Category: Nevin Manimala

J Cancer Res Clin Oncol. 2023 Jan 21. doi: 10.1007/s00432-023-04588-3. Online ahead of print.

ABSTRACT

BACKGROUND: The most prevalent subtype of breast cancer (BC) is luminal hormonal-positive breast cancer. The neoadjuvant chemotherapy regimens have side effects, emphasizing the need to identify new startegies.

OBJECTIVE: Analyze the complete pathologic response (pCR) rate and overall response in a low-risk hormone-positive subset of patients receiving neoadjuvant hormone treatment (NAHT) with or without Palbociclib (a CDK4/CDK6 inhibitor) to boost NAHT effectiveness.

MATERIALS AND METHODS: Based on the upfront 21-gene Oncotype DX or low-risk Breast Recurrence Score assay (RS™), the SAFIA trial is designed as a prospective multicenter international, double-blind neoadjuvant phase-III trial that selects operable with luminal BC patients that are HER2-negative for the induction hormonal therapy with Fulvestrant 500 mg ± Goserelin (F/G) followed by randomization of responding patients to palbociclib versus placebo. The pCR rate served as the study’s main outcome, while the secondary endpoint was a clinical benefit.

RESULTS: Of the 354 patients enrolled, 253 initially responded and were randomized to either F/G fulvestrant with palbociclib or placebo. Two hundred twenty-nine were eligible for the evaluation of the pathologic response. No statistically significant changes were observed in the pCR rates for the patients treated with the F/G therapy with placebo or palbociclib (7% versus 2%, respectively) per the Chevallier classification (Class1 + Class2) (p = 0.1464) and 3% versus 10% assessed per Sataloff Classification (TA, NA/NB) (p = 0.3108). Palbociclib did not increase the rate of complete pathological response.

CONCLUSION: Neoadjuvant hormonal therapy is feasible in a selected population with a low RS score of < 31 CLINICAL TRIAL: NCT03447132.

PMID:36680581 | DOI:10.1007/s00432-023-04588-3

Neuroradiology. 2023 Jan 21. doi: 10.1007/s00234-022-03111-8. Online ahead of print.

ABSTRACT

PURPOSE: This study assessed the position of the termination of the conus medullaris (the point where the spinal cord tapers to an end) and thecal sac (the sheath of dura mater that surrounds the spinal cord and caudal nerve roots) in a large pediatric population, to characterise the nature of the pediatric Gaussian distribution and assess whether age affected the distribution. The study further aimed to assess the effect of gender on termination positions.

METHODS: A total of 520 MRI spine studies of children aged between 1 month and 19 years old were collected from two pediatric tertiary referral centres in the UK and Italy. Studies with pathological findings were excluded, and normal scans were found using keyword search algorithms on a database of radiologists’ reports. The reported scans were individually assessed and reviewed by two experienced neuroradiologists. The termination points of the conus medullaris and thecal sac were determined for each study. Local IRB approvals were sought.

RESULTS: The results showcased a Gaussian distribution in both conus medullaris (r=0.8997) and thecal sac termination levels (r=0.9639). No statistically significant results were noted with increasing age for the termination positions of the conus medullaris or thecal sac (p = 0.154, 0.063). No statistical significance was observed with gender variation with either anatomical landmark. A weak positive correlation was observed between the termination levels of the conus medullaris and the thecal sac (r=0.2567) CONCLUSION: Termination levels across all pediatric age range followed a Gaussian distribution. Knowledge of normal termination levels has relevant clinical implications, including the assessment of patients with suspected spinal dysraphism.

PMID:36680571 | DOI:10.1007/s00234-022-03111-8

Inflamm Bowel Dis. 2023 Jan 21:izac273. doi: 10.1093/ibd/izac273. Online ahead of print.

ABSTRACT

BACKGROUND: Inflammatory bowel disease (IBD) is associated with an increased risk of osteoporosis and bone fracture. The aims of this study were to (1) confirm the association between IBD and low bone density and (2) test for shared risk variants across diseases.

METHODS: The study cohort included patients from the Michigan Genomics Initiative. Student’s t tests (continuous) and chi-square tests (categorical) were used for univariate analyses. Multivariable logistic regression was performed to test the effect of IBD on osteoporosis or osteopenia. Publicly available genome-wide association summary statistics were used to identify variants that alter the risk of IBD and bone density, and Mendelian randomization (MR) was used to identify causal effects of genetically predicted IBD on bone density.

RESULTS: There were 51 405 individuals in the Michigan Genomics Initiative cohort including 10 378 (20.2%) cases of osteoporosis or osteopenia and 1404 (2.7%) cases of IBD. Patients with osteoporosis or osteopenia were more likely to be older (64 years of age vs 56 years of age; P < .001), female (67% vs 49%; P < .001), and have a lower body mass index (29 kg/m2 vs 30 kg/m2; P < .001). IBD patients with (odds ratio, 4.60; 95% confidence interval, 3.93-5.37) and without (odds ratio, 1.77; 95% confidence interval, 1.42-2.21) steroid use had a significantly higher risk of osteoporosis or osteopenia. Twenty-one IBD variants associated with reduced bone mineral density at P ≤ .05 and 3 IBD risk variants associated with reduced bone mineral density at P ≤ 5 × 10-8. Of the 3 genome-wide significant variants, 2 increased risk of IBD (rs12568930-T: MIR4418;ZBTB40; rs7236492-C: NFATC1). MR did not reveal a causal effect of genetically predicted IBD on bone density (MR Egger, P = .30; inverse variance weighted, P = .63).

CONCLUSIONS: Patients with IBD are at increased risk for low bone density, independent of steroid use. Variants in or near ZBTB40 and NFATC1 are associated with an increased risk of IBD and low bone density.

PMID:36680554 | DOI:10.1093/ibd/izac273

Dev Sci. 2023 Jan 21:e13373. doi: 10.1111/desc.13373. Online ahead of print.

ABSTRACT

Recent years have seen a flourishing of Natural Language Processing models that can mimic many aspects of human language fluency. These models harness a simple, decades-old idea: It is possible to learn a lot about word meanings just from exposure to language, because words similar in meaning are used in language in similar ways. The successes of these models raise the intriguing possibility that exposure to word use in language also shapes the word knowledge that children amass during development. However, this possibility is strongly challenged by the fact that models use language input and learning mechanisms that may be unavailable to children. Across three studies, we found that unrealistically complex input and learning mechanisms are unnecessary. Instead, simple regularities of word use in children’s language input that they have the capacity to learn can foster knowledge about word meanings. Thus, exposure to language may play a simple but powerful role in children’s growing word knowledge. Highlights Natural Language Processing (NLP) models can learn that words are similar in meaning from higher-order statistical regularities of word use. Unlike NLP models, infants and children may primarily learn only simple co-occurrences between words. We show that infants’ and children’s language input is rich in simple co-occurrence that can support learning similarities in meaning between words. We find that simple co-occurrences can explain infants’ and children’s knowledge that words are similar in meaning. This article is protected by copyright. All rights reserved.

PMID:36680539 | DOI:10.1111/desc.13373

Health Inf Manag. 2023 Jan 21:18333583221144662. doi: 10.1177/18333583221144662. Online ahead of print.

ABSTRACT

BACKGROUND: Healthcare data frequently lack the specificity level needed to achieve clinical and operational objectives such as optimising bed management. Pneumonia is a disease of importance as it accounts for more bed days than any other lung disease and has a varied aetiology. The condition has a range of SNOMED CT concepts with different levels of specificity.

OBJECTIVE: This study aimed to quantify the importance of the specificity of an SNOMED CT concept, against well-established predictors, for forecasting length of stay for pneumonia patients.

METHOD: A retrospective data analysis was conducted of pneumonia admissions to a tertiary hospital between 2011 and 2021. For inclusion, the primary diagnosis was a subtype of bacterial or viral pneumonia, as identified by SNOMED CT concepts. Three linear mixed models were constructed. Model One included known predictors of length of stay. Model Two included the predictors in Model One and SNOMED CT concepts of lower specificity. Model Three included the Model Two predictors and the concepts with higher specificity. Model performances were compared.

RESULTS: Sex, ethnicity, deprivation rank and Charlson Comorbidity Index scores (age-adjusted) were meaningful predictors of length of stay in all models. Inclusion of lower specificity SNOMED CT concepts did not significantly improve performance (ΔR² = 0.41%, p = .058). SNOMED CT concepts with higher specificity explained more variance than each of the individual predictors (ΔR² = 4.31%, p < .001).

CONCLUSION: SNOMED CT concepts with higher specificity explained more variance in length of stay than a range of well-studied predictors.

IMPLICATIONS: Accurate and specific clinical documentation using SNOMED CT can improve predictive modelling and the generation of actionable insights. Resources should be dedicated to optimising and assuring clinical documentation quality at the point of recording.

PMID:36680531 | DOI:10.1177/18333583221144662

Pediatr Int. 2023 Jan;65(1):e15359. doi: 10.1111/ped.15359.

ABSTRACT

BACKGROUND: This non-randomized intervention study aimed to evaluate the effect of supplementing infant formula with biotin on biotin metabolism and on development.

METHODS: We enrolled healthy Japanese infants (n = 84) and assigned them to groups offered Formula A (total biotin, 0.5 μg/100 kcal) or Formula B (total biotin, 2.4 μg/100 kcal) until they were 6 months of age, and completed an additional follow up to age 36 months. Urinary biotin concentrations were measured at 1 and 6 months, and were compared among breast-fed, Formula A-fed, and Formula B-fed infants at each age. In a follow-up subgroup analysis, we compared scores on the Ages and Stages Questionnaire, version 3 (ASQ-3), from 9 to 36 months among infants continuously fed Formula A, Formula B, or breastmilk.

RESULTS: No adverse events occurred during the intervention period. At 1 month, urinary biotin concentrations were highest in Formula B-fed infants and lowest in Formula A-fed infants. At 6 months, Formula B-fed infants retained higher biotin levels than Formula A-fed and breast-fed infants. Both differences were statistically significant (P < 0.05). The breast-fed, Formula A-fed, and Formula B-fed groups had similar ASQ scores at 9-36 months.

CONCLUSIONS: Biotin supplementation of infant formula contributed to improving biotin status in formula-fed infants. The results support the official approval of the use of biotin in infant formula by the government of Japan in 2014.

PMID:36680523 | DOI:10.1111/ped.15359

Med Phys. 2023 Jan 21. doi: 10.1002/mp.16232. Online ahead of print.

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) detection with B-mode and contrast-enhanced ultrasound (CUS) imaging often varies between subjects, especially in patients with background cirrhosis. Various factors contribute to this variability, including the tumor blood flow, tumor size, internal echoes, and its location in livers with diffuse fibro-cirrhotic changes OBJECTIVE: Towards improving lesion detection, this study evaluates a vasodilator, hydralazine, to enhance the visibility of HCC by reducing its blood flow relative to the surrounding liver tissue.

METHODS: HCC were analyzed for tumor visibility measured for B-mode, CUS, and hydralazine-augmented-contrast ultrasound (HyCUS) in an autochthonous HCC rat model. 21 tumors from 12 rats were studied. B-mode and CUS images were acquired before hydralazine injection. Rats received an intravenous hydralazine injection of 5 mg/kg, then images were acquired 20 min later. Four rats were used as controls. The difference in echo intensity of the lesion and the surrounding tissue was used to determine the visibility index (VI).

RESULTS: The visibility index for HCC was found to be significantly improved with the use of HyCUS imaging compared to traditional B-mode and CUS imaging. The visibility index for HCC was 16.5 ± 2.8 for HyCUS, compared to 5.3 ± 4.8 for B-mode and 4.1 ± 3.8 for CUS. The differences between HyCUS and the other imaging modalities were statistically significant, with p-values of 0.001 and 0.02, respectively. Additionally, when compared to control cases, HyCUS showed higher discrimination of HCC (VI = 6.4 ± 1.2) with a p-value of 0.003, while B-mode (VI = 6.7 ± 1.4, p = 0.5) and CUS (VI = 6.4 ± 1.2, p = 0.3) showed lower discrimination.

CONCLUSION: Vascular blood flow modulation by hydralazine enhances the visibility of HCC. HyCUS offers a potential problem-solving method for detecting HCC when B-mode and CUS are unsuccessful, especially with background fibro-cirrhotic liver disease. Future evaluation of the approach in humans will determine its translatability for clinical applications. This article is protected by copyright. All rights reserved.

PMID:36680519 | DOI:10.1002/mp.16232

Health Inf Manag. 2023 Jan 21:18333583221144665. doi: 10.1177/18333583221144665. Online ahead of print.

ABSTRACT

BACKGROUND: Medical certification of cause of death (MCCD) provides valuable data regarding disease burden in a community and for formulating health policy. Inaccurate MCCDs can significantly impair the precision of national health information.

OBJECTIVE: To evaluate the accuracy of cause of death certificates prepared at two tertiary cancer care hospitals in Northern India during the study period (May 2018 to December 2020).

METHOD: A retrospective observational study at two tertiary cancer care hospitals in Varanasi, India, over a period of two and a half years. Medical records and cause of death certificates of all decedents were examined. Demographic characteristics, administrative details and cause of death data were collected using the WHO recommended death certificates. Accuracy of death certification was validated by electronic medical records and errors were graded.

RESULTS: A total of 778 deaths occurred in the two centres during the study period. Of these, only 30 (3.9%) certificates were error-free; 591 (75.9%) certificates had an inappropriate immediate cause of death; 231 (29.7%) certificates had incorrectly labelled modes of death as the immediate cause of death; and 585 (75.2%) certificates had an incorrect underlying cause of death. The majority of certificates were prepared by junior doctors and were significantly associated with higher certification errors.

CONCLUSION: A high rate of errors was identified in death certification at the cancer care hospitals during the study period. Inaccurate MCCDs related to cancers can potentially influence cancer statistics and thereby affect policy making for cancer control.

IMPLICATIONS: This study has identified the pressing need for appropriate interventions to improve quality of certification through training of doctors.

PMID:36680503 | DOI:10.1177/18333583221144665

Cell J. 2023 Jan 1;25(1):45-50. doi: 10.22074/cellj.2022.557259.1041.

ABSTRACT

OBJECTIVE: Preeclampsia (PE) is a pregnancy related disorder with prevalence of 6-7%. Insufficient trophoblastic invasion leads to incomplete remodeling of spiral arteries and consequent decrease in feto-placental perfusion. Altered placental expression of tissue inhibitors of matrix metalloproteinase (TIMPs) is considered to be involved in this process while the balance between matrix metalloproteinases (MMPs) and TIMPs contributes to remodeling of the placenta and uterine arteries by degradation and refurbishing of extracellular matrix (ECM). Therefore, TIMPs, fetal expression pattern was evaluated with the aim of its potential to be used as a determinant for the (early) detection of PE.

MATERIALS AND METHODS: In this case-control study, cell free fetal RNA (cffRNA) released by placenta into the maternal blood was used to determine expression patterns of TIMP1, 2, 3 and 4 in the severe preeclamptic women in comparison with the normal pregnant women. Whole blood from 20 preeclamptic and 20 normal pregnant women in their 28-32 weeks of gestational age was collected. The second control group consisted of 20 normal pregnant women in either 14 or 28 weeks of gestation (each 10). cffRNA was extracted from plasma and real-time polymerase chain reaction (PCR) was done to determine the expression levels of TIMP1, 2, 3 and 4 genes.

RESULTS: Statistical analysis of the results showed significant higher expression of TIMP1-4 in the preeclamptic women in comparison with the control group (P=0.029, 0.037, 0.037 and 0.049, respectively). Also, an increased level of TIMPs expression was observed by comparing 14 to 28 weeks of gestational age in the normal pregnant women in the second control group.

CONCLUSION: An increased cffRNA expression level of TIMPs may be correlated with the intensity of placental vascular defect and may be used as a determinant of complicated pregnancies with severe preeclampsia.

PMID:36680483 | DOI:10.22074/cellj.2022.557259.1041

Early Interv Psychiatry. 2023 Jan 21. doi: 10.1111/eip.13400. Online ahead of print.

ABSTRACT

AIM: The study aimed to assess changes in adolescent visits due to eating disorders (EDs) during the pandemic.

METHOD: A retrospective evaluation of adolescents diagnosed with an ED during two periods: June 2019-February 2020 (pre-pandemic) and June 2021-February 2022 (during the pandemic) at an adolescent medicine clinic in Tukey was conducted. The number of patients diagnosed with an ED between these dates was compared with the number of overall attended outpatient appointments. Baseline data for patients with Anorexia Nervosa (AN) and the requirement of hospitalization for all cases were compared.

RESULTS: Of the 3708 visits in the pre-pandemic period 46 (1.2%) were diagnosed with an ED. This was 69 (2.2%) of 3149 visits during the pandemic which was statistically significant (p = 0.003). The percentage of males to females changed from 2.2% to 11.6% (p = 0.065). Distribution of the type of ED did not change (p = 0.280), although the percentage of atypical AN increased from 6.5% to 17.4%. Mean age, BMI, calorie intake and hospital admissions did not significantly change.

CONCLUSION: Our findings support the increase in adolescent EDs during COVID-19. Particular attention should be given to males and Atypical AN cases.

PMID:36680467 | DOI:10.1111/eip.13400