Abstract: Background/Objetives: Elderly populations are under-represented in inflammatory bowel disease (IBD) clinical trials, with limited data on phenotype, treatment patterns, outcomes and comorbidities. The main objective of this study was to evaluate, in an elderly cohort with IBD, demographic and disease characteristics, comorbidity, polypharmacy and treatment patterns according to the development of IBD at or before old age. Secondarily, the same analysis was done based on the type of IBD: ulcerative colitis (UC) or Crohn's disease (CD).Material and methods: Observational, single-center, retrospective study including 118 patients diagnosed with IBD and aged 65 years or older seen at the IBD office of the Regional University Hospital of Malaga between September and November 2022. Data were recorded on demographic, disease-related and IBD treatment-related variables, comorbidities and polypharmacy. A descriptive and analytical study was undertaken according to the age of IBD onset and type of IBD.Results: Of the patients included, 50.8% were male, 55.1% had CD and 44.9% UC. IBD onset was before age 65 years in 69.5% and ≥65 years in 30.5%. Elderly with IBD who debuted

Abstract: Background and Clinical Significance: Acute necrotizing encephalopathy (ANE) represents a severe complication of influenza virus infection, mainly described in children. We report the cases of two young girls with ANE associated with influenza virus infection, diagnosed by MRI cerebral scan. Case Presentation: A 7-year-old girl with a history of a previous episode of ANE presented with a worsening soporous state and seizures. In the second case, an otherwise healthy 5-year-old girl presented with fever, seizures and marked neurological deterioration. In both cases, nasopharyngeal swab testing was positive for influenza virus A, while cerebral MRI indicated ANE. Despite aggressive treatment with high-dose corticosteroids and a five-day course of immunoglobulins, the ultimate prognosis was poor in both patients. ANE is a serious complication of viral infections in children, with a high mortality rate and a broad spectrum of neurological sequelae. To date, the pathophysiology and management of influenza virus-induced ANE remain uncertain. Although ANE is usually sporadic, familial and recurrent cases have been reported, and a RANBP2 mutation has occasionally been associated. Conclusions: Rapid recognition of neurological symptoms and suspicion of a viral trigger, especially in influenza-like illnesses, are both essential for the timely administration of effective therapy. Further research is needed to clarify the pathophysiology of ANE and establish the best therapeutic strategies to fight such a deadly disease.

Abstract: Background/Objectives: The physiological basis underlying symptomatic versus asymptomatic premature ventricular contractions (PVC) remains poorly understood. However, symptomatic PVC can significantly impair quality of life. In patients without structural heart disease, symptom intensity is crucial for guiding management strategies and determining the need for medical or surgical intervention. In this study, we aimed for the first time to examine the associations be-tween PVC symptoms and cardiac interoception. Methods: The study included 34 participants with PVC (20 women; median age = 42 years; 17 participants had asymptomatic PVC) without concomitant disorders. Interoception was assessed through interoceptive accuracy (IA) probed by two behavioral tests—mental tracking (MT) and heartbeat detection (HBD)—and the neurophysi-ological marker of cardiac interoception, the heartbeat-evoked potentials (HEPs). Symptom inten-sity scores reported by patients served as the response variable in the regression analysis, with IA and HEP as predictors. Other factors such as sex, age, percent of body fat, trait anxiety, and alexithymia were added to the models as confounding variables. Results: IAMT was significantly higher in patients with symptomatic PVC. IAMT and HEP modulation for the HBD task were asso-ciated with symptom intensity. A combined regression model incorporating both metrics showed the highest predictive accuracy for symptom severity. Adding confounding variables improved model quality (lower AIC); however, only the male sex emerged as a significant negative predictor for symptom intensity. Conclusions: Our findings confirm a significant association between in-teroception and PVC symptom severity. Integrating behavioral and neurophysiological interocep-tion measures enhances symptom prediction accuracy, suggesting new ways to develop diagnos-tic and non-invasive treatment strategies targeting interoception in PVC management.

Abstract: Male infertility is a significant global health issue, comprising approx. 50% of all infertility cases. Semen cryopreservation, a critical component of assisted reproductive technologies (ART), is a method commonly used in a wide range of situations, including gonadotoxic treatments such as radiation or chemotherapy, hazardous occupational exposures, or various medical conditions. Although historically viewed as potentially damaging to sperm, recent findings suggest that cryopreservation, when performed with appropriate techniques, may in fact enhance semen quality by improving the proportion of healthy spermatozoa, particularly in terms of their morphological parameters. The aim of this study was to evaluate the impact of cryopreservation on sperm morphology and viability, utilizing advanced morphological assessments pre- and post-freezing. Semen samples from 97 patients were analyzed, revealing significant improvements in morphology, with increased percentages of normal sperm and reductions in deformation indices post-thaw. The findings indicate that optimized cryopreservation protocols may support the selection of higher-quality sperm, offering valuable benefits for ART applications. These results challenge certain past assumptions regarding the impact of cryopreservation and underscore the need for refined freezing techniques to maintain and potentially enhance semen quality for reproductive use.

Abstract:

Intratumoral microbiota, the diverse community of microorganisms residing within tumor tissues, represent an emerging and intriguing field in cancer biology. These microbial populations are distinct from the well-studied gut microbiota, offering novel insights into tumor biology, cancer progression, and potential therapeutic interventions. Recent studies have explored the use of certain antibiotics to modulate intratumoral microbiota and enhance the efficacy of cancer therapies, showing promising results. Antibiotics can alter intratumoral microbiota’s composition, which may have a major role in promoting cancer progression and immune evasion. Certain bacteria within tumors can promote immunosuppression and resistance to therapies. By targeting these bacteria, antibiotics can help create a more favorable environment for chemotherapy, targeted therapy and immunotherapy to act effectively. Some bacteria within the tumor microenvironment produce immunosuppressive molecules that inhibit the activity of immune cells. The combination of antibiotics and other cancer therapies holds significant promise for creating a synergistic effect and enhancing the immune response against cancer. In this review we analyze several preclinical studies that have been conducted to demonstrate the synergy between antibiotics and other cancer therapies and discuss possible clinical implications.

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.