Category: Nevin Manimala

Int J Cancer. 2023 Aug 23. doi: 10.1002/ijc.34699. Online ahead of print.

ABSTRACT

Evidence on the potential causal links of long-term air pollution exposure with lung cancer incidence (reflected by mortality and hospital admission) was limited, especially based on large cohorts. We examined the relationship between lung cancer and long-term exposure to particulate matter (PM, including PM_2.5 , PM₁₀ and PM_10-2.5 ) and nitrogen dioxide (NO₂ ) among a large cohort of general Chinese adults using causal inference approaches. The study included 575 592 participants who were followed up for an average of 8.2 years. The yearly exposure of PM and NO₂ was estimated through satellite-based random forest approaches and the ordinary kriging method, respectively. Marginal structural Cox models were used to examine hazard ratios (HRs) of mortality and hospital admission due to lung cancer following air pollution exposure, adjusting for potential confounders. The HRs of mortality due to lung cancer were 1.042 (95% confidence interval [CI]: 1.033-1.052), 1.032 (95% CI:1.024-1.041) and 1.052 (95% CI:1.041-1.063) for each 1 μg/m³ increase in PM_2.5 , PM₁₀ and NO₂ , respectively. In addition, we observed statistically significant effects of PMs on hospital admission due to lung cancer. The HRs (95%CI) were 1.110 (1.027-1.201), 1.067 (1.020-1.115) and 1.079 (1.010-1.153) for every 1 μg/m³ increase in PM_2.5 , PM₁₀ , PM_10-2.5 , respectively. Furthermore, we found larger effect estimates among the elderly and those who exercised more frequently. We provided the most comprehensive evidence of the potential causal links between two outcomes of lung cancer and long-term air pollution exposure. Relevant policies should be developed, with special attention to protecting the vulnerable groups of the population.

PMID:37611179 | DOI:10.1002/ijc.34699

Environ Sci Technol. 2023 Aug 23. doi: 10.1021/acs.est.3c04529. Online ahead of print.

ABSTRACT

Wastewater-based testing (WBT) for SARS-CoV-2 has rapidly expanded over the past three years due to its ability to provide a comprehensive measurement of disease prevalence independent of clinical testing. The development and simultaneous application of WBT measured biomarkers for research activities and for the pursuit of public health goals, both areas with well-established ethical frameworks. Currently, WBT practitioners do not employ a standardized ethical review process, introducing the potential for adverse outcomes for WBT professionals and community members. To address this deficiency, an interdisciplinary workshop developed a framework for a structured ethical review of WBT. The workshop employed a consensus approach to create this framework as a set of 11 questions derived from primarily public health guidance. This study retrospectively applied these questions to SARS-CoV-2 monitoring programs covering the emergent phase of the pandemic (3/2020-2/2022 (n = 53)). Of note, 43% of answers highlight a lack of reported information to assess. Therefore, a systematic framework would at a minimum structure the communication of ethical considerations for applications of WBT. Consistent application of an ethical review will also assist in developing a practice of updating approaches and techniques to reflect the concerns held by both those practicing and those being monitored by WBT supported programs.

PMID:37611169 | DOI:10.1021/acs.est.3c04529

J Addict Med. 2023 Aug 23. doi: 10.1097/ADM.0000000000001217. Online ahead of print.

ABSTRACT

OBJECTIVES: Little contemporary research has explored phencyclidine (PCP) use in people with alcohol use disorder. Therefore, we sought to determine the prevalence of PCP positivity on urine toxicology screening among patients admitted for alcohol withdrawal, identify correlates of PCP positivity, and investigate PCP positivity’s relationship to length of stay (LOS) and risk of facility readmission.

METHODS: This was a retrospective study of patients admitted to a dual-diagnosis medically assisted withdrawal unit for alcohol withdrawal from 2014 to 2019. Univariate tests and logistic regression were used to investigate potential correlates of PCP positivity on admission toxicology screening (primary outcome). Multivariable linear regression models and survival analyses analyzing LOS and risk of readmission (secondary outcomes) were also developed.

RESULTS: Ninety of 3731 patients (2.4%) screened positive for PCP. There were significant associations on univariate testing between PCP positivity and age, race, homeless status, and urine toxicology positivity for amphetamines, benzodiazepines, barbiturates, cocaine, tetrahydrocannabinol, and oxycodone. On multivariate logistic regression, only tetrahydrocannabinol, barbiturates, and cocaine positivity were associated with PCP positivity. Multivariate logistic regression and survival analysis found no statistically significant associations between PCP positivity and LOS or risk of readmission.

CONCLUSIONS: This study provides rare analysis of contemporary data on PCP use among patients undergoing medically assisted alcohol withdrawal. Phencyclidine positivity was uncommon, but use appears considerably higher among this patient population than the general population. There was no significant association between PCP positivity and LOS or readmission risk.

PMID:37611166 | DOI:10.1097/ADM.0000000000001217

Blood Adv. 2023 Aug 23:bloodadvances.2023010652. doi: 10.1182/bloodadvances.2023010652. Online ahead of print.

ABSTRACT

Early-stage pediatric nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) can be treated effectively with low-intensity chemotherapy, most frequently cyclophosphamide in combination with vinblastine and prednisone (CVP). Descriptive histological risk factors based on the disease-defining lymphocyte predominant cells (LP cells) as used within the Fan classification, are less predictive in early-stage patients. We used deep learning-based cell detection and spatial analysis on digitized biopsy slides from 53 early-stage pediatric NLPHL patients to quantitatively assess LP cell histomorphometry. We found that poor responding patients had significantly fewer LP cells per cluster and lower LP cell density than good responding patients. In our exploratory analysis, we found no correlation between Fan classes or B cell pattern variables and therapy response. We hypothesize that the relationship between poor treatment response and decreased LP cell density may be explained by differences in LP cell proliferation.

PMID:37611165 | DOI:10.1182/bloodadvances.2023010652

Pharmacogenet Genomics. 2023 Aug 24. doi: 10.1097/FPC.0000000000000506. Online ahead of print.

ABSTRACT

OBJECTIVES: Many studies were conducted to determine the association between genetic polymorphisms in CYP2B6 c.516G>T and cyclophosphamide (CYC) efficacy or toxicity, no studies were focused on both clinical efficacy and toxicity of CYC. This study aimed to investigate the relationship between the CYP2B6 c.516G>T polymorphism (rs 3745274) and 17 different parameters related to CYC efficacy and tolerability in Egyptian patients with lupus nephritis (LN).

METHODS: A prospective cohort study on 142 LN patients with a mean age of 36.26 was conducted at Kasr Al Ainy School of Medicine, Cairo University, Egypt after the exclusion of 14 patients due to receiving an interacting medication with CYC. All clinical parameters related to CYC efficacy or toxicity were recorded and compared between the different genotypes.

RESULTS: There was a statistically significant difference between different genotypes in 11 out of 13 of the studied efficacy-related parameters. Many of the studied clinical parameters revealed that CYC’s efficacy was associated with the presence of the T allele. There was a statistically significant difference between different genotypes in hepatotoxicity, diarrhea, and blood-related toxicities.

CONCLUSION: To our knowledge, this study is the first study that focused on studying 17 different parameters related to CYC efficacy and tolerability. Our findings paint a picture of the function that CYP2B6 polymorphisms play in Egyptian LN patients. Pre-treatment evaluation of CYP2B6 rs 3745274 may account for some individual differences in treatment response.

PMID:37611146 | DOI:10.1097/FPC.0000000000000506

Int J Clin Exp Hypn. 2023 Aug 23:1-12. doi: 10.1080/00207144.2023.2246512. Online ahead of print.

ABSTRACT

Test anxiety comprises cognitive, physiological, and behavioral reactions due to anxiety about failure or a lower academic performance score on an exam or evaluation. This study examined the effect of self-hypnosis on reducing test anxiety among upper secondary school students using a quantitative methodology with a pre-experimental design. The prevalence of test anxiety was measured using the Friedben Test Anxiety Scale (FTAS) and students’ demographic data were collected. Twenty-two 16-year-old students with moderate to high test anxiety were selected for a self-hypnosis intervention over a period of 5 weeks. The FTAS questionnaire was administered 4 times: at baseline, 3rd week, 5th week, and at follow-up (3 weeks after the intervention). Students’ test anxiety differences were statistically significant across 4 time points. Self-hypnosis intervention decreased students’ overall test anxiety scores and in the 3 constructs: social, cognitive, and tenseness. The outcomes indicate that self-hypnosis training can help students cope with test anxiety and should be further explored for managing test anxiety in school settings.

PMID:37611140 | DOI:10.1080/00207144.2023.2246512

Am J Clin Pathol. 2023 Aug 23:aqad103. doi: 10.1093/ajcp/aqad103. Online ahead of print.

ABSTRACT

OBJECTIVES: Data regarding bone marrow (BM) sampling and cytogenetic testing rates for identification of translocation (11q13;14q32) and their changes over time in a multiple myeloma (MM) population are limited. We analyzed these metrics at a clinic specializing in the treatment of MM.

METHODS: A total of 760 BM aspirate samples from 351 patients were collected between August 2004 and October 2021. We analyzed BM sampling statistics, cytogenetic testing frequency, and the incidence rates for the t(11;14) translocation in a single clinic specializing in the treatment of MM.

RESULTS: We report that most (54.4%) patients had only 1 aspirate collected; the main reason (64.6%) for BM collection was to confirm disease progression. Less than half (47.5%) of BM samples collected for evaluation of MM disease had cytogenetic testing, but the rates have markedly increased in recent years. Our data demonstrated an incidence rate of 19.3% for t(11;14).

CONCLUSIONS: This report suggests that some patients may need to retest for this genetic aberration due to the possibility of false negatives and the potential benefit of identifying the t(11;14) marker for patients who may be candidates for a highly effective targeted therapy consisting of the BCL-2 inhibitor venetoclax.

PMID:37611113 | DOI:10.1093/ajcp/aqad103

Sci Transl Med. 2023 Aug 23;15(710):eadi0252. doi: 10.1126/scitranslmed.adi0252. Epub 2023 Aug 23.

ABSTRACT

Improvements in COVID-19 treatments, especially for the critically ill, require deeper understanding of the mechanisms driving disease pathology. The complement system is not only a crucial component of innate host defense but can also contribute to tissue injury. Although all complement pathways have been implicated in COVID-19 pathogenesis, the upstream drivers and downstream effects on tissue injury remain poorly defined. We demonstrate that complement activation is primarily mediated by the alternative pathway, and we provide a comprehensive atlas of the complement alterations around the time of respiratory deterioration. Proteomic and single-cell sequencing mapping across cell types and tissues reveals a division of labor between lung epithelial, stromal, and myeloid cells in complement production, in addition to liver-derived factors. We identify IL-6 and STAT1/3 signaling as an upstream driver of complement responses, linking complement dysregulation to approved COVID-19 therapies. Furthermore, an exploratory proteomic study indicates that inhibition of complement C5 decreases epithelial damage and markers of disease severity. Collectively, these results support complement dysregulation as a key druggable feature of COVID-19.

PMID:37611083 | DOI:10.1126/scitranslmed.adi0252

Eur Heart J. 2023 Aug 23:ehad477. doi: 10.1093/eurheartj/ehad477. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Bicuspid aortic valve (BAV) is the most common congenital heart anomaly. Lifetime morbidity and whether long-term survival varies according to BAV patient-sub-groups are unknown. This study aimed to assess lifetime morbidity and long-term survival in BAV patients in the community.

METHODS: The authors retrospectively identified all Olmsted County (Minnesota) residents with an echocardiographic diagnosis of BAV from 1 January 1980 to 31 December 2009, including patients with typical valvulo-aortopathy (BAV without accelerated valvulo-aortopathy or associated disorders), and those with complex valvulo-aortopathy (BAV with accelerated valvulo-aortopathy or associated disorders).

RESULTS: 652 consecutive diagnosed BAV patients [median (IQR) age 37 (22-53) years; 525 (81%) adult and 127 (19%) paediatric] were followed for a median (IQR) of 19.1 (12.9-25.8) years. The total cumulative lifetime morbidity burden (from birth to age 90) was 86% (95% CI 82.5-89.7); cumulative lifetime progression to ≥ moderate aortic stenosis or regurgitation, aortic valve surgery, aortic aneurysm ≥45 mm or z-score ≥3, aorta surgery, infective endocarditis and aortic dissection was 80.3%, 68.5%, 75.4%, 27%, 6% and 1.6%, respectively. Survival of patients with typical valvulo-aortopathy [562 (86%), age 40 (28-55) years, 86% adults] was similar to age-sex-matched Minnesota population (P = .12). Conversely, survival of patients with complex valvulo-aortopathy [90 (14%), age 14 (3-26) years, 57% paediatric] was lower than expected, with a relative excess mortality risk of 2.25 (95% CI 1.21-4.19) (P = .01).

CONCLUSION: The BAV condition exhibits a high lifetime morbidity burden where valvulo-aortopathy is close to unavoidable by age 90. The lifetime incidence of infective endocarditis is higher than that of aortic dissection. The most common BAV clinical presentation is the typical valvulo-aortopathy with preserved expected long-term survival, while the complex valvulo-aortopathy presentation incurs higher mortality.

PMID:37611071 | DOI:10.1093/eurheartj/ehad477

Orbit. 2023 Aug 23:1-6. doi: 10.1080/01676830.2023.2248621. Online ahead of print.

ABSTRACT

Graves’-associated upper eyelid retraction (GAUER) is the commonest manifestation of orbitopathy in adults. Surgical management typically follows a 3-step staged approach commencing with orbital decompression. The rationale behind this is that certain surgical interventions can influence the parameters and outcomes of subsequent procedures. We performed a systematic review and meta-analysis evaluating the effects of orbital decompression on GAUER in adult patients with Graves’ orbitopathy. All original English, non-pediatric studies meeting the study inclusion criteria from the last 20 years were included. The characteristics of margin reflex distance 1 (MRD-1) pre- and post-orbital decompression of 688 orbits were collected, and a meta-analysis of 472 orbits was performed. The average reduction in MRD-1 across 688 orbits was found to be 0.40 mm. Meta-analysis of 6 applicable articles demonstrated that orbital decompression decreases MRD-1 by an average of 0.35 mm (n = 472, p = .007, 95% CI = [0.08, 0.63]). This study demonstrates that although statistically significant, orbital decompression does not appear to have a clinically significant effect on GAUER. This has implications for clinical practice, namely the likely requirement of eyelid surgery following or in combination with orbital decompression, and the importance of counselling patients on this preoperatively.

PMID:37611061 | DOI:10.1080/01676830.2023.2248621