Plasma Drug Values of DOACs in Patients Presenting with Gastrointestinal Bleeding: A Prospective Observational Study.

Background and Objectives: Anticoagulants are a well-known risk factor for gastrointestinal bleeding (GIB). In recent years, direct oral anticoagulants (DOACs) have taken a leading role in the treatment and prevention of thromboembolic incidents. The aim of this study was to investigate the prevalence of DOAC-treated patients with GIB whose plasma drug concentrations exceeded the cut-off values reported in the literature and to evaluate their clinical characteristics. Materials and Methods: Patients who were admitted to the Intensive Care Unit in the period 2/2020-3/2022 due to GIB were prospectively included in the study and classified into three groups according to the prescribed type of DOAC (apixaban, rivaroxaban, and dabigatran). For all participants, it was determined if the measured plasma drug levels exceeded the maximum serum concentration (Cmax) or trough serum concentration (Ctrough) obtained from the available data. A comparison of clinical parameters between the patients with and without excess drug values was performed. Results: There were 90 patients (54.4% men) included in the study, of whom 27 were treated with dabigatran, 24 with apixaban, and 39 with rivaroxaban. According to Cmax, there were 34 (37.8%), and according to Ctrough, there were 28 (31.1%) patients with excess plasma drug values. A statistically significant difference regarding excess plasma drug values was demonstrated between DOACs according to both Cmax (p = 0.048) and Ctrough (p < 0.001), with the highest rate in the group treated with dabigatran (55.6% for Cmax and 59.3% for Ctrough). Multivariate logistic regression showed that age (OR 1.177, p = 0.049) is a significant positive and glomerular filtration rate (OR 0.909, p = 0.016) is a negative predictive factor for excess plasma drug values. A total of six (6.7%) patients had fatal outcomes. Conclusions: Plasma drug concentrations exceed cut-off values reported in the literature in more than one-third of patients with GIB taking DOAC, with the highest rate in the dabigatran group. Clinicians should be more judicious when prescribing dabigatran to the elderly and patients with renal failure. In these patients, dose adjustment, plasma drug monitoring, or substitution with other, more appropriate DOACs should be considered.

Assessment of Gallbladder Drainage Methods in the Treatment of Acute Cholecystitis: A Literature Review.

Gallbladder drainage is a treatment option in high-risk surgical patients with moderate or severe acute cholecystitis. It may be applied as a bridge to cholecystectomy or a definitive treatment option. Apart from the simple and widely accessible percutaneous cholecystostomy, new attractive techniques have emerged in the previous decade, including endoscopic transpapillary gallbladder drainage and endoscopic ultrasound-guided gallbladder drainage. The aim of this paper is to present currently available drainage techniques in the treatment of AC; evaluate their technical and clinical effectiveness, advantages, possible adverse events, and patient outcomes; and illuminate the decision-making path when choosing among various treatment modalities for each patient, depending on their clinical characteristics and the accessibility of methods.

Characteristics and clinical outcomes of patients with acute gastrointestinal bleeding related to anticoagulant or antiplatelet therapy: a retrospective study.

AIM: To investigate the demographic characteristics, endoscopic and laboratory findings, comorbidities and mortality rate of patients with gastrointestinal bleeding related to anticoagulant or antiplatelet therapy. METHODS: We reviewed the records of patients admitted for gastrointestinal bleeding to the Intensive Care Unit of the Department of Gastroenterology, University Hospital Split, between 2015 and 2019. The characteristics and clinical outcomes of patients taking anticoagulant/antiplatelet therapy were analyzed. RESULTS: The study enrolled 1367 patients, 434 (31.7%) of whom received anticoagulant/antiplatelet therapy (mean age 74.9±10.7 years; 64.3% men). The most frequently prescribed drug was acetylsalicylic acid (56.7%), the most common bleeding site was the stomach (41.3%), and the most prevalent cause of bleeding was ulcer (61.6%). Patients taking anticoagulant/antiplatelet therapy who died had significantly higher creatinine (P=0.011) and lower albumin (P=0.015). In the multivariate analysis, the factors that negatively affected survival were older age, higher creatinine, and lower albumin. Patients taking anticoagulant/antiplatelet therapy had slightly lower in-hospital mortality (8.3%) compared with other patients (10.3%). CONCLUSION: Although anticoagulant/antiplatelet therapy increases the risk of gastrointestinal bleeding, it does not directly affect the outcome, which is mainly determined by age and comorbidities.

Which factors influence liver stiffness measured by real-time two dimensional shear wave elastography in patients on maintenance hemodialysis?

AIM: To evaluate liver stiffness (LS) by real-time two-dimensional shear wave elastography (RT 2D-SWE) and to assess its correlation with the mean arterial pressure (MAP) in patients on maintenance hemodialysis (MHD). The secondary aim was to identify biological and biochemical parameters associated with elevated LS. METHODS: This study enrolled patients treated with MHD in the Split University Hospital from December 2017 through February 2018. LS was measured after a HD session using RT 2D-SWE. Mean arterial pressure was measured before RT-2D-SWE was performed. RESULTS: The study enrolled 47 patients with the mean±standard deviation age of 68.48±14.33 years. Arterial hypertension was diagnosed in 70.2% of patients. Liver stiffness >7 kPa, suggesting clinically relevant fibrosis, was found in 59.5% of patients. Arterial pressure was significantly correlated with LS (ρ=0.38, P=0.008). C-reactive protein (ρ=0.548, P=0.023), parathyroid hormone (ρ=0.507, P=0.038), and total bilirubin (ρ=0.423, P=0.020) were correlated with elevated LS. CONCLUSION: Mean arterial pressure is correlated with increased LS in patients on MHD. Our results emphasize the importance of proper regulation of arterial blood pressure and indicate that LS should always be interpreted in combination with laboratory parameters. Further prospective studies with larger series are needed.

OPPORTUNISTIC SCREENING FOR COLORECTAL CANCER IN HIGH-RISK PATIENTS IN FAMILY MEDICINE PRACTICES IN THE REPUBLIC OF CROATIA.

Colorectal cancer is a malignant neoplasm which has an increasing incidence and represents a global public health problem. The majority of patients are diagnosed after the age of 50, and the risk of developing it over lifetime is 5%. Development of preventive, diagnostic and treatment methods has resulted in a significant reduction in mortality and other negative clinical outcomes. Precisely because of the efficient method of prevention and early detection of this disease, numerous countries, including Croatia, have organized national colorectal cancer screening and monitoring programs. However, these programs are primarily organized for the population with the usual, i.e. average risk of developing colorectal cancer. High-risk groups include persons with endoscopically detected and removed colon polyps, persons surgically treated for colon cancer, persons with a positive family history of colorectal cancer, persons with inflammatory bowel diseases, individuals and families with hereditary disorders or genetic mutations that increase the risk of this disease several fold, persons with acromegaly, and patients who have undergone ureterosigmoidostomy. Recommendations for the detection and monitoring of high-risk groups are often not defined clearly, and some of the existing ones are based mostly on scarce scientific evidence. It is commonly accepted that screening in high-risk groups should start at an earlier age, with shorter intervals between follow-ups. The basic diagnostic method for screening and monitoring in these patient groups is endoscopic monitoring, or colonoscopy. The aim of this review paper is to present the characteristics of the abovementioned risk groups and provide clear screening recommendations.

CROATIAN GUIDELINES FOR THE DIAGNOSIS AND TREATMENT OF NONALCOHOLIC FATTY LIVER DISEASE.

Nonalcoholic fatty liver disease (NAFLD) is a term describing excessive accumulation of fat in hepatocytes, and is associated with metabolic syndrome and insulin resistance. NAFLD prevalence is on increase and goes in parallel with the increasing prevalence of metabolic syndrome and its components. That is why Croatian guidelines have been developed, which cover the screening protocol for patients with NAFLD risk factors, and the recommended diagnostic work-up and treatment of NAFLD patients. NAFLD screening should be done in patients with type 2 diabetes mellitus, or persons with two or more risk factors as part of metabolic screening, and is carried out by noninvasive laboratory and imaging methods used to detect fibrosis. Patient work-up should exclude the existence of other causes of liver injury and determine the stage of fibrosis as the most important factor in disease prognosis. Patients with initial stages of fibrosis continue to be monitored at the primary healthcare level with the management of metabolic risk factors, dietary measures, and increased physical activity. Patients with advanced fibrosis should be referred to a gastroenterologist/hepatologist for further treatment, monitoring, and detection and management of complications.

Liver and spleen stiffness and their ratio assessed by real-time two dimensional-shear wave elastography in patients with liver fibrosis and cirrhosis due to chronic viral hepatitis.

OBJECTIVES: To investigate the performance of real-time 2D shear wave elastography (RT 2D-SWE) for non-invasive staging of liver disease in patients with chronic viral hepatitis (CVH). MATERIALS AND METHODS: Naive CVH patients underwent liver (LS) and spleen stiffness (SS) measurements by an intercostal approach. Patients with ALT >3× upper limit of normal, cholestasis as revealed by dilated intrahepatic biliary tree, and liver congestion were excluded. Results were expressed in kPa and compared to histological stage (Ishak) of liver fibrosis (LF). Patients with decompensated liver cirrhosis (LC) were diagnosed using standard clinical, ultrasound, and endoscopic criteria. RESULTS: Of 123 patients, LS was successfully measured in 79.7% and SS in 53.7%. LS accurately differentiated between liver disease stages, with cut-off values of 8.1 (AUC 0.991) for F ≥ 3, 10.8 kPa (AUC 0.954) for F ≥ 5, and 27 kPa (AUC 0.961) for decompensated LC. SS was significantly different between non-cirrhotic stages (F0-4) and LC (cut-off 24 kPa; AUC 0.821). While both LS and SS increased with liver disease progression, the difference between them decreased, as reflected by the stiffness ratio index. CONCLUSIONS: RT 2D-SWE can accurately differentiate between the stages of LF, and can distinguish LF from LC and compensated from decompensated LC. KEY POINTS: • RT 2D-SWE is an accurate method for assessment of liver fibrosis. • RT 2D-SWE is applicable in 80% of patients with chronic viral hepatitis. • RT 2D-SWE accurately differentiates compensated from decompensated liver cirrhosis. • Both liver and spleen stiffness increase with progression of liver fibrosis. • In cirrhosis, the difference between liver and spleen stiffness decreases.

Real-time two-dimensional shear wave ultrasound elastography of the liver is a reliable predictor of clinical outcomes and the presence of esophageal varices in patients with compensated liver cirrhosis.

AIM: Primary: to evaluate predictivity of liver stiffness (LS), spleen stiffness (SS), and their ratio assessed by real-time 2D shear wave elastography (RT-2D-SWE) for adverse outcomes (hepatic decompensation, hepatocellular carcinoma or death; "event") in compensated liver cirrhosis (LC) patients. Secondary: to evaluate ability of these measures to discriminate between cirrhotic patients with/without esophageal varices (EV). METHODS: Predictivity of LS, SS, and LS/SS was assessed in a retrospectively analyzed cohort of compensated LC patients (follow-up cohort) and through comparison with incident patients with decompensated cirrhosis (DC) (cross-sectional cohort). Both cohorts were used to evaluate diagnostic properties regarding EV. RESULTS: In the follow-up cohort (n=44) 18 patients (40.9%) experienced an "event" over a median period of 28 months. LS≥21.5 kPa at baseline was independently associated with 3.4-fold (95% confidence interval [CI] 1.16-10.4, P=0.026) higher risk of event. Association between SS and outcomes was weaker (P=0.056), while there was no association between LS/SS ratio and outcomes. Patients with DC (n=43) had higher LS (35.3 vs 18.3 kPa, adjusted difference 65%, 95% CI 43%-90%; P<0.001) than compensated patients at baseline. Adjusted odds of EV increased by 13% (95% CI 7.0%-20.0%; Plt;0.001) with 1 kPa increase in LS. At cut-offs of 19.7 and 30.3 kPa, LS and SS had 90% and 86.6% negative predictive value, respectively, to exclude EV in compensated patients. CONCLUSION: This is the first evaluation of RT-2D-SWE as a prognostic tool in LC. Although preliminary and gathered in a limited sample, our data emphasize the potential of LS to be a reliable predictor of clinical outcomes and the presence of EV in LC patients.

Depression and serum interleukin-6 levels in patients on dialysis.

BACKGROUND: Depression is a common psychiatric problem in patients undergoing dialysis. Several studies have been performed to validate the association between depression and inflammation in haemodialysis patients. The levels of proinflammatory cytokines are increased in chronic renal failure patients, as in depression. The objective of this study was to compare the incidence of depression in the patients on dialysis (on hemodialysis /HD/ and on continuous ambulatory peritoneal dialysis /CAPD/), and a relationship between depression and the presence of inflammation. SUBJECTS AND METHODS: 88 patients (52 on HD and 36 on CAPD) were enrolled in this study. Depressive symptoms were measured with the Beck Depression Inventory (BDI). The BDI is a 21-item self-report instrument, and the elevated symptoms of depression were defined as a BDI score ≥16. HD patients were treated with high-flux polysulphone biocompatible dialyzers and CAPD patients were treated with usual dwell time (4-6 hours during the day and 8-10 hours at night). The presence of an inflammatory state was assesded by determinations of plasma interleukin-6 (IL-6) levels. RESULTS: Depression (BDI ≥16) was present in 28.4% of dialysis patients, 35% of patients on hemodialysis (HD) and 18.1% of patients on continous ambulatory peritoneal dialysis (CAPD). The BDI score was significantly lower in CAPD patients comparing to HD patients, as well as the levels of albumin, C-reactive protein (CRP) and interleukin-6 (IL-6). IL-6 serum levels were similar in patients with depression and patients without depression in the whole group, as in HD patients. In CAPD patients without depression IL-6 levels were significantly lower. CONCLUSIONS: The prevalence of depression was higher in HD comparing to CAPD patients. Although IL-6 level was higher in HD compared to CAPD patients, the relationship between depression and presence of inflammation parametars were observed in CAPD, but not in HD patients.

Mortality in high-risk patients with bleeding Mallory-Weiss syndrome is similar to that of peptic ulcer bleeding. Results of a prospective database study.

OBJECTIVE: The aim of this study was to identify the predictive factors influencing mortality in patients with bleeding Mallory-Weiss syndrome in comparison with peptic ulcer bleeding. MATERIAL AND METHODS: Between January 2005 and December 2009, 281 patients with endoscopically confirmed Mallory-Weiss syndrome and 1530 patients with peptic ulcer bleeding were consecutively evaluated. The 30-day mortality and clinical outcome were related to the patients' demographic data, endoscopic, and clinical characteristics. RESULTS: The one-year cumulative incidence for bleeding Mallory-Weiss syndrome was 7.3 cases/100,000 people and for peptic ulcer bleeding 40.4 cases/100,000 people. The age-standardized incidence for both bleeding Mallory-Weiss syndrome and peptic ulcer bleeding remained unchanged during the observational five-year period. The majority of patients with bleeding Mallory-Weiss syndrome were male patients with significant overall comorbidities (ASA class 3-4). Overall 30-day mortality rate was 5.3% for patients with bleeding Mallory-Weiss syndrome and 4.6% for patients with peptic ulcer bleeding (p = 0.578). In both patients with bleeding Mallory-Weiss syndrome and peptic ulcer bleeding, mortality was significantly higher in patients over 65 years of age and those with significant overall comorbidities (ASA class 3-4). CONCLUSION: The incidence of bleeding Mallory-Weiss syndrome and peptic ulcer bleeding has not changed over a five-year observational period. The overall 30-day mortality was almost equal for both bleeding Mallory-Weiss syndrome and peptic ulcer bleeding and was positively correlated to older age and underlying comorbid illnesses.

Bronchoalveolar pH and inflammatory biomarkers in newly diagnosed IPF and GERD patients: a case-control study.

BACKGROUND: Several studies have suggested that idiopathic pulmonary fibrosis (IPF) may be related to repeated aspiration of gastric contents over long periods of time. We aimed to investigate differences between pH measured directly in the lung, and biomarkers of acute inflammation in patients with newly diagnosed IPF and in patients with newly diagnosed GERD. MATERIAL AND METHODS: All subjects (N=61) underwent collection of medical history, physical examination, pulmonary function testing, bronchoscopy, endoscopy, arterial blood gas analyses, and biochemical testing. RESULTS: Previously diagnosed GERD was found in 56.7%, typical symptoms of reflux in 80%, and Helicobacter pylori in gastric biopsy specimens in 76.6% of the cases. pH in peripheral branches of bronchi in the cases was 5.32 ± 0.44 and was 6.27 ± 0.31 (p<0.001) in the control group. The average values of LDH, ALP, and CRP in bronchoalveolar aspirate and in serum, as well as TNF-alpha in bronchoalveolar aspirate, were significantly higher in IPF patients. CONCLUSIONS: The more acidic environment in the bronchoalveolar aspirate of the IPF subjects could contribute to the development or progression of IPF, possibly via changes in local metabolism or by damaging local cells and tissue. However, further studies with larger numbers of patients are required to clarify the role of gastric fluid aspiration in IPF pathogenesis. Our preliminary work has identified inflammatory biomarkers LDH, ALP, and TNF-alpha as potentially important in the pathologic processes in IPF. Further research is needed to determine their importance in clinical intervention and patient care.

North vs south differences in acute peptic ulcer hemorrhage in Croatia: hospitalization incidence trends, clinical features, and 30-day case fatality.

AIM: To assess the seven-year trends of hospitalization incidence due to acute peptic ulcer hemorrhage (APUH) and associated risk factors, and examine the differences in these trends between two regions in Croatia. METHODS: The study collected sociodemographic, clinical, and endoscopic data on 2204 patients with endoscopically confirmed APUH who were admitted to the Clinical Hospital Center "Sestre Milosrdnice," Zagreb and Clinical Hospital Center Split between January 1, 2005 and December 31, 2011. We determined hospitalization incidence rates, 30-day case fatality rate, clinical outcomes, and incidence-associated factors. RESULTS: No differences were observed in APUH hospitalization incidence rates between the regions. Age-standardized one-year cumulative APUH hospitalization incidence rate calculated using the European Standard Population was significantly higher in Zagreb than in Split region (43.2/100 000 vs 29.2/100,000). A significantly higher APUH hospitalization incidence rates were observed in the above 65 years age group. Overall 30-day case fatality rate was 4.9%. CONCLUSION: The hospitalization incidence of APUH in two populations did not change over the observational period and it was significantly higher in the Zagreb region. The incidence of acute duodenal ulcer hemorrhage also remained unchanged, whereas the incidence of acute gastric ulcer hemorrhage increased. The results of this study allow us to monitor epidemiological indicators of APUH and compare data with other countries.

Is endoscopic ultrasound a promising technique in the diagnosis and treatment of liver diseases?

Percutaneous ultrasound has been a longstanding method in the diagnostics and interventional procedures of liver diseases. In some countries, its use is restricted to radiologists, limiting access for other clinicians, such as gastroenterologists. Endoscopic ultrasound, as a novel technique, plays a crucial role in diagnosis and treatment of digestive diseases. However, its use is sometimes recommended for conditions where no clear advantage over percutaneous ultrasound exists, leaving the impression that clinicians sometimes resort to an endoscopic approach due to the unavailability of percutaneous options.

Predictive factors of rebleeding and mortality following endoscopic hemostasis in bleeding peptic ulcers.

BACKGROUND/AIMS: To identify predictive factors of rebleeding and mortality after endoscopic therapy in patients with high risk peptic ulcers. METHODOLOGY: Patients hospitalized due to bleeding from high-risk peptic ulcers (Forrest classes Ia, Ib, IIa and IIb) during a five-year study, received endoscopic hemostatic therapy (diluted epinephrine injection, clipping or both) in addition to proton pump inhibitors. We looked for clinical, endoscopic and laboratory parameters that had influenced rebleeding and mortality in these patients. RESULTS: Among all patients (804) with peptic ulcer bleeding, 251 high-risk ulcer pateints received endoscopic hemostasis treatment. Thirty-four of them (13.5%) experienced in-hospital rebleeding. Majority of these achieved permanent hemostasis after second endoscopic treatment, while 14 (5.6%) needed surgery. Eighteen patients died (7.2%). Among parameters studied, severe anaemia, systolic and diastolic hypotension, shock presence, low Rockall score, ulcer size and time to hemostasis were factors which predicted rebleeding. Mortality predictive factors were: severe anaemia, hypotension, shock presence, lower Rockall and physical status scores, ulcer size and Forrest class. Conclusions: Early assesment of clinical and endoscopic predictive factors of rebleeding and mortality in patients with high-risk peptic ulcer bleeding could provide optimal therapeutical measures and follow-up. It could further reduce rebleeding and mortality rates in these patients.-16 months vs. 59.5 months, IQR=37.5-68.5 months, p<0.001) and the rate of death was lower (16.7% [2/12] vs. 83.3% [5/6], p=0.006). Logistic regression showed that a shorter duration of endoscopic interval increased the rate of resectability of gastric cancer (p<0.001) and a higher rate of unresectable gastric cancer and longer duration of endoscopic interval increased death (p=0.029 and p=0.004, respectively). CONCLUSIONS: After treatment of esophageal cancer, endoscopic examination at 12-month intervals is important to lower the rate of death due to metachronous gastric cancer.

Primary extragastrointestinal stromal tumor of the sigmoid mesocolon with metastatic spread to greater omentum: case report.

A 71-year-old female complained of abdominal pain, weight loss and abdominal distension. Gynecologic examination revealed a hardly movable, palpable mass in the lower abdomen, reaching the umbilicus. An abdominal ultrasound and computed tomography (CT) scan suggested a large abdominal mass with the possible origin in the left ovary and without significant lymph node enlargements. The patient subsequently underwent complete evacuation of tumor tissue, omentectomy and total abdominal hysterectomy and bilateral salpingo-ovariectomy. Immunohistochemical examination revealed strongly positive staining of tumor cells for CD117. The final pathologic diagnosis was a primary extragastrointestinal stromal tumor (EGIST) of the sigmoid mesocolon with omental metastasis. The differential diagnosis of the tumor presented in the lower abdomen should consider the EGIST as well.

Detection of Sarcopenia in Patients with Liver Cirrhosis Using the Bioelectrical Impedance Analysis.

Bioelectrical impedance analysis (BIA) is a body composition assessment method. We aimed to determine its accuracy in the detection of sarcopenia in patients with liver cirrhosis (LC), using skeletal muscle index (SMI) at the level of third lumbar vertebra (L3-SMI) obtained using multislice computed tomography as the reference method. Patients with LC were enrolled in the period October 2019-March 2022 and follow-ups were conducted until January 2023. Their BIA parameters were compared against L3-SMI, and BIA cut-off values were proposed using AUROC analysis. Patients underwent outcome analysis based on obtained clinical characteristics. A total of 106 patients were included. We found a fair correlation between BIA parameters with the L3-SMI. We determined cut-off values of ≤11.1 kg/m2 for BIA-SMI (Se 73%, Sp 66%, AUROC 0.737, p < 0.001) and ≤5.05° for phase angle (PA) (Se 79%, Sp 60%, AUROC 0.762, p < 0.001) in the detection of sarcopenia. The relative risk of death was 2.2 times higher in patients with skeletal muscle mass (SMM) ≤ 36.5 kg. SMM was significantly associated with outcome in Kaplan-Meier analysis. This non-invasive and simple method that showed fair performances and a very good outcome prediction could provide for the unmet need for fast and affordable detection of sarcopenia in patients with LC and should be further evaluated.

Obesity, Gut Microbiota, and Metabolome: From Pathophysiology to Nutritional Interventions.

Obesity is a disorder identified by an inappropriate increase in weight in relation to height and is considered by many international health institutions to be a major pandemic of the 21st century. The gut microbial ecosystem impacts obesity in multiple ways that yield downstream metabolic consequences, such as affecting systemic inflammation, immune response, and energy harvest, but also the gut-host interface. Metabolomics, a systematized study of low-molecular-weight molecules that take part in metabolic pathways, represents a serviceable method for elucidation of the crosstalk between hosts' metabolism and gut microbiota. In the present review, we confer about clinical and preclinical studies exploring the association of obesity and related metabolic disorders with various gut microbiome profiles, and the effects of several dietary interventions on gut microbiome composition and the metabolome. It is well established that various nutritional interventions may serve as an efficient therapeutic approach to support weight loss in obese individuals, yet no agreement exists in regard to the most effective dietary protocol, both in the short and long term. However, metabolite profiling and the gut microbiota composition might represent an opportunity to methodically establish predictors for obesity control that are relatively simple to measure in comparison to traditional approaches, and it may also present a tool to determine the optimal nutritional intervention to ameliorate obesity in an individual. Nevertheless, a lack of adequately powered randomized trials impedes the application of observations to clinical practice.

The influence of etiologic factors on clinical outcome in patients with peptic ulcer bleeding.

BACKGROUND: Peptic ulcer bleeding remains an important cause of morbidity and mortality. AIM: The aim of this study was to evaluate the prevalence of non-steroidal anti-inflammatory drugs (NSAID) use, Helicobacter pylori infection and non-H. pylori-non-NSAIDs causes of peptic ulcer bleeding and to identify the predictive factors influencing the rebleeding rate and in-hospital mortality in patients with bleeding peptic ulcer. METHODS: A total of 1,530 patients with endoscopically confirmed peptic ulcer bleeding were evaluated consecutively between January 2005 and December 2009. The 30-day mortality and clinical outcome were related to patient's demographic data, endoscopic and clinical characteristics. RESULTS: The age-standardized 1-year cumulative incidence for peptic ulcer bleeding was 40.4 cases/100,000 people. The proportion of patients over 65 years increased from 45.7 % in 2005 to 61.4 % in 2009 (p = 0.007). Overall 30-day mortality rate was 4.6 %, not significantly different for conservatively and surgically treated patients (4.9 vs. 4.1 %, p = 0.87). Mortality was significantly higher in patients over 65 years of age and those with in-hospital bleeding recurrence. Patients with non-H. pylori-non-NSAID idiopathic ulcers had significantly higher 30-day mortality rate than those with H. pylori ulcers and NSAID-H. pylori ulcers (7.1 vs. 0 vs. 0.8 %, p = 0.001 and p = 0.007, respectively). There was no statistically significant difference between patients with NSAID ulcers and non-H. pylori-non-NSAID idiopathic ulcers in terms of 30-day mortality rate (5.3 vs. 7.1 %, p = 0.445). CONCLUSION: The incidence of peptic ulcer bleeding has not changed over a 5-year observational period. The overall 30-day mortality was positively correlated to older age, underlying comorbid illnesses, in-hospital bleeding recurrence and the absence of H. pylori infection.

Gastroesophageal reflux disease and pulmonary function: a potential role of the dead space extension.

BACKGROUND: To evaluate the differences in the existence and size of dead space in patients with and without Gastroesophageal Reflux Disease (GERD and non-GERD) expressed through the size of intrapulmonary shunt (QS/QT). MATERIAL/METHODS: The study enrolled 86 subjects - 43 patients referred for endoscopy because of symptoms of GERD (heartburn, acid regurgitation, dysfagia) and 43 healthy subjects with similar anthropometric characteristics without GERD symptoms. Based on endoscopy findings, patients were classified into the erosive reflux disease (ERD) group and non-erosive reflux disease (NERD) group. Spirometry values, single-breath diffusing capacity of the lung for carbon monoxide (DLCO) and intrapulmonary shunt (venous shunt - QS/QT) determined by the oxygen method were measured in all participants. RESULTS: Statistically significant differences between GERD and non-GERD groups in FVC (p=0.034), FEV1 (p=0.002), FEV1/FVC (p=0.001), and PEF (p=0.001) were observed. There were no statistically significant differences in FEF 25% (p=0.859), FEF 50% (p=0.850), and FEF 75% (p=0.058). Values of DLCO (p=0.006) and DLCO/VA (p=0.001) were significantly lower and QS/QT was significantly higher (p=0.001) in the GERD group than in the non-GERD group. However, in both groups the average values of DLCO and DLCO/VA expressed as a percentage of predictive values were within normal range, while the value of QS/QT in the GERD group showed pathological (6.0%) mean value (normal value ≤ 5.0%). There were no significant differences in respiratory function test results between patients with ERD and NERD. CONCLUSIONS: Our results suggest that microaspiration of stomach contents may cause surfactant damage, development of microatelectasis, and dead space expansion with consequent increase of intrapulmonary (venous) shunt.

Prognostic significance of matrix metalloproteinases 2 and 9 in endometrial cancer.

We investigated the prognostic significance of matrix metalloproteinases 2 (MMP 2) and 9 (MMP 9) in endometrial cancer (EC). The expression of MMP 2 and MMP 9 was analyzed immunohistochemically in 73 primary EC patients. In most cases, the gelatinases were predominantly localized to epithelial cell of tumor origin. In univariate analysis histological type, tumor grade, FIGO (1988) surgical stage and high stromal MMP 2 expression were identified as a significant determinant for EC recurrence, while epithelial MMP 2 expression and epithelial and stromal MMP 9 expression were not. Multivariate analysis revealed a subgroup of patient age > or = 63.6 years with endometrioid adenocarcinoma and papillary serous carcinoma, all FIGO (2009) stage I disease where strong staining of stromal MMP 2 increase risk of EC recurrence (p = 0.037).