Multilevel Characteristics of Cumulative Symptom Burden in Young Survivors of Childhood Cancer.

Importance: Symptom burden and its characteristics among survivors of pediatric cancers aged 8 to 18 years remain understudied. Objective: To examine the prevalence of symptom burden among young childhood cancer survivors and identify associations with sociodemographic, clinical, and psychological resilience skills, and health-related quality of life (HRQOL). Design, Setting, and Participants: A cross-sectional analysis using data collected from November 1, 2017, to January 31, 2019, in a survivorship clinic at a US-based comprehensive cancer center was conducted. Participants included 302 dyads of children aged 8 to 18 years who survived at least 5 years beyond diagnosis and their primary caregivers. Data analysis was performed from March 13, 2023, to February 29, 2024. Exposures: Diagnosis, caregiver-reported family conflict, self-reported caregiver anxiety, neighborhood-level social vulnerability, and survivor-reported meaning and purpose. Main Outcomes and Measures: Novel symptom-level burden, integrating the attributes of severity and daily activity interference using the pediatric version of the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events, global cumulative symptom burden, and HRQOL using the EuroQol-5D. Multinomial logistic regression identified characteristics associated with symptom burden; linear regression assessed symptom burden and HRQOL associations. Results: Among 302 survivors (mean [SD] age, 14.2 [2.9] years, mean [SD] time since diagnosis, 10.9 [2.9] years; 153 [50.7%] male), 186 (62.0%) had low, 77 (25.7%) moderate, and 37 (12.3%) high global cumulative symptom burden. Greater caregiver anxiety was associated with moderate (risk ratio [RR], 1.56; 95% CI, 1.09-2.24) global symptom burden. Greater neighborhood deprivation was associated with moderate global symptom burden (RR, 4.86; 95% CI, 1.29-18.26). Survivors with greater meaning/purpose were less likely to have moderate (RR, 0.42; 95% CI, 0.29-0.61) and high (RR, 0.27; 95% CI, 0.16-0.46) global symptom burden. The burden of individual symptoms displayed similar patterns. Low (Cohen d, -0.60; 95% CI, -0.87 to -0.32) and moderate/high (d, -0.98; 95% CI, -1.53 to -0.43) general pain, moderate/high numbness (d, -0.99; 95% CI, -1.69 to -0.29), and moderate/high worry (d, -0.55; 95% CI, -0.99 to -0.11) were associated with lower HRQOL. Conclusions and Relevance: In this cross-sectional study of young childhood cancer survivors, symptom burden was prevalent. Caregiver anxiety and disparity-related neighborhood factors were associated with greater symptom burden, whereas meaning and purpose was a protective factor. Greater specific symptom burden contributed to poorer HRQOL. The findings suggest that interventions targeting resilience and neighborhood adversity may alleviate symptom burden and improve HRQOL.

Intratesticular Testosterone and Its Precursors among Azoospermic Men: A Pilot Study.

PURPOSE: The study aimed to comprehensively analyze testosterone and precursor concentrations in the testicular interstitial fluid (TIF) of men with azoospermia, exploring their significance in the testicular microenvironment and their correlation with testicular sperm retrieval outcomes. MATERIALS AND METHODS: We analyzed 37 TIF samples, including 5 from men with obstructive azoospermia (OA) and 32 from men with non-obstructive azoospermia (NOA). Liquid chromatography with tandem mass spectrometry quantified testosterone and precursor levels. Comparative assessments of the outcomes of testicular sperm retrieval were performed between the OA and NOA groups as well as among men with NOA. RESULTS: Men with NOA who had not undergone hormone treatment exhibited significantly higher intratesticular concentrations of testosterone (median 1,528.1 vs. 207.5 ng/mL), androstenedione (median 10.6 vs. 1.9 ng/mL), and 17-OH progesterone (median 13.0 vs. 1.8 ng/mL) than men diagnosed with OA. Notably, in the subgroup of patients with NOA subjected to medical treatment, men with successful sperm retrieval had significantly reduced levels of androstenedione (median androstenedione 5.7 vs. 18.5 ng/mL, p=0.004). Upon a more detailed analysis of these men who underwent hormone manipulation treatment, the testosterone/androstenedione ratio (indicative of HSD17B3 enzyme activity) was markedly increased in men with successful sperm retrieval (median: 365.8 vs. 165.0, p=0.008) compared with individuals with NOA who had unsuccessful sperm recovery. Furthermore, within the subset of men with NOA who did not undergo medical treatment before microdissection testicular sperm extraction but achieved successful sperm retrieval, the ratio of 17-OH progesterone/progesterone (indicative of CYP17A1 activity) was substantially higher. CONCLUSIONS: The study suggests distinct testosterone biosynthesis pathways in men with compromised spermatogenesis and those with normal spermatogenesis. Among NOA men with successful retrieval after hormone optimization therapy, there was decreased androstenedione and increased HSD17B3 enzyme activity. These findings have diagnostic and therapeutic implications for the future.

Meal effects on gastric bioelectrical activity utilizing body surface gastric mapping in healthy subjects.

BACKGROUND: Gastric sensorimotor disorders are prevalent. While gastric emptying measurements are commonly used, they may not fully capture the underlying pathophysiology. Body surface gastric mapping (BSGM) recently emerged to assess gastric sensorimotor dysfunction. This study assessed varying meal size on BSGM responses to inform test use in a wider variety of contexts. METHODS: Data from multiple healthy cohorts receiving BSGM were pooled, using four different test meals. A standard BSGM protocol was employed: 30-min fasting, 4-h post-prandial, using Gastric Alimetry® (Alimetry, New Zealand). Meals comprised: (i) nutrient drink + oatmeal bar (482 kcal; 'standard meal'); (ii) oatmeal bar alone; egg and toast meal, and pancake (all ~250 kcal). Gastric Alimetry metrics included BMI-adjusted Amplitude, Principal Gastric Frequency, Gastric Alimetry Rhythm Index (GA-RI) and Fed:Fasted Amplitude Ratio (ff-AR). KEY RESULTS: 238 participants (59.2% female) were included. All meals significantly increased amplitude and frequency during the first postprandial hour (p < 0.05). There were no differences in postprandial frequency across meals (p > 0.05). The amplitude and GA-RI of the standard meal (n = 110) were significantly higher than the energy bar alone (n = 45) and egg meal (n = 65) (all p < 0.05). All BSGM metrics were comparable across the three smaller meals (p > 0.05). A higher symptom burden was found in the oatmeal bar group versus the standard meal and pancake meal (p = 0.01, 0.003, respectively). CONCLUSIONS & INFERENCES: The consumption of lower calorie meals elicited different postprandial responses, when compared to the standard Gastric Alimetry meal. These data will guide interpretations of BSGM when applied with lower calorie meals.

Gene Co-Expression and miRNA Regulation: A Path to Early Intervention in Colorectal Cancer.

Early diagnosis and intervention are pivotal in reducing colorectal cancer (CRC) incidence and enhancing patient outcomes. In this study, we focused on three genes, AQP8, GUCA2B, and SPIB, which exhibit high co-expression and play crucial roles in suppressing early-stage CRC. Our objective was to identify key miRNAs that can mitigate CRC tumorigenesis and modulate the co-expression network involving these genes. We conducted a comprehensive analysis using large-scale tissue mRNA data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus to validate the co-expression of AQP8, GUCA2B, and SPIB, and to assess their diagnostic and prognostic significance in CRC. mRNA-miRNA interactions were examined using MiRNet and the Encyclopedia of RNA Interactomes. Furthermore, using various molecular techniques, we conducted miRNA inhibitor transfection experiments in HCT116 cells to evaluate their effects on cell growth, migration, and gene/protein expression. Our findings revealed that, compared to normal tissues, AQP8, GUCA2B, and SPIB exhibited high co-expression and were downregulated in CRC, particularly during tumorigenesis. OncoMirs, hsa-miR-182-5p, and hsa-miR-27a-3p, were predicted to regulate these genes. MiRNA inhibition experiments in HCT116 cells demonstrated the inhibitory effects of miR-27a-3p and miR-182-5p on GUCA2B mRNA and protein expression. These miRNAs promoted the proliferation of CRC cells, possibly through their involvement in the GUCA2B-GUCY2C axis, which is known to promote tumor growth. While the expressions of AQP8 and SPIB were barely detectable, their regulatory relationship with hsa-miR-182-5p remained inconclusive. Our study confirms that hsa-miR-27a-3p and hsa-miR-182-5p are oncomiRs in CRC. These miRNAs may contribute to GUCY2C dysregulation by downregulating GUCA2B, which encodes uroguanylin. Consequently, hsa-miR-182-5p and hsa-miR-27a-3p show promise as potential targets for early intervention and treatment in the early stages of CRC.

The effects of diabetes, hypertension and subsequent health control behavior on the survival of a Taiwan cohort aged over 50 years.

Purpose: This study used the Taiwan Longitudinal Study in Aging from 1996 to 2011 to investigate the effects of diabetes, hypertension, and healthy living behaviors of those aged over 50 years on the survival status in Taiwan. Methods: Among the 5,131 participants aged 50 years and above in the 1996 survey were included in this study. Cox's proportional hazards model was used to examine the incidence of diabetes, hypertension, and related mortality risk in those aged over 50 years. Results: After adjusting for age, gender, education level, diabetes, hypertension, health behavior, and leisure activity, results from the Cox model show that the elderly without diabetes have a lower mortality risk than those with diabetes. Regular exercise was associated with a lower risk of mortality. The hazard ratios of elderly with regular exercise were 0.78 (95 % CI: 0.64-0.96) for two times a week or less, 0.81 (95 % CI: 0.69-0.96) for 3-5 times a week, and 0.84 (95 % CI: 0.77-0.93) for 6 + times a week, respectively. On the other hand, leisure activity positively reduces mortality risk. For example, the hazard ratios of the elderly with watching TV and reading were 0.63 (95 % CI: 0.55-0.72) and 0.80 (95 % CI: 0.72-0.89), respectively. Moreover, smoking can increase mortality risk 23 % whether the elderly are with diabetes or hypertension or not. Conclusions: Regarding preventing and controlling chronic diseases in the future, continuously encouraging improvement in health behavior and engaging in leisure activities for the middle-aged and over should be considered essential markers.

Health insurance among survivors of childhood cancer following affordable care act implementation.

BACKGROUND: The Affordable Care Act (ACA) increased private non-employer health insurance options, expanded Medicaid eligibility, and provided pre-existing health conditions protections. We evaluated insurance coverage among long-term adult survivors of childhood cancer pre/post-ACA implementation. METHODS: Using the multicenter Childhood Cancer Survivor Study, we included participants from two cross-sectional surveys: pre-ACA (2007-2009; survivors: N = 7,505; siblings: N = 2,175) and post-ACA (2017-2019; survivors: N = 4,030; siblings: N = 987). A subset completed both surveys (1,840 survivors; 646 siblings). Multivariable regression models compared post-ACA insurance coverage and type (private/public/uninsured) between survivors and siblings and identified associated demographic and clinical factors. Multinomial models compared gaining and losing insurance vs staying the same among survivors and siblings who participated in both surveys. RESULTS: The proportion with insurance was higher post-ACA (survivors pre-ACA 89.1% to post-ACA 92.0% [+2.9%]; siblings pre-ACA 90.9% to post-ACA 95.3% [+4.4%]). Post-ACA insurance coverage was greater among those age 18-25 (survivors: 15.8% vs < 2.3% ages 26+; siblings +17.8% vs < 4.2% ages 26+). Survivors were more likely to have public insurance than siblings post-ACA (18.4% vs 6.9%; odds ratios [OR]=1.7, 95%CI 1.1-2.6). Survivors with severe chronic conditions (OR = 4.7, 95%CI 3.0-7.3) and those living in Medicaid expansion states (OR = 2.4, 95%CI 1.7-3.4) had increased odds of public insurance coverage post-ACA. Among the subset completing both surveys, low/mid income survivors (<$60,000) experienced both insurance losses and gains in reference to highest household income survivors (≥$100,000), relative to odds of keeping the same insurance status. CONCLUSIONS: Post-ACA, more childhood cancer survivors and siblings had health insurance, although disparities remain in coverage.

The benefits of leisure activities on healthy life expectancy for older people with diabetes.

PURPOSE: The purpose of this study is to examine whether leisure activities can help reduce years lived with disability and increase healthy life expectancy of diabetics aged 50 years and above. METHODS: Analysis was based on five waves of follow-up survey data (Taiwan Longitudinal Study of Aging, TLSA) from 1996 to 2011. A total of 5131 participants aged 50 years and above in 1996 were included in the analysis, and gender, leisure activity participation, and diabetes mellitus were used as primary variables to examine the variation trend in health status in the participants. The health status in the various waves of surveys was measured using the activities of daily living scale, and nondisabled was defined as healthy. A multivariate logistic regression model was used to calculate the life expectancy (LE) and healthy life expectancy (HLE) of the people aged 50 years and above. RESULTS: The diabetes older people with a high frequency of leisure activities have longer HLE than those with lower activity frequency. Using 50-year-old diabetic women as an example, the LE (HLE) of those with six or more leisure activities and those with three or fewer leisure activities was 30.40 (25.34) and 24.90 (20.87), respectively. The LE (HLE) of men with the same conditions was 24.79 (22.68) and 20.30 (18.45), respectively. CONCLUSIONS: This study used life expectancy and healthy life expectancy as markers to evaluate health benefits and provided evidence that leisure activities can help extend the life span and maintain the health status of middle-aged and older diabetics.

New Onset and Exacerbation of Autoimmune Bullous Dermatosis Following COVID-19 Vaccination: A Systematic Review.

BACKGROUND: Cases of autoimmune bullous dermatosis (AIBD) have been reported following COVID-19 vaccination. OBJECTIVE: We aimed to provide an overview of clinical characteristics, treatments, and outcomes of AIBDs following COVID-19 vaccination. METHODS: We conducted a systematic review and searched the Embase, Cochrane Library, and Medline databases from their inception to 27 March 2024. We included all studies reporting ≥ 1 patient who developed new-onset AIBD or experienced flare of AIBD following at least one dose of any COVID-19 vaccine. RESULTS: We included 98 studies with 229 patients in the new-onset group and 216 in the flare group. Among the new-onset cases, bullous pemphigoid (BP) was the most frequently reported subtype. Notably, mRNA vaccines were commonly associated with the development of AIBD. Regarding the flare group, pemphigus was the most frequently reported subtype, with the mRNA vaccines being the predominant vaccine type. The onset of AIBD ranged from 1 to 123 days post-vaccination, with most patients displaying favorable outcomes and showing improvement or resolution from 1 week to 8 months after treatment initiation. CONCLUSIONS: Both new-onset AIBD and exacerbation of pre-existing AIBD may occur following COVID-19 vaccination. Healthcare practitioners should be alert, and post-vaccination monitoring may be essential.

Multilevel Social Determinants of Patient-Reported Outcomes in Young Survivors of Childhood Cancer.

In this study, the social determinants of patient-reported outcomes (PROs) in young survivors of childhood cancer aged <18 years are researched. This cross-sectional study investigated social determinants associated with poor PROs among young childhood cancer survivors. We included 293 dyads of survivors receiving treatment at St. Jude Children's Research Hospital who were <18 years of age during follow-up from 2017 to 2018 and their primary caregivers. Social determinants included family factors (caregiver-reported PROs, family dynamics) and county-level deprivation (socioeconomic status, physical environment via the County Health Rankings & Roadmaps). PROMIS measures assessed survivors' and caregivers' PROs. General linear regression tested associations of social determinants with survivors' PROs. We found that caregivers' higher anxiety was significantly associated with survivors' poorer depression, stress, fatigue, sleep issues, and reduced positive affect (p < 0.05); caregivers' sleep disturbances were significantly associated with lower mobility in survivors (p < 0.05). Family conflicts were associated with survivors' sleep problems (p < 0.05). Residing in socioeconomically deprived areas was significantly associated with survivors' poorer sleep quality (p < 0.05), while higher physical environment deprivation was associated with survivors' higher psychological stress and fatigue and lower positive affect and mobility (p < 0.05). Parental, family, and neighborhood factors are critical influences on young survivors' quality of life and well-being and represent new intervention targets.

Using an mHealth approach to collect patient-generated health data for predicting adverse health outcomes among adult survivors of childhood cancer.

Introduction: Cancer therapies predispose childhood cancer survivors to various treatment-related late effects, which contribute to a higher symptom burden, chronic health conditions (CHCs), and premature mortality. Regular monitoring of symptoms between clinic visits is useful for timely medical consultation and interventions that can improve quality of life (QOL). The Health Share Study aims to utilize mHealth to collect patient-generated health data (PGHD; daily symptoms, momentary physical health status) and develop survivor-specific risk prediction scores for mitigating adverse health outcomes including poor QOL and emergency room admissions. These personalized risk scores will be integrated into the hospital-based electronic health record (EHR) system to facilitate clinician communications with survivors for timely management of late effects. Methods: This prospective study will recruit 600 adult survivors of childhood cancer from the St. Jude Lifetime Cohort study. Data collection include 20 daily symptoms via a smartphone, objective physical health data (physical activity intensity, sleep performance, and biometric data including resting heart rate, heart rate variability, oxygen saturation, and physical stress) via a wearable activity monitor, patient-reported outcomes (poor QOL, unplanned healthcare utilization) via a smartphone, and clinically ascertained outcomes (physical performance deficits, onset of/worsening CHCs) assessed in the survivorship clinic. Participants will complete health surveys and physical/functional assessments in the clinic at baseline, 2) report daily symptoms, wear an activity monitor, measure blood pressure at home over 4 months, and 3) complete health surveys and physical/functional assessments in the clinic 1 and 2 years from the baseline. Socio-demographic and clinical data abstracted from the EHR will be included in the analysis. We will invite 20 cancer survivors to investigate suitable formats to display predicted risk information on a dashboard and 10 clinicians to suggest evidence-based risk management strategies for adverse health outcomes. Analysis: Machine and statistical learning will be used in prediction modeling. Both approaches can handle a large number of predictors, including longitudinal patterns of daily symptoms/other PGHD, along with cancer treatments and socio-demographics. Conclusion: The individualized risk prediction scores and added communications between providers and survivors have the potential to improve survivorship care and outcomes by identifying early clinical presentations of adverse events.

Financial hardship and neighborhood socioeconomic disadvantage in long-term childhood cancer survivors.

BACKGROUND: Long-term survivors of childhood cancer face elevated risk for financial hardship. We evaluate whether childhood cancer survivors live in areas of greater deprivation and the association with self-reported financial hardships. METHODS: We performed a cross-sectional analysis of data from the Childhood Cancer Survivor Study between 1970 and 1999 and self-reported financial information from 2017 to 2019. We measured neighborhood deprivation with the Area Deprivation Index (ADI) based on current zip code. Financial hardship was measured with validated surveys that captured behavioral, material and financial sacrifice, and psychological hardship. Bivariate analyses described neighborhood differences between survivors and siblings. Generalized linear models estimated effect sizes between ADI and financial hardship adjusting for clinical factors and personal socioeconomic status. RESULTS: Analysis was restricted to 3475 long-term childhood cancer survivors and 923 sibling controls. Median ages at time of evaluation was 39 years (interquartile range [IQR] = 33-46 years and 47 years (IQR = 39-59 years), respectively. Survivors resided in areas with greater deprivation (ADI ≥ 50: 38.7% survivors vs 31.8% siblings; P < .001). One quintile increases in deprivation were associated with small increases in behavioral (second quintile, P = .017) and psychological financial hardship (second quintile, P = .009; third quintile, P = .014). Lower psychological financial hardship was associated with individual factors including greater household income (≥$60 000 income, P < .001) and being single (P = .048). CONCLUSIONS: Childhood cancer survivors were more likely to live in areas with socioeconomic deprivation. Neighborhood-level disadvantage and personal socioeconomic circumstances should be evaluated when trying to assist childhood cancer survivors with financial hardships.

The relationship between cardiorespiratory fitness and inhibitory control following acute stress: An ERP study.

Although the relationships among acute stress, cardiorespiratory fitness (CRF), and cognitive function have been examined, whether CRF is related to behavioral and neuroelectric indices of inhibitory control following acute stress remains unknown. The purpose of the current study was to investigate the combined influence of acute stress and CRF on inhibitory control. Participants, aged 20-30 years, were stratified into the Higher-Fit (n = 31) and the Lower-Fit (n = 32) groups, and completed a Stroop task following the modified Maastricht Acute Stress Test (MAST) in the stress condition and the sham-MAST in the non-stress condition, during which electroencephalography was recorded. Behavioral (i.e., response time and accuracy) and neuroelectric (N2 and P3b components of the event-related potential) outcomes of inhibitory control were obtained. While the Higher-Fit group demonstrated shorter response times and higher accuracy than the Lower-Fit group following both the MAST and the sham-MAST, they also exhibited selective benefits of acute stress on inhibitory control performance (i.e., decreased response times and diminished interference scores). CRF-dependent alterations in neuroelectric indices were also observed, with the Higher-Fit group displaying smaller N2 and greater P3b amplitudes than the Lower-Fit group following the sham-MAST, and increased N2 and attenuated P3b amplitudes following the MAST. Collectively, these findings not only confirm the positive relationship between CRF and inhibitory control but also provide novel insights into the potential influence of CRF on inhibitory control and associated neuroelectric activity following acute stress.

Human Leukocyte Antigens and Sulfamethoxazole/Cotrimoxazole-Induced Severe Cutaneous Adverse Reactions: A Systematic Review and Meta-Analysis.

Importance: Sulfamethoxazole (SMX) and cotrimoxazole (CTX), a fixed-dose combination of SMX and trimethoprim in a 5:1 ratio, are antibacterial sulfonamides commonly used for treating various diseases. A substantial prevalence of severe cutaneous adverse reactions (SCARs) following the administration of these drugs has been reported. However, the association between human leukocyte antigen (HLA) genotypes and SMX/CTX-induced SCARs has remained unclear. Objective: To investigate the association between HLA genotypes and SMX/CTX-induced SCARs. Data sources: A comprehensive search was conducted in CENTRAL (Cochrane Library), MEDLINE, and Embase from inception to January 17, 2023. Study Selection: Case-control studies that recruited patients who had experienced SCARs following SMX or CTX were included, and HLA alleles were analyzed. Data Extraction and Synthesis: Two independent authors extracted data on study characteristics and outcome data. The Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline and the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were followed. The Newcastle-Ottawa Scale for case-control studies was used to assess study quality. Odds ratios (ORs) were calculated using a random-effects model for meta-analysis. Main Outcomes and Measures: The prespecified outcome was the OR comparing SMX/CTX-induced SCARs with healthy or SMX/CTX-tolerant controls based on different HLA alleles. Results: Six studies involving 322 patients with SCAR were included, including 236 patients with Stevens-Johnson syndrome/toxic epidermal necrolysis, 86 with drug reaction with eosinophilia and systemic symptoms, 8448 healthy controls, and 229 tolerant controls. Significant associations were found in HLA-A*11:01 (OR, 2.10; 95% CI, 1.11-4.00), HLA-B*13:01 (OR, 5.96; 95% CI, 1.58-22.56), HLA-B*15:02 (OR, 2.23; 95% CI, 1.20-4.14), HLA-B*38:02 (OR, 3.47; 95% CI, 1.42-8.48), and HLA-C*08:01 (OR, 2.63; 95% CI, 1.07-6.44) compared with tolerant controls. In the Stevens-Johnson syndrome/toxic epidermal necrolysis subgroup, significant associations were found in HLA-B*15:02 (OR, 3.01; 95% CI, 1.56-5.80) and HLA-B*38:02 (OR, 5.13; 95% CI, 1.96-13.47). In the drug reaction with eosinophilia and systemic symptoms subgroup, significant associations were found in HLA-A*68:01 (OR, 12.86; 95% CI, 1.09-151.34), HLA-B*13:01 (OR, 23.09; 95% CI, 3.31-161.00), HLA-B*39:01 (OR, 4.56; 95% CI, 1.31-15.82). Conclusions and Relevance: The results of this systematic review and meta-analysis suggest that multiple HLA alleles (HLA-A*11:01, HLA-B*13:01, HLA-B*15:02, HLA-B*38:02, and HLA-C*0801) are associated with SMX/CTX-induced SCARs.

Cardiopulmonary functional capacity in Taiwanese children with atrial septal defects.

BACKGROUND: Most existing studies measure atrial septal defect (ASD) outcomes based on morbidity rate such as atrial arrhythmias and heart failure rather than the functional assessment of physical capacity post-procedure. Few studies have evaluated cardiopulmonary function in ASD children. This study represents the largest sample population in the current research, encompassing a total of 122 Taiwanese children with ASD who had undergone treatment, to evaluate cardiopulmonary functional capacity through the implementation of cardiopulmonary exercise testing (CPET), and to investigate whether variations in treatment may impact their cardiopulmonary function. METHODS: This is a retrospective cohort study with the data collected from January 2010 to December 2021. All patients and controls (age-, sex-, and body mass index -matched) underwent CPET and pulmonary function testing. RESULTS: In total, 122 ASD patients (surgically closed ASDs 27, transcatheter closed ASDs 48, and follow-up unrepaired ASD 47) and 244 healthy controls were recruited. The ASD group exhibited lower peak metabolic equivalent (MET), peak oxygen consumption (VO2, p <0.001), peak minute ventilation (p = 0.028) along with MET and VO2 at the anaerobic threshold (AT) (p =0.012) compared to the control group. No statistically significant differences were observed in the pulmonary function test. Among surgically closed, transcatheter closed and unrepaired ASD sub-groups, no significant variances were seen in CPET and pulmonary function tests. CONCLUSION: Taiwanese ASD children exhibited diminished exercise capacity and cardiopulmonary performance compared to their healthy counterparts. Differences among specific ASD treatments in cardiopulmonary tests were non-significant.

Clinical validation of the VIPUN™ gastric monitoring system versus manometry for the evaluation of gastric motility.

BACKGROUND: Gastrointestinal dysmotility is frequently suspected in patients with gastroparesis, functional dyspepsia, and ileus, and in the intensive care unit. Monitoring of gastric motility in clinical practice remains challenging. A novel technology was developed to meet the medical need for a widely available bedside tool to monitor gastric motility continuously. The VIPUN™ Gastric Monitoring System (GMS) comprises a nasogastric feeding tube with intragastric balloon to allow for measuring gastric contractions. AIMS: To compare the performance of the VIPUN GMS versus a reference technique (manometry). METHODS: In this validation study in healthy subjects, the investigational catheter and a solid-state manometry catheter were placed in the stomach concomitantly. Motility was recorded for 2.5 h: 2 h in a fasting state, followed by a 400-kcal liquid meal, and monitoring of the fed state for the remaining half hour. The performance of both systems was compared by automated recognition and manual identification of the contractile activity. Data are presented as mean (standard deviation). KEY RESULTS: The analysis set comprised 13 healthy subjects (6 women, age: 27.5 (8.1) years, BMI: 22.2 (2.46) kg/m2 ). Automatically-recognized contractility was strongly correlated between the two techniques (endpoint: contraction duration; Spearman ρ = 0.96, p < 0.001). A correlation was also observed between the number of individual contractions identified by expert gastroenterologists on both technologies independently (ρ = 0.71, p = .007) and between the contractions identified by the experts and by the GMS software (ρ = 0.87, p = 0.001). No serious or unanticipated adverse events occurred. CONCLUSIONS & INFERENCES: The observed strong correlations with the gold standard, manometry, validate the performance of the VIPUN GMS as a gastric monitoring system.

Small-Molecule Inhibitors and Biologics for Palmoplantar Psoriasis and Palmoplantar Pustulosis: A Systematic Review and Network Meta-Analysis.

BACKGROUND: The comparative efficacy of biologics and small-molecule inhibitors in treating palmoplantar psoriasis (PP) and palmoplantar pustulosis (PPP) remains uncertain. OBJECTIVE: The aim was to perform a systematic review and network meta-analysis (NMA) to compare the efficacy of biologics and small-molecule inhibitors for the treatment of PP and PPP. METHODS: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were searched for eligible studies from inception to May 13, 2023. This NMA was conducted and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension Statement for Network Meta-Analyses guidelines. Frequentist random-effects models NMA was performed with the surface under the cumulative ranking curve calculated for ranking. Our primary outcome was the proportion of patients achieving a clear/minimal Palmoplantar Psoriasis/Pustulosis Physician Global Assessment score (PPPGA 0/1 or PPPPGA 0/1) response at 12-16 weeks. Secondary outcomes consisted of the percentage of overall improvement in palmoplantar score and of improvement ≥ 75%, at 12-16 weeks. RESULTS: The study comprised a total of 29 randomized controlled trials (RCTs), involving 4798 psoriasis patients with palmoplantar diseases. For PP, 16 RCTs with nine different treatments, including adalimumab, apremilast, bimekizumab, etanercept, guselkumab, infliximab, ixekizumab, secukinumab, and ustekinumab were included for the analysis. In the NMA of PP, secukinumab 300 mg ranked highest (odds ratio [OR] 33.50, 95% confidence interval [CI] 4.37-256.86) in achieving PPPGA 0/1, followed by guselkumab 100 mg (OR 18.68, 95% CI 10.07-34.65). In the case of PPP, seven RCTs with six treatments, including apremilast, etanercept, guselkumab, imsidolimab, spesolimab, and ustekinumab, were included for the analysis. In the NMA of PPP, although no treatment demonstrated a significant difference compared to placebo in achieving PPPPGA 0/1, guselkumab 100 mg showed the greatest statistically significant improvement in the palmoplantar score (weighted mean difference 31.73, 95% CI 19.89-43.57) as a secondary outcome. CONCLUSION: Among all available biologics and small-molecule inhibitors, secukinumab 300 mg and guselkumab 100 mg had the most favorable efficacy in treating PP and PPP, respectively.

Health-Related quality of life and DNA Methylation-Based aging biomarkers among survivors of childhood cancer.

BACKGROUND: Childhood cancer survivors are at high risk for morbidity and mortality and poor patient-reported outcomes, typically health-related-quality-of-life (HRQOL). However, associations between DNA methylation (DNAm)-based aging biomarkers and HRQOL have not been evaluated. METHODS: DNAm was generated with Infinium EPIC BeadChip on blood-derived DNA (median[range] for age at blood draw = 34.5[18.5-66.6] years) and HRQOL was assessed with age at survey (32.3[18.4-64.5] years) from 2,206 survivors in the St Jude Lifetime Cohort. DNAm-based aging biomarkers, including epigenetic age using multiple clocks (eg, GrimAge) and others (eg, DNAmB2M beta-2-microglobulin; DNAmADM: adrenomedullin), were derived from the DNAm Age Calculator (https://dnamage.genetics.ucla.edu). HRQOL was assessed using the Medical Outcomes Study 36-Item Short-Form Health Survey to capture eight domains, and physical and mental component summaries (PCS and MCS). General linear models evaluated associations between HRQOL and epigenetic age acceleration (EAA, eg, EAA_GrimAge) or other age-adjusted DNAm-based biomarkers (eg, ageadj_DNAmB2M) after adjusting for age at blood draw, sex, cancer treatments, and DNAm-based surrogate for smoking pack-years. All P values were 2-sided. RESULTS: Worse HRQOL was associated with greater EAA_GrimAge (PCS ß[95%CI]=-0.18[-0.251,-0.11] years, P = 1.85 × 10-5; and four individual HRQOL domains), followed by ageadj_DNAmB2M (PCS: -0.08[-0.124,-0.037], P = .003; and three individual HRQOL domains), and ageadj_DNAmADM (PCS: -0.082[-0.125,-0.039], P = .002; and two HRQOL domains). EAA_Hannum (Hannum clock) was not associated with any HRQOL. CONCLUSIONS: Overall and domain-specific measures of HRQOL are associated with DNAm measures of biological aging. Future longitudinal studies should test biological aging as a potential mechanism underlying the association between poor HRQOL and increased risk of clinically assessed adverse health outcomes.

Epidemiology of functional dyspepsia and gastroparesis as diagnosed in Flemish-Belgian primary care: A registry-based study from the Intego database.

BACKGROUND: Dyspepsia is a prevalent condition in the general population. Besides organic causes, the differential diagnosis of dyspepsia includes functional dyspepsia (FD) and gastroparesis (GP) which share similar pathophysiological mechanisms and clinical presentation. So far, no study investigated the prevalence of FD and GP in a primary care in Belgium. METHODS: Data were obtained from Intego, a Flemish-Belgian general practice-based morbidity registration network. From 586,164 patients between 2000 and 2021, we selected patients with ICD-10 code for FD and GP. Patients with organic gastrointestinal diseases were excluded. We determined demographics and comorbidities of FD/GP. For prevalence and incidence calculation, we included those who consulted their general practitioners at least once in the given year. Pair-wise comparison was conducted to access the impact of comorbidities on risk of FD/GP. KEY RESULTS: Between 2011 and 2021, the prevalence of FD/GP ranged from 1.03% to 1.21%. The incidence of FD/GP ranged from 109 to 142 per 100,000 adults. In total 5242 cases of FD/GP were identified. These cases shared commonly coexisting diagnoses of gastroesophageal reflux disease (18.8%), irritable bowel syndrome (17.1%), and chronic constipation (18.7%). Patients with somatization/anxiety/depression had significantly higher risk of FD/GP, compared to the control (OR 1.38, 95% CI 1.19-1.61, p < 0.01). CONCLUSIONS AND INFERENCES: The prevalence (1.03%-1.21%) and incidence (109-142/100,000) of FD/GP in primary care over last decade appear to conflict with epidemiological research in the general population. The discrepancies suggest a potential lack of awareness of FD and GP among physicians and/or patients in Flemish-Belgium.

Association of the minimal cyclophosphamide equivalent dose and outcome of microdissection testicular sperm extraction in patients with persistent azoospermia after chemotherapy.

Objective: To investigate whether the minimal cyclophosphamide equivalent dose (mCED), a novel approach for estimating alkylating agent exposure, is associated with the sperm retrieval rates by microdissection testicular sperm extraction (mTESE) in azoospermic postchemotherapy cancer survivors. Design: A retrospective cohort study conducted between 2002 and 2017. Setting: An academic medical center. Patients: A total of 28 azoospermic postchemotherapy cancer survivors who underwent mTESE. Interventions: Chemotherapy exposure and mCED calculation. Main Outcome Measures: The primary outcome was the association between the mCED and sperm retrieval rate using mTESE. The mCED value for each patient's regimen received was estimated using the lowest recommended dosing regimen from the range of recommended doses at the time of administration. Results: Spermatozoa were successfully retrieved in 11 (39.3%) of the patients. Age at the time of receiving chemotherapy and mCED were significant factors associated with sperm retrieval. An mCED of <4,000 mg/m2 had a higher sperm retrieval rate (10/14, 71.4%) than an mCED of >4,000 mg/m2 (0/8, 0). The hormone levels were not significantly different when comparing patients with and without successful sperm retrieval. Seminoma, nonseminomatous germ cell tumor, and acute lymphoblastic leukemia had favorable sperm retrieval rates-100% (2/2), 66.7% (2/3), and 66.7% (2/3), respectively-although the numbers of patients in each group were small. Conclusion: Among this cohort of patients with cancer who required chemotherapy regimens, successful sperm retrieval by mTESE was only noted among cancer survivors receiving an mCED of <4,000 mg/m2.

Oral Dexmedetomidine Achieves Superior Effects in Mitigating Emergence Agitation and Demonstrates Comparable Sedative Effects to Oral Midazolam for Pediatric Premedication: A Systematic Review and Meta-Analysis of Randomized Controlled Studies.

Background: Oral midazolam is the most commonly used sedative premedication agent in pediatric patients. While effective, oral midazolam cannot reduce the incidence of emergence agitation. Oral dexmedetomidine may be effective in providing satisfactory sedation and reduce the incidence of emergence agitation, although the results of different randomized controlled trials are conflicting. Methods: This study enrolled randomized controlled trials (RCTs) examining premedication with oral dexmedetomidine versus oral midazolam in pediatric patients undergoing general anesthesia. PubMed, the Cochrane Library, Embase, and the Web of Science database were searched from their inception until June 2023. The outcomes were the incidence of satisfactory preoperative sedation, satisfactory sedation during separation from parents, satisfactory sedation during anesthesia induction using an anesthesia mask, and the incidence of emergence agitation. Results: A total of 9 RCTs comprising 885 patients were analyzed. Our data revealed comparable effects of dexmedetomidine and midazolam with respect to satisfactory preoperative sedation and a satisfactory incidence of sedation during parental separation and mask acceptance before anesthesia induction. Notably, our data revealed that the rate of emergence agitation was significantly lower in pediatric patients receiving dexmedetomidine (n = 162) than in those receiving midazolam (n = 159) (odds ratio = 0.16; 95% confidence interval: 0.06 to 0.44; p < 0.001; I2 = 35%). Conclusions: Data from this meta-analysis revealed comparable effects for premedication with oral dexmedetomidine or oral midazolam with respect to satisfactory sedation; furthermore, premedication with oral dexmedetomidine more effectively mitigated emergence agitation in pediatric patients receiving general anesthesia compared with oral midazolam.