Nevin Manimala

Prostate. 2021 Oct 26. doi: 10.1002/pros.24260. Online ahead of print.

ABSTRACT

BACKGROUND: The Gleason scoring system is the most widely used method to assess prostate adenocarcinoma pathology however interobserver variability is significant. Gleason score, PSA level, and clinical stage comprise the NCCN risk stratification that guides treatment decision making. Given the importance of an accurate Gleason score and wide interobserver variability, referral centers routinely review outside pathology at the time of consultation. We sought to address the impact a secondary pathology review had on radiation therapy treatment recommendations in men with prostate cancer at our institution.

METHODS: We retrospectively collected patient data on 342 patients seen at our institution from January 2012 to December 2018. Clinicopathologic data were used to subdivide patients into risk groups and available treatment options per NCCN criteria. Cases reviewed by our genitourinary pathologist (GUP) were compared with reports from outside pathologists. Inter-rater reliability between pathologists was assessed with weighted Cohen’s kappa statistic and agreement of treatment options was determined by McNemar’s exact tests.

RESULTS: GUP scored more cores positive in 16.47% of cases on secondary review. Primary Gleason score was changed in 12.28% of patients and secondary score in 26.02% of cases. Total Gleason score was different in 29.24% of cases, 19.01% were downgraded and 10.23% upgraded. The weighted kappa statistic was 0.759 (95% confidence interval [CI]: 0.711, 0.807). 18.77% of patients were assigned to a different NCCN risk group following secondary review. The weighted kappa statistic comparing NCCN risk stratification was 0.802 (95% CI: 0.754, 0.850). Secondary review influenced radiation therapy recommendations pertaining to brachytherapy boost and androgen deprivation therapy in men with high risk disease (χ² = 5.33, p = 0.0386; χ² = 8.05, p = 0.0072, respectively). Kappa statistic was found to be highest when GUP assessed high-risk disease versus all other categories (κ = 0.823, 95% CI: 0.750, 0.895).

CONCLUSIONS: We found nearly one in five men (18.7%) was assigned a different NCCN risk group and thus offered potentially different treatment options after a secondary pathology review at our institution. Given the inherent nature of prostate cancer and lung disease-specific survival associated with modern therapies, our study demonstrates the importance of a secondary pathology review and its potential impact on radiation therapy recommendations.

PMID:34698410 | DOI:10.1002/pros.24260

Allergy. 2021 Oct 26. doi: 10.1111/all.15152. Online ahead of print.

NO ABSTRACT

PMID:34698405 | DOI:10.1111/all.15152

J Med Virol. 2021 Oct 26. doi: 10.1002/jmv.27408. Online ahead of print.

ABSTRACT

The pro-inflammatory (Th1) cytokines namely IL-2, IL-6, IL-12, IFN-γ, TNF-α are vital in the clearance of HIV infection. This prospective cohort study aimed to evaluate the polymorphisms of Th1 cytokine genes and their corresponding plasma cytokine levels in HIV-1 positive and exposed uninfected (EU) infants born to HIV-1 positive mothers. CD4 count, viral load of HIV-1 positive mothers was done using commercially available reagents. Cytokine genotyping analysis and levels was done in 20 HIV-1 positive and 54 EU infants. The polymorphisms of Th1 cytokines were done using PCR-SSP method. Plasma cytokine levels estimated using Bio-Plex-Pro cytokine assay (BIO-RAD; USA).Results revealed treatment status of the mothers and viral load were the two confounding factors having significant effect on HIV status of the infant. TNF-α GG genotype is significantly higher in EU infants as compared to HIV-1 positive infants. GG genotype was associated with high TNF- α levels in HIV-1 positive infants but the difference was not statistically significant. HIV-1 positive infants with -IFN-γ (+874) TT genotype was significantly associated with high IFN-γ levels. To the best of our knowledge this is the first study reporting the role of Th1 cytokine gene polymorphisms and their corresponding plasma cytokine levels in HIV-1 positive and EU infants from India. This article is protected by copyright. All rights reserved.

PMID:34698402 | DOI:10.1002/jmv.27408

Acta Obstet Gynecol Scand. 2021 Oct 26. doi: 10.1111/aogs.14254. Online ahead of print.

ABSTRACT

INTRODUCTION: To determine the impact on preterm birth (PTB) of a history of large loop excision of the transformation zone (LLETZ)-alone compared with a history of previous preterm birth-alone (PPTB) or a history of both (LLETZ+PPTB). Secondary analyses were performed to evaluate the impact of antenatal interventions, depth of cervical excision, and patient risk factors on PTB rate in each cohort.

MATERIAL AND METHODS: A retrospective observational cohort study of women referred to a tertiary Antenatal Prematurity Prevention Clinic with a history of LLETZ, PPTB, or LLETZ+PPTB. Information was collated from routinely collected clinical data on patient demographics, previous obstetric history, LLETZ dimensions, antenatal investigations/interventions, and gestation at delivery.

RESULTS: A total of 1231 women with singleton pregnancies were included, 543 with history of LLETZ-alone, 607 with a history of PPTB-alone and 81 with a history of LLETZ+PPTB. PTB rates were 8.8% in the LLETZ-alone group, which mirrored the PTB rate in the local background obstetric population (8.9%) compared with 28.7% in the PPTB-alone and 37.0% in the LLETZ+PPTB cohorts. PTB rates were higher in LLETZ cohorts treated with antenatal intervention (cervical cerclage or progesterone pessary) and there was no evidence of an effect of intervention on risk of PTB in post-excision patients with identified shortened mid-trimester cervical length. Logistic regression modeling identified PPTB as a strong predictor of recurrent PTB. Excision depth was correlated with gestation at delivery in the LLETZ-alone group (r = -0.183, p < 0.01) although this only reached statistical significance at depths of 20 mm or more (odds ratio [OR] 3.40, 95% CI 1.04-1.11, p = 0.04). Depth of excision was not correlated with delivery gestation in the LLETZ+PPTB group (r = -0.031, p = 0.82).

CONCLUSIONS: PPTB has a greater impact on subsequent PTB risk compared with depth of cervical excisional treatment. The value and nature of antenatal interventions should be investigated in the post-excision population.

PMID:34698370 | DOI:10.1111/aogs.14254

J Burn Care Res. 2021 Oct 26:irab206. doi: 10.1093/jbcr/irab206. Online ahead of print.

ABSTRACT

This study conducted to analyze and compare the epidemiological and clinical characteristics of hydrogen fluoride exposed patients based on major burn criteria for the appropriate emergency department (ED) response to a mass casualty chemical spill. This retrospective cross-sectional study included the records of patients (n = 199) who visited the ED of Gumi City University Hospital from September 27, 2012, to October 20, 2012. Subjects were included in the major burn group (MBG) if they presented with wounds that required referral to a burn center according to the American Burn Association guidelines or in the non-major burn group (NMBG) if not. Males were predominant in both the MBG (n = 55, 48 males) and NMBG (n = 144, 84 males; p < 0.05). The most prevalent timeline for visiting the ED was the phase which included 9-32 hours post-leak of HF, including 45 patients (81.8%) in the MBG and 122 patients (84.7%) in the NMBG (p < 0.001). The respiratory tract was the site of greatest damage in patients in both the MBG and NMBG (n=47, 85.5% versus n=142, 98.6%, p < 0.001). Regarding dispositions, all patients in the NMBG were discharged (n=144, 100%); however, 8 patients (14.5%) in the MBG underwent other dispositions (discharge againt medical advice, 5 patients; admission, 1; death, 2, p < 0.05). Patient outcomes after major chemical contamination events should be characterized in future studies to maximize the quality of patient care.

PMID:34698345 | DOI:10.1093/jbcr/irab206

Am J Clin Pathol. 2021 Oct 26:aqab176. doi: 10.1093/ajcp/aqab176. Online ahead of print.

ABSTRACT

OBJECTIVES: To assess the efficacy of a method to circumvent CD20-positive antigen masking by rituximab for flow cytometry analysis of B-cell malignancies in hematology patients.

METHODS: Mononuclear cells (MNCs) from 10 healthy individuals and 5 untreated patients with B-cell malignancies were sensitized with rituximab. Patients’ diagnoses included chronic lymphocytic leukemia, hairy cell leukemia, and follicular lymphoma. MNCs were isolated by gradient density centrifugation. An EDTA/glycine acid (EGA) elution method was used to dissociate CD20-rituximab complexes; afterwards, CD20-positive immunoreactivity was assessed by flow cytometry. A saturation curve was built based on serial dilutions of rituximab. Median fluorescent intensities of CD20-positive signals were obtained before sensitization with rituximab and after its elution with EGA.

RESULTS: CD20-positive signals were not detectable by flow cytometry after rituximab sensitization of B cells. CD20-sensitized vs CD20-unsensitized, CD20-sensitized vs CD20-eluted, and CD20-eluted vs CD20-negative control (NC) MNC populations exhibited statistical differences (P = .001), while CD20-sensitized vs CD20-NC populations did not (P = .499), confirming CD20 antigen masking by rituximab.

CONCLUSIONS: Rituximab interfered with the flow cytometry protocol for CD20 determination on normal and neoplastic B cells. The EGA method efficiently eluted rituximab, allowing for accurate identification of CD20-positive B cells.

PMID:34698343 | DOI:10.1093/ajcp/aqab176

Health Policy Plan. 2021 Oct 26:czab120. doi: 10.1093/heapol/czab120. Online ahead of print.

ABSTRACT

Community health workers (CHWs) are a vital part of the health infrastructure in Uganda and in many other low- and middle-income countries. While the need for CHWs is clear, it is less clear how they should dispense health products to maximize the health benefits to their community. In this study, we assess the cost-effectiveness of several competing CHW distribution strategies in the context of treatment for child diarrhea. We used data from a 4-armed cluster-randomized controlled trial to assess the cost-effectiveness of 1) free distribution of oral rehydration salts (ORS) via home deliveries prior to diarrhea onset (free delivery arm), 2) free distribution via vouchers where households retrieved the treatment from a central location (voucher arm), 3) a door-to-door sales model (home sales arm), and 4) a control arm where CHWs carried out their activities as normal. We assessed the cost-effectiveness from the implementor’s perspective and a societal perspective, in terms of cost per case treated with ORS and cost per disability adjusted life-year (DALY) averted. Free delivery was the most effective strategy and the cheapest from a societal perspective. Although implementor costs were highest in this arm, cost savings comes from households using fewer resources to seek treatment outside the home (transport, doctor fees, and treatment costs). From the implementors’ perspective, free delivery costs $2.19 per additional case treated and $56 per DALY averted relative to the control. Free delivery was also extremely cost-effective relative to home sales and vouchers but there was a large degree of uncertainty around the comparison with vouchers. Free distribution of ORS by CHWs prior to diarrhea onset is extremely cost-effective compared to other CHW distribution models. Implementers of CHW programs should consider free home delivery of ORS.

PMID:34698342 | DOI:10.1093/heapol/czab120

Trop Med Infect Dis. 2021 Oct 7;6(4):182. doi: 10.3390/tropicalmed6040182.

ABSTRACT

There is a gap in the epidemiological data on obesity and COVID-19 mortality in low and middle-income countries worst affected by the COVID-19 pandemic, including Peru. In this ecological study, we explored the association between body mass index (BMI), the prevalence of overweight and obesity, and the COVID-19 mortality rates in 25 Peruvian regions, adjusted for confounding factors (mean age in the region, mean income, gender balance and number of Intensive Care Unit (ICU) beds) using multiple linear regression. We retrieved secondary region-level data on the BMI average and prevalence rates of overweight and obesity in individuals aged ≥ 15 years old, from the Peruvian National Demographics and Health Survey (ENDES 2020). COVID-19 death statistics were obtained from the National System of Deaths (SINADEF) from the Peruvian Ministry of Health and were accurate as of 3 June 2021. COVID-19 mortality rates (per 100,000 habitants) were calculated among those aged ≥ 15 years old. During the study period, a total of 190,046 COVID-19 deaths were registered in individuals aged ≥ 15 years in 25 Peruvian regions. There was association between the BMI (r = 0.74; p = 0.00001) and obesity (r = 0.76; p = 0.00001), and the COVID-19 mortality rate. Adjusted for confounding factors, only the prevalence rate of obesity was associated with COVID-19 mortality rate (β = 0.585; p = 0.033). These findings suggest that as obesity prevalence increases, the COVID-19 mortality rates increase in the Peruvian population ≥ 15 years. These findings can help to elucidate the high COVID-19 mortality rates in Peru.

PMID:34698315 | DOI:10.3390/tropicalmed6040182

Trop Med Infect Dis. 2021 Sep 29;6(4):177. doi: 10.3390/tropicalmed6040177.

ABSTRACT

While there has been a tremendous decline in malaria disease burden in the remote parts of Malaysia, little is known about malaria incidence in its urban localities. This study aimed to analyze trends of malaria cases in urban Kuala Lumpur, Malaysia. All suspected cases presented to a university hospital in Kuala Lumpur from January 2005 to December 2020 were examined by microscopy. Infection status was analyzed using descriptive statistics and curve estimation analysis. Of 3105 blood films examined, 92 (3%) were microscopically confirmed malaria cases. Plasmodium vivax infections accounted for the majority (36.9%) of all malaria cases. Nearly half (47.8%) of cases were found among foreign cases (p < 0.001). The majority of foreign cases were male (86.4%) and came from Southeast Asian countries (65.9%). The curve estimation analysis showed significant decreases in malaria cases due to P. vivax (R² = 0.598; p < 0.001) and Plasmodium falciparum (R² = 0.298, p = 0.029), but increases for Plasmodium knowlesi (R² = 0.325, p = 0.021) during the 16 years. This study showed that malaria incidence in urban Kuala Lumpur is low and has remained stable since 2005. However, P. knowlesi has played a significant role in the increase in overall malaria in the area, highlighting the importance of continued vigilance and improved surveillance.

PMID:34698312 | DOI:10.3390/tropicalmed6040177

Vision (Basel). 2021 Sep 28;5(4):44. doi: 10.3390/vision5040044.

ABSTRACT

Gastropod mollusks are convenient model organisms for studying the functioning of the visual system. The purpose of this work is to estimate the value of the optical sensitivity to white light for the camera-like eyes of gastropod mollusks and humans and analyze its effect on the spatial resolving power in two regions of the retina: in the center-for single photoreceptors of the first/second type in a mollusk and single cones in humans-and in the periphery-for single photoreceptors of the first/second type in a mollusk, as well as for single rods/cones and their groups, subject to spatial summation in humans. The methods of histology, light and transmission electron microscopy, morphometry, calculations and methods of statistical analysis are used in the work. In a mollusk, with a fixed pupil area, the value of the optical sensitivity of the eye to white light in the center of the retina for single photoreceptors of the first/second type is 0.5/0.006 μm²·sr and in the periphery of the retina, 0.9/0.009 μm²·sr. In humans, at the minimum and maximum pupil area, respectively, the value of the optical sensitivity of the eye to white light in the center of the retina (foveola) for single cones varies from 0.00053 to 0.028 μm²·sr, and in the periphery of the retina (far periphery) for single rods from 0.011 to 0.575 μm²·sr, for single cones from 0.025 to 1.319 μm²·sr, for the groups of rods from 3859 to 204,094 μm²·sr and for the groups of cones from 2.5 to 131 μm²·sr. The value of the optical sensitivity of the eyes to white light for single photoreceptors of the first/second type in both regions of the retina in a mollusk, as well as for single cones in the center and groups of rods/cones in the periphery of the retina in humans, corresponds to the ambient light conditions during periods of activity and does not affect the spatial resolving power.

PMID:34698309 | DOI:10.3390/vision5040044