinically important difference (MCID). Results Eighty-three subjects completed the evaluations. Patients had anosmia (n = 39), hyposmia (n = 27), and parosmia (n = 17). The mean duration of OD was 49.1 ± 46.9 months. Seventy-seven patients received 2 injections. Transient epistaxis was the primary adverse event (46.2%). The mean injected PRP volume ranged from 1.4 to 1.7 mL. TDI significantly increased after both first and second injections across all OD subgroups. MCID was achieved in 49.4% after a first injection and 28.9% after a second. MCID was reached in 63 cases (75.9%) from baseline to final evaluation. Baseline TDI strongly predicted post-second injection TDI ( r s = .919; P = .001), but the first PRP response didn’t significantly predict second response ( r s = −.201; P = .069). TDI did not significantly change in the control groups. MCID was achieved in 22.2% and 40% controls at the first and second TDI evaluations. Conclusion and Relevance Two injections of PRP demonstrate significant improvement in psychophysical olfactory evaluations. Future studies are needed to determine the optimal number of injections and identify predictors of therapeutic effectiveness.
OBJECTIVE:To investigate the prevalence and findings of esophageal manometric abnormalities underlying dysphagia in laryngopharyngeal reflux disease (LPRD). METHODS:Three independent investigators conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) systematic literature search in PubMed, Scopus, and Cochrane databases for studies reporting manometry and high-resolution manometry (HRM) findings in LPRD patients. Methodological bias analysis was conducted with two validated bias tools. RESULTS:Twenty-four papers met the inclusion criteria (2337 patients). The LPRD diagnosis was based on objective testing in 3/24 (12.5%) studies, with one study using hypopharyngeal-esophageal impedance-pH testing. Manometric studies consistently suggested increased upper esophageal sphincter baseline and residual pressures, whereas lower esophageal sphincter baseline and relaxation pressures were decreased in LPRD patients. Esophageal body motility was characterized by a high prevalence of ineffective swallows, and impaired bolus clearance. Reflex mechanisms were also altered. There was substantial heterogeneity across studies for LPRD diagnosis, exclusion criteria, and manometric parameters, which were reported with the Chicago classification 3.0/4.0 in 10/24 (42%) studies. The mean MINORS was 7.5 ± 2.4, highlighting an overall low quality of studies. CONCLUSION:This systematic review suggests a trend toward ineffective esophageal motility, esophageal sphincter hypotension, or impaired dynamics in patients with swallowing, voice, and breathing LPRD-related symptoms and findings. Further prospective controlled studies including patients with a demonstrated LPRD are needed to establish the prevalence of esophageal abnormalities in LPRD.
Subretinal injections (SI) are used to deliver gene therapies for inherited retinal diseases, yet the optimal injection parameters remain undefined. This study used theoretical and experimental models to quantify the relationship between injection pressure, flow dynamics, and residual flow. A theoretical model (TM) was developed based on the Hagen-Poiseuille law and the theory of a jet immersed in the same liquid. An experimental model (EM) was constructed to allow for measuring flow and residual flow across injection pressures ranging from 0 to 20 psi. We assessed the effects of ambient pressure, injection system tubing length, and syringe priming technique. A minimum pressure of 6 psi was required to generate a detectable flow in the EM. Jet speed increased with the square root of injection pressure, aligning with theoretical predictions. Residual flow persisted for 28-47 seconds after injection and increased logarithmically with injection pressure. Elevated ambient pressure (45 mmHg) only reduced flow at lower injection pressures. The "lock-and-load" priming method decreased jet speed and increased residual flow compared to the "load-and-lock" method. Both TM and EM quantified SI flow dynamics, with EM demonstrating residual flow at all tested pressures. To minimize complications, clinicians should use the lowest injection pressure and allow sufficient time for the cannula to be withdrawn from the subretinal space.
Despite improved survival in recent years, long-term outcomes in patients surviving progressive multifocal leukoencephalopathy beyond the first year remain poorly defined. This international multicenter retrospective study aimed to characterize the three-year prognosis of patients with progressive multifocal leukoencephalopathy who had survived at least one year, identify factors associated with favorable outcomes and late mortality, and determine recurrence rate. Data were collected through standardized questionnaires across forty-one centers in twelve countries. Patients were eligible if they met the 2013 diagnostic criteria for definite progressive multifocal leukoencephalopathy of the American Academy of Neurology, survived at least one year after diagnosis, and had documented follow-up three years after diagnosis. Demographic, clinical, virological, and radiological data were retrieved at diagnosis, one year, and three years. Functional status was assessed using the modified Rankin Scale, with scores of 0-2 defining a favorable outcome. Generalized linear mixed models identified independent predictors of three-year functional status and late mortality. Among 1877 screened cases, 245 patients met inclusion criteria. The most common underlying causes of immunosuppression were HIV infection (48%), autoimmune/inflammatory diseases (26%), and hematological malignancies (18%). At three years, 220 patients (89.8% of the cohort) were alive and 188 (85.5% of survivors) had neurological sequelae, most frequently motor or cognitive impairment. Overall, 112/245 (45.7%) achieved a favorable functional outcome. HIV-associated progressive multifocal leukoencephalopathy (OR 2.36, 95% CI 1.05-5.28) was associated with a favourable outcome, whereas higher modified Rankin Scale score at diagnosis (OR 0.48, 95% CI 0.35-0.66) and higher number of affected brain regions on baseline MRI (OR 0.78, 95% CI 0.64-0.95) were independently associated with poorer functional outcome. Among variables collected one year after diagnosis, good functional status at that time was significantly associated with long-term favorable outcome (OR 0.01, 95% CI <0.01-0.03). Twenty-five patients (10.2%) died after the first year, with mortality associated with higher lesion burden at diagnosis and primary immunodeficiency as underlying disease. Even beyond the first year, progressive multifocal leukoencephalopathy remained the leading cause of death (11/25). Recurrence occurred in seven patients (2.9%) and was almost always fatal (6/7). This study provides a comprehensive evaluation of long-term outcomes among survivors of progressive multifocal leukoencephalopathy. These findings present a nuanced picture: while most remain neurologically impaired, nearly half achieve functional independence at three years. The results emphasize the prognostic relevance of the initial clinical and radiological burden and early functional trajectory and highlight the need for research into mechanisms driving disease recurrence.
