Nevin Manimala

J Radiat Res. 2022 Nov 24:rrac078. doi: 10.1093/jrr/rrac078. Online ahead of print.

ABSTRACT

Although mammalian fetuses have been suggested to be sensitive to radiation, an increased frequency of translocations was not observed in blood lymphocytes from atomic bomb (A-bomb) survivors who were exposed to the bomb in utero and examined as adults. Since experiments using hematopoietic cells of mice and rats confirmed this finding, it was hypothesized that either irradiated fetal hematopoietic stem cells (f-HSCs) cannot generate exchange-type chromosomal aberrations or cells bearing induced aberrations are eliminated before the animals reach adulthood. In the present study, pregnant mice (12.5-15.5 days post coitum [dpc]) were irradiated with 2 Gy of X-rays and long-term HSCs (LT-HSCs) were isolated 24 h later. Multicolor fluorescence in situ hybridization (mFISH) analysis of LT-HSC clones proliferated in vitro showed that nine out of 43 (21%) clones from fetuses and 21 out of 41 (51%) clones from mothers bore translocations. These results indicate that cells with translocations can arise in mouse f-HSCs but exist at a lower frequency than in the mothers 24 h after X-ray exposure. Thus, it seems likely that translocation-bearing f-HSCs are generated but subsequently disappear, so that the frequency of lymphocyte translocations may decrease and reach the control level by the time the animals reach adulthood.

PMID:36420765 | DOI:10.1093/jrr/rrac078

Cancer Med. 2022 Nov 24. doi: 10.1002/cam4.5470. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: In general, there are not many studies exploring the clinical value of adjuvant chemotherapy or maintenance chemotherapy (AC/MC) after induction chemotherapy and concurrent chemoradiotherapy (IC+CCRT+AC/MC). The purpose of this study was to establish a clinical nomogram for the use of AC/MC in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC).

MATERIAL AND METHODS: Two centers (Guangzhou Medical University Cancer Center [N = 1226] and Zhongshan People’s Hospital [N = 150]) recruited 1376 patients with LA-NPC. All the patients underwent IC+CCRT; 560 patients received AC with cisplatin/nedaplatin plus docetaxel/paclitaxel (TP) or cisplatin/nedaplatin plus fluorouracil (PF), and 81 patients received MC with S-1. Multivariate Cox regression was used to confirm optimal predictors of progression-free survival (PFS), and a nomogram was established to identify patients into low-risk and high-risk cohorts. Additionally, bootstrap internal validation was performed to further verify our nomogram.

RESULTS: After propensity score matching (PSM), the survival curves were not statistically different between IC+CCRT+AC/MC and IC+CCRT (all p > 0.05). Then, a nomogram was developed based on variables that were screened by univariate and multivariate Cox regression, including N stage, cumulative platinum dose during CCRT, body mass index (BMI), IC cycles, IC regimen and cervical lymph node (CLN) necrosis and infiltration of adjacent tissues. The results of the nomogram showed that the high-risk cohort had greatly worse 5-year DMFS, LRFS, PFS and OS compared to low-risk cohort (all p < 0.05), and subgroup analysis found that the 5-year DMFS, PFS and OS of patients treated with IC+CCRT+AC/MC were better than those treated with IC+CCRT in high-risk cohort (all p < 0.05). Notably, the incidence of adverse effects for IC+CCRT+AC cohort was higher than that for IC+CCRT+MC cohort, especially leukocytopenia and neutropenia. IC+CCRT and IC+CCRT+MC were associated with similar incidences of adverse effects.

CONCLUSIONS: The addition of AC or MC to IC+CCRT could improve the DMFS of patients with high-risk NPC and prolong their survival. Additionally, our findings suggest a potential role of AC/MC following IC plus CCRT in the treatment of high-risk LA-NPC.

PMID:36420689 | DOI:10.1002/cam4.5470

Musculoskeletal Care. 2022 Nov 24. doi: 10.1002/msc.1716. Online ahead of print.

ABSTRACT

INTRODUCTION: The aim of this study was to evaluate patient reported outcome measures using the EQ5D-5L and EQ5D-5L visual analogue scale (VAS) following elective shoulder and elbow orthopaedic list delays. This was further correlated with patients’ intention to proceed with the planned surgery.

METHODS: Patients on the waiting list for more than 26 weeks were included in the study. Telephone interviews were conducted utilising the EQ5D-5L and the EQ5D-5L VAS at the time of addition to the waiting list and presently.

RESULTS: 75 out of 324 screened patients were eligible. 62 (82.7%) patients still wanted to proceed with their planned procedure while 13 (17.3%) patients in the other group no longer wanted to proceed. There was no statistically significant difference in the mean age, gender, initial trial of conservative treatment and limb laterality between these groups (p < 0.05). There was a statistically significant difference in the mean duration of being on the waiting list between these groups (40.4 ± 19 vs. 62.9 ± 17.5 weeks respectively). Furthermore, statistically significant differences (p < 0.05) in the current EQ5D-5L VAS scores were observed between these groups (52.4 vs. 65.8 respectively).

CONCLUSION: This study has shown that majority of patients on elective shoulder and elbow orthopaedic lists with prolonged waiting list delays and improved EQ5D-5L scores are likely to decline the planned procedure and vice versa. Nevertheless, the unplanned ‘watchful waiting’ caused by the COVID-19 pandemic and leading to patients deciding to decline surgery, is not a substitute for timely planned surgery to alleviate patients’ suffering.

PMID:36420684 | DOI:10.1002/msc.1716

Hum Psychopharmacol. 2022 Nov 24:e2858. doi: 10.1002/hup.2858. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the impact of solriamfetol, a dopamine and norepinephrine reuptake inhibitor, on on-the-road driving performance in participants with narcolepsy.

METHODS: In this randomised, double-blind, placebo-controlled, crossover study, driving performance during a 1 h on-road driving test was assessed at 2 and 6 h post-dose following 7 days of treatment with solriamfetol (150 mg/day for 3 days, followed by 300 mg/day for 4 days) or placebo. The primary endpoint was standard deviation of lateral position (SDLP) at 2 h post-dose.

RESULTS: The study included 24 participants (54% male; mean age, 40 years); 22 had evaluable SDLP data. At 2 h post-dose, median SDLP was significantly lower (improved) with solriamfetol compared with placebo (19.08 vs. 20.46 cm [median difference, -1.9 cm], p = 0.002). Four participants on solriamfetol and 7 on placebo had incomplete driving tests. At 6 h post-dose, median SDLP was not statistically significantly different with solriamfetol compared with placebo (19.59 vs. 19.78 cm [median difference, -1.1 cm], p = 0.125). Three participants on solriamfetol and 10 on placebo had incomplete driving tests. Common adverse events (≥5%) included headache, decreased appetite, and somnolence.

CONCLUSIONS: Solriamfetol 300 mg/day improved on-the-road driving performance, at 2 h post-administration in participants with narcolepsy.

PMID:36420633 | DOI:10.1002/hup.2858

Artif Organs. 2022 Nov 24. doi: 10.1111/aor.14465. Online ahead of print.

ABSTRACT

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) became an accepted therapy for the treatment of severe acute respiratory distress syndrome and chronic obstructive pulmonary disease. However, ECMO systems are still prone to thrombus formation and decrease of gas exchange over time. Therefore, it is necessary to conduct qualified studies to identify parameters for optimization of ECMO systems, and especially the oxygenator. However, commercially marketed oxygenators are not always appropriate and available for certain research use cases. Therefore, we aimed to design an oxygenator, which is suitable for various test conditions such as blood tests, numerical simulation, and membrane studies, and can be modified in membrane area size and manufactured in laboratory.

METHODS: Main design criteria are a homogeneous blood flow without stagnation zones, low pressure drop, manufacturability in the lab, size variability with one set of housing parts and cost-efficiency. Our newly designed oxygenator was tested comparatively regarding blood cell damage, gas transfer performance and pressure drop to prove the validity of the design in accordance with a commercial device.

RESULTS: No statistically significant difference between the tested oxygenators was detected and our new oxygenator demonstrated sufficient hemocompatibility. Furthermore, our variable oxygenator has proven that it can be easily manufactured in the laboratory, allows to use various membrane fiber configurations and can be reopened easily and non-destructively for analysis after use, and the original geometry is available for numerical simulations.

CONCLUSION: Therefore, we consider this newly developed device as a valuable tool for basic experimental and numerical research on the optimization of oxygenators.

PMID:36420613 | DOI:10.1111/aor.14465

Scand J Med Sci Sports. 2022 Nov 24. doi: 10.1111/sms.14278. Online ahead of print.

ABSTRACT

The purpose was to investigate effect of a school-based physical activity (PA)-intervention among 11-and 12-year-olds (6^th – and 7^th graders) across four years. Seven primary schools in Horten municipality in Norway received 45 minutes daily extra PA as part of the curriculum. The intervention started in 2015 with follow-up in 2016 to 2019. The effect was measured after one to four years of participation, among the same children (6^th – to 7^th -grade) and among new children starting in 6^th grade. Two control schools received no additional PA beyond the regular PA at school. The Self-reported Strength and Difficulties Questionnaire (SDQ-S) focusing on internalizing and externalizing difficulties were administrated. A statistical model for repeated measurements was used and adjusted for parents’ educational level, sex, age, and waist-to-height ratio (WHtR). The significance level was p≤0.01. In total, 1221 children completed the SDQ-S. SDQ-S scores were stable, and difficulties were relatively low. The control group had significantly lower SDQ-S scores than the intervention group at start, indicating fewer difficulties. The adjusted effect within the intervention schools showed a borderline significant increase in total difficulty score between 2018 and 2019 (mean difference: 1.02, 95%CI: (-1.82, -0.23, p 0.01). Educational level showed a weak negative correlation with total difficulty score (r=-0.1). No significant change was reported within the control schools. Few psychosocial health problems among 11- and 12-year-olds were detected. The borderline increase in total difficulty score that that was seen for the intervention schools, is believed to be of limited clinical relevance.

PMID:36420609 | DOI:10.1111/sms.14278

Vet Surg. 2022 Nov 24. doi: 10.1111/vsu.13913. Online ahead of print.

ABSTRACT

OBJECTIVE: To document variations in the application of equine prosthetic laryngoplasty among equine surgeons.

STUDY DESIGN: Cross-sectional survey.

SAMPLE POPULATION: Six hundred and seventy-eight equine surgeons performing prosthetic laryngoplasty.

METHODS: An online questionnaire was sent to equine surgeons, including diplomates of the American College of Veterinary Surgeons and European College of Veterinary Surgeons. Questions focused on participant profile, surgical technique, antimicrobial therapy, and concurrent procedures. Descriptive statistical analysis was performed on the survey output.

RESULTS: Complete responses were received from 128/678 individuals, mostly from experienced surgeons. Most participants used 2 prostheses (106/128, 82.8%) and a single loop was the most common method used to anchor the prosthesis in the cricoid (95/128, 74.2%) and arytenoid (125/128, 97.7%) cartilages. Use of general anesthesia was common, although 46/128 (35.9%) participants now performed most laryngoplasty surgery with standing sedation. The material used as a prosthesis varied among surgeons, although participants typically aimed to achieve grade 2 intraoperative arytenoid abduction. Participants most commonly administered perioperative systemic antimicrobial therapy for 1-3 days (57/128, 44.5%) and 48/128 (37.5%) used local antimicrobial therapy.

CONCLUSION: Most surgeons performed laryngoplasty with 2 prostheses, a single loop construct at the muscular process of the arytenoid cartilage and systemic antimicrobial therapy. There was variation in the preferred method of surgical restraint, prosthesis material selection, and use of local antimicrobial therapy.

CLINICAL SIGNIFICANCE: Long-established techniques remain popular in clinical practice despite evidence that variations offer advantages, particularly in relation to biomechanics. Other factors are also likely to influence technique selection in a clinical context.

PMID:36420588 | DOI:10.1111/vsu.13913

Korean J Intern Med. 2022 Nov 24. doi: 10.3904/kjim.2022.084. Online ahead of print.

ABSTRACT

BACKGROUND/AIMS: Secondary infection with influenza virus occurs in critically ill patients and is associated with substantial morbidity and mortality; however, there is limited information about it in patients with severe coronavirus disease 2019 (COVID-19). Thus, we investigated the clinical outcomes of and risk factors for secondary infections in patients with severe COVID-19.

METHODS: This study included patients with severe COVID-19 who were admitted to seven hospitals in South Korea between February 2020 to February 2021. Multivariate logistic regression analyses were performed to assess factors associated with the risk of secondary infections.

RESULTS: Of the 348 included patients, 104 (29.9%) had at least one infection. There was no statistically significant difference in the 28-day mortality (17.3% vs. 12.3%, p = 0.214), but in-hospital mortality was higher (29.8% vs. 15.2%, p = 0.002) in the infected group than in the non-infected group. The risk factors for secondary infection were a high frailty scale (odds ratio [OR], 1.314; 95% confidence interval [CI], 1.123 to 1.538; p = 0.001), steroid use (OR, 3.110; 95% CI, 1.164 to 8.309; p = 0.024), and the application of mechanical ventilation (OR, 4.653; 95% CI, 2.533 to 8.547; p < 0.001).

CONCLUSIONS: In-hospital mortality was more than doubled in patients with severe COVID-19 and secondary infections. A high frailty scale, the use of steroids and application of mechanical ventilation were risk factors for secondary infection.

PMID:36420564 | DOI:10.3904/kjim.2022.084

Korean J Intern Med. 2022 Nov 24. doi: 10.3904/kjim.2022.283. Online ahead of print.

ABSTRACT

BACKGROUND/AIMS: The Korean Diabetes Association (KDA) guidelines recommend adults aged ≥ 40 years and adults aged ≥ 30 years with diabetes risk factors for diabetes screening. This study aimed to determine the age threshold for diabetes screening in Korean adults.

METHODS: This study was based on the analyses of Korean adults aged ≥ 20 years using the Korea National Health and Nutrition Examination Survey (KNHANES) and the National Health Insurance Service-National Sample Cohort (NHIS-NSC). To evaluate screening effectiveness, we calculated the number needed to screen (NNS).

RESULTS: NNS to detect diabetes decreased from 63 to 34 in the KNHANES and from 71 to 42 in the NHIS-NSC between the ages of 30-34 and 35-39. When universal screening was applied to adults aged ≥ 35, the NNS was similar to that of adults aged ≥ 40. Compared to the KDA guidelines, the rate of missed screening positive in adults aged ≥ 20 decreased from 4.0% to 0.2% when the newly suggested screening criteria were applied.

CONCLUSIONS: Universal screening for adults aged ≥ 35 and selective screening for adults aged 20 to 34, considering diabetes risk factors, may be appropriate for detecting prediabetes and diabetes in South Korea.

PMID:36420563 | DOI:10.3904/kjim.2022.283

Int J Biostat. 2022 Nov 24. doi: 10.1515/ijb-2022-0001. Online ahead of print.

ABSTRACT

This paper proposes a new flexible discrete triplet Lindley model that is constructed from the balanced discretization principle of the extended Lindley distribution. This model has several appealing statistical properties in terms of providing exact and closed form moment expressions and handling all forms of dispersion. Due to these, this paper explores further the usage of the discrete triplet Lindley as an innovation distribution in the simple integer-valued autoregressive process (INAR(1)). This subsequently allows for the modeling of count time series observations. In this context, a novel INAR(1) process is developed under mixed Binomial and the Pegram thinning operators. The model parameters of the INAR(1) process are estimated using the conditional maximum likelihood and Yule-Walker approaches. Some Monte Carlo simulation experiments are executed to assess the consistency of the estimators under the two estimation approaches. Interestingly, the proposed INAR(1) process is applied to analyze the COVID-19 cases and death series of different countries where it yields reliable parameter estimates and suitable forecasts via the modified Sieve bootstrap technique. On the other side, the new INAR(1) with discrete triplet Lindley innovations competes comfortably with other established INAR(1)s in the literature.

PMID:36420542 | DOI:10.1515/ijb-2022-0001