Daily, oral FMT for long-term maintenance therapy in ulcerative colitis: results of a single-center, prospective, randomized pilot study.

BACKGROUND: Fecal microbiota transplantation (FMT) is a promising new strategy in the treatment of Inflammatory Bowel Disease, but long-term delivery systems are lacking. This randomized study was designed as a safety and feasibility study of long-term FMT in subjects with mild to moderate UC using frozen, encapsulated oral FMT (cFMT). METHODS: Subjects were randomized 1:1 to receive FMT induction by colonoscopy, followed by 12 weeks of daily oral administration of frozen encapsulated cFMT or sham therpay. Subjects were followed for 36 weeks and longitudenal clinical assessments included multiple subjective and objective markers of disease severity. Ribosomal 16S bacterial sequencing was used to assess donor-induced changes in the gut microbiota. Changes in T regulatory (Treg) and mucosal associated invariant T (MAIT) cell populations were evaluated by flow cytometry as an exploratory endpoint. RESULTS: Twelve subjects with active UC were randomized: 6 subjects completed the full 12-week course of FMT plus cFMT, and 6 subjects received sham treatment by colonic installation and longitudinal oral placebo capules. Chronic administration of cFMT was found to be safe and well-tolerated but home storage concerns exist. Protocol adherence was high, and none of the study subjects experienced FMT-associated treatment emergent adverse events. Two subjects that received cFMT achieved clinical remission versus none in the placebo group (95% CI = 0.38-infinity, p = 0.45). cFMT was associated with sustained donor-induced shifts in fecal microbial composition. Changes in MAIT cell cytokine production were observed in cFMT recipients and correlated with treatment response. CONCLUSION: These pilot data suggest that daily encapsulated cFMT may extend the durability of index FMT-induced changes in gut bacterial community structure and that an association between MAIT cell cytokine production and clinical response to FMT may exist in UC populations. Oral frozen encapsulated cFMT is a promising FMT delivery system and may be preferred for longterm treatment strategies in UC and other chronic diseases but further evaluations will have to address home storage concerns. Larger trials should be done to explore the benefits of cFMT and to determine its long-term impacts on the colonic microbiome. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02390726). Registered 17 March 2015, https://clinicaltrials.gov/ct2/show/NCT02390726?term=NCT02390726&draw=2&rank=1 .

Lessons from the Transition to Relational Teletherapy During COVID-19.

When the World Health Organization declared the coronavirus outbreak a pandemic, clinicians were challenged to maintain continuity of care. Teletherapy became the primary means of service delivery for many who had never or only sparingly used it. The Family Institute at Northwestern University, in response to encouraging findings with respect to the effectiveness of teletherapy and recognizing advantages with respect to access to care, launched our teletherapy services in 2018. As a relationship-based organization, we were keen to exploit the opportunity that teletherapy provides to integrate additional members of the client system into the treatment. Over these two plus years, we have learned a great deal. Our learning was greatly accelerated by our transition to a 100% teletherapy practice in the wake of the pandemic. Teletherapy is a different context. Intentionally managing the context's constraints and exploiting its strengths is key to providing high-quality couple and family therapy. This step is often overlooked or resisted when teletherapy is an occasional add-on to a face-to-face practice.

Persistent Complications of Child Sexual Abuse: Sexually Compulsive Behaviors, Attachment, and Emotions.

Child sexual abuse has the potential to cause distress for the victim across the lifespan. Romantic relationships may be particularly difficult for victims of child sexual abuse. This retrospective study examined differences in adult romantic attachment, sexually compulsive behaviors, and emotion regulation by history of child sexual abuse in a large, nonclinical sample. Those with a history of child sexual abuse reported more attachment anxiety in romantic relationships and engaged in more sexually compulsive behaviors. Overall, males displayed more sexually compulsive behaviors than females regardless of history of sexual abuse. Males with a history of sexual abuse displayed the greatest number of sexually compulsive behaviors. Surprisingly, no differences were observed in emotion regulation or attachment avoidant behaviors by history of child sexual abuse. Future research should seek to replicate current findings and examine emotion regulation difficulties experienced as a result of trauma.

Type 1 diabetes and celiac disease: clinical overlap and new insights into disease pathogenesis.

Type 1 diabetes (T1D) and celiac disease (CD) are autoimmune diseases with clinical and pathogenic overlap. The mean prevalence of CD in patients with T1D is about 8 %. Classic intestinal symptoms of CD may not be present in T1D leading to the recommendation for active case finding in this higher risk group. Screening is done with sensitive and specific serologies including tissue transglutaminase (tTG) IgA and deaminated gliadin peptide (DGP) IgA and IgG. Positive serologies are confirmed by the presence of villous atrophy and increased intraepithelial lymphocytes on duodenal biopsy. A strict gluten free diet is recommended, although this can pose challenges for T1D patients who already have dietary restrictions. In aggregate, it appears as if the gluten free diet may help T1D management. T1D and CD have overlapping genetic and environmental risk factors. Among these, non-HLA genetic factors and the gut microbiome are among recent developments that will be discussed in this review.

Surgical outcomes of epiretinal membranes associated with combined hamartoma of the retina and retinal pigment epithelium.

PURPOSE: To determine the surgical outcomes of epiretinal membranes associated with combined hamartoma of the retina and retinal pigment epithelium after pars plana vitrectomy and membrane peeling with or without assistance of autologous plasmin enzyme. METHODS: Retrospective review of 11 pediatric eyes that underwent pars plana vitrectomy with membrane peeling with or without autologous plasmin enzyme. Preoperative and postoperative assessments of visual function and retinal architecture were performed by indirect ophthalmoscopy, optical coherence tomography imaging, fundus photography, and measurement of visual acuity. RESULTS: The mean age of the patients was 4.6 years (range, 1-14). Mean follow-up was 15.6 months (range, 6-42 months). The lesions were located solely in the macula in 8 of 11 (73%) patients and in the macula and posterior pole in 3 of 11 (27%) patients. Of the 11 eyes, 6 were preoperatively injected with autologous plasmin enzyme to assist in removal of the posterior hyaloid. All 11 patients (100%) had complete macular reattachment postoperatively. Eight of 11 (73%) showed improved visual acuity postoperatively, and 3 of 11 showed stabilized vision. Eight eyes required only one surgery. Four eyes (36.6%) had recurrences of epiretinal membrane, and three of these eyes required additional surgery. Of the eyes with preoperative plasmin injection, 4 of 6 (66%) showed an improvement in visual acuity whereas 2 of 6 (33%) showed stabilization of visual acuity. Four of five without plasmin showed visual improvement, and one of five had stabilization of vision. CONCLUSION: In the pediatric population, pars plana vitrectomy with membrane peeling with or without the use of autologous plasmin enzyme for epiretinal membrane associated with combined hamartomas of the retina and retinal pigment epithelium can result in improved retinal architecture and visual acuity. Visual acuity may improve despite recurrence of the epiretinal membrane.

Initial post marketing experience with lacosamide in adult patients with epilepsy.

The outcomes of adult epilepsy patients prescribed lacosamide for additional seizure control. Responders were defined as having at least a 50% decrease in seizure frequency Sixty-seven patients were evaluated. Forty-six out of 67 patients (69%) were responders. Twelve of 14 patients not taking sodium channel-acting AEDs were responders (86%) and 34/53 patients taking sodium channel-acting AEDs were responders (64%) (difference not significant).

Serotonin 1B autoreceptors originating in the caudal dorsal raphe nucleus reduce expression of fear and depression-like behavior.

BACKGROUND: Serotonin 1B (5-HT(1B)) autoreceptors regulate release of serotonin from terminals of dorsal raphe nucleus (DRN) projections. Expression of 5-HT(1B) in the DRN inversely correlates with behavioral measures of emotion, and viral-mediated overexpression of 5-HT(1B) receptors in the middle DRN inversely reduces measures of fear and anxiety in unstressed rats. Because the caudal subregion of the DRN is important in translating stress into emotional dysregulation, we explored behavioral functions of 5-HT(1B) autoreceptors in the caudal DRN. METHODS: We manipulated 5-HT(1B) autoreceptor function in rats using either viral-mediated gene transfer into the caudal DRN or systemic injections of the 5-HT(1B) agonist 3-(1,2,5,6-tetrahydro-4-pyridyl)-5-propoxypyrrolo[3,2-b]pyridine (CP-94253). Rats were tested in forced swim test, open field test, and contextual fear conditioning. RESULTS: Overexpression of 5-HT(1B) in the caudal DRN increased swimming in the forced swim test. It did not alter locomotion or thigmotaxis in the open field test but did reduce conditioned freezing. Freezing was reduced when 5-HT(1B) overexpression was present only during testing but not training. The CP-94253 exerted an inverted U-shaped dose response curve on conditioned freezing, with most pronounced effects seen at 1 mg/kg. At this dose, CP-94253 administered before a fear retention test reduced freezing both during that session and in subsequent drug-free testing, but only when drug was paired with re-exposure to the fear context. CONCLUSIONS: The 5-HT(1B) autoreceptors originating in the caudal DRN regulate behavioral expression of helplessness and fear. Because systemic pharmacologic treatment with a 5-HT(1B) agonist facilitates reductions in fear, 5-HT(1B) receptors may be a target for the treatment of certain anxiety disorders.

Glaucoma tube shunt implantation through the ciliary sulcus in pseudophakic eyes with high risk of corneal decompensation.

PURPOSE: To summarize our clinical experience with implanting Baerveldt glaucoma tube shunts through the ciliary sulcus in eyes with a posterior chamber intraocular lens and shallow anterior chambers, corneal transplants, guttata or edema. PATIENTS AND METHODS: A retrospective interventional nonrandomized noncomparative case series. Main outcome measure was postoperative corneal status. Secondary outcome measures included postoperative intraocular pressure (IOP), visual acuity and complications. RESULTS: Thirty-six eyes of 32 patients were identified through chart review. Follow-up period was 21.8+/-16.6 months (mean+/-standard deviation, range: 4.0 to 58.5 mo). At final visit, all 23 preoperative clear native corneas and 6 of 7 corneal transplants remained clear. Thus, of the 30 preoperative clear corneas, only 1 decompensated. Preoperative IOP was 27.9+/-11.8 mm Hg (range: 12 to 59 mm Hg), reduced postoperatively to 10.1+/-3.9 mm Hg (range: 2 to 21 mm Hg, P=0.0001), a reduction of 58.2%+/-19.3% (range: 5.0% to 95.4%). Final IOP was >or=5 and