Development of clinical tools to estimate the breathing effort during high-flow oxygen therapy: A multicenter cohort study.

INTRODUCTION AND OBJECTIVES: Quantifying breathing effort in non-intubated patients is important but difficult. We aimed to develop two models to estimate it in patients treated with high-flow oxygen therapy. PATIENTS AND METHODS: We analyzed the data of 260 patients from previous studies who received high-flow oxygen therapy. Their breathing effort was measured as the maximal deflection of esophageal pressure (ΔPes). We developed a multivariable linear regression model to estimate ΔPes (in cmH2O) and a multivariable logistic regression model to predict the risk of ΔPes being >10 cmH2O. Candidate predictors included age, sex, diagnosis of the coronavirus disease 2019 (COVID-19), respiratory rate, heart rate, mean arterial pressure, the results of arterial blood gas analysis, including base excess concentration (BEa) and the ratio of arterial tension to the inspiratory fraction of oxygen (PaO2:FiO2), and the product term between COVID-19 and PaO2:FiO2. RESULTS: We found that ΔPes can be estimated from the presence or absence of COVID-19, BEa, respiratory rate, PaO2:FiO2, and the product term between COVID-19 and PaO2:FiO2. The adjusted R2 was 0.39. The risk of ΔPes being >10 cmH2O can be predicted from BEa, respiratory rate, and PaO2:FiO2. The area under the receiver operating characteristic curve was 0.79 (0.73-0.85). We called these two models BREF, where BREF stands for BReathing EFfort and the three common predictors: BEa (B), respiratory rate (RE), and PaO2:FiO2 (F). CONCLUSIONS: We developed two models to estimate the breathing effort of patients on high-flow oxygen therapy. Our initial findings are promising and suggest that these models merit further evaluation.

Predictors of intubation in COVID-19 patients treated with out-of-ICU continuous positive airway pressure.

BACKGROUND: As delayed intubation may worsen the outcome of coronavirus disease 2019 (COVID-19) patients treated with continuous positive airway pressure (CPAP), we sought to determine COVID-specific early predictors of CPAP failure. METHODS: In this observational retrospective multicentre study, we included all COVID-19 patients treated with out-of-ICU CPAP, candidates for intubation in case of CPAP failure. From these patients, we collected demographic and clinical data. RESULTS: A total of 397 COVID-19 patients were treated with CPAP for respiratory failure, with the therapeutic goal of providing intubation in case of CPAP failure. Univariable analysis showed that, age, lactate dehydrogenase (LDH) and white cell counts were all significantly lower in patients with successful CPAP treatment compared to those failing it and undergoing subsequent intubation. The percentage changes between baseline and CPAP application in the ratio of partial pressure arterial oxygen (PaO2) and fraction of inspired oxygen (FiO2), PaO2, respiratory rate and ROX index were higher in patients experiencing successful CPAP compared to those failing it. FiO2 and male gender were also significantly associated with intubation. Multivariable analysis adjusting for age, gender, Charlson comorbidity index, percentage change in PaO2/FiO2 or PaO2 and FiO2 separately, lactate, white blood cell count, LDH and C-reactive protein levels led to an area under the curve of 0.818 and confirmed that age, LDH and percentage increase in PaO2/FiO2 are predictors of intubation. CONCLUSIONS: In COVID-19 patients requiring CPAP, age, LDH and percentage change in PaO2/FiO2 after starting CPAP are predictors of intubation.

Changes in admissions, and hospitalization outcomes of IBD patients in an Italian tertiary referral center over a 13-year period.

OBJECTIVE: The management of Inflammatory Bowel Disease (IBD) has changed significantly in recent years, mainly due to the introduction of biologic medications, however, other factors may also have a role. The aim of this study was to evaluate the evolution of IBD admissions, including trends, modality of admission and rates of surgical intervention, in a tertiary care center. PATIENTS AND METHODS: Hospitalization of patients with a diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) were identified between 2000 and 2013, using ICD-9-CM codes for IBD, from our hospital database. The following parameters were evaluated for each admission: type of admission (ordinary vs. day care service), mode of admission (elective vs. emergency care, for ordinary admissions only), admission code, surgical procedures and complication rates. Comparison between pre- and post-biologic therapy introduction years was also performed. RESULTS: Between 2000 and 2013 a total of 8834 IBD-related admissions were recorded. Hospitalizations increased linearly reaching a peak in 2006, with a downward trend in the following years. The downward trend was especially marked for patients younger than 40 years. No significant differences in hospitalization trends between CD and UC were recorded. Disease flare represented the cause of hospitalization in approximately 50% of cases. Overall, 10.8% of patients underwent surgery with no difference between the two conditions. Complications occurred in 28.7% of admissions. CONCLUSIONS: Hospitalizations for IBD patients have decreased in recent years, especially in younger patients. However, a significant proportion of patients are still admitted to complete diagnostic workup, indicating the need to better implement outpatient services. A clear reduction in surgery occurrence over time could not be observed in our study.

COVID-19 in celiac disease: a multicentric retrospective cohort study.

OBJECTIVE: Celiac disease (CD) is an autoimmune disorder, characterized by increased susceptibility to bacterial and viral infections. Therefore, the CD patients could be exposed to an increased risk of contracting SARS-CoV-2, a virus for which the WHO declared a pandemic status in March 2020. This study aims to investigate the incidence of SARS-CoV-2 infection in CD patients, to assess the impact of CD on the risk of contracting this virus. PATIENTS AND METHODS: This retrospective multicentric cohort study evaluated 542 celiac patients, who answered a questionnaire concerning both the underlying disease (adherence to the gluten-free diet, residual symptoms) and the possible SARS-CoV-2 infection (swab outcome, presence and characteristics of symptoms and type of treatment received), referring to the period between 20th January 2020 and 27th October 2020. RESULTS: Five patients (0.92%) tested positive; of these, 2 were asymptomatic and 3 developed symptoms of COVID-19. The incidence of SARS-CoV-2 infection in CD patients was not significantly different from the general population. The ratio of positive/diagnostic swabs tends to be higher in CD patients than in the general population (IR: 0.15; 0.06; p=0.06), whereas the number of subjects who performed the swab in this group is significantly lower (IR: 0.06; 0.15; p<0.001). CONCLUSIONS: Although CD patients are more susceptible to infections, the incidence of SARS-CoV-2 infection in our sample was not significantly different from the general population. However, the positive/diagnostic swabs ratio seems to be higher, probably also due to the lower number of patients tested.

How to define a quadruple aim framework to assess value in critical pathway of the patients with Clostridioides difficile infection.

OBJECTIVE: The study aims to define the set of Key Performance Indicators (KPIs) required to assess the Value delivered by managing patients with Clostridioides difficile infection through a Critical Pathway. We used the quadruple aim Value-Based approach, and we validated the set of KPIs with the Delphi method. MATERIALS AND METHODS: The study focuses on patients on board a Critical Pathway on Clostridioides difficile Infection and targeted towards a Fecal Microbiota Transplantation (FMT). FMT has been used to successfully treat recurrent Clostridium difficile infection. A two-round e-Delphi survey collecting data was conducted in 2019-2020 to validate the Value-Based evaluation tool. The Value-Based criteria taken into account are Clinical Outcomes, Experience of Care, Per-capita cost, Physician's burnout. RESULTS: The two rounds led to the validation of 50 items, and four primary clinical outcomes (Mortality rate, length of stay, readmission and complications related to the illness). CONCLUSIONS: The evaluation tool included is validated in its totality and can provide a comprehensive overview of the Value created by the Critical pathway for patients with Clostridioides difficile. We can extend the approach illustrated in this study can also to evaluate other Critical pathways.

Increased Faecalibacterium abundance is associated with clinical improvement in patients receiving rifaximin treatment.

Compositional and functional alterations of the gut microbiota are involved in the pathogenesis of several gastrointestinal diseases. Rifaximin is often used to induce disease remission due to its eubiotic effects on the gut microbiota. To investigate the correlation between changes in the gut microbiota composition and symptoms improvement in patients who present a clinical response to rifaximin treatment. Patients with ulcerative colitis (UC), Crohn's disease (CD), irritable bowel syndrome (IBS) and diverticular disease (DD) undergoing rifaximin treatment for clinical indication were enrolled in the study. Rifaximin was administered at the dose of 1,200 mg/day for 10 days. Faecal samples were collected at baseline and at the end of treatment; clinical improvement was assessed by Mayo score for UC, CD Activity Index (CDAI) for CD, IBS severity scoring system (IBS-SSS) for IBS and global symptomatic score (GSS) for DD. Twenty-five patients were included in the analysis and a clinical improvement was recorded for 10/25 (40%) of them. Microbial alpha diversity showed a slight increase in clinical responders (P=0.271), while it decreased in patients who did not improved (P=0.05). A significant post-treatment increase in Faecalibacterium abundance was observed in patients with a positive response (log2FC 1.959, P=0.042). Roseburia abundance decreased in both groups, whereas Ruminococcus decreased only in patients who clinically improved. Clinical improvement consequent to rifaximin treatment is associated with an increase in Faecalibacterium abundance. Achieving a positive shift in the gut microbiota composition seems a key event to obtain a clinical benefit from treatment.

Laboratory handling practice for faecal microbiota transplantation.

AIMS: Faecal microbiota transplantation (FMT) consists of the infusion of faeces from a healthy donor to the gastrointestinal tract of a recipient patient to treat disease associated with alterations in gut microbiota. The objective of this article was to describe laboratory workflow of an FMT laboratory to provide tips for preparing the faecal suspensions to be infused. METHODS AND RESULTS: Twenty-stool solutions obtained from ten donors were prepared using two different protocols: magnet plate emulsion (MPE) and Seward StomacherTM Emulsion (SSE). We evaluated parameters such as preparation time, handiness, and aerobic and anaerobic microbial count. For three donors, we monitored bacterial counts after defrosting at different time-points. MPE requires more time than SSE. In terms of microbial load, both methods showed similar values, with small and statistically differences (P ≤ 0·05) regarding anaerobes in favour of SSE. Frozen aliquots showed the same bacterial load values after defrosting. CONCLUSION: Although both methods allow an easy and available preparation of a stool suspension, SSE seems more suitable, particularly for stool banking. Aerobic and anaerobic species are preserved with both protocols; and safety for laboratory operators is guaranteed. SIGNIFICANCE AND IMPACT OF THE STUDY: In recent years, FMT has become a fascinating and interesting subject. Nevertheless, there are no real guidelines describing laboratory facilities and procedures. This paper aims to be a useful and simple guide to increase the number FMT centres as much possible.

Randomised clinical trial: faecal microbiota transplantation by colonoscopy plus vancomycin for the treatment of severe refractory Clostridium difficile infection-single versus multiple infusions.

BACKGROUND: Faecal microbiota transplantation (FMT) is a highly effective treatment against recurrent Clostridium difficile infection. Far less evidence exists on the efficacy of FMT in treating severe Clostridium difficile infection refractory to antibiotics. AIM: To compare the efficacy of two FMT-based protocols associated with vancomycin in curing subjects with severe Clostridium difficile infection refractory to antibiotics. METHODS: Subjects with severe Clostridium difficile infection refractory to antibiotics were randomly assigned to one of the two following treatment arms: (1) FMT-S, including a single faecal infusion via colonoscopy followed by a 14-day vancomycin course, (2) FMT-M, including multiple faecal infusions plus a 14-day vancomycin course. In the FMT-M group, all subjects received at least two infusions, while those with pseudomembranous colitis underwent further infusions until the disappearance of pseudomembranes. The primary outcome was the cure of refractory severe Clostridium difficile infection. RESULTS: Fifty six subjects, 28 in each treatment arm, were enrolled. Twenty one patients in the FMT-S group and 28 patients in the FMT-M group were cured (75% vs 100%, respectively, both in per protocol and intention-to-treat analyses; P = 0.01). No serious adverse events associated with any of the two treatment protocols were observed. CONCLUSIONS: A pseudomembrane-driven FMT protocol consisting of multiple faecal infusions and concomitant vancomycin was significantly more effective than a single faecal transplant followed by vancomycin in curing severe Clostridium difficile infection refractory to antibiotics. Clinical-Trials.gov registration number: NCT03427229.

Fecal microbiota transplantation for the treatment of patients with ulcerative colitis and other gastrointestinal conditions beyond Clostridium difficile infection: an update.

Fecal microbiota transplantation (FMT) is the transplantation of microbial gut contents from a healthy individual into the gastrointestinal tract of a person with a disease, with a view to increasing the recipient's gut microbial diversity and bacterial richness and restoring microbial homeostasis. FMT has been proven to be a safe and effective treatment for Clostridium difficile infection (CDI) and it is now a recommended treatment for recurrent or refractory infection. FMT is not currently recommended for use outside of CDI due to concerns regarding outcome and safety; however, several case series and randomized controlled trials have described its use in a research environment for a few gastrointestinal conditions related to intestinal dysbiosis including ulcerative colitis (UC), Crohn's disease (CD) and irritable bowel syndrome (IBS). The most successful reports of the clinical efficacy of FMT in gastrointestinal conditions outside of CDI have been in treating UC. We summarize the current literature regarding the use of FMT in UC, including methodology, clinical efficacy and safety concerns, and identify pitfalls and areas for future development. We also describe the available evidence to date on the use of FMT in CD, IBS and other conditions related to intestinal dysbiosi.

Nutrition and IBD: Malnutrition and/or Sarcopenia? A Practical Guide.

Malnutrition is a major complication of inflammatory bowel disease (IBD). This mini review is focusing on main determinants of malnutrition in IBD, the most important components of malnutrition, including lean mass loss and sarcopenia, as an emerging problem. Each one of these components needs to be well considered in a correct nutritional evaluation of an IBD patient in order to build a correct multidisciplinary approach. The review is then focusing on possible instrumental and clinical armamentarium for the nutritional evaluation.

Predictors of failure after single faecal microbiota transplantation in patients with recurrent Clostridium difficile infection: results from a 3-year, single-centre cohort study.

OBJECTIVES: Faecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection (CDI). Although a single faecal infusion is usually sufficient to eradicate CDI, a considerable number of patients need multiple infusions to be cured. The aim of this study was to identify predictors of failure after single faecal infusion in patients with recurrent CDI. METHODS: We included patients with recurrent CDI prospectively treated with FMT by colonoscopy. By means of univariate and multivariate analysis, variables including female gender, age, number of CDI recurrences, severity of CDI, hospitalization, inadequate bowel preparation, unrelated donor, and use of frozen faeces, were assessed to predict failure after single faecal infusion. RESULTS: Sixty-four patients (39 women; mean age 74 years) were included. Of them, 44 (69%) were cured by a single faecal infusion, whereas 20 (31%) needed repeat infusions. Overall, FMT cured 62 of 64 (97%) patients. In the subgroup of patients with severe CDI, only eight of 26 (30%) were cured with a single infusion. At multivariate analysis, severe CDI (OR 24.66; 95% CI 4.44-242.08; p 0.001) and inadequate bowel preparation (OR 11.53; 95% CI 1.71-115.51; p 0.019) were found to be independent predictors of failure after single faecal infusion. CONCLUSIONS: Severe CDI and inadequate bowel preparation appear to be independent predictors of failure after single faecal infusion in patients treated with FMT by colonoscopy for recurrent CDI. Our results may help to optimize protocols and outcomes of FMT in patients with recurrent CDI.

The role of diet on gut microbiota composition.

Gut microbiota is characterized by an inter-individual variability due to genetic and environmental factors. Among the environmental ones, dietary habits play a key role in the modulation of gut microbiota composition. There are main differences between the intestinal microbiota of subjects fed with prevalent Western diet and that of subjects with a diet rich in fibers. Specific changes in the composition of gut microbiota have been demonstrated among subjects according to a different dietary intake. A particular diet may promote the growth of specific bacterial strains, driving hosts to a consequent alteration of fermentative metabolism, with a direct effect on intestinal pH, which can be responsible for the development of a pathogenic flora. Moreover, a high-fat diet can promote the development of a pro-inflammatory gut microbiota, with a consequent increase of intestinal permeability and, consequently, of circulating levels of lipopolysaccharides. In this review, we discuss the direct role of the diet in the composition of gut microbiota and about the possible clinical consequences.

Efficacy and Mechanisms of Action of Fecal Microbiota Transplantation in Ulcerative Colitis: Pitfalls and Promises From a First Meta-Analysis.

BACKGROUND: Inflammatory bowel disease (IBD) is the results of a chronic inflammatory process deriving from disequilibrium between self-microbiota composition and immune response. METHODS: New evidence, coming from Clostridium difficile infection, clearly showed that active and powerful modulation of microbiota composition by fecal microbiota composition (FMT) is safe, easy to perform, and efficacious, opening new frontiers in gastrointestinal and extra-intestinal diseases. FMT has been proposed also for IBD as well as other non-gastrointestinal conditions related to intestinal microbiota dysfunctions, with good preliminary data. RESULTS: In this setting, ulcerative colitis (UC) represents one of the most robust potential indications for FMT after C difficile colitis. CONCLUSIONS: In the present review, we focus on FMT and its application on ulcerative colitis, clarifying mechanisms of actions and efficacy data, trough completion of a meta-analysis on available randomized, controlled trial data in UC. Because microbiota is so crucially involved in this topic, a short review of microbial alterations in UC will also be performed.

Randomised clinical trial: faecal microbiota transplantation by colonoscopy vs. vancomycin for the treatment of recurrent Clostridium difficile infection.

BACKGROUND: Faecal microbiota transplantation (FMT) from healthy donors is considered an effective treatment against recurrent Clostridium difficile infection. AIM: To study the effect of FMT via colonoscopy in patients with recurrent C. difficile infection compared to the standard vancomycin regimen. METHODS: In an open-label, randomised clinical trial, we assigned subjects with recurrent C. difficile infection to receive: FMT, short regimen of vancomycin (125 mg four times a day for 3 days), followed by one or more infusions of faeces via colonoscopy; or vancomycin, vancomycin 125 mg four times daily for 10 days, followed by 125-500 mg/day every 2-3 days for at least 3 weeks. The latter treatment did not include performing colonoscopy. The primary end point was the resolution of diarrhoea related to C. difficile infection 10 weeks after the end of treatments. RESULTS: The study was stopped after a 1-year interim analysis. Eighteen of the 20 patients (90%) treated by FMT exhibited resolution of C. difficile-associated diarrhoea. In FMT, five of the seven patients with pseudomembranous colitis reported a resolution of diarrhoea. Resolution of C. difficile infection occurred in 5 of the 19 (26%) patients in vancomycin (P < 0.0001). No significant adverse events were observed in either of the study groups. CONCLUSIONS: Faecal microbiota transplantation using colonoscopy to infuse faeces was significantly more effective than vancomycin regimen for the treatment of recurrent C. difficile infection. The delivery of donor faeces via colonoscopy has the potential to optimise the treatment strategy in patients with pseudomembranous colitis.

High-dose rocuronium for rapid-sequence induction and reversal with sugammadex in two myasthenic patients.

The anesthetic management of patients affected by myasthenia gravis is usually challenging in elective surgery and even more so in emergency procedures. The difficulties involved are several-fold, ranging from the choice of an appropriate muscle relaxant (i.e. one that enables safe and rapid airway management) to neuromuscular monitoring and normal muscular recovery. Additionally, optimizing patient conditions - either pharmacologically or with plasmapheresis - before intervention is well beyond the realm of possibility. We discuss the anesthetic management of two myasthenic patients undergoing emergency surgery (for sigmoid perforation and upper gastrointestinal bleeding respectively). In both cases, we opted for rapid-sequence induction with high-dose rocuronium to prevent inhalation of gastric contents. We also report on the implication of neuromuscular monitoring. We found that the rocuronium-sugammadex combination was a useful and effective option in the emergency setting.

Systematic review: Sprue-like enteropathy associated with olmesartan.

BACKGROUND: The onset of a sprue-like enteropathy in association with olmesartan therapy has been recently reported. AIMS: To perform a systematic review of the literature and describe three additional cases of olmesartan-associated enteropathy. METHODS: Electronic and manual bibliographic searches were performed to identify original reports in which subjects who were undertaking olmesartan developed a sprue-like enteropathy. Because of the scarcity of studies with adequate sample size, case series with less than 10 patients and case reports were also considered. Data extraction was performed independently by two reviewers. RESULTS: A total of 11 publications met our pre-defined inclusion criteria, for an overall number of 54 patients (including our series). Almost all patients presented with diarrhoea and weight loss. Normocytic normochromic anaemia and hypoalbuminaemia were the commonest laboratory defects at presentation. Antibody testing for coeliac disease was always negative. Variable degrees of duodenal villous atrophy were present in 98% of patients, while increased intra-epithelial lymphocytes were documented in only 65% of cases. After discontinuation of olmesartan, all reported patients achieved resolution of signs and symptoms. CONCLUSIONS: Although the available evidence is limited, the olmesartan-associated sprue-like enteropathy may be considered as a distinct clinical entity, and should be included in the differential diagnosis when serological testing for coeliac disease is negative.