Intraperitoneal Haemorrhage Secondary to Rupture of Right Colic Artery Pseudoaneurysm: A Case Report and Literature Review.

This article presents the case of a 58-year-old woman who presented feeling unwell with pain in the right upper abdomen for three days. She had a history of splenic infarcts, was on lifelong warfarin and had recently returned from a trip to Gambia. She was admitted to the hospital under suspicion of sepsis of unknown origin, and a CT scan later revealed haemoperitoneum along with a pseudoaneurysm of the right colic artery. After initially responding to resuscitation, the patient deteriorated haemodynamically, and a decision was made to perform a laparotomy, revealing a ruptured right colic artery pseudoaneurysm. In this article, the authors highlight the challenges of managing a complex unwell patient with a ruptured right colic artery pseudoaneurysm, emphasising the importance of a multi-disciplinary team approach and shared decision-making and reviewing the available literature.

The Implementation of a Rib Fracture Pathway at a Small District General Hospital to Improve Patient Care.

Background and objective Rib fractures are common presentations to the emergency department following blunt thoracic trauma. Despite this injury causing significant morbidity and mortality, no national guidelines exist to guide the acute management of this condition. In light of this, this quality improvement project was conducted at a district general hospital (DGH) with the aim of assessing the impact of using a simple rib fracture management pathway. Methods A retrospective review of paper notes and electronic databases of patients with a recorded diagnosis of "rib fractures" were reviewed. Following this, a management pathway was designed and then implemented, which incorporated BMJ Best Practices and local hospital needs. The study then assessed the impact of the pathway. Results Prior to implementing the pathway, a total of 47 individual patients were included in the statistical analysis. Of the patients analysed, 44% were older than 65 years. Of note, 89% received regular paracetamol for analgesia, 41% received regular nonsteroidal anti-inflammatory drugs (NSAIDs), and 69% received regular opioids. Advanced analgesics such as patient-controlled analgesia (PCA) and nerve blocks were poorly used; for instance, a PCA was used in only 13% of cases. Only 6% of patients received daily pain team reviews and only 44% of patients were seen by physiotherapists within the first 24 hours. Additionally, 93% of patients who were admitted under general surgery had a STUMBL (STUdy of the Management of BLunt chest wall trauma) prognostic score >10. Post-pathway implementation, a total of 22 individual patients were included in the statistical analysis. Of them, 52% were older than 65 years. The use of simple analgesia was unchanged. However advanced analgesia was better escalated, and PCAs were used 43% of the time. The involvement of other healthcare professionals improved; 59% were reviewed by the pain team in the first 24 hours, 45% received daily pain team reviews, and 54% received advanced analgesia. Conclusion Based on our findings, implementing a simple rib fracture pathway is effective at improving the management of rib fracture patients admitted to our DGH.

The epidemiology of head injuries at 2019 Rugby Union World Cup.

INTRODUCTION: The sequelae of concussion are of growing concern within Rugby. World Rugby has introduced rule changes to improve player welfare and reduce head injury frequency. We aimed to report the incidence of head injuries and head injury assessment (HIA) at the 2019 Rugby World Cup (RWC). METHODS: We reviewed all 45 tournament matches and recorded the number of head injuries, the injured player's position, and the mechanism of injury; whether the player had an HIA; and if they returned to play following injury. We compared these findings with previous RWCs. RESULTS: We recorded 68 head injuries (1.33/game). Thirty-six players (52.9%) were removed from the field of play for an HIA. Of these, 23 (63.9%) failed and therefore considered to have concussion. The head injury rate in 2019 was 37.8 per 1000 player hours, which increased from previous tournaments (22.0 in 2015, 14.6 in 2011, and 4.7 in 2007). The concussion rate was 23 per 1000 player hours in 2019, which was lower than 29 in 2015. In 2019, 63.9% of HIAs were failed compared to 48.7% in 2015. We identified 17 cases where medical staff did not attend to a player suffering a head injury on-field. Of these, four players underwent an HIA after the match doctor reviewed the incident. CONCLUSION: We recorded a higher rate of head injuries, and a player was more likely to fail their HIA than in previous tournaments. These findings may represent a greater awareness from medical staff and the benefits of education. However, 25% of head injuries not receiving an initial on-field assessment provide room for improvement.

A Developmental Perspective on Young Children's Understandings of Paired Graphics Conventions From an Analogy Task.

The present study investigated children's understanding development of multiple graphics, here paired conventions commonly used in primary school textbooks. Paired graphics depicting everyday objects familiar to the children were used as the basis for an analogy task that tested their comprehension of five graphics conventions. This task required participants to compare pictures in a base pair in order to complete a target pair by choosing the correct picture from five alternative possibilities. Four groups of children aged 5, 6, 8, and 10 years old respectively (total N = 105), completed 45 analogy task items built around nine conceptual domains. Results showed mainly an overall increase of comprehension performance with age for all the tested conventions. There were also differences between the five conventions and an interaction between age and convention type. Further, children's explanation of the conventions (justification of the choices in the analogy task) were also analyzed. This investigation showed the analogy task answers were a more reliable measure of the "actual" level of understanding of the conventions than the justification themselves. The findings show that younger students tried to actively compare the pictures of the pairs and to search for a relevant meaning of the pairs, however, the youngest children have a limited capacity to interpret paired graphic conventions and our results suggests that this aspect of graphic conventions develops slowly but effectively over the course of children's schooling. Because "graphicacy" knowledge and skills are not typically taught in primary school classrooms (in contrast with literacy and numeracy), its development is likely acquired incidentally with increasing exposure to varied paired graphics during primary school education. Given the high reliance of today's educational resources on graphics-based explanations, the results from this study may signal a need for (i) for more attention to learning graphics conventions (and more generally to graphics explanations) from teachers in primary school and (ii) for a better design of the graphics with their contextual accompanying texts and captions, from designers.

Rib fracture fixation as a tool for extubation in a resource-poor environment.

An elderly female with multiple comorbidities was involved in a pedestrian vehicle accident and sustained blunt chest trauma, arriving at a resource-poor hospital in rural South Africa. She had multiple bilateral rib fractures with a unilateral flail segment that caused her to develop respiratory failure. She was intubated and sent to the intensive care unit (ICU) for ventilation. She developed hospital and ventilator acquired pneumonia. She subsequently had hypoxic arrests on two separate occasions and two failed extubations. Despite inadequate access to provisions, this patient was taken to theatre for rib fracture fixation as an attempt to improve her lung function and get her off the ventilator. She was extubated two days after the procedure and discharged from ICU 4 days thereafter. On her follow-up, she reported that she had returned to normal daily living and tasks.

Bishop-Koop jejunostomy in an adult following proximal small bowel anastomotic breakdown.

This case involves a proximal penetrating small bowel injury and the use of a Bishop-Koop anastomosis in a 33-year-old man. This case highlights the use of alternative methods used to prevent a proximal small bowel stoma in a rural setting. The Bishop-Koop anastomosis was originally designed for neonates in cases of intestinal anomalies such as atresia, volvulus and apple-peel syndrome. A literature search for the use of the Bishop-Koop anastomosis in adults, although scanty, is included in this article. We believe this article will benefit readers and that this method may be considered in breakdown of proximal small bowel injuries, to prevent a high-output stoma.

Intussusception of the vermiform appendix.

Appendicitis is a common presentation to an acute general surgical on call team. It can be a difficult diagnosis at times, particularly in sexually active young women, in whom it is often surgically challenging. This case is of a relatively straightforward diagnosis, taken for laparoscopic appendicectomy that resulted in performing an open right hemicolectomy for a necrotic, intussuscepted appendix. Histology ultimately revealed the cause of intussusception and resultant infarction of the appendix to be endometriosis.

Caecal schwannoma: a rare cause of per rectal bleeding in a 72-year-old man.

The presence of per rectal (PR) bleeding in elderly people usually alerts us to the possibility of colonic malignancy, particularly if a concomitant altered bowel habit is present, without a history of the symptom. We present a case where the cause of PR bleeding turned out to be a caecal schwannoma. Caecal schwannoma is a rare tumour of the gastrointestinal tract of mesenchymal origin and diagnosis prior to radical surgical resection is difficult. Endoscopic biopsy often fails to provide an adequate specimen and immunohistochemistry is essential to the diagnosis.

Glycovariant anti-CD37 monospecific protein therapeutic exhibits enhanced effector cell-mediated cytotoxicity against chronic and acute B cell malignancies.

TRU-016 is a SMIP(TM) (monospecific protein therapeutic) molecule against the tetraspanin transmembrane family protein CD37 that is currently in Phase 2 trials in Chronic Lymphocytic Leukemia (CLL) and Non-Hodgkin Lymphoma (NHL). In an attempt to enhance the ADCC function of SMIP-016, the chimeric version of TRU-016, SMIP-016(GV) was engineered with a modification in a glycosylation site in the Fc domain. The wild-type and glycovariant SMIP proteins mediate comparable Type I antibody-like direct cytotoxicity in the presence of anti-human Fc crosslinker and show a similar tyrosine phosphorylation pattern post-treatment. However, NK cells stimulated with the SMIP-016(GV) exhibit enhanced activation and release 3-fold more interferon-γ compared with SMIP-016. SMIP-016(GV) shows enhanced ADCC function against cells expressing CD37 with NK cell effectors derived from both normal and CLL-affected individuals. Enhanced ADCC is observed against CLL cells and is sustained at concentrations of SMIP-016(GV) as low at 5E(-6) µg/mL on cells expressing minimal CD37 antigen. In support of the biological relevance of this, SMIP-016(GV) mediates effective ADCC against primary acute lymphoblastic leukemia (ALL) cells with low surface expression of CD37. Collectively, these data suggest potential use of the novel therapeutic agent SMIP-016(GV) with enhanced effector function for B cell malignancies, including CLL and ALL therapy.

An integrative review of the side effects related to the use of magnesium sulfate for pre-eclampsia and eclampsia management.

BACKGROUND: Pre-eclampsia/eclampsia is one of the most common causes of maternal and perinatal morbidity and mortality in low and middle income countries. Magnesium sulfate is the drug of choice for prevention of seizures as part of comprehensive management of the disease. Despite the compelling evidence for the effectiveness of magnesium sulfate, concern has been expressed about its safety and potential for toxicity, particularly among providers in low- and middle-income countries. The purpose of this review was to determine whether the literature published in these global settings supports the concerns about the safety of use of magnesium sulfate. METHODS: An integrative review of the literature was conducted to document the known incidences of severe adverse reactions to magnesium sulphate, and specific outcomes of interest related to its use. All types of prospective clinical studies were included if magnesium sulfate was used to manage pre-eclampsia or eclampsia, the study was conducted in a low- or middle-income country, and the study included the recording of the incidence of any adverse side effect resulting from magnesium sulfate use. RESULTS: A total of 24 studies that compared a magnesium sulfate regimen against other drug regimens and examined side effects among 34 subject groups were included. The overall rate of absent patellar reflex among all 9556 aggregated women was 1.6%, with a range of 0-57%. The overall rate of respiratory depression in 25 subject groups in which this outcome was reported was 1.3%, with a range of 0-8.2%. Delay in repeat administration of magnesium sulfate occurred in 3.6% of cases, with a range of 0-65%. Calcium gluconate was administered at an overall rate of less than 0.2%. There was only one maternal death that was attributed by the study authors to the use of magnesium sulfate among the 9556 women in the 24 studies. CONCLUSION: Concerns about safety and toxicity from the use of magnesium sulfate should be mitigated by findings from this integrative review, which indicates a low incidence of the most severe side effects, documented in studies that used a wide variety of standard and modified drug regimens. Adverse effects of concern to providers occur infrequently, and when they occurred, a delay of repeat administration was generally sufficient to mitigate the effect. Early screening and diagnosis of the disease, appropriate treatment with proven drugs, and reasonable vigilance for women under treatment should be adopted as global policy and practice.

Hemoglobin and serum ferritin levels in women using copper-releasing or levonorgestrel-releasing intrauterine devices: a systematic review.

BACKGROUND: The use of intrauterine devices as a contraceptive method has been steadily growing in developing countries. Anemia in reproductive-age women is a growing concern in those settings. STUDY DESIGN: A systematic review of studies with measured hemoglobin and serum ferritin at baseline and after 1 year of use of copper intrauterine devices (IUDs) or a levonorgestrel-releasing intrauterine system (LNG IUS) was performed. RESULTS: Fourteen studies involving copper IUDs in nonanemic women and 4 studies in anemic women and 6 involving the LNG IUS met the criteria for the systematic review. Meta-analyses for hemoglobin changes showed significant decreases for users of copper IUDs and an increase for the LNG IUS, but with limited data. In general, ferritin levels followed the same pattern. CONCLUSION: Decreases in hemoglobin mean values in copper IUD users were not sufficient to induce anemia in previously nonanemic women. Women who are borderline anemic would likely benefit from using the LNG IUS.

Automated generation of turn mimetics: proof of concept study for the MC4 receptor.

An algorithm has been devised for the automatic design of peptide turn mimetics, particularly applicable to peptide-activated GPCRs. The method is based on flexible alignments using a new design paradigm and scoring system that aims to reduce the molecular weight of the compound and preferentially lead to drug like molecules. The process can be applied either as a de novo design or a virtual screening tool. Its use has been demonstrated by the design of novel double digit nanomolar ligands for the melanocortin 4 receptor (MC4). The method is, in principle, applicable to any type of receptor, including orphan receptors.

Design and synthesis of tricyclic corticotropin-releasing factor-1 antagonists.

Antagonists of the corticotropin-releasing factor (CRF) neuropeptide should prove to be effective in treating stress and anxiety-related disorders. In an effort to identify antagonists with improved physicochemical properties, new tricyclic CRF(1) antagonists were designed, synthesized, and tested for biological activity. As a result of studies aimed at establishing a relationship between structure and CRF(1) binding affinity, NBI 35965 (12a) was identified as a high-affinity antagonist with a pK(i) value of 8.5. Compound 12a proved to be a functional CRF(1) antagonist with pIC(50) values of 7.1 and 6.9 in the in vitro CRF-stimulated cAMP accumulation and ACTH production assays, respectively, and 12a also reduced CRF or stress induced ACTH production in vivo.

Oxadiazols: a new class of rationally designed anti-human immunodeficiency virus compounds targeting the nuclear localization signal of the viral matrix protein.

Despite recent progress in anti-human immunodeficiency virus (HIV) therapy, drug toxicity and emergence of drug-resistant isolates during long-term treatment of HIV-infected patients necessitate the search for new targets that can be used to develop novel antiviral agents. One such target is the process of nuclear translocation of the HIV preintegration complex. Previously we described a class of arylene bis(methylketone) compounds that inhibit HIV-1 nuclear import by targeting the nuclear localization signal (NLS) in the matrix protein (MA). Here we report a different class of MA NLS-targeting compounds that was selected using computer-assisted drug design. The leading compound from this group, ITI-367, showed potent anti-HIV activity in cultures of T lymphocytes and macrophages and also inhibited HIV-1 replication in ex vivo cultured lymphoid tissue. The virus carrying inactivating mutations in MA NLS was resistant to ITI-367. Analysis by real-time PCR demonstrated that the compound specifically inhibited nuclear import of viral DNA, measured by two-long terminal repeat circle formation. Evidence of the existence of this mechanism was provided by immunofluorescent microscopy, using fluorescently labeled HIV-1, which demonstrated retention of the viral DNA in the cytoplasm of drug-treated macrophages. Compounds inhibiting HIV-1 nuclear import may be attractive candidates for further development.

Rational design, synthesis, and structure-activity relationships of aryltriazoles as novel corticotropin-releasing factor-1 receptor antagonists.

Following the discovery of the very high binding affinity of 4-anilinopyrimidines against corticotropin-releasing factor receptor-1 (CRF(1)) (e.g., 1, K(i) = 2 nM), a new series of triazoles bearing different groups has been synthesized and evaluated. The compounds were prepared by cyclizations of N-acyl-S-methylisothioureas with alkylhydrazines or by cyclizations with hydrazine followed by alkylation. While members of this series showed potent binding affinity against CRF(1) receptor, there were important differences between the different regio- (7 and 12) and stereoisomeric aryltriazoles where the R(1) or R(2) side chain in 7 has an asymmetric center. In terms of overall potency, aryltriazole analogues such as 7r bearing an N-(alpha-branched benzyl)-N-propylamino side chain were the most potent, followed by analogues such as 7a, with an N-bis(cyclopropyl)methyl-N-propylamino side chain, and analogues such as 7m, with an N-(alpha-branched aliphatic)-N-propylamino side chain. While the N-propyl group was crucial for high potency, we hypothesized that the terminal methyl mimicked the 5-methyl of pyrazolo[1,5-a]pyrimidines 3 and 4. Correlation of the low-energy conformers of compounds of type 3 and 7 generated by computational analyses was very good. The size and shape of the N-alkyl group dramatically changed the potency of the triazoles, which is in contrast to the SAR seen for bicyclic CRF(1) antagonists. In general, the S-enantiomer was much more potent than the corresponding R-isomer. Furthermore, to a limited extent in the aryltriazole series the substituent on the 5-phenyl ring changed the potency up to 9-fold. (S)-1-Methyl-3-[N-(4-fluorophenylpentyl)-N-propyl]amino-5-(2-methoxy-4-dichlorophenyl)-1H-[1,2,4]triazole [(S)-7r] showed very potent binding affinity (K(i) = 2.7 nM) to CRF(1) receptors with an IC(50) of 49 nM in a cAMP inhibition assay.