Clinical Considerations Research Articles

Identifying the predictive value of fractional exhaled nitric oxide (FeNO) for uncontrolled asthma in 3-7-year-old Thai children.

Fractional exhaled nitric oxide (FeNO) is the method for monitoring airway inflammation. However, a singular FeNO value cutoff may not adequately represent the control status across different ages and demographics. This study aimed to evaluate the correlation between FeNO values and asthma control levels, identifying an optimal cutoff point for children aged 3 to 7 years. This cross-sectional study was conducted at Naresuan University Hospital from April 1, 2023 to July 31, 2023. Inclusion criteria were asthmatic patients aged 3 to 7 years who were capable of following commands. Exclusion criteria included children who had a coronavirus disease 2019 (COVID-19) infection, those experiencing difficulty breathing, or unable to perform the FeNO measurement. Eligible patients were classified according to their level of asthma control and underwent FeNO testing. Out of 108 participants who successfully completed FeNO measurements, a significant difference in FeNO values was observed across controlled, partially controlled, and uncontrolled asthma groups, with uncontrolled asthma presenting significantly higher values. The optimal FeNO cutoff point for predicting uncontrolled asthma was identified as ≥15 ppb with a sensitivity 46.7%, specificity 86.0%, positive predictive value (PPV) 35.0%, negative predictive value (NPV) 90.9%. This study established a significant correlation between FeNO levels and uncontrolled asthma, FeNO cutoff point ≥15 ppb as the optimal value in predicting uncontrolled asthma in Thai children aged 3-7 years. Factors such as uncontrolled allergic rhinitis, symptoms at onset, smoking exposure, treatment compliance, and inhaled corticosteroid (ICS) usage were associated with FeNO values. The application of FeNO measurement should be integrated with clinical assessments and consideration of these associated factors.

Customized 3D-Printed Mesh, Membrane, Bone Substitute, and Dental Implant Applied to Guided Bone Regeneration in Oral Implantology: A Narrative Review.

Background: The new frontiers of computer-based surgery, technology, and material advances, have allowed for customized 3D printed manufacturing to become widespread in guided bone regeneration (GBR) in oral implantology. The shape, structural, mechanical, and biological manufacturing characteristics achieved through 3D printing technologies allow for the customization of implant-prosthetic rehabilitations and GBR procedures according to patient-specific needs, reducing complications and surgery time. Therefore, the present narrative review aims to elucidate the 3D-printing digital radiographic process, materials, indications, 3D printed manufacturing-controlled characteristics, histological findings, complications, patient-reported outcomes, and short- and long-term clinical considerations of customized 3D printed mesh, membranes, bone substitutes, and dental implants applied to GBR in oral implantology. Methods: An electronic search was performed through MEDLINE/PubMed, Scopus, BioMed Central, and Web of Science until 30 June 2024. Results: Three-dimensionally printed titanium meshes and bone substitutes registered successful outcomes in vertical/horizontal bone defect regeneration. Three-dimensionally printed polymeric membranes could link the advantages of conventional resorbable and non-resorbable membranes. Few data on customized 3D printed dental implants and abutments are available, but in vitro and animal studies have shown new promising designs that could improve their mechanical properties and tribocorrosion-associated complications. Conclusions: While 3D printing technology has demonstrated potential in GBR, additional human studies are needed to evaluate the short- and long-term follow-up of peri-implant bone levels and volumes following prosthetic functional loading.

Prenatal Surgery for Open Fetal Spina Bifida in Patients with Obesity: A Review of Current Evidence and Future Directions.

Background: Obesity rates have significantly increased globally, affecting up to 40% of women of childbearing age in the United States. While prenatal repair of open fetal spina bifida has shown improved outcomes, most fetal surgery centers exclude patients with a body mass index (BMI) ≥ 35 kg/m2 based on criteria from the Management of Myelomeningocele Study (MOMS) trial. This exclusion raises concerns about healthcare equity and highlights a significant knowledge gap regarding the safety and efficacy of fetal spina bifida repair in patients with obesity. Objective: To review the current state of knowledge regarding open fetal surgery for fetal spina bifida in patients with obesity, focusing on safety, efficacy, and clinical considerations. Methods: A comprehensive literature search was conducted using the PubMed and EMBASE databases, covering articles from the inception of the databases to April 2024. Studies discussing fetal surgery for neural tube defects and documenting BMI measurements and their impact on surgical outcomes, published in peer-reviewed journals, and available in English were included. Quantitative data were extracted into an Excel sheet, and data synthesis was conducted using the R programming language (version 4.3.3). Results: Three retrospective studies examining outcomes of prenatal open spina bifida repair in a total of 43 patients with a BMI ≥ 35 kg/m2 were identified. These studies did not report significant adverse maternal or fetal outcomes compared to patients with lower BMIs. Our pooled analysis revealed a perinatal mortality rate of 6.1% (95% CI: 1.76-18.92%), with 28.0% (95% CI: 14.0-48.2%) experiencing the premature rupture of membranes and 82.0% (95% CI: 29.2-98.0%) delivering preterm (<37 weeks). Membrane separation was reported in 10.3% of cases (95% CI: 3.3-27.7%), the mean gestational age at birth was 34.3 weeks (95% CI: 32.3-36.3), and the average birth weight was 2651.5 g (95% CI: 2473.7-2829.4). Additionally, 40.1% (95% CI: 23.1-60.0%) required a ventriculoperitoneal shunt. Conclusion: While current evidence suggests that fetal spina bifida repair may be feasible in patients with obesity, significant limitations in the existing body of research were identified. These include small sample sizes, retrospective designs, and a lack of long-term follow-up data. There is an urgent need for large-scale, prospective, multicenter studies to definitively establish the safety and efficacy of fetal spina bifida repair in patients with obesity. Such research is crucial for developing evidence-based guidelines, improving clinical outcomes, and addressing healthcare disparities in this growing patient population with obesity.

Harms with placebo in trials of biological therapies and small molecules as maintenance therapy in inflammatory bowel disease: a systematic review and meta-analysis

Randomised placebo-controlled trials for the induction of inflammatory bowel disease (IBD) remission involve potential harms to those receiving placebo. Whether these harms are also apparent with placebo during maintenance of remission trials in IBD is unclear. We aimed to examine the potential harms associated with receiving placebo in trials of licensed biologics and small molecules for maintenance of remission of ulcerative colitis and luminal Crohn's disease in a meta-analysis. We performed a systematic review and meta-analysis. We searched several medical literature databases including MEDLINE (from Jan 1, 1946, to May 31, 2024), Embase and Embase Classic (Jan 1, 1947, to May 31, 2024), and the Cochrane Central Register of Controlled Trials from database inception to May 31, 2024, for randomised placebo-controlled trials of licensed biologics and small molecules for maintenance of remission in adults with IBD reporting data on adverse events over a period of 20 weeks or more. There were no language restrictions or prespecified exclusion criteria. We extracted summary data and pooled data using a random-effects model for any treatment-emergent adverse event, drug-related adverse event, infection, worsening of IBD activity, withdrawal due to adverse events, serious adverse events, serious infection, serious worsening of IBD activity, or venous thromboembolic events, reporting relative risks (RRs) for placebo versus active drug with 95% CIs for each outcomes. The protocol for this meta-analysis was registered with PROSPERO (CRD42024542624). Our search identified 10 826 citations, of which 45 trials including 16 562 patients (10 319 [62·3%] receiving active drug and 6243 [37·7%] placebo) were eligible. The risks of any treatment-emergent adverse event (7297/9546 [76·4%] patients on active drug vs 4415/5850 [75·5%] on placebo; RR 1·01, 95% CI 0·99-1·04; I2 =47%), serious infection (260/10 242 [2·5%] vs 155/6149 [2·5%]; 0·97, 0·79-1·19; I2 =0%), or venous thromboembolic event (12/4729 [0·3%] vs 9/2691 [0·3%]; 0·72, 0·31-1·66; I2 =0%) were not significantly lower with active drug than placebo. The risks of any infection (3208/8038 [39·9%] vs 1713/4809 [35·6%]; 1·14, 1·05-1·23; I2 =60%) or any drug-related adverse event (1094/2997 [36·5%] vs 609/1950 [31·2%]; 1·24, 1·02-1·50; I2 =75%) were higher with active drug than placebo. However, the risks of any worsening of IBD activity (1038/8090 [12·8%] vs 1181/5191 [22·8%]; 0·58, 0·52-0·64; I2 =40%), any withdrawal due to adverse events (610/10 282 [5·9%] vs 561/6207 [9·0%]; 0·71, 0·60-0·84; I2 =43%), any serious adverse events (1066/10 292 [10·4%] vs 742/6198 [12·0%]; 0·85, 0·77-0·94; I2 =17%), or any serious worsening of IBD activity (101/5707 [1·8%] vs 143/3640 [3·9%]; 0·55, 0·42-0·71; I2 =0%) were lower with active drug than placebo. 21 randomised controlled trials were judged as low risk of bias across all domains. In maintenance of remission trials in IBD, placebo was associated with some clinically significant potential harms. Patients should be counselled about these before participating in clinical trials and consideration given to alternative designs to test novel drugs in IBD. None.

Immediate and Successful Management of Avulsed Teeth: A Case Reports

Avulsion and midroot fractures of teeth present significant challenges in dental trauma management. These case reports outlines the successful management of avulsed after a lapse of 2hrs in 1st case report and 24hrs in 2nd case report and midroot fractured tooth, focusing on immediate steps, long-term strategies, and clinical considerations. Midroot fractures often present with compromised structural integrity, necessitating stabilization and protection of the tooth to prevent further damage. Splinting techniques stabilize the tooth and promote healing of periodontal tissues. However, careful monitoring is crucial to assess for potential complications such as inflammatory root resorption and external root resorption. In both the cases extraoral root canal treatment was done for avulsed tooth and then reimplanted into the socket and stabilisation was done using splinting. Followup up was done at regular intervals of one and 3 months which showed no resorption or perapical changes, lack of clinical symptoms In conclusion, the management of avulsed and midroot fractured teeth requires long-term treatment strategies. Favorable outcomes can be achieved, preserving tooth function, and esthetics in patients with traumatic dental injuries.

Short Bowel Syndrome: A Case Series and Review of Literature

Short Bowel Syndrome, defined as remaining small bowel in continuity of less than 200 cm, is a disorder with varied presentations and frequent and often difficult-to-manage complications. The most commonly encountered complications are mainly nutritional, gastrointestinal and nephrological. Anticoagulation and bone disorders due to micronutrient and drug malabsorption, among other causes, are also encountered. The clinical follow-ups and considerations necessary vary between patients. Functional, pathophysiological, etiological, clinical and anatomical classifications exist to help physicians predict the required interventions. Herein, we summarise our experience with three cases with differing presentations and prognoses. We discuss the problems encountered during their management in light of the existing literature and guidelines. Specialised units and a multi-departmental approach remain vital in managing intestinal failure and short bowel syndrome; better tools and further research are yet to be required.

REPRODUCTIVE HEALTH IN TRANS AND GENDER DIVERSE PATIENTS: Mind the gap: a nationwide audit of LGBTQ+ inclusion in fertility care providers in the United Kingdom.

We describe a first-of-its-kind audit of LGBTQ+ inclusivity in fertility care providers across the United Kingdom. Despite efforts being made to improve LGBTQ+ inclusion in fertility care, our results paint a picture of widespread gaps in clinical and cultural expertise alongside significant barriers to LGBTQ+ inclusion. LGBTQ+ patients comprise one of the fastest-growing user demographics in fertility care, yet they remain under-represented in fertility research, practice, and discourse. Existing studies have revealed significant systemic barriers, including cisheteronormativity, discrimination, and gaps in clinical expertise. In this article, we present a checklist of measures that clinics can take to improve LGBTQ+ inclusion in fertility care, co-created with members of the LGBTQ+ community. This checklist focuses on three key areas: cultural competence, clinical considerations, and online presence. The cultural competence criteria encompass inclusive communication practices, a broad understanding of LGBTQ+ healthcare needs, and knowledge of treatment options suitable for LGBTQ+ individuals. Clinical considerations include awareness of alternative examination and gamete collection techniques for transgender and gender diverse patients, the existence of specific clinical pathways for LGBTQ+ patients, and sensitivity to the psychological aspects of fertility care unique to this demographic. The online presence criteria evaluate provider websites for the use of inclusive language and the availability of LGBTQ+-relevant information. The checklist was used as the foundation for an audit of fertility care providers across the UK in early 2024. Our audit identified a widespread lack of LGBTQ+ inclusion, particularly for transgender and gender diverse patients, highlighting deficiencies in clinical knowledge and cultural competence. Our work calls attention to the need for further efforts to understand the barriers to inclusive and competent LGBTQ+ fertility care from both healthcare provider and patient perspectives.

Transcatheter Aortic Valve Replacement is Ready for Most Low-risk Patients: A Systematic Review of the Literature.

Transcatheter aortic valve replacement (TAVR) has undergone rapid expansion, emerging as a viable therapeutic option for low-risk patients in lieu of surgical aortic valve replacement. This paper aims to provide a review of the scientific evidence concerning TAVR in low-risk patients, encompassing both observational and clinical trial data. Furthermore, a substantial proportion of low-risk patients possesses a bicuspid aortic valve, necessitating careful examination of the pertinent anatomic and clinical considerations to TAVR that is highlighted in this review. Additionally, the review expands upon some of the unique challenges associated with alternate access in low-risk patients evaluated for TAVR. Last, this review outlines the pivotal role of a multidisciplinary heart team approach in the execution of all TAVR procedures and the authors' vision of 'minimalist TAVR' as a new era in low-risk TAVR.

Clinical Considerations for Integrating Ethical Principles of Beneficence in the Development of Evidence-Based Interventions: The case of Pediatric Misophonia.

Misophonia is a condition involving decreased tolerance and intense responses to specific sounds, often those that are human-generated and repetitive in nature. Misophonia frequently onsets during childhood and is associated with significant distress, impairment, and diminished quality of life. While misophonia research remains nascent and no definitive practice guidelines exist at present, extant studies offer several promising potential avenues in intervention development for adults with misophonia. However, such research is comparatively limited for youth. Before widespread adoption of promising treatments, it is important to consider the potential for harm or non-beneficence that may arise from the mis-informed application of such treatments. In this article, we identify several potential pitfalls within intervention development for pediatric misophonia and provide recommendations to circumvent them. To that end, we focus on the following three topic areas: (a) challenges arising when psychological mechanisms are not considered in intervention development, (b) importation of a cognitive-behavior therapy (CBT) framework for obsessive-compulsive spectrum disorders without nuanced tailoring to misophonia, and (c) neglecting to include individuals with lived experience in the process of intervention development research. Considering these key areas within misophonia intervention development will be critical for upholding beneficence and minimizing harm in treatment of misophonia across the lifespan.

Reforming clinical negligence in England: lessons about patients' and providers' values from medical injury resolution in New Zealand and the United States of America

England's current review of clinical negligence and consideration of alternatives (such as no-fault compensation) should be welcomed. Valuing what patients and families want, and need, after harm in healthcare necessitates a system that enables their needs to be met. Medical negligence litigation is misaligned with patients' needs after harm events. By contrast, alternatives (such as no-fault and communication-and-resolution programmes) offer opportunities to place patients', families' and providers' values at the forefront of resolution efforts. This article offers empirical insights and lessons from two alternative systems for resolving medical injuries: New Zealand's (NZ's) administrative compensation scheme, and the US communication-and-resolution programmes (CRPs). The review in England presents an exciting opportunity to design a system for responding to medical injuries that harnesses the strengths of alternative approaches for resolving medical injuries, while also improving on the challenges with treatment injury in NZ.

Validation of endoplasmic reticulum stress-related gene signature to predict prognosis and immune landscape of patients with non-small cell lung cancer.

Lung cancer is one of the most common cancers worldwide, with the incidence increasing each year. It is crucial to improve the prognosis of patients who have lung cancer. Non-Small Cell Lung Cancer (NSCLC) accounts for the majority of lung cancer. Though its prognostic significance in NSCLC has not been often documented, Endoplasmic Reticulum (ER) stress has been identified to be implicated in tumour malignant behaviours and resistance to treatment. This work aimed to develop a gene profile linked to ER stress that could be applied to predictive and risk assessment for non-small cell lung cancer. Data from 1014 NSCLC patients were sourced from The Cancer Genome Atlas (TCGA) database, integrating clinical and Ribonucleic Acid (RNA) information. Diverse analytical techniques were utilized to identify ERS-associated genes associated with patients' prognoses. These techniques included Kaplan-Meier analysis, univariate Cox regression, Least Absolute Shrinkage and Selection Operator regression analysis (LASSO) regression, and Pearson correlation analysis. Using a risk score model obtained from multivariate Cox analysis, a nomogram was created and validated to classify patients into high- and low-risk groups. The study employed the CIBERSORT algorithm and Single-Sample Gene Set Eenrichment Analysis (ssGSEA) to investigate the tumour immune microenvironment. We used the Genomics of Drug Sensitivity in Cancer (GDSC) database and R tools to identify medicines that could be responsive. Four genes - FABP5, C5AR1, CTSL, and LTA4H - were chosen to create the risk model. Overall Survival (OS) was considerably lower (P< 0.05) in the high-risk group. When it came to predictive accuracy, the risk model outperformed clinical considerations. Several medication types that are sensitive to high-risk groups were chosen. Our study has produced a gene signature associated with ER stress that may be employed to forecast the prognosis and therapeutic response of non-small cell lung cancer patients.

Impella 5.5: A Systematic Review of the Current Literature.

Impella 5.5 (Abiomed, Danvers, MA, USA) is a temporary mechanical circulatory support device used for patients in cardiogenic shock. This review provides a comprehensive overview of the device's clinical effectiveness, safety profile, patient outcomes, and relevant procedural considerations. We conducted a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using the PubMed/MEDLINE database. The search query included articles available from October 6, 2022, through January 13, 2023. Our initial search identified 75 studies. All records were screened by 2 independent reviewers using the Covidence software for adherence to our inclusion criteria, and 8 retrospective cohort studies were identified as appropriate for inclusion. Across the included studies, the sample size ranged from 4 to 275, with predominantly male cohorts. Indications for Impella support varied, and the duration of support ranged from 9.8 to 70 days. Overall, Impella support appeared to be associated with favorable survival rates and manageable complications in various patient populations. Complications associated with Impella use included bleeding, stroke, and device malfunctions. Two studies compared prolonged and Food and Drug Administration-approved Impella support, showing similar outcomes and adverse events. Impella 5.5 continues to be an attractive option for bridging patients to definitive therapy. Survival during and after Impella 5.5 was favorable for patients regardless of initial indication. However, device use was associated with several important complications, which calls for judicious use and a precontemplated exit strategy. Limitations of this literature review include biases inherent to the retrospective studies included, such as selection and publication bias.

B - 74 The Effect of Perimenopause on Women’s Executive Functioning: a Systematic Review

Abstract Objective This systematic review aims to examine the existing literature on the impact of perimenopause/menopause on cognitive function, identify overlaps with adult ADHD symptoms, and provide evidence-based recommendations for distinguishing between the two conditions, guiding clinical practice and identifying considerations for selection of neuropsychological testing with this population. Data Selection A search of electronic databases, including PubMed, PsycINFO, and MEDLINE, will be conducted to identify relevant peer-reviewed studies published between 2000 and 2024. Studies examining cognitive changes during perimenopause/menopause, diagnostic challenges in distinguishing perimenopause/menopause-related cognitive decline from adult ADHD symptoms, and interventions for accurate assessment and management will be included. Data extraction and synthesis will be performed following PRISMA guidelines. Data Synthesis The analysis will review a range of literature on the cognitive changes associated with perimenopause/menopause, including deficits in attention, memory, and executive function, which may overlap with symptoms of adult ADHD. Attention will be paid to looking for distinct patterns of cognitive impairment and hormonal profiles between perimenopause/menopause-related cognitive decline and adult ADHD. Various screening tools and neuropsychological assessments will be examined for their utility in differentiating between the two conditions. Conclusions The current systematic review, with its focus on the impact of menopause and perimenopause on women’s cognitive functioning, particularly executive functioning, has the potential to significantly advance our understanding in this area. It will be able to provide clinical recommendations and considerations for individuals administering and interpreting neuropsychological testing with this population. Recommendations for best practices will be proposed, potentially revolutionizing the way we approach and manage these conditions.

Harnessing machine learning technique for improved detection and classification of heart failure

Artificial Intelligence (AI) performs exercises recently performed by people utilizing AI and profound learning, Right now simulated intelligence is changing cardiovascular medication identifying problems, therapeutics, risk appraisals, clinical consideration, and medication advancement. The death rates in medical clinics for patients with cardiovascular breakdown display a scope of 10.6% at 30 days, 23.0% at 1 year, and 43.3% at 5 years. Cardiovascular breakdown (HF) patients need customized restorative and careful treatment, in this way early finding is pivotal. The 85% precise Brain Organization (NN) archetypal made this conceivable. By applying our calculation, simulated intelligence can assist with examining crude cardiovascular imaging information from echocardiography, processed tomography, and heart attractive reverberation imaging and EKG accounts. Unpleasant Sets (RS) and strategic relapse (LR) choice trees to analyze congestive cardiovascular breakdown and computerized reasoning to identify future impermanence and destabilization incidents have further developed cardiac illness results. This examination inspects how computer- based intelligence has changed pretty much every area of HF determination, avoidance, and the executives

Antirheumatic Drugs : Mechanisms, Therapeutic Efficacy, and Clinical Considerations in Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes inflammation and damage to joints and other tissues. Antirheumatic drugs, including disease-modifying antirheumatic drugs (DMARDs), biologic agents, and non-steroidal anti-inflammatory drugs (NSAIDs), play a crucial role in the treatment and management of RA. This review examines the mechanisms of action, clinical efficacy, and adverse effects of these drugs. We also explore emerging therapies and future directions for RA management, highlighting the importance of individualized treatment strategies to improve patient outcomes while minimizing potential risks.

Whole-Body Multiparametric PET in Clinical Oncology: Current Status, Challenges, and Opportunities.

The interpretation of clinical oncologic PET studies has historically used static reconstructions based on SUVs. SUVs and SUV-based images have important limitations, including dependence on uptake times and reduced conspicuity of tracer-avid lesions in organs with high background uptake. The acquisition of dynamic PET images enables additional PET reconstructions via Patlak modeling, which assumes that a tracer is irreversibly trapped by tissues of interest. The resulting multiparametric PET images capture a tracer's net trapping rate (Ki) and apparent volume of distribution (VD), separating the contributions of bound and free tracer fractions to the PET signal captured in the SUV. Potential benefits of multiparametric PET include higher quantitative stability, superior lesion conspicuity, and greater accuracy for differentiating malignant and benign lesions. However, the imaging protocols necessary for multiparametric PET are inherently more complex and time-intensive, despite the recent introduction of automated or semiautomated scanner-based reconstruction packages. In this Review, we examine the current state of multiparametric PET in whole-body oncologic imaging. We summarize the Patlak methodology and relevant tracer kinetics, discuss clinical workflows and protocol considerations, and highlight clinical challenges and opportunities. We aim to help oncologic imagers make informed decisions about whether to implement multiparametric PET in their clinical practices.

Metabolic benefits afforded by estradiol and testosterone in both sexes: clinical considerations.

Testosterone (T) and 17β-estradiol (E2) are produced in male and female humans and are potent metabolic regulators in both sexes. When E2 and T production stops or decreases during aging, metabolic dysfunction develops and promotes degenerative metabolic and vascular disease. Here, we discuss the shared benefits afforded by E2 and T for metabolic function human females and males. In females, E2 is central to bone and vascular health, subcutaneous adipose tissue distribution, skeletal muscle insulin sensitivity, antiinflammatory immune function, and mitochondrial health. However, T also plays a role in female skeletal, vascular, and metabolic health. In males, T's conversion to E2 is fundamental to bone and vascular health, as well as prevention of excess visceral adiposity and the promotion of insulin sensitivity via activation of the estrogen receptors. However, T and its metabolite dihydrotestosterone also prevent excess visceral adiposity and promote skeletal muscle growth and insulin sensitivity via activation of the androgen receptor. In conclusion, T and E2 are produced in both sexes at sex-specific concentrations and provide similar and potent metabolic benefits. Optimizing levels of both hormones may be beneficial to protect patients from cardiometabolic disease and frailty during aging, which requires further study.

Molecular profiling METex14+ non-small cell lung cancer (NSCLC): Impact of histology

ObjectivesMET exon 14 skipping alterations (METex14+) represent a heterogeneous subgroup of non-small cell lung cancer (NSCLC) with distinct biological and genomic features. We characterized this heterogeneity in a large cohort, integrating genomic and transcriptomic profiling with clinical outcomes, to elucidate the histologic and molecular traits and survival patterns of METex14+ NSCLC. Materials and methodsNSCLC tissue samples (n = 28,739) underwent DNA-based next-generation sequencing (592 genes, NextSeq) or whole-exome sequencing (NovaSeq), RNA-sequencing including whole transcriptome sequencing (WTS, NovaSeq), and PD-L1 IHC (Dako 22C3) at Caris Life Sciences. Immune cell fractions were estimated from bulk RNA sequencing (quanTIseq). Real-world survival data (mOS) was calculated from insurance claims. Statistical analyses employed Chi-square, Fisher’s exact, or Mann-Whitney U and log-rank tests and were corrected for hypothesis testing where applicable. ResultsA total of 711 METex14+ cases were detected. Of 575 cases of defined histology, 77 (13.6 %) were squamous (Sq), 474 (82.3 %) were nSq (non-squamous), and 24 (4.1 %) were adenosquamous. Mutations in POT1 and BRCA2 were enriched, and amplifications in MDM2, HMGA2, CDK4, and MET were common in METex14+ tumors. TMB-high and TP53 mutated tumors were reduced in METex14+ independent of histology. KEAP1 (2.1 vs 14.7 %) and STK11 mutations (0.8 vs 17.1 %) were reduced only in METex14+ nSq (vs METex14+ Sq, q < 0.05). While the prevalence of PD-L1 high tumors was enriched in METex14+ independent of histology, T-cell inflamed tumors were enriched only in nSq METex14+. B-cells and CD8+ T-cells (1.07–1.43-fold) were enriched in nSq METex14+, and dendritic cells (0.32 fold) were reduced only in METex14+ Sq. METex14+ tumors had a modest improvement in mOS compared to METex14- tumors (mOS = 22.9 m vs 18.6 m, HR = 0.914, p = 0.04). Moreover, METex14+ tumors who received immunotherapy (IO) had a modest improvement in survival (mOS = 27.5 m vs 21.8 m; HR = 0.803, p = 0.03) compared to those who did not receive IO. METex14+ nSq tumors were associated with improved mOS compared to METex14+ Sq tumors (mOS = 27.7 vs 8.9 m, HR = 0.493, p < 0.0001). ConclusionMETex14+ alterations are a heterogeneous subgroup of NSCLC. Our analysis reveals that METex14+ nSq exhibit improved survival compared to METex14+ Sq. The distinct genomic and transcriptomic variations across histologies warrant clinical consideration.

Evaluation of efficacy of cholecalciferol and silymarin in improving lower urinary tract symptoms of benign prostatic hyperplasia: A double-blind, randomized, controlled trial.

Benign prostatic hyperplasia (BPH) mainly leads to lower urinary tract symptoms (LUTS) in aging men. The present study investigates the role of cholecalciferol, Silymarin, and their combined administration in patients with BPH suffering from LUTS. This double-blind, randomized, controlled trial enrolled 80 participants (50-80 years) diagnosed with BPH, from March 2019 to March 2020. Based on serum 25-(OH) vitamin D levels we formed subgroups, each receiving specific interventions. Measurements of International Prostate Symptom Score (IPSS), Maximal Urinary Flow Rate (Q-max), Prostate Volume (PV), Post-Void Residual (PVR), and Prostate-Specific Antigen (PSA) were recorded at baseline and following 3 months of follow-up. Participants with serum concentration of 25-(OH) vitamin D below 20 ng/ml simultaneously received cholecalciferol and Silymarin that significantly improved IPSS, irritation, obstruction, PV, and PVR. In those with concentrations ⩾20 ng/ml, a single use of Silymarin significantly reduced IPSS, irritation, obstruction, and PVR. Adjustment of confounding variables revealed independent and significant effects of both cholecalciferol and Silymarin on PVR, IPSS, and obstruction. Cholecalciferol also improved irritation, while Silymarin reduced prostate volume. These findings highlight potential therapeutic benefits for BPH-associated LUTS, encouraging further exploration and clinical consideration. In this investigation, combination therapy with cholecalciferol at 50,000 IU/w for 8 weeks and Silymarin at a dosage of 480 mg for 3 months resulted in a notable improvement in the IPSS score, PV, and PVR, as well as both irritative and obstructive symptoms. However, the total PSA and free PSA amounts did not reach a significant difference.

Vascularized Interpositional Connective Tissue Graft: An Alternative in Esthetically Demanding Regions. A Case Report and Literature Review

Objective: This case report aims to showcase the utilization of a vascularized interpositional pedicle connective tissue graft and a Maryland bridge as an alternative treatment to bone graft and implant placement. Clinical considerations: The case report illustrated the success of a well-thought-out alternative treatment plan to implant placement, achieving esthetically pleasing and functional results. Conclusion: The vascularized interpositional pedicle connective tissue graft can serve as a less invasive alternative that achieves an esthetically pleasing outcome.