Nevin Manimala

World J Urol. 2024 Feb 22;42(1):95. doi: 10.1007/s00345-024-04787-8.

ABSTRACT

PURPOSE: The primary objective was to establish whether blood-based leucine-rich alpha-2-glycoprotein (LRG1) can predict outcomes in patients with locally advanced prostate cancer undergoing androgen-deprivation therapy (ADT) and radiotherapy (RT) and to determine how it may relate to 92 immune-oncology (I-O)-related proteins in this setting.

METHODS: Baseline blood level of LRG1 from patients treated with ADT and RT enrolled in the CuPCa (n = 128) and IMRT (n = 81) studies was measured using ELISA. A longitudinal cohort with matched blood samples from start of ADT, start of RT, and end of RT protocol from 47 patients from the IMRT cohort was used to establish levels of I-O proteins by high-multiplexing Proximal Extension Assay by Olink Proteomics. Statistical analyses using Kaplan-Meier, Cox regression, and LIMMA analyses were applied to predict the prognostic value of LRG1 and its correlation to I-O proteins.

RESULTS: High baseline levels of LRG1 predicted a low frequency of treatment failure in patients undergoing ADT + RT in both the CuPCa and the IMRT cohorts. LRG1 was moderately correlated with CD4, IL6, and CSF1. We identified I-O proteins predicting metastatic failure (MF) at different timepoints.

CONCLUSION: LRG1 biomarker is associated with I-O proteins and can be used to improve stratification and monitoring of prostate cancer patients undergoing ADT + RT. This work will require further in-depth analyses in independent cohorts with treatment outcome data.

PMID:38386171 | DOI:10.1007/s00345-024-04787-8

Invest New Drugs. 2024 Feb 22. doi: 10.1007/s10637-024-01424-4. Online ahead of print.

ABSTRACT

Patients with metastatic lung adenocarcinoma (MLA) and malignant pleural effusion (MPE) without driver gene mutations have a poor prognosis. None of the standard treatment strategies is recommended for such patients. We retrospectively analyzed the efficacy of the first-line treatment for this specific population: standard platinum-based doublet chemotherapy (CT), CT plus an immune checkpoint inhibitor (CT plus ICI), and CT plus bevacizumab (CT plus Bev). A total of 323 eligible patients were enrolled: CT alone (n = 166), CT plus Bev (n = 72), and CT plus ICI (n = 85). Treatment efficacy assessments were performed every two cycles according to the RECIST guidelines. The endpoints were overall survival (OS) and progression-free survival (PFS). Kaplan-Meier (K‒M) curves and the log-rank test were used to compare OS and PFS. p < 0.05 was the threshold of significance (statistical software: SPSS). The median follow-up was 11.4 months (range, 2.1-49.6 months). PFS and OS in the CT plus ICI/CT plus Bev cohort were significantly longer than those in the CT group (PFS: 7.8/6.4/3.9 months, p < 0.0001; OS: 16.4/15.6/9.6 months, p < 0.0001, respectively). CT plus Bev had better PFS and OS than CT plus ICI/CT in PD-L1 < 1% patients (PFS: 8.4/5.0/3.8 months, p < 0.0001; OS: 15.6/12.9/9.3 months, p < 0.0001). Among patients with PD-L1 1-49%, CT plus ICI led to a longer PFS and OS (PFS: 8.9/5.8/4.2 months, p = 0.009; OS: 24.2/18.8/11.5 months, p = 0.03). In the cohort with PD-L1 ≥ 50%, CT plus ICI was still the best first-line treatment (PFS: 19.7/13.8/9.6 months, p = 0.033; OS: 27.2/19.6/14.9 months, p = 0.047). In driver gene-negative MLA with MPE, CT plus Bev or ICI better controlled MPE and significantly prolonged survival compared to CT alone. PD-L1 expression (negative/positive) may be a key factor influencing the choice of CT plus Bev or ICI.

PMID:38386170 | DOI:10.1007/s10637-024-01424-4

J Robot Surg. 2024 Feb 22;18(1):84. doi: 10.1007/s11701-024-01837-6.

ABSTRACT

Whilst surgeons and robotic companies are key stakeholders involved in the adoption of robotic assisted surgery (RS), the public’s role is overlooked. However, given that patients hold ultimate power over their healthcare decisions, public acceptance of RS is crucial. Therefore, this study aims to identify public understanding, opinions, and misconceptions about RS. An online questionnaire distributed between February and May 2021 ascertained the views of UK adults on RS. The themes of questions included familiarity, experience and comfort with RS, opinions on its ethical implications, and the impact of factual information provided to the participant. The data were evaluated using thematic and statistical analysis, including assessing for statistical differences in age, gender, education level, and presence in the medical field. Overall, 216 responses were analysed. Participants were relatively uninformed about RS, with a median knowledge score of 4.00(2.00-6.00) on a 10-point Likert scale. Fears surrounding increased risk, reduced precision and technological failure were identified, alongside misconceptions about its autonomous nature. However, providing factual information in the survey about RS statistically increased participant comfort (p = < 0.0001). Most (61.8%) participants believed robot manufacturers were responsible for malfunctions, but doctors were held accountable more by older, less educated, and non-medical participants. Our findings suggest that there is limited public understanding of RS. The numerous common misconceptions identified present a major barrier to the widespread acceptance of RS, since inaccurate fears about its nature could discourage potential patients from engaging with robotic procedures.

PMID:38386115 | DOI:10.1007/s11701-024-01837-6

Skeletal Radiol. 2024 Feb 22. doi: 10.1007/s00256-024-04613-7. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the impact of deep learning (DL) reconstruction in enhancing image quality and nerve conspicuity in LSP MRN using DESS sequences. Additionally, a geometric image combination (GIC) method to improve DESS signals’ combination was proposed.

MATERIALS AND METHODS: Adult patients undergoing 3.0 Tesla LSP MRN with DESS were prospectively enrolled. The 3D DESS echoes were separately reconstructed with and without DL and DL-GIC combined reconstructions. In a subset of patients, 3D T2-weighted short tau inversion recovery (STIR-T₂w) sequences were also acquired. Three radiologists rated 4 image stacks (‘DESS S₂‘, ‘DESS S₂ DL’, ‘DESS GIC DL’ and ‘STIR-T₂w DL’) for bulk motion, vascular suppression, nerve fascicular architecture, and overall nerve conspicuity. Relative SNR, nerve-to-muscle, -fat, and -vessel contrast ratios were measured. Statistical analysis included ANOVA and Wilcoxon signed-rank tests. p < 0.05 was considered statistically significant.

RESULTS: Forty patients (22 females; mean age = 48.6 ± 18.5 years) were enrolled. Quantitatively, ‘DESS GIC DL’ demonstrated superior relative SNR (p < 0.001), while ‘DESS S₂ DL’ exhibited superior nerve-to-background contrast ratio (p value range: 0.002 to < 0.001). Qualitatively, DESS provided superior vascular suppression and depiction of sciatic nerve fascicular architecture but more bulk motion as compared to ‘STIR-T₂w DL’. ‘DESS GIC DL’ demonstrated better nerve visualization for several smaller, distal nerve segments than ‘DESS S₂ DL’ and ‘STIR-T₂w DL’.

CONCLUSION: Application of a DL reconstruction with geometric image combination in DESS MRN improves nerve conspicuity of the LSP, especially for its smaller branch nerves.

PMID:38386108 | DOI:10.1007/s00256-024-04613-7

Ophthalmologie. 2024 Feb 22. doi: 10.1007/s00347-024-01989-8. Online ahead of print.

ABSTRACT

BACKGROUND: Various vital dyes exist on the market for intraoperative internal limiting membrane (ILM) identification. The aim of this study was to verify the added value of these dyes for ILM identification and in the difficulty of ILM peeling during pars plana vitrectomy (ppV) by a single surgeon highly experienced in this operation.

MATERIAL AND METHODS: In this study 400 ppV surgical reports involving ILM peeling were retrospectively analyzed. Intraoperative assessment of identification or difficulty of intraoperative ILM peeling had to be documented in the surgical report. The total group consisted of 2 cohorts each with 200 surgical reports (first cohort without selective vital dyes, period 2004-2006; second cohort with vital dyes in the majority of ppVs, period 2013-2020).

RESULTS: The difference between both groups in terms of intraoperative identification of ILM was statistically significant (p < 0.001); however, no statistically significant difference (p = 0.951) was found between the two groups in terms of difficulty of ILM peeling. In logistic regression analysis neither patient gender, age, eye side, lens status nor posterior vitreous limiting membrane status were significantly associated with ILM identification.

CONCLUSION: The introduction of intravital dyes represents a decisive advancement in retinal surgery. In the investigated sample this benefit was evident from two precisely defined surgical cohorts of a single highly experienced surgeon. This underlines the additional benefit of using selective vital dyes to identify ILM in macular surgery for less experienced surgeons.

PMID:38386092 | DOI:10.1007/s00347-024-01989-8

Arch Orthop Trauma Surg. 2024 Feb 22. doi: 10.1007/s00402-024-05252-2. Online ahead of print.

ABSTRACT

BACKGROUND: It is estimated that one-third of patients presenting with unilateral joint pain have contralateral osteoarthritis (OA) at first presentation. Most studies have primarily examined White patient cohorts. The purpose of this study was to determine the prevalence of contralateral joint OA for patients presenting for unilateral total knee (TKA), unicompartmental knee (UKA) or total hip arthroplasty (THA) among Asian, Native Hawaiian/Pacific Islander and White patients.

METHODS: Bilateral radiographic reports at initial presentation of 2,312 subjects who underwent unilateral arthroplasties (332 UKAs, 933 TKAs and 1,047 THAs) were reviewed. The presence of contralateral OA was recorded and compared by racial group and type of arthroplasty performed. Parametric statistical analyses were performed to determine differences between groups. Multivariable analyses were completed for each arthroplasty group to determine the influence on the presence of contralateral OA, presented as odds ratios and 95% confidence intervals.

RESULTS: Contralateral joint OA was present in 86.7%, 90.4% and 70.4% of UKA, TKA and THA patients, respectively. Concurrent hip OA was present in 41.6% and 59.5% of UKA and TKA patients. No racial differences in the prevalence of contralateral knee OA were found for knee arthroplasty patients. White patients (74.6%) had a greater prevalence of contralateral hip OA compared to Asians (66.5%, p = 0.037) amongst THA recipients. Increased age and body mass index were significantly associated with the presence of contralateral knee OA. Increased age, being male and being White were significant contributors for the presence of contralateral hip OA.

CONCLUSION: The prevalence of contralateral joint OA and concurrent hip OA is high in all three racial groups. Due to the extensive prevalence of contralateral and concurrent knee and hip OA, bilateral radiographic evaluation should be considered for all patients presenting with unilateral hip or knee pain due to OA.

PMID:38386068 | DOI:10.1007/s00402-024-05252-2

Arch Orthop Trauma Surg. 2024 Feb 22. doi: 10.1007/s00402-024-05231-7. Online ahead of print.

ABSTRACT

INTRODUCTION: This study elaborates on previous research to compare length of stay, complication rates, and total cost between patients undergoing robotic assisted total knee arthroplasty (rTKA) and conventional total knee arthroplasty (cTKA). We hypothesized that patients undergoing rTKA would have reduced length of stay, lower complication rates, improved perioperative outcomes, and higher total healthcare costs than those undergoing cTKA.

METHODS: Data were collected from the National Inpatient Sample Database Healthcare Cost and Utilization Project between the years 2016-2019. Patients undergoing rTKA and cTKA were identified under International Classification of Diseases, 10th revision codes (ICD-10-CM/PCS). Length of stay, specific complications, and total costs were examined at time point. SPSS (v 27.0 8, IBM Corp. Armonk, NY) was utilized to compare demographic and analytical statistics between rTKA and cTKA. rTKA and cTKA were compared both before and after propensity matching.

RESULTS: 17,249 rTKA (3.09%) and 541,122 cTKA (96.91%) were included. Compared to cTKA patients, rTKA patients had reduced average length of stay of 1.91 days (p < 0.001), higher average total cost of $67133.34 (p < 0.001), reduced periprosthetic infection (OR = 0.027, p < 0.001), periprosthetic dislocation (OR = 0.117, p < 0.001), periprosthetic mechanical complication (OR = 0.315, p < 0.001), pulmonary embolism (OR = 0.358, p < 0.001), transfusion (OR = 0.366, p < 0.001), pneumonia (OR = 0.468, p = 0.002), deep vein thrombosis (OR = 0.479, p = 0.001), and blood loss anemia (OR = 0.728, p < 0.001). These differences remained statistically significant even after propensity matching.

CONCLUSIONS: This study supports our hypothesis that rTKA is associated with fewer complications, but higher average total cost than cTKA. Our study shows that rTKA can be safely performed in older and sicker patients. Future studies assessing the impacts of these findings on patient reported outcomes would provide further insight into the benefits of rTKA. Furthermore, identifying patient specific factors that place them at risk for increased complications with cTKA as opposed to rTKA could provide surgeons insight on the method of TKA that maximizes patient outcomes while minimizing healthcare cost.

PMID:38386067 | DOI:10.1007/s00402-024-05231-7

Arterioscler Thromb Vasc Biol. 2024 Feb 22. doi: 10.1161/ATVBAHA.123.319789. Online ahead of print.

ABSTRACT

BACKGROUND: ANGPTL3 (angiopoietin-like protein 3) is a circulating protein with a key role in maintaining lipoprotein homeostasis. A monoclonal antibody against ANGPTL3 is an approved and well-tolerated treatment to reduce lipoproteins in familial hypercholesterolemia homozygotes. However, the reduction of hepatic ANGPTL3 synthesis using an antisense oligonucleotide unexpectedly resulted in a dose-dependent increase in liver lipid content and circulating transaminases, resulting in the termination of the clinical trial. Meanwhile, the use of silencing RNAs remains an area of active investigation. Our study sought to investigate whether intracellular downregulation of ANGPTL3 may lead to a primary increase in neutral lipids within the hepatocyte.

METHODS: We downregulated ANGPTL3 by silencing RNA in primary human hepatocytes 3-dimensional spheroids, HepG2/LX-2 3-dimensional spheroids, and in HepG2, Hep3B2, and Huh7 cultured in 2 dimensions.

RESULTS: ANGPTL3 downregulation increased neutral lipids in all models investigated. Interestingly, ANGPTL3 induced lower intracellular deiodinase type 1 protein levels resulting in a reduction in beta-oxidation and causing an increase in triglycerides stored in lipid droplets.

CONCLUSIONS: In conclusion, intracellular ANGPTL3 downregulation by silencing RNA led to an increase in triglycerides content due to a reduction in energy substrate utilization resembling a primary intracellular hepatocyte hypothyroidism.

PMID:38385290 | DOI:10.1161/ATVBAHA.123.319789

Womens Health (Lond). 2024 Jan-Dec;20:17455057241231420. doi: 10.1177/17455057241231420.

ABSTRACT

BACKGROUND: Menstrual hygiene management plays a significant role in the achievement of sustainable development goals, including good health and well-being, quality education, gender equality, women’s empowerment, and sanitation. Even though the United Nations emphasizes menstrual hygiene management as a global public health and human rights issue, studies from different parts of the world have shown there is a lack of policies in this area that affects adolescent girls.

OBJECTIVE: The study aimed to assess the menstrual-related knowledge and practices of adolescent girls (10-18 years) attending urban and rural public schools of district Khairpur of province Sindh of Pakistan.

DESIGN: This research is an analytical cross-sectional study design.

METHODS: Adolescent girls (n = 310), 159 girls from urban and 159 girls from rural schools, were enrolled. Data were collected through self-administered questionnaires. Knowledge was considered satisfactory if the participant scored ⩾12/20, and <12/20 was considered unsatisfactory knowledge. Practice scores were considered good for >10 and poor for <10. Statistical Package for the Social Science (SPSS) version 20.0 was used for data analysis. Descriptive statistics such as mean and standard deviation were calculated. The chi-square test was used to assess and compare the differences between practices and knowledge of menstrual hygiene management between urban and rural adolescent school girls.

RESULTS: We found significant differences in menstrual hygiene management among adolescent girls between urban and rural areas. Approximately two-thirds of the total school girls thought that school management had inadequate resources and toilet facilities (rural: 76% versus urban: 62%). The major source of knowledge in adolescent rural and urban girls for menstrual-related matters was mothers. More girls from the urban school (81%) were aware of using sanitary pads during menstruation. The majority of the girls from urban areas showed satisfactory knowledge whereas only 38% of rural girls were shown to have satisfactory results. Nearly 71% of urban girls were found to have good practices when compared with rural girls (12%).

CONCLUSION: With further importance by the United Nations on female education in less developed regions, where the health of women is usually given less importance, policies are required on the inclusion of reproductive health of female adolescents in the curriculum.

PMID:38385267 | DOI:10.1177/17455057241231420

J Biosoc Sci. 2024 Feb 22:1-24. doi: 10.1017/S0021932024000051. Online ahead of print.

ABSTRACT

A barrier to meeting the goal of universal health coverage in India is the inequality in utilisation of health services between indigenous and non-indigenous people. This study aimed to explore the determinants of utilisation, or non-utilisation, of public healthcare services among the Santals, an indigenous community living in West Bengal, India. The study holistically explored the utilisation of public healthcare facilities using a framework that conceptualised service coverage to be dependent on a set of determinants – viz. the nature and severity of the ailment, availability, accessibility (geographical and financial), and acceptability of the healthcare options and decision-making around these further depends on background characteristics of the individual or their family/household. This cross-sectional study adopts ethnographic approach for detailed insight into the issue and interviewed 422 adult members of Santals living in both rural (Bankura) and urban (Howrah) areas of West Bengal for demographic, socio-economic characteristics and healthcare utilisation behaviour using pre-tested data collection schedule. The findings revealed that utilisation of the public healthcare facilities was low, especially in urban areas. Residence in urban areas, being female, having higher education, engaging in salaried occupation and having availability of private allopathic and homoeopathic doctors in the locality had higher odds of not utilising public healthcare services. Issues like misbehaviour from the health personnel, unavailability of medicine, poor quality of care, and high patient load were reported as the major reasons for non-utilisation of public health services. The finding highlights the importance of improving the availability and quality of care of healthcare services for marginalised populations because these communities live in geographically isolated places and have low affordability of private healthcare. The health programme needs to address these issues to improve the utilisation and reduce the inequality in healthcare utilisation, which would be beneficial for all segments of Indian population.

PMID:38385266 | DOI:10.1017/S0021932024000051