Nevin Manimala

Lab Med. 2022 Mar 14:lmac014. doi: 10.1093/labmed/lmac014. Online ahead of print.

ABSTRACT

OBJECTIVE: The T-cell receptor β constant region 1 (TRBC1) antibody can identify T-cell clonality and distinguish pathological from normal T cells. This study aims to establish optimal cutpoints for establishing monotypia and validate the diagnostic abilities of the TRBC1 antibody when used as a reflex test in conjunction with an existing T-cell antibody panel.

MATERIALS AND METHODS: We used 46 normal peripheral blood specimens and examined 8 patients with reactive lymphoproliferations to determine the normal biological range of TRBC1 on CD4+ and CD8+ T cells. We also evaluated 43 patient specimens that were submitted for investigation of a lymphoproliferative disorder for CD2/CD3/CD4/CD5/CD7/CD8/CD16/CD26/CD45/CD56/TCR αβ/TCR γδ, along with TRBC1 expression. The results were compared to TCR gene rearrangement patterns using polymerase chain reaction (PCR) analysis.

RESULTS: Statistical analysis established differing cutoff points for establishing monotypia dependent on restricted TRBC1 or TRBC2 usage. Direct comparison with molecular analysis indicated that no specimen identified with the restricted expression of TRBC1 was reported as polyclonal by PCR with a concordance rate of 97% between a clonal PCR result and monotypic TRBC1 expression.

CONCLUSION: Incorporation of the TRBC1 antibody using statistically derived cutoff points in a reflex setting for the evaluation of a suspected T-cell neoplasm improves the identification of clonal T-cell populations by flow cytometry and correlates well with molecular methods.

PMID:35285909 | DOI:10.1093/labmed/lmac014

Eur J Orthod. 2022 Mar 14:cjac006. doi: 10.1093/ejo/cjac006. Online ahead of print.

ABSTRACT

AIM: To assess whether the efficacy of external tooth bleaching differs between untreated and orthodontically treated teeth.

MATERIALS AND METHOD: Three groups of subjects were formed; group Debonded included 24 consecutive orthodontically treated patients evaluated immediately after removal of fixed appliances. The Retention group included 24 consecutive orthodontically treated patients in the phase of retention. The Untreated group consisted of 24 arbitrarily selected undergraduate dental students without history of fixed-appliances orthodontic therapy. Each of the above three groups was further randomized into two subgroups, Bleaching and Placebo. Each subgroup received either a 38% hydrogen peroxide bleaching treatment or a placebo agent, respectively. Tooth colour changes were assessed at seven timepoints: 1 day before intervention; on the day of intervention before and after treatment; and at 7, 14, 21, and 90 days for parameters L*, a*, b*, and ΔΕ in all upper incisors and canines with the use of a reflectance spectrophotometer. Intra-rater agreement was estimated with the Intra-class Correlation Coefficient and method’s error was calculated using the Repeatability Coefficient. Regarding tooth colour changes, an analysis of variance was used to assess differences between groups.

RESULTS: Bleaching was associated with an increase of the L* value and decrease of b* and a* values in both orthodontically treated and untreated teeth. Parameters ΔE, L*, and b* exhibited statistically significant differences between the Bleaching-Untreated and Bleaching-Retention subgroups. In the Bleaching subgroups, statistically significant differences were found between different teeth for all parameters.

CONCLUSIONS: Previous exposure to fixed orthodontic appliance influenced the efficacy of external tooth bleaching. The effect of bleaching was higher after orthodontic treatment and with longer period in retention. Canines changed in colour more than incisors, and the effect was reduced over time.

PMID:35285904 | DOI:10.1093/ejo/cjac006

Interact Cardiovasc Thorac Surg. 2022 Mar 14:ivac068. doi: 10.1093/icvts/ivac068. Online ahead of print.

ABSTRACT

OBJECTIVES: Presentation, management and outcomes in the aortic dissection (AD) of ascending thoracic aortic aneurysm (ATAA) differ in gender and age. The purpose of this study is to investigate the dissection properties of male and female ATAAs.

METHODS: Peeling tests were performed to quantitatively determine the delamination strength and dissection energy of 41 fresh ATAA samples (22 males and 19 females) in relatively young (≤65 years) and elderly (>65 years) patients. The delamination strength of the ATAAs was further correlated with patient ages for males and females. The histological investigation was employed to characterize the dissected morphology.

RESULTS: For elderly patients, circumferential and longitudinal delamination strengths of the female ATAAs were statistically significantly lower than those of the males (circumferential: 31 ± 6 vs 42 ± 6 mN/mm, P < 0.01; longitudinal: 35 ± 7 vs 49 ± 10 mN/mm, P = 0.02). No significant differences were found in the delamination strength between males and females for relatively young patients. The circumferential and longitudinal delamination strengths were significantly decreased and strongly correlated with patient ages for females. However, these correlations were not present in males. Dissection routes propagated in the aortic media to create ruptured surfaces for all specimens. Peeling tests of the male ATAAs generate rougher surfaces than females.

CONCLUSIONS: There is a higher propensity of AD occurrence for the elderly females as compared to males with matched ages. Surgeons should be cognizant of the risk of AD onset later in life, especially in females.

PMID:35285896 | DOI:10.1093/icvts/ivac068

JAMA Neurol. 2022 Mar 14. doi: 10.1001/jamaneurol.2022.0048. Online ahead of print.

ABSTRACT

IMPORTANCE: Cryptogenic strokes constitute approximately 40% of ischemic strokes in young adults, and most meet criteria for the embolic stroke of undetermined source (ESUS). Two randomized clinical trials, NAVIGATE ESUS and RESPECT ESUS, showed a high rate of stroke recurrence in older adults with ESUS but the prognosis and prognostic factors among younger individuals with ESUS is uncertain.

OBJECTIVE: To determine rates of and factors associated with recurrent ischemic stroke and death and new-onset atrial fibrillation (AF) among young adults.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter longitudinal cohort study with enrollment from October 2017 to October 2019 and a mean follow-up period of 12 months ending in October 2020 included 41 stroke research centers in 13 countries. Consecutive patients 50 years and younger with a diagnosis of ESUS were included. Of 576 screened, 535 participants were enrolled after 1 withdrew consent, 41 were found to be ineligible, and 2 were excluded for other reasons. The final follow-up visit was completed by 520 patients.

MAIN OUTCOMES AND MEASURES: Recurrent ischemic stroke and/or death, recurrent ischemic stroke, and prevalence of patent foramen ovale (PFO).

RESULTS: The mean (SD) age of participants was 40.4 (7.3) years, and 297 (56%) participants were male. The most frequent vascular risk factors were tobacco use (240 patients [45%]), hypertension (118 patients [22%]), and dyslipidemia (109 patients [20%]). PFO was detected in 177 participants (50%) who had transthoracic echocardiograms with bubble studies. Following initial ESUS, 468 participants (88%) were receiving antiplatelet therapy, and 52 (10%) received anticoagulation. The recurrent ischemic stroke and death rate was 2.19 per 100 patient-years, and the ischemic stroke recurrence rate was 1.9 per 100 patient-years. Of the recurrent strokes, 9 (64%) were ESUS, 2 (14%) were cardioembolic, and 3 (21%) were of other determined cause. AF was detected in 15 participants (2.8%; 95% CI, 1.6-4.6). In multivariate analysis, the following were associated with recurrent ischemic stroke: history of stroke or transient ischemic attack (hazard ratio, 5.3; 95% CI, 1.8-15), presence of diabetes (hazard ratio, 4.4; 95% CI, 1.5-13), and history of coronary artery disease (hazard ratio, 10; 95% CI, 4.8-22).

CONCLUSIONS AND RELEVANCE: In this large cohort of young adult patients with ESUS, there was a relatively low rate of subsequent ischemic stroke and a low frequency of new-onset AF. Most recurrent strokes also met the criteria for ESUS, suggesting the need for future studies to improve our understanding of the underlying stroke mechanism in this population.

PMID:35285869 | DOI:10.1001/jamaneurol.2022.0048

JAMA. 2022 Mar 14. doi: 10.1001/jama.2022.2832. Online ahead of print.

ABSTRACT

IMPORTANCE: Older patients and those with comorbidities who are infected with SARS-CoV-2 may be at increased risk of hospitalization and death. Sotrovimab is a neutralizing antibody for the treatment of high-risk patients to prevent COVID-19 progression.

OBJECTIVE: To evaluate the efficacy and adverse events of sotrovimab in preventing progression of mild to moderate COVID-19 to severe disease.

DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial including 1057 nonhospitalized patients with symptomatic, mild to moderate COVID-19 and at least 1 risk factor for progression conducted at 57 sites in Brazil, Canada, Peru, Spain, and the US from August 27, 2020, through March 11, 2021; follow-up data were collected through April 8, 2021.

INTERVENTIONS: Patients were randomized (1:1) to an intravenous infusion with 500 mg of sotrovimab (n = 528) or placebo (n = 529).

MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of patients with COVID-19 progression through day 29 (all-cause hospitalization lasting >24 hours for acute illness management or death); 5 secondary outcomes were tested in hierarchal order, including a composite of all-cause emergency department (ED) visit, hospitalization of any duration for acute illness management, or death through day 29 and progression to severe or critical respiratory COVID-19 requiring supplemental oxygen or mechanical ventilation.

RESULTS: Enrollment was stopped early for efficacy at the prespecified interim analysis. Among 1057 patients randomized (median age, 53 years [IQR, 42-62], 20% were ≥65 years of age, and 65% Latinx), the median duration of follow-up was 103 days for sotrovimab and 102 days for placebo. All-cause hospitalization lasting longer than 24 hours or death was significantly reduced with sotrovimab (6/528 [1%]) vs placebo (30/529 [6%]) (adjusted relative risk [RR], 0.21 [95% CI, 0.09 to 0.50]; absolute difference, -4.53% [95% CI, -6.70% to -2.37%]; P < .001). Four of the 5 secondary outcomes were statistically significant in favor of sotrovimab, including reduced ED visit, hospitalization, or death (13/528 [2%] for sotrovimab vs 39/529 [7%] for placebo; adjusted RR, 0.34 [95% CI, 0.19 to 0.63]; absolute difference, -4.91% [95% CI, -7.50% to -2.32%]; P < .001) and progression to severe or critical respiratory COVID-19 (7/528 [1%] for sotrovimab vs 28/529 [5%] for placebo; adjusted RR, 0.26 [95% CI, 0.12 to 0.59]; absolute difference, -3.97% [95% CI, -6.11% to -1.82%]; P = .002). Adverse events were infrequent and similar between treatment groups (22% for sotrovimab vs 23% for placebo); the most common events were diarrhea with sotrovimab (n = 8; 2%) and COVID-19 pneumonia with placebo (n = 22; 4%).

CONCLUSIONS AND RELEVANCE: Among nonhospitalized patients with mild to moderate COVID-19 and at risk of disease progression, a single intravenous dose of sotrovimab, compared with placebo, significantly reduced the risk of a composite end point of all-cause hospitalization or death through day 29. The findings support sotrovimab as a treatment option for nonhospitalized, high-risk patients with mild to moderate COVID-19, although efficacy against SARS-CoV-2 variants that have emerged since the study was completed is unknown.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04545060.

PMID:35285853 | DOI:10.1001/jama.2022.2832

J Vis Exp. 2022 Feb 22;(180). doi: 10.3791/62643.

ABSTRACT

Cardiac reprogramming has become a potentially promising therapy to repair a damaged heart. By introducing multiple transcription factors, including Mef2c, Gata4, Tbx5 (MGT), fibroblasts can be reprogrammed into induced cardiomyocytes (iCMs). These iCMs, when generated in situ in an infarcted heart, integrate electrically and mechanically with the surrounding myocardium, leading to a reduction in scar size and an improvement in heart function. Because of the relatively low reprogramming efficiency, purity, and quality of the iCMs, characterization of iCMs remains a challenge. The currently used methods in this field, including flow cytometry, immunocytochemistry, and qPCR, mainly focus on cardiac-specific gene and protein expression but not on the functional maturation of iCMs. Triggered by action potentials, the opening of voltage-gated calcium channels in cardiomyocytes leads to a rapid influx of calcium into the cell. Therefore, quantifying the rate of calcium influx is a promising method to evaluate cardiomyocyte function. Here, the protocol introduces a method to evaluate iCM function by calcium (Ca²⁺) flux. An αMHC-Cre/Rosa26A-Flox-Stop-Flox-GCaMP3 mouse strain was established by crossing Tg(Myh6-cre)1Jmk/J (referred to as Myh6-Cre below) with Gt(ROSA)26Sor^{tm38(CAG-GCaMP3)Hze}/J (referred to as Rosa26A-Flox-Stop-Flox-GCaMP3 below) mice. Neonatal cardiac fibroblasts (NCFs) from P0-P2 neonatal mice were isolated and cultured in vitro, and a polycistronic construction of MGT was introduced to NCFs, which led to their reprogramming to iCMs. Because only successfully reprogrammed iCMs will express GCaMP3 reporter, the functional maturation of iCMs can be visually assessed by Ca²⁺ flux with fluorescence microscopy. Compared with un-reprogrammed NCFs, NCF-iCMs showed significant calcium transient flux and spontaneous contraction, similar to CMs. This protocol describes in detail the mouse strain establishment, isolation and selection of neonatal mice hearts, NCF isolation, production of retrovirus for cardiac reprogramming, iCM induction, the evaluation of iCM Ca²⁺ flux using our reporter line, and related statistical analysis and data presentation. It is expected that the methods described here will provide a valuable platform to assess the functional maturation of iCMs for cardiac reprogramming studies.

PMID:35285824 | DOI:10.3791/62643

Aging Ment Health. 2022 Mar 14:1-9. doi: 10.1080/13607863.2022.2046692. Online ahead of print.

ABSTRACT

OBJECTIVES: In this article, we assess the feasibility and acceptability and the effect of the Plan Ahead for community dwelling older adults. In addition, we investigated the effects of the program. In addition, we aimed to examine whether the completion of the specific Future Care Planning depended on the participants’ competence level.

METHODS: In this single group feasibility study, trained facilitators delivered the program to a sample of 234 community-residing older adults. Participants completed both pre, post assessments about the acceptability of the program and their completion of the recommended future care planning activities.

RESULTS: Based on participant’s report on the usefulness and satisfaction of the program after the completion of the program, we found that participants reported high levels of acceptance of the program. Participation rates also confirmed the feasibility of the program. In terms of effects of program implementation, statistically significant changes were noted for several outcomes, such as resource building and FCP activities. In particular, we found that these gains were particularly robust for participants in the low competence group.

CONCLUSION: Pilot program results suggest the feasibility of a short community program enhancing proactive planning for future care needs among older adults residing in their community.

PMID:35285774 | DOI:10.1080/13607863.2022.2046692

Australas Psychiatry. 2022 Mar 14:10398562221077887. doi: 10.1177/10398562221077887. Online ahead of print.

ABSTRACT

OBJECTIVE: This longitudinal study examined changes in psychological outcomes of perioperative frontline healthcare workers at one of Australia’s most COVID-19 affected hospitals, following the surge and decline of a pandemic wave.

METHOD: A single-centred longitudinal online survey was conducted between 26 May and 17 November 2020. Recruitment was via poster advertisement and email invitation. The survey was sent out every 4 weeks, resulting in seven time-points.

RESULTS: In total, 385 survey results were analysed from 193 staff (about 64% response rate), 72 (37%) of whom completed the survey more than once. The prevalence of moderate-to-severe anxiety and depressive symptoms peaked at 27% and 25%, respectively, during the pandemic surge. Up to 35% displayed post-traumatic stress disorder (PTSD) symptoms. Although not statistically significant, the trend of depressive and PTSD symptoms worsened over time, especially among females and anaesthetic/surgical trainees, despite subsidence of the pandemic curve. Technicians and anaesthetic/scrub nurses were the at-risk groups with worst psychological outcomes.

CONCLUSION: We found persistent mental health impacts on frontline perioperative HCWs despite subsidence of the pandemic wave. Further research is needed to determine the extent and trajectory of such impacts with larger sample sizes to determine generalisability to frontline HCWs in general.

PMID:35285740 | DOI:10.1177/10398562221077887

Zhongguo Zhong Yao Za Zhi. 2022 Feb;47(4):951-958. doi: 10.19540/j.cnki.cjcmm.20210901.301.

ABSTRACT

The present study established the spectrum-effect relationship model of flavonoids in Citri Reticulatae Pericarpium(CRP) from 15 batches of Liujunzi Decoction and statistically analyzed the correlation between chemical peaks and efficacy to identify the main effective components. HPLC fingerprints of flavonoids in CRP from 15 batches of Liujunzi Decoction were established. HPLC analysis was carried out on the Venusil XBP C_(18)(L) column(4.6 mm×250 mm, 5 μm) at 30 ℃ with acetonitrile-water(containing 0.1% formic acid) as mobile phase for gradient elution, a flow rate of 1.0 mL·min~(-1), and detection wavelength of 300 nm to obtain chemical fingerprints. Additionally, the effects of flavonoids from CRP in 15 batches of Liujunzi Decoction on the content of GAS, MTL, and VIP, TFF3 mRNA expression, and percentage of CD3~+ T-cells of model rats with spleen deficiency were determined. The spectrum-effect relationship model was established by gray correlation analysis. The results showed that the main characteristic peaks with great contribution to the regulation of gastrointestinal tract were peak 16(vicenin-2), peak 63(sinensetin), peak 64(isosinensetin), peak 65(nobiletin), peak 67(3,5,6,7,8,3′,4′-heptemthoxyflavone), peak 68(tangeretin), and peak 69(5-desmethylnobiletin). Therefore, there was a linear correlation between flavonoids from CRP in Liujunzi Decoction and the efficacy, and the medicinal effect was achieved by multi-component action. This study is expected to provide a new idea for exploring the material basis of the effect, i.e., regulating qi prior to replenishing qi, of CRP in Liujunzi Decoction.

PMID:35285194 | DOI:10.19540/j.cnki.cjcmm.20210901.301

Int J Nurs Pract. 2022 Mar 13:e13049. doi: 10.1111/ijn.13049. Online ahead of print.

ABSTRACT

AIM: To determine the effectiveness of auscultatory, colorimetric capnometry and pH measurement methods for confirmation of correct nasogastric tube placement in critically ill patients.

BACKGROUND: Incorrect nasogastric tube placement causes serious complications.

DESIGN: This was a methodological and comparative study.

METHODS: The study sample consisted of 88 new insertions of nasogastric feeding tubes between April 2018-2019. Results from the ‘auscultatory’, ‘pH’ and ‘colorimetric capnometry’ methods were compared with the location of the nasogastric tube as determined through radiography. Descriptive statistics, Eta analysis and the Cohen kappa compliance test as well as sensitivity and specificity were conducted.

RESULTS: There was a weak agreement (26.3%) between the auscultation and radiological evaluation for confirming nasogastric tube placement. The pH measurement and colorimetric capnometry methods were not correlated with radiological evaluation. Stomach pH increased as patient age increased and use of the colorimetric capnometry method failed to confirm the oesophageal and duodenal location. The specificity of the auscultation was low, and both the specificity and sensitivity pH methods were low.

CONCLUSION: It was determined that auscultation, measuring pH and colorimetric capnometry were unreliable methods for confirming placement of nasogastric tubes. It is recommended to confirm initial placement of the nasogastric tube with radiography and to develop effective and reliable non-radiological measurement methods that can be performed at the bedside.

PMID:35285146 | DOI:10.1111/ijn.13049