Allergy in Cancer Care: Antineoplastic Therapy-Induced Hypersensitivity Reactions.

As the backbone of oncological treatments, systemic chemotherapy is still one of the main pawns in cancer care, alone or in combination with newer targeted agents. All chemotherapy agents can be associated with a type of adverse event called an infusion reaction, which can be characterized as unpredictable, non-dose related, and unexplained by the cytotoxic profile of the drug. For some of these events, a certain immunological mechanism can be identified by blood or skin testing. In this case, we can speak of true hypersensitivity reactions that occur as a response to an antigen/allergen. The current work summarizes the main antineoplastic therapy agents and their susceptibility to induce hypersensitivity reactions and also includes a review of clinical presentation, diagnostic methods in hypersensitivity reactions, and perspectives to overcome these negative events in the treatment of patients suffering from various types of cancer.

The Colon Endoscopic Bubble Scale (CEBuS): a two-phase evaluation study.

BACKGROUND: To date, no scale has been validated to assess bubbles associated with bowel preparation. This study aimed to develop and assess the reliability of a novel scale - the Colon Endoscopic Bubble Scale (CEBuS). METHODS: This was a multicenter, prospective, observational study with two online evaluation phases of 45 randomly distributed still colonoscopy images (15 per scale grade). Observers assessed images twice, 2 weeks apart, using CEBuS (CEBuS-0 - no or minimal bubbles, covering < 5 % of the surface; CEBuS-1 - bubbles covering 5 %-50 %; CEBuS-2 - bubbles covering > 50 %) and reporting the clinical action (do nothing; wash with water; wash with simethicone). RESULTS: CEBuS provided high levels of agreement both in evaluation Phase 1 (4 experts) and Phase 2 (6 experts and 13 non-experts), with almost perfect intraobserver reliability: kappa 0.82 (95 % confidence interval 0.75-0.88) and 0.86 (0.85-0.88); interobserver agreement - intraclass correlation coefficient (ICC) 0.83 (0.73-0.89) and 0.90 (0.86-0.94). Previous endoscopic experience had no influence on agreement among experts vs. non-experts: kappa 0.86 (0.80-0.91) vs. 0.87 (0.84-0.89) and ICC 0.91 (0.87-0.94) vs. 0.90 (0.86-0.94), respectively. Interobserver agreement on clinical action was ICC 0.63 (0.43-0.78) in Phase 1 and 0.77 (0.68-0.84) in Phase 2. Absolute agreement on clinical action per scale grade was 85 % (82-88) for CEBuS-0, 21 % (16-26) for CEBuS-1, and 74 % (70-78) for CEBuS-2. CONCLUSION: CEBuS proved to be a reliable instrument to standardize the evaluation of colonic bubbles during colonoscopy. Assessment in daily practice is warranted.

SRED-ARCE Recommendations for Minimally Invasive Interventions During the COVID-19 Pandemic in Romania.

The Romanian Society of Digestive Endoscopy (SRED) and the Romanian Association of Endoscopic Surgery (ARCE) have decided to establish a joint working group to elaborate specific recommendations for organizing the diagnostic and the minimally invasive interventional procedures, in the context of the COVID-19 pandemic. The recommendations are based on the guidelines of the international societies of endoscopy and gastroenterology (ESGE / BSG / ASGE / ACG / AGA), respectively endoscopic surgery (EAES SAGES) (4-8), on the experience of countries severely affected by the pandemic (Italy, France, Spain, USA, Germany, etc.) and they will be applied within the limits of measures imposed at local and governmental level by the competent authorities. On the other hand, these recommendations should have a dynamic evolution, depending on the upward or downward trend of the COVID-19 pandemic at regional and local level, but also according to the findings of professional and academic societies, requiring regular reviews based on the publica tion of further recommendations or international clinical trials. The objectives of the SRED and ARCE recommendations target the endoscopic and laparoscopic surgery activities, to support their non discriminatory used for diagnostic or therapeutic purposes, pursuing the demonstrated benefits of these procedures, in safe conditions for patients and medical staff.

Adalimumab versus infliximab in treating post-operative recurrence of Crohn's disease: a national cohort study.

AIM: Perform a comparison between adalimumab (ADA) and infliximab (IFX) in treating post-operative recurrence of Crohn's disease (a comparative analysis of efficacy and safety). METHODS: From the 267 patients treated with Adalimumab or Infliximab between January 2005 and June 2014 in Romania, 44 received anti- TNF (tumor necrosis factor) therapy for prevention of post-operative recurrence. A comparison between patients treated with IFX and ADA was made with the Chi- square and t- student test, with the aid of the statistical program Mini Tab 17. RESULTS: Twenty-one patients received IFX and 23 ADA. This included 49% males (22/44), with a mean age of 41 years, mean disease duration of 6 years, and 84.1% had previously received azathioprine. The IFX group is comparable with the ADA group regarding most of the parameters, except for therapy duration. Mean duration of therapy was 33 months. The rate of complete response was comparable between the two groups: 67% in the IFX group vs. 78.3% in the ADA group, the same as the rate of re-resection, 19.1% vs. 4.4% and the rate of endoscopic recurrence, 29 vs. 33% at 12 months. Risk factors for postoperative recurrence (POR) (male sex, younger age, ileocolonic location, stricturing or penetrating behaviour) were studied, only ileocolonic location was found to be associated with Crohn's disease recurrence in patients treated with ADA. CONCLUSIONS: Overall infliximab and aalimumab are equally efficient in patients with resected Crohn's disease (CD) with a complete response of 72.7%, a rate of re-resection of 11.4 % and a rate of endoscopic recurrence of 35%. Ileocolonic location might be a predictive factor for loss of response to adalimumab in resected Crohn's disease patients.

Effectiveness of entecavir treatment and predictive factors for virologic response.

INTRODUCTION: Entecavir (ETV) is a potent inhibitor of hepatitis B virus (HBV) replication. In patients adherent to treatment, virologic remission rates of > 95 % can be maintained with entecavir at 3-5 years. AIM AND METHODS: A cohort study was performed, including all subjects who received ETV for chronic hepatitis B, in the South- Eastern Romania. We assessed viral response, HBeAg loss and seroconversion, HBsAg loss and seroconversion, biochemical response. Comparison of categorical data was performed by Chi2-test or Fisher´s exact where applicable. RESULTS: Data from 533 patients were available: predominantly males (64 %), 82.6 % nucleotide naive, 23.1 % HBe-Ag positive, 78.2 % with elevated ALT, 8 % with cirrhosis. The median follow up was 24 months (range 12-48 months). Rate of undetectable HBV DNA increased constantly from year 1 to 3, reaching 91.2 %. Positive predictive factors for virologic response were low score of fibrosis (p-0.006), low level of HBV DNA (p-0.003), while negative predictive factors were: HBe antigen positive status (p-value < 0.001), prior IFN therapy (p 0.015). Virologic rebound was found in 7.8 % (breakthrough in 0.8 %). Rate of HBe Ag loss increases with the therapy duration, reaching 47.83 % in year 3,with two positive predictive factors: Male sex (p = 0.007), and undetectable HBV DNA at 24 weeks (p = 0.002). The percentage of HBs Ag loss was 1.31 %. CONCLUSIONS: ETV maintained and even increased the high initial response rate (from 78 % to 91.2 %). Low score of fibrosis, low level of HBV DNA, HBe antigen negative status, absence of prior interferon therapy predict a good virologic response. Virologic rebound was found in a higher rate in our population, due probably to a poor drug compliance. Lamivudine-resistant patients usually respond well to ETV, but 15.62 % are non-responders, suspect of Entecavir resistance.

Acute Pancreatitis and Type 2 Diabetes Mellitus: The Chicken-Egg Paradox-A Seven-Year Experience of a Large Tertiary Center.

(1) Background: Preexisting type 2 diabetes mellitus (T2DM) has been shown in some studies as a risk factor and a severity factor for acute pancreatitis (AP). In this study, we aimed to demonstrate the link between T2DM and AP using data from a large retrospective epidemiological registry in a tertiary center. (2) Methods: We conducted a retrospective, large-cohort study of 1855 cases of AP and recurrent AP drawn from the seven-year consecutive hospitalization electronic health records of the largest acute-care tertiary teaching center in Romania. (3) Results: We observed a significant association between T2DM and a more severe course of the disease, and between T2DM and admission to the intensive care unit (ICU) due to AP, in our cohort using a chi-square test. However, we did not see a meaningful difference in comparing LoS-ICU between T2DM-AP and OAP (other known cause of AP). AP patients with T2DM had a greater probability of a severe course of the disease and were more likely to be admitted to the ICU than to the OAP. (4) Conclusions: The association between T2DM and AP remains a topic very representative of the "chicken-egg paradox". We need further research on DM-related AP and their bidirectional association as our study is limited by its retrospective design.

Hypertriglyceridemia-Induced Acute Pancreatitis-The Milky Way Constellation-The Seven-Year Experience of a Large Tertiary Centre.

(1) Background: Hypertriglyceridemia (HTG) is a well-known metabolic condition associated with an increased risk of acute pancreatitis. In this study, we tried to establish whether there are any significant disparities concerning recurrence rate, intensive care unit (ICU) admission, hospital (ICU and total) length of stay (LoS), morphology, severity and age between HTG-induced acute pancreatitis and any other known cause of pancreatitis (OAP). (2) Methods: The research was a retrospective unicentric cohort study, using information from the Bucharest Acute Pancreatitis Index (BUC-API) registry, a database of 1855 consecutive cases of acute pancreatitis. (3) Results: We found a weak association between HTG-AP and recurrence. The HTG-AP patients were younger, with a median of 44.5 years, and had a longer ICU stay than the OAP patients. In addition, we identified that the HTG-AP patients were more likely to develop acute peripancreatic fluid collection (APFC), to be admitted in ICU, to have a more severe course of disease and to be cared for in a gastroenterology ward. (4) Conclusions: Hypertriglyceridemia-induced APs have a more severe course. The typical patient with HTG-AP is a middle-aged male, with previous episodes of AP, admitted in the gastroenterology ward, with a longer ICU stay and longer length of hospitalization, more likely to evolve in a severe acute pancreatitis (SAP) and with a higher probability of developing APFC.

Alcoholic Acute Pancreatitis, a Retrospective Study about Clinical Risk Factors and Outcomes-A Seven-Year Experience of a Large Tertiary Center.

(1) Background: Alcohol consumption is one of the main causes of acute pancreatitis. (2) Material and Methods: In this unicentric retrospective cohort study, we selected 1855 patients from the Bucharest Acute Pancreatitis Index (BUC-API) who presented with acute pancreatitis. We investigated correlations between Alcoholic Acute Pancreatitis (AAP) and the rate of complications, cost, length of hospitalization and rate of recurrence. (3) Results: We found a moderately strong association between AAP and recurrence (p < 0.01) and observed that the disease is likelier to evolve with pseudocysts and walled-off necrosis than other forms of AP. Patients with AAP are less likely to have a morphologically normal pancreas than patients suffering from AP of other causes (p < 0.01), but a low probability of requiring intensive care unit admission (p < 0.01) significantly lowers daily cost (Md = 154.7 EUR compared to Md = 204.4 EUR) (p < 0.01). (4) Conclusions: This study's data show that patients with AAP have a greater rate of pseudocyst occurrence, lower intensive care unit admittance rate and lower cost of hospitalization than patients with AP of other causes. Typical Sketch: A middle-aged male tobacco smoker with recurrent AP, lower risk of in-hospital mortality and complications such as pseudocysts; treated in a gastroenterological ward and discharged at-will.

Defining the Failure of Medical Therapy for Inflammatory Bowel Disease in the Era of Advanced Therapies: A Systematic Review.

BACKGROUND: The expansion of advanced therapies for inflammatory bowel disease created a lag between the development of these new therapies and their incorporation and use in daily practice. At present, no clear definitions for treatment optimization, treatment failure or criteria to abandon therapy are available. We aimed to centralize criteria for a nonresponse to all available molecules and to summarize guideline principles for treatment optimization. METHODS: We conducted a systematic review of studies that reported criteria for the treatment response to all advanced therapies (infliximab, adalimumab, golimumab, ustekinumab, vedolizumab and tofacitinib) in patients with inflammatory bowel disease. RESULTS: Across trials, criteria for a response of both patients with ulcerative colitis and Crohn's disease are heterogenous. Investigators use different definitions for clinical and endoscopic remission, and endoscopic response and outcomes are assessed at variable time points. Current society guidelines provide heterogenous recommendations on treatment optimization. Most available data on loss of response concern anti-TNF molecules, and newer therapies are not included in the guidelines. CONCLUSION: The lack of clear definitions and formal recommendations provide the premise for empirical treatment strategies and premature abandonment of therapies.

Epidemiological trends in acute pancreatitis: A retrospective cohort in a tertiary center over a seven year period.

BACKGROUND: Acute pancreatitis (AP) remains a major cause of hospitalization and mortality with important health-related costs worldwide. Using an electronic database of a large tertiary center, we estimated the incidence, etiology, severity and costs of hospitalized AP cases in southern Romania. AIM: To estimate the incidence, cost and tobacco usage of hospitalized AP cases in southern Romania and to update and upgrade the knowledge we have on the etiology, severity (in regard to Revised Atlanta Classification), outcome, morphology and local complications of AP. METHODS: We performed an electronic health care records search on AP patients treated at Emergency University Hospital of Bucharest (Spitalul Universitar de Urgența București) between 2015 and 2022. The incidence, etiology, and severity were calculated; potential risk factors were evaluated, and the hospitalization costs of AP were documented and analyzed. The cohort of this study is part of the BUCharest - Acute Pancreatitis Index registry. RESULTS: A total of 947 consecutive episodes of AP where the patients were hospitalized in the gastroenterology department were analyzed, with 79.45% as 1st episode and the rest recurrent. The majority of the patients were males (68.9%). Alcoholic (45.7%), idiopathic (16.4%) and biliary (15.2%) were the main causes. The incidence was estimated at 29.2 episodes/100000 people. The median length of stay was 7 d. The median daily cost was 747.96 RON (165 EUR). There was a high prevalence of active tobacco smokers (68.5%). The prevalence of severe disease was 11.1%. The admission rate to the intensive care unit was 4.6%, with a mortality rate of 38.6%. The overall mortality was 5.5%. CONCLUSION: We estimated the incidence of AP at 29.2 episodes that required hospitalization per 100000 people. The majority of our cases were found in males (68.9%) and were related to alcohol abuse (45.7%). Out of the cases we were able to find data regarding tobacco usage, the majority were active smokers (68.5%). Most patients had a mild course (54.4%), with a mortality rate of 5.5%. Interstitial AP prevailed (45.3%). The median daily cost of hospitalization was 747.96 RON (165 EUR).

Acute Pancreatitis-Drivers of Hospitalisation Cost-A Seven-Year Retrospective Study from a Large Tertiary Center.

(1) Introduction: Acute pancreatitis (AP) remains a global burden of cost for healthcare services. We found a high degree of heterogeneity in cost-related reports and a scarcity of data regarding the cost of AP episodes in European and Asian populations. We aimed to estimate the median daily cost of hospitalisation (DCH) of AP in our population. Our secondary aims included estimating the total cost of hospitalisation (TCH) and the total cost of AP in Romania, as well as assessing the correlation between median DCH and ward, age, sex, length of stay (LoS), intensive care unit (ICU), outcome, severity, morphology, and aetiology of AP. (2) Material and methods: This retrospective cohort study included 1473 cases recruited from the electronic health records of the University Emergency Hospital of Bucharest. Statistical tests used included Kolmogorov-Smirnov, Kruskal-Wallis with post-hoc Dunn-Bonferroni, and Pearson correlation two-tailed. (3) Results: We found a median DCH of AP of USD 203.8 and a median TCH of USD 1360.5. The total yearly cost of AP in Romania was estimated at around USD 19 million. The majority of males with AP (61.8%) were mostly discharged as healed/ameliorated (83.8%); a majority had local complications (55.4%), which were mostly alcohol-related (35.1%). Regarding the aetiology, biliary-related AP was a cost driver, with significant statistical differences observed in all studied groups (p < 0.01). Morphology assessment revealed that acute necrotic collections were associated with high cost and meaningful disparities among the groups (p < 0.01). Cost was also associated with severity, with significant deviations among all groups (p < 0.01). Outcome-at-discharge as deceased correlated with higher costs, with substantial differences within groups (p < 0.01). The need for an intensive care unit was also a large driver of cost (p < 0.01). Females were prone to more expensive costs (p < 0.01). Surgical cases necessitated more financial resources (p < 0.01). (4) Conclusions: To the best of our knowledge, this is the first study on the cost of AP in Romania. Our findings showed that the drivers of increased AP costs might be older age, ICU, intra-hospital mortality, severe AP, local complications such as acute necrotic collections, biliary aetiology, and female sex. We found large heterogeneity and scarcity regarding cost-related data in the literature.

Real-World Endoscopic and Histologic Outcomes in Ulcerative Colitis Patients: A Retrospective Cohort Study.

BACKGROUND: Histologic activity has emerged as an aspirational therapeutic goal in ulcerative colitis management. It is not yet a formal treatment target in ulcerative colitis. However, it could be used as an adjunct to mucosal healing to represent a deeper level of healing. We investigated mucosal and histologic remission rates and potential predictors of these outcomes in a cohort of UC patients. METHODS: We conducted a retrospective analysis of data collected from UC patients enrolled in an ongoing prospective cohort study. Mucosal healing was defined as Mayo endoscopic score = 0. RESULTS: A total of 131 patients with ulcerative colitis were enrolled in our study and were prospectively followed for a median length of 2 years (range 0-5 years), totaling 266 study visits. Mucosal healing was recorded for 27 patients at 70 (26%) different study visits. For patients with mucosal healing, histologic remission was achieved in 18/27 (66%) patients. On univariate analysis, sustained clinical remission, SIBDQ scores ≥ 5.5, CRP ≤ 5 mg/dL and absence of corticotherapy were associated with mucosal healing and SIBDQ scores ≥ 5.5 and CRP ≤ 5 mg/dL with histologic healing, respectively. After logistic regression analysis, none of the investigated factors were associated with mucosal and histologic healing. The number of CD8+ intraepithelial lymphocytes (IELs) was significantly greater than the number of CD4+ IELs in periods of disease activity, as well as during mucosal healing (p < 0.01 in both cases). CONCLUSIONS: Mucosal healing and histologic remission rates are low in real-life settings. The results of univariate analysis indicate that a good quality of life (SIBDQ score) and normal inflammatory markers (CRP) are associated with mucosal and histologic healing. However, frequently used patient- and disease-related factors, including mucosal healing, are not reliable predictors for histologic remission. Greater CD8+ lymphocyte involvement and higher CD8+/CD4+ distribution can have a meaningful impact on understanding the pathogenesis and natural history of ulcerative colitis, as well as future treatment options for lymphocyte-targeting medications.

Accessory renal arteries - a source of hypertension: A case report.

BACKGROUND: Secondary hypertension is a relatively rare condition most commonly caused by renovascular disease due to atherosclerotic vascular disease or fibromuscular dysplasia. Although accessory renal arteries are frequent, to date, only six cases of secondary hypertension determined by their existence have been reported. CASE SUMMARY: We describe a case of a 39-year-old female who came to the emergency department with an urgent hypertensive crisis and hypertensive encephalopathy. Despite normal renal arteries, the computed tomography angiography revealed an inferior polar artery with 50% stenosis of its diameter. Conservative treatment with amlodipine, indapamide and perindopril was adopted, leading to blood pressure control within one month. CONCLUSION: To the best of our knowledge, there are controversies regarding accessory renal arteries as a potential etiology for secondary hypertension, but the seven similar cases already described, along with the current case, could reinforce the necessity of more studies concerning this subject.

Duodenal Gangliocytic Paragangliomas-Case Series and Literature Review.

Duodenal gangliocytic paragangliomas are rare neuroendocrine tumors primarily localized in the periampullary area. Though mostly asymptomatic, they can present with various symptoms, most often jaundice, anemia and abdominal pain. The present paper is a case series report, describing our personal experience with patients presenting to the Emergency Unit with different symptoms due to duodenal gangliocytic paraganglioma. Endoscopic resection is safe and indicated in most of the cases, being also associated with lower medical costs. EUS plays a central role in the pre-resection management and in surveillance, and immunostaining is decisive to ascertain the tumor histologic origin. In addition to reporting our experience, we researched the literature regarding these rare tumors and performed a comprehensive review.

Tissue and Circulating MicroRNA-31, MicroRNA-200b, and MicroRNA-200c Reflects Disease Activity in Crohn's Disease Patients: Results from the BIOMIR Study.

BACKGROUND AND AIMS: MicroRNAs (miR) have altered expression in multiple autoimmune disorders including inflammatory bowel disease. The aim of the study was to assess the tissue and circulating miR-31, miR-200b, and miR-200c expression levels as potential biomarkers for intestinal disease activity in patients with Crohn's disease (CD). METHODS: The study included 45 patients with histopathological confirmed CD and active disease (defined as fecal calprotectin >50 µg/g and Simple Endoscopic Score (SES) of CD >3), and 21 subjects as controls for the validation cohort. Demographic and clinical data, biomarkers (fecal calprotectin), endoscopy data, the expression levels of miR-31, miR-200b, and miR-200c in tissue and serum were assessed (by RT-PCR). Receiver operating characteristic analysis was performed to assess the miR-31, miR-200b, and miR-200c expression levels as potential biomarkers for active CD. RESULTS: Mean fecal calprotectin was 1540±890 µg/g. Mean SES-CD was 8.9±4.2. Tissue and circulating miR- 31 were significantly correlated with fecal calprotectin (r=0.81, r=0.83, p<0.01) and with SES-CD (r=0.82, r=0.79, p<0.01). The expression level of miR-31 was significantly upregulated in CD tissue cases compared to the control tissue samples (6.24±1.57 vs. 3.70±1.44; p <0.01). Similarly, serum miR-31 expression levels in CD patients were significantly upregulated compared to the control serum samples (0.78±0.42 vs. -2.07±1.00; p<0.01). The expression levels of tissue miR-200b and miR-200c were significantly upregulated in CD tissue cases compared to the control tissue samples (-5.25±0.93 vs. -4.69±0.80, p=0.03 for miR-200b, and -0.86±0.96 vs. 0.39±0.66, p<0.01 for miR-200c). Similarly, serum miR-200b and miR-200c expression levels in CD patients were significantly upregulated compared to the control serum samples (p < 0.05). Receiver operating characteristic analysis revealed that the expression levels of the selected miRNAs could help to discriminate active CD patients from healthy controls with very good specificity and sensitivity. CONCLUSIONS: Tissue and circulating miR-31, miR-200b, and miR-200c reflect disease activity in CD patients and can be used as biomarkers for active disease.

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.

Pathophysiology of sepsis-induced cholestasis: A review.

Sepsis is a critical condition resulting from the excessive activation of the inflammatory/immune system in response to an infection, with high mortality if treatment is not administered promptly. One of the many possible complications of sepsis is liver dysfunction with consequent cholestasis. The aim of this paper is to review the main mechanisms involved in the development of cholestasis in sepsis. Cholestasis in a septic patient must raise the suspicion that it is the consequence of the septic condition and limit the laborious attempts of finding a hepatic or biliary disease. Prompt antibiotic administration when sepsis is suspected is essential and may improve liver enzymes. Cholestasis is a syndrome with a variety of etiologies, among which sepsis is frequently overlooked, despite a number of studies and case reports in the literature demonstrating not only the association between sepsis and cholestasis but also the role of cholestasis as a prognostic factor for sepsis-induced death.

Romanian Guidelines for the Diagnosis and Treatment of GERD-induced Respiratory Manifestations.

BACKGROUND AND AIMS: Gastroesophageal reflux disease (GERD) is a common condition present in daily practice with a wide range of clinical phenotypes. In this line, respiratory conditions may be associated with GERD. The Romanian Societies of Gastroenterology and Neurogastroenterology, in association with the Romanian Society of Pneumology, aimed to create a guideline regarding the epidemiology, diagnosis and treatment of respiratory conditions associated with GERD. METHODS: Delphi methodology was used and eleven common working groups of experts were created. The experts reviewed the literature according to GRADE criteria and formulated 34 statements and recommendations. Consensus (>80% agreement) was reached for some of the statements after all participants voted. RESULTS: All the statements and the literature review are presented in the paper, together with their correspondent grade of evidence and the voting results. Based on >80% voting agreement, a number of 22 recommendations were postulated regarding the diagnosis and treatment of GERD-induced respiratory symptoms. The experts considered that GERD may cause bronchial asthma and chronic cough in an important number of patients through micro-aspiration and vagal-mediated tracheobronchial reflex. GERD should be suspected in patients with asthma with suboptimal controlled or after exclusion of other causes, also in nocturnal refractory cough which needs gastroenterological investigations to confirm the diagnosis. Therapeutic test with double dose proton pump inhibitors (PPI) for 3 months is also useful. GERD induced respiratory conditions are difficult to treat; however,proton pump inhibitors and laparoscopic Nissen fundoplication are endorsed for therapy. CONCLUSIONS: This guideline could be useful for the multidisciplinary management of GERD with respiratory symptoms in current practice.

Mucinous appendiceal neoplasm: A case report.

BACKGROUND: Primary appendiceal tumors are histologically diverse and have an insidious onset and few specific clinical manifestations. In the majority of cases, these tumors are discovered after appendectomy during pathological exam of the resected tissue. Treatment may include appendectomy (simple or radical) and right hemicolectomy depending on factors such as histological type, tumor size and lymph node/organ involvement. The aim of this case study is to describe a rare case of a giant appendicular mucocele and raise awareness of this condition and its management options and follow-up protocol. CASE SUMMARY: We present the case of a 43-year-old patient who presented to our emergency department with mild right lower quadrant pain. After the initial check-up and imaging exams, he underwent surgery, where a giant 20 cm × 13 cm appendicular tumor was found and resected. Appendicular mucocele was suspected due to the macroscopic appearance and was later confirmed by the pathological exam. The patient's postoperative evolution was uneventful, and after discharge, he was included in our follow-up program. CONCLUSION: In conclusion, mucinous appendiceal neoplasms embody a rare pathology; they are asymptomatic or have few, unspecific clinical signs and in many cases are discovered after appendectomy.

Surrogate markers of mucosal healing in inflammatory bowel disease: A systematic review.

BACKGROUND: Mucosal healing (MH) has emerged as a key therapeutic target in inflammatory bowel disease (IBD), and achievement of this goal is documented by endoscopy with biopsy. However, colonoscopy is burdensome and invasive, and substitution with an accurate noninvasive biomarker is desirable. AIM: To summarize published data regarding the performance of noninvasive biomarkers in assessing MH in IBD patients. METHODS: We conducted a systematic review of studies that reported the performance of biomarkers in diagnosing MH in patients with IBD. The main outcome measure was to review the diagnostic accuracy of serum and fecal markers that showed promising utility in assessing MH. RESULTS: We screened 1301 articles, retrieved 46 manuscripts and included 23 articles for full-text analysis. The majority of the included manuscripts referred to fecal markers (12/23), followed by circulatory markers (8/23); only 3/23 of the included manuscripts investigated combined markers (serum and/or fecal markers). Fecal calprotectin (FC) was the most investigated fecal marker for assessing MH. In ulcerative colitis, for cutoff levels ranging between 58 mcg/g and 490 mcg/g, the sensitivity was 89.7%-100% and the specificity was 62%-93.3%. For Crohn's disease, the cutoff levels of FC ranged from 71 mcg/g to 918 mcg/g (sensitivity 50%-95.9% and specificity 52.3%-100%). The best performance for a serum marker was observed for the endoscopic healing index, which showed a comparable accuracy to the measurement of FC and a higher accuracy than the measurement of serum C-reactive protein. CONCLUSION: Several promising biomarkers of MH are emerging but cannot yet substitute for endoscopy with biopsy due to issues with reproducibility and standardization.