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Acute Stroke Management in the Caribbean: A Scoping Review Protocol
No full textIntroduction Stroke is a leading cause of death and disability in the Caribbean, yet there is limited published information on the availability and utilisation of diagnostic imaging and treatment methods. Inequities in healthcare infrastructure, access to neuroimaging and acute treatment options may contribute to poorer outcomes following stroke, particularly in the low-resource settings that characterise most of the Caribbean region. The objective of this review is to map the literature on access to diagnostic and therapeutic modalities for adult stroke care in the Caribbean to identify potential limitations in acute treatment and examine how restricted access may impact outcomes. The resulting data can help inform strategies for improving access to stroke care in resource-limited communities. Methods and analysis We will apply a three-step strategy based on the Joanna Briggs Institute methodological framework: first, a limited search to identify relevant articles; second, selection of key search terms; third, implementation into a comprehensive search strategy. The query will range from 1 January 1995 to 1 June 2025 (date of final search). Search results will be extracted and screened by two independent reviewers, and findings will be presented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. We will consider studies focusing on ischaemic and haemorrhagic stroke in the Caribbean, emphasising access to diagnostic imaging, stroke centres, prehospital management and emergent treatment. Studies examining acute stroke management capacity within the region will be considered. Studies will be excluded if they: focus exclusively on primary stroke prevention, postacute care, longitudinal care pathways for stroke victims or paediatric populations; are unrelated to stroke diagnosis or treatment or are conducted outside the Caribbean. Ethics and dissemination This protocol aims to perform secondary analysis of previously published literature; therefore, ethical approval is not required. The results of this review will be disseminated through academic conferences and peer-reviewed publication
Insights Into Immunogenicity and Therapeutic Strategies to Mitigate the Immune Response in Infantile-Onset Pompe Disease: A Comprehensive Systematic Literature Review
No full textINTRODUCTION: Pompe disease, a rare autosomal recessive metabolic myopathy, is primarily treated with enzyme replacement therapy (ERT); however, ERT response depends on several factors, including ERT initiation age, dose, and cross-reactive immunological material (CRIM) status, especially in infantile-onset Pompe disease (IOPD). AIM: This systematic literature review (SLR) focused on three research questions (1): how CRIM status is determined in patients with IOPD in clinical practice, and how CRIM-negative status impacts outcomes (2); how health professionals use CRIM status to inform their decisions on immune tolerance induction (ITI) regimens; and (3) which regimens are used in real-world clinical practice. METHODS: The SLR was conducted using Embase and PubMed databases covering the literature from January 1, 2003, to August 4, 2022. The search terms used were Pompe or IOPD and cross-reactive immunological material or CRIM. Data extraction was performed using pre-designed tables in Microsoft Excel. Among those identified, 54, 51, and 69 studies provided meaningful data for the respective research questions. The key theme was the importance of early diagnosis/treatment. Recently, there has been a major shift from direct CRIM testing using western blotting and mutation analysis to CRIM status prediction based on genetic variant analysis. The ITI regimen was mostly prescribed for CRIM-negative patients and some CRIM-positive cases in a prophylactic/naïve setting at ERT initiation to prevent the development of high antibodies and for IOPD patients irrespective of CRIM status in the ERT-experienced setting due to the presence of high and sustained anti-drug antibody levels. The frequently reported ITI regimen includes a short rituximab and methotrexate course in an ERT naïve setting, with/without intravenous immunoglobulin. CRIM-negative patients receiving ITI with ERT have better clinical outcomes than those not receiving the ITI regimen. Presently, the ITI regimen used in CRIM-positive patients is variable and based on physician preference, family history, or specific variants. CONCLUSION: The study concluded that CRIM status determination is important in patients with IOPD and impacts management approaches. ITI use has been predominantly reported in CRIM-negative patients to improve the clinical outcomes, with other important factors being early initiation of ERT and treatment above label dose of alglucosidase alpha and many are doing upto 40 mg/kg/2 weeks
Risk of Postoperative Complications Following Total Knee or Hip Arthroplasty Associated with Patients Who Consume Alcohol: A Systematic Review Protocol
No full textInTouch Week of September 22, 2025
No full textMajor Clinical Affiliate Metropolitan Celebrates 150 Years Phillip Capozzi, M.D., Library Hosts College History Celebration and Exhibit Dedication Ph.D. Lab Coat Ceremony Marks a Milestone in Biomedical Discovery Dr. Okeoma Unlocks Hidden Clues for Potential HIV Treatment New Area of Concentration in Health Systems Management Launched TCDM Celebrates Grand Opening of the Albuquerque Campus Faculty Spotlight: Srihari S. Naidu, M.D., FACP, FACC, FAHA, FSCAI, Pushing Boundaries in Treating Cardiovascular Diseasehttps://touroscholar.touro.edu/in_touch/1375/thumbnail.jp
Regulation of Kynureninase by Estrogen Stimulation in Estrogen-Receptor Positive Breast Cancer
No full textBreast cancer remains the second leading cause of death in women worldwide, with estrogen receptor (ER)-positive subtypes comprising over 70% of cases. Endocrine therapies, such as tamoxifen, are the primary treatment for ER-positive breast cancer; however, resistance inevitably develops, highlighting the need for alternative therapeutic strategies. Growing evidence suggests that the kynurenine pathway plays a significant role in breast cancer progression and metastasis. The kynurenine pathway metabolizes 95% of the amino acid tryptophan, generating metabolites such as kynurenine, kynurenic acid, 3-hydroxykynurenine, and ultimately Nicotinamide Adenine Dinucleotide (NAD). To better understand the impact of estrogen signaling on the kynurenine pathway, kynureninase expression of a key enzyme kynureninase (encoded by KYNU) was analyzed in MCF7 cells stimulated with estrogen, with and without tamoxifen treatment, using reverse transcription quantitative PCR (RT-qPCR) and Western blot analysis. The results showed that estrogen stimulation significantly downregulated kynureninase expression at both the mRNA and protein levels. In contrast, tamoxifen treatment prevented downstream ER signaling, as evidenced by increased kynureninase levels. These findings suggest that estrogen signaling through the ER suppresses KYNU expression, potentially contributing to a pro-tumorigenic environment in ER-positive breast cancer by accumulating upstream kynurenine pathway metabolites. These results could be a basis for further research into novel therapeutic strategies targeting the kynurenine pathway and improving outcomes for patients with ER-positive breast cancer
The Role of G6PD Variants and 3D Genomic Structure in the Development of Pulmonary Hypertension
No full textPulmonary hypertension is an under-recognized global health epidemic which is estimated to affect 1% of the population. It is associated with sustained mean pulmonary artery pressure greater than 20 mmHg, pulmonary artery remodeling, smooth muscle and endothelial cell proliferation and subsequent increased right ventricle hypertrophy due to increased afterload. Glucose-6-phosphate dehydrogenase (G6PD) is one of the key enzymes in the pentose phosphate pathway and has been previously linked to the development of pulmonary hypertension. G6PD deficiency is the most common human enzymopathy which affects approximately 400 million people worldwide and is a result of agricultural and epidemiological evolution in different parts of the world. G6PD, a X-linked gene, is highly polymorphic and more than 200 single nucleotide polymorphisms are found within the coding region. One G6PD variant, Mediterranean Ser188Phe, G6PDS188F, results in 80-90% decrease in G6PD activity and is known to be protective against vascular disease. Another G6PD variant, African Asn126Asp, G6PDN126D, results in 10-20% decrease in G6PD activity and increases susceptibility to vascular disease. The mechanism associated with the development of pulmonary hypertension is still unclear. The literature suggests that many variables contribute to the development of pulmonary hypertension such as metabolic reprogramming, epigenetics (DNA and histone methylation, histone acetylation), and altered gene expression. Consequently, we postulate that African variant G6PDN126D but not Mediterranean variant G6PDS188F, increases pulmonary artery remodeling and the risk of developing pulmonary hypertension, by modifying 3D genomic organization and DNA methylation that increases maladaptive signaling molecules.
Sprague-Dawley rats underwent CRISPR-Cas9 genome editing in which there was a substitution of either N126D or S188F in the G6PD coding region, and these animals and their age-matched wild-type littermates were randomly injected with Sugen-5416 (SU; 20mg/kg S.C. suspended in DMSO) and kept in ambient condition (normoxia; Nx). After 8 weeks, hemodynamic measurements revealed that G6PDN126D + SU/Nx rats had increased right ventricle systolic pressure, while G6PDS188F + SU/Nx did not, indicating that only G6PDN126D + SU/Nx rats developed pulmonary hypertension. G6PDN126D + SU/Nx rat lungs were formalin-fixed, and then paraffin embedded, and further wall thickness assessments displayed pulmonary artery remodeling. Interestingly, metabolomic analysis displayed that G6PDN126D + SU/Nx rat lungs had metabolic reprogramming resulting in increases glutathione disulfide and 2-hydroxyglutarate, which are indicative of increased oxidoreductive stress. The TCA cycle was upregulated in G6PDN126D + SU/Nx rat lungs, causing increased energy to shunt through the purine salvage pathway to break down purines into uric acid, which is known to occur in pulmonary hypertension. Vasoactive mediators were altered in G6PDN126D + SU/Nx but not G6PDS188F + SU/Nx rat lungs, leading to increased inositol triphosphate and calcium signaling, thrombin-antithrombin complex, and decreased nitric oxide. Serpine1, a gene that encodes plasminogen activator inhibitor-1 (PAI-1), was upregulated in G6PDN126D + SU/Nx rat lungs only, and resulted in binding to NOS3, which accounted for the decreased nitric oxide, and induced senescence and migration of smooth muscle cells.
Unbiased bulk RNASeq revealed that genes encoding chromatin related proteins, oncoproteins, plasminogen activator inhibitor-1, cytokines, and chemokines, were upregulated in G6PDN126D + SU/Nx compared with G6PDS188F + SU/Nx rat lungs. Further single nucleus RNA sequencing depicted that more cell types of G6PDN126D + SU/Nx rat lungs had upregulated Serpine1 and inflammatory cytokines. Upon more specific clustering of the cell types, it was shown that basophils and endothelial progenitor cells were present in the lungs of G6PDN126D + SU/Nx rats only. Next, we assessed how epigenetics was altered in these G6PD variants with whole genome methylation studies and found that Tet1, Tet2 and Tet3 were increased in G6PDS188F rat lungs and there was a 3.4-fold difference in 5-hmC to 5-mC in G6PDS188F + SU/Nx rat lungs, indicating that these lungs favor demethylation and transcriptional activation. Upon investigation of the 3D genome via Hi-C sequencing, we determined that there are changes in transcription activation via the presence of topologically associated domains and correspond loops in the chromatin at the gene loci of Tet2 on chromosome 2 for G6PDS188F rat lungs. These data suggest that perhaps epigenetics and the organization of the 3D-genome are interrelated in maintaining Tet2 driven transcriptional activation in G6PDS188F rat lungs, and this maintenance protects G6PDS188F rats, but not G6PDN126D rats from the maladaptive signaling molecules that occur during the development of Sugen-5416 induced pulmonary hypertension.
Understanding how gene expression is altered at the physiological, epigenetics, and 3D-genomic organization gives further insight into the role of G6PD variants in vascular disease. Elucidating the role of ethnic G6PD polymorphisms in tyrosine kinase inhibitor (TKI)-induced experimental PH will give critical insight into translational medicine. Furthermore, these findings suggest that carefully screening patients who are given TKIs for diseases such as cancer is necessary
InTouch Week of December 22, 2025
No full textMarking the Moments of 2025 NYMC and Hudson Regional Health Form Academic Affiliation Simultaneous Heart-Kidney Transplant Brings Higher Risk A Closer Look at Medical Careers The Latest Issue of TCDM Apex is Available Faculty Spotlight: From Response to Real Impacthttps://touroscholar.touro.edu/in_touch/1385/thumbnail.jp
Treatment Response to Antiseizure Medications in People With Newly Diagnosed Focal Epilepsy
No full textImportance: Epilepsy affects approximately 65 million people worldwide, and 60% have focal seizures. Predicting seizure response and drug resistance to antiseizure medications (ASMs) in people with focal epilepsy remains difficult. Objective: To describe the expected short- and long-term response to treatment with ASMs in people with focal epilepsy using recognized definitions by the International League Against Epilepsy. Design, Setting, and Participants: The Human Epilepsy Project is an international, prospective, observational cohort study that followed up people with newly diagnosed focal epilepsy for up to 6 years between 2012 and 2020. Data were analyzed from 2023 to 2024. The Human Epilepsy Project was conducted at 34 tertiary epilepsy centers across the US, Australia, and Europe. Participants with confirmed diagnosis of focal epilepsy aged 12 to 60 years were enrolled within 4 months of treatment initiation with ASM(s). Data were analyzed from February 2024 to July 2024. Exposure: ASM (variable). Main Outcomes and Measures: The primary outcome was seizure freedom, defined as a period without seizures for 12 months or 3 times the longest pretreatment seizure-free interval, whichever was longer. Treatment response was categorized as sensitive, meaning seizure free receiving 2 or fewer adequate ASM trials; resistant, meaning having 2 or more adequate ASM trials fail; or indeterminate (neither treatment sensitive nor resistant). Results: Among 448 enrolled participants, 267 (59.6%) were female, and median (IQR) participant age was 32 (21-44) years at treatment initiation. Median (IQR) follow-up duration was 3.13 (2.33-3.55) years. Most achieved seizure freedom (267 participants of 448 [59.6%]), largely without relapse (223 [83.5%]). There were 245 treatment-sensitive participants (54.7%), 102 treatment-resistant participants (22.8%), and 101 indeterminate participants (22.5%). Among treatment-sensitive participants, most (217 [89.3%]) responded to monotherapy and half (121 [49.4%], or 27% of total cohort) became seizure free while receiving their first ASM. In the first year of treatment, 251 participants (63%) had ongoing or worsening seizures. Median time to first seizure freedom was 12.1 months (95% CI, 9.7-16.1). This occurred earlier in those who never relapsed (median, 2.2 months; 95% CI, 0.8-3.2) than those who did (median, 7.4 months; 95% CI, 4.0-10.7). Those with infrequent pretreatment seizures were 0.30-fold less likely to be treatment resistant than those with very frequent seizures (hazard ratio, 0.30; 95% CI, 0.14-0.64; P =.002; Holm-Bonferroni-corrected P =.006). Participants with self-reported comorbid psychological disorders were 1.78-fold more likely to be treatment resistant than those without (relative risk, 1.78; 95% CI, 1.26-2.52; P =.001). Conclusions and Relevance: In the Human Epilepsy Project multicenter prospective cohort study, most people with newly diagnosed focal epilepsy took more than a year and more than 1 ASM to become seizure free. Drug resistance can be identified earlier in those with frequent pretreatment seizures, and a history of psychiatric comorbidities at epilepsy diagnosis is an important prognostic factor. Trial Registration: ClinicalTrials.gov Identifier: NCT02126774
Predictors and Patterns of Nonurothelial Recurrence After Nephroureterectomy for Upper Tract Urothelial Carcinoma (UCAN Collaboration)
No full textPurpose:After radical nephroureterectomy for upper tract urothelial carcinoma, 25% of patients experience distant metastasis within 5 years. Nonurothelial recurrence is associated with poor prognosis and survival, with ∼80% of patients dying within 2 years. We evaluated predictors, patterns, and timing of recurrences after radical nephroureterectomy, and the association between recurrence location and cancer-specific survival.Materials and Methods:Separate competing risk regression models were conducted with each site as the outcome and all other recurrence sites as the competing risk. A Cox proportional hazards model was used to evaluate predictors and the association between cancer-specific survival and recurrence site, adjusting for time from surgery to recurrence. A separate model including multiple sites (yes/no) was used to evaluate the association with cancer-specific survival, also adjusting for recurrence sites.Results:Two thousand one hundred seventy-seven patients with upper tract urothelial carcinoma underwent radical nephroureterectomy between January 2000 and February 2021 in 7 institutions, with 454 developing nonurothelial recurrence (survivor median follow-up, 34 [IQR 11-70] months). Improved cancer-specific survival rates were seen in lung and lymph node metastasis compared with other sites (HR 0.60, 95% CI 0.37-0.97, P =.038; HR 0.65, 95% CI 0.41-1.02, P =.063, respectively). Recurrence to multiple concurrent nonurothelial sites was associated with worse cancer-specific survival rates (HR 1.68, 95% CI 1.30-2.17, P \u3c.001). Significant recurrence associations included tumor size, high stage/grade, and tumor location. There were no statistically significant survival differences based on timing of recurrence.Conclusions:Recurrences were common within 2 years. Lung/lymph node recurrences portended the most favorable cancer-specific survival rates. Understanding the timing and location of recurrence can tailor surveillance strategies