Corrected and republished from: "VP4 Is a Determinant of Alpha-Defensin Modulation of Rotaviral Infection".

IMPORTANCE: Rotavirus is a leading cause of severe diarrhea in young children. Like other fecal-oral pathogens, rotaviruses encounter abundant, constitutively expressed defensins in the small intestine. These peptides are a vital part of the vertebrate innate immune system. By investigating the impact that defensins from multiple species have on the infectivity of different strains of rotavirus, we show that some rotaviral infections can be inhibited by defensins. We also found that rotaviruses may have evolved resistance to defensins in the intestine of their host species, and some even appropriate defensins to increase their infectivity. Because rotaviruses infect a broad range of animals and rotaviral infections are highly prevalent in children, identifying immune defenses against infection and how they vary across species and among viral genotypes is important for our understanding of the evolution, transmission, and zoonotic potential of these viruses as well as the improvement of vaccines.

VP4 Is a Determinant of Alpha-Defensin Modulation of Rotaviral Infection.

Fecal-oral pathogens encounter constitutively expressed enteric alpha-defensins in the intestine during replication and transmission. Alpha-defensins can be potently antiviral and antibacterial; however, their primary sequences, the number of isoforms, and their activity against specific microorganisms often vary greatly between species, reflecting adaptation to species-specific pathogens. Therefore, alpha-defensins might influence not only microbial evolution and tissue tropism within a host but also species tropism and zoonotic potential. To investigate these concepts, we generated a panel of enteric and myeloid alpha-defensins from humans, rhesus macaques, and mice and tested their activity against group A rotaviruses, an important enteric viral pathogen of humans and animals. Rotaviral adaptation to the rhesus macaque correlated with resistance to rhesus enteric, but not myeloid, alpha-defensins and sensitivity to human alpha-defensins. While mouse rotaviral infection was increased in the presence of mouse enteric alpha-defensins, two prominent genotypes of human rotaviruses were differentially sensitive to human enteric alpha-defensins. Furthermore, the effects of cross-species alpha-defensins on human and mouse rotaviruses did not follow an obvious pattern. Thus, exposure to alpha-defensins may have shaped the evolution of some, but not all, rotaviruses. We then used a genetic approach to identify the viral attachment and penetration protein, VP4, as a determinant of alpha-defensin sensitivity. Our results provide a foundation for future studies of the VP4-dependent mechanism of defensin neutralization, highlight the species-specific activities of alpha-defensins, and focus future efforts on a broader range of rotaviruses that differ in VP4 to uncover the potential for enteric alpha-defensins to influence species tropism. IMPORTANCE Rotavirus is a leading cause of severe diarrhea in young children. Like other fecal-oral pathogens, rotaviruses encounter abundant, constitutively expressed defensins in the small intestine. These peptides are a vital part of the vertebrate innate immune system. By investigating the impact that defensins from multiple species have on the infectivity of different strains of rotavirus, we show that some rotaviral infections can be inhibited by defensins. We also found that some, but not all, rotaviruses may have evolved resistance to defensins in the intestine of their host species, and some even appropriate defensins to increase their infectivity. Because rotaviruses infect a broad range of animals and rotaviral infections are highly prevalent in children, identifying immune defenses against infection and how they vary across species and among viral genotypes is important for our understanding of the evolution, transmission, and zoonotic potential of these viruses as well as the improvement of vaccines.

Clinical utility of methicillin-resistant Staphylococcus aureus nasal PCR to streamline antimicrobial use in treatment of diabetic foot infection with or without osteomyelitis.

BACKGROUND: Diabetic Foot Infection (DFI) guidelines recommend empiric methicillin-resistant Staphylococcus aureus (MRSA)-targeted therapy in settings where there is high prevalence of MRSA infections or in cases of severe infection; however, they do not provide recommendations for de-escalation. This approach has the potential to increase unnecessary use of broad-spectrum antibiotics; therefore, additional strategies are needed to optimize appropriate antibiotic use. This study evaluates the effect of MRSA nasal PCR testing on MRSA-targeted antibiotic use and clinical outcomes in patients with DFI. METHODS: This was a retrospective quasi-experimental study of patients admitted to South Texas Veterans Health Care System for DFI, with or without osteomyelitis (OM), who had an MRSA nasal PCR and culture data. Eligible patients were identified from the Corporate Data Warehouse and reviewed via electronic health record. Patients were allocated into two groups: PRE (5/1/2019-4/30/2020) and POST (12/1/2020-11/30/2021) protocol implementation for de-escalation or avoidance of MRSA-targeted antibiotics. The primary outcome was median (interquartile range [IQR]) hours of empiric inpatient MRSA-targeted antibiotic therapy. A Wilcoxon Rank Sum test was used to assess the difference between the groups for the primary outcome. Secondary outcomes included the proportion of patients needing MRSA coverage added back for MRSA after de-escalation, hospital readmission, length of hospital stay (LOS), patient mortality, and acute kidney injury. RESULTS: A total of 151 patients were included (83 PRE; 68 POST). Most patients were male (98% PRE; 97% POST) with a median age of 64 (IQR, 56-72) years. Incidence of MRSA in DFI in the cohort was 14.7% overall (12% PRE and 17.6% POST). MRSA was detected via nasal PCR in 12% of patients 15.7% PRE and 7.4% POST). After protocol implementation, there was a significant decrease in empiric MRSA-targeted antibiotic therapy use, from a median of 72 (IQR, 27-120) hours in the PRE group, to 24 (IQR, 12-72) hours in the POST group (p < 0.01). No significant differences were found for other secondary outcomes. CONCLUSION: This study of patients presenting to a Veterans Affairs (VA) hospital with DFI identified a statistically significant decrease in median duration of MRSA-targeted antibiotic use post-protocol implementation. This suggests a favorable effect of MRSA nasal PCR for de-escalation or avoidance of MRSA-targeted antibiotics in DFI.

Comparative-Effectiveness of Oral Beta-Lactams and Fluoroquinolones for Stepdown Therapy in Patients with Enterobacterales Bloodstream Infections: A Retrospective Cohort Study.

Background: This study compares treatment failure for patients who received oral beta-lactams (BLs) and fluoroquinolones (FQs) for stepdown treatment of Enterobacterales bloodstream infections (BSIs). Methods: We conducted a single-center, retrospective, age- and sex-matched, cohort study, at a Veterans Affairs (VA) hospital in South Texas. Eligible patients were at least 18 years of age with a monomicrobial BSI treated with a single oral BL or FQ antibiotic. Treatment failure was defined as recurrence or all-cause mortality within 90 days of documented BSI. Bivariate (chi-square, Fisher's Exact, and Wilcoxon Rank Sum) and multivariate (logistic regression) statistical tests were used to compare groups. Results: A total of 130 patients were included in this study, with 65 patients per group. Groups were well balanced with respect to exact age, sex assigned at birth, Caucasian race, source control, intensive care unit admission, and Charlson Comorbidity Index. Importantly, 60% of patients in the BL group had cultures that were resistant to FQs and 71% were prescribed cefpodoxime. Patients in the BL group had higher median (interquartile range [IQR]) Pitt bacteremia scores than those in the FQ group: 2 (1-4) vs. 1 (1-2), p=0.04. Patients in the BL group also had a higher median (IQR) duration of intravenous (IV) antibiotics than those in the FQ group: 5 (3-7) vs. 4 (3-5), p=0.02. Treatment failure was statistically comparable for patients in the BL and FQ groups: 15% vs. 12%, p=0.61. This finding was consistent in a multivariate logistic regression model with group (BL vs. FQ) as the independent variable, treatment failure as the dependent variable, and Pitt bacteremia score and duration of IV antibiotics as covariates (OR: 0.76, 95% CI: 0.27-2.18). One patient in the FQ group experienced Clostridioides difficile infection. Conclusion: This study suggests that BLs may be as effective as FQs for oral stepdown treatment of Enterobacterales BSI without the potential associated risks. Furthermore, in the setting of FQ-resistant Enterobacterales BSI secondary to urinary source, third generation oral cephalosporins (i.e., cefpodoxime) may be reasonable alternatives.

Direct percutaneous endoscopic gastrostomy for nutritional support in patients with aerodigestive tract cancers.

BACKGROUND: Conventional pull-through percutaneous endoscopic gastrostomy (PEG) risks infection and tumour implantation in head and neck cancers. Endoscopically inserted direct gastrostomy has lower rates of complications but is underutilised. AIMS: To describe the endoscopic steps for direct gastrostomy insertion and review our single-centre experience to assess the technical feasibility and safety. METHODS: Patients who underwent endoscopic direct gastrostomy insertion between December 2016 and June 2021 were included. A 24Fr introducer kit for gastrostomy feeding tube (Avanos Healthcare, Australia) was used. Patient and tumour characteristics, procedural data and 30-day outcomes were recorded. RESULTS: Thirty patients underwent direct PEG insertion (mean age 64 years and 24 male). All were planned for or currently undergoing radiotherapy. Twenty-six (87%) of 30 cases were performed under conscious sedation over a median procedure time of 21 min (interquartile range 11 min). No tumour seeding was seen, and one case of PEG-site infection was observed. CONCLUSIONS: Direct PEG is safe and effective and should be considered for patients with aerodigestive tract cancer in need of nutritional support.

Treatment of HR+/HER2- breast cancer in urban mainland China: results from the CancerMPact Survey 2019.

PURPOSE: To report the treatment utilization patterns for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer in urban mainland China (CancerMPact®). METHODS: The results presented are from an online survey conducted in September 2019 with 45 physicians treating breast cancer patients from 11 cities in mainland China. RESULTS: Surveyed physicians reported that Stage I HR+/HER2(-) breast cancer patients are often treated with surgery alone (42%), whereas the use of surgery in combination with systemic therapy with or without radiotherapy increases in later stages (Stage II 67%, Stage III 77%). Doxorubicin-cyclophosphamide (AC)-based regimens were the most common in both the neoadjuvant and adjuvant settings in HR+/HER2(-) breast cancer patients, across all stages. In metastatic patients, use of surgery and radiotherapy decreases in favor of utilization of systemic therapy alone. Pre- and post-menopausal metastatic patients were frequently treated with hormone therapy or AC-based regimens in first line. Regardless of the first-line therapy administered, capecitabine-based regimens were commonly used in second line. In third line, chemotherapy regimens containing capecitabine or gemcitabine were given to nearly 40% of HR+/HER2(-) breast cancer patients. There were no standard of care regimens established for fourth or greater lines of treatment. In metastatic HR+/HER2(-) breast cancer, physicians reported 50% objective response rates in first-line settings with a progression-free survival of 16 months. CONCLUSION: HR+/HER2(-) breast cancer patients in urban mainland China were prescribed chemotherapy regimens more frequently than CDK4/6 inhibitors. Treatment practices varied, with physicians reporting the use of multiple modalities and treatment regimens for their patients.

Quality of upper GI endoscopy: a prospective cohort study on impact of endoscopist education.

BACKGROUND AND AIMS: Guidelines on quality of upper GI (UGI) endoscopy have been proposed by the British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE). However, these guidelines have not been evaluated in clinical practice. We aimed to measure the impact of endoscopist education on the quality of gastroscopy based on these guidelines and the association between compliance with guidelines and the detection of clinically significant premalignant pathology such as Barrett's esophagus (BE), esophageal squamous dysplasia, gastric intestinal metaplasia (GIM), and Helicobacter pylori. METHODS: Endoscopists participated in a 1-hour education session on recommended performance measures and endoscopic detection of premalignant pathologies. A controlled before and after study was performed, measuring compliance with guidelines and rates of detection of pathology in control and intervention groups. RESULTS: Over 2 years, 2719 procedures were performed: 1412 in the control group and 1307 in the intervention group. The proportion of procedures complying with guidelines was higher in the intervention group. The use of biopsy sampling protocols (eg, management of precancerous conditions of the stomach, 52% vs 91%; P = .007) and standardized terminology (eg, Forrest classification, 24% vs 68%; P < .001) was significantly higher. Detection of H pylori was higher in the intervention group (5.5% vs 9.8%, P = .003). Minimum inspection time of 7 minutes was associated with detection of BE (7.4% vs 2.0%, P < .001). CONCLUSIONS: A simple endoscopist education session enhanced the quality of UGI endoscopy by improving compliance with BSG and ESGE recommendations and increasing the detection of clinically significant pathology. A minimum inspection time of 7 minutes was associated with increased diagnostic yield and may be a feasible quality indicator for clinical practice.

Evaluation of Endoscopic Practices and Outcomes in Follow-up of Gastric Ulcers.

GOAL: The aim of this study was to evaluate current practice in gastric ulcer follow-up to establish diagnostic yield and predictors of malignancy. BACKGROUND: Repeat gastroscopy is routinely performed to confirm gastric ulcer healing and exclude malignancy. However, the incidence of malignancy at follow-up endoscopy is low, without consensus regarding case selection and timing. STUDY: New gastric ulcers diagnosed on gastroscopy at 2 institutions in Australia were identified through keyword search of endoscopy reports over a 5-year period (2013 to 2017). Data collected included patient demographics, clinical presentation, and endoscopic and histologic findings from initial and subsequent gastroscopies. RESULTS: Of 795 patients, repeat gastroscopy was performed in 440 (55%). Malignancy was diagnosed in 52 (7%) with 83% identified at initial gastroscopy. Eight cancers were identified at repeat gastroscopy with malignancy yield of 2% (8/440). Three were diagnosed in patients with benign initial ulcer histology (3/286, 1%). One cancer was diagnosed during follow-up in a patient with benign histology but no repeat gastroscopy (1/286, 0.3%). Predictors of benign ulcers were absence of endoscopic suspicion [odds ratio (OR) 0.1 (0.03-0.13), P≤0.005], complete healing on repeat gastroscopy [OR 0.5 (0.34-0.70), P=0.036] and benign initial histology [OR 0.12 (0.43-0.90), P≤0.005]. CONCLUSIONS: Seven percent of new gastric ulcers were malignant with most identified with biopsy on initial gastroscopy. Malignancy yield from follow-up gastroscopy was 2%. Diagnostic yield of endoscopic follow-up may be low in ulcers with benign appearance and adequate histology. However, current practice of repeat gastroscopy is warranted in the absence of patient-based and lesion-based predictors of malignancy.

Quality of Life in Chronic Limb Threatening Ischaemia: Systematic Review and Meta-Analysis.

OBJECTIVE: To assess the comparative effectiveness and temporal changes in quality of life (QoL) outcomes after revascularisation, major lower extremity amputation (MLEA), and conservative management (CM) in chronic limb threatening ischaemia (CLTI). DATA SOURCES: MEDLINE, Embase, PsycINFO, CINAHL, and Web of Science. REVIEW METHODS: A systematic review and meta-analysis were performed on QoL measured by any QoL instrument in adult patients with CLTI after open surgery (OS), endovascular intervention (EVI), MLEA, or CM. Randomised controlled trials and prospective observational studies published in any language between 1 January 1990 and 21 May 2021 were included. There was a pre-specified measurement time point of six months. Random effects meta-analysis was conducted on total scores for each QoL instrument. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations approach (PROSPERO registration: CRD42021253953). RESULTS: Fifty-five studies with 8 909 patients were included. There was significant heterogeneity in the methods used to measure QoL, and the study characteristics. In particular, 14 different QoL instruments were used with various combinations of disease specific and generic instruments within each study. A narrative summary is therefore presented. Comparative effectiveness data showed there was reasonable certainty that QoL was similar between OS and EVI at six months. Temporal outcomes suggested small to moderate improvements in QOL six months after OS and EVI compared with baseline. Limited data indicated that QoL can be maintained or slightly improved after MLEA or CM. Treatment effects were overestimated owing to small study effects, selective non-reporting, attrition, and survivorship bias. CONCLUSION: QoL after OS and EVI appears to be similar. Revascularisation may provide modest QoL benefits, while MLEA or CM can maintain QoL. However, certainty of evidence is generally low or very low, and interpretation is hampered by significant heterogeneity. There is a need for a CLTI specific QoL instrument and methodological standardisation in QoL studies.

Toward Understanding COVID-19 Recovery: National Institutes of Health Workshop on Postacute COVID-19.

Over the past year, the SARS-CoV-2 pandemic has swept the globe, resulting in an enormous worldwide burden of infection and mortality. However, the additional toll resulting from long-term consequences of the pandemic has yet to be tallied. Heterogeneous disease manifestations and syndromes are now recognized among some persons after their initial recovery from SARS-CoV-2 infection, representing in the broadest sense a failure to return to a baseline state of health after acute SARS-CoV-2 infection. On 3 to 4 December 2020, the National Institute of Allergy and Infectious Diseases, in collaboration with other Institutes and Centers of the National Institutes of Health, convened a virtual workshop to summarize existing knowledge on postacute COVID-19 and to identify key knowledge gaps regarding this condition.

Unraveling the Mysteries of Acute Flaccid Myelitis: Scientific Opportunities and Priorities for Future Research.

Since 2014, cases of acute flaccid myelitis (AFM) have been reported in the United States in increasing numbers biennially, occurring in the late summer and early fall. Although there is unlikely to be a single causative agent of this syndrome, non-polio enteroviruses, including enterovirus D-68 (EV-D68), have had epidemiological and laboratory associations with AFM. Much remains to be known about AFM and AFM-associated enteroviruses, including disease pathogenesis and the best strategies for development of therapeutics or preventive modalities including vaccines. To catalyze research that addresses these scientific and clinical gaps, the National Institute of Allergy and Infectious Diseases convened a workshop entitled "AFM Preparedness: Addressing EV-D68 and Other AFM-Associated Enteroviruses" on 19-20 February 2020.

Validation of Available Extended-Spectrum-Beta-Lactamase Clinical Scoring Models in Predicting Drug Resistance in Patients with Enteric Gram-Negative Bacteremia Treated at South Texas Veterans Health Care System.

Extended-spectrum-beta-lactamase (ESBL)-producing Enterobacteriaceae are increasingly common; however, predicting which patients are likely to be infected with an ESBL pathogen is challenging, leading to increased use of carbapenems. To date, five prediction models have been developed to distinguish between patients infected with ESBL pathogens. The aim of this study was to validate and compare each of these models to better inform antimicrobial stewardship. This was a retrospective cohort study of patients with Gram-negative bacteremia treated at the South Texas Veterans Health Care System over 3 months from 2018 to 2019. We evaluated isolate, clinical syndrome, and score variables for the five published prediction models/scores: Italian "Tumbarello," Duke, University of South Carolina (USC), Hopkins clinical decision tree, and modified Hopkins. Each model was assessed using the area under the receiver operating characteristic curve (AUROC) and Pearson correlation. One hundred forty-five patients were included for analysis, of which 20 (13.8%) were infected with an ESBL Escherichiacoli or Klebsiella spp. The most common sources of infection were genitourinary (55.8%) and gastrointestinal/intraabdominal (24.1%), and the most common pathogen was E. coli (75.2%). The prediction model with the strongest discriminatory ability (AUROC) was Tumbarello (0.7556). The correlation between prediction model score and percent ESBL was strongest with the modified Hopkins model (R2 = 0.74). In this veteran population, the modified Hopkins and Duke prediction models were most accurate in discriminating between Gram-negative bacteremia patients when considering both AUROC and correlation. However, given the moderate discriminatory ability, many patients with ESBL Enterobacteriaceae (at least 25%) may still be missed empirically.

Endoscopic features of buried Barrett's mucosa.

BACKGROUND AND AIMS: Buried Barrett's mucosa is defined as intestinal metaplasia that is "buried" under the normal-appearing squamous epithelium. This can occur in Barrett's esophagus with or without previous endoscopic therapy. Dysplasia and neoplasia within buried Barrett's mucosa have also been reported. However, endoscopic features of buried Barrett's mucosa have not been described. At our tertiary referral center for Barrett's esophagus, several endoscopic features have been observed in patients who were found to have buried Barrett's mucosa on histology. These features are squamous epithelium which is (1) darker pink on white-light and darker brown on narrow-band imaging and/or (2) has a slightly raised or nodular appearance. It was also observed that either of these 2 features is frequently seen adjacent to a Barrett's mucosa island. This study aimed to (1) evaluate the diagnostic accuracy of these endoscopic features, and (2) evaluate the frequency of endoscopically identifiable buried Barrett's mucosa in patients with dysplastic Barrett's esophagus, before and after endoscopic eradication therapy. METHODS: This was a retrospective analysis of a prospectively observed cohort of all cases of dysplastic Barrett's esophagus referred to St Vincent's Hospital, Melbourne. Endoscopy documentation software and histopathology reports of esophageal biopsy and EMR specimens between March 2013 and March 2019 were searched for terms "buried" or "subsquamous" Barrett's mucosa. Endoscopic reports, images, and histopathology reports of suspected buried Barrett's mucosa were then reviewed to apply the endoscopic features and correlate with the histologic diagnosis. RESULTS: In a cohort of 506 patients with dysplastic Barrett's esophagus, 33 (7%) patients (73% male, median age at referral 70.5 years) had buried Barrett's mucosa on histology. Twenty-seven (82%) patients had previous treatment for dysplastic Barrett's esophagus; radiofrequency in 2 (6%), EMR in 4 (12%), and both modalities in 21 (64%). Six (18%) had no previous treatment. Histologically confirmed buried Barrett's mucosa was suspected at endoscopy in 26 patients (79%). Endoscopic features were (1) darker pink or darker brown mucosa underneath squamous epithelium (24%), (2) raised areas underneath squamous mucosa (27%), and both features present concurrently (27%). These features were associated with adjacent islands of Barrett's esophagus in 48%. Forty-four cases of buried Barrett's mucosa were suspected endoscopically, and these were sampled by biopsy (50%) and EMR (50%). Buried Barrett's mucosa was confirmed in 26 cases, with a positive predictive value of endoscopic suspicion of 59%. Eighteen cases of endoscopically suspected buried Barrett's mucosa had no buried Barrett's mucosa on histology; inflammation or reflux was identified in 12 (67%) patients. Dysplasia was identified within buried Barrett's mucosa in 12 (36%) patients; 5 intramucosal adenocarcinoma, 1 high-grade dysplasia, and 6 low-grade dysplasia. Endoscopic features of buried Barrett's mucosa were observed in 11 of 12 cases harboring dysplasia or neoplasia, compared with 15 of 21 cases of buried Barrett's mucosa without dysplasia. CONCLUSIONS: In this retrospective analysis of prospectively observed patients with dysplastic Barrett's esophagus, buried Barrett's mucosa was identified in 7%, including treatment-naive patients. The proposed endoscopic features of buried Barrett's mucosa were seen in 79% of patients with histology confirmed disease. These endoscopic features may predict the presence of buried Barrett's mucosa, which may contain dysplasia or neoplasia. An overlap between the endoscopic features of inflammation, reflux, and buried Barrett's mucosa was observed. Future prospective studies are required to develop and validate endoscopic criteria for identifying buried Barrett's mucosa.

Quantifying early gastric cancer in Australia: What is the opportunity for gastric endoscopic submucosal dissection?

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) is the recommended treatment for early gastric cancer (EGC). However, there are challenges in attaining expertise in ESD in countries where the incidence of gastric cancer and proportion diagnosed at an early stage of disease are relatively low. This study aims to establish the proportion of gastric cancer meeting histological criteria for EGC, which may be suitable for ESD, in a Western population. METHODS: Gastric cancers reported to the Victorian Cancer Registry between January 2011 and December 2016 were analyzed. EGC was defined as tumor confined to mucosa (T1a) or submucosa (T1b). Histology reports were analyzed using Japanese and European guidelines to identify potential ESD candidates. Criteria for extended ESD were based on grade of differentiation, tumor depth, lymphovascular and perineural invasion, and ulceration. RESULTS: Twenty percent of 1217 gastric cancers was EGC (237 cases), with detailed histopathology reports suitable for evaluating ESD criteria recorded in 182 cases. Standard and extended ESD criteria were met in 46% (84/182) and 75% (132/182), respectively. Actual treatment of the 237 EGC was endoscopic in 14% (n = 33) and surgery in 86% (n = 204). Endoscopically treated EGCs were more likely to be stage T1a and located in the proximal stomach. CONCLUSIONS: EGCs represented 20% of reported gastric adenocarcinomas with the majority fulfilling criteria for ESD. ESD should be considered in the management algorithm and discussed at tumor board meetings involving interventional endoscopists. To increase utilization of ESD, systems need to be implemented to improve training, accreditation, and access to ESD.

Suboptimal use of pharmacological venous thromboembolism prophylaxis in cirrhotic patients.

BACKGROUND: Cirrhosis was previously perceived as a haemorrhagic disease state due to frequent associations with coagulopathy and bleeding. However, the coagulopathy of cirrhosis is complex with defects in both procoagulant and anticoagulant factors. Derangements in common laboratory indices of coagulation do not accurately reflect bleeding risk or protection from thrombotic events. AIMS: To assess the rate of pharmacological prophylaxis for venous thromboembolism (VTE) among hospital inpatients with cirrhosis and analyse factors associated with prophylaxis being inappropriately withheld. METHODS: A retrospective cohort study was performed in a tertiary teaching hospital. Patients included were admitted for greater than 48 h with discharge diagnosis codes corresponding to chronic liver disease and/or cirrhosis. The use of VTE chemoprophylaxis with enoxaparin was assessed in cirrhotic patients and non-cirrhotic controls. Patient data collected included contraindications to prophylaxis, known high-risk varices, international normalised ratio (INR), creatinine, bilirubin, haemoglobin and platelet count. RESULTS: Of 108 patients with cirrhosis eligible for VTE prophylaxis, 61 (56.5%) received prophylaxis compared to 104 (96.3%) non-cirrhotic patients. Platelets and INR were significantly different between those who did and did not receive VTE prophylaxis. On multivariate analysis, platelet count and INR were independent predictors for VTE not being administered. CONCLUSION: The administration of chemoprophylaxis in accordance with the hospital guidelines was suboptimal in patients with cirrhosis. Platelet count and INR were independent predictors of prophylaxis use. Our results suggest persistent misperceptions that prolonged INR and thrombocytopenia predict bleeding risk in cirrhosis.

Liver transplantation: a systematic review of long-term quality of life.

BACKGROUND & AIMS: Liver transplantation is the only curative intervention for terminal liver disease. Accurate long-term quality of life (QOL) data are required in the context of improved surgical outcomes and increasing post-transplant survival. This study reviews the long-term QOL after primary liver transplantation in adult patients surviving 5 or more years after surgery. METHODS: A literature search was conducted on PubMed for all studies matching the eligibility criteria between January 2000 and October 2013. Bibliographies of included studies were also reviewed. Two authors independently performed screening of titles and abstracts. Consensus for studies included for review was achieved by discussion between authors based on predetermined eligibility criteria. Quality appraisal and data tabulation were performed using predetermined forms. Results were synthesized by narrative review. RESULTS: Twenty-three studies (5402 patients) were included. QOL following liver transplantation remains superior to preoperative status up to 20 years post-operatively. More post-operative complications predicted worse QOL scores especially in physical domains. Benefits in functional domains persist long-term with independence in self-care and mobility. Employment rates recover in the short-term but decline after 5 years, and differ significantly between various aetiologies of liver disease. Overall QOL improves to a similar level as the general population, but physical function remains worse. Participation in post-operative physical activity is associated with superior QOL outcomes in liver transplant recipients compared to the general population. QOL improvements are similar compared to lung, kidney and heart transplantation. Heterogeneity between studies precluded quantitative analysis. CONCLUSIONS: Liver transplantation confers specific long-term QOL and functional benefits when compared to preoperative status. This information can assist in providing a more complete estimate of the overall health of liver transplant recipients and the effectiveness of surgery. Guidelines for future studies are provided.