Category: Nevin Manimala

J Assoc Res Otolaryngol. 2023 Dec 11. doi: 10.1007/s10162-023-00920-3. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Tinnitus would benefit from an objective biomarker. The goal of this study is to identify plasma biomarkers of constant and chronic tinnitus among selected circulating inflammatory proteins.

METHODS: A case-control retrospective study on 548 cases with constant tinnitus and 548 matched controls from the Swedish Tinnitus Outreach Project (STOP), whose plasma samples were examined using Olink’s Inflammatory panel. Replication and meta-analysis were performed using the same method on samples from the TwinsUK cohort. Participants from LifeGene, whose blood was collected in Stockholm and Umeå, were recruited to STOP for a tinnitus subtyping study. An age and sex matching was performed at the individual level. TwinsUK participants (n = 928) were selected based on self-reported tinnitus status over 2 to 10 years. Primary outcomes include normalized levels for 96 circulating proteins, which were used as an index test. No reference standard was available in this study.

RESULTS: After adjustment for age, sex, BMI, smoking, hearing loss, and laboratory site, the top proteins identified were FGF-21, MCP4, GDNF, CXCL9, and MCP-1; however, these were no longer statistically significant after correction for multiple testing. Stratification by sex did not yield any significant associations. Similarly, associations with hearing loss or other tinnitus-related comorbidities such as stress, anxiety, depression, hyperacusis, temporomandibular joint disorders, and headache did not yield any significant associations. Analysis in the TwinsUK failed in replicating the top candidates. Meta-analysis of STOP and TwinsUK did not reveal any significant association. Using elastic net regularization, models exhibited poor predictive capacity tinnitus based on inflammatory markers [sensitivity = 0.52 (95% CI 0.47-0.57), specificity = 0.53 (0.48-0.58), positive predictive value = 0.52 (0.47-0.56), negative predictive values = 0.53 (0.49-0.58), and AUC = 0.53 (0.49-0.56)].

DISCUSSION: Our results did not identify significant associations of the selected inflammatory proteins with constant tinnitus. Future studies examining longitudinal relations among those with more severe tinnitus and using more recent expanded proteomics platforms and sampling of cerebrospinal fluid could increase the likelihood of identifying relevant molecular biomarkers.

PMID:38079022 | DOI:10.1007/s10162-023-00920-3

Dysphagia. 2023 Dec 11. doi: 10.1007/s00455-023-10636-4. Online ahead of print.

ABSTRACT

The older population is growing exponentially causing greater demands on healthcare. Malnutrition, dysphagia, sarcopenia and weakness are highly prevalent diseases in the older population. Previous research (Byun et al. in BMC Geriatr 19(356):1-7, 2019; Fujishima et al. in Geriatr Gerontol Int 19:91-97, 2019; Hernandez et al. in Nutr Hosp 32(4):1830-1836, 2015; Nagano et al. in J Nutr Health Aging 23(3):256-265.5, 2019; Nishioka et al. in Clin Nutr 36(4):1089-1096, 2017; Robinson et al. in Clin Nutr 37(4):1121-1132, 2018, https://doi.org/10.1016/j.clnu.2017.08.016 ) has shown that these disorders are frequently associated, in many cases, preventable using screenings and intervention. This study utilized the National Hospital Discharge Survey of 2008 from the National Center of Health Statistics as secondary data to examine the associations amongst these four variables as well as possible correlations with age, days of care in the acute care hospital setting and frequency of rehabilitative and nutritional interventions received by these patients. Out of 165,630 cases, a sample size of 59,029 cases ages 65 and above were filtered by the researchers for desired diagnoses and procedure codes. After this, all neurological diagnoses were filtered and excluded by the researchers, resulting in 2458 cases. Using the Chi square test of independence, findings revealed significant associations between the variables of malnutrition and dysphagia (χ² (1) = 1882.618, p = 0.001), dysphagia and weakness (χ² (1) = 21.069, p = 0.001) and malnutrition weakness (χ² (1) = 88.434, p = 0.001). The point biserial correlation coefficient was calculated to examine possible associations between these four conditions and age as well as days of care. A significant negative correlation was found between malnutrition and age (rpb (2456) = – 0.043, p = 0.05). In addition, days of care were significantly correlated with malnutrition (r(2456) = 0.138, p = 0.001) and inversely significantly correlated with dysphagia (r(2456) = – 110, p = 0.001), weakness (r(2456) = – 0.060, p = 0.001) and sarcopenia (r(2456) = – 0.041, p = 0.05). Lastly, the study found a large disparity between cases that received rehabilitative and nutritional intervention and those that didn’t.

PMID:38078983 | DOI:10.1007/s00455-023-10636-4

Tech Coloproctol. 2023 Dec 11;28(1):9. doi: 10.1007/s10151-023-02874-3.

ABSTRACT

BACKGROUND: Laparoscopic and now robotic colorectal surgery has rapidly increased in prevalence; however, little is known about how uptake varies by region and sociodemographics. The aim of this study was to quantify the uptake of minimally invasive colorectal surgery (MIS) over time and variations by region, sociodemographics and ethnicity.

METHODS: Retrospective analysis of routinely collected healthcare data (Clinical Practice Research Datalink linked to Hospital Episode Statistics) for all adults having elective colorectal resectional surgery in England from 1 January 2006 to 31 March 2020. Sociodemographics between modalities were compared and the association between sociodemographic factors, region and year on MIS was compared in multivariate logistic regression analysis.

RESULTS: A total of 93,735 patients were included: 52,098 open, 40,622 laparoscopic and 1015 robotic cases. Laparoscopic surgery surpassed open in 2015 but has plateaued; robotic surgery has rapidly increased since 2017, representing 3.2% of cases in 2019. Absolute differences up to 20% in MIS exist between regions, OR 1.77 (95% CI 1.68-1.86) in South Central and OR 0.75 (95% CI 0.72-0.79) in the North West compared to the largest region (West Midlands). MIS was less common in the most compared to least deprived (14.6% of MIS in the most deprived, 24.8% in the least, OR 0.85 95% CI 0.81-0.89), with a greater difference in robotic surgery (13.4% vs 30.5% respectively). Female gender, younger age, less comorbidity, Asian or ‘Other/Mixed’ ethnicity and cancer indication were all associated with increased MIS.

CONCLUSIONS: MIS has increased over time, with significant regional and socioeconomic variations. With rapid increases in robotic surgery, national strategies for procurement, implementation, equitable distribution and training must be created to avoid worsening health inequalities.

PMID:38078978 | DOI:10.1007/s10151-023-02874-3

Eur J Nucl Med Mol Imaging. 2023 Dec 11. doi: 10.1007/s00259-023-06526-4. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the feasibility of reducing the acquisition time for continuous dynamic positron emission tomography (PET) while retaining acceptable performance in quantifying kinetic metrics of 2-[¹⁸F]-fluoro-2-deoxy-D-glucose ([¹⁸F]FDG) in tumors.

METHODS: In total, 78 oncological patients underwent total-body dynamic PET imaging for ≥ 60 min, with 8, 20, and 50 patients receiving full activity (3.7 MBq/kg), half activity (1.85 MBq/kg), and ultra-low activity (0.37 MBq/kg) of [¹⁸F]FDG, respectively. The dynamic data were divided into 21-, 30-, 45- and ≥ 60-min groups. The kinetic analysis involved model fitting to derive constant rates (V_B, K₁ to k₃, and Ki) for both tumors and normal tissues, using both reversible and irreversible two-tissue-compartment models. One-way ANOVA with repeated measures or the Freidman test compared the kinetic metrics among groups, while the Deming regression assessed the correlation of kinetic metrics among groups.

RESULTS: All kinetic metrics in the 30-min and 45-min groups were statistically comparable to those in the ≥ 60-min group. The relative differences between the 30-min and ≥ 60-min groups ranged from 12.3% ± 15.1% for K₁ to 29.8% ± 30.0% for V_B, and those between the 45-min and ≥ 60-min groups ranged from 7.5% ± 8.7% for Ki to 24.0% ± 24.3% for V_B. However, this comparability was not observed between the 21-min and ≥ 60-min groups. The significance trend of these comparisons remained consistent across different models (reversible or irreversible), administrated activity levels, and partial volume corrections for lesions. Significant correlations in tumor kinetic metrics were identified between the 30-/45-min and ≥ 60-min groups, with Deming regression slopes > 0.813. In addition, the comparability of kinetic metrics between the 30-min and ≥ 60-min groups were established for normal tissues.

CONCLUSION: The acquisition time for dynamic PET imaging can be reduced to 30 min without compromising the ability to reveal tumor kinetic metrics of [¹⁸F]FDG, using the total-body PET/CT system.

PMID:38078950 | DOI:10.1007/s00259-023-06526-4

Acta Vet Hung. 2023 Dec 11. doi: 10.1556/004.2023.00878. Online ahead of print.

ABSTRACT

Calprotectin (CP) is an inflammatory marker. The aim of the current study was to investigate oxidative stress and changes in CP in cattle with traumatic reticuloperitonitis (TRP). The study was divided into two groups, experimental (TRP) and healthy control group, with 10 animals in each group. Total leucocyte count, neutrophil and lymphocyte counts were higher in the TRP group compared to the control group and this increase was statistically significant (P < 0.001). The level of malondialdehyde (MDA) in TRP group was statistically significantly higher than the control group (P < 0.001). The level of glutathione (GSH) in the TRP group was statistically significantly lower than in the control group (P < 0.001). Serum Amyloid A (SAA) and CP values were higher in the TRP group and this difference was statistically significant (P < 0.001). It was concluded as a result of ROC analysis that CP, which has similar values with SAA, can be used diagnostically to confirm the inflammatory status in cattle with TRP.

PMID:38078926 | DOI:10.1556/004.2023.00878

Endocr Connect. 2023 Dec 1:EC-23-0363. doi: 10.1530/EC-23-0363. Online ahead of print.

ABSTRACT

OBJECTIVE: Pituitary dysfunction following mild traumatic brain injury can have serious physical and psychological consequences making diagnosis and treatment essential. To the best of our knowledge, this study is the first to study the prevalence of pituitary dysfunction following mild traumatic brain injury in an all-female population following detailed endocrinological work up after screening for pituitary dysfunction in female athletes.

DESIGN: Retrospective cohort study.

METHODS: Hormone screening blood tests, including serum blood values for thyroid-stimulating hormone, free thyroxin, insulin-like growth factor 1, prolactin, cortisol, follicle stimulating hormone, luteinizing hormone, oestrogen, and progesterone were taken in 133 female athletes. Results were repeatedly outside the reference value in 88 women necessitating further endocrinological evaluation. Two of those were lost to follow up and further endocrinological evaluation was performed in 86 participants.

RESULTS: Six women (4.6%, n = 131) were diagnosed with hypopituitarism, four (3.1%) with central hypothyroidism and two with growth hormone deficiency (1.5%). Ten women (7.6%) had hyperprolactinemia, four (3.1%) of them had prolactinoma. Medical treatment was initiated in 13 (9.9%) women. Significant prognostic factors were not found.

CONCLUSIONS: As 12.2% of female athletes with a history of mild traumatic brain injury had pituitary dysfunction (hypopituitarism 4.6%, hyperprolactinemia 7.6%), we conclude that pituitary dysfunction is an important consideration in post-concussion care. Hyperprolactinemia in the absence of prolactinoma may represent pituitary or hypothalamic injury following mild traumatic brain injury.

PMID:38078923 | DOI:10.1530/EC-23-0363

Traffic Inj Prev. 2023 Dec 11:1-9. doi: 10.1080/15389588.2023.2287405. Online ahead of print.

ABSTRACT

Objective: Develop corridor-level network screening models to identify high-risk corridors where safety improvements could be implemented to reduce fatal and injury (FI) crashes. Methods: A novel corridor definition focused on context classification and lane count was developed and applied to urban and suburban four-lane divided arterial roadways in Florida. Negative binomial regression models were developed for multi- and single-vehicle crashes using 80% of the corridors (training set). Crash frequency predictions were obtained from the developed corridor models and similar site-level models from the Highway Safety Manual (HSM) models for the remaining 20% of the corridors (testing set). Results from all models were adjusted using the empirical Bayes (EB) method. Results: A total of 130 corridors were identified across seven counties. These corridors contained approximately 349 km (217 miles) of roadway and experienced 11,437 multi-vehicle and 746 single-vehicle crashes that resulted in fatalities or injuries from 2017 to 2021. After applying the HSM site-level models and the developed corridor-level models to the testing set (both with and without EB adjustments), the corridor-level models with EB adjustments were the most accurate for corridor crash prediction. Applying the corridor-level models with EB adjustments to the testing set gave a predicted value of 386.44 crashes/year, which was the closest to the observed crash frequency of 383.20 crashes/year. From the corridor-level models, a 3.48-km (2.16-mile) high-risk corridor in Miami-Dade County was identified and analyzed site-by-site using the HSM methodology to identify specific sites within the corridor where safety improvements could provide the most FI crash reductions. Conclusions: The corridor-level models were more accurate and statistically reliable than similar HSM models while being less data intensive. They also only required corridor-level data rather than data for each intersection and segment. By using readily available data, the methods in this paper can be easily replicated by agencies to develop their own network screening corridor-level models and expedite the identification of corridors in need of safety improvements to reduce FI crashes. Existing site-level network screening methods can be used to supplement the developed corridor-level methodology by identifying high-risk sites within identified high-risk corridors.

PMID:38078886 | DOI:10.1080/15389588.2023.2287405

Am J Respir Crit Care Med. 2023 Dec 11. doi: 10.1164/rccm.202306-1107OC. Online ahead of print.

ABSTRACT

RATIONALE: Passenger lymphocyte syndrome (PLS) may complicate minor ABO mismatched lung transplantation (LuTX) via donor-derived red cell antibody-induced hemolysis.

OBJECTIVES: To ascertain the incidence and specificity of PLS-relevant antibodies amongst the study population as well as the dynamics of hemolysis parameters and the transfusion requirement of patients with or without PLS were the main objectives of this study.

METHODS: In this cohort study, 1011 patients who received LuTX between January 2010 and June 2019 were studied retrospectively. Prospectively, 87 LuTX (July 2019 to June 2021) were analyzed. Post-operative ABO antibody and hemolytic marker determinations, transfusion requirement, and duration of post-operative hospital care were analyzed. Retrospectively, blood group A recipients of O grafts with PLS were compared to those without.

MEASUREMENTS AND MAIN RESULTS: PLS affected 18.18% (retrospective) and 30.77% (prospective) of A recipients receiving O grafts, 5.13% of B recipients of O grafts, and 20% of AB patients receiving O transplants. Anti-A and anti-A1 were the predominant PLS-inducing antibodies, followed by anti-B and anti-A,B. Significantly lower hemoglobin values (median 7.4 versus 8.3 g/dL; p=0.0063) and an approximately twice as high percentage of patients requiring blood transfusions were seen in PLS. No significant differences in other laboratory markers, duration of hospital stay or other complications after LuTX were registered.

CONCLUSIONS: Minor ABO incompatible LuTX recipients are at considerable risk of developing clinically significant PLS. Post-transplant monitoring combining red cell serology and hemolysis marker determination appears advisable not to overlook hemolytic episodes which necessitate antigen-negative transfusion therapy.

PMID:38078854 | DOI:10.1164/rccm.202306-1107OC

Front Genet. 2023 Nov 23;14:1286561. doi: 10.3389/fgene.2023.1286561. eCollection 2023.

ABSTRACT

Polygenic risk score (PRS) predictions often show bias toward the population of available genome-wide association studies (GWASs), which is typically of European ancestry. This study aimed to assess the performance differences of ancestry-specific PRS and test the implementation of multi-ancestry PRS to enhance the generalizability of low-density lipoprotein (LDL) cholesterol predictions in the East Asian (EAS) population. In this study, we computed ancestry-specific and multi-ancestry PRSs for LDL using data obtained from the Global Lipid Genetics Consortium, while accounting for population-specific linkage disequilibrium patterns using the PRS-CSx method in the United Kingdom Biobank dataset (UKB, n = 423,596) and Taiwan Biobank dataset (TWB, n = 68,978). Population-specific PRSs were able to predict LDL levels better within the target population, whereas multi-ancestry PRSs were more generalizable. In the TWB dataset, covariate-adjusted R ² values were 9.3% for ancestry-specific PRS, 6.7% for multi-ancestry PRS, and 4.5% for European-specific PRS. Similar trends (8.6%, 7.8%, and 6.2%) were observed in the smaller EAS population of the UKB (n = 1,480). Consistent with R ² values, PRS stratification in EAS regions (TWB) effectively captured a heterogenous variability in LDL blood cholesterol levels across PRS strata. The mean difference in LDL levels between the lowest and highest EAS-specific PRS (EAS_PRS) deciles was 0.82, compared to 0.59 for European-specific PRS (EUR_PRS) and 0.76 for multi-ancestry PRS. Notably, the mean LDL values in the top decile of multi-ancestry PRS were comparable to those of EAS_PRS (3.543 vs. 3.541, p = 0.86). Our analysis of the PRS prediction model for LDL cholesterol further supports the issue of PRS generalizability across populations. Our targeted analysis of the EAS population revealed that integrating non-European genotyping data with a powerful European-based GWAS can enhance the generalizability of LDL PRS.

PMID:38075701 | PMC:PMC10704094 | DOI:10.3389/fgene.2023.1286561

Front Genet. 2023 Nov 23;14:1285274. doi: 10.3389/fgene.2023.1285274. eCollection 2023.

ABSTRACT

Objective: According to the 2020 data from the World Health Organization (WHO), cancers stand as one of the foremost contributors to global mortality. Revealing novel cancer risk factors and protective factors is of paramount importance in the prevention of disease occurrence. Studies on the relationship between chemokines and cancer are ongoing; however, due to the coordination of multiple potential mechanisms, the specific causal association remains unclear. Methods: We performed a bidirectional Mendelian randomization analysis to explore the causal association between serum chemokines and pan-carcinoma. All data is from the GWAS catalog and IEU Open GWAS database. The inverse-variance weighted (IVW) method is primarily employed for assessing the statistical significance of the findings. In addition, the significance threshold after the multiple hypothesis test (Bonferroni) was 0.0013, and the evidence of a potential association was considered if the p-value < 0.05, but remained greater than Bonferroni’s threshold. Results: The results indicate that CCL1 (odds ratio, OR = 1.18), CCL2 (OR = 1.04), CCL8 (OR = 1.36), CCL14 (Colorectal, OR = 1.08, Small intestine, OR = 0.77, Lung, OR = 1.11), CCL15 (OR = 0.85), CCL18 (Breast, OR = 0.95, Prostate, OR = 0.96), CCL19 (Lung, OR = 0.66, Prostate, OR = 0.92), CCL20 (Lung, OR = 0.53, Thyroid, OR = 0.76), CCL21 (OR = 0.62), CCL22 (OR = 2.05), CCL23 (OR = 1.31), CCL24 (OR = 1.06), CCL27 (OR = 1.49), CCL28 (OR = 0.74), CXCL5 (OR = 0.95), CXCL9 (OR = 3.60), CXCL12 (Breast, OR = 0.87, Small intestine, OR = 0.58), CXCL13 (Breast, OR = 0.93, Lung, OR = 1.29), CXCL14 (Colon, OR = 1.40) and CXCL17 (OR = 1.07) are potential risk factors for cancers. In addition, there was a reverse causal association between CCL1 (OR = 0.94) and CCL18 (OR = 0.94) and breast cancer. Sensitivity analysis results were similar. The results of the other four MR Methods were consistent with the main results, and the leave-one-out method showed that the results were not driven by a Single nucleotide polymorphism (SNP). Moreover, there was no heterogeneity and pleiotropy in our analysis. Conclusion: Based on the two-sample MR Analysis method, we found that chemokines might be upstream factors of cancer pathogenesis. These results might provide new insights into the future use of chemokines as potential targets for cancer prevention and treatment. Our results also provide important clues for tumor prevention, and changes of serum chemokine concentration may be recognized as one of the features of precancerous lesions in future clinical trials.

PMID:38075694 | PMC:PMC10702354 | DOI:10.3389/fgene.2023.1285274