Characteristics of intussusception in the period of arbitrary Rotavirus vaccination.

BACKGROUND: In November 2011, rotavirus (RV) vaccine was launched in Japan as a voluntary vaccination to prevent RV-associated gastroenterocolitis. We examined the characteristics of intussusception following RV vaccination in our two centers. METHODS: We investigated intussusception patients <16 years old from January 2006 to September 2020. Patients were categorized according to the period (before [Group A] or after the introduction of arbitrary RV vaccination [Group B]). The patient characteristics and treatment of intussusception were retrospectively investigated. RESULTS: During the study period, 560 patients (group A, n = 233; group B, n = 327) were identified. The distribution of patients who were 0-6 months old was not significantly different between the groups (group A, n = 12, 5.2%; group B, n = 18, 5.5%). Among these 18 patients in Group B, 7 were vaccinated against RV, and 10 were not. One patient was excluded due to incomplete data. On comparing patients with and without RV vaccination, the mean age at the onset of intussusception was 3.3 ± 0.4 versus 4.0 ± 0.3 months (P = 0.19), the mean interval from the onset to treatment was 7.5 ± 2.4 versus 16.0 ± 2.2 h (P = 0.03), the time of the contrast enema for treatment was 9.1 ± 3.3 versus 7.7 ± 2.8 min (P = 0.76), and the final pressure of the contrast enema was 92.5 ± 4.4 versus 92.2 ± 4.4 cmH2 O (P = 0.97). CONCLUSIONS: Arbitrary RV vaccination did not influence the age distribution of intussusception, and the interval from the onset to treatment was significantly shorter in the patients with RV vaccination than in those without it. Recognizing the presence of intussusception following RV vaccination enables accurate treatment.

Promoting improved healing: Lessons learned from the fetus

Background: It has long been known that the fetal response to skin injury is regenerative, with a lack of abnormal collagen deposition or scar, and restoration of normal dermal architecture. This response is associated with minimal inflammation.We have shown that the decreased inflammation is due to decreased production of pro-inflammatory cytokine production compared to the adult response. In addition, we have shown fetal tendon and the fetal heart can heal by regeneration, with restoration of structure and function, and is also associated with decreased proinflammatory cytokine production and decreased inflammation. We hypothesized that strategies targeting inflammation and associated oxidative stress could be used in adult diseases. We have identified diabetic wounds, acute lung injury, and colitis where inflammation and oxidative stress plays a central role in the pathogenesis the disease. Material(s) and Method(s): We have developed a novel strategy using nanotechnology to target inflammation and oxidative stress. We have conjugated novel cerium oxide nanoparticles, which act as potent scavengers of reactive oxygen species, to the anti-inflammatory microRNA miR146a, which suppresses the NFkB pathway and the production of the pro-inflammatory cytokines IL-6 and IL-8. Result(s): In diabetic wounds, impaired healing is associated with chronic inflammation and oxidative stress. We have demonstrated, in both small and large diabetic animals models, that CNP-miR146a can decrease inflammation and oxidative stress and correct the diabetic wound healing impairment and promote regeneration, similar to rates of healing in non-diabetic animals. We have also examined other disease states where inflammation and oxidative stress is pathogenic. Following acute lung injury, inflammation and oxidative stress leads to the development of adult respiratory distress syndrome or ARDS, the number one cause of mortality with COVID-19, and is associated with a 30-50% mortality. Inflammation and oxidative stress play a central role in the pathogenesis of ARDS. We have shown in models of acute lung injury, including bleomycin, LPS, MRSA, ventilator induced lung injury (VILI) and mustard gas, that CNP-miR146a decreases inflammation and oxidative stress, promotes regeneration and restoration of function, and decreased mortality. Finally, pathogenic inflammation plays a central role in the development of colitis or inflammatory bowel disease. We have shown that CNP-miR146a enemas can prevent progression of disease, restore weight gain, and lacks the adverse effects of systemic immunosuppression. Conclusion(s): We have used our understanding of the mechanisms of fetal regeneration following injury, which progresses with minimal inflammation and oxidative stress, to develop strategies targeting these processes to promote regeneration in adult disease.

Bilious Emesis and Failure to Pass Meconium in the Nursery

Introduction: In this case we review important newborn nursery management strategies and unique surgical diagnostic measures in a severe case of intestinal obstruction due to small left colon syndrome (SLCS) - illustrating an impressive relationship between intestinal dysmotility and meconium plug formation that increases risk of intestinal perforation in the newborn. Case Description: We present a case of an infant born to a mother with symptomatic COVID-19, who at 24 hours of life was treated for failure to pass meconium with a glycerin suppository and went on to develop bilious emesis and severe abdominal distention as feeding continued over the next several hours. After a normal upper GI, a barium enema identified a distal obstruction and the pediatric surgical team used rectal irrigation to remove a large meconium plug which mimicked the appearance of the descending colon on plain film, ultimately leading to the diagnosis of SLCS. The infant went on to stool normally after removal, however due to the severity of his initial clinical picture, a multi-disciplinary team was consulted, and concluded that given the severity of the meconium plug, a workup for cystic fibrosis was indicated, but deferred a rectal biopsy for Hirschprung disease due to normal return of bowel function upon removal of the obstruction. Discussion: Meconium plug syndrome is a transient distal GI obstruction in the lower colon or rectum with thick meconium and is thought to be due to poor intestinal motility. A contrast enema is typically diagnostic, showing a decrease in bowel caliber distal to the plug, and therapeutic, as the plug is often passed during the procedure. A sharp transition zone at the splenic flexure followed by a narrow descending colon on imaging is consistent with SLCS with a meconium plug at the transition zone. Infants presenting with both meconium plug syndrome and SLCS may require an evaluation for an underlying diagnosis of cystic fibrosis or Hirschprung disease. Delayed meconium passage is present in 11.9% of infants diagnosed with cystic fibrosis, while 15% of infants with meconium plugs have an aganglionic segment on rectal biopsy, indicative of Hirschprung disease. The decision to perform additional tests in an infant with SLCS should be guided by the patient's clinical course and in conjunction with a pediatric surgical team. Conclusion: Although intestinal obstruction in the newborn is rather rare, it is imperative that it is promptly diagnosed and treated to avoid negative outcomes. Despite being considered a mild form of obstruction due to its transient nature, meconium plug syndrome can lead to an impressive clinical illness and urgent consultation with a surgical team is vital due to the risk of intestinal perforation if the obstruction is not relieved.

How Does the COVID-19 Pandemic Affect Pediatric Patients with Intussusception Treated by Ultrasound-Guided Hydrostatic Enema Reduction?

BACKGROUND: The pandemic of COVID-19 has significantly influenced the epidemiology of intussusception. Nevertheless, the effects of the COVID-19 pandemic on the operation of ultrasound-guided hydrostatic enema reduction (USGHER) for intussusception have been largely unknown. METHODS: The data of pediatric patients with intussusception who were treated by USGHER from January to March of 2019 (Control Group), 2020 (Study Group 1), and 2021 (Study Group 2) in a large Chinese medical institution were retrospectively collected and analyzed. RESULTS: We enrolled 246 patients, including 90 cases in Control Group, 70 in Study Group 1, and 86 in Study Group 2 (p = 0.042). The time from the onset of symptoms to the hospital visit and the time from the hospital visit to performing the ultrasound in Study Group 1 was significantly longer than that in Control Group and Study Group 2 (p = 0.036, p = 0.031, respectively). The number of patients with bloody stool and the longest invaginated length of intussusception in Study Group 1 increased significantly compared with patients in the other two groups (p = 0.007, p = 0.042, respectively). Comparisons of neither the pressure of enema nor the time of duration when performing USGHER present statistical significance among the three groups (p = 0.091, p = 0.085, respectively). For all enrolled pediatric patients, there was no perforation case involved, and recurrence of intussusception occurred in few cases. CONCLUSIONS: Besides the negative impacts on the incidence of intussusception, the COVID-19 pandemic might have led to the diagnostic delay of intussusception and the deterioration of patients' clinical manifestations, but it did not significantly affect the operation of USGHER and patients' clinical outcome.

FAECAL MICROBIOTA TRANSPLANT IN ULCERATIVE COLITIS (FMTUC) – A RANDOMISED CLINICAL TRIAL FEASIBILITY STUDY

Background Dysbiosis of the gut microbiota may be responsible for the pathogenesis of ulcerative colitis (UC). Restoration of gut microbiota diversity by means of faecal microbiota transplantation (FMT) is of increasing interest as a therapeutic option in the management of UC. The aims of this phase II feasibility study are to estimate the magnitude of treatment response to FMT in treatment-naïve patients with newly diagnosed UC, evaluate donor and patient recruitment rates and determine optimal study conditions for phase III study (ISRCTN 58082603). Methods Treatment-naïve patients with histologically confirmed UC below the sigmoid were recruited. Subjects were randomised to single FMT enema, five daily enemas and control group. All groups received antibiotic for 10 days and bowel preparation 48 hours before the interventions. They were followed up for 12 weeks with quality of life (QOL) scores (IBDex, CUCQ-32) and 16S RNA study on faecal samples. Endoscopic (Mayo score) and histological assessments were performed at the baseline and week 12. The primary endpoints were endoscopic remission of UC and rate of persistent microbial engraftment at 12 weeks. Secondary endpoints included QoL and mucosal cytokine profiling with IL-10. Clinical remission was defined as Mayo score ≤ 2 with an endoscopic Mayo score of 0. Results Eighteen UC patients were recruited between July 2016 and February 2020 until the COVID-19 pandemic, of those five achieved clinical remission. One subject from the control group withdrew at week 4 due to worsening symptoms. 72% improved Mayo and QOL scores, and 44% avoided medical treatment. Clinical remission was more observed among subjects with lower baseline QoL and mild-moderate disease, although this did not reach statistical significance (P=0.173). No correlation between FMT dose, frequency and clinical remission were observed. The 16S evaluation of the faecal samples demonstrated successful engraftment of FMT and showed a similar faecal microbiota profile amongst the intervention groups, which was markedly different from the control group. Coprococcus was found to be much more abundant amongst subjects who responded to the FMT intervention. This study also suggested an inverse correlation between IL-10 and the severity of UC. Conclusions FMT intervention protocols were well adhered and 94% completion rate, though the recruitment period was much longer than the original plan due to some unforeseen interruptions. Yet, this feasibility study demonstrated potential for employing this method for a larger multicentre RCT to further evaluate FMT dose and frequency effects. The correlation between IL-10 and IL-10 producing microorganisms should be sought in the future study.

Pilot study of an adult bowel management program for fecal incontinence.

OBJECTIVE: Bowel management programs are efficacious in pediatric patients with fecal incontinence or intractable constipation unresponsive to standard treatment. No studies have been done examining outcomes in adults. The objective of this study was to assess continence and quality of life outcomes in adults who have underwent bowel management program. METHODS: A retrospective review of patients 16 or older at the time they underwent a bowel management program for fecal incontinence or constipation was performed. Data collected included intake and follow-up stool and urinary continence, patient-reported outcomes measures (Cleveland Clinic Constipation Score, Baylor Continence Scale, Vancouver Symptom Score for Dysfunctional Elimination), and an age-adjusted health-related quality of life measure. RESULTS: The cohort included 38 patients with a median age of 19 years (range: 16-55) when they underwent our program. 50% of patients were female and the majority (33, 87%) were White. The most common diagnosis was anorectal malformation (16, 42%) followed by functional constipation (10, 27%). Stool continence rates improved after undergoing the program (52.7% prior to 87.6% at follow-up, p<0.01). There was significant improvement in the Baylor Continence Scale, Cleveland Clinic Constipation Score, and PedsQL (p<0.05). CONCLUSIONS: Adult patients who underwent a bowel management program for severe fecal incontinence or constipation show significant improvement in stool continence rates, patient-reported outcomes measures, and quality of life. A bowel management program (in-person or via telemedicine) is a feasible treatment strategy for adult patients who fail standard management of fecal incontinence or constipation and should be offered when appropriate. LEVEL OF EVIDENCE: III.

Faecal Microbiota Transplant in Ulcerative Colitis (FMTUC) - A randomised clinical trial feasibility study

Background: Dysbiosis of the gut microbiota may be responsible for the pathogenesis of ulcerative colitis (UC). Restoration of gut microbiota diversity by means of faecal microbiota transplantation (FMT) is of increasing interest as a therapeutic option in the management of UC. The aims of this phase II feasibility study are to estimate the magnitude of treatment response to FMT in treatment-naïve patients with newly diagnosed UC, evaluate donor and patient recruitment rates and determine optimal study conditions for phase III study (ISRCTN 58082603). Methods: Treatment-naïve patients with histologically confirmed UC below the sigmoid were recruited. Subjects were randomised to three arms;single FMT enema, five daily enemas and control. All groups received antibiotic for 10 days and bowel preparation 48 hours before the interventions. They were followed up for 12 weeks with quality of life (QOL) scores (IBDex, CUCQ-32) and 16S RNA study on faecal samples. Endoscopic (Mayo score) and histological assessments were performed at the baseline and week 12. The primary endpoints were endoscopic remission of UC and rate of persistent microbial engraftment at 12 weeks. Secondary endpoints included QoL and mucosal cytokine profiling with IL-10. Clinical remission was defined as Mayo score ≤ 2 with an endoscopic Mayo score of 0. Results: Eighteen UC patients were recruited between July 2016 and February 2020 until the COVID-19 pandemic, of those five achieved Clinical remission. One subject from the control group withdrew at week 4 due to worsening symptoms. 72% improved Mayo and QOL scores, and 44% avoided medical treatment. Clinical remission was more observed among subjects with lower baseline QoL and mildmoderate disease, although this did not reach statistical significance (P=0.173). No correlation between FMT dose, frequency and clinical remission were observed. The 16S evaluation of the faecal samples demonstrated successful engraftment of FMT and showed a similar faecal microbiota profile amongst the intervention groups, which was markedly different from the control group. Coprococcus was found to be much more abundant amongst subjects who responded to the FMT intervention. This study also suggested an inverse correlation between IL-10 and the severity of UC. Conclusion: FMT intervention protocols were well adhered and achieved 94% completion rate, though the recruitment period was much longer than the original plan due to unforeseen interruptions. Yet, this feasibility study demonstrated potential for employing this method for a larger multicentre RCT to further evaluate FMT dose and frequency effects. The correlation between IL-10 and IL-10 producing microorganisms should be sought in the future study.

Covid-19 vaccine does not increase the likelihood of disease exacerbation in ibd: Results from a population-based study

Background: While short-term safety data of COVID-19 vaccination has been reassuring, it is theoretically possible that the vaccineassociated immune activation could trigger immune dysregulation and thus exacerbation of IBD. We used the epi-Israeli IBD Research Nucleus (IIRN) database to perform a population-based study exploring the effect of COVID-19 vaccination on disease course in IBD patients. Methods: We included all IBD patients insured in two of the four Israeli HMOs, covering 35% of the population, by validated algorithms, and selected those who received two doses of Pfizer BNT162b2 vaccine. These were matched to unvaccinated IBD patients by demographics, parameters of disease severity at baseline generated by hierarchical clustering of laboratory data, and length of time from previous exacerbation to baseline. The primary outcome was rate of IBD exacerbation as defined by proxies of hospitalizations, treatment escalation, and commencement of corticosteroid or enema. The study period was December, 2020 to June, 2021 Results: 707 pairs of vaccinated and unvaccinated IBD patients were compared. The pairs matched exactly for gender, district, IBD type and disease severity, and ±1 year for age at IBD diagnosis and at vaccination. Mean age was 38.5±13.5 years and median follow-up was 98 days (IQR 16-143). No difference in the outcome was found between the groups from the 2nd vaccination to the end of follow-up, with risk of exacerbation in vaccinated patients of 29% and risk in unvaccinated patients 26% (p=0.3). Conclusion: COVID-19 vaccinated IBD patients demonstrated a rate of IBD exacerbation following vaccination that was no different from that of unvaccinated patients. The multifaceted immune activation induced by the vaccine did not result in worsening IBD disease course. These results provide further reassurance for IBD patients receiving the vaccine.

Ileocolic intussusception in pediatric SARS-CoV-2 patients: experience at a tertiary pediatric center.

PURPOSE: COVID-19 disease can manifest with intussusception in pediatric patients, but prevalence of abnormalities on ultrasounds performed for intussusception is uncertain. We aim to report our experience in children with COVID-19 presenting with suspected intussusception imaged with ultrasound. METHODS: Children under 18 years who had an ultrasound for possible intussusception underwent retrospective analysis and were tested for COVID-19 between April 1 and December 14, 2020. Patients' demographic, clinical, radiological and surgical characteristics were reviewed. RESULTS: Twenty-four COVID-19-positive patients were identified; 19 boys with mean age 3 years (range: 3 months-18 years). Ultrasound was abnormal in 11 patients (11/24, 46%). Sonographic features of enterocolitis were documented in seven children (7/24, 29%). Three boys (3/24, 13%) were found to have ileocolic intussusception on ultrasound and underwent air enema with failed reduction (3/3, 100%), precipitating surgical reductions, all with favorable outcomes. One patient (1/24, 4%) was found to have a long segment of persistent small bowel-small bowel intussusception which was surgically repaired. CONCLUSION: Given the known association between failed reduction at air enema and delayed presentation, heightened awareness for intussusception in the setting of COVID-19 should be maintained, though more often, the etiology was attributed to other GI manifestations of COVID-19.

Global vision and clinical reasoning in complexity: An endangered competency in Internal Medicine in the CoViD era. Case series in an Internal Medicine unit CoViD-free

Background: During SARS-CoV-2 pandemic management of internist patient is even more complex: hospital acquired infection, resources devolved to CoViD-19, round visit with PPE, minor interrelation, post-CoViD patients. Presentation of the case series: 1. A 75-year old man had dysphagia, fever, low back pain, shoulder pain. Anamnesis: CoViD pneumonia (P/F143, TTS18/20), goiter, bladder neoplasm, T2DM. CT showed pneumomediastinum, pneumotorax, iliopsoas haematoma. He underwent broad spectrum antibiotic, arthrocentesis, culture tests. We concluded for pneumomediastinum due to CoViD-19 pneumonia, MSSA sepsis, septic arthritis, dysphagia due to goiter and pneumomediastinum, UTI. He is transferred to OSCO (surgery delayed) - 2. A 72-year old woman presented respiratory failure, fever, bacterial pneumonia. Anamnesis: stroke at age 50, APS diagnosis, AOCP, kidney failure. We performed antibiotics. Near to discharge, she had profuse haematemesis due to acute esophageal necrosis. She underwent PPI infusion and tests for risk factors and triggers (as APS or neoplasm). - 3. A 45-year old man had severe sepsis and intestinal obstruction. Anamnesis: paraplegia, previous intestinal obstruction. He underwent antibiotics, rehydration, NGT. Colonoscopy and gastrografin enema ruled out stenosis, but occlusion persisted. After collegial discussion surgical approach was proposed, but the patient had unfavorable outcome due to CoViD-19 infection. Discussion: These cases share high level of complexity: need of subintensive care, difficult management of patients' need. Clinical judgment, assessment of EBM priorities are essentials, underestimated skills.

Traditional Chinese Medicine Enema Therapy in a Patient With a Confirmed Negative SARS-CoV-2 Test in the Respiratory Tract but Positive in the Intestinal Tract: A Case Report.

We report the case of a 43-year-old man who was infected with SARS-CoV-2 in February 2020 and actively cooperated with treatment in the hospital. During the course of treatment, we found that the respiratory SARS-CoV-2 nucleic acid became negative, but remained positive in the intestinal tract. As a result, we adjusted the treatment plan to include traditional Chinese medicine enema treatment. The patient had negative intestinal SARS-CoV-2 nucleic acid test within 4 days, and the subsequent repeated review of intestinal SARS-CoV-2 nucleic acid was negative, and the virus was undetectable. It is suggested that traditional Chinese medicine enema treatment may be helpful to remove the SARS-CoV-2 in the intestines of patients with COVID-19 infection, and may support the treatment of patients with respiratory SARS-CoV-2 nucleic acid negative and positive in the intestinal tract.