Category: Nevin Manimala

J Magn Reson Imaging. 2023 Dec 2. doi: 10.1002/jmri.29162. Online ahead of print.

ABSTRACT

BACKGROUND: Pancreatic ductal adenocarcinoma (PDA) is the third leading cause of cancer-related death in the United States. However, early response assessment using the current approach of measuring changes in tumor size on computed tomography (CT) or MRI is challenging.

PURPOSE: To investigate the feasibility of hyperpolarized (HP) [1-¹³ C]pyruvate MRI to quantify metabolism in the normal appearing pancreas and PDA, and to assess changes in PDA metabolism following systemic chemotherapy.

STUDY TYPE: Prospective.

SUBJECTS: Six patients (65.0 ± 7.6 years, 2 females) with locally advanced or metastatic PDA enrolled prior to starting a new line of systemic chemotherapy.

FIELD STRENGTH/SEQUENCE: 3-T, T1-weighted gradient echo, metabolite-selective ¹³ C echoplanar imaging.

ASSESSMENT: Time-resolved HP [1-¹³ C]pyruvate data were acquired before (N = 6) and 4-weeks after (N = 3) treatment initiation. Pyruvate metabolism, as quantified by pharmacokinetic modeling and metabolite area-under-the-curve ratios, was assessed in manually segmented PDA and normal appearing pancreas ROIs (N = 5). The change in tumor metabolism before and 4-weeks after treatment initiation was assessed in primary PDA (N = 2) and liver metastases (N = 1), and was compared to objective tumor response defined by response evaluation criteria in solid tumors (RECIST) on subsequent CTs.

STATISTICAL TESTS: Descriptive tests (mean ± standard deviation), model fit error for pharmacokinetic rate constants.

RESULTS: Primary PDA showed reduced alanine-to-lactate ratios when compared to normal pancreas, due to increased lactate-to-pyruvate or reduced alanine-to-pyruvate ratios. Of the three patients who received HP [1-¹³ C]pyruvate MRI before and 4-weeks after treatment initiation, one patient had a primary tumor with early metabolic response (increase in alanine-to-lactate) and subsequent partial response according to RECIST, one patient had a primary tumor with relatively stable metabolism and subsequent stable disease by RECIST, and one patient had metastatic PDA with increase in lactate-to-pyruvate of the liver metastases and corresponding progressive disease according to RECIST.

DATA CONCLUSION: Altered pyruvate metabolism with increased lactate or reduced alanine was observed in the primary tumor. Early metabolic response assessed at 4-weeks after treatment initiation correlated with subsequent objective tumor response assessed using RECIST.

LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

PMID:38041836 | DOI:10.1002/jmri.29162

J Immigr Minor Health. 2023 Dec 2. doi: 10.1007/s10903-023-01572-4. Online ahead of print.

ABSTRACT

This study aims to assess relationships between previous stroke diagnosis and demographic or disability status variables, stratified by U.S. citizenship status. The 2019 and 2021 National Health Interview Survey data were analyzed for both descriptive statistics and logistic regression models. Age, sex, income level, race/ethnicity, health insurance status, and indicators of disability common after stroke were predictor variables of interest. For each disability predictor variable, higher odds of having stroke were seen regardless of citizenship status, except for the ‘difficulty remembering’ variable. For U.S. citizens, increasing age corresponded with higher odds of stroke diagnosis. For noncitizens, odds ratios decreased from 40.3 (95% CI 38.88-41.82) for the 40-65 age group to 29.6 (95% CI 28.38-30.77) in the 80 + group, when compared with the 18-39 age reference group. Female noncitizens had higher odds of stroke, while male citizens had higher odds. Non-Hispanic Black citizens had higher odds of stroke, while the other racial/ethnic groups had higher odds for noncitizens. The results indicated the existence of several socio-demographic disparities in stroke. Notably, noncitizens experienced stroke at a younger age and reported more severe disability outcomes after stroke diagnosis than citizens.

PMID:38041795 | DOI:10.1007/s10903-023-01572-4

Langenbecks Arch Surg. 2023 Dec 2;408(1):454. doi: 10.1007/s00423-023-03181-z.

ABSTRACT

BACKGROUND: Rectal prolapse is a distressing condition for patients and no consensus exists on optimal surgical management. We compared outcomes of two common perineal operations (Delorme’s and Altemeier’s) used in the treatment of rectal prolapse.

METHODS: A systematic search of multiple electronic databases was conducted. Peri- and post-operative outcomes following Delorme’s and Altemeier’s procedures were extracted. Primary outcomes included recurrence rate, anastomotic dehiscence rate and mortality rate. The secondary outcomes were total operative time, volume of blood loss, length of hospital stay and coloanal anastomotic stricture formation. Revman 5.3 was used to perform all statistical analysis.

RESULTS: Ten studies with 605 patients were selected; 286 underwent Altemeier’s procedure (standalone), 39 had Altemeier’s with plasty (perineoplasty or levatoroplasty), and 280 had Delorme’s. Recurrence rate [OR: 0.66; 95% CI [0.44-0.99], P = 0.05] was significantly lower and anastomotic dehiscence [RD: 0.05; 95% CI [0.00-0.09], P = 0.03] was significantly higher in the Altemeier’s group. However, sub group analysis of Altemeier’s with plasty failed to show significant differences in these outcomes compared with the Delorme’s procedure. Length of hospital stay was significantly more following an Altemeier’s operation compared with Delorme’s [MD: 3.05, 95% CI [0.95 – 5.51], P = 0.004]. No significant difference was found in total operative time, intra-operative blood loss, coloanal anastomotic stricture formation and mortality rates between the two approaches.

CONCLUSIONS: A direct comparison of two common perineal procedures used in the treatment of rectal prolapse demonstrated that the Altemeier’s approach was associated with better outcomes. Future, well-designed high quality RCTs with long-term follow up are needed to corroborate our findings.

PMID:38041773 | DOI:10.1007/s00423-023-03181-z

Community Ment Health J. 2023 Dec 2. doi: 10.1007/s10597-023-01213-y. Online ahead of print.

ABSTRACT

This study examined the intersectional effects of gender, race, and socioeconomic status (SES) on mental health service utilization (MHSU) employing the intersectionality framework. Data was extracted from Canadian Community Health Survey 2015-2016 with a total of 85,619 sample. Covariate adjusted prevalence ratio (aPR) and the predicted probability of MHSU from intersectional analyses were estimated using Poisson regression with robust variance. The prevalence of MHSU was 15.04% overall, 19.61% among women, 10.27% among men, 21.56% among white women and 11.12% among white men. The study observed overall significant intersectional effect of SES by gender and race on MHSU. For instance, white men with the lowest income were more likely to have MHSU compared to their counterparts. Similarly, the predicted probability of MHSU decreased with the increase of SES that varied by gender and race. Two-way and three-way interactions also confirmed statistical significance (p-interaction < 0.05) of intersectional effect of gender, race, and SES. The observed socioeconomic differences in MHSU across gender and racial groups can be explained by intersectionality.

PMID:38041771 | DOI:10.1007/s10597-023-01213-y

Egypt Heart J. 2023 Dec 2;75(1):99. doi: 10.1186/s43044-023-00427-5.

ABSTRACT

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a hereditary myocardial disorder, often due to sarcomere gene mutations, characterized by the left ventricular hypertrophy. Current treatments offer symptomatic relief but lack specificity. Mavacamten, an allosteric inhibitor, has shown significant improvements in HCM patients in trials, reducing the requirement for invasive treatments. This meta-analysis assesses Mavacamten’s efficacy and safety as a targeted HCM intervention.

METHODS: This study examined four randomized controlled trials comparing Mavacamten to placebo in HCM patients. Each trial had a unique primary endpoint, and secondary outcomes included improvements in NYHA-FC, eligibility for septal reduction therapy (SRT) or undergoing it, adverse events (serious and treatment-related), atrial fibrillation, and non-sustained ventricular tachycardia. Statistical analysis involved calculating risk ratios (RRs) and assessing heterogeneity.

RESULTS: The four included studies showed minimal risk of bias and involved 503 patients with HCM (273 Mavacamten and 230 placebo). Mavacamten significantly increased the primary endpoint (RR 2.15, 95% CI 1.20-3.86, P = 0.01) and ≥ 1 NYHA-FC class (RR 2.21, 95% CI 1.48-3.3, P = 0.0001). Mavacamten group had lower rates of SRT compared to those receiving placebo (RR, 0.30, 95% CI 0.22-0.40; P < 0.00001). No significant differences existed in rates adverse events between the Mavacamten and placebo groups.

CONCLUSIONS: Our study suggests that Mavacamten may have therapeutic benefits for HCM patients, as indicated by its positive impact on certain endpoints. Further research with larger samples, longer follow-up, and comprehensive analysis is needed to understand Mavacamten’s safety and efficacy in HCM patients.

PMID:38041770 | DOI:10.1186/s43044-023-00427-5

Biochem Genet. 2023 Dec 2. doi: 10.1007/s10528-023-10580-w. Online ahead of print.

ABSTRACT

Data on the role of CYP2D6 and CYP3A4/5 polymorphisms in relation to risperidone (RIS) pharmacokinetics (PK) in children are relatively limited and inconsistent. This is partially attributable to the limited coverage of CYP2D6 and CYP3A4/5 metabolizer phenotypes, particularly those of poor and ultrarapid metabolizers (PMs and UMs), which has led to calls for studies of populations with a non-European background that may carry variants that are less frequent in Europeans. Children ≤ 18 years old with at least 8 weeks of a RIS-based regimen were recruited from three autism centers in Riyadh, Saudi Arabia. The primary outcomes measured were plasma concentrations of RIS and 9-hydroxyrisperidone (9-OH-RIS) and their dose-adjusted (C/D) ratios as a function of phenotypes and activity score (AS). For accurate DNA genotyping, targeted pharmacogenomic testing with the Axiom PharmacoFocus Array was performed via examination of a broad collection of probesets targeting CYP2D6 and CYP3A4/5 variants. The frequency of genotypes/phenotypes and the impact of their allele translation and phenoconversion-predicted enzyme activity were examined. The final cohort included 83 individuals. The most common CYP2D6 phenotype in our population was normal metabolizers (NMs, 66.3%). Inconsistent with some previous studies, the three phenotypes of intermediate metabolizers (IMs), NMs, and UMs were significantly different in terms of RIS concentration, the RIS/9-OH-RIS ratio, the RIS C/D ratio and the 9-OH-RIS C/D ratio. According to AS analyses, there were statistically significant differences in the RIS concentration (P = 0.013), RIS/9-OH-RIS ratio (P < 0.001) and RIS C/D ratio (P = 0.030) when patients were categorized into AS ≤ 1 vs. AS > 1. None of the CYP3A4/5 star allele translated phenotypes revealed a significant influence on any of the RIS PK parameters. Notably, neither CYP2D6 nor CYP3A4/5 phenotyping demonstrated a significant impact on the total active moiety, suggesting that other gene variants could modulate RIS PK. The study confirmed the previously reported partial impact of the CYP2D6 gene on RIS PK. However, future studies using contemporary genotyping techniques targeting a wide range of variants in other candidate genes must be conducted to further examine their interactive effects on RIS PK and the clinical response.

PMID:38041757 | DOI:10.1007/s10528-023-10580-w

Ir J Med Sci. 2023 Dec 2. doi: 10.1007/s11845-023-03583-4. Online ahead of print.

ABSTRACT

OBJECTIVE: The current study assessed the knowledge of the medical students regarding the nature of radiation, associated risks, and protective measures.

METHOD: A cross-sectional study was conducted among international students enrolled in different medical colleges/universities in Xian, PR China. A self-developed and self-reported questionnaire was used for the current study. The descriptive statistics was carried out to summarize the finding of the study. Chi-square and Fisher exact tests were conducted to assess the association of the demographics with knowledge level.

RESULTS: A total of 796 students responded among 980. Most of the participants fell in the age range of 20-25 years (42.6%), being male (67.1%) and having bachelor’s education (56.7%). Participants with previous experience was 58.7%. The age group of 20-25 years (p < 0.001), being male (p < 0.001), having bachelor education (p < 0.001), and previous experience (p = 0.009) was significantly associated with moderate to good knowledge. The overall knowledge about the nature of radiation (96%) and associated risk (82%) was good, but regarding protection, 59% of the participants showed good knowledge.

CONCLUSION: Most of the participants showed satisfactory result. However, the knowledge regarding protection measures was poor in almost half of the population.

PMID:38041750 | DOI:10.1007/s11845-023-03583-4

Pediatr Nephrol. 2023 Dec 2. doi: 10.1007/s00467-023-06224-1. Online ahead of print.

ABSTRACT

BACKGROUND: Split kidney function (SKF) is critical for treatment decision in pediatric patients with hydronephrosis and is commonly measured using renal scintigraphy (RS). Non-contrast-enhanced magnetic resonance urography (NCE-MRU) is increasingly used in clinical practice. This study aimed to investigate the feasibility of using NCE-MRU as an alternative to estimate SKF in pediatric patients with hydronephrosis, compared to RS.

METHODS: Seventy-five pediatric patients with hydronephrosis were included in this retrospective study. All patients underwent NCE-MRU and RS within 2 weeks. Kidney parenchyma volume (KPV) and texture analysis parameters were obtained from T2-weighted (T2WI) in NCE-MRU. The calculated split KPV (SKPV) percent and texture analysis parameters percent of left kidney were compared with the RS-determined SKF.

RESULTS: SKPV showed a significant positive correlation with SKF (r = 0.88, p < 0.001), while inhomogeneity was negatively correlated with SKF (r = – 0.68, p < 0.001). The uncorrected and corrected prediction models of SKF were established using simple and multiple linear regression. Bland-Altman plots demonstrated good agreement of both predictive models. The residual sum of squares of the corrected prediction model was lower than that of the uncorrected model (0.283 vs. 0.314) but not statistically significant (p = 0.662). Subgroup analysis based on different MR machines showed correlation coefficients of 0.85, 0.95, and 0.94 between SKF and SKPV for three different scanners, respectively (p < 0.05 for all).

CONCLUSIONS: NCE-MRU can be used as an alternative method for estimating SKF in pediatric patients with hydronephrosis when comparing with RS. Specifically, SKPV proves to be a simple and universally applicable indicator for predicting SKF. A higher resolution version of the Graphical abstract is available asSupplementary information.

PMID:38041747 | DOI:10.1007/s00467-023-06224-1

Neurosurg Rev. 2023 Dec 2;46(1):323. doi: 10.1007/s10143-023-02210-1.

ABSTRACT

The endoscopic transventricular transchoroidal approach facilitates entry into the posterior part of the third ventricle, allowing a visualization field from the foramen of Monro to the pineal region through this anatomical corridor. Combined surgery to treat the target lesion and possible endoscopic third ventriculostomy (ETV) can be performed through a single burr hole. A detailed description of this surgical technique is given, and a series of cases from our center is presented. This retrospective study included patients with lesions in the pineal region or posterior zone of the third ventricle who underwent surgery between 2004 and 2022 in our center for tumor biopsy or endoscopic cyst fenestration. In nine cases, the transchoroidal approach was performed. Demographic and clinical variables were collected: sex, age at diagnosis, clinical presentation, characteristics of the lesion, pathological diagnosis, characteristics of the procedure, complications, subsequent treatments, evolution, follow-up time, and degree of success of the endoscopic procedure. The mean and range of the quantitative variables and frequency of the qualitative variables were analyzed, together with the statistical significance (p < 0.05). Surgical planning was carried out by performing a preoperative MRI, calculating the ideal entry point and trajectory for each case. The preoperative planning of the surgical technique is described in detail. Of our sample, 55.6% were women, with a mean age of 35 years (7-78). The most common clinical presentation was intracranial hypertension (55.6%), with or without a focus. Eight patients presented hydrocephalus at diagnosis. The most frequent procedure was endoscopic biopsy with ETV (66.7%). The pathological diagnosis varied widely. Procedure-related complications included one case of self-limited bleeding of the choroidal fissure at its opening and one intraventricular hemorrhage due to tumor bleeding in the postoperative period. Non-procedure-related complications comprised two ETV failures and one case of systemic infection, while late complications included one case of disease progression and one case of radionecrosis. Four patients died, one due to poor neurological evolution after post-surgical tumor bleeding and three due to causes unrelated to the procedure. The rest of the patients had a favorable evolution and were asymptomatic or stable. The transchoroidal approach through a single burr hole is a feasible and safe option for access to the posterior part of the third ventricle. Proper planning of each case is necessary to avoid complications.

PMID:38041741 | DOI:10.1007/s10143-023-02210-1

Eur J Clin Microbiol Infect Dis. 2023 Dec 2. doi: 10.1007/s10096-023-04720-8. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the performance of core genome multilocus sequence typing (cgMLST) for genotyping Mycobacterium tuberculosis (M.tuberculosis) Strains in regions where the lineage 2 strains predominate.

METHODS: We compared clustering by whole-genome SNP typing with cgMLST clustering in the analysis of WGS data of 6240 strains from five regions of China. Using both the receiver operating characteristic (ROC) curve and epidemiological investigation to determine the optimal threshold for defining genomic clustering by cgMLST. The performance of cgMLST was evaluated by quantifying the sensitivity, specificity and concordance of clustering between two methods. Logistic regression was used to gauge the impact of strain genetic diversity and lineage on cgMLST clustering.

RESULTS: The optimal threshold for cgMLST to define genomic clustering was determined to be ≤ 10 allelic differences between strains. The overall sensitivity and specificity of cgMLST averaged 99.6% and 96.3%, respectively; the concordance of clustering between two methods averaged 97.1%. Concordance was significantly correlated with strain genetic diversity and was 3.99 times (95% CI, 2.94-5.42) higher in regions with high genetic diversity (π > 1.55 × 10^-4) compared to regions with low genetic diversity. The difference missed statistical significance, while concordance for lineage 2 strains (96.8%) was less than that for lineage 4 strains (98.3%). CONCLUSION : cgMLST showed a discriminatory power comparable to whole-genome SNP typing and could be used to genotype clinical M.tuberculosis strains in different regions of China. The discriminative power of cgMLST was significantly correlated with strain genetic diversity and was slightly lower with strains from regions with low genetic diversity.

PMID:38041721 | DOI:10.1007/s10096-023-04720-8