Nevin Manimala

Vet Comp Oncol. 2022 Sep 16. doi: 10.1111/vco.12858. Online ahead of print.

ABSTRACT

Extracellular vesicles (EVs) are cell-derived membrane-bound vesicles involved in many biological processes such as tumour progression. For years, ultracentrifugation (UC) has been considered the gold standard for EV isolation but limited purity and integrity allowed the diffusion of alternative techniques. In this study, EVs were isolated from a canine mammary tumour cell line using UC and size exclusion chromatography (SEC) and analysed for size and concentration by nanoparticle tracking analysis (NTA) and for protein expression by western blot (WB). EV autocrine effect on cell proliferation, migration and invasiveness was then evaluated in vitro. In all samples, particles were in the EV size range (50-1000 nm), with a higher concentration in UC than in SEC samples (10¹¹ and 10¹⁰ particles/ml respectively), and expressed EV markers (Alix, CD9). Functional assays did not show statistically significant difference among conditions, but EV treatment slightly increased cell proliferation and invasiveness and treatment with SEC-isolated EVs slightly enhanced cell migration compared to UC-isolated EVs. In conclusion, the main differences between the two isolation techniques are the quantity of the final EV-product and slight differences on EV functionality, which should be further explored to better highlight the real autocrine effect of tumoral EVs. This article is protected by copyright. All rights reserved.

PMID:36111535 | DOI:10.1111/vco.12858

Int Wound J. 2022 Sep 16. doi: 10.1111/iwj.13956. Online ahead of print.

ABSTRACT

This meta-analysis aims to systemically evaluate the efficacy of vacuum sealing drainage (VSD) combined with autologous platelet-rich plasma (PRP) in the treatment of diabetic foot ulcers (DFU). The China HowNet, China Biomedical Literature, VIP periodical resource integration service platform, Wanfang, Embase, Cochrane Central, and PubMed databases were retrieved using the computer. The retrieval period was up to July 2021. Randomised controlled trials on VSD combined with PRP in the treatment of DFU were collected. Those trials that met the inclusion criteria were included for meta-analysis using RevMan 5.3 software. A total of 13 articles were included. In the trial group, 477 patients with DFU were treated with VSD combined with PRP, while in the control group, 482 patients with DFU were treated with conventional dressings and/or VSD. The meta-analysis showed that, compared with the control group, VSD combined with PRP has significant advantages in shortening healing time (standardised mean difference [SMD] = -0.87, 95% confidence interval [CI]: -1.07 to -0.67, P < .00001), improving ulcer healing rates (odds ratio = 4.01, 95% CI: 2.95 ~ 5.46, P < .00001), and reducing hospital stays (mean difference = -15.29, 95% CI: -16.05 to -14.54, P < .00001), but the differences in dressing change times (SMD = -1.27, 95% CI: -2.71 to 0.17, P = .08) and hospitalisation expenses (SMD = -0.16, 95% CI: -13.40 to 13.07, P = .98) were not statistically significant. VSD combined with autologous PRP has good curative efficacy in the treatment of DFU and is a better treatment option. However, this treatment is limited in patients with platelet dysfunction, thrombocytopenia, leukaemia, and poor general condition.

PMID:36111514 | DOI:10.1111/iwj.13956

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2022 Sep 15;36(9):1126-1131. doi: 10.7507/1002-1892.202204011.

ABSTRACT

OBJECTIVE: To compare the effectiveness between three-dimensional (3D) printed porous titanium alloy cage (3D Cage) and poly-ether-ether-ketone cage (PEEK Cage) in the posterior lumbar interbody fusion (PLIF).

METHODS: A total of 66 patients who were scheduled to undergo PLIF between January 2018 and June 2019 were selected as the research subjects, and were divided into the trial group (implantation of 3D Cage, n=33) and the control group (implantation of PEEK Cage, n=33) according to the random number table method. Among them, 1 case in the trial group did not complete the follow-up exclusion study, and finally 32 cases in the trial group and 33 cases in the control group were included in the statistical analysis. There was no significant difference in gender, age, etiology, disease duration, surgical segment, and preoperative Japanese Orthopaedic Association (JOA) score between the two groups (P>0.05). The operation time, intraoperative blood loss, complications, JOA score, intervertebral height loss, and interbody fusion were recorded and compared between the two groups.

RESULTS: The operations of two groups were completed successfully. There was 1 case of dural rupture complicated with cerebrospinal fluid leakage during operation in the trial group, and no complication occurred in the other patients of the two groups. All incisions healed by first intention. There was no significant difference in operation time and intraoperative blood loss between groups (P>0.05). All patients were followed up 12-24 months (mean, 16.7 months). The JOA scores at 1 year after operation in both groups significantly improved when compared with those before operation (P<0.05); there was no significant difference between groups (P>0.05) in the difference between pre- and post-operation and the improvement rate of JOA score at 1 year after operation. X-ray film reexamination showed that there was no screw loosening, screw rod fracture, Cage collapse, or immune rejection in the two groups during follow-up. At 3 months and 1 year after operation, the rate of intervertebral height loss was significantly lower in the trial group than in the control group (P<0.05). At 3 and 6 months after operation, the interbody fusion rating of trial group was significantly better in the trial group than in the control group (P<0.05); and at 1 year after operation, there was no significant difference between groups (P>0.05).

CONCLUSION: There is no significant difference between 3D Cage and PEEK Cage in PLIF, in terms of operation time, intraoperative blood loss, complications, postoperative neurological recovery, and final intervertebral fusion. But the former can effectively reduce vertebral body subsidence and accelerate intervertebral fusion.

PMID:36111476 | DOI:10.7507/1002-1892.202204011

Epidemiol Psychiatr Sci. 2022 Sep 16;31:e65. doi: 10.1017/S204579602200049X.

ABSTRACT

AIMS: Lithium has long been believed to reduce the risk of suicide and suicidal behaviour in people with mood disorders. Previous meta-analyses appeared to support this belief, but excluded relevant data due to the difficulty of conducting meta-analysis of rare events. The current study is an updated systematic review and meta-analysis that includes all eligible data, and evaluates suicide, non-fatal suicidal behaviour (including suicidal ideation) and suicide attempts.

METHODS: We searched PubMed, PsycINFO and Embase and some trial registers. We included all randomised trials comparing lithium and placebo or treatment as usual in mood disorders published after 2000, to ensure suicide was reliably reported. Trial quality was assessed using the Cochrane Risk of Bias tool. Pooled data were analysed using Fisher’s Exact test. In addition, meta-analysis was conducted using various methods, prioritizing the Exact method. All trials were included in the analysis of suicide initially, regardless of whether they reported on suicide or not. We conducted a sensitivity analysis with trials that specifically reported on suicides and one that included trials published before 2000. Pre-specified subgroup analyses were performed involving suicide prevention trials, trials excluding people already taking lithium, trials involving people with bipolar disorder exclusively and those involving people with mixed affective diagnoses. Non-fatal suicidal behaviour and suicide attempts were analysed using the same methods, but only trials that reported these outcomes were included. PROSPERO registration: CRD42021265809.

RESULTS: Twelve eligible studies involving 2578 participants were included. The pooled suicide rate was 0.2% for people randomised to lithium and 0.4% with placebo or treatment as usual, which was not a statistically significant difference; odds ratio (OR) = 0.41 (95% confidence interval 0.03-2.49), p = 0.45. Meta-analysis using the Exact method produced an OR of 0.42 (95% confidence interval 0.01-4.5). The result was not substantially different when restricted to 11 trials that explicitly reported suicides and remained statistically non-significant when including 15 trials published before 2000 (mostly in the 1970s). There were no significant differences in any subgroup analysis. There was no difference in rates of all non-fatal suicidal behaviour in seven trials that reported this outcome, or in five trials that reported suicide attempts specifically. Meta-analyses using other methods also revealed no statistically significant differences.

CONCLUSIONS: Evidence from randomised trials is inconclusive and does not support the idea that lithium prevents suicide or suicidal behaviour.

PMID:36111461 | DOI:10.1017/S204579602200049X

Infect Control Hosp Epidemiol. 2022 Sep 16:1-7. doi: 10.1017/ice.2022.66. Online ahead of print.

ABSTRACT

OBJECTIVE: From January 1, 2018, until July 31, 2020, our hospital network experienced an outbreak of vancomycin-resistant enterococci (VRE). The goal of our study was to improve existing processes by applying machine-learning and graph-theoretical methods to a nosocomial outbreak investigation.

METHODS: We assembled medical records generated during the first 2 years of the outbreak period (January 2018 through December 2019). We identified risk factors for VRE colonization using standard statistical methods, and we extended these with a decision-tree machine-learning approach. We then elicited possible transmission pathways by detecting commonalities between VRE cases using a graph theoretical network analysis approach.

RESULTS: We compared 560 VRE patients to 86,684 controls. Logistic models revealed predictors of VRE colonization as age (aOR, 1.4 (per 10 years), with 95% confidence interval [CI], 1.3-1.5; P < .001), ICU admission during stay (aOR, 1.5; 95% CI, 1.2-1.9; P < .001), Charlson comorbidity score (aOR, 1.1; 95% CI, 1.1-1.2; P < .001), the number of different prescribed antibiotics (aOR, 1.6; 95% CI, 1.5-1.7; P < .001), and the number of rooms the patient stayed in during their hospitalization(s) (aOR, 1.1; 95% CI, 1.1-1.2; P < .001). The decision-tree machine-learning method confirmed these findings. Graph network analysis established 3 main pathways by which the VRE cases were connected: healthcare personnel, medical devices, and patient rooms.

CONCLUSIONS: We identified risk factors for being a VRE carrier, along with 3 important links with VRE (healthcare personnel, medical devices, patient rooms). Data science is likely to provide a better understanding of outbreaks, but interpretations require data maturity, and potential confounding factors must be considered.

PMID:36111457 | DOI:10.1017/ice.2022.66

Pharmacoepidemiol Drug Saf. 2022 Sep 16. doi: 10.1002/pds.5541. Online ahead of print.

ABSTRACT

PURPOSE: Our objective was to describe differences in telemedicine use among women with metastatic breast cancer (mBC) by race, age and geographic region.

METHODS: This was a retrospective cohort study of women with recurrent or de novo mBC treated in U.S. community cancer practices that initiated a new line of therapy between March 2020 and February 2021. Multivariable modified Poisson regression models were used to calculate adjusted rate ratios (OR) and robust 95% confidence intervals (CI) associated with telemedicine visits within 90 days of therapy initiation.

RESULTS: Overall, among 3412 women with mBC, 751 (22%) patients had telemedicine visits following therapy initiation, with lower risks observed among older women (<50 years: 24%; 50-64 years: 22%; 65-74 years: 21%; ≥75 years: 20%). Greater telemedicine use was observed among Asian women (35%) compared to White (21%), Black (18%) and Hispanic (21%) women. Fewer telemedicine visits occurred in Southern (12%) and Midwestern (17%) states versus Northeastern (37%) or Western (36%) states. In multivariable models, women ages ≥75 years had significantly lower risks of telemedicine visits (RR=0.76, 95% CI 0.62-0.95) compared to ages <50 years. Compared to patients in Northeastern states, women in Midwestern (RR=0.46, 95% CI 0.37-0.57) and Southern (RR=0.31, 95% CI 0.26-0.37) states had significantly lower risks of telemedicine visits; but not women in Western states (RR=0.96, 95% CI 0.83-1.12). No statistically significant differences in telemedicine use were found between racial groups in overall multivariable models.

CONCLUSIONS: In this study of community cancer practices, older mBC patients and those living in Southern and Midwestern states were less likely to have telemedicine visits. Preferences for communication and delivery of care may have implications for measurement of exposures and endpoints in pharmacoepidemiologic studies of cancer patients.

PMID:36111444 | DOI:10.1002/pds.5541

Headache. 2022 Sep 16. doi: 10.1111/head.14390. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare effects of an initial dose of calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) antagonists on gastrointestinal (GI) motility in patients with migraine and to explore if the mechanistic difference contributes to GI adverse events (AEs).

BACKGROUND: Different frequencies of constipation have been observed between CGRP mAbs that target the ligand (galcanezumab [GMB]) or receptor (erenumab [ERE]).

METHODS: Patients (n = 65) with migraine without significant GI symptoms were enrolled in a multi-center, single-blind phase IV clinical trial (NCT04294147) and randomized 1:1 to receive GMB (240 mg; n = 33) or ERE (140 mg; n = 32). GI whole and regional transit times were assessed using a wireless motility capsule 1 week before and 2 weeks after mAb administration. The primary endpoint was change from baseline in colonic transit time (CTT) within each treatment group. Other measures included GI Symptom Rating Scale (GSRS), Bristol Stool Form Scale (BSFS), and spontaneous bowel movement (SBM) evaluation. AEs were monitored throughout the study.

RESULTS: Baseline characteristics indicated significant GI transit time variability with minimal GI reported symptoms. While not statistically significant, a numerical mean increase in CTT was observed in ERE patients (n = 28, mean [SD] at baseline: 33.8 [29.4] h; least square [LS] mean [SE] change: 5.8 [5.7] h, 95% confidence interval [CI] -5.7 to 17.2, p = 0.320), while GMB decreased CTT (n = 31, mean [SD] at baseline: 29.3 [24.5] h; LS mean [SE] change: -5.4 [5.4] h, 95% CI -16.2 to 5.5, p = 0.328) compared to baseline. No meaningful changes were observed in other regional transit times. ERE significantly reduced BSFS (LS mean [SE] score -0.5 [0.2], p = 0.004) and SBM (LS mean [SE] -1.2 [0.5], p = 0.0120), and increased GSRS-constipation compared to baseline (LS mean [SE] score 0.3 [0.1], p = 0.016). GMB increased GSRS-constipation (LS mean [SE] score 0.4 [0.1], p = 0.002). There were no discontinuations due to or serious AEs. A higher percentage of treatment-emergent AEs were reported with ERE than GMB (ERE: nine of 32 [28.1%] versus GMB: three of 33 [9.1%]), with constipation the most frequently reported (ERE: five of 32 [15.6%] versus GMB one of 33 [3.0%]).

CONCLUSION: While the primary endpoint of this study was not met, secondary and tertiary endpoints support a within- and between-treatment change in GI effects suggesting possible mechanistic differences between ligand (GMB) and receptor (ERE) antagonism.

PMID:36111429 | DOI:10.1111/head.14390

Monaldi Arch Chest Dis. 2022 Sep 13. doi: 10.4081/monaldi.2022.2314. Online ahead of print.

ABSTRACT

The ADBR2 gene has been studied for its possible relationship with the development and clinical course of chronic obstructive pulmonary disease (COPD), including response to beta-2 agonists, with existing data being contentious on the subject. So, the purpose of this study was to look into the potential impact of the arginine-16-glycine (Arg16Gly) polymorphism on the clinical course and drug utilization in COPD patients. Data show that patients with Arg16Arg have a lower number of hospital admissions for exacerbations (p=0.048), but only in the total number of exacerbations, including those treated out-patients (p=0.086). Each glycine (Gly) copy was associated with a higher number of exacerbations (OR: 0.25; 95% CI: 0.00-055; p=0.048). The number of exacerbations after LABA/LAMA treatment was similar across groups, indicating that all ADRB2 variants responded well to the treatment. Furthermore, there were no statistically significant differences in mMRC and CAT values across all study visits. Interestingly, groups differed in their use of antibiotics (AB) at all visits, with Arg16Arg being associated with the least amount of AB use. There was also a link discovered between clycine copies and increased use of glucocorticoids. As a result, Arg16Gly is involved in the clinical course of COPD as well as the utilization of drug groups. Based on the findings, we can speculate that the cross-talk between the ADRB2 gene and the corticosteroid receptor is altered in patients with the Gly16Gly genotype.

PMID:36111412 | DOI:10.4081/monaldi.2022.2314

Eur J Cardiothorac Surg. 2022 Sep 2;62(4):ezac415. doi: 10.1093/ejcts/ezac415.

ABSTRACT

OBJECTIVES: This retrospective study investigated the correlation between the angular position of the left ventricular assist device (LVAD) inflow cannula and relapsing low-flow alarms.

METHODS: Medical charts were reviewed of all patients with HeartMate 3 LVAD support for relapsing low-flow alarms. A standardized protocol was created to measure the angular position with a contrast-enhanced computed tomography scan. Statistics were done using a gamma frailty model with a constant rate function.

RESULTS: For this analysis, 48 LVAD-supported patients were included. The majority of the patients were male (79%) with a median age of 57 years and a median follow-up of 30 months (interquartile range: 19-41). Low-flow alarm(s) were experienced in 30 (63%) patients. Angulation towards the septal-lateral plane showed a significant increase in low-flow alarms over time with a constant rate function of 0.031 increase in low-flow alarms per month of follow-up per increasing degree of angulation (P = 0.048). When dividing this group using an optimal cut-off point, a significant increase in low-flow alarms was observed when the septal-lateral angulation was 28° or more (P = 0.001). Anterior-posterior and maximal inflow cannula angulation did not show a significant difference.

CONCLUSIONS: This study showed an increasing number of low-flow alarms when the degrees of LVAD inflow cannula expand towards the septal-lateral plane. This emphasizes the importance of the LVAD inflow cannula angular position to prevent relapsing low-flow alarms with the risk of diminished quality of life and morbidity.

PMID:36111410 | DOI:10.1093/ejcts/ezac415

Hypertens Pregnancy. 2022 Sep 16:1-6. doi: 10.1080/10641955.2022.2124417. Online ahead of print.

ABSTRACT

BACKGROUND: The aim was to determine the effect of regional anesthesia (RA) on postoperative vital functions in contrast to general endotracheal anesthesia (GEA) after the cesarean section.

METHODS: Prospective cohort study included consecutive term pregnant women delivered by cesarean section (GEA, n = 284; RA, n = 249).

RESULTS: Higher levels of blood pressure and heart rate, as well as lower levels of pulse oximetry were found for GEA in contrast to RA (p < 0.001). The application of RA presented less side-effects (p < 0.05).

CONCLUSIONS: RA for cesarean section should be preferred when balancing the risks and benefits for the mother and fetus.

PMID:36111407 | DOI:10.1080/10641955.2022.2124417