Multicenter Study Research Articles

First external validity study of the Fagotti score in ovarian cancer

Epithelial ovarian cancer is mostly discovered at the stage of peritoneal carcinosis. Complete cytoreductive surgery improves overall survival. The Fagotti score is a predictive score of resectability based on peritoneal laparoscopic exploratory. Our aim was to study the inter-observer concordance in an external validation of the Fagotti score. An observational, prospective, multicenter study was conducted using the Francogyn research network. The primary outcome was inter-observer concordance of the Fagotti score. 15 patients in which an ovarian mass was discovered were included. For each patient, the first exploratory laparoscopy before any treatment/chemotherapy was recorded. This bank of 15 videos was subject to blind review accompanied by a Fagotti score rating by 11 gynecological surgeons specializing in oncology. A total of 165 blind reviews were performed. Inter-observer concordance was very good for the Fagotti score with an intraclass correlation coefficient (ICC) of 0.83 [95% CI 0.71; 0.93]. Inter-observer concordance for the adjusted Fagotti score, which accounts for unexplorable areas with extensive carcinomatosis, resulted in an ICC of 0.64 [95% CI 0.46; 0.82]. According to the reviewers, the three least explorable parameters were mesentery involvement, stomach infiltration and liver damage. The ICC of the explorable Fagotti score, i.e. score with deletion of the parameters most often unexplored by laparoscopy, was 0.86 [0.75–0.94]. This study confirms the reproducibility of the Fagotti score during first assessment laparoscopies in cases of advanced ovarian cancer. The explorable Fagotti score has an equivalent or better inter-observer concordance than the Fagotti score.

SARS-CoV-2 vaccination in the first year after hematopoietic cell transplant or chimeric antigen receptor T cell therapy: A prospective, multicenter, observational study.

The optimal timing of vaccination with SARS-CoV-2 vaccines after cellular therapy is incompletely understood. The objectives of this study are to determine whether humoral and cellular responses after SARS-CoV-2 vaccination differ if initiated <4 months versus 4-12 months after cellular therapy. We conducted a multicenter prospective observational study at 30 cancer centers in the United States. SARS-CoV-2 vaccination was administered as part of routine care. We obtained blood prior to and after vaccinations at up to five time points and tested for SARS-CoV-2 spike (anti-S) IgG in all participants and neutralizing antibodies for Wuhan D614G, Delta B.1.617.2, and Omicron B.1.1.529 strains, as well as SARS-CoV-2-specific T cell receptors (TCRs), in a subgroup. We enrolled 466 allogeneic hematopoietic cell transplant (HCT; n=231), autologous HCT (n=170), and chimeric antigen receptor T cell (CAR-T cell) therapy (n=65) recipients between April 2021 and June 2022. Humoral and cellular responses did not significantly differ among participants initiating vaccinations <4 months vs 4-12 months after cellular therapy. Anti-S IgG ≥2,500 U/mL was correlated with high neutralizing antibody titers and attained by the last time point in 70%, 69%, and 34% of allogeneic HCT, autologous HCT, and CAR-T cell recipients, respectively. SARS-CoV-2-specific T cell responses were attained in 57%, 83%, and 58%, respectively. Pre-cellular therapy SARS-CoV-2 infection or vaccination were key predictors of post-cellular therapy immunity. These data support mRNA SARS-CoV-2 vaccination prior to, and reinitiation three to four months after, cellular therapies with allogeneic HCT, autologous HCT, and CAR-T cell therapy.

The Lebanese percreta group: A retrospective cohort study of both radical and conservative management outcomes of abnormally invasive placenta.

The aim of the present study was to illustrate the outcomes of abnormally invasive placenta (AIP) cases managed in three leading centers in Lebanon. We conducted a retrospective multicenter cohort study. Patients managed conservatively (cesarean delivery with successful placental separation) or radically (cesarean hysterectomy) were included in the study. Data included patient characteristics, surgical outcomes (blood loss, operative time, transfusion, partial bladder resection), maternal outcomes (death, length of stay, ICU admission, postoperative hemoglobin level) and neonatal outcomes (Apgar score, neonatal weight, admission to neonatal intensive care unit, neonatal death). The study included 189 patients. In the radical treatment subgroup (141/189), patients were para 3 and delivered at 34 4/7 weeks in average, bled 1.5 L and were transfused with three packed red blood cells, with operative time averaging 160 min. A total of 36% were admitted to the ICU and patients stayed on average for 1 week despite partial bladder resection in 19% of cases. Unscheduled radical delivery occurred at a lower gestational age, was associated with more blood loss, higher rate and volume of transfusion, and risk of maternal and neonatal death. In addition, patients delivered in an unscheduled fashion experienced higher rates of partial bladder resection and longer interventions. In the conservative treatment subgroup, on average patients were para 2 and delivered at 36 weeks, bled 800 mL on average with low rates of transfusion (35%) and ICU admission (22.9%). With regard to neonatal outcomes, the average neonatal birth weight was 2.4 kg in the radical subgroup and 2.5 kg in the conservative subgroup. Neonatal death occurred in 5.4% of cases requiring radical management while it occurred in 2% of patients treated conservatively. Through their multidisciplinary approach, the three centers demonstrated that management of AIP in Lebanon has led to excellent outcomes with no maternal mortality occurring in scheduled radical treatment. By comparison of the three leading centers, pitfalls in each center were identified and addressed.

Real-world study of lazertinib as second-line or greater treatment in advanced non-small cell lung cancer.

Lazertinib is an oral, third-generation EGFR-TKI, which specifically targets the EGFR T790M mutation along with activating mutations Ex19del and L858R. More real-world data are needed to evaluate its efficacy and safety in treating locally advanced and metastatic non-small cell lung cancer (NSCLC) following prior EGFR TKI treatment. This multicenter retrospective study was conducted at seven university hospitals affiliated to the Catholic Medical Center (CMC) in Korea. A clinical data warehouse (CDW) platform was used to access and extract information. A total of 48 patients were assessed. The majority were female (75%) and diagnosed with adenocarcinoma (95.8%). All patients had the EGFR mutation at diagnosis, 27 (56.3%) had the exon 19 deletion, 20 (41.7%) had the L858R mutation, and one (2.0%) had the exon 18 mutation. The median progression-free survival (PFS) was 15.4 months. At 6, 12, and 18 months, PFS rates were 79.1%, 53.6%, and 27.3%, respectively. When PFS was analyzed by prior TKI duration (<18 months vs. >18 months), significant differences were noted at the 6 and 9-month mark (p = 0.013 and p = 0.010, respectively). In multivariate analysis for PFS, only prior TKI duration and ECOG score showed statistical significance (p = 0.026 and p = 0.049, respectively). In the multivariate analysis for OS, ECOG score showed statistical significance (p = 0.006). Among 48 patients, 34 (70.8%) experienced adverse events (AEs) related to lazertinib. The most frequent AEs were skin reaction (29.8%), diarrhea (21.3%), and peripheral neuropathy (20.8%). The results suggest that lazertinib is effective in second or more line settings, with tolerable safety profile. More patient data are necessary to find possible prognostic markers associated with patient outcome.

Characterization of acute-on-chronic liver diseases: A multicenter prospective cohort study

BACKGROUND Acute-on-chronic liver disease (AoCLD) accounts for the majority of patients hospitalized in the Department of Hepatology or Infectious Diseases. AIM To explore the characterization of AoCLD to provide theoretical guidance for the accurate diagnosis and prognosis of AoCLD. METHODS Patients with AoCLD from the Chinese Acute-on-Chronic Liver Failure (ACLF) study cohort were included in this study. The clinical characteristics and outcomes, and the 90-d survival rate associated with each clinical type of AoCLD were analyzed, using the Kaplan-Meier method and the log-rank test. RESULTS A total of 3375 patients with AoCLD were enrolled, including 1679 (49.7%) patients with liver cirrhosis acute decompensation (LC-AD), 850 (25.2%) patients with ACLF, 577 (17.1%) patients with chronic hepatitis acute exacerbation (CHAE), and 269 (8.0%) patients with liver cirrhosis active phase (LC-A). The most common cause of chronic liver disease (CLD) was HBV infection (71.4%). The most common precipitants of AoCLD was bacterial infection (22.8%). The 90-d mortality rates of each clinical subtype of AoCLD were 43.4% (232/535) for type-C ACLF, 36.0% (36/100) for type-B ACLF, 27.0% (58/215) for type-A ACLF, 9.0% (151/1679) for LC-AD, 3.0% (8/269) for LC-A, and 1.2% (7/577) for CHAE. CONCLUSION HBV infection is the main cause of CLD, and bacterial infection is the main precipitant of AoCLD. The most common clinical type of AoCLD is LC-AD. Early diagnosis and timely intervention are needed to reduce the mortality of patients with LC-AD or ACLF.

Does higher performance in a national licensing examination predict better quality of care? A longitudinal observational study of Ethiopian anesthetists.

Ethiopia made a national licensing examination (NLE) for associate clinician anesthetists a requirement for entry into the practice workforce. However, there is limited empirical evidence on whether the NLE scores of associate clinicians predict the quality of health care they provide in low-income countries. This study aimed to assess the association between anesthetists' NLE scores and three selected quality of patient care indicators. A multicenter longitudinal observational study was conducted between January 8 and February 7, 2023, to collect quality of care (QoC) data on surgical patients attended by anesthetists (n = 56) who had taken the Ethiopian anesthetist NLE since 2019. The three QoC indicators were standards for safe anesthesia practice, critical incidents, and patient satisfaction. The medical records of 991 patients were reviewed to determine the standards for safe anesthesia practice and critical incidents. A total of 400 patients responded to the patient satisfaction survey. Multivariable regressions were employed to determine whether the anesthetist NLE score predicted QoC indicators. The mean percentage of safe anesthesia practice standards met was 69.14%, and the mean satisfaction score was 85.22%. There were 1,120 critical incidents among 911 patients, with three out of five experiencing at least one. After controlling for patient, anesthetist, facility, and clinical care-related confounding variables, the NLE score predicted the occurrence of critical incidents. For every 1% point increase in the total NLE score, the odds of developing one or more critical incidents decreased by 18% (aOR = 0.82; 95% CI = 0.70 = 0.96; p = 0.016). No statistically significant associations existed between the other two QoC indicators and NLE scores. The NLE score had an inverse relationship with the occurrence of critical incidents, supporting the validity of the examination in assessing graduates' ability to provide safe and effective care. The lack of an association with the other two QoC indicators requires further investigation. Our findings may help improve education quality and the impact of NLEs in Ethiopia and beyond.

Expectations, needs and mid-term outcomes in people accessing to secondary findings from ES: 1st French mixed study (FIND Study).

Generation and subsequently accessibility of secondary findings (SF) in diagnostic practice is a subject of debate around the world and particularly in Europe. The French FIND study has been set up to assess patient/parent expectations regarding SF from exome sequencing (ES) and to collect their real-life experience until 1 year after the delivery of results. 340 patients who had ES for undiagnosed developmental disorders were included in this multicenter mixed study (quantitative N = 340; qualitative N = 26). Three groups of actionable SF were rendered: predisposition to late-onset actionable diseases; genetic counseling; pharmacogenomics. Participants expressed strong interest in obtaining SF and a high satisfaction level when a SF is reported. The medical actionability of the SF reinforced parents' sense of taking action for their child and was seen as an opportunity. While we observed no serious psychological concerns, we showed that these results could have psychological consequences, in particular for late-onset actionable diseases SF, within families already dealing with rare diseases. This study shows that participants remain in favor of accessing SF despite the potential psychological, care, and lifestyle impacts, which are difficult to anticipate. The establishment of a management protocol, including the support of a multidisciplinary team, would be necessary if national policy allows the reporting of these data.

Unmet rehabilitation needs in the first 6 months post-injury in a trauma centre population with moderate-to-severe traumatic injuries.

To describe the needs for subacute inpatient rehabilitation and community-based healthcare services, rehabilitation, and social support in patients with moderate-to-severe traumatic injury in the first 6 months post-injury. Further, to explore associations between sociodemographic and clinical characteristics and unmet needs. Multicentre prospective cohort study. Of 601 persons (75% males), mean (standard deviation) age 47 (21) years, admitted to trauma centres in 2020 with moderate-to-severe injury, 501 patients responded at the 6-month follow-up and thus were included in the analyses. Sociodemographic and injury-related characteristics were recorded at inclusion. Estimation of needs was assessed with the Rehabilitation Complexity Scale Extended-Trauma and the Needs and Provision Complexity Scale on hospital discharge. Provision of services was recorded 6months post-injury. Multivariable logistic regressions explored associations between baseline variables and unmet inpatient rehabilitation and community-based service needs. In total, 20% exhibited unmet needs for subacute inpatient rehabilitation, compared with 60% for community-based services. Predictors for unmet community-based service needs included residing in less central areas, profound injury severity, severe head injury, and rehabilitation referral before returning home. Inadequate provision of healthcare and rehabilitation services, particularly in the municipalities, resulted in substantial unmet needs in the first 6 months following injury.

Efficacy of Chlorhexidine Impregnated Wipes for the Local Dysbiosis in Atopic Dogs: A Multicentric Prospective Study

(1) Background: Dysbiosis is frequently observed in Canine Atopic Dermatitis (CAD). Antimicrobial treatment may be necessary to treat flare ups and the use of topical treatments is beneficial to prevent the development of bacterial resistance. Wipes are an easy way to apply antiseptic agents on the skin. The aim of this study was to evaluate the benefits of 3% chlorhexidine impregnated wipes (Pyoskin® wipes, MP Labo, France) on local areas of dysbiosis in dogs with CAD. (2) Methods: A total of 20 dogs suffering from CAD presented with localised areas of dysbiosis were included in this study. Affected areas were cleansed with the daily application of chlorhexidine wipes once a day for 14 days. Follow-up visits were scheduled after one and two weeks. Clinical signs (lesions and pruritus), dysbiosis scored by cytological counts (cocci and Malassezia) and investigator and owner global appreciation were evaluated. (3) Results: A statistically significant decrease in clinical scores and cytological counts were observed as soon as D7 and until D14. Both owner and investigator appreciation were considered high (4) Conclusions: The use of chlorhexidine impregnated wipes is a useful and easy way to manage localised dysbiosis in atopic dogs and allows limiting of systemic medication to prevent bacterial resistance.

The effect of an intraoperative patient-specific, surgery-specific haemodynamic algorithm in improving textbook outcomes for hepatobiliary–pancreatic surgery: a multicentre retrospective study

The effect of an intraoperative patient-specific, surgery-specific haemodynamic algorithm in improving textbook outcomes for hepatobiliary–pancreatic surgery: a multicentre retrospective study

A dermocosmetic regimen is effective and safe for mild to moderate acne in subjects of all skin phototypes

AbstractBackgroundAcne vulgaris is a chronic inflammatory skin condition with a multifactorial pathogenesis. The clinical appearance of acne and its sequelae may differ according to phototypes. Data regarding the potential benefit of dermocosmetics (DC) regardless of phototype are lacking and assessing acne improvement can be difficult, given the lack of visual support in people with skin of colour. A DC regimen, combining a cleanser and a cream, both containing thermal spring water, has been developed for the management of mild‐to‐moderate acne, for all skin phototypes studied.ObjectivesTo assess the efficacy and local tolerance of a DC routine in mild‐to‐moderate acne and to visualize the clinical improvement in all skin phototypes.MethodsIn an open‐labelled, multicentre clinical study, subjects of any phototype aged above 11 years and above with mild (N = 48, 55.2%) or moderate (N = 39, 44.8%) facial acne applied the DC twice daily for 56 days. No other acne care was allowed. Acne severity, as well as inflammatory and noninflammatory lesion counts, were assessed at baseline, Days 28 and 56. Photographs were taken using a novel imaging tool based on multimodal acquisition, to show clinical improvement over time.ResultsEighty‐seven subjects, 41 adults and 46 adolescents, were included; 59.8% were female and were aged between 11 and 44 years. The total acne lesion count decreased by 34%, the noninflammatory lesion count by 28%, and the inflammatory lesion count by 52% at Day 56. All % changes were statistically significant (p &lt; 0.05). The GEA score decreased, with 25% of subjects showing at least a one‐grade improvement at Day 28 and 59% at Day 56. Local tolerance was excellent.ConclusionsThe tested DC care is beneficial for the improvement of acne and is very well tolerated in all skin phototypes studied.

Age- and Sex-Dynamic Fluctuations and Reference Intervals for Alkaline Phosphatase Among the Spanish Population.

Interpretation of alkaline phosphatase (ALP) activity is essential for the diagnosis of certain diseases. ALP changes during life and may vary between different populations. To establish reference intervals (RIs) and percentile charts for ALP activity in the Spanish population through a multicentric observational study and to compare the RIs to those defined in other countries. A total of 662 350 ALP measurements from individuals ages 0 to 99 years from 9 Spanish tertiary care centers collected between 2020 and 2022 were analyzed. This study is the largest published in the literature to date. Continuous percentile charts for ALP according to sex and age were established which can be used as RIs. Higher levels are reached during the first weeks of life. In puberty, a differential evolution is observed in both sexes, reaching a peak at 10 to 13 years of age in boys and remaining stable in girls at this age. Significant differences were also observed in adults, higher in men between ages 20 and 49 years and between ages 50 and 79 years in women, as reported in some countries. ALP activity follows an age- and sex-dependent fluctuation with geographic differences. It is important to have appropriate reference values for each population in order to allow for a correct diagnostic interpretation and early diagnosis of diseases related to ALP abnormalities.

Olaparib in recurrent IDH mutant high-grade glioma: a phase 2 multicenter study of the POLA Network

Olaparib in recurrent IDH mutant high-grade glioma: a phase 2 multicenter study of the POLA Network

Cerebellum/liver index on baseline 18F-FDG PET/CT to improve prognostication in post-transplant lymphoproliferative disorders: a multicenter retrospective study

BackgroundBesides International Prognostic Index (IPI) score, baseline prognostic factors of post-transplant lymphoproliferative disorders (PTLD) are poorly identified due to the rarity of the disease. New indexes derived from healthy organ uptake in baseline 18F-FDG PET/CT have been studied in immunocompetent lymphoma patients. The aim of this study is to evaluate the performances of the cerebellum-to-liver uptake ratio (denoted as CLIP) as a prognostic factor for PFS and OS. This retrospective multicenter study is based on patients with PTLD included in the K-VIROGREF cohort. The previously published threshold of 3.24 was used for CLIP in these analyses.ResultsA total of 97 patients was included with a majority of monomorphic diffuse large B-cell lymphoma subtype (78.3%). Both IPI score (≥ 3) and CLIP (< 3.24) were significant risk factors of PFS with corresponding hazard ratios of 2.0 (1.0–4.0) and 2.4 (1.3–4.5) respectively. For OS, CLIP was not significant and resulted in a hazard ratio of 2.6 (p = 0.059). Neither IPI score or Total Metabolic Tumor Volume reached significance for OS.ConclusionCLIP is a promising predictor of PFS and perhaps OS in PTLD. Further prospective studies are needed to confirm these results.

Cell-free DNA screening for common autosomal trisomies using rolling-circle replication in twin pregnancies.

To evaluate the performance of prenatal screening for common autosomal trisomies in twin pregnancies through the use of rolling-circle replication (RCR)-cfDNA as a first-tier test. Prospective multicenter study. Women who underwent prenatal screening for trisomy (T) 21, 18 and 13 between January 2019 and March 2022 in twin pregnancies were included. Patients were included in two centers. The primary endpoint was the rate of no-call results in women who received prenatal screening for common autosomal trisomies by RCR-cfDNA at the first attempt, compared to that in prospectively collected samples from 16,382 singleton pregnancies. The secondary endpoints were the performance indices of the RCR-cfDNA. 862 twin pregnancies underwent screening for T21, T18 and T13 by RCR-cfDNA testing at 10-33weeks' gestation. The RCR-cfDNA tests provided a no-call result from the first sample obtained from the patients in 107 (0.7%) singleton and 17 (2.0%) twin pregnancies. Multivariable regression analysis demonstrated that significant independent predictors of test failure were twin pregnancy and in vitro fertilization conception. All cases of T21 (n=20/862; 2.3%), T18 (n=4/862; 0.5%) and T13 (n=1/862; 0.1%) were correctly detected by RCR-cfDNA (respectively, 20, 4 and 1 cases). Sensitivity was 100% (95% CI, 83.1%-100%), 100% (95% CI 39.8%-100%) and 100% (95% CI 2.5%-100%) for T21, T18 and T13, respectively, in twin pregnancies. The RCR-cfDNA test appears to have good accuracy with a low rate of no-call results in a cohort of twin pregnancies for the detection of the most frequent autosomal trisomies.

Prognostic Impact of Metabolic Syndrome and Steatotic Liver Disease in Hepatocellular Carcinoma Using Machine Learning Techniques

Metabolic dysfunction-associated steatotic liver disease (MASLD) currently represents the predominant cause of chronic liver disease and is closely linked to a significant increase in the risk of hepatocellular carcinoma (HCC), even in the absence of liver cirrhosis. In this retrospective multicenter study, machine learning (ML) methods were employed to investigate the relationship between metabolic profile and prognosis at diagnosis in a total of 219 HCC patients. The eXtreme Gradient Boosting (XGB) method demonstrated superiority in identifying mortality predictors in our patients. Etiology was the most determining prognostic factor followed by Barcelona Clinic Liver Cancer (BCLC) and Eastern Cooperative Oncology Group (ECOG) classifications. Variables related to the development of hepatic steatosis and metabolic syndrome, such as elevated levels of alkaline phosphatase (ALP), uric acid, obesity, alcohol consumption, and high blood pressure (HBP), had a significant impact on mortality prediction. This study underscores the importance of metabolic syndrome as a determining factor in the progression of HCC secondary to MASLD. The use of ML techniques provides an effective tool to improve risk stratification and individualized therapeutic management in these patients.

Applications of artificial intelligence for machine- and patient-specific quality assurance in radiation therapy: current status and future directions.

Machine- and patient-specific quality assurance (QA) is essential to ensure the safety and accuracy of radiotherapy. QA methods have become complex, especially in high-precision radiotherapy such as intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT), and various recommendations have been reported by AAPM Task Groups. With the widespread use of IMRT and VMAT, there is an emerging demand for increased operational efficiency. Artificial intelligence (AI) technology is quickly growing in various fields owing to advancements in computers and technology. In the radiotherapy treatment process, AI has led to the development of various techniques for automated segmentation and planning, thereby significantly enhancing treatment efficiency. Many new applications using AI have been reported for machine- and patient-specific QA, such as predicting machine beam data or gamma passing rates for IMRT or VMAT plans. Additionally, these applied technologies are being developed for multicenter studies. In the current review article, AI application techniques in machine- and patient-specific QA have been organized and future directions are discussed. This review presents the learning process and the latest knowledge on machine- and patient-specific QA. Moreover, it contributes to the understanding of the current status and discusses the future directions of machine- and patient-specific QA.

Clinical characteristics and factors affecting disease severity in hospitalized tick-borne encephalitis patients in Norway from 2018 to 2022.

To describe the clinical characteristics and factors associated with disease severity in a Norwegian cohort of hospitalized patients with tick-borne encephalitis (TBE). This observational multicenter study included hospitalized patients with TBE in the endemic area in the southeastern region of Norway from 2018 to 2022. Clinical signs and findings from laboratory tests, EEG, CT and MRI scans were recorded. Patient characteristics were compared among those with mild, moderate, and severe TBE, and factors associated with disease severity were identified. Nearly all eligible patients were included in the final cohort (153/189 participants, 81%). The median age was 56 years, 63% were men, and 7% were vaccinated against TBE; no participants were fully vaccinated. TBE presented as mild (meningeal) disease in 31% of patients and as moderate or severe (encephalitic) disease in 54% and 14% of patients, respectively. We found that 46% of the patients had a monophasic course, 64% had hyponatremia, and 7% presented with central nervous system (CNS) symptoms without pleocytosis in cerebrospinal fluid (CSF). Dysesthesia, a symptom previously not described, was reported in 10% of the patients. Most objective findings were related to the CNS. Preexisting comorbidities, CRP and CSF protein levels were predictors of more severe disease. This novel presentation of a large Norwegian cohort supports TBE as a serious disease in the southeastern region of Norway. The majority of hospitalized patients presented with encephalitis, and fewer presented with meningitis. Comorbidities, CRP and CSF protein levels were associated with more severe disease. Prosjekt #2,296,959 - The Norwegian Tick-borne Encephalitis Study - NOTES. Acute phase characteristics and long-term outcomes. - Cristin.

Scanning the aged to minimize missed injury: An EAST multicenter study.

Despite the high incidence of blunt trauma in older adults, there is a lack of evidence-based guidance for computed tomography (CT) imaging in this population. We aimed to identify an algorithm to guide use of a Pan-Scan (Head/C-spine/Torso) or a Selective Scan (Head/C-spine ± Torso). We hypothesized that a patient's initial history and exam could be used to guide imaging. We prospectively studied blunt trauma patients aged 65+ at 18 Level I/II trauma centers. Patients presenting >24 h after injury or who died upon arrival were excluded. We collected history and physical elements and final injury diagnoses. Injury diagnoses were categorized into CT body regions of Head/C-spine or Torso (chest, abdomen/pelvis, and T/L spine). Using machine learning and regression modeling as well as a priori clinical algorithms based, we tested various decision rules against our dataset. Our priority was to identify a simple rule which could be applied at the bedside, maximizing sensitivity (Sens) and negative predictive value (NPV) to minimize missed injuries. We enrolled 5,498 patients with 3,082 injuries. Nearly half (47.1%, n = 2,587) had an injury within the defined CT body regions. No rule to guide a Pan-Scan could be identified with suitable Sens/NPV for clinical use. A clinical algorithm to identify patients for Pan-Scan, using a combination of physical exam findings and specific high-risk criteria, was identified and had a Sens of 0.94 and NPV of 0.86 This rule would have identified injuries in all but 90 patients (1.6%) and would theoretically spare 11.9% (655) of blunt trauma patients a torso CT. Our findings advocate for Head/Cspine CT in all geriatric patients with the addition of torso CT in the setting of positive clinical findings and high-risk criteria. Prospective validation of this rule could lead to streamlined diagnostic care of this growing trauma population. Level 2, Diagnostic Tests or Criteria.

Sacubitril/valsartan for the treatment of non-obstructive hypertrophic cardiomyopathy: An open label randomized controlled trial (SILICOFCM).

Sacubitril/valsartan treatment reduces mortality and hospitalizations in heart failure with reduced ejection fraction but has limited application in hypertrophic cardiomyopathy (HCM). The aim of this study was to evaluate the effect of sacubitril/valsartan on peak oxygen consumption (VO2) in patients with non-obstructive HCM. This is a phase II, randomized, open-label multicentre study that enrolled adult patients with symptomatic non-obstructive HCM (New York Heart Association class I-III) who were randomly assigned (2:1) to receive sacubitril/valsartan (target dose 97/103 mg) or control for 16 weeks. The primary endpoint was a change in peak VO2. Secondary endpoints included echocardiographic measures of cardiac structure and function, natriuretic peptides and other cardiac biomarkers, and Minnesota Living with Heart Failure quality of life. Between May 2018 and October 2021, 354 patients were screened for eligibility, 115 patients (mean age 58 years, 37% female) met the study inclusion criteria and were randomly assigned to sacubitril/valsartan (n = 79) or control (n = 36). At 16 weeks, there was no significant change in peak VO2 from baseline in the sacubitril/valsartan (15.3 [4.3] vs. 15.9 [4.3] ml/kg/min, p = 0.13) or control group (p = 0.47). No clinically significant changes were found in blood pressure, cardiac structure and function, plasma biomarkers, or quality of life. In patients with HCM, a 16-week treatment with sacubitril/valsartan was well tolerated but had no effect on exercise capacity, cardiac structure, or function.