Category: Nevin Manimala

JAMA Netw Open. 2024 Oct 1;7(10):e2437148. doi: 10.1001/jamanetworkopen.2024.37148.

ABSTRACT

IMPORTANCE: Elevated ambient fine particulate matter (PM2.5) air pollution exposure has been associated with poor health outcomes across several domains, but its associated outcomes among lung transplant recipients are poorly understood.

OBJECTIVE: To investigate whether greater PM2.5 exposure at the zip code of residence is associated with a higher hazard for mortality and graft failure in patients with lung transplants.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used panel data provided by the United Network for Organ Sharing, which includes patients receiving transplants across all active US lung transplant programs. Adult patients who received lung transplants between May 2005 and December 2016 were included, with a last follow-up of September 10, 2020. Data were analyzed from September 2022 to May 2023.

EXPOSURE: Zip code-level annual PM2.5 exposure was constructed using previously published North American estimates.

MAIN OUTCOMES AND MEASURES: The primary outcome was time to death or lung allograft failure after lung transplant. A gamma shared frailty Cox proportional hazards model was used to produce unadjusted and adjusted hazard ratios (HRs) to estimate the association of zip code PM2.5 exposure at the time of transplant with graft failure or mortality.

RESULTS: Among 18 265 lung transplant recipients (mean [SD] age, 55.3 [13.2] years; 7328 female [40.2%]), the resident zip code’s annual PM2.5 exposure level was greater than or equal to the Environmental Protection Agency (EPA) standard of 12μg/m3 for 1790 patients (9.8%) and less than the standard for 16 475 patients (90.2%). In unadjusted analysis, median graft survival was 4.87 years (95% CI, 4.57-5.23 years) for recipients living in high PM2.5 areas and 5.84 years (95% CI, 5.71-5.96 years) for recipients in the low PM2.5 group. Having an annual PM2.5 exposure level greater than or equal to the EPA standard 12 μg/m3 was associated with an increase in the hazard of death or graft failure (HR, 1.11; 95% CI, 1.05-1.18; P < .001) in the unadjusted analysis and after adjusting for covariates (HR, 1.08; 95% CI, 1.01-1.15; P = .02). Each 1 μg/m3 increase in exposure was associated with an increase in the hazard of death or graft failure (adjusted HR, 1.01; 95% CI, 1.00-1.02; P = .004) when treating PM2.5 exposure as a continuous variable.

CONCLUSIONS AND RELEVANCE: In this study, elevated zip code-level ambient PM2.5 exposure was associated with an increased hazard of death or graft failure in lung transplant recipients. Further study is needed to better understand this association, which may help guide risk modification strategies at individual and population levels.

PMID:39418024 | DOI:10.1001/jamanetworkopen.2024.37148

JAMA Netw Open. 2024 Oct 1;7(10):e2440047. doi: 10.1001/jamanetworkopen.2024.40047.

ABSTRACT

IMPORTANCE: Associations of body mass index (BMI) with survival in pancreatic ductal adenocarcinoma (PDA) have substantial variability in literature, potentially due to heterogeneous patient populations and retrospective analyses. Additionally, BMI may inadequately describe body composition (ie, morphomics; including subcutaneous and visceral fats, muscle, and fascia), which might have independent biological roles and associations with survival.

OBJECTIVE: To study the associations of BMI and morphomics with survival and metabolomics in metastatic PDA.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study prospectively collected patient data, imaging, and serum on the phase 3 trial (Avenger500), which investigated the efficacy and safety of 5-fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX) versus modified FOLFIRINOX plus devimistat. The randomized trial accrued 528 patients with chemotherapy-naive, metastatic PDA from Europe, Israel, Korea, and the US between 2018 and 2020. In the present study, per-protocol patients with L1 to L4, T10 to T12 vertebral levels were evaluated. Data analysis occurred from January 2023 to April 2024.

EXPOSURE: Patient data were collected by clinical staff. Morphomics were analyzed from baseline imaging. Metabolites were extracted from baseline serum.

MAIN OUTCOME AND MEASURES: A multifaceted statistical approach evaluated associations of BMI and morphomics with progression-free survival (PFS) and overall survival (OS). Associations of morphomics with metabolites were also studied.

RESULTS: Of the 528 initial patients, 476 (median [IQR] age, 63 [56-68] years; 280 male [58.8%]; median [IQR] BMI, 25.0 [22.1-25.9]) were evaluable for the present study. BMI (obese [≥30] compared with normal [18.5-24.9]) was not associated with OS (hazard ratio [HR], 0.90; 95% CI, 0.67-1.22; P for trend = .33). More subcutaneous fat was associated with longer OS (HR, 0.62; 95% CI, 0.41-0.94; P for trend = .02). Higher visceral fat density was associated with shorter PFS (HR, 1.74; 95% CI, 1.23-2.48; P for trend = .002) and OS (HR, 1.50; 95% CI, 1.12-2.00; P for trend = .008). A higher muscle-to-fascia ratio was associated with longer PFS (HR, 0.58; 95% CI, 0.40-0.84; P for trend = .005) and OS (HR, 0.56; 95% CI, 0.41-0.75; P for trend = 1.7 × 10-4). Subcutaneous fat was positively associated with long-chain fatty acid metabolism including pristanic acid, decanoylcarnitine, decenoylcarnitine, and octanoylcarnitine. Muscle-to-fascia was positively associated with metabolites including acetylcarnosine (β = 0.34; 95% CI, 0.21-0.47; P = 1.27 × 10-6).

CONCLUSIONS AND RELEVANCE: In cohort study of patients with metastatic PDA, BMI was not associated with survival. Higher visceral fat density, subcutaneous fat area, and muscle-to-fascia ratio were associated with survival independent of BMI. The latter 2 were associated with higher levels of animal product metabolism. These findings could represent novel focuses for prognostication and intervention to improve survival of patients with PDA.

PMID:39418020 | DOI:10.1001/jamanetworkopen.2024.40047

JAMA Ophthalmol. 2024 Oct 17. doi: 10.1001/jamaophthalmol.2024.4297. Online ahead of print.

ABSTRACT

IMPORTANCE: Evidence is limited to support therapies to treat submacular hemorrhage (SMH) secondary to neovascular age-related macular degeneration (AMD) as an adjunct to anti-vascular endothelial growth factor therapy (anti-VEGF).

OBJECTIVE: To determine if intravitreal tissue plasminogen activator (TPA) or gas improves visual acuity or promotes resolution of SMH secondary to neovascular AMD in eyes treated with ranibizumab.

DESIGN, SETTING, AND PARTICIPANTS: This was a double-masked, sham-controlled, factorial randomized clinical trial and feasibility study that recruited participants from June 2014 to March 2019, with 12 months’ follow-up. Included in the trial were patients from 4 UK vitreoretinal units who had fovea-involving SMH of at least 1 disc area secondary to neovascular AMD and were evaluated within 14 days of onset.

INTERVENTIONS: Study eyes received baseline ranibizumab and were then randomized 2:1:1:1 to 1 of 4 intravitreal treatments: sham injection, perfluoropropane (C3F8), TPA, or combined C3F8 and TPA (C3F8 + TPA). All eyes received monthly pro re nata ranibizumab therapy over 12 months. Outcome assessors were masked to intervention assignment.

MAIN OUTCOME AND MEASURE: Best-corrected visual acuity (BCVA) at month 3.

RESULTS: Fifty-three of 56 participants (95%; mean [SD] age, 81.5 [8.1] years; 33 female [59%]) reached the primary end point. Study eyes were randomized to the following intravitreal treatments: sham injection (n = 23), C3F8 (n = 11), TPA (n = 11), or C3F8 + TPA (n = 11). On factorial analysis, the combined TPA groups had significantly better month 3 mean logMAR BCVA than those not receiving TPA: 0.66 vs 0.98 (μd = -0.32; 95% CI, -0.58 to -0.07; P = .02). There was no statistically significant difference comparing groups that did vs did not receive C3F8: 0.80 vs 0.90 (μd = -0.11; 95% CI, -0.37 to 0.16; P = .43). The combined TPA groups were less likely to have SMH present at month 1 (10 of 18 [55.6%] vs 21 of 24 [87.5%]; P = .03), a benefit not evident in the combined gas groups. The mean logMAR BCVA at 3 months was not significantly different between the groups: monotherapy control, 0.99; C3F8, 0.97 (vs control μd = -0.02; 95% CI, -0.48 to 0.44); TPA, 0.70 (vs control μd = -0.29; 95% CI, -0.79 to 0.21); combined C3F8 and TPA, 0.71 (vs control μd = -0.36; 95% CI, -0.82 to 0.11); P = .11. No safety differences were identified across the treatment groups.

CONCLUSIONS AND RELEVANCE: Results of this randomized clinical trial suggest that TPA may increase the chance of visual acuity gain when added to ranibizumab therapy for neovascular AMD in eyes with SMH, warranting consideration of additional clinical trials.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01835067.

PMID:39418015 | DOI:10.1001/jamaophthalmol.2024.4297

J Otolaryngol Head Neck Surg. 2024 Jan-Dec;53:19160216241288811. doi: 10.1177/19160216241288811.

ABSTRACT

IMPORTANCE: At present, there is no consensus on the concentration of epinephrine/physiological saline for subcutaneous injection into external auditory canal (EAC) under general anesthesia in otoendoscopic surgery. A randomized controlled trial (RCT) research is needed to provide reference, as this concentration can provide satisfactory surgical field clarity while maintaining patients’ hemodynamic stability.

OBJECTIVE: Comparison of the effect of subcutaneous injection of different concentrations of epinephrine/physiological saline into EAC under general anesthesia in otoendoscopic surgery on surgical field clarity and hemodynamics.

DESIGN: This double-blind, RCT study was about the effect of topical epinephrine injection in otoendoscopic surgery.

SETTING: This study was conducted at a single institution.

PARTICIPANTS: This study included 168 patients conformed to the inclusion criteria.

INTERVENTION: Patients were randomized to receive different concentrations of epinephrine/physiological saline injection (1:5000, 1:10,000, 1:20,000, or 1:40,000) into the junction of bone and cartilage at posterior wall of EAC during surgery.

MAIN OUTCOME MEASURES: Surgical field clarity was assessed with surgical field clarity grading scale and tympanic membrane flap flipping time. Hemodynamic changes were monitored by clinical parameters of blood pressure, heart rate, and ST segment of ECG.

RESULTS: There were no statistically-significant differences in surgical field clarity grade (P = .577) and tympanic membrane flap flipping time (P = .490) among 4 concentration groups. Epinephrine injection did cause an increase in hemodynamic parameters when compared with baseline (P < .05). Compared with the relatively-lower concentration groups (1:20,000 and 1:40,000), the relatively-higher concentration groups (1:5000 and 1:10,000) had more significant and long-lasting effect until 30 minutes after injection.

CONCLUSIONS AND RELEVANCE: Four concentration groups of topical epinephrine injection in otoendoscopic surgery have the same effect on surgical field clarity. For the stability of patients’ hemodynamics, we would prefer to recommend the use of concentrations with minimal impact on hemodynamics, ranging from 1:20,000 to 1:40,000.

TRIAL REGISTRATION: Clinical Trial Registry-China: ChiCTRI1800016647.

PMID:39418011 | DOI:10.1177/19160216241288811

Eur Arch Paediatr Dent. 2024 Oct 17. doi: 10.1007/s40368-024-00948-w. Online ahead of print.

ABSTRACT

PURPOSE: The aim of the present was to assess the association between MIH and tooth agenesis (TA) in orthodontic patients from the Federal University of Rio Grande do Norte, Natal, Brazil.

METHODS: A cross-sectional study was performed to evaluate the presence of MIH and TA in a sample of 371 pretreatment orthodontic records from patients aged 9-18 years. Statistical analyses were performed using the Chi-square and Fisher’s exact tests, and logistic regressions.

RESULTS: There was a statistically significant association between the prevalence of tooth agenesis and MIH. A higher percentage of third molar agenesis, maxillary premolar agenesis, and mandibular second premolar agenesis was observed among children with MIH-affected teeth. Patients with MIH had a 2.43 times greater chance of third molar agenesis, and a 5.88 times higher likelihood of mandibular premolar agenesis.

CONCLUSION: There is a weak association between MIH and TA. Furthermore, the presence of hypomineralised molars increases the risk of tooth agenesis.

PMID:39417959 | DOI:10.1007/s40368-024-00948-w

Environ Sci Pollut Res Int. 2024 Oct 17. doi: 10.1007/s11356-024-35261-y. Online ahead of print.

ABSTRACT

This study evaluated the biofuel production potential of two algal species, Chlorella pyrenoidosa and Scenedesmus abundans, under stress conditions induced by nutrient supplementation or starvation at varying light intensities. Central composite face-centered design response surface methodology (CCFD-RSM) was employed to optimize stress conditions by varying the sodium nitrate (NaNO₃), potassium dihydrogen phosphate (KH₂PO₄), dipotassium hydrogen phosphate (K₂HPO₄), cultivation time, and light intensity. The study included both C. pyrenoidosa and S. abundans, which presented increased biomass yields when subjected to nutrient starvation. Under the optimized conditions, the dry biomass yield was 98.26 mg/L for C. pyrenoidosa and 110 mg/L for S. abundans. Lipid yields were approximately 22.47% for C. pyrenoidosa and 29.06% for S. abundans under these optimized growth conditions. The optimized parameters for maximum biomass and lipid production were identified as C. pyrenoidosa, and the optimized conditions required 0.805 g/L NaNO₃, 0.052 g/L K₂HPO₄, 0.099 g/L KH₂PO₄, 17 days of culture, and 5168.39 lx of light intensity. For S. abundans, the optimal conditions were 1.065 g/L NaNO₃, 0.071 g/L K₂HPO₄, 0.058 g/L KH₂PO₄, 22 days of cultivation, and 2897 lx of light intensity. Overall, both C. pyrenoidosa and S. abundans have emerged as promising candidates for sustainable biodiesel production, highlighting their potential under stress conditions induced by nutrient modulation and variable light intensities.

PMID:39417936 | DOI:10.1007/s11356-024-35261-y

Mycotoxin Res. 2024 Oct 17. doi: 10.1007/s12550-024-00563-0. Online ahead of print.

ABSTRACT

Aflatoxin B1 (AFB1) is a fungal toxin consistently found as a contaminant in food products such as cereals, nuts, spices, and oilseeds. AFB1 exposure can lead to hepatotoxicity, cancer, immune suppression, reproductive deficiency, nutritional dysfunction, and growth impairment. AFB1 has also been listed as one of the most potent human carcinogens by the International Agency for Research on Cancer. Although the correlation between AFB1 exposure and cancer initiation and progression is already reported in the literature, very little information is available about what molecular pathways are affected during cancer development. Considering this, we first selected AFB1-responsive genes involved in five deadliest cancer types including lung, colorectal, liver, stomach, and breast cancers from the Comparative Toxicogenomics Database (CTD). Then, using the PANTHER database, a statistical overrepresentation test was performed to identify the significantly affected pathways in each cancer type. The gonadotropin-releasing hormone receptor (GnRHR) pathway, the CCKR signaling pathway, and angiogenesis were found to be the most affected pathways in lung, breast, liver, and stomach cancers. In addition, AFB1 toxicity majorly impacted apoptosis and Wnt signaling pathways in liver and stomach cancers, respectively. Moreover, the most affected pathways in colorectal cancer were the Wnt, CCKR, and GnRHR pathways. Furthermore, gene analysis was also performed for the most affected pathways associated with each cancer and identified thirteen key genes (e.g., FOS, AKT1) that may serve as biological markers for a particular type of AFB1-induced cancer as well as for in vitro AFB1 toxicological studies using specific cancer cell lines.

PMID:39417919 | DOI:10.1007/s12550-024-00563-0

Discov Oncol. 2024 Oct 17;15(1):568. doi: 10.1007/s12672-024-01456-5.

ABSTRACT

OBJECTIVE: This study aims to investigate the causal relationship between cervical carcinoma in situ and antibody-mediated immune responses, providing a scientific basis for the prevention and treatment of cervical carcinoma in situ.

METHODS: A bidirectional Mendelian Randomization (MR) approach was utilized, leveraging two Genome-Wide Association Studies (GWAS) related to cervical carcinoma in situ and antibody-mediated immune responses to collect Single Nucleotide Polymorphism (SNP) data. Multiple statistical methods, including the inverse-variance weighted (IVW) method, MR-Egger regression, weighted median, and weighted mode, were utilized. Antibody-mediated immune response-related SNPs were used as instrumental variables (IVs) for a forward MR analysis of cervical carcinoma in situ, while cervical carcinoma in situ-related SNPs served as IVs for a reverse MR analysis of antibody-mediated immune responses.

RESULTS: The forward MR analysis revealed significant causal associations between two SNPs, GCST90006901 (P = 0.012, OR (95%CI) = 1.167(1.034-1.317)) and GCST90006909 (P < 0.001, OR (95%CI) = 1.805(1.320-2.467)), within antibody-mediated immune responses and the occurrence of cervical carcinoma in situ. The reverse MR analysis demonstrated that cervical carcinoma in situ exerts influence on multiple SNPs associated with antibody-mediated immune responses. Specifically, GCST90006891 (P = 0.018, OR (95%CI) = 1.164(1.027-1.319)) and GCST90006894 (P = 0.048, OR (95%CI) = 1.074 (1.001-1.153)) showed positive effects, while GCST90006899 (P = 0.022, OR (95%CI) = 0.935(0.882-0.990)) and GCST90006911 (P = 0.0193, OR (95%CI) = 1.226(1.034-1.454)) exhibited distinct trends of influence.

CONCLUSION: The Mendelian Randomization analysis indicates a clear causal relationship between antibody-mediated immune responses and the prevalence of cervical carcinoma in situ, with cervical carcinoma in situ also exerting a certain degree of influence on antibody-mediated immune responses. This finding provides important insights into the interaction mechanism between the two and suggests avenues for developing effective prevention and control strategies.

PMID:39417906 | DOI:10.1007/s12672-024-01456-5

Arch Dermatol Res. 2024 Oct 17;316(10):697. doi: 10.1007/s00403-024-03434-x.

ABSTRACT

Amidst the existing literature on the effect of isotretinoin on serum interleukin-17 levels in acne patients, the effects of oral antibiotics azithromycin and doxycycline on serum interleukin-17 is scarce. We conducted an investigator blinded randomized interventional study to compare the effect of doxycycline, azithromycin and isotretinoin on inflammatory markers and Interleukin-17A (IL-17A) levels in acne. Patients were randomized and received the treatment according to treatment arm till 12 weeks. At baseline and 12 weeks/treatment completion, clinical improvement and Red-cell-distribution width (RDW),Neutrophil-lymphocyte ratio(NLR),Platelet-lymphocyte ratio(PLR), Mean-Platelet volume(MPV), Platelet-distribution width(PDW) and Interleukin-17A levels were analysed. P-value < 0.05 was considered statistically significant. Out of 120 patients, 110 patients completed the study. Baseline Global acne grading scale (GAGS) in doxycycline, azithromycin or isotretinoin group was 24.32 ± 3.119, 24.12 ± 2.804 and 25.10 ± 3.985 respectively and post-treatment was 5.216 ± 1.88, 7.265 ± 2.17 and 2.769 ± 1.08. All the drugs caused a statistically significant decrease in RDW and IL-17 A levels. Baseline levels of IL-17 A were significantly higher in patients with higher GAGS and post-acne scarring. One of the limitations of our study was that we excluded severe nodulocystic acne patients thereby these results have to be carefully extrapolated.

PMID:39417892 | DOI:10.1007/s00403-024-03434-x

Arch Dermatol Res. 2024 Oct 17;316(10):698. doi: 10.1007/s00403-024-03431-0.

ABSTRACT

Basal cell carcinoma (BCC) is a slowly progressive, locally aggressive and rarely metastasizing cancer, and although its mortality is low, its morbidity and cost of disease are high. While BCC is more common, cutaneous malignant melanoma (CMM) is significant due to its higher mortality rate. These patients can be treated, but recurrence, metastasis and mortality may occur in such patients. Various environmental, phenotypic and genotypic factors, especially ultraviolet (UV) radiations, play a role in the etiology of BCC and CMM. Histopathological examination continues to be the “gold standard” in their diagnosis. Spexin (SPX) and DARS2 are newly discovered proteins linked to many diseases, including cancer. These proteins may have an effect on the development and expression of skin cancers such as BCC and CMM. In this study, we evaluated the potential of SPX and DARS2 expressions as immunohistochemical biomarkers in the differential diagnosis of BCC and CMM. This study was conducted retrospectively using samples taken from the pathology laboratory. A total of 180 patient samples were used. The control group consisted of healthy skin tissues of the patients, and the other groups consisted of BCC and CMM tissues of the same patients. Tissue samples of all three groups were evaluated immunohistochemically with SPX and DARS2. The immunoreactivity of SPX was found to be higher in BCC and CMM tissue samples than in healthy skin tissues in the control group. DARS2 immunoreactivity was found to be higher in CMM tissues compared to the other two groups, and statistically significant in BCC tissues when compared with healthy control group tissues. SPX can be used as an immunohistochemical biomarker in the diagnosis of BCC and CMM. Since DARS2 expression is statistically more significant in CMM tissues than in BCC tissues, it can be used in differential diagnosis.

PMID:39417889 | DOI:10.1007/s00403-024-03431-0