BACKGROUND: Several organizations have proposed guidelines or clinical decision tools for the management of patients with disorders of gut-brain interactions (DGBI) affecting the lower digestive tract including irritable bowel syndrome and chronic idiopathic constipation. Such algorithms are based on sequential therapeutic trials and modifying the treatment strategy based on efficacy and adverse events.
OBJECTIVE: The aims of this review are to evaluate the evidence for efficacy of second- and third-line pharmacotherapies and to assess the evidence for the alternative option to manage subgroups of patients with symptoms suggestive of lower DGBI based on diagnostic tests or documented dysfunctions. The preeminent tests to identify such subgroups that present with symptoms that overlap with lower DGBI are detailed: digital rectal examination as well as anorectal manometry and balloon expulsion for evacuation disorders, detailed measurements of colonic transit, and diagnosis of bile acid diarrhea or carbohydrate malabsorption based on biochemical measurements. The review also addresses the cost implications of screening to exclude alternative diagnoses and the costs of therapy associated with the therapeutic options following an algorithmic approach to treatment from the perspective of society, insurer, or patient. Finally, the costs of the diagnostic tests to identify actionable biomarkers and the evidence of efficacy of individualized therapy based on formal diagnosis or documentation of abnormal functions are detailed in the review.

The objective of this review is to summarize pertinent literature looking at family dynamics and/or adherence to treatment in pediatric functional constipation. A structured systematic literature search was conducted on MEDLINE, Embase, and Web of Science core collection libraries from the years 2000 to 2023 using specific search terms: constipation, treatment adherence, family dynamics, parenting style, and pediatrics. Seventy-one publications were identified and included for review. After screening based on alignment to the review, 20 publications remained. These publications were placed into three categories depending on their intent and findings: (1) recommendations to further increase adherence, (2) studies analyzing factors of adherence, and (3) studies stating a need for a better understanding of family factors. A future area of research is identifying the associations between family factors on adherence to constipation treatment regimens. Results from such studies would increase the amount of positive treatment outcomes and decrease unnecessary healthcare costs.

BACKGROUND: Pediatric colorectal specialists care for patients with a variety of defecation disorders. Anorectal (AR) manometry testing is a valuable tool in the diagnosis and management of these children. This paper provides a summary of AR manometry techniques and applications as well as a review of AR manometry findings in pediatric patients with severe defecation disorders referred to a pediatric colorectal center. This is the first study describing multi-year experience using a portable AR manometry device in pediatric patients.
METHODS: An electronic medical record review was performed (1/2018 to 12/2023) of pediatric patients with defecation disorders who had AR manometry testing. Demographics, diagnostic findings, and outcomes are described.
RESULTS: A total of 297 unique patients (56.9% male, n = 169) had AR manometry testing. Of these, 72% (n = 188) had dyssynergic defecation patterns, of which 67.6% (n = 127) had fecal soiling prior to treatment. Pelvic rehabilitation (PR) was administered to 35.4% (n = 105) of all patients. A total of 79.5% (n = 58) of the 73 patients that had fecal soiling at initial presentation and completed PR with physical therapy and a bowel management program were continent after therapy. AR manometry was well tolerated, with no major complications.
CONCLUSIONS: AR manometry is a simple test that can help guide the management of pediatric colorectal surgical patients with defecation disorders. As a secondary finding, PR is a useful treatment for patients with dyssynergic stooling.

Parkinson\'s disease (PD) is a neurodegenerative disorder that affects people\'s health. Constipation is probably one of the most prominent gastrointestinal symptoms (non-motor symptoms) of PD with devastating consequences. The aim of this research work is to formulate a functional food product, supplemented with inulin, cocoa, and Moringa, which can be an adjuvant in the treatment of constipation. The product was prepared according to a muffin or \"Chilean cake\" recipe; this basic muffin was prepared with additions of inulin (MI), inulin + cacao (MIC), and inulin + Moringa (MIM). A physical-chemical analysis of the macronutrients and an antioxidant capacity assessment of the samples were conducted, as well as a sensory evaluation performed by a group of people suffering from Parkinson\'s disease. A statistically significant difference was observed in the soluble (p = 0.0023) and insoluble (p = 0.0015) fiber values between the control samples and all samples. Furthermore, inulin + cacao improved the antioxidant capacity and folate intake compared to the control. Inulin alone has been shown to have antioxidant capacity according to ABTS (262.5728 ± 34.74 μmol TE/g) and DPPH (9.092518 ± 10.43 μmol TE/g) assays. A sensory evaluation showed a preference for the product with inulin and for the product with inulin + cacao, with a 78% purchase intention being reported by the subjects who evaluated the products. The incorporation of inulin and cacao improved the nutritional value of the muffins; the dietary fiber, antioxidant capacity and folate content are some of the features that stood out. A bakery product enriched with inulin, cocoa and Moringa could serve as a nutritional strategy to enhance nutritional value, thus helping in the treatment of constipation.

OBJECTIVE: This study aims to explore the risk factors associated with frozen shoulder patients and further analyze the relationship between gender and diabetes with frozen shoulder.
METHODS: We have reviewed the data of 1205 frozen shoulder patients in China\'s Xinjiang region from 2018 to 2023. The collected information included patients\' gender, occupation, place of origin, marital status, age, the season of disease onset, duration of illness, etiology, surgical history, hypertension, diabetes, respiratory diseases, knee joint disease, hyperlipidemia, cardiovascular diseases, cervical spondylosis, lumbar disc herniation, rheumatoid arthritis, hyperuricemia, sleep quality, smoking and alcohol consumption, and constipation. We have used multifactor logistic regression analysis to identify the risk factors for a frozen shoulder.
RESULTS: Single-factor logistic regression analysis showed that the number of females, patients with diabetes, knee joint disease, constipation, and patients with poor sleep quality in the observation group are higher than in the control group (P < 0.05). There were no statistically significant differences between the two groups in terms of occupation, place of origin, marital status, age, season of disease onset, duration of illness, etiology, surgical history, hypertension, respiratory diseases, hyperlipidemia, cardiovascular diseases, cervical spondylosis, lumbar disc herniation, rheumatoid arthritis, hyperuricemia, smoking, and alcohol consumption history (P > 0.05). Multivariate analysis showed that the final model included four variables: gender, diabetes history, sleep, and constipation. Among them, the OR values of gender and diabetes history were more significant than 1, indicating that they were independent risk factors for frozen shoulder, while the OR values of sleep and constipation were less than 1, suggesting that they were negatively associated with the occurrence of frozen shoulder.
CONCLUSIONS: The results of this study suggest that gender and diabetes are independent risk factors for frozen shoulder. Additionally, poor sleep quality and constipation also can be correlated with the occurrence of a frozen shoulder.

Opioids are the gold standard for the treatment of chronic pain but are limited by adverse side effects. In our earlier work, we showed that Heat shock protein 90 (Hsp90) has a crucial role in regulating opioid signaling in spinal cord; Hsp90 inhibition in spinal cord enhances opioid anti-nociception. Building on these findings, we injected the non-selective Hsp90 inhibitor KU-32 by the intrathecal route into male and female CD-1 mice, showing that morphine anti-nociceptive potency was boosted by 1.9-3.5-fold in acute and chronic pain models. At the same time, tolerance was reduced from 21-fold to 2.9 fold and established tolerance was rescued, while the potency of constipation and reward was unchanged. These results demonstrate that spinal Hsp90 inhibition can improve the therapeutic index of morphine. However, we also found that systemic non-selective Hsp90 inhibition blocked opioid pain relief. To avoid this effect, we used selective small molecule inhibitors and CRISPR gene editing to identify 3 Hsp90 isoforms active in spinal cord (Hsp90α, Hsp90β, and Grp94) while only Hsp90α was active in brain. We thus hypothesized that a systemically delivered selective inhibitor to Hsp90β or Grp94 could selectively inhibit spinal cord Hsp90 activity, resulting in enhanced opioid therapy. We tested this hypothesis using intravenous delivery of KUNB106 (Hsp90β) and KUNG65 (Grp94), showing that both drugs enhanced morphine anti-nociceptive potency while rescuing tolerance. Together, these results suggest that selective inhibition of spinal cord Hsp90 isoforms is a novel, translationally feasible strategy to improve the therapeutic index of opioids.

暂无摘要。

BACKGROUND: Patient selection is extremely important in obstructed defecation syndrome (ODS) and rectal prolapse (RP) surgery. This study assessed factors that guided the indications for ODS and RP surgery and their specific role in our decision-making process using a machine learning approach.
METHODS: This is a retrospective analysis of a long-term prospective observational study on female patients reporting symptoms of ODS who underwent a complete diagnostic workup from January 2010 to December 2021 at an academic tertiary referral center. Clinical, defecographic, and other functional tests data were assessed. A supervised machine learning algorithm using a classification tree model was performed and tested.
RESULTS: A total of 400 patients were included. The factors associated with a significantly higher probability of undergoing surgery were follows: as symptoms, perineal splinting, anal or vaginal self-digitations, sensation of external RP, episodes of fecal incontinence and soiling; as physical examination features, evidence of internal and external RP, rectocele, enterocele, or anterior/middle pelvic organs prolapse; as defecographic findings, intra-anal and external RP, rectocele, incomplete rectocele emptying, enterocele, cystocele, and colpo-hysterocele. Surgery was less indicated in patients with dyssynergia, severe anxiety and depression. All these factors were included in a supervised machine learning algorithm. The model showed high accuracy on the test dataset (79%, p < 0.001).
CONCLUSIONS: Symptoms assessment and physical examination proved to be fundamental, but other functional tests should also be considered. By adopting a machine learning model in further ODS and RP centers, indications for surgery could be more easily and reliably identified and shared.

UNASSIGNED: The aim of this study is to compare the effects of osteopathic manipulative therapy home program (OMT-H) versus abdominal massage home program (AMHP) in treating constipation in children with cerebral palsy (CP).
UNASSIGNED: Twenty-nine children with CP with a mean age of 12.2 ± 3.76 years, who were constipated and were not on medication, were divided into three randomized groups: (i) control group (n = 10), (ii) AMHP (n = 10), and (iii) OMT-H (n = 9). In AMHP and OMT-H groups, treatment was applied as 20-min sessions every other day for 10 sessions for 3 weeks. Modified Constipation Assessment Scale (MCAS), Rome III criteria, and the Bristol Stool Form Scale (BSFS) were used for evaluation before treatment and once a week during treatment.
UNASSIGNED: While there was no change in constipation symptoms in the control group, there was an improvement in constipation symptoms after treatment in the AMHP and OMT-H groups (AMHP, P = 0.003; OMT-H, P = 0.000014). While the treatment showed to be effective from the first week in the OMT-H group, the change in BSFS (P = 0.026) and MCAS sub-parameters was found to be superior.
UNASSIGNED: AMHP and OMT-H are effective and beneficial in treating constipation. In children with CP, OMT-H was found to be quicker and more successful compared with AMHP. The OMT-H can be effectively used in clinical practice in relieving constipation in CP.

BACKGROUND: Chagas disease causes digestive anatomic and functional changes, including the loss of the myenteric plexus and abnormal esophageal radiologic and manometric findings.
OBJECTIVE: To evaluate the association of abnormal esophageal radiologic findings, cardiac changes, distal esophageal contractions, and complaints of dysphagia and constipation in upper (UES) and lower (LES) esophageal sphincter basal pressure in Chagas disease patients.
METHODS: The study evaluated 99 patients with Chagas disease and 40 asymptomatic normal volunteers. The patients had normal esophageal radiologic examination (n=61) or esophageal retention without an increase in esophageal diameter (n=38). UES and LES pressure was measured with the rapid pull-through method in a 4-channel water-perfused round catheter. Before manometry, the patients were asked about dysphagia and constipation and submitted to electrocardiography and chest radiography.
RESULTS: The amplitude of esophageal distal contraction decreased from controls to chagasic patients with esophageal retention. The proportion of failed and simultaneous contractions increased in patients with abnormal radiologic examination (P<0.01). There were no significant differences in UES and LES pressure between the groups. UES pressure was similar between Chagas disease patients with cardiomegaly (n=27, 126.5±62.7 mmHg) and those without it (n=72, 144.2±51.6 mmHg, P=0.26). Patients with constipation had lower LES pressure (n=23, 34.7±20.3 mmHg) than those without it (n=76, 42.9±20.5 mmHg, P<0.03).
CONCLUSIONS: Chagas disease patients with absent or mild esophageal radiologic involvement had no significant changes in UES and LES basal pressure. Constipation complaints are associated with decreased LES basal pressure.