Category: Nevin Manimala

Int J Surg. 2023 Nov 22. doi: 10.1097/JS9.0000000000000912. Online ahead of print.

ABSTRACT

BACKGROUND: There is no standard management for small cell esophageal carcinoma (SCEC). The purpose of this multicenter, retrospective study (ChiSCER) was to investigate the treatment, outcomes, and risk factors impacting on survival endpoints in patients with limited-stage SCEC (LS-SCEC).

MATERIALS AND METHODS: Consecutive patients with LS-SCEC from 14 institutions between 2000 to 2020 in China were enrolled. Survival curves were constructed using the Kaplan-Meier method and compared by log-rank test. Univariate and multivariate Cox regression models and propensity score matching (PSM) analysis were adopted in prognostic analysis. Results were reported as hazard ratio (HR), 95% confidence interval (CI), and P value. Statistical significance was set as P value<0.05 in a two-tailed test.

RESULTS: Among 458 LS-SCEC patients, the median age was 63 (interquartile range [IQR], 57-68) years, 318 (69%) were males. Eighty-four (18%), 167 (36%), and 207 (45%) patients received chemotherapy (CT) alone, CT plus definitive radiotherapy (CT+RT), and CT plus radical surgery (CT+S), respectively. With a median follow-up time of 58.7 (95% CI, 48.9-68.6) months, the median OS and 3-year OS rate for all patients 24.3 (95% CI, 21.6-27) months and 37.3% (95% CI, 32.8%-42.5%), respectively. Multivariate analysis indicated that treatment modes, Karnofsky performance status (KPS), TNM stage, and CT cycle were independent prognostic factors for overall survival (OS) (P<0.05). Compared with CT alone, patients treated with CT+RT (HR, 0.57, 95% CI, 0.41-0.8, P=0.001) or CT+S (HR, 0.59, 95% CI, 0.42-0.82, P=0.002) had an improved OS, with no significant survival differences between CT+S and CT+RT groups after multivariate and PSM analyses (P>0.05). Subgroup analysis indicated that compared with CT+RT, patients with tumor location at lower 1/3 (HR, 0.59, 95% CI, 0.37-0.93, P=0.03) or tumor length>5 cm (HR 0.52, 95% CI, 0.3-0.9, P=0.02) could obtain significant OS benefit from CT+S. Patients with tumor location at middle 1/3 (HR 1.55, 95% CI, 1.03-2.36, P=0.04) or tumor length≤5 cm (HR 1.49, 95% CI, 1.02-2.17, P=0.04) favored CT+RT. Distant metastasis accounted for 73.7% of all treatment failures after multidisciplinary treatments.

CONCLUSION: Surgery and RT were equally effective local therapies for patients with LS-SCEC. The personalized decision of local therapy should be made after comprehensive considerations on tumor location, length, comorbidities, and organ preservation.

PMID:37995095 | DOI:10.1097/JS9.0000000000000912

Europace. 2023 Nov 2;25(11):euad330. doi: 10.1093/europace/euad330.

ABSTRACT

AIMS: The validated HCM Risk-Kids model provides accurate individualized estimates of sudden cardiac death risk in children with hypertrophic cardiomyopathy (HCM). A second validated model, PRIMaCY, also provides individualized estimates of risk, but its performance and clinical impact has not been independently investigated. The aim of this study was to investigate the clinical impact of using the PRIMaCY sudden cardiac death (SCD) risk model in childhood HCM.

METHODS AND RESULTS: The estimated 5-year SCD risk was calculated for children meeting diagnostic criteria for HCM in a large single-centre cohort using PRIMaCY (clinical and genetic) and HCM Risk-Kids model, and model performance was assessed. Three hundred one patients [median age 10 (interquartile range 4-14)] were followed up for an average of 4.9 (±3.8) years, during which 30 (10.0%) reached the SCD or equivalent event endpoint. Harrell’s C-statistic for the clinical and genetic models was 0.66 [95% confidence interval (CI) 0.52-0.8] and 0.66 (95% CI 0.54-0.80) with a calibration slope of 0.19 (95% CI 0.04-0.54) and 0.26 (95% CI -0.03-0.62), respectively. The number needed to treat to potentially treat one life-threatening arrhythmia for the PRIMaCY clinical, PRIMaCY genetic, and HCM Risk-Kids models was 13.7, 14.5, and 9.4, respectively.

CONCLUSION: Although PRIMaCY has a similar discriminatory ability to that reported for HCM Risk-Kids, estimated risk estimates did not correlate well with observed risk. A higher proportion of patients met implantable cardioverter-defibrillator thresholds using PRIMaCY model compared with HCM Risk-Kids. This has important clinical implications as these patients will be exposed to a lifetime risk of complications and inappropriate therapies.

PMID:37995093 | DOI:10.1093/europace/euad330

Dermatol Ther (Heidelb). 2023 Nov 23. doi: 10.1007/s13555-023-01060-5. Online ahead of print.

ABSTRACT

Psoriasis is associated with various comorbidities with a notable psychosocial burden. This systematic literature review explores the burden of depression in patients with psoriasis, comparing it with that experienced by patients with other chronic medical conditions. Embase via Ovid, PubMed, and Cochrane Database of Systematic Reviews via Ovid were searched for peer-reviewed studies published in English between January 1, 2016 and December 6, 2021 that reported real-world evidence or observational studies involving at least 100 adults (age ≥ 18 years) with general (unspecified) or plaque psoriasis experiencing symptoms of depression (but not restricted to patients with a clinical diagnosis). Any report of depression or suicidality was eligible for inclusion. Systematic literature reviews reporting depression/suicidality in other chronic medical conditions were also included. Statistical analysis was not performed; the study was descriptive only. A total of 1744 records were identified, and after several defined screenings by two independent reviewers for publication year, relevance, and sample size, 82 publications were included. Psoriasis was significantly associated with depression. The prevalence of depression in patients with psoriasis ranged from 0.2% to 74.6%, with incidence from 4.83 to 91.9 per 1000 person-years. The prevalence of depression was generally higher among patients with more severe psoriasis than those with less severe disease (as determined by Psoriasis Area Severity Index [PASI] scoring system) and was more prevalent among women than men with psoriasis. Depression in psoriasis significantly reduced quality of life, including factors such as sexual dysfunction, sleep difficulties, subjective well-being, and addictions. Comorbid hypertension, hyperlipidemia, psoriatic arthritis, obesity, inflammatory bowel disease, diabetes, and statin use were all associated with increased depression risk in patients with psoriasis. This systematic literature review found that the burden of depression in psoriasis is no lower than in other chronic medical conditions. Greater awareness of the psychological impact of psoriasis would improve care and management, which should incorporate psychological interventions.

PMID:37995052 | DOI:10.1007/s13555-023-01060-5

EJNMMI Res. 2023 Nov 23;13(1):101. doi: 10.1186/s13550-023-01051-9.

ABSTRACT

BACKGROUND: Radioembolization is one therapeutic option for the treatment of locally early-stage hepatocellular carcinoma. The aim of this study was to evaluate the distribution of Lipiodol® ultra-fluid and microspheres and to simulate their effectiveness with different beta emitters (⁹⁰Y, ¹⁸⁸Re, ³²P, ¹⁶⁶Ho, ¹³¹I, and ¹⁷⁷Lu) on VX2 tumors implanted in the liver of 30 New Zealand rabbits.

RESULTS: Twenty-three out of 30 rabbits had exploitable data: 14 in the group that received Lipiodol® ultra-fluid (group L), 6 in the group that received microspheres (group M), and 3 in the control group (group C). The histologic analysis showed that the Lipiodol® ultra-fluid distributes homogeneously in the tumor up to 12 days after injection. The X-ray μCT images showed that Lipiodol® ultra-fluid has a more distal penetration in the tumor than microspheres. The entropy (disorder of the system) in the L group was significantly higher than in the M group (4.06 vs 2.67, p = 0.01). Equivalent uniform biological effective doses (EUBED) for a tumor-absorbed dose of 100 Gy were greater in the L group but without statistical significance except for ¹⁷⁷Lu (p = 0.03). The radionuclides ranking by EUBED (from high to low) was ⁹⁰Y, ¹⁸⁸Re, ³²P, ¹⁶⁶Ho, ¹³¹I, and ¹⁷⁷Lu.

CONCLUSIONS: This study showed a higher ability of Lipiodol® ultra-fluid to penetrate the tumor that translated into a higher EUBED. This study confirms ⁹⁰Y as a good candidate for radioembolization, although ³²P, ¹⁶⁶Ho, and ¹⁸⁸Re can achieve similar results.

PMID:37995042 | DOI:10.1186/s13550-023-01051-9

Am J Cardiovasc Drugs. 2023 Nov 23. doi: 10.1007/s40256-023-00616-2. Online ahead of print.

ABSTRACT

INTRODUCTION: Cangrelor is a potent intravenous non-thienopyridine P2Y12 inhibitor. We conducted a network meta-analysis to study the efficacy and safety of cangrelor as compared with the oral P2Y12 inhibition, clopidogrel, or placebo in acute coronary syndromes.

METHODS: This meta-analysis followed the Cochrane collaboration guidelines and the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) protocols. Outcomes of interest included all-cause mortality, myocardial infarction, stent thrombosis, target vessel revascularization, major bleeding, minor bleeding, and the need for blood transfusion.

RESULTS: The analysis was comprised of 6 studies including 26,444 patients treated with cangrelor, clopidogrel, or placebo. There were no statistically significant differences in the incidence of all-cause mortality, myocardial infarction, stent thrombosis, target vessel revascularization, or major bleeding. Cangrelor was associated with a higher risk of minor bleeding than clopidogrel or placebo, with no difference in requiring blood transfusion.

CONCLUSION: Cangrelor has comparable outcomes to clopidogrel in patients with acute coronary syndromes and can be used as a reliable alternative in this population.

PMID:37995040 | DOI:10.1007/s40256-023-00616-2

Environ Sci Pollut Res Int. 2023 Nov 23. doi: 10.1007/s11356-023-31047-w. Online ahead of print.

ABSTRACT

The correlation between air pollution and neurodegenerative diseases has garnered growing attention. Although observational studies have indicated a potential link between air pollution and neurodegenerative disease, establishing a causal relationship remains uncertain. To address this gap, we performed a two-sample Mendelian randomization analysis utilizing genetic instruments. This analysis aimed to investigate the causal connections between PM_2.5, PM₁₀, NO₂, and NO_X exposure and the occurrence of Parkinson’s disease (PD) and Alzheimer’s disease (AD). We implemented a series of filtering steps to identify suitable genetic instruments that demonstrated significant associations (P < 5 × 10^-8) with PM_2.5, PM₁₀, NO₂, and NO_X. These instruments were derived from a comprehensive genome-wide association study (GWAS) encompassing up to 456,380 participants in the UK Biobank. To obtain summary statistics for PD (N = 482,730) and AD risk (N = 63,926), we utilized the most recent GWAS datasets available. For our primary analysis, we employed the inverse-variance weighted approach for two-sample MR. A multivariable MR (MVMR) was also performed to verify the impact of air pollution exposure on the risk of PD and AD. To ensure the robustness of our findings, sensitivity analyses and heterogeneity assessments were performed. In two-sample MR, by employing the inverse-variance weighted method, our result suggested that genetically NO₂ exposure showed a significant association with an elevated risk of PD (OR = 4.07, 95% CI: 1.13 to 19.62, P = 0.034) and genetically PM₁₀ exposure exhibited a significant association with a heightened risk of AD (OR = 1.93, 95% CI: 1.03-3.59, P = 0.040). Further MVMR analysis demonstrated that the causal effect between NO₂ and PD disappeared (OR = 3.489, 95% CI: 0.01 to 2.1e + 03, P = 0.703), and only PM₁₀ was associated with an increased risk of AD (OR = 6.500, 95% CI: 1.10 to 38.51, P = 0.039). Sensitivity analysis showed no detectable heterogeneity and pleiotropy (P > 0.05). Our findings demonstrate that NO₂ and PM₁₀ exposure may contribute to a risk of PD and AD, respectively. Future research is necessary to elucidate potential physiopathological mechanisms.

PMID:37995032 | DOI:10.1007/s11356-023-31047-w

Environ Monit Assess. 2023 Nov 23;195(12):1522. doi: 10.1007/s10661-023-12152-2.

ABSTRACT

Environmental pollution by anthropogenic activity is still a highly relevant global problem. Aquatic animals are a specifically endangered group of organisms due to their continuous direct contact with the contaminated environment. Concentrations of selected trace elements in the grass carp (Ctenopharyngodon idella) (n = 36) blood serum/clot were monitored. Possible effects of the elements on selected biochemical and oxidative markers were evaluated. The concentrations of trace elements (Al, Ba, Be, Bi, Cd, Co, Cr, Cu, Fe, Ga, Mn, Mo, Ni, Pb, Sr, Tl, and Zn) were analysed in the fish blood serum and blood clot by inductively coupled plasma optical emission spectrometry (ICP OES). A general scheme of decreasing concentrations of trace elements in the blood serum samples was: Zn ˃ Fe ˃ Sr ˃ Ba ˃ Ni ˃ Al ˃ Cu ˃ Be ˃ Co; < LOQ (below limit of quantification): Bi, Cd, Cr, Ga, Mn, Mo, Pb, Tl; and in the case of the blood clot, the scheme was as follows: Fe ˃ Zn ˃ Sr ˃ Al ˃ Ni ˃ Ba ˃ Cu ˃ Be ˃ Co ˃ Mn; < LOQ (below limit of quantification): Bi, Cd, Cr, Ga, Mo, Pb, Tl. Significant differences among the seasons were detected. The Spearman R correlation coefficients and linear or non-linear regression were used to evaluate direct relationships between trace elements and selected blood biomarkers. The correlation analysis between biochemical parameters (Na, K, P, Mg, AST, ALT, ALP, GGT, TAG, TP, urea, glucose) and trace elements (Al, Ba, Be, Cu, Fe, Ni, Sr, and Zn) concentrations confirmed statistically significant interactions in both seasons (summer and autumn). The regression analysis between oxidative stress markers (ROS, GPx, creatinine, uric acid, and bilirubin) and elements (Al, Ba, Co, Cu, Fe, Ni, and Sr) content confirmed statistically significant interactions. The results point to numerous connections between the observed elements and the physiological parameters of freshwater fish.

PMID:37995020 | DOI:10.1007/s10661-023-12152-2

Geroscience. 2023 Nov 23. doi: 10.1007/s11357-023-00999-9. Online ahead of print.

ABSTRACT

Nicotinamide riboside (NR) increases blood levels of NAD+, a cofactor central to energy metabolism, and improves brain function in some rodent models of neurodegeneration. We conducted a placebo-controlled randomized pilot study with the primary objective of determining safety of NR in older adults with mild cognitive impairment (MCI). Twenty subjects with MCI were randomized to receive placebo or NR using dose escalation to achieve, and maintain, a final dose of 1 g/day over a 10-week study duration. The primary outcome was post-treatment change from baseline measures of cognition (Montreal Cognitive Assessment, MoCA). Predefined secondary outcomes included post-treatment changes in cerebral blood flow (CBF); blood NAD+ levels; and additional neurocognitive, psychometric, and physical performance tests. DNA methylation was assessed in peripheral blood mononuclear cells (PBMCs) as an exploratory outcome. The target NR dose was safely achieved as evidenced by a 2.6-fold increase in blood NAD+ in the NR group (p < 0.001, 95% CI [17.77, 43.49]) with no between-group difference in adverse event reporting. MoCA and other neurocognitive and psychometric metrics remained stable throughout the study. NR reduced CBF in the default mode network (DMN) with greatest differences observed in the left inferior parietal lobe (IPL) (DMN p = 0.013, μ = 0.92, 95% CI [0.23, 1.62]; left IPL p = 0.009, μ = 1.66, 95% CI [0.5, 2.82]). Walking speed in the placebo group significantly improved across the study duration suggestive of a practice effect but did not change in the NR group (p = 0.0402 and p = 0.4698, respectively). Other secondary outcome measures remained stable. Global methylation analyses indicated a modest NR-associated increase in DNA methylation and concomitant reduction in epigenetic age as measured by PhenoAge and GrimAge epigenetic clock analyses. In summary, NR significantly increased blood NAD+ concentrations in older adults with MCI. NR was well tolerated and did not alter cognition. While CBF was reduced by NR treatment, statistical significance would not have withstood multiple comparisons correction. A larger trial of longer duration is needed to determine the potential of NR as a strategy to improve cognition and alter CBF in older adults with MCI. ClinicalTrials.gov NCT02942888.

PMID:37994989 | DOI:10.1007/s11357-023-00999-9

Ann Intensive Care. 2023 Nov 23;13(1):114. doi: 10.1186/s13613-023-01208-8.

ABSTRACT

BACKGROUND: The effectiveness of high-flow nasal cannula oxygen therapy (HFNC) in patients with acute respiratory failure due to COVID-19 remains uncertain. We aimed at assessing whether HFNC is associated with reduced risk of intubation or mortality in patients with acute respiratory failure due to COVID-19 compared with conventional oxygen therapy (COT).

METHODS: In this systematic review and meta-analysis, we searched MEDLINE, Embase, Web of Science, and CENTRAL databases for randomized controlled trials (RCTs) and observational studies comparing HFNC vs. COT in patients with acute respiratory failure due to COVID-19, published in English from inception to December 2022. Pediatric studies, studies that compared HFNC with a noninvasive respiratory support other than COT and those in which intubation or mortality were not reported were excluded. Two authors independently screened and selected articles for inclusion, extracted data, and assessed the risk of bias. Fixed-effects or random-effects meta-analysis were performed according to statistical heterogeneity. Primary outcomes were risk of intubation and mortality across RCTs. Effect estimates were calculated as risk ratios and 95% confidence interval (RR; 95% CI). Observational studies were used for sensitivity analyses.

RESULTS: Twenty studies were analyzed, accounting for 8383 patients, including 6 RCTs (2509 patients) and 14 observational studies (5874 patients). By pooling the 6 RCTs, HFNC compared with COT significantly reduced the risk of intubation (RR 0.89, 95% CI 0.80 to 0.98; p = 0.02) and reduced length of stay in hospital. HFNC did not significantly reduce the risk of mortality (RR 0.93, 95% CI 0.77 to 1.11; p = 0.40).

CONCLUSIONS: In patients with acute respiratory failure due to COVID-19, HFNC reduced the need for intubation and shortened length of stay in hospital without significant decreased risk of mortality. Trial registration The study was registered on the International prospective register of systematic reviews (PROSPERO) at https://www.crd.york.ac.uk/prospero/ with the trial registration number CRD42022340035 (06/20/2022).

PMID:37994981 | DOI:10.1186/s13613-023-01208-8

Environ Monit Assess. 2023 Nov 23;195(12):1524. doi: 10.1007/s10661-023-12147-z.

ABSTRACT

One of the major present challenges in the building sector is to construct sustainable and low-energy buildings with a healthy, safe, and comfortable environment. This study is designed to explore long-term impacts of indoor environmental quality (IEQ) parameters in a historic technical school building on the health and comfort of students. The main objective is to identify environmental problems in schools and to direct public policy towards the enhancement of in-service historic buildings. The collected data on five consecutive days in various seasons from five different classrooms indicate allergy in 45% and asthma in 10% of students. Environmental factors, such as temperature, draught, noise, or light, affected 51% of students’ attention. Low temperature, unpleasant air, noise, and draught were found to be the most frequent concerns for students. The lowest temperature was measured during spring at 17.6 °C, the lowest humidity of 21.1% in winter, the largest CO₂ amount in the air in autumn at 2041 ppm level, and the greatest total volatile organic compounds (TVOC) as 514 µg/m³. The experimental and statistical analysis results suggest the necessity of a comprehensive restoration of the building with a focus on enhancement of IEQ as well as replacement of old non-standard materials. An effective ventilation system is also necessary. The building requires major renovations to preserve its historic features while safeguarding the well-being and comfort of students and staff. Further research is needed on acoustics, lighting, and energy factors as well as the health effects of old building materials.

PMID:37994965 | DOI:10.1007/s10661-023-12147-z