The Cellular and Synaptic Architecture of the Mechanosensory Dorsal Horn.

The deep dorsal horn is a poorly characterized spinal cord region implicated in processing low-threshold mechanoreceptor (LTMR) information. We report an array of mouse genetic tools for defining neuronal components and functions of the dorsal horn LTMR-recipient zone (LTMR-RZ), a role for LTMR-RZ processing in tactile perception, and the basic logic of LTMR-RZ organization. We found an unexpectedly high degree of neuronal diversity in the LTMR-RZ: seven excitatory and four inhibitory subtypes of interneurons exhibiting unique morphological, physiological, and synaptic properties. Remarkably, LTMRs form synapses on between four and 11 LTMR-RZ interneuron subtypes, while each LTMR-RZ interneuron subtype samples inputs from at least one to three LTMR classes, as well as spinal cord interneurons and corticospinal neurons. Thus, the LTMR-RZ is a somatosensory processing region endowed with a neuronal complexity that rivals the retina and functions to pattern the activity of ascending touch pathways that underlie tactile perception.

Esophageal Lichen Planus: A Descriptive Multicenter Report.

GOALS: To better understand the characteristics, treatment approaches, and outcomes of patients with esophageal lichen planus (ELP). BACKGROUND: ELP is a rare, often unrecognized and misdiagnosed disorder. Data on this unique patient population are currently limited to small, single-center series. STUDY: A multicenter, retrospective descriptive study was conducted of adults diagnosed with ELP over a 5-year period, between January 1, 2015, and October 10, 2020, from 7 centers across the United States. RESULTS: Seventy-eight patients (average age 65 y, 86% female, 90% Caucasian) were included. Over half had at least 1 extraesophageal manifestation. Esophageal strictures (54%) and abnormal mucosa (50%) were frequent endoscopic findings, with the proximal esophagus the most common site of stricture. Approximately 20% had normal endoscopic findings. Topical steroids (64%) and/or proton pump inhibitors (74%) dominated management; endoscopic response favored steroids (43% vs. 29% respectively). Almost half of the patients required switching treatment modalities during the study period. Adjunctive therapies varied significantly between centers. CONCLUSIONS: Given its at times subtle clinical and endoscopic signs, a high index of suspicion and biopsy will improve ELP diagnosis, especially in those with extraesophageal manifestations. Effective therapies are lacking and vary significantly. Prospective investigations into optimal treatment regimens are necessary.

Development of a Preliminary Question Prompt List as a Communication Tool for Adults With Achalasia: A Modified Delphi Study.

BACKGROUND: Question prompt lists (QPLs) are structured sets of disease-specific questions that enhance patient-physician communication by encouraging patients to ask questions during consultations. AIM: The aim of this study was to develop a preliminary achalasia-specific QPL created by esophageal experts. METHODS: The QPL content was derived through a modified Delphi method consisting of 2 rounds. In round 1, experts provided 5 answers to the prompts "What general questions should patients ask when given a new diagnosis of achalasia" and "What questions do I not hear patients asking, but given my expertise, I believe they should be asking?" In round 2, experts rated questions on a 5-point Likert scale. Questions considered "essential" or "important" were accepted into the QPL. Feedback regarding the QPL was obtained in a pilot study wherein patients received the QPL before their consultation and completed surveys afterwards. RESULTS: Nineteen esophageal experts participated in both rounds. Of 148 questions from round 1, 124 (83.8%) were accepted into the QPL. These were further reduced to 56 questions to minimize redundancy. Questions were categorized into 6 themes: "What is achalasia," "Risks with achalasia," "Symptom management in achalasia," "Treatment of achalasia," "Risk of reflux after treatment," and "Follow-up after treatment." Nineteen patients participated in the pilot, most of whom agreed that the QPL was helpful (84.2%) and recommended its wider use (84.2%). CONCLUSIONS: This is the first QPL developed specifically for adults with achalasia. Although well-received in a small pilot, follow-up studies will incorporate additional patient feedback to further refine the QPL content and assess its usability, acceptability, and feasibility.

Achalasia Quality Indicator Adherence.

BACKGROUND: Quality indicators (QIs) are formal ways to track health care performance and outcomes, guide quality improvement, and identify gaps in care delivery. We developed twelve quality indicators for achalasia management which cover the domains of patient education, diagnosis, and treatment of achalasia. AIM: To determine adherence to established quality indicators for achalasia management. METHODS: We performed a retrospective, multicenter evaluation of care patterns for adult patients greater than 18 years old with newly diagnosed achalasia from January 2018 to May 2020. A balanced random patient sample was obtained at four large academic medical centers. Independent electronic health record chart abstraction was performed using a standardized form to determine adherence to applicable QIs. Pooled and de-identified data were analyzed to identify gaps in care. RESULTS: A total of 120 patients were included and the overall adherence to applicable quality indicators across all centers was 86%. The median follow-up for all patients from time of diagnosis to end of study was 511 days. Clinicians adhered to all applicable quality indicators in 49 patients (39%). The quality indicator domain with the poorest adherence was patient education (67%), with 50% of patients having had a documented discussion of the risks of gastroesophageal reflux disease following surgical or endoscopic myotomy. CONCLUSIONS: Gaps in the quality of achalasia care delivery were identified, the largest of which relates to patient education about treatment risks. These findings highlight a potential area for future quality improvement studies and form the basis for developing fully specified quality measures.

Gastroenterology Clinic Follow-Up Reduces Gastroenterology-Specific Readmissions Among Patients With Severe Ulcerative Colitis.

BACKGROUND AND AIMS: Readmission within 30 days occurs in up to 18% of admitted patients with ulcerative colitis (UC). The importance of postdischarge follow-up with a gastroenterologist as well as the optimal follow-up interval is unknown. METHODS: We conducted a retrospective cohort study of patients with UC who were admitted to Stanford University Hospital between 2010 and 2020. We included adult patients with UC who were admitted for a UC flare. Patients with a colectomy during hospitalization or with Clostridium difficile infection at the index hospitalization were excluded. The primary outcome was time to readmission for a gastroenterology (GI) indication, and the primary predictor (time dependent) was follow-up with a GI provider. Patients were followed for 180 days after discharge. Data were analyzed using a Cox proportional hazards model. RESULTS: Of the 223 patients hospitalized with UC during the study period, 25% (n = 57) were readmitted within 180 days, with 13.9% occurring within 30 days. Early follow-up (within 7 days) was observed in 29% (n = 65) of patients, while 30-day follow-up was seen in 68.7% (n = 153), and follow-up within 180 days was seen in 198 (89%) patients. In the adjusted Cox proportional hazards model, GI follow-up was associated with fewer readmissions (hazard ratio, 0.42; 95% confidence interval, 0.22-0.81; P = .009). Early follow-up was strongly associated with a reduced risk of readmission (hazard ratio, 0.24; 95% 95% confidence interval, 0.09-0.69; P = .008). Follow-up in 7 days was associated with fewer readmissions (P < .0001). CONCLUSIONS: Outpatient GI follow-up after UC hospitalization reduces readmissions, with the greatest reduction occurring among patients followed up within 1 week of discharge.

In recently discharged ulcerative colitis patients, time to follow-up with a gastroenterologist was tightly related to the risk of readmission. Follow-up within 1 week offered the best protection. Efforts to improve postdischarge coordination are likely to improve quality.

Development and modification of a dysphagia question prompt list to improve patient-physician communication: Incorporating both esophageal expert and patient perspectives.

BACKGROUND: Question prompt lists (QPLs) are structured sets of disease-specific questions, intended to encourage question-asking by patients and enhance patient-physician communication. To date, a dysphagia-specific QPL has not been developed for patients with esophageal dysphagia symptoms. We aim to develop a dysphagia-specific QPL incorporating both esophageal expert and patient perspectives, applying rigorous methodology. METHODS: The QPL content was generated applying a two-round modified Delphi (RAND/UCLA) method among 11 experts. In round one, experts provided five answers to the prompts: "What general questions should patients ask when being seen for dysphagia?" and "What questions do I not hear patients asking but, given my experience, I believe they should be asking?" In round two, experts rated proposed questions on a 5-point Likert scale. Responses rated as "essential" or "important", determined by an a priori median threshold of ≥4.0, were accepted for inclusion. Subsequently, 20 patients from Stanford Health Care were enrolled to modify the preliminary QPL, to incorporate their perspectives and opinions. Patients independently rated questions applying the same 5-point Likert scale. At the end, patients were encouraged to propose additional questions to incorporate into the QPL by open-endedly asking "Are there questions we didn't ask, that you think we should?" KEY RESULTS: Eleven experts participated in both voting rounds. Of 85 questions generated from round one, 60 (70.6%) were accepted for inclusion, meeting a median value of ≥4.0. Questions were combined to reduce redundancy, narrowing down to 44 questions. Questions were categorized into the following six themes: 1. "What is causing my dysphagia?"; 2. "Associated symptoms"; 3. "Testing for dysphagia"; 4. "Lifestyle modifications"; 5. "Treatment for dysphagia"; and 6. "Prognosis". The largest number of questions covered "What is causing my dysphagia" (27.3%). Twenty patients participated and modified the QPL. Of the 44 questions experts agreed were important, only 30 questions (68.2%) were accepted for inclusion. Six patients proposed 10 additional questions and after incorporating the suggested questions, the final dysphagia-specific QPL created by esophageal experts and modified by patients consisted of 40 questions. CONCLUSIONS & INFERENCES: Incorporating expert and patient perspectives, we developed a dysphagia-specific QPL to enhance patient-physician communication. Our study highlights importance of incorporating patient perspective when developing such a communication tool. Further studies will measure the impact of this communication tool on patient engagement.

Anaplerotic triheptanoin diet enhances mitochondrial substrate use to remodel the metabolome and improve lifespan, motor function, and sociability in MeCP2-null mice.

Rett syndrome (RTT) is an autism spectrum disorder (ASD) caused by mutations in the X-linked MECP2 gene that encodes methyl-CpG binding protein 2 (MeCP2). Symptoms range in severity and include psychomotor disabilities, seizures, ataxia, and intellectual disability. Symptom onset is between 6-18 months of age, a critical period of brain development that is highly energy-dependent. Notably, patients with RTT have evidence of mitochondrial dysfunction, as well as abnormal levels of the adipokines leptin and adiponectin, suggesting overall metabolic imbalance. We hypothesized that one contributor to RTT symptoms is energy deficiency due to defective nutrient substrate utilization by the TCA cycle. This energy deficit would lead to a metabolic imbalance, but would be treatable by providing anaplerotic substrates to the TCA cycle to enhance energy production. We show that dietary therapy with triheptanoin significantly increased longevity and improved motor function and social interaction in male mice hemizygous for Mecp2 knockout. Anaplerotic therapy in Mecp2 knockout mice also improved indicators of impaired substrate utilization, decreased adiposity, increased glucose tolerance and insulin sensitivity, decreased serum leptin and insulin, and improved mitochondrial morphology in skeletal muscle. Untargeted metabolomics of liver and skeletal muscle revealed increases in levels of TCA cycle intermediates with triheptanoin diet, as well as normalizations of glucose and fatty acid biochemical pathways consistent with the improved metabolic phenotype in Mecp2 knockout mice on triheptanoin. These results suggest that an approach using dietary supplementation with anaplerotic substrate is effective in improving symptoms and metabolic health in RTT.