Disease Grade Research Articles

Quantifying choroidal and retinal thicknesses variations via optical coherence tomography in different stages of pediatric keratoconus

PurposeKeratoconus (KCN) is characterized by corneal thinning and bulging, leading to vision impairment. Assessing choroidal thickness (CT) in pediatric KCN ( pKCN) patients can provide insights for better understanding and managing the disease. CT may serve as a potential indicator of disease activity in KCN patients. This study aims to evaluate CT and retinal thickness (RT) in different stages of pKCN patients and compare the findings with an age-matched control group.Methods and patientsThis cross-sectional study included patients under 18 years old who met specific criteria. CT and RT was measured in all subjects using an optical coherence tomography device (Spectralis OCT, version 6.0, Heidelberg Engineering, Germany) with enhanced depth imaging mode, without pupil dilation. Mean CT and RT in pKCN was compared with healthy subjects and assessed among different disease grades using the ABCD grading method.ResultsThe study included 125 eyes (66 patients) in the pKCN group and 42 control eyes (21 individuals). Grade 2 KCN showed the highest prevalence at 26.4% (N = 33), while grades 3 and 1 had prevalence rates of 24% (N = 30). CT in all specified areas (all P-values < 0.001), as well as RT in the subfoveal area (P-value < 0.001) and 1500 μm nasal to the fovea (P-value = 0.025), were significantly greater in the pKCN group compared to controls. Furthermore, CT and RT differed significantly among the pKCN grades (P-values < 0.001).ConclusionCT was found to be elevated in pKCN patients, similar to adult KCN cases. CT could potentially serve as a clinical marker for disease activity in pKCN; however, further studies are needed.

Care of children with posterior urethral valves after initial endoscopic incision/ablation: what a nephrologist needs to know.

Posterior urethral valves (PUV) are the most common cause of congenital urethral obstruction and are unique in the challenges they pose in management. Endoscopic ablation/incision of the valves is usually offered as the primary treatment of choice. Following this, a range of different clinical patterns are observed, each with varying bladder dysfunction and continence issues and associated with different grades of chronic kidney disease. This review outlines a systematic approach that could help pediatric nephrologists, pediatricians, and pediatric urologists, as well as nursing and allied health specialists, assess these children and develop well-informed management plans. The need for surveillance for bladder dysfunction (incidence approximately 55%), identification of red flags for progression to kidney failure (incidence approximately 20%), and multidisciplinary approach to care are presented, with a focus on reducing long-term morbidity in patients and difficulties for the families. Where possible, an alternative in resource-constrained situations is suggested. We also briefly outline the role of pharmacotherapy, assisted bladder emptying/drainage, and other interventions that have a role in the medium- to long-term management of these patients.

Diagnostic value of transvaginal contrast-enhanced ultrasound in identifying benign and malignant endometrial lesions and assessing myometrial invasion.

The objective of this study was to evaluate the diagnostic value of transvaginal contrastenhanced ultrasound (CEUS) in differentiating benign from malignant endometrial lesions and assessing the extent of myometrial invasion. A total of 70 patients who underwent surgery for endometrial lesions at the authors' hospital were selected. Transvaginal ultrasound examination and CEUS were performed for quantitative and qualitative analysis. Based on the CEUS results, an International Federation of Gynecology and Obstetrics (FIGO) disease grade was assigned and compared with pathological findings. Postmenopausal vaginal bleeding is a key clinical manifestation of endometrial carcinoma. Among the patients with endometrial carcinoma, compared with normal myometrium, the lesion areas exhibited a greater rate of rise (defined as enhanced intensity divided by enhancement time) and a shorter half-clearance time (P<0.05). These findings suggest that in endometrial carcinoma, the contrast agent displays a "fast-in/fast-out/hyperenhancement" perfusion pattern. In contrast, the characteristic perfusion pattern for benign endometrial lesions is low enhancement (P<0.05). The diagnostic accuracy of CEUS in detecting myometrial invasion was 88% (22 of 25 cases). Transvaginal CEUS is a practical and effective diagnostic imaging method for distinguishing between benign and malignant endometrial lesions. It can also be used to evaluate the depth of myometrial invasion in patients with early-stage endometrial carcinoma.

Association between Immune-Related Adverse Events and Atezolizumab in Previously Treated Patients with Unresectable Advanced or Recurrent Non-Small Cell Lung Cancer.

Real-world, large-scale studies on the association between immune-related adverse events (irAE) and immune checkpoint inhibitor therapy effectiveness are limited. We evaluated overall survival (OS) and progression-free survival based on the occurrence and grade of irAEs. We used data from Japanese patients with unresectable advanced or recurrent non-small cell lung cancer (NSCLC) who received atezolizumab and were enrolled in J-TAIL, a multicenter, prospective, single-arm observational study. Among the 1,002 patients, 190 (19.0%) developed irAEs. The most common irAEs were skin disorders (3.8%) of any grade and interstitial lung disease (1.5%) of grade ≥3. Patients who developed irAEs within 4 or 6 weeks of treatment initiation had higher baseline C-reactive protein levels than those without irAEs. OS was longer in patients with irAEs [HR, 0.66; 95% confidence interval (CI), 0.54-0.82], particularly in those with low-grade irAEs (HR, 0.45; 95% CI, 0.33-0.62), than in patients without irAEs. The HR (95% CI) for OS in patients with low-grade and high-grade skin or endocrine disorder-related irAEs was 0.42 (0.28-0.64) and 0.37 (0.15-0.88), respectively. The HR (95% CI) for OS in patients with low-grade and high-grade irAEs other than skin or endocrine disorders was 0.44 (0.30-0.65) and 1.27 (0.96-1.69), respectively. In patients with unresectable advanced or recurrent NSCLC treated with atezolizumab in real-world settings, irAEs are associated with a clinical benefit except in those with high-grade irAEs other than skin and endocrine disorders. Immune checkpoint inhibitors are useful for treating NSCLC but can cause life-threatening irAEs. This study had a large sample size and stratified the analysis by irAE type and grade. The results suggest that improved management of irAEs may improve the therapeutic effect of atezolizumab.

A Multicenter Cohort Study on DNA Methylation for Endometrial Cancer Detection in Cervical Scrapings.

The increasing incidence of endometrial cancer (EC) has highlighted the need for improved early detection methods. This study aimed to develop and validate a novel DNA methylation classifier, EMPap, for EC detection using cervical scrapings. EMPap incorporated the methylation status of BHLHE22 and CDO1, along with age and body mass index (BMI), into a logistic regression model to calculate the endometrial cancer methylation (EM) score for identifying EC in cervical scrapings. We enrolled 1297 patients with highly suspected EC, including 196 confirmed EC cases, and assessed the EMPap performance in detecting EC. EMPap demonstrated robust diagnostic accuracy, with an area under the curve of 0.93, sensitivity of 90.3%, and specificity of 89.3%. It effectively detected EC across various disease stages, grades, and histological subtypes, and consistently performed well across patient demographics and symptoms. EMPap correctly identified 87.5% of the type II ECs and 53.8% of premalignant lesions. Notably, compared with transvaginal ultrasonography (TVS) in patients with postmenopausal bleeding, EMPap exhibited superior sensitivity (100% vs. 82.0%) and specificity (85.2% vs. 38.5%). In asymptomatic postmenopausal women, EMPap maintained high sensitivity (89.5%) and negative predictive value (NPV) (98.3%). This study demonstrated the potential of EMPap as an effective tool for EC detection. Despite the limited sample size, EMPap showed promise for identifying type II EC and detecting over 50% of premalignant lesions. As a DNA methylation classifier, EMPap can reduce unnecessary uterine interventions and improve diagnosis and outcomes.

Impact of surgical intervention on overall survival in malignant pleural mesothelioma: A population-based cohort study with propensity score matching

BackgroundMalignant pleural mesothelioma (MPM) is a rare and aggressive cancer with limited treatment options. This study aims to assess the impact of surgical intervention on overall survival (OS) in patients with MPM and to identify prognostic factors influencing survival outcomes. MethodsData from the SEER-17 Database between 2000 and 2019 were analyzed. Patients were categorized into surgery and no-surgery groups. Survival analyses were conducted using Kaplan-Meier curves and Cox proportional hazards models. Propensity score matching (PSM) was applied to reduce biases. ResultsThe study included a total of 3901 MPM patients, with 1190 in the surgery group and 2711 in the no-surgery group. The median OS for the entire cohort was 10 months. The surgery group had a median OS of 15 months compared to 8 months in the no-surgery group (p < 0.001). The 1-year and 5-year OS rates for surgery patients were 56.9% and 11.2%, respectively, while for no-surgery patients, they were 34.9% and 3.7% (p < 0.001). Multivariate analysis indicated that no-surgery was an independent risk factor for worse OS (HR 1.38, 95% CI 1.21-1.39, p < 0.001). After PSM, no-surgery remained an independent risk factor influencing OS. Subgroup analysis indicated that surgery benefited most groups except those aged ≥80 years, bilateral disease, N3 stage, and certain histological grades. ConclusionSurgical intervention significantly improves survival in patients with MPM. However, benefits vary across subgroups, and careful consideration of patient-specific factors is essential.

Airway Mucus Plugs on Chest Computed Tomography Are Associated with Exacerbations in COPD.

Mucus plugs were visually-identified on baseline chest computed tomography (CT) scans from smokers with Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 2-4 COPD enrolled in two multicenter cohort studies: Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) and COPDGene. Associations between ordinal mucus plug score categories (0/1-2/≥3) and prospectively-ascertained AEs, defined as worsening respiratory symptoms requiring systemic steroids and/or antibiotics (moderate-to-severe) and/or ER/hospitalization (severe), were assessed using multivariable-adjusted zero-inflated Poisson regression; subjects were exacerbation-free at enrollment. Among 3,250 participants in COPDGene (mean±SD age 63.7±8.4 years, FEV1 50.6%±17.8% predicted, 45.1% female) and 1,716 participants in ECLIPSE (age 63.3±7.1 years, FEV1 48.3%±15.8% predicted, 36.2% female), 44.4% and 46.0% had mucus plugs, respectively. The incidence rates of AEs were 61.0 (COPDGene) and 125.7 (ECLIPSE) per 100 person-years. Relative to those without mucus plugs, the presence of 1-2 and ≥3 mucus plugs was associated with increased risk (adjusted rate ratio, aRR [95%CI]=1.07[1.05-1.09] and 1.15[1.1-1.2] in COPDGene; aRR=1.06[1.02-1.09] and 1.12[1.04-1.2] in ECLIPSE, respectively) for prospective moderate-to-severe AEs. The presence of 1-2 and ≥3 mucus plugs was also associated with increased risk for severe AEs during follow-up (aRR=1.05[1.01-1.08] and 1.09[1.02-1.18] in COPDGene; aRR=1.17[1.07-1.27] and 1.37[1.15-1.62] in ECLIPSE, respectively). CT-based mucus plugs are associated with an increased risk for future COPD AEs.

Accelerated hazard prediction based on age time-scale for women diagnosed with breast cancer using a deep learning method

Breast cancer is the most common cancer in women. Previous studies have investigated estimating and predicting the proportional hazard rates and survival in breast cancer. This study deals with predicting accelerated hazards (AH) rate based on age categories in breast cancer patients using deep learning methods. The AH has a time-dependent structure whose rate changes according to time and variable effects. We have collected data related to 1225 female patients with breast cancer at the Mandarin University of Medical Sciences. The patients' demographic and clinical characteristics including family history, age, history of tobacco use, hysterectomy, first menstruation age, gravida, number of breastfeeding, disease grade, marital status, and survival status have been recorded. Initially, we dealt with predicting three age groups of patients: ≤ 40, 41–60, and ≥ 61 years. Then, the prediction of accelerated risk value based on age categories for each breast cancer patient through deep learning and the importance of variables using LightGBM is discussed. Improving clinical management and treatment of breast cancer requires advanced methods such as time-dependent AH calculation. When the behavioral effect is assumed as a time scale change between hazard functions, the AH model is more appropriate for randomized clinical trials. The study results demonstrate the proper performance of the proposed model for predicting AH by age categories based on breast cancer patients' demographic and clinical characteristics.

Perioperative systemic therapy, current paradigm and ongoing clinical trials in upper tract urothelial cancer.

To provide of comprehensive overview of existing and future paradigms for perioperative systemic therapy in the treatment of upper tract urothelial carcinoma. Contemporary treatment paradigms for the management of upper tract urothelial carcinoma focus on use of neoadjuvant cisplatin based chemotherapy for high grade disease primarily based on two small single arm phase II clinical trials. More robust evidence from a phase III randomized clinical trial exists for the use of adjuvant platinum based chemotherapy for invasive disease after radical nephroureterectomy, but there are significant concerns about renal function and platinum eligibility after nephroureterectomy. There are currently ongoing clinical trials for nonplatinum based perioperative systemic therapies including checkpoint inhibitors/immunotherapy as well as antibody-drug conjugates, but currently no recommendation can be made for these approaches. Current evidence supports neoadjuvant cisplatin chemotherapy in the setting of high grade disease or concern for significant renal dysfunction after radical nephroureterectomy or platinum based adjuvant chemotherapy in eligible patients with advanced disease after surgery. While there is no established role for nonplatinum based therapies yet, multiple ongoing trials exploring use of immunotherapies and antibody-drug conjugates as monotherapy or combination may provide new therapeutic options in this population.

Minimizing overtreatment and maximizing oncologic outcomes in upper tract urothelial carcinoma

Purpose of review An update on the latest advances in the management of upper tract urothelial carcinoma (UTUC), with an emphasis on strategies to optimize oncologic outcomes while minimizing overtreatment. Recent findings Recent high-quality trials have changed the landscape of UTUC treatment. Emerging tools including 3D histology and measurement of cell free tumor DNA may improve diagnostic accuracy of disease grading and staging, and be used in monitoring treatment response. Novel therapies show promise of reducing low-grade UTUC disease recurrence at the cost of significant side-effects. Platinum-based neoadjuvant chemotherapy in high-grade/muscle-invasive disease showed complete pathological response in a subset of patients, but difficult to predict responders. Adjuvant platinum-based chemotherapy exhibited a clear survival benefit, but immunotherapy did not, suggesting possible overtreatment with these agents. Molecularly-targeted therapies in metastatic UTUC have shown the greatest recent oncologic advances, but exhibit a high adverse event-rate. Summary Low-grade UTUC has the potential for overtreatment, as it exhibits low metastatic-potential and excellent survival. For high-grade and advanced-stage UTUC, these carry high mortality rates and require more aggressive treatment, but studies are limited by inaccurate grading and staging which can lead to overtreatment especially in the neoadjuvant setting. Emerging technologies will help improve diagnostic accuracy and noninvasive monitoring of treatment response.

Pediatric non-nasopharyngeal head and neck squamous cell carcinoma: Analysis of the Surveillance, Epidemiology, and End Results (SEER) program with review of the literature

BackgroundDespite its prevalence in adults, head and neck squamous cell carcinoma (HNSCC) is considered a rare entity in pediatrics where lymphomas, neural tumors, and soft tissue sarcomas predominate in the head and neck. Given the association of squamous cell carcinoma with the human papillomavirus, a risk factor that may be present from birth, and the difficulties in staging this disease for prognostication in children, it is important to revisit nationally collected data for prevalence and outcomes assessments. ObjectiveTo examine a publicly available national database to describe the incidence, pathology, treatment, and survival of pediatric HNSCC. To review the available literature regarding management, outcomes, and risk factors for this disease process. MethodsThe National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) tumor database was queried to identify pediatric subjects ages 0 to 19 diagnosed HNSCC between 1973 and 2019. ResultsTwo-hundred ninety-two cases were identified. Subjects were 62.7 % male (n = 183) and the average age was 15.4 years (range 2–19, median 16). Subjects were 65.8 % white (n = 192), 22.9 % black (n = 67), 8.9 % Asian/Pacific Islander (n = 26), 1 % American Indian (n = 3), and 1.4 % unknown (n = 4). The most common primary sites were nasopharynx (45.9 %), oral cavity (30.5 %), larynx (8.6 %), salivary gland (4.1 %), nasal cavity & paranasal sinus (3.4 %), and lip (2.7 %). There was no statistically significant difference between primary subsite and age, race, histologic grade, or extent of disease. The 5-year overall survival was 83.6 %. DiscussionHead and neck squamous cell carcinoma is more likely to present in older children and is more prevalent in White populations. The nasopharynx is the most common subsite involved, which differs from adult populations in which non-nasopharyngeal subsites including the larynx, oral cavity, and oropharynx are most frequently affected. ConclusionHead and neck squamous cell carcinoma is rare in pediatric patients but should not be overlooked by physicians in the differential diagnosis, particularly in teenagers. Further study is needed to determine whether this represents a unique entity or can be staged and treated according to adult guidelines.

Herbal materials used as soil amendments alleviate root rot of Panax ginseng

Root rot is a serious soil-borne fungal disease that seriously affects the yield and quality of Panxa ginseng. To develop a sustainable strategy for alleviating ginseng root rot, an herb-based soil amendment is suggested in this study. Mixed powers of medicinal herbs (MP) and corn stalks (CS) were used as soil amendments, respectively, along with a control group (CK) without treatment. The application of MP and CS led to significant relief from ginseng root rot. The disease index (%) represents both the incidence rate and symptom severity of the disease. The disease index of the MP and CS group was 18.52% and 25.93%, respectively, lower than that of CK (40.74%). Correspondingly, three soil enzyme activities improved; the antifungal components in the soil increased; and the relative abundances of root rot pathogens decreased in response to MP Soil enzyme activities were negatively correlated with disease grades. MP group also led to possible interactive changes in the communities of soil fungi and chemical components. In conclusion, our results suggest that the use of herb-based soil amendments has significant potential as an ecological and effective approach to controlling root rot disease of ginseng by the changing rhizosphere fungal community and soil compositions.

Text mining approach for feature extraction and cartilage disease grade classification using knee MRI radiology reports

MRI radiology reporting processes can be improved by exploiting structured and semantically labelled data that can be fed to artificial intelligence (AI) tools. AI-based tools assisting radiology reporting can help to automatically individuate cartilage grading in textual magnetic resonance imaging (MRI) reports, thus supporting clinicians' decisions regarding medical imaging utilisation, diagnosis and treatment. In this study, we extracted information (clinical findings, observations, anatomical regions, etc.) and classified knee cartilage degradation from medical reports utilising transfer-learning techniques applied to the Bidirectional Encoder Representations from Transformers (BERT) model and its variants, pre-trained on an Italian-language corpus. To realise this objective, we used a dataset of 750 MRI knee reports written by three radiologists who contributed to a manual annotation process to perform text classification (TC) and named entity recognition (NER) tasks. The dataset was obtained from an internal database of the IRCCS SYNLAB SDN. Seventy percent of the dataset was used for training, 10% was used for validation and 20% was used for testing. The best-performing configurations for NER and TC tasks were based on the pre-trained BERT model. The macro F1-scores obtained with the NER and TC models are 0.89 and 0.81, respectively. The accuracies calculated on the test set for both tasks are 0.96 and 0.99, respectively.

Simultaneous treatment of large hiatal hernias during Roux-en-Y gastric bypass: technical considerations and outcome.

Roux-en-Y gastric bypass (RYGB) is the preferred surgical option for patients with proven gastroesophageal reflux disease and obesity grade ≥ II (BMI ≥ 35kg/m2). Data on simultaneous treatment of larger hiatal hernias during RYGB are scarce. From 2012 until 2022, data from all consecutive patients undergoing gastric bypass procedures were collected and retrospectively analyzed. The characteristics and surgical outcomes of patients undergoing RYGB alone (RYGBa) versus RYGB with simultaneous treatment of a large hiatal hernia (RYGB-HH) were compared. Out of 573 patients who received RYGB, we identified 12 simultaneously treated for large hiatal hernia. The characteristics of RYGB-HH versus RYGBa patients were higher age (55 vs. 44years; p = 0.004) and lower BMI (39.2 vs. 46.9kg/m2; p = 0.001). Duration of surgery in the RYGB-HH group was longer (144min vs. 98min; p < 0.001), while complications > Clavien-Dindo II were similar compared to the RYGBa group (8.3 vs. 9.4%, p = 0.56). Length of stay did not differ among the groups (4 vs. 5.5days, p = 0.051). At a median follow-up of 12months, there was no clinical recurrence of hiatal hernia in the RYGB-HH group. Simultaneous treatment of large hiatal hernias during Roux-en-Y gastric bypass surgery prolongs operation time but seems feasible and safe in the hands of experienced surgeons.

Targeted Genetic Sequencing Analysis of 223 Cases of Pseudomyxoma Peritonei Treated by Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Shows Survival Related to GNAS and KRAS Status.

Pseudomyxoma peritonei (PMP) is an unusual condition with unique behaviour caused by a mucinous neoplasm, usually arising from the appendix. The aim of this study was to evaluate the prevalence of genomic alterations in clinical specimens of PMP using a targeted assay and correlate the findings with clinical, pathological and outcome data. Sequencing data from 223 patients were analysed. The median follow-up interval was 48 months. The primary neoplasm was appendiceal in 216 patients, ovarian in 4, urachal in 2 and renal in one. We confirmed common mutations in GNAS and KRAS (42% each) with significant co-occurrence of variants in these genes. TP53 mutations were found in 8%. Other mutations were rare but included novel mutations in BAP1 and ERBB4. Of 17 patients with acellular peritoneal mucin, 6 (35%) were positive for DNA mutations. The non-appendiceal cases generally showed a similar mutational landscape to the appendiceal lesions with GNAS and KRAS commonly mutated, although one urachal lesion showed multi-hit TP53 mutation without variants in either GNAS or KRAS. Survival was significantly associated with the grade of the primary neoplasm, the grade of the peritoneal disease, the completeness of cytoreduction score and with mutation in either GNAS, KRAS or both. The hazard ratio (HR) associated with mutation in GNAS and/or KRAS was 1.87 (p = 0.004). Survival outcome was more closely associated with the grade of the peritoneal disease than with the grade of the primary neoplasm. Our findings support the developing concept that mutational analysis may provide prognostic information in patients with PMP.

A novel smartphone application for bladder cancer management (BCM App): Design, development, and usability evaluation

BACKGROUND: Providing clinical guidelines to clinicians using innovative technologies seems practical and useful. This study aimed to design, develop, and evaluate a smartphone application to assist urologists in managing bladder cancer (BCM App). MATERIALS AND METHODS: The study was conducted in three phases, following the user-centered design model, at the urology clinic of Khorshid Hospital (Isfahan, Iran) in 2021. Components and functionalities for BCM App were specified in three focus group sessions with urologists and urology residents using clinical guidelines. Adopting the Delphi technique, the participants completed a questionnaire addressing issues including educating and informing clinicians, performing clinical calculations, representing graphical information, and recording patient information. A conceptual model for the app was designed, and the final product was developed. The usability of the BCM App was evaluated using the think-aloud technique by usability experts and end-users. RESULTS: The app’s components were categorized into three groups: Patient evaluation, disease staging and management, and patient follow-up. The app’s main components included “bladder cancer classification,” “disease grading and staging,” “management based on the disease stages,” “principles of intravesical treatment,” and “classifying follow-ups by disease stages.” Moreover, the most prominent app’s functionalities were “using staging and grading table,” “using American Urological Association risk stratification,” “calculating disease stages,” “calculating patient’s follow-up,” and “recording patient information.” The usability evaluation results revealed that the BCM App was at a “highly acceptable” level. CONCLUSION: To design and develop a smartphone app for managing bladder cancer, the involvement of urologists is crucial. Apart from assisting urologists in effectively managing bladder cancer, the proposed app has the potential to enhance residents’ knowledge and streamline their access to evidence.

Randomized Phase II Trial of Amrubicin Plus Irinotecan Versus Cisplatin Plus Irinotecan in Chemo-naïve Patients With Extensive-Disease Small-Cell Lung Cancer: Results of the Japan Multinational Trial Organization (JMTO) LC 08-01

BackgroundWe conducted a randomize phase II study to evaluate the efficacy and safety of topoisomerase II inhibitor amrubicin plus topoisomerase I inhibitor irinotecan (AI) compared with cisplatin plus irinotecan (PI) as first-line therapy in patients with extensive-disease (ED) small-cell lung cancer (SCLC). Patients and MethodsChemo-naïve patients with pathologically proven ED-SCLC (including limited disease (LD) SCLC with malignant effusion) were enrolled. Patients were randomized 1:1 to receive either AI (amrubicin 90mg/m2 on day 1 and irinotecan 50mg/m2 on days 1 and 8 of a 21-day cycle) or PI (cisplatin 60mg/m2 on day 1 and irinotecan 60mg/m2 on days 1, 8 and 15 of a 28-day cycle). The primary endpoint was overall survival proportion at 1 year. ResultsA total of 100 patients were randomly assigned to AI (n = 50) or to PI (n = 50). The 1-year overall survival proportions were 68.0% (95% confidence interval (CI): 56.2-82.2%) for AI and 59.2% (46.9-74.7%) for PI (1-sided P = .18). Median survival time was 14.8 months for AI and 13.5 months for PI with a hazard ratio (HR) of 0.618 (0.398-0.961, stratified log-rank test P = .031). Median progression-free survival time was 4.8 months for AI and 5.4 months for PI (stratified log-rank test, P = .54). Objective response rate was 70.0% (55.4-82.1%) for AI and 55.1% (40.2-69.3%) for PI (Fisher exact test, P = .15). There was no significant difference in hematological toxicity, whereas rates of vomiting, loss of appetite, diarrhea, and elevated serum creatinine are more frequent in PI. Interstitial lung disease (Grade 2 or 3) developed in 5 patients in AI and in 1 patient in PI. There was no treatment-related death. ConclusionAlthough the study did not meet its primary endpoint, AI showed promising efficacy and good tolerability in chemo-naïve patients with ED-SCLC.

Comparative analysis of reduced toxicity conditioning regimens between fludarabine plus melphalan and fludarabine plus busulfex in adult patients with acute lymphoblastic leukemia.

Reduced-toxicity conditioning (RTC) regimens aim to mitigate regimen-related toxicity while maintaining anti-leukemic efficacy in allogeneic hematopoietic stem cell transplantation (allo-HSCT). We assessed outcomes of RTC regimens utilizing melphalan versus intravenous busulfan combined with fludarabine in adult acute lymphoblastic leukemia (ALL) patients. A retrospective analysis was conducted with 149 consecutive adult ALL patients (median age 51, range 18-60) in remission undergoing allo-HSCT. Patients received either fludarabine 150 mg/BSA plus 2 days of melphalan 70 mg/BSA (FM140, n = 76) from 2009 to 2015 or fludarabine plus 3 days of busulfan 3.2 mg/kg (FB9.6, n = 73) from 2016 to 2021. At 5 years post-HSCT, FM140 demonstrated superior disease-free survival (53.4% vs. 30.5%, p = 0.007) and lower cumulative relapse (27.4% vs. 46.8%, p = 0.026) than FB9.6. Five-year overall survival and non-relapse mortality did not significantly differ. FM140 exhibited a higher incidence of acute graft-versus-host disease (GVHD) grades II-IV (49.3% vs. 30.3%, p = 0.016), though rates of acute GVHD grades III-IV and chronic GVHD were similar. Multivariate analysis identified Philadelphia chromosome and minimal residual disease positive status, and FB9.6 conditioning as predictors of increased relapse and poorer disease-free survival. FM140 RTC regimen displayed significantly reduced relapse and superior disease-free survival compared to FB9.6 in ALL patients undergoing allo-HSCT, highlighting its current clinical utility.

Do collaterals to infarct bed in STE-ACS patients undergoing emergent percutaneous coronary revascularization matter? An assessment of a prospective pool for in-hospital course

BackgroundLimited data exist on the role of coronary collaterals circulation (CCC) in patients with ST-elevation acute coronary syndrome (STE-ACS). This study aimed to assess CCC and the in-hospital course of patients with CCC undergoing primary percutaneous coronary intervention (pPCI). MethodsThe study included consecutive STE-ACS patients undergoing pPCI. Good CCC was defined as Rentrop collateral score (RCS) of 2–3. Patients with good and poor CCC were compared regarding clinical characteristics, angiographic patterns, and hospital course. ResultsIn the sample of 4683 patients, mean age was 55.6 ± 11 years, and 78.8 % were male. Good CCC was observed in 499 (10.7 %) patients. The rate of intra-procedure slow-flow/no-reflow (SF/NR) was 29.9 % vs. 20.5 % (p < 0.001), and the rate of composite adverse clinical outcomes (CACO) was 21.2 % vs. 19 % (p = 0.225) for patients with good and poor CCC, respectively. Multivariable analysis identified left ventricular end-diastolic pressure (LVEDP), multi-vessel disease (MVD), and thrombus grade ≥4 as independent predictors of good CCC, with adjusted odds ratios of 0.98 [0.97–0.99], 1.69 [1.35–2.10], and 3.45 [2.64–4.52], respectively. In propensity-matched cohorts, the intra-procedure SF/NR rate was 29.9 % vs. 26.9 % (p = 0.292), and the rate of CACO was 21.2 % vs. 23.4 % (p = 0.403) for patients with good and poor CCC, respectively. ConclusionAngiographic evidence of good CCC in STE-ACS patients was limited. Good CCC was associated with a higher prevalence of MVD, high thrombus burden, and low pre-procedure LVEDP, resulting in a higher incidence of intra-procedure SF/NR. However, the CACO did not differ significantly between patients with good and poor CCC.

The prognostic significance of androgen receptor expression in gliomas

Androgen receptor (AR) overexpression has been identified in gliomas and its stem cells, suggesting that AR plays an important role in tumor carcinogenesis. The prognostic significance of AR overexpression in gliomas remains unknown. AR mRNA expression in gliomas and relevant clinical data were obtained from The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases. AR expression levels were compared across gliomas of different histopathologic grades and molecular subtypes. Kaplan–Meier analyses in patients with different AR expression levels were investigated for the potential prognostic values of AR. Compared with normal brain tissue, gliomas show significantly higher AR mRNA expression (p < 0.01). AR mRNA expression was more prominent in higher grade disease and in worse prognostic molecular subtypes (p < 0.01). AR protein is more abundant in glioblastoma than in lower grade gliomas (LGG) (grade 2/3) (p < 0.0001). This is corroborated by a linear association between AR mRNA and protein expression (r = 0.65). In LGG, both higher AR mRNA and protein expression was associated with significantly worse overall survival (OS). Five-year OS for LGG patients with high versus low AR expression were 59.1% and 73.3%, respectively (p < 0.0001). AR expression is not prognostic for OS within glioblastoma patients. Gender was not associated with AR expression or prognosis. Higher AR expression levels are associated with higher grade disease and histopathologic features predicting poorer prognosis in lower grade gliomas. Higher gene expression in LGG patients is correlated with poor prognosis but not in the glioblastoma cohort suggesting saturated expression/functions of AR in glioblastoma.