Acute Kidney Injury in Severe COVID-19 Has Similarities to Sepsis-Associated Kidney Injury: A Multi-Omics Study.

OBJECTIVE: To compare coronavirus disease 2019 (COVID-19) acute kidney injury (AKI) to sepsis-AKI (S-AKI). The morphology and transcriptomic and proteomic characteristics of autopsy kidneys were analyzed. PATIENTS AND METHODS: Individuals 18 years of age and older who died from COVID-19 and had an autopsy performed at Mayo Clinic between April 2020 to October 2020 were included. Morphological evaluation of the kidneys of 17 individuals with COVID-19 was performed. In a subset of seven COVID-19 cases with postmortem interval of less than or equal to 20 hours, ultrastructural and molecular characteristics (targeted transcriptome and proteomics analyses of tubulointerstitium) were evaluated. Molecular characteristics were compared with archived cases of S-AKI and nonsepsis causes of AKI. RESULTS: The spectrum of COVID-19 renal pathology included macrophage-dominant microvascular inflammation (glomerulitis and peritubular capillaritis), vascular dysfunction (peritubular capillary congestion and endothelial injury), and tubular injury with ultrastructural evidence of mitochondrial damage. Investigation of the spatial architecture using a novel imaging mass cytometry revealed enrichment of CD3+CD4+ T cells in close proximity to antigen-presenting cells, and macrophage-enriched glomerular and interstitial infiltrates, suggesting an innate and adaptive immune tissue response. Coronavirus disease 2019 AKI and S-AKI, as compared to nonseptic AKI, had an enrichment of transcriptional pathways involved in inflammation (apoptosis, autophagy, major histocompatibility complex class I and II, and type 1 T helper cell differentiation). Proteomic pathway analysis showed that COVID-19 AKI and to a lesser extent S-AKI were enriched in necroptosis and sirtuin-signaling pathways, both involved in regulatory response to inflammation. Upregulation of the ceramide-signaling pathway and downregulation of oxidative phosphorylation in COVID-19 AKI were noted. CONCLUSION: This data highlights the similarities between S-AKI and COVID-19 AKI and suggests that mitochondrial dysfunction may play a pivotal role in COVID-19 AKI. This data may allow the development of novel diagnostic and therapeutic targets.

Expression of Immune Checkpoint Receptors in Placentae With Infectious and Non-Infectious Chronic Villitis.

Pregnancy is an immunological paradox whereby maternal immunity accepts a genetically unique fetus (or fetuses), while maintaining protective innate and adaptive responses to infectious pathogens. This close contact between the genetically diverse mother and fetus requires numerous mechanisms of immune tolerance initiated by trophoblast cell signals. However, in a placental condition known as villitis of unknown etiology (VUE), there appears to be a breakdown in this tolerance allowing maternal cytotoxic T-cells to traffic into the placenta to destroy fetal villi. VUE is associated with several gestational complications and an increased risk of recurrence in a subsequent pregnancy, making it a significant obstetrical diagnosis. The cause of VUE remains unclear, but dysfunctional signaling through immune checkpoint pathways, which have a critical role in blunting immune responses, may play an important role. Therefore, using placental tissue from normal pregnancy (n=8), VUE (n=8) and cytomegalovirus (CMV) infected placentae (n=4), we aimed to identify differences in programmed cell death 1 (PD-1), programmed death ligand-1 (PD-L1), LAG3 and CTLA4 expression between these etiologies by immunohistochemistry (IHC). Results demonstrated significantly lower expression of PD-L1 on trophoblast cells from VUE placentae compared to control and CMV infection. Additionally, we observed significantly higher counts of PD-1+ (>100 cells/image) and LAG3+ (0-120 cells/image) cells infiltrating into the villi during VUE compared to infection and control. Minimal CTLA4 staining was observed in all placentae, with only a few Hofbauer cells staining positive. Together, this suggests that a loss of tolerance through immune checkpoint signaling may be an important mechanism leading to the activation and trafficking of maternal cells into fetal villi during VUE. Further mechanistic studies are warranted to understand possible allograft rejection more clearly and in developing effective strategies to prevent this condition from occurring in utero.

Surface color spectrophotometry in a murine model of steatosis: an accurate technique with potential applicability in liver procurement.

Steatosis is the most important prognostic histologic feature in the setting of liver procurement. The currently utilized diagnostic methods, including gross evaluation and frozen section examination, have important shortcomings. Novel techniques that offer advantages over the current tools could be of significant practical utility. The aim of this study is to evaluate the accuracy of surface color spectrophotometry in the quantitative assessment of steatosis in a murine model of fatty liver. C57BL/6 mice were divided into a control group receiving normal chow (n = 19), and two steatosis groups receiving high-fat diets for up to 20 weeks-mild steatosis (n = 10) and moderate-to-severe steatosis (n = 19). Mouse liver surfaces were scanned with a hand-held spectrophotometer (CM-600D; Konica-Minolta, Osaka, Japan). Spectral reflectance data and color space values (L*a*b*, XYZ, L*c*h*, RBG, and CMYK) were correlated with histopathologic steatosis evaluation by visual estimate, digital image analysis (DIA), as well as biochemical tissue triglyceride measurement. Spectral reflectance and most color space values were very strongly correlated with histologic assessment of total steatosis, with the best predictor being % reflectance at 700 nm (r = 0.91 [0.88-0.94] for visual assessment, r = 0.92 [0.88-0.95] for DIA of H&E slides, r = 0.92 [0.87-0.95] for DIA of oil-red-O stains, and r = 0.78 [0.63-0.87] for biochemical tissue triglyceride measurement, p < 0.0001 for all). Several spectrophotometric parameters were also independently predictive of large droplet steatosis. In conclusion, hepatic steatosis can accurately be assessed using a portable, commercially available hand-held spectrophotometer device. If similarly accurate in human livers, this technique could be utilized as a point-of-care tool for the quantitation of steatosis, which may be especially valuable in assessing livers during deceased donor organ procurement.

Do probiotics prevent antibiotic-associated diarrhoea? Results of a multicentre randomized placebo-controlled trial.

BACKGROUND: Antibiotic-associated diarrhoea (AAD) is a side-effect of antibiotic consumption and probiotics have been shown to reduce AAD. METHODS: A multicentre, double-blind, placebo-controlled, randomized trial was conducted to evaluate the role of Lactobacillus casei DN114001 (combined as a drink with two regular yoghurt bacterial strains) in reducing AAD and Clostridioides difficile infection in patients aged over 55 years. The primary outcome was the incidence of AAD during 2 weeks of follow-up. RESULTS: A total of 1127 patients (mean age ± standard deviation: 73.6 ± 10.5) were randomized to the active group (N = 549) or placebo group (N = 577). Both groups were followed up as per protocol. The proportion of patients experiencing AAD during follow-up was 19.3% (106/549) in the probiotic group vs 17.9% (103/577) in the placebo group (unadjusted odds ratio 1.10, 95% confidence interval 0.82-1.49, P = 0.53). CONCLUSIONS: No significant evidence was found of a beneficial effect of the specific probiotic formulation in preventing AAD in this elderly population drawn from a number of different UK hospitals. However, in the UK and in many other healthcare systems there have, in recent years, been many changes in antibiotic stewardship policies, an overall decrease in incidence in C. difficile infection, as well as an increased awareness of infection prevention, and modifications in nursing practice. In light of these factors, it is impossible to conclude definitively from the current trial that the study-specific probiotic formulation has no role in preventing AAD, and it is our view that further trials may be indicated, controlling for these variables.

Uterine inflammatory myofibroblastic tumors in pregnant women with and without involvement of the placenta: a study of 6 cases with identification of a novel TIMP3-RET fusion.

Uterine inflammatory myofibroblastic tumors (IMTs) have been reported in association with pregnancy and, in some instances, secondarily involve the placenta. The clinicopathological spectrum of these tumors in the setting of pregnancy is not well defined. We investigated the clinical, morphologic, immunohistochemical, molecular cytogenetic, and genetic features of 6 uterine IMTs occurring in pregnant women. Each tumor was discovered at parturition, and none was identified by prenatal ultrasound. Patient age ranged from 25 to 41 years (mean 31.5). Tumor size ranged from 1.5 to 9 cm (mean 4.7). Four of 6 had usual IMT features, with at least focal deciduoid change in 3. Necrosis was identified in 3 tumors; and multinucleated cells, in 3 tumors. Sex hormone receptor expression was consistent with estrogen receptor negative or focally weakly positive and progesterone receptor diffusely moderately or moderately to strongly positive in all 6 tumors. ALK immunohistochemistry was strongly positive in 5 tumors, and all of these had an ALK rearrangement detected by break-apart fluorescence in situ hybridization. Subsequent RNA sequencing of these 5 tumors identified a TIMP3-ALK fusion in 4 and a THBS1-ALK in 1. In the ALK-negative tumor, RNA sequencing detected a novel TIMP3-RET fusion that was confirmed by RET break-apart fluorescence in situ hybridization. Follow-up was available for 2 of 6 patients 5 and 19 months after diagnosis. Neither patient developed recurrence. ALK immunohistochemistry will distinguish most uterine IMTs, but if ALK expression and gene studies are negative, in the appropriate morphologic context, evaluation of other tyrosine kinase genes known to be more commonly altered in extrauterine IMTs such as ROS1, NTRK3, PDGFRß, and RET may be necessary for diagnostic confirmation.

The placenta: A site of end-organ damage after Fontan operation. A case series.

BACKGROUND: Placental insufficiency may be the cause of the high preterm birth rate in women after Fontan operation. In this study we reviewed the clinical course and pregnancy outcome of women with Fontan physiology with a focus on placental pathology. METHODS: We reviewed clinical charts and placental pathology from 7 women with Fontan physiology who had pregnancies at Mayo Clinic, Rochester, Minnesota. The review was limited to cases where placental pathologic specimens were rigorously examined. RESULTS: Seven women had 13 deliveries between 2002 and 2018. Only 2 of 13 deliveries were at term (>37 weeks). Mean maternal age at time of last delivery was 27.5 ±â€¯3.2 years. Preeclampsia was noted during 2 pregnancies and 2 women had preterm premature rupture of membranes at 24 and 35 weeks gestation, respectively. Placental abruption with bleeding occurred in 2 pregnancies. An additional 4 pregnancies were complicated by intrauterine growth restriction (IUGR). Median placental weight was 441.5 g (IQR 305.5-622.5 g). Median placental weight percentile for gestational age was 10th to 25th, but varied greatly; two placentas were <10th percentile and 5 were >90th percentile for gestational age. Two umbilical cords contained a single umbilical artery. Prominent subchorionic fibrin deposition was a consistent feature in all placentas. Villous hypermaturity was noted in 4 placentas. CONCLUSIONS: Fontan physiology may be associated with poor placental health. High systemic venous pressure and low cardiac output may contribute to stagnation of placental blood flow and result in subchorionic fibrin deposition and variable villous hypoplasia. This may explain the high preterm birth rate in women with Fontan physiology. Preterm deliveries and small-for-gestational-age (SGA) newborns should be anticipated in this patient population. Analysis of placental pathology may help determine both candidacy for future pregnancy and long-term effects of pregnancy for women with Fontan physiology.

Synthesis of multi-omic data and community metabolic models reveals insights into the role of hydrogen sulfide in colon cancer.

Multi-omic data and genome-scale microbial metabolic models have allowed us to examine microbial communities, community function, and interactions in ways that were not available to us historically. Now, one of our biggest challenges is determining how to integrate data and maximize data potential. Our study demonstrates one way in which to test a hypothesis by combining multi-omic data and community metabolic models. Specifically, we assess hydrogen sulfide production in colorectal cancer based on stool, mucosa, and tissue samples collected on and off the tumor site within the same individuals. 16S rRNA microbial community and abundance data were used to select and inform the metabolic models. We then used MICOM, an open source platform, to track the metabolic flux of hydrogen sulfide through a defined microbial community that either represented on-tumor or off-tumor sample communities. We also performed targeted and untargeted metabolomics, and used the former to quantitatively evaluate our model predictions. A deeper look at the models identified several unexpected but feasible reactions, microbes, and microbial interactions involved in hydrogen sulfide production for which our 16S and metabolomic data could not account. These results will guide future in vitro, in vivo, and in silico tests to establish why hydrogen sulfide production is increased in tumor tissue.

Potential contribution of the uterine microbiome in the development of endometrial cancer.

BACKGROUND: Endometrial cancer studies have led to a number of well-defined but mechanistically unconnected genetic and environmental risk factors. One of the emerging modulators between environmental triggers and genetic expression is the microbiome. We set out to inquire about the composition of the uterine microbiome and its putative role in endometrial cancer. METHODS: We undertook a study of the microbiome in samples taken from different locations along the female reproductive tract in patients with endometrial cancer (n = 17), patients with endometrial hyperplasia (endometrial cancer precursor, n = 4), and patients afflicted with benign uterine conditions (n = 10). Vaginal, cervical, Fallopian, ovarian, peritoneal, and urine samples were collected aseptically both in the operating room and the pathology laboratory. DNA extraction was followed by amplification and high-throughput next generation sequencing (MiSeq) of the 16S rDNA V3-V5 region to identify the microbiota present. Microbiota data were summarized using both α-diversity to reflect species richness and evenness within bacterial populations and ß-diversity to reflect the shared diversity between bacterial populations. Statistical significance was determined through the use of multiple testing, including the generalized mixed-effects model. RESULTS: The microbiome sequencing (16S rDNA V3-V5 region) revealed that the microbiomes of all organs (vagina, cervix, Fallopian tubes, and ovaries) are significantly correlated (p < 0.001) and that there is a structural microbiome shift in the cancer and hyperplasia cases, distinguishable from the benign cases (p = 0.01). Several taxa were found to be significantly enriched in samples belonging to the endometrial cancer cohort: Firmicutes (Anaerostipes, ph2, Dialister, Peptoniphilus, 1-68, Ruminococcus, and Anaerotruncus), Spirochaetes (Treponema), Actinobacteria (Atopobium), Bacteroidetes (Bacteroides and Porphyromonas), and Proteobacteria (Arthrospira). Of particular relevance, the simultaneous presence of Atopobium vaginae and an uncultured representative of the Porphyromonas sp. (99 % match to P. somerae) were found to be associated with disease status, especially if combined with a high vaginal pH (>4.5). CONCLUSIONS: Our results suggest that the detection of A. vaginae and the identified Porphyromonas sp. in the gynecologic tract combined with a high vaginal pH is statistically associated with the presence of endometrial cancer. Given the documented association of the identified microorganisms with other pathologies, these findings raise the possibility of a microbiome role in the manifestation, etiology, or progression of endometrial cancer that should be further investigated.

Arterial compliance may be reduced by ingestion of red wine.

The aim of this study was to assess the effect of alcohol on blood pressure and arterial compliance over 24 h in a group of volunteers, comparing the same group of subjects on two consecutive but separate days, one with alcohol intake (alcohol day) and one free of alcohol (control day). We studied 18 healthy subjects (mean age 34.2 years, range 25-53). The subjects received the two days in random order. On the alcohol day, the subjects were asked to drink two glasses of red wine (12% ethanol) between 1830 hours and 0430 hours. Measurements of heart rate, blood pressure and QKD interval (Q wave to Korotkoff (K) sound, diastolic phase (D) using Diasys Integra (Novacor, France)) were recorded (usually 1500 hours to 1500 hours). Three 'ingestion' periods were defined, from 1500 hours to 1830 hours ('before'), 1900 hours to 0430 hours ('during') and from 0430 hours to the following afternoon ('after') on both the alcohol day and on the control day. Red wine increased heart rate during alcohol ingestion and reduced arterial compliance after ingestion. The significant effect of interaction between day and ingestion period on heart rate, diastolic blood pressure and QKD were found, suggesting that the differences in response among the ingestion periods depended on whether alcohol has been consumed that day. For the first time our study indicates the effect of alcohol on 24 h arterial stiffness in a healthy group of volunteers.

Introduction of an electronic physiological early warning system: effects on mortality and length of stay.

BACKGROUND: The Worthing physiological scoring system (PSS) was first validated in 2005 as a tool to predict hospital mortality on admission and was subsequently introduced into clinical practice at Worthing Hospital, UK. Five years on, this study was conducted to determine the effects on mortality and length of stay (LOS) after the introduction of electronic alerting software using the PSS. In addition, we investigated whether the Worthing PSS predictive ability could be improved by addition of further variables. METHODS: Prospective observational study conducted in the acute medical unit, Worthing Hospital, UK. Patient physiological data on admission and discharge/transfer were collected between February and July 2010 from the electronic alerting software VitalPAC™. Patient characteristics, co-morbidity, outcomes, and biochemistry data were taken from the hospital administration and pathology systems. RESULTS: The observed mortality reduction from 8.3% to 5.2% over 5 yr was not statistically significant after adjustment for admission Worthing PSS score. Median LOS was reduced from 4 to 2 days, but this reflected an increase in short stay admissions. Worthing PSS was not significantly improved with the addition of biochemical variables or patient co-morbidity. A score taken before admission to a medical ward showed an improved predictive ability when compared with the initial admission score, but further analysis found no additional clinical benefit. CONCLUSIONS: The introduction of an electronic alerting PSS did not lead to a reduction in mortality when adjusted for severity of illness defined by physiological variables. Predictive performance was not enhanced by the addition of biochemical variables and co-morbidities.

Influence of cohorting patients with Clostridium difficile infection on risk of symptomatic recurrence.

BACKGROUND: Cohorting of patients with Clostridium difficile infection (CDI) is recommended when single side-rooms are unavailable. Although patients may remain infectious after cessation of diarrhoea, continued cohorting may place them at increased risk of reinfection. AIM: To identify risk factors for CDI recurrence and to determine whether cohorting of patients is associated with increased risk of recurrence. METHODS: Data describing patient demographics, comorbidity, CDI severity and treatment were collected for 248 CDI patients at our hospital between October 2008 and June 2011. The primary outcome was symptomatic recurrence within 30 days of diagnosis. FINDINGS: One hundred and thirty-eight (55.6%) CDI patients were admitted to the cohort ward. These patients were more likely to have severe CDI (odds ratio: 1.95; 95% confidence interval: 1.10-3.46; P = 0.022) and receive vancomycin (1.59; 0.94-2.68; P = 0.083) than patients who were not cohorted. Twenty-six patients (10.5%) suffered recurrence (21 cohorted and five not cohorted). Urinary infection on admission (5.16; 2.10-12.64; P < 0.001), cohorting (3.77; 1.37-10.35; P = 0.01) and concomitant antibiotics (2.07; 0.91-4.72; P = 0.083) were associated with increased risk of recurrence. On multivariate analysis, cohorting (3.94; 1.23-12.65; P = 0.021) and urinary infection (4.27; 1.62-11.24; P = 0.003) were significant predictors of recurrence. CONCLUSION: Patients admitted to a C. difficile cohort ward may be at increased risk of recurrence because they are at increased risk of reinfection. Hospitals using cohort wards to control C. difficile should manage patient flow through the cohort to minimize this risk.

First time and repeat cardioversion of atrial tachyarrhythmias - a comparison of outcomes.

INTRODUCTION: Repeat cardioversion may be necessary in over 50% of patients with persistent atrial fibrillation (AF), but identifying responders remains challenging. This study evaluates the long-term success of direct current cardioversion (DCCV) and the clinical and echocardiographical parameters that influence them, in over 1000 sedation-cardioversion procedures undertaken at Eastbourne General Hospital between 1996 and 2006. METHODS: A total of 770 patients of mean age (SD) 70.1(10.1) underwent 1013 DCCVs (first n = 665, repeat n = 348) for atrial tachyarrhythmias from 1996 to 2006. Time to persistent arrhythmia recurrence was compared between first and multiple DCCV, and the effect of age, gender, presence of heart disease, left atrial size, fractional shortening, arrhythmia duration, anti-arrhythmic drug therapy (AAD) and other concomitant cardiac medication was evaluated using the Kaplan-Meier method and Cox's Proportional-hazards model. RESULTS: In all, 33% of first and 29% of repeat DCCVs were in sinus rhythm (SR) at 12 months (m). There was no difference in median time to arrhythmia recurrence (SE) between first and multiple procedures: 1.5 +/- 0.1 m (1.3-1.7) and 1.5 +/- 0.0 m (1.4-1.6) respectively, p = 0.45. AAD use was significantly higher, arrhythmia duration shorter and more diabetic patients underwent repeat procedures. Amiodarone, OR 0.56, p = 0.04, sotalol, OR 0.61, p = 0.02 and arrhythmia duration, < 6 m, OR 0.72, p = 0.03 were independent predictors of improved outcome in first procedures only. In patients undergoing first procedures on amiodarone or sotalol, median time to arrhythmia recurrence was longer and 12 m SR rates higher, 6.0 +/- 2.4 m (42%) than those who had a repeat procedure on the same medication, 1.5 +/- 0.1 m (33%), p = 0.06. CONCLUSIONS: The efficacy of first and subsequent DCCV procedures is similar, achieving a similar proportion of SR maintenance at 1 year. However, the benefits of AAD therapy are the greatest following first time procedures. Concomitant AAD therapy should be considered for all first time procedures for persistent AF.

Elective laparoscopic sigmoid resection for diverticular disease has fewer complications than conventional surgery: a meta-analysis.

BACKGROUND: We performed a meta-analysis of published literature comparing the complications after open and laparoscopic elective sigmoidectomy for diverticular disease. METHODS: Electronic databases were searched from January 1991 to March 2009. A systematic review was performed to obtain a summative outcome. RESULTS: Nineteen comparative studies involving 2,383 patients were analyzed. There were 1,014 patients in the laparoscopic group and 1,369 patients in the open group. There was no significant heterogeneity among any of the complications analyzed. Patients in the laparoscopic sigmoid resection group had fewer wound infections (fixed effects model: risk ratio [RR], .54; 95% confidence interval [CI], .36-.80; z, -3.05; P < .01; random effects model: RR, .59; 95% CI, .39-.89; z, -2.54; P < .05), blood transfusions (fixed effects model: RR, .25; 95% CI, .10-.60; z, -3.10; P < .01; random effects model: RR, .28; 95% CI, .11-.68; z, -2.81; P < .01), and ileus rates (fixed effects model: RR, .37; 95% CI, .20-.66; z, -3.34; P = .001; random effects model: RR, .37; 95% CI, .20-.68; z, -3.21; P = .001) compared with open sigmoid resections. No difference was seen for medical complications, need for rehospitalization, and reoperation. CONCLUSIONS: Laparoscopic sigmoid resection is safe and has fewer postoperative surgical complications. This approach should be considered for elective cases, however, more randomized controlled trials are required to strengthen the evidence.

A meta-analysis comparing side to end with colonic J-pouch formation after anterior resection for rectal cancer.

BACKGROUND: A meta-analysis of published literature comparing J-pouch with side to end anastomosis after anterior resection (AR) for rectal cancer. METHODS: Electronic databases were searched from January 1980 to March 2009. A systematic review was performed to obtain a summative outcome. RESULTS: Four randomized controlled trials involving 273 patients were analysed. One hundred and thirty-eight patients were in the J-pouch and 135 in the side to end anastomosis (STEA) group. No significant difference in surgically related outcomes was established (hospital stay, operative time, estimated blood loss, overall morbidity and mortality). Resting pressures at 24 months post-operatively were lower in J-pouch group compared with STEA and approached statistical significance [random effects model: SMD = -1.23, 95% CI (-2.47, -0.01), z = -1.94, P = 0.053]. No statistical difference was found in volumetric parameters (Volume at which the patient first experiences a sensation to defaecate and maximal tolerable volume). No statistical difference except urgency at 6 months [P < 0.05] was elicited in functional outcomes (use of enemas, bowel medications, pads, incomplete defaecation and stool frequency) between J-pouch and STEA groups. CONCLUSIONS: J-pouch or STEA are acceptable and safe options after AR for rectal cancer. Either approach may be considered according to surgeon choice. A randomized controlled trial including a larger number of patients is required to strengthen the evidence.

Impact of an intervention to control Clostridium difficile infection on hospital- and community-onset disease; an interrupted time series analysis.

Strategies to reduce rates of Clostridium difficile infection (CDI) generally recommend isolation or cohorting of active cases and the reduced use of cephalosporin and quinolone antibiotics. Data supporting these recommendations come predominantly from the setting of epidemic disease caused by ribotype 027 strains. We introduced an initiative involving a restrictive antibiotic policy and a CDI-cohort ward at an acute, 820-bed teaching hospital where ribotype 027 strains account for only one quarter of all CDI cases. Antibiotic use and monthly CDI cases in the 12 months before and the 15 months after the initiative were compared using an interrupted time series analysis and segmented regression analysis. The initiative resulted in a reduced level of cephalosporin and quinolone use (22.0% and 38.7%, respectively, both p <0.001) and changes in the trends of antibiotic use such that cephalosporin use decreased by an additional 62.1 defined daily doses (DDD) per month (p <0.001) and antipseudomonal penicillin use increased by 20.7 DDD per month (p = 0.011). There were no significant changes in doxycycline or carbapenem use. Although the number of CDI cases each month was falling before the intervention, there was a significant increase in the rate of reduction after the intervention from 3% to 8% per month (0.92, 95% CI 0.86-0.99, p = 0.03). During the study period, there was no change in the proportion of cases having their onset in the community, nor in the proportion of ribotype 027 cases. CDI cohorting and restriction of cephalosporin and quinolone use are effective in reducing CDI cases in a setting where ribotype 027 is endemic.

Botulinum toxin vs glyceryltrinitrate for the medical management of chronic anal fissure: a meta-analysis.

OBJECTIVE: The objective of this review was to analyse systematically the prospective randomized controlled trials on the effectiveness of botulinum toxin (BTX) and glyceryltrinitrate (GTN) for the pharmacological management of chronic anal fissure (CAF). METHOD: A systematic review of the literature was undertaken. Prospective randomized controlled trials on the effectiveness of BTX and GTN for the management of CAF were selected according to specific criteria and analysed to generate summative data. RESULTS: Six studies encompassing 355 patients with CAF were retrieved from electronic databases. Only three randomized controlled trials on 180 patients qualified for the meta-analysis according to inclusion criteria. There were 90 patients in BTX and 90 in the GTN group. BTX and GTN were equally effective in healing/improving the CAF. There was no statistically significant difference between the two pharmacotherapies [RR 1.29 (0.98-1.70) 95% CI, z = -1.83, P = 1.93, Fig. 1]. However, there was statistically significant heterogeneity among the trials (Q = 4.03, df = 1, P = 0.042). On fixed effect model, GTN was associated with higher incidence of total side effects [fixed effect model RR 0.14 (0.05-0.40) 95% CI, z = -3.71, P = 0.0002] and headache [RR 0.07 (0.02-0.20) 95% CI, z = -5.05, P = 0.0007] among patients of CAF. CONCLUSION: Botulinum toxin is as effective as GTN for the management of CAF but it is associated with a lower complication rate. BTX can be recommended as a first-line therapy for chemical sphincterotomy in patients of CAF. However, a major and multi-centre randomized controlled trial is required to support this treatment approach in order to establish stronger evidence.

The efficacy of diltiazem and glyceryltrinitrate for the medical management of chronic anal fissure: a meta-analysis.

OBJECTIVE: The objective of this review is to systematically analyze the prospective randomized controlled trials on the effectiveness of diltiazem (DTZ) and glyceryltrinitrate (GTN) for the pharmacological management of chronic anal fissure (CAF). MATERIALS AND METHODS: A systematic review of the literature was undertaken. Prospective randomized controlled trials on the effectiveness of DTZ for the management of CAF were selected according to specific criteria and analyzed to generate summative data. RESULTS: Five studies encompassing 263 patients with CAF were retrieved from the electronic databases. Only two randomized controlled trials on 103 patients qualified for the meta-analysis. There were 53 patients in the DTZ group and 50 patients in the GTN group. Both DTZ and GTN were equally effective for the treatment of CAF (random-effect model risk ratio [RR] 0.29 [90.06-1.33] 95% confidence interval [CI], z=0.62, p=0.536). However, there was significant heterogeneity between the trials. GTN was associated with higher side effects rate (fixed-effect model RR 0.45 [0.28-0.73] 95% CI, z= -3.22, p=0.001) and higher headache rate (fixed-effect model RR 0.33 [0.17-0.64] 95% CI, z= -3.27, p=0.001) as compared to DTZ. There was no statistically significant recurrence rate of CAF between two pharmacotherapies (fixed-effect model RR 0.66 [0.18-2.41] 95% CI, z= -0.62, p=0.535). CONCLUSION: Both DTZ and GTN are equally effective and can be used for the management of CAF. However, GTN is associated with a higher rate of side effects (headache/anal irritation), and it should be replaced by DTZ. The recurrence rate of CAF after the use of both pharmacotherapies is equal.

Worthing physiological scoring system: derivation and validation of a physiological early-warning system for medical admissions. An observational, population-based single-centre study.

BACKGROUND: Several physiological scoring systems (PSS) have been proposed for identifying those at risk of deterioration. However, the chosen specific physiological values chosen and the scores allocated have not been prospectively validated. In this study, we investigate the relative contributions of the ventilatory frequency, heart rate, arterial pressure, temperature, oxygen saturation, and conscious level to mortality in order to devise a robust scoring system. All data were collected on admission to the emergency unit. Precise 'intervention-calling scores' could then be derived to trigger interventions. METHODS: Our observational, population-based single-centred study took place in a 602-bedded district general hospital. Patients admitted to the emergency care unit at Worthing general hospital during an initial study period between July and November 2003 (n = 3184) and a further validation period between October and November 2005 (n = 1102) were included. RESULTS: Multivariate logistic regression analysis demonstrated that a ventilatory frequency > or = 20 min(-1), heart rate > or =102 min(-1), systolic blood pressure < or = 99 mm Hg, temperature <35.3 degrees C, oxygen saturation < or = 96%, and disturbed consciousness were associated with an increase in mortality. The Worthing PSS was developed from the regression coefficients associated with each variable. The model showed good discrimination with an area under the receiver operating characteristic curve, 0.74, excluding age as a variable. The discrimination of this system was significantly better than the early-warning scoring system. CONCLUSIONS: A simple validated scoring system to predict mortality in medical patients with precise 'intervention-calling scores' has been developed.

Identifying the sick: can biochemical measurements be used to aid decision making on presentation to the accident and emergency department.

BACKGROUND: Early and accurate identification of patients who may benefit from aggressive optimal medical intervention is essential if improved outcomes in terms of survival are to be achieved. We studied the usefulness of routine clinical measurements and/or markers of metabolic abnormality in the early identification of those patients at greatest risk of deterioration on presentation to the accident and emergency department. METHODS: We conducted a prospective observational study in the accident and emergency department of a 602-bed district general hospital. Routine clinical measurements (heart rate, systolic blood pressure, temperature, oxygen saturation in room air, level of consciousness and ventilatory frequency) and venous blood analysis for metabolic markers (pH, bicarbonate, standard base excess, lactate, anion gap, strong ion difference, and strong ion gap) and biochemical markers (Na+, K+, Ca2+, Cl-, PO4- albumin, urea and creatinine) were recorded from unselected consecutive hospital admissions over two 3-month periods (September-November 2002 and February-April 2003). RESULTS: Logistic regression analysis showed that neither conventional clinical measurements upon presentation to the accident and emergency department nor venous biochemical and metabolic indices have good discriminatory ability when used as single predictors of either hospital mortality or length of hospital stay. Selecting variables from all the clinical and venous blood measurements gave a parsimonious model containing only age, heart rate, phosphate and albumin (area under the receiver operating characteristic curve, 0.82 [95% CI 0.76, 0.87]). CONCLUSIONS: A combination of clinical and venous biochemical measurements in the accident and emergency department proved the best predictors of hospital mortality. Consequently, they may be helpful as a triage tool in the accident and emergency department to help identify patients at risk of deterioration.