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Aim: To evaluate the prognostic impact at admission of 10 biochemical indices for prediction postoperative myocardial injury (PMI) and/or hospital death in hip fracture (HF) patients. Methods: In 1273 consecutive patients with HF (mean age 82.9 ± 8.7 years, 73.5% women), clinical and laboratory parameters were collected prospectively, and outcomes were recorded. Multiple logistic regression and receiver-operating characteristic analyses (the area under the curve, AUC) were preformed, the number needed to predict (NNP) outcome was calculated. Results: Age ≥ 80 years and IHD were the most prominent clinical factors associated with both PMI (with cardiac troponin I rise) and in-hospital death. PMI occurred in 555 (43.6%) patients and contributed to 80.3% (49/61) of all deaths (mortality rate 8.8% vs. 1.9% in non-PMI patients). The most accurate biochemical predictive markers were parathyroid hormone > 6.8 pmol/L, urea > 7.5 mmol/L, 25(OH)vitamin D < 25 nmol/L, albumin < 33 g/L, and ratios gamma-glutamyl transferase (GGT) to alanine aminotransferase > 2.5, urea/albumin ≥ 2.0 and GGT/albumin ≥ 7.0; the AUC for developing PMI ranged between 0.782 and 0.742 (NNP: 1.84–2.13), the AUC for fatal outcome ranged from 0.803 to 0.722, (NNP: 3.77–9.52). Conclusions: In HF patients, easily accessible biochemical indices at admission substantially improve prediction of hospital outcomes, especially in the aged >80 years with IHD.

BACKGROUND AND AIM Our aim was to evaluate the efficacy and safety of a lumen-apposing metal stent with an electrocautery-enhanced delivery system (EDS-LAMS) for endoscopic ultrasound (EUS)-guided drainage of pancreatic fluid collections (PFCs) in regular clinical practice. METHODS A retrospective and subsequent prospective analysis was undertaken of all patients who underwent EUS-guided drainage of their PFCs using the EDS-LAMS at 17 tertiary therapeutic endoscopy centers. RESULTS Two hundred eight cases of EDS-LAMS deployment were attempted in 202 patients (mean age 52.9 years) at time of evaluation. Ninety-seven patients had pancreatic pseudocysts (PPs), 75 walled-off pancreatic necrosis (WOPN), 10 acute peripancreatic fluid collections (APFCs), 6 acute necrotic collections (ANCs), and 14 postoperative collections (POCs). Procedural technical success was achieved in 202/208 cases (97.1%). Maldeployment occurred in 7/208 cases (3.4%). Clinical success was achieved in 142/160 (88.8%) patients (PP 90%, WOPN 85.2%, APFC 100%, ANC 75%, POC 100%). Delayed adverse events included stent migration in 15/202 (7.4%), stent occlusion and infection in 16/202 (7.9%), major bleeding in 4/202 (2%), and buried EDS-LAMS in 2/202 (1%). PFC recurrence occurred in 13/142 (9.2%) patients; 9/202 (4.5%) required surgical or radiological intervention for PFC management after EDS-LAMS insertion. CONCLUSIONS This large international multicenter study evaluating the EDS-LAMS for drainage of PFCs in routine clinical practice suggests that the EDS-LAMS are safe and effective for drainage of all types of PFCs; however, further endoscopic therapy is often required for WOPN. Major bleeding was a rare complication in our cohort.

Background:There are unmet needs in objective prognostic indicators for Hip Fracture (HF) outcomes.Objectives:To evaluate the determinants and prognostic impact of elevated serum urea, a key factor of nitrogen homeostasis, in predicting hospital mortality, inflammatory complications and length of stay in HF patients.Methods:In 1819 patients (mean age 82.8±8.1 years; 76.4% women) with osteoporotic HF, serum urea level at admission along with 22 clinical and 35 laboratory variables were analysed and outcomes recorded. The results were validated in a cohort of 455 HF patients (age 82.1±8.0 years, 72.1% women).Results:Elevated serum urea levels (>7.5mmol/L) at admission were prevalent (44%), independently determined by chronic kidney disease, history of myocardial infarction, anaemia, hyperparathyroidism, advanced age and male gender, and significantly associated with higher mortality (9.4% vs. 3.3%, p20 days: 31.2% vs. 26.2%, p=0.021). The predictive value of urea was superior to other risk factors, most of which lost their discriminative ability when urea levels were normal. Patients with two abnormal parameters at admission, compared to subjects with the normal ones, had 3.6-5.6 -fold higher risk for hospital mortality, 2.7-7.8-fold increase in risk for HPIR and 1.3-1.7-fold higher risk for prolonged hospital stay. Patients with increased admission urea and a high inflammatory response had 9.7 times greater mortality odds compared to patients without such characteristics.Conclusion:In hip fracture patients admission serum urea is an independent and valuable predictor of hospital outcomes, in particular, mortality.

Alexander Fisher,1–3 Wichat Srikusalanukul,1 Leon Fisher,4 Paul N Smith2,3 1Department of Geriatric Medicine, The Canberra Hospital, ACT Health, Canberra, Australia; 2Department of Orthopaedic Surgery, The Canberra Hospital, ACT Health, Canberra, Australia; 3Australian National University Medical School, Canberra, ACT, Australia; 4Department of Gastroenterology, Frankston Hospital, Peninsula Health, Melbourne, Australia Purpose: To estimate the discriminative value of serum P1NP/βCTX ratio and albumin levels in hospitalized orthogeriatric patients with and without nonvertebral fractures. Methods: In 1,239 orthogeriatric patients (mean age 78.1±9.52 years, 69.1% women) including 854 (68.9%) with osteoporotic nonvertebral fractures (455 [36.7%] with hip fracture [HF]) and 385 (31.1%) without fractures, markers of bone formation (procollagen type 1 N-terminal propeptide [P1NP], osteocalcin [OC], and bone resorption (beta-C-terminal cross-linking telopeptide of type 1 collagen [βCTX]), indices of mineral metabolism, and parameters of liver and renal functions were assessed; data on clinical and laboratory characteristics were collected prospectively. Results: Both lower serum P1NP/βCTX ratio and albumin concentration (as continuous or categorical variables) were independently associated with fracture presence in multivariate logistic regressions. Compared with the highest P1NP/βCTX tertile, the prevalence of HF, after adjustment for multiple covariates, was 3-fold higher in the lowest tertile and 1.5 times higher in the middle tertile; presence of any fracture was 2.3- and 1.6-fold higher, respectively; patients with albumin levels in the lowest tertile had multivariate odds ratio (OR) of 4.6 for HF and 2.8 for any fracture, in the middle tertile the ORs were 2.2 and 1.3, respectively. The P1NP/βCTX

This narrative review summarises the benefits, risks and appropriate use of acid-suppressing drugs (ASDs), proton pump inhibitors and histamine-2 receptor antagonists, advocating a rationale balanced and individualised approach aimed to minimise any serious adverse consequences. It focuses on current controversies on the potential of ASDs to contribute to infections-bacterial, parasitic, fungal, protozoan and viral, particularly in the elderly, comprehensively and critically discusses the growing body of observational literature linking ASD use to a variety of enteric, respiratory, skin and systemic infectious diseases and complications (Clostridium difficile diarrhoea, pneumonia, spontaneous bacterial peritonitis, septicaemia and other). The proposed pathogenic mechanisms of ASD-associated infections (related and unrelated to the inhibition of gastric acid secretion, alterations of the gut microbiome and immunity), and drug-drug interactions are also described. Both probiotics use and correcting vitamin D status may have a significant protective effect decreasing the incidence of ASD-associated infections, especially in the elderly. Despite the limitations of the existing data, the importance of individualised therapy and caution in long-term ASD use considering the balance of benefits and potential harms, factors that may predispose to and actions that may prevent/attenuate adverse effects is evident. A six-step practical algorithm for ASD therapy based on the best available evidence is presented.

Pancreatic haemangiomas are a rare cause of pancreatic lesions in adults. Diagnosis is challenging as they are seldom suspected and difficult to differentiate on imaging. Historically, pancreatic haemangiomas have been managed surgically despite their benign nature, largely due to diagnostic uncertainty. We present the case of a 69-year-old woman who, through combination of radiological, biochemical and endoscopic investigations, was diagnosed with pancreatic haemangioma and managed conservatively, avoiding the morbidity and mortality associated with surgical resection of a benign lesion.

Osteoporosis (OP) and osteoporotic fractures (OFs) are common multifactorial and heterogenic disorders of increasing incidence. Helicobacter pylori (H.p.) colonizes the stomach approximately in half of the world’s population, causes gastroduodenal diseases and is prevalent in numerous extra-digestive diseases known to be associated with OP/OF. The studies regarding relationship between H.p. infection (HPI) and OP/OFs are inconsistent. The current review summarizes the relevant literature on the potential role of HPI in OP, falls and OFs and highlights the reasons for controversies in the publications. In the first section, after a brief overview of HPI biological features, we analyze the studies evaluating the association of HPI and bone status. The second part includes data on the prevalence of OP/OFs in HPI-induced gastroduodenal diseases (peptic ulcer, chronic/atrophic gastritis and cancer) and the effects of acid-suppressive drugs. In the next section, we discuss the possible contribution of HPI-associated extra-digestive diseases and medications to OP/OF, focusing on conditions affecting both bone homeostasis and predisposing to falls. In the last section, we describe clinical implications of accumulated data on HPI as a co-factor of OP/OF and present a feasible five-step algorithm for OP/OF risk assessment and management in regard to HPI, emphasizing the importance of an integrative (but differentiated) holistic approach. Increased awareness about the consequences of HPI linked to OP/OF can aid early detection and management. Further research on the HPI–OP/OF relationship is needed to close current knowledge gaps and improve clinical management of both OP/OF and HPI-related disorders.

The data on predictive value of the routinely obtained preoperative biochemical parameters in hip fracture (HF) patients are limited. The aims of this study were to examine in older HF patients (1) the relationships between a broad set of routine laboratory parameters at admission and in-hospital mortality, and (2) evaluate the prognostic value the biomarkers and clinical characteristics (alone or in combination) provide to predict a fatal outcome.In 1820 consecutive patients with low-trauma osteoporotic HF aged60 years (mean age 82.8 ± 8.1 years; 76.4% women; 65% community-dwelling) 35 laboratory variables along with 20 clinical and socio-demographic characteristics at admission were analysed. The validation cohort included data on 455 older (≥60 years of age) HF patients (mean age 82.1 ± 8.0 years, 72.1% women).The mortality rate was 6% (n = 109). On univariate analysis 14 laboratory and 8 clinical parameters have been associated with in-hospital mortality. Multiple regression analyses determined 7 variables at admission as independent indicators of a fatal outcome: 4 biomarkers (albumin33 g/L; alanine aminotransferase/gamma-glutamyl transferase ratio [GGT/ALT]2.5; parathyroid hormone [PTH]6.8 pmol/L; 25(OH)vitamin D 25 nmol/L) and 3 pre-fracture clinical conditions (history of myocardial infarction, chronic kidney disease [GFR60 ml/min/1.73 mIn HF patients, seven easily identifiable at admission characteristics, including 4 biomarkers, are strong and independent indicators of in-hospital mortality and can be used for risk stratification and individualised management.

Aim: To investigate the association of the neutrophil to lymphocyte ratio (NLR) at admission with presence of fracture, comorbid conditions, and its prognostic value for short-term outcomes in orthogeriatric patients. Methods: On 415 consecutive patients (mean age 78.8 ±8.7[SD] years, 281 women, 255 with a non-vertebral bone fracture, including 167 with a hip fracture, HF) admitted to the Department of Orthopaedic Surgery at the Canberra hospital (2010 - 2011) data on clinical and laboratory characteristics were collected prospectively. The validation dataset included 294 consecutive patients (mean age 82.1 ± 8.0 years, 72.1% women) with HF. Results: Multivariate regression revealed four variables, presence of HF, hypoalbuminaemia (6.8 pmol/L), as independent determinants of admission NLR≥5.1. There was a dose-graded relationship between presence of fracture, especially HF, postoperative complications and levels of NLR categorized as tertiles. Compared to patients with NLR100mg/L after the 3rd postoperative day), respectively, while in subjects with NLR>8.5 (third tertile) these risks were 2.6-, 4.9-, 5.9- and 4.5-times higher, respectively; subjects with NLR>8.5 had a 9.7 times higher chance of dying in the hospital compared to patients with NLR 5.1-8.5; the NLR retained its significance on multivariate analyses. The NLR ≥5.1 predicted postoperative myocardial injury with an area under the curve (AUC) of 0.626, CRP>100mg/L with AUC of 0.631 and the NLR >8.5 predicted in-hospital mortality with an AUC of 0.793, showing moderately high sensitivity (86.7%, 80% and 90%, respectively) and negative predictive value (92.9%, 71.2%, 99.6%, respectively), but low specificity. Admission NLR was superior to other, except hypoalbuminaemia, prognostic markers; combined use of both NLR≥5.1 and albumin

Aim: To asses liver markers in older patients with hip fracture (HF) in relation to age, comorbidities, metabolic characteristics and short-term outcomes. Methods: In 294 patients with HF (mean age 82.0±7.9 years, 72.1% women) serum alanine aminotransferase (ALT), gammaglutamyltransferase (GGT), alkaline phosphatase (ALP), albumin, bilirubin, 25(OH)vitaminD, PTH, calcium, phosphate, magnesium, adiponectin, leptin, resistin, thyroid function and cardiac troponin I were measured. Results: Elevated ALT, GGT, ALP or bilirubin levels on admission were observed in 1.7% - 9.9% of patients. With age GGT, ALT and leptin decrease, while PTH and adiponectin concentrations increase. Higher GGT (>30U/L, median level) was associated with coronary artery disease (CAD), diabetes mellitus (DM), and alcohol overuse; lower ALT (≤20U/L, median level) with dementia; total bilirubin >20μmol/L with CAD and alcohol overuse; and albumin >33g/L with CAD. Multivariate adjusted regression analyses revealed ALT, ALP, adiponectin, alcohol overuse and DM as independent and significant determinants of GGT (as continuous or categorical variable); GGT for each other liver marker; and PTH for adiponectin. The risk of prolonged hospital stay (>20 days) was about two times higher in patients with GGT>30U/L or adiponectin >17.14 ng/L (median level) and 4.7 times higher if both conditions coexisted. The risk of in-hospital death was 3 times higher if albumin was

Ventricular standstill (VS) is a potentially fatal arrhythmia that is usually associated with syncope, if prolonged and is rarely asymptomatic[1]. Its mechanism involves either a lack of supraventricular impulse or an interruption in the transmission of these signals from the atria to the ventricles, resulting in a sudden loss of cardiac output[2]. Although rare, ventricular arrhythmias have been associated with intravenous (IV) erythromycin. However, to our knowledge, VS has not been reported following the administration of IV erythromycin. The Authors describe a rare case of asymptomatic VS and subsequent third-degree atrioventricular block, following the administration of IV erythromycin in a 49-year-old woman with borderline hypokalemia. Through this case, the Authors highlight the importance of cardiac monitoring and electrolyte replacement when administering IV erythromycin, as well as discuss several other mechanisms that contribute to ventricular arrhythmias. LEARNING POINTS Intravenous erythromycin is associated with prolongation of the QTc interval and ventricular arrhythmias. Ventricular standstill is a rare but potentially fatal arrhythmia, and may have an association with the administration of intravenous erythromycin. Cardiac monitoring in patients with baseline QTc prolongation and correction of electrolyte disturbances are important when administering intravenous erythromycin.

Background/aim We describe a simulation and scenario-based model of training in gastrointestinal endoscopic hemostasis, which combines acquisition of procedural and problem-solving skills in a close to reality simulated clinical setting. Methods Two day courses in endoscopic hemostasis were conducted at the Clinical Training and Education Centre, the University of Western Australia, Perth, Australia. In total, 23 trainees were enrolled. The Erlangen Endo-Trainer simulator, porcine specimens of esophagus, stomach, and duodenum with a range of simulated bleeding sources, a separate catheter and a pump to simulate massive bleeding, and a full arm model with injectable veins were used. The SimMan monitor and software package were used to simulate hemodynamic parameters and electrocardiogram. Faculty members adjusted the rate of bleeding and vital parameters. The exercise was video recorded. On the first day, the group underwent simulator training in techniques of endoscopic hemostasis. On the second day, participants were scenario-based trained in full management of a "bleeding patient," which included resuscitation, sedation, endoscopy, and hemostasis, acting as leaders in teams of three. The course was evaluated by participants using a standardized questionnaire. Results A complex clinical setting of acute gastrointestinal bleeding was recreated with a high degree of realism. All participants reported that the simulated clinical scenario was a positive learning experience, helpful in managing complications and performing complex problem-solving tasks in a dynamic environment. Conclusions Scenario and simulation-based training in endoscopic hemostasis may provide an opportunity to improve procedural skills and acquire practical experience in managing this medical emergency, which requires the ability to process, integrate, and adequately and quickly respond to complex information in unexpected conditions working as a team leader.

Background and Aim: We report our single-centre experience with endoscopic ultrasound guided fine needle aspiration (EUS-FNA) of solid pancreatic lesions with regard to clinical utility, diagnostic accuracy and safety. Methods: We prospectively reviewed data on 100 consecutive EUS-FNA procedures performed in 93 patients (54 men, mean age 60.6 ± 12.9 years) for evaluation of solid pancreatic lesions. Final diagnosis was based on a composite standard: histologic evidence at surgery, or non-equivocal malignant cytology on FNA and follow-up. The operating characteristics of EUS-FNA were determined. Results: The location of the lesions was pancreatic head in 73% of cases, the body in 20% and the tail in 7%. Mean lesion size was 35.1 ± 12.9 mm. The final diagnosis revealed malignancy in 87 cases, including adenocarcinomas (80.5%), neuroendocrine tumours (11.5%), lymphomas (3.4%) and other types (4.6%). The FNA findings were: 82% interpreted as malignant cytology, 1% as suspicious for neoplasia, 1% as atypical, 7% as benign process and 9% as non-diagnostic. No false-positive results were observed. There was a false-negative rate of 5%. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 94.3%, 100%, 100%, 72.2% and 95%, respectively. In 23 (88.5%) of 26 aspirated lymph nodes malignancy was found. Minor complications occurred in two patients. Conclusions: Our experience confirms that EUS-FNA in patients with suspected solid pancreatic lesions is safe and has a high diagnostic accuracy. This technique should be considered the preferred test when a cytological diagnosis of a pancreatic mass lesion is required.

Purpose: To examine serum levels of GGT activity and biomarkers of iron metabolism in relation to parameters of bone and mineral metabolism in elderly patients with and without osteoporotic bone fractures in the absence of overt liver diseases. Methods: In a cross-sectional study of 416 older (>60 years) patients (168 subjects with hip fracture, 89 with other fractures of the peripheral skeleton and 160 without any fracture; mean age 78.9 ± 8.7 years; 282 women) we simultaneously measured serum levels of two bone formation markers (osteocalcin, OC; procollagen type 1 Nterminal propeptide, P1NP), bone resorption marker (β- isomerised carboxy-terminal cross-linking telopeptide of type I collagen, βCTX), their ratios (PINP/OC, PINP/βCTX, OC/βCTX), 25(OH) vitamin D, PTH, calcium, phosphate, magnesium, GGT activity, other liver function tests and indices of iron metabolism (serum ferritin, iron, transferrin and transferrin saturation [TSAT]). Results: Multivariate regression analyses demonstrated significant bidirectional links between P1NP and GGT, P1NP/OC ratio and GGT, P1NP and TSAT, OC and ferritin, GGT and ferritin. GGT, ferritin and TSAT were independent indicators of βCTX, while ferritin and TSAT were also independent predictors of the P1NP/OC ratio, and TSAT was an independent predictor of the P1NP/βCTX ratio. In multivariate regression, P1NP, βCTX, P1NP/βCTX ratio, ferritin, magnesium and age were independent indicators of fracture. Conclusions: The study highlighted the bidirectional links between serum GGT activity, indices of iron and bone metabolism and the role of GGT and iron homeostasis in maintaining bone health and identified indicators for osteoporotic fractures. The GGT- and iron-related factors contributing to bone integrity warrant further investigations.

Summary Background No specific preventive strategy exists for acute gastrointestinal haemorrhage in hip fracture patients. Aims To determine the effectiveness of prophylactic use of proton pump inhibitors in patients with risk factors for acute gastrointestinal haemorrhage. Methods Prospective two-stage study of 822 consecutive older (≥60 years) hip fracture patients. Results Acute gastrointestinal haemorrhage occurred in 16 (3.9%) of 407 patients and was associated with increased length of hospital stay (28.7 vs. 15.9; P = 0.0027) and mortality (18.8% vs. 4.3%; P = 0.043). Multiple analysis identified five independent risk factors for acute gastrointestinal haemorrhage: pre-existing peptic ulcer (OR 4.3; P = 0.043), current smoking (OR 3.1; P = 0.023), post-operative use of an antiplatelet agent (OR 6.5; P = 0.046), post-operative use of non-steroidal anti-inflammatory drug/cyclo-oxygenase-2 inhibitor (OR 4.9; P = 0.06) and blood group O (OR 1.7; P = 0.046). These risk factors were highly sensitive and had a negative predictive value of 99.8%. Prophylactic use of proton pump inhibitors in patients with risk factor for acute gastrointestinal haemorrhage significantly reduced the incidence of this complication (0.72% in treated patients vs. 13.4% in untreated; P

The liver plays a central role in vitamin D metabolism. Our aim was to determine the prevalence and type of vitamin D-parathyroid hormone (PTH) disturbance in ambulatory patients with noncholestatic chronic liver disease (CLD) and its relationship with disease severity and liver function.We studied 100 consecutive outpatients (63 men, 37 women; mean age, 49.0 +/- 12.1 [SD] y) with noncholestatic CLD caused by alcohol (n = 40), hepatitis C (n = 38), hepatitis B (n = 12), autoimmune hepatitis (n = 4), hemochromatosis (n = 4), and nonalcoholic steatohepatitis (n = 2); 51 patients had cirrhosis. Serum concentrations of 25-hydroxyvitamin D (25[OH]D), PTH, calcium, phosphate, magnesium, creatinine, and liver function tests were determined.Serum 25(OH)D levels were inadequate in 91 patients: vitamin D deficiency (50 nmol/L) was found in 68 patients and vitamin D insufficiency (50-80 nmol/L) was found in 23 patients. Secondary hyperparathyroidism (serum PTH,6.8 pmol/L) was present in 16 patients. The prevalence of vitamin D deficiency was significantly higher in cirrhotic vs noncirrhotic patients (86.3% vs 49.0%; P = .0001). In Child-Pugh class C patients, 25(OH)D levels were significantly lower than in class A patients (22.7 +/- 10.0 nmol/L vs 45.8 +/- 16.8 nmol/L; P.001). Serum 25(OH)D independently correlated with international normalized ratio (negatively; P = .018) and serum albumin (positively; P = .007). Serum 25(OH)D levels of less than 25 nmol/L predicted coagulopathy, hyperbilirubinemia, hypoalbuminemia, increased alkaline phosphatase, and anemia and thrombocytopenia.Vitamin D inadequacy is common in noncholestatic CLD and correlates with disease severity, but secondary hyperparathyroidism is relatively infrequent. Management of CLD should include assessment of vitamin D status in all patients and replacement when necessary.