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The burden of cardiovascular disease in Latin America and the Caribbean, 1990-2019: An analysis of the global burden of disease study
No full textINTRODUCTION: Cardiovascular disease (CVD) remains the leading cause of death globally, including the Latin America and the Caribbean (LAC) region. However, limited research has been conducted on the burden of CVD in this region. Our study aims to investigate the burden of CVD and related risk factors (RFs) in the LAC.
METHODS: We used data from the Global Burden of Disease (GBD) 2019 to examine CVD prevalence in 33 LAC countries. Prevalence, mortality, and incidence were analyzed using Bayesian regression tools, demographic methods, and mortality-to-incidence ratios. Disability-adjusted life years (DALYs) were calculated, and RFs were evaluated under the GBD\u27s comparative risk assessment framework.
RESULTS: Between 1990 and 2019, CVD raw rates in the LAC increased by 116.7 %, while age-standardized prevalence decreased (-9.2 %). CVD raw mortality rose by 71.2 %, but age-standardized death rates fell by 69.8 %. Ischemic heart disease remained the most prevalent condition, with higher rates in men, while women had higher rates of stroke. Age-standardized DALYs decreased by 70.9 %. DALY rates varied across countries and were consistently higher in males. Leading RFs included HTN, high LDL, dietary risks, and elevated BMI.
CONCLUSIONS: Despite progress in reducing the CVD burden in the LAC region, the impact on mortality and morbidity, particularly related to ischemic heart disease, remains substantial. Tailored interventions are necessary, considering country-specific variations in socio-economic factors, healthcare infrastructure, and political stability
Psychological factors associated with binge eating among women with infertility
No full textEating disorder pathology, including binge eating, is highly prevalent among women diagnosed with infertility. Binge eating has a range of consequences that may undermine fertility outcomes, yet population-specific risk and protective factors are unknown. Identifying factors associated with binge eating among this unique population may inform more sensitive and effective prevention and intervention efforts. In this cross-sectional observational study, women diagnosed with infertility completed validated self-report measures of psychiatric symptoms, eating disorder pathology, overvaluation of shape and weight (OSW), infertility distress, infertility acceptance, and trait mindfulness. Mann-Whitney U tests and two-part zero-inflated Poisson regression analyses were performed to identify associations between these factors and the presence and frequency of binge eating. In our sample (N = 188), 39.4 % endorsed recent binge eating (n = 74). These participants reported higher symptoms of anxiety (p \u3c .001), depression (p \u3c .001), OSW (p \u3c .001), dietary restraint (p \u3c .001), body mass index (\u3c 0.001), and lower mindfulness (p = .003) relative to those who denied binge eating. There were no group differences in infertility distress or acceptance. In a two-part zero-inflated Poisson regression model, higher OSW was the only factor significantly independently associated with higher odds of binge eating, whereas increased depression severity was significantly independently associated with greater binge eating frequency. Ultimately, OSW and depression may be particularly important treatment targets for women with infertility engaging in binge eating, above and beyond related psychological risk factors. Implications for future research and clinical practice are discussed
Long-Term Safety of Abrocitinib in Moderate-to-Severe Atopic Dermatitis: Integrated Analysis by Age
No full textBACKGROUND: Abrocitinib has a manageable long-term safety profile for patients with moderate-to-severe atopic dermatitis. Identifying populations at higher risk of adverse events will help optimize dose selection.
OBJECTIVE: To evaluate abrocitinib long-term safety by age.
METHODS: Data (cutoff: September 25, 2021) from JADE clinical trials were pooled in a consistent-dose cohort (patients who received the same abrocitinib dose throughout exposure) or a variable-dose cohort (patients who received abrocitinib 200 mg [12 wk], were randomly assigned later to receive abrocitinib 200 mg, 100 mg, or placebo [up to 40 wk], and assigned to receive abrocitinib 200 mg or 100 mg in the long-term study). Data were stratified post hoc by age at baseline (12 to \u3c 18 y; 18 to \u3c 40 y, 40 to \u3c 65 y, and ≥65 y). Incidence rates of treatment-emergent adverse events (TEAEs) of special interest were assessed.
RESULTS: Analysis included 3,802 patients (exposure: 5,214 patient-years). The incidence rates for serious adverse events, TEAEs leading to study discontinuation, serious infections, herpes zoster, thrombocytopenia, lymphopenia, nonmelanoma skin cancer, malignancies (excluding nonmelanoma skin cancer), major cardiovascular events, and venous thromboembolism were numerically higher in patients aged 65 years or older than in younger patients. Overall, adolescents had the lowest rates for TEAEs of special interest.
CONCLUSIONS: Abrocitinib has a manageable long-term safety profile. TEAEs of special interest were lower in adolescents and higher in the 65-years-old or older age group. Risk of specific TEAEs was numerically higher in patients aged 65 years or older treated with abrocitinib 200 mg and underscores the importance of dose selection in older patients
ASO Visual Abstract: Conversion from Minimally Invasive Surgical Approaches to Open Surgery Among Endometrial Cancer Patients in the SGO Clinical Outcomes Registry
No full textIncorporating Circulating Tumor DNA Testing Into Clinical Trials: A Position Paper by the National Cancer Institute GI Oncology Circulating Tumor DNA Working Group
No full textPURPOSE: Circulating tumor DNA (ctDNA) is an emerging tool in the evaluation of GI cancers. Challenges remain in defining its utility and role as a primary end point in therapeutic trials. The National Cancer Institute (NCI) ctDNA GI working group was created to evaluate current data and provide guidance on the inclusion of ctDNA in GI cancer trials.
METHODS: The NCI GI steering committee assigned four task force members to serve as co-chairs for the working group. Co-chairs identified experts within each GI disease group to form a panel that convened to review data and provide recommendations. The group focused on ctDNA\u27s role as a potential surrogate for assessing prognosis and guiding treatment decisions that may enhance GI cancer trials. A manuscript was drafted, circulated, revised, and voted on by the panel. The final draft was reviewed by the Cancer Therapy Evaluation Program.
RESULTS: Further data are required to support ctDNA as a primary end point for late-phase therapeutic trials, particularly in studies that could change the standard-of-care. However, the group supports ctDNA as a primary efficacy end point for phase II studies and as a noninvasive evaluation strategy for new drug development. Incorporation of ctDNA as a biomarker in trial design must consider the specific context of disease biology of the GI cancer subtypes. ctDNA should be incorporated as an exploratory end point across a variety of disease settings and indications. Several practical considerations were identified to optimize the incorporation of ctDNA in future trial design.
CONCLUSION: Prospective trials are required to clarify the role of ctDNA as a valid surrogate end point for progression-free or overall survival in GI cancers
TP53-Mutated Acute Myeloid Leukemia: Review of Treatment and Challenges
No full textPatients with acute myeloid leukemia (AML) harboring mutations in TP53 (TP53-MT) have poor responses to current therapies and unfavorable prognoses. Despite the recognition of variant TP53 as an adverse feature of AML, an optimal treatment regimen has not yet been established, underlining a critical need for new, more effective therapeutic combinations and novel treatments. We present the case of a patient with TP53-MT AML and marked myelodysplasia who developed primary refractory disease after induction therapy with the intensive chemotherapy regimen of liposomal daunorubicin and cytarabine. Our patient\u27s optimal response to second induction chemotherapy with FLAG-Ida prompted an exploration of established and investigational treatment regimens for this specific high-risk AML subtype. Therefore, we performed a comprehensive literature review of findings from studies exploring AML therapies, focusing on outcomes for patients with TP53-MT AML. The summary provided here reveals the complexity of defining the therapeutic responses of patients with the heterogeneous TP53-MT genetic background and the challenges in treating this high-risk form of AML. Future work must continue to investigate novel therapies and combinations to improve patient outcomes in this vulnerable population
Enhanced Small Extracellular Vesicle Uptake by Activated Interneurons Improves Stroke Recovery in Mice
No full textNeuronal circuitry remodelling, which comprises excitatory and inhibitory neurons, is critical for improving neurological outcomes after a stroke. Preclinical studies have shown that small extracellular vesicles (sEVs) have a therapeutic effect on stroke recovery. However, it is highly challenging to use sEVs to specifically target individual neuronal populations to enhance neuronal circuitry remodelling after stroke. In the present study, using a chemogenetic approach to specifically activate peri-infarct cortical interneurons in combination with the administration of sEVs derived from cerebral endothelial cells (CEC-sEVs), we showed that the CEC-sEVs were preferentially taken up by the activated neurons, leading to significant improvement of functional outcome after stroke, which was associated with augmentation of peri-infarct cortical axonal/dendritic outgrowth and of axonal remodelling of the corticospinal tract. The ultrastructural and Western blot analyses revealed that neurons with internalization of CEC-sEVs exhibited significantly reduced numbers of damaged mitochondria and proteins that mediate dysfunctional mitochondria, respectively. Together, these data indicate that the augmented uptake of CEC-sEVs by activated peri-infarct cortical interneurons facilitates neuronal circuitry remodelling and functional recovery after stroke, which has the potential to be a novel therapy for improving stroke recovery
A contemporary, multiinstitutional analysis of transcription factor lineage in pituitary adenomas: comparative study of neuroimaging, histopathology, and clinical outcomes
No full textOBJECTIVE: Pituitary adenomas (PAs) are common lesions that often present with endocrinopathy and/or visual symptoms. Classification of PAs has historically been based on functional status and histopathological staining of anterior pituitary hormones. In 2017, the WHO revised the classification of PAs, establishing cell lineages identified by the transcription factors (TFs) PIT1, TPIT, and SF1. The clinical behavior of PA subtypes based on TF typing, including growth patterns, response to treatment, and recurrence rates, is unknown. The authors aimed to assess clinical presentation and outcomes according to TF lineage in a contemporary series of PAs.
METHODS: A retrospective multicenter clinical study of patients undergoing resection of PAs between June 2017 and August 2021 was performed. Included tumors underwent immunohistochemical staining for WHO-defined TFs (TPIT, PIT1, and SF1). Clinical data including demographics, tumor characteristics, extent of resection, and clinical outcomes pertaining to tumor control and hormonal remission were assessed.
RESULTS: A total of 238 patients were included in the analysis, with the following clinical breakdown of PA subtypes: nonfunctional PAs (n = 150, 63.0%); growth hormone-secreting PAs causing acromegaly (n = 53, 22.3%); adrenocorticotropic hormone-secreting PAs causing Cushing\u27s disease (n = 30, 12.6%); and prolactinomas (n = 2, 0.8%). The most common TFs identifying cell lineages were SF1 (n = 104 samples, 43.7%), TPIT (n = 53, 22.3%), and PIT1 (n = 46, 19.3%). Thirty-five samples (14.7%) were positive for two TFs. Prevalence of suprasellar extension was highest in SF1 tumors (91.3%) and lowest in PIT1 tumors (54.3%), and varied significantly across groups (p \u3c 0.001). Cavernous sinus and clival/sphenoid invasion also varied among TF subtypes, with the highest rates seen in PIT1 PAs (p = 0.002). Although no significant differences in progression-free survival (PFS) were noted across TF subtypes, among nonfunctional PAs the median PFS for SF1, PIT1, and TPIT TFs were 83 months, 26 months, and 45 months, respectively (p = 0.002). Nonfunctional PIT1 PAs had a significantly shorter PFS/recurrence-free survival compared to functional PIT1 tumors (HR 59.45, 95% CI 2.54-1394, p = 0.01).
CONCLUSIONS: The modern WHO diagnosis of PAs incorporates pituitary TF staining to standardize classification according to PA cell lineage. TF designation is associated with major clinical and endocrine variables including PA extension, extrasellar growth patterns, Ki-67 labeling index, and PFS among patients with PA subtypes
Establishing a Successful Research Infrastructure for Orthopaedic Surgery Residents
No full textResearch among orthopaedic surgery residents provides numerous benefits, which include but are not limited to development of critical thinking skills, greater understanding of study design and statistical analysis, strengthened fellowship applications, networking, and the ability to practice evidence based medicine. Research has been increasingly emphasized among orthopaedic surgery residency directors, and residency programs have uniformly implemented protected research time into their formal clinical training. Despite this, there are few resources describing the ability to conduct research effectively during residency. The purpose of this review is to provide an outline for implementing a successful, productive, high-output, resident-centric, research infrastructure leveraging resources available at clinical orthopaedic surgery residencies
Serum metal ion levels in patients with failed total shoulder arthroplasty
No full textBACKGROUND: Shoulder arthroplasty systems are transitioning toward modular prosthesis options with the goal of reducing complication profiles and increasing range of motion. Modularity may increase the potential for fretting, corrosion, and subsequent release of metal ions. The purpose of this study was to identify associations between implant designs, metallurgy, patient characteristics, and serum metal ion levels in patients undergoing revision shoulder arthroplasty.
METHODS: Fifty-one patients who underwent revision shoulder arthroplasty were retrospectively reviewed based on prospectively collected data. All patients had serum metal ion levels (titanium, cobalt, chromium) measured in parts per billion (ppb) before their revision arthroplasty. Trends and correlations to serum ion levels were examined based on implant materials, number of modular components, and patient characteristics.
RESULTS: Twenty-one patients had anatomic total shoulder arthroplasty (aTSA), and 30 had reverse total shoulder arthroplasty (rTSA). The average age at primary arthroplasty was 64.7 years (49.0-84.0). The average term of implant was 4.83 years (0.18-21.0). Forty-six patients (90%) had titanium-based humeral stems. Twenty-one (100%) aTSA humeral heads were composed of cobalt chrome. Five patients with aTSA had hybrid titanium and polyethylene glenoid components. In those with rTSA, 30 (100%) had glenoid components composed of titanium baseplates and cobalt chrome glenospheres. Titanium ion levels were significantly higher in patients with greater than 7 total modular components (12.6 vs. 6.09 ppb, P = .008). Titanium ion levels were significantly higher in patients with greater than 4 modular components when excluding screws (12.1 vs. 5.06, P = .038). The number of modular components did not have a statistically significant effect on cobalt or chromium serum ion levels. Patients with intraoperative metallosis during revision surgery had titanium ion levels 10.51 units higher on average (P = .009) than those without metallosis. There was no difference in titanium (P = .63), cobalt (P = .29), or chromium (P = .58) levels in those patients with a proven infection compared to those without.
CONCLUSIONS: Increasing modularity in primary TSA should be weighed with the potential for increased serum metal ion levels, particularly titanium. Although the systemic effects of elevated serum titanium remain largely unknown, it may be a predictor for occult corrosion or need for revision. Metallosis poses challenges in the revision setting; however, the implications of increased serum metal ion levels on clinical outcomes after revision shoulder arthroplasty requires further studies