Impact of frailty on post-operative outcomes following subarachnoid hemorrhage: A systematic review and meta-analysis.

BACKGROUND: Subarachnoid hemorrhage (SAH) is associated with high rates of mortality and morbidity, particularly among elderly patients. The presence of frailty may impact survival rates in patients with SAH. In this study, we aim to investigate the impact of frailty on the clinical outcomes in SAH patients. METHODS: We conducted a systematic review and meta-analysis following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Relevant papers through December 2023 were retrieved from PubMed, Scopus, Web of science, and Embase. RESULTS: A total of 5 studies met inclusion/exclusion criteria with an aggregate 39,221 non-frail patients (mean age 52.4 ± 5.2 yr; 62.1 % Female), and 79,416 frail patients (mean age 61.1 ± 5.4 yr; 69.0 % Female). Frailty was significantly associated with higher mortality ratio (Odds ratio (OR)= 2.09; CI [1.04: 4.20], p= 0.04), and increased length of hospital stay (OR= 1.40; CI [1.07: 1.83], p= 0.015). Additionally, frailty was associated with higher odds of external ventricular drain insertion, the need of tracheostomy/endoscopic gastrostomy, increased risk of deep vein thrombosis, and postoperative neurological complications. CONCLUSION: Frailty is associated with worse clinical outcomes and higher mortality rates in SAH patients. Our findings highlight that frailty, when considered alongside other established prognostic factors, serves as crucial predictor for peri-operative complications and overall hospital course in SAH patients.

T2*-Relaxometry MRI to Assess Third Trimester Placental and Fetal Brain Oxygenation and Placental Characteristics in Healthy Fetuses and Fetuses With Congenital Heart Disease.

BACKGROUND: Congenital heart disease (CHD) has been linked to impaired placental and fetal brain development. Assessing the placenta and fetal brain in parallel may help further our understanding of the relationship between development of these organs. HYPOTHESIS: 1) Placental and fetal brain oxygenation are correlated, 2) oxygenation in these organs is reduced in CHD compared to healthy controls, and 3) placental structure is altered in CHD. STUDY TYPE: Retrospective case-control. POPULATION: Fifty-one human fetuses with CHD (32 male; median [IQR] gestational age [GA] = 32.0 [30.9-32.9] weeks) and 30 from uncomplicated pregnancies with normal birth outcomes (18 male; median [IQR] GA = 34.5 [31.9-36.7] weeks). FIELD STRENGTH/SEQUENCE: 1.5 T single-shot multi-echo-gradient-echo echo-planar imaging. ASSESSMENT: Masking was performed using an automated nnUnet model. Mean brain and placental T2* and quantitative measures of placental texture, volume, and morphology were calculated. STATISTICAL TESTS: Spearman's correlation coefficient for determining the association between brain and placental T2*, and between brain and placental characteristics with GA. P-values for comparing brain T2*, placenta T2*, and placental characteristics between groups derived from ANOVA. Significance level P < 0.05. RESULTS: There was a significant positive association between placental and fetal brain T2* (⍴ = 0.46). Placental and fetal brain T2* showed a significant negative correlation with GA (placental T2* ⍴ = -0.65; fetal brain T2* ⍴ = -0.32). Both placental and fetal brain T2* values were significantly reduced in CHD, after adjusting for GA (placental T2*: control = 97 [±24] msec, CHD = 83 [±23] msec; brain T2*: control = 218 [±26] msec, CHD = 202 [±25] msec). Placental texture and morphology were also significantly altered in CHD (Texture: control = 0.84 [0.83-0.87], CHD = 0.80 [0.78-0.84]; Morphology: control = 9.9 [±2.2], CHD = 10.8 [±2.0]). For all fetuses, there was a significant positive association between placental T2* and placental texture (⍴ = 0.46). CONCLUSION: Placental and fetal brain T2* values are associated in healthy fetuses and those with CHD. Placental and fetal brain oxygenation are reduced in CHD. Placental appearance is significantly altered in CHD and shows associations with placental oxygenation, suggesting altered placental development and function may be related. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

Timeliness of surgery for early-stage lung cancer: Patient factors and predictors.

Objectives: Time-to-treatment initiation is an important consideration for patients undergoing thoracic surgery for early-stage lung cancer because delays have the potential to adversely affect outcomes. This study seeks to quantify time-to-treatment initiation for patients with clinical stage I lung cancer, explore patient factors and predictors that lead to an increased time-to-treatment initiation, and compare surgeon perception of appropriate time-to-treatment initiation to the results. Methods: Time-to-treatment initiation was determined for patients enrolled in the Mount Sinai Initiative for Early Lung Cancer Research on Treatment study who underwent surgical resection for clinical stage I lung cancer between March 2016 and December 2021. The following dates were determined: (1) date of first suspicious radiologic imaging, (2) date of first biopsy, and (3) date of surgery. A total of 15 thoracic surgeons who participated in the Mount Sinai Initiative for Early Lung Cancer Research on Treatment were assessed on their perception on time-to-treatment initiation. Results: For 638 patients, median time from first suspicious imaging findings to biopsy was 40 days, biopsy to surgery was 37 days, and suspicious imaging to surgery was 84 days. Significant factors that resulted in longer time-to-treatment initiation in the multivariate analysis were African American or Black race (P = .005), vascular disease (P = .01), and median household income less than $75,000 (P = .04). Although the surgeon's perception was that the average time from biopsy to surgery was 28 days, it was longer for 63.5% of participants; surgeon perception of maximum time between diagnosis and surgery was 84 days and longer for 28.7% of participants. Conclusions: Patient factors such as race, income, and comorbidities were found to have differences in time-to-treatment initiation. Delays to surgery exceeded the expectations of thoracic surgeons.

Chirped Laser Pulse Control of Vibronic Wavepackets and Energy Transfer in Phycocyanin 645.

Photosynthetic organisms use light-harvesting complexes to increase the spectrum of light that they absorb from solar photons. Recent ultrafast spectroscopic studies have revealed that efficient (sub-ps) energy transfer is mediated by vibronic coherence in the phycobiliprotein phycocyanin 645 (PC645). Here, we report studies that employ broadband pump-probe spectroscopy with linearly chirped excitation pulses to further investigate the relationship between vibronic state preparation and energy transfer dynamics in PC645. Negatively chirped pulse excitation is found to enhance wavepackets of a high-frequency mode (1580 cm-1) and increase the rate of downhill energy transfer, while on the other hand, positively chirped pulses suppress these oscillatory features and decrease this rate. Model calculations incorporating the influence of the chirped pump pulse are used to understand its effect on initial state preparation. These results provide mechanistic insight into how the overall nonequilibrium rate of energy transfer is influenced by initial state preparation.

Large-scale CRISPR screen reveals context-specific genetic regulation of retinal ganglion cell regeneration.

Many genes are known to regulate retinal regeneration following widespread tissue damage. Conversely, genes controlling regeneration following limited cell loss, per degenerative diseases, are undefined. As stem/progenitor cell responses scale to injury levels, understanding how the extent and specificity of cell loss impact regenerative processes is important. Here, transgenic zebrafish enabling selective retinal ganglion cell (RGC) ablation were used to identify genes that regulate RGC regeneration. A single cell multiomics-informed screen of 101 genes identified seven knockouts that inhibited and eleven that promoted RGC regeneration. Surprisingly, 35 of 36 genes known/implicated as being required for regeneration following widespread retinal damage were not required for RGC regeneration, and seven even enhanced regeneration kinetics, including proneural factors neurog1, olig2, and ascl1a. Mechanistic analyses revealed ascl1a disruption increased the propensity of progenitor cells to produce RGCs; i.e., increased "fate bias". These data demonstrate plasticity in how Müller glia can convert to a stem-like state and context-specificity in how genes function during regeneration. Increased understanding of how the regeneration of disease-relevant cell types is specifically controlled will support the development of disease-tailored regenerative therapeutics.

Single-modulator, dual comb serrodyne spectroscopy.

Dual optical frequency comb spectroscopy allows for high speed, broadband measurements without any moving parts. Here, we combine differential chirp downconversion to probe large spectral bandwidths and serrodyne modulation to separate the positive and negative sidebands in a single modulator. As an initial demonstration, we apply this approach to measure a sharp cavity resonance to illustrate the system performance. We then measure methane transitions in the near-infrared and compare the resulting spectra to models based upon the current spectroscopic databases. The serrodyne method has lower hardware requirements compared to many existing approaches, and its simplicity enables a high degree of mutual coherence between the two combs. Further, this method is readily amenable to chip-scale photonic integration.

A nonoscillatory, millisecond-scale embedding of brain state provides insight into behavior.

The most robust and reliable signatures of brain states are enriched in rhythms between 0.1 and 20 Hz. Here we address the possibility that the fundamental unit of brain state could be at the scale of milliseconds and micrometers. By analyzing high-resolution neural activity recorded in ten mouse brain regions over 24 h, we reveal that brain states are reliably identifiable (embedded) in fast, nonoscillatory activity. Sleep and wake states could be classified from 100 to 101 ms of neuronal activity sampled from 100 µm of brain tissue. In contrast to canonical rhythms, this embedding persists above 1,000 Hz. This high-frequency embedding is robust to substates, sharp-wave ripples and cortical on/off states. Individual regions intermittently switched states independently of the rest of the brain, and such brief state discontinuities coincided with brief behavioral discontinuities. Our results suggest that the fundamental unit of state in the brain is consistent with the spatial and temporal scale of neuronal computation.

Electrophile Determines Cellular Phenotypes among XPO1-Targeting Small Molecules.

Covalent drug discovery has experienced a renaissance, with numerous electrophilic small molecules recently gaining FDA approval. Many structurally diverse electrophilic small molecules target exportin-1 (XPO1/CRM1) at cysteine 528, including the selective inhibitor of nuclear export (SINE) selinexor, which was FDA-approved as an anticancer agent in 2019. Emerging evidence supports additional pharmacological classes of XPO1 modulators targeting Cys528, including the selective inhibitors of transcriptional activation (SITAs) and probes that induce rapid degradation of XPO1. Here, we analyzed structure-activity relationships across multiple structural series of XPO1 Cys528-targeting probes. We observe that the electrophilic moiety of Cys528-targeting small molecules plays a decisive role in the cellular behavior observed, with subtle changes in electrophile structure being sufficient to convert XPO1-targeting probes to different pharmacological classes. This investigation represents a unique case study in which the electrophile functionality used to target a specific cysteine determines the pharmacological effect among diverse XPO1-targeting small molecules.

In vitro evaluation of flow diverter performance using a human fibrinogen-based flow model.

OBJECTIVE: Fibrin deposition represents a key step in aneurysm occlusion, promoting endothelization of implants and connective tissue organization as part of the aneurysm-healing mechanism. In this study, the authors introduce a novel in vitro testing platform for flow diverters based on human fibrinogen. METHODS: A flow diverter was deployed in 4 different glass models. The glass models had the same internal parent artery (4 mm) and aneurysm (8 mm) diameters with varying parent artery angulations (paraophthalmic, sidewall, bifurcation, and slightly curved models). The neck size and area were 4 mm and 25 mm2, respectively. Human fibrinogen (330 mg/dl) was circulated within the glass models at varying flow rates (0, 3, 4, and 5 ml/sec) with or without heparin, calcium chloride, and thrombin for as long as 6 hours or until complete fibrin coverage of the flow diverter's neck was achieved. Aneurysm neck coverage was defined as macroscopic fibrin deposition occluding the flow diverters' pores. Flow characteristics after flow diverter deployment were assessed with computational fluid dynamics analysis. The effects of flow rates, heparin, calcium chloride, and thrombin on fibrin deposition rates were tested using 1-way ANOVA and the Tukey test. RESULTS: A total of 84 replicates were performed. Human fibrin did not accumulate on the flow diverter stents under static conditions. The fibrin deposition rate on the aneurysm neck was significantly greater with the 5 ml/sec flow rate as compared to 3 ml/sec for all models. The paraophthalmic model had the highest inflow velocity of 48.7 cm/sec. The bifurcation model had the highest maximum shear stress (SS) and maximum normalized shear stress values at the device cells at 843.3 dyne/cm2 and 35.1 SS/SSinflow, respectively. The fibrin deposition rates of the paraophthalmic and bifurcation models were significantly higher than those of sidewall and slightly curved models for all additive or flow rate comparisons (p = 0.001 for all comparisons). The incorporation of thrombin significantly increased the fibrin deposition rates across all models (p = 0.001 for all models). CONCLUSIONS: Rates of fibrin deposition varied widely across different configurations and additive conditions in this novel in vitro model system. Fibrin accumulation started at the aneurysm inflow zone where flow velocity and shear stress were the highest. The primary factors influencing fibrin deposition included flow velocities, shear stress, and the addition of thrombin at a physiological concentration. Further research is needed to test the clinical utility of fibrinogen-based models for patient-specific aneurysms.

White Matter Hyperintensities and Mild TBI in Post-9/11 Veterans and Service Members.

INTRODUCTION: The neurobehavioral significance of white matter hyperintensities (WMHs) seen on magnetic resonance imaging after traumatic brain injury (TBI) remains unclear, especially in Veterans and Service Members with a history of mild TBI (mTBI). In this study, we investigate the relation between WMH, mTBI, age, and cognitive performance in a large multisite cohort from the Long-term Impact of Military-relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium. MATERIALS AND METHODS: The neuroimaging and neurobehavioral assessments for 1,011 combat-exposed, post-9/11 Veterans and Service Members (age range 22-69 years), including those with a history of at least 1 mTBI (n = 813; median postinjury interval of 8 years) or negative mTBI history (n = 198), were examined. RESULTS: White matter hyperintensities were present in both mTBI and comparison groups at similar rates (39% and 37%, respectively). There was an age-by-diagnostic group interaction, such that older Veterans and Service Members with a history of mTBI demonstrated a significant increase in the number of WMHs present compared to those without a history of mTBI. Additional associations between an increase in the number of WMHs and service-connected disability, insulin-like growth factor-1 levels, and worse performance on tests of episodic memory and executive functioning-processing speed were found. CONCLUSIONS: Subtle but important clinical relationships are identified when larger samples of mTBI participants are used to examine the relationship between history of head injury and radiological findings. Future studies should use follow-up magnetic resonance imaging and longitudinal neurobehavioral assessments to evaluate the long-term implications of WMHs following mTBI.

Disparities in unintentional drowning fatalities in Texas, USA, 1999-2020.

BACKGROUND: Drowning is the third-leading cause of unintentional injury death worldwide. Although the USA as a whole bears a heavy burden, with approximately 4000 drowning fatalities annually, Texas stands out as a high-risk state for drowning due to its large population, suitable climate for year-round aquatic activities and availability of water-related recreational opportunities. METHODS: Using mortality data from the Centers for Disease Control and Prevention Wide-ranging ONline Data for Epidemiologic Research online database, this retrospective, cross-sectional study overviews the magnitude and patterns of fatal unintentional drownings among Texans from 1999 to 2020. RESULTS: Over the 22-year period, 7737 Texans died from unintentional drowning. An average of 352 drowning deaths occurred annually, with a rate of 1.4 deaths per 100 000 population. The highest proportion of unintentional drownings occurred in natural water settings (eg, lakes, ponds or rivers), accounting for 40% of fatal drownings. Children aged 1-4 years had the highest drowning death rate compared with all other age groups. Male Texans had a drowning death rate three times higher than that of female Texans. Black Texans had a higher drowning death rate than White Texans and Asian or Pacific Islander Texans. CONCLUSIONS: Drowning remains a significant public health issue in Texas. Data on high-risk groups and settings should be used to strengthen drowning prevention efforts and policy initiatives and encourage more research to address the multifaceted factors contributing to drowning.

Cbl and Cbl-b ubiquitin ligases are essential for intestinal epithelial stem cell maintenance.

Receptor tyrosine kinases (RTKs) control stem cell maintenance vs. differentiation decisions. Casitas B-lineage lymphoma (CBL) family ubiquitin ligases are negative regulators of RTKs, but their stem cell regulatory roles remain unclear. Here, we show that Lgr5+ intestinal stem cell (ISC)-specific inducible Cbl-knockout (KO) on a Cblb null mouse background (iDKO) induced rapid loss of the Lgr5 Hi ISCs with transient expansion of the Lgr5 Lo transit-amplifying population. LacZ-based lineage tracing revealed increased ISC commitment toward enterocyte and goblet cell fate at the expense of Paneth cells. Functionally, Cbl/Cblb iDKO impaired the recovery from radiation-induced intestinal epithelial injury. In vitro, Cbl/Cblb iDKO led to inability to maintain intestinal organoids. Single-cell RNA sequencing in organoids identified Akt-mTOR (mammalian target of rapamycin) pathway hyperactivation upon iDKO, and pharmacological Akt-mTOR axis inhibition rescued the iDKO defects. Our results demonstrate a requirement for Cbl/Cblb in the maintenance of ISCs by fine-tuning the Akt-mTOR axis to balance stem cell maintenance vs. commitment to differentiation.

Triple Aspiration Versus Conventional Aspiration Techniques: A Randomized In-Vitro Evaluation.

BACKGROUND AND PURPOSE: A single aspiration maneuver using a large volume syringe is a common and effective technique for aspiration thrombectomy. Multiple aspiration cycles using large aspiration syringes has been proposed as a means to improve efficacy over single aspiration. In this study, we sought to investigate the efficacy of a "triple aspiration technique" where a large volume syringe is cycled three times prior to catheter retraction during aspiration thrombectomy. MATERIALS AND METHODS: A 3D-printed adult vasculature was used as a benchtop thrombectomy platform. Fibrin-rich and red blood cell-rich clots were prepared in centrifuge tubes using human plasma, red blood cells, and calcium chloride. Next, clots were placed in the carotid terminus of the model, and the performances of three different aspiration techniques-triple syringe, single syringe, and continuous pump aspiration-were compared in a randomized manner (1:1:1). Outcomes of interest included first-pass efficacy (FPE), complete clot removal (final mTICI 2c/3), the number of thrombectomy attempts to achieve mTICI 2c/3, vacuum pressure, and distal embolization. The distal emboli were detected using a 70-micron cell strainer placed at the outflow of the model and quantified using an image processing algorithm. The vacuum pressures were measured using a pressure transducer (Honeywell, NC, USA). RESULTS: A total of 102 replicates were performed, 34 for each technique. The triple aspiration technique provided a significantly higher rate of FPE than the syringe and pump aspiration techniques (67.6% vs. 41.1%, p= 0.02). Additionally, the triple aspiration technique achieved complete clot removal with a significantly lower number of thrombectomy attempts compared to single syringe aspiration (1.2 ± 0.5 vs. 1.8 ± 0.8, p=0.005). The triple aspiration technique generated significantly higher vacuum pressure than both the single syringe and vacuum pump aspiration (28.3 ± 0.2 vs. 27.2 ± 0.3 (p= 0.002) and 26.2 ± 0.4 (p=0.001), respectively). The differences in complete clot removal and distal embolization parameters were not statistically significantly different across the groups. CONCLUSIONS: Our findings suggest that the triple aspiration technique can improve FPE rates and vacuum pressure in aspiration thrombectomy. Further studies are needed to examine the safety and efficacy of triple aspiration in the clinical setting. ABBREVIATIONS: AcommA = anterior communicating artery; FPE = first pass efficacy; ICA = internal carotid artery; MCA = middle cerebral artery; MT = mechanical thrombectomy; mTICI = modified thrombolysis in cerebral infarction scale; PcommA = posterior communicating artery.

Generation and Characterization of Ex Vivo Expanded Tumor-infiltrating Lymphocytes From Renal Cell Carcinoma Tumors for Adoptive Cell Therapy.

Autologous therapeutic tumor-infiltrating lymphocyte (TIL) therapy is a promising strategy to enhance antitumor immunity. Optimization of ex vivo TIL expansion could expand current immunotherapy options. Previous attempts to generate TIL in renal cell carcinoma (RCC) have been technically challenging. We applied a second-generation manufacturing process, currently used to generate the melanoma TIL product lifileucel, in RCC. Resected primary and metastatic RCC samples were processed using the Gen 2 manufacturing process comprising of pre-Rapid Expansion Protocol (pre-REP) and REP steps. We assessed REP TILs for viability and performed phenotypic and functional characterization. We correlated the tumor immune microenvironment (TIME) with successful TIL expansion. Eight of 11 RCC samples underwent successful REP. Three failed cases demonstrated low CD8/FoxP3 ratio and high expression of PD-1 within FoxP3 cells. Expression of exhaustion markers differed between the TIME and expanded TILs; the latter had a TIM3-high/PD-1-low phenotype but retained functional capacity comparable to lifileucel. The Gen 2 manufacturing process used for lifileucel successfully expanded functional TILs from RCC samples, enabling further study in a clinical trial. TIME features such as low CD8/FoxP3 ratio and high PD-1 expression within FoxP3 cells warrant study as potential biomarkers of successful TIL expansion.

Increased PVR Expression on Bone Marrow Macrophages May Promote Resistance to TIGIT Blockade in Multiple Myeloma.

PURPOSE: TIGIT blockade in our ex vivo models of bone marrow (BM) reduced the number of malignant plasma cells (PCs) in only half of patients with multiple myeloma (MM). Here we wanted to investigate whether increased expression of TIGIT ligands may inhibit T cell immune response promoting resistance to TIGIT blockade. EXPERIMENTAL DESIGN: We first characterized the number and phenotype of BM macrophages in the different stages of disease by multi-parameter flow cytometry. We assessed the effect of TIGIT ligands on PC survival performing experiments with ex vivo BM model and analyzed changes in gene expression by using Nanostring technology and real-time PCR. RESULTS: Frequency of BM macrophages was significantly decreased in MM which was accompanied by changes in their immunophenotype. Moreover, we found a higher number of malignant PCs in ex vivo BM cells cultured onto PVR and nectin-2 compared to control, suggesting that both ligands may support PC survival. In addition, presence of PVR, but not nectin-2, overcame the therapeutic effect of TIGIT blockade or exogenous IL-2. Furthermore, presence of exogenous IL-2 increased TIGIT expression on both CD4+ and CD8+ T cells and, indirectly, PVR on BM macrophages. Consistently, PVR reduced the number of cytotoxic T cells and promoted a gene signature with reduced effector molecules. CONCLUSIONS: IL-2 induced TIGIT on T cells in the BM where increased PVR expression resulted in cytotoxic T cell inhibition promoting PC survival and resistance to TIGIT blockade.

Geometric deep learning-guided Suzuki reaction conditions assessment for applications in medicinal chemistry.

Suzuki cross-coupling reactions are considered a valuable tool for constructing carbon-carbon bonds in small molecule drug discovery. However, the synthesis of chemical matter often represents a time-consuming and labour-intensive bottleneck. We demonstrate how machine learning methods trained on high-throughput experimentation (HTE) data can be leveraged to enable fast reaction condition selection for novel coupling partners. We show that the trained models support chemists in determining suitable catalyst-solvent-base combinations for individual transformations including an evaluation of the need for HTE screening. We introduce an algorithm for designing 96-well plates optimized towards reaction yields and discuss the model performance of zero- and few-shot machine learning. The best-performing machine learning model achieved a three-category classification accuracy of 76.3% (±0.2%) and an F 1-score for a binary classification of 79.1% (±0.9%). Validation on eight reactions revealed a receiver operating characteristic (ROC) curve (AUC) value of 0.82 (±0.07) for few-shot machine learning. On the other hand, zero-shot machine learning models achieved a mean ROC-AUC value of 0.63 (±0.16). This study positively advocates the application of few-shot machine learning-guided reaction condition selection for HTE campaigns in medicinal chemistry and highlights practical applications as well as challenges associated with zero-shot machine learning.

Cumulative Donor-Specific Antibody Threshold Predicts Platelet Transfusion Response in HLA-Alloimmunized Patients.

Up to a third of multiply transfused patients with hemato-oncologic conditions develop immune-mediated platelet transfusion refractoriness. Yet factors that influence post-transfusion platelet corrected count increments (CCI) in patients with human leukocyte antigen (HLA)-alloimmune platelet transfusion refractoriness remain less well elucidated. Recent advances in HLA antibody characterization using fluorescent bead-based platforms enable the study of donor-specific antibody (DSA) avidity (as measured by mean fluorescence intensity, MFI) and its impact on HLA-alloimmune platelet transfusion refractoriness. In this large retrospective study of 2,012 platelet transfusions among 73 HLA-alloimmunized patients, we evaluated the impact of cumulative HLA DSA-MFI alongside other donor, platelet component, and patient characteristics on CCI at 2 and 24-hours post-transfusion. As part of a quality improvement initiative, we also developed and tested a computerized algorithm to optimize donor-recipient histocompatibility based on cumulative DSA-MFI and sought other actionable predictors of CCI. In multivariate analyses, cumulative HLA DSA-MFI ≥ 10,000, major/bidirectional ABO-mismatch, splenomegaly, transfusion reactions, and platelet storage in additive solution negatively impacted 2-hour but not 24-hour post-transfusion CCI. The DSA-MFI threshold of 10,000 was corroborated by greater antibody-mediated complement activation and significantly more CCI failures above this threshold, suggesting the usefulness of this value to inform "permissive platelet mismatching" and to optimize CCI. Further, DSA-MFI decreases were deemed feasible by the computer-based algorithm for HLA-platelet selection in a pilot cohort of 8 patients (122 transfusions) evaluated before and after algorithm implementation. Where HLA-selected platelets are unavailable, ABO-identical/minor-mismatched platelet concentrates may enhance 2-hour CCI in heavily HLA-alloimmunized patients with platelet transfusion refractoriness.

Voices of Wisdom: Geriatric Interviews on Self-Management of Type 2 Diabetes in the United States-A Systematic Review and Metasynthesis.

This review is aimed at unraveling the intricacies of diabetic self-management among geriatric people, drawing on current insights and understanding the complex paths geriatric people navigate. A wide search was conducted in health-oriented databases, including CINAHL, Embase, PsycINFO, MEDLINE, PubMed, Web of Science, and Cochrane Library, while gray literature was excluded. The search combined keywords and subject headings, focusing on the geriatric population, diabetes, self-management, and qualitative research. A three-tiered screening process was employed, with titles and then abstracts initially reviewed. Full-text analysis followed, with disagreements resolved among reviewers. In total, there were 248 participants included across these eight studies. Positive attitudes and perceptions were found to play a significant role in optimizing diabetes self-care outcomes. Support from family and friends was identified as crucial for self-care, while healthcare professionals often lacked adequate support and encouragement. Participants emphasized the importance of listening to their bodies and acknowledging hidden issues. These themes collectively highlight the multifaceted aspects of diabetes self-care and the impact of various factors on the self-management experiences of geriatric individuals with diabetes. The goal of this review is not to objectify self-management as a treatment strategy but to emphasize the importance of cultivating positive attitudes, respecting individual values, and addressing cultural and ethnic differences in healthcare practices to enhance self-management in this population. By embracing cultural diversity, understanding barriers, and respecting individual values, healthcare professionals and policymakers can improve the quality of life for the geriatric population living with diabetes.

Workload and spirometry associated with untethered swimming in horses.

BACKGROUND: Swimming has been used empirically for rehabilitation and conditioning of horses. However, due to challenges imposed by recording physiological parameters in water, the intensity of free swimming effort is unknown. OBJECTIVES: Measure the physiological workload associated with untethered swimming in horses. Five fit Arabian endurance horses were assessed while swimming in a 100 m-long indoor pool. Horses were equipped with a modified ergospirometry facemask to measure oxygen consumption (V̇O2) and ventilatory parameters (inspired/expired volumes, VI, VE; peak inspiratory/expiratory flows, PkVI, PkVE; respiratory frequency, Rf; minute ventilation, VE; inspiratory/expiratory durations and ratios, tI, tE, tI/ttot, tE/ttot); and an underwater electrocardiogram that recorded heart rate (HR). Postexercise venous blood lactate and ammonia concentrations were measured. Data are reported as median (interquartile ranges). RESULTS: Horses showed bradypnea (12 breaths/min (10-16)) for the first 30 s of swimming. V̇O2 during swimming was 43.2 ml/(kg.min) (36.0-56.6). Ventilatory parameters were: VI = 16.7 L (15.3-21.8), VE = 14.7 L (12.4-18.9), PkVI = 47.8 L/s (45.8-56.5), PkVE = 55.8 L/s (38.3-72.5), Rf = 31.4 breaths/min (20.0-33.8), VE = 522.9 L/min (414.7-580.0), tI = 0.5 s (0.5-0.6), tE = 1.2 s (1.1-1.6), tI/ttot = 0.3 (0.2-0.4), tE/ttot = 0.7 (0.6-0.8). Expiratory flow tracings showed marked oscillations that coincided with a vibrating expiratory sound. HR was 178.0 bpm (148.5-182.0), lactate = 1.5 mmol/L (1.0-1.9) and ammonia = 41.0 µmol/L (36.5-43.5). CONCLUSIONS: Free (untethered) swimming represents a submaximal, primarily aerobic exercise in horses. The breathing pattern during swimming is unique, with a relatively longer apneic period at the beginning of the exercise and an inspiratory time less than half that of expiration.