Abstract:

Objectives: To evaluate the impact of diabetes mellitus (DM) on the outcome of Schlemm’s canal based minimally invasive glaucoma surgery (MIGS). Methods: In a retrospective interventional cohort study, post- operative intraocular pressure (IOP) and intracameral bleeding were analyzed in 25 diabetic and 84 non-diabetic patients with primary open angle glaucoma (POAG) or ocular hypertension (OH). Results: The mean follow-up period for all 109 eyes was 35.3±24.8 months. There was no significant difference in pre-operative IOP between diabetic and non-diabetic cohorts. However, the post-surgical IOP between 3 months and 2 years was significantly higher in the diabetic cohort (P=0.019 to 0.001). The 3-year survival probability of achieving an IOP≦15 mmHg was 17.8±0.09% in diabetic patients, significantly lower than the 30.4±0.06% observed in non- diabetic patients (P=0.042 Log-rank test). The 3-year survival probability of achieving an IOP≦18 mmHg was 56.7±0.12% in diabetic patients compared to 79.5±0.05% in non-diabetic patients, indicating a marginally significant difference between diabetic and non-diabetic cohorts (P=0.065). When the random effect of diabetes mellitus (DM) was analyzed alongside the fixed effects of preoperative IOP, age, refractive error and extent of canal opening using a multivariate linear mixed model, DM emerged as a significant risk factor for higher postoperative IOP at both 6 and 12 months (P<0.001). Conclusions: Diabetes mellitus is a significant risk factor for poor outcomes following Schlemm’s canal based MIGS, particularly in achieving lower postoperative IOP.

Abstract: A 2-year-old male neutered domestic shorthair cat was presented with a progressive history of tetraparesis, ataxia, and inappetence over 4 days. A physical exam revealed mucopurulent nasal discharge and stertor. Neurologic exam revealed a multifocal neurolocalization. The cat was non-ambulatory tetraparetic and developed seizures while in-hospital. Hematologic assessment revealed anemia, hypoalbuminemia and hyperglobulinemia. Magnetic resonance imaging (MRI) of the brain revealed multifocal meningeal contrast enhancement in the brainstem and cervical spine, as well as mandibular and retropharyngeal lymphadenopathy. Cerebrospinal fluid revealed marked neutrophilic pleocytosis, no infectious organisms were seen. Toxoplasma IgG/IgM and cryptococcus antigen latex agglutination were negative. Mandibular and abdominal lymph nodes were aspirated, and cytology revealed mixed inflammation. Nanopore sequencing specifically identified FCoV-1 RNA in spinal fluid and anal swab, but not in urine. This method serves as a novel and rapid PCR sequencing technique for the antemortem diagnosis of feline infectious peritonitis. The cat was treated with anticonvulsants (phenobarbital and levetiracetam), an antibiotic (ampicillin/clavulanic acid), and GS-441524. Neurologic signs did not improve on an antibiotic alone but improved significantly after two subcutaneous injections of GS-441524. The cat received an 84-day course of GS-441524 and, at the time of manuscript preparation (over 12 months after diagnosis), remained ambulatory and seizure-free without recurrence of neurologic signs and no detectable viral shedding in feces.

Abstract: Background: Hyperkalemia is a common electrolyte disorder in patients with heart failure and reduced ejection fraction (HFrEF). Renin-angiotensin-aldosterone system inhibitors (RAASi) have been shown to improve survival and decrease hospitalization rates, although they may increase the serum potassium levels. Hyperkalemia has significant clinical and economic implications, and is associated with increased healthcare resource utilization. The main objective of this study was to analyze the management of hyperkalemia and the associated medical costs in a cohort of patients with HFrEF. Methods: An observational, longitudinal, retrospective, single-center retrospective study was made in patients with HFrEF who started follow-up in a specialized heart failure unit between 2010 and 2021. Results: The study population consisted of 1181 patients followed-up on for 64.6 ± 38.8 months. During follow-up, 11,059 control visits were conducted, documenting 438 episodes of hyperkalemia in 262 patients (22.2%). Of the hyperkalemia episodes, 3.0% required assistance in the Emergency Department, 1.4% required hospitalization, and only 0.2% required admission to the Intensive Care Unit. No episode required renal replacement therapy. Reduction or withdrawal of RAASi was necessary in 69.9% of the hyperkalemia episodes. The total cost of the 438 hyperkalemia episodes was €89,178.82; the expense during the first year accounted for 48.8% of the total cost. Conclusions: Hyperkalemia is common in patients with HFrEF. It is often accompanied by a modification of treatment with RAASi. Hyperkalemia generates substantial costs in terms of healthcare resources and medical care, especially during the first year.

Abstract: Canine high-grade glioma (HGG) is among the deadliest and most treatment-resistant forms of canine cancer. Successful, widespread treatment is challenged by heterogeneity in tumor cells and the tumor microenvironment and tumor evolution following treatment. Immunotherapy is theoretically a strong novel therapy, since HGG-generated immunosuppression is a substantial malignancy mechanism. Immunotherapy has improved survival times overall, but has been associated with extremely poor outcomes in French bulldogs. Given this breed-specific observation, we hypothesized that within the French bulldog breed, there are key transcriptomic differences when compared to other breeds, and that their tumors change differently in response to immunotherapy. Using bulk RNA sequencing, French bulldog tumors were confirmed to differ substantially from boxer and Boston terrier tumors, with only 15.9% overlap in significant differentially expressed genes (DEGs). In upregulated DEGs, the magnitude of changes in expression post-treatment compared to pre-treatment was markedly greater in French bulldogs. Gene set enrichment analysis confirmed that following treatment, French bulldog tumors showed enrichment of key immune-associated pathways previously correlated with poor prognosis. Overall, this study confirmed that French bulldog HGG transcriptomes differ from boxer and Boston terrier transcriptomes, further refining description of the canine glioma transcriptome and providing important information to guide novel therapy development.

Abstract: Flea-borne typhus (FBT), due to Rickettsia typhi and R. felis, is an infection typically causing fever, headache, rash, hepatitis, and thrombocytopenia. About one-quarter of patients suffer pulmonary, neurologic, hematologic, renal, hepatic, cardiac, ocular or other complications. In the 21st century, the incidence of FBT has increased in both Texas and California compared to the 1990s. In this paper, county-level epidemiological data for the number of cases of FBT occurring in Texas for two decades, 1990-1999 and 2010-2019, were compared with respect to county of residence, urbanization, and climatic region. Human population growth in Texas has promoted FBT by increased urbanization and abundance of pet dogs and cats, stray/feral dogs and cats, and opossums. Increasing temperatures in Texas in the new millennium has increased the flea-borne transmission of FBT by promoting host infestation and flea feeding and defecation, accelerating the flea life cycle, and increasing rickettsial replication within the flea. Increased opossums and stray cats and dogs in the urban/suburban landscape has increased the risk of flea transfer to humans and their pets.

Abstract:

Aim: This study aimed to explore the correlation between the FIB-5 and FIB-4 indices, which assess liver fibrosis, and the grouped duration of heart failure (HF) in a cohort of subjects from the National Health and Nutrition Examination Survey (NHANES) 2015-2020. Methods: The study included 468 participants categorized into three groups based on HF duration: Group 1 (≤1 year, n=91), Group 2 (1-5 years, n=87), and Group 3 (>5 years, n=290). Data were analyzed using Pearson and Spearman correlation analyses to assess relationships between FIB-5, FIB-4, and HF duration. Clinical variables such as age, BMI, ALT, AST, albumin, and platelet count were also considered.Results: The analysis revealed significant correlation between FIB-5 with age (Pearson correlation (r) = -0.29, p<0.0001) but not for HF duration across groups (Spearman correlation (ρ) = -0.010, p=0.8217). The FIB-4 index did not show significant associations with the HF duration group (p=0.6326). The regression analysis also showed no significant predictive relationship between FIB-5 or FIB-4 and the duration of heart failure, further supporting the lack of association between fibrosis indices and HF duration in this cohort.Conclusion: The study found no significant correlation between the FIB-5 and FIB-4 indices and the duration of heart failure in this cohort. These findings suggest that while these fibrosis scores are useful in liver assessment, they may not directly reflect the duration of heart failure in this population. Further studies are needed to explore other potential biomarkers for HF duration.

Abstract: Classic health-related quality of life (HRQOL) metrics are cumbersome, time-intensive, and subject to biases based on the subject’s native language, educational level, and cultural values. Natural language processing (NLP) converts text into quantitative metrics. Sentiment analysis enables subject matter experts to construct domain-specific lexicons that assign a value of either negative (-1) or positive (1) to certain words. The growth of telehealth provides opportunities to apply sentiment analysis to transcripts of adult spinal deformity patient visits to derive a novel and less biased HRQOL metric. In this study, we demonstrate the feasibility of constructing a spine-specific lexicon for sentiment analysis to derive an HRQOL metric for adult spinal deformity patients from their preoperative telehealth visit transcripts. We asked each of twenty-five (25) adult patients seven open-ended questions about their spinal conditions, treatment, and quality of life during telehealth visits. We analyzed the Pearson correlation between our sentiment analysis HRQOL metric and established HRQOL metrics (Scoliosis Research Society-22 questionnaire [SRS-22], 36-Item Short Form Health Survey [SF-36], and Oswestry Disability Index [ODI]). The results show statistically significant correlations (0.43–0.74) between our sentiment analysis metric and the conventional metrics. This provides evidence that applying NLP techniques to patient transcripts can yield effective HRQOL metrics.

Abstract: Drug repurposing, identifying FDA-approved drugs for new indications, reduces the time and money required for a drug to reach the clinic and capitalizes on the increasing number of publicly available online data. Attrition rates for repurposing studies are lower than compared to drug discovery. Still, repurposing candidates often fail downstream despite their biological relevance, attributing to a lack of safety and/or efficacy. Current approaches may be limited in separating biological signals from technical noise and incorporating relevant clinical information to evaluate promising candidates in preclinical analyses. Many drug repurposing approaches have been developed; however, a gold standard has yet to be determined. In addition, repurposing analyses often yield many potential candidates that require further prioritization to ensure clinical viability. Thus, prioritization of the optimal candidates by incorporating more information from available resources is critical. Here, we reviewed prioritization criteria and developed a workflow implementing 1) drug-specific, 2) target-specific, and 3) disease-specific considerations to address challenges in current drug repurposing efforts. Our workflow streamlines drug candidate prioritization using a stepwise evaluation process and vetted resources for each consideration to guide researchers in better predicting the most robust candidates and facilitating the most promising ones for clinical adoption.

Abstract:

Background: Atrophic vulvovaginitis (VVA), a prevalent condition resulting from estrogen deficiency after menopause, is characterized by symptoms such as vaginal dryness, itching, burning, dyspareunia, and urinary discomfort. Standard treatment involves systemic estrogen replacement therapy (HRT) and localized estrogen treatments, such as estriol. However, many women with moderate to severe VVA may not fully benefit from estrogen therapy alone. Non-hormonal adjunctive treatments, such as pelvic floor exercises (e.g., Kegel exercises), are being explored to enhance clinical outcomes. Objectives: This study investigates the combined effect of local estriol therapy and Kegel exercises in improving VVA symptoms in postmenopausal women. Methods: Fifty postmenopausal women diagnosed with VVA were enrolled and divided into three severity groups: mild, moderate, and severe. All participants received estriol therapy (0.5 mg vaginal tablets daily for 10 days each month) for the first three months. Following this, Kegel exercises were introduced for an additional three months, alongside continued estriol therapy. Symptom improvement was evaluated after six months, with outcomes categorized as complete remission, partial remission, or no remission. Results: Significant improvements in symptom remission were observed, particularly in the moderate and severe groups. In the mild VVA group, 81.82% achieved complete remission with the combined therapy, compared to 68.18% with estriol alone. In the severe group, complete remission was observed in 40% of patients receiving the combined therapy, compared to 20% with estriol therapy alone. These findings suggest that Kegel exercises enhance the effectiveness of estriol by improving local blood circulation, which facilitates better estrogen absorption and distribution. Conclusion: The addition of Kegel exercises to local estriol therapy significantly improves symptom remission rates, especially in moderate and severe VVA cases. This approach offers a promising strategy for managing postmenopausal VVA, particularly in cases that do not fully respond to estrogen therapy alone.

Abstract: Historically, EGFR and KRAS mutations were believed to be mutually exclusive. However, over the past few years, there have been emerging case reports showing the co-existence of both mutations in a single case. The majority of these co-occurring alterations were detected in samples collected from patients at resistance to tyrosine kinase inhibitor (TKI) treatment, indicating a potential functional role in driving resistance to therapy. These co-occurring tumor genomic alterations are not necessarily mutually exclusive, and evidence suggests that multiple clonal and sub-clonal cancer cell populations can co-exist and contribute to EGFR TKI resistance. We have reported such a case of concomitant EGFR and KRAS mutation in a 64 year old female. This case highlights the importance of continuous molecular testing in managing NSCLC, especially in cases with rare mutation profiles. The emergence of new mutations during treatment can significantly impact the course of therapy and patient outcomes. In this case, the detection of both EGFR and KRAS mutations guided the selection of an appropriate targeted therapeutic strategy, including the use of Amivantamab.