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Background: GSK3326595 is a potent, selective, reversible protein arginine methyltransferase 5 (PRMT5) inhibitor under investigation for treatment of myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML). In preclinical models of AML, PRMT5 inhibition decreased proliferation and increased cell death, supporting additional clinical research in myeloid neoplasms. Objectives: To determine the clinical activity, safety, tolerability, dosing, additional measures of clinical activity, pharmacokinetics, and pharmacodynamics of GSK3326595. Design: In part 1 of this open-label, multicenter, multipart, phase I/II study, adults with relapsed/refractory myeloid neoplasms (e.g., MDS, CMML, and AML) received monotherapy with 400 or 300 mg oral GSK3326595 once daily. Study termination occurred prior to part 2 enrollment. Methods: Clinical activity was determined by the clinical benefit rate (CBR; proportion of patients achieving complete remission (CR), complete marrow remission (mCR), partial remission, stable disease (SD) >8 weeks, or hematologic improvement). Adverse events (AEs) were assessed by incidence and severity. Exploratory examination of spliceosome mutations was performed to determine the relationship between genomic profiles and clinical response to GSK3326595. Results: Thirty patients with a median age of 73.5 years (range, 47-90) were enrolled; 13 (43%) and 17 (57%) received 400 and 300 mg of GSK3326595, respectively. Five (17%) patients met CBR criteria: 4 (13%) with SD >8 weeks and 1 (3%) achieving mCR. Of five patients with clinical benefit: three had SRSF2 mutation, one U2AF1, and one was splicing factor wild-type. Frequent GSK3326595-related AEs were decreased platelet count (27%), dysgeusia (23%), fatigue (20%), and nausea (20%). GSK3326595 had rapid absorption, with a T max of approximately 2 h and a terminal half-life of 4-6 h. Conclusion: GSK3326595 monotherapy had limited clinical activity in heavily pretreated patients despite robust target engagement. The safety profile was broadly consistent with other published PRMT5 inhibitor studies. Trial registration: ClinicalTrials.gov: NCT03614728.

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A clinical study to determine the effectiveness and safety of a medication called GSK3326595 in patients with cancers that affect the blood and bone marrow What is this study about? This summary provides the results of a study performed to see how safe and effective treatment with a once daily, oral medication called GSK3326595 was in patients with blood and bone marrow cancers. What are PRMT5 inhibitors? GSK3326595 belongs to a class of medications known as PRMT5 inhibitors. PRMT5 is an enzyme that is involved in many processes in cells. In cancers, too much PRMT5 activity can cause excessive cell growth. This study was performed to see if blocking of PRMT5 by GSK3326595 would help treat patients with blood and bone marrow cancers. What patients were in this study? The patients included in this study had previously received many other cancer treatments. Most patients with these types of cancers have few treatment options and usually pass away due to their disease. What were the results? Five of the 30 patients (17%) included in the study had a response to treatment, including 4 patients with stable disease for more than 8 weeks and 1 patient with complete marrow remission for approximately 8 months. Of the 93% of patients that completed the study, 83% died. Ultimately, all 30 patients discontinued study treatment, mostly due to progression of their disease. The most frequent side effects related to GSK3326595 treatment that occurred in ⩾20% of patients were a decrease in the number of cells that help the blood clot, change in taste bud sense, fatigue, and nausea. The side effects caused by GSK3326595 were similar to what is seen with other PRMT5 inhibitors. Treatment with GSK3326595 provided limited benefits in this patient population and no future studies are planned for GSK3326595 at this time. Additional studies are needed for PRMT5 inhibitors, including combination therapies, to determine which patients with blood and bone marrow cancers could potentially benefit from treatment.

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The increasing prevalence of hazardous chemical incidents in the United States necessitates the implementation of analytically robust, rapid, and reliable screening techniques for toxicant mixture analysis to understand short- and long-term health impacts of environmental exposures. A recent chemical disaster in East Palestine, Ohio has underscored the importance of thorough contamination assessment. On February 03, 2023, a Norfolk Southern train derailment prompted a chemical spill and fires. An open burn involving over 100,000 gal of vinyl chloride was conducted three days later. Hazardous compounds were released into air, water, and soil. To provide time-sensitive exposure data for emergency response, this study outlines a novel methodology for rapid characterization of chemical contamination of environmental media to support disaster response efforts. A controlled static headspace sampling system, in conjunction with a high-resolution proton transfer reaction time-of-flight mass spectrometer (PTR-TOF-MS), was developed to characterize volatile organic compounds (VOCs) in surface water samples collected near the East Palestine train derailment site. Spatial variations were observed in the chemical composition of surface water samples collected at different locations. Hydrocarbons were found to be the most abundant chemical group of all surface water samples, contributing 50 % to 97 % to the total headspace VOC mass. Compounds commonly detected in surface water samples, including benzene, styrene, xylene, and methyl tert-butyl ether (MTBE) were also observed in most surface water samples, with aqueous concentrations typically at ng/L levels. This study demonstrated the potential of the proposed methodology to be applied for rapid field screening of volatile chemicals in water samples in order to enable fast emergency response to chemical disasters and environmental hazards.

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Elucidating the mechanisms by which late-life neurodegeneration causes cognitive decline requires understanding why some individuals are more resilient than others to the effects of brain change on cognition (cognitive reserve). Currently, there is no way of measuring cognitive reserve that is valid (e.g. capable of moderating brain-cognition associations), widely accessible (e.g. does not require neuroimaging and large sample sizes), and able to provide insight into resilience-promoting mechanisms. To address these limitations, this study sought to determine whether a machine learning approach to combining standard clinical variables could (i) predict a residual-based cognitive reserve criterion standard and (ii) prospectively moderate brain-cognition associations. In a training sample combining data from the University of California (UC) Davis and the Alzheimer's Disease Neuroimaging Initiative-2 (ADNI-2) cohort (N = 1665), we operationalized cognitive reserve using an MRI-based residual approach. An eXtreme Gradient Boosting machine learning algorithm was trained to predict this residual reserve index (RRI) using three models: Minimal (basic clinical data, such as age, education, anthropometrics, and blood pressure), Extended (Minimal model plus cognitive screening, word reading, and depression measures), and Full [Extended model plus Clinical Dementia Rating (CDR) and Everyday Cognition (ECog) scale]. External validation was performed in an independent sample of ADNI 1/3/GO participants (N = 1640), which examined whether the effects of brain change on cognitive change were moderated by the machine learning models' cognitive reserve estimates. The three machine learning models differed in their accuracy and validity. The Minimal model did not correlate strongly with the criterion standard (r = 0.23) and did not moderate the effects of brain change on cognitive change. In contrast, the Extended and Full models were modestly correlated with the criterion standard (r = 0.49 and 0.54, respectively) and prospectively moderated longitudinal brain-cognition associations, outperforming other cognitive reserve proxies (education, word reading). The primary difference between the Minimal model-which did not perform well as a measure of cognitive reserve-and the Extended and Full models-which demonstrated good accuracy and validity-is the lack of cognitive performance and informant-report data in the Minimal model. This suggests that basic clinical variables like anthropometrics, vital signs, and demographics are not sufficient for estimating cognitive reserve. Rather, the most accurate and valid estimates of cognitive reserve were obtained when cognitive performance data-ideally augmented by informant-reported functioning-was used. These results indicate that a dynamic and accessible proxy for cognitive reserve can be generated for individuals without neuroimaging data and gives some insight into factors that may promote resilience.

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INTRODUCTION: For over 60 years, spinal cord stimulation has endured as a therapy through innovation and novel developments. Current practice of neuromodulation requires proper patient selection, risk mitigation and use of innovation. However, there are tangible and intangible challenges in physiology, clinical science and within society. AREAS COVERED: We provide a narrative discussion regarding novel topics in the field especially over the last decade. We highlight the challenges in the patient care setting including selection, as well as economic and socioeconomic challenges. Physician training challenges in neuromodulation is explored as well as other factors related to the use of neuromodulation such as novel indications and economics. We also discuss the concepts of technology and healthcare data. EXPERT OPINION: Patient safety and durable outcomes are the mainstay goal for neuromodulation. Substantial work is needed to assimilate data for larger and more relevant studies reflecting a population. Big data and global interconnectivity efforts provide substantial opportunity to reinvent our scientific approach, data analysis and its management to maximize outcomes and minimize risk. As improvements in data analysis become the standard of innovation and physician training meets demand, we expect to see an expansion of novel indications and its use in broader cohorts.

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Dolor Crónico , Estimulación de la Médula Espinal , Humanos , Estimulación de la Médula Espinal/métodos , Dolor Crónico/terapia , Resultado del Tratamiento

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Background: This study investigates the association between the Geriatric Nutritional Risk Index (GNRI), a measure of malnutrition risk, and 30-day postoperative complications following revision total hip arthroplasty (rTHA). Methods: The American College of Surgeons National Surgical Quality Improvement Program database was queried for all patients ≥65 who underwent aseptic rTHA between 2015 and 2021. The final study population (n = 7119) was divided into 3 groups based on preoperative GNRI: normal/reference (GNRI >98) (n = 4342), moderate malnutrition (92 ≤ GNRI ≤98) (n = 1367), and severe malnutrition (GNRI <92) (n = 1410). Multivariate logistic regression analysis was conducted to investigate the association between preoperative GNRI and 30-day postoperative complications. Results: After controlling for significant covariates, the risk of experiencing any postoperative complications was significantly higher with both moderate (odds ratio [OR] 2.08, P < .001) and severe malnutrition (OR 8.79, P < .001). Specifically, moderate malnutrition was independently and significantly associated with deep vein thrombosis (OR 1.01, P = .044), blood transfusions (OR 1.78, P < .001), nonhome discharge (OR 1.83, P < .001), readmission (OR 1.27, P = .035), length of stay >2 days (OR 1.98, P < .001), and periprosthetic fracture (OR 1.54, P = .020). Severe malnutrition was independently and significantly associated with sepsis (OR 3.67, P < .001), septic shock (OR 3.75, P = .002), pneumonia (OR 2.73, P < .001), urinary tract infection (OR 2.04, P = .002), deep vein thrombosis (OR 1.01, P = .001), pulmonary embolism (OR 2.47, P = .019), acute renal failure (OR 8.44, P = .011), blood transfusions (OR 2.78, P < .001), surgical site infection (OR 2.59, P < .001), nonhome discharge (OR 3.36, P < .001), readmission (OR 1.69, P < .001), unplanned reoperation (OR 1.97, P < .001), length of stay >2 days (OR 5.41, P < .001), periprosthetic fractures (OR 1.61, P = .015), and mortality (OR 2.63, P < .001). Conclusions: Malnutrition has strong predictive value for short-term postoperative complications and has potential as an adjunctive risk stratification tool for geriatric patients undergoing rTHA.

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Tetrachloroethylene (PCE) is a widely utilized volatile chemical in industrial applications, including dry cleaning and metal degreasing. Exposure to PCE potentially presents a significant health risk to workers as well as communities near contamination sites. Adverse health effects arise not only from PCE, but also from PCE degradation products, such as trichloroethylene (TCE) and vinyl chloride (VC). PCE, TCE, and VC can contaminate water, soil, and air, leading to exposure through multiple pathways, including inhalation, ingestion, and dermal contact. This study focused on a community setting in Martinsville, Indiana, a working-class Midwestern community in the United States, where extensive PCE contamination has occurred due to multiple contamination sites (referring to 'plumes'), including a Superfund site. Utilizing proton transfer reaction time-of-flight mass spectrometry (PTR-TOF-MS), PCE, TCE, and VC concentrations were measured in the exhaled breath of 73 residents from both within and outside the plume areas. PCE was detected in 66 samples, TCE in 26 samples, and VC in 68 samples. Our results revealed a significant positive correlation between the concentrations of these compounds in exhaled breath and indoor air (Pearson correlation coefficients: PCE = 0.75, TCE = 0.71, and VC = 0.89). This study confirms the presence of PCE and its degradation products in exhaled breath in a community exposure investigation, demonstrating the potential of using exhaled breath analysis in monitoring exposure to environmental contaminants. This study showed the feasibility of utilizing PTR-TOF-MS in community investigations to assess exposure to PCE and its degradation products by measuring these compounds in exhaled breath and indoor air.

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Contaminación del Aire Interior , Pruebas Respiratorias , Tetracloroetileno , Humanos , Pruebas Respiratorias/métodos , Contaminación del Aire Interior/análisis , Tetracloroetileno/análisis , Masculino , Femenino , Adulto , Espiración , Persona de Mediana Edad , Exposición a Riesgos Ambientales/análisis , Indiana , Monitoreo del Ambiente/métodos

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Alkenes are fundamental functional groups which feature in various materials and bioactive molecules; however, efficient divergent strategies for their stereodefined synthesis are difficult. In this regard, numerous synthetic methodologies have been developed to construct carbon-carbon bonds with regio- and stereoselectivity, enabling the predictable and efficient synthesis of stereodefined alkenes. In fact, an appealing alternative approach for accessing challenging stereodefined alkene molecular frameworks could involve the sequential selective activation and cross-coupling of strong bonds instead of conventional C-C bond formation. In this study, we introduce a series of programmed site- and stereoselective strategies that capitalizes on the versatile reactivity of readily accessible polymetalloid alkenes (i.e. polyborylated alkenes), through a tandem cross-coupling reaction, which is catalyzed by an organometallic Rh-complex to produce complex molecular scaffolds. By merging selective C-B and remote C-H bond functionalization, we achieve the in situ generation of polyfunctional C(sp2)-nucleophilic intermediates. These species can be further modified by selective coupling reactions with various C-based electrophiles, enabling the formation of C(sp2)-C(sp3) bond for the generation of even more complex molecular architectures using the readily available starting polyborylated-alkenes. Mechanistic and computational studies provide insight into the origins of the stereoselectivities and C-H activation via a 1,4-Rh migration process.

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Nanocluster aerosol (NCA: particles in the size range of 1-3 nm) are a critically important, yet understudied, class of atmospheric aerosol particles. NCA efficiently deposit in the human respiratory system and can translocate to vital organs. Due to their high surface area-to-mass ratios, NCA are associated with a heightened propensity for bioactivity and toxicity. Despite the human health relevance of NCA, little is known regarding the prevalence of NCA in indoor environments where people spend the majority of their time. In this study, we quantify the formation and transformation of indoor atmospheric NCA down to 1 nm via high-resolution online nanoparticle measurements during propane gas cooking in a residential building. We observed a substantial pool of sub-1.5 nm NCA in the indoor atmosphere during cooking periods, with aerosol number concentrations often dominated by the newly formed NCA. Indoor atmospheric NCA emission factors can reach up to ∼1016 NCA/kg-fuel during propane gas cooking and can exceed those for vehicles with gasoline and diesel engines. Such high emissions of combustion-derived indoor NCA can result in substantial NCA respiratory exposures and dose rates for children and adults, significantly exceeding that for outdoor traffic-associated NCA. Combustion-derived indoor NCA undergo unique size-dependent physical transformations, strongly influenced by particle coagulation and condensation of low-volatility cooking vapors. We show that indoor atmospheric NCA need to be measured directly and cannot be predicted using conventional indoor air pollution markers such as PM2.5 mass concentrations and NO x (NO + NO2) mixing ratios.

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BACKGROUND: Subjective cognitive decline (SCD), i.e. self/other-reported concerns on one's cognitive functioning without objective evidence of significant decline, is an indicator of dementia risk. There is little consensus on reliability and validity of the available SCD measures. Therefore, introducing a novel and psychometrically sound measure of SCD is timely. OBJECTIVE: The psychometric properties of a new SCD measure, the McCusker Subjective Cognitive Impairment Inventory-Self-Report (McSCI-S), are reported. METHODS: Through review of previously published measures as well as our clinical and research data on people with SCD, we developed a 46-item self-report questionnaire to assess concerns on six cognitive domains, namely, memory, language, orientation, attention and concentration, visuoconstruction abilities and executive function. The McSCI-S was examined in a cohort of 526 participants using factor analysis, item response theory analysis and receiver operating characteristic (ROC) curve. RESULTS: A unidimensional model provided acceptable fit (CFI = 0.94, TLI = 0.94, RMSEA [90% CI] = 0.052 [.049, 0.055], WRMR = 1.45). The McSCI-S internal consistency was excellent (.96). A cut-off score of ≥24 is proposed to identify participants with SCDs. Higher McSCI-S scores were associated with poorer general cognition, episodic verbal memory, executive function and greater memory complaints and depressive scores (P < .001), controlling for age, sex and education. CONCLUSIONS: Excellent reliability and construct validity suggest the McSCI-S estimates SCDs with acceptable accuracy while capturing self-reported concerns for various cognitive domains. The psychometric analysis indicated that this measure can be used in cohort studies as well as on individual, clinical settings to assess SCDs.

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Disfunción Cognitiva , Psicometría , Autoinforme , Humanos , Femenino , Masculino , Anciano , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/psicología , Reproducibilidad de los Resultados , Cognición , Anciano de 80 o más Años , Persona de Mediana Edad , Pruebas Neuropsicológicas/normas , Valor Predictivo de las Pruebas , Curva ROC

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BACKGROUND: Triplet or quadruplet therapies incorporating proteasome inhibitors, immunomodulators, and anti-CD38 antibodies have led to prolonged survival among patients with newly diagnosed multiple myeloma; however, most patients have a relapse. Frontline lenalidomide therapy has increased the number of patients with lenalidomide-refractory disease at the time of the first relapse. METHODS: In this phase 3, randomized, open-label trial, we evaluated belantamab mafodotin, pomalidomide, and dexamethasone (BPd), as compared with pomalidomide, bortezomib, and dexamethasone (PVd), in lenalidomide-exposed patients who had relapsed or refractory myeloma after at least one line of therapy. The primary end point was progression-free survival. Disease response and safety were also assessed. RESULTS: A total of 302 patients underwent randomization; 155 were assigned to the BPd group, and 147 to the PVd group. At a median follow-up of 21.8 months (range, <0.1 to 39.2), the 12-month estimated progression-free survival with BPd was 71% (95% confidence interval [CI], 63 to 78), as compared with 51% (95% CI, 42 to 60) with PVd (hazard ratio for disease progression or death, 0.52; 95% CI, 0.37 to 0.73; P<0.001). Data on overall survival were immature. The percentage of patients with a response to treatment (partial response or better) was 77% (95% CI, 70 to 84) in the BPd group and 72% (95% CI, 64 to 79) in the PVd group; 40% (95% CI, 32 to 48) and 16% (95% CI, 11 to 23), respectively, had a complete response or better. Grade 3 or higher adverse events occurred in 94% of the patients in the BPd group and 76% of those in the PVd group. Ocular events occurred in 89% of the patients who received BPd (grade 3 or 4 in 43%) and 30% of those who received PVd (grade 3 or 4 in 2%); ocular events in the BPd group were managed with belantamab mafodotin dose modification. Ocular events led to treatment discontinuation in 9% of the patients in the BPd group and in no patients in the PVd group. CONCLUSIONS: Among lenalidomide-exposed patients with relapsed or refractory myeloma, BPd conferred a significantly greater benefit than PVd with respect to progression-free survival, as well as deeper, more durable responses. Ocular events were common but were controllable by belantamab mafodotin dose modification. (Funded by GSK; DREAMM-8 ClinicalTrials.gov number, NCT04484623; EudraCT number, 2018-004354-21.).

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Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Dexametasona , Mieloma Múltiple , Supervivencia sin Progresión , Talidomida , Humanos , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/mortalidad , Dexametasona/efectos adversos , Dexametasona/uso terapéutico , Dexametasona/administración & dosificación , Talidomida/análogos & derivados , Talidomida/efectos adversos , Talidomida/uso terapéutico , Talidomida/administración & dosificación , Masculino , Femenino , Persona de Mediana Edad , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Adulto , Anciano de 80 o más Años , Bortezomib/efectos adversos , Bortezomib/uso terapéutico , Bortezomib/administración & dosificación , Lenalidomida/efectos adversos , Lenalidomida/uso terapéutico , Lenalidomida/administración & dosificación , Estimación de Kaplan-Meier , Recurrencia

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BACKGROUND: The hypoplastic mandible in the congenital condition Pierre Robin sequence (PRS) displaces the base of the tongue posteriorly, which results in upper airway obstruction (UAO) that can potentially be corrected with mandibular distraction osteogenesis (MDO). Jaw thrust (JT) is routinely performed during evaluation of the airway; similar to MDO, it projects the mandible and tongue anteriorly to open the airway. The authors demonstrate that JT can be used as a criterion to predict successful MDO outcomes in infants with PRS. METHODS: The study was a single-center, retrospective chart review of infants diagnosed with PRS between 2016 and 2023. Data regarding their demographics, comorbid diagnoses, JT success, airway anomalies, laryngeal grade of view, apnea-hypopnea index, and perioperative course were statistically analyzed. RESULTS: Of the 16 patients included in the study, 11 had successful relief of their airway obstruction with JT and proceeded with MDO. The unsuccessful JT group had significantly greater proportions of females, birth prematurity, gastrostomies, tracheostomies, and longer hospital stays. In the successful JT group, both the mean laryngeal grade of view ( P =0.029) and mean apnea-hypopnea index ( P =0.025) improved significantly post-MDO. Post-MDO tracheostomy was also avoided in all but 1 patient who was not previously tracheostomized. CONCLUSIONS: There is no widely accepted algorithm to guide craniofacial surgeons on the optimal intervention for relieving UAO in infants with PRS. In our institutional experience, patients whose preoperative JT relieved UAO also successfully relieved UAO with MDO. In patients with PRS, JT may be a useful criterion for selecting appropriate candidates for MDO.

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Obstrucción de las Vías Aéreas , Mandíbula , Osteogénesis por Distracción , Síndrome de Pierre Robin , Humanos , Osteogénesis por Distracción/métodos , Femenino , Estudios Retrospectivos , Masculino , Síndrome de Pierre Robin/cirugía , Obstrucción de las Vías Aéreas/cirugía , Lactante , Resultado del Tratamiento , Mandíbula/cirugía , Mandíbula/anomalías , Recién Nacido

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Heart failure (HF) is a life-threatening disorder and is treated by drug therapies and surgical interventions such as heart transplantation and left ventricular assist device (LVAD). However, these treatments can lack effectiveness in the long term and are associated with issues such as donor shortage in heart transplantation, and infection, stroke, or gastrointestinal bleeding in LVADs. Therefore, alternative therapeutic strategies are still needed. In this respect, stem cell therapy has been introduced for the treatment of HF and numerous preclinical and clinical studies are employing a range of stem cell varieties. These stem cells, such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), have been shown to improve cardiac function and attenuate left ventricular remodeling. IPSCs, which have a capacity for unlimited proliferation and differentiation into cardiomyocytes, are a promising cell source for myocardial regeneration therapy. In this review, we discuss the following topics: (1) what are iPSCs; (2) the limitations and solutions for the translation of iPSC-CMs practically; and (3) the current therapeutic clinical trials.

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Insuficiencia Cardíaca , Células Madre Pluripotentes Inducidas , Miocitos Cardíacos , Medicina Regenerativa , Humanos , Células Madre Pluripotentes Inducidas/citología , Miocitos Cardíacos/citología , Medicina Regenerativa/métodos , Insuficiencia Cardíaca/terapia , Animales , Regeneración , Trasplante de Células Madre/métodos , Diferenciación Celular

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Purpose: The objective of this study was to determine the risk factors and the rate of reoperation after closed reduction percutaneous pinning (CRPP) of isolated closed single-digit proximal phalanx fractures. Methods: A retrospective cohort study was conducted for patients who underwent CRPP of non-thumb closed proximal phalanx fractures between 2010 and 2020 at two level-I trauma centers and two community teaching hospitals. Demographics, fracture, and treatment characteristics were collected. The primary outcome measure was reoperation. Secondary outcome measures were complication and reoperation specifically for digital stiffness. Results: Of the 115 patients who underwent surgical treatment, 46 patients (40.0%) had a complication and 13 patients (11.3%) underwent reoperation at a mean of 6.7 months-most of which (84.6%) were for digital stiffness. Conclusions: Surgeons and patients may be aware that CRPP of closed extra-articular proximal phalanx fractures carries considerable rates of complication and reoperation. Type of study/level of evidence: Therapeutic III.

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Objetivo: Comparar el diagnóstico y manejo de la anemia durante el embarazo en mujeres de zonas urbanas y rurales. Métodos: Estudio descriptivo transversal, basado en un análisis de una encuesta nacional de salud del 2022. Se incluyeron registros de 18 889 mujeres con un embarazo en los últimos 5 años. Se estimaron frecuencias y porcentajes ponderados; además se aplicó la prueba chi cuadrado a un nivel de significancia del 0,05. Resultados: Al 94 % de mujeres se les realizó el descarte de anemia, este procedimiento fue más frecuente en zonas urbanas (94,9 %), comparado a las rurales (91,1 %). La mayor parte de las mujeres no recibió el diagnóstico de anemia, pero no hubo diferencias entre las zonas rurales (29,8 %) y urbanas (28,3 %). Respecto a la indicación y cumplimiento del tratamiento para la anemia, esto fue significativamente mayor en las parejas urbanas, con un porcentaje de 96,7 % y 65,5 %, respectivamente. Conclusión: En las zonas urbanas, fue mayor el porcentaje de mujeres en quienes se realizó descarte de anemia, así como la indicación del tratamiento y su cumplimiento. El diagnóstico de anemia no mostró diferencias entre ambas zonas(AU)

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Objective: To compare the diagnosis and management of anemia during pregnancy in urban and rural women. Methods: Cross-sectional descriptive study, based on an analysis of a national health survey from 2022. Records of 18889 women with a pregnancy in the last 5 years were included. Frequencies and weighted percentages were estimated; in addition, the chi-square test was applied at a significance level of 0.05. Results: 94% of women were screened for anemia; this procedure was more frequent in urban areas (94.9%) compared to rural areas (91.1%). Most women were not diagnosed with anemia, but there was no difference between rural (29.8%) and urban (28.3%) areas. Regarding indication and adherence to treatment for anemia, this was significantly higher in urban couples, at 96.7% and 65.5%, respectively. Conclusion: In urban areas, the percentage of women of anemia ruling out, as well as treatment indication and compliance was higher. The diagnosis of anemia showed no differences between the two areas(AU)

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Humanos , Femenino , Embarazo , Adolescente , Adulto , Embarazo , Estado Nutricional , Anemia , Población Rural , Factores Socioeconómicos , Población Urbana , Hierro de la Dieta/administración & dosificación

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OBJECTIVE: In dementia research, the Driving Scenes test from the Neuropsychological Assessment Battery has been shown to relate to memory, dementia diagnosis, and functional impairment. The aim of the current study was to examine Driving Scenes and its component scores, and their relationships with cognition and daily functioning, in a mixed dementia clinic sample. METHOD: One hundred U.S. military veterans between the ages of 55 and 88 were administered a full neuropsychological protocol that included Driving Scenes. RESULTS: The Driving Scenes score and its subscores were strongly related to memory skills, and there were additional subscore associations with language and visuospatial functions. Driving Scenes uniquely predicted reported bill payment difficulties and tendency to get lost while driving, which were not predicted by other performances across cognitive domains. CONCLUSION: Driving Scenes is a clinically and functionally relevant measure of memory. Although the Driving Scenes total score remains useful in dementia evaluations, component scores and error scores contribute additional practical information.

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Purpose: Concerns regarding the ongoing opioid epidemic have led to the implementation of standardized postoperative opioid-prescribing protocols for many common hand surgical procedures. This study investigated patient- and procedure-specific factors affecting adherence to a standardized postoperative opioid-prescribing protocol after cubital tunnel surgery. Methods: A retrospective review of patients who underwent primary cubital tunnel surgery within one academic medical system between October 1, 2016 (after the implementation of a standardized postoperative opioid-prescribing protocol) and March 1, 2020 was performed. Patients aged <18 years or with a history of revision surgery, prior traumatic ulnar nerve injury, additional concurrent surgical procedures, or a surgeon not participating in the protocol were excluded. Patient demographics, comorbidities, prior opioid history, and surgical variables were recorded. The primary outcome was adherence to the standardized postoperative opioid-prescribing protocol. A bivariate statistical analysis was performed. Results: Ninety-eight patients were included. The median initial postoperative prescription amount was 75 morphine equivalent units (100% of protocol target) for 78 patients (80% of cohort) who underwent in situ decompression and 75 morphine equivalent units (50% of protocol target) for 20 patients (20% of cohort) who underwent decompression with ulnar nerve transposition. Forty-nine percent of initial opioid prescriptions adhered to protocol, compared with 26% below target and 26% above target. In the bivariate analysis, recent opioid prescriptions within 3 months preoperatively were associated with improved prescriber protocol adherence; longer tourniquet time and anterior transposition were associated with prescriptions below target, and in situ decompression was associated with prescriptions above target. Conclusions: Variation in postoperative opioid-prescribing patterns persists despite the implementation of a standardized postoperative opioid-prescribing protocol. Recent opioid prescriptions were associated with protocol adherence, possibly reflecting increased provider vigilance in this patient population. Differing target prescription amounts for in situ decompression versus decompression with anterior transposition may be unnecessary. Type of study/level of evidence: Therapeutic IV.

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Dehydration is an overlooked modifiable risk factor that should be optimized prior to elective total hip arthroplasty (THA) to reduce postoperative complications and inpatient costs. All primary THA from 2005 - 2019 were queried from the National Surgical Quality Improvement Program database, and patients were compared based on dehydration status: blood urea nitrogen (BUN): creatinine ratio (Cr) (BUN/Cr) < 20 (nondehydrated), 20 ≤ BUN/Cr ≤ 25 (moderately dehydrated), 25 < BUN/Cr (severely dehydrated). A subgroup analysis involving only elderly patients > 65 years and normalized gender-adjusted Cr values was also performed. The analysis included 212,452 patients who underwent THA. Adjusted multivariate logistic regression analysis showed that the severely dehydrated cohort had a greater risk of overall complications, postoperative anemia requiring transfusion, nonhome discharge, and increased length of stay (all p < 0.01). Among the elderly, dehydrated patients had a greater risk of postoperative transfusion, cardiac complications, and nonhome discharge (all p < 0.01). BUN/Cr > 20 is an important preoperative diagnostic tool to identify at-risk dehydrated patients. Providers should optimize dehydration to prevent complications, decrease costs, and improve discharge planning. (Journal of Surgical Orthopaedic Advances 33(1):017-025, 2024).

Asunto(s)

Artroplastia de Reemplazo de Cadera , Nitrógeno de la Urea Sanguínea , Deshidratación , Complicaciones Posoperatorias , Humanos , Masculino , Femenino , Anciano , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Factores de Riesgo , Persona de Mediana Edad , Tiempo de Internación/estadística & datos numéricos , Creatinina/sangre , Estudios Retrospectivos , Periodo Preoperatorio , Anciano de 80 o más Años , Anemia

RESUMEN

Background: The aim of this study was to assess the efficacy of the Model for End-Stage Liver Disease (MELD) score in predicting postoperative complications following total shoulder arthroplasty (TSA). Methods: The American College of Surgeons National Surgical Quality Improvement database was queried for all patients who underwent TSA between 2015 and 2019. The study population was subsequently classified into two categories: those with a MELD score ≥ 10 and those with a MELD score < 10. A total of 5265 patients undergoing TSA between 2015 and 2019 were included in this study. Among these, 4690 (89.1%) patients had a MELD score ≥ 10, while 575 (10.9%) patients had a MELD score < 10. Postoperative complications within 30 days of the TSA were collected. Multivariate logistic regression analysis was conducted to explore the correlation between a MELD score ≥ 10 and postoperative complications. The anchor based optimal cutoff was calculated by receiver operating characteristic analysis to determine the MELD score cutoff that most accurately predicts a specific complication. Youden's index (J) determined the optimal cutoff point calculation for the maximum sensitivity and specificity; these were deemed to be "acceptable" if the area under curve (AUC) was greater than 0.7 and "excellent" if greater than 0.8. Results: Multivariate regression analysis found a MELD score ≥ 10 to be independently associated with higher rates of reoperation (OR, 2.08; P = .013), cardiac complications (OR, 3.37; P = .030), renal complications (OR, 7.72; P = .020), bleeding transfusions (OR, 3.23; P < .001), and nonhome discharge (OR, 1.75; P < .001). The receiver operating characteristic analysis showed that AUC for a MELD score cutoff of 7.61 as a predictor of renal complications was 0.87 (excellent) with sensitivity of 100.0% and specificity of 70.0%. AUC for a MELD score cutoff of 7.76 as a predictor of mortality was 0.76 (acceptable) with sensitivity of 81.8% and specificity of 71.0%. Conclusion: A MELD score ≥ 10 was correlated with high rates of reoperation, cardiac complications, renal complications, bleeding transfusions, and nonhome discharge following TSA. MELD score cutoffs of 7.61 and 7.76 were effective in predicting renal complications and mortality, respectively.

RESUMEN

Background: Dehydration is a modifiable risk factor that should be optimized prior to all surgical procedures. The aim of this study was to determine the effects of dehydration on postoperative complications following total shoulder arthroplasty (TSA). Methods: The American College of Surgeons National Surgical Quality Improvement database was queried for all patients who underwent TSA between 2015 and 2019 and a total of 16,993 patients were included in this study. The study population was subsequently classified into 3 categories: 8498 (50.0%) nondehydrated patients with blood urea nitrogen/creatinine (BUN/Cr) < 20, 4908 (28.9%) moderately dehydrated patients with 20 ≤ BUN/Cr ≤ 25, and 3587 (21.1%) severely dehydrated patients with 25 < BUN/Cr. A subgroup analysis involving only elderly patients aged > 65 years and normalized gender-adjusted Cr values was also performed. Postoperative complications within 30 days of the TSA were collected. Multivariate logistic regression analysis was conducted to explore the correlation between dehydration and postoperative complications. Results: Adjusted multivariate logistic regression analysis showed that the severely dehydrated cohort had a greater risk of postoperative transfusion, mortality, nonhome discharge, and increased length of stay (all P < .05). The moderately dehydrated cohort had a greater risk of wound dehiscence (P = .044). Among the elderly, severely dehydrated patients had a greater risk of cardiac complications, postoperative transfusion, mortality, nonhome discharge, and increased length of stay (all P < .05). Finally, the elderly moderately dehydrated cohort had a greater risk of postoperative transfusion and nonhome discharge (all P < .05). Conclusion: BUN/Cr ratio is an important preoperative diagnostic tool to identify at-risk dehydrated patients. Providers should optimize dehydration to prevent complications, decrease costs, and improve discharge planning.