Safety, Efficacy and Persistence of Advanced Therapies in Inflammatory Bowel Disease: Results from ORIGINS. A Retrospective Observational Study.

BACKGROUND AND AIMS: Real-world assessments of efficacy and safety of advanced therapies used for inflammatory bowel disease (IBD) patients are limited. We aimed to report safety, efficacy and treatment persistence of new molecules (infliximab, adalimumab, vedolizumab, tofacitinib, ustekinumab) in a retrospective multicentric national Romanian analysis. METHODS: We conducted a nationwide, retrospective observational multicentric study. Data were collected retrospectively from electronic and paper files. Patients who started on one of the five investigated molecules during December 2019-December 2021 were included. The main outcome measures were clinical remission, endoscopic healing, persistence on treatment and safety data. RESULTS: A total of 678 adult patients from 24 Romanian IBD centers with a diagnosis of ulcerative colitis or Crohn's disease were included. Participants had previously failure to one (268, 39.5%), two (108, 15%) or more treatment lines and only 38% (259) were biologic naïve. In the 24 months study period, most patients were started on vedolizumab (192, 28%), followed by adalimumab, infliximab, ustekinumab and tofacitinib. In biologic-naïve patients, most physicians (72%) preferred anti-TNF treatment as first line biologic (93 patients started on infliximab, 92 on adalimumab), followed by vedolizumab, ustekinumab and tofacitinib. During follow-up, 71% (470, p=0.05) of patients achieved clinical remission and 36% (134, p=0.03) achieved mucosal healing. The 6 months milestone for persistence was reached in 78% (530) of cases. Almost half of patients (47%, 316 patients) persisted on their current treatment for over 12 months. Overall, an adverse reaction was reported for 67 (10.4%) patients, with no lethal events. CONCLUSIONS: Population of biologic-experienced IBD patients in Romania is increasing and is becoming more difficult to achieve long-term disease control. Discontinuation rates for advanced therapies are high.

Predictors of spontaneous bacterial peritonitis in Romanian adults with liver cirrhosis: Focus on the neutrophil-to-lymphocyte ratio.

Spontaneous bacterial peritonitis (SBP) is a severe complication of liver cirrhosis whose diagnosis is based on a polymorphonuclear leukocyte (PMN) value >250 mm3, yet this PMN value cannot identify all existing types. The aim of our study was to determine the clinical and biological factors that were associated with SBP and predict its occurrence, focusing on the neutrophil-to-lymphocyte ratio (NLR) as one of them. Our retrospective study included 216 patients with liver cirrhosis who were hospitalized between December 2019 and January 2010 at the Emergency County Clinical Hospital of 'St. Apostle Andrew' in Constanta, Romania. Demographic, clinical, and laboratory data were collected from patient observation sheets. The patients were divided into two groups: One group of patients with SBP and the other without SBP. The diagnosis of SBP was made when patients presented with PMN >250 mm3 and other causes of secondary bacterial peritonitis were excluded. The mean age of the patients was 61.25±10.67 years, and the alcoholic etiology of liver cirrhosis was most common (44%). Univariate logistic regression analysis showed that there was an association between biological parameters, such as serum white blood cells, total platelet count, total bilirubin, serum albumin, international normalized ratio, creatinine, erythrocyte sedimentation rate (ESR), serum sodium, alkaline reserve, and NLR, and clinical parameters, such us upper gastrointestinal bleeding and cardiac comorbidities in the occurrence of SBP. Multivariate analysis identified ESR and NLR as predictive factors in the occurrence of SBP. The area under the curve (AUC) was 0.916 [P<0.001, 95% confidence interval (CI) 0.870-0.949] for ESR and AUC was 0.963 (P<0.001, 95% CI 0.928-0.984) for NLR, respectively. In conclusion, the combination of these 2 biological parameters is useful in identifying or excluding SBP.

Spontaneous bacterial peritonitis: update on diagnosis and treatment.

Spontaneous bacterial peritonitis (SBP) is a common complication in patients with liver cirrhosis, with an increased risk of mortality. For this reason, a diagnostic paracentesis should be performed in all patients with ascites and clinical features with high diagnostic suspicion. Although literature data abound in identifying new diagnostic markers in serum or ascites, they have not yet been validated. The final diagnosis requires the analysis of ascites and the presence of > 250 mm3 neutrophil polymorphonuclear (PMN) in ascites. If previous data showed that the most common microorganisms identified were represented by gram-negative bacteria, we are currently facing an increase in gram-positive bacteria and multidrug-resistant bacteria. Although prompt and effective treatment is required to prevent outcomes, this becomes challenging as first-line therapies may become ineffective leading to worsening prognosis and increased in-hospital mortality. In this paper we will make a brief review of existing data on the diagnosis and treatment of SBP.

Spontaneous bacterial peritonitis mortality trends of cirrhotic patients in the last decade in Constanta County.

Spontaneous bacterial peritonitis (SBP) is a complication of liver cirrhosis with an increased in-hospital mortality rate. For this reason, the aim of the present study was to examine the main predictors of mortality in order to be able to identify high-risk patients in time and to guide the optimal treatment for prognosis improvement. We retrospectively collected demographic, clinical, laboratory and treatment data as well as data regarding length of stay and cost of hospitalization from 72 patients diagnosed with SBP between January 2010 and December 2019 in the Emergency Clinical Hospital St. Apostle Andrew, Constanta, Romania. Patients were divided into two groups: Those who survived and those who died. Logistic regression was used to identify a possible association between these factors and the increased risk of mortality. Univariate analysis revealed that clinical factors (fever, chills, and hepatic encephalopathy), biological factors such as serum and ascites leukocyte value, polymorphonuclear percentage (PMN), erythrocyte sedimentation rate (ESR) value, previous SBP episodes, and the presence of complications such as acute kidney injury (AKI), sepsis, and systemic inflammatory response syndrome (SIRS) were significantly associated with in-hospital mortality in patients with SBP. Multivariate analysis revealed that SIRS (P=0.0010) and fever (P=0.0258) were significantly associated with in-hospital mortality in patients with SBP. Findings of the present study suggest that, SIRS and fever were independent predictive factors of mortality in cirrhotic patients with SBP.

Non-invasive Ultrasonographic Score for Assessment of the Severity of Inflammatory Bowel Disease.

Intestinal ultrasound and shear wave elastography have gained increasing interest because of their promising results in the assessment of inflammatory bowel disease. The aim of this study was to find an ultrasonographic score to replace invasive endoscopic procedures for the management of these patients. The score includes ultrasound parameters that correlate well with clinical severity scales and inflammatory markers: bowel wall thickness, the Limberg score, disease extension and acoustic radiation force impulse measurements. The score proved to be well correlated with the Harvey Bradshaw Index, the Mayo score, C-reactive protein and fecal calprotectin. For Crohn's disease, a cutoff value of 8 points could identify active disease with 81.81% sensitivity and 83% specificity, while for ulcerative colitis, a cutoff value of 7 points could discriminate between remission and relapse with 86.85% sensitivity and 94% specificity. In conclusion, our ultrasonographic score can differentiate relapse from remission in inflammatory bowel disease.

Assessment of severity of acute pancreatitis over time.

In recent years there has been an increase in the incidence of acute pancreatitis worldwide. In spite of efforts to improve the treatment and care of patients with acute pancreatitis, to develop imaging investigations and interventional diagnostic and treatment techniques and to facilitate patients' access to them, acute pancreatitis continues to be associated with significant mortality and morbidity, and the treatment of patients suffering from this disease entails significant costs for healthcare systems. Researchers are in a permanent quest to get to a global consensus for stratifying the severity of acute pancreatitis. We need this in order to offer the proper management for each patient diagnosed with this condition and to improve hospital and health system strategies. Over the years, it has been attempted to develop algorithms to support a swift assessment of patients with acute pancreatitis with a prediction of disease severity as close to reality as possible for optimal management. This has led to the development of classifications of severity and severity scores. These require a permanent updating to keep up with the technical and technological developments involved in investigating and treating the patient and encompassing the most recent studies. The goal of this paper is to go through these classifications and scores, emphasizing factors that should be taken into account, and reflecting upon their utility and upon the necessity of improving them.

Nonalcoholic Fatty Liver Disease: Status Quo.

Nonalcoholic liver disease (NAFLD) is a hot topic for gastroenterologists and hepatologists and clinical practitioners must be kept abreast with the rapid progress of knowledge in this field. The Romanian Society of Gastroenterology and Hepatology (RSGH) has elaborated this review dedicated to evidence-based data on pathogenesis, diagnosis and therapy of this condition. The term NAFLD includes two distinct conditions, with different histologic features and prognosis: non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH), the second with the highest risk of evolution to cirrhosis and its complications, including hepatocellular carcinoma (HCC). Non-alcoholic fatty liver disease is considered the hepatic manifestation of the metabolic syndrome. Therefore, NAFLD is associated not only with an increase of liver-related mortality, but also of the overall mortality, especially cardiovascular and malignancies. Noninvasive techniques, such as biological tests and elastography can be used for the evaluation of NAFLD patients. Liver biopsy should be recommended in selected cases, for diagnostic, therapeutic and prognostic purposes. Patients with NAFLD would benefit from their lifestyle changes by progressive weight loss through exercise and low fat and sugar diet. Pharmacotherapy should be reserved for patients with NASH, particularly for those with significant fibrosis. Until now, there are no FDA approved therapies for NASH.