Comprehensive combined analysis of physician-initiated phase II and III clinical trials on a cultured human corneal endothelial cell product for treating bullous keratopathy.

To evaluate the efficacy and safety of a cultured human corneal endothelial cell (cHCEC) product in eyes with bullous keratopathy (BK). Combined analysis of multicenter phase II and III clinical trials. This analysis involved 15 BK eyes in the phase II trial and 12 BK eyes in the phase III trial that underwent cHCEC transplant therapy. Safety was assessed in all the cases. Efficacy was assessed in 17 cases with exclusion of the low- and medium-dose groups in the phase II trial. The primary endpoint was a corneal endothelial cell density of 1000 cells/mm2 or more at 24 weeks post-transplant, which was attained in 94.1% of the eyes (16 of 17), with a 95% CI of 71.3-99.9%. Additionally, 82.4% of the eyes (14 of 17) met the secondary endpoint of reduction in corneal thickness to less than 630 µm without corneal epithelial edema within the same time frame, with a 95% CI of 56.6-96.2%. The mean decrease in corneal thickness from baseline to 24 weeks post-transplant was -187.4 µm (95% CI, -240.2 µm to -134.5 µm). Furthermore, all the eyes exhibited improvement in best-corrected visual acuity from baseline to 24 weeks post-transplant (95% CI, 80.5-100.0%). By 24 weeks post-transplant, 88.9% of the patients (24 of 27) had experienced adverse events, which were mostly local, mild, and transient. The cHCEC product of this study reconstitutes the corneal endothelial layer with high cellular density and restores corneal thickness and improves visual acuity.

Outcomes of Patients With Early and Locally Advanced Lung Cancer: Protocol for the Italian Lung Cancer Observational Study (LUCENT).

BACKGROUND: Lung cancer, predominantly non-small cell lung cancer (NSCLC), remains a formidable challenge, necessitating an in-depth understanding of evolving treatment paradigms. The Italian Lung Cancer Observational Study (LUCENT) addresses this need by investigating the outcomes of patients with early and locally advanced lung cancer in Italy. OBJECTIVE: With a focus on real-world data and patient registries, this study aims to provide comprehensive insights into clinical, psychosocial, and economic impacts, contributing to informed decision-making in health care. METHODS: LUCENT is a prospective observational multicenter cohort study enrolling patients eligible for minimally invasive manual, robot-assisted, or traditional open surgery. The study will develop a web-based registry to collect longitudinal surgical, oncological, and socioeconomic outcome data. The primary objectives include performance assessment through the establishment of national benchmarks based on risk-adjusted outcomes and processes of care indicators. The secondary objectives encompass economic and psychosocial impact assessments of innovative technologies and treatment pathways. The multicenter design ensures a diverse and representative study population. RESULTS: The evolving landscape of NSCLC treatment necessitates a nuanced approach with consideration of the dynamic shifts in therapeutic strategies. LUCENT strives to fill existing knowledge gaps by providing a platform for collecting and analyzing real-world data, emphasizing the importance of patient-reported outcomes in enhancing the understanding of the disease. By developing a web-based registry, the study not only facilitates efficient data collection but also addresses the limitations of traditional methods, such as suboptimal response rates and costs associated with paper-and-pencil questionnaires. Recruitment will be conducted from January 01, 2024, to December 31, 2026. Follow-up will be performed for a minimum of 2 years. The study will be completed in the year 2028. CONCLUSIONS: LUCENT's potential implications are substantial. Establishing national benchmarks will enable a thorough evaluation of outcomes and care processes, guiding clinicians and policymakers in optimizing patient management. Furthermore, the study's secondary objectives, focusing on economic and psychosocial impacts, align with the contemporary emphasis on holistic cancer care. Insights gained from this study may influence treatment strategies, resource utilization, and patient well-being, thereby contributing to the ongoing refinement of lung cancer management. TRIAL REGISTRATION: ClinicalTrials.gov NCT05851755; https://clinicaltrials.gov/study/NCT05851755. ISRCTN 67197140; https://www.isrctn.com/ISRCTN67197140. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/57183.

Effect of extending the period from oral administration of 5-aminolevulinic acid hydrochloride to photodynamic diagnosis during transurethral resection for non-muscle invasive bladder cancer on diagnostic accuracy and safety: a single-arm multicenter phase III trial.

BACKGROUND: In Japan, the authorized period (2-4 h) between oral administration of 5-aminolevulinic acid hydrochloride (5-ALA) and transurethral resection for non-muscle invasive bladder cancer (NMIBC) may restrict photodynamic diagnosis (PDD) usage. Therefore, this prospective, single-arm, phase III study aimed to evaluate the diagnostic accuracy and safety of PDD at an extended administration period (4-8 h). METHODS: From January 2022 to May 2023, 161 patients with NMIBC were enrolled from eight hospitals. The primary endpoint was the blue light (BL) sensitivity of pathologically positive biopsies. The secondary endpoints were a comparison of the specificity and positive and negative prediction rates under BL and white light (WL) conditions. RESULTS: A total of 1242 specimens comprising 337 histological NMIBC specimens were analyzed. BL-sensitivity was 95.3%. Its lower limit of 95% confidence interval (92.4-97.3%) exceeded the threshold (70%) of non-inferiority to authorized usage. Sensitivity and specificity were significantly higher and lower for BL than those for WL (95.3% vs. 61.1%, P < 0.001; 52.7% vs. 95.2%, P < 0.001), respectively. The positive and negative predictive rates were significantly lower and higher for BL than those for WL (42.9% vs. 82.7%, P < 0.001; 96.8% vs. 86.8%, P < 0.001), respectively. Of the 145 patients receiving 5-ALA, 136 (93.8%) and 75 (51.7%) experienced 377 adverse events and 95 adverse reactions, respectively, most of which were grade 1 or 2. CONCLUSION: For extended period, the efficacy of PDD for NMIBC was similar to that of authorized period, in terms of higher sensitivity and lower specificity compared with WL, and the safety was acceptable.

Occurrence and predictors of laboratory abnormalities during outpatient parenteral antimicrobial therapy - A multicenter cohort study to inform laboratory test monitoring.

OBJECTIVES: Evidence on the optimal frequency of laboratory testing during outpatient parenteral antimicrobial therapy (OPAT) is lacking. Therefore, we investigated how often and when laboratory abnormalities occur during OPAT and which factors are associated with these abnormalities. METHODS: We performed a multicenter cohort study in four Dutch hospitals among adult patients receiving OPAT and collected routinely obtained laboratory test results. Incidence and incidence rates were calculated for various laboratory abnormalities. Survival analysis was performed to visualize the time to the first occurrence of laboratory abnormalities and Poisson regression analysis to compare the number of abnormalities in the first and second 30 OPAT days among patients receiving OPAT for ≥60 days. Predictors were identified using a multivariable Cox proportional hazard regression model. RESULTS: 45.1% of 1152 included patients developed laboratory abnormalities, but only 2% led to OPAT discontinuation. Hepatotoxicity was most common (33.9 events/1000 OPAT days), with a time-dependent decrease in the occurrence of the first hepatotoxic event, while hypokalemia was rare (1.7 events/1000 OPAT days). In the subgroup of patients receiving ≥60 days of OPAT, nephrotoxicity was more common in days 31-60. We observed partly toxicity-specific associations between antibiotic type, concomitant medication, baseline laboratory values, patient characteristics, and the occurrence of laboratory abnormalities. CONCLUSIONS: While laboratory abnormalities are frequently observed during OPAT, they rarely lead to discontinuation of OPAT. Specific patient, treatment and laboratory characteristics were associated with the occurrence of laboratory abnormalities. Based on our results, we recommend a more personalized laboratory monitoring policy with less blood sampling.

Development and Validation of a Computed Tomography-Based Model for Noninvasive Prediction of the T Stage in Gastric Cancer: Multicenter Retrospective Study.

BACKGROUND: As part of the TNM (tumor-node-metastasis) staging system, T staging based on tumor depth is crucial for developing treatment plans. Previous studies have constructed a deep learning model based on computed tomographic (CT) radiomic signatures to predict the number of lymph node metastases and survival in patients with resected gastric cancer (GC). However, few studies have reported the combination of deep learning and radiomics in predicting T staging in GC. OBJECTIVE: This study aimed to develop a CT-based model for automatic prediction of the T stage of GC via radiomics and deep learning. METHODS: A total of 771 GC patients from 3 centers were retrospectively enrolled and divided into training, validation, and testing cohorts. Patients with GC were classified into mild (stage T1 and T2), moderate (stage T3), and severe (stage T4) groups. Three predictive models based on the labeled CT images were constructed using the radiomics features (radiomics model), deep features (deep learning model), and a combination of both (hybrid model). RESULTS: The overall classification accuracy of the radiomics model was 64.3% in the internal testing data set. The deep learning model and hybrid model showed better performance than the radiomics model, with overall classification accuracies of 75.7% (P=.04) and 81.4% (P=.001), respectively. On the subtasks of binary classification of tumor severity, the areas under the curve of the radiomics, deep learning, and hybrid models were 0.875, 0.866, and 0.886 in the internal testing data set and 0.820, 0.818, and 0.972 in the external testing data set, respectively, for differentiating mild (stage T1~T2) from nonmild (stage T3~T4) patients, and were 0.815, 0.892, and 0.894 in the internal testing data set and 0.685, 0.808, and 0.897 in the external testing data set, respectively, for differentiating nonsevere (stage T1~T3) from severe (stage T4) patients. CONCLUSIONS: The hybrid model integrating radiomics features and deep features showed favorable performance in diagnosing the pathological stage of GC.

Optimal results through enhanced recovery: Achieving textbook outcomes with high compliance in elective liver surgery.

BACKGROUND: Existing studies suggest a positive correlation between high compliance with enhanced recovery programs (ERP) and improved outcomes. While individual outcome measures have advantages, composite benchmarks, such as textbook outcome (TO), offer a more comprehensive assessment of healthcare performance. Given the link between ERP and postoperative outcomes, this study aims to investigate the impact of ERP on TO attainment after liver surgery (LS). METHODS: A prospective multicenter cohort of patients undergoing LS and exposed to ERP from 2016 to 2022 in France was analyzed. The primary outcome was to compare the rates of TO achieved between patients with high ERP compliance (>70%) and those with low ERP compliance (<70%) after LS. RESULTS: A total of 706 patients were included in the study, and 217 (30.7%) achieved TO: 170 patients with high ERP compliance (24%) versus 47 patients (6.6%) with low ERP compliance attained TO (p < 0.001). High ERP compliance was associated to an increased likelihood of achieving TO [odds ratio (OR) = 1.49 (95% CI: 1.01, 2.24); p = 0.049], while cholangiocarcinoma [OR = 0.11 (95% CI: 0.02, 0.39); p = 0.003], high complexity LS [OR = 0.22 (95% CI: 0.13, 0.36); p < 0.001], intraoperative hypotension requiring vasopressors [OR = 0.29 (95% CI: 0.10, 0.68); p = 0.010], and post-operative ileus [OR = 0.08 (95% CI: 0.00, 0.37); p = 0.013] were negatively associated to the likelihood of achieving TO. CONCLUSIONS: Patients with high ERP compliance after LS experience elevated rates of TO, compared to those with low ERP compliance.

Parathyroid carcinoma and atypical parathyroid tumor: analysis of an Italian database.

OBJECTIVE: Atypical parathyroid tumor (aPT) and parathyroid carcinoma (PC) are extremely rare parathyroid neoplasms, accounting together for <2% of all parathyroid tumors. They often present an overlapping clinical phenotype, sharing clinical, biochemical, and some histological features. They are distinguished only by the presence of local invasion, and lymph nodes or distant metastasis, which are all absent in aPTs. To date, only few studies have compared clinical presentation and features between aPTs and PCs. Our purpose was to conduct a retrospective study on a multicenter Italian database of aPT and PC patients. DESIGN AND METHODS: We comparatively analyzed main features of aPT (n = 57) and PC (n = 74) patients collected at 15 major endocrinology and endocrine surgery centers in Italy. RESULTS AND CONCLUSIONS: Atypical parathyroid tumors and PCs showed no significant differences in many clinical features and presented similar values of elevated parathyroid hormone and total serum calcium. Renal complications, namely nephrolithiasis and nephrocalcinosis, appeared to be more common in PC, with a significantly higher rate of renal colic, regardless of total serum calcium levels and 24-h calciuria. Parathyroid carcinomas showed significantly higher postoperative disease persistence and recurrence rates, presumably due to an uncomplete resection of the primary tumor in 23.5% of cases and/or presence of unremoved active metastasis, but they had similar disease-free mean time after surgery than aPT. To deepen the study of malignant parathyroid tumors, the institution of a novel Italian retro-prospective multicenter registry of aPTs and PCs is currently ongoing, and a dedicated PC European registry has been recently activated.

Forced randomization: the what, why, and how.

BACKGROUND: When running a randomized controlled trial (RCT), a clinical site may face a situation when an eligible trial participant is to be randomized to the treatment that is not available at the site. In this case, there are two options: not to enroll the participant, or, without disclosing to the site, allocate the participant to a treatment arm with drug available at the site using a built-in feature of the interactive response technology (IRT). In the latter case, one has employed a "forced randomization" (FR). There seems to be an industry-wide consensus that using FR can be acceptable in confirmatory trials provided there are "not too many" instances of forcing. A better understanding of statistical properties of FR is warranted. METHODS: We described four different IRT configurations with or without FR and illustrated them using a simple example. We discussed potential merits of FR and outlined some relevant theoretical risks and risk mitigation strategies. We performed a search using Cortellis Regulatory Intelligence database (IDRAC) ( www.cortellis.com ) to understand the prevalence of FR in clinical trial practice. We also proposed a structured template for development and evaluation of randomization designs featuring FR and showcased an application of this template for a hypothetical multi-center 1:1 RCT under three experimental settings ("base case", "slower recruitment", and "faster recruitment") to explore the effect of four different IRT configurations in combination with three different drug supply/re-supply strategies on some important operating characteristics of the trial. We also supplied the Julia code that can be used to reproduce our simulation results and generate additional results under user-specified experimental scenarios. RESULTS: FR can eliminate refusals to randomize patients, which can cause frustration for patients and study site personnel, improve the study logistics, drug supply management, cost-efficiency, and recruitment time. Nevertheless, FR carries some potential risks that should be reviewed at the study planning stage and, ideally, prospectively addressed through risk mitigation planning. The Cortellis search identified only 9 submissions that have reported the use of FR; typically, the FR option was documented in IRT specifications. Our simulation evidence showed that under the considered realistic experimental settings, the percentage of FR is expected to be low. When FR with backfilling was used in combination with high re-supply strategy, the final treatment imbalance was negligibly small, the proportion of patients not randomized due to the lack of drug supply was close to zero, and the time to complete recruitment was shortened compared to the case when FR was not allowed. The drug overage was primarily determined by the intensity of the re-supply strategy and to a smaller extent by the presence or absence of the FR feature in IRT. CONCLUSION: FR with a carefully chosen drug supply/re-supply strategy can result in quantifiable improvements in the patients' and site personnel experience, trial logistics and efficiency while preventing an undesirable refusal to randomize a patient and a consequential unblinding at the site. FR is a useful design feature of multi-center RCTs provided it is properly planned for and carefully implemented.

Effectiveness of ulinastatin in critical care patients in real world: a retrospective multi-center study.

OBJECTIVES: Ulinastatin has been applied in various diseases associated with inflammation, but its effectiveness lacks real-world evidence. We aimed to evaluate the effectiveness of ulinastatin based on a real-world database in the intensive care unit (ICU) patients. METHODS: This was a retrospective cohort study. ICU patient data from multi-centers in China were collected. Propensity score matching (PSM) was applied. The effectiveness of ulinastatin was evaluated by mortality, length of stay in the ICU and mechanical ventilation duration. Kaplan-Meier method was used to estimate the hazard ratio and plot the survival curve. RESULTS: A total of 2036 patients were analyzed after PSM. Mortality was significantly lower in the ulinastatin group than in the non-ulinastatin group (hazard ratio for death: 0.77; 95% confidence interval: 0.62-0.96; p = 0.018). Ulinastatin significantly reduced mortality at 28 days (10.0% vs. 13.6%), 60 days (13.9% vs. 18.2%) and 90 days (14.7% vs. 18.5%), length of stay in the ICU (median 8.0 d vs. 13.0 d), and mechanical ventilation duration (median 24.0 h vs. 25.0 h; p < 0.05). CONCLUSIONS: Ulinastatin was beneficial for patients in the ICU, mainly by reducing mortality, length of ICU stay, and mechanical ventilation duration. This study provides evidence of the clinical effectiveness of ulinastatin.

Bicanalicular stent versus mono-canalicular stent for post-oncological lacrimal duct reconstruction: A retrospective cohort study.

BACKGROUND: Bicanalicular and mono-canalicular stent intubations were developed for post-oncological lacrimal duct reconstruction; however, comparative analysis between the two surgical modalities is lacking. This study aimed to compare the surgical outcomes between the two types of stents at a single institution. MATERIALS AND METHODS: Briefly, 75 eyes of 75 patients who underwent lacrimal reconstruction combined with lacrimal stent intubation were enrolled in this study and were divided into bicanalicular stent intubation and mono-canalicular stent intubation groups. The clinical characteristics, follow-up, and prognosis were compared between the two groups. RESULTS: Bicanalicular and mono-canalicular stent intubations were performed in 36 eyes (36 patients; Group A) and 39 eyes (39 patients; Group B), respectively. The difference in stent duration between Groups A and B was statistically significant. Three eyes in Group A and one eye in Group B experienced postoperative stent prolapse. Two eyes in Group B showed punctum stenosis and one eye had punctal ectropion. Seven eyes in Group A had canalicular slitting. There were no statistically significant differences in the mean preoperative Munk scores between the two groups. There were no statistically significant differences in the mean Munk scores and mean VAS scores at 1 week postoperatively, before stent removal, and 3 months after stent removal between the two groups. CONCLUSION: Bicanalicular and mono-canalicular stent intubations were equally effective in ensuring lacrimal duct patency and in preventing postoperative epiphora. Appropriate cases and stent selection can reduce the incidence of postoperative complications.

Clinical evaluation of direct composite versus zirconia resin-bonded fixed dental prostheses for a single missing anterior tooth: a short-term multicenter retrospective study.

OBJECTIVES: This study aimed to compare the outcome of a simplified direct composite resin-bonded fixed dental prostheses without reinforcing fibers (CR-RBFDP) and resin-bonded fixed dental prostheses using zirconia (Zr-RBFDP). METHODS: The clinical records of five private practice dental clinics and one university hospital were analyzed. Failure was defined as a RBFDP that was removed or remade for any reason. Survival analyses were performed using log-rank tests. RESULTS: A total of 45 patients (CR-RBFDP, n = 17; Zr-RBFDP, n = 28) were followed up for 3 years. Among the CR-RBFDP cases, 1 case of framework fracture and 2 cases of discoloration occurred, whereas among the Zr-RBFDP cases, 1 case of debonding occurred. The mean duration of observation was 21.9 months. The 3-year survival rate was 92.3% for CR-RBFDP and 91.7% for Zr-RBFDP. Log-rank test showed no significant difference (p = 0.78). CONCLUSIONS: Within the limitations of this short-term retrospective study, the survival rate of CR-RBFDP was not significantly different from that of Zr-RBFDP. Contrary to concerns regarding material strength, CR-RBFDP showed reliable results. This direct composite restoration has the advantages of being less invasive and being completed in a single visit. CLINICAL SIGNIFICANCE: Despite differences in material strength, CR-RBFDPs without fiber reinforcement showed reliable short-term clinical results. This direct composite restoration has the advantage of being less invasive and can be restored in a single visit.

Improvement of survival outcomes of cholangiocarcinoma by ultrasonography surveillance: Multicenter retrospective cohorts.

Background: Most cholangiocarcinoma (CCA) patients present with late stage of disease because of the difficulty to diagnosis at an early stage, resulting in poor survival of CCA patients. The Cholangiocarcinoma Screening and Care Program showed that ultrasound screening was an effective tool for detecting early stage CCA. This study aims to evaluate the survival outcome of patients diagnosed by ultrasound screening (US) compared to walk-in symptomatic patients. Methods: The retrospective clinical data and medical records for this study were accessed in June 30, 2021. 5-year survival rates (5-YSR) and median survival time (MST) of CCA were calculated using the Kaplan-Meier method. Multivariate analyses were performed for significant factors from univariate analyses. Results: A total of 711 histologically proven CCA cases were examined including ultrasound screening and walk-in groups. The screening group having 5-YSR was 53.9 %, and MST was of 67.2 months, while walk-in group, the 5-YSR was 21.9 % and MST was 15.6 months (p < 0.001). In addition, multivariate analyses revealed that screening program was an independent factor to predict a good outcome of CCA patients when compared with walk-in group (p = 0.014). Conclusion: US is an effective tool for detecting early stage CCA leading to improve clinical outcome of CCA patients. Practically, US should be considered as a first tool for screening CCA in risk populations.

Dedifferentiated liposarcoma of the extremities: a Korean multi-center study of 107 cases.

BACKGROUND: Dedifferentiated liposarcoma of the extremities (DDL-E) is rare in comparison to that of the retroperitoneum. Its clinical features and surgical principle for resection margins at the dedifferentiated and the well-differentiated components are yet to be elucidated. METHODS: This retrospective multi-center study examined patients diagnosed with DDL-E from August 2004 to May 2023 at 5 sarcoma centers. Clinical features, oncologic outcomes, and prognostic factors were analyzed. RESULTS: A total of 107 patients were reviewed. The 5-year local recurrence free survival (LRFS), metastasis-free survival (MFS) and disease specific survival (DSS) were 84.7%, 78.6%, and 87.8%, respectively. Other primary malignancies and extrapulmonary metastasis were observed in 27 and 4 patients, respectively. The independent risk factor for local recurrence was R1/2 margin at the dedifferentiated component of the tumor. Metastasis was associated with tumor size in univariate analysis. The independent risk factor for DSS was tumor grade. Previous unplanned excision, de novo presentation, tumor depth, absence of the well-differentiated component, infiltrative border, R1/2 margin at the well-differentiated component were not associated with oncologic outcomes. CONCLUSIONS: This is the largest study examining DDL-E to-date. Localized DDL-E has low potential for metastasis and carries an excellent prognosis. Other primary malignancy and extrapulmonary metastasis are more frequent in DDL-E, thus close monitoring of other sites during follow-up is recommended. While wide resection margin is the standard surgical approach for DDL-E, further investigation into moderated wide resection margin at the well-differentiated component is warranted.

Development of a predictive model for patients with bone metastases referred to palliative radiotherapy: Secondary analysis of a multicenter study (the PRAIS trial).

BACKGROUND: The decision to administer palliative radiotherapy (RT) to patients with bone metastases (BMs), as well as the selection of treatment protocols (dose, fractionation), requires an accurate assessment of survival expectancy. In this study, we aimed to develop three predictive models (PMs) to estimate short-, intermediate-, and long-term overall survival (OS) for patients in this clinical setting. MATERIALS AND METHODS: This study constitutes a sub-analysis of the PRAIS trial, a longitudinal observational study collecting data from patients referred to participating centers to receive palliative RT for cancer-induced bone pain. Our analysis encompassed 567 patients from the PRAIS trial database. The primary objectives were to ascertain the correlation between clinical and laboratory parameters with the OS rates at three distinct time points (short: 3 weeks; intermediate: 24 weeks; prolonged: 52 weeks) and to construct PMs for prognosis. We employed machine learning techniques, comprising the following steps: (i) identification of reliable prognostic variables and training; (ii) validation and testing of the model using the selected variables. The selection of variables was accomplished using the LASSO method (Least Absolute Shrinkage and Selection Operator). The model performance was assessed using receiver operator characteristic curves (ROC) and the area under the curve (AUC). RESULTS: Our analysis demonstrated a significant impact of clinical parameters (primary tumor site, presence of non-bone metastases, steroids and opioid intake, food intake, and body mass index) and laboratory parameters (interleukin 8 [IL-8], chloride levels, C-reactive protein, white blood cell count, and lymphocyte count) on OS. Notably, different factors were associated with the different times for OS with only IL-8 included both in the PMs for short- and long-term OS. The AUC values for ROC curves for 3-week, 24-week, and 52-week OS were 0.901, 0.767, and 0.806, respectively. CONCLUSIONS: We successfully developed three PMs for OS based on easily accessible clinical and laboratory parameters for patients referred to palliative RT for painful BMs. While our findings are promising, it is important to recognize that this was an exploratory trial. The implementation of these tools into clinical practice warrants further investigation and confirmation through subsequent studies with separate databases.

The Efficacy of Glecaprevir/Pibrentasvir in Chronic Hepatitis C Patients and the Impact of the COVID-19 Pandemic: Multicenter Real-Life Data.

Objective: This study aimed to demonstrate the real-life efficacy and safety of glecaprevir /pibrentasvir in the treatment of chronic hepatitis C, as well as to identify the problems caused by the COVID-19 pandemic in the follow-up and treatment of patients. Materials and Methods: The study was conducted retrospectively with the participation of researchers from universities or training and research hospitals. It included patients with chronic hepatitis C who were over 18 years of age, treatment-naïve or treatment-experienced, had detectable HCV RNA and were receiving glecaprevir/pibrentasvir treatment. Results: Only 188 of the 385 patients who participated in the study came to the follow-up visit 12 weeks after treatment, and all of them had a sustained virological response. It was thought that a significant portion of the 177 patients who did not come to the follow-up visit at 12 weeks after treatment refrained from coming to the hospital due to the COVID-19 pandemic. None of the patients who attended the follow-up visits required treatment discontinuation due to adverse events. Conclusion: Glecaprevir/pibrentasvir is a highly effective and relatively safe drug in the treatment of chronic hepatitis C. The COVID-19 pandemic has negatively affected the follow-up and treatment processes of patients. New measures are needed for the follow-up and treatment of patients with chronic hepatitis C during pandemics.

Healthy Change Intervention: A Cluster RCT in Preschooler Mothers in Mexico and the United States.

OBJECTIVE: To assess effects of Healthy Change intervention on maternal perception of her child's body weight (MPCW), maternal feeding style, and obesogenic home environment. METHODS: A randomized control trial was conducted, consisting of two arms: the intervention group received the Healthy Change program, and the control group received the Hygiene and Accident Prevention program. A total of 356 mother-preschool child dyads participated, 182 in the intervention group and 174 in the control group, residing in Mexico and the United States. Data were collected at baseline and after the program through self-administered questionnaires completed by mothers and child anthropometric measurements. RESULTS: Although no significant between-group difference in pre- and post-intervention change of MPCW was found, sub-analyses revealed that a higher proportion of mothers in the intervention group accurately perceived their child's body weight at the study endpoint using categorical (67% vs. 57.1%, p < 0.005) and visual scales (48.9% vs. 41.8%, p < 0.015). Additionally, more mothers of overweight children in the intervention group accurately perceived their children's overweight and obese status compared to those in the control group (29.8% vs. 10.3%, X2 = 4.26, df = 1, p < 0.039). The intervention group also displayed a higher proportion of mothers with authoritative feeding style (26.4% vs. 16.5%, p < 0.036) and significantly higher family nutrition and physical activity scores (29.1 vs. 28.0, p < 0.000) at the study endpoint. CONCLUSIONS FOR PRACTICE: Healthy Change Intervention led to improved accuracy of MPCW, a shift toward maternal authoritative feeding styles, and positive changes in obesogenic home environments.

Efficacy and safety of linaclotide in treatment-resistant chronic constipation: A multicenter, open-label study.

BACKGROUND: This study aimed to evaluate the efficacy and safety of linaclotide in patients with chronic constipation (CC) or irritable bowel syndrome with constipation (IBS-C) who did not respond to treatment with magnesium oxide (MgO). METHODS: This study was designed as a multicenter, open-label, single-arm, exploratory study. Patients with CC or IBS-C who took MgO and those meeting the medication initiation criteria were administered linaclotide at a daily dosage of 500 µg for 12 weeks. The primary endpoint was a change in the Japanese version of the Patient Assessment of Constipation Quality of Life (JPAC-QOL) score from baseline, which was evaluated by using a paired t-test. KEY RESULTS: The patients' mean age (± standard deviation) was 67.6 ± 13.82 years. The full analysis set included 61 patients. The JPAC-QOL total score was 1.60 at baseline and 0.70 at 12 weeks, with a significant mean change of -0.89 ± 0.721 (p < 0.001). Several secondary endpoints also showed improvement. The frequency of spontaneous bowel movement (SBM) and complete SBM increased by 2.70 ± 7.254 (p < 0.01) and 2.81 ± 5.254 times, respectively (p < 0.001). The Bristol Stool Form Scale, abdominal bloating severity, and straining severity scores improved by 1.33 ± 1.274 (p < 0.001), -0.16 ± 0.563 (p < 0.05), and -0.46 ± 0.795 (p < 0.001) points, respectively. The safety analysis set included 65 patients, 7 of whom had diarrhea, which improved with dose reduction and drug withdrawal. CONCLUSION & INFERENCES: The study was conducted in an older adult population, similar to real clinical practice. Linaclotide may be an option for treating CC that shows an inadequate response to conventional therapy.

Transoral laser microsurgery for supraglottic carcinomas: results of a prospective multicenter trial (SUPRATOL).

Background: A limited number of single institutions have published retrospective cohort studies on transoral laser microsurgery for supraglottic laryngectomy (TLM-SGL). These studies have shown that the oncologic outcomes of TLM-SGL are comparable to those of open SGL. However, there is limited information available regarding swallowing rehabilitation and quality of life (QoL). Patients and methods: SUPRATOL is a prospective, multicenter trial assessing the functional outcomes of TLM-SGL +/- adjuvant radio-(chemo)-therapy. The primary endpoint was aspiration-free swallowing at 12 months, as established using fibreoptic endoscopic evaluation of swallowing (FEES) and defined as a grade < 6 on the penetration-aspiration scale. Secondary endpoints were swallowing- and voice-related QoL, the prevalence of temporary and permanent tracheostomy and percutaneous gastrostomy, local control, laryngectomy-free survival, overall survival, and disease-free survival, as well as the influence of treatment centers on outcomes. Results: From April 2015 to February 2018, 102 patients were recruited from 26 German Otorhinolaryngology (ORL) hospitals. All patients had TLM-SGL and 96.1% underwent uni- or bilateral, mostly selective neck dissection. To 47.0% of patients, adjuvant radio-(chemo)-therapy (R(C)T) was administered. The median follow-up period was 24.1 months. At 12-month follow-up, completed by 84.3% of patients, 98.2%, 95.5%, and 98.8% were free of aspiration when tested with saliva, liquid, or pulp. Adjuvant R(C)T, pT category, and type of resection had no significant influence on swallowing rehabilitation. A total of 40.2% of patients had been tracheotomized, and in 46.1% of patients, a PEG tube was inserted. At the 24-month follow-up, 5.3% of patients still required a tracheostomy, and 8.0% continued to use a percutaneous endoscopic gastrostomy (PEG) tube. Deterioration of swallowing- and voice-related QoL was observed immediately after treatment, but patients recovered, and baseline values were reached again. The Kaplan-Meier 2-year rates for local control, laryngectomy-free survival, overall survival, and disease-free survival were 88%, 92%, 93%, and 82%, respectively. Conclusions: Our prospective multicenter trial shows that, at 12 months post-TLM-SGL +/- R(C)T, 95.5%-98.8% of patients achieved aspiration-free swallowing. Morbidity was higher than previously reported. The rates of permanent tracheostomy and gastrostomy tube placement correspond to previous cohort studies. The 2-year oncologic outcomes are within the reported range. Clinical trial registration: https://drks.de/search/en/trial/DRKS00004641, identifier (DRKS00004641).

Study Protocol and Mission for the Tohoku Registry of Acute Aortic Dissection (TRAD).

Background: Acute aortic dissection (AAD) is a life-threatening condition that imposes a significant socioeconomic burden on society. The Tohoku Registry of Acute Aortic Dissection (TRAD) is a collaboration of 13 tertiary referral hospitals in the Tohoku region of Japan designed to investigate all aspects of AAD treatment in this district, and to address significant clinical questions to help understand its dynamic pathology and develop optimal strategies for treating AAD. Methods and Results: Comprehensive cases developing type A and type B AAD, including those with prehospital cardiopulmonary arrest transported to TRAD centers, over 5 years from 2017 to 2022 are registered. The TRAD dataset encompasses prehospital information, diagnostic imaging findings, treatment modalities, and outcomes for each case. After discharge, patients will be followed up for 10 years for survival, aortic events and inspection data. Conclusions: We believe that this multicenter registry of AAD analyses will clarify the current short-term outcomes of recent surgical, endovascular, and medical treatments in the Tohoku region, and provide insights into the long-term outcomes of different treatment modalities to achieve extended life expectancy in reasonably good health.