Resultados a largo plazo del tratamiento de la degeneración macular asociada a la edad neovascular mediante fármacos antiangiogénicos: revisión de la bibliografía / Long-term results of treatment of neovascular age-related macular degeneration using antiangiogenic drugs: A review of the literature

La degeneración macular asociada a la edad (DMAE) constituye una de las principales causas de la pérdida de agudeza visual (AV) en los mayores de 50 años en el mundo, siendo la DMAE neovascular (DMAEn) la causante del 80% de los casos de pérdida de visión severa debido a esta enfermedad. Hace ya más de una década que se emplean los fármacos antifactor de crecimiento del endotelio vascular (anti-VEGF) para el tratamiento de esta enfermedad, cambiando drásticamente el pronóstico visual de estos pacientes. Sin embargo, los primeros estudios de los que se disponían datos de los resultados eran a corto plazo. En la actualidad existen ya diferentes series publicadas de los resultados de la DMAE a largo plazo tras el tratamiento con anti-VEGF, siendo el objetivo de la presente revisión sintetizar dichos resultados. El seguimiento medio de los estudios incluidos fue de 8,2 años (rango: 5-12 años). La AV inicial media fue 55,3 letras del Early Treatment Diabetic Retinopathy Study (ETDRS) (rango: 45,6-65) siendo la AV final media 50,1 letras (rango: 33,0-64,3), existiendo una pérdida media de 5,2 letras. Al final del seguimiento un 29,4% de los pacientes mantuvieron una AV>70 letras. El 67,9% de los pacientes se mantuvo estable al final del seguimiento (<15 letras de pérdida), existiendo una pérdida severa (≥15 letras) del 30,1%. La fibrosis y la atrofia fueron las principales causas de pérdida de AV a largo plazo, presentándose al final del seguimiento en un 52,5% y un 60,5%, respectivamente.(AU)

Age-related macular degeneration (AMD) is one of the main causes of visual acuity (VA) loss in people over 50 years of age worldwide, with neovascular AMD (nAMD) accounting for 80% of cases of severe vision loss due to this disease. Anti-vascular endothelial growth factor (anti-VEGF) drugs have been used for the treatment of this disease for more than a decade, changing drastically the visual prognosis of these patients. However, initial studies reporting data on outcomes were short term. Currently, there are different series published on the long-term results of AMD after treatment with anti-VEGF, and the aim of this review is to synthesize these results. The mean follow-up of the included studies was 8.2 years (range 5-12 years). The mean initial VA was 55.3 letters in the Early Treatment Diabetic Retinopathy Study (ETDRS) (range 45.6-65) and the mean final VA was 50.1 letters (range 33.0-64.3), with a mean loss of 5.2 letters. At the end of follow-up, 29.4% of the patients maintained a VA>70 letters. The 67.9% of patients remained stable at the end of follow-up (<15 letter loss), with a severe loss (≥15 letters) of 30.1%. Fibrosis and atrophy were the main causes of long-term VA loss, occurring at the end of follow-up in 52.5% and 60.5%, respectively.(AU)

Comprehensive profiling of enhancer RNA in stage II/III colorectal cancer defines two prognostic subtypes with implications for immunotherapy / El perfil completo del ARN potenciador en el cáncer colorrectal en estadio II/III define dos subtipos de pronóstico con implicaciones para la inmunoterapia

Background: Recently, enhancer RNAs (eRNAs) have garnered attention as pivotal biomarkers for the onset and progression of cancer. However, the landscape of eRNAs and the implications of eRNA-based molecular subtypes in stage II/III colorectal cancer (CRC) remain largely unexplored. Methods: Comprehensive profiling of eRNAs was conducted on a public stage II/III CRC cohort with total RNA-seq data. We used unsupervised clustering of prognostic eRNAs to establish an eRNA-based subtyping system. Further evaluations included molecular characteristics, immune infiltration, clinical outcomes, and drug responses. Finally, we validated the eRNA-based subtyping system in The Cancer Genome Atlas (TCGA) CRC cohort. Results: We identified a total of 6453 expressed eRNAs, among which 237 were prognostic. A global upregulation of eRNAs was observed in microsatellite-stable (MSS) CRCs when compared to microsatellite instability-high (MSI-H) CRCs. Through consensus clustering, two novel molecular subtypes, termed Cluster 1(C1) and Cluster 2(C2), were further identified. C1, associated with the activation of epithelial–mesenchymal transition (EMT), hypoxia, and KRAS signaling pathways, showed poorer prognosis. C2, correlated with the canonical CRC subtype, exhibited superior survival outcomes. In addition, C1 showed enrichment with immune infiltration and more sensitivity to immune checkpoint inhibitors. Conclusion: Our study unravels the molecular heterogeneity of stage II/III CRC at the eRNA level and highlights the potential applications of the novel eRNA-based subtyping system in predicting prognosis and guiding immunotherapy.(AU)

The prognosis and treatment of newly diagnosed bone metastasis of head and neck squamous cell cancer: an analysis of racial disparity / El pronóstico y el tratamiento de las metástasis óseas recién diagnosticadas de cáncer de células escamosas de cabeza y cuello: un análisis de la disparidad racial

Objective: There is a lack of research investigating racial disparity in newly diagnosed head and neck squamous cell carcinoma with isolated bone metastases (HNSCC-BM). This study aims to investigate the clinical characteristics and prognostic factors in HNSCC-BM patients from different racial backgrounds to aid clinical decision making and management. Methods: We retrieved data from the Surveillance, Epidemiology, and End Results (SEER) database for 345 cases of HNSCC-BM that were diagnosed between 2010 and 2017. Survival was compared using univariate and multivariate Cox proportional hazards models, Kaplan–Meier analysis, and log-rank tests. We also used propensity score matching to adjust for confounders. Results: In white patients, those who were over 40 years of age had a significantly shorter survival (HR, 4.49; 95% CI 1.03–19.56; P < 0.05). Female black patients were found to survive longer compared to male patients (HR, 0.34; 95% CI 0.15–0.76; P < 0.01). Single (never married) Asians had shorter survival than married Asians (HR, 4.68; 95% CI 1.34–16.41; P < 0.05). In all three racial groups, patients who received radiotherapy in addition to chemotherapy did not survive longer than those receiving chemotherapy (P > 0.05). In Asian patients, those who underwent surgery at the primary site combined with chemoradiotherapy had significantly better survival outcomes than those who received chemoradiotherapy (HR: 0.10, 95% CI 0.01–0.88; P = 0.01). Conclusion: Prognostic factors differ between HNSCC-BM patients from different racial backgrounds.(AU)

Nomogram for predicting overall survival after curative gastrectomy using inflammatory, nutritional and pathological factors / Nomograma para predecir la supervivencia global después de una gastrectomía curativa utilizando factores inflamatorios, nutricionales y patológicos

Purpose: To establish a nomogram for predicting the overall survival (OS) in patients with gastric cancer (GC) based on inflammatory, nutritional and pathological factors. Methods: GC patients underwent curative gastrectomy from January 2012 to June 2017 in our hospital were included, and were classified into training set and validation set with a ratio of 7:3. Then variables associated with OS were analyzed using univariate and multivariate Cox regression analysis. Nomograms predicting OS were built using variables from multivariable Cox models. Finally, Kaplan–Meier curve and Log-rank test were also conducted to analyze the 1-yr, 3-yr and 5-yr OS to validate the efficiency of risk stratification of the nomogram. Results: A total of 366 GC patients were included. After univariate and multivariate Cox regression analysis, age (HR = 1.52, 95% CI = 1.01–2.30, P = 0.044), CA50 (HR = 1.90, 95% CI = 1.12–3.21, P = 0.017), PNI (HR = 1.65, 95% CI = 1.13–2.39, P = 0.009), SII (HR = 1.46, 95% CI = 1.03–2.08, P = 0.036), T stage (HR = 2.26, 95% CI = 1.01–5.05, P = 0.048; HR = 7.24, 95% CI = 3.64–14.40, P < 0.001) were independent influencing factors on the survival time of GC patients. Five factors including CEA, prognostic nutritional index (PNI), systemic immune-inflammation index (SII), ln (tumor size), T stage, and N stage were identified and entered the nomogram, which showed good discrimination and calibration in both sets. On internal validation, 1-yr, 3-yr and 5-yr nomogram demonstrated a good discrimination with an area under the ROC curve (AUC) of 0.77, 0.84 and 0.86, respectively. The AUC for 1-yr, 3-yr and 5-yr nomogram in validation set was 0.77, 0.79 and 0.81, respectively. The OS in low risk group of training cohort and validation cohort was significantly higher than that of intermediate risk group and high risk group, respectively...(AU)

The ypT may better predict the efficacy of neoadjuvant chemoradiotherapy than tumor regression grade in locally advanced rectal cancer patients diagnosed ypT1-4N0 / El ypT puede predecir mejor la eficacia de la quimiorradioterapia neoadyuvante que el grado de regresión tumoral en pacientes con cáncer de recto localmente avanzado diagnosticados ypT1-4N0

Purpose: This study aimed to assess the impact of ypT stage and tumor regression grade (TRG) on the long-term prognosis of patients with locally advanced rectal cancer (LARC) stage ypT1-4N0 after neoadjuvant chemoradiotherapy (NCRT). Methods: We retrospectively analyzed 585 patients with histologically diagnosed middle-low LARC (cT3-4 or cN + by pelvic MRI) from 2014 to 2019. All patients underwent NCRT, followed by total mesorectal excision. Disease-free survival (DFS) rates were compared among patients with different ypT stages and TRGs by Kaplan–Meier survival analysis. The chi-square test was used to analyze the relationship between clinicopathological or therapeutic factors and ypT stage. Results: The median follow‐up was 35.8 months (range 2.8–71.8 months). The 3-year DFS was 79.5%. A better 3-year DFS was achieved in patients with a pathologic complete response (94.0% vs. 74.3%, p < 0.001) and those in the ypT0-2 (86.5% vs. 66.6%, p < 0.001), ypN0 (85.0% vs. 60.2%, p < 0.001), and TRG0 + 1 (83.1% vs. 73.0%, p = 0.004) subgroups. A total of 309 patients (52.8%) achieved stage ypT1-4N0 after surgery. Among these patients, the ypT1-2N0 subgroup achieved a significantly higher 3-year DFS than the ypT3-4N0 subgroup (85.4% vs. 72.8%, p = 0.018); in contrast, the 3-year DFS did not significantly differ between the TRG1 and TRG2 + 3 subgroups (79.9% vs. 81.1%, p = 0.833). In the ypT1-2N0 or ypT3-4N0 subgroup, different TRG had no significant effect on failure patterns. Conclusions: For LARC patients with a ypT1-4N0 status after NCRT, ypT stage may be a more effective predictor of long-term prognosis than TRG.(AU)

Predictive value of TCM tongue characteristics for chemotherapy-induced myelosuppression in patients with lung cancer.

This study aimed to investigate the clinical predictors, including traditional Chinese medicine tongue characteristics and other clinical parameters for chemotherapy-induced myelosuppression (CIM), and then to develop a clinical prediction model and construct a nomogram. A total of 103 patients with lung cancer were prospectively enrolled in this study. All of them were scheduled to receive first-line chemotherapy regimens. Participants were randomly assigned to either the training group (n = 52) or the test group (n = 51). Tongue characteristics and clinical parameters were collected before the start of chemotherapy, and then the incidence of myelosuppression was assessed after treatment. We used univariate logistic regression analysis to identify the risk predictors for assessing the incidence of CIM. Moreover, we developed a predictive model and a nomogram using multivariate logistic regression analysis. Finally, we evaluated the predictive performance of the model by examining the area under the curve value of the receiver operating characteristic, calibration curve, and decision curve analysis. As a result, a total of 3 independent predictors were found to be associated with the CIM in multivariate regression analysis: the fat tongue (OR = 3.67), Karnofsky performance status score (OR = 0.11), and the number of high-toxic drugs in chemotherapy regimens (OR = 4.78). Then a model was constructed using these 3 predictors and it exhibited a robust predictive performance with an area under the curve of 0.82 and the consistent calibration curves. Besides, the decision curve analysis results suggested that applying this predictive model can result in more net clinical benefit for patients. We established a traditional Chinese medicine prediction model based on the tongue characteristics and clinical parameters, which could serve as a useful tool for assessing the risk of CIM.

Retrospective analysis of predictive factors for AVF dysfunction in patients undergoing MHD.

To construct an early clinical prediction model for AVF dysfunction in patients undergoing Maintenance Hemodialysis (MHD) and perform internal and external verifications. We retrospectively examined clinical data from 150 patients diagnosed with MHD at Hefei Third People's Hospital from January 2014 to June 2023. Depending on arteriovenous fistula (AVF) functionality, patients were categorized into dysfunctional (n = 62) and functional (n = 88) cohorts. Using the least absolute shrinkage and selection operator(LASSO) regression model, variables potentially influencing AVF functionality were filtered using selected variables that underwent multifactorial logistic regression analysis. The Nomogram model was constructed using the R software, and the Area Under Curve(AUC) value was calculated. The model's accuracy was appraised through the calibration curve and Hosmer-Lemeshow test, with the model undergoing internal validation using the bootstrap method. There were 11 factors exhibiting differences between the group of patients with AVF dysfunction and the group with normal AVF function, including age, sex, course of renal failure, diabetes, hyperlipidemia, Platelet count (PLT), Calcium (Ca), Phosphorus, D-dimer (D-D), Fibrinogen (Fib), and Anastomotic width. These identified factors are included as candidate predictive variables in the LASSO regression analysis. LASSO regression identified age, sex, diabetes, hyperlipidemia, anastomotic diameter, blood phosphorus, and serum D-D levels as 7 predictive factors. Unconditional binary logistic regression analysis revealed that advanced age (OR = 4.358, 95% CI: 1.454-13.062), diabetes (OR = 4.158, 95% CI: 1.243-13.907), hyperlipidemia (OR = 3.651, 95% CI: 1.066-12.499), D-D (OR = 1.311, 95% CI: 1.063-1.616), and hyperphosphatemia (OR = 4.986, 95% CI: 2.513-9.892) emerged as independent risk factors for AVF dysfunction in MHD patients. The AUC of the predictive model was 0.934 (95% CI: 0.897-0.971). The Hosmer-Lemeshow test showed high consistency between the model's predictive results and actual clinical observations (χ2 = 1.553, P = .092). Internal validation revealed an AUC of 0.911 (95% CI: 0.866-0.956), with the Calibration calibration curve nearing the ideal curve. Advanced age, coexisting diabetes, hyperlipidemia, blood D-D levels, and hyperphosphatemia are independent risk factors for AVF dysfunction in patients undergoing MHD.

Distinct experiences and care needs of advanced cancer patients with good ECOG performance status: a qualitative phenomenological study.

BACKGROUND: Advanced cancer patients with good Eastern Cooperative Oncology Group (ECOG) performance status (score 0-1) are underrepresented in current qualitative reports compared with their dying counterparts. AIM: To explore the experiences and care needs of advanced cancer patients with good ECOG. DESIGN: A qualitative phenomenological approach using semi-structured interview was employed. Data was analyzed using the Colaizzi's method. SETTING/PARTICIPANTS: Purposive sample of terminal solid cancer patients on palliative care aged 18-70 years with a 0-1 ECOG score were recruited from a tertiary general hospital. RESULTS: Sixteen participants were interviewed. Seven themes were generated from the transcripts, including experiencing no or mild symptoms; independence in self-care, decision-making, and financial capacity; prioritization of cancer growth suppression over symptom management; financial concerns; hope for prognosis and life; reluctance to discuss death and after-death arrangements; and use of complementary and alternative medicine (CAM) and religious coping. CONCLUSIONS: Advanced cancer patients with good ECOG have distinct experiences and care needs from their dying counterparts. They tend to experience no or mild symptoms, demonstrate a strong sense of independence, and prioritize cancer suppression over symptom management. Financial concerns were common and impact their care-related decision-making. Though being hopeful for their prognosis and life, many are reluctant to discuss death and after-death arrangements. Many Chinese patients use herbal medicine as a CAM modality but need improved awareness of and accessibility to treatment options. Healthcare professionals and policy-makers should recognize their unique experiences and needs when tailoring care strategies and policies.

Implementation of a light therapy team to administer photobiomodulation therapy: A standardized protocol to prevent and treat oral mucositis in the pediatric hematopoietic stem cell transplant population.

BACKGROUND: Oral mucositis (OM) is a painful and common complication of hematopoietic stem cell transplant (HSCT). The Children's Oncology Group recently published guidelines recommending photobiomodulation (PBM) for preventing and treating OM in pediatric HSCT patients. However, this is a rarely used intervention in pediatric hospitals. PROCEDURE: Patients undergoing allogeneic HSCT, or autologous HSCT for a neuroblastoma diagnosis, had PBM administered from the first day of conditioning to transplant Day +20. We successfully developed a standardized treatment protocol and workflow to ensure consistent and uniform delivery of PBM. In addition, clinical patient data were compared before and after PBM implementation. RESULTS: The administration of PBM at our center was feasible, but required dedicated staff. A registered nurse (RN) was determined to be the best fit to deliver PBM. Sixty-two patients received PBM from October 2022 to September 2023; patients from 2021 before PBM implementation were used for comparison. Patients receiving PBM were more likely (p = .03) to engage in teeth brushing (56/62 = 90%) compared to baseline (61/81 = 75%). Mean days of OM decreased from 11.3 to 9 days; patients who received PBM were less likely (p < .001) to be discharged on total parental nutrition (TPN) (11/62 = 18%) compared to baseline (50/82 = 61%). OM-related supportive care costs (TPN and patient-controlled anesthesia [PCA]) were lower (p = .02) for those who received PBM (median cost = $31,229.87 vs. $37,370.66). CONCLUSION: PBM, as the standard of care in the pediatric HSCT population, is safe, feasible, and well-tolerated. At our center, a dedicated RN was critical to providing standardized treatment and ensuring sustainability.

[Study on mechanism of icariin-induced ferroptosis in HepG2 hepatoma carcinoma cells through PPARG/FABP4/GPX4 pathway].

The aim of this study was to explore the mechanism of icaritin-induced ferroptosis in hepatoma HepG2 cells. By bioinformatics screening, the target of icariin's intervention in liver cancer ferroptosis was selected, the protein-protein interaction(PPI) network was constructed, the related pathways were focused, the binding ability of icariin and target protein was evaluated by molecular docking, and the impact on patients' survival prognosis was predicted and the clinical prediction model was built. CCK-8, EdU, and clonal formation assays were used to detect cell viability and cell proliferation; colorimetric method and BODIPY 581/591 C1 fluorescent probe were used to detect the levels of Fe~(2+), MDA and GSH in cells, and the ability of icariin to induce HCC cell ferroptosis was evaluated; RT-qPCR and Western blot detection were used to verify the mRNA and protein levels of GPX4, xCT, PPARG, and FABP4 to determine the expression changes of these ferroptosis-related genes in response to icariin. Six intervention targets(AR, AURKA, PPARG, AKR1C3, ALB, NQO1) identified through bioinformatic analysis were used to establish a risk scoring system that aids in estimating the survival prognosis of HCC patients. In conjunction with patient age and TNM staging, a comprehensive Nomogram clinical prediction model was developed to forecast the 1-, 3-, and 5-year survival of HCC patients. Experimental results revealed that icariin effectively inhibited the activity and proliferation of HCC cells HepG2, significantly modulating levels of Fe~(2+), MDA, and lipid peroxidation ROS while reducing GSH levels, hence revealing its potential to induce ferroptosis in HCC cells. Icariin was found to diminish the expression of GPX4 and xCT(P<0.01), inducing ferroptosis in HCC cells, potentially in relation to inhibition of PPARG and FABP4(P<0.01). In summary, icariin induces ferroptosis in HCC cells via the PPARG/FABP4/GPX4 pathway, providing an experimental foundation for utilizing the traditional Chinese medicine icariin in the prevention or treatment of HCC.

US-guided Percutaneous Radiofrequency Ablation for Secondary Hyperparathyroidism: Long-term Outcomes and Prognostic Factors.

Background Although favorable outcomes have been reported with radiofrequency ablation (RFA) for secondary hyperparathyroidism (SHPT), the long-term efficacy remains insufficiently investigated. Purpose To evaluate the long-term efficacy and safety of US-guided percutaneous RFA in patients with SHPT undergoing dialysis and to identify possible predictors associated with treatment failure. Materials and Methods This retrospective study included consecutive patients with SHPT with at least one enlarged parathyroid gland accessible for RFA who were undergoing dialysis at seven tertiary centers from May 2013 to July 2022. The primary end point was the proportion of patients with parathyroid hormone (PTH) levels less than or equal to 585 pg/mL at the end of follow-up. Secondary end points were the proportion of patients with normal calcium and phosphorus levels, the technical success rate, procedure-related complications, and improvement in self-rated hyperparathyroidism-related symptoms (0-3 ranking scale). The Wilcoxon signed rank test and generalized estimating equation model were used to evaluate treatment outcomes. Univariable and multivariable regression analyses identified variables associated with treatment failure (recurrent or persistent hyperparathyroidism). Results This study included 165 patients (median age, 51 years [IQR, 44-60 years]; 92 female) and 582 glands. RFA effectively reduced PTH, calcium, and phosphorus levels, with targeted ranges achieved in 78.2% (129 of 165), 72.7% (120 of 165), and 60.0% (99 of 165) of patients, respectively, at the end of follow-up (mean, 51 months). For the RFA sessions, the technical success rate was 100% (214 of 214). Median symptom scores (ostealgia, arthralgia, pruritus) decreased (all P < .001). Regarding complications, only hypocalcemia (45.8%, 98 of 214) was common. Treatment failure occurred in 36 patients (recurrent [n = 5] or persistent [n = 31] hyperparathyroidism). The only potential independent predictor of treatment failure was having less than four treated glands (odds ratio, 17.18; 95% CI: 4.34, 67.95; P < .001). Conclusion US-guided percutaneous RFA was effective and safe in the long term as a nonsurgical alternative for patients with SHPT undergoing dialysis; the only potential independent predictor of treatment failure was a lower number (<4) of treated glands. © RSNA, 2024 Supplemental material is available for this article.

Interaction of Vitamin D Supplements and Marine n-3 Fatty Acids on Digestive Tract Cancer Prognosis.

A meta-analysis suggested that marine n-3 polyunsaturated fatty acids (PUFAs), e.g., eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), might reduce cancer mortality. However, a randomized clinical trial of marine n-3 PUFA and vitamin D supplementation failed to verify this benefit. This study aimed to investigate the potential interaction between vitamin D supplementation and serum EPA and DHA levels. This post hoc analysis of the AMATERASU trial (UMIN000001977), a randomized controlled trial (RCT), included 302 patients with digestive tract cancers divided into two subgroups stratified by median serum levels of EPA + DHA into higher and lower halves. The 5-year relapse-free survival (RFS) rate was significantly higher in the higher half (80.9%) than the lower half (67.8%; hazard ratio (HR), 2.15; 95% CI, 1.29-3.59). In the patients in the lower EPA + DHA group, the 5-year RFS was significantly higher in the vitamin D (74.9%) than the placebo group (49.9%; HR, 0.43; 95% CI, 0.24-0.78). Conversely, vitamin D had no effect in the higher half, suggesting that vitamin D supplementation only had a significant interactive effect on RFS in the lower half (p for interaction = 0.03). These results suggest that vitamin D supplementation may reduce the risk of relapse or death by interacting with marine n-3 PUFAs.

Develop prediction model to help forecast advanced prostate cancer patients' prognosis after surgery using neural network.

Background: The effect of surgery on advanced prostate cancer (PC) is unclear and predictive model for postoperative survival is lacking yet. Methods: We investigate the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database, to collect clinical features of advanced PC patients. According to clinical experience, age, race, grade, pathology, T, N, M, stage, size, regional nodes positive, regional nodes examined, surgery, radiotherapy, chemotherapy, history of malignancy, clinical Gleason score (composed of needle core biopsy or transurethral resection of the prostate specimens), pathological Gleason score (composed of prostatectomy specimens) and prostate-specific antigen (PSA) are the potential predictive variables. All samples are divided into train cohort (70% of total, for model training) and test cohort (30% of total, for model validation) by random sampling. We then develop neural network to predict advanced PC patients' overall. Area under receiver operating characteristic curve (AUC) is used to evaluate model's performance. Results: 6380 patients, diagnosed with advanced (stage III-IV) prostate cancer and receiving surgery, have been included. The model using all collected clinical features as predictors and based on neural network algorithm performs best, which scores 0.7058 AUC (95% CIs, 0.7021-0.7068) in train cohort and 0.6925 AUC (95% CIs, 0.6906-0.6956) in test cohort. We then package it into a Windows 64-bit software. Conclusion: Patients with advanced prostate cancer may benefit from surgery. In order to forecast their overall survival, we first build a clinical features-based prognostic model. This model is accuracy and may offer some reference on clinical decision making.

[An analysis on clinical characteristics and prognosis-related risk factors in patients with drug-induced liver injury].

Objective: To explore the drugs and clinical characteristics causing drug-induced liver injury (DILI) in recent years, as well as identify drug-induced liver failure, and chronic DILI risk factors, in order to better manage them timely. Methods: A retrospective investigation and analysis was conducted on 224 cases diagnosed with DILI and followed up for at least six months between January 2018 and December 2020. Univariate and multivariate logistic regression analyses were used to identify risk factors for drug-induced liver failure and chronic DILI. Results: Traditional Chinese medicine (accounting for 62.5%), herbal medicine (accounting for 84.3% of traditional Chinese medicine), and some Chinese patent medicines were the main causes of DILI found in this study. Severe and chronic DILI was associated with cholestatic type. Preexisting gallbladder disease, initial total bilirubin, initial prothrombin time, and initial antinuclear antibody titer were independent risk factors for DILI. Prolonged time interval between alkaline phosphatase (ALP) and alanine aminotransferase (ALT) falling from the peak to half of the peak (T(0.5ALP) and T(0.5ALT)) was an independent risk factor for chronic DILI [area under the receiver operating characteristic curve (AUC) = 0.787, 95%CI: 0.697~0.878, P < 0.001], with cutoff values of 12.5d and 9.5d, respectively. Conclusion: Traditional Chinese medicine is the main contributing cause of DILI. The occurrence risk of severe DILI is related to preexisting gallbladder disease, initial total bilirubin, prothrombin time, and antinuclear antibodies. T(0.5ALP) and T(0.5ALT) can be used as indicators to predict chronic DILI.

Predictors of post stroke cognitive impairment: VITATOPS cognition substudy.

INTRODUCTION: Post stroke cognitive impairment (PSCI) is a common complication of ischemic stroke. PSCI can involve different depending on clinical and stroke related characteristics. The aim of this study is to determine the factors associated with impairments in specific cognitive domains. METHODS: The Vitamins to Prevent Stroke (VITATOPS) trial is a large, multinational randomised controlled trial. In this substudy, consecutive patients admitted for ischaemic stroke or transient ischaemic attack (TIA) at a tertiary hospital in Singapore were included. PSCI was defined as impairment of any of the six cognitive subgroups - visuoconstruction, attention, verbal memory, language, visual memory and visuomotor function - that were assessed annually for up to five years. Univariate and multivariate Cox proportional hazard models were used to determine factors associated with impairments in each of these cognitive domains. RESULTS: A total of 736 patients were included in this study, of which 173 (23.5 %) developed cognitive impairment. Out of the six cognitive domains, the greatest proportion of patients had an impairment in visuoconstruction (26.4 %) followed by attention (19.8 %), verbal memory (18.3 %), language (17.5 %), visual memory (17.3 %) and visuomotor function (14.8 %). Patients with posterior circulation cerebral infarction (POCI) as the index stroke subtype had higher rates of cognitive impairment. Further subgroup analyses show that Indian race and advanced age were predictive of language impairment, whilst fewer years of education and POCI were predictive of verbal memory impairment. POCI was predictive of visual memory impairment, and advanced age and POCI were predictive of visuomotor function impairment. CONCLUSION: We identified visuoconstruction and attention domains to be the most affected in our Asian cohort of PSCI. Advanced age, lower levels of education, posterior circulation strokes and concomitant comorbidities such as peripheral artery disease are independent predictors of PSCI.

Impact of chrono-radiotherapy on the prognosis and treatment-related toxicity in patients with locally advanced nasopharyngeal carcinoma: A multicenter propensity-matched study.

The timing of radiotherapy (RT) delivery has been reported to affect both cancer survival and treatment toxicity. However, the association among the timing of RT delivery, survival, and toxicity in locally advanced nasopharyngeal carcinoma (LA-NPC) has not been investigated. We retrospectively reviewed patients diagnosed with LA-NPC who received definitive RT at multiple institutions. The median RT delivery daytime was categorized as morning (DAY) and night (NIGHT). Seasonal variations were classified into the darker half of the year (WINTER) and brighter half (SUMMER) according to the sunshine duration. Cohorts were balanced according to baseline characteristics using propensity score matching (PSM). Survival and toxicity outcomes were evaluated using Cox regression models. A total of 355 patients were included, with 194/161 in DAY/NIGHT and 187/168 in WINTER/SUMMER groups. RT delivered during the daytime prolonged the 5-year overall survival (OS) (90.6% vs. 80.0%, p = 0.009). However, the significance of the trend was lost after PSM (p = 0.068). After PSM analysis, the DAY cohort derived a greater benefit in 5-year progression-free survival (PFS) (85.6% vs. 73.4%, p = 0.021) and distant metastasis-free survival (DMFS) (89.2% vs. 80.8%, p = 0.051) in comparison with the NIGHT subgroup. Moreover, multivariate analysis showed that daytime RT was an independent prognostic factor for OS, PFS, and DMFS. Furthermore, daytime RT delivery was associated with an increase in the incidence of leukopenia and radiation dermatitis. RT delivery in SUMMER influenced only the OS significantly (before PSM: p = 0.051; after PSM: p = 0.034). There was no association between toxicity and the timing of RT delivery by season. In LA-NPC, the daytime of radical RT served as an independent prognostic factor. Furthermore, RT administered in the morning resulted in more severe toxic side effects than that at night, which needs to be confirmed in a future study.

Cancer risk and male Infertility: Unravelling predictive biomarkers and prognostic indicators.

In recent years, there has been a global increase in cases of male infertility. There are about 30 million cases of male infertility worldwide and male reproductive health is showing rapid decline in last few decades. It is now recognized as a potential risk factor for developing certain types of cancer, particularly genitourinary malignancies like testicular and prostate cancer. Male infertility is considered a potential indicator of overall health and an early biomarker for cancer. Cases of unexplained male factor infertility have high levels of oxidative stress and oxidative DNA damage and this induces both denovo germ line mutations and epimutations due to build up of 8-hydroxy 2 deoxygunaosine abase which is highly mutagenic and also induces hypomethylation and genomic instability. Consequently, there is growing evidence to explore the various factors contributing to an increased cancer risk. Currently, the available prognostic and predictive biomarkers associated with semen characteristics and cancer risk are limited but gaining significant attention in clinical research for the diagnosis and treatment of elevated cancer risk in the individual and in offspring. The male germ cell being transcriptionally and translationally inert has a highly truncated repair mechanism and has minimal antioxidants and thus most vulnerable to oxidative injury due to environmental factors and unhealthy lifestyle and social habits. Therefore, advancing our understanding requires a thorough evaluation of the pathophysiologic mechanisms at the DNA, RNA, protein, and metabolite levels to identify key biomarkers that may underlie the pathogenesis of male infertility and associated cancer. Advanced methodologies such as genomics, epigenetics, proteomics, transcriptomics, and metabolomics stand at the forefront of cutting-edge approaches for discovering novel biomarkers, spanning from infertility to associated cancer types. Henceforth, in this review, we aim to assess the role and potential of recently identified predictive and prognostic biomarkers, offering insights into the success of assisted reproductive technologies, causes of azoospermia and idiopathic infertility, the impact of integrated holistic approach and lifestyle modifications, and the monitoring of cancer susceptibility, initiation and progression. Comprehending these biomarkers is crucial for providing comprehensive counselling to infertile men and cancer patients, along with their families.

Rare but Still There: A Scoping Review on Endometriosis-Associated Ovarian Cancer.

Endometriosis is a medical condition affecting at least up to 10% of women of reproductive age. This condition occurs when ectopic endometrial glands and stroma implant outside the uterus and there are several theories regarding the underlying origins of the disease. Endometriosis is one of the major causes of severe dysmenorrhoea, chronic pelvic pain and infertility. While endometriosis is generally a non-malignant condition, it rarely may transform into an invasive cancer, and increase the risk for epithelial ovarian cancer, notably endometrioid or clear cell ovarian cancer. Despite the increased risk, the mechanisms behind the development of endometriosis-associated ovarian cancer (EAOC) are not yet well understood. Recent investigations have delved into the intricate interplay between endometriosis and EAOC, exploring pathways involving oxidative stress, inflammation, hyperestrogenism, and the discovery of genetic mutations within endometriotic lesions that hint at a transition towards invasive carcinoma. Efforts have been made to identify intermediary lesions between endometriosis and EAOC, which may enable earlier detection of endometriosis at risk of malignant transformation or even prevention of the transformation altogether. However, given the rarity of this malignancy, there is still the risk of late or missed diagnosis, with the risk of inappropriate management being offered to the patient, and the higher risk of poor prognosis and increased morbidity and mortality. This scoping review aims to summarize existing data on EAOC, with a focus on endometrioid and clear cell histologic subtypes. It also provides insights into its identification, prognosis, and delineating management strategies, seeking to provide a holistic understanding of the complexities surrounding EAOC, facilitating further research and the development of more effective prevention and treatment approaches.

Predicting COVID-19 Re-Positive Cases in Malnourished Older Adults: A Clinical Model Development and Validation.

Purpose: Building and validating a clinical prediction model for novel coronavirus (COVID-19) re-positive cases in malnourished older adults. Patients and Methods: Malnourished older adults from January to May 2023 were retrospectively collected from the Department of Geriatrics of the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine. They were divided into a "non-re-positive" group and a "re-positive" group based on the number of COVID-19 infections, and into a training set and a validation set at a 7:3 ratio. The least absolute shrinkage and selection operator (LASSO) regression analysis was used to identify predictive factors for COVID-19 re-positivity in malnourished older adults, and a nomogram was constructed. Independent influencing factors were screened by multivariate logistic regression. The model's goodness-of-fit, discrimination, calibration, and clinical impact were assessed by Hosmer-Lemeshow test, area under the curve (AUC), calibration curve, decision curve analysis (DCA), and clinical impact curve analysis (CIC), respectively. Results: We included 347 cases, 243 in the training set, and 104 in the validation set. We screened 10 variables as factors influencing the outcome. By multivariate logistic regression analysis, preliminary identified protective factors, risk factors, and independent influencing factors that affect the re-positive outcome. We constructed a clinical prediction model for COVID-19 re-positivity in malnourished older adults. The Hosmer-Lemeshow test yielded χ2 =5.916, P =0.657; the AUC was 0.881; when the threshold probability was >8%, using this model to predict whether malnourished older adults were re-positive for COVID-19 was more beneficial than implementing intervention programs for all patients; when the threshold was >80%, the positive estimated value was closer to the actual number of cases. Conclusion: This model can help identify the risk of COVID-19 re-positivity in malnourished older adults early, facilitate early clinical decision-making and intervention, and have important implications for improving patient outcomes. We also expect more large-scale, multicenter studies to further validate, refine, and update this model.