Development of thrombocytopenia is associated with improved survival in patients treated with immunotherapy

Background: Immune-related adverse events are associated with efficacy of immune checkpoint inhibitors (ICIs). We hypothesize that immune-mediated thrombocytopenia could be a biomarker for response to ICIs. Materials & methods: This retrospective study included 215 patients with metastatic malignancies treated with ICIs. Patients were stratified by nadir platelet count. Outcomes of interest were progression-free survival and overall survival. Results: On multivariate analysis, grade 1 thrombocytopenia was positively associated with overall survival compared with patients who did not develop thrombocytopenia (hazard ratio [HR]= 0.28 [95% CI: 0.13–0.60]; p = 0.001), while grade 2–4 thrombocytopenia was not (HR= 0.36 [95% CI: 0.13–1.04]; p = 0.060). There was no association between degree of thrombocytopenia and progression-free survival. Conclusion: Follow-up studies are warranted to substantiate the predictive significance of thrombocytopenia in patients receiving ICIs

EFFECT OF AUTOLOGOUS PLATELET-RICH PLASMA ON DISTRACTION OSTEOGENESIS IN THE MANDIBLE OF RABBITS: A MORPHOLOGIC AND MORPHOMETRIC APPROACH

Distraction osteogenesis of the jaws is a common surgical practice in the treatment of pediatric craniofacial deformities. Autologous platelet rich plasma (PRP) has been used to increase the healing potential of bones in humans during distraction osteogenesis. This article aims to study the morphometric and morphologic parameters resulting from the effect of PRP on bone healing after mandibular distraction in rabbits. Right mandibular distraction was performed in 12 rabbits divided equally into 2 groups. PRP and physiological saline were injected, according to a defined protocol, in the callus following distraction of the experimental and control groups respectively. The rabbits were sacrificed after a consolidation period of 45 days and the mandibles were surgically removed. Bone mineral density, radiographic analysis, mechanical properties and histological features of the lengthened bones were assessed using radiographic examination, dual X-ray absorptiometry, biomechanical testing and histology. Results showed that the regenerate bone density, the amount of trabeculation in addition to the bone mineral density and mineral content, as measured by absorptiometry, were better with PRP but not significantly different between groups. Two radiographs revealed a more consistent healing in the experimental mandibles compared with erratic outcomes in corresponding controls. Two of the latter could not be subjected to any mechanical testing because the mandibular parts, connected with fibrous tissue, were separated. Consequently, the biomechanical test depicted greater maximal loads in the experimental group. The histological studies exhibited more ossification and less connective tissue fibers in the experimental group. PRP accelerated healing of mandibles in rabbits following distraction and improved their biomechanical properties. These findings have significant clinical implications on reducing the period of consolidation of the mandibles which may not be immobilized like other bones for long period tim

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Predictors of Outcome in Patients With Fibrolamellar Carcinoma: Analysis of the National Cancer Database

Background: Fibrolamellar carcinoma (FLC) is a very rare liver tumor. We aimed to retrospectively analyze the clinicopathological factors and treatment modalities affecting overall survival (OS) in FLC. The objective of the study was to identify predictors of survival in FLC. Patients and methods: Using the National Cancer Database, we identified 496 patients diagnosed with FLC between 2004 and 2015. Clinicopathological, treatment, and survival data were collected. Results: Hepatic resection was performed on 254 (51.2%) patients, liver-directed therapy on 13 (2.6%) patients, and liver transplantation on 15 (3.0%) patients. Median OS by stage were 142.1, 87.2, 32.3, and 14.1 months for stages 1, 2, 3, and 4, respectively. Metastatectomy was not associated with superior median OS (23.4 vs. 10.5 months, p=0.163). Age ≤40, low Charlson-Deyo comorbidity score, early stage and hepatic resection were independently associated with longer OS. Conclusion: Our study reports current trends in FLC management, and identifies independent predictors of OS

A Bibliometric Analysis of COVID-19 Research Activity: A Call for Increased Output

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) has impacted many countries across all inhabited continents, and is now considered a global pandemic, due to its high rate of infectivity. Research related to this disease is pivotal for assessing pathogenic characteristics and formulating therapeutic strategies. The aim of this paper is to explore the activity and trends of COVID-19 research since its outbreak in December 2019. METHODS: We explored the PubMed database and the World Health Organization (WHO) database for publications pertaining to COVID-19 since December 2019 up until March 18, 2020. Only relevant observational and interventional studies were included in our study. Data on COVID-19 incidence were extracted from the WHO situation reports. Research output was assessed with respect to gross domestic product (GDP) and population of each country. RESULTS: Only 564 publications met our inclusion criteria. These articles came from 39 different countries, constituting 24% of all affected countries. China produced the greatest number of publications with 377 publications (67%). With respect to continental research activity, Asian countries had the highest research activity with 434 original publications (77%). In terms of publications per million persons (PPMPs), Singapore had the highest number of publications with 1.069 PPMPs. In terms of publications per billion-dollar GDP, Mauritius ranked first with 0.075. CONCLUSION: COVID-19 is a major disease that has impacted international public health on a global level. Observational studies and therapeutic trials pertaining to COVID-19 are essential for assessing pathogenic characteristics and developing novel treatment options

Estrogens control inflammation in experimental colitis.

There is now a wealth of experimental evidence indicating that the deficit in endogenous estrogen facilitates the onset of inflammation that can be antagonized by estrogen replacement therapy. This work investigated the role of estrogen in the control of intestinal inflammation in a panel of colitis models, focusing on the morphological changes, the activity of mast cells, the expression of cytokines (IL-1beta, IL-6, and TNF-alpha), fibronectin and reactive oxygen species. Two hundred adult male rats were divided into 4 groups: colitis was induced in Group I and Group II but only the latter was treated with estrogen; Group III received estrogen only, and Group IV saline. Colitis was induced in 4 models using: iodoacetamide; iodoacetamide + enteropathogenic E. coli; 2, 4, 6-Trinitrobenzene sulfonic acid; and dextran sulfate sodium salt. Macroscopic and microscopic evaluations of abdominal structures as well as molecular analysis were made on days 7, 14, 28 and 56. There was a significant improvement in the health condition of the estrogen-treated rats: the inflammation scores were reduced by at least 10-15&#x0025;, the number of mast cells in the colon decreased by 30&#x0025;, fibronectin expression was only 50&#x0025; and reactive oxygen species decreased by 30&#x0025;. In addition, there was a significant decrease in TNF-alpha, IL-6 and IL-1beta expression by about 25&#x0025;. In conclusion, there was an improvement in the inflammatory status in all estrogen-treated groups through the duration of the experiment at all-time points. In addition, there was less tissue necrosis as depicted by less fibronectin and a marked antioxidant effect