Severe gastric variceal haemorrhage due to splenic artery thrombosis and consecutive arterial bypass

<p>Abstract</p> <p>Background</p> <p>Upper gastrointestinal haemorrhage is mainly caused by ulcers. Gastric varicosis due to portal hypertension can also be held responsible for upper gastrointestinal bleeding. Portal hypertension causes the development of a collateral circulation from the portal to the caval venous system resulting in development of oesophageal and gastric fundus varices. Those may also be held responsible for upper gastrointestinal haemorrhage.</p> <p>Case presentation</p> <p>In this study, we describe the case of a 69-year-old male with recurrent severe upper gastrointestinal bleeding caused by arterial submucosal collaterals due to idiopathic splenic artery thrombosis. The diagnosis was secured using endoscopic duplex ultrasound and angiography. The patient was successfully treated with a laparoscopic splenectomy and complete dissection of the short gastric arteries, resulting in the collapse of the submucosal arteries in the gastric wall. Follow-up gastroscopy was performed on the 12^thpostoperative week and showed no signs of bleeding and a significant reduction in the arterial blood flow within the gastric wall. Subsequent follow-up after 6 months also showed no further gastrointestinal bleeding as well as subjective good quality of life for the patient.</p> <p>Conclusion</p> <p>Submucosal arterial collaterals must be excluded by endosonography via endoscopy in case of recurrent upper gastrointestinal bleeding. Laparoscopic splenectomy provides adequate treatment in preventing any recurrent bleeding, if gastric arterial collaterals are caused by splenic artery thrombosis.</p

Progestin Receptor-Mediated Reduction of Anxiety-Like Behavior in Male Rats

BACKGROUND: It is well known progesterone can have anxiolytic-like effects in animals in a number of different behavioral testing paradigms. Although progesterone is known to influence physiology and behavior by binding to classical intracellular progestin receptors, progesterone's anxiety reducing effects have solely been attributed to its rapid non-genomic effects at the GABA A receptor. This modulation occurs following the bioconversion of progesterone to allopregnanolone. Seemingly paradoxical results from some studies suggested that the function of progesterone to reduce anxiety-like behavior may not be entirely clear; therefore, we hypothesized that progesterone might also act upon progestin receptors to regulate anxiety. METHODOLOGY/PRINCIPAL FINDINGS: To test this, we examined the anxiolytic-like effects of progesterone in male rats using the elevated plus maze, a validated test of anxiety, and the light/dark chamber in the presence or absence of a progestin receptor antagonist, RU 486. Here we present evidence suggesting that the anxiolytic-like effects of progesterone in male rats can be mediated, in part, by progestin receptors, as these effects are blocked by prior treatment with a progestin receptor antagonist. CONCLUSION/SIGNIFICANCE: This indicates that progesterone can act upon progestin receptors to regulate anxiety-like behavior in the male rat brain

Integrins as therapeutic targets: lessons and opportunities.

The integrins are a large family of cell adhesion molecules that are essential for the regulation of cell growth and function. The identification of key roles for integrins in a diverse range of diseases, including cancer, infection, thrombosis and autoimmune disorders, has revealed their substantial potential as therapeutic targets. However, so far, pharmacological inhibitors for only three integrins have received marketing approval. This article discusses the structure and function of integrins, their roles in disease and the chequered history of the approved integrin antagonists. Recent advances in the understanding of integrin function, ligand interaction and signalling pathways suggest novel strategies for inhibiting integrin function that could help harness their full potential as therapeutic targets

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries

Is Interposition Arthroplasty a Viable Option for Treatment of Moderate to Severe Hallux Rigidus? A Systematic Review and Meta-analysis

Category: Midfoot/Forefoot Introduction/Purpose: Hallux rigidus is a painful arthritis of the first metatarsophalangeal joint that causes progressive loss of mobility. Treatment options include activity modifications, analgesics, corticosteroids, and surgery. Arthrodesis of the MTP joint is considered the gold standard treatment for hallux rigidus, but it is often reserved for advanced. Interposition arthroplasty uses a spacer taken from an autograft, allograft, or synthetic material. For patients with severe arthritic diseases who would like to preserve MTP joint function, interposition arthroplasty may be a viable option. The purpose of this systematic review is to investigate patient outcomes after undergoing interposition arthroplasty of the MTP joint. The objectives are to determine if this technique is practical for patients who would prefer to avoid arthrodesis, and to systematically analyze post-operative improvement. Methods: The systematic review was performed following PRISMA (Preferred Reporting Items for Systematic Review and Meta-analyses) guidelines. Medline, pubmed, Embase, and Cohrane Database of Systematic Reviews (CDRS) were searched for publications from 2000 to 2017. Duplicates were then removed, and titles and abstracts were reviewed to confirm the relevance f the study. Studies were included if they reported results of first MTP joint interposition arthroplasty in one of the well-known scoring systems: AOFAS, FFI, or SF-36. Studies also were also required to have a 12 month follow up. Systematic review and data extraction were performed on all selected studies. Means were recorded and placed in tables for all variables including scoring results and complication rates. A linear regression model comparing the change in preoperative to postoperative AOFAS scores between the autogenous versus allogenous interposition materials was performed. Results: Database searches produced 574 articles for review. 15 of these were included in the systematic review. Mean AOFAS score was improved from 41.35 preoperatively to 83.17 postoperatively. Mean pain, function, and alignment scores improved from preoperative values of 14.9, 24.9, and 10 to postoperative values of 33.3, 35.8, and 14.5. Mean dorsiflexion increased from 21.27 degrees (5-30) to 42.03 degrees (25-71). Mean ROM improved from 21.06 to 46.43 degrees. Eighty-seven percent of patients were satisfied to highly satisfied with their surgery and would choose surgery again. Joint space increased by 0.8 mm to 2.5 mm. The most common complications included metatarsalgia (13.9%), loss of ground contact (9.7%), osteonecrosis (5.4%), great toe weakness (4.8%), hypoesthesia (4.2%), decreased push off power (4.2%), and callous formation (4.2%). Conclusion: The management of hallux rigidus remains heavily debated. This systematic review of the current literature suggests that interposition arthroplasty is a viable short and intermediate term treatment for hallux rigidus in terms of patient satisfaction, pain scores, and AOFAS scores. Further studies with greater sample sizes, more uniform methods, and longer follow-up times are needed to further support the superiority of interposition arthroplasty