Tag: pubmed

Indian J Pathol Microbiol. 2022 Oct-Dec;65(4):851-855. doi: 10.4103/ijpm.ijpm_109_21.

ABSTRACT

BACKGROUND: Tumor budding (TB) is a morphological finding believed to play an important role in determining the prognosis in many cancers.

AIM: Our aim is to evaluate the prognostic importance of TB in endometrial carcinomas.

SETTINGS AND DESIGN: Two-hundred-eleven endometrial cancers were obtained from 2008 to 2015 that were comprised of those having undergone surgical staging with a hysterectomy and at least 5 years followed up.

MATERIAL AND METHODS: All hematoxylin and eosin stained slides were reevaluated for the status of TB.

STATISTICAL ANALYSIS: Nonparametric tests, the Kaplan-Meier method, the Log-rank test, and Cox proportional hazard regression were used.

RESULTS AND CONCLUSION: TB was found to correlated with larger diameter (P = 0.000), nonendometrioid (P = 0.038), mixed cell types (P = 0.005), higher grade (P = 0.000), deeper invasion of the myometrium (P = 0.000), cervical stromal invasion (P = 0.000), advanced pT (P = 0.011), lymph node involvement (P = 0.000), lymphovascular invasion (P = 0.000), and advanced stage (P = 0.000). The presence of TB worsens the 5-year overall survival (OS) (P = 0.0001). In cases such as grade 1, pT1, or stage 1 endometrial carcinomas, the presence of TB decreases the OS rate (P = 0.00017, P = 0.0016, P < 0.0001). Our result suggested that the presence of TB adversely affects the prognosis. It was concluded that TB could be a valuable prognostic parameter.

PMID:36308192 | DOI:10.4103/ijpm.ijpm_109_21

Indian J Pathol Microbiol. 2022 Oct-Dec;65(4):839-843. doi: 10.4103/ijpm.ijpm_1472_20.

ABSTRACT

INTRODUCTION: High-grade urothelial carcinoma has a different molecular pathway than superficial low grade urothelial carcinoma, and is characterized by genomic instability. The high tumor mutation burden leads to neoantigen formation, evoking an immune response. The immune response has been keenly studied in last two decades and programmed death ligand-1 (PDL-1) has emerged as acceptable immunohistochemical marker for assessment of response to therapy, prognostication and patient selection for immunotherapy. The targeting of PD-1 and PDL-1 by checkpoint inhibitors (CPIs) is an attractive strategy to unblock the inhibitor and induce cytotoxic cell death. However, the presence of complementary and companion diagnostic testing with multiple PDL-1 assays and platforms for various CPIs make a diagnostic quagmire. Thus, it is the need of hour to harmonize these assays. In this undertaken study we evaluated the concordance in PD-L1 expression between the two PD-L1 clones: SP263 and SP142, in treatment naïve muscle invasive bladder cancer (MIBC).

METHODS: We evaluated Ventana PD-L1 “SP263 and SP142” qualitative immunohistochemical assay using rabbit monoclonal anti-PD-L1 clones in evaluation of PDL-1 immunoexpression on Ventana autostainer platform. The study includes 30 muscle invasive urothelial carcinomas, with 10 of 30 having nodal metastasis.

RESULTS: SP263 assay was statistically more sensitive than SP142 for tumor cell (TC) scoring (P = 0.0009), whereas SP142 was more sensitive for immune cell (IC) scoring (P = 0.0067). There was no statistical significant discordance for TC or IC scoring between primary tumor and metastatic lymph node.

CONCLUSION: PD-L1 testing status can be done on both primary tumor and metastatic site, however in metachronous metastatic setting, testing on recent metastatic site should be preferred. The harmonization of immunoexpression between 2 PD-L1 clones could not be achieved.

PMID:36308190 | DOI:10.4103/ijpm.ijpm_1472_20

Indian J Pathol Microbiol. 2022 Oct-Dec;65(4):828-831. doi: 10.4103/ijpm.ijpm_93_21.

ABSTRACT

CONTEXT: Though mast cells infiltrate solid tumors, the exact role of mast cells in tumor biology is controversial. Mast cell density (MCD) may vary depending on its location in the tumor and tumor vascularity. MCD may influence the tumor aggressiveness.

AIMS: This study evaluates MCD and tumor vascularity in different histopathological grades of adenocarcinoma prostate.

SETTINGS AND DESIGN: Descriptive study with purposive sampling.

METHODS AND MATERIAL: The subjects of study were 42 adenocarcinoma patients. 20 cases were of intermediate grade (Gleason score 2-7) and 22 were of high-grade (Gleason score 8-10). Histological diagnosis was made by examining sections stained with hematoxylin and eosin. Additional sections from the same block were stained for mast cells using Giemsa stains as per standard protocol. Mast cell count was done in minimum six random high-power microscopy fields in four different regions- intratumoral, peritumoral, stromal and perivascular regions.

STATISTICAL ANALYSIS USED: SSPS software version 13.0. Descriptive statistics, Student’s t test and ANOVA test.

RESULTS: In high-grade adenocarcinoma, mast cell counts were higher in perilesional, stromal and perivascular regions, whereas it was lower in intralesional areas as compared to the intermediate grade. However, statistical significance was observed only for the perivascular region. There was significantly higher number of blood vessels in high-grade adenocarcinoma as compared to intermediate grade adenocarcinoma.

CONCLUSIONS: In this study, perilesional mast cells and vascularity increased with increased severity of adenocarcinoma. These findings suggest a possible influence of mast cells on the tumor microenvironment such as vessel density and aggressiveness of tumor. However, further studies are required to substantiate results of this study.

PMID:36308188 | DOI:10.4103/ijpm.ijpm_93_21

Diabetes Technol Ther. 2022 Oct 28. doi: 10.1089/dia.2022.0331. Online ahead of print.

ABSTRACT

To assess the compliance of “integrated” continuous glucose monitoring (CGM) systems with U.S. Food and Drug Administration (FDA) requirements, the calculation of confidence intervals on agreement rates, i.e., the percentage of CGM measurements lying within a certain deviation of a comparator method, is stipulated. However, despite the existence of numerous approaches that could yield different results, a specific procedure for calculating confidence intervals is not described anywhere. This report therefore proposes a suitable statistical procedure to allow transparency and comparability between CGM systems. Three existing methods were applied to six datasets from different CGM performance studies. The results indicate that a bootstrap-based method that accounts for the clustered structure of CGM data is reliable and robust. We thus recommend its use for the estimation of confidence intervals of agreement rates. A software implementation of the proposed method is freely available (https://github.com/IfDTUlm/CGM_Performance_Assessment).

PMID:36306521 | DOI:10.1089/dia.2022.0331

AIDS Patient Care STDS. 2022 Oct 27. doi: 10.1089/apc.2022.0072. Online ahead of print.

ABSTRACT

Pre-exposure prophylaxis (PrEP) is a lifesaving medical intervention that protects against human immunodeficiency virus (HIV), but to date, PrEP uptake has been limited. PrEP utilization and adherence among youth, including stigmatized and highly vulnerable young sexual and gender minorities, have been exceptionally low across all regions, leading to preventable HIV transmission. Considering the scientific value of measuring and understanding predictors or associations of PrEP adherence, our study team validated two scales: a PrEP Difficulties Scale and a PrEP Confidence Scale tested within the Adolescent Trials Network P3 study (2019-2021). Data from sexual and gender minorities who were prescribed PrEP across nine domestic sites were evaluated (N = 235). Descriptive statistics, exploratory factor analysis, and correlation coefficients are reported herein. Results for the PrEP Difficulties Scale yielded a four-factor solution (Disclosure, Health Effects, Logistics, and Cost), and results for the PrEP Confidence Scale produced a three-factor solution (Scheduling, Distraction, and Planning). Factor loadings and Cronbach’s alphas suggested good internal consistency for both scales. PrEP Confidence Scale subscales were correlated with PrEP adherence, and subscales of both scales were associated with dimensions of social support and PrEP-related stigma. Given the persistence of preventable HIV infections among key populations, multi-level barriers and facilitators to medication adherence, and expansion of PrEP modalities, the PrEP Difficulties Scale and PrEP Confidence Scale have the potential to enhance intervention, exploratory, and mechanistic HIV prevention research. ClinicalTrials.gov Identifier: NCT03320512.

PMID:36306520 | DOI:10.1089/apc.2022.0072

Diabetes Technol Ther. 2022 Oct 28. doi: 10.1089/dia.2022.0365. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate influence of daytime vs nighttime continuous glucose monitoring (CGM)-based metrics on A1C in adults with type 1 diabetes.

RESEARCH DESIGN AND METHODS: CGM data from 407 adults with type 1 diabetes (age 39 ± 15 years, diabetes duration 20 ± 12 years, A1C 7.3 ± 1.4% and 55% female) from two studies were included in this analysis. The association between daytime (6 AM to 10.59 PM) and nighttime (11PM to 5.59 AM) CGM variables such as mean glucose, time in range (TIR; 70-180 mg/dL), time in tight target range (TTIR; 70-140 mg/dL) and time above range (TAR >180 mg/dl) was examined within five A1C categories (<7%, 7- 7.9%, 8-8.9%, 9-9.9%, and ≥10%).

RESULTS: Although mean glucose was increasing with higher A1C, there was no statistical difference in mean glucose between daytime vs nighttime within five A1C groups [143.2±22.7 vs143.6±25.0 for A1C <7%, 171.4±17.3 vs 175.3±28.8 for A1C 7.0-7.9%, 193.4±19.4 vs 195.3±29.5 for A1C 8.0-8.9%, 214.9±28.8 vs 219.7±36.1 for A1C 9.0-9.9% and 244.0±39.0 vs 239.9±50.9 for A1C ≥10%, p>0.05]. Similarly, there was no difference various CGM metrics by daytime vs nighttime within five A1C groups. Differences between five A1C groups’ daytime vs nighttime mean glucose, TIR, TTIR and TAR were also not statistically significant (all p>0.05) Conclusion: Daytime vs nighttime glycemic control has similar influence on A1C in adults with type 1 diabetes.

PMID:36306519 | DOI:10.1089/dia.2022.0365

JMIR Public Health Surveill. 2022 Oct 28. doi: 10.2196/31237. Online ahead of print.

ABSTRACT

BACKGROUND: HIV disproportionately affects sexual minority men (SMM) in the U.S.

OBJECTIVE: We sought to determine past HIV post-exposure prophylaxis (PEP) use and current and prior pre-exposure prophylaxis (PrEP) use among an online sample of cisgender and transgender men who have sex with men.

METHODS: In 2019, HIV-negative and unknown status SMM (n = 63,015) were recruited via geosocial networking apps, social media, and other online venues to participate in a brief eligibility screening survey. Individuals were asked about past PEP and current and prior PrEP use. We examined associations of demographics, socioeconomic indicators, and recent club drug use on PEP and PrEP use, as well as the association between past PEP use on current and prior PrEP use using generalized linear models and multinomial logistic regression. Statistical significance was considered at p < 0.001 given the large sample size; 99.9% confidence intervals are reported.

RESULTS: Prior PEP use was reported by 11.3% of participants, with current or prior PrEP use reported by 22.0% and 8.1%, respectively. Nearly half (46.0%) of past PEP users were current PrEP users, and another 39.9% of participants who reported past PEP use also reported prior PrEP use. In multivariable analysis, past PEP use was associated with current (RRR = 23.53; 99.9% CI: 14.03-39.46) and prior PrEP use (RRR = 52.14; 99.9% CI: 29.39-92.50). Compared to white men, Black men had higher prevalence of past PEP use and current PrEP use, Latinx men had higher prevalence of PEP use but no significant difference in PrEP use, and those considered of another race/ethnicity reported higher prevalence of past PEP use and lower current PrEP use. Past PEP use and current PrEP use were highest in the Northeast, with those in the Midwest and South reporting significantly lower PEP and PrEP use. A significant interaction of Black race/ethnicity by past PEP use on current PrEP use was found (RRR = 0.57; 99.9% CI: 0.37-0.87), indicating Black men who previously used PEP were less likely to report current PrEP use. Participants who reported recent club drug use were significantly more likely to report past PEP use and current or prior PrEP use compared to those without recent use.

CONCLUSIONS: PrEP use continues to be the predominate HIV prevention strategy for SMM compared to PEP, but many current PrEP users had previously used PEP for HIV prevention. Higher rates of past PEP use and current PrEP use among Black SMM is noteworthy given disproportionate burden of HIV. Nonetheless, understanding the disconnect linking PEP users to PrEP among Black SMM is an important avenue for future research. Further efforts are also needed to increase PrEP use among Latinx SMM given increasing disparity between Latinx and white SMM in the U.S.

PMID:36306518 | DOI:10.2196/31237

JCO Clin Cancer Inform. 2022 Oct;6:e2200082. doi: 10.1200/CCI.22.00082.

ABSTRACT

PURPOSE: The Bone Metastases Ensemble Trees for Survival Decision Support Platform (BMETS-DSP) provides patient-specific survival predictions and evidence-based recommendations to guide multidisciplinary management for symptomatic bone metastases. We assessed the clinical utility of the BMETS-DSP through a pilot prepost design in a simulated clinical environment.

METHODS: Ten Radiation Oncology physicians reviewed 55 patient cases at two time points: without and then with the use of BMETS-DSP. Assessment included 12-month survival estimate, confidence in and likelihood of sharing estimates with patients, and recommendations for open surgery, systemic therapy, hospice referral, and radiotherapy (RT) regimen. Paired statistics compared pre- versus post-DSP outcomes. Reported statistical significance is P < .05.

RESULTS: Pre- versus post-DSP, overestimation of true minus estimated survival time was significantly reduced (mean difference -2.1 [standard deviation 4.1] v -1 month [standard deviation 3.5]). Prediction accuracy was significantly improved at cut points of < 3 (72 v 79%), ≤ 6 (64 v 71%), and ≥ 12 months (70 v 81%). Median ratings of confidence in and likelihood of sharing prognosis significantly increased. Significantly greater concordance was seen in matching use of 1-fraction RT with the true survival < 3 months (70 v 76%) and < 10-fraction RT with the true survival < 12 months (55 v 62%) and appropriate use of open surgery (47% v 53%), without significant changes in selection of hospice referral or systemic therapy.

CONCLUSION: This pilot study demonstrates that BMETS-DSP significantly improved physician survival estimation accuracy, prognostic confidence, likelihood of sharing prognosis, and use of prognosis-appropriate RT regimens in the care of symptomatic bone metastases, supporting future multi-institutional validation of the platform.

PMID:36306499 | DOI:10.1200/CCI.22.00082

J Clin Oncol. 2022 Oct 28:JCO2102726. doi: 10.1200/JCO.21.02726. Online ahead of print.

ABSTRACT

PURPOSE: Oxaliplatin-based adjuvant chemotherapy in patients with stage III colon cancer (CC) for 6 months remains a standard in high-risk stage III patients. Data are lacking as to whether early discontinuation of all treatment (ETD) or early discontinuation of oxaliplatin (EOD) could worsen the prognosis.

MATERIALS AND METHODS: We studied the prognostic impact of ETD and EOD in patients with stage III CC from the ACCENT/IDEA databases, where patients were planned to receive 6 months of infusional fluorouracil, leucovorin, and oxaliplatin or capecitabine plus oxaliplatin. ETD was defined as discontinuation of treatment and EOD as discontinuation of oxaliplatin only before patients had received a maximum of 75% of planned cycles. Association between ETD/EOD and overall survival and disease-free survival (DFS) were assessed by Cox models adjusted for established prognostic factors.

RESULTS: Analysis of ETD and EOD included 10,447 (20.9% with ETD) and 7,243 (18.8% with EOD) patients, respectively. Compared with patients without ETD or EOD, patients with ETD or EOD were statistically more likely to be women, with Eastern Cooperative Oncology Group performance status ≥ 1, and for ETD, older with a lower body mass index. In multivariable analyses, ETD was associated with a decrease in disease-free survival and overall survival (hazard ratio [HR]: 1.61, P < .001 and HR: 1.73, P < .001), which was not the case for EOD (HR: 1.07, P = .3 and HR: 1.13, P = .1). However, patients who received < 50% of the planned cycles of oxaliplatin had poorer outcomes.

CONCLUSION: In patients treated with 6 months of oxaliplatin-based chemotherapy for stage III CC, ETD was associated with poorer oncologic outcomes. However, this was not the case for EOD. These data favor discontinuing oxaliplatin while continuing fluoropyrimidine in individuals with significant neurotoxicity having received > 50% of the planned 6-month chemotherapy.

PMID:36306483 | DOI:10.1200/JCO.21.02726

Phonetica. 2022 Oct 28. doi: 10.1515/phon-2022-2024. Online ahead of print.

ABSTRACT

Glottalized sonorants are a rare sound type that has been under scrutiny for a number of reasons of general relevance to the phonetic theory. It has been claimed that the timing of glottalization of glottalized sonorants may shift in accordance with the position in the syllable onset (pre-glottalization) or coda (post-glottalization), to provide a cue for its place of articulation; other studies argued against this claim. The paper investigates acoustic properties of the glottalized lateral in Rikvani Andi, a one-village dialect of Andi (East Caucasian). Based on the data from elicitations and free narratives, we consider the acoustic correlates that have been argued in the literature to differentiate glottalized sonorants from their modal counterparts, including aperiodicity, intensity, duration and spectral tilt. In Rikvani Andi, all of the correlates prove to be statistically significant in recordings of isolated words, but the differences tend to decrease in free narratives. The timing of glottalization does not support the existing generalizations – while the glottalized lateral only occurs in Rikvani Andi in the syllable onset, it tends to be mid- to post-glottalized. We discuss two possible explanations of why the Rikvani Andi glottalized sonorant fails to comply with typological expectations.

PMID:36306469 | DOI:10.1515/phon-2022-2024