RESUMEN
PURPOSE: Nivolumab plus relatlimab and nivolumab plus ipilimumab have been approved for advanced melanoma on the basis of the phase II/III RELATIVITY-047 and phase III CheckMate 067 trials, respectively. As no head-to-head trial comparing these regimens exists, an indirect treatment comparison was conducted using patient-level data from each trial. METHODS: Inverse probability of treatment weighting (IPTW) adjusted for baseline characteristic differences. Minimum follow-ups (RELATIVITY-047, 33 months; CheckMate 067, 36 months) were selected to best align assessments. Outcomes included progression-free survival (PFS), confirmed objective response rate (cORR), and melanoma-specific survival (MSS) per investigator; overall survival (OS); and treatment-related adverse events (TRAEs). A Cox regression model compared PFS, OS, and MSS. A logistic regression model compared cORRs. Subgroup analyses were exploratory. RESULTS: After IPTW, key baseline characteristics were balanced for nivolumab plus relatlimab (n = 339) and nivolumab plus ipilimumab (n = 297). Nivolumab plus relatlimab demonstrated similar PFS (hazard ratio [HR], 1.08 [95% CI, 0.88 to 1.33]), cORR (odds ratio, 0.91 [95% CI, 0.73 to 1.14]), OS (HR, 0.94 [95% CI, 0.75 to 1.19]), and MSS (HR, 0.86 [95% CI, 0.67 to 1.12]) to nivolumab plus ipilimumab. Subgroup comparisons showed larger numerical differences favoring nivolumab plus ipilimumab with acral melanoma, BRAF-mutant melanoma, and lactate dehydrogenase >2 × upper limit of normal, but were limited by small samples. Nivolumab plus relatlimab was associated with fewer grade 3-4 TRAEs (23% v 61%) and any-grade TRAEs leading to discontinuation (17% v 41%). CONCLUSION: Nivolumab plus relatlimab demonstrated similar efficacy to nivolumab plus ipilimumab in the overall population, including most-but not all-subgroups, and improved safety in patients with untreated advanced melanoma. Results should be interpreted with caution.
RESUMEN
Background: Published guidelines that help clinicians identify patients who would benefit from the co-prescription of intranasal naloxone (IN) exclude "palliative care patients." In the absence of clear care standards, palliative care (PC) clinicians may experience uncertainty in how to approach IN co-prescriptions. Objective: Explore the attitudes of PC clinicians in the United States of America who work at regional health care institutions regarding IN prescriptions for patients they prescribe opioids for. Methods: An 18-question electronic survey was distributed to PC clinicians that practice at institutions in Wisconsin or Minnesota with at least 10 other PC clinicians between February and May 2023. The survey explored clinical scenarios in which respondents would and would not prescribe IN. Results: Fifty-six PC clinicians responded to the survey-response rate 41%. Most respondents (90.9%) did not feel IN prescriptions should be reserved for patients with a full code status; 67.9% of respondents felt that IN prescriptions are reasonable for certain patients with a terminal illness and comfort goals of care. Neither prognosis, duration of opioid therapy, nor dose of opioid therapy were significant factors in determining whether most respondents prescribed IN for their patients. Most respondents (81.8%) felt clinician counseling and patient consent were essential before prescribing IN. Conclusion: Most PC clinicians in our survey felt that IN prescriptions can be appropriate for patients they prescribe opioids for. Bystander safety was an emerging rationale for why respondents chose to prescribe IN for their patients. Despite public health efforts to make IN more freely available, most respondents felt clinician counseling was essential before prescribing IN for their patients.
RESUMEN
This study investigates the nanoscale self-assembly from mixtures of two symmetrical poly(ethylene oxide)-poly(propylene oxide)-pol(ethylene oxide) (PEO-PPO-PEO) block copolymers (BCPs) with different lengths of PEO blocks and similar PPO blocks. The blended BCPs (commercially known as Pluronic F88 and L81, with 80 and 10% PEO, respectively) exhibited rich phase behavior in an aqueous solution. The relative viscosity (ηrel) indicated significant variations in the flow behavior, ranging from fluidic to viscous, thereby suggesting a possible micellar growth or morphological transition. The tensiometric experiments provided insight into the intermolecular hydrophobic interactions at the liquid-air interface favoring the surface activity of mixed-system micellization. Dynamic light scattering (DLS) and small-angle neutron scattering (SANS) revealed the varied structural morphologies of these core-shell mixed micelles and polymersomes formed under different conditions. At a concentration of ≤5% w/v, Pluronic F88 exists as molecularly dissolved unimers or Gaussian chains. However, the addition of the very hydrophobic Pluronic L81, even at a much lower (<0.2%) concentration, induced micellization and promoted micellar growth/transition. These results were further substantiated through molecular dynamics (MD) simulations, employing a readily transferable coarse-grained (CG) molecular model grounded in the MARTINI force field with density and solvent-accessible surface area (SASA) profiles. These findings proved that F88 underwent micellar growth/transition in the presence of L81. Furthermore, the potential use of these Pluronic mixed micelles as nanocarriers for the anticancer drug quercetin (QCT) was explored. The spectral analysis provided insight into the enhanced solubility of QCT through the assessment of the standard free energy of solubilization (ΔG°), drug-loading efficiency (DL%), encapsulation efficiency (EE%), and partition coefficient (P). A detailed optimization of the drug release kinetics was presented by employing various kinetic models. The [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] MTT assay, a frequently used technique for assessing cytotoxicity in anticancer research, was used to gauge the effectiveness of these QCT-loaded mixed nanoaggregates.
Asunto(s)
Micelas , Poloxámero , Polietilenglicoles , Poloxámero/química , Polietilenglicoles/química , Portadores de Fármacos/química , Interacciones Hidrofóbicas e Hidrofílicas , Humanos , Glicoles de Propileno/química , Viscosidad , Simulación de Dinámica MolecularRESUMEN
The role of extracellular vesicles (EVs) in human health and disease has garnered considerable attention over the past two decades. However, while several types of EVs are known to interact dynamically with the extracellular matrix and there is great potential value in producing high-fidelity EV micropatterns, there are currently no label-free, high-resolution, and tunable platform technologies with this capability. We introduce Light-induced Extracellular Vesicle Adsorption (LEVA) as a powerful solution to rapidly advance the study of matrix- and surface-bound EVs and other particles. The versatility of LEVA is demonstrated using commercial GFP-EV standards, EVs from glioblastoma bioreactors, and E. coli outer membrane vesicles (OMVs), with the resulting patterns used for single EV characterization, single cell migration on migrasome-mimetic trails, and OMV-mediated neutrophil swarming. LEVA will enable rapid advancements in the study of matrix- and surface-bound EVs and other particles, and should encourage researchers from many disciplines to create novel diagnostic, biomimetic, immunoengineering, and therapeutic screening assays.
RESUMEN
BACKGROUND: The neonatal phase is vital for child survival, with a substantial portion of deaths occurring in the first month. Neonatal mortality rates differ significantly between Vietnam (10.52/1000 live births) and the United States (3.27/1000). In response to these challenges, interventions such as the Helping Babies Breathe (HBB) program have emerged, aiming to enhance the quality of care provided during childbirth, and the postpartum period in low-resource settings. PURPOSE: The purpose of this study was to explore stakeholder perceptions of the HBB program in Vietnam postpandemic, aiming to identify requisites for resuming training. METHODS: Utilizing qualitative content analysis, 19 in-person semistructured interviews were conducted with diverse stakeholders in 2 provinces of Central Vietnam. RESULTS: The content analysis revealed following 5 main themes: (1) the pandemic's impact on HBB training; (2) resource needs for scaling up HBB training as the pandemic abates; (3) participants' perceptions of the pandemic's effect on HBB skills and knowledge; (4) the pandemic's influence on a skilled neonatal resuscitation workforce; and (5) future prospects and challenges for HBB training in a postpandemic era. IMPLICATIONS FOR PRACTICE AND RESEARCH: This research highlights the importance of sustainable post-HBB training competencies, including skill assessment, innovative knowledge retention strategies, community-based initiatives, and evidence-based interventions for improved healthcare decision-making and patient outcomes. Healthcare institutions should prioritize skill assessments, refresher training, and collaborative efforts among hospitals, authorities, non-government organizations, and community organizations for evidence-based education and HBB implementation.
Asunto(s)
Investigación Cualitativa , Resucitación , Humanos , Vietnam , Recién Nacido , Resucitación/educación , Femenino , Masculino , Adulto , Asfixia Neonatal/terapia , Mortalidad Infantil , LactanteRESUMEN
Cartilage is a strong and flexible connective tissue that has many forms and functions in our body. While cartilage exhibits some forms of limited repair, for the most part, it is not particularly regenerative. Thus, in situations where patients require cartilage reconstruction, surgeons may use autografts to replace missing or damaged tissue. Cartilage tissues from different regions of the body exhibit histological differences and are in limited supply. Thus, it is important to characterize these differences to determine the most appropriate autograft source. In the case of microtia, a congenital deformity where the pinna is underdeveloped, reconstruction commonly utilizes cartilage sourced from a patient's own costal cartilage. This presents a potential morbidity risk. In this study, we evaluate the histological characteristics of microtia cartilage compared with normal auricular and costal cartilage obtained from human patients undergoing surgical resection. Histochemistry was used to evaluate cellularity, lipid content, and ECM content. Using a Bayesian statistical approach, we determined that while costal cartilage is the standard tissue donor, the microanatomy of microtia cartilage more closely reflects normal auricular cartilage than costal cartilage. Therefore, microtia cartilage may serve as an additional reservoir for cartilage during reconstruction.
Asunto(s)
Microtia Congénita , Cartílago Costal , Cartílago Auricular , Humanos , Microtia Congénita/cirugía , Cartílago Auricular/trasplante , Cartílago Costal/trasplante , Procedimientos de Cirugía Plástica/métodos , Masculino , Autoinjertos , Femenino , Adulto , Adolescente , Trasplante AutólogoRESUMEN
Background: India has been estimated to have 14 % of malnourished population and a high TB incidence burden with a 26.9 lakh cases. Malnutrition and diabetes mellitus are major risk factors for tuberculosis infection. Malnutrition in patients with both tuberculosis and diabetes (TB-DM) population worsens the disease severity, treatment outcomes and increases morbidity and mortality risk. Objective: To assess the nutritional status in patients with TB-DM compared with patients with TB and DM alone. Method: Records from January 2016 to November 2020 for patients admitted to Kasturba Hospital, Manipal were assessed. Data pertaining to glycemic parameters, nutritional parameters, and other relevant laboratory parameters were extracted for assessment. The study population were divided into three groups i.e. patients with TB-DM, TB and DM. The statistical association was carried out with one-way ANOVA method, considering p < 0.05 as statistically significant. Results: A total of 291 patients were included, with 97 patients in each group; among those, male and female were 86.27 % and 13.73 % respectively. Cardiovascular co-morbidity was predominant in the DM (68.04 %) and TB-DM (26.8 %) group. The mean value of HbA1c (10.47 %) was found to be highest for the TB-DM group. Low levels of albumin were reported by 71.91 % of patients of the TB group, whereas 73.68 % patients in TB-DM group had vitamin D deficiency. Moreover, higher prevalence of low MCV and MCH in the TB-DM group suggest an increased risk of iron-deficiency anemia. Conclusion: The findings of our study reflect the need for implementation of nutritional support in patients with TB-DM.
RESUMEN
Background: Strong provider recommendation can increase uptake of human papillomavirus (HPV) vaccination. Therefore, we developed and implemented a provider education intervention on communication strategies for recommending HPV vaccination with clinic-level audit and feedback (HPV: Communicating about HPV to Adults and Teens [HPV CHAT]). We aimed to evaluate the effect of HPV CHAT on HPV vaccine uptake in seven family medicine and pediatric clinics in a large urban health system (USA). Methods: We used a quasi-experimental design, where the eligible population included people aged 9-26 years with at least one encounter in June 2020-February 2023 at one of the participating community health clinics. We used interrupted time-series analysis to assess changes in the prevalence of HPV vaccine uptake. We used segmented Poisson regression with a log link function to estimate prevalence ratios (PR) and 95% confidence limits (CL) for level (immediate) and slope (over time) changes with adjustment for seasonality using Fourier transformation. Results: Our study population comprised 60,328 observations in which the median age was 17 years (interquartile range: 13-21). A majority (58%) were female and 87% were racial/ethnic minorities. Overall, we observed no sizeable effect of the intervention on HPV vaccination uptake. Nonetheless, heterogeneity was observed by age group with modest increases in individuals aged 9-12 and 13-17 years. Conclusion: Our provider feedback intervention had minimal effect on increasing prevalence of HPV vaccination in seven family medicine and pediatric clinics. Novel strategies are needed to address provider barriers related to HPV vaccination.
RESUMEN
Improving human papillomavirus (HPV) vaccination is a national priority but uptake declined following the coronavirus pandemic. A strong predictor of HPV vaccination in the USA is a strong provider recommendation. Therefore, we developed a brief, asynchronous training on HPV vaccine recommendations in clinical and community settings as part of a multisite quality improvement initiative. This paper aims to describe the implementation and initial outcomes of the training provided. A 20-minute training on HPV vaccine bundled recommendations, motivational interviewing, and brief responses to patient concerns (Communicating about HPV vaccination to Adults and Teens; HPV CHAT) was implemented at seven safety-net clinics, two practice-based research network clinics, and nine county immunization clinics. We integrated training with clinical care teams; thus, we assessed immediate training outcomes across their different clinical roles compared to pre-training. In April-May 2022, HPV CHAT training was launched. One hundred eighty-seven people participated in the training and completed the pre-/postevaluation surveys. Knowledge about the HPV vaccine guidelines improved with notable changes in correctly reporting vaccine eligibility (P < .05). A significant change in participants' confidence when addressing safety concerns and answering questions about the HPV vaccine (clinicians, 26.8% and 17.1%; nurses, 29.0% and 23.2%, and clinical staff, 18.2% and 37.7%) was observed. At post-test, more than 85% of clinicians and nurses reported their plan to routinely recommend the HPV vaccine. This quality improvement initiative demonstrated implementation feasibility of a brief HPV vaccine training that improved provider and clinical staff knowledge, confidence, and intention to routinely recommend HPV vaccination.
The human papillomavirus (HPV) vaccine is key to cancer prevention. Despite this fact, HPV vaccination is not widely accepted. Studies have shown that a strong recommendation can lead to HPV vaccination. Therefore, virtual educational training (Communicating about HPV vaccination to Adults and Teens; HPV CHAT) was developed to equip clinicians, nurses, and clinical staff with communication tools to support HPV recommendation and respond to patient concerns. HPV CHAT, a quality improvement initiative, was launched across numerous community and county clinical teams. To capture HPV CHAT training impact, pre- and post-evaluation surveys were disseminated alongside the training to capture training impact. After HPV CHAT implementation, training participants reported a positive impact on confidence and knowledge items; these findings were observed across all clinical roles in varying degrees. Overall, this quality improvement initiative successfully improved communication skill self-efficacy and knowledge across different clinical roles. This paper discusses training implementation strategies and the changes in knowledge and confidence after participating in the training.
Asunto(s)
Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Adulto , Adolescente , Humanos , Infecciones por Papillomavirus/prevención & control , Padres/educación , Vacunas contra Papillomavirus/uso terapéutico , Personal de Salud/educación , Vacunación , Virus del Papiloma Humano , Conocimientos, Actitudes y Práctica en SaludAsunto(s)
Asma , Niño , Humanos , Asma/tratamiento farmacológico , Instituciones de Atención AmbulatoriaRESUMEN
BACKGROUND: Disparities in birth outcomes continue to exist in the United States, particularly for low-income, publicly insured women. Doula support has been shown to be a cost-effective intervention in predominantly middle-to-upper income White populations, and across all publicly insured women at the state level. This analysis extends previous studies by providing an estimate of benefits that incorporates variations in averted outcomes by race and ethnicity in the context of one region in Texas. The objectives of this study were to determine (1) whether the financial value of benefits provided by doula support exceeds the costs of delivering it; (2) whether the cost-benefit ratio differs by race and ethnicity; and (3) how different doula reimbursement levels affect the cost-benefit results with respect to pregnant people covered by Medicaid in central Texas. METHODS: We conducted a forward-looking cost-benefit analysis using secondary data carried out over a short-term time horizon taking a public payer perspective. We focused on a narrow set of health outcomes (preterm delivery and cesarean delivery) that was relatively straightforward to monetize. The current, usual care state was used as the comparison condition. RESULTS: Providing pregnant people covered by Texas Medicaid with access to doulas during their pregnancies was cost-beneficial (benefit-to-cost ratio: 1.15) in the base model, and 65.7% of the time in probabilistic sensitivity analyses covering a feasible range of parameters. The intervention is most cost-beneficial for Black women. Reimbursing doulas at $869 per client or more yielded costs that were greater than benefits, holding other parameters constant. CONCLUSIONS: Expanding Medicaid pregnancy-related coverage to include doula services would be cost-beneficial and improve health equity in Texas.
Asunto(s)
Doulas , Medicaid , Embarazo , Recién Nacido , Estados Unidos , Femenino , Humanos , Análisis Costo-Beneficio , Texas , CesáreaRESUMEN
The condition known as Takayasu's disease or Takayasu's arteritis is a type of vascular inflammation that affects the large and medium arteries. It can lead to a reduction in blood flow to various parts of the body, and it can cause severe complications. Patients with this disease may not have specific symptoms, which can lead to their diagnosis not being confirmed. Takayasu's disease is believed to be a probable cause of stroke in young patients. Although stroke is a common cause of morbidity, it is usually not an initial presentation in Takayasu's disease. In this study, a young female with left-sided hemiparesis was diagnosed with Takayasu's disease after a clinical and angiographic examination.
RESUMEN
Background: The purpose of this study was to determine how accurately parents measure their preschool child's weight and height with increasing levels of instruction. Methods: Parents measured their child's (n = 30 dyads) weight (own weight scale) and height (soft tape measure) using three levels of instruction: instructional guide (level 1); guide, demonstration video (level 2); and guide, video, and virtual monitoring (level 3), which were compared to researcher measurements (electronic weight scale, Stadiometer). Paired t-tests were used to determine differences between researcher and parent measurements and between the three parent levels. Inaccurate classifications were calculated using parent-measured values for the four categories (underweight, healthy, overweight, obese). Results: Raw mean parent-measured weights (17.4 ± 2.3 kg) differed from researcher by 0.2 kg (level 1), 0.3 kg (level 2), and 0.1 kg (level 3). Raw mean parent-measured heights (104.0 ± 5.9 cm) differed from researcher by 0.9 cm (level 1, p = 0.005), 0.4 cm (level 2, NS), and 0.3 cm (level 3, NS). Across all levels, 48.9% and 65.5% parents overmeasured their children's weights and heights, respectively. Using parent-measured values, 29.4% of children were classified high while 70.5% were classified low. Parents were more likely to make errors if their children were on the borderline between any of the two weight categories. Conclusion: Findings indicate that an instructional guide with demonstration video is helpful in improving the parents' accuracy of their children's weights and heights. More research is needed to determine accuracy in population other than White parents with high education levels and children under overweight and obese category.
RESUMEN
Recurrence of cardiac sarcoidosis (CS) and giant cell myocarditis (GCM) after heart transplant is rare, with rates of 5% in CS and 8% in GCM. We aim to identify all reported cases of recurrence in the literature and to assess clinical course, treatments, and outcomes to improve understanding of the conditions. A systematic review, utilizing Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines, was conducted by searching MEDLINE/PubMed and Embase of all available literature describing post-transplant recurrent granulomatous myocarditis, CS, or GCM. Data on demographics, transplant, recurrence, management, and outcomes data were collected from each publication. Comparison between the 2 groups were made using standard statistical approaches. Post-transplant GM recurrence was identified in 39 patients in 33 total publications. Reported cases included 24 GCM, 12 CS, and 3 suspected cases. Case reports were the most frequent form of publication. Mean age of patients experiencing recurrence was 42 years for GCM and 48 years for CS and favored males (62%). Time to recurrence ranged from 2 weeks to 9 years post-transplant, occurring earlier in GCM (mean 1.8 vs 3.0 years). Endomyocardial biopsies (89%) were the most utilized diagnostic method over cardiac magnetic resonance and positron emission tomography. Recurrence treatment regimens involved only steroids in 40% of CS, whereas other immunomodulatory regimens were utilized in 70% of GCM. In conclusion, GCM and CS recurrence after cardiac transplantation holds associated risks including concurrent acute cellular rejection, a higher therapeutic demand for GCM recurrence compared with CS, and mortality. New noninvasive screening techniques may help modify post-transplant monitoring regimens to increase both early detection and treatment of recurrence.
Asunto(s)
Cardiomiopatías , Trasplante de Corazón , Miocarditis , Sarcoidosis , Adulto , Humanos , Masculino , Biopsia , Cardiomiopatías/diagnóstico , Cardiomiopatías/etiología , Cardiomiopatías/patología , Células Gigantes/patología , Trasplante de Corazón/efectos adversos , Miocarditis/diagnóstico , Miocarditis/etiología , Miocarditis/terapia , Sarcoidosis/diagnóstico , Sarcoidosis/patologíaRESUMEN
BACKGROUND AND AIM: Cardiac sarcoidosis (CS) is the second most common cause of death in patients with sarcoidosis and data pertaining to its diagnosis and management is limited. We sought to describe diagnostic modalities and management of patients with CS in the United States, based on a national registry questionnaire. METHODS: We conducted a retrospective study based on a national registry investigating 3,835 respondents to the Foundation for Sarcoidosis Research Questionnaire. The registry includes patient surveys completed between June 2014 and August 2019. Summary and univariate analyses were performed. RESULTS: A total of 394 patients (10.3%) with CS were identified; 57% (n=223) were women and 81% (n=317) were white. The mean (±SD) age at diagnosis was 45 years (±13). CS was the initial presentation of sarcoidosis in 30%. Multiorgan involvement (≥3 organs) was present in 68%. Two-thirds of patients were admitted at least once to the hospital. Cardiac magnetic resonance imaging (74.4%) was the most common diagnostic modality used followed by positron emission tomography (PET) scan (59.3%) and cardiac biopsy (n=52, 13%). Most patients received corticosteroids (86%) and steroid-sparing medications (61%) including methotrexate (26%) and tumor necrosis factor (TNF) inhibitors (19%). A combined cardioverter defibrillator and pacemaker (39%) was the most common cardiac device implanted. CONCLUSIONS: The prevalence of CS in this cohort was higher than previously described. CS was a common initial presentation of sarcoidosis. The diagnosis was most likely made using cMRI. Steroids, methotrexate and infliximab are the most common medications used. Conduction abnormalities and arrhythmias often occurred.
RESUMEN
BACKGROUND AND AIM: Inhalational exposures have been hypothesized to play a role in the pathogenesis of sarcoidosis. Herein, we describe a cohort of US Military personnel diagnosed with sarcoidosis during or after deployment to Southwest Asia and Afghanistan, who experienced complex inhalational exposures to burn-pits and desert dust. METHODS: Consecutive military personnel at four sub-specialty clinics across the United States were screened for deployment to Southwest Asia and Afghanistan and diagnosis of sarcoidosis based on 1999 ATS/ERS/WASOG Statement on Sarcoidosis. Detailed demographic, deployment and exposure data was collected. The data combined was analyzed after de-identification and local IRB approval. RESULTS: Twenty-one patients met our case definition. Seventeen patients were male and 62% had extrapulmonary involvement, including 38% with musculoskeletal involvement. Conclusions: Our study suggests that the sarcoidosis in military personnel to Southwest Asia can be diagnosed many years after deployment. To our knowledge, this is the first case series to describe a group of military personnel diagnosed with sarcoidosis and exposures specific to military deployment to Southwest Asia.
RESUMEN
Untreated myocardial infarction (MI) can potentially lead to many fatal complications which require immediate management. One of them is ventricular septal rupture (VSR) which necessitates the hemodynamic stabilization and closure of the septal rupture. Conventional treatment strategy involves surgical repair; however, percutaneous transcatheter repair using an occluder device is a promising upcoming approach. We conducted a detailed review of various published articles and examined the trends in incidence, risk factors, and pathophysiology of MI leading to VSR followed by an in-depth analysis of the various management strategies for the same. In the current clinical scenario, thrombolysis is an imperative management strategy that has been shown to decrease the occurrence of VSR by manifolds, more specifically in patients having ST-elevated MI. Delayed surgical closure remains the main treatment for post-infarction VSR. Other newer modalities, such as percutaneous closure devices and mechanical circulatory supports, are attractive alternative or complementary strategies to treat such patients, both postoperatively and perioperatively. However, earlier surgical repair in VSR increases the risk of mortality, and the optimal timing for VSR closure remains controversial. Despite surgical closure of VSR being the traditional treatment, it presents a considerably high operative risk. Although newer interventions such as percutaneous closure devices and mechanical circulatory supports provide impressive outcomes, their efficacy in high-risk patients remains inconclusive.
RESUMEN
Ultrafiltration is an effective method to get rid of fluid retention and congestion in patients with acute decompensated heart failure (HF) without affecting the circulating volume. Although its efficacy in comparison to diuretics is debatable, the evaluation of our analysis is based on various studies that comprise published clinical trials on ultrafiltration and studies comparing the efficacy of diuretics and ultrafiltration. Apart from this, we also look at literature that provides shortcomings of the said procedure and its scope for future advancements. Heart failure ultimately leads to volume overload, which is a highly concerning complication. Diuretics have been used as a first-line treatment for fluid overload but are becoming inefficacious due to the development of resistance and renal dysfunction. Ultrafiltration, on the other hand, is an attractive alternative to counter volume overload and congestion, which are unresponsive to medical therapy. There is also evidence that it significantly decreases the probability of future episodes of decompensation. There are, however, disagreements about whether ultrafiltration is an effective method to improve mortality in these patients. There is a lack of conclusive studies demonstrating the superiority of one fluid removal method over another. Hence, it is imperative to continue searching for the most effective method to treat congestion. Priority should be given to more mechanistic studies regarding ultrafiltration.
RESUMEN
Sarcoidosis is a complex systemic disease. Our study aimed to (1) identify novel alleles associated with sarcoidosis susceptibility; (2) provide an in-depth evaluation of HLA alleles and sarcoidosis susceptibility and (3) integrate genetic and transcription data to identify risk loci that may more directly impact disease pathogenesis. We report a genome-wide association study of 1335 sarcoidosis cases and 1264 controls of European descent (EA) and investigate associated alleles in a study of African Americans (AA: 1487 cases and 1504 controls). The EA and AA cohort was recruited from multiple United States sites. HLA alleles were imputed and tested for association with sarcoidosis susceptibility. Expression quantitative locus and colocalization analysis were performed using a subset of subjects with transcriptome data. Forty-nine SNPs in the HLA region in HLA-DRA, -DRB9, -DRB5, -DQA1 and BRD2 genes were significantly associated with sarcoidosis susceptibility in EA, rs3129888 was also a risk variant for sarcoidosis in AA. Classical HLA alleles DRB1*0101, DQA1*0101 and DQB1*0501, which are highly correlated, were also associated with sarcoidosis. rs3135287 near HLA-DRA was associated with HLA-DRA expression in peripheral blood mononuclear cells and bronchoalveolar lavage from subjects and lung tissue and whole blood from GTEx. We identified six novel SNPs (out of the seven SNPs representing the 49 significant SNPs) and nine HLA alleles associated with sarcoidosis susceptibility in the largest EA population. We also replicated our findings in an AA population. Our study reiterates the potential role of antigen recognition and/or presentation HLA class II genes in sarcoidosis pathogenesis.