Treatment with fostamatinib in patients with immune thrombocytopenia: Experience from the Andalusian region in Spain-The Fostasur Study.

Immune thrombocytopenia (ITP) is characterized by low platelet counts (PLTs) and an increased risk of bleeding. Fostamatinib, a spleen tyrosine kinase inhibitor, has been approved as a second-line treatment for ITP. Real-world data on fostamatinib are lacking. This observational, retrospective, multicentre study, conducted in the Andalusia region of Spain, evaluated 44 adult primary ITP patients (47.7% female; median age 58 years; newly diagnosed ITP 6.8%; persistent 13.6%; chronic 79.5%; median four prior treatments) after ≥ 4 weeks of fostamatinib therapy. The median PLT at the initiation of fostamatinib was 15 × 109/L. Common reasons for starting fostamatinib were refractoriness or intolerance to prior therapy, oral medication preference, history of thrombosis and cardiovascular risk. Dosing was individualized based on efficacy and tolerance. After 2 weeks, global response rate was 56.8% (response and complete response). Response rates were 70.5%, 62.5% and 64% at 4 weeks, 12 weeks and at the end of the study respectively. Adverse events were mild, and no patients discontinued as a result. This real-world study demonstrated a response rate similar to fostamatinib as seen in the pivotal clinical trials while including newly diagnosed patients and allowing for individualized dosing.

Robotic-assisted vertical sleeve gastrectomy in adolescents: Do BMI limits apply?

BACKGROUND: Robotic-assisted vertical sleeve gastrectomy (VSG) in adolescent patients has been shown to have comparable outcomes to laparoscopic VSG. Recent data suggests that metabolic and bariatric surgery (performed using robotic and laparoscopic techniques) in patients with BMI ≥ 50 kg/m2 have a higher risk of adverse events compared to those with BMI < 50 kg/m2. The aim of this study was to compare the outcomes of robotic-assisted VSG in adolescents with a BMI above and below 50 kg/m2. METHODS: A retrospective analysis of all adolescents undergoing robotic-assisted VSG between January 2014 and December 2020. Subjects were categorized based on preoperative BMI; Group 1 (BMI < 50 kg/m2) or Group 2 (BMI ≥ 50 kg/m2). Data collection included patient demographics, preoperative BMI, total operative time, access time (i.e., total time for port-placement), 30 day complications, and 30 day hospital readmissions. Analysis was performed using chi-square, Fisher's Exact, and student t-test. RESULTS: Total of 115 subjects (Group 1 N = 64 and Group 2 N = 51) were included. No differences in age or ethnicity were detected; however, Group 2 had a higher percentage of male patients (27.5% vs. 4.7%, respectively, p = 0.001). Mean operative times (Group 1 = 122.2 min vs. Group 2 = 121.6 min) and access times (Group 1 = 19.1 min vs. Group 2 = 19.7 min) were similar between groups. Thirty day complication rates were similar between groups (p = 0.133); however, there was a higher rate of hospital readmission in Group 1. CONCLUSION: While recent data demonstrate an increased likelihood of adverse events occurring among patients with BMI ≥ 50 kg/m2 undergoing robotic surgery, we observed no differences in intraoperative or early postoperative outcomes based on BMI in this robotic-assisted pediatric cohort.

Management of acquired hemophilia A: results from the Spanish registry.

The Spanish Acquired Hemophilia A (AHA) Registry is intended to update the status of AHA in Spain. One hundred and fifty-four patients were included and retrospectively followed for a median of 12 months. Patients were predominantly male (56.3%), with median age at diagnosis of 74 years. AHA was more frequently idiopathic (44.1%) and autoimmune disorder-associated (31.7%). Thirty-four percent of patients were on antithrombotic therapy at diagnosis. Hemostatic treatment was used in 70% of patients. Recombinant activated factor VII was more frequently infused (60.3% vs 20.6% activated prothrombin complex concentrate). Only 1 patient did not achieve control of hemorrhage. Complete remission (CR) was achieved by 84.2% of cases after immunosuppressive therapy. Steroids alone were less efficient than the other strategies (68.2% vs 87.2%, P = .049), whereas no differences existed among these (steroids/cyclophosphamide, 88.5%, vs steroids/calcineurin inhibitors, 81.2%, vs rituximab-based regimens, 87.5%). Female sex and high inhibitor levels influenced CR negatively. Thirty-six deaths (23.8%) were reported. Main causes of death were infection (15 patients, 9.9%) and hemorrhage (5 patients, 3.3%). All hemorrhage-related and half the infection-related deaths occurred within 2 months of diagnosis. Prior antithrombotic therapy was inversely associated with survival, irrespective of age. Median age of nonsurvivors was significantly higher (79 vs 73 years in survivors). Patients dying of infection were older than the other nonsurvivors (85 vs 78 years). In summary, fatal infection in the first months is common in our series. Antithrombotic therapy is associated with mortality. Particular care should be taken to avoid misdiagnosis.

Pediatric trauma triage: A Pediatric Trauma Society Research Committee systematic review.

BACKGROUND: Significant variability exists in the triage of injured children with most systems using mechanism of injury and/or physiologic criteria. It is not well established if existing triage criteria predict the need for intervention or impact morbidity and mortality. This study evaluated existing evidence for pediatric trauma triage. Questions defined a priori were as follows: (1) Do prehospital trauma triage criteria reduce mortality? (2) Do prehospital trauma scoring systems predict outcomes? (3) Do trauma center activation criteria predict outcomes? (4) Do trauma center activation criteria predict need for procedural or operative interventions? (5) Do trauma bay pediatric trauma scoring systems predict outcomes? (6) What secondary triage criteria for transfer of children exist? METHODS: A structured, systematic review was conducted, and multiple databases were queried using search terms related to pediatric trauma triage. The literature search was limited to January 1990 to August 2019. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology was applied with the methodological index for nonrandomized studies tool used to assess the quality of included studies. Qualitative analysis was performed. RESULTS: A total of 1,752 articles were screened, and 38 were included in the qualitative analysis. Twelve articles addressed questions 1 and 2, 21 articles addressed question 3 to 5, and five articles addressed question 6. Existing literature suggest that prehospital triage criteria or scoring systems do not predict or reduce mortality, although selected physiologic parameters may. In contrast, hospital trauma activation criteria can predict the need for procedures or surgical intervention and identify patients with higher mortality; again, physiologic signs are more predictive than mechanism of injury. Currently, no standardized secondary triage/transfer protocols exist. CONCLUSION: Evidence supporting the utility of prehospital triage criteria for injured children is insufficient, while physiology-based trauma system activation criteria do appropriately stratify injured children. The absence of strong evidence supports the need for further prehospital and secondary transfer triage-related research. LEVEL OF EVIDENCE: Systematic review study, level II.

Single incision laparoscopic proficiency correlates with residency training level.

BACKGROUND: With experience, certain psychomotor skills should translate from standard laparoscopy to single-incision laparoscopy (SIL). We proposed to compare all surgical postgraduate year (PGY) levels and determine if experience translated to improved SIL skills. METHODS: Surgical residents of all PGY levels (1-5) at our institution were included. Baseline surveys were obtained to determine resident level of exposure to both SIL and standard laparoscopic cases. Participants performed the following tasks: running of the bowel, endoloop placement, extracorporeal suture tying, and intracorporeal suture tying. Tasks were performed on a commercially provided simulated inanimate organ model. Participants were given 5 min to complete each task. Data were collected and analyzed by an impartial-certified Fundamentals of Laparoscopic Surgery proctor. RESULTS: A total of 31 residents participated in the study. Overall, there was minimal SIL exposure among all residents. As expected, PGY level correlated with increased ability to complete assigned tasks within the allotted time. There was a statistically significant difference in the number of individuals able to complete a task based on PGY level for all given tasks (P = 0.005). With increased difficulty, the percentage of higher level residents able to complete the task decreased (100% PGY5 completed running of bowel versus 0% intracorporeal knot tying). CONCLUSIONS: Certain psychomotor skills did appear to translate to SIL skills. However, further dedicated SIL training may help to better develop certain laparoscopic skills devoted to SIL.

Laparoscopic Pediatric Inguinal Hernia Repair: A Pilot Study in a Novel Guinea Pig Animal Model.

BACKGROUND: The purpose of this study was to compare different techniques for pediatric laparoscopic inguinal hernia repair. We hypothesize that the amount of dissection performed at the internal ring, with or without division of the peritoneum, will impact healing and thus long-term success of the repair. METHODS: Following the Institution's Animal Care and Use Committee approval (708024-4), 20 Hartley guinea pigs underwent laparoscopic repair of their natural open internal rings. The guinea pigs were divided equally into four surgical groups: intracorporeal suture repair (IS), hernia dissection and division with intracorporeal suture (DDIS) repair, subcutaneous endoscopically assisted ligation (SEAL), and Yueng (HOOK) repair. After a 6-week survival period, a necropsy was performed. Repairs were evaluated and tested under pressures up to 30 mmHg. The suture was then removed to assess primary healing. Experimental data were analyzed using chi-square test. RESULTS: There were no perioperative or postoperative complications. On initial evaluation, before suture removal, repair integrity was as follows: 5/10 IS, 10/10 DDIS, 7/10 SEAL, and 7/10 HOOK (P = .09). After suture removal, repair integrity was as follows: 3/10 IS, 10/10 DDIS, 5/10 SEAL, and 6/10 HOOK (P = .01). CONCLUSION: Overall, dissecting and dividing the sac with intracorporeal suture (DDIS) closure had the best outcome. This method appears to best replicate standard open high ligation.

Operative vs Nonoperative Management of Pediatric Blunt Pancreatic Trauma: Evaluation of the National Trauma Data Bank.

BACKGROUND: Traumatic pancreatic injury is associated with significant morbidity and mortality. We evaluated the differences in outcomes among children with blunt pancreatic injuries managed operatively and nonoperatively. STUDY DESIGN: The National Trauma Data Bank was evaluated from 2002 to 2011. Patients less than18 years of age with blunt pancreatic injuries and Abbreviated Injury Scale (AIS) scores ≥ 3 were identified. Patients were divided into nonoperative (NO), operative (O), and delayed operative (DO; operation performed 48 hours or more after admission) groups. Outcomes evaluated were total length of stay (LOS), ICU use/LOS, complications, and death. Univariate comparisons were performed using Fisher's exact and Kruskal-Wallis rank tests. Multivariable analyses were performed using robust regression and logistic regression. RESULTS: There were 424 cases analyzed. Mean (± SD) age was 10.6 ± 5.3 years, and mean Injury Severity Score (ISS) was 23.4 ± 13.4. Operative groups differed by age (p = 0.002), AIS severity (p = 0.04), and concomitant head injury (p = 0.01), but were similar with regard to sex, race, and ISS. Length of stay was significantly higher in the DO group compared with the NO or O groups; the NO group had the lowest LOS (covariate-adjusted: 18.7 days vs 11.8 days, p < 0.001 and 12.6 days, p < 0.001, respectively) and infection rates (10.2% vs 1.6% and 6.2%, respectively, p = 0.04). The ICU LOS was greatest in the DO group (vs NO, p = 0.03; O, p = 0.29), as was the likelihood of ICU use (vs NO, p = 0.02; O, p = 0.75). Groups did not differ with respect to outcomes including death (p = 0.94) and overall complication rate (p = 0.63). CONCLUSIONS: Overall, children managed nonoperatively have equivalent or better outcomes when compared with operative and delayed operative management in regard to death, overall complications, LOS, ICU LOS, and ICU use.

Antineoplastic effects of Rhodiola crenulata treatment on B16-F10 melanoma.

Melanoma is an aggressive form of skin cancer with limited treatment options for advanced stage disease. Early detection and wide surgical excision remain the initial mode of treatment for primary tumors thus preventing metastases and leading to improved prognosis. Through this work, we have evaluated the antineoplastic effects of Rhodiola crenulata (R. crenulata) root extracts on the B16-F10 melanoma cell line, both in vitro and in vivo. We observed that R. crenulata treatment resulted in increased cell death as well as a reduction in tumor cell proliferation and migration in vitro. Additionally, we observed that R. crenulata decreased the expression of integrin ß1 and vimentin and increased the expression of E-cadherin. Further, in mice treated with a topical R. crenulata-based cream therapy, tumors were more likely to have a radial growth pattern, a reduction in mitotic activity, and an increase in tumor necrosis. We also observed that mice drinking water supplemented with R. crenulata displayed a reduction of metastatic foci in disseminated models of melanoma. Collectively, these findings suggest that R. crenulata exhibits striking antitumorigenic and antimetastatic properties and that this extract may harbor potential novel adjuvant therapy for the treatment of melanoma.

Rhodiola crenulata inhibits Wnt/ß-catenin signaling in glioblastoma.

BACKGROUND: Rhodiola crenulata is a perennial plant that grows in the high altitudes of Eastern Europe and Asia. R crenulata has been used for many years in Eastern traditional medicine for a variety of medicinal purposes and it has been shown to elicit antineoplastic effects. The purpose of this study is to determine if R crenulata extract exhibits antitumor properties on glioblastoma multiforme (GBM), the most common and aggressive primary brain tumor. MATERIALS AND METHODS: Human U87 GBM cells were treated with 200 µg/mL of R crenulata or vehicle control. Cell proliferation was measured via MTS assay and clonogenic assay. The expressions of glial fibrillary acidic protein, a protein marker of differentiation, E-cadherin, and non-phospho active ß-catenin were measured with immunocytochemistry. Neurosphere assay was performed in low attachment plates. Activity of the Wnt/ß-catenin transcriptional activation was assessed via a dual-luciferase assay. RESULTS: MTS and clonogenicity assays revealed a decrease in proliferation with R crenulata therapy with an increased sensitivity to radiation. Immunocytochemistry revealed that R crenulata induced glial fibrillary acidic protein and E-cadherin expression suggestive of a more differentiated state. In agreement with the change in differentiation neurosphere formation was decreased upon treatment with R crenulata. ß-Catenin dual reporter assay revealed a decrease in Wnt promoter activity after treatment with R crenulata; this was supported by a decrease in nuclear localization of ß-catenin. CONCLUSIONS: Treatment with R crenulata extract effectively suppresses proliferation, stimulates differentiation, and eliminates tumorsphere formation of GBM cells in vitro. The observed effects are associated with inhibition of Wnt/ß-catenin signaling pathway.