Stress hyperglycemia is associated with poor outcome in critically ill patients with pulmonary hypertension.

Background and objective: Stress hyperglycemia is common in critically ill patients and is associated with poor prognosis. Whether this association exists in pulmonary hypertension (PH) patients is unknown. The present cohort study investigated the association of stress hyperglycemia with 90-day all-cause mortality in intensive care unit (ICU) patients with PH. Methods: Data of the study population were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. A new index, the ratio of admission glucose to HbA1c (GAR), was used to evaluate stress hyperglycemia. The study population was divided into groups according to GAR quartiles (Q1-Q4). The outcome of interest was all-cause mortality within 90 days, which was considered a short-term prognosis. Result: A total of 53,569 patients were screened. Ultimately, 414 PH patients were enrolled; 44.2% were male, and 23.2% were admitted to the cardiac ICU. As the GAR increased from Q2 to Q4, the groups had lower creatinine levels, longer ICU stays, and a higher proportion of renal disease. After adjusting for confounding factors such as demographics, vital signs, and comorbidities, an elevated GAR was associated with an increased risk of 90-day mortality. Conclusion: Stress hyperglycemia assessed by the GAR was associated with increased 90-day mortality in ICU patients with PH.

Sex Differences in Dilated Cardiomyopathy Prognosis.

Dilated cardiomyopathy (DCM) is the most common type of cardiomyopathy, and it often has a poor outcome. Sex differences in the prognosis of patients with DCM remain controversial. The present meta-analysis aimed to investigate whether sex plays a role in the outcome of patients with DCM and to provide real-world information on these potential sex differences for physicians and patients.We searched the PubMed, Cochrane, and EMBASE databases for published cohort studies up to February 16, 2020 that reported sex-specific prognostic outcomes (e.g., all-cause mortality; sudden cardiac death (SCD) ) in patients with DCM.Finally, 5 clinical cohort studies with a total of 5,709 patients were included. The results showed that males with DCM had a higher risk of all-cause mortality than females (HR: 1.61, 95% CI: 1.36~1.90; P < 0.00001). Next, the included studies were divided into short-term (< 5 years) and long-term (≥ 5 years) outcome groups by follow-up duration. Males showed a higher risk of all-cause mortality in both subgroups (< 5 years, HR: 1.59, 95% CI: 1.13~2.23; P = 0.008; ≥ 5 years, HR: 1.65, 95% CI: 1.33~2.05; P < 0.00001). In addition, the risks of SCD (HR: 1.80, 95% CI: 1.63~2.61; P = 0.002) and cardiovascular mortality in males (HR: 1.67, 95% CI: 1.25~2.23; P = 0.0005) were higher than those in females.The evidence from the published studies suggested that compared with females, males with DCM had an increased risk of all-cause mortality, cardiovascular mortality, and SCD.

Colonic Transendoscopic Enteral Tubing: Route for a Novel, Safe, and Convenient Delivery of Washed Microbiota Transplantation in Children.

AIM: Colonic transendoscopic enteral tubing (TET) has been used for delivering fecal microbiota transplantation by washed preparation since 2015, which was recently named as washed microbiota transplantation (WMT). However, there are few reports available regarding the feasibility and safety of these studies in low-age population. This study is aimed at evaluating the safety, feasibility, and value of colonic TET in 3-7 years old children. METHODS: All patients aged 3-7 years who underwent colonic TET in our center for WMT or medication were prospectively evaluated. The feasibility and safety of TET were evaluated. A questionnaire was completed by the children's parents to evaluate the children's response to the colonic TET as well as the parent's satisfaction. RESULTS: Forty-seven children were included (mean age 5 years). TET was implemented into the colon of all the patients, and the success rate of the procedure was 100%. The median retention time of TET tube within the colon was 6 (IQR 5-7) days in 45 patients with tube falling out spontaneously, and the maximum retention time was up to 21 days. Multivariate analysis demonstrated that endoscopic clip number (P = 0.009) was an independent contributing factor for the retaining time of tube. With increase in the number of large clips, the retention time of TET tube was prolonged. No discomfort was reported during injection of the microbiota or medication suspension through the TET tube. During the follow-up, no severe adverse events were observed. All children's parents were satisfied with TET. Interestingly, the proportion of children's parents choosing TET as the delivery way of WMT increased from 29.79% before to 70.21% after TET (P < 0.001). CONCLUSIONS: This study, for the first time, demonstrates that colonic TET is a novel, safe, and convenient colonic delivery way for WMT and medication in children aged 3-7 years.

Association of angiotensin converting enzyme inhibitors and angiotensin II receptor blockers with risk of COVID-19, inflammation level, severity, and death in patients with COVID-19: A rapid systematic review and meta-analysis.

An association among the use of angiotensin converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) with the clinical outcomes of coronavirus disease 2019 (COVID-19) is unclear. PubMed, EMBASE, MedRxiv, and BioRxiv were searched for relevant studies that assessed the association between application of ACEI/ARB and risk of COVID-19, inflammation level, severity COVID-19 infection, and death in patients with COVID-19. Eleven studies were included with 33 483 patients. ACEI/ARB therapy might be associated with the reduced inflammatory factor (interleukin-6) and elevated immune cells counts (CD3, CD8). Meta-analysis showed no significant increase in the risk of COVID-19 infection (odds ratio [OR]: 0.95, 95%CI: 0.89-1.05) in patients receiving ACEI/ARB therapy, and ACEI/ARB therapy was associated with a decreased risk of severe COVID-19 (OR: 0.75, 95%CI: 0.59-0.96) and mortality (OR: 0.52, 95%CI: 0.35-0.79). Subgroup analyses showed among the general population, ACEI/ARB therapy was associated with reduced severe COVID-19 infection (OR: 0.79, 95%CI: 0.60-1.05) and all-cause mortality (OR: 0.31, 95%CI: 0.13-0.75), and COVID-19 infection (OR: 0.85, 95% CI: 0.66-1.08) were not increased. Among patients with hypertension, the use of an ACEI/ARB was associated with a lower severity of COVID-19 (OR: 0.73, 95%CI: 0.51-1.03) and lower mortality (OR: 0.57, 95%CI: 0.37-0.87), without evidence of an increased risk of COVID-19 infection (OR: 1.00). On the basis of the available evidence, ACEI/ARB therapy should be continued in patients who are at risk for, or have COVID-19, either in general population or hypertension patients. Our results need to be interpreted with caution considering the potential for residual confounders, and more well-designed studies that control the clinical confounders are necessary to confirm our findings.

Colonic transendoscopic tube-delivered enteral therapy (with video): a prospective study.

BACKGROUND: Colonic transendoscopic enteral tubing (TET) refers to colonic transendoscopic tube-delivered enteral therapy. Colonic TET has been successfully used for frequent colonic administration of drugs or multiple fecal microbiota transplantations (FMTs). This prospective observational study aimed to evaluate possible factors affecting methodology, feasibility and safety of colonic TET. METHODS: Patients who underwent colonic TET at our center from October 2014 to November 2018 were included. The feasibility, efficacy, and safety of TET were evaluated. RESULTS: In total, 224 patients were analyzed. The success rate of TET was 100%. The median retention time of TET tube within the colonic lumen was 8.5 (IQR 7-11) days in 158 patients with tube falling out spontaneously, and the maximum retention time was up to 28 days. These patients were divided into the short-retention group (≤ 8.5 days) and the long-retention group (> 8.5 days). Univariate and multivariate analysis demonstrated that the type of endoscopic clip (p = 0.001) was an independent factor for the retention time. The larger clips as well as a greater number of clips significantly affected the retention time (p = 0.013). No severe adverse event was observed during and after TET. CONCLUSIONS: Colonic TET is a feasible, practical, and safe colon-targeted drug delivery technique with a high degree of patients' satisfaction. Two to four large endoscopic clips are recommended to maintain stability of the TET tube within the colon for over 7 days.

Efficacy of faecal microbiota transplantation in Crohn's disease: a new target treatment?

The efficacy of faecal microbiota transplantation (FMT) in Crohn's disease (CD) remains unclear due to lack of data. This study aimed to assess the value of FMT in treating CD-related clinical targets. The use of FMT for CD as a registered trial (NCT01793831) was performed between October 2012 and December 2017. Seven therapeutic targets included abdominal pain, diarrhoea, hematochezia, fever, steroid-dependence, enterocutaneous fistula and active perianal fistula. Each target was recorded as 1 (yes) or 0 (no) during the long-term follow-up for each patient. The primary outcome was the rate of improvement in each therapeutic target. Overall, 174 patients completed the follow-up. The median follow-up duration was 43 (interquartile range, 28-59) months. The median score of the total targets was 2 (range, 1-4) before FMT, and it decreased significantly at 1, 3, 6, 12, 24 and 36 months after FMT (P < 0.001 respectively). At 1 month after FMT, 72.7% (101/139), 61.6% (90/146), 76% (19/25) and 70.6% (12/17) of patients achieved improvement in abdominal pain, diarrhoea, hematochezia and fever respectively. Furthermore, 50% (10/20) of steroid-dependent patients achieved steroid-free remission after FMT. The present findings indicate that it is important to understand the efficacy of FMT in CD as a targeted therapy, especially for abdominal pain, hematochezia, fever and diarrhoea.

The recognition and attitudes of postgraduate medical students toward fecal microbiota transplantation: a questionnaire study.

BACKGROUND: Physicians and medical students in the world do not have high awareness of fecal microbiota transplantation (FMT). This study aimed to explore the recognition and attitude of postgraduate medical students towards FMT and to create awareness for it. METHODS: A self-administered questionnaire was distributed to first-year Chinese postgraduate medical students across six medical universities. Basic descriptive statistical analyses were performed. RESULTS: A total of 1828 eligible questionnaires were included into analysis. 47.76% of students did not know FMT prior to this survey. Respondents with a high-level recognition of FMT were more willing to donate feces or receive FMT therapy than those with a low-level recognition (80.26% vs. 69.62%, p = 0.000 and 56.80% vs. 41.45%, p = 0.000). The respondents from a leading institution of FMT in China showed better awareness compared with others, and 42.26% of them knew about FMT from medical lectures. The main reasons for respondents not supporting FMT were: limited reported clinical evidence (67.94%), raw technology (42.56%), and lack of analysis of patient willingness or cost-effectiveness (36.71%). However, the life-saving value (84.41%), the automatic purification system (38.68%), low expenses (36.00%), and convenient delivering ways (35.67%) were the major considerations for supporting FMT. CONCLUSIONS: This study revealed the low recognition level of postgraduate medical students about FMT. Therefore, medical education should not neglect the knowledge of FMT. Studies of FMT and standardized FMT should be carried out to promote its development.

A novel quick transendoscopic enteral tubing in mid-gut: technique and training with video.

BACKGROUND: This study aimed to evaluate the feasibility, safety, and value of a quick technique for transendoscopic enteral tubing (TET) through mid-gut. METHODS: A prospective interventional study was performed in a single center. A TET tube was inserted into mid-gut through the nasal orifice and fixed on the pylorus wall by one tiny titanium endoscopic clip under anesthesia. The feasibility, safety, success rate, and satisfaction with TET placement were evaluated for enteral nutrition or fecal microbiota transplantation. RESULTS: A total of 86 patients underwent mid-gut TET. The success rate of the TET procedure was 98.8% (85/86). Mean tubing time of the TET procedure was 4.2 ± 1.9 min. 10 cases of procedure was enough for training of general endoscopist to shorten the procedure time (7.0 min vs 4.0 min, p < 0.05). 97.7% (84/86) of patients were satisfied with the TET placement. Procedure-related and tube-related adverse events were observed in 8.1% (7/86) and 7.0% (6/86) of patients respectively. There were no moderate to severe adverse events during tube extubation. CONCLUSIONS: TET through mid-gut is a novel, convenient, reliable and safe procedure for mid-gut administration with a high degree of patient satisfaction. TRIAL REGISTRATION: This research was retrospectively registered with clinicaltrials.gov. Trial registration date: 29th November 2017. TRIAL REGISTRATION NUMBER: NCT03335982 .

Multiple fresh fecal microbiota transplants induces and maintains clinical remission in Crohn's disease complicated with inflammatory mass.

The ancient Chinese medical literature, as well as our prior clinical experience, suggests that fecal microbiota transplantation (FMT) could treat the inflammatory mass. We aimed to evaluate the efficacy and safety of multiple fresh FMTs for Crohn's disease (CD) complicated with intraabdominal inflammatory mass. The "one-hour FMT protocol" was followed in all patients. Twenty-five patients were diagnosed with CD and related inflammatory mass by CT or MRI. All patients received the initial FMT followed by repeated FMTs every 3 months. The primary endpoint was clinical response (improvement and remission) and sustained clinical remission at 12 months. Secondary endpoints were improvement in size of phegmon/abscess based upon cross-sectional imaging and safety of FMT. 68.0% (17/25) and 52.0% (13/25) of patients achieved clinical response and clinical remission at 3 months post the initial FMT, respectively. The proportion of patients at 6 months, 12 months and 18 months achieving sustained clinical remission with sequential FMTs was 48.0% (12/25), 32.0% (8/25) and 22.7% (5/22), respectively. 9.5% (2/21) of patients achieved radiological healing and 71.4% (15/21) achieved radiological improvement. No severe adverse events related to FMT were observed. This pragmatic study suggested that sequential fresh FMTs might be a promising, safe and effective therapy to induce and maintain clinical remission in CD with intraabdominal inflammatory mass.

Fecal microbiota transplantation cured epilepsy in a case with Crohn's disease: The first report.

Fecal microbiota transplantation (FMT) is a promising strategy that involves reconstruction of gut microbiota. Recently, it has been considered as a treatment of Crohn's disease (CD) and certain neurological diseases. Here, to the best of our knowledge, we report the first case that used FMT to achieve remission of intestinal and neurological symptoms in a girl with CD and a 17-year history of epilepsy. During the 20 mo of follow-up, FMT has proved its efficacy in preventing relapse of seizures after withdrawing the antiepileptic drugs. Furthermore, this finding highlights the role of microbiota-gut-brain axis and inspires a novel treatment for epilepsy through remodeling gut microbiota.

Clinical efficacy maintains patients' positive attitudes toward fecal microbiota transplantation.

Few studies have been conducted on the attitudes of patients seeking fecal microbiota transplantation (FMT). This study aimed to investigate the reasons for patients with Crohn's disease (CD) seeking FMT and their attitude changes after FMT.In this prospective study, all included patients were diagnosed with CD for at least 6 months and intended to receive FMT. A questionnaire was designed to investigate the history of medical visits and patients' attitudes toward FMT. Only refractory patients who failed to clinically respond to previous treatment were selected for undergoing FMT. Three months after the first FMT, patients were required to complete the second questionnaire on attitudes toward the first FMT.A total of 207 patients with CD were included for questionnaire survey. In 118 refractory patients, 94.07% sought FMT because they had no other choice. In 89 nonrefractory patients, 78.65% sought FMT for the reason that they wanted to achieve better clinical results or even a cure, although the current treatment was effective for them. In all, 118 refractory patients received FMT. Three months after the first FMT, 88.98% (105/118) patients completed the questionnaire on patients' attitudes toward FMT. Of these 105 patients, 56.19% reported to have satisfactory clinical efficacy and 74.29% were willing to receive the second FMT. Moreover, 89.52% (94/105) showed their willingness to recommend FMT to other patients.In conclusion, this study at least first time demonstrated that patients with CD were willing to accept FMT due to its efficacy.

Short-Term Surveillance of Cytokines and C-Reactive Protein Cannot Predict Efficacy of Fecal Microbiota Transplantation for Ulcerative Colitis.

OBJECTIVE: There were no reports on predicting long-term efficacy of fecal microbiota transplantation (FMT) for ulcerative colitis (UC). This study aimed to detect short-term changes of cytokines and C-reactive protein (CRP) in patients with UC undergoing FMT, and to evaluate the predictive value of CRP and cytokines for the long-term efficacy of FMT. METHODS: Nineteen patients with moderate to severe UC (Mayo score ≥ 6) were treated with single fresh FMT through mid-gut. Serum samples were collected before and three days post-FMT. Clinical responses were evaluated by a minimum follow-up of three months. Patients with clinical improvement and remission at the assessment point of three-month were included as response group, while patients without clinical improvement or remission were included as non-response group. Serum concentrations of cytokines (IL-1ß, IL-2, IL-4, IL-6, IL-10, IL-11, IL-17A, IFN-γ, TNF, TNFR-1, TNFR-2, MCP-1, G-CSF, GM-CSF) and CRP were assayed to predict the clinical response of FMT. RESULTS: In total, 10.5% (2/19) of patients achieved clinical remission and 47.4% (9/19) achieved clinical improvement (Response group, including clinical remission and clinical improvement), 42.1% (8/19) failed to benefit from FMT (Non-response group). In both Response group and Non-response group, the level of CRP at three days after FMT didn't show significant decrease compared with that before FMT (p>0.05). However, in Response group, CRP level at three months after FMT decreased significantly than that before FMT (p<0.05). Compared with healthy controls (n = 9), patients with UC showed a higher baseline level of serum IL-6, TNFR-2 and G-CSF, and a lower level of IL-2 and IL-4 (p<0.05). In both Response group and Non-response group, none of the eleven detectable cytokines showed a significant difference between the value at three days after FMT and that before FMT (p>0.05). CONCLUSIONS: Patients with moderate to severe UC presented a complex disorder of cytokines. However, the efficacy of FMT for UC might not be predicted by the short-term surveillance of cytokines and CRP.