Nevin Manimala

Arch Gynecol Obstet. 2022 Mar 5. doi: 10.1007/s00404-022-06458-8. Online ahead of print.

ABSTRACT

ΟBJECTIVE: This study aimed at comparing survival outcomes between systematic axillary lymph node dissection (ALND) vs sentinel lymph node and axillary lymph node dissection only if sentinel positive (SLN ± ALND) in early-stage, clinically node-negative breast cancer patients. ΜETHODS: A systematic review and meta-analysis adhered to PRISMA guidelines was performed. Included studies were prospective randomized controlled trials (RCTs) comparing survival outcomes of ALND vs. SLN ± ALND in early-stage, node-negative breast cancer patients. Patients enrolled were only those with tumor size lower than 4 cm, clinically negative nodes and treated with breast-conservative surgery. Primary endpoints were locoregional recurrence, overall death and cancer-related death. RESULTS: There were four studies included in the analysis, enrolling overall 2982 patients, of which 1494 in ALND arm and 1488 in the SLN ± ALND arm. No statistically significant difference was observed in locoregional recurrence, breast cancer-related death and overall death. Locoregional recurrence was observed in 2.8% (ALND) vs. 4.1% (SLND ± ALND), (RR 0.69, 95% CI 0.20-2.30). Overall death rate was 7.0% vs. 6.8% respectively, (RR 1.00, 95% CI 0.73-1.39, I² = 28.7%). Breast cancer-related death was 3.6% vs. 3.5%, respectively (SLN ± ALND), (RR 1.11, 95% CI 0.70-1.78, I² = 0%). No statistically significant difference was observed in any of secondary study outcomes. CONCLUSIONS: Systematic axillary axillary lymph node dissection provides no survival benefit compared with sentinel lymph node dissection for early-stage clinically node-negative breast cancer patients.

PMID:35249123 | DOI:10.1007/s00404-022-06458-8

Prostate Cancer Prostatic Dis. 2022 Mar 5. doi: 10.1038/s41391-022-00516-7. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate the safety and efficacy transcatheter arterial chemoembolization (TACE) for the treatment of refractory gross hematuria (RGH) and urinary retention (UR) secondary to localized advanced prostate cancer (PCa).

PATIENTS AND METHODS: Thirty-two patients (mean age 72.5 years, range 60-89) with advanced PCa-related RGH that failed conventional therapy were included. Twenty-two of these patients had catheter-dependent due to PCa-related UR. TACE was performed with epirubicin (EPI)-eluting HepaSpheres (HS) plus intra-arterial (IA) infusion of docetaxel. Technical success, adverse events (AEs), overall survival (OS), control of RGH, removal of indwelling catheters, and local disease control, were evaluated.

RESULTS: Technical success was achieved in 100% without major AEs. Mean follow up post-TACE was 27 months (range 8-56 months) with a mean OS of 30 months. GRH stopped within 5 days after TACE in all patients, 26 (86.7%) of these patients exhibited good bleeding control during a mean follow-up of 24 months; 17 (77.3%) of the 22 patients with UR had recovered spontaneous urination, 15 (88.2%) patients were catheter-free at their last follow-up with a mean of 24 months. BS was obtained in 73.3% (22/30) of patients at a mean follow-up of 29 months. At the last visit, 22 patients had a mean of 36 months follow-up and the mean percentage reduction in prostate volume was 55.5%, with a statistically different from baseline (P = 0.022). Negative biopsy results were obtained in 84.2% (16/19) of the patients at 12-47 months after TACE. Compared with baseline values, there was a significant improvements in IPSS, QoL, Q_max, and PVR (all P < 0.05).

CONCLUSIONS: TACE using EPI-eluting HS plus IA infusion of docetaxel is a safe and effective treatment option for the advanced PCa patients with GRH and UR, and it could be considered as an alternative if there was no other therapeutic choice.

PMID:35249108 | DOI:10.1038/s41391-022-00516-7

Psychopathology. 2022 Mar 4:1-9. doi: 10.1159/000522309. Online ahead of print.

ABSTRACT

INTRODUCTION: The concept of mentalization is of central importance not only in modern psychotherapy but also in geriatric psychotherapy. In relation to older people, deficits in some aspects of the ability to mentalize, such as the theory of mind (ToM), affect perception, and metacognitive skills, are known. However, little is known about the mentalization ability of older people with mental disorders. The aim of the present study was to investigate the mentalizing abilities of older patients with depressive and anxious symptoms.

METHODS: In this study, the ability to mentalize using the Mentalization Questionnaire (MZQ), the HEALTH-49 questionnaire, Trail-Making Test (executive functions), and Reading-the-Mind-in-the-eyes-test (ToM) was studied in a clinical (n = 150) and a nonclinical comparison sample of people (n = 150) in different age groups (40-54, 55-69, ≥70). The evaluation of the data was conducted with different statistical methods, especially variance and regression analyses.

RESULTS: The clinical sample of all age groups showed significantly poorer mentalizing skills than the nonclinical samples. There were large correlations to health-related aspects. Additionally, in the regression analysis, only the setting variable (clinical vs. nonclinical) had an influence on the MZQ score and neither gender, education, executive functions nor ToM had a significant influence. Age also had no effect and did not correlate with MZQ scores but did correlate negatively with ToM.

CONCLUSIONS: The results show the importance of mentalization concepts for mental disorders in patients in the second half of life. There are indications of an imbalance of different aspects of mentalizing ability, especially between self- and other-related mentalizing abilities. Improving this balance could be a goal of therapeutic interventions.

PMID:35249029 | DOI:10.1159/000522309

J Clin Virol. 2022 Feb 19;148:105119. doi: 10.1016/j.jcv.2022.105119. Online ahead of print.

ABSTRACT

BACKGROUND: Rapid antigen detection tests (RADT) are commonly used as SARS-CoV-2 diagnostic tests both by medical professionals and laypeople. However, the performance of RADT in vaccinated individuals has not been fully investigated.

OBJECTIVES: RT-qPCR and rapid antigen detection testing were performed to evaluate the performance of the Standard Q COVID-19 Ag Test in detecting SARS-CoV-2 breakthrough infections in vaccinated individuals.

STUDY DESIGN: Two swab specimens, one for RT-qPCR and one for RADT, were collected from vaccinated individuals in an outpatient clinic. For comparison of RADT performance in vaccinated and unvaccinated individuals, a dataset already published by this group was used as reference.

RESULTS: During the delta wave, a total of 696 samples were tested with both RT-qPCR and RADT that included 692 (99.4%) samples from vaccinated individuals. Of these, 76 (11.0%) samples were detected SARS-CoV-2 positive by RT-qPCR and 45 (6.5%) samples by the Standard Q COVID-19 Ag test. Stratified by Ct values, sensitivity of the RADT was 100.0%, 94.4% and 81.1% for Ct ≤ 20 (n=18), Ct ≤ 25 (n=36) and Ct ≤ 30 (n=53), respectively. Samples with Ct values ≥ 30 (n=23) were not detected. Overall RADT specificity was 99.7% and symptom status did not affect RADT performance. Notably, RADT detected 4 out of 4 samples of probable Omicron variant infection based on single nucleotide polymorphism analysis.

CONCLUSION: Our results show that RADT testing remains a valuable tool in detecting breakthrough infections with high viral RNA loads.

PMID:35248992 | DOI:10.1016/j.jcv.2022.105119

Public Health. 2022 Mar 3;205:83-89. doi: 10.1016/j.puhe.2022.01.010. Online ahead of print.

ABSTRACT

OBJECTIVES: The aim of the present analysis is to identify the reasons for accepting or rejecting the invitation to be screened by the Faecal Immunochemical Test as part of the free Danish screening programme for colorectal cancer (CRC).

STUDY DESIGN: A cross-sectional representative survey of 15,072 Danish citizens aged 50-80 years was collected in 2019 via a Web-based questionnaire administered by Statistics Denmark. Among the net sample of 6807 respondents (45%), 177 were excluded because of current treatment for colorectal disease.

METHODS: To determine the reasons for accepting or refusing the invitation to be screened for CRC, a latent class analysis was conducted, which allowed participants to provide several reasons for acceptance or rejection of screening.

RESULTS: The most important reason for participating in CRC screening was the active public programme. A further reason for participation was the perceived risk for CRC, mainly in combination with the public programme. The reasons for participation did not differ between individuals who had participated and those who intended to participate when offered. Among participants who declined screening, the most frequent reasons were that they forgot to participate or that they were concerned about the unpleasant test procedure. Among individuals who intended to decline screening, a perceived low risk for CRC was the most frequently cited reason.

CONCLUSIONS: Recommendation from a general practitioner (GP) was not given as a frequent reason for CRC screening participation which is discussed as a challenge to participation rates in population based screening program The main reasons reported for non-participation in CRC screening (i.e. forgot to participate or the unpleasant test procedure) might be addressed by a stronger endorsement from GPs.

PMID:35248951 | DOI:10.1016/j.puhe.2022.01.010

Ecotoxicol Environ Saf. 2022 Mar 3;234:113371. doi: 10.1016/j.ecoenv.2022.113371. Online ahead of print.

ABSTRACT

BACKGROUND: The aim of this study was to investigate alterations in gut microbiota after exposure to air pollutants during pregnancy and its mediation effect in inducing adverse pregnancy outcomes (APOs).

METHODS: Participants (n = 916) were enrolled between 2017 and 2018 from a prospective cohort study of pregnant women in Guangzhou, China. The relative abundance of fecal microbiota was profiled using 16SrRNA V4 region sequencing. Exposure to air pollutants in each trimester of pregnancy was assessed using measurements from the nearest monitoring station. APOs including pre-term birth (PTB), post-term birth (POTB), low birth weight (LBW), macrosomia fetus (MF), birth defects (BDs), pathological cesarean section (PCS) and postpartum hemorrhage (PPH)) were determined by referring to reliable clinical records and diagnostic criteria. Univariate analysis, multivariate analysis and mediation analysis were performed to estimate the association among air pollutants, gut microbiota and APOs.

RESULTS: Air pollutants exposure during pregnancy was significantly correlated with the alterations in the gut microbiota, and increased risks of various APOs by 1.07-1.36-fold (P < 0.05). The mediation analyses indicated that alterations in Eggerthella, Phascolarctobacterium and Clostridium partially mediated the effects of air pollutants exposure (PM_2.5, PM₁₀, O₃, NO₂ and SO₂) on APOs. The relative abundance of f_Micrococcaceae explained 11.39%, 64.90% and 54.80% of the correlation between SO₂, PM_2.5, PM₁₀ and POTB, respectively; whereas g_Rothia explained 11.97%, 67.80% and 54.50%, respectively. g_Parabacteroides explained 53.0% of the correlation between PM_2.5 and PTB.

CONCLUSIONS: Increased air pollutants exposure during pregnancy may induce adverse pregnancy outcomes via alteration of the gut microbiota.

PMID:35248925 | DOI:10.1016/j.ecoenv.2022.113371

Arch Gerontol Geriatr. 2022 Feb 26;101:104668. doi: 10.1016/j.archger.2022.104668. Online ahead of print.

ABSTRACT

BACKGROUND: This study examined whether the hemoglobin concentration is correlated with the hippocampal volume using voxel-based morphometry (VBM).

METHODS: This cross-sectional study included 1923 community dwellers, aged 40‒89 years, from the sixth wave of the National Institute for Longevity Sciences, Longitudinal Study of Aging. The hemoglobin levels were determined through blood examination. The regional cortical volumes were evaluated using three-dimensional T1-weighted magnetic resonance images. Following preprocessing with a statistical parametric mapping software, a VBM analysis of covariance design was implemented to identify the regional gray matter volumes related to hemoglobin concentration, while adjusting for age, sex, education, body mass index, depressive symptoms, alcohol consumption status, smoking status, medical history, and the estimated glomerular filtration rate.

RESULTS: VBM analysis revealed a significantly positive correlation between the hemoglobin concentration and gray matter volume in the bilateral anterior hippocampus and the amygdala clusters as well as in the cingulate and middle temporal gyri, cerebellum, and superior sagittal and transverse sinuses.

CONCLUSIONS: The hemoglobin concentration could be positively associated with the hippocampal volume among community-dwelling middle-aged and older adults, which highlights the importance of monitoring the hemoglobin concentration in older adults to decrease the possibility of neurodegeneration.

PMID:35248921 | DOI:10.1016/j.archger.2022.104668

J Chromatogr B Analyt Technol Biomed Life Sci. 2022 Mar 2;1195:123204. doi: 10.1016/j.jchromb.2022.123204. Online ahead of print.

ABSTRACT

A specific and sensitive thin layer chromatographic method coupled with fluorescence detection for determination of flibanserin (FLN) that treats woman hypoactive sexual desire disorder was developed. The proposed method depends on the enhancement of FLN native fluorescence intensity via the exposure of the developed TLC plate to concentrated hydrochloric acid vapors. Herein, an evaporation setup needed for HCl vapors exposure step was designed for the first time to ensure a uniform distribution of the vapors throughout the developed bands on the plate. Chloroform: methanol (9.5: 0.5, v/v) was the optimum mobile phase that gave a compact band (R_f= 0.44 ± 0.02) using TLC aluminium plates precoated with silica gel G 60F₂₅₄ as a stationary phase. After exposure of the developed TLC plate to HCl vapors, the FLN bands emission intensities were measured after excitation at 275 nm. Conferring ICH guidelines, the linearity range was 20.0 – 1500.0 ng/band with a good linear relationship (r= 0.9998). Detection and quantitation limits were 5.12 and 15.50 ng/band, respectively. Also, the method was validated for accuracy, precision, robustness, specificity and selectivity. Statistical analysis verified the suitability of the proposed method for estimation of FLN in tablets and in human plasma with acceptable recoveries (98.07-101.45%).

PMID:35248898 | DOI:10.1016/j.jchromb.2022.123204

Cancer Epidemiol Biomarkers Prev. 2022 Mar 3:cebp.0724.2021. doi: 10.1158/1055-9965.EPI-21-0724. Online ahead of print.

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) has a strong epigenetic component that is accompanied by frequent DNA methylation (DNAm) alterations in addition to heritable genetic risk. It is of interest to understand the interrelationship of germline genetics, DNAm, and CRC risk.

METHODS: We performed a genome-wide methylation quantitative trait locus (meQTL) analysis in 1355 people, assessing the pairwise associations between genetic variants and lymphocytes methylation data. In addition, we used penalized regression with cis-genetic variants +/- 1Mb of methylation to identify genome-wide heritable DNAm. We evaluated the association of genetically predicted methylation with CRC risk based on GWAS of over 125,000 cases and controls using the multivariate sMiST as well as univariately via examination of marginal association with CRC risk.

RESULTS: Of the 142 known CRC genome-wide association studies (GWAS) loci, 47 were identified as meQTLs. We identified 4 novel CRC associated loci (NID2, ATXN10, KLHDC10 and CEP41) that reside over 1Mb outside of known CRC loci and 10 secondary signals within 1Mb of known loci.

CONCLUSIONS: Leveraging information of DNAm regulation into genetic association of CRC risk reveals novel pathways in CRC tumorigenesis. Our summary statistics-based framework sMiST provides a powerful approach by combining information from the effect through methylation and residual direct effects of the meQTLs on disease risk. Further validation and functional follow-up of these novel pathways are needed.

IMPACT: Using genotype, DNA methylation, GWAS, we identified four new CRC risk loci. We studied the landscape of genetic regulation of DNA methylation via single-SNP and multi-SNP meQTL analyses.

PMID:35247911 | DOI:10.1158/1055-9965.EPI-21-0724

Biosens Bioelectron. 2022 Feb 24;206:114117. doi: 10.1016/j.bios.2022.114117. Online ahead of print.

ABSTRACT

The innovation of this work lies in the trace detection of inflammatory biomarkers (IL-6, hs-CRP) in human exhaled breath condensate on the developed EBC-SURE platform as a point-of-care aid for respiratory disorder diagnosis. The unique design of the EBC-SURE leverages non-faradaic electrochemical impedance spectroscopy to capture target-specific biomolecular interactions for highly sensitive biomarker detection. For sensor calibration, EBC-SURE’s performance is assessed to measure the response of the sensor to a known concentration by spike and recovery analysis with a recovery error of <20% and an extended dynamic range over 3-log orders. The lowest detection limits for IL-6 and hs-CRP detection in EBC were found to be 3.2 pg/mL and 4 pg/mL respectively. The intra-assay and inter-assay efficacy of EBC-SURE for its usage as a diagnostic device was established through repeatability and reproducibility (over 48 h s) performance testing. The percentage variations (<20%) met the Clinical and Laboratory Standards Institute standards (CLSI) indicating a highly stable performance for robust biomarker detection. EBC-SURE generated highly selective IL-6 and hs-CRP responses in the presence of other non-specific cytokines. Statistical validation methods- Correlation and Bland Altman analysis established the one-to-one agreement between EBC-SURE and the reference method. Correlation analysis generated a Pearson’s R value of 0.99 for IL-6 and hs-CRP. Bland-Altman analysis indicated a good agreement between both the methods with all data points confined within the ±2SD limits. We have demonstrated EBC-SURE’s ability in detecting inflammatory biomarkers in human breath condensate towards developing a non-invasive technology that can quantify biomarker levels associated with healthy and acute inflammatory conditions.

PMID:35247857 | DOI:10.1016/j.bios.2022.114117