Nevin Manimala

JAMA Neurol. 2022 Nov 14. doi: 10.1001/jamaneurol.2022.4178. Online ahead of print.

ABSTRACT

IMPORTANCE: Physical activity is associated with cognitive health, even in autosomal dominant forms of dementia. Higher physical activity is associated with slowed cognitive and functional declines over time in adults carrying autosomal dominant variants for frontotemporal lobar degeneration (FTLD), but whether axonal degeneration is a potential neuroprotective target of physical activity in individuals with FTLD is unknown.

OBJECTIVE: To examine the association between physical activity and longitudinal neurofilament light chain (NfL) trajectories in individuals with autosomal dominant forms of FTLD.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included individuals from the ALLFTD Consortium, which recruited patients from sites in the US and Canada. Symptomatic and asymptomatic adults with pathogenic variants in one of 3 common genes associated with FTLD (GRN, C9orf72, or MAPT) who reported baseline physical activity levels and completed annual blood draws were assessed annually for up to 4 years. Genotype, clinical measures, and blood draws were collected between December 2014 and June 2019; data were analyzed from August 2021 to January 2022. Associations between reported baseline physical activity and longitudinal plasma NfL changes were assessed using generalized linear mixed-effects models adjusting for baseline age, sex, education, functional severity, and motor symptoms.

EXPOSURES: Baseline physical activity levels reported via the Physical Activity Scale for the Elderly. To estimate effect sizes, marginal means were calculated at 3 levels of physical activity: 1 SD above the mean represented high physical activity, 0 SD represented average physical activity, and 1 SD below the mean represented low physical activity.

MAIN OUTCOMES AND MEASURES: Annual plasma NfL concentrations were measured with single-molecule array technology.

RESULTS: Of 160 included FTLD variant carriers, 84 (52.5%) were female, and the mean (SD) age was 50.7 (14.7) years. A total of 51 (31.8%) were symptomatic, and 77 carried the C9orf72 variant; 39, GRN variant; and 44, MAPT variant. Higher baseline physical activity was associated with slower NfL trajectories over time. On average, NfL increased 45.8% (95% CI, 22.5 to 73.7) over 4 years in variant carriers. Variant carriers with high physical activity demonstrated 14.0% (95% CI, -22.7 to -4.3) slower NfL increases compared with those with average physical activity and 30% (95% CI, -52.2 to -8.8) slower NfL increases compared with those with low physical activity. Within genotype, C9orf72 and MAPT carriers with high physical activity evidenced 18% to 21% (95% CI, -43.4 to -7.2) attenuation in NfL, while the association between physical activity and NfL trajectory was not statistically significant in GRN carriers. Activities associated with higher cardiorespiratory and cognitive demands (sports, housework, and yardwork) were most strongly correlated with slower NfL trajectories (vs walking and strength training).

CONCLUSIONS AND RELEVANCE: In this study, higher reported physical activity was associated with slower progression of an axonal degeneration marker in individuals with autosomal dominant FTLD. Physical activity may serve as a primary prevention target in FTLD.

PMID:36374516 | DOI:10.1001/jamaneurol.2022.4178

JAMA Neurol. 2022 Nov 14. doi: 10.1001/jamaneurol.2022.4038. Online ahead of print.

ABSTRACT

IMPORTANCE: The Stroke of Known Cause and Underlying Atrial Fibrillation (STROKE AF) trial found that approximately 1 in 8 patients with recent ischemic stroke attributed to large- or small-vessel disease had poststroke atrial fibrillation (AF) detected by an insertable cardiac monitor (ICM) at 12 months. Identifying predictors of AF could be useful when considering an ICM in routine poststroke clinical care.

OBJECTIVE: To determine the association between commonly assessed risk factors and poststroke detection of new AF in the STROKE AF cohort monitored by ICM.

DESIGN, SETTING, AND PARTICIPANTS: This was a prespecified analysis of a randomized (1:1) clinical trial that enrolled patients between April 1, 2016, and July 12, 2019, with primary follow-up through 2020 and mean (SD) duration of 11.0 (3.0) months. Eligible patients were selected from 33 clinical research sites in the US. Patients had an index stroke attributed to large- or small-vessel disease and were 60 years or older or aged 50 to 59 years with at least 1 additional stroke risk factor. A total of 496 patients were enrolled, and 492 were randomly assigned to study groups (3 did not meet inclusion criteria, and 1 withdrew consent). Patients in the ICM group had the index stroke within 10 days before insertion. Data were analyzed from October 8, 2021, to January 28, 2022.

INTERVENTIONS: ICM monitoring vs site-specific usual care (short-duration external cardiac monitoring).

MAIN OUTCOMES AND MEASURES: The ICM device automatically detects AF episodes 2 or more minutes in length; episodes were adjudicated by an expert committee. Cox regression multivariable modeling included all parameters identified in the univariate analysis having P values <.10. AF detection rates were calculated using Kaplan-Meier survival estimates.

RESULTS: The analysis included the 242 participants randomly assigned to the ICM group in the STROKE AF study. Among 242 patients monitored with ICM, 27 developed AF (mean [SD] age, 66.6 [9.3] years; 144 men [60.0%]; 96 [40.0%] women). Two patients had missing baseline data and exited the study early. Univariate predictors of AF detection included age (per 1-year increments: hazard ratio [HR], 1.05; 95% CI, 1.01-1.09; P = .02), CHA2DS2-VASc score (per point: HR, 1.54; 95% CI, 1.15-2.06; P = .004), chronic obstructive pulmonary disease (HR, 2.49; 95% CI, 0.86-7.20; P = .09), congestive heart failure (CHF; with preserved or reduced ejection fraction: HR, 6.64; 95% CI, 2.29-19.24; P < .001), left atrial enlargement (LAE; HR, 3.63; 95% CI, 1.55-8.47; P = .003), QRS duration (HR, 1.02; 95% CI, 1.00-1.04; P = .04), and kidney dysfunction (HR, 3.58; 95% CI, 1.35-9.46; P = .01). In multivariable modeling (n = 197), only CHF (HR, 5.06; 95% CI, 1.45-17.64; P = .05) and LAE (HR, 3.32; 1.34-8.19; P = .009) remained significant predictors of AF. At 12 months, patients with CHF and/or LAE (40 of 142 patients) had an AF detection rate of 23.4% vs 5.0% for patients with neither (HR, 5.1; 95% CI, 2.0-12.8; P < .001).

CONCLUSIONS AND RELEVANCE: Among patients with ischemic stroke attributed to large- or small-vessel disease, CHF and LAE were associated with a significantly increased risk of poststroke AF detection. These patients may benefit most from the use of ICMs as part of a secondary stroke prevention strategy. However, the study was not powered for clinical predictors of AF, and therefore, other clinical characteristics may not have reached statistical significance.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02700945.

PMID:36374508 | DOI:10.1001/jamaneurol.2022.4038

J Cosmet Dermatol. 2022 Nov 14. doi: 10.1111/jocd.15500. Online ahead of print.

ABSTRACT

BACKGROUND: Wrinkles are the most visible sign in skin aging and for which many people seek different aesthetic procedures. Treatment options varies from invasive to non-invasive procedures. Combining platelet rich plasma and fractional carbon dioxide laser (CO₂ ) has been used frequently for showing promising results in treating photoaged skin generally and wrinkles specifically since the microscopic thermal zones created by the fractional laser facilitates the delivery of the plasma into the dermis which aids the process of collagen induction and skin rejuvenation.

AIM OF THE WORK: To compare and assess the clinical efficacy of fractional CO₂ laser alone versus combined fractional CO₂ laser and platelet rich plasma in treatment of facial rhytides (in terms of size, depth, and overall appearance).

SUBJECTS AND METHODS: Twenty-six female patients were selected and each face was split into 2 halves a control side (Laser + saline) and an experimental side (Laser + platelet rich plasma). Treatment plan was 1 laser session per month for a total of 4 sessions. Clinical objective evaluation was done by the Antera camera in addition to assessment by two blinded dermatologists.

RESULTS: The combined treatment was as effective in improving wrinkles as fractional CO₂ laser alone. Antera camera scores showed statistical significance in overall wrinkles measurements on each side equally.

CONCLUSION: Both treatment modalities gave optimum cosmetic results with no significant difference noticed when compared with each other, although overall satisfaction with wrinkles and skin were statistically greater than the initial satisfaction scores.

PMID:36374507 | DOI:10.1111/jocd.15500

Jpn J Radiol. 2022 Nov 14. doi: 10.1007/s11604-022-01358-y. Online ahead of print.

ABSTRACT

PURPOSE: The purpose of this study was to find useful imaging features on non-contrast-enhanced magnetic resonance imaging (MRI) that can divide patients with thymic epithelial tumor (TET) into clinical stage I-II and III-IV groups under assumption that contrast media are contraindicated.

MATERIALS AND METHODS: This retrospective study included 106 patients (median age, 60 years; range, 27-82 years; 62 women) with surgically resected TET who underwent MRI between August 1986 and July 2015. All cases were classified according to the 2015 WHO classification and staged using the eighth edition of the TNM system. Two radiologists independently evaluated 14 categories of MRI findings; the findings in patients with stage I-II were compared with those of patients with stage III-IV using a logistic regression model. Disease-specific survival associated with significant findings was calculated using the Kaplan-Meier method.

RESULTS: Univariate analysis showed that stage III-IV patients were more likely to have tumors with an irregular contour, heterogeneity on T1WI, low-signal intensity on T2WI, irregular border with lung, findings of great vessel invasion (GVI) (hereafter, GVI sign), pericardial thickening/nodule, and lymphadenopathy (all, P < 0.01). On multivariable analysis, only two findings, irregular border between tumor and lung (odds ratio [OR], 272.8; 95% CI 26.6-2794.1; P < 0.001) and positive GVI sign (OR, 49.3; 95% CI 4.5-539.8; P = 0.001) remained statistically significant. Patients with one or both features had significantly worse survival (log-rank test, P < 0.001).

CONCLUSION: For patients with TET who are unable to receive contrast for preoperative staging, the two image findings of an irregular border between tumor and lung and the positive GVI sign on non-contrast-enhanced MRI could be helpful in determining stage III-IV disease which is associated with a worse survival.

PMID:36374474 | DOI:10.1007/s11604-022-01358-y

Sleep Breath. 2022 Nov 14. doi: 10.1007/s11325-022-02744-6. Online ahead of print.

ABSTRACT

PURPOSE: To analyze relative efficacies of mandibular advancement devices (MAD) in sleep apnea treatment.

METHODS: From eligible randomized controlled trials (RCT), MADs were classified based on their mechanistic designs. Data on apnea-hypopnea index (AHI), Epworth sleepiness scale (ESS), nadir oxygen saturation (minSaO₂), and sleep efficiency (SE%) from RCTs were then analyzed in network meta-analyses, and relative ranking of different MADs was computed based on P scores (a method of ranking similar to SUCRA). Similar analyses were conducted based on the different brands of MADs.

RESULTS: There were no statistically significant differences between MADs in any of the outcomes analyzed. However, the P-scores, based on the point estimates and standard errors of the network estimates, ranked some MADs higher than others in some of the outcomes. Of the different mechanistic designs, the highest P scores were achieved for attached midline traction (P score = 0.84) and unattached bilateral interlocking (P score = 0.78) devices for AHI reduction, attached bilateral traction (P score = 0.78) and unattached bilateral interlocking (P score = 0.76) for ESS, monobloc (P score = 0.91) and unattached bilateral interlocking (P score = 0.64) for minSaO₂, and unattached bilateral interlocking (P score = 0.82) and attached bilateral traction (P score = 0.77) for SE%. Notable findings in the network meta-analyses based on MAD brands, of the limited number of studies that specified them were the effects of SomnoDent Flex™, TAP™, and IST® in their effects on AHI reduction, with P scores of 0.94, 0.83, and 0.82, respectively. Monobloc decreased supine-AHI the most (- 44.46 [- 62.55; – 26.36], P score = 0.99), and unattached bilateral interlocking had the greatest effect on REM-AHI (- 11.10 [- 17.10; – 5.10], P score = 0.87).

CONCLUSIONS: Findings from this study show clinically (but not statistically) significant differences between MADs in terms of their relative efficacy when analyzed for different sleep apnea treatment outcomes and sleep apnea phenotypes.

PMID:36374442 | DOI:10.1007/s11325-022-02744-6

J Cancer Surviv. 2022 Nov 14. doi: 10.1007/s11764-022-01292-y. Online ahead of print.

ABSTRACT

PURPOSE: The study aimed to determine the feasibility of remotely delivered exercise (tele-exercise) for older, rural cancer survivors and to explore the effects of tele-exercise on physical function, physical activity, and patient-reported outcomes.

METHODS: Participants were rural cancer survivors age ≥ 60 years (79% female; mean age 70.4 ± 5.7) randomly assigned to the remotely delivered EnhanceFitness (tele-EF) exercise program, inclusive of aerobic, strength, and balance training and led by American Council on Exercise certified instructors for 1 h, 3 days/week for 16 weeks (n = 20) or to a waitlist control group (n = 19). We assessed feasibility, physical function, accelerometer-measured physical activity, and patient-reported outcomes at baseline and post intervention.

RESULTS: Among those screened as eligible, 44 (64%) consented to participate with 39 randomized after completing baseline measures. Attrition was equivalent between groups (n = 1, each) with 95% completing the study. The median class attendance rate was 86.9% (interquartile range: 79-94%). Compared to controls, tele-EF participants had statistically significant improvement in the five-time sit-to-stand test (- 3.4 vs. – 1.1 s, p = 0.03, effect size = 0.44), mean daily light physical activity (+ 38.5 vs 0.5 min, p = 0.03, effect size = 0.72) and step counts (+ 1977 vs. 33, p = 0.01, effect size = 0.96). There were no changes in self-efficacy for exercise, fatigue, or sleep disturbance between groups.

CONCLUSIONS: Findings indicate that tele-EF is feasible in older, rural cancer survivors and results in positive changes in physical function and physical activity.

IMPLICATIONS FOR CANCER SURVIVORS: Tele-EF addresses common barriers to exercise for older, rural cancer survivors, including limited accessible opportunities for professional instruction and supervision.

PMID:36374436 | DOI:10.1007/s11764-022-01292-y

Clin Rheumatol. 2022 Nov 14. doi: 10.1007/s10067-022-06438-y. Online ahead of print.

ABSTRACT

PURPOSE: The purpose of this study was to identify a biomarker that can predict the efficacy of rituximab (RTX) in the treatment of rheumatoid arthritis (RA) patients.

METHODS: Utilized weighted gene co-expression network analysis (WGCNA) and LASSO regression analysis of whole blood transcriptome data (GSE15316 and GSE37107) related to RTX treatment for RA from the GEO database, the critical modules, and key genes related to the efficacy of RTX treatment for RA were found. The biological functions were further explored through enrichment analysis. The area under the ROC curve (AUC) was validated using the GSE54629 dataset.

RESULTS: WGCNA screened 71 genes for a dark turquoise module that were correlated with the efficacy of RTX treatment for RA (r = 0.42, P < 0.05). Through the calculation of gene significance (GS) and module membership (MM), 12 important genes were identified; in addition, 21 important genes were screened by the LASSO regression model; two key genes were obtained from the intersection between the important genes. Then, BANK1 (AUC = 0.704, P < 0.05) was identified as a potential biomarker to predict the efficacy of RTX treatment for RA by ROC curve evaluation of the treatment and validation groups. BANK1 gene expression was significantly decreased after RTX treatment, and a statistically significant difference was found (log FC = – 2.08, P < 0.05). Immune cell infiltration analysis revealed that the infiltration of CD4 + T cell memory subset was increased in the group with high BANK1 expression, and a statistically significant difference was found (P < 0.05).

CONCLUSIONS: BANK1 can be used as a potential biomarker to predict the response of RTX treatment in RA patients. Key Points • Identifying the hub genes BANK1 as a potential biomarker to predict the response of RTX treatment in RA patients and confirming it in validation data. • Using the WGCNA approach and LASSO analyses to identify the BANK1 in a data set consisting of two GEO data merged and assessing the correlations between BANK1 and immune infiltration by CIBERSORT algorithm.

PMID:36374432 | DOI:10.1007/s10067-022-06438-y

Anat Sci Int. 2022 Nov 14. doi: 10.1007/s12565-022-00694-3. Online ahead of print.

ABSTRACT

This study aims to evaluate the position, morphometric, and morphological features of the temporozygomatic suture (TZS) located on the zygomatic arch (ZA) in dry adult human skulls. Thirty-two crania were evaluated. Measurements for the TZS were carried out using the ImageJ software. Morphometric measurements were carried out bilaterally in 23 crania and unilaterally in 9 crania (right: 4, left: 5). A total of 55 TZSs were analyzed. Localization of the TZS was determined according to the reference landmarks on the ZA. Morphologic features of the TZS evaluated in terms of “joint shape type” and “suture margin pattern”. Descriptive statistics of the morphometric and morphologic variables were calculated. A statistically significant difference between the right and left sides was observed for the localization of the TZS (p < 0.05). TZS is located more anteriorly on the left side than the right side. Based on the “joint shape type”, four types of TZS were observed: Type 1 (angular) (34.55%), Type 2 (curvy) (34.55%), Type 3 (oblique) (14.55%), Type 4 (horizontal) (16.36%). Based on the “suture margin pattern”, five types of TZS were observed: Type A (linear) (12.73%), Type B (denticulate) (34.55%), Type C (serrated) (23.64%), Type D (mixt) (21.82%), Type E (fused) (7.27%). No significant association between the type and lateralization was found for both morphologic classifications. To the best of our knowledge, this is the first published report regarding the localization and morphologic classification of the TZS in adult human crania. Considering the TZS with its morphometric and morphological features may contribute to clinical or forensic medical evaluations.

PMID:36374372 | DOI:10.1007/s12565-022-00694-3

Environ Monit Assess. 2022 Nov 14;195(1):104. doi: 10.1007/s10661-022-10728-y.

ABSTRACT

In many regions across the world, including river basins, population growth and land development have enhanced the demand for land and other natural resources. The anthropogenic activities can be detrimental to the vital ecosystems that sustain the river basin region. This work assessed the impact of human modification on land surface temperature (LST) for the Ramganga basin in India. It has been hypothesised that the footprints of anthropogenic activities in the region have been connected to the LST fluctuation for the region, which could indicate environmental degradation. The LST variation between 2000 and 2016 has been estimated to test this hypothesis. The spatio-temporal correlation between human modification and LST has been computed. LST has been calculated with MODIS satellite data in the Google earth engine (GEE) platform, and anthropogenic activities can be visualised using an LU/LC map of the basin created by the Classification and Regression (CART) technique. The statistical parameters (average, maximum and standard deviation) of annual temperature for each pixel in 17 years (2000-2016) have been assessed to establish the links with human modification. The result of this work portrays a positive correlation of 0.705 between maximum LST and human modification. The forest class in the basin region has the lowest average human modification value (0.37), and it also possesses the lowest mean LST of 26.72 °C. Similarly, the settlement class has the highest average human modification value (0.85), and the mean LST temperature of this class has been on the higher side, having a value of 31.07 °C.

PMID:36374362 | DOI:10.1007/s10661-022-10728-y

Clin Oral Investig. 2022 Nov 14. doi: 10.1007/s00784-022-04769-3. Online ahead of print.

ABSTRACT

OBJECTIVES: This prospective study introduced a digitally designed sectioning guide and evaluated its feasibility for the extraction of horizontally impacted lower third molars.

MATERIALS AND METHODS: This study included 38 horizontally impacted lower third molars, randomly divided into experimental and control groups. The teeth were extracted using a 3D-printed titanium surgical guide in the experimental group; free-hand extractions were performed in the control group. The surgical duration, tooth sectioning duration, cortical bone perforation, and postoperative complications, including pain, swelling, trismus, dry socket, infection, and hemorrhage, were evaluated.

RESULTS: Although not statistically significant, guided surgery tended to reduce the number of tooth sectioning steps compared to free-hand extractions. There were no cases of cortical bone perforation in the experimental group. Although the surgical duration was greater in the experimental group (p < 0.05), there were no differences in postoperative pain, swelling, and trismus. There were no cases of postoperative infection and hemorrhage in either group.

CONCLUSIONS: 3D-printed titanium surgical guides had superior accuracy and safety compared to free-hand surgery. Further studies with larger sample sizes are required to verify these findings.

CLINICAL RELEVANCE: The template improved the safety of tooth sectioning during impacted lower third molar surgery and resulted in a more predictable extraction. The narrow sectioning groove could fit comfortably with hypertrophic soft tissues in the posterior mandible.

PMID:36374352 | DOI:10.1007/s00784-022-04769-3