Pursuing Clinical Predictors and Biomarkers for Progression in ILD: Analysis of the Pulmonary Fibrosis Foundation (PFF) Registry.

INTRODUCTION: Pulmonary fibrosis is a characteristic of various interstitial lung diseases (ILDs) with differing etiologies. Clinical trials in progressive pulmonary fibrosis (PPF) enroll patients based on previously described clinical criteria for past progression, which include a clinical practice guideline for PPF classification and inclusion criteria from the INBUILD trial. In this study, we compared the ability of past FVC (forced vital capacity) progression and baseline biomarker levels to predict future progression in a cohort of patients from the PFF Patient Registry. METHODS: Biomarkers previously associated with pathobiology and/or progression in pulmonary fibrosis were selected to reflect cellular senescence (telomere length), pulmonary epithelium (SP-D, RAGE), myeloid activation (CXCL13, YKL40, CCL18, OPN) and fibroblast activation (POSTN, COMP, PROC3). RESULTS: PFF or INBUILD-like clinical criteria was used to separate patients into past progressor and non-past progressor groups, and neither clinical criterion appeared to enrich for patients with greater future lung function decline. All baseline biomarkers measured were differentially expressed in patient groups compared to healthy controls. Baseline levels of SP-D and POSTN showed the highest correlations with FVC slope over one year, though correlations were low. CONCLUSIONS: Our findings provide further evidence that prior decline in lung function may not predict future disease progression for ILD patients, and elevate the need for molecular definitions of a progressive phenotype. Across ILD subtypes, certain shared pathobiologies may be present based on the molecular profile of certain biomarker groups observed. In particular, SP-D may be a common marker of pulmonary injury and future lung function decline across ILDs.

The mental health burden of food allergies: Insights from patients and their caregivers from the Food Allergy Research & Education (FARE) Patient Registry.

Background: Food allergies impose a large psychosocial burden, including mental, emotional, and social aspects, on both patients and their caregivers. Patients, caregivers, and their families often experience anxiety, isolation, and fear around food allergies. Objective: To assess the real-world mental health burden of food allergies, using the Food Allergy Research & Education (FARE) Patient Registry (NCT04653324). Methods: Self-reported data from patients with food allergies, and their caregivers, were analyzed from the FARE Food Allergy History and Mental Health Concerns surveys. Odds ratios were also calculated as a measure of association between patient food allergy characteristics and the likelihood of having mental health concerns or a formal mental health diagnosis. Results: The FARE Patient Registry included 1680 patients/caregivers. Anxiety (54%) and panic (32%) were the most common emotions that patients reported as a result of eating the food that produced an allergic reaction. About two-thirds of patients reported mental health concerns related to food allergies (62%), including anxiety after an allergic reaction, anxiety about living with food allergies, and concerns about food avoidance. Caregivers also experienced fear for the safety of their children, and often sought mental health care to cope with worry related to caring for patients with food allergies. The likelihood of having food allergy-related mental health concerns was increased for patients experiencing more than 1 reaction per year (OR 1.68-1.90) and was lowered for patients having a formal mental health diagnosis (OR 0.43). Caregivers filling out the FARE survey for pediatric patients (OR 4.03) and experiencing food allergy-related mental health concerns (OR 2.36) were both significant predictors for having a formal mental health diagnosis. Conclusion: Our study highlights a continuing unmet need for mental health screening and support as part of the management of patients with food allergies.

The clinical burden of food allergies: Insights from the Food Allergy Research & Education (FARE) Patient Registry.

Background: Food allergies are serious and potentially life-threatening, and often place a large burden on patients and their caregivers, including impacts on quality of life. Objective: To assess the real-world patient burden of food allergies, using self-reported data available from the Food Allergy Research & Education (FARE) Patient Registry (NCT04653324). Methods: The FARE Patient Registry is voluntary and captures real-world experiences of adults and pediatric patients in the United States, and their caregivers, through a series of surveys assessing patient health and experiences with food allergies. Self-reported data were descriptively analyzed. Results: The FARE study cohort included 5587 patients with food allergies; 82% had multiple food allergies and 62% were aged <18 years. About half of the patients were first diagnosed by an allergist/immunologist (53%), most commonly with a skin prick test (71%) or a serum immunoglobulin E test (62%). This analysis found that food allergies (most commonly peanut [66%], tree nuts [61%], egg [43%], and milk [37%]) impart a large clinical burden on patients, many of whom experience food-related allergic reactions and comorbidities. Many patients experienced >1 food-related allergic reaction per year (42%), with 46% experiencing food-induced anaphylaxis. Half of all food-related allergic reactions occurred at home. Accidental exposures to food allergens were experienced by 77% of patients. The most common allergic comorbidities reported by patients with food allergies were atopic dermatitis (48%), asthma (46%), and allergic rhinitis (39%). The clinical burden of food allergies were found to be greater in patients with multiple food allergies, and different for adults versus pediatric patients. Conclusion: This is the first study to assess patient experience and disease burden information from patients contributing to the FARE Patient Registry, thus providing a unique insight into the lives of patients in the United States with food allergies. These insights may assist clinicians and other public health stakeholders in the management of patients with food allergies.

Evaluation and model to achieve sex parity in cataract surgical coverage in Theni district, India.

BACKGROUND/AIMS: To propose an approach to determine the target ratio of cataract surgical rates (CSRs) of female to male subpopulations to increase sex parity in cataract surgical coverage (CSC), based on the sex gap in cataract burden and incidence, and demonstrate its application to Theni district, India. METHODS: A population-based longitudinal study between January 2016 and April 2018. We recruited 24 327 participants using random cluster sampling. We conducted detailed eye examinations of 7087 participants aged ≥40 years (4098 females, 2989 males). We fit exponential models to the age-specific and sex-specific cataract burden and estimated annual incidence rates. We developed a spreadsheet-based planning tool to compute the target CSR ratio of female to male subpopulations. RESULTS: Among those aged ≥40 years, cataract burden was 21.4% for females and 17.5% for males (p<0.05). CSC was 73.9% for females versus 78.6% for males (p<0.05), with an effective CSC of 52.6% for females versus 57.6% for males (p<0.05). Treating only incident cataracts each year requires a target CSR ratio of female to male subpopulations of 1.30, while addressing in addition 10% of the coverage backlog for females and 5% for males requires a target CSR ratio of 1.48. CONCLUSIONS: The female population in Theni district, as in many low-income and middle-income countries, bears a higher cataract burden and lower CSC. To enhance sex parity in coverage, both the higher number of annual incident cataracts and the larger backlog in females will need to be addressed.

Clinical diagnosis of viral hepatitis: Current status and future strategies.

Viral hepatitis (VH) is a significant public health issue with tremendous potential to aggravate into chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Recent decade has witnessed remarkable uprising in the drug development and effective treatment of VH. An upsurge is seen in identification of antiviral therapies with low rates of viral resistance, the improvement of Hepatitis B Virus (HBV) vaccination and the development of direct-acting antivirals for Hepatitis C Virus (HCV). But unfortunately, the "2030 worldwide eradication" objective of World Health Organization (WHO) is still unmet. It can be largely attributed to the deficit faced by the healthcare system concerning screening and diagnosis. A timely, accurate and comprehensive screening; encompassing maximum population coverage is essential to combat this disease. However, advancements in VH diagnostics remain inadequate and with a marginal use in routine practice. This paper deliberates upon the lacunae in traditional and prevailing diagnostic methodology of viral hepatitis, especially their inadequacy in meeting the unique situations prevailing low- and middle-income countries (LMIC).

Idiopathic Pulmonary Fibrosis: Where do We Stand and How Far to Go?

Idiopathic pulmonary fibrosis is a progressive and incurable lung disease characterized by collagen deposition, alveolar inflammation, fibroblast proliferation, and the destruction of lung tissue structures. It is a rare yet severe condition with a high mortality rate, typically leading to death within 3-5 years of diagnosis. The clinical presentation of idiopathic pulmonary fibrosis (IPF) involves a gradual and substantial loss of lung function, ultimately resulting in respiratory failure. Despite more than half a century of intensive research, the origin of IPF remains a mystery. Despite its unknown etiology, several genetic and non-genetic factors have been linked to IPF. Recent significant advancements have been made in the field of IPF diagnosis and treatment. Two oral small-molecule drugs, pirfenidone and nintedanib, have recently gained approval for the treatment of IPF. Pirfenidone exhibits antifibrotic, antioxidant, and anti-inflammatory properties, while nintedanib is a tyrosine kinase inhibitor with selectivity for vascular endothelial growth factor (VEGF) receptors, prostaglandin F (PGF) receptors, and fibroblast growth factor (FGF) receptors. Both of these compounds are capable of slowing down the progression of the disease with an acceptable safety profile. This review provides a brief introduction, historical background, epidemiological insights, and an exploration of various environmental risk factors that may influence the lung microenvironment and contribute to the advancement of IPF. The review also delves into the diagnosis, signaling pathways, and ongoing clinical trials worldwide. A thorough review of the literature was conducted using PubMed and Google Scholar to gather information on various aspects of IPF. Numerous potential drugs are currently under investigation in clinical trials, and the completion of this process is crucial to the ultimate goal of finding a cure for IPF patients. The investigation of the role of genes, surfactant proteins, infectious agents, biomarkers, and epigenetic changes holds the promise of offering earlier and more accurate understanding and diagnosis of IPF. This information could be instrumental in the development of new therapeutic approaches for treating IPF and is expected to be of great interest to researchers.

Comparison of cataract surgery outcomes between a secondary and a tertiary eye hospital in Tamil Nadu, India.

PURPOSE: To examine the difference in post-operative visual outcomes of cataract surgeries between a tertiary and secondary centre at Aravind Eye Hospitals in Tamil Nadu, India. METHODS: Our retrospective cross-sectional study analysed cataract surgeries at a secondary centre and its associated tertiary centre in 2021. Our main outcome measures were postoperative best corrected visual acuity (BCVA), spherical equivalent, and intraoperative and postoperative complications. Two-sample proportion tests and logistic regression analyses were performed. RESULTS: The analysis of 32,302 cataract surgeries in 2021 of which 4357 were performed at the secondary centre and 27,945 were performed at the tertiary centre showed that the tertiary centre operated on more advanced cataract condition (p < 0.001). Intraoperative (p < 0.001) and post-operative complication rates (p < 0.001) were higher in the tertiary centre. The odds of effective outcomes (BCVA > = 6/12) controlling for all covariates are poorer (p < 0.0001) in the tertiary centre for both phacoemulsification (phaco) and manual small incision cataract surgeries (MSICS). CONCLUSION: World Health Organization recommendations for the effective outcome of cataract surgery are met by both the tertiary and secondary centres, but the odds of effective outcomes in the tertiary centre was lower after adjusting for all known factors. Further investigations of the causes of poor vision in both phaco and MSICS in the tertiary centre are needed to improve the situation.

Intraoperative neuromonitoring predicts postoperative deficits in severe pediatric spinal deformity patients.

PURPOSE: To evaluate intraoperative monitoring (IOM) alerts and neurologic deficits during severe pediatric spinal deformity surgery. METHODS: Patients with a minimum Cobb angle of 100° in any plane or a scheduled vertebral column resection (VCR) with minimum 2-year follow-up were prospectively evaluated (n = 243). Preoperative, immediate postoperative, and 2-year postoperative neurologic status were reported. Radiographic data included preoperative and 2-year postoperative coronal and sagittal Cobb angles and deformity angular ratios (DAR). IOM alert type and triggering event were recorded. SRS-22r scores were collected preoperatively and 2-years postoperatively. RESULTS: IOM alerts occurred in 37% of procedures with three-column osteotomy (n = 36) and correction maneuver (n = 32) as most common triggering events. Patients with IOM alerts had greater maximum kyphosis (101.4° vs. 87.5°) and sagittal DAR (16.8 vs. 12.7) (p < 0.01). Multivariate regression demonstrated that sagittal DAR independently predicted IOM alerts (OR 1.05, 95% CI 1.02-1.08) with moderate sensitivity (60.2%) and specificity (64.8%) using a threshold value of 14.3 (p < 0.01). IOM alerts occurred more frequently in procedures with new postoperative neurologic deficits (17/24), and alerts with both SSEP and TCeMEP signals were associated with new postoperative deficits (p < 0.01). Most patients with new deficits experienced resolution at 2 years (16/20) and had equivalent postoperative SRS-22r scores. However, patients with persistent deficits had worse SRS-22r total score (3.8 vs. 4.2), self-image subscore (3.5 vs. 4.1), and function subscore (3.8 vs. 4.3) (p ≤ 0.04). CONCLUSION: Multimodal IOM alerts are associated with sagittal kyphosis, and predict postoperative neurologic deficits. Most patients with new deficits experience resolution of their symptoms and have equivalent 2-year outcomes. LEVEL OF EVIDENCE: II.

Identification of naturally occurring compounds as alternatives to radiation therapy for treatment of small cell lung cancer.

Radiation resistance is one of the major problems in the treatment of small cell lung cancer (SCLC). Most of these patients are given radiation as first-line treatment and it was observed that the initial response in these patients is very good. However, they show relapse in a few months which is also associated with resistance to treatment. Thus, targeting the mechanism by which these cells develop resistance could be an important strategy to improve the survival chances of these patients. From the RNA-Seq data analysis, it was identified that CHEK1 gene was overexpressed. Chk1 protein which is encoded by the CHEK1 gene is an important protein that is involved in radiation resistance in SCLC. It is known to favour the cells to deal with replicative stress. CHEK1 is the major cause for developing radiation resistance in SCLC. Thus, natural compounds that could also serve as potential inhibitors for Chk1 were explored. Accordingly; the compounds were screened based on ADME, docking and MM-GBSA scores. MD simulations were performed for the selected protein-ligand complexes and the results were compared to the co-crystallised ligand, 3-(indol-2-yl)indazole. The results showed that compound INC000033832986 could be a natural alternative to the commercial ligand for the prevention of SCLC.Communicated by Ramaswamy H. Sarma.

Cataract surgery workload estimates in Theni district, India.

BACKGROUND/AIMS: To estimate the annual cataract surgery workload in Theni district, Tamil Nadu, India based on current utilisation of cataract services, prevalence of blindness and vision impairment (VI), and cataract burden-reduction goals. METHODS: We conducted a population-based longitudinal study between January 2016 and April 2018. We recruited 24 327 participants based on a random cluster sampling method; 7127 participants were ≥40 years. During the year following initial enrolment, we tracked utilisation of eye care services; and at the end of the 1-year period, we conducted a detailed eye examination of participants age ≥40. RESULTS: In the sample age ≥40 years, 13.0% had a visually significant cataract, and 17.8% had prior cataract surgery in at least one eye. The prevalence of cataract blindness based on presenting visual acuity in the better eye (PVABE)<3/60 was 0.34% and VI (PVABE<6/12) was 9.92%. 3.10% of the study population had obtained cataract surgery during 1 year, resulting in a cataract surgical rate of 9085. We estimated the effective cataract surgical coverage (eCSC) to be 54.5% and the CSC to be 75.7%, implying a sizeable quality gap. Prevalence, utilisation and coverage varied by age and gender. We estimated that a goal of eliminating the backlog of VI (PVABE<6/12) in 5 years would increase the annual cataract surgery workload by 11.5% from the current level. CONCLUSIONS: Our estimates of cataract surgery workloads under different scenarios can provide a useful input into planning of eye health services in Theni district.

Evaluation of surgical fixation methods for the implantation of melt electrowriting-reinforced hyaluronic acid hydrogel composites in porcine cartilage defects.

The surgical repair of articular cartilage remains an ongoing challenge in orthopedics. Tissue engineering is a promising approach to treat cartilage defects; however, scaffolds must (i) possess the requisite material properties to support neocartilage formation, (ii) exhibit sufficient mechanical integrity for handling during implantation, and (iii) be reliably fixed within cartilage defects during surgery. In this study, we demonstrate the reinforcement of soft norbornene-modified hyaluronic acid (NorHA) hydrogels via the melt electrowriting (MEW) of polycaprolactone to fabricate composite scaffolds that support encapsulated porcine mesenchymal stromal cell (pMSC, three donors) chondrogenesis and cartilage formation and exhibit mechanical properties suitable for handling during implantation. Thereafter, acellular MEW-NorHA composites or MEW-NorHA composites with encapsulated pMSCs and precultured for 28 days were implanted in full-thickness cartilage defects in porcine knees using either bioresorbable pins or fibrin glue to assess surgical fixation methods. Fixation of composites with either biodegradable pins or fibrin glue ensured implant retention in most cases (80%); however, defects treated with pinned composites exhibited more subchondral bone remodeling and inferior cartilage repair, as evidenced by micro-computed tomography (micro-CT) and safranin O/fast green staining, respectively, when compared to defects treated with glued composites. Interestingly, no differences in repair tissue were observed between acellular and cellularized implants. Additional work is required to assess the full potential of these scaffolds for cartilage repair. However, these results suggest that future approaches for cartilage repair with MEW-reinforced hydrogels should be carefully evaluated with regard to their fixation approach for construct retention and surrounding cartilage tissue damage.

Use of multiple rods and proximal junctional kyphosis in adult spinal deformity surgery.

OBJECTIVE: Multiple rods are utilized in adult spinal deformity (ASD) surgery to increase construct stiffness. However, the impact of multiple rods on proximal junctional kyphosis (PJK) is not well established. This study aimed to investigate the impact of multiple rods on PJK incidence in ASD patients. METHODS: ASD patients from a prospective multicenter database with a minimum follow-up of 1 year were retrospectively reviewed. Clinical and radiographic data were collected preoperatively, at 6 weeks postoperatively, at 6 months postoperatively, at 1 year postoperatively, and at every subsequent year postoperatively. PJK was defined as a kyphotic increase of > 10° in the Cobb angle from the upper instrumented vertebra (UIV) to UIV+2 as compared with preoperative values. Demographic data, radiographic parameters, and PJK incidence were compared between the multirod and dual-rod patient cohorts. PJK-free survival analysis was performed using Cox regression to control for demographic characteristics, comorbidities, level of fusion, and radiographic parameters. RESULTS: Overall, 307/1300 (23.62%) cases utilized multiple rods. Cases with multiple rods were more likely to be revisions (68.4% vs 46.5%, p < 0.001), to be posterior only (80.7% vs 61.5%, p < 0.001), involve more levels of fusion (mean 11.73 vs 10.60, p < 0.001), and include 3-column osteotomy (42.9% vs 17.1%, p < 0.001). Patients with multiple rods also had greater preoperative pelvic retroversion (mean pelvic tilt 27.95° vs 23.58°, p < 0.001), greater thoracolumbar junction kyphosis (-15.9° vs -11.9°, p = 0.001), and more severe sagittal malalignment (C7-S1 sagittal vertical axis 99.76 mm vs 62.23 mm, p < 0.001), all of which corrected postoperatively. Patients with multiple rods had similar incidence rates of PJK (58.6% vs 58.1%) and revision surgery (13.0% vs 17.7%). The PJK-free survival analysis demonstrated equivalent PJK-free survival durations among the patients with multiple rods (HR 0.889, 95% CI 0.745-1.062, p = 0.195) after controlling for demographic and radiographic parameters. Further stratification based on implant metal type demonstrated noninferior PJK incidence rates with multiple rods in the titanium (57.1% vs 54.6%, p = 0.858), cobalt chrome (60.5% vs 58.7%, p = 0.646), and stainless steel (20% vs 63.7%, p = 0.008) cohorts. CONCLUSIONS: Multirod constructs for ASD are most frequently utilized in revision, long-level reconstructions with 3-column osteotomy. The use of multiple rods in ASD surgery does not result in an increased incidence of PJK and is not affected by rod metal type.

Impact of practicing internal benchmarking on continuous improvement of cataract surgery outcomes: a retrospective observational study at Aravind Eye Hospitals, India.

OBJECTIVE: We aim to assess the effectiveness of a cataract surgery outcome monitoring tool used for continuous quality improvement. The objectives are to study: (1) the quality parameters, (2) the monitoring process followed and (3) the impact on outcomes. DESIGN AND PROCEDURES: In this retrospective observational study we evaluated a quality improvement (QI) method which has been practiced at the focal institution since 2012: internal benchmarking of cataract surgery outcomes (CATQA). We evaluated quality parameters, procedures followed and clinical outcomes. We created tables and line charts to examine trends in key outcomes. SETTING: Aravind Eye Care System, India. PARTICIPANTS: Phacoemulsification surgeries performed on 718 120 eyes at 10 centres (five tertiary and five secondary eye centres) from 2012 to 2020 were included. INTERVENTIONS: An internal benchmarking of surgery outcome parameters, to assess variations among the hospitals and compare with the best hospital. OUTCOME MEASURES: Intraoperative complications, unaided visual acuity (VA) at postoperative follow-up visit and residual postoperative refractive error (within ±0.5D). RESULTS: Over the study period the intraoperative complication rate decreased from 1.2% to 0.6%, surgeries with uncorrected VA of 6/12 or better increased from 80.8% to 89.8%, and surgeries with postoperative refractive error within ±0.5D increased from 76.3% to 87.3%. Variability in outcome measures across hospitals declined. Additionally, benchmarking was associated with improvements in facilities, protocols and processes. CONCLUSION: Internal benchmarking was found to be an effective QI method that enabled the practice of evidence-based management and allowed for harnessing the available information. Continuous improvement in clinical outcomes requires systematic and regular review of results, identifying gaps between hospitals, comparisons with the best hospital and implementing lessons learnt from peers.

Perioperative Complications and Health-related Quality of Life Outcomes in Severe Pediatric Spinal Deformity.

STUDY DESIGN: Prospective multicenter cohort study. OBJECTIVE: To evaluate perioperative complications and mid-term outcomes for severe pediatric spinal deformity. SUMMARY OF BACKGROUND DATA: Few studies have evaluated the impact of complications on health-related quality of life (HRQoL) outcomes in severe pediatric spinal deformity. METHODS: Patients from a prospective, multicenter database with severe pediatric spinal deformity (minimum of 100 degree curve in any plane or planned vertebral column resection (VCR)) with a minimum of 2-years follow-up were evaluated (n=231). SRS-22r scores were collected preoperatively and at 2-years postoperatively. Complications were categorized as intraoperative, early postoperative (within 90-days of surgery), major, or minor. Perioperative complication rate was evaluated between patients with and without VCR. Additionally, SRS-22r scores were compared between patients with and without complications. RESULTS: Perioperative complications occurred in 135 (58%) patients, and major complications occurred in 53 (23%) patients. Patients that underwent VCR had a higher incidence of early postoperative complications than patients without VCR (28.9% vs. 16.2%, P =0.02). Complications resolved in 126/135 (93.3%) patients with a mean time to resolution of 91.63 days. Unresolved major complications included motor deficit (n=4), spinal cord deficit (n=1), nerve root deficit (n=1), compartment syndrome (n=1), and motor weakness due to recurrent intradural tumor (n=1). Patients with complications, major complications, or multiple complications had equivalent postoperative SRS-22r scores. Patients with motor deficits had lower postoperative satisfaction subscore (4.32 vs. 4.51, P =0.03), but patients with resolved motor deficits had equivalent postoperative scores in all domains. Patients with unresolved complications had lower postoperative satisfaction subscore (3.94 vs. 4.47, P =0.03) and less postoperative improvement in self-image subscore (0.64 vs. 1.42, P =0.03) as compared to patients with resolved complications. CONCLUSION: Most perioperative complications for severe pediatric spinal deformity resolve within 2-years postoperatively and do not result in adverse HRQoL outcomes. However, patients with unresolved complications have decreased HRQoL outcomes.

Form and Function: Technique for Free Functional Gracilis Harvest With Greater Saphenous Vein for Large Skin Paddle.

Free functional gracilis transfer is a technique for restoration of upper extremity function following brachial plexus injury, as well as muscle loss from traumatic, oncologic, and congenital causes. However, when used for the latter applications, a functional muscle as well as large skin paddle can be required. Historically, skin paddle size was limited by venous outflow of the gracilis flap, using 1 or 2 venae comitantes, and large unreliable skin paddles resulting in partial necrosis. Therefore, to restore form and function, we herein present a technique of free functional gracilis muscle harvest with inclusion of adjacent greater saphenous vein for inclusion of a large skin paddle with 2 venous drainage systems.

E-cigarette use and prevalence of lung diseases among the U.S. population: a NHANES survey.

The primary aim of this study was to evaluate epidemiological characteristics and prevalence of lung disease among e-cigarettes users in the United States. A population-based, cross-sectional survey was performed using the National Health and Nutrition Examination Survey (NHANES) of 2015-2018. Adults using e-cigarettes (SMQ900), traditional smoking (SMQ020: > 100 cigarettes in lifetime or SMQ040: current cigarettes use), and dual smoking (e-cigarettes and traditional smoking) were identified and compared in their sociodemographic characteristics and prevalence of lung diseases (Asthma: MCQ010 and COPD: MCQ160O). We used the chi square test (categorical variables) and Mann-Whitney test and unpaired-student t test (continuous variables). p-value <0.05 was used as a reference. We excluded respondents <18 years and missing data on demographics and outcomes. Out of 178,157 respondents, 7745 (4.35%), 48,570 (27.26%), and 23,444 (13.16%) were e-cigarette smokers, traditional smokers, and dual smokers, respectively. Overall prevalence of asthma was 15.16% and COPD was 4.26%. E-cigarette smokers were younger in comparison to traditional smokers (median: 25 years vs 62 years; p < 0.0001). In females (49.34% vs 37.97%), Mexican (19.82% vs 13.35%), annual household income above $100,000 (23.97% vs 15.56%), prevalence of e-cigarette smoking was higher in comparison to traditional smoking (p < 0.0001). The prevalence of COPD was higher among dual smokers in comparison to e-cigarette and traditional smoking (10.14% vs 0.25% vs 8.11%; p < 0.0001). Prevalence of asthma was higher among dual and e-cigarette smokers in comparison with traditional smokers and non-smokers (22.44% vs 21.10% vs 14.46% vs 13.30%; p < 0.0001). Median age (Q1-Q3) was lower at which asthma (7 years (4-12) vs 25 years (8-50)) was diagnosed first among e-cigarettes smokers in comparison with traditional smokers. In a mixed effect multivariable logistic regression analysis, we found higher odds of asthma among e-cigarette users in comparison with non-smokers (Odds ratio (OR): 1.47; 95% Confidence Interval (CI): 1.21-1.78; p = 0.0001). Chronic Obstructive Pulmonary Disease (COPD) respondents were also associated with 11.28 higher odds of e-cigarette utilization (Oddsratio (OR): 11.28; 95% Confidence Interval (CI): 5.59-22.72; p < 0.0001). We conclude the higher prevalence of e-cigarette users is seen among the younger population, female, Mexican race, and annual income above $100,000 in comparison to traditional smokers. Chronic Obstructive Pulmonary Disease (COPD) and asthma were both more prevalent in dual smokers. As asthma was more prevalent and diagnosed at an early age in e-cigarette smokers, more prospective studies are needed to understand the effects of e-cigarette among the population at risk to mitigate the sudden rise in utilization and to create awareness.

The repertoire of mutational signatures in tobacco- and non-tobacco-induced oral cancer.

The use of tobacco products is one of the established contributors toward the development and spread of oral cancer. Additionally, recent research has indicated oral microbiome, infections with Human papilloma virus (HPV), Epstein-Barr virus (EBV), Candida as significant contributing factors to this disease along with lifestyle habits. Deregulation of cellular pathways envisaging metabolism, transcription, translation, and epigenetics caused by these risk factors either individually or in unison is manifold, resulting in the increased risk of oral cancer. Globally, this cancer continues to exist as one of the major causes of cancer-related mortalities; the numbers in the developing South Asian countries clearly indicate yearly escalation. This review encompasses the variety of genetic modifications, including adduct formation, mutation (duplication, deletion, and translocation), and epigenetic changes evident in oral squamous cell carcinoma (OSCC). In addition, it highlights the interference caused by tobacco products in Wnt signaling, PI3K/Akt/mTOR, JAK-STAT, and other important pathways. The information provided also ensures a comprehensive and critical revisit to non-tobacco-induced OSCC. Extensive literature survey and analysis has been conducted to generate the chromosome maps specifically highlighting OSCC-related mutations with the potential to act as spectacles for the early diagnosis and targeted treatment of this disease cancer.

Distal junctional kyphosis in adult cervical deformity patients: where does it occur?

PURPOSE: To evaluate the impact of the lowest instrumented vertebra (LIV) on Distal Junctional kyphosis (DJK) incidence in adult cervical deformity (ACD) surgery. METHODS: Prospectively collected data from ACD patients undergoing posterior or anterior-posterior reconstruction at 13 US sites was reviewed up to 2-years postoperatively (n = 140). Data was stratified into five groups by level of LIV: C6-C7, T1-T2, T3-Apex, Apex-T10, and T11-L2. DJK was defined as a kyphotic increase > 10° in Cobb angle from LIV to LIV-1. Analysis included DJK-free survival, covariate-controlled cox regression, and DJK incidence at 1-year follow-up. RESULTS: 25/27 cases of DJK developed within 1-year post-op. In patients with a minimum follow-up of 1-year (n = 102), the incidence of DJK by level of LIV was: C6-7 (3/12, 25.00%), T1-T2 (3/29, 10.34%), T3-Apex (7/41, 17.07%), Apex-T10 (8/11, 72.73%), and T11-L2 (4/8, 50.00%) (p < 0.001). DJK incidence was significantly lower in the T1-T2 LIV group (adjusted residual = -2.13), and significantly higher in the Apex-T10 LIV group (adjusted residual = 3.91). In covariate-controlled regression using the T11-L2 LIV group as reference, LIV selected at the T1-T2 level (HR = 0.054, p = 0.008) or T3-Apex level (HR = 0.081, p = 0.010) was associated with significantly lower risk of DJK. However, there was no difference in DJK risk when LIV was selected at the C6-C7 level (HR = 0.239, p = 0.214). CONCLUSION: DJK risk is lower when the LIV is at the upper thoracic segment than the lower cervical segment. DJK incidence is highest with LIV level in the lower thoracic or thoracolumbar junction.

Use of the Global Alignment and Proportion score to predict postoperative health-related quality of life in adult spinal deformity surgery.

OBJECTIVE: The purpose of this study was to validate the Global Alignment and Proportion (GAP) score as a predictor of health-related quality of life (HRQOL) outcomes for patients undergoing adult spinal deformity (ASD) surgery. METHODS: This was a retrospective cohort study of patients with ASD undergoing long-segment spine fusions (≥ 5 vertebrae fused) at a single institution over a 2-year period (n = 85). Radiographic parameters were measured at preoperative, 6-week postoperative, 1-year postoperative, and 2-year postoperative visits. GAP scores were calculated using 4 sagittal parameters: relative pelvic version, relative lumbar lordosis, lordosis distribution index, and relative spinopelvic alignment. Patients were stratified into 3 GAP categories at each time point: proportioned (score 0-2), moderately disproportioned (score 3-6), and severely disproportioned (score ≥ 7). HRQOL outcomes were collected at preoperative, 1-year postoperative, and 2-year postoperative visits; these measures included patient self-reported outcome measures (i.e., PROMIS), Scoliosis Research Society-22 spinal deformity questionnaire (SRS-22), and Oswestry Disability Index (ODI) scores. RESULTS: Overall, 42% of cases were revision surgeries and 96.5% of patients underwent fusion to the sacrum. The mean preoperative GAP score significantly improved from preoperative (7.84) to immediate postoperative (3.31) assessment (p < 0.001). Similarly, the percentage of patients categorized as proportioned improved from 9.4% at preoperative to 45.9% at immediate postoperative evaluation. The preoperative GAP score or category was not significantly associated with any preoperative HRQOL outcome metrics. The immediate postoperative GAP score was not correlated with any 1-year HRQOL outcomes. However, the immediate postoperative GAP score was significantly associated with 2-year SRS-22 outcomes, including SRS-22 function (r = -0.35, p < 0.01), self-image (r = -0.27, p = 0.044), and subtotal (r = -0.35, p < 0.01) scores. As compared to severely disproportioned patients, proportioned patients had better SRS-22 pain (4.08 vs 3.17, p = 0.04), satisfaction (4.40 vs 3.50, p = 0.02), and subtotal (4.01 vs 3.27, p = 0.036) scores. The immediate postoperative GAP score was also significantly associated with 2-year PROMIS outcomes, including PROMIS pain (r = 0.31, p = 0.023) and physical function (r = -0.35, p < 0.01) scores. As compared to severely disproportioned patients, proportioned patients had better PROMIS pain (53.18 vs 63.60, p = 0.025) and physical function (41.66 vs 34.18, p = 0.017) scores. Postoperative GAP score or category did not predict any ODI outcomes. CONCLUSIONS: The postoperative GAP score is a predictor of long-term HRQOL outcomes following ASD surgery, and proportioned patients are more likely to have less pain and be satisfied with their surgery. However, the postoperative GAP score does not predict outcomes as measured by ODI.