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Heart, Lung & Circulation Jun 2024Acute pulmonary embolism (PE) is a significant cause of mortality in the hospital setting. The objective of this study was to outline the long-term outcomes after...
AIM
Acute pulmonary embolism (PE) is a significant cause of mortality in the hospital setting. The objective of this study was to outline the long-term outcomes after surgical and non-surgical management for patients with massive and submassive PE.
METHODS
Population cohort observational study evaluating all patients who presented to three tertiary hospitals in the state of Western Australia with access to cardiothoracic services over 5 years (2013-2018). Reviewed notes of all patients as well as radiology, linked mortality data and all available echocardiography studies at the primary hospital.
RESULTS
In total, 245 patients were identified, of which 41 received surgical management and 204 non-surgical management; demographic data was similar. Clinically, the surgical group had higher rates of shock requiring vasopressors, severe bradycardia, or cardiopulmonary resuscitation prior to intervention. The 28-day mortality was not statistically significantly different between the surgical embolectomy group (2/41 [4.2%]) and the non-surgical group (17/201 [8.3%]) (p=0.382). There was no difference in 12-month mortality, including when this was adjusted for vasopressors, right ventricular (RV) strain, troponin, and brain natriuretic peptide. In the massive PE sub-group, 28-day mortality was not significantly different: 2/29 (6.9%) surgical group vs 7/34 (20.2%) non-surgical group (p=0.064). Higher rates of severe RV impairment and dilatation were present in the surgical group. All patients with available echocardiography studies at outpatient follow-up returned to normal or mild RV impairment.
CONCLUSION
Patients who presented with massive or submassive PE had similar outcomes whether treated with surgical or non-surgical management. Surgical embolectomy is a safe option in a cardiothoracic centre setting.
PubMed: 38942622
DOI: 10.1016/j.hlc.2024.03.014 -
Organic Letters Jun 2024A light-mediated cyclization reaction initiated by an atom transfer radical addition (ATRA) of haloalkanes onto alkenes was exploited for the synthesis of functionalized...
A light-mediated cyclization reaction initiated by an atom transfer radical addition (ATRA) of haloalkanes onto alkenes was exploited for the synthesis of functionalized dihydrobenzofurans. Initial investigation indicated that the dimeric gold catalyst [Au(μ-dppm)Cl] can effectively be used for intermolecular ATRA reactions. Further, the reactivity was applied in a cascade-like cyclization for the preparation of dihydrobenzofuran derivatives. With the presented photochemical approach, the functionalization can be achieved directly from -allylphenols in yields of up to 96% under mild conditions.
PubMed: 38941620
DOI: 10.1021/acs.orglett.4c01626 -
JMIR Research Protocols Jun 2024Osteoarthritis (OA) is a disabling condition that affects more than one-third of people older than 65 years. Currently, 80% of these patients report movement...
Assessment of the Feasibility of Objective Parameters as Primary End Points for Patients Affected by Knee Osteoarthritis: Protocol for a Pilot, Open Noncontrolled Trial (:SMILE:).
BACKGROUND
Osteoarthritis (OA) is a disabling condition that affects more than one-third of people older than 65 years. Currently, 80% of these patients report movement limitations, 20% are unable to perform major activities of daily living, and approximately 11% require personal care. In 2014, the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) recommended, as the first step in the pharmacological treatment of knee osteoarthritis, a background therapy with chronic symptomatic slow-acting osteoarthritic drugs such as glucosamine sulfate, chondroitin sulfate, and hyaluronic acid. The latter has been extensively evaluated in clinical trials as intra-articular and oral administration. Recent reviews have shown that studies on oral hyaluronic acid generally measure symptoms using only subjective parameters, such as visual analog scales or quality of life questionnaires. As a result, objective measures are lacking, and data validity is generally impaired.
OBJECTIVE
The main goal of this pilot study with oral hyaluronic acid is to evaluate the feasibility of using objective tools as outcomes to evaluate improvements in knee mobility. We propose ultrasound and range of motion measurements with a goniometer that could objectively correlate changes in joint mobility with pain reduction, as assessed by the visual analog scale. The secondary objective is to collect data to estimate the time and budget for the main double-blind study randomized trial. These data may be quantitative (such as enrollment rate per month, number of screening failures, and new potential outcomes) and qualitative (such as site logistical issues, patient reluctance to enroll, and interpersonal difficulties for investigators).
METHODS
This open-label pilot and feasibility study is conducted in an orthopedic clinic (Timisoara, Romania). The study includes male and female participants, aged 50-70 years, who have been diagnosed with symptomatic knee OA and have experienced mild joint discomfort for at least 6 months. Eight patients must be enrolled and treated with Syalox 300 Plus (River Pharma) for 8 weeks. It is a dietary supplement containing high-molecular-weight hyaluronic acid, which has already been marketed in several European countries. Assessments are made at the baseline and final visits.
RESULTS
Recruitment and treatment of the 8 patients began on February 15, 2018, and was completed on May 25, 2018. Data analysis was planned to be completed by the end of 2018. The study was funded in February 2019. We expect the results to be published in a peer-reviewed clinical journal in the last quarter of 2024.
CONCLUSIONS
The data from this pilot study will be used to assess the feasibility of a future randomized clinical trial in OA. In particular, the planned outcomes (eg, ultrasound and range of motion), safety, and quantitative and qualitative data must be evaluated to estimate in advance the time and budget required for the future main study. Finally, the pilot study should provide preliminary information on the efficacy of the investigational product.
TRIAL REGISTRATION
ClinicalTrials.gov NCT03421054; https://clinicaltrials.gov/study/NCT03421054.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)
RR1-10.2196/13642.
Topics: Humans; Osteoarthritis, Knee; Pilot Projects; Feasibility Studies; Hyaluronic Acid; Male; Female; Aged; Middle Aged; Quality of Life; Endpoint Determination
PubMed: 38941599
DOI: 10.2196/13642 -
ACS Applied Materials & Interfaces Jun 2024Li-ion battery degradation and safety events are often attributed to undesirable metallic lithium plating. Since their release, Li-ion battery electrodes have been made...
Li-ion battery degradation and safety events are often attributed to undesirable metallic lithium plating. Since their release, Li-ion battery electrodes have been made progressively thicker to provide a higher energy density. However, the propensity for plating in these thicker pairings is not well understood. Herein, we combine an experimental plating-prone condition with robust mesoscale modeling to examine electrode pairings with capacities ranging from 2.5 to 6 mAh/cm and negative to positive (N/P) electrode areal capacity ratio from 0.9 to 1.8 without the need for extensive aging tests. Using both experimentation and a mesoscale model, we identify a shift from conventional high state-of-charge (SOC) type plating to high overpotential (OP) type plating as electrode thickness increases. These two plating modes have distinct morphologies, identified by optical microscopy and electrochemical signatures. We demonstrate that under operating conditions where these plating modes converge, a high propensity of plating exists, revealing the importance of predicting and avoiding this overlap for a given electrode pairing. Further, we identify that thicker electrodes, beyond a capacity of 3 mAh/cm or thickness >75 μm, are prone to high OP, limiting negative electrode (NE) utilization and preventing cross-sectional oversizing the NE from mitigating plating. Here, it simply contributes to added mass and volume. The experimental thermal gradient and mesoscale model either combined or independently provide techniques capable of probing performance and safety implications of mild changes to electrode design features.
PubMed: 38941578
DOI: 10.1021/acsami.4c02516 -
Blood Advances Jun 2024Megakaryocytes (MKs) produce platelets, and like other hematopoietic progenitors they are involved in homeostatic aspects of their bone marrow niche. MKs release and...
Megakaryocytes (MKs) produce platelets, and like other hematopoietic progenitors they are involved in homeostatic aspects of their bone marrow niche. MKs release and endocytose various factors, such as platelet factor 4 (PF4/CXCL4). Here we show that the intra-α-granular proteoglycan, serglycin (SRGN) plays a key role in this process by retaining PF4 and perhaps other factors during MK maturation. Immature, SRGN-/- MKs released ~80% of their PF4 and conditioned media from these cells negatively affected wild-type MK differentiation in vitro. This was replicated in wild-type MKs, by treatment with the polycation surfen, a known inhibitor of glycosaminoglycan/protein interactions. In vivo, SRGN-/- mice had an interstitial accumulation of PF4, TGFβ-1, IL-1β, and TNF-α in their bone marrow and increased numbers of immature MKs, consistent with their mild thrombocytopenia. SRGN-/- mice also had reduced numbers of hematopoietic stem cells and multipotent progenitors, reduced laminin, and increased collagen I deposition. These findings demonstrate that MKs depend on SRGN and its charged glycosaminoglycans to balance the distribution of PF4 and perhaps other factors between their α-granules and their adjacent extracellular spaces. Disrupting this balance negatively affects MK development and bone marrow microenvironment homeostasis.
PubMed: 38941534
DOI: 10.1182/bloodadvances.2024012995 -
Medicine Jun 2024Taiwan is an aging society, and the number of people with dementia is rapidly increasing. Due to a decline in cognitive and physical function, older adults with dementia...
BACKGROUND
Taiwan is an aging society, and the number of people with dementia is rapidly increasing. Due to a decline in cognitive and physical function, older adults with dementia not only gradually lose the ability to complete daily living tasks on their own, but are also at a higher risk of falls and injurious falls. It is important to develop interventions that combine cognitive and exercise training for older adults with dementia to promote or maintain their cognitive and physical functions and reduce their risk of falls. This study aimed to investigate the feasibility and effect of cognitive-based board games and multi-component exercise interventions on cognitive function, physical fitness, and fall risk in older adults with dementia.
METHODS
This was a quasi-experimental study with a single-group pretest and post-test design. The study participants were 41 community-dwelling older adults with mild to moderate dementia. They received cognitive-based board games and multi-component exercise interventions once a week for 12 weeks. The interventions included 1 hour of exercise training and 1 hour of cognitive training. Scores for the Taiwan version of the Montreal Cognitive Assessment (MoCA-T), physical fitness, and the St. Thomas Risk Assessment Tool for Falling Elderly Inpatients (STRATIFY) were measured as outcome indicators at baseline and after the 12-week period.
RESULTS
The overall MoCA-T score increased significantly (effect size = 0.402), with participants with mild dementia showing a greater increase (effect size = 0.522) than those with moderate dementia (effect size = 0.310). Participants' physical fitness performance improved. Female participants exhibited significant improvements in the 30-second chair stand test (effect size = 0.483) and 8-foot up-and-go test (effect size = 0.437). The fall risk score decreased by 0.05 points, the change was not significant.
CONCLUSION
The cognitive-based board game and multi-component exercise interventions used in this study are beneficial for improving cognitive function and physical fitness in older adults with dementia. These interventions are feasible and suitable for promotion among community-dwelling and institution-dwelling older adults with mild cognitive impairment or dementia to delay the decline in cognitive and physical function.
Topics: Humans; Female; Male; Aged; Dementia; Feasibility Studies; Exercise Therapy; Accidental Falls; Aged, 80 and over; Taiwan; Cognition; Physical Fitness; Games, Recreational; Independent Living
PubMed: 38941425
DOI: 10.1097/MD.0000000000038640 -
Medicine Jun 2024This is a prospective cohort study to investigate the effects of instrumented lumbar fusion surgery on psychiatric problems, including anxiety, insomnia, and depression,... (Observational Study)
Observational Study
This is a prospective cohort study to investigate the effects of instrumented lumbar fusion surgery on psychiatric problems, including anxiety, insomnia, and depression, in patients with degenerative spinal stenosis, as well as on pain and the activities of daily living. Surgery was performed in the patients with Schizas grade C or D spinal stenosis with; if a patient's quality of life was impaired for at least 3 months or if patient had neurologic deficits. Finally, 69 patients were reviewed. Beck anxiety inventory, insomnia severity index, geriatric depression scale short form-Korean, visual analog scale for back pain, visual analog scale for leg pain, and Oswestry disability index was measured on the day surgery was decided on (T1), the day before surgery (T2), the day before discharge (T3), and 6 months after surgery (T4). The patients had mild degrees of anxiety, insomnia, and depression at T1, and Beck anxiety inventory, insomnia severity index, visual analog scale for back pain, visual analog scale for leg pain, and Oswestry disability index improved significantly by T4. In elderly patients with degenerative spinal stenosis, instrumented lumbar fusion surgery improves not only pain and activities of daily living, but also anxiety and insomnia. However, there was no improvement in depression over the 6-month follow-up period.
Topics: Humans; Aged; Spinal Stenosis; Female; Male; Spinal Fusion; Prospective Studies; Lumbar Vertebrae; Activities of Daily Living; Anxiety; Quality of Life; Depression; Sleep Initiation and Maintenance Disorders; Aged, 80 and over; Pain Measurement; Middle Aged
PubMed: 38941422
DOI: 10.1097/MD.0000000000038719 -
PloS One 2024A growing increase in the number of serious infections caused by multidrug resistant bacteria (MDR) is challenging our society. Despite efforts to discover novel...
A growing increase in the number of serious infections caused by multidrug resistant bacteria (MDR) is challenging our society. Despite efforts to discover novel therapeutic options, few antibiotics targeting MDR have been approved by the Food and Drug Administration (FDA). Lactic acid bacteria have emerged as a promising therapeutic alternative due to their demonstrated ability to combat MDR pathogens in vitro. Our previous co-culture studies showed Lacticaseibacillus rhamnosus CRL 2244 as having a potent killing effect against carbapenem-resistant Acinetobacter baumannii (CRAB) strains. Here we report that cell-free conditioned media (CFCM) samples obtained from Lcb. rhamnosus CRL 2244 cultures incubated at different times display antimicrobial activity against 43 different pathogens, including CRAB, methicillin-resistant Staphylococcus aureus (MRSA) and carbapenemase Klebsiella pneumoniae (KPC)-positive strains. Furthermore, transwell and ultrafiltration analyses together with physical and chemical/biochemical tests showed that Lcb. rhamnosus CRL 2244 secretes a <3 kDa metabolite(s) whose antimicrobial activity is not significantly impaired by mild changes in pH, temperature and various enzymatic treatments. Furthermore, sensitivity and time-kill assays showed that the bactericidal activity of the Lcb. rhamnosus CRL 2244 metabolite(s) enhances the activity of some current FDA approved antibiotics. We hypothesize that this observation could be due to the effects of Lcb. rhamnosus CRL 2244 metabolite(s) on cell morphology and the enhanced transcriptional expression of genes coding for the phenylacetate (PAA) and histidine catabolic Hut pathways, metal acquisition and biofilm formation, all of which are associated with bacterial virulence. Interestingly, the extracellular presence of Lcb. rhamnosus CRL 2244 induced the transcription of the gene coding for the CidA/LgrA protein, which is involved in programmed cell death in some bacteria. Overall, the findings presented in this report underscore the promising potential of the compound(s) released by Lcb. rhamnosus CRL2244 as an alternative and/or complementary option to treat infections caused by A. baumannii as well as other MDR bacterial pathogens.
Topics: Lacticaseibacillus rhamnosus; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Microbial Sensitivity Tests; Acinetobacter baumannii; Drug Synergism; Methicillin-Resistant Staphylococcus aureus; Culture Media, Conditioned; Bacterial Proteins
PubMed: 38941324
DOI: 10.1371/journal.pone.0306273 -
European Journal of Endocrinology Jun 2024To assess whether clinical and imaging characteristics predict hormonal subtype, growth, and adrenalectomy for incidental adrenal cortical adenomas (ACA).
OBJECTIVE
To assess whether clinical and imaging characteristics predict hormonal subtype, growth, and adrenalectomy for incidental adrenal cortical adenomas (ACA).
DESIGN
Single center cohort study.
METHODS
Consecutive adult patients with incidental ACA diagnosed between 2000 and 2016.
RESULTS
Of 1516 patients with incidental ACA (median age 59 years, 62% women), 699 (46%) had nonfunctioning adenomas (NFA), 482 (31%) had mild autonomous cortisol secretion (MACS), 62 (4%) had primary aldosteronism (PA), 39 (3%) had Cushing syndrome (CS), 18 (1%) had PA and MACS (PA-MACS), and 226 (15%) had incomplete workup. Age, sex, tumor size, and tumor laterality, but not unenhanced computed tomography Hounsfield units (HU), were associated with hormonal subtypes. In a multivariable analysis, ≥1cm growth was associated with younger age (odds ratio per 5-year increase, OR=0.8, P=0.0047) and longer imaging follow-up (OR=1.2 per year, P<.0001). Adrenalectomy was performed in 355 (23%) patients, including 38% of MACS and 15% of NFA. Adrenalectomy for NFA and MACS was more common in younger patients (OR=0.79 per 5-year increase, P=0.002), larger initial tumor size (OR=2.3 per 1-cm increase, P<.0001), ≥1cm growth (OR=15.3, P<.0001), and higher post-dexamethasone cortisol (OR=6.6 for >5 vs <1.8 mcg/dL, P=0.002).
CONCLUSIONS
Age, sex, tumor size, and laterality were associated with ACA hormonal subtype and can guide diagnosis and management. Tumor growth was more common with younger age and longer follow-up. Unenhanced HU did not predict hormonal subtype or growth. Adrenalectomy for MACS and NFA was mainly performed in younger patients with larger tumor size, growth, and elevated post-dexamethasone cortisol.
PubMed: 38941271
DOI: 10.1093/ejendo/lvae078 -
Angewandte Chemie (International Ed. in... Jun 2024Layer-stacking behaviors are crucial for two-dimensional covalent organic frameworks (2D COFs) to define their pore structure, physicochemical properties, and functional...
Layer-stacking behaviors are crucial for two-dimensional covalent organic frameworks (2D COFs) to define their pore structure, physicochemical properties, and functional output. So far, fine control over the stacking mode without complex procedures remains a grand challenge. Herein, we proposed a "key-cylinder lock mimic" strategy to synthesize 2D COFs with a tunable layer-stacking mode by taking advantage of ionic liquids (ILs). The staggered (AB) stacking (unlocked) COFs were exclusively obtained by incorporating ILs of symmetric polarity and matching molecular size; otherwise, commonly reported eclipsed (AA) stacking (locked) COFs were observed instead. Mechanistic study revealed that AB stacking was induced by a confined interlocking effect (CIE) brought by anions and bulky cations of the ILs inside pores ("key" and "cylinder", respectively). Excitingly, this strategy can speed up production rate of crystalline powders (e.g., COF-TAPT-Tf@BmimTf2N in merely 30 minutes) under mild reaction conditions. This work highlights the enabling role of ILs to tailor the layer stacking of 2D COFs and promotes further exploration of their stacking mode-dependant applications.
PubMed: 38941108
DOI: 10.1002/anie.202408453