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Κυριακή 4 Απριλίου 2021

Establishment and characterization of 38 novel patient-derived primary cancer cell lines using multi-region sampling revealing intra-tumor heterogeneity of gallbladder carcinoma

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Abstract

Gallbladder carcinoma (GBC) is a lethal biliary tract malignant neoplasm. Patient-derived primary cancer cell lines (PDPCs) are appropriate models to explore biological characteristics and potential therapeutics; however, there is a lack of PDPCs in GBC. In this study, we aimed to establish and characterize the GBC PDPCs, and further investigated the intra-tumor heterogeneity (ITH). Multi-region sampling (3–9 regions) of the operable tumor tissue samples was used to establish PDPCs. Short tandem repeat genotyping for cell authentication and karyotyping was performed, followed by whole-exome sequencing and RNA sequencing to assess the ITH at the genetic and transcriptional levels, respectively. Thirty-eight PDPCs were successfully established from seven GBC patients and characterized. ITH was observed with a median of 38.3% mutations being heterogeneous (range, 26.6–59.4%) across all patients. Similar with other tumor types, TP53 mutations were always truncal. In addition, there were three genes, KMT2C, CDKN2A, and ARID1A, with truncal mutations in at least two patients. A median of 370 differentially expressed genes (DEGs) was identified per patient. Distinct expression patterns were observed between major histocompatibility complex (MHC) class I and II genes. We found the expression of MHC class II genes in the PDPC samples was closely regulated by CIITA, while that of MHC class I genes were not correlated with CIITA expression. The PDPCs established from GBC patients can serve as novel in vitro models to identify the ITH, which may pave a crucial molecular foundation for enhanced understanding of tumorigenesis and progression.

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Geriatric assessment and medical preoperative screening (GrAMPS) program for older hernia patients

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Abstract

Purpose

The incidence of older adults undergoing inguinal and ventral hernia repairs is increasing. Older adults are disproportionately affected by age-related risk factors, which are often under-recognized and may adversely affect surgical outcomes. These age-related risk factors often termed "geriatric syndromes," include multimorbidity, frailty, cognitive impairment, depression, obesity, functional impairment, polypharmacy, and poor subjective health. The aim of this study was to identify the prevalence of age-related risk factors in older patients undergoing elective hernia repair.

Methods

Patients aged 60 years or older with a planned elective surgical repair of a ventral or inguinal hernia were prospectively enrolled in a clinic. Subjects completed several validated screening tools for geriatric syndromes.

Results

Seventy patients completed preoperative assessments (mean age: 68.5 years). In total, 24 (34.3%) screened positive for previously unrecognized objective cognitive impairment (Mini-Cog) and 33 (47.1%) for a subjective memory concern. Sixty patients (85.7%) met criteria for polypharmacy. Additionally, 48 (68.6%) screened positive for either pre-frailty (37, 52.9%) or frailty (11, 15.7%), and 66 (94.3%) had multimorbidity. Twenty-five (35.7%) patients self-rated their health as "poor" or "fair," and 18 (25.7%) patients endorsed some functional impairment.

Conclusions

There is a high prevalence of age-related risk factors in older patients undergoing elective hernia repair. Further, these factors are often unrecognized and underappreciated despite their potential to significantly impact informed consent and shared decision making. Additional study is required to define the impact of these age-related risk factors on surgical outcomes, which will inform preoperative risk assessment and optimization through modifiable risk reduction.

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A Stakeholder-Engaged Process for Adapting an Evidence-Based Intervention for Posttraumatic Stress Disorder for Peer Delivery

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Abstract

Purpose

Peer providers represent a growing sector of the U.S. workforce, yet guidance is needed on best practices for adapting behavioral health interventions for peer delivery.

Methods

We utilized the Framework for Reporting Adaptations and Modifications to Evidence-based interventions (FRAME; Wiltsey Stirman et al. 2013, 2019) to describe how we systematically adapted Skills Training in Affective and Interpersonal Regulation (STAIR) for posttraumatic stress disorder (PTSD) for peer delivery. Our process was iterative and relied on engagement of multiple stakeholders, including a work group of organizational leaders (N = 5), peer interventionists (N = 4), intervention experts (N = 2), and trial participants (N = 18). The FRAME was used to guide rapid coding across multiple data sources, including researcher field notes, meeting minutes, and intervention manual documents, and content analysis of semi-structured interviews with peer interventionists and trial participants.

Results

Phase 1 (pre-trial) focused on modifications for fit with the local context and peer model. Key modifications focused on improving intervention design and packaging, removing clinical and stigmatizing language, and addressing peer interventionist training gaps. We used a hybrid approach to delivery, whereby we integrated peer model principles (self-disclosure, mutuality) into a directive approach. Phase 2 (trial) included reactive fidelity-consistent adaptations, such as additional educational resources. Phase 3 (post-trial) focused on adaptations to support roll-out of the intervention at the peer organization (e.g., group format).

Conclusion

Our stakeholder-engaged process may serve as a helpful exemplar to others tailoring interventions for peer delivery. Future research is needed to understand the role of stakeholder engagement and adaptation in implementation success.

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MiR-193a-3p Promotes Fracture Healing via Targeting PTEN Gene

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Abstract

The aim of this study was to investigate the role and potential mechanism of miR-193a-3p in fracture healing. The 70 fragility fracture patients and 45 healthy controls were enrolled in this study. Quantitative real-time PCR (qRT-PCR) was used for the measurement of the expression levels of miR-193a-3p and PTEN. MTT assay and flow cytometry were used to detect cell viability and apoptosis in the mouse osteoblastic cell line MC3T3-E1. Luciferase reporter assay was performed to confirm the correlation of miR-193a-3p with PTEN. The serum expression level of miR-193a-3p showed no significant change in fracture patients 7 days after fixation treatment, but over time, there was a significant decrease in the expression at 14 days and 21 days after treatment (P < 0.01). Overexpression of miR-193a-3p significantly enhanced cell viability and inhibited cell apoptosis in MC3T3-E1 cells (P < 0.001). Serum P TEN level in fracture patients was increased gradually during the fracture healing process (P < 0.01). PTEN was demonstrated to be a target gene of miR-9-5p and reversed the effect of miR-193a-3p on cell viability and apoptosis (P < 0.001). miR-193a-3p promoted fracture healing via regulating PTEN and may serve as a novel potential target for enhancing bone repair of fragility fracture.

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Right-sided Zenker’s diverticulum resected using intraoperative neuromonitoring

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Abstract

Right-sided Zenker's diverticulum is a rare pharyngoesophageal diverticulum. The risk of intraoperative injury of the recurrent laryngeal nerve is high during transcervical diverticulectomy because this nerve presents many variations of extralaryngeal bifurcation before entry into the larynx. We present a case of right-sided Zenker's diverticulum that was safely resected with the use of intraoperative neuromonitoring to prevent right recurrent laryngeal nerve injury. A 55-year-old man complaining of chronic cough and regurgitation of ingested food was diagnosed as having right-sided Zenker's diverticulum and underwent open transcervical diverticulectomy and cricopharyngeal myotomy. The location of the right recurrent laryngeal nerve was accurately determined during dissection by intermittent stimulation using a monopolar stimulation probe of an intraoperative neuromonitoring system to avoid injury. The postoperative course was uneventful, and postoperative evaluation showed no vocal cord paralysis. Intraoperative neuromonitoring may be beneficial during transcervical diverticulectomy for right-sided Zenker's diverticulum nearby the right recurrent laryngeal nerve, which can present with many variations of extralaryngeal bifurcation.

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No evidence for an effect of working from home on neck pain and neck disability among Swiss office workers: Short-term impact of COVID-19

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Abstract

Purpose

The aim of this study was to investigate the effect of working from home on neck pain (NP) among office workers during the COVID-19 pandemic.

Methods

Participants from two Swiss organisations, aged 18–65 years and working from home during the lockdown (n = 69) were included. Baseline data collected in January 2020 before the lockdown (office work) were compared with follow-up data in April 2020 during lockdown (working from home). The primary outcome of NP was assessed with a measure of intensity and disability. Secondary outcomes were quality of workstation ergonomics, number of work breaks, and time spent working at the computer. Two linear mixed effects models were fitted to the data to estimate the change in NP.

Results

No clinically relevant change in the average NP intensity and neck disability was found between measurement time points. Each working hour at the computer increased NP intensity by 0.36 points (95% CI: 0.09 to 0.62) indicating strong evidence. No such effect was found for neck disability. Each work break taken reduced neck disability by 2.30 points (95% CI:  − 4.18 to  − 0.42, evidence). No such effect was found for NP intensity. There is very strong evidence that workstation ergonomics was poorer at home.

Conclusion

The number of work breaks and hours spent at the computer seem to have a greater effect on NP than the place of work (office, at home), measurement time point (before COVID-19, during lockdown) or the workstation ergonomics. Further research should investigate the effect of social and psychological factors.

Trial registration

ClinicalTrials.gov, NCT04169646. Registered 15 November 2019—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04169646.

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Catheter Ablation of Atrial Fibrillation in Heart Failure: from Evidences to Guidelines

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Abstract

Purpose of Review

Catheter ablation of atrial fibrillation in heart failure seems to be the way to improve the quality of life, life expectance, and prognosis. In this review, we outline the growing role of this therapy and which patients can benefit from it.

Recent Findings

While previous studies comparing rate control and rhythm control had not demonstrated the superiority of rhythm control in the prognosis of patients with atrial fibrillation and heart failure, recent findings seem to demonstrate that catheter ablation of atrial fibrillation reduces mortality and hospitalization for heart failure and improves the quality of life, when compared to medical therapy alone.

Summary

An early rhythm-control strategy in atrial fibrillation may reduce cardiovascular death, stroke, hospitalization for HF, or acute coronary syndrome. Catheter ablation in heart failure is an effective and safe solution to obtain a rhythm control and, therefore, to improve outcomes. A better selection of the patients could help to avoid futile procedures and to identify patients requiring a closer follow-up, to redo procedures, or the addition of antiarrhythmic drugs.

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The comparison of STA-MCA bypass and BMT for symptomatic internal carotid artery occlusion disease: a systematic review and meta-analysis of long-term outcome

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Abstract

Background

Superficial temporal artery (STA)-middle cerebral artery (MCA) bypass surgery is now being widely used in moyamoya disease, and its therapeutic value in SICAO remains divergent.

Methods

A systematic search was performed in PubMed, EMBASE, and Cochrane Databases in Feb. 2020 and updated in Jun. 2019. We have strict inclusion and exclusion criteria. Cochrane Bias Risk Assessment Tool was used to assess the quality of included RCTs. Review Manager 5.3 was used for analysis results in terms of comparing the STA-MCA bypass and BMT. For dichotomous variable outcomes, risk ratios (RRs) and 95% confidence intervals (95%CIs) were calculated for the assessment.

Results

The total patient cohort consisted of 2419 patients, of whom 1188 (49.1%) patients had been grouped in STA-MCA bypass and 1231 (50.9%) patients had been divided into the BMT group. Mean follow-up of included patients was 29 months. The RR of the seven studies was 1.01, and the 95% confidence interval was .89–1.15, with statistical significance, Z = .13, P = .89, sustaining that STA-MCA bypass was not superior to BMT in symptomatic carotid artery occlusion disease.

Conclusions

STA-MCA bypass and BMT were associated with similar rates of a composite of long-term stroke. And the risk of long-term overall stroke was mildly higher with BMT. At present, each patient should receive more precise treatment, by reasonably assessing the individual differences of each patient to reduce the recurrence rate of stroke.

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Πέμπτη 1 Απριλίου 2021

Sphenoid Sinus: Pneumatization and Septation Patterns in a Hispanic Population

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Introduction: Pneumatization of the sphenoid sinus (SS) varies widely among different ethnic groups. Information regarding the prevalence and significance of SS variants among Hispanic groups is limited. This study aims to describe and analyze pneumatization and septation patterns of the SS in a Hispanic population. Methods: A total of 160 paranasal sinus computed tomographies were reviewed by a head and neck-specialized radiologist and 2 otolaryngologists. R esults: The postsellar and sellar types were the most frequent patterns of pneumatization observed, with a prevalence of 52.5 and 40%, respectively. Accessory septations were present in 59.4% of the patients. Septa were inserting over the internal carotid artery (ICA) in 43.8% and over the optic nerve in 17.5% of the population. No significant association (p #x3e; 0.05) was observed when comparing the different accessory septation patterns among the types of the SS. The frequency of septa inserting on the ICA was significantly higher in postsellar types (p #x3c; 0.001). Pneumatization of the anterior clinoid process, pterygoid processes, and greater wing was present in 20, 17.5, and 45.9% of the sinuses, respectively. Onodi cells were encountered in 40% of the sinuses. There were no significant differences in any of the pneumatization and septation variables when compared by gender and age (p #x3e; 0.05). Discussion/Conclusion: Differences regarding anatomical variants and septations of the SS were observed in our study when compared with findings reported in other ethnic groups. Preoperative assessment of the anatomical variants of the SS in Mexican patients is imperative to select the most optimal surgical approach and prevent iatrogenic injuries to related neurovascular structures.
ORL
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Pragmatic Skills in Children with Hearing Loss: Comparison Between Cochlear Implants and Hearing Aids Users

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Abstract

Pragmatic language ability denotes the ability to use language in a social context. There is a lack of research that has compared children's pragmatic skills with hearing loss with those of hearing peers. This study questioned whether children with a cochlear implant would show better pragmatic skills than children with hearing aids. 52 children were included in three groups: cochlear implant (n = 16), hearing aid (n = 16), and normal hearing (n = 20). The participants' pragmatic skills were evaluated using the Persian version of the children's communication checklist. Of the 52 participants recruited, 22 (42.3%) were males, and 30 (57.7%) were females. The mean age of the CI, HA, and NH group participants was 75.19 ± 10.80, 72.19 ± 8.68, and 68.90 ± 6.78 months, respectively (P > 0.05). There was a significant difference between the mean scores of Speech Output and Syntax between the groups (CI, HA and NH) (P < 0.001). The hearing-impaired children show acceptable pragmatic skills in comparison with NH children. Specialists, such as teachers and clinicians, should be alert of the abilities and difficulties that the hearing-impaired children might be facing in the regular classroom.

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Τετάρτη 31 Μαρτίου 2021

An improved predictive model for postoperative pulmonary complications after free flap reconstructions in the head and neck

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Abstract

Background

Commonly used predictive models for postoperative pulmonary complications (PPCs) do not perform when applied to head and neck cases. A head and neck‐specific risk prediction tool is needed.

Methods

Data on 794 free flap head and neck surgery cases at a single center were abstracted from the electronic medical record. Each case was reviewed for the development of PPCs. A predictive model was developed and was then compared to existing predictive models for PPCs.

Results

The least absolute shrinkage and selection operator procedure identified age, alcohol use, history of congestive heart failure, preoperative packed cell volume, preoperative oxygen saturation, and preoperative metabolic equivalents as predictors of PPCs in the head and neck population. The model demonstrated an area under the receiving operating characteristic curve of 0.75 (0.69–0.80) with moderately good calibration. Comparisons to the performance of existing models demonstrate superior performance.

Conclusions

The model for the development of PPCs developed in this article displays superior performance to existing models.

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