Category: Nevin Manimala

Ig Sanita Pubbl. 2023 Jan-Feb;80(1):13-26.

ABSTRACT

BACKGROUND: COVID-19 has hit every country in the world. Almost a quarter of a billion cases and nearly 5 million deaths reported globally as of late September 2021. Compared to over 6 billion doses of COVID-19 vaccine administered, the pandemic does not seem to disappear. The duration of protective immunity is currently not defined. Primary immune responses are inevitably declining and the continuous transmission of increasingly worrying viral variants.

OBJECTIVE: The primary objective of the study is to evaluate the antibody response at 120 and 180 days in employees of an hospital of Marche (Italy) who have completed the vaccination cycle with Pzifer-Biontech vaccine and to highlight the correlation with quantitative and qualitative variables. The secondary objective is to study the nature and frequency of adverse events in relation to variables such as comorbidity, age, gender, working areas and developed antibody titer.

MATERIALS AND METHODS: An observational retrospective study was carried out to evaluate the antibody response at 120 and 180 days. Subjects receiving a double dose of vaccine at least 21 days apart and those receiving the second dose of the same vaccine between 18 January 2021 and 31 March 2021 shall be considered. The study included non-probability sampling of convenience. All parties have provided informed written consent to access personal and clinical data.

RESULTS: The sample is composed by 1.115 subjects. The results of the study reveal an important immune response detected by IgG dosage, both at 120 and 180 days after the second dose of Sars-Cov-2 vaccine mRNA BNT162b2 vaccine (Pzifer-Biontech), other than very rare exceptions. Antibody values are higher among hospital workers compared to those working in other areas, both 120 and 180 days. These values are even higher in the health professionals who provide assistance in wards with positive Covid patients, both at 120 days (p=0.06) and at 180 days; the mean values of IgG are statistically higher in direct assistance of Covid patients at 180 days(p=0.029). The most frequent adverse drug events after the second dose of vaccine were pain at the site of inoculation of the vaccine (70.7%), fatigue (35%) and arthralgia (19%). It was finally shown that people with diabetes or smokers had an average antibody response statistically lower than 120 days and 180 days from the second dose.

DISCUSSION AND CONCLUSION: This study leads to the conclusion that the second dose of vaccine Sars-Cov-2 vaccine mRNA BNT162b2 vaccine allows a consistent antibody response. Further multicentric studies are needed to investigate the antibody response to vaccination Sars-Cov-2 mRNA BNT162b2.

PMID:36749593

JAMA Netw Open. 2023 Feb 1;6(2):e2255098. doi: 10.1001/jamanetworkopen.2022.55098.

ABSTRACT

IMPORTANCE: A civil war that lasted for about 6 months in the North Wollo zone of Ethiopia destroyed numerous health care facilities. However, no studies have been conducted to determine the association of the war with vaccination dropout in the area.

OBJECTIVE: To assess the association of war with vaccination dropout among children younger than 2 years in the North Wollo zone.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cross-sectional study was conducted in the North Wollo zone from April 1 to June 30, 2022. Participants included children younger than 2 years and their mothers. A multistage sampling technique was used to select the participants.

MAIN OUTCOMES AND MEASURES: A vaccination dropout rate (yes or no) was assessed by interviewing mothers.

RESULTS: The study included 449 children younger than 2 years and their mothers, 291 (64.8%) of whom were 20 to 34 years of age. Almost all of the mothers (426 [94.9%]) were married. More than half of the mothers (271 [60.4%]) had a primary level education. Seventy-one children (15.8%) in the area received all basic vaccinations. One hundred ninety-eight children (44.1%) who started vaccination prior to the war dropped out of the immunization program. Additionally, 64 children (14.3%) born during the war did not receive any vaccination. Losing a family member (adjusted odds ratio [AOR], 3.11 [95% CI, 1.63-5.93]; P = .001), not being informed about catch-up vaccination (AOR, 2.18 [95% CI, 1.39-3.43]; P < .001), being a rural resident (AOR, 2.22 [95% CI, 1.37-3.58]; P < .001), home birth (AOR, 1.75 [95% CI, 1.11-2.77]; P = .002), and length of war (AOR for 5 months, 0.51 [95% CI, 0.28-0.93; P = .04]) were associated with the outcome variable.

CONCLUSIONS AND RELEVANCE: The findings of this cross-sectional study suggest that nearly 60% of children in the North Wollo zone remained undervaccinated or unvaccinated. Stakeholders should make coordinated efforts to overcome the humanitarian crisis in the area and optimize the accessibility of health services.

PMID:36749587 | DOI:10.1001/jamanetworkopen.2022.55098

Curr Med Res Opin. 2023 Feb 7:1-31. doi: 10.1080/03007995.2023.2177380. Online ahead of print.

ABSTRACT

OBJECTIVE: Type 2 diabetes mellitus (T2DM) and impaired kidney function are associated with a higher risk of poor outcomes of COVID-19. We conducted a retrospective study in hospitalized T2DM patients with COVID-19 to assess the association between in-hospital mortality and admission values of different hematological/biochemical parameters, including estimated glomerular filtration rate (eGFR), plasma glucose and C-peptide (as a marker of beta-cell function).

METHODS: The study included T2DM patients with confirmed SARS-CoV-2 infection who were consecutively admitted to our Institution between October 1, 2020 and April 1, 2021.

RESULTS: Patients (n = 74) were categorized into survivors (n = 55) and non-survivors (n = 19). Non-survivors exhibited significantly higher median WBC count, D-dimer, neutrophil-to-lymphocyte ratio, hsCRP, and procalcitonin levels, as well as significantly lower median serum 25(OH)D levels compared to survivors. Non-survivors exhibited significantly higher median admission plasma glucose (APG) values compared to survivors (210 vs 166 mg/dL; p = 0.026). There was no statistically significant difference in median values of plasma C-peptide between non-survivors and survivors (3.55 vs 3.24 ng/mL; p = 0.906). A significantly higher percentage of patients with an eGFR < 60 mL/min/1.73 m² was observed in the non-survivor group as compared to the survivor group (57.9% vs 23.6%; p = 0.006). A multivariate analysis performed by a logistic regression model after adjusting for major confounders (age, sex, body mass index, major comorbidities) showed a significant inverse association between eGFR values and risk of in-hospital mortality (OR, 0.956; 95% CI, 0.931-0.983; p = 0.001). We also found a significant positive association between WBC count and risk of in-hospital mortality (OR, 1.210; 95% CI, 1.043-1.404; p = 0.011).

CONCLUSIONS: Admission eGFR and WBC count predict in-hospital COVID-19 mortality among T2DM patients, independently of traditional risk factors, APG and random plasma C-peptide. Hospitalized patients with COVID-19 and comorbid T2DM associated with impaired kidney function at admission should be considered at high risk for adverse outcomes and death.

PMID:36749566 | DOI:10.1080/03007995.2023.2177380

Adv Ther. 2023 Feb 7. doi: 10.1007/s12325-023-02433-0. Online ahead of print.

ABSTRACT

INTRODUCTION: This study was conducted to elucidate the safety of roxadustat, an oral medication, in patients with non-dialysis-dependent (NDD) or incident dialysis dialysis-dependent (ID-DD) chronic kidney disease (CKD).

METHODS: Safety results from four phase 3, randomized, open-label studies comparing roxadustat to an erythropoiesis-stimulating agent (ESA) in men and women with NDD or ID-DD CKD with anemia were pooled and evaluated. Endpoints were time to major adverse cardiovascular event (MACE; myocardial infarction, stroke, and all-cause mortality) and MACE+ (MACE plus congestive heart failure or unstable angina requiring hospitalization), all-cause mortality, and treatment-emergent adverse events (TEAEs). MACE and MACE+ were evaluated for non-inferiority at 1.8- and 1.3-margins using hazard ratios (HRs) and 95% confidence intervals (CIs). TEAEs were descriptively summarized.

RESULTS: In total, 2142 patients were evaluated (1083 roxadustat; 1059 ESA). Roxadustat was comparable to ESA for risk of MACE (HR 0.79, 95% CI 0.61-1.02), MACE+ (HR 0.78, 95% CI 0.62-0.98), and all-cause mortality (HR 0.78, 95% CI 0.57-1.05). TEAEs were comparable between roxadustat and ESA groups, including any TEAE [incidence rate per 100 (IR/100) patient-exposure years 56.1 vs. 53.5], TEAEs leading to study drug discontinuation (IR/100 patient-exposure years 6.7 vs. 5.1), and TEAEs leading to death (IR/100 patient-exposure years 6.9 vs. 7.4).

CONCLUSION: There was no evidence of increased risk of cardiovascular events or mortality with roxadustat compared with ESA in patients with anemia who have NDD or ID-DD CKD. Although TEAEs occurred commonly in both the roxadustat and ESA groups, patients infrequently discontinued the study drug because of an adverse event.

CLINICAL TRIAL REGISTRATION NUMBERS: DOLOMITES, 1517-CL-0610 [NCT02021318]; HIMALAYAS, FGCL-4592-063 [NCT02052310]; SIERRAS, FGCL-4592-064 [NCT02273726]; and ROCKIES, D5740C00002 [NCT02174731].

PMID:36749544 | DOI:10.1007/s12325-023-02433-0

J Mol Neurosci. 2023 Feb 7. doi: 10.1007/s12031-023-02104-3. Online ahead of print.

ABSTRACT

Cytohesin-4 (CYTH4) is a member of the PSCD family. Members of this family appear to mediate the regulation of protein sorting and membrane trafficking. In previous studies, CYTH4 has been linked with multiple brain diseases, but not glioma, the most common type of brain tumor. We utilized multiple glioma single-cell RNA sequencing datasets and bulk data from the TCGA and CGGA and conducted GSEA and KEGG and GO analyses. Biomarker potential was tested via ROC curve analysis. Radar plots were used to study TMB and MSI correlations. Immune cell studies were conducted using CIBERSORT. All statistical analyses were performed in R software and GraphPad Prism 9. CYTH4 was overexpressed in the glioma macrophage population in several single-cell RNA sequencing datasets and was most correlated with M2 macrophages. CYTH4 expression was higher in tumor tissues and was correlated with survival and WHO grade. ROC curves suggested CYTH4 overexpression to be a potential glioma biomarker. GSEA results indicated a relationship between CYTH4 and apoptosis, and PPI analysis supported a pyroptosis correlation. KEGG and GO analysis results linked CYTH4 with antigen processing and presentation and neutrophil activities. In summary, the study identified a CYTH4/pyroptosis/M2 macrophage axis. CYTH4 was upregulated in M2 macrophages in glioma and affected pyroptosis. CYTH4 overexpression is a potential biomarker predicting a poor prognosis.

PMID:36749492 | DOI:10.1007/s12031-023-02104-3

Med Oncol. 2023 Feb 7;40(3):91. doi: 10.1007/s12032-023-01949-3.

ABSTRACT

A significant mortality rate is associated with oral cancer, particularly in cases of late-stage diagnosis. Since the last decades, oral cancer survival rates have only gradually improved despite advances in treatment. This poor success rate is mainly due to the development of secondary tumors, local recurrence, and regional failure. Invasive treatments frequently have a negative impact on the aesthetic and functional outcomes of survivors. Novel approaches are thus needed to manage this deadly disease in light of these statistics. In photodynamic therapy (PDT), a light-sensitive medication called a photosensitizer is given first, followed by exposure to light of the proper wavelength that matches the absorbance band of the photosensitizer. The tissue oxygen-induced cytotoxic free radicals kill tumor cells directly, harm the microvascular structure, and cause inflammatory reactions at the targeted sites. In the case of early lesions, PDT can be used as a stand-alone therapy, and in the case of advanced lesions, it can be used as adjuvant therapy. The current review article discussed the uses of PDT in oral cancer therapy based on recent advances in this field.

PMID:36749489 | DOI:10.1007/s12032-023-01949-3

Pharmacol Rep. 2023 Feb 7. doi: 10.1007/s43440-023-00455-7. Online ahead of print.

ABSTRACT

BACKGROUND: Perioperative anesthetic and/or analgesic demand present considerable variation, and part of that variation appears to be genetic in origin. Here we investigate the impact of common polymorphisms in OPRM1, COMT, SLC6A4, ABCB1, and CYP2B6 genes, on the intra-operative consumption of remifentanil and propofol, as well as the postoperative analgesic needs, in patients subjected to thyroidectomy surgery.

METHODS: We conducted a prospective cohort study with 90 patients scheduled to undergo elective thyroidectomy, under total intravenous anesthesia achieved by target control infusion (TCI) of propofol and remifentanil. Postoperative analgesics were administered by protocol and on-demand by the individual patient. Genotyping was established by PCR-RFLP methods. Genotyping data, intra-operative hemodynamics, and total consumption of remifentanil and propofol, as well as postoperative analgesic needs and pain perception, were recorded for each individual.

RESULTS: Patients with the ABCB1 3435TT genotype appeared to experience significantly less pain within one hour post-operatively, compared to C carriers [mean VAS (SD) = 0.86 (1.22) vs. 2.42 (1.75); p = 0.017], a finding limited to those seeking rescue analgesic treatment. Intra-operatively, homozygotes patients for the minor allele of OPRM1 A118G and CYP2B6 G516T appeared to consume less remifentanil [mean (SD) = 9.12 (1.01) vs. 13.53 (5.15), for OPRM1 118GG and A carriers] and propofol [median (range) = 14.95 (11.53, 1359.5) vs. 121.4 (1.43, 2349.4), for CYP2B6 516TT and G carriers, respectively] but the difference was not statistically significant in our sample.

CONCLUSIONS: The ABCB1 C3435T polymorphism appears to affect the postoperative perception of surgical pain among patients with low pain threshold. The small number of minor allele homozygotes for the OPRM1 A118G and CYP2B6 G516T polymorphisms precludes a definitive conclusion regarding the inclusion of the latter in a TCI-programming algorithm, based on the results of this study.

CLINICAL TRIAL REGISTRATION NUMBER: ACTRN12616001598471.

PMID:36749481 | DOI:10.1007/s43440-023-00455-7

Rheumatol Ther. 2023 Feb 7. doi: 10.1007/s40744-022-00523-z. Online ahead of print.

ABSTRACT

INTRODUCTION: Currently there is limited data to drive clinical decision making regarding the choice of biologic/targeted synthetic disease-modifying antirheumatic drugs (DMARD); thus, head-to-head comparisons are needed to help guide prescribing. In recent years, significant advancements have helped clarify the mechanistic basis of the clinical associations of autoantibodies in rheumatoid arthritis (RA). This study evaluated the effectiveness of abatacept versus tofacitinib in anti-cyclic citrullinated peptide (CCP+) patients with rheumatoid arthritis (RA).

METHODS: CorEvitas (formerly known as CORRONA) Registry patients aged ≥ 18 years, who were CCP+ before initiating abatacept or tofacitinib (December 2012 onwards through October 2019), had 6-month follow-up data (baseline and 6-month Clinical Disease Activity Index [CDAI]), and were not in remission at index were included. Patients were frequency matched 1:1 by prior biologic use before propensity score matching (PSM). Primary (mean change [D] in CDAI) and secondary outcomes 6 months after index were compared using mixed-effects models adjusted for variables that remained unbalanced after PSM.

RESULTS: Following PSM, most baseline characteristics for 291 patient pairs were well balanced between treatments, although fewer patients initiating abatacept versus tofacitinib received prior non-TNFi biologic DMARDs, and patients initiating abatacept versus tofacitinib had a higher physician global assessment score, patient-reported fatigue, and modified Health Assessment Questionnaire (mHAQ). In adjusted analyses, there were no significant differences in mean [D] from baseline in CDAI at 6 months with abatacept versus tofacitinib (P = 0.936). Patients naïve for b/tsDMARDs initiating abatacept had a numerically greater mean [D] in CDAI at 6 months versus tofacitinib, although this difference was not statistically significant (P = 0.662). There were no significant differences for any secondary outcomes.

CONCLUSIONS: In adjusted analyses, CCP+ patients with RA initiating treatment with abatacept versus tofacitinib did not show a statistically significant difference in reducing disease activity or improving patient-reported outcomes.

PMID:36749478 | DOI:10.1007/s40744-022-00523-z

Int Urol Nephrol. 2023 Feb 7. doi: 10.1007/s11255-023-03506-3. Online ahead of print.

ABSTRACT

INTRODUCTION: Chronic anemia, iron overload, and iron chelation therapy are the main contributing factors for renal complications in thalassemia, e.g., nephrolithiasis, glomerular disease, and renal tubular dysfunction. The prevalence and associated factors for developing renal dysfunctions in Thai patients with thalassemia, however, remained limited. This study aimed to determine the prevalence and risk factors of renal dysfunctions in patients with thalassemia.

METHODS: A cross-sectional study was conducted on adult patients with thalassemia disease at Srinagarind Hospital, Khon Kaen University, Thailand. All patients were evaluated for complete blood count, blood chemistry, urinalysis, and urine biochemistry. Renal tubular dysfunction was defined as existing in at least one of the following parameters including; proteinuria, hypercalciuria, hypouricemia with uricosuria, or hypophosphatemia with phosphaturia. Logistic regression analysis was used to identify associated factors for renal dysfunctions.

RESULTS: Of 105 patients, renal tubular dysfunction was found in 60 patients (57.1%). In multivariate analysis of the clinical risk factors for renal tubular dysfunction in thalassemia patients, age per 10 year increase (adjusted odds ratio [AOR] = 1.4, 95% CI: 1.0-2.0, p value 0.01) and Hb E/beta-thalassemia (AOR = 3.6, 95% CI: 1.3-10.3, p value 0.01) were statistically proven to be associated with renal tubular dysfunction. Hyperuricosuria was a significantly associated factor for microhematuria. (AOR = 2.9, 95% CI: 1.1-8.0, p value 0.03).

CONCLUSIONS: Renal dysfunctions are prevalent in thalassemia patients, with older age and Hb E/beta-thalassemia genotype as significant risk factors for renal tubular dysfunction. Hyperuricosuria is a risk factor for microhematuria. Renal dysfunctions should be recognized and monitored in aging patients with Hb E/beta-thalassemia.

PMID:36749473 | DOI:10.1007/s11255-023-03506-3

Forensic Sci Med Pathol. 2023 Feb 7. doi: 10.1007/s12024-023-00583-9. Online ahead of print.

ABSTRACT

The Abbreviated Injury Scale (AIS) and Injury Severity Score (ISS) are important evaluation tools used in clinical practice to determine the degree of injury in patients with trauma. However, they are not suitable for forensic practice and their use in forensic applications is limited. This study aimed to present a system that can objectively and quantitatively determine the severity of postmortem injuries and that can be applied to forensic medicine. Subsequently, we applied this system to individual postmortem cases and analyzed the injuries identified during autopsy. We performed a retrospective study of 119 autopsies performed between 2018 and 2021. Data were categorized and analyzed using the Forensic Injury Severity Score Template (FISST), a scoring system developed based on the AIS and ISS. The mean FISST scores were as follows: men, 53.6; women, 46.8; 20-65 years old, 55.6; older than 65 years, 41.4; natural death, 13.8; unnatural death, 66.3; and all deaths, 51.8. Statistically significant differences in the FISST scores were found between natural and unnatural deaths, suicidal and accidental deaths, and trauma-related death subtypes. Injuries identified during autopsy can be objectively and quantitatively evaluated using FISST. We suggest that FISST is a useful tool in forensic medicine because it is tailor-made for injury evaluation from a postmortem perspective.

PMID:36749470 | DOI:10.1007/s12024-023-00583-9