Category: Nevin Manimala

J Clin Oncol. 2022 Nov 11:JCO2201637. doi: 10.1200/JCO.22.01637. Online ahead of print.

ABSTRACT

PURPOSE: We sought to evaluate the independent and interactive associations of planned treatment duration, celecoxib use, physical activity, body mass index (BMI), diabetes mellitus, and vitamin B6 with oxaliplatin-induced peripheral neuropathy (OIPN) among patients with stage III colon cancer enrolled in a clinical trial.

METHODS: We conducted a prospective, observational study of 2,450 patients with stage III colon cancer enrolled in the CALGB/SWOG 80702 trial, randomly assigned to 6 versus 12 cycles of adjuvant fluorouracil, leucovorin, and oxaliplatin chemotherapy with or without 3 years of celecoxib. OIPN was reported using the Common Terminology Criteria for Adverse Events (CTCAE) during and following completion of chemotherapy and the FACT/GOG-NTX-13 15-17 months after random assignment. Multivariate analyses were adjusted for baseline sociodemographic and clinical factors.

RESULTS: Patients assigned to 12 treatment cycles, relative to 6, were significantly more likely to experience higher-grade CTCAE- and FACT/GOG-NTX-13-reported neuropathy and longer times to resolution, while neither celecoxib nor vitamin B6 intake attenuated OIPN. Exercising ≥ 9 MET-hours per week after treatment relative to < 9 was associated with improvements in FACT/GOG-NTX-13-reported OIPN (adjusted difference in means, 1.47; 95% CI, 0.49 to 2.45; P = .003). Compared with patients with baseline BMIs < 25, those with BMIs ≥ 25 were at significantly greater risk of developing higher-grade CTCAE-reported OIPN during (adjusted odds ratio, 1.18; 95% CI, 1.00 to 1.40; P = .05) and following completion (adjusted odds ratio, 1.23; 95% CI, 1.01 to 1.50; P = .04) of oxaliplatin treatment. Patients with diabetes were significantly more likely to experience worse FACT/GOG-NTX-13-reported neuropathy relative to those without (adjusted difference in means, -2.0; 95% CI, -3.3 to -0.73; P = .002). There were no significant interactions between oxaliplatin treatment duration and any of these potentially modifiable exposures.

CONCLUSION: Lower physical activity, higher BMI, diabetes, and longer planned treatment duration, but not celecoxib use or vitamin B6 intake, may be associated with significantly increased OIPN severity.

PMID:36367997 | DOI:10.1200/JCO.22.01637

Hematology. 2022 Dec;27(1):1217-1222. doi: 10.1080/16078454.2022.2140980.

ABSTRACT

OBJECTIVES: This study evaluates the efficacy and safety of plasmapheresis without plasma transfusion tandem with chemotherapy in treating multiple myeloma (MM).

METHOD: This retrospective study involves seventy-two patients, newly diagnosed with multiple myeloma, divided into two groups; one with plasmapheresis without plasma transfusion tandem with the chemotherapy group (Trial group), while the second was chemotherapy group (Control group). The levels of Plasma Globulin, β2-microglobulin, Creatinine, Vascular endothelial growth factor (VEGF), and IL-6 were monitored after plasmapheresis, at initial diagnosis, and after four chemotherapy courses. Overall response rate of groups after four courses of chemotherapy was analyzed, and the adverse events were recorded.

RESULTS AND DISCUSSION: The baseline data showed that sixty-seven percent of patients were at the ISS III stage and showed more severe renal insufficiency in the Trial group. The Plasma Globulin, β2-microglobulin, VEGF and IL-6 levels were significantly different between the two groups during the initial diagnosis. After three times plasmapheresis, Plasma Globulin, β2-microglobulin, VEGF, and IL-6 were significantly reduced in the plasmapheresis group. The Creatinine levels were also lowered, but the differences were not statistically significant. After four courses of chemotherapy, the levels of VEGF and IL-6 in the two groups were significantly reduced than the initial diagnosis; the differences were statistically considerable. No adverse events were found in the trial group as compared to the control group.

CONCLUSION: Plasmapheresis reduces Globulin, β2-microglobulin, serum VEGF and IL-6 levels in MM, improves renal functions, and releases some patients from dialysis dependence.

PMID:36367991 | DOI:10.1080/16078454.2022.2140980

J Proteome Res. 2022 Nov 11. doi: 10.1021/acs.jproteome.2c00371. Online ahead of print.

ABSTRACT

Untargeted liquid chromatography-mass spectrometry metabolomics studies are typically performed under roughly identical experimental settings. Measurements acquired with different LC-MS protocols or following extended time intervals harbor significant variation in retention times and spectral abundances due to altered chromatographic, spectrometric, and other factors, raising many data analysis challenges. We developed a computational workflow for merging and harmonizing metabolomics data acquired under disparate LC-MS conditions. Plasma metabolite profiles were collected from two sets of maternal subjects three years apart using distinct instruments and LC-MS procedures. Metabolomics features were aligned using metabCombiner to generate lists of compounds detected across all experimental batches. We applied data set-specific normalization methods to remove interbatch and interexperimental variation in spectral intensities, enabling statistical analysis on the assembled data matrix. Bioinformatics analyses revealed large-scale metabolic changes in maternal plasma between the first and third trimesters of pregnancy and between maternal plasma and umbilical cord blood. We observed increases in steroid hormones and free fatty acids from the first trimester to term of gestation, along with decreases in amino acids coupled to increased levels in cord blood. This work demonstrates the viability of integrating nonidentically acquired LC-MS metabolomics data and its utility in unconventional metabolomics study designs.

PMID:36367990 | DOI:10.1021/acs.jproteome.2c00371

Health Secur. 2022 Nov 11. doi: 10.1089/hs.2022.0037. Online ahead of print.

ABSTRACT

This article reports on an assessment of the value of 4 widely recognized standards of health sector emergency preparedness as predictors of effective preparedness for, and response to, the COVID-19 pandemic in the United States. The standards are sponsored by the National Health Security Preparedness Index (NHSPI), the Trust for America’s Health (TFAH), the Emergency Management Accreditation Program (EMAP), and the Public Health Accreditation Board (PHAB). The measure of effectiveness was states’ cumulative COVID-19 deaths per 100,000 population, from January 21, 2020, through January 20, 2022. Linear regression analysis found no statistically significant associations when controlling for 3 intervening variables. Cross-tabulation of states’ preparedness status with their COVID-19 death rates found that high NHSPI and TFAH preparedness scores were generally, but not uniformly, associated with lower death rates. EMAP and PHAB accreditation had negligible association with low or high death rates. Lack of accreditation was associated with lower death rates. Higher prior state public health spending related to COVID-19 preparedness and higher state household income, an indicator of state economic strength, were associated with lower death rates. States with Democratic control of the legislative and executive branches of government generally had substantially lower death rates than states with Republican control. A science-based, practice-oriented research initiative is recommended to improve the predictive power of health sector preparedness standards and to enhance protection for US residents from large-scale future health threats.

PMID:36367989 | DOI:10.1089/hs.2022.0037

Ther Hypothermia Temp Manag. 2022 Nov 11. doi: 10.1089/ther.2022.0017. Online ahead of print.

ABSTRACT

This study aims to explore the value of lithotomy position thermal sleeve application during lower abdominal surgery in patients with hypothermia. A total of 100 patients who underwent urinary, gastrointestinal, or gynecological operations were included in this study. The patients were randomly divided into two groups: the test group (n = 50) and the control group (n = 50). In the control group, the environment, fluid, patient upper abdomen, and pasted 3 L stone-cut pants were heated. In the test group, the lithotomy position surgical warmer was used based on environment, fluid, and upper abdomen warming. The various indicators present in the two groups were compared and analyzed using the Statistical Package for Social Sciences 19.0. Before the operation, the body temperature was 36.73°C ± 0.28°C in the test group and 36.74°C ± 0.29°C in the control group; the difference between the two groups was not statistically significant (p > 0.05). In the test group, the entry temperature was 36.83°C ± 0.04°C; after 2 hours of operation, it became 37.21°C ± 0.03°C. There were no significant changes in body temperature after 4 hours of operation, basic body temperature was maintained (36.80°C ± 0.02°C). In the control group, the entry temperature was 36.54°C ± 0.05°C; however, it became 35.94°C ± 0.07°C after 2 hours of operation, making the patient prone to developing hypothermia. The differences between the two groups were statistically significant (p < 0.05). In patients undergoing urinary, anorectal, or gynecological operations, the use of a warming intervention during surgery in the lithotomy position can effectively stabilize body temperature and reduce the occurrence of postoperative shivering. ClinicalTrials.gov ID: ChiCTR2100046522.

PMID:36367979 | DOI:10.1089/ther.2022.0017

J Integr Complement Med. 2022 Nov 11. doi: 10.1089/jicm.2022.0610. Online ahead of print.

ABSTRACT

Introduction: Multiple sclerosis (MS) is a progressive disease of the central nervous system that can result in highly variable effects on mobility and sensorimotor function. Persons with MS (pwMS) often use complementary and alternative approaches, such as acupuncture, to address these symptoms. However, studies of acupuncture on these symptoms have been hindered by methodologic flaws, which have limited the ability to draw conclusions about its efficacy. The purpose of this study was to examine the feasibility of an acupuncture intervention on a wide range of sensorimotor and mobility measurements in pwMS. Methods: Using a randomized crossover design, subjects experienced acupuncture or a no treatment control condition twice weekly for 4 weeks, followed by a 4-week washout period, and then crossed over to the other condition for 4 weeks. Strength, sensation, spasticity, gait, and balance were measured for all subjects, both before and after each condition. Results: Seven of the 12 subjects who started the program completed all phases. No subjects experienced adverse effects. No statistically significant changes were observed in the gait or balance measures. Small statistically significant changes were observed in upper extremity strength. Sensation and spasticity were unaffected. Discussion: The variability of MS suggests that a wide array of testing procedures be utilized, however, this may have led to difficulty with completing all phases of the study. Acupuncture did not result in changes in mobility in pwMS. Some improvements in upper extremity strength were observed. It is unclear whether these changes represent the effect of acupuncture or the inherent variability of MS.

PMID:36367978 | DOI:10.1089/jicm.2022.0610

J Med Internet Res. 2022 Nov 9. doi: 10.2196/40701. Online ahead of print.

ABSTRACT

BACKGROUND: Social media provide an ideal medium for breeding and reinforcing vaccine hesitancy, especially during public health emergencies. Algorithmic recommendation technology and users’ selective exposure and group pressure leads to online echo chambers, causing vaccination promotion inefficiently. Avoiding or breaking echo chambers largely relies on key users’ behavior.

OBJECTIVE: To eliminate the impact of echo chambers on vaccine hesitancy during public health emergencies on social media, this research aimed to develop a framework to quantify echo chamber effect in users’ topic-selection and attitude-contagion about COVID-19 vaccines or vaccinations, detect online opinion leaders and structural hole spanners based on network-attributes, and explore the relationship of their behavior patterns and network locations, as well as the relationship of network locations and impact on topic-based and attitude-based echo chambers.

METHODS: We called Sina Weibo API to crawl tweets related to COVID-19 vaccine or vaccination and user information on Weibo, a Chinese social media. Adapting social network analysis, we examined low echo chamber effect based on topic in representational networks of information, based on attitude in communication flow networks of users, under different interactive mechanisms (retweeting, commenting). Statistical and visual analysis were used to characterize behavior patterns of key users (opinion leaders, structural hole spanners), and explore their function in avoiding or breaking topic-based and attitude-based echo chambers.

RESULTS: Users showed low echo chamber effect in vaccine-related topic selection and attitude interaction. For the former, the homophily was more obvious in retweeting than in commenting, while for latter, it’s opposite. Speakers, replicators, and monologists tended to be opinion leaders, while common users, retweeters, networkers tended to be structural hole spanners. Both leaders and spanners tended to be bridgers to disseminate diverse topics and communicate with users holding cross-cutting attitudes towards COVID-19 vaccines. Besides, users who tended to echo single topic might bridge multiple attitudes, while users who focused on diverse topics also tended to be bridgers for different attitudes.

CONCLUSIONS: This research not only revealed low echo chamber effect in vaccine hesitancy, but also dug out reasons behind it from the perspective of users, offering insights for research about echo chamber’s form, degree, formation, and depolarization, social capital, stakeholder theory, user portraits, dissemination pattern of topic and sentiment, providing strategies for public health and public opinion managers to cooperate to avoid or correct echo chamber chaos, and promote online vaccine campaign.

PMID:36367965 | DOI:10.2196/40701

Chronic Obstr Pulm Dis. 2022 Oct 31. doi: 10.15326/jcopdf.2022.0326. Online ahead of print.

ABSTRACT

INTRODUCTION: Antiplatelet therapy has been associated with fewer exacerbations and reduced respiratory symptoms in COPD. Whether platelet activation is associated with respiratory symptoms in COPD is unknown.

METHODS: Former smokers with spirometry-confirmed COPD had urine 11-dehydro-thromboxane B2 (11dTxB2), plasma soluble CD40L (sCD40L) and soluble P-selectin (sP-selectin) repeatedly measured during a 6-9-month study period. Multivariate mixed-effects models adjusted for demographics, clinical characteristics, and medication use evaluated the association of each biomarker with respiratory symptoms, health status, and quality of life.

RESULTS: Among 169 participants (average age 66.5±8.2 years, 51.5% female, 47.5±31 pack-years, FEV₁ percent predicted 53.8±17.1), a 100% increase in 11dTxB2 was associated with worse respiratory symptoms reflected by higher scores on the COPD Assessment Test (β 0.77, 95% confidence interval [CI]: 0.11-1.4), Ease of Cough and Sputum Clearance Questionnaire (ECSC) β 0.77, 95%CI: 0.38-1.2, worse health status (Clinical COPD Questionnaire [CCQ] β 0.13, 95%CI: 0.03-0.23) and worse quality of life (St. George’s Respiratory Questionnaire [SGRQ] β 1.9, 95%CI: 0.39-3.4). No statistically significant associations were observed for sCD40L or sP-selectin. There was no consistent statistically significant effect modification of the relationship between urine 11dTxB2 and respiratory outcomes by history of cardiovascular disease, subclinical coronary artery disease, antiplatelet therapy, or COPD severity.

CONCLUSIONS: In stable moderate-severe COPD, elevated urinary 11-dehydro-thromboxane B2, a metabolite of the platelet activation product thromboxane A2, was associated with worse respiratory symptoms, health status, and quality of life.

PMID:36367951 | DOI:10.15326/jcopdf.2022.0326

Transplantation. 2022 Oct 29. doi: 10.1097/TP.0000000000004383. Online ahead of print.

ABSTRACT

BACKGROUND: The effectiveness of the fourth BNT162b2 vaccination in reducing the rate and severity of coronavirus disease 2019 (COVID-19) caused by the Omicron variant in renal transplant recipients (RTRs) is unknown.

METHODS: Interviews were conducted with 447 RTRs regarding the status and timing of the fourth vaccination, prior vaccinations, and preceding COVID-19 infection. RTRs with polymerase chain reaction-confirmed COVID-19 infection from December 1, 2021, to the end of March 2022 were considered to have been infected with the Omicron variant and were interviewed to determine their disease severity. In a subgroup of 74 RTRs, the humoral response to the fourth dose was analyzed. In 30 RTRs, microneutralization assays were performed to reveal the humoral response to wild-type, Delta, and Omicron variant isolates before and after the fourth dose.

RESULTS: Of 447 RTRs, 144 (32.2%) were infected with the Omicron variant, with 71 (49.3%) of the infected RTRs having received the fourth vaccine dose. RTRs who did not receive the fourth dose before the infection had more serious illness. In a subgroup of 74 RTRs, the fourth dose elicited a positive humoral response in 94.6% (70/74), with a significant increase in geometric mean titer for receptor-binding domain immunoglobulin G and neutralizing antibodies (P < 0.001). The humoral responses to the Omicron variant before and after the fourth dose were significantly lower than the responses to the wild-type and the Delta variants.

CONCLUSION: Overall, the fourth BNT162b2 dose was effective in reducing the rate and severity of Omicron disease in RTRs, despite the reduced humoral response to the variant.

PMID:36367927 | DOI:10.1097/TP.0000000000004383

J Phys Chem B. 2022 Nov 11. doi: 10.1021/acs.jpcb.2c04610. Online ahead of print.

ABSTRACT

By analyzing the Kubo-cluster-cumulant expansion of the potential of mean force of polypeptide chains corresponding to backbone-local interactions averaged over the rotation of the peptide groups about the C^α···C^α virtual bonds, we identified two important kinds of “along-chain” correlations that pertain to extended chain segments bordered by turns (usually the β-strands) and to the folded spring-like segments (usually α-helices), respectively, and are expressed as multitorsional potentials. These terms affect the positioning of structural elements with respect to each other and, consequently, contribute to determining their packing. Additionally, for extended chain segments, the correlation terms contribute to propagating the conformational change at one end to the other end, which is characteristic of allosteric interactions. We confirmed both findings by statistical analysis of the virtual-bond geometry of 77 950 proteins. Augmenting coarse-grained and, possibly, all-atom force fields with these correlation terms could improve their capacity to model protein structure and dynamics.

PMID:36367920 | DOI:10.1021/acs.jpcb.2c04610