Multicenter Pilot Study Research Articles

Wearable sensor-based performance status assessment in cancer: A pilot multicenter study from the Alliance for Clinical Trials in Oncology (A19_Pilot2).

Clinical performance status is designed to be a measure of overall health, reflecting a patient's physiological reserve and ability to tolerate various forms of therapy. Currently, it is measured by a combination of subjective clinician assessment and patient-reported exercise tolerance in the context of daily living activities. In this study, we assess the feasibility of combining objective data sources and patient-generated health data (PGHD) to improve the accuracy of performance status assessment during routine cancer care. Patients undergoing routine chemotherapy for solid tumors, routine chemotherapy for hematologic malignancies, or hematopoietic stem cell transplant (HCT) at one of four sites in a cancer clinical trials cooperative group were consented to a six-week prospective observational clinical trial (NCT02786628). Baseline data acquisition included cardiopulmonary exercise testing (CPET) and a six-minute walk test (6MWT). Weekly PGHD included patient-reported physical function and symptom burden. Continuous data capture included use of a Fitbit Charge HR (sensor). Baseline CPET and 6MWT could only be obtained in 68% of study patients, suggesting low feasibility during routine cancer treatment. In contrast, 84% of patients had usable fitness tracker data, 93% completed baseline patient-reported surveys, and overall, 73% of patients had overlapping sensor and survey data that could be used for modeling. A linear model with repeated measures was constructed to predict the patient-reported physical function. Sensor-derived daily activity, sensor-derived median heart rate, and patient-reported symptom burden emerged as strong predictors of physical function (marginal R2 0.429-0.433, conditional R2 0.816-0.822). Trial Registration: Clinicaltrials.gov Id NCT02786628.

Gestalt clinical severity score (GCSS) as a predictor of patient severity of illness or injury

ObjectiveTo determine if clinical judgement is accurate to predict the severity of injury or illness, and can be used at patient arrival when other formal scoring systems are not yet available. DesignA multicenter pilot study using a prospective observational convenience sample of patients arriving by EMS to the emergency department (ED) or Trauma Center. SettingTwo urban, Level 1 trauma centers at academic tertiary care hospitals. PatientsMedical and trauma patients age 18 and older transported by EMS (N = 216). Exclusion criteria (prior to arrival): intubation, assisted ventilation (BVM or NPPV), CPR in progress, prisoners, or previously present motor or speech deficits. MeasurementsCompletion of a novel 15-point scale of Verbal, Motor, and Facial Expression within 1–2 min of arrival by a clinician outside of the treatment team. Primary endpoint was the immediate disposition from the ED or Trauma Center: Home, Brief Observation (<24 h), Admission to Floor, ICU (OR and IR as surrogates since these patients ultimately go to the ICU), or Morgue. ResultsUnivariate analysis revealed a strong, positive monotonic correlation between GCSS and disposition (Rho = 0.693, p < .0001). Multivariable logistic regression revealed the “best” model included GCSS and age (group 18–44 years old versus all the other age groups) (p < .0001). There was a 156% increase in the odds of being discharged home (versus being admitted) for a one-unit increase in GCSS (OR = 2.56, 95% CI 1.94, 3.37). ConclusionsPhysicians can make accurate predictions of severity of injury and illness using a gestalt method and the scoring system we have developed as patient disposition correlates well with GCSS score. GCSS is most accurate with the 18–44 age group.

Wearable sensor-based performance status assessment in cancer: A pilot multicenter study from the Alliance for Clinical Trials in Oncology (A19_Pilot2)

Wearable sensor-based performance status assessment in cancer: A pilot multicenter study from the Alliance for Clinical Trials in Oncology (A19_Pilot2)

Epidemiology of Digestive Surgical Emergencies in a Sub-Saharan African Country: A Multicentre Pilot Study Protocol.

Digestive surgical emergencies remains one of the main general surgery activities. Despite the associated mortality rate in low income countries, epidemiologic data about this subject is rare and multicenter studies are even more. We aimed to study an epidemiology of digestive surgical emergencies in Senegal by multicenter protocol. it will a prospective multicenter pilot study from May to July 2022. The patients were from General surgery departments of these teaching hospital in Senegal: Dakar Principal Hospital, Aristide le Dantec Hospital, Dalal Jamm hospital and Saint-Louis Regional Hospital. The Schwartz formula was used. We used a proportion of abdominal surgical emergency of 20%. We had a sample size of 246 patients. this research protocol will be submitted to Ethics committee of four hospital that included. The results of this study can help to get better the management of our digestives emergencies and at the same time improve mortality rate. Digestive surgical emergencies is a public health issueBecause of high mortality rate in poorest countries, epidemiological data in Senegal must be knownThese information can help to lower associated mortality.

Multicenter experience of using Fortelyzin during staged reperfusion therapy of acute ischemic stroke in anterior circulation

To evaluate the safety and efficacy of Fortelyzin in the performance of staged reperfusion therapy for acute ischemic stroke (intravenous thrombolytic therapy plus mechanical thrombectomy) in anterior circulation within the FORTA RF multicenter pilot study. The study included 72 patients with acute ischemic stroke in anterior circulation, who underwent staged reperfusion therapy in four vascular centers of the Russian Federation from December 2019 to January 2023. The mean time from illness onset to hospitalization was 94.5 minutes in the Fortelyzin group and 97.2 min in the Actilyse group (p=0.78). The time from the moment of hospitalization to the admission of the patient to the X-ray operating room was significantly lower in the Fortelyzin group (p=0.002). The incidence of symptomatic hemorrhagic transformations in the Fortelyzin group was 6%, in the Actilyse group - 8% (p=0.75). A favorable functional outcome in the first group was observed in 47% of patients, in the control group in 42% (p=0.66). Mortality in both groups did not differ significantly and amounted to 22% and 25%, respectively. The first results of the FORTA RF multicenter study demonstrate the safety and efficacy of Fortelyzin in staged reperfusion therapy compared to Actilyse.

Sofosbuvir plus velpatasvir for 8 weeks in patients with acute hepatitis C: The HepNet acute HCV-V study

EASL guidelines recommend 8 weeks of treatment with sofosbuvir plus velpatasvir (SOF/VEL) for the treatment of acute or recently acquired HCV infection, but only 6- and 12-week data are available. Therefore, the aim of this study was to evaluate the safety and efficacy of a shortened 8-week SOF/VEL treatment for acute HCV monoinfection. In this investigator-initiated, prospective, multicentre, single-arm study, we recruited 20 adult patients with acute HCV monoinfection from nine centers in Germany. Patients received SOF/VEL (400/100mg) as a fixed-dose combination tablet once daily for 8 weeks. The primary efficacy endpoint was the proportion of patients with sustained virological response 12 weeks after the end of treatment (SVR12). The median HCV RNA viral load at baseline was 104,307 IU/ml; the distribution of HCV genotypes was as follows: GT1a/1b/2/3/4: n= 12/1/1/3/3. Thirteen (65%) of the 20 patients were taking medication for HIV pre-exposure prophylaxis. SVR12 was achieved in all patients who complied with the study protocol (n= 18/18 [100%], per protocol analysis), but the primary endpoint was not met in the intention-to-treat analysis (n= 18/20 [90%]) because two patients were lost to follow-up. One serious adverse event (unrelated to study drug) occurred during 12 weeks of post-treatment follow-up. The 8-week treatment with SOF/VEL was well tolerated and highly effective in all adherent patients with acute HCV monoinfection. Early treatment of hepatitis C might effectively prevent the spread of HCV in high-risk groups. NCT03818308. The HepNet acute HCV-V study (NCT03818308), an investigator-initiated, single-arm, multicenter pilot study, demonstrates the efficacy and safety of 8 weeks of daily treatment with the fixed-dose combination sofosbuvir/velpatasvir (400/100mg) in patients with acute hepatitis C virus (HCV) infection. All patients who completed therapy and were followed-up achieved sustained virologic response. Thus, early treatment with SOF/VEL which might effectively prevent the spread of HCV in high-risk groups can be recommended for patients with acute HCV monoinfection.

LEAP Pilot: Low Molecular Weight Heparin Vs. Aspirin Postpartum

Background Expert opinion from the American Society for Hematology (ASH), the Royal College of Obstetricians and Gynecologists, UK, as well as the 'Society of Obstetricians and Gynecologists of Canada guidelines recommend a minimum of 6 weeks of prophylactic LMWH for patients with a history of venous thromboembolism (VTE) or high-risk thrombophilia. There are no randomized controlled trials (RCTs) determining the optimal duration of anticoagulation postpartum. A 2014 Cochrane review concluded that there is insufficient evidence on which to base thromboprophylaxis in the pregnancy postpartum setting, and high-quality randomized trials are warranted. Clinical trials and meta-analyses have suggested that ASA administered daily post-operatively may be non-inferior to LMWH for VTE prophylaxis; (RR 0.76; 95% CI, 0.37- 1.56 in one study), with a similar safety profile. Furthermore, in 2018 Anderson et al. demonstrated clinical safety and non-inferiority of a combination of 5 days of rivaroxaban followed by 81mg of ASA for 30 days after total hip arthroplasty and 9 days after total knee arthroplasty. The principal question to be addressed in a large definitive randomized controlled trial (RCT) is whether a combination of prophylactic LMWH for 3 weeks followed by low-dose ASA for the following 3 weeks is non-inferior to the standard of care of prophylactic LMWH for 6 weeks postpartum. This single-center pilot RCT addresses enrollment, adherence and feasibility required prior to conducting a definitive trial. Study Design and Methods Inclusion criteria: 1) Personal history of VTE prior to pregnancy and not prescribed therapeutic anticoagulation 2) Family history of VTE and antithrombin deficiency, protein C or protein S deficiency 3) Combined thrombophilia or homozygous for factor V Leiden mutation or prothrombin gene mutation, regardless of family history. Sample size: 50 patients, 25 patients treated according to each strategy. Primary outcomes: 1) Enrollment/consent rate 2) Adherence to study protocol 3) Loss to follow-up/missing data. Secondary outcomes: 1) VTE rate 2) Bleeding rate three months following delivery 3) Quality of life assessment (QoL) (Duke Anticoagulation Satisfaction Scale). Results The enrollment rate was 69.2%, with 18 of 26 patients agreeing to participate. Of the 18 recruited, one was randomized in error, one had an early pregnancy loss, and one developed a superficial vein thrombosis antenatally due to non-compliance with antepartum anticoagulation, leaving 15 patients satisfying inclusion criteria. 9 patients have completed their 3-month postpartum follow-up, with no patients lost to follow-up. The adherence to treatment at 3 weeks was 96.4% and 94.0% in Group A (LMWH and ASA) and B (LMWH), respectively (p=0.7). At 6 weeks postpartum, there was a trend toward greater treatment compliance in Group A vs Group B (98.2 vs 94.1%); however, this was not statistically significant (p=0.52). With regards to secondary outcomes, there was no VTE documented in either treatment group. One patient in each group reported mild gingival bleeding. No other bleeding events were reported. The QoL assessment score in Group A improved by 56% following the change from LMWH to ASA (39.5 to 16.8), whilst it deteriorated in Group B by 2% (24.5 vs 25.2). At 6 weeks postpartum, the QoL score improved by 33.3% in Group A vs Group B (P=0.01). Conclusion Our data shows promising enrollment, adherence, loss to follow-up and feasibility of our ongoing pilot trial. The results of this study will be used to design first a multicenter pilot study then a large definitive multicentered trial. Demonstration of non-inferiority of ASA and LMWH to LMWH will lead to a shorter course of LMWH postpartum, potentially reducing bleeding risk, need for subcutaneous injections, as well as cost, while improving quality of life. If the definitive trial does not show non-inferiority, the results will provide evidence that six weeks of postnatal thromboprophylaxis with LMWH is warranted.

Brentuximab Vedotin Combined with Chemotherapy in Newly Diagnosed, Early-Stage, Unfavorable-Risk Hodgkin Lymphoma: Extended Follow-up with Evaluation of Baseline Metabolic Tumor Volume and PET2

INTRODUCTION: While the majority of patients with early-stage (ES), bulky Hodgkin lymphoma (HL) can be cured with modern approaches, approximately 15% of patients with bulky HL relapse. Improving upfront approaches while minimizing long-term adverse effects remains integral. We previously reported the results of a multicenter pilot study of 4 cycles of brentuximab vedotin (BV) and doxorubicin, vinblastine, and dacarbazine (AVD) followed by 1 of 4 approaches if positron emission tomography (PET)-4 negative. The treatment program was highly active and well-tolerated. We now present extended results and prognostic evaluation of baseline metabolic tumor volume (MTV) and PET2 results. METHODS: Full methodology has been published (Kumar et al., J. Clin Oncol. 2021). Briefly, patients with untreated HL were enrolled into 1 of 4 sequential cohorts. In cohort 1 (C1), eligible patients had any of the following unfavorable (UF) risk factors: bulky mediastinal mass, ESR ≥ 50 mm/h or ≥ 30 mm/h if B symptoms, extranodal involvement, > 2 lymph node sites, or infradiphragmatic disease. The same criteria applied to C2, except for bulk being defined by the Memorial Sloan Kettering (MSK) definition (maximal transverse or coronal diameter of the largest mass > 7 cm). In C3 and C4, all patients were required to have MSK criteria bulk. All cohorts received BV-AVD x 4. Patients with a PET-negative response after 4 cycles received 30-Gy involved site radiation therapy (ISRT) in C1, 20-Gy ISRT in C2, 30-Gy consolidative-volume RT (CVRT) in C3, and no RT in C4. For 84 patients at MSK, baseline MTV was measured using the 41% maximum standard uptake value (SUV) threshold method. Interim PET after 2 cycles was interpreted using the 5-point scale with scores ≤ 3 considered negative. Survival data was updated through July 1, 2022. Progression-free (PFS) and overall survival (OS) probabilities were estimated by the Kaplan-Meier method and compared for various features using the log-rank test, with a p-value of ≤ 0.05 statistically significant. RESULTS: Of 117 patients enrolled, 116 completed chemotherapy. With a median followup of 4.6 years (6.7, 5.3, 4.5, and 3.3 years for C1-4), there were 8 progression events and 2 deaths. Since original publication, 1 further progression occurred amongst a patient in C4. The median PFS and OS have not been reached in either group. The overall 4-year PFS and OS were 93% and 98%, respectively. The 4-year PFS for C1-4 was 93%, 96%, 90%, and 93%, respectively (p=0.78). Next, outcomes were compared by MTV and PET2. Among 84 patients assessed for baseline MTV, median MTV was 150 (range 13-827) cm3. Using the median MTV to stratify patients, overall 4-year PFS in the MTV-high (n=43) versus MTV-low (n=41) group was 91% versus 100%, respectively (p=0.047). Fourteen patients (12%) had positive PET2. Four-year PFS in the PET2 positive versus negative group was 79% versus 95%, respectively (p=0.02). By MTV and PET2, 4-year PFS for the MTV-low/PET2-negative (n=36), MTV-low/PET2-positive (n=5), MTV-high/PET2-negative (n=38), and MTV-high/PET2-positive (n=5) groups was 100%, 100%, 95%, and 60%, respectively (p=0.001) (Figure 1). Within these 4 groups, there were 4 progression events, 2 within the MTV-high/PET2-negative group and 2 within the MTV-high/PET2-positive group. The 2 patients in the MTV-high/PET2-negative group had Deauville score (DS) 2 on PET2 and then developed DS4 on PET4; 1 received salvage R-ICE (concomitant CD20 expression) followed by autologous transplant (autoSCT), and 1 received salvage pembrolizumab-GVD followed by autoSCT. The 2 patients within the MTV-high/PET2-positive group had DS4 on PET2 and PET4. One patient received salvage augmented ICE followed by radiation and autoSCT. The other patient had a negative biopsy of PET4 disease and completed CVRT, but relapsed 2 months later and received salvage augmented ICE and autoSCT. All 4 of these patients remain without disease after a median follow-up post autoSCT of 65 (28-86) months. CONCLUSIONS: We report extended followup of short-course BV-AVD followed by various doses/fields of RT, including no RT, in ES, bulky HL. The BV-AVD program remains highly active and well-tolerated, including in the absence of consolidative RT for certain patients. Baseline MTV and PET2 identifies an unfavorable cohort at higher risk of treatment failure. Trials in ES, bulky HL should evaluate stratified treatment paradigms using baseline MTV and PET2. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Transdermal Glomerular Filtration Rate Measurement: Clinical Results From a Pilot Multicenter Study Establishing Feasibility and Efficacy

Transdermal Glomerular Filtration Rate Measurement: Clinical Results From a Pilot Multicenter Study Establishing Feasibility and Efficacy

A randomized, controlled multicenter feasibility pilot trial on imaging confirmed uncomplicated acute appendicitis: Appendectomy vs. symptomatic treatment in pediatric patients (the APPSYPP) trial study protocol

IntroductionImaging-confirmed uncomplicated acute appendicitis can be effectively and safely treated with antibiotics in most adults and children. Symptomatic treatment may have similar efficacy and safety. Methods and analysisThe APPSYPP trial is a randomized national multicenter feasibility superiority pilot study comparing appendectomy with symptomatic treatment in children with imaging-confirmed uncomplicated acute appendicitis. Inclusion criteria: 1) age ≥ 7 and < 16 years, 2) imaging-confirmed uncomplicated acute appendicitis and 3) CRP ≤ 65 mg/l. Patients are randomized to receive emergency laparoscopic appendectomy or symptomatic treatment. To ensure patient safety, symptomatically treated patients are hospitalized for at least 24 h receiving standard practice intravenous fluids and analgesics according to standard clinical practice. Primary outcome is 30-day treatment success defined by the absence of any treatment failure criteria. In appendectomy, treatment failure is defined as normal appendiceal histopathology or any postintervention complication requiring general anesthesia. In symptomatic treatment, treatment failure is defined as 1) inability for hospital discharge without appendectomy within 48 h after randomization with a finding of histopathologically inflamed appendix, 2) appendectomy during the initial hospital stay due to clinical progression of appendicitis with complicated acute appendicitis both histopathologically and surgically, 3) appendectomy with a histopathological finding of acute appendicitis after hospital discharge, or 4) any complication of appendicitis requiring general anesthesia. Detailed predefined secondary outcomes will be analyzed. Ethics and disseminationStudy was approved by Ethics Committee of Helsinki University Hospital (ID:HUS/1993/2021), conducted in compliance with the declaration of Helsinki with results disseminated in peer-reviewed scientific journals.Trial registration: ClinicalTrials.gov (NCT05289713). Strengths and limitations of this study•To our knowledge, this is the first randomized controlled trial (RCT) in children comparing appendectomy to symptomatic treatment in imaging-confirmed uncomplicated acute appendicitis.•The multicenter nationwide study design limits selection bias and improves the generalizability of the results also enabling sufficient patient enrollment.•Sample size is small based on the feasibility design and a larger RCT will be needed and initiated in the future based on the results of this pilot RCT.

180-degree immersive VR motion visualization in the treatment of haemophilic ankle arthropathy.

Patients with haemophilic arthropathy suffer chronic pain that affects and restricts their quality of life. Visualization of movement through immersive virtual reality is used for pain management. To evaluate the efficacy of 180-degree immersive VR motion visualization therapy in patients with haemophilic ankle arthropathy. Prospective, multicentre pilot study. Fifteen adult patients with bilateral haemophilic ankle arthropathy were recruited (mean age: 42.73±12.36 years). The intervention lasted 4weeks, with daily home sessions of 180-degree immersive motion visualization. The patients were given virtual reality glasses to use with their smartphones. From the YouTube mobile app® they accessed the recorded video with access from the He-Mirror App®. The study variables were joint state (Haemophilia Joint Health Score), pressure pain threshold (pressure algometer), muscle strength (dynamometry) and range of motion (goniometry). Three evaluations were performed: at baseline (T0), after the intervention (T1) and at the end of a 16-week follow-up period (T2). No patient developed ankle hemarthrosis during the experimental phase. In the repeated measures analysis we found statistically significant differences in joint state (F=51.38; η2 p =.63), pressure pain threshold of the lateral malleolus (F=12.34; η2 p =.29) and range of motion (F=11.7; η2 p =.28). Therapy using immersive motion visualization does not cause hemarthrosis. This intervention can improve joint condition, pressure pain threshold and range of motion in patients with ankle arthropathy. Changes greater than the MDC were reported in more than 40% of patients for the variables pressure pain threshold, anterior tibialis strength and range of motion, which were considered clinically relevant.

ROBOTIC-ASSISTED BRONCHOSCOPY: A POTENTIAL NEW TOOL FOR CAVITARY PULMONARY LESIONS

ROBOTIC-ASSISTED BRONCHOSCOPY: A POTENTIAL NEW TOOL FOR CAVITARY PULMONARY LESIONS

Volume sweep imaging lung teleultrasound for detection of COVID-19 in Peru: a multicentre pilot study

ObjectivesPulmonary disease is a significant cause of morbidity and mortality in adults and children, but most of the world lacks diagnostic imaging for its assessment. Lung ultrasound is a portable,...

Journal-related Activities and Other Special Activities at the 2022 American Society of Anesthesiologists Meeting

Journal-related Activities and Other Special Activities at the 2022 American Society of Anesthesiologists Meeting

Intradialytic parenteral nutrition using a standard amino acid solution not for renal failure in maintenance hemodialysis patients with malnutrition: a multicenter pilot study

BackgroundStandard amino acid solutions have recently been removed from the contraindications for use in dialysis patients in Japan. However, the details of their safety and efficacy in these patients are still not known. In this study, we investigated the safety and efficacy of intradialytic parenteral nutrition (IDPN) using ENEFLUID® injection containing standard amino acids, glucose, electrolytes, fats, and water-soluble vitamins in maintenance hemodialysis patients with malnutrition.MethodsThis clinical trial was designed as a multicenter, prospective, non-randomized, open-label, single-arm, observational pilot study. The participants were patients on maintenance hemodialysis who were in the nutritional high-risk group according to the Nutritional Risk Index for Japanese Hemodialysis Patients. One bag of ENEFLUID® injection was administered during every hemodialysis session for 12 weeks. The primary endpoint was change in serum transthyretin levels between before and after the 12-week period. As safety endpoints, we evaluated changes in body fluid volume and blood biochemical tests, including blood urea nitrogen and electrolytes, as well as blood glucose variability using flash glucose monitoring (FGM).ResultsThe mean age and body mass index of the 13 participants were 79.0 ± 10.7 years and 18.0 ± 1.7 kg/m2, respectively. No significant changes were observed in nutritional parameters, including serum transthyretin, between before and after the start of the study. After IDPN initiation, there was no obvious fluid overload or significant changes in blood biochemical tests, including electrolytes, and the treatment could be safely continued for 12 weeks. In the FGM analysis, asymptomatic hypoglycemia during hemodialysis was observed at the beginning of the study, but there was a trend toward improvement after 12 weeks (area over the curve < 70 mg/dl per dialysis session: 747.5 ± 1333.9 to 21.6 ± 54.3, P = 0.09).ConclusionsIDPN using ENEFLUID® injection can be safely continued, although it does not significantly improve markers of nutritional status. It also showed the potential to ameliorate asymptomatic hypoglycemia during hemodialysis sessions. More detailed studies of the improvement in nutritional indicators are needed.Trial registration: This study was registered with the University Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR) on May 9, 2021 (registration ID, UMIN000044051).

534P A pilot study of neoadjuvant olaparib for patients with HRD-positive advanced ovarian cancer

Olaparib, a PARP inhibitor, has demonstrated efficacy as maintenance therapy in patients with newly diagnosed BRCA mutated or homologous recombination deficiency (HRD)-positive advanced ovarian cancer and as maintenance therapy in platinum-sensitive recurrent ovarian cancer. Furthermore, a synergistic effect between PARP inhibitors and immune checkpoint inhibitors has been suggested in preclinical studies and the efficacy of the combination is being demonstrated in clinic. However, the efficacy and safety of PARP inhibitors alone or in combination with immune checkpoint inhibitors as neoadjuvant therapy are unknown. This is an open-label, multicenter pilot study evaluating the efficacy and safety of olaparib alone (cohort 1) or in combination with pembrolizumab (cohort 2) as neoadjuvant therapy in patients with HRD-positive stage III-IV ovarian cancer. In cohort 1 (n=10), patients received olaparib 300 mg orally twice daily for 6 weeks. In cohort 2 (n=20), patients received olaparib 300 mg orally twice daily for 6 weeks and pembrolizumab 200 mg was administered intravenously every 3 weeks for 2 cycles. The major inclusion criteria included newly diagnosed HRD-positive International Federation of Gynecology and Obstetrics (FIGO) stage III-IV high-grade serous or endometrioid ovarian, fallopian or primary peritoneal cancer. The primary endpoint was objective response rate (ORR) based on RECIST version 1.1. The results of cohort 1 are presented here. In total, 10 patients were enrolled in cohort 1. The median age was 67.5 (59-68), and all patients had high-grade serous carcinoma histology. Three patients had stage IIIC, 2 patients had stage IVA, and 5 patients had stage IVB. ORR was 50% (95% CI, 18.7-81.3). The proportion of grade 3 or higher adverse events was 40%, and the proportion of treatment discontinuation due to adverse events was 10%. Common adverse events were nausea (n=7), diarrhea (n=4) and fatigue (n=2). Neoadjuvant olaparib monotherapy showed efficacy and tolerability in patients with HRD-positive advanced ovarian cancer. A pilot study of neoadjuvant combination treatment of olaparib plus pembrolizumab (cohort 2) is ongoing.

Efficacy and Safety of Lanreotide Autogel and Temozolomide Combination Therapy in Progressive Thoracic Neuroendocrine Tumors (Carcinoid): Results from the Phase 2 ATLANT Study

Introduction: Lanreotide autogel (LAN) and temozolomide (TMZ) are guidelines-recommended monotherapies for thoracic neuroendocrine tumors (carcinoids; T-NETs), but prospective data for both combined and monotherapies are lacking. ATLANT (NCT02698410) evaluated efficacy and safety of LAN/TMZ in progressive T-NETs. Methods: ATLANT was a 12-month, Italian, phase 2, single-arm, open-label, multicenter pilot study. Eligible patients had unresectable, locally advanced/metastatic, well-/moderately differentiated T-NETs with radiological progression. Patients received subcutaneous LAN 120 mg every 28 days and oral TMZ 250 mg/day for 5 consecutive days every 28-day cycle. Main endpoints are disease control rate (DCR) at 9 months (primary; investigator-assessed), median progression-free survival (PFS), biomarkers, and safety. Results: The number of patients was 40; 60% were male. Primary tumor site was lung (90%) and thymus (10%). Carcinoid type was typical (20.0%) and atypical (52.5%). DCR at 9 months was 35.0% (95% confidence interval (CI) 20.63–51.68; nonacceptability threshold ≤10%, p < 0.0001; not significantly above clinically relevant threshold ≥30%, p = 0.2968). DCR between 7.5 and 10.5 months (sensitivity analysis) was 45.0% (95% CI: 29.26–61.51) and clinically relevant (p = 0.0320 at ≥30% threshold). Median PFS was 37.1 (95% CI: 24.1–52.9) weeks. No association was observed between biomarker variations (chromogranin A, neuron-specific enolase, somatostatin receptor type-2, Ki-67, 6-O-methylguanine-DNA-methyl-transferase) and DCR or PFS. Most patients (97.5%) had treatment-emergent adverse events (TEAEs); 72.5% had treatment-related TEAEs. TEAEs were mainly grade 1/2. No unanticipated TEAEs were reported. Conclusions: This study showed that the LAN/TMZ combination has promising efficacy in progressive T-NETs, and was well tolerated. Larger studies are warranted to support the clinical benefits of LAN/TMZ in patients with T-NETs.

A Pilot Study Assessing a Closed-Loop System for Goal-Directed Fluid Therapy in Abdominal Surgery Patients.

Background: This prospective multicentre pilot study of patients scheduled for elective major abdominal surgery aimed to validate the fluid challenge (FC) proposed by the closed-loop (CL) system via anaesthesiologist assessment. Methods: This was a phase II trial consisting of two inclusion stages (SIMON method). Each FC (250 mL saline solution for 10 min) proposed by the CL was systematically validated by the anaesthesiologist who could either confirm or refuse the FC or give FC without the CL system. A ≥ 95% agreement between the CL and the anaesthesiologist was considered acceptable. Results: The study was interrupted after interim analysis of the first 19 patients (10 men, median age = 61 years, median body mass index = 26 kg/m2). The anaesthesiologists accepted 165/205 (80%) of fluid boluses proposed by the CL. Median cardiac index (CI) was 2.9 (interquartile: IQ (2.7; 3.4) L/min/m2) and the median coefficient of variation (CV) for CI was 13% (10; 17). Fifteen out of nineteen patients (79%) had a mean CI > 2.5 L/min/m2 or spent > 85% surgery time with pulse pressure variation < 13%. No adverse events related to the CL were reported. Conclusion: In this study of patients scheduled for elective major abdominal surgery, the agreement between CL and anaesthesiologist for giving fluid challenge was 80%, suggesting that CL cannot replace the physician but could help in decision making.

Within-subject biological variation estimates using an indirect data mining strategy. Spanish multicenter pilot study (BiVaBiDa).

The estimates of biological variation (BV) have traditionally been determined using direct methods, which present limitations. In response to this issue, two papers have been published addressing these limitations by employing indirect methods. Here, we present a new procedure, based on indirect methods that analyses data collected within a multicenter pilot study. Using this method, we obtain CVI estimates and calculate confidence intervals (CI), using the EFLM-BVD CVI estimates as gold standard for comparison. Data were collected over a 18-month period for 7 measurands, from 3 Spanish hospitals; inclusion criteria: patients 18-75 years with more than two determinations. For each measurand, four different strategies were carried out based on the coefficient of variation ratio (rCoeV) and based on the use of the bootstrap method (OS1, RS2 and RS3). RS2 and RS3 use symmetry reference change value (RCV) to clean database. RS2 and RS3 had the best correlation for the CVI estimates with respect to EFLM-BVD. RS2 used the symmetric RCV value without eliminating outliers, while RS3 combined RCV and outliers. When using the rCoeV and OS1strategies, an overestimation of the CVI value was obtained. Our study presents a new strategy for obtaining robust CVI estimates using an indirect method together with the value of symmetric RCV to select the target population. The CVI estimates obtained show a good correlation with those published in the EFLM-BVD database. Furthermore, our strategy can resolve some of the limitations encountered when using direct methods such as calculating confidence intervals.

ПРЕДИКТОРЫ ТЯЖЕЛОГО ТЕЧЕНИЯ И ОЦЕНКА ЭФФЕКТИВНОСТИ СТУПЕНЧАТОЙ КОМПЛЕКСНОЙ КОНСЕРВАТИВНОЙ ТЕРАПИИ БРОНХОЭКТАЗОВ, НЕ СВЯЗАННЫХ С МУКОВИСЦИДОЗОМ, У ДЕТЕЙ

The purpose of the study was to determine the predictors of severe bronchiectasis (BE) not associated with cystic fibrosis (CF) in children and to evaluate the effectiveness of a stepwise complex conservative therapy. Materials and methods of the study: study design - multicenter cohort prospective pilot study. 67 hospitalized pediatric patients aged from 11 months up to 17 years old (52% boys and 48% girls) with BE caused by previous pneumonia (22%), primary ciliary dyskinesia (22%), bronchial asthma (13%), Williams-Campbell syndrome (7%), bronchial foreign bodies (7%), gastroesophageal reflux disease (6%), bronchopulmonary dysplasia (6%), postinfectious bronchiolitis obliterans (5%), allergic bronchopulmonary aspergillosis (3%), chronic granulomatous disease (3%), AIDS (1%), protracted bacterial bronchitis (1%), and brain-lung-thyroid syndrome (1%) were observed. Predictors of severe BE were determined based on a comparison of groups of patients with mild (up to 4 exacerbations of BE per year) and moderate (from 4 to 6 exacerbations) course of BE (n=31) and patients with severe course of BE (&gt;6 exacerbations per year, n=36). At the second stage of the study, in patients with changes in the severity of the course of BE, who were followed in dynamics (n=42), the frequency of exacerbations was assessed during the year after the appointment of a stepwise complex conservative therapy, which included, depending on the severity, daily drainage massage, exercise therapy, auxiliary devices for the respiratory tract clearance, long-term anti-inflammatory azithromycin, inhaled/intravenous antibiotics, and/or respiratory support. Results: the clinical picture of severe BE occurring with &gt;6 exacerbations per year compared with mild/moderate course of the disease (≤6 exacerbations per year) is characterized by a statistically significantly more frequent registration of dyspnea (86% and 45%, p&lt;0.001), exercise intolerance (69% and 39%, p=0.012), wet rales (89% and 61%, p=0.011), finger clubbing (17% and 0%, p=0.027). The prognostic model for determining the likelihood of severe BE not associated with CF in children includes the age of manifestation, a positive result of bacteriological examination of sputum/aspirates from the respiratory tract, localization of BE in the middle lobe of the right lung and/or lingual segments, and dyspnea. The appointment of gradual conservative therapy for BE, depending on the severity/frequency of exacerbations, makes it possible to statistically significantly reduce the severity of BE (p&lt;0.001) and the median of exacerbations during the year from 9.00 [3.25-12.00] before treatment to 2.00 [1.00-3.00] after treatment (p&lt;0.001). Conclusion: BEs are heterogeneous in severity, which determines the choice of therapy. Conservative therapy of BE not associated with CF in children has a stepwise principle depending on the severity of the course. Its appointment could therefore reduce the frequency of exacerbations.