Prospective Treatment Study Research Articles

Impact of Donor Statin Treatment on Graft-versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation

Some retrospective studies have suggested that long-term donor statin use may protect against graft-versus-host disease (GVHD) in patients receiving cyclosporine (CSP)-based immunosuppression after allogeneic hematopoietic cell transplantation (HCT), but prospective studies of short-term treatment of donors with statin have shown conflicting results. We conducted 2 consecutive prospective clinical trials to assess whether donor statin treatment was associated with protection against severe acute GVHD (aGVHD). In a single-arm phase II trial (study 1), we evaluated whether short-term statin treatment of HLA-matched related donors for 14 days before HCT prevented grade III-IV aGVHD. In a prospective observational cohort study (study 2), we evaluated whether longer-term (>14 days) donor statin use was required for GVHD-protective effects. Study 1 was terminated after 6 of the 35 recipients (17%) developed grade III-IV GVHD. For study 2, we identified 135 patients whose unrelated donors had received long-term treatment with statins up to the time of HCT and 4942 patients whose donors had not received long-term statin treatment. The adjusted odds ratio for grade III-IV aGVHD (statin versus no statin) was .83 (95% confidence interval [CI], .46 to 1.50; P=.54). Multivariable analysis showed no statistically significant differences between the 2 groups in the risk of grade II-IV aGVHD, chronic GVHD, nonrelapse mortality, recurrent malignancy, or overall mortality. Among patients receiving CSP-based immunosuppression, including 35 with donors receiving long-term statin treatment and 973 with donors who did not receive statins, the adjusted odds ratio of grade III-IV aGVHD was .30 (95% CI, .07 to 1.35; P=.12). In study 1, short-term statin treatment of donors was ineffective in preventing grade III-IV GVHD. In study 2, in the prespecified subgroup of recipients given CSP-based immunosuppression, nondefinitive evidence suggested that donor statin use was associated with a reduced risk of severe aGVHD.

Diversity of Participants in Williams Syndrome Intervention Studies.

This study describes participant diversity in Williams syndrome (WS) intervention studies. A literature search was conducted to identify prospective treatment studies including participants with WS. Data was extracted on the reporting of and information provided on age, sex, cognitive ability, socioeconomic status, race, and ethnicity. Eleven eligible articles were identified. Reporting rates of demographic factors varied considerably, with the highest rates for age and sex (100%) and the lowest reporting rates for race (18%) and ethnicity (9%). Combining demographic data from the two studies that reported on race and/or ethnicity (n = 33), 88% of participants were White. The combined participant mean age was 20.9 years. There is a low frequency of reporting on several demographic factors including socioeconomic status, race, and ethnicity in WS intervention studies. There is a need for increased representation of racial and ethnic minority groups, older participants, and more cognitively impaired patients in WS research.

Comparison of Risk and Severity of Helicobacter Pylori Infection in Non-Native Versus US Native Pediatric Patients.

Helicobacter pylori (HP) infection is associated with gastritis, peptic ulcer disease (PUD) in the stomach and duodenum, and an increased risk of gastric cancer. The risk of infection, secondary symptoms, and negative outcomes is known to be increased in low- and middle-income countries and vastly less substantial in the United States and Europe. Current North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines recommend endoscopic diagnosis and susceptibility-guided therapy, which is not reflected by current adult guidelines for therapy. In this study, we complete a single-center retrospective review of HP risk by nativity status, as well as the results of the use of standard empiric therapy in HP and PUD patients. We retrospectively reviewed all endoscopies with patients aged 1-21 years with a known nativity status and identified all HP diagnoses. We also completed the classification of Kyoto scores and classified patients as gastritis versus PUD. Treatment records were obtained, as well as downstream documentation of the impact of empiric therapy. HP prevalence and severity were compared between non-native and native US populations. In total 332 patients were identified, with 59 HP diagnoses. However, 64 patients were immigrants, and 268 were US natives. Totally 39.1% of all immigrant patients had an endoscopically identified HP infection, compared to only 12.7% of US native patients (P < 0.01, relative risk 3.07). HP severity was worse in immigrant patients (Kyoto score 1.5 versus 0.89; P = 0.008). Empiric high-dose amoxicillin triple therapy was equally effective in reducing symptoms in gastritis versus PUD patients. Immigrant patients have a substantially higher risk and severity of HP infection than US natives. Empiric therapy remains highly effective at relieving symptoms. These findings in aggregate suggest that North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines may not adequately serve non-native pediatric patients, with an additional prospective multicenter study needed to confirm. In addition, a prospective study of treatment based on stool antigen tests, as well as a larger prospective study of empiric therapy, may suggest alterations to our approach in line with recent changes to adult Gastroenterology practice.

Brain morphometric features predict depression symptom phenotypes in late-life depression using a deep learning model.

Our objective was to use deep learning models to identify underlying brain regions associated with depression symptom phenotypes in late-life depression (LLD). Diagnosed with LLD (N = 116) and enrolled in a prospective treatment study. Cross-sectional. Structural magnetic resonance imaging (sMRI) was used to predict five depression symptom phenotypes from the Hamilton and MADRS depression scales previously derived from factor analysis: (1) Anhedonia, (2) Suicidality, (3) Appetite, (4) Sleep Disturbance, and (5) Anxiety. Our deep learning model was deployed to predict each factor score via learning deep feature representations from 3D sMRI patches in 34 a priori regions-of-interests (ROIs). ROI-level prediction accuracy was used to identify the most discriminative brain regions associated with prediction of factor scores representing each of the five symptom phenotypes. Factor-level results found significant predictive models for Anxiety and Suicidality factors. ROI-level results suggest the most LLD-associated discriminative regions in predicting all five symptom factors were located in the anterior cingulate and orbital frontal cortex. We validated the effectiveness of using deep learning approaches on sMRI for predicting depression symptom phenotypes in LLD. We were able to identify deep embedded local morphological differences in symptom phenotypes in the brains of those with LLD, which is promising for symptom-targeted treatment of LLD. Future research with machine learning models integrating multimodal imaging and clinical data can provide additional discriminative information.

CASSIOPE: A prospective noninterventional study of cabozantinib treatment following prior vascular endothelial growth factor (VEGF) -targeted therapy in patients with advanced renal cell carcinoma (aRCC).

4529 Background: Cabozantinib is a tyrosine kinase inhibitor approved as monotherapy for aRCC in the USA, and as first-line therapy for patients with intermediate or poor risk aRCC, or after previous VEGF-targeted therapy in Europe. In the METEOR trial, a substantial proportion of patients required cabozantinib dose modifications. We report a real-world study of cabozantinib use for aRCC. Methods: CASSIOPE was a non-interventional prospective cohort study (conducted Apr 2018–May 2022; NCT03419572). Enrollment spanned 11 European countries (91 sites) where cabozantinib is marketed for aRCC. Patients had aRCC and had received ≥ 1 prior VEGF-targeted therapy (excluding cabozantinib). Decision to initiate cabozantinib was made prior to enrolment. The primary endpoint was cabozantinib usage (dose interruptions, reductions or discontinuations due to AEs) in the second- (2L) or later- (≥ 3L) line settings. Secondary endpoints included objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and tolerability. Data were analyzed descriptively for patients with safety follow-up after ≥ 1 cabozantinib dose. Results: In total, 679 patients were included (73.0% male; median [range] age 67.0 [29–93] yrs; 85.7% clear-cell aRCC; 80.3% prior nephrectomy). Median (range) observation period was similar for 2L (n = 335; 8.51 [0.2–15.4] mo) and ≥ 3L cabozantinib (n = 343; 9.26 [0.0–15.0] mo). Usage data are shown. For the overall population, ORR (95% CI) and median (95% CI) PFS according to local assessment were 21.9% (17.5%–26.9%) and 7.8 (6.3–8.7) mo for 2L cabozantinib, and 38.0% (32.7%–43.5%) and 8.7 (7.6–9.6) mo for ≥ 3L cabozantinib. Median OS (95% CI) was 13.0 (12.6–not calculated [NC]) mo for 2L, and 17.1 (13.8–NC) mo for ≥ 3L cabozantinib. Most patients (90.4%) reported treatment-related AEs (Grade 1, 71.1%; Grade 2, 70.3% of patients), most commonly any grade diarrhea (52.4%), palmar-plantar erythrodysesthesia syndrome (27.2%), decreased appetite (25.5%), hypertension (21.9%), asthenia (21.6%), fatigue (20.5%) and nausea (20.3%). Conclusions: In this real-world study, tolerability of ≥ 2L cabozantinib was consistent with the METEOR trial safety profile: cabozantinib dose modifications due to AEs were common, but discontinuation rates due to AEs were substantially less frequent. Cabozantinib activity was maintained across lines. Clinical trial information: NCT03419572 . [Table: see text]

Diet quality and anthropometric indices of patients undergone bariatric surgery: the prospective Tehran obesity treatment study

BackgroundPatients undergone bariatric surgery (BS) has long-term risks including decrease in diet quality, nutritional deficiencies and weight regain. This study focus on assessing dietary quality and food group components in patients one year after BS, the relationship between dietary quality score and anthropometric indices, and also evaluating the trend of body mass index (BMI) of these patients three years after BS.MethodsA total of 160 obese patients (BMI ≥ 35 kg/m2) were undergone sleeve gastrectomy (SG) (n = 108) or gastric bypass (GB) (n = 52), participated in this study. They were assessed for dietary intakes using three 24-hour dietary recalls one year after surgery. Dietary quality was assessed using food pyramid for post BS patients and healthy eating index (HEI). Anthropometric measurements were taken pre-surgery and 1, 2 and 3 years after operation.ResultsThe mean age of patients was 39.9 ± 11 years (79% female). The mean ± SD percentage of excess weight loss was 76.6 ± 21.0 one year after surgery. Intake patterns are generally (up to 60%) not consistent with the food pyramid. The mean total HEI score was 64 ± 12 out of 100. More than %60 of participants is exceeding the recommendations for saturated fat and sodium. The HEI score did not show significant relationship with anthropometric indices. The mean of BMI in SG group increased over three years of follow up, while in GB group, there were no significant differences in BMI during three years of follow up.ConclusionsThese findings showed that patients had not healthy pattern intake one year after BS. Diet quality did not show significant relationship with anthropometric indices. The trend of BMI three years after surgery was different based on surgery types.

Urine Metabolomic Signature of People Diagnosed with Balkan Endemic Nephropathy and Other Types of Chronic Kidney Disease Compared with Healthy Subjects in Romania

Metabolomic analysis methods were employed to determine biomarkers for various chronic kidney diseases (CKDs). Modern analytical methods were developed and applied successfully to find a specific metabolomic profile in urine samples from CKD and Balkan endemic nephropathy (BEN) patients. The aim was to explore a specific metabolomic profile defined by feasible/easy-to-identify molecular markers. Urine samples were collected from patients with CKDs and BEN, and from healthy subjects from endemic and nonendemic areas in Romania. Metabolomic analysis of urine samples, extracted by the liquid-liquid extraction (LLE) method, was performed by gas chromatography-mass spectrometry (GC-MS). The statistical exploration of the results was performed through a principal component analysis (PCA) evaluation. Urine samples were statistically analyzed using a classification based on six types of metabolites. Most urinary metabolites are distributed in the center of a loading plot, meaning that these compounds do not represent significant markers for BEN. One of the most frequent and higher-concentration urinary metabolites in BEN patients was p-Cresol, a phenolic compound that implies a severe injury of the renal filtration function. The presence of p-Cresol was associated with protein-bound uremic toxins, which have specific functional groups such as indole and phenyl. In prospective studies for future investigation, prevention, and disease treatment, we suggest a larger sample size, sample extraction using other methods, and analysis using other chromatography techniques coupled with mass spectrometry, which can generate a more significant data set for statistical analysis.

Prospective Observational Study of Prevalence, Assessment and Treatment of Pancreatic Exocrine Insufficiency in Patients with Inoperable Pancreatic Malignancy (PANcreatic Cancer Dietary Assessment-PanDA).

Pancreatic exocrine insufficiency (PEI) in patients with advanced pancreatic cancer (aPC) is well documented, but there is no consensus regarding optimal screening. Patients diagnosed with aPC referred for palliative therapy were prospectively recruited. A full dietetic assessment (including Mid-Upper Arm Circumference (MUAC), handgrip and stair-climb test), nutritional blood panel, faecal elastase (FE-1) and 13C-mixed triglyceride breath tests were performed. prevalence of dietitian-assessed PEI (demographic cohort (De-ch)); design (diagnostic cohort (Di-ch)) and validation (follow-up cohort (Fol-ch)) of a PEI screening tool. Logistic and Cox regressions were used for statistical analysis. Between 1 July 2018 and 30 October 2020, 112 patients were recruited (50 (De-ch), 25 (Di-ch) and 37 (Fol-ch)). Prevalence of PEI (De-ch) was 64.0% (flatus (84.0%), weight loss (84.0%), abdominal discomfort (50.0%) and steatorrhea (48.0%)). The derived PEI screening panel (Di-ch) included FE-1 (normal/missing (0 points); low (1 point)) and MUAC (normal/missing (>percentile 25) (0 points); low (2 points)) and identified patients at high-risk (2-3 total points) of PEI [vs. low-medium risk (0-1 total points)]. When patients from the De-ch and Di-ch were analysed together, those classified by the screening panel as "high-risk" had shorter overall survival (multivariable Hazard Ratio (mHR) 1.86 (95% CI 1.03-3.36); p-value 0.040). The screening panel was tested in the Fol-ch; 78.4% patients classified as "high-risk", of whom 89.6% had dietitian-confirmed PEI. The panel was feasible for use in clinical practice (64.8% patients completed all assessments), with high acceptability (87.5% would repeat it). Most patients (91.3%) recommended dietetic input for all patients with aPC. PEI is present in most patients with aPC; early dietetic input provides a holistic nutritional overview, including, but not limited to, PEI. This proposed screening panel may help to prioritise those at higher risk of PEI, requiring urgent dietitian input. Its prognostic role needs further validation.

Video enhanced visual analysis of hemiparetic gait muscle selection: A pilot study

This paper summarizes the use of video enhanced visual analysis (VEVA) as a muscle selection assistance method for abnormal foot postures in adults with upper motor neuron syndrome (UMNS) treated with botulinum neurotoxin (BoNT-A) in a real-world setting.This pilot study used a prospective treatment study design with persons in an outpatient, rehabilitation hospital. Participants had acquired brain injury (ABI) of >6-month duration who had a spastic ankle foot deformity amenable to treatment with botulinum toxin A and able to independently ambulate a minimum of 10 m. Participants were evaluated before abobotulinumtoxinA injection (500 U–1500 U) to the identified lower limb muscles and four to five weeks post injection. Main Outcome Measures: Temporal spatial data (self-selected and maximal walking velocities (SSWV/MWV); step length and stance time); Modified Ashworth Scale (MAS); Tardieu Scale (TS) and ankle Passive Range of Motion (PROM) change from baseline to follow-up (f/u).Data is presented on ten of the eleven consecutive participants enrolled in the study. One participant withdrew due to study unrelated opposite ankle pain before reassessment. Mean SSWV increased post treatment by 21% in the barefoot condition and 8% when walking with shoes. For the MWV condition, there was a 15% mean increase post treatment in the barefoot condition and 10% when walking with shoes. Participants showed improved symmetry in step length and stance time in both post-treatment walking conditions. Ankle MAS and TS improved with knee flexed or extended. Ankle PROM increased post treatment with knee flexed by 8° and knee extended by 11.7°. VEVA in addition to clinical evaluation appears to facilitate muscle identification and selection of ankle deformities for treatment with BoNT-A. Our findings show marked improvement in ankle MAS, TS and PROM as indicators of pharmacological activity and increase in SSWV as a marker of functional improvement.

Prospective Study of Percutaneous Ozone Treatment of Cervicobrachial Neuralgia (CBN) Due To Disc Herniation

Introduction: In case of conservative treatment failure in cervical disc herniation, many surgical procedures are offered. Percutaneous surgery seems to have the best benefits. Ozone discolysis is one of the emerging treatments. However, no standardized procedure for this discolysis is yet available. The purpose of this work was to describe our procedure that we have been practicing since 2016 and to assess its results. Methods: From July 2016 to June 2021, we conducted a prospective study in the neurosurgery department of Yalgado Ouedraogo. All consenting patients with cervical disc herniation and conservative treatment failure who have benefited ozone discolysis were included. These patients were reassessed (VAS and neurological examination) at one week, two weeks, one month, three months. Results: Thirty-four cases were retained, representing 39.5% of cervical disc herniation surgeries. Main indications were disabling cervicobrachial neuralgia (CBN) (88.2%) and hyperalgesia CBN (8.8%). Discolysis concerned 1 (52.9%); 2 (29.4%) and 3 (17.6%) levels. At 1 week, 2 weeks, 1 month and 3 months after discolysis were respectively noted 61.8%; 85.3%; 85.3% and 91.2% asymptomatic patients. Pending conventional surgery, discolysis was performed in 1 case (2.9%) of left C5 root plegia resulting in total recovery. No complications were noted. No complications were noted. Conclusion: Cervical discolysis with ozone had very satisfactory results with certain benefits for the patient and his surgeon. It was a good alternative to surgery in our country where the neurosurgeon is the first and only resort in case of cervical disc herniation with failure of conservative treatment.

Efficacy of elotuzumab for multiple myeloma in reference to lymphocyte counts and kappa/lambda ratio or B2 microglobulin

Novel therapeutic drugs have dramatically improved the overall survival of patients with multiple myeloma. We sought to identify the characteristics of patients likely to exhibit a durable response to one such drug, elotuzumab, by analyzing a real-world database in Japan. We analyzed 179 patients who underwent 201 elotuzumab treatments. The median time to next treatment (TTNT) with the 95% confidence interval was 6.29 months (5.18–9.20) in this cohort. Univariate analysis showed that patients with any of the following had longer TTNT: no high risk cytogenic abnormalities, more white blood cells, more lymphocytes, non-deviated κ/λ ratio, lower β2 microglobulin levels (B2MG), fewer prior drug regimens, no prior daratumumab use and better response after elotuzumab treatment. A multivariate analysis showed that TTNT was longer in patients with more lymphocytes (≥ 1400/μL), non-deviated κ/λ ratio (0.1–10), lower B2MG (< 5.5 mg/L) and no prior daratumumab use. We proposed a simple scoring system to predict the durability of the elotuzumab treatment effect by classifying the patients into three categories based on their lymphocyte counts (0 points for ≥ 1400/μL and 1 point for < 1400/μL) and κ/λ ratio (0 points for 0.1–10 and 1 point for < 0.1 or ≥ 10) or B2MG (0 points for < 5.5 mg/L and 1 point for ≥ 5.5 mg/L). The patients with a score of 0 showed significantly longer TTNT (p < 0.001) and better survival (p < 0.001) compared to those with a score of 1 or 2. Prospective cohort studies of elotuzumab treatment may be needed to validate the usefulness of our new scoring system.

External Validation of the IHS4-55 in a European Antibiotic-Treated Hidradenitis Suppurativa Cohort

Background: Previously, a new dichotomous outcome was developed, calculated as 55% reduction in the International Hidradenitis Suppurativa 4 (IHS4-55) score. It was validated in datasets of adalimumab and placebo-treated HS patients. External validation is an important aspect of clinical outcomes. Objectives: We aimed to externally validate the novel dichotomous IHS4-55 in a non-biologic treated dataset of HS patients. Methods: Data from a previously published European-wide prospective clinical study of antibiotic treatment of HS patients were used to assess the association of IHS4-55 achievement with individual reduction in inflammatory nodules, abscesses, and draining tunnels. Moreover, the associations between IHS4-55 positivity and achievement of the minimal clinically important differences (MCIDs) for Dermatology Life Quality Index (DLQI), Numerical Rating Scale (NRS) Pain, and NRS Pruritus were analyzed. Results: Data were obtained from 283 individual patients, of which 36.4% (103/283) were treated with clindamycin and rifampicin and 63.6% (180/283) with tetracyclines for 12 weeks. Achievers of the IHS4-55 demonstrated a significant reduction the counts of inflammatory nodules, abscesses, and draining tunnels (all p < 0.001). Additionally, IHS4-55 achievers had an odds ratio for achieving the MCID of DLQI, NRS Pain, and NRS Pruritus of 2.16 (95% CI 1.28–3.65, p < 0.01), 1.79 (95% CI 1.10–2.91, p < 0.05), and 1.95 (95% CI 1.18–3.22, p < 0.01), respectively. Conclusions: This study shows the external validity of the novel IHS4-55 by demonstrating a significant association between IHS4-55 achievement and a reduction in inflammatory lesion counts as well as achievement of MCIDs for DLQI, NRS Pain, and NRS Pruritus in an antibiotic-treated cohort. These findings support the use of the IHS4-55 as a novel primary outcome measure in clinical trials.

Factors associated with refusal of preventive therapy after initial willingness to accept treatment among college students with latent tuberculosis infection in Shandong, China

BackgroundPreventive therapy of latent tuberculosis infection (LTBI) is an important component of tuberculosis (TB) control. Research on acceptance of TB preventive therapy (TPT) is an important topic. Current studies focus on acceptability and compliance. However, it is unclear whether LTBI patients will start TPT after accepting treatment. The study assessed the factors associated with TPT refusal after initial willingness to accept treatment.MethodsData were derived from a baseline survey of prospective study of LTBI treatment among college students in Shandong Province, China. A total of 723 students initially willing to accept TPT were included in the analysis. Stepwise logistic regression was used to explore the individual- and family-level characteristic variables that factors associated with TPT refusal after initial willingness to accept treatment.ResultsOf the 723 LTBI college students who initially had acceptance willingness, 436 (60.3%) finally refused TPT. At the individual level, non-medical students were more likely to refuse TPT [odds ratio (OR) = 4.87, 95% confidence interval (CI): 3.10–7.67)], as were students with moderate physical activity (OR = 1.45, 95% CI: 1.04–2.04). Students with boarding experience (OR = 0.49, 95% CI: 0.31–0.78) and a high level of knowledge about TB (OR = 0.97, 95% CI: 0.95–0.99) were less likely to refuse TPT. At the family level, those with high father’s educational level (OR = 1.50, 95% CI: 1.07–2.10) or high household income (OR = 1.80, 95% CI: 1.20–2.71) were more likely to refuse TPT after initially accepting treatment.ConclusionsFactors associated with TPT refusal after initial willingness to accept treatment, such as personal (type of students, physical activity, boarding experiences, knowledge of TB) and family characteristics (father’s education level, household income) among college student with LTBI, might help identify persons for whom tailored interventions could improve the start of LTBI treatment.

Resultados a longo prazo após tratamento endovascular da aorta em pacientes com doenças da aorta torácica

Abstract Background Endovascular treatments for thoracic aortic diseases have been adopted rapidly, and long-term studies are relevant for durability evaluation. Objective To evaluate the long-term results of a prospective observational study of endovascular treatment in patients with thoracic aortic diseases who underwent percutaneous implantation of self-expandable endoprostheses. Methods Procedural success was defined as the absence of endoleak into the aneurysm or dissection-induced false lumen, no migration, and no conversion to open surgery. Intraoperative, postoperative, and late postoperative outcomes were evaluated in terms of complications, mortality, and evolution of the endoprosthesis over a follow-up of up to 179 months (median: 46 months). Results A total of 150 endoprostheses were implanted in 112 patients. Primary success was observed in 100 (82.14%) patients. Immediate mortality occurred in 7 patients (6.25%). Late mortality occurred in 31 patients (27.68%), 10 (8.93%) of whom died from cardiovascular causes, 12 (10.71%) from non-cardiovascular causes, and 2 (1.78%) from natural causes, while 7 (6.25%) had no diagnosis for cause of death. Types I, II, and IV endoleaks occurred during hospitalization in 4 (3.57%), 5 (4.46%), and 3 (2.68%) patients, respectively. Late types I and IV endoleaks occurred in 5 (4.46%) and 3 (2.68%) patients respectively. Twenty-two patients (19.64%) had clinical complications in the immediate postoperative period. Actuarial survival free from death from cardiovascular causes was 79.3% (95% confidence interval, 67.0-91.7%) at 132 months. Conclusions The low levels of intraoperative and postoperative complications demonstrate that endovascular treatment is safe and effective. The high rate of late survival for these critically ill patients indicates that the endovascular technique is beneficial for treatment of thoracic aortic diseases in terms of long-term outcomes.

Vascular endothelial growth factor, tissue factor, coagulation and fibrinolysis markers in slow-flow vascular malformations: a prospective study of treatment with sirolimus.

Slow-flow vascular malformations (VMs), especially those with venous components, can be complicated by localized intravascular coagulopathy (LIC), responsible for pain and impaired quality of life. Several studies have shown the effectiveness of mTOR inhibitors (especially sirolimus) on slow-flow VMs but its effect on coagulation has been poorly studied, especially in children. Our study shows that venous and combined VMs are associated with coagulation abnormalities and provides novel evidence that sirolimus improves coagulopathy in venous malformations. However we did not clearly evidence predictive biomarkers of response to sirolimus but this is the first study attempting to highlight predictive markers of response to sirolimus.

Preliminary study of elastic-tension digital neoprene orthoses for proximal interphalangeal joint flexion contracture

Flexion contracture of the proximal interphalangeal joint (PIPJ) is one of the most frequent complications in finger trauma. Orthoses are the most widely used method to optimize total end-range time (TERT). No previous studies showed that an elastic tension orthosis could be applied for longer than 12 h. We aimed to demonstrate that the elastic-tension digital neoprene orthosis (ETDNO) can achieve higher TERT and therefore better range of motion than other elastic-tension orthoses (ETO) described in the literature. A prospective study of treatment of PIPJ flexion contracture included 10 PIP joints in 8 patients who met the selection criteria. They were instructed to use the ETDNO for around 23 h per day as far as possible, during a period of 3 weeks. Patients reported a mean TERT of 20.6 h a day. PIPJ contracture improved by a mean Torque Range of Motion (TROM) of 23.5° at 500 g and 22.9° at 800 g of passive extension force during the 3-week treatment. Based on the results of this study, the ETDNO appears to offer a highly effective approach for improving PIPJ flexion contracture, increasing range of motion in extension. ETDNO’s efficacy probably lies in the significantly improved comfort and low-profile design, enabling excellent compliance and thus optimizing TERT. Level of evidenceLevel III.

Possible association between vitamin B12 deficiency and restless legs syndrome

Restless Legs Syndrome (RLS) can be defined as a sleep disorder. However, whether changes in the serum vitamin B12 levels are involved in the pathophysiological mechanism of RLS remains unclear. Our study aimed to determine whether vitamin B12 levels are independently related to the occurrence of RLS. The serum vitamin B12 levels of 80 patients with RLS and 80 age- and gender-matched healthy controls (HC) were retrospectively analyzed. Serum vitamin B12 levels in the RLS group were significantly reduced, while the levels of creatinine, and homocysteine were higher (P<0.05). In addition, multivariate logistic regression revealed serum vitamin B12 to be independently associated with RLS (p<0.05; odds ratio=0.97; 95% confidence interval: 0.96-0.98). Pearson correlation analysis indicated that serum vitamin B12 level was negatively correlated with the International Restless Legs Scales (IRLS) score, and the 24-item Hamilton Depression Rating Scale (HAMD24) score (r=-0.025, P=0.023, r=-0.295, P=0.001). Patients with RLS had significant vitamin B12 deficiency compared to HC. Such deficiency significantly affects severity of symptoms and depression symptoms. In addition, decreased serum vitamin B12 levels are independently associated with the development of RLS, which illustrates the complex relationship between vitamin B12 and RLS. Prospective vitamin B12 treatment studies are needed to confirm this relationship and to evaluate the efficacy of vitamin B12 as a treatment for RLS patients.

Therapeutics prior to mesenchymal stromal cell therapy improves outcome in equine orthopedic injuries.

Mesenchymal stromal (stem) cells (MSCs) have been studied to treat many common orthopedic injuries in horses. However, there is limited information available on when and how to use this treatment effectively. The aim of this retrospective study is to report case features, treatment protocols, and clinical outcomes in horses treated with MSCs. 65 horses presenting with tendinous, ligamentous, and articular injuries, and treated with MSCs prepared by a single laboratory between 2016 and 2019. Outcome information was available for 26 horses. Signalment, clinical signs, diagnostic methods, treatment protocol features (prior and concurrent therapies, cell origin, dose, application site and number), and effective outcomes were analyzed. The analysis was focused on comparing the effect of different MSC treatment protocols (eg, autologous vs allogeneic) on outcome rather than the effectiveness of MSC treatment. MSC treatment resulted in 59.1% (clinical lameness) to 76.9% (imaging structure) improvement in horses with diverse ages, breeds, sex, and lesions. The use of other therapeutic methods before MSC application (eg, anti-inflammatories, shockwave, laser, icing, resting, bandage and stack wrap, intra-articular injections, and/or surgical debridement) was shown to be statistically more effective compared to MSCs used as the primary therapeutic procedure (P < .05). Autologous versus allogeneic treatment outcomes were not significantly different. A prospective MSC treatment study with standardization and controls to evaluate the different features of MSC treatment protocols is needed. The various case presentations and treatment protocols evaluated can be used to inform practitioners who are currently using MSCs in clinical practice.

6 Extended-release Naltrexone and Case Management for Treatment of Alcohol Used Disorder in the Emergency Department

ObjectivesAssess the feasibility of initiating treatment for alcohol use disorder with extended-release Naltrexone (XR-Naltrexone) and case management services in the emergency department (ED), and estimate the intervention’s impact on daily alcohol consumption (DAC) and quality of life (QOL).DesignThis is a twelve week, prospective open-label single-arm study of a multimodal treatment for AUD consisting of monthly XR-naltrexone injections and case management services initiated at an single urban academic ED. Participants were actively drinking adult ED patients with known or suspected AUD and AUDIT-C score > 4. The main feasibility outcomes were the proportions of participants enrolled/approached, completed/enrolled, and continuing naltrexone after the trial/enrolled. Efficacy outcomes were the change in DAC (drinks/day, 14g ethanol/drink) measured by 14-day timeline follow back, and the change in QOL measured with single-item Kemp QOL scale.Results179 patients were approached and 32 enrolled (18%). 25/32 (78%) completed all visits, 22/32 (69%) continued naltrexone after the trial. Baseline DAC was 7.6 drinks/day (IQR 4.5, 13.4) and mean QOL 3.6 (SD 1.7) on a 7-point scale. After 12 weeks of treatment, median DAC change was -7.5 drinks/day (Hodges- Lehman 95% CI -8.6, -5.9). Mean QOL change was 1.2 points (95% CI 0.5, 1.9; P< 0.01).ConclusionsWe found initiation of treatment of AUD with XR-naltrexone and case management is feasible in an ED setting and observed significant reductions in drinking with improved quality of life in the short term. Multi-center RCTs are needed to further validate these findings.Trial Registrationclinicaltrials.gov NCT04094584No, authors do not have interests to disclose ObjectivesAssess the feasibility of initiating treatment for alcohol use disorder with extended-release Naltrexone (XR-Naltrexone) and case management services in the emergency department (ED), and estimate the intervention’s impact on daily alcohol consumption (DAC) and quality of life (QOL). Assess the feasibility of initiating treatment for alcohol use disorder with extended-release Naltrexone (XR-Naltrexone) and case management services in the emergency department (ED), and estimate the intervention’s impact on daily alcohol consumption (DAC) and quality of life (QOL). DesignThis is a twelve week, prospective open-label single-arm study of a multimodal treatment for AUD consisting of monthly XR-naltrexone injections and case management services initiated at an single urban academic ED. Participants were actively drinking adult ED patients with known or suspected AUD and AUDIT-C score > 4. The main feasibility outcomes were the proportions of participants enrolled/approached, completed/enrolled, and continuing naltrexone after the trial/enrolled. Efficacy outcomes were the change in DAC (drinks/day, 14g ethanol/drink) measured by 14-day timeline follow back, and the change in QOL measured with single-item Kemp QOL scale. This is a twelve week, prospective open-label single-arm study of a multimodal treatment for AUD consisting of monthly XR-naltrexone injections and case management services initiated at an single urban academic ED. Participants were actively drinking adult ED patients with known or suspected AUD and AUDIT-C score > 4. The main feasibility outcomes were the proportions of participants enrolled/approached, completed/enrolled, and continuing naltrexone after the trial/enrolled. Efficacy outcomes were the change in DAC (drinks/day, 14g ethanol/drink) measured by 14-day timeline follow back, and the change in QOL measured with single-item Kemp QOL scale. Results179 patients were approached and 32 enrolled (18%). 25/32 (78%) completed all visits, 22/32 (69%) continued naltrexone after the trial. Baseline DAC was 7.6 drinks/day (IQR 4.5, 13.4) and mean QOL 3.6 (SD 1.7) on a 7-point scale. After 12 weeks of treatment, median DAC change was -7.5 drinks/day (Hodges- Lehman 95% CI -8.6, -5.9). Mean QOL change was 1.2 points (95% CI 0.5, 1.9; P< 0.01). 179 patients were approached and 32 enrolled (18%). 25/32 (78%) completed all visits, 22/32 (69%) continued naltrexone after the trial. Baseline DAC was 7.6 drinks/day (IQR 4.5, 13.4) and mean QOL 3.6 (SD 1.7) on a 7-point scale. After 12 weeks of treatment, median DAC change was -7.5 drinks/day (Hodges- Lehman 95% CI -8.6, -5.9). Mean QOL change was 1.2 points (95% CI 0.5, 1.9; P< 0.01). ConclusionsWe found initiation of treatment of AUD with XR-naltrexone and case management is feasible in an ED setting and observed significant reductions in drinking with improved quality of life in the short term. Multi-center RCTs are needed to further validate these findings. We found initiation of treatment of AUD with XR-naltrexone and case management is feasible in an ED setting and observed significant reductions in drinking with improved quality of life in the short term. Multi-center RCTs are needed to further validate these findings.

Prospective comparison of one-year survival in patients treated operatively and nonoperatively for spinal metastatic disease: results of the Prospective Observational study of Spinal metastasis Treatment (POST)

<h3>BACKGROUND CONTEXT</h3> Several investigations have touted that surgery for spinal metastases not only preserves ambulatory ability, but also improves survival. Many of these investigations may be confounded by selection and indication bias. Controversy remains regarding the utility of surgery for patients with spinal metastases and no neurologic deficits. <h3>PURPOSE</h3> We planned an analysis that accounted for confounding by indication and compared patients treated operatively and nonoperatively for spinal metastases who were enrolled in the Prospective Observational study of Spinal metastasis Treatment (POST). <h3>PATIENT SAMPLE</h3> We considered 87 instances of surgical intervention and 122 cases of nonoperative treatment enrolled between 2017-2019. <h3>OUTCOME MEASURES</h3> Survival at one year following treatment initiation. <h3>METHODS</h3> The primary outcome was survival at one year following treatment initiation. The primary predictor was treatment, categorized as operative or nonoperative management. Crossovers were handled via statistical cloning. Unadjusted comparisons between the operative and nonoperative cohorts were made using chi-square tests for categorical variables and the Wilcoxon rank-sum test for non-parametric, continuous data. Survival was assessed using Kaplan-Meier curves. We developed a propensity score around the likelihood for surgical intervention using age, biologic sex, co-morbidities, primary tumor, neurologic symptoms and NESMS at presentation based on our conceptual model. The propensity score was used in final adjusted models for survival at one year. <h3>RESULTS</h3> Fifty percent of the cohort died by one year following presentation. In the operative group, the mortality rate was 46% at one year, as compared to 54% in the nonoperative cohort. This represented a 25% reduction in the odds of mortality (OR 0.75; 95% CI 0.43, 1.30) but was not significantly different (p=0.3). Following propensity score adjustment, surgical intervention offered a 28% reduction in the odds of mortality (OR 0.72; 95% CI 0.40, 1.29) but still did not demonstrate statistical significance (p=0.27). <h3>CONCLUSIONS</h3> While it is interesting that propensity adjustment slightly increased the advantage for surgery, the estimated 25%-28% reduction in the odds of mortality should be balanced against the risks associated with these high-intensity interventions and the relatively high mortality rate, irrespective of treatment strategy. This may be especially important in instances where the metastatic process is largely asymptomatic. <h3>FDA DEVICE/DRUG STATUS</h3> This abstract does not discuss or include any applicable devices or drugs.