Risk Groups Research Articles

Construction of a disulfidptosis-associated lncRNAs risk model to predict prognosis and immuno-infiltration analysis of lung adenocarcinoma

Objective: To develop a risk model based on LncRNAs associated with disulfidptosis to forecast the prognosis and assess immune infiltration of Lung adenocarcinoma (LUAD). Methods: This study employed a bioinformatics approach. The study was conducted from March 29, 2023 and concluded on July 1, 2023 at Guangzhou University of Chinese Medicine, Guangzhou, China. Transcriptomic data specific to LUAD were collected from TCGA database. Disulfidptosis-related LncRNAs were preliminarily screened using co-expression analysis, followed by screening using Lasso regression and Cox regression to identify LncRNAs. Subsequently, prognostic prediction models were constructed. To assess the model, survival analysis, subject operating characteristic curves, and calibration curves were employed. To evaluate the tumor microenvironment, the “estimate” package was used, while the “ggpubr” package was utilized to visualize the variations. Additionally, we employed CIBERSORT to examine immune cell infiltration abundance. Results: A prognostic prediction model was constructed using five LncRNAs. The high-risk group displayed a shorter overall survival and progression-free survival (P<0.05). The concordance index was calculated as 0.704 (95% CI: 0.654-0.754). GSEA analysis reveals that high risk group is associated with the cell cycle pathway and steroid hormone biosynthesis pathway, while the low-risk group is associated with hematopoietic cell pathway and allograft rejection pathway. Immune cell infiltration analysis indicated associations between the prognostic model and activated T cells CD4 memory, T cells CD8, etc. Conclusions: The risk model of Disulfidptosis-related LncRNAs can predict the prognosis of LUAD and evaluate the immune infiltration, providing a new direction for the treatment of LUAD. doi: https://doi.org/10.12669/pjms.40.10.9025 How to cite this: Liu J, Nie H, Du W, Song W. Construction of a disulfidptosis-associated lncRNAs risk model to predict prognosis and immuno-infiltration analysis of lung adenocarcinoma. Pak J Med Sci. 2024;40(10):2368-2372. doi: https://doi.org/10.12669/pjms.40.10.9025 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

PRODIGY score predicts respiratory depression in the post-anesthesia care unit: A post-hoc analysis.

Surgical patients who experience respiratory depressive episodes (RDEs) during their post-anesthesia care unit (PACU) admission are at a higher risk of developing subsequent respiratory complications in general care wards. A risk assessment tool for PACU RDEs has not been previously assessed. The PRediction of Opioid-induced respiratory Depression In patients monitored by capnoGraphY (PRODIGY) score is an assessment tool that uses baseline patient variables to categorize patients into low, intermediate, or high risk groups for RDEs in general care wards. This study assessed whether PRODIGY groups are associated with PACU RDEs. This analysis utilized data from a previous observational trial of PACU RDEs detected by capnography. PRODIGY scores were retrospectively calculated, and the number and duration of respiratory alerts were compared among PRODIGY groups. Twenty-six (29.9%) patients were classified as low risk, 29 (33.3%) as intermediate risk, and 32 (36.8%) as high risk. A total of 3,580 alerts were recorded in the PACU, 47% of which were apnea episodes lasting ≥ 10 seconds. The total number and duration of alerts were highest in high risk group patients (median 56 [IQR 12 - 87] alerts per patient vs 22 [9 - 37] in low risk and 26 [13 - 42] in intermediate risk patients, P = 0.035; 303 [123 - 885] seconds vs 177 [30 - 779] in low risk and 301 [168 - 703] in intermediate risk patients, P = 0.042). Poisson regression analysis indicated that the rate of RDEs in the high PRODIGY risk group was higher than in the intermediate (rate ratio estimate = 2.01 [95% CI 1.86 - 2.18], P < 0.001) and low (rate ratio estimate = 2.25 [95% confidence interval 2.07 - 2.45], P < 0.001) risk groups. This analysis suggests that the PRODIGY score may be useful in assessing the risk of PACU RDEs. Trial Registration: https://www.clinicaltrials.gov/ct2/show/NCT02707003.

Longitudinal liquid biopsy predicts clinical benefit from immunotherapy in advanced non-small cell lung cancer

High heterogeneity in clinical benefit characterizes the use of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC). We prospectively enrolled 113 advanced NSCLC patients treated with ICIs and performed liquid biopsy at the time of ICI start (T1), after 3 weeks (T2) and at the time of radiological evaluation (T3). Molecular variables were associated with outcome endpoints: cfDNA quantification, its dynamic change (∆T2–T1), variant allele frequency (VAF) of the gene with the highest frequency detected at baseline with NGS (maxVAF) and its dynamic change (∆T2–T1). At multivariate analysis, PD-L1 negativity, T1 cfDNA, cfDNA increase (∆T2–T1), and T2 VAF were significantly associated with shorter progression-free survival (PFS); PD-L1 negativity, squamous histology, T1 cfDNA, cfDNA (∆T2–T1) increase, and T2 maxVAF affected overall survival (OS). Among high PD-L1 expressing patients treated in first-line, elevated T2 maxVAF and cfDNA increase (∆T2–T1) correlated with worse PFS; higher T2 maxVAF and cfDNA increase (∆T2–T1) with worse OS. Derived integrated models were used to build nomograms and categorize different risk groups.

Comparing the measurement properties of the EQ-5D-5L, SF-6Dv2, QLU-C10D and FACT-8D among survivors of classical Hodgkin's lymphoma.

This study aimed to evaluate the measurement properties of EQ-5D-5L, SF-6Dv2, QLU-C10D, and FACT-8D in survivors of Classical Hodgkin's Lymphoma (CHL). A cross-sectional, web-based survey was conducted from May to August 2022 to collect data. Chinese value sets were used to estimate the utility scores for EQ-5D-5L, SF-6Dv2, and QLU-C10D, while the Australian value set was used for FACT-8D. The measurement properties assessed included ceiling and floor effects, convergent validity (assessing associations between similar dimensions/utility scores using Spearman's rank correlation and intraclass correlation coefficient), and known-group validity (measures could differentiate health-related quality of life (HRQoL) between risk groups). A total of 534 CHL survivors participated in the survey and completed the questionnaire. All dimensions of EQ-5D-5L, SF-6D (except for vitality), QLU-C10D, and FACT-8D showed ceiling effects, ranging from 18 to 91.6%. The EQ-5D-5L demonstrated the higher ceiling effects compared to other measures, with 33% of patients reporting full health on this scale. All 30 pairs of associations between similar dimensions from the four measures were statistically significant, with correlation coefficients ranging from 0.29 to 0.77. Regarding utility scores, the EQ-5D-5L utility score showed a stronger correlation with SF-6Dv2 than with the other two measures. Statistically significant correlations of utility scores between the four measures were observed. EQ-5D-5L can significantly differentiate HRQoL among all known-groups, while SF-6Dv2, QLU-C10D, and FACT-8D showed a less strong discriminant ability. EQ-5D-5L outperformed SF-6Dv2 in terms of agreement with cancer-specific PRMs and discriminant ability. However, SF-6Dv2 showed stronger associations with similar dimensions of QLU-C10D and FACT-8D, indicating high convergent validity. The generic PBMs are sensitive enough to measure HRQoL in survivors of CHL.

Early oncological outcomes of delayed radical prostatectomy: A prospective, international, follow‐up analysis of the COVIDSurg‐Cancer study

AbstractObjectivesThe objective of this study is to compare the early oncological outcomes of delayed (&gt;90 days) versus scheduled (≤90 days) radical prostatectomy (RP).Patients and methodsPatients with prostate cancer due to undergo surgery between March 2020 and June 2020 who were enrolled in the COVIDSurg‐Cancer international, observational study were prospectively followed up for 1 year. Time to surgery was defined as the difference between the operation date and the multi‐disciplinary team decision to offer surgery. The primary outcome was the positive surgical margin (PSM) rate. Biochemical recurrence (BCR), upgradation and upstaging were secondary oncological outcomes. The Independent t‐test and Mann Whitney U test were used to compare means between groups and regression models and were used to investigate factors associated with the primary outcome.ResultsFour hundred seventy‐six (78.7%) patients underwent RP from 605 that were eligible. Three hundred seven (64.5%) patients underwent scheduled RP, and 169 (35.5%) underwent delayed RP. A small proportion of men (n = 35, 6.8%) did not undergo RP within the 1‐year follow‐up period. More men with high‐risk disease (72.8%) underwent scheduled RP compared to men with intermediate‐risk disease (60.2%) (p &lt; 0.05). There was no statistically significant difference in the PSM rate between the two groups (p = 0.512). Delay in surgery was not associated with an increased PSM or BCR on univariable or multivariable analyses. There was statistically significantly greater upstaging (p &lt; 0.05) in the delayed group but no difference in upgradation.ConclusionHigh‐risk men were prioritised for surgery during the COVID‐19 pandemic. Our prospective data support previous retrospective, cancer‐registry evidence suggesting no adverse oncological impact after delaying RP across all risk groups. Our study is limited by the short follow‐up period, and therefore, longer term conclusions cannot be drawn.

If the first child is breech, overall outcomes for families with two children are similar regardless of the mode of the first birth

Cesarean section for breech presentation is often recommended. However, cesarean section affects future reproduction. The aim of this study was to assess the effect of mode of the first birth in breech on outcomes of the second birth and the two births together. This is a register-based nationwide cohort study including 23 062 women with a first singleton birth in breech ≥ 34 gestational weeks and a subsequent singleton birth in Sweden 2000–2019. Exposure was mode of first delivery. Main maternal outcome was a composite of fourth-degree perineal injury, postpartum hemorrhage requiring blood transfusion, hysterectomy, or death. Main infant outcome was a composite of stillbirth, extremely preterm birth (< 28 weeks), moderate to severe hypoxic ischemic encephalopathy, therapeutic hypothermia, or death. Outcomes were analyzed using multivariable logistic regression. In the first birth, the infant composite outcome affected < 1% in both groups but the risk was higher in the vaginal breech group (13/1525), compared with the breech CS group (27/21 537), aOR 7.06, 95% CI 2.91–17.1. In the second birth, the infant composite outcome affected < 1% in both groups but the risk was lower for the first vaginal breech group (3/1525) compared with the first breech CS group (152/21 537), aOR 0.26, 95% CI 0.08–0.84. There was no significant difference between the groups in risk of composite infant outcome in the two births assessed together, or in risk of composite maternal outcome. In total, the chance of a two-children family without maternal or infant severe adverse composite outcome was high and similar regardless mode of the breech first birth.

The Saudi thoracic society guidelines for vaccinations in adult patients with chronic respiratory diseases

Abstract: Adult patients with chronic respiratory diseases (CRDs) are considered high risk group who are more likely to experience worse clinical outcomes if they acquire viral or bacterial infections. Vaccination is the best preventive tool to reduce the risk of infection and disease occurrence and to reduce the level of severity of complications associated with the various vaccine-preventable infections. These guidelines were developed by the Saudi Thoracic Society task force to emphasize the critical importance of improving the vaccine coverage rates in adult patients with CRD. They are intended to serve as a reference for healthcare practitioners managing CRD patients. The guidelines aimed to review the current knowledge related to vaccination efficacy in adult patients with CRD, based on the recent evidence and recommendations. Integrating the administration of the recommended vaccines in routine healthcare, such as during outpatient visits or before hospital discharge, is crucial for improving the vaccination rates in high-risk patients. The key strategies to address this public health priority include simplifying vaccination guidelines to enhance their accessibility and implementation by healthcare providers, increasing awareness in both the patients and healthcare providers that vaccines are not only intended for children. Additional strategies include maintaining continuous surveillance and advance research to discover novel vaccines. This approach aims to expand the range of preventable diseases and improve overall health and well-being. Vaccine hesitancy remains a significant challenge that necessitates a clear understanding of the community concerns. Providing appropriate education and communication, as well as addressing these concerns, are the crucial steps toward improving vaccine acceptance and uptake. By implementing these guidelines and multifaceted strategies, healthcare systems can optimize vaccine coverage and protection for patients with CRD, reduce the burden of vaccine-preventable complications, and improve the clinical outcomes in this vulnerable population.

COVID-19 Vaccine Preferences in General Populations in Canada, Germany, the United Kingdom, and the United States: Discrete Choice Experiment.

Despite strong evidence supporting COVID-19 vaccine efficacy and safety, a proportion of the population remains hesitant to receive immunization. Discrete choice experiments (DCEs) can help assess preferences and decision-making drivers. We aim to (1) elicit preferences for COVID-19 vaccines in Canada, Germany, the United Kingdom, and the United States; (2) understand which vaccine attributes people there value; and (3) gain insight into the choices that different population subgroups make regarding COVID-19 vaccines. Participants in the 2019nCoV-408 study were aged ≥18 years; self-reported antivaccinationists were excluded. A DCE with a series of 2 hypothetical vaccine options was embedded into a survey to determine participant treatment preferences (primary objective). Survey questions covered vaccine preference, previous COVID-19 experiences, and demographics, which were summarized using descriptive statistics to understand the study participants' backgrounds. In the DCE, participants were provided choice pairs: 1 set with and 1 without an "opt-out" option. Each participant viewed 11 unique vaccine profiles. Vaccine attributes consisted of type (messenger RNA or protein), level of protection against any or severe COVID-19, risk of side effects (common and serious), and potential coadministration of COVID-19 and influenza vaccines. Attribute level selections were included for protection and safety (degree of effectiveness and side effect risk, respectively). Participants were stratified by vaccination status (unvaccinated, or partially or fully vaccinated) and disease risk group (high-risk or non-high-risk). A conditional logit model was used to analyze DCE data to estimate preferences of vaccine attributes, with the percentage relative importance calculated to allow for its ranking. Each model was run twice to account for sets with and without the opt-out options. The mean age of participants (N=2000) was 48 (SD 18.8) years, and 51.25% (1025/2000) were male. The DCE revealed that the most important COVID-19 vaccine attributes were protection against severe COVID-19 or any severity of COVID-19 and common side effects. Protection against severe COVID-19 was the most important attribute for fully vaccinated participants, which significantly differed from the unvaccinated or partially vaccinated subgroup (relative importance 34.8% vs 30.6%; P=.049). Avoiding serious vaccine side effects was a significantly higher priority for the unvaccinated or partially versus fully vaccinated subgroup (relative importance 10.7% vs 8.2%; P=.044). Attributes with significant differences in the relative importance between the high-risk versus non-high-risk subgroups were protection against severe COVID-19 (38.2% vs 31.5%; P<.000), avoiding common vaccine side effects (12% vs 20.5%; P<.000), and avoiding serious vaccine side effects (9.7% vs 7.5%; P=.002). This DCE identified COVID-19 vaccine attributes, such as protection against severe COVID-19, that may influence preference and drive choice and can inform vaccine strategies. The high ranking of common and serious vaccine side effects suggests that, when the efficacy of 2 vaccines is comparable, safety is a key decision-making factor.

The Integrated Transcriptome Bioinformatics Analysis of Energy Metabolism-Related Profiles for Dorsal Root Ganglion of Neuropathic Pain.

Neuropathic pain (NP) is a debilitating disease and is associated with energy metabolism alterations. This study aimed to identify energy metabolism-related differentially expressed genes (EMRDEGs) in NP, construct a diagnostic model, and analyze immune cell infiltration and single-cell gene expression characteristics of NP. GSE89224, GSE123919, and GSE134003 were downloaded from the Gene Expression Omnibus. Differentially expressed genes (DEGs) analysis and an intersection with highly energy metabolism-related modules in weighted gene co-expression network analysis (WGCNA) was performed in GSE89224. Least absolute shrinkage and selection operator (LASSO), random forest, and logistic regression were used for model genes selection. NP samples were divided into high- and low-risk groups and different disease subtypes based on risk score of LASSO algorithm and consensus clustering analysis, respectively. Immune cell composition was estimated in different risk groups and NP subtypes. Datasets 134,003 were performed for identification of single-cell DEGs and functional enrichment. Cell-cell communications and pseudo-time analysis to reveal the expression profile of NP. A total of 38 EMRDEGs were obtained and are majorly enriched in metabolism about glioma and inflammation. LASSO, random forest, and logistic regression identified 6 model genes, which were Itpr1, Gng8, Socs3, Fscn1, Cckbr, and Camk1. The nomogram, based on six model genes, had a good predictive ability, concordance, and diagnostic value. The comparisons between different risk groups and NP subtypes identified important pathways and different immune cells component. The immune infiltration results majorly associated with inflammation and energy metabolism. Single-cell analysis revealed cell-cell communications and cells differentiation characteristics of NP. In conclusion, our results not only elucidate the involvement of energy metabolism in NP but also provides a robust diagnostic tool with six model genes. These findings might give insight into the pathogenesis of NP and provide effective therapeutic regimens for the treatment of NP.

Cognitive function characteristics and influencing factors in patients with depressive disorders: a 5-year follow-up report based on the epidemiological survey of mental disorders in Shandong Province, China

ObjectiveCognitive impairment represents a notable feature of depressive disorders. Comprehending its characteristics and influencing factors is vital for patient rehabilitation.MethodsThis study is based on the 2015 Shandong Province epidemiological survey of mental disorders, from which 871 individuals meeting DSM-IV criteria for depressive disorders were selected as the research group. Using 1:1:1 matching by sex, age, and residence, we randomly selected 825 individuals with no DSM-IV diagnosis but positive on GHQ-12 and additional risk assessments as the elevated risk control group, and 825 with negative screenings as the minimal risk control group. In 2020, a follow-up survey was conducted, resulting in a final analysis of 1,855 cases. The survey included demographic data, various clinical information, and a series of screening and questionnaire assessments.ResultsThe current depressive group scored lower on the MoCA than the non-depressive group (t=8.86, P&amp;lt;0.01). The research group scored lower on the MoCA than the elevated and minimal risk group (F=11.98, P&amp;lt;0.01). The depression-unremitted group scored lower than the depression-remitted group (t=6.44, P&amp;lt;0.01). The Analysis indicated that males, with better life quality, poor early psychological status and, and longer education were associated with higher MoCA scores. Conversely, older age, rural residency, employment, current depression, and poor marital were associated with lower MoCA scores.ConclusionIndividuals with depression commonly suffer cognitive impairment, which tends to partially improve as depression remits. Individual cognitive function is influenced by early psychological health, depressive status, quality of life, age, sex, educational level, residence, occupational, and marital status.

Systematic review of the economic impact of novel Mycobacterium tuberculosis specific antigen-based skin tests for detection of TB infection compared with tuberculin skin test and interferon-gamma release assays.

The Purified Protein Derivative tuberculin skin tests (TST) and blood-based Mycobacterium tuberculosis (M.tb) specific interferon-gamma release assays (IGRA) are the currently used tests for identifying individuals with TB infection for preventive treatment. However, challenges around access and implementation have limited their use. Novel M.tb specific skin tests (TBST) such as Diaskintest, ESAT6-CFP10 (C-TST), C-Tb (also known as Cy-Tb), and DPPD may provide accurate and scalable options but evidence synthesis on their economic impact is lacking. We conducted two separate systematic reviews to compare the costs and cost-effectiveness of (1) the novel skin tests TBST (primary), and (2) TST and IGRA tests (secondary), to support WHO guideline development. We searched for articles presenting economic evaluations of the diagnostic tests using a health provider perspective and related to TB infection in humans. We considered papers written in English, Chinese or Russian. In the primary review, eight studies for novel TBST were found. One study in Brazil assessed cost-effectiveness of C-TST and Diaskintest and seven in Russia assessed the Diaskintest, while none evaluated C-Tb or DPPD. The review showed on average, Diaskintest kit costs (in 2021 USD) $1.60 (1.50 - 1.70), while full unit costs were estimated at $5.07. C-TST unit cost was $9.96. The second review found 32 articles on IGRA and/or the TST. These presented an average TST full unit cost of $37.88, and $87.81 for IGRA. Studies' quality for TBST was limited while high-quality studies were found for TST and IGRA tests. In conclusion, there is limited evidence regarding the costs and cost-effectiveness of novel TBST. Conversely, there is substantial evidence for TST and IGRA tests, but most studies were performed in high-income and low-TB burden settings and their cost-effectiveness varied between and within risk groups without clear economic consensus.

Low-grade gliomas of the brainstem in children: stratification into risk groups and the assessment of the effectiveness of targeted therapy

Low-grade gliomas of the brainstem in children: stratification into risk groups and the assessment of the effectiveness of targeted therapy

Application of the world guidelines for falls prevention and management’s risk stratification algorithm to patients on a frailty intervention pathway and the potential utility of sensory impairment information

BackgroundThe 2022 world guidelines for falls prevention and management suggest measuring sensory function including dizziness, vision, and hearing. These variables are not included in the falls risk stratification algorithm. This study sought to investigate the utility of the guidelines and potential avenues for improvement. This study applied the falls risk stratification recommendations and reviewed the individual sensory impairment risk factor variables predictive of falls and falls risk grouping in those assessed by a frailty intervention team (FIT) based in an emergency department (ED).MethodsPatients over 65 years old who attended the ED and had a comprehensive geriatric assessment carried out by FIT over a period of four months were included in this retrospective cross-sectional study. Patient characteristics, medication, physical and sensory function status data was retrieved and analysed with respect to falls and falls risk grouping.ResultsData was gathered retrospectively from 392 patients. Excluding those with missing data, almost all attendees were in the high-risk of falls category (n = 170, 43.4%), or the low-risk category (n = 149, 38.0%). Few people were in the intermediate-risk category (n = 19, 4.8%). Hearing loss and dizziness were significantly associated with falls incidence, whereas vision and balance were not. Hearing loss, balance and dizziness were significantly associated with risk grouping, whereas vision was not.ConclusionsMost older adults included in the analysis fell into the low- or high-risk categories, with a minority in the intermediate-risk category. This suggests that the inclusion criteria for the intermediate category could be altered for greater sensitivity. While impaired balance and vision were the most common impairments, hearing status, balance and dizziness were associated with risk group. These results, through a practical application of the world guidelines for falls to an acute clinical sample, raise the possibility of refining the falls risk stratification criteria, and highlight the capacity for additional sensory intervention to mitigate falls risk.

The Correlates of Psychological Resilience in Turkish Adolescents During The COVID-19 Pandemic: A Systematic Review

Adolescents, already in a vulnerable state due to the challenges of adolescence, were among risk groups to develop psychosocial and emotional problems during the COVID-19 pandemic. Research conducted with adolescents identified psychological resilience as one of the protective factors which helped them cope better with pandemic-related adversities. The aim of this systematic review is to determine the correlates of Turkish adolescents’ psychological resilience to gain a better understanding of its protective role during the pandemic. Using the related keywords (Turkish adolescents, students, psychological resilience, COVID-19 Pandemic) and limiting the publication period as 2020-2024, a database search was conducted, in which 340 articles were identified. 10 articles that met the eligibility criteria were included in the systematic review. By reviewing the articles systematically, doing exercise, emotional flexibility, spirituality, hope, parental and peer support, financial support, psycho-education programs supporting pandemic-specific coping, and certain personality traits including openness to new experience, extraversion, conscientiousness, and agreeableness were identified as variables that are positively correlated with psychological resilience. On the other hand, fear of COVID-19, anxiety, depression, post traumatic stress disorder (PTSD), smartphone addiction, playing digital games, online education, exam anxiety and neuroticism are variables that have negative correlation with psychological resilience. Based on the results, it appears that during the COVID-19 pandemic, psychological resilience, in relation with other individual and social/contextual protective factors, functioned as a psychological buffer against psychological problems for Turkish adolescents.

External evaluation of Brain Injury Guideline (BIG) low risk criteria for traumatic brain injury

BackgroundFewer than 20 % of traumatic brain injury (TBI) cases with traumatic intracranial hemorrhage (ICH) result in clinical deterioration. The Brain Injury Guideline (BIG) criteria were published in 2014 and categorize patients with TBI into three risk groups (BIG 1, 2, and 3) based on CT scan findings, neurological examination, anti-coagulant/platelet medications, and intoxication. Early data is promising, suggesting no instances of neurosurgical intervention or death in the low-risk BIG1 category within 30 days. We sought to externally validate the BIG criteria and identify patients with TBI at low risk of clinical deterioration. We hypothesized that patients meeting the BIG1 low risk criteria have less than a 1 % risk of death or neurosurgical intervention. MethodsWe performed a retrospective cohort study of a level 1 trauma center's trauma registry records from 2011 to 2022 to identify patients with head trauma. We abstracted demographics, injury characteristics, clinical course, CT imaging results, and outcomes, and we categorized patients according to the BIG criteria. The Clopper-Pearson Exact method was used to estimate outcome frequency with confidence intervals. The primary outcome was death or neurosurgical intervention within 30 days. Secondary outcomes included progression on repeat head CT (RHCT), ICU admission with neurocritical care intervention, and TBI-related hospital readmission within 30 days. ResultsA total of 1714 patients with TBI with ICH were identified from the trauma registry. 325 patients were excluded due to missing data, pregnancy, incarceration, polytrauma, or GCS < 13, leaving 1389 for analysis. 193 patients (13.9 %) were classified as BIG1. No patients classified as BIG1 experienced the primary outcome measures of death or neurosurgical intervention (95 % confidence interval [CI]: 0 %–1.9 %). The number of patients who experienced the secondary outcome measures of progression on RHCT, ICU admission with neurocritical care intervention, or TBI-related hospital readmission within 30 days were 9 (4.7 %, 95 % CI: 2.2 %–8.7 %), 1 (0.5 %, 95 % CI: 0 %–2.9 %), and 4 (2.1 %, 95 % CI: 0.6 %–5.2 %), respectively. ConclusionBIG1 criteria identified a low-risk subset of patients with TBI with ICH. However, an upper 95 % CI of 1.9 % does not exclude the risk of neurologic deterioration being <1 %. Validation of these criteria in larger cohorts is warranted.

Infections Deaths in Acute Lymphoblastic Leukemia More Frequent in High Risk Leukemia

Abstract Background Acute lymphoblastic leukemia (ALL) in children currently has more than 90% survival in higher resource countries. However, in less resource countries, the survival rates are lower and infections are frequent causes. Risks for infections and poor outcomes vary during the chemotherapy phases. There is a paucity of data concerning the frequencies of the chemotherapy phase where the event is more probable. Our primary objective is to describe infections frequencies and outcomes of infection in children and also to look for association with risk factors. Methods Patients (Pts) were treated according to ALLIC-BFM-2010 protocol, a simpler branch of the BFM-AEIOP protocol and accrued prospectively. The main question is comparing outcomes of two randomizations using higher dose chemotherapy based on the leukemia risk. The risk severity was based on levels of measurable residual disease (&amp;lt;0.1, 0.1-10, &amp;gt;10 %,) and categorized in high (HR), intermediate (IR), and low (LR) risks. In SR Pts with B-cell-precursor ALL two doses of daunorubicin were prescribed in induction compared with four doses in all others. In consolidation, high-dose methotrexate was administered at 5g/m2 for SR/IR T-cell ALL and at 2g/m2 for SR/IR B-precursor-ALL. Consolidation for HR pts consisted of three intensive polychemotherapy blocks. Only T-ALL and HR pts age &amp;gt; 1 year received prophylactic cranial radiotherapy (12 Gy). Therapeutic cranial radiotherapy was reserved for pts with initial CNS. We performed a descriptive analysis, comparison of frequencies and proportions using Fisher test/Ji2. For time to event proportion we used Cox Analysis. Results 2232 de novo ALL pts were analyzed. Median age 5y (IQR 3-10), 56.3% were males. 2.1% had Down Syndrome; 24% categorized as HR, 56% as IR, and 20% as LR. The Immunophenotype analysis mostly B lineage (88.8%) and less T lineage (11.2%). The majority (96.7%) of pts achieved complete remission. Estimated mean time of survival was 8.8 years (ES 0.099, CI 95% 8.38-8.77) and the overall survival rate was 74 % (0.01). Trial wide, 518 (23.2%) pts died, 59 (2.6%) pts had criteria for clinical sepsis and 459 (20%) for not related sepsis causes. According to phase of the protocol, in less than one month from diagnosis, 21 events (35.6%) were observed; from 2-3 months 9 events (15.3%), from 4-6 months 6 events, (10.2%) and afterwards 23 events (39%) (p-value 0.000). No difference was found on T vs B immunophenotype, sex, age or Down syndrome. (P-value NS). However significant differences were found on risk groups 26/538 pts (4.8%) died on HR, 24/1248 (1.9%) in IR and 9/433 (2.1%) on standard risk (p-value 0.009). There was an association between the rates of sepsis and death on pts randomized to I and II protocols (p-value 0.007 and P-value 0.007). Conclusion In this large cohort of pts, we could demonstrate association between sepsis and mortality in those high-risk groups and in those pts randomized to higher chemotherapy doses. These results will allow to establish strategies to prevent infections or maximize medical interventions preventing poor infectious outcomes in high-risk groups.

Daratumumab-Based Therapeutic Approaches and Clinical Outcomes in Multiple Myeloma and other Plasma Cell Dyscrasias: Insights from a Nationwide Real-World Chart Review Study.

Singapore leads Southeast Asia in the routine use of daratumumab for multiple myeloma and other plasma cell dyscrasias. This retrospective review analyzed 112 patients who received daratumumab between 2012 and 2020. Tolerability, and efficacy based on prior lines (PL) of therapy, cytogenetic risk group, and the presence of renal impairment were presented. Infusion-related reactions occurred in 26.8% of patients. Grades 1 and 2 hematological and non-hematological adverse events were observed in 14.3% and 33.9% of patients, respectively. After a median follow-up of 16.9 months, there was no significant difference in overall response rates (ORR) (86% versus 76.3%, p = 0.082) or depth of response (≥ complete response (CR), 35.1% versus 28.9%, p = 0.469) between myeloma patients with and without renal dysfunction. Newly diagnosed and relapsed/refractory patients had an ORR of 92% and 76.3%, and a ≥ VGPR (very good partial response) rate of 80% and 55.3%, respectively. Median progression-free survival (PFS) was better for patients with 0/1 PL compared to ≥ 2 PLs (19.8 versus 6.2 months, p < 0.001), with a deeper response (≥ CR, 38.5% versus 16.7%, p = 0.033). Forty-six and a half percentage of patients had high-risk FISH abnormalities, and those with 0/1 PL had a significantly better ORR than those with ≥ 2 PLs (83.3% vsersus 47.1%, p = 0.022), achieving an ORR similar to that of the general cohort (80.2%, p = 0.905). In conclusion, positioning daratumumab in earlier lines of therapy leads to better outcomes and may mitigate the impact of high-risk FISH abnormalities.

The unique CARWL score stratifies locally advanced nasopharyngeal cancer patients receiving concurrent chemoradiotherapy into risk groups for radiation-induced trismus

PurposeTo determine the utility of the novel CARWL score, which integrates C-reactive protein-to-albumin ratio (CAR) and significant weight loss (SWL), in stratifying the locally advanced nasopharyngeal carcinoma (LA-NPC) patients into significantly different radiation-induced trismus (RIT) risk groups following definitive C-CRT.Patients and methodsThis retrospective study analyzed the medical records of 286 LA-NPC patients who received C-CRT between January 2010 and December 2022. The maximum mouth opening (MMO) was measured before the C-CRT, at 1, 3, 6, 9, and 12 months, and every 6 months after that during the follow-up. Additionally, the CAR value just before the commencement of C-CRT and SWL defined as a weight loss > 5% in the preceding six months were documented for each patient. RIT was defined as a MMO ≤ 35 mm.ResultsThe optimal CAR cut-off was 3.03 (area under the curve: 87.3%; sensitivity: 82.6%; specificity: 80.9%, J-index: 0.635), using receiver operating characteristic (ROC) curve analysis, with RIT incidence being the event. We stratified the patients into three CARWL score groups. CARWL-0: CAR < 3.0 and WL ≤ 5.0% (N = 92), CARWL-1: CAR < 3.0 and WL > 5.0% or CAR ≥ 3.0 (N = 99), and WL ≤ 5.0% and CARWL-2: CAR > 3.0 and WL > 5.0% (N = 95). The incidence of RIT increased significantly across CARWL score groups (8.7% for CARWL-0, 23.2% for CARWL-1, and 44.2% for CARWL-2; P < 0.001).ConclusionThe current study indicated that the novel CARWL scoring system is efficient in precisely stratifying LA-NPC patients into distinct RIT risk groups after C-CRT.

Atherosclerotic vascular lesion in the coal industry workers of average and high fatal risk groups

Introduction. Experts do not take into account the presence of subclinical atherosclerosis when stratifying risk on the SCORE scale, however, it is the main substrate for the occurrence of cardiovascular disasters. Most primary cardiovascular events occur in low cardiovascular risk groups, which requires timely detection of atherosclerosis and preventive measures to preserve the working population's ability to work and reduce the economic burden of treatment of cardiovascular diseases. The study aims to research the incidence of atherosclerosis in workers of the main professions of the coal industry in the South of Kuzbass in groups of medium and high risk of fatal events on the SCORE scale. Materials and methods. We divided the subjects into two groups using the SCORE scale: high-risk (main) — from 5 to 9%, which included 60 people, and moderate-risk group — from 2 to 4% (comparison) — 70 employees. The average age of the first was 50.98±0.43 years, the comparison group was 49.96±0.35 years (p=0.070). The scientists examined the indicators of blood pressure, lipid, carbohydrate and purine metabolism, and performed an ultrasound examination of the main arteries. Results. The incidence of atherosclerotic plaques in at least one vascular basin was 80.0% in the main group and 78.6% in the comparison group, p=0.845. The frequency of carotid artery atheromas in the high-risk group on the SCORE scale (52.7%) did not significantly differ from the comparison group (54.3%), p=0.862; a similar pattern in the arteries of the lower extremities: 80.0% vs. 70.0%, respectively, p=0.203. The frequency of carotid artery atheromas in the high-risk group on the SCORE scale (52.7%) did not significantly differ from the comparison group (54.3%), p=0.862; a similar pattern in the arteries of the lower extremities: 80.0% vs. 70.0%, respectively, p=0.203. The combination of thickening of the intima of vessels and the presence of atheromas tended to be more frequent in the main group — 83.6% compared with those in the comparison group — 70.1%, p=0.076 Limitations. The study is limited by the number of examined patients who underwent periodic medical examination at the Scientific Research Institute of Complex Problems of Hygiene and Occupational Diseases. Conclusion. The incidence of atherosclerosis among employees of coal enterprises turned out to be very high and did not statistically differ in the groups of medium and high fatal risk stratified on the SCORE scale, which requires more thorough screening and measures of enhanced angioprotective prevention, even in people with a low risk of fatal cardiovascular disasters. Ethics. All the subjects signed an informed consent to participate in the study, the Protocol of which corresponded to the requirements of the Bioethical Committee of the Research Institute of Complex Problems of Hygiene and Occupational Diseases, executed in accordance with the Helsinki Declaration of the World Medical Association "Ethical Principles of conducting medical research with human participation as a subject" as amended in 2013 and the "Rules of Good Clinical Practice" approved by the order Ministry of Health of the Russian Federation No. 200n dated April 1, 2016.

Identification and experimental validation of a sialylation–related long noncoding RNA signature for prognosis of bladder cancer

BackgroundThe dysregulation of sialylation plays a pivotal role in cancer progression and metastasis, impacting various aspects of tumor behavior. This study aimed to investigate the prognostic significance of long non-coding RNAs (lncRNAs) in relation to sialylation. Additionally, we aimed to develop a signature of sialylation-related lncRNAs in the context of bladder cancer.MethodsThis study used transcriptomic data and clinical information from the TCGA (the Cancer Genome Atlas) database to screen for sialylation-related lncRNAs and constructed a prognostic model. The relationships between these lncRNAs and biological pathways, immune cell infiltration, drug sensitivity, etc., were analyzed, and the expression of some lncRNAs was validated at the cellular level.ResultsThis study identified 6 prognostic lncRNAs related to sialylation and constructed a risk score model with high predictive accuracy and reliability. The survival period of patients in the high-risk group was significantly lower than that of the low-risk group, and it was related to various biological pathways and immune functions. In addition, this study found differences in the sensitivity of patients in different risk groups to chemotherapy drugs, providing a reference for personalized treatment.ConclusionIn this study, we examined the relationship between sialylation-related lncRNA and the prognosis of bladder cancer, providing new molecular markers and potential targets for diagnosis and treatment. Our research revealed correlations between sialylation-related lncRNA characteristics and clinicopathological features, potential mechanisms, somatic mutations, immune microenvironment, chemotherapy response, and predicted drug sensitivity in bladder cancer. Additionally, in vitro cellular studies were conducted to validate these findings and lay the groundwork for future clinical applications.