Clinical Course and Risk Factors for In-Hospital Mortality of 205 Patients with SARS-CoV-2 Pneumonia in Como, Lombardy Region, Italy.

The aim of this study is to explore risk factors for in-hospital mortality and describe the effectiveness of different treatment strategies of 205 laboratory-confirmed cases infected with SARS-CoV-2 during the Lombardy outbreak. All patients received the best supportive care and specific interventions that included the main drugs being tested for repurposing to treat COVID-19, such as hydroxychloroquine, anticoagulation and antiviral drugs, steroids, and interleukin-6 pathway inhibitors. Clinical, laboratory, and treatment characteristics were analyzed with univariate and multivariate logistic regression methods to explore their impact on in-hospital mortality. Univariate analyses showed prognostic significance for age greater than 70 years, the presence of two or more relevant comorbidities, a P/F ratio less than 200 at presentation, elevated LDH (lactate dehydrogenase) and CRP (C-reactive protein) values, intermediate- or therapeutic-dose anticoagulation, hydroxychloroquine, early antiviral therapy with lopinavir/ritonavir, short courses of steroids, and tocilizumab therapy. Multivariable regression confirmed increasing odds of in-hospital death associated with age older than 70 years (OR 3.26) and a reduction in mortality for patients treated with anticoagulant (-0.37), antiviral lopinavir/ritonavir (-1.22), or steroid (-0.59) therapy. In contrast, hydroxychloroquine and tocilizumab have not been confirmed to have a significant effect in the treatment of SARS-CoV-2 pneumonia. Results from this real-life single-center experience are in agreement and confirm actual literature data on SARS-CoV-2 pneumonia in terms of both clinical risk factors for in-hospital mortality and the effectiveness of the different therapies proposed for the management of COVID19 disease.

Haematemesis and acute dysphagia: oesophagogastroduodenoscopy or CT-which one first?

We present an uncommon case of a patient presenting at the emergency department for severe vomiting, persisting for at least 12 hours, without nausea or abdominal pain. She initially referred vomiting food eaten several hours earlier and eventually a single episode of haematemesis with emission of a small amount of red blood and clots. She also reported the occurrence of acute dysphagia for solid food. The patient underwent oesophagogastroduodenoscopy (OGD), which showed that the lumen was almost completely narrowed by a submucosal bluish bulging from midoesophagus (19 cm from the incisors) to the cardia (located at 35 cm from the incisors). She therefore underwent chest CT showing a 15 cm long intramural oesophageal haematoma. Although the combination of vomiting and haematemesis is usually associated with Mallory-Weiss syndrome, in which a prompt OGD has a key role in the patient management, when these symptoms are associated with acute dysphagia, a possible intramural haematoma might be suspected. In this case, chest CT should take precedence, because it allows a quick and complete diagnostic appraisal. However, in this setting, although OGD can directly show typical findings (bluish swelling mucosa with or without a superficial tears), it might increase the risk of oesophageal haematoma rupture and intraluminal bleeding.

Linked color imaging reduces the miss rate of neoplastic lesions in the right colon: a randomized tandem colonoscopy study.

BACKGROUND: Linked color imaging (LCI) is a newly developed image-enhancing endoscopy technology that provides bright endoscopic images and increases color contrast. We investigated whether LCI improves the detection of neoplastic lesions in the right colon when compared with high definition white-light imaging (WLI). METHODS: Consecutive patients undergoing colonoscopy were randomized (1:1) after cecal intubation into right colon inspection at first pass by LCI or by WLI. At the hepatic flexure, the scope was reintroduced to the cecum under LCI and a second right colon inspection was performed under WLI in previously LCI-scoped patients (LCI-WLI group) and vice versa (WLI-LCI group). Lesions detected on first- and second-pass examinations were used to calculate detection and miss rates, respectively. The primary outcome was the right colon adenoma miss rate. RESULTS: Of the 600 patients enrolled, 142 had at least one adenoma in the right colon, with similar right colon adenoma detection rates (r-ADR) in the two groups (22.7 % in LCI-WLI and 24.7 % in WLI-LCI). At per-polyp analysis, double inspection of the right colon in the LCI-WLI and WLI-LCI groups resulted in an 11.8 % and 30.6 % adenoma miss rate, respectively (P < 0.001). No significant difference in miss rate was found for advanced adenomas or sessile serrated lesions. At per-patient analysis, at least one adenoma was identified in the second pass only (incremental ADR) in 2 of 300 patients (0.7 %) in the LCI - WLI group and in 13 of 300 patients (4.3 %) in the WLI - LCI group (P = 0.01). CONCLUSIONS: LCI could reduce the miss rate of neoplastic lesions in the right colon.

Educational strategies for colonoscopy bowel prep overcome barriers against split-dosing: A randomized controlled trial.

BACKGROUND: A split-dose (SD) regimen is crucial for colonoscopy quality. Compliance with SD for early morning colonoscopy is generally poor. The present study evaluated whether pre-colonoscopy counselling, in addition to a dedicated leaflet, might increase SD uptake. METHODS: Consecutive 50-69-year-old patients undergoing screening colonoscopy before 10 a.m. were randomized to either receive written information only on bowel preparation (Written Group, WG) or written and oral instructions (Written and Oral Group, WaOG). The leaflet strongly encouraged SD adoption. The primary endpoint was the number of patients adopting SD in each group. The secondary endpoints were predictors of SD uptake, compliance with preparation schemes and cleansing adequacy. RESULTS: A total of 286 patients (143 WG, 143 WaOG) were enrolled (mean age 59.6 ± 6.1 years, men 49.3%). SD was adopted by 114 and 125 patients in the WG and WaOG, respectively (79.7% versus 87.4%, p = 0.079). No significant differences were observed for the proportion of patients with full compliance with preparation scheme (97.9% versus 97.2%, p = 0.99) and of procedures with adequate bowel cleansing (95.6% versus 95.1%, p = 0.77). At multivariate analysis, a > 1 h travel time to the endoscopy service was inversely correlated with SD uptake (odds ratio (OR) 0.30, 95% confidence interval (CI) 0.09-0.98). CONCLUSIONS: Our leaflet guaranteed satisfactory uptake of SD and excellent adherence to the preparation scheme for early morning colonoscopy. Its use might marginalize the need for additional oral instructions, particularly in open-access settings.

Granulocyte-Monocyte Apheresis in Steroid-Dependent, Azathioprine-Intolerant/Resistant Moderate Ulcerative Colitis: A Prospective Multicenter Study.

BACKGROUND: Granulocyte-monocyte apheresis has been proposed for the treatment of ulcerative colitis, although it is limited by costs and variability of results. AIM: To assess effectiveness of granulocyte-monocyte apheresis in patients with steroid-dependent, azathioprine-intolerant/resistant moderate ulcerative colitis. METHODS: Consecutive patients fulfilling inclusion criteria were prospectively enrolled, treated by apheresis, and followed up for 12 months. The primary end point of the study was steroid-free clinical remission at 12 months, with no need for biologic therapy or surgery. RESULTS: From January to December 2013, 33 patients were enrolled. After one year of follow-up, 12 (36%) patients had clinical remission, were steroid-free, and had no need for biological therapy or surgery; 3 (9%) cases showed a clinical response (but not clinical remission). Moreover, 12 (36%) patients required biologic therapy, 4 (12%) underwent colectomy, and in the other 2 (6%) a reduction, but not withdrawal, of steroid dose was achieved. CONCLUSIONS: Our study shows that a standard course of granulocyte-monocyte apheresis is associated with a 36% steroid-free clinical remission in patients with steroid-dependent, azathioprine-intolerant or resistant moderate ulcerative colitis. Apheresis might represent an alternative to biologic therapy or surgery in this specific subgroup of patients. This trial is registered with Clinicaltrial.gov NCT03189888.

Accuracy of capsule colonoscopy and computed tomographic colonography in individuals with positive results from the fecal occult blood test.

BACKGROUND & AIMS: Computed tomographic colonography (CTC) is a reliable option for screening subjects who are unable or unwilling to undergo optical colonoscopy (OC). A colon capsule (PillCam Colon2 [CC2]; GivenImaging Ltd., Yokneam, Israel) has shown promising results in detecting polyps larger than 6 mm. We compared the accuracy of CC2 and CTC in identifying individuals with at least 1 polyp greater than 6 mm and subjects' attitude toward the procedures. METHODS: Fifty individuals (mean age, 59.2 ± 5.8 y; 58% male) with positive results from the immunochemical fecal occult blood test (iFOBT-positive) underwent CC2, CTC, and OC. The unblinded colonoscopy, integrating OC, CTC, and CC2 results, was used as the reference standard. In a per-patient analysis, the accuracy of CC2 and CTC were assessed for individuals with at least 1 polyp 6 mm or larger. Individuals were asked to choose which procedure they would be willing to repeat between CTC and CC2. RESULTS: The combination of OC, CTC, and CC2 identified 16 cases with at least 1 polyp 6 mm or larger (reference standard). CTC identified the polyps with 88.2% sensitivity, 84.8% specificity, a 3.0 positive likelihood ratio, and a 0.07 negative likelihood ratio. CC2 identified the polyps with 88.2% sensitivity, 87.8% specificity, a 3.75 positive likelihood ratio, and a 0.06 negative likelihood ratio. Thirty-nine subjects (78%) said they preferred CC2 to CTC. CONCLUSIONS: CC2 and CTC detect polyps 6 mm and larger with high levels of accuracy; these techniques are effective in selecting iFOBT-positive individuals who do not need to be referred for colonoscopy. CC2 seems to be better tolerated than CTC, and could be a reliable alternative to CTC for iFOBT-positive individuals who are unable or unwilling to undergo OC. ClinicalTrials.gov number: NCT01744509.

Hyoscine N-butylbromide for adenoma detection during colonoscopy: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Hyoscine N-butylbromide (HBB), commonly used during colonoscopy to facilitate cecal intubation, has been proposed to increase the adenoma detection rate (ADR). AIMS: To evaluate whether HBB administration increases the adenoma detection rate and influences patients' tolerance. METHODS: Consecutive colonoscopy outpatients were randomized after cecal intubation to receive either 20mg HBB or placebo i.v. The number, size, histology and location of polyps were recorded. The air retained in the abdomen was either indirectly estimated by ΔAC (difference in the abdominal circumference measured before and after colonoscopy) or directly evaluated by patients' perception (visual analogic scale, range 0-100). RESULTS: 402 patients (44% male; mean age 57.7±12.5years) received either HBB or placebo. No differences in ADR (31.7% vs. 28%, p=0.48), advanced-ADR (7.4% vs. 10.5%, p=0.35) were observed between HBB and placebo group, respectively. A significantly lower detection rate of flat/depressed lesions was observed in the HBB group (0.5% vs. 5.5%, p=0.003). The ΔAC and the bloating perception were comparable between the two groups (p=0.22 and p=0.48, respectively). CONCLUSIONS: HBB administered before colonoscope withdrawal does not increase adenoma detection rate and seems to hamper the visualization of flat/depressed lesions. This finding raises concerns on the indiscriminate use of HBB during colonoscopy.

Constipation in the elderly: management strategies.

Constipation is a highly prevalent and bothersome disorder that negatively affects patients' social and professional lives and places a great economic burden on both patients and national health services. An accurate determination of the prevalence of constipation is difficult because of the various definitions used, but many epidemiological studies have shown that it affects up to 20% of the population at any one time. Although constipation is not a physiological consequence of normal aging, decreased mobility and other co-morbid medical conditions may contribute to its prevalence in older adults. Functional constipation is diagnosed when no secondary causes can be identified. Patients have some unusual beliefs about their bowel habits. Systematic attention to history, examination and investigation, especially in older people, can be highly effective in resolving problems and in enhancing quality of life. There is a considerable range of treatment modalities available for patients with constipation, but the clinical evidence supporting their use varies widely. However, if constipation is not managed proactively, patients can experience negative consequences, such as anorexia, nausea, bowel impaction or bowel perforation. The clinical benefits of various traditional pharmacological and non-pharmacological agents remain unclear. The first steps in the treatment of simple constipation include increasing intake of dietary fibre and the use of a fibre supplement. Patients with severe constipation or those unable to comply with the recommended intake of fibre may benefit from the addition of laxatives. More recently, newer agents (e.g. tegaserod and lubiprostone), have been approved for the treatment of patients with chronic constipation. Additional work is needed to determine what role, if any, these agents may play in the treatment of patients with chronic constipation. The purpose of this review is to identify evidence-based interventions for the prevention and management of constipation in the elderly.

The impact of narrow band imaging in screening colonoscopy: a randomized controlled trial.

BACKGROUND & AIMS: Narrow band imaging (NBI) is an imaging technique that allows a better definition of capillary pattern and improves the contrast between adenomas and the surrounding mucosa. Conflicting data exist on the ability of NBI to improve detection of colonic neoplasm; the impact of NBI is being tested in several screening scenarios. We evaluated whether the routine use of NBI, compared with white light (WL), during the withdrawal phase of screening colonoscopy improved adenoma detection. METHODS: This randomized controlled study included consecutive 50- to 69-year-old patients with positive immunologic fecal occult blood tests. They were randomly assigned to groups that were examined with WL (n = 108) or NBI (n = 103) during the withdrawal phase of their colonoscopies. The primary end point was the adenoma detection rate. The prevalence of non-polypoid and the total number of adenomas were also evaluated. RESULTS: The number of total and mean per-patient adenomas were 201 (1.95 +/- 2.3) and 198 (1.83 +/- 2.1) in the NBI and WL groups, respectively (P = .69). The adenoma detection rates were 57.3% for patients examined by NBI and 58.3% for those examined by WL (P = .88). A total of 41 non-polypoid adenomas were identified (26 in the NBI and 15 in the WL groups, P = .16). The flat adenoma detection rates were 21.4% and 9.3% in the NBI and WL groups, respectively (P = .019). CONCLUSIONS: The routine use of NBI in screening colonoscopy did not increase the adenoma detection rate. NBI seems to improve the detection of flat adenomas, although additional studies are necessary.

High- versus low-dose proton pump inhibitors after endoscopic hemostasis in patients with peptic ulcer bleeding: a multicentre, randomized study.

BACKGROUND: The most effective schedule of proton pump inhibitor (PPI) administration following endoscopic hemostasis of bleeding ulcers remains uncertain. METHODS: Patients with actively bleeding ulcers and those with nonbleeding visible vessel or adherent clot were treated with epinephrine injection and/or thermal coagulation, and randomized to receive intravenous PPIs according to an intensive regimen (80 mg bolus followed by 8 mg/h as continuous infusion for 72 h) or a standard regimen (40 mg bolus daily followed by saline infusion for 72 h). After the infusion, all patients were given 20 mg PPI twice daily orally. The primary end point was the in-hospital rebleeding rate, as ascertained at the repeat endoscopy. RESULTS: Bleeding recurred in 28 of 238 patients (11.8%) receiving the intensive regimen, and in 19 of 236 (8.1%) patients receiving the standard regimen (P= 0.18). Most rebleeding episodes occurred during the initial 72-h infusion: 18 (7.6%) and 19 events (8.1%) in the intensive and standard groups, respectively (P= 0.32). Mean units of blood transfused were 1.7 +/- 2.1 in the intensive and 1.5 +/- 2.1 in the standard regimen group (P= 0.34). The duration of hospital stay was <5 days for 88 (37.0%) and 111 patients (47.0%) in the intensive and standard groups (P= 0.03). There were fewer surgical interventions in the standard versus intensive regimen (1 vs 3). Five patients in each treatment group died. CONCLUSIONS: Following endoscopic hemostasis of bleeding ulcers, standard-dose PPIs infusion was as effective as a high-dose regimen in reducing the risk of recurrent bleeding. (ClinicalTrials.gov number, NCT00374101).

Tumour necrosis factor alpha in segmental colitis associated with diverticula.

The pathogenesis of segmental colitis associated with diverticula (SCAD) is unclear, but tumour necrosis factor alpha (TNF-alpha) has been shown to play a pivotal role in the pathogenesis of inflammatory bowel diseases. The aim of this study was to assess TNF-alpha levels in patients with SCAD. In a post hoc analysis of a prospective multicenter study, tissue samples from 13 patients diagnosed with SCAD were subjected to histological analyses. The severity of the inflammation was assessed by means of a histological score and histomorphometry (number of inflammatory cells/mm2). Immunohistochemical staining with an antibody against TNF-alpha was performed on all biopsies and the degree of staining expressed as the percentage of positive stromal cells/1000 counted (TNF-alpha score). Matched patients with irritable bowel syndrome (IBS) were used as controls. Over-expression of TNF-alpha was found in all SCAD patients (38.6 +/- 10.4%), and it was associated with a high histological score (2.5 +/- 0.5) and neutrophil cell count (16.3 +/- 3/mm2). These values were distinctly higher than those found in the IBS controls. Our data suggest that TNF-alpha activity is involved in SCAD pathogenesis, similarly to what occurs in Crohn's disease and ulcerative colitis.

Pregnancy before and after the diagnosis of inflammatory bowel diseases: retrospective case-control study.

BACKGROUND AND AIM: Inflammatory bowel diseases (IBD) commonly affect women during the reproductive years. The aim of the present study was to evaluate the reproductive histories of patients with ulcerative colitis (UC) and Crohn's disease (CD) considering pregnancies occurring before and after the diagnosis. METHOD: Case-control study evaluating IBD patients, interviewed by questionnaire about outcome of pregnancy and course of disease. RESULTS: A total of 502 pregnancies from 199 patients in the prediagnosis group and 121 pregnancies from 90 patients in the post-diagnosis group were respectively compared with 996 and 204 pregnancies recorded in a control population. In prediagnosis pregnancies, CD was associated with increased risk of preterm delivery (odds ratio [OR] 4.62, 95% confidence interval [CI] 2.77-7.73; P < 0.001 vs controls and OR 3.52, 95% CI 1.75-7.07; P < 0.001 vs UC) and lower birthweight (P < 0.001 vs UC and controls). In post-diagnosis pregnancies, the rate of live births was lower, but not statistically significant in IBD (OR 0.22, 95% CI 0.04-1.25; P = 0.08) and the birthweight was significantly lower in CD than in UC (P < 0.03) and in controls (P < 0.02). In post-diagnosis pregnancies, a higher incidence of congenital abnormalities was found in IBD patients (5.5% vs 0.0%). The spontaneous abortion rate and therapeutic abortions were significantly higher in post than in prediagnosis pregnancies. Neither disease activity at conception nor treatment appeared to influence the outcome of pregnancy. CONCLUSIONS: CD in the preclinical phase has some influence on pregnancy. In patients with IBD our data suggest that conception should not be discouraged. However, because of a modest increase in mild congenital abnormalities and abortions rates, pregnancy in IBD patients should be closely monitored.

Gender and disease activity influence health-related quality of life in inflammatory bowel diseases.

BACKGROUND/AIMS: Measurement of health related quality of life (HRQoL) is a new tool to evaluate patients with inflammatory bowel disease (IBD). The aims of this study were to verify reliability and responsiveness of a disease-specific questionnaire [Italian Questionnaire on Quality of Life (IQQoL)], and to assess the relationship between clinical and demographic variables and HRQoL in IBD patients. METHODOLOGY: The IQQoL was submitted to all IBD patients consecutively seen at eight participating Hospitals, and re-administered at follow-up visits. The IQQoL covers intestinal and systemic symptoms, emotional and social function. The higher the score, the worse the HRQoL. RESULTS: 249 patients were enrolled, 106 with Crohn's disease (CD) and 143 with ulcerative colitis (UC). IQQoL was re-administered to 134 patients: 98 with unchanged, 17 with worsened and 19 with improved disease activity. The IQQoL was stable over time in patients with stable clinical conditions, and very responsive to change both in patients with improved and worsened disease activity. HRQoL was inversely correlated with disease activity, both in CD and UC. Perception of HRQoL was significantly worse in women than in men. CONCLUSIONS: The IQQoL is a reliable and responsive instrument to assess HRQoL in IBD patients. Active disease is related to poor HRQoL perception. In CD, women, mainly if young, have a worse HRQoL perception than men.

High-dose senna compared with conventional PEG-ES lavage as bowel preparation for elective colonoscopy: a prospective, randomized, investigator-blinded trial.

OBJECTIVE: To compare the efficacy and patient acceptance of an oral high dose of senna to conventional polyethylene glycol-electrolyte lavage solution (PEG-ES) in adults undergoing elective colonoscopy. METHODS: Consecutive outpatients referred for elective colonoscopy were prospectively randomly assigned to receive, the day before the procedure, either 24 tablets of 12 mg senna, divided into two doses at 1 p.m. and 9 p.m. (senna group, n=191), or standard 4-L PEG-ES (PEG-ES group, n=92). The overall quality of colon cleansing (primary outcome measure) and cleansing in the right colon were evaluated using the Aronchick scoring scale (1=excellent to 4=inadequate) by the investigator/endoscopist who was blinded to the treatment assignment. Patient acceptance and the safety of the preparation were assessed by a nurse, using a structured questionnaire covering compliance with the dosing, overall tolerance of the preparation (1=none or mild discomfort to 4=severely distressing), and adverse events. RESULTS: The quality of colon cleansing, overall tolerance of the preparation, and compliance were significantly better with senna; overall cleansing was excellent or good in 90.6% of patients in the senna group and in 79.7% in the PEG-ES group (p= 0.003). The percentage of procedures rescheduled because of insufficient colon cleansing was 7.3% in the PEG-ES group and 2.6% in the senna group (p=0.035). Multivariate logistic regression modeling showed the PEG-ES preparation as negative independent predictor of unsuccessful bowel cleansing. The incidence of adverse reactions was similar in the two groups; patients who received senna experienced significantly less nausea and vomiting, but more abdominal pain. CONCLUSIONS: An oral high dose of senna is a valid alternative to standard PEG-ES for outpatient colonoscopy preparation.

Single bolus of midazolam versus bolus midazolam plus meperidine for colonoscopy: a prospective, randomized, double-blind trial.

BACKGROUND: The aim of this study was to determine whether a single bolus of meperidine in addition to midazolam improves patient tolerance during colonoscopy. METHODS: Consecutive patients undergoing outpatient colonoscopy were randomly assigned in double-blind fashion to receive a single rapid intravenous bolus of 5 mg of midazolam and placebo (Group A, n = 125) or 5 mg midazolam plus 50 mg meperidine (Group B, n = 128). Tolerance (4-point scale: 1 excellent, 4 unbearable), pain (4-point scale: 1 none, 4 severe) and willingness to undergo another colonoscopy were assessed 24 to 48 hours later in a telephone interview conducted by an independent observer blinded to the regimen of sedative medication. RESULTS: Significantly more patients in Group A reported moderate or severe pain (28% vs. 9%; p < 0.001), poor or unbearable tolerance (18% vs. 6%; p < 0.01) and unwillingness to undergo colonoscopy again in the future (14% vs. 5%; p < 0.05). By multivariate analysis, randomization to the midazolam group and younger age were the only variables independently associated with the risk of reporting at least one of these outcomes. Recovery time, frequency of oxygen desaturation, and need for supplemental oxygen were not significantly different between the 2 groups. CONCLUSIONS: The addition of a single bolus of meperidine to midazolam improves patient tolerance and lessens pain during colonoscopy without significantly increasing the frequency of side effects or prolonging recovery time.