Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

Antibody immunosuppressive therapy in solid-organ transplant: Part I

Currently, a wide variety of both polyclonal and monoclonal antibodies are being routinely utilized to prevent and treat solid organ rejection. More commonly, these agents are also administered in order to delay introduction of calcineurin inhibitors, especially in patients with already compromised renal function. While these antibody therapies dramatically reduced the incidence of acute rejection episodes and improved both short and long-term graft survival, they are also associated with an increased incidence of opportunistic infections and neoplastic complications. Therefore, effective patient management must necessarily balance these risks against the potential benefits of the therapy

Evidence of new pathogenic Theileria species in dogs

Babesiosis, caused by tick-borne haematozoan organisms of the genus Babesia, is a parasitic disease of domestic and wild mammals. Canine Babesidae have historically been classified as “large Babesia” (Babesia canis) and “small Babesia” (Babesia gibsoni) based on the size of their intraerythrocytic forms. Recent publications, however, suggest that the diversity of piroplasm species infecting dogs might be greater than previously appreciated. Sequencing and phylogenetic analysis of the ssrRNA gene has revealed that canine piroplasms are found in three clades, ‘true’ Babesia sp. (B. canis and B. gibsoni), Theileria annae and Theileria-like group (B. conradae). This newly recognised piroplasm T. annae appears to be hyperendemic in northwest Spain. The vector for this emergent canine infection remains undescribed, although the Ixodeshexagonus is suspected based on their presence upon the dogs in NW Spain and the relative absence of others. These observations have introduced a major change in the approach to the epidemiology of babesiosis in dogs. More clinical samples and data will need to be collected and analyzed to understand the importance of Theileria species in dogs

Effects of tacrolimus on hemispheric water content and cerebrospinal fluid levels of glutamate, hypoxanthine, interleukin-6, and tumor necrosis factor-alpha following controlled cortical impact injury in rats

OBJECT: Disturbance of calcium homeostasis contributes to evolving tissue damage and energetic impairment following traumatic brain injury (TBI). Calcium-mediated activation of calcineurin results in production of tissue-damaging nitric oxide and free oxygen radicals. Inhibition of calcineurin induced by the immunosuppressant tacrolimus (FK506) has been shown to reduce structural and functional damage after ischemia. The aims of the present study were to investigate time- and dose-dependent short-term antiedematous effects of tacrolimus following TBI. METHODS: A left temporoparietal contusion (controlled cortical impact injury [CCII]) was induced in 51 male Sprague-Dawley rats. Tacrolimus (1 or 3 mg/kg body weight) was administered by a single intraperitoneal injection at 5 minutes, 30 minutes, or 4 hours after CCII occurred. Control rats received physiological saline. Water contents of traumatized and nontraumatized hemispheres, as well as cerebrospinal fluid (CSF) levels of mediators reflecting tissue damage (the proinflammatory cytokines interleukin [IL]-6 and tumor necrosis factor [TNF]-alpha, the excitotoxin glutamate, and the adenosine triphosphate-degradation product hypoxanthine), were determined 24 hours after trauma. Although CSF levels of IL-6 and TNFalpha were completely suppressed by tacrolimus at all time points and at both concentrations, CSF levels of glutamate and hypoxanthine, as well as edema formation, were only marginally influenced. Significant reduction of cerebral water content was confined to nontraumatized hemispheres. In addition, the higher dose of tacrolimus failed to exert significant antiedematous effects on traumatized hemispheres. CONCLUSIONS: Under the present study design, the potency of tacrolimus in reducing edema formation following CCII seems limited. However, its immunosuppressive effects could be of value in influencing the posttraumatic inflammatory response known to aggravate tissue damage