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DEN Open Apr 2025For early gastrointestinal lesions, size is an important factor in the selection of treatment. Virtual scale endoscope (VSE) is a newly developed endoscope that can...
OBJECTIVES
For early gastrointestinal lesions, size is an important factor in the selection of treatment. Virtual scale endoscope (VSE) is a newly developed endoscope that can measure size more accurately than visual measurement. This study aimed to investigate whether VSE measurement is accurate for early gastrointestinal lesions of various sizes and morphologies.
METHODS
This study prospectively enrolled patients with early gastrointestinal lesions ≤20 mm in size visually. Lesion sizes were measured in the gastrointestinal tract visually, on endoscopic resection specimens with VSE, and finally on endoscopic resection specimens using a ruler. The primary endpoint was the normalized difference (ND) of VSE measurement. The secondary endpoints were the ND of visual measurement and the variation between NDs of VSE and visual measurements. ND was calculated as (100 × [measured size - true size] / true size) (%). True size was defined as size measured using a ruler.
RESULTS
This study included 60 lesions from April 2022 to December 2022, with 20 each in the esophagus, stomach, and colon. The lesion size was 14.0 ± 6.3 mm (mean ± standard deviation). Morphologies were protruded, slightly elevated, and flat or slightly depressed type in 8, 24, and 28 lesions, respectively. The primary endpoint was 0.3 ± 8.8%. In the secondary endpoints, the ND of visual measurement was -1.7 ± 29.3%, and the variability was significantly smaller in the ND of VSE measurement than in that of visual measurement ( < 0.001, F-test).
CONCLUSIONS
VSE measurement is accurate for early gastrointestinal lesions of various sizes and morphologies.
PubMed: 38903962
DOI: 10.1002/deo2.386 -
Frontiers in Immunology 2024We aimed to evaluate the efficacy, safety, and immunogenicity of a SARS-CoV-2 mRNA vaccine (Omicron BA.5) LVRNA012 given as the booster in immunized but SARS-CoV-2... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
We aimed to evaluate the efficacy, safety, and immunogenicity of a SARS-CoV-2 mRNA vaccine (Omicron BA.5) LVRNA012 given as the booster in immunized but SARS-CoV-2 infection-free adults in China.
METHODS
This is a single-center, randomized, double-blind, placebo-controlled phase 3 clinical trial enrolling healthy adult participants (≥18 years) who had completed two or three doses of inactivated COVID-19 vaccines at least 6 months before, in Bengbu, Anhui province, China. Eligible participants were randomly assigned (1:1) to receive a booster intramuscular vaccination with an LVRNA012 vaccine (100ug) or placebo. The primary endpoint was the protective efficacy of a booster dose of the LVRNA012 vaccine or placebo against symptomatic COVID-19 of any severity 14 days after vaccination. Laboratory-confirmed COVID-19 infections were identified from 14 days to 180 days after intervention, with active surveillance for symptomatic illness 8 times per month between 7 to 90 days and at least once per month between 90 to 180 days after intervention.
RESULTS
2615 participants were recruited and randomly assigned in a 1:1 ratio to either the vaccine group (1308) or the placebo group (1307). A total of 141 individuals (46 in the LVRNA012 group and 95 in the placebo group) developed symptomatic COVID-19 infection 14 days after the booster immunization, showing a vaccine efficacy of 51.9% (95% CI, 31.3% to 66.4%). Most infections were detected 90 days after intervention during a period when XBB was prevalent in the community. Adverse reactions were reported by 64% of participants after the LVRNA012 vaccination, but most of them were mild or moderate. The booster vaccination with the LVRNA012 mRNA vaccine could significantly enhance neutralizing antibody titers against the Omicron variant XBB.1.5 (GMT 132.3 [99.8, 175.4]) than did those in the placebo group (GMT 12.5 [8.4, 18.7]) at day 14 for the previously immunized individuals.
CONCLUSION
The LVRNA012 mRNA vaccine is immunogenic, and shows robust efficacy in preventing COVID-19 during the omicron-predominate period.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov, identifier NCT05745545.
Topics: Humans; COVID-19 Vaccines; Male; Female; COVID-19; Adult; Double-Blind Method; SARS-CoV-2; Middle Aged; Antibodies, Viral; Immunogenicity, Vaccine; Immunization, Secondary; mRNA Vaccines; Vaccine Efficacy; Young Adult; China; Antibodies, Neutralizing; Vaccines, Synthetic
PubMed: 38903523
DOI: 10.3389/fimmu.2024.1407826 -
Frontline Gastroenterology Jul 2024Upadacitinib is a Janus kinase inhibitor, which has recently been approved for treating Crohn's disease. There are limited real-world studies on the outcomes of...
BACKGROUND
Upadacitinib is a Janus kinase inhibitor, which has recently been approved for treating Crohn's disease. There are limited real-world studies on the outcomes of upadacitinib in Crohn's disease.
OBJECTIVE
Our aim was to evaluate the outcomes of upadacitinib in a real-world Crohn's disease cohort.
METHODS
We conducted a retrospective, multicentre, cohort study over a 2-year period across National Health Service (NHS) Lothian and Royal Devon University Healthcare NHS Foundation Trust. The primary outcome was treatment persistence at week 24. Secondary endpoints were corticosteroid-free clinical remission (Harvey-Bradshaw Index (HBI)<5) and biomarker remission (C-reactive protein (CRP)≤5 mg/L and faecal calprotectin (FCAL)<250 µg/g) at 12, 24 and 52 weeks. We recorded adverse events.
RESULTS
135 patients commenced upadacitinib as of the 1 January 2024, of which 93 patients with active Crohn's disease were included with a minimum of 12 weeks follow-up. The median follow-up time was 25 weeks (IQR 15-42 weeks). 82% of the cohort had exposure to at least two classes of advanced therapies, and 52% had exposure to at least three classes of advanced therapies. Treatment persistence was 87.1% at week 12, 81.7% at week 24 and 62.8% at week 52. Rates of clinical remission were 64% (42/66), 48% (22/46) and 38% (8/21) at weeks 12, 24 and 52, respectively. Significant reductions in HBI, CRP and FCAL were observed during follow-up. 14% (13/91) had a hospitalisation due to Crohn's disease. Adverse events occurred in 40% (37/93) of the cohort, of which 12% (11/93) were serious.
CONCLUSION
Upadacitinib was effective in a real-world, highly refractory, Crohn's disease cohort with good persistence.
PubMed: 38903490
DOI: 10.1136/flgastro-2024-102668 -
Cureus May 2024COVID-19 is a viral disease that can manifest acutely in the respiratory tract and other organs. In this study, we aimed to investigate potential long-term damage to the...
COVID-19 is a viral disease that can manifest acutely in the respiratory tract and other organs. In this study, we aimed to investigate potential long-term damage to the heart from COVID-19. For this study, we divided 97 consecutive unselected COVID-19 patients aged 18-80 years at a cardiology practice in Cologne, Germany, into two groups based on the severity of their infection. We performed a resting ECG and a resting transthoracic echocardiography three and six months after SARS-CoV2 infection. The key discriminator determining disease severity was bed confinement or hospital admission. Group 1 included patients with less severe COVID-19, whereas group 2 contained more severe cases. Heart rate as the primary ECG endpoint was lower by a statistically significant amount for the entire study population (p=0.024), subdivided by gender (p <0.001, p <0.001) and in group 1 p =0.003 compared to three months. QTc time and repolarization disturbances as primary ECG endpoints and the echocardiographic primary endpoints, left ventricular ejection fraction, and left ventricular end-diastolic diameter (LVEDD), showed no relevant difference between the subgroups at three and six months or between the measurements taken at each point. In contrast, LVEDD normalized to body surface area was statistically significantly lower at six months in women in group 1 compared to group 2 (p=0.048) and in the overall study population at six months compared with the data after three months (p=0.034). E/E' was statistically lower at six months than at three months in the whole population (p=0.004) and in women (p=0.031). All measured echocardiographic and electrocardiographic mean values were within the normal range in all groups and follow-up controls. Overall, the prospective study conducted showed no significant evidence of long-term cardiac damage from COVID-19 disease, as evidenced by electrocardiographic and echocardiographic examinations at three and six months after infection.
PubMed: 38903385
DOI: 10.7759/cureus.60641 -
Cardiovascular Endocrinology &... Sep 2024The correlation between diabetes and aortic dissection is not fully understood yet, although in literature many studies have suggested that there may be an association...
BACKGROUND
The correlation between diabetes and aortic dissection is not fully understood yet, although in literature many studies have suggested that there may be an association between the two conditions. The purpose of this study is to evaluate whether diabetes represents a short- and long-term risk factor for mortality from type A acute aortic dissection.
MATERIALS AND METHODS
A total of 340 patients with the diagnosis of type A acute aortic dissection underwent aortic surgery between January 2002 and March 2023. The sample was divided into 2 cohorts according to the presence of diabetes ( = 34) or not ( = 306).
RESULTS
The mean age was 66 (±12.4) years and 60.9% were male. The primary endpoint was 30-day mortality. Hospital mortality was 12 (35.3%) for the diabetes group and 70 (22.9%) for nondiabetes group ( = 0.098). Overall survival at 10 years was 48.3% [95% confidence interval (CI): 41.6-54.7%], while the 10-year survival for people with diabetes was 29.5% (95% CI: 13.2-47.9%) and for nondiabetes group 50.6% (95% CI: 43.4-57.3%) (Log-rank, = 0.024).
CONCLUSION
Diabetes was not found to be a risk factor associated with 30-day mortality in patients undergoing surgery for type A acute aortic dissection. It was a risk factor for long-term survival, but this may be related to diabetes complications.
PubMed: 38903248
DOI: 10.1097/XCE.0000000000000306 -
Frontiers in Neurology 2024Clazosentan, a selective endothelin receptor subtype A antagonist, reduces vasospasm-related morbidity and all-cause mortality following aneurysmal subarachnoid...
INTRODUCTION
Clazosentan, a selective endothelin receptor subtype A antagonist, reduces vasospasm-related morbidity and all-cause mortality following aneurysmal subarachnoid hemorrhage (SAH) in the Japanese population, as demonstrated by a recent randomized phase 3 trial. However, evidence to suggest clazosentan should be prioritized over the current standard of care to prevent cerebral vasospasm is still lacking. Therefore, we investigated the efficacy and safety of clazosentan in comparison with conventional postoperative management in real-world clinical practice.
METHODS
We conducted a single-center, retrospective, observational cohort study using prospectively collected data from consecutive patients with aneurysmal SAH. After clazosentan was approved for use in Japan, the conventional postoperative management protocol, composed of intravenous fasudil chloride and oral cilostazol (control group, April 2021 to March 2022), was changed to the clazosentan protocol (clazosentan group, April 2022 to March 2023). The primary endpoint was the incidence of vasospasm-related symptomatic infarction. The secondary endpoints were favorable functional outcomes (modified Rankin scale score < 3) at discharge, angiographic vasospasm, and the need for rescue therapy for delayed cerebral ischemia.
RESULTS
The analysis included 100 and 81 patients in the control and clazosentan groups, respectively. The incidence of vasospasm-related symptomatic infarction was significantly lower in the clazosentan group than in the control group (6.2% vs. 16%, = 0.032). Multiple logistic analyses demonstrated that the use of clazosentan was independently associated with fewer incidence of vasospasm-related symptomatic infarct (23.8% vs. 47.5%, odds ratio 0.34 [0.12-0.97], = 0.032). Clazosentan was significantly associated with favorable outcomes at discharge (79% vs. 66%, = 0.037). Moreover, both the incidence of angiographic vasospasm (25.9% vs. 44%, = 0.013) and the need for rescue therapy (16.1% vs. 34%, = 0.006) was lower in the clazosentan group. The occurrence of pulmonary edema was significantly higher with clazosentan use (19.8% vs. 5%, = 0.002), which did not result in morbidity.
CONCLUSION
A postoperative management protocol centering on clazosentan was associated with the reduced vasospasm-related symptomatic infarction and improved clinical outcomes compared to the conventional management protocol in Japanese clinical practice. Clazosentan might be a promising treatment option for counteracting cerebral vasospasm after aneurysmal SAH.
PubMed: 38903164
DOI: 10.3389/fneur.2024.1413632 -
Annals of Palliative Medicine Jun 2024Bone metastases are a common and debilitating consequence of advanced cancer, often necessitating palliative radiation therapy (RT) for pain relief. Reirradiation (reRT)...
Bone metastases are a common and debilitating consequence of advanced cancer, often necessitating palliative radiation therapy (RT) for pain relief. Reirradiation (reRT) of bone metastases is often considered after lack of pain relief following an initial course of RT, after a partial but unsatisfying pain response to an initial course of radiotherapy, or after pain recurrence following a complete or partial pain response to an initial course of RT. The NCIC CTG SC.20 trial, a landmark multicenter, randomized, non-blinded, controlled non-inferiority trial, addressed the critical question of optimal dose fractionation for reRT in this patient population. This trial compared the efficacy and toxicity of a single 8 Gy fraction to multiple fractions totaling 20 Gy in 850 patients with painful bone metastases requiring reRT. The primary endpoint was overall pain response at 2 months, with secondary endpoints of quality of life (QoL) measures, functional interference, and toxicity profiles assessed using patient-reported questionnaires and the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30. The intention-to-treat analysis revealed no significant difference in pain response between the two arms, meeting the pre-specified non-inferiority criteria. The per-protocol analysis suggested a potential benefit for a subset of patients receiving multiple fractions, although this was not statistically robust. Acute toxicities were more prevalent in the multiple fractions arm, with implications for patient comfort and healthcare utilization. Importantly, responders to reRT reported significant improvements in functional interference and QoL. The trial's findings support the use of a patient-centric approach to palliative RT, highlighting the viability of a single 8 Gy fraction as a less toxic and more convenient treatment option, albeit with consideration for individual patient circumstances. These results have significant implications for clinical practice, potentially reducing healthcare burdens while optimizing patient convenience during palliative care for painful bone metastases.
PubMed: 38902990
DOI: 10.21037/apm-24-15 -
Trials Jun 2024Disease recurrence remains one of the biggest concerns in patients after resection of pancreatic ductal adenocarcinoma (PDAC). Despite (neo)adjuvant systemic therapy,...
Recurrent disease detection after resection of pancreatic ductal adenocarcinoma using a recurrence-focused surveillance strategy (RADAR-PANC): protocol of an international randomized controlled trial according to the Trials within Cohorts design.
BACKGROUND
Disease recurrence remains one of the biggest concerns in patients after resection of pancreatic ductal adenocarcinoma (PDAC). Despite (neo)adjuvant systemic therapy, most patients experience local and/or distant PDAC recurrence within 2 years. High-level evidence regarding the benefits of recurrence-focused surveillance after PDAC resection is missing, and the impact of early detection and treatment of recurrence on survival and quality of life is unknown. In most European countries, recurrence-focused follow-up after surgery for PDAC is currently lacking. Consequently, guidelines regarding postoperative surveillance are based on expert opinion and other low-level evidence. The recent emergence of more potent local and systemic treatment options for PDAC recurrence has increased interest in early diagnosis. To determine whether early detection and treatment of recurrence can lead to improved survival and quality of life, we designed an international randomized trial.
METHODS
This randomized controlled trial is nested within an existing prospective cohort in pancreatic cancer centers in the Netherlands (Dutch Pancreatic Cancer Project; PACAP) and the United Kingdom (UK) (Pancreas Cancer: Observations of Practice and survival; PACOPS) according to the "Trials within Cohorts" (TwiCs) design. All PACAP/PACOPS participants with a macroscopically radical resection (R0-R1) of histologically confirmed PDAC, who provided informed consent for TwiCs and participation in quality of life questionnaires, are included. Participants randomized to the intervention arm are offered recurrence-focused surveillance, existing of clinical evaluation, serum cancer antigen (CA) 19-9 testing, and contrast-enhanced computed tomography (CT) of chest and abdomen every three months during the first 2 years after surgery. Participants in the control arm of the study will undergo non-standardized clinical follow-up, generally consisting of clinical follow-up with imaging and serum tumor marker testing only in case of onset of symptoms, according to local practice in the participating hospital. The primary endpoint is overall survival. Secondary endpoints include quality of life, patterns of recurrence, compliance to and costs of recurrence-focused follow-up, and the impact on recurrence-focused treatment.
DISCUSSION
The RADAR-PANC trial will be the first randomized controlled trial to generate high level evidence for the current clinical equipoise regarding the value of recurrence-focused postoperative surveillance with serial tumor marker testing and routine imaging in patients after PDAC resection. The Trials within Cohort design allows us to study the acceptability of recurrence-focused surveillance among cohort participants and increases the generalizability of findings to the general population. While it is strongly encouraged to offer all trial participants treatment at time of recurrence diagnosis, type and timing of treatment will be determined through shared decision-making. This might reduce the potential survival benefits of recurrence-focused surveillance, although insights into the impact on patients' quality of life will be obtained.
TRIAL REGISTRATION
Clinicaltrials.gov, NCT04875325 . Registered on May 6, 2021.
Topics: Humans; Carcinoma, Pancreatic Ductal; Pancreatic Neoplasms; Neoplasm Recurrence, Local; Randomized Controlled Trials as Topic; Pancreatectomy; Time Factors; Quality of Life; Prospective Studies; Multicenter Studies as Topic; Treatment Outcome; Predictive Value of Tests; Netherlands; United Kingdom; Research Design; Early Detection of Cancer
PubMed: 38902836
DOI: 10.1186/s13063-024-08223-5 -
Cardiovascular Diabetology Jun 2024This study sought to elucidate the associations of cardiometabolic index (CMI), as a metabolism-related index, with all-cause and cardiovascular mortality among the...
BACKGROUND
This study sought to elucidate the associations of cardiometabolic index (CMI), as a metabolism-related index, with all-cause and cardiovascular mortality among the older population. Utilizing data from the National Health and Nutrition Examination Survey (NHANES), we further explored the potential mediating effect of inflammation within these associations.
METHODS
A cohort of 3029 participants aged over 65 years old, spanning six NHANES cycles from 2005 to 2016, was enrolled and assessed. The primary endpoints of the study included all-cause mortality and cardiovascular mortality utilizing data from National Center for Health Statistics (NCHS). Cox regression model and subgroup analysis were conducted to assess the associations of CMI with all-cause and cardiovascular mortality. The mediating effect of inflammation-related indicators including leukocyte, neutrophil, lymphocyte, systemic immune-inflammation index (SII), neutrophil to lymphocyte ratio (NLR) were evaluated to investigate the potential mechanism of the associations between CMI and mortality through mediation package in R 4.2.2.
RESULTS
The mean CMI among the enrolled participants was 0.74±0.66, with an average age of 73.28±5.50 years. After an average follow-up period of 89.20 months, there were 1,015 instances of all-cause deaths and 348 cardiovascular deaths documented. In the multivariable-adjusted model, CMI was positively related to all-cause mortality (Hazard Ratio (HR)=1.11, 95% CI=1.01-1.21). Mediation analysis indicated that leukocytes and neutrophils mediated 6.6% and 13.9% of the association of CMI with all-cause mortality.
CONCLUSION
Elevated CMI is positively associated with all-cause mortality in the older adults. The association appeared to be partially mediated through inflammatory pathways, indicating that CMI may serve as a valuable indicator for poor prognosis among the older population.
Topics: Humans; Male; Aged; Female; Inflammation; Nutrition Surveys; Cardiovascular Diseases; Risk Assessment; Cause of Death; United States; Cardiometabolic Risk Factors; Aged, 80 and over; Time Factors; Prognosis; Inflammation Mediators; Age Factors; Neutrophils; Lymphocyte Count; Biomarkers
PubMed: 38902748
DOI: 10.1186/s12933-024-02251-w -
Med (New York, N.Y.) Jun 2024The QUATTRO-II trial examined the efficacy and safety of capecitabine+oxaliplatin+irinotecan (CAPOXIRI)+bevacizumab (BEV) vs. 5-fluorouracil+folinic...
BACKGROUND
The QUATTRO-II trial examined the efficacy and safety of capecitabine+oxaliplatin+irinotecan (CAPOXIRI)+bevacizumab (BEV) vs. 5-fluorouracil+folinic acid+oxaliplatin+irinotecan (FOLFOXIRI)+BEV in metastatic colorectal cancer (mCRC).
METHODS
In this phase II study (ClinicalTrials.gov: NCT04097444; jRCTs041190072), patients were randomized (1:1) to FOLFOXIRI+BEV or CAPOXIRI+BEV. The induction treatment in the FOLFOXIRI+BEV/CAPOXIRI+BEV arms was continued for 8/6 cycles (maximum 12/8 cycles if feasible), and the maintenance treatment was 5-fluorouracil/leucovorin+BEV or capecitabine+BEV at the investigators' discretion. The primary endpoint was progression-free survival (PFS), with the two arms deemed equivalent if the hazard ratio (HR) of the point estimate was 0.80 < HR < 1.25. Secondary endpoints were overall response rate (ORR), overall survival (OS), incidence of adverse events (AEs), and patient-reported outcomes.
FINDINGS
Overall, 51 and 52 patients were randomized to FOLFOXIRI+BEV and CAPOXIRI+BEV, respectively. The study met its primary endpoint; PFS at median follow-up of 23.7 months was 10.6 months (95% confidence interval [CI], 7.7-13.3) in the FOLFOXIRI+BEV arm vs. 10.9 months (95% CI, 9.3-14.3) in the CAPOXIRI+BEV arm (HR 1.114 [0.80 < HR < 1.25], p = 0.654). In the FOLFOXIRI+BEV vs. CAPOXIRI+BEV arms, the 2-year OS rate (95% CI) was 65.5% (49.5%-77.6%) vs. 74.3% (59.8%-84.2%), and the ORR (95% CI) was 76.5% (62.5%-87.2%) vs. 84.6% (71.9%-93.1%). Major (grade ≥3) AEs in the FOLFOXIRI+BEV vs. CAPOXIRI+BEV arms were neutropenia (68.6% vs. 40.4%), febrile neutropenia (9.8% vs. 11.5%), diarrhea (7.8% vs. 17.3%), and appetite loss (7.8% vs. 17.3%).
CONCLUSION
CAPOXIRI+BEV was well tolerated with reduced hematological toxicity and efficacy comparable to those of FOLFOXIRI+BEV, providing a potentially convenient first-line treatment alternative to FOLFOXIRI+BEV in patients with mCRC.
FUNDING
Chugai Pharmaceutical Co., Ltd.
PubMed: 38901425
DOI: 10.1016/j.medj.2024.05.012