METHODS: Retrospective analysis was performed on the FLEXOR registry, which was created as a TOWER group (Team of Worldwide Endourological Researchers, research wing of the Endourological Society) endeavor. Patients who underwent retrograde intrarenal surgery (RIRS) for renal stones from January 2018 to August 2021 were enrolled from 20 centers globally. A total of 6663 patients whose data were available for analysis were divided into Group 1 (Reusable scopes, 4808 patients) versus Group 2 (Disposable scopes, 1855 patients).
RESULTS: The age and gender distribution were similar in both groups. The mean stone size was 11.8 mm and 9.6 mm in Groups 2 and 1, respectively (p 2 cm stones, lower pole stones and of higher Hounsfield unit. Thulium fiber laser (TFL) was used more in Group 2 (p
OBJECTIVE: This study aims to comprehensively explore the diverse mechanisms of cancer drug resistance, assess the evolution of resistance detection methods, and identify strategies for overcoming this challenge. The evolution of resistance detection methods and identification strategies for overcoming the challenge.
METHODS: A comprehensive literature review was conducted to analyze intrinsic and acquired drug resistance mechanisms, including altered drug efflux, reduced uptake, inactivation, target mutations, signaling pathway changes, apoptotic defects, and cellular plasticity. The evolution of mutation detection techniques, encompassing clinical predictions, experimental approaches, and computational methods, was investigated. Strategies to enhance drug efficacy, modify pharmacokinetics, optimizoptimizee binding modes, and explore alternate protein folding states were examined.
RESULTS: The study comprehensively overviews the intricate mechanisms contributing to cancer drug resistance. It outlines the progression of mutation detection methods and underscores the importance of interdisciplinary approaches. Strategies to overcome drug resistance challenges, such as modulating ATP-binding cassette transporters and developing multidrug resistance inhibitors, are discussed. The study underscores the critical need for continued research to enhance cancer treatment efficacy.
CONCLUSION: This study provides valuable insights into the complexity of cancer drug resistance mechanisms, highlights evolving detection methods, and offers potential strategies to enhance treatment outcomes.
MATERIALS AND METHODS: The antisolvent precipitation method was used for formulation of nanoparticles. Factorial design (32) was utilized as a tool to analyze the effect of Ch and TGP concentration on particle size and entrapment efficiency of nanoparticles.
RESULTS: Formulated nanoparticles showed high entrapment efficiency (67.19±0.42-83.36±0.23%) and small size (53.3-383.1 nm). The present investigation involved utilization of two biological membranes (egg and tomato) as biological barriers for drug release. The study revealed that drug release from tomato membranes was retarded (as compared to egg membranes) but the release pattern matched that of egg membranes. All formulations followed the Baker-Lansdale model of drug release irrespective of the two different biological barriers. Stability studies were carried out for 45 days and exhibited less variation in particle size as well as a reduction in entrapment efficiency. Simvastatin loaded PEC stabilized nanoparticles exhibited better control on growth of human breast cancer cell lines than simple simvastatin. An unusual anticancer effect of simvastatin nanoparticles is also supported by several other research studies.
CONCLUSION: The present study involves first-time synthesis of Ch-TGP polyelectrolyte complex stabilized nanoparticles of simvastatin against MCF-7 cells. It recommends that, in future, theoretical modeling and IVIVC should be carried out for perfect designing of delivery systems.
MATERIALS AND METHODS: Data from adults who underwent flexible ureteroscopy in 20 centers worldwide were retrospectively reviewed (January 2018-August 2021). Patients with ureteral stones, concomitant bilateral procedures, and combined procedures were excluded. One-to-one propensity score matching for age, gender, and stone characteristics was performed. Stone-free rate was defined as absence of fragments >2 mm on imaging within 3 months after surgery. Multivariable logistic regression analysis was performed to evaluate independent predictors of being stone-free.
RESULTS: Of 2,075 included patients, holmium:YAG laser with MOSES technology was used in 508 patients and thulium fiber laser in 1,567 patients. After matching, 284 patients from each group with comparable baseline characteristics were included. Pure dusting was applied in 6.0% of cases in holmium:YAG laser with MOSES technology compared with 26% in thulium fiber laser. There was a higher rate of basket extraction in holmium:YAG laser with MOSES technology (89% vs 43%, P < .001). Total operation time and lasing time were similar. Nine patients had sepsis in thulium fiber laser vs none in holmium:YAG laser with MOSES technology (P = .007). Higher stone-free rate was achieved in thulium fiber laser (85% vs 56%, P < .001). At multivariable analysis, the use of thulium fiber laser and ureteral access sheath ≥8F had significantly higher odds of being stone-free. Lasing time, multiple stones, stone diameter, and use of disposable scopes showed significantly lower odds of being stone-free.
CONCLUSIONS: This real-world study favors the use of thulium fiber laser over holmium:YAG laser with MOSES technology in flexible ureteroscopy for renal stones by way of its higher single-stage stone-free rate.
OBJECTIVES: To describe the demographic and disease features of the full cohort of patients enrolled in the United in Fight against prOstate cancer (UFO) registry.
DESIGN: The UFO registry was a multi-national, longitudinal, observational study of patients with PC presenting to participating tertiary care hospitals in eight Asian countries/regions.
METHODS: Patients with high-risk localized PC (HRL), non-metastatic biochemically recurrent, or metastatic PC were consecutively enrolled from September 14, 2015 until September 1, 2020 and followed for up to 5 years.
RESULTS: Among the full cohort of 3635 patients, 425 had HRL, 389 had non-metastatic biochemically recurrent, and 2821 had metastatic PC. Median follow-up time was 4.2, 4.2, and 2.6 years, respectively. At first diagnosis, the mean age ranged from 65.7 to 69.1 years, 38.5% had extra-capsular tumor extension, 34.0% had regional lymph node metastases, and 65.1% had distant metastases. Quality-of-life scores at enrollment were significantly worse in patients with metastatic disease. Decisions to start therapy were mainly driven by treatment guidelines and disease progression. The decision to discontinue hormonal therapy was often due to disease progression. Few patients received novel hormonal therapies despite their availability.
CONCLUSION: The UFO registry provides a detailed, contemporary picture of the characteristics, treatment, and outcomes of patients with PC in Asia. There is an unmet medical need to improve access to novel agents in Asia, aiming to improve quality of life and clinical outcomes.
TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT02546908, Registry Identifier: NOPRODPCR4001.
METHODS: Inclusion criteria: age ≥ 18 years, normal renal/calyceal system anatomy, calculi of any size, number, and position.
STUDY PERIOD: January 2018 and August 2021. Stone-free status: absence of fragments > 2 mm, assessed post procedure according to the local protocol (KUB X-Ray and/or ultrasound or non-contrast CT scan).
RESULTS: Twenty centers from fifteen countries enrolled 6669 patients. There were 4407 (66.2%) men. Mean age was 49.3 ± 15.59 years. Pain was the most frequent symptom indication for intervention (62.6%). 679 (10.2%) patients underwent RIRS for an incidental finding of stones. 2732 (41.0%) patients had multiple stones. Mean stone size was 10.04 ± 6.84 mm. A reusable flexible ureteroscope was used in 4803 (72.0%) procedures. A sheath-less RIRS was performed in 454 (6.8%) cases. Holmium:YAG laser was used in 4878 (73.1%) cases. A combination of dusting and fragmentation was the most common lithotripsy mode performed (64.3%). Mean operation time was 62.40 ± 17.76 min. 119 (1.8%) patients had an intraoperative injury of the ureter due to UAS insertion. Mean postoperative stay was 3.62 ± 3.47 days. At least one postoperative complication occurred in 535 (8.0%) patients. Sepsis requiring intensive care admission occurred in 84 (1.3%) patients. Residual fragments were detected in 1445 (21.7%) patients. Among the latter, 744 (51.5%) patients required a further intervention.
CONCLUSION: Our database contributes real-world data to support to a better understanding of modern RIRS practice and outcomes.
METHODS: We systematically searched MEDLINE, Embase, and Cochrane databases until November 2022 for randomized controlled PEP prophylaxis trials. We invited authors to share individual patient data, including PEP risk profile and prophylaxes used. PEP incidence rates for different prophylaxis were calculated. Efficacy was compared using multilevel logistic regression and expressed as relative risk (RR). Subgroup analysis evaluated the role of patient and ERCP-related risk factors in developing PEP.
RESULTS: Data from 11 studies, including 6430 patients, were analyzed. After adjusting for risk factors, rectal NSAIDs (RR 0.69, 95%CI 0.54-0.88) and peri-procedural high-volume intravenous fluid (IVF) (RR 0.40, 95%CI 0.21-0.79) were effective in reducing PEP incidence, while no benefit was noted with pancreatic duct (PD) stents (RR 1.25, 95%CI 0.91-1.73). In patients receiving rectal NSAIDs (n = 2617), difficult cannulation (RR 1.99, 1.45-2.73), contrast injection into the pancreatic duct (PD) (RR2.37, 1.68-3.32), and prior history of PEP (RR 1.90, 1.06-3.41) were associated with increased PEP risk.
CONCLUSION: This IPDMA confirms that rectal NSAIDs and peri-procedural IVF are effective PEP prophylactic strategies. Further studies focusing on combination therapy or the development of personalized PEP risk calculators are needed to improve prophylactic strategies.
METHODS: ACLF patients recruited from the APASL-ACLF Research Consortium (AARC) were followed up till 30 days, death or transplantation, whichever earlier. Clinical details, including dynamic grades of HE and laboratory data, including ammonia levels, were serially noted.
RESULTS: Of the 3009 ACLF patients, 1315 (43.7%) had HE at presentation; grades I-II in 981 (74.6%) and grades III-IV in 334 (25.4%) patients. The independent predictors of HE at baseline were higher age, systemic inflammatory response, elevated ammonia levels, serum protein, sepsis and MELD score (p
METHODS: Detailed phenotyping and next-generation sequencing (panel and exome).
RESULTS: Our analysis revealed 224 pathogenic/likely pathogenic variants (54 (24%) of which are novel) in 123 genes with established or tentative links to skeletal dysplasia. In addition, we propose 5 genes as candidate disease genes with suggestive biological links (WNT3A, SUCO, RIN1, DIP2C, and PAN2). Phenotypically, we note that our cohort spans 36 established phenotypic categories by the International Skeletal Dysplasia Nosology, as well as 18 novel skeletal dysplasia phenotypes that could not be classified under these categories, e.g., the novel C3orf17-related skeletal dysplasia. We also describe novel phenotypic aspects of well-known disease genes, e.g., PGAP3-related Toriello-Carey syndrome-like phenotype. We note a strong founder effect for many genes in our cohort, which allowed us to calculate a minimum disease burden for the autosomal recessive forms of skeletal dysplasia in our population (7.16E-04), which is much higher than the global average.
CONCLUSION: By expanding the phenotypic, allelic, and locus heterogeneity of skeletal dysplasia in humans, we hope our study will improve the diagnostic rate of patients with these conditions.
METHODS: Patients with MAFLD-ACLF were recruited from the AARC registry. The diagnosis of MAFLD-ACLF was made when the treating unit had identified the etiology of chronic liver disease (CLD) as MAFLD (or previous nomenclature such as NAFLD, NASH, or NASH-cirrhosis). Patients with coexisting other etiologies of CLD (such as alcohol, HBV, HCV, etc.) were excluded. Data was randomly split into derivation (n=258) and validation (n=111) cohorts at a 70:30 ratio. The primary outcome was 90-day mortality. Only the baseline clinical, laboratory features and severity scores were considered.
RESULTS: The derivation group had 258 patients; 60% were male, with a mean age of 53. Diabetes was noted in 27%, and hypertension in 29%. The dominant precipitants included viral hepatitis (HAV and HEV, 32%), drug-induced injury (DILI, 29%) and sepsis (23%). MELD-Na and AARC scores upon admission averaged 32±6 and 10.4±1.9. At 90 days, 51% survived. Non-viral precipitant, diabetes, bilirubin, INR, and encephalopathy were independent factors influencing mortality. Adding diabetes and precipitant to MELD-Na and AARC scores, the novel MAFLD-MELD-Na score (+12 for diabetes, +12 for non-viral precipitant) and MAFLD-AARC score (+5 for each) were formed. These outperformed the standard scores in both cohorts.
CONCLUSION: Almost half of MAFLD-ACLF patients die within 90 days. Diabetes and non-viral precipitants such as DILI and sepsis lead to adverse outcomes. The new MAFLD-MELD-Na and MAFLD-AARC scores provide reliable 90-day mortality predictions for MAFLD-ACLF patients.
METHODS: In this work, we present a general overview of INPST activities and showcase the specific use of Twitter as a powerful networking tool that was used to host a one-week "2021 INPST Twitter Networking Event" (spanning from 31st May 2021 to 6th June 2021) based on the application of the Twitter hashtag #INPST.
RESULTS AND CONCLUSION: The use of this hashtag during the networking event period was analyzed with Symplur Signals (https://www.symplur.com/), revealing a total of 6,036 tweets, shared by 686 users, which generated a total of 65,004,773 impressions (views of the respective tweets). This networking event's achieved high visibility and participation rate showcases a convincing example of how this social media platform can be used as a highly effective tool to host virtual Twitter-based international biomedical research events.
METHODS: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.
RESULTS: There were 91,373 stroke admissions in the 4 months immediately before compared to 80,894 admissions during the pandemic months, representing an 11.5% (95% confidence interval [CI] -11.7 to -11.3, p < 0.0001) decline. There were 13,334 IVT therapies in the 4 months preceding compared to 11,570 procedures during the pandemic, representing a 13.2% (95% CI -13.8 to -12.7, p < 0.0001) drop. Interfacility IVT transfers decreased from 1,337 to 1,178, or an 11.9% decrease (95% CI -13.7 to -10.3, p = 0.001). Recovery of stroke hospitalization volume (9.5%, 95% CI 9.2-9.8, p < 0.0001) was noted over the 2 later (May, June) vs the 2 earlier (March, April) pandemic months. There was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was noted in 3.3% (1,722/52,026) of all stroke admissions.
CONCLUSIONS: The COVID-19 pandemic was associated with a global decline in the volume of stroke hospitalizations, IVT, and interfacility IVT transfers. Primary stroke centers and centers with higher COVID-19 inpatient volumes experienced steeper declines. Recovery of stroke hospitalization was noted in the later pandemic months.
OBJECTIVE: To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning.
EVIDENCE REVIEW: We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence.
FINDINGS: In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572 000 deaths and 15.2 million DALYs), and stomach cancer (542 000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819 000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601 000 deaths and 17.4 million DALYs), TBL cancer (596 000 deaths and 12.6 million DALYs), and colorectal cancer (414 000 deaths and 8.3 million DALYs).
CONCLUSIONS AND RELEVANCE: The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equity in cancer care.