Eligible Patients Research Articles

Personalized mechanical ventilation guided by ultrasound in patients with acute respiratory distress syndrome (PEGASUS): study protocol for an international randomized clinical trial

BackgroundAcute respiratory distress syndrome (ARDS) is a frequent cause of hypoxemic respiratory failure with a mortality rate of approximately 30%. Identifying ARDS subphenotypes based on “focal” or “non-focal” lung morphology has the potential to better target mechanical ventilation strategies of individual patients. However, classifying morphology through chest radiography or computed tomography is either inaccurate or impractical. Lung ultrasound (LUS) is a non-invasive bedside tool that can accurately distinguish “focal” from “non-focal” lung morphology. We hypothesize that LUS-guided personalized mechanical ventilation in ARDS patients leads to a reduction in 90-day mortality compared to conventional mechanical ventilation.MethodsThe Personalized Mechanical Ventilation Guided by UltraSound in Patients with Acute Respiratory Distress Syndrome (PEGASUS) study is an investigator-initiated, international, randomized clinical trial (RCT) that plans to enroll 538 invasively ventilated adult intensive care unit (ICU) patients with moderate to severe ARDS. Eligible patients will receive a LUS exam to classify lung morphology as “focal” or “non-focal”. Thereafter, patients will be randomized within 12 h after ARDS diagnosis to receive standard care or personalized ventilation where the ventilation strategy is adjusted to the morphology subphenotype, i.e., higher positive end-expiratory pressure (PEEP) and recruitment maneuvers for “non-focal” ARDS and lower PEEP and prone positioning for “focal” ARDS. The primary endpoint is all-cause mortality at day 90. Secondary outcomes are mortality at day 28, ventilator-free days at day 28, ICU length of stay, ICU mortality, hospital length of stay, hospital mortality, and number of complications (ventilator-associated pneumonia, pneumothorax, and need for rescue therapy). After a pilot phase of 80 patients, the correct interpretation of LUS images and correct application of the intervention within the safe limits of mechanical ventilation will be evaluated.DiscussionPEGASUS is the first RCT that compares LUS-guided personalized mechanical ventilation with conventional ventilation in invasively ventilated patients with moderate and severe ARDS. If this study demonstrates that personalized ventilation guided by LUS can improve the outcomes of ARDS patients, it has the potential to shift the existing one-size-fits-all ventilation strategy towards a more individualized approach.Trial registrationThe PEGASUS trial was registered before the inclusion of the first patient, https://clinicaltrials.gov/ (ID: NCT05492344).

Niraparib maintenance therapy using an individualised starting dose in patients with platinum-sensitive recurrent ovarian cancer (NORA): final overall survival analysis of a phase 3 randomised, placebo-controlled trial

Niraparib significantly prolonged progression-free survival versus placebo in patients with platinum-sensitive, recurrent ovarian cancer (PSROC), regardless of germline BRCA mutation (gBRCAm) status, in NORA. This analysis reports final data on overall survival (OS). This randomised, double-blind, placebo-controlled, phase 3 trial enrolled patients across 30 centres in China between 26 September 2017 and 2 February 2019 (clinicaltrials.gov, NCT03705156). Eligible patients had histologically confirmed, recurrent, (predominantly) high-grade serous epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal carcinoma (no histological restrictions for those with gBRCAm) and had received ≥2 prior lines of platinum-based chemotherapy. Patients were randomised (2:1) to receive niraparib or placebo, with stratification by gBRCAm status, time to recurrence following penultimate platinum-based chemotherapy, and response to last platinum-based chemotherapy. Following a protocol amendment, the starting dose was individualised: 200mg/day for patients with bodyweight <77kg and/or platelet count <150×103/μL at baseline and 300mg/day otherwise. OS was a secondary endpoint. Totally, 265 patients were randomised to receive niraparib (n=177) or placebo (n=88), and 249 (94.0%) received an individualised starting dose. As of 14 August 2023, median follow-up for OS was 57.9 months (IQR, 54.8-61.6). Median OS (95% CI) with niraparib versus placebo was 51.5 (41.4-58.9) versus 47.6 (33.3-not evaluable [NE]) months, with hazard ratio [HR] of 0.86 (95% CI, 0.60-1.23), in the overall population; 56.0 (36.1-NE) versus 47.6 (31.6-NE) months, with HR of 0.86 (95% CI, 0.46-1.58), in patients with gBRCAm; and 46.5 (41.0-NE) versus 46.9 (31.8-NE) months, with HR of 0.87 (95% CI, 0.56-1.35), in those without. No new safety signals were identified, and myelodysplastic syndromes/acute myeloid leukaemia occurred in three (1.7%) niraparib-treated patients. Niraparib maintenance therapy with an individualised starting dose demonstrated a favourable OS trend versus placebo in PSROC patients, regardless of gBRCAm status. Zai Lab (Shanghai) Co., Ltd; National Major Scientific and Technological Special Project for "Significant New Drugs Development" in 2018, China [grant number 2018ZX09736019].

Discontinuation of imatinib in patients with oligometastatic gastrointestinal stromal tumour who are in complete radiological remission: a prospective multicentre phase II study.

Metastatic gastrointestinal stromal tumour (GIST) is considered incurable, and life-long treatment with tyrosine kinase inhibitors is recommended. We investigated whether selected patients with metastatic GIST may remain in durable remission despite imatinib discontinuation. In this 1-group, prospective, multicentre phase II trial selected patients with oligometastatic (≤3 metastases) GIST discontinued imatinib treatment. Eligible patients had been treated with imatinib >5 years without progression and had no radiologically detectable metastases after metastasectomy, radiofrequency ablation (RFA) or complete response to imatinib. The primary endpoint was progression-free survival (PFS) 3-years after stopping imatinib. Overall survival (OS) and quality of life (QoL) were secondary endpoints. The trial closed prematurely due to slow accrual. Between January 5, 2017, and June 5, 2019, 13 patients were enrolled, of whom 12 discontinued imatinib. The median follow-up time was 55 months (range, 36 to 69) after study entry. Five (42%) of the 12 eligible patients remained progression free, and seven (58%) progressed with a median time to progression 10 months. Median PFS was 23 months and the estimated 3-year PFS 41%. Six of the seven patients who progressed restarted imatinib, and all six responded. Three-year OS was 100%, and all patients were alive at the time of the study analysis. QoL measured 5 and 11 months after discontinuation of imatinib demonstrated improvement compared to the baseline. A substantial proportion of selected patients with oligometastatic GIST treated with imatinib and metastasis surgery/RFA may remain disease-free for ≥3 years with improved QoL after stopping of imatinib.

Empagliflozin to prevent progressive adverse remodelling after myocardial infarction (EMPRESS-MI): rationale and design.

Patients with a reduced left ventricular ejection fraction (LVEF) following an acute myocardial infarction (MI) are at risk of progressive adverse cardiac remodelling that can lead to the development of heart failure and death. The early addition of a sodium-glucose cotransporter 2 (SGLT2) inhibitor to standard treatment may delay or prevent progressive adverse remodelling in these patients. EMpagliflozin to PREvent worSening of left ventricular volumes and Systolic function after Myocardial Infarction (EMPRESS-MI) is a randomized, double-blind, placebo-controlled, multi-centre trial designed to assess the effect of empagliflozin on cardiac remodelling evaluated using cardiovascular magnetic resonance (CMR) in 100 patients with left ventricular systolic dysfunction following MI. Eligible patients were those ≥12h and ≤14days following acute MI, with an LVEF <45% by CMR. Patients were randomized to empagliflozin 10mg once a day or matching placebo. The primary outcome will be change in left ventricular end-systolic volume indexed to body surface area over 24weeks from randomization. Secondary endpoints include measures of left ventricular and atrial volumes, left ventricular mass, LVEF, and circulating cardiac biomarkers. EMPRESS-MI will assess the effect of the SGLT2 inhibitor empagliflozin on cardiac remodelling in patients with left ventricular systolic dysfunction after an acute MI.

Efficacy and Safety of Surgical Resection in Elderly Patients with Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

: With increased life expectancy, the management of elderly hepatocellular carcinoma (HCC) patients became a crucial issue, yet it is still challenging due to comorbidities and high surgical risks. While surgical resection is considered as primary treatment for eligible HCC patients, systematic evidence on its outcomes in elderly patients remains scarce. In this review, we aimed to analyze the efficacy and safety outcomes of surgical resection in elderly HCC patients. : The studies included in this meta-analysis were selected from Ovid-MEDLINE, Ovid-Embase, CENTRAL, KoreaMed, KMbase, and KISS databases following a predefined protocol. Efficacy outcomes included overall survival and disease-free survival, while the safety outcomes included postoperative mortality and complications. : Patients in the elderly group (≥65 years) who underwent surgery exhibited non-inferior overall survival (hazard ratio [HR], 1.26; 95% confidence interval [CI], 0.92 to 1.74) and disease-free survival (HR, 1.03; 95% CI, 0.99 to 1.08) compared to the non-elderly group. Overall postoperative mortality exhibited no statistical difference (odds ratio [OR], 1.07; 95% CI, 0.87 to 1.31), but 30-day, 90-day, and in-hospital mortality were higher in the elderly group. The incidence of overall complications was higher in the elderly group (OR, 1.44; 95% CI, 1.22 to 1.69). Sensitivity analysis for the super elderly group (≥80 years) showed significantly higher in-hospital mortality compared to the non-super elderly group (OR, 2.51; 95% CI, 1.16 to 5.45). : The efficacy outcome of surgical resection in the elderly HCC patients was not worse than that in the non-elderly HCC patients, while in-hospital mortality and complications rates were higher. Therefore, surgical resection should be purposefully considered in the elderly population, with careful candidate selection.

“Advocates for Each Other”: The creation and evaluation of a pragmatic peer navigation program for black patients in primary care with uncontrolled hypertension

BackgroundBlack individuals in the U.S. and in our primary care clinic experience worse control of blood pressure compared to White individuals. ObjectiveTo address this inequity, our objectives were to (1) elicit from patients and community members their ideas for barriers and facilitators to blood pressure control; and (2) use their input to design and pilot a navigator program for Black patients in our clinic to improve blood pressure management. Patient involvementWe conducted three focus groups with 27 individuals and identified two main areas of need that informed the peer navigator program: (1) community-based services and (2) skill development for hypertension self-management. MethodsPeer navigators from the Black community called participants at least monthly for 6–12 months and connected them with medical and social services. Available blood pressure data was used as the primary outcome to measure change pre- to post-peer navigation program. ResultsAmong 499 eligible patients in the clinic, 53 (10.6%) enrolled in the peer navigation program. For those with baseline and follow-up blood pressure data, mean systolic blood pressure decreased from 155.9 to 142.4 mmHg after the program (change of −13.6, 95% CI −24.7 to −2.4) for the enrolled patients (N = 17) and from 139.1 to 137.1 mmHg (change of −2.5, −4.8 to 1.9) for unenrolled, comparison patients (N = 183). DiscussionThis community-informed peer navigation program to support Black patients with uncontrolled hypertension led to a 11.1 mmHg greater decrease in average systolic blood pressure for enrolled patients compared to the comparison group. However, the enrolled group started with a significantly higher systolic blood pressure at baseline with more room for improvement. While this study was conducted during the pandemic years, low uptake of this program needs to be addressed in expansion efforts. Practical valueClinic-based peer navigation for hypertension improved blood pressure control and was highly regarded by the subset of enrolled patients. Increasing uptake and sustainable funding for non-billable clinic roles remain areas of need. FundingGrant from the Pacific Hospital Preservation & Development Authority.

Pain response in single-fraction 8-Gy radiotherapy for painful non-bone-metastasis tumors: a single-center retrospective study.

The effectiveness of single-fraction 8-Gy radiotherapy for painful bone metastases has been verified in numerous randomized controlled trials. However, few reports have described the effectiveness of single-fraction 8-Gy radiotherapy in painful tumors other than bone metastases. We conducted a retrospective analysis to evaluate the pain response to single-fraction 8-Gy radiotherapy in painful non-bone-metastasis tumors. We included patients who had received single-fraction 8-Gy radiotherapy for such tumors between January 2017 and December 2022, excluding those with brain metastases, hematological tumors and those who received re-irradiation. Pain response assessment was based on the best responses documented in the medical records and conducted by two radiation oncologists. A total of 36 eligible patients were included in this study. The irradiation sites included primary lesions in eight patients, lymph node metastases in eight, muscle metastases in seven, pleural dissemination in four, skin/subcutaneous metastases in four and other sites in five. Pain response was assessed in 24 patients after radiotherapy. Pain response rate was 88% in evaluable patients; 21 of the 24 patients experienced response. The median assessment date for pain response was 37days (range: 8-156days) after radiotherapy. Re-irradiation was performed in four patients (11%). Single-fraction 8-Gy radiotherapy seemed to be a promising treatment option for painful non-bone-metastasis tumors and warrants further investigation.

Chemoradiotherapy versus surgery after neoadjuvant chemoimmunotherapy in patients with stage III NSCLC: a real-world multicenter retrospective study

PurposeThe optimal treatment after neoadjuvant chemoimmunotherapy for patients with stage III non-small cell lung cancer (NSCLC) is unclear. This study aimed at comparing the efficacy and safety of chemoradiotherapy and surgery after neoadjuvant chemoimmunotherapy in stage III NSCLC.Materials and methodsWe conducted a real-world multicenter retrospective study on patients with stage III NSCLC who received surgery or chemoradiotherapy after neoadjuvant chemoimmunotherapy between October 2018 and December 2022. Progression-free survival (PFS) and overall survival (OS) were assessed from the initiation of neoadjuvant treatment and estimated by the Kaplan‒Meier method. Univariate and multivariate Cox regression models were used to examine potential prognostic factors. One-to-one propensity score matching (PSM) was used to further minimize confounding.ResultsA total of 239 eligible patients were enrolled, with 104 (43.5%) receiving surgery and 135 (56.5%) receiving CRT. After 1:1 PSM, 1- and 2-year PFS rates in patients receiving radical surgery (rSurgery group) vs. patients receiving definitive cCRT (dCCRT group) were 80.0% vs. 79.2% and 67.2% vs. 53.1%, respectively (P = 0.774). One- and 2-year OS rates were 97.5% vs. 97.4% and 87.3% vs. 89.9%, respectively (P = 0.558). Patients in the dCCRT group had a numerically lower incidence of distant metastases compared to those in the rSurgery group (42.9% vs. 70.6%, P = 0.119). The incidence of treatment-related adverse events was similar in both groups, except that the incidence of grade 3/4 hematological toxicity was significantly higher in the dCCRT group (30.0% vs. 10.0%, P = 0.025).ConclusionFollowing neoadjuvant chemoimmunotherapy, definitive concurrent chemoradiotherapy may achieve noninferior outcomes to radical surgery in stage III NSCLC.

Ventriculoperitoneal shunting obstruction: a multicentre clinical audit for cerebrospinal fluid parameters and its prediction role.

Shunt obstruction is a type of ventriculoperitoneal shunt (VPS) failure. Whether changes in cerebrospinal fluid (CSF) parameters can influence shunt outcomes or not is debatable. In this study, we retrospectively included adult hydrocephalus patients who received VPS from 6 general hospitals in different provinces of China from November 2013 to September 2021. The inclusion criteria: Patients with hydrocephalus of all etiologies underwent shunt surgery from 6 general hospitals in different provinces of China were included in the study. The exclusion criteria: 1.Patients under the age of 18; 2.Patients who had previous shunt surgery; 3. Shunt failurefromother factors; 4.Patients died from other causes; 5. Patients with incomplete data. The CSF of shunt patients had been analyzed at the time of shunt insertion. The CSF samples were collected and analyzed when the shunt was implanted. The relationship between CSF parameters and the incidence rate of shunt obstruction in one year was analyzed. A total of 717 eligible patients from 6 hospitals were included, of whom 59(8.23%) experienced obstruction. Multivariate logistic regression analysis identified that protein level(odds ratio [OR] 1.161, 95% CI 1.005 ~ 1.341, p = 0.043), decreased glucose level(< 2.5 mmol/L)(odds ratio 3.784, 95% confidence interval 1.872 ~ 7.652, p = 0.001) and protein level increase(> 0.45 g/L) (odds ratio 3.653, 95% confidence interval 1.931 ~ 6.910, p = 0.001)were independent risk factors of shunt obstruction. This study suggested that increased protein level (> 0.45 g/L) and decreased glucose level (< 2.5 mmol/L) in CSF indicated an increased risk of shunt obstruction in a patient with hydrocephalus. Thus, shunt surgery should be more carefully considered when the CSF glucose and protein were abnormal.

Comprehensive 3-dimensional Positional and Morphological Analyses of Condyle and Glenoid Fossa in Patients with Skeletal Class II Malocclusion following Bimaxillary Orthognathic Surgery.

This study aimed to comprehensively and quantitatively characterize 3-dimensional (3D) positional and morphological changes of the condyle and glenoid fossa in patients with skeletal Class II malocclusion treated with bimaxillary orthognathic surgery. Twenty eligible patients treated at our institution from January 2016 to December 2021 with more than 12 months of postoperative follow-up were retrospectively enrolled. Radiographic data of cone-beam computed tomography (CBCT) for each patient were collected at 3 stages: 1 week preoperatively (T0), immediately after surgery (T1), and at least 12 months postoperatively (T2). Positional changes, surface and volumetric alterations of condyle, and bone remodeling in glenoid fossa were measured and compared based on voxel- and surface registrations in visual 3D methods. Most patients exhibited a tendency for condyles to shift posteriorly, laterally, superiorly, and rotated outward, downward, and forward immediately after surgery. Posterior, medial, superior movement and outward, upward, and backward rotation of condyles were observed during follow-up (T1-T2). Bone resorption frequently occurred in the posterior area of condylar surfaces, while bone remodeling was more common in the anterior region of the glenoid fossa. Reduced volume of the condyle was found in most cases, which was not associated with the amount of mandibular advancement. Overall, the condyle and its corresponding glenoid fossa remained relatively stable during the follow-up. Our results reveal positional and morphological alterations in the condyle and the glenoid fossa after bimaxillary orthognathic surgery in patients with skeletal class II malocclusion. These changes predominantly fall within the spectrum of physical adaption.

Treatment trajectories of gender incongruent Austrian youth seeking gender-affirming hormone therapy

ObjectiveThe aim of this study was to describe the treatment trajectories of Austrian children and adolescents with gender incongruence seeking gender-affirming medical care.MethodsPatients who presented with gender incongruence at the pediatric outpatient clinic for differences in sex development at a large university hospital in Austria from January 2008 to December 2022 were included in a retrospective chart review, and analyzed regarding referral numbers, patient characteristics, treatment trajectories, fertility preservation, and legal gender marker changes.ResultsOf 310 eligible patients, 230 (74.2%) were assigned female at birth (AFAB), and 80 (25.8%) were assigned male at birth (AMAB). The number of referrals increased steeply from 2008 to 2018, whereafter it stabilized at around 50 per year. At the time of initial presentation, the median age of patients was 15.6 years (IQR 14.3-16.8). AMAB individuals tended to be younger (median 14.9 years, IQR 13.9-16.8) than AFAB individuals (median 15.8 years, IQR 14.4-16.8; p= 0.012). 207 (66,8%) completed the assessment process and were eligible for gender affirming medical treatment (GAMT). Of those, 89% (186/207) commenced gender affirming hormone therapy in the pediatric outpatient clinic (79/186 received GnRHa monotherapy, 91/186 GnRHa and sex steroids, and 16/186 sex steroid monotherapy). Of the 54 AMAB individuals receiving GAMT, 6 (11.1%) completed fertility preservation prior to therapy initiation. Only 1/132 AFAB adolescents receiving GAMT completed fertility preservation. Chest masculinization surgery was performed in 22 cases (16.7%), and breast augmentation in two cases (3.7%) between the ages of 16 and 18. Changes in legal gender marker were common, with 205 individuals (66.1%) having changed their legal gender marker.ConclusionThis is the first time that treatment trajectories, fertility preservation rates, and changes of legal gender marker have been described in Austrian adolescents with gender incongruence seeking GAMT. The majority received GAMT and changed their legal gender marker, while gender affirming surgery rates were low, and utilization of fertility preservation treatment options was rare.

Stem cell therapy outcome for diabetic erectile dysfunction: A pilot analysis

Background Many males encounter the condition of erectile dysfunction (ED), particularly individuals diagnosed with type 2 diabetes mellitus (DM). Stem cell therapy is a burgeoning treatment modality being explored for individuals with erectile dysfunction in the context of type 2 DM. Nevertheless, the available body of clinical evidence supporting its efficacy remains limited. This study aims to assess the effectiveness and safety of umbilical cord-derived mesenchymal stem cell (MSC) therapy in managing erectile dysfunction (ED) resulting from type 2 DM. Methods A randomized, double-blind, placebo-controlled trial was conducted at Dr. Cipto Mangunkusumo Hospital in Indonesia from October 2020 to January 2023. A total of 26 eligible patients were randomly assigned to two groups: one receiving intracavernosal injections of MSC and the other receiving a placebo. Follow-up assessments were conducted at baseline, month one, and month three. The primary outcomes were measured using the IIEF-5 questionnaire and dorsal artery peak systolic velocity (PSV). Metabolic markers were used as secondary outcomes. Results The IIEF-5 scores for both groups showed a significant increase (p &lt; 0.001) from baseline to month three. There was no significant difference observed between the MSC and placebo groups. Moreover, no significant differences were observed in the PSV of the dorsal artery between the two groups (p&gt;0.05). There were no significant differences in metabolic markers between the groups. The incidence of mild post-injection pain was reported by only 11% of individuals, indicating a low occurrence of adverse events. Conclusions Intracavernous administration of MSC did not demonstrate superior efficacy compared to a placebo in improving metabolic or erectile function in diabetic males with erectile dysfunction. Additional research utilizing larger sample sizes and more extended follow-up periods is necessary.

Increasing the Use of Enteral Antibiotics in Hospitalized Children With Uncomplicated Infections.

Route of administration is an important component of antimicrobial stewardship. Early transition from intravenous to enteral antibiotics in hospitalized children is associated with fewer catheter-related adverse events, as well as decreased costs and length of stay. Our aim was to increase the percentage of enteral antibiotic doses for hospital medicine patients with uncomplicated common bacterial infections (community-acquired pneumonia, skin and soft tissue infection, urinary tract infection, neck infection) from 50% to 80% in 6 months. We formed a multidisciplinary team to evaluate key drivers and design plan-do-study-act cycles. Interventions included provider education, structured discussion at existing team huddles, and pocket-sized printed information. Our primary measure was the percentage of antibiotic doses given enterally to patients receiving other enteral medications. Secondary measures included antibiotic cost, number of peripheral intravenous catheters, length of stay, and 7-day readmission. We used statistical process control charts to track our measures. Over a 6-month baseline period and 12 months of improvement work, we observed 3183 antibiotic doses (888 in the baseline period, 2295 doses during improvement work). We observed an increase in the percentage of antibiotic doses given enterally per week for eligible patients from 50% to 67%. We observed decreased antibiotic costs and fewer peripheral intravenous catheters per encounter after the interventions. There was no change in length of stay or readmissions. We observed increased enteral antibiotic doses for children hospitalized with common bacterial infections. Interventions targeting culture change and communication were associated with sustained improvement.

The effects of endometrial thickness on outcomes of pregnancy following embryo transfer: A retrospective cohort.

The safety of assisted reproductive technology can be assessed by examining birth weight as an outcome measure. The objective of this study was to evaluate the effect of endometrial thickness during embryo transfer on newborn birth weight and preterm labor. We conducted a retrospective cohort study at the infertility department of a teaching hospital affiliated with a university of medical sciences. Eligible women were ≥18 years old and conceived a singleton pregnancy with embryo transfer and an endometrial thickness of ≥7 mm. None of the patients had diabetes, blood hypertension, and polycystic ovarian syndrome. We assessed maternal and newborn characteristics and perinatal pregnancy outcomes. In total, 100 eligible patients with a mean (SD) age of 32.8 (6.2) years were included. The mean endometrial thickness during embryo transfer was 9.1 (1.2) mm, and the mean birth weight was 3040.7 (565.3)g. There were no statistically significant associations between endometrial thickness and preterm labor (p=0.215) and between endometrial thickness and stillbirth or intra-uterine fetal death (p=0.880). However, after adjusting for confounding factors, the association of endometrial thickness with birth weight was statistically significant [b=124.6 (51.6), p=0.018]. Within the range of ≥7mm, endometrial thickness during embryo transfer is a predictor of newborn weight; however, it is not related to the risk of preterm labor, stillbirth, or intra-uterine fetal death.

Phase II study to determine the anti-tumor activity and safety of simlukafusp alfa (FAP-IL2v) combined with atezolizumab in esophageal cancer.

Reported here are results from the esophageal squamous cell carcinoma (SCC) cohort of a Phase II, non-comparative, basket study, evaluating the anti-tumor activity and safety of FAP-IL2v plus atezolizumab in patients with advanced/metastatic solid tumors (NCT03386721). Eligible patients had an Eastern Cooperative Oncology Group performance status of 0-1; measurable metastatic, persistent, or recurrent esophageal SCC; progression on ≥1 prior therapy; and were checkpoint inhibitor naive. Patients received FAP-IL2v 10 mg plus atezolizumab 1200 mg intravenously every 3 weeks, or FAP-IL2v weekly for 4 weeks, then every 2 weeks, plus atezolizumab 840 mg intravenously every 2 weeks. Primary endpoint was investigator-assessed objective response rate (ORR). In the response-evaluable population (N=34), best confirmed ORR was 20.6% (95% confidence interval [CI]: 10.4-36.8) with a complete response (CR) seen in one patient and partial responses (PR) in six patients. Disease control rate was 44.1% (CR=2.9%; PR=17.6%; stable disease [SD]=23.5%) and median duration of response was 10.1 months (95% CI: 5.6-26.7). Median progression-free survival was 1.9 months (95% CI: 1.8-3.7). Analysis of response by PD-L1 expression (Ventana SP263) resulted in an ORR of 26.7 % for patients with PD-L1-positive tumors (tumor area positivity [TAP] cut-off ≥1%; n=15) and 7.1% for patients with PD-L1-negative tumors (TAP cut-off <1%; n=14). Overall, the treatment combination was tolerable and adverse events were consistent with the known safety profiles of each drug. FAP-IL2v plus atezolizumab demonstrated clinical activity and was tolerable in patients with previously treated esophageal SCC.

A randomized double-blind active-controlled clinical trial on the efficacy of topical basil (Ocimum basilicum) oil in knee osteoarthritis

BackgroundBasil is a widely used herb in Persian medicine and is gaining recognition as a functional food worldwide.Aim of the studyThis trial aimed to assess the effectiveness of a traditional formulation of basil oil in comparison with diclofenac gel in treating knee osteoarthritis, considering its established anti-inflammatory, anti-nociceptive, and anti-oxidative properties.Materials and methodsOne hundred eligible patients were equally randomized to the traditional basil oil (containing sesame oil) and diclofenac gel groups. They used their respective topical treatments thrice daily for 4 weeks. Various measurements were taken at the beginning of the study, 2, and 4 weeks after starting the intervention, including the 8-m walk test, knee pain (based on visual analog scale), flexion angle of the knee joint, analgesic consumption, and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire.ResultsNo significant differences were observed between the basil oil and diclofenac gel groups in any of the measured outcomes. However, significant improvements were noted within each group for most variables.ConclusionTopical application of the traditional formulation of basil oil appears to improve clinical symptoms and certain functional indicators of knee osteoarthritis to a similar extent as diclofenac gel. This suggests that basil oil could be considered an effective management option for this condition.Clinical Trial Registration:https://irct.behdasht.gov.ir/, identifier IRCT2017081711341N7.

The effect of non-pooled multi-donor faecal microbiota transplantation for inducing clinical remission in patients with chronic pouchitis: Results from a multicentre randomised double-blinded placebo-controlled trial (MicroPouch).

To investigate if treatment with non-pooled multi-donor faecal microbiota transplantation (FMT) for four weeks was superior to placebo to induce clinical remission in patients with chronic pouchitis. The study was a randomised double-blinded placebo-controlled study with a 4-week intervention period and 12-month follow-up. Eligible patients with chronic pouchitis were recruited from five Danish hospitals. Participants were randomised to non-pooled multi-donor FMT derived from four faecal donors, or placebo. Treatment was delivered daily by enema for two weeks followed by every second day for two weeks. Disease severity was accessed at inclusion and 30-day follow-up, using the Pouchitis Disease Activity Index (PDAI); PDAI <7 was considered equivalent to clinical remission. Faecal samples from participants and donors were analysed by shotgun metagenomic sequencing. Inclusion was stopped after inclusion of 30 participants who were randomised 1:1 for treatment with FMT or placebo. There was no difference in participants achieving clinical remission between the two groups at 30-day follow-up, relative risk 1.0 (95%CI(0.55;1.81)). Treatment with FMT resulted in a clinically relevant increase in adverse events compared to placebo, incidence rate ratio 1.67 (95%CI(1.10;2.52)); no serious adverse events within either group. Faecal microbiota transplantation statistically significantly increased the similarity of participant faecal microbiome to the faecal donor microbiome at 30-days follow-up (p=0.01), which was not seen after placebo. Non-pooled multi-donor FMT was comparable to placebo in inducing clinical remission in patients with chronic pouchitis but showed a clinically relevant increase in adverse events compared to placebo.

Development and validation of a nomogram for predicting specific mortality risk: A study of competing risk model based on real endometrial cancer patients.

This study aimed to construct a competing risk prediction model for predicting specific mortality risks in endometrial cancer patients from the SEER database based on their demographic characteristics and tumor information. We collected relevant clinical data on patients with histologically confirmed endometrial cancer in the SEER database between 2010 and 2015. Univariate and multivariate competing risk models were used to analyze the risk factors for endometrial cancer-specific death, and a predictive nomogram was constructed. C-index and receiver operating characteristic curve (ROC) at different time points were used to verify the accuracy of the constructed nomogram. There were 26 109 eligible endometrial cancer patients in the training cohort and 11 189 in the validation cohort. Univariate and multivariate analyses revealed that Age, Marriage, Grade, Behav, FIGO, Size, Surgery, SurgOth, Radiation, ParaAortic_Nodes, Peritonea, N positive, DX_liver, and DX_lung were independent prognostic factors for specific mortality in endometrial cancer patients. Based on these factors, a nomogram was constructed. Internal validation showed that the nomogram had a good discriminative ability (C-index = 0.883 [95% confidence interval [CI]: 0.881-0.884]), and the 1-, 3-, and 5-year AUC values were 0.901, 0.886 and 0.874, respectively. External validation indicated similar results (C-index = 0.883 [95%CI: 0.882-0.883]), and the 1-, 3-, and 5- AUC values were 0.908, 0.885 and 0.870, respectively. We constructed a competing risk model to predict the specific mortality risk among endometrial cancer patients. This model has favorable accuracy and reliability and can provide a reference for the development and update of endometrial cancer prognostic risk assessment tools.

Real-World Clinical Burden of Newly Diagnosed Heart failure in Thai Patients.

There are limited data on the burden of newly diagnosed patients with heart failure (HF) in Thailand. Thus, this study aimed to fully understand the hospitalization, rehospitalization, mortality rates, demographics and characteristics, and quality of care in these patients. A retrospective review of all eligible adult patients' medical records from 2018 and 2019 was conducted at five hospitals.The patients were newly diagnosed with HF, as indicated by the International Classification of Diseases (ICD)-10 code "I50." Descriptive statistics was used to investigate patients' hospital burden and clinical outcome data. There were 1134 patients newly diagnosed with HF, classified as HF with reduced ejection fraction (HFrEF), HF with preserved ejection fraction (HFpEF), and HF with mildly reduced ejection fraction (HFmrEF) (44.0, 40.0, and 16.0%, respectively). The male-to-female ratios in HFmrEF and HFpEF were similar. In contrast, the proportion of men with HFrEF was greater. The mean age of all patients was 66.0years. The hospitalization rate was 1.3. Rehospitalization rates for HF-related issues were 0.1, 0.2, 0.4, and 0.5 at 30days, 60days, 180days, and 1year, respectively. The percentage of deaths from all causes among these patients was 9.8%, while the percentage of deaths from cardiovascular-related causes was 8.5%. Only a small proportion of patients received a target dose of guideline-directed medical therapy (GDMT). The study revealed that the characteristics, hospitalization rate for HF, and in-hospital mortality rate among newly diagnosed patients with HF were higher compared to similar studies conducted in Thailand and other countries. Moreover, a high quality of care is needed to improve the morbidity and mortality associated with HF in Thailand.

Digital health interventions for remote follow-up after mild traumatic brain injury

Background After a mild traumatic brain injury (mild TBI,) a significant number of patients may experience persistent symptoms and disabilities for months to years. Early identification and timely management of persistent symptoms may help to reduce the long-term impacts of mild TBIs. There is currently no formalised method for identifying patients with persistent symptoms after mild TBI once they are discharged from emergency department. Objective Assess the feasibility of a remote monitoring tool for early identification of persistent symptoms after mild TBI in the outpatient setting using digital tools. Methods Electronic surveys were sent to patients with mild TBI who presented to the emergency department at a Major Trauma Centre in England. The surveys were completed at three different timepoints (within days of injury (S1), 1 month (S2), and 3 months (S3) after injury). The indicators used to assess feasibility were engagement, number of eligible patients for follow-up evidence of need for the intervention, and consistency with the literature. Feedback was sought from participants. Results Of the 200 people invited to participate, 134 (67.0%) completed S1, 115 (57.5%) completed S2, and 95 (47.5%) completed S3. The rates of persistent symptoms ranged from 17.9%–62.6% depending on the criteria used, and we found a significant proportion of the participants experienced morbidity 1 and 3 months after injury. The electronic follow-up tool was deemed an acceptable and user-friendly method for service delivery by participants. Conclusion Using digital tools to monitor and screen mild TBI patients for persistent symptoms is feasible. This could be a scalable, cost-effective, and convenient solution which could improve access to healthcare and reduce healthcare inequalities. This could enable early identification of patients with further medical needs and facilitate timely intervention to improve the clinical workflows, patient satisfaction, and health outcomes for people with persistent morbidities after mild TBIs.