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BMJ Open Diabetes Research & Care Jun 2024We previously reported predictors of mortality in 1786 adults with diabetes or stress hyperglycemia (glucose>180 mg/dL twice in 24 hours) admitted with COVID-19 from...
INTRODUCTION
We previously reported predictors of mortality in 1786 adults with diabetes or stress hyperglycemia (glucose>180 mg/dL twice in 24 hours) admitted with COVID-19 from March 2020 to February 2021 to five university hospitals. Here, we examine predictors of readmission.
RESEARCH DESIGN AND METHODS
Data were collected locally through retrospective reviews of electronic medical records from 1786 adults with diabetes or stress hyperglycemia who had a hemoglobin A1c (HbA1c) test on initial admission with COVID-19 infection or within 3 months prior to initial admission. Data were entered into a Research Electronic Data Capture (REDCap) web-based repository, and de-identified. Descriptive data are shown as mean±SD, per cent (%) or median (IQR). Student's t-test was used for comparing continuous variables with normal distribution and Mann-Whitney U test was used for data not normally distributed. X test was used for categorical variable.
RESULTS
Of 1502 patients who were alive after initial hospitalization, 19.4% were readmitted; 90.3% within 30 days (median (IQR) 4 (0-14) days). Older age, lower estimated glomerular filtration rate (eGFR), comorbidities, intensive care unit (ICU) admission, mechanical ventilation, diabetic ketoacidosis (DKA), and longer length of stay (LOS) during the initial hospitalization were associated with readmission. Higher HbA1c, glycemic gap, or body mass index (BMI) were not associated with readmission. Mortality during readmission was 8.0% (n=23). Those who died were older than those who survived (74.9±9.5 vs 65.2±14.4 years, p=0.002) and more likely had DKA during the first hospitalization (p<0.001). Shorter LOS during the initial admission was associated with ICU stay during readmission, suggesting that a subset of patients may have been initially discharged prematurely.
CONCLUSIONS
Understanding predictors of readmission after initial hospitalization for COVID-19, including older age, lower eGFR, comorbidities, ICU admission, mechanical ventilation, statin use and DKA but not HbA1c, glycemic gap or BMI, can help guide treatment approaches and future research in adults with diabetes.
Topics: Humans; COVID-19; Patient Readmission; Male; Female; Hyperglycemia; Middle Aged; Retrospective Studies; Aged; Glycated Hemoglobin; SARS-CoV-2; Diabetes Mellitus; Hospitalization; Adult; Risk Factors; Aged, 80 and over; Blood Glucose
PubMed: 38937276
DOI: 10.1136/bmjdrc-2024-004167 -
ENeuro Jun 2024Elevated intraocular pressure (IOP) triggers glaucoma by damaging the output neurons of the retina called retinal ganglion cells (RGCs). This leads to the loss of RGC...
Elevated intraocular pressure (IOP) triggers glaucoma by damaging the output neurons of the retina called retinal ganglion cells (RGCs). This leads to the loss of RGC signaling to visual centers of the brain such as the dorsolateral geniculate nucleus (dLGN), which is critical for processing and relaying information to the cortex for conscious vision. In response to altered levels of activity or synaptic input, neurons can homeostatically modulate postsynaptic neurotransmitter receptor numbers, allowing them to scale their synaptic responses to stabilize spike output. While prior work has indicated unaltered glutamate receptor properties in the glaucomatous dLGN, it is unknown whether glaucoma impacts dLGN inhibition. Here, using DBA/2J mice, which develop elevated IOP beginning at 6-7 months of age, we tested whether the strength of inhibitory synapses on dLGN thalamocortical relay neurons is altered in response to the disease state. We found an enhancement of feed-forward disynaptic inhibition arising from local interneurons along with increased amplitude of quantal inhibitory synaptic currents. A combination of immunofluorescence staining for the GABA-α1 receptor subunit, peak-scaled nonstationary fluctuation analysis, and measures of homeostatic synaptic scaling pointed to an approximately 1.4-fold increase in GABA receptors at post-synaptic inhibitory synapses, although several pieces of evidence indicate a non-uniform scaling across inhibitory synapses within individual relay neurons. Together, these results indicate an increase in inhibitory synaptic strength in the glaucomatous dLGN, potentially pointing toward homeostatic compensation for disruptions in network and neuronal function triggered by increased IOP. Elevated eye pressure in glaucoma leads to loss of retinal outputs to the dorsolateral geniculate nucleus (dLGN), which is critical for relaying information to the cortex for conscious vision. Alterations in neuronal activity, as could arise from excitatory synapse loss, can trigger homeostatic adaptations to synaptic function that attempt to maintain activity within a meaningful dynamic range, although whether this occurs uniformly at all synapses within a given neuron or is a non-uniform process is debated. Here, using a mouse model of glaucoma, we show that dLGN inhibitory synapses undergo non-uniform upregulation due to addition of post-synaptic GABA receptors. This is likely to be a neuronal adaptation to glaucomatous pathology in an important sub-cortical visual center.
PubMed: 38937109
DOI: 10.1523/ENEURO.0263-24.2024 -
Redox Biology Jun 2024The effects of low energy availability (LEA) on the immune system are poorly understood. This study examined the effects of 14 days of LEA on immune cell redox balance...
INTRODUCTION
The effects of low energy availability (LEA) on the immune system are poorly understood. This study examined the effects of 14 days of LEA on immune cell redox balance and inflammation at rest and in response to acute exercise, and exercise performance in female athletes.
METHODS
Twelve female endurance athletes (age: 26.8 ± 3.4 yrs, maximum oxygen uptake (V˙O): 55.2 ± 5.1 mL × min × kg) were included in a randomized, single-blinded crossover study. They were allocated to begin with either 14 days of optimal energy availability diet (OEA, 52 ± 2 kcal × kg fat free mass (FFM) × day) or LEA diet (22 ± 2 kcal × kg FFM × day), followed by 3 days of refueling (OEA) with maintained training volume. Peripheral blood mononuclear cells (PBMCs) were isolated, and plasma obtained at rest before and after each dietary period. The PBMCs were used for analysis of mitochondrial respiration and HO emission and specific proteins. Exercise performance was assessed on cycle by a 20-min time trial and time to exhaustion at an intensity corresponding to ∼110 % V˙O).
RESULTS
LEA was associated with a 94 % (P = 0.003) increase in PBMC NADPH oxidase 2 protein content, and a 22 % (P = 0.013) increase in systemic cortisol. LEA also caused an alteration of several inflammatory related proteins (P < 0.05). Acute exercise augmented HO emission in PBMCs (P < 0.001) following both OEA and LEA, but to a greater extent following LEA. LEA also reduced the mobilization of white blood cells with acute exercise. After LEA, performance was reduced in both exercise tests (P < 0.001), and the reduced time trial performance remained after the 3 days of refueling (P < 0.001).
CONCLUSION
14 days of LEA in female athletes increased cortisol levels and had a pronounced effect on the immune system, including increased capacity for ROS production, altered plasma inflammatory proteome and lowered exercise induced mobilization of leukocytes. Furthermore, LEA resulted in a sustained impairment in exercise performance.
PubMed: 38936255
DOI: 10.1016/j.redox.2024.103250 -
Developmental Cognitive Neuroscience Jun 2024Adolescent risk-taking has been attributed to earlier-developing motivational neurocircuitry that is poorly controlled by immature executive-control neurocircuitry....
Adolescent risk-taking has been attributed to earlier-developing motivational neurocircuitry that is poorly controlled by immature executive-control neurocircuitry. Functional magnetic resonance imaging findings of increased ventral striatum (VS) recruitment by reward prospects in adolescents compared to adults support this theory. Other studies found blunted VS recruitment by reward-predictive cues in adolescents compared to adults. Task features may explain this discrepancy but have never been systematically explored. Adolescents and adults performed a novel reward task that holds constant the expected value of all rewards but varies whether rewards are dependent on vigilance-intensive responding versus making a lucky choice during a relaxed response window. We examined group by sub-task contrast differences in activation of VS and more motoric regions of striatum in response to anticipatory cues. Reward anticipation in both task conditions activated portions of striatum in both groups. In voxel-wise comparison, adults showed greater anticipatory recruitment of VS in trials involving choice during a relaxed time window, not in the more vigilance-demanding trials as hypothesized. In accord with our hypotheses, however, adults showed greater activation in dorsal striatum and putamen volumes of interest during reward anticipation under vigilance-demanding conditions. Following trial outcome notifications, adolescents showed greater activation of the VS during reward notification but lower activation during loss notification. These data extend findings of cross-sectional age-group differences in incentive-anticipatory recruitment of striatum, by demonstrating in adults relatively greater recruitment of motor effector regions of striatum by attentional and motor demands.
PubMed: 38936253
DOI: 10.1016/j.dcn.2024.101412 -
International Journal of Surgery Case... Jun 2024Pierre Robin Sequence (PRS) is a rare and complex condition that often necessitates the collaboration of a full medical team from various disciplines to save the lives...
INTRODUCTION AND IMPORTANCE
Pierre Robin Sequence (PRS) is a rare and complex condition that often necessitates the collaboration of a full medical team from various disciplines to save the lives of babies with this genetic mutation, characterized by three clinical manifestations: glossoptosis, micrognathia, and cleft palate. Treatment primarily involves freeing upper airway obstructions and enhancing nutrition to allow the babies to lead a normal life. The lip-tongue adhesion procedure has been identified in medical literature as the recommended approach to addressing the issues associated with Pierre Robin sequence, and this method was successfully adopted in this case.
CASE PRESENTATION
2.5 kg, a newborn male baby with an abnormal position of the tongue and the inability to breastfeed and feed normally, without any medical, family, or social history. Following an examination, it was discovered that the baby had a posterior position of the tongue, micrognathia, and a cleft palate, leading to a diagnosis of Pierre Robin Sequence (Figs. 1, 2). Preparations for the baby's surgery have commenced. The baby was solely fed intravenously and provided with an oxygen mask for 25 days until all necessary consultations were completed and the baby's readiness for surgery and general anesthesia was confirmed. The surgical plan involved attaching the tongue to the lower lip to enhance the tongue's muscular strength, addressing the posterior position issue, and delaying the palate repair until the age of 1.5 years.
CLINICAL DISCUSSION
PRS is a clinical entity characterized by the triad of mandibular hypoplasia (small jaw), glossoptosis (hypotonic, retracted tongue) and respiratory obstruction that require a multidisciplinary team for initial evaluation and management and maintenance care. TLA is a simple and effective procedure for increasing the cross-sectional area of oropharyngeal port.
CONCLUSION
Handling airway obstruction in Pierre Robin Sequence involves various factors, and there is no universal treatment that can address all cases. Appropriate airway management strategies and feeding programs are essential for each individual with PRS. Our review highlights that TLA is a straightforward surgical procedure with minimal or no short-term complications. TLA should be considered as the primary surgical intervention when relief is needed.
PubMed: 38936141
DOI: 10.1016/j.ijscr.2024.109932 -
Poultry Science Jun 2024A total of 378 Cobb-500 male broilers were used to evaluate the effects of 2 fiber sources, differing in hydration capacity and fermentability, on gastrointestinal tract...
Effect of dietary supplementation of two fiber sources differing on fermentability and hydration capacity on performance, nutrient digestibility and cecal fermentation in broilers from 1 to 42 d of age.
A total of 378 Cobb-500 male broilers were used to evaluate the effects of 2 fiber sources, differing in hydration capacity and fermentability, on gastrointestinal tract development, apparent ileal digestibility and performance from 1 to 42d of age. There were 9 replicates per each of the 3 dietary treatments, all in mash form: a wheat-soybean control (CON) diet, CON diet diluted with 1.5% of wood lignocellulose (LC diet) as a non-fermentable insoluble fiber with high hydration capacity; and CON diluted with 1.5% of a mixture of fibers (ISFC diet) containing both lignified insoluble fiber and a prebiotic soluble fiber fraction from fructooligosaccharides. Additionally, the fermentability of both fiber sources (LC and ISFC) was determined by in vitro using cecal inoculum from broilers fed the experimental diets. Both LC and ISFC treatments impaired by 4% feed conversion ratio only during the first 7d (P = 0.003) compared with CON group. In the grower period (21-42d), the ISFC group showed the best growth (P = 0.039), and at 42d tended to show the highest body weight (P = 0.095). This agrees well with the highest ileal dry matter (P = 0.033) and organic matter (P = 0.043) digestibility observed in ISFC group and the similar trend observed for ileal protein digestibility (P = 0.099) at 42d. Also, at 42 d, absolute and relative (% body weight) digestive tract weights (P ≤ 0.041) and empty gizzard weights (P ≤ 0.034) were greater for LC and ISFC groups compared to CON. The cecal molar proportion of valeratewas greatest in ISFC group (P = 0.039). In vitro gas production was higher for ISFC than for LC substrate when using either a diet-adapted or non-adapted cecal inoculum (P < 0.05). These results show the interest in combining IF with prebiotic highly fermentable fiber, such as fructooligosaccharides, in broilers to improve nutrient digestibility and finishing performance.
PubMed: 38936073
DOI: 10.1016/j.psj.2024.103957 -
ESMO Open Jun 2024Adrenocortical carcinoma (ACC) is one of the most lethal endocrine malignancies and there is a lack of clinically useful markers for prognosis and patient...
BACKGROUND
Adrenocortical carcinoma (ACC) is one of the most lethal endocrine malignancies and there is a lack of clinically useful markers for prognosis and patient stratification. Therefore our aim was to identify clinical and genetic markers that predict outcome in patients with ACC.
METHODS
Clinical and genetic data from a total of 162 patients with ACC were analyzed by combining an independent cohort consisting of tumors from Yale School of Medicine, Karolinska Institutet, and Düsseldorf University (YKD) with two public databases [The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO)]. We used a novel bioinformatical pipeline combining differential expression and messenger RNA (mRNA)- and DNA-dependent survival. Data included reanalysis of previously conducted whole-exome sequencing (WES) for the YKD cohort, WES and RNA data for the TCGA cohort, and RNA data for the GEO cohort.
RESULTS
We identified 3903 significant differentially expressed genes when comparing ACC and adrenocortical adenoma, and the mRNA expression levels of 461/3903 genes significantly impacted survival. Subsequent analysis revealed 45 of these genes to be mutated in patients with significantly worse survival. The relationship was significant even after adjusting for stage and age. Protein-protein interaction showed previously unexplored interactions among many of the 45 proteins, including the cancer-related proteins DNA polymerase delta 1 (POLD1), aurora kinase A (AURKA), and kinesin family member 23 (KIF23). Furthermore 14 of the proteins had significant interactions with TP53 which is the most frequently mutated gene in the germline of patients with ACC.
CONCLUSIONS
Using a multiparameter approach, we identified 45 genes that significantly influenced survival. Notably, many of these genes have protein interactions not previously implicated in ACC. These findings may lay the foundation for improved prognostication and future targeted therapies.
PubMed: 38935991
DOI: 10.1016/j.esmoop.2024.103617 -
ESMO Open Jun 2024Low muscle mass (MM) predicts unfavorable outcomes in cancer. Protein intake supports muscle health, but oncologic recommendations are not well characterized. The...
Feasibility of two levels of protein intake in patients with colorectal cancer: findings from the Protein Recommendation to Increase Muscle (PRIMe) randomized controlled pilot trial.
BACKGROUND
Low muscle mass (MM) predicts unfavorable outcomes in cancer. Protein intake supports muscle health, but oncologic recommendations are not well characterized. The objectives of this study were to evaluate the feasibility of dietary change to attain 1.0 or 2.0 g/kg/day protein diets, and the preliminary potential to halt MM loss and functional decline in patients starting chemotherapy for stage II-IV colorectal cancer.
PATIENTS AND METHODS
Patients were randomized to the diets and provided individualized counseling. Assessments at baseline, 6 weeks, and 12 weeks included weighed 3-day food records, appendicular lean soft tissue index (ALSTI) by dual-energy X-ray absorptiometry to estimate MM, and physical function by the Short Physical Performance Battery (SPPB) test.
RESULTS
Fifty patients (mean ± standard deviation: age, 57 ± 11 years; body mass index, 27.3 ± 5.6 kg/m; and protein intake, 1.1 ± 0.4 g/kg/day) were included at baseline. At week 12, protein intake reached 1.6 g/kg/day in the 2.0 g/kg/day group and 1.2 g/kg/day in the 1.0 g/kg/day group (P = 0.012), resulting in a group difference of 0.4 g/kg/day rather than 1.0 g/kg/day. Over one-half (59%) of patients in the 2.0 g/kg/day group maintained or gained MM compared with 44% of patients in the 1.0 g/kg/day group (P = 0.523). Percent change in ALSTI did not differ between groups [2.0 g/kg/day group (mean ± standard deviation): 0.5% ± 4.6%; 1.0 g/kg/day group: -0.4% ± 6.1%; P = 0.619]. No differences in physical function were observed between groups. However, actual protein intake and SPPB were positively associated (β = 0.37; 95% confidence interval 0.08-0.67; P = 0.014).
CONCLUSION
Individualized nutrition counselling positively impacted protein intake. However, 2.0 g/kg/day was not attainable using our approach in this population, and group contamination occurred. Increased protein intake suggested positive effects on MM and physical function, highlighting the potential for nutrition to attenuate MM loss in patients with cancer. Nonetheless, muscle anabolism to any degree is clinically significant and beneficial to patients. Larger trials should explore the statistical significance and clinical relevance of protein interventions.
PubMed: 38935990
DOI: 10.1016/j.esmoop.2024.103604 -
JMIR Bioinformatics and Biotechnology May 2024The etiology of ischemic stroke is multifactorial. Several gene mutations have been identified as leading causes of cerebral autosomal dominant arteriopathy with...
BACKGROUND
The etiology of ischemic stroke is multifactorial. Several gene mutations have been identified as leading causes of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary disease that causes stroke and other neurological symptoms.
OBJECTIVE
We aimed to identify the variants of NOTCH3 and thrombophilia genes, and their complex interactions with other factors.
METHODS
We conducted a hierarchical cluster analysis (HCA) on the data of 100 patients diagnosed with ischemic stroke. The variants of NOTCH3 and thrombophilia genes were identified by polymerase chain reaction with confronting 2-pair primers and real-time polymerase chain reaction. The overall preclinical characteristics, cumulative cutpoint values, and factors associated with these somatic mutations were analyzed in unidimensional and multidimensional scaling models.
RESULTS
We identified the following optimal cutpoints: creatinine, 83.67 (SD 9.19) µmol/L; age, 54 (SD 5) years; prothrombin (PT) time, 13.25 (SD 0.17) seconds; and international normalized ratio (INR), 1.02 (SD 0.03). Using the Nagelkerke method, cutpoint 50% values of the Glasgow Coma Scale score; modified Rankin scale score; and National Institutes of Health Stroke Scale scores at admission, after 24 hours, and at discharge were 12.77, 2.86 (SD 1.21), 9.83 (SD 2.85), 7.29 (SD 2.04), and 6.85 (SD 2.90), respectively.
CONCLUSIONS
The variants of MTHFR (C677T and A1298C) and NOTCH3 p.R544C may influence the stroke severity under specific conditions of PT, creatinine, INR, and BMI, with risk ratios of 4.8 (95% CI 1.53-15.04) and 3.13 (95% CI 1.60-6.11), respectively (P<.05). It is interesting that although there are many genes linked to increased atrial fibrillation risk, not all of them are associated with ischemic stroke risk. With the detection of stroke risk loci, more information can be gained on their impacts and interconnections, especially in young patients.
PubMed: 38935968
DOI: 10.2196/56884 -
JMIR Formative Research Jun 2024Urinary incontinence (UI) affects millions of women with substantial health and quality-of-life impacts. Supervised pelvic floor muscle training (PFMT) is the...
BACKGROUND
Urinary incontinence (UI) affects millions of women with substantial health and quality-of-life impacts. Supervised pelvic floor muscle training (PFMT) is the recommended first-line treatment. However, multiple individual and institutional barriers impede women's access to skilled care. Evidence suggests that digital health solutions are acceptable and may be effective in delivering first-line incontinence treatment, although these technologies have not yet been leveraged at scale.
OBJECTIVE
The primary objective is to describe the effectiveness and safety of a prescribed digital health treatment program to guide PFMT for UI treatment among real-world users. The secondary objectives are to evaluate patient engagement following an updated user platform and identify the factors predictive of success.
METHODS
This retrospective cohort study of women who initiated device use between January 1, 2022, and June 30, 2023, included users aged ≥18 years old with a diagnosis of stress, urgency, or mixed incontinence or a score of >33.3 points on the Urogenital Distress Inventory Short Form (UDI-6). Users are prescribed a 2.5-minute, twice-daily, training program guided by an intravaginal, motion-based device that pairs with a smartphone app. Data collected by the device or app include patient-reported demographics and outcomes, adherence to the twice-daily regimen, and pelvic floor muscle performance parameters, including angle change and hold time. Symptom improvement was assessed by the UDI-6 score change from baseline to the most recent score using paired 2-tailed t tests. Factors associated with meeting the UDI-6 minimum clinically important difference were evaluated by regression analysis.
RESULTS
Of 1419 users, 947 met inclusion criteria and provided data for analysis. The mean baseline UDI-6 score was 46.8 (SD 19.3), and the mean UDI-6 score change was 11.3 (SD 19.9; P<.001). Improvement was reported by 74% (697/947) and was similar across age, BMI, and incontinence subtype. Mean adherence was 89% (mean 12.5, SD 2.1 of 14 possible weekly uses) over 12 weeks. Those who used the device ≥10 times per week were more likely to achieve symptom improvement. In multivariate logistic regression analysis, baseline incontinence symptom severity and maximum angle change during pelvic floor muscle contraction were significantly associated with meeting the UDI-6 minimum clinically important difference. Age, BMI, and UI subtype were not associated.
CONCLUSIONS
This study provides real-world evidence to support the effectiveness and safety of a prescribed digital health treatment program for female UI. A digital PFMT program completed with visual guidance from a motion-based device yields significant results when executed ≥10 times per week over a period of 12 weeks. The program demonstrates high user engagement, with 92.9% (880/947) of users adhering to the prescribed training regimen. First-line incontinence treatment, when implemented using this digital program, leads to statistically and clinically substantial symptom improvements across age and BMI categories and incontinence subtypes.
PubMed: 38935967
DOI: 10.2196/58551