Efficacy of early anti-inflammatory treatment with high doses of intravenous anakinra with or without glucocorticoids in patients with severe COVID-19 pneumonia.

BACKGROUND: IL-1 plays a pivotal role in the inflammatory response during cytokine storm syndromes. OBJECTIVE: Our aim was to analyze the efficacy and safety of early anti-inflammatory treatment (AIT) with intravenous anakinra with or without glucocorticoids in coronavirus disease 2019 (COVID-19) pneumonia. METHODS: We performed a retrospective single-center cohort study of patients admitted for COVID-19 pneumonia from February 26 to April 29, 2020, to assess the efficacy of early AIT with intravenous anakinra (100 mg every 8 hours for 3 days, with tapering) alone or in combination with a glucocorticoid (intravenous methylprednisolone, 1-2 mg/kg daily, with tapering). The standard of care (SOC) treatment was hydroxychloroquine and/or azithromycin with or without antivirals and anticoagulants. Late rescue AIT with anakinra or tocilizumab was also evaluated. Treatment effect on overall survival was assessed by a propensity score-adjusted Cox model. RESULTS: A total of 128 patients were analyzed; 63 patients received early AIT (30 received anakinra alone and 33 received anakinra plus a glucocorticoid) at admission, and 65 patients did not receive early AIT and were used as controls; of the latter 65 patients, 44 received the SOC treatment alone and 21 received the SOC treatment plus late rescue AIT. After adjustment for all the unbalanced baseline covariates, early AIT reduced the hazard of mortality by 74% (adjusted hazard ratio [HR] = 0.26; P < .001). The effect was similar in patients receiving anakinra alone (adjusted HR = 0.28; P = .04) and anakinra plus a glucocorticoid (adjusted HR = 0.33; P = .07). Late rescue treatment did not show a significant advantage over SOC treatment alone (adjusted HR = 0.82; P = .70). CONCLUSIONS: This study suggests, on a larger series of patients with COVID-19 pneumonia, the potential efficacy and safety of the early use of high doses of intravenous anakinra with or without glucocorticoids.

Low Fibrinogen Levels Are Associated with Bleeding After Varices Ligation in Thrombocytopenic Cirrhotic Patients.

INTRODUCTION AND AIM: EVBL is a procedure frequently performed in cirrhotic patients for primary prophylaxis of bleeding. Patients with cirrhosis display various degrees of alteration of common coagulation parameters, and it is not known whether these alterations may predict post-EVBL bleeding. To evaluate factors predictive of post-endoscopic variceal band ligation (EVBL) bleeding in cirrhotic patients with thrombocytopenia. METHODS: We included 109 patients with cirrhosis undergoing EVBL for primary prophylaxis of variceal bleeding. Common coagulation parameters (INR, fibrinogen levels) and complete haemogram were obtained in all patients and evaluated subdividing patients in bleeders and non bleeders following EVBL. RESULTS: The incidence of post-EVBL bleeding was 5.5% (6 patients). INR and platelet counts, considered as continuous or dichotomous variables according to common cut-offs (i.e., INR>1.5, platelet count <50x109/L) were not predictors of post-EVBL bleeding. Patients who bled had significantly lower fibrinogen levels [146 mg/dL (98 - 262) versus 230 mg/dL (104 - 638), P=0.009], and no other biochemical or clinical predictors of bleeding were identified. A fibrinogen cut-off of 179 mg/dL had 98.6% negative predictive value for bleeding. CONCLUSION: low fibrinogen levels are associated with an increased risk of bleeding following prophylactic EVBL in cirrhotic patients, and might be used to stratify patients' risk. However, due to their preliminary nature, these findings need to be confirmed in larger populations.

Epidemiology and natural history of gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is highly prevalent in Western countries, particularly when considering its most classic symptom that is heartburn. This symptom is very frequent in the community and ranges from 10% to more than 30%, according to the various population-based studies. This disease is much more represented in Europe and USA than in Asiatic countries. It has been shown that GERD prevalence increases in parallel with the remarkable growth of obesity, as this condition is able to favor all the pathogenetic mechanisms leading to it. Current information regarding the phenotypic presentation of GERD shows that there are two main phenotypic manifestations, that are erosive reflux disease (ERD) and non-erosive reflux disease (NERD) and the latter includes the majority of patients (up to 70%). The major complication of GERD is the development of Barrett esophagus, a pre-malignant lesion potentially leading to esophageal adenocarcinoma. Data from medical literature on the natural history of this disease are scant and mainly retrospective, so the interpretation of them is very difficult. However, they seem to suggest that both NERD and mild esophagitis tend to remain as such overtime and the progression from NERD to ERD, from mild to severe ERD and from ERD to Barrett's esophagus may occur only in a small number of cases, ranging from 0% to 30%, 10-22% and 1-13%, respectively. Future studies should help us in elucidating better the real transition from one category to another and to do this, we have to exclude from the world of GERD all the functional conditions that nowadays can be easily recognized by means of impedance-pH monitoring.

Low serum trough levels are associated with post-surgical recurrence in Crohn's disease patients undergoing prophylaxis with adalimumab.

BACKGROUND: Whether therapeutic drug monitoring of biologic therapy can predict the efficacy of adalimumab to prevent postoperative Crohn's disease recurrence is unknown. AIM: To investigate whether adalimumab trough levels and anti-adalimumab antibodies correlate with endoscopic and clinical outcomes in a series of patients treated with prophylactic adalimumab monotherapy after resective surgery. METHODS: Post hoc analysis of a randomized, mesalamine-controlled trial. Adalimumab trough levels and antibodies were analysed every 8 weeks for 2 years using an homogeneous mobility shift assay. RESULTS: At two years, 1/6 patient had clinical recurrence and 1/6 patient had endoscopic and clinical recurrence. At baseline (9.5 vs. 14.4 mcg/mL) and during follow-up [7.5 (4.4-9.8) vs. 13.9 (8.9-23.6)mcg/mL, p<0.01], median adalimumab trough levels in patients with clinical or endoscopic recurrence were lower than in those who maintained remission. Persistent antibodies-against-adalimumab were detected in the patient with both endoscopic and clinical recurrence. CONCLUSION: Measurement of adalimumab trough levels and anti-adalimumab antibodies after surgery could be useful to further reduce postoperative recurrence.

Narrow-band imaging with magnifying endoscopy is accurate for detecting gastric intestinal metaplasia.

AIM: To investigate the predictive value of narrow-band imaging with magnifying endoscopy (NBI-ME) for identifying gastric intestinal metaplasia (GIM) in unselected patients. METHODS: We prospectively evaluated consecutive patients undergoing upper endoscopy for various indications, such as epigastric discomfort/pain, anaemia, gastro-oesophageal reflux disease, suspicion of peptic ulcer disease, or chronic liver diseases. Patients underwent NBI-ME, which was performed by three blinded, experienced endoscopists. In addition, five biopsies (2 antrum, 1 angulus, and 2 corpus) were taken and examined by two pathologists unaware of the endoscopic findings to determine the presence or absence of GIM. The correlation between light blue crest (LBC) appearance and histology was measured. Moreover, we quantified the degree of LBC appearance as less than 20% (+), 20%-80% (++) and more than 80% (+++) of an image field, and the semiquantitative evaluation of LBC appearance was correlated with IM percentage from the histological findings. RESULTS: We enrolled 100 (58 F/42 M) patients who were mainly referred for gastro-esophageal reflux disease/dyspepsia (46%), cancer screening/anaemia (34%), chronic liver disease (9%), and suspected celiac disease (6%); the remaining patients were referred for other indications. The prevalence of Helicobacter pylori (H. pylori) infection detected from the biopsies was 31%, while 67% of the patients used proton pump inhibitors. LBCs were found in the antrum of 33 patients (33%); 20 of the cases were classified as LBC+, 9 as LBC++, and 4 as LBC+++. LBCs were found in the gastric body of 6 patients (6%), with 5 of them also having LBCs in the antrum. The correlation between the appearance of LBCs and histological GIM was good, with a sensitivity of 80% (95%CI: 67-92), a specificity of 96% (95%CI: 93-99), a positive predictive value of 84% (95%CI: 73-96), a negative predictive value of 95% (95%CI: 92-98), and an accuracy of 93% (95%CI: 90-97). The NBI-ME examination overlooked GIM in 8 cases, but the GIM was less than 5% in 7 of the cases. Moreover, in the 6 false positive cases, the histological examination showed the presence of reactive gastropathy (4 cases) or H. pylori active chronic gastritis (2 cases). The semiquantitative correlation between the rate of LBC appearance and the percentage of GIM was 79% (P < 0.01). CONCLUSION: NBI-ME achieved good sensitivity and specificity in recognising GIM in an unselected population. In routine clinical practice, this technique can reliably target gastric biopsies.

Lactulose breath test to assess oro-cecal transit delay and estimate esophageal dysmotility in scleroderma patients.

OBJECTIVES: To assess the correlation between delayed oro-cecal transit time (OCTT) and esophageal motility abnormalities in a cohort of systemic sclerosis (SSc) patients. METHODS: We prospectively enrolled 50 consecutive SSc patients and 60 healthy volunteers (HVs) as controls. Both groups underwent glucose breath test (GBT) to exclude small intestine bacterial overgrowth, lactulose hydrogen, and octanoic acid breath tests (LHBT and OBT) to measure OCTT and gastric emptying (GE), respectively, and manometry to assess esophageal motility. RESULTS: Thirty-one (63%) SSc patients presented ineffective esophageal motility (IEM) compared with 3 HVs (5%; P<0.01), 37 (74%) had an abnormal OCTT compared with 4 HVs (7%; P <0.01), and 16 (32%) had an altered GE compared with 4 HVs (7%; P <0.01). The median OCTT and gastric t½ were longer in SSc than in HVs (165 min vs. 101 min and 125 min vs. 78 min, respectively; P <0.01). A delayed GE was present in 12/37 (32%), whereas IEM in 27/37 (73%) SSc patients with prolonged OCTT. The prevalence of IEM increased in parallel with the prolongation of OCTT (31% when OCTT<150 min, 73% when OCTT≥150 min, and up to 85% when OCTT>180 min, P<0.01). CONCLUSIONS: Abnormalities of both esophageal and small intestine motility are frequent in SSc patients and esophageal motility is altered in most cases with small bowel involvement. Delayed GE plays a limited role in prolonging OCTT. LHBT is a non-invasive, cheap, well-tolerated diagnostic tool that may be useful to estimate intestinal involvement and also to estimate a higher risk of esophageal hypomotility in SSc patients.