Background: Our genomic understanding of lymphomas, a heterogeneous group of neoplasms, has grown exponentially. The latest World Health Organization (WHO) and International Consensus classifications reflect the importance of genetic assessment in the diagnosis and prognostication of and therapeutic decision making in lymphoid neoplasms. To address this clinical need for routinely available and timely testing, we aimed to validate the Ion AmpliSeq Liverpool Lymphoid Network Panel (IALLNP; Thermo Fisher Scientific, Waltham, MA, USA). Methods: We clinically validated the IALLNP on the Ion Torrent Genexus Sequencer (Thermo Fisher Scientific). The panel detects single-nucleotide variants (SNVs) and insertions/deletions (indels) in 60 clinically relevant genes. The validation set included a commercial control and 54 DNA samples covering the spectrum of clinically aggressive and indolent lymphomas. Results: After optimizing for poor coverage regions, recurrent artifacts, and false-negative calls, the panel showed good performance in terms of depth of coverage, on-target reads, and uniformity. Its sensitivity for SNVs and indels at a lower limit of detection of 5% variant allele frequency (VAF) was 100%. Specificity in variant-negative samples was 100%, and the mean per-sample number of false-positive variants—which were easily identifiable and excluded upon interrogation of raw data—was 0.4. The panel demonstrated 92.8% reproducibility; however, all nonreproducible variants fell below the 5% VAF analytical threshold. Conclusions The IALLNP is an accurate and reproducible next-generation sequencing panel that delivers genetic results for lymphoid neoplasms in a clinically meaningful timeframe.

Background/Aims: MicroRNA (miRNA) isoforms (isomiRs) broaden the regulatory landscape of canonical miRNAs, but their role in metabolic dysfunction-associated steatotic liver disease (MASLD) remains unknown. We aimed to characterize the hepatic isomiR landscape in MASLD and define their association with disease activity and fibrosis. Methods: Small RNA (sRNA) sequencing was performed on liver biopsies from 79 patients across the histological spectrum of MASLD. IsomiRs were annotated and quantified. Their association to disease activity and fibrosis score was assessed by differential expression, ordinal regression, and machine learning. Parallel mRNA sequencing and pathway enrichment were used to map isomiR–mRNA interactions and regulatory networks, which were validated against an independent dataset. Results: MiRNAs accounted for 75% of sRNAs in liver tissue, of which 67% were isomiRs. Across MASLD severity, 173 isomiRs correlated with disease activity and 58 with fibrosis stage. Key findings included a miR-122 isomiR uniquely targeting INSIG1 (cholesterol metabolism) and a miR-21 isomiR targeting PPARA and HMGCS2 (lipid and fibrosis pathways). Integration with mRNA data revealed 33 dysregulated pathways, including PPAR signaling, insulin resistance, and TGF-β response. Several novel isomiRs from miR-26b, let-7c, and miR-32 families were also linked to lipid metabolism and fibrosis progression. Conclusions IsomiRs represent the majority of hepatic miRNAs and uncover novel regulatory networks masked by canonical miRNA analysis. These findings provide new insights into the molecular heterogeneity of MASLD, highlight candidate pathways driving disease progression, and identify potential biomarkers and therapeutic targets for precision hepatology.

OBJECTIVE

To perform a cost comparison of the 5-year total direct medical costs of iStent inject® W vs. trabeculectomy vs. glaucoma medications for the treatment of primary open-angle glaucoma, with and without phacoemulsification, from the perspective of Filipino patients.

This cost-comparative analysis compared total private sector costs of surgery, post-operative care, and medication usage over 5 years on combined phacoemulsification (combined) or standalone (SA) procedures using iStent inject W, trabeculectomy, and glaucoma medications for the general population and senior citizens/individuals with disabilities. Data, including unit costs and frequencies, were obtained from published literature and local primary research. Scenario analysis consisted of three payment models: 100% out-of-pocket (OOP), coverage from PhilHealth public health insurance, and combined subsidies from both private and PhilHealth insurance.

iStent inject W was less costly than glaucoma medications in all scenarios and patient populations. When compared with trabeculectomy, iStent inject W, was less costly in all patient populations in the OOP scenario, providing savings of 5% for SA procedures and 5% to 6% for combined procedures. It was also less costly as a combined procedure in all populations in the combined private health and PhilHealth insurance scenario, offering 6% savings in the general population and 9% in elderly and disabled patients. However, it was costlier by 1% in the PhilHealth scenario. As an SA procedure, it was costlier vs. trabeculectomy in both populations in the PhilHealth and PhilHealth plus private health insurance scenarios by 18% to 22% and 101% to 109%, respectively. The highest incremental cost for iStent inject W was US$1,662 vs. trabeculectomy as an SA procedure in the general population under the combined private health and PhilHealth insurance scenario.

For Filipino glaucoma patients who are treated in the private sector, iStent inject W, whether combined or as an SA procedure, may be cost-saving compared with glaucoma medications over a 5-year period; however, it may be costlier compared with trabeculectomy depending on health insurance coverage scenarios.

CONTEXT

Accurate diagnosis of onychomycosis is important since misdiagnosis can lead to inappropriate therapy, delayed diagnosis of other nail conditions, and antifungal resistance. Dermoscopy is an emerging diagnostic tool, particularly valuable in the resource-poor settings.

The study aimed to evaluate the accuracy of dermoscopy as a point-of-care tool in diagnosing distal subungual onychomycosis (DSO) at a tertiary hospital.

An observational, prospective, and cross-sectional study was conducted among 22 clinically diagnosed DSO patients using convenience sampling at a tertiary hospital from November 2019 to September 2021.

Participants underwent gross nail examination, dermoscopy, potassium hydroxide (KOH), and periodic acid-Schiff (PAS) examinations.

Sensitivity, specificity, predictive value, and likelihood ratios (LRs) of the dermoscopic patterns were obtained using KOH and PAS results as the reference standard.

Fifty-one nails were submitted but 2 were lost during the processing, leaving 49 nails for analysis. The most common pattern was jagged edge with spikes (65.3%). Individual patterns yielded only low-to-moderate sensitivity (32.4%–73.5%). However, combining all patterns increased sensitivity to 91.2% (95% confidence interval: 76.3–98.1). Ruin appearance showed the highest specificity (100%) and positive predictive value (100%). LRs were not significant enough to draw the conclusions.

Dermoscopy may serve as an on-site, adjunct tool in the diagnosis of DSO, especially when the combination of patterns is considered. Ruin appearance maybe particularly useful in ruling in DSO. However, confirmation using mycological and histopathological tests remains essential.

BACKGROUND: Using Systematic Assessment of Geriatric Elements in Atrial Fibrillation (SAGE-AF) data, determine how well the rich mix of demographic, clinical history, geriatric assessments, and clinically adjudicated events can predict two-year survival. METHODS: Subjects were recruited from participating outpatient practices if they had non-valvular AF, were 65 or over with CHA₂DS₂-VASc scores of at least 2, and were candidates for anticoagulation. Demographics, clinical history, and geriatric qualities of life were assessed by interview and medical records review using standardized protocols and repeated at one and two years. Events identified were abstracted and submitted for adjudication using standard definitions of events and categories. Non-mortality event categories included hospitalizations (cardiovascular, bleeding, other), bleeding (major, clinically relevant non-major, minor), and seven major adverse cardiovascular events. RESULTS: The 1245 subjects experienced 1960 events, primarily hospitalizations (935) and/or bleeding (817); 114 subjects (9.2%) died during two years of follow-up. Events initially abstracted to more than one category (172) were combined, resulting in 1788 unique incidents. Most subjects had zero or one event (69%) and fewer than 7% had more than 3 types. Most variables were significant in bivariate analysis. Using multiple logistic regression with two-year survival as the outcome variable, the best-fit model included event number and type, number of unique incidents, and number of bleeding events (R² = 0.511, C = 93.1) with sensitivity = 97.9% and specificity = 44.7%. CONCLUSIONS Two-year survival was high. This model, if validated, could have major implications for treatment of patients with AF. Patients in the large group with no or one event are at very low risk of death (under 2%). The small group with high risk for further complications, including death, deserve reassessment to determine if this trajectory can be altered.

Prior research suggests metformin has anti-cancer effects, yet data are limited. We examined the association between diabetes treatment (metformin versus sulfonylurea) and risk of incident diabetes-related and non- diabetes-related cancers in US veterans.This retrospective cohort study included US veterans, without cancer, aged ≥ 55 years, who were new users of metformin or sulfo-nylureas for diabetes between 2001 to 2012. Cox proportional hazards models, with propensity score-matched inverse probability of treatment weighting (IPTW) were constructed. A total of 88,713 veterans (mean age 68.6 ± 7.8 years; 97.7% male; 84.1% White, 12.6% Black, 3.3% other race) were followed for 4.2 ± 3.0 years. Among metformin users (n = 60,476), there were 858 incident diabetes-related cancers (crude incidence rate [IR; per 1,000 person-years] = 3.4) and 3,533 non-diabetes-related cancers (IR = 14.1). Among sulfonylurea users (n = 28,237), there were 675 incident diabetes-related cancers (IR = 5.5) and 2,316 non-diabetes-related cancers (IR = 18.9). After IPTW adjustment, metformin use was associated with a lower risk of incident diabetes-related cancer (hazard ratio [HR] = 0.66, 95% CI 0.58-0.75) compared to sulfonylurea use. There was no association between treatment group (metformin versus sulfonylurea) and non-diabetes-related cancer (HR = 0.96, 95% CI 0.89-1.02). Of diabetes-related cancers, metformin users had lower incidence of liver (HR = 0.39, 95% CI 0.28-0.53), colorectal (HR = 0.75, 95% CI 0.62-0.92), and esophageal cancers (HR = 0.54, 95% CI 0.36-0.81). Among US veterans, metformin users had lower incidence of diabetes-related cancer, particularly liver, colorectal, and esophageal cancers, as compared to sulfonylurea users. Use of metformin was not associated with non-diabetes-related cancer. Further studies are needed to understand how metformin use impacts cancer incidence in different patient populations.

Prior research suggests metformin has anti-cancer effects, yet data are limited. We examined the association between diabetes treatment (metformin versus sulfonylurea) and risk of incident diabetes-related and non- diabetes-related cancers in US veterans.This retrospective cohort study included US veterans, without cancer, aged ≥ 55 years, who were new users of metformin or sulfo-nylureas for diabetes between 2001 to 2012. Cox proportional hazards models, with propensity score-matched inverse probability of treatment weighting (IPTW) were constructed. A total of 88,713 veterans (mean age 68.6 ± 7.8 years; 97.7% male; 84.1% White, 12.6% Black, 3.3% other race) were followed for 4.2 ± 3.0 years. Among metformin users (n = 60,476), there were 858 incident diabetes-related cancers (crude incidence rate [IR; per 1,000 person-years] = 3.4) and 3,533 non-diabetes-related cancers (IR = 14.1). Among sulfonylurea users (n = 28,237), there were 675 incident diabetes-related cancers (IR = 5.5) and 2,316 non-diabetes-related cancers (IR = 18.9). After IPTW adjustment, metformin use was associated with a lower risk of incident diabetes-related cancer (hazard ratio [HR] = 0.66, 95% CI 0.58-0.75) compared to sulfonylurea use. There was no association between treatment group (metformin versus sulfonylurea) and non-diabetes-related cancer (HR = 0.96, 95% CI 0.89-1.02). Of diabetes-related cancers, metformin users had lower incidence of liver (HR = 0.39, 95% CI 0.28-0.53), colorectal (HR = 0.75, 95% CI 0.62-0.92), and esophageal cancers (HR = 0.54, 95% CI 0.36-0.81). Among US veterans, metformin users had lower incidence of diabetes-related cancer, particularly liver, colorectal, and esophageal cancers, as compared to sulfonylurea users. Use of metformin was not associated with non-diabetes-related cancer. Further studies are needed to understand how metformin use impacts cancer incidence in different patient populations.

Prior research suggests metformin has anti-cancer effects, yet data are limited. We examined the association between diabetes treatment (metformin versus sulfonylurea) and risk of incident diabetes-related and non- diabetes-related cancers in US veterans.This retrospective cohort study included US veterans, without cancer, aged ≥ 55 years, who were new users of metformin or sulfo-nylureas for diabetes between 2001 to 2012. Cox proportional hazards models, with propensity score-matched inverse probability of treatment weighting (IPTW) were constructed. A total of 88,713 veterans (mean age 68.6 ± 7.8 years; 97.7% male; 84.1% White, 12.6% Black, 3.3% other race) were followed for 4.2 ± 3.0 years. Among metformin users (n = 60,476), there were 858 incident diabetes-related cancers (crude incidence rate [IR; per 1,000 person-years] = 3.4) and 3,533 non-diabetes-related cancers (IR = 14.1). Among sulfonylurea users (n = 28,237), there were 675 incident diabetes-related cancers (IR = 5.5) and 2,316 non-diabetes-related cancers (IR = 18.9). After IPTW adjustment, metformin use was associated with a lower risk of incident diabetes-related cancer (hazard ratio [HR] = 0.66, 95% CI 0.58-0.75) compared to sulfonylurea use. There was no association between treatment group (metformin versus sulfonylurea) and non-diabetes-related cancer (HR = 0.96, 95% CI 0.89-1.02). Of diabetes-related cancers, metformin users had lower incidence of liver (HR = 0.39, 95% CI 0.28-0.53), colorectal (HR = 0.75, 95% CI 0.62-0.92), and esophageal cancers (HR = 0.54, 95% CI 0.36-0.81). Among US veterans, metformin users had lower incidence of diabetes-related cancer, particularly liver, colorectal, and esophageal cancers, as compared to sulfonylurea users. Use of metformin was not associated with non-diabetes-related cancer. Further studies are needed to understand how metformin use impacts cancer incidence in different patient populations.

Sex difference has shown in the arthritis diseases in human population and animal models. We investigate how the sex and symmetry vary among mouse models with different genomic backgrounds. Disease data of sex and limbs accumulated in the past more than two decades from four unique populations of murine arthritis models were analyzed. They are (1) interleukin-1 receptor antagonist (IL-1ra) deficient mice under Balb/c background (Balb/c KO); (2) Mice with collagen II induced arthritis under DBA/1 background; (3) Mice with collagen II induced arthritis under C57BL/6 (B6) background and (4) A F2 generation population created by Balb/c KO X DBA/1 KO.Our data shows that there is a great variation in sexual dimorphism for arthritis incidence and severity of arthritis in mice harboring specific genetic modifications. For a F2 population, the incidence of arthritis was 57.1% in female mice and 75.6% in male mice. There was a difference in severity related to sex in two populations: B6.DR1/ B6.DR4 (P < 0.001) and F2 (P = 0.023) There was no difference Balb/c parental strain or in collagen-induced arthritis (CIA) in DBA/1 mice. Among these populations, the right hindlimbs are significantly higher than the scores for the left hindlimbs in males (P < 0.05). However, when examining disease expression using the collagen induced arthritis model with DBA/1 mice, sex-dimorphism did not reach statistical significance, while left hindlimbs showed a tendency toward greater disease expression over the right. Sexual dimorphism in disease expression in mouse models is strain and genomic background dependent. It sets an alarm that potential variation in sexual dimorphism among different racial and ethnic groups in human populations may exist. It is important to not only include both sexes and but also pay attention to possible variations caused by disease expression and response to treatment in all the studies of arthritis in animal models and human populations.