Delayed Presentation of Isolated Complete Pancreatic Transection as a Result of Sport-Related Blunt Trauma to the Abdomen

Introduction: Blunt abdominal trauma is a rare but well-recognized cause of pancreatic transection. A delayed presentation of pancreatic fracture following sport-related blunt trauma with the coexisting diagnostic pitfalls is presented. Case Report: A 17-year-old rugby player was referred to our specialist unit after having been diagnosed with traumatic pancreatic transection, having presented 24 h after a sporting injury. Despite haemodynamic stability, at laparotomy he was found to have a diffuse mesenteric hematoma involving the large and small bowel mesentery, extending down to the sigmoid colon from the splenic flexure, and a large retroperitoneal hematoma arising from the pancreas. The pancreas was completely severed with the superior border of the distal segment remaining attached to the splenic vein that was intact. A distal pancreatectomy with spleen preservation and evacuation of the retroperitoneal hematoma was performed. Discussion/Conclusion: Blunt pancreatic trauma is a serious condition. Diagnosis and treatment may often be delayed, which in turn may drastically increase morbidity and mortality. Diagnostic difficulties apply to both paraclinical and radiological diagnostic methods. A high index of suspicion should be maintained in such cases, with a multi-modality diagnostic approach and prompt surgical intervention as required

Zygapophyseal Joint Orientation and Facet Tropism and Their Association with Lumbar Disc Prolapse

Study Design Cross-sectional study. Purpose To evaluate the association between zygapophyseal joint angle (ZJA), facet tropism (FT), and lumbar intervertebral disc prolapse (IVDP). Overview of Literature Several studies have shown that FT increases the risk of IVDP and have postulated that a more sagittally oriented zygapophyseal joint provides less mechanical resistance to axial torque, thereby exerting excessive rotational strain on the intervertebral disc, resulting in an annular tear. In contrast, other studies have found no definitive association between FT and IVDP. Therefore, conclusive evidence regarding the role of FT in the pathogenesis of disc prolapse is currently lacking. Methods Magnetic resonance imaging scans of 426 patients with single-level lumbar IVDP were analyzed. Right and left ZJAs of the lumbar segments were measured on axial sections. The frequency and severity of FT were determined by calculating the absolute difference between the right and left ZJAs. Patients without IVDP at L4–L5 and L5–S1 served as controls for those with IVDP at L4–L5 and L5–S1, respectively. Chi-square test and t-test were used to compare the severity and frequency of FT between patients with and without IVDP. The receiver operating characteristic analysis was performed to determine the critical FT values that were predictive of IVDP. Results Patients with IVDP exhibited a higher frequency (L4–L5: 47% vs. 15.08%; L5–S1: 39.62% vs. 22.69%; p=0.001) and severity (L4–L5: 7.85°±3.5° vs. 4.05°±2.62°; L5–S1: 7.30°±3.07° vs. 4.82°±3.29°; p <0.001) of FT than those without IVDP. Critical FT values of 5.7° at L4–L5 and 6° at L5–S1 increased the likelihood of IVDP by a factor of 2.89 and 1.75, respectively. Conclusions Our results confirm the existence of a significant association between lumbar IVDP and FT; however, a causal relationship could not be ascertained

Combined sequential use of HAP and ART scores to predict survival outcome and treatment failure following chemoembolization in hepatocellular carcinoma: a multi-center comparative study.

BACKGROUND: The prognosis of patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) is variable, despite a myriad of prognostic markers. We compared and integrated the established prognostic models, HAP and ART scores, for their accuracy of overall survival (OS) prediction. RESULTS: In both training and validation sets, HAP and ART scores emerged as independent predictors of OS (p<0.01) with HAP achieving better prognostic accuracy (c-index: 0.68) over ART (0.57). We tested both scores in combination to evaluate their combined ability to predict OS. Subgroup analysis of BCLC-C patients revealed favorable HAP stage (p<0.001) and radiological response after initial TACE (p<0.001) as positive prognostic factors. PATIENTS AND METHODS: Prognostic scores were studied using multivariable Cox regression and c-index analysis in 83 subjects with Barcelona Clinic Liver Cancer (BCLC) A/B stage from UK and Italy (training set), and 660 from Korea and Japan (validation set), all treated with conventional TACE. Scores were further validated in an separate analysis of patients with BCLC-C stage disease (n=63) receiving initial TACE. CONCLUSION: ART and HAP scores are validated indices in patients with intermediate stage HCC undergoing TACE. The HAP score is best suited for screening patients prior to initial TACE, whilst sequential ART assessment improves early detection of chemoembolization failure. BCLC-C patients with low HAP stage may be a subgroup where TACE should be explored in clinical studies

MTL-CEBPA, a Small Activating RNA Therapeutic Upregulating C/EBP-α, in Patients with Advanced Liver Cancer: A First-in-Human, Multicenter, Open-Label, Phase I Trial.

PURPOSE: Transcription factor C/EBP-α (CCAAT/enhancer-binding protein alpha) acts as a master regulator of hepatic and myeloid functions and multiple oncogenic processes. MTL-CEBPA is a first-in-class small activating RNA oligonucleotide drug that upregulates C/EBP-α. PATIENTS AND METHODS: We conducted a phase I, open-label, dose-escalation trial of MTL-CEBPA in adults with advanced hepatocellular carcinoma (HCC) with cirrhosis, or resulting from nonalcoholic steatohepatitis or with liver metastases. Patients received intravenous MTL-CEBPA once a week for 3 weeks followed by a rest period of 1 week per treatment cycle in the dose-escalation phase (3+3 design). RESULTS: Thirty-eight participants have been treated across six dose levels (28-160 mg/m2) and three dosing schedules. Thirty-four patients were evaluable for safety endpoints at 28 days. MTL-CEBPA treatment-related adverse events were not associated with dose, and no maximum dose was reached across the three schedules evaluated. Grade 3 treatment-related adverse events occurred in nine (24%) patients. In 24 patients with HCC evaluable for efficacy, an objective tumor response was achieved in one patient [4%; partial response (PR) for over 2 years] and stable disease (SD) in 12 (50%). After discontinuation of MTL-CEBPA, seven patients were treated with tyrosine kinase inhibitors (TKIs); three patients had a complete response with one further PR and two with SD. CONCLUSIONS: MTL-CEBPA is the first saRNA in clinical trials and demonstrates an acceptable safety profile and potential synergistic efficacy with TKIs in HCC. These encouraging phase I data validate targeting of C/EBP-α and have prompted MTL-CEBPA + sorafenib combination studies in HCC

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Autologous bone marrow stem cells in the treatment of chronic liver disease

Chronic liver disease (CLD) is increasing worldwide yet there has been no major advance in effective therapies for almost five decades. There is mounting evidence that adult haematopoietic stem cells (HSC) are capable of differentiating into many types of tissue, including skeletal and cardiac muscle, neuronal cells, pneumocytes and hepatocytes. These recent advances in regenerative medicine have brought hope for patients with liver cirrhosis awaiting transplantation. New findings in adult stem cell biology are transforming our understanding of tissue repair raising hopes of successful regenerative hepatology. Although all clinical trials to date have shown some improvement in liver function and CD34 + cells have been used safely for BM transplantation for over 20 years, only randomised controlled clinical trials will be able to fully assess the potential clinical benefit of adult stem cell therapy for patients with CLD. This article focuses on the potential of bone marrow stem cells (BMSCs) in the management of CLD and the unresolved issues regarding their role. We also outline the different mechanisms by which stem cells may impact on liver disease