Category: Nevin Manimala

Otol Neurotol. 2022 Jun 17. doi: 10.1097/MAO.0000000000003547. Online ahead of print.

ABSTRACT

OBJECTIVE: To analyze the relationship of electrode array (EA) type and position on hearing preservation longevity following cochlear implantation.

STUDY DESIGN: Retrospective chart review.

SETTING: Tertiary referral center.

PATIENTS: Adult cochlear implant recipients between 2013 and 2019 with hearing preserved postoperatively and postoperative CT scans.

INTERVENTIONS: CT scan analysis of EA position. Stepwise regression to determine influence of EA position, EA type, and patient demographics on postoperative low frequency hearing.

MAIN OUTCOME MEASURES: Low frequency pure tone average (LFPTA), LFPTA shift, angular insertion depth, base insertion depth, scalar position, mean perimodiolar distance.

RESULTS: Of 792 cochlear implant recipients, 121 had preoperative LFPTA ≤80 dB HL with 60 of the 121 (49.6%) implanted with straight, 32 (26.4%) with precurved, styletted, and 29 (24.0%) implanted precurved, nonstyletted EA. Mean follow up was 28.6 months (range 1-103). There was no statistically significant difference in activation, 6- and 12-month, and last follow-up LFPTA (125, 250, and 500 Hz) shift based on EA type (straight p = 0.302, precurved, styletted p = 0.52, precurved, nonstyletted p = 0.77). Preoperative LFPTA and age of implantation were significant predictors of LFPTA shift at activation, accounting for 30.8% of variance (F[2, 113] = 26.603, p < 0.0001). LFPTA shift at activation, scalar position, and base insertion depth were significant predictors of variability and accounted for 39.1% of variance in LFPTA shift at 6 months (F[3, 87] = 20.269, p < 0.0001). Only LFPTA shift at 12 months was found to be a significant predictor of LFPTA shift at last follow up, accounting for 41.0% of variance (F[1, 48] = 32.653, p < 0.0001).

CONCLUSIONS: Patients had excellent long-term residual hearing regardless of EA type. Age, preoperative acoustic hearing, and base insertion depth may predict short term preservation, while 12-month outcomes significantly predicted long-term hearing preservation.

PMID:35709407 | DOI:10.1097/MAO.0000000000003547

Spec Care Dentist. 2022 Jun 16. doi: 10.1111/scd.12747. Online ahead of print.

ABSTRACT

AIMS: To assess the presence of alterations suggestive of reduced bone mineral density (BMD) by using mandibular cortical index (MCI) in panoramic radiographs of cirrhotic individuals and to evaluate their relationship with other characteristics of hepatic cirrhosis (HC).

METHODS AND RESULTS: This is an observational case-control study assessing the medical records of 165 cirrhotic patients matched by sex and age with healthy individuals. MELD (model of end stage liver disease) score, etiology, complications, comorbidities, and serum levels of vitamin D were collected. MCI was used to obtain BMD. Binary logistic regression was used to test associations and the risk estimates were expressed in odds ratio. Most of the sample consisted of men (73.93%) with median age of 56 years old. In the study group, the mean value of MELD was 16.5 and hepatitis C was the main etiology of HC (33.9%). Cirrhotic individuals are 3.99 times more likely to present alterations suggestive of reduced BMD (p = .00). There was no statistical significance in the association of MCI with levels of vitamin D, comorbidities, etiology or cirrhosis complications.

CONCLUSIONS: MCI suggestive of reduced BMD is more likely to be identified in panoramic radiographs of cirrhotic individuals than of healthy ones.

PMID:35709388 | DOI:10.1111/scd.12747

Aesthet Surg J. 2022 Jun 16:sjac158. doi: 10.1093/asj/sjac158. Online ahead of print.

ABSTRACT

BACKGROUND: Since the association between anaplastic large cell lymphoma (ALCL) and textured breast implants has led to the recall of Allergan Biocell (Irvine, CA, USA) devices, plastic surgeons have been faced with the challenge of caring for patients with these implants in situ. Cosmetic and reconstructive surgeons have been contacting patients with these implants in order to encourage them to follow up and discuss the most appropriate risk reduction strategies.

OBJECTIVES: To evaluate patient concerns about the risk of breast implant associated ALCL and compare management differences between cosmetic and reconstruction patients.

METHODS: A retrospective review was performed of 432 patients with macro textured implants that presented to clinic after being contacted (121 reconstructive and 311 cosmetic). These records were analyzed for their presenting concerns, surgery wait times and management plans. Statistical analysis was performed to compare the cohorts and odds ratios were computed to determine the association between patient concerns and their choice of management.

RESULTS: After consultation, 59.5% of the reconstruction cohort and 49.5% of the cosmetic cohort scheduled implant removal or exchange. The reconstructive population had a higher rate of ALCL concern (62.7%), however both cohorts had a significant odds ratio demonstrating an expressed fear of ALCL likely contributed to their subsequent clinical management (1.66 OR cosmetic, 2.17 OR reconstructive).

CONCLUSIONS: Although the risk of ALCL appears to be more concerning to the reconstructive population, both cohorts were equally motivated to have their implants removed. Informing patients about their ALCL risk is crucial to ensure a patient supported risk reduction plan.

PMID:35709374 | DOI:10.1093/asj/sjac158

J Appl Stat. 2021 Sep 1;48(16):3251-3252. doi: 10.1080/02664763.2021.1973388. eCollection 2021.

ABSTRACT

[This corrects the article DOI: 10.1080/02664763.2016.1142945.].

PMID:35709375 | PMC:PMC9041910 | DOI:10.1080/02664763.2021.1973388

Blood. 2022 Jun 16:blood.2021015325. doi: 10.1182/blood.2021015325. Online ahead of print.

ABSTRACT

Detailed genomic and epigenomic analyses of MECOM (the MDS1 and EVI1 complex locus) have revealed that inversion or translocation of chromosome 3 drive inv(3)/t(3;3) myeloid leukemias via structural rearrangement of an enhancer which upregulates transcription of EVI1. Here we identify a novel, previously unannotated oncogenic RNA-splicing derived isoform of EVI1 which is frequently present in inv(3)/t(3;3) AML and directly contributes to leukemic transformation. This EVI1 isoform is generated by oncogenic mutations in the core RNA splicing factor SF3B1, which is mutated in >30% of inv(3)/t(3;3) myeloid neoplasm patients and thereby represents the single most commonly co-occurring genomic alteration in inv(3)/t(3;3) patients. SF3B1 mutations are statistically uniquely enriched in inv(3)/t(3;3) myeloid neoplasm patients and patient-derived cell lines compared with other forms of AML and promote mis-splicing of EVI1 generating an in-frame insertion of six amino acids at the 3′ end of the second Zinc finger domain of EVI1. Expression of this EVI1 splice variant enhanced the self-renewal of hematopoietic stem cells and introduction of mutant SF3B1 in mice bearing the humanized inv(3)(q21q26) allele resulted in generation of this novel EVI1 isoform in mice and hastened leukemogenesis in vivo. The mutant SF3B1 spliceosome depends upon an exonic splicing enhancer within EVI1 exon 13 to promote usage of a cryptic branch point and aberrant 3′ splice site within intron 12 resulting in the generation of this isoform. These data provide a mechanistic basis for the frequent co-occurrence of SF3B1 mutations as well as new insights into the pathogenesis of myeloid leukemias harboring inv(3)/t(3;3).

PMID:35709354 | DOI:10.1182/blood.2021015325

Traffic Inj Prev. 2022 Jun 16:1-7. doi: 10.1080/15389588.2022.2086979. Online ahead of print.

ABSTRACT

OBJECTIVE: While a large amount of work has been conducted on different types of crash injury severity models, model selection uncertainty remains a critical issue in traffic safety research. The objective of this study is to handle model selection uncertainty by combining multiple models.

METHODS: Motorcycle crashes in Michigan from 2010 to 2014 are collected for the analysis. A model averaging approach is used to integrate useful information from three commonly used crash injury severity models: multinomial logit model, ordered logit model, and ordered probit model to deal with the situation where the model selection uncertainty exists in crash data analysis. The ratios of model posterior probabilities between models are used to quantify the model selection uncertainty. In addition, the effectiveness of the method is illustrated by comparing it with the single-best model.

RESULTS: The ratios of model posterior probabilities among models approximate to 1. It means that three models have the same importance in statistical analysis of motorcycle injury severity, resulting in model selection uncertainty. The comparison between the results of model averaging approach and single-best model shows that the single-best model tends to overestimate the effects of risk factors on motorcycle injury severities because of ignoring the model selection uncertainty; parameter errors and confidence intervals of model averaging are greater and wider than those of the single-best model due to between-model uncertainty included in the model averaging; some risk factors are significant in the model averaging approach while not in the single-best model. Results from model averaging approach reveal that drunk or riding under influence, angle/sideswipe/head on crashes, speed limit of 35 mph or higher, and signal control play significant roles in the motorcycle crashes.

CONCLUSIONS: The study contributes to the existing crash injury-severity literature by developing a model averaging approach to explore the relationship between motorcyclist’s injury-severity and its contributing factors. The model averaging approach overcomes the limitations of the current crash injury-severity modeling approaches by (1) revealing the potential model selection uncertainty among injury-severity models with model posterior probabilities; (2) more reliably accounting for the effects of risk factors on motorcyclist’ injury severities through integrating all information from the candidate models; and (3) better presenting the underlying unreliability of the analysis results from each individual model.

PMID:35709312 | DOI:10.1080/15389588.2022.2086979

Eur J Prev Cardiol. 2022 Jun 16:zwac079. doi: 10.1093/eurjpc/zwac079. Online ahead of print.

ABSTRACT

AIMS: In patients with coronary heart disease (CHD), we investigated whether it is possible to accurately assess the probability of short-term control of risk factors (blood pressure, cholesterol, smoking) based on individual and large-area residential characteristics.

METHODS AND RESULTS: We merged individual data of participants from EUROASPIRE V who were hospitalized for CHD (2014-2017) and interviewed and examined for risk factor control (2016-2017), with large-area residential data provided by Eurostat for Nomenclature of Territorial Units for Statistics (NUTS) regions using postal codes. Data from 2562 CHD patients in 16 countries were linked to data from 60 NUTS 2 and 121 NUTS 3 regions. The median time between hospitalization and interview was 14 months. We developed prediction models to assess the probability of risk factor control at interview using data from the time of hospitalization: (i) baseline models including 35 variables on patients’ demographic, clinical, and socio-economic characteristics and (ii) extended models additionally considering nine variables on large-area residential characteristics. We calculated and internally validated c-indices to assess the discriminative ability of prediction models. Baseline models showed good discrimination with c-indices of 0.69, 0.70, and 0.76 for blood pressure control, cholesterol control, and smoking cessation, respectively. Extended models for blood pressure, cholesterol, and smoking yielded improved c-indices of 0.72, 0.71, and 0.78, respectively.

CONCLUSION: Our results indicate that the probability of risk factor control in CHD patients can be accurately assessed using individual and large-area residential characteristics, allowing for an identification of patients who are less likely to achieve risk factor targets.

PMID:35709302 | DOI:10.1093/eurjpc/zwac079

PLoS One. 2022 Jun 16;17(6):e0266371. doi: 10.1371/journal.pone.0266371. eCollection 2022.

ABSTRACT

PURPOSE: Higher levels of serum 25-hydroxyvitamin D 25(OHD) are associated with better prognosis in breast and colorectal cancer. However, the evidence is still inconclusive for bladder cancer (BC). Herein, we investigated the diagnosis and prognosis roles of serum levels of 25(OHD) in suspected BC patients presented by hematuria.

METHODS: This prospective cohort study involved suspected patients of BC presented with hematuria. Patients were evaluated by CT urogram, office cystoscopy and urine cytology with subsequent inpatient biopsy for positive findings. Baseline blood samples were collected for measurement of 25(OHD) by electrochemiluminescence binding assay at the time of diagnosis. Patients with non-muscle-invasive BC (NMIBC) underwent transurethral resection of bladder tumor (TURBT) and adjuvant intravesical chemotherapy or BCG instillation. Patients were followed up for their recurrence status during 10 to 24 months. Recurrence was defined as the first time of NMIBC pathological relapse during the follow up period.

RESULTS: A total of 115 patients were included in the final analysis. Patients had proven pathological BC (64 with NMIBC, and 20 with muscle invasive) and 31 patients were considered as control group. Controls were those patients with BC-free workup (including cytology, cystoscopy, and upper tract imaging). BC group showed a lower level of 25(OHD) than control group 16.47±5.88 versus 28.99±3.19 ng/mL (p<0.001). In addition, muscle invasive group also showed a lower level than NMIBC group 13.17±4.5 versus 17.49±5.04 ng/mL (P = 0.003). During the follow-up period of, tumor recurrence occurred in 16 (25%) of NMIBC patients. The baseline 25(OHD) were decreased in patients who experienced early recurrence; without being statistically significant (15.99 ± 5.17 vs. 18.38 ± 5.14 ng/mL; p = 0.08). 25(OHD) deficiency/insufficiency occurred in 5 (16.1%) and 64 (76.2%) in control and BC patients, respectively, (odds-ratios (OR): 2.13; 95% confidence intervals (CI), 1.52-2.99; P < 0.0001).

CONCLUSION: Serum 25(OHD) is significantly decreased in BC patients especially those with tumor muscle invasive group. However, the baseline serum 25(OHD) does not predict the recurrence in the NMIBC patients.

PMID:35709298 | DOI:10.1371/journal.pone.0266371

PLoS Genet. 2022 Jun 16;18(6):e1010251. doi: 10.1371/journal.pgen.1010251. Online ahead of print.

ABSTRACT

More than a decade of genome-wide association studies (GWASs) have identified genetic risk variants that are significantly associated with complex traits. Emerging evidence suggests that the function of trait-associated variants likely acts in a tissue- or cell-type-specific fashion. Yet, it remains challenging to prioritize trait-relevant tissues or cell types to elucidate disease etiology. Here, we present EPIC (cEll tyPe enrIChment), a statistical framework that relates large-scale GWAS summary statistics to cell-type-specific gene expression measurements from single-cell RNA sequencing (scRNA-seq). We derive powerful gene-level test statistics for common and rare variants, separately and jointly, and adopt generalized least squares to prioritize trait-relevant cell types while accounting for the correlation structures both within and between genes. Using enrichment of loci associated with four lipid traits in the liver and enrichment of loci associated with three neurological disorders in the brain as ground truths, we show that EPIC outperforms existing methods. We apply our framework to multiple scRNA-seq datasets from different platforms and identify cell types underlying type 2 diabetes and schizophrenia. The enrichment is replicated using independent GWAS and scRNA-seq datasets and further validated using PubMed search and existing bulk case-control testing results.

PMID:35709291 | DOI:10.1371/journal.pgen.1010251

PLoS One. 2022 Jun 16;17(6):e0270150. doi: 10.1371/journal.pone.0270150. eCollection 2022.

ABSTRACT

We urgently need answers to basic epidemiological questions regarding SARS-CoV-2 infection in pregnant and postpartum women and its effect on their newborns. While many national registries, health facilities, and research groups are collecting relevant data, we need a collaborative and methodologically rigorous approach to better combine these data and address knowledge gaps, especially those related to rare outcomes. We propose that using a sequential, prospective meta-analysis (PMA) is the best approach to generate data for policy- and practice-oriented guidelines. As the pandemic evolves, additional studies identified retrospectively by the steering committee or through living systematic reviews will be invited to participate in this PMA. Investigators can contribute to the PMA by either submitting individual patient data or running standardized code to generate aggregate data estimates. For the primary analysis, we will pool data using two-stage meta-analysis methods. The meta-analyses will be updated as additional data accrue in each contributing study and as additional studies meet study-specific time or data accrual thresholds for sharing. At the time of publication, investigators of 25 studies, including more than 76,000 pregnancies, in 41 countries had agreed to share data for this analysis. Among the included studies, 12 have a contemporaneous comparison group of pregnancies without COVID-19, and four studies include a comparison group of non-pregnant women of reproductive age with COVID-19. Protocols and updates will be maintained publicly. Results will be shared with key stakeholders, including the World Health Organization (WHO) Maternal, Newborn, Child, and Adolescent Health (MNCAH) Research Working Group. Data contributors will share results with local stakeholders. Scientific publications will be published in open-access journals on an ongoing basis.

PMID:35709239 | DOI:10.1371/journal.pone.0270150