Bharucha, Adil E.

ABSTRACT Background Treatment options for medically‐refractory faecal incontinence ( FI )—including anorectal biofeedback, dextranomer injection, and sacral nerve stimulation—are limited and outcomes are often suboptimal. Anal or vaginal insert devices are infrequently used. Aims We evaluated the safety and effectiveness of a new anal insert device (StaySure) in patients with FI. Methods Patients with FI for ≥ 6 months and ≥ 4 moderate or large FI episodes during a 4‐week baseline entered a 2–4 week fitting/run‐in period to individualise device size (10 or 13 mm) followed by a 4‐week treatment period. Outcomes included effectiveness, safety, and quality of life (QoL). The primary outcome was the proportion achieving a ≥ 50% reduction in FI frequency. Results Of 124 enrolled patients, 98, 71, and 61 progressed through the baseline, fitting/run‐in, and treatment phases respectively, with few exclusions due to device intolerance. In the intent‐to‐treat cohort of 59 participants (93% women), mean ( SD ) number of days with FI declined from 13.2 (7.0) to 6.3 (6.9), and FI weekly episodes declined from 5.4 (6.9) to 2.1 (5.1) (69% reduction; p < 0.001) with similar results for both device sizes. The primary endpoint was achieved in 76.3% of participants; 54.2% achieved ≥ 75% reduction. The FIQoL overall score increased from a mean ( SD ) of 1.9 (0.6) to 2.3 (0.6) ( p < 0.001), indicating improved QoL . Improvements in FI frequency, FIQoL exceeded minimal clinically important difference thresholds, confirming clear clinical benefit. No treatment‐related serious adverse events were reported. Conclusions The StaySure anal insert device is safe, well tolerated, and effective in reducing FI in patients with moderate to severe symptoms refractory to conservative therapies. Trial Registration ClinicalTrials.gov identifier: NCT03898778

ABSTRACT Background Chronic megacolon is an uncommon neurogastrointestinal disorder typically characterized by a persistent increase in colonic diameter. Methods Our aim was to identify adults with medical treatment‐refractory constipation without radiographic criteria for megacolon but with increased colonic compliance (refractory constipation with colonic hypercompliance (RCCH)), and to compare the colonic compliance in 7 identified patients with “RCCH” to colonic compliance in 10 patients with chronic megacolon by radiographic criteria (i.e., megacolon) and 40 healthy volunteers. After endoscopic placement, compliance of left or transverse colon was measured using a 10‐cm‐long infinitely compliant balloon connected to an electronically controlled rigid piston barostat. The barostat inflated the balloon from 0 to 44 mmHg in 4‐mmHg steps at 30‐s intervals to measure colonic compliance (pressure‐volume relationship). Eligibility criteria for inclusion were increased colonic compliance based on a functional assessment without meeting radiographic criteria for megacolon (i.e., RCCH). In the three groups, we compared colonic volumes at intra‐balloon pressure of 8, 16, 20, 32, and 44 mmHg, the pressure at half maximum volume, and the slope of the colonic compliance curve using ANOVA on ranks and Dunn's pairwise comparison test. Other features of colonic motility were documented. Results Colonic volumes at all pressures (8‐44 mmHg) and the pressure at half maximum volume were significantly greater in patients with megacolon and RCCH than in healthy controls ( p < 0.001 for both), but compliance was not significantly different between RCCH and megacolon. Conclusion A subset of patients with medically‐refractory chronic constipation has colonic compliance similar to that of patients with megacolon.

Background While SARS-CoV-2 vaccines are highly effective in healthy individuals, the magnitude and durability of humoral and cellular responses in patients with solid malignancies receiving chemotherapy remain understudied. Previous reports suggest that patients with cancer may not mount adequate immune response after SARS-CoV-2 vaccination. Additionally, most studies focused on humoral responses, while data regarding cellular immune responses are scarce. In this study, we evaluated humoral and cellular responses in patients with solid tumors receiving chemotherapy compared to healthy individuals up to one year after vaccinations. Methods Patients aged ≥18 who were willing to receive the SARS-CoV-2 vaccine were enrolled. Anti-SARS-CoV-2 immunoassays were used to detect antibodies against nucleocapsid and spike proteins. Human IFN-γ Fluorospot assay was used to determine antigen−specific T-cell responses. Data were compared between groups using Mann−Whitney test for continuous variables and Fisher’s exact test for categorical variables. Results A total of 67 subjects (47 patients with cancer and 20 healthy individuals) were included. 1–3 months following the second vaccine doses, 96% of patients with cancer and 100% of healthy individuals demonstrated a positive humoral response. While the positivity rate was not significantly different, patients with cancer had significantly lower spike IgG antibodies than healthy individuals. However, this difference diminished at 6 months when patients with cancer had increased antibodies compared to decreased antibodies in the healthy cohort and no difference was noticed at 12-month. Patients with cancer developed a similar antigen-specific T-cell response as healthy individuals at 1–3 months, 6 months and 12 months. There were no significant differences when comparing patients aged ≤ 55 years vs. &gt;55 years, stages I-III vs. IV, single vs. multiple chemotherapy, and BNT162b2 vs. mRNA-1273 vaccines. There was a significant moderate correlation between neutralization and antibody levels at 12 months. However, despite patients with cancer having a significantly higher COVID risk score, there were no significant differences in COVID-19 infection and hospitalization between patients with cancer and healthy individuals. Conclusion Despite initial impaired antibody responses to SARS-CoV-2 vaccinations, patients with solid malignancies receiving chemotherapy effectively generated long-term cellular and humoral responses by 6 and 12 months, leading to similar infection and hospitalization rates compared to healthy individuals.

Abstract Background Up to 80% of persons with Parkinson's disease (PwPD) have dysphagia. However, existing studies are based on small cohorts and the relationship between dysphagia and other motor and nonmotor symptoms (NMS) remains incompletely understood. Objectives To evaluate the relationship between motor and NMS in PwPD with vs without dysphagia. Methods Among 20,365 PwPD in the Michael J. Fox Foundation database who completed ≥2 NMS surveys, 12,678 (62%) reported dysphagia on ≥1 survey. We examined associations between dysphagia and: (1) self‐reported motor symptoms (UPDRS Part II), other NMS, quality of life (QoL), comorbidity score, depression, and daily activities at baseline; and (2) development of new NMS. Results Compared to PwPD without dysphagia, those with dysphagia were more likely to have had PD for >5 years, more severe motor and NMS, higher comorbidity scores, and a greater impairment in daily activities ( P < 0.001). The prevalence of dysphagia increased with the severity of motor symptoms at the index survey ( P < 0.001). At baseline, all NMS were significantly associated with dysphagia. Compared to PwPD who did not have dysphagia, PwPD with dysphagia were at increased risk of developing every NMS, even after adjusting for ages at PD diagnosis and index survey, sex, cognitive impairment, UPDRS, NMS and comorbidity scores. For most NMS, the risk of progression was greater in those with cognitive impairment or elevated NMS scores. Conclusions Dysphagia in PwPD is associated with more severe motor and non‐motor symptoms, reduced QoL, and an increased risk of future NMS.

Abstract Background Small studies suggest that constipation is a common symptom associated with a worse prognosis in patients with Parkinson's disease (PD). Objectives The aim was to compare the association between constipation, motor, and other non‐motor symptoms (NMS) in PD patients at baseline and in future. Methods Using the Fox Insight database, we compared baseline characteristics, risk of progressive motor symptoms, and incidence of NMS between PD patients with versus without constipation. Results Of 20,352 participants, 16,611 (82%) reported infrequent bowel movements and/or excessive straining, 15,594 (77%) had incomplete evacuation, and 14,165 (70%) reported both symptoms. Patients with constipation were generally older, white, women, had PD >5 years, and had higher NMS and comorbidity scores ( P < 0.001). Constipation was significantly associated with worse motor symptoms and most NMS , especially fecal incontinence (odds ratio [ OR] = 1.65; 95% confidence interval [CI], 1.49–1.82), dysphagia ( OR = 1.20; 95% CI = 1.12–1.29), talking/moving during sleep ( OR = 1.39; 95% CI = 1.30–1.48), and urinary urgency ( OR = 1.23; 95% CI = 1.16–1.32). Constipation was associated with a small, but statistically significant increased risk of some progressive motor symptoms. At a mean median follow‐up of 2.8 years, constipation was associated with an increased risk of incident gastrointestinal, autonomic, neuropsychiatric, sleep‐related, sensory NMS , such as dysphagia (hazard ratio [ HR] = 1.43; 95% CI = 1.35–1.51), fecal incontinence ( HR = 1.87; 95% CI = 1.74–2.01), falls ( HR = 1.44; 95% CI = 1.35–1.52), hallucinations ( HR = 1.65; 95% CI = 1.52–1.79), cognitive impairment ( HR = 1.38; 95% CI = 1.30–1.47), and talking/moving during sleep ( HR = 1.65; 95% CI = 1.55–1.75). Conclusions Constipation is a common symptom associated with severity of motor and other NMS and portends a worse prognosis in persons with PD.

ABSTRACTBackground and AimsBowel diaries are used to characterize the severity of fecal incontinence (FI) but have not been adequately validated for this purpose. Our aims were to validate a new bowel diary and to compare the characteristics of FI as assessed with a bowel diary and a validated questionnaire.MethodsIn this four‐center prospective study, patients with a history of FI and asymptomatic controls completed a 28‐day bowel diary and validated questionnaires to evaluate bowel habits and FI, quality of life related to FI (FIQoL), and PROMIS scales for anxiety, depression, and self‐efficacy.ResultsAmong 59 participants with FI and 29 asymptomatic controls, the bowel diary was 97% sensitive and 93% specific for distinguishing between FI participants and controls. Over 28 days, FI participants experienced an average [SD] of 31.1 [50.7] FI episodes, consisting of staining (12.6 [14.9]), some stool (12.5 [20.3]), or a full bowel movement (4.4 [8.5]). Correlations between the questionnaire and diary were statistically significant for frequency (Spearman ρ = 0.5, p < 0.001), amount (ρ = 0.4, p < 0.001), and awareness of FI (ρ = 0.3, p = 0.04). In 71% of participants, there was agreement between the consistency of FI as reported in the questionnaire and the diary. More severe FI was associated with poorer FIQoL (p = 0.002). Anxiety, depression, and self‐efficacy scores did not significantly affect the agreement between the frequency of FI reported in the diary and questionnaire.ConclusionThis bowel diary effectively discriminates between healthy participants and those with FI. There is significant, albeit modest, agreement between the characteristics of FI recorded with a diary and a questionnaire.

Fecal incontinence (FI) is the involuntary and recurrent loss of stool. FI significantly affects both physical and social well-being, while imposing a substantial economic burden. The global prevalence of FI is approximately 8%. Risk factors include advanced age, diarrhea, anal sphincter damage from obstetric trauma or anorectal surgery, pelvic floor abnormalities (such as rectal prolapse), inflammatory bowel disease, and neurological conditions. Despite greater understanding of the impact of FI and advances in diagnostic techniques and treatment options, management remains inconsistent, likely because of limited awareness of available therapies. Patients often benefit from conservative treatments, including dietary modifications, fiber supplementation, antidiarrheal agents, and physical therapy, especially when these are tailored to specific symptoms and rigorously applied. Next level options include anorectal biofeedback therapy, the perianal injectable bulking agent dextranomer, or anal/vaginal barrier devices, which can be effective for patients if tolerated. Transanal irrigation may be considered for patients with neurogenic bowel and fecal retention to aid in rectal cleansing and prevent FI. Sacral neuromodulation is the preferred surgical treatment of FI. Noninvasive anal electrical and percutaneous tibial nerve stimulation are not superior to placebo in controlled trials. Translumbosacral magnetic stimulation was beneficial in an uncontrolled trial; sham-controlled trials are necessary. Owing to limited long-term efficacy, anal sphincteroplasty is typically reserved for younger patients with obstetric anal sphincter defects. Colostomy is considered a last resort. Injection of autologous muscle cells into the external anal sphincter has shown promise in small uncontrolled trials, although it has not yielded significant results in most controlled trials.

ABSTRACTBackgroundThe carbon‐13 spirulina gastric emptying breath test (GEBT) is approved to identify delayed, but not accelerated, gastric emptying (GE). We compared the utility of the GEBT to scintigraphy for diagnosing abnormal GE in patients with diabetes mellitus.MethodsTwenty‐eight patients with diabetes ate a 230‐kcal test meal labeled with technetium 99 m and 13C‐spirulina, after which 10 scintigraphic images and breath samples (baseline, 15, 30, 45, 60, 90, 120, 150, 180, 210, and 240 min) were collected on 2 occasions 1 week apart. We assessed the accuracy of 13C‐spirulina GEBT excretion rate (percent dose multiplied by 1000 [kPCD] min−1) values to predict scintigraphic half‐life and distinguish between normal, delayed, and accelerated GE and the intraindividual reproducibility of the GEBT.Key ResultsScintigraphy revealed normal, delayed, and accelerated GE, respectively, in 17 (30%), 29 (52%), and 10 (18%) test results. GE T½ values measured with scintigraphy and GEBT were highly concordant within individuals; the intraindividual reproducibility was 34% (scintigraphy) and 15% (GEBT). Compared to current criteria, the kPCD150 (150 min) and kPCD180 values provided equally sensitive (90%) and more specific (81% vs. 67%) approach for distinguishing between delayed versus normal/accelerated GE. A new metric (kPCD60–kPCD15 min) was 90% sensitive and 83% specific for distinguishing between accelerated versus normal/delayed GE. These findings were used to create nomograms and an algorithm for interpreting GEBT results.Conclusions and InferencesAmong patients with poorly controlled diabetes, the 13C‐spirulina GEBT can accurately and precisely assess GE and effectively distinguish between normal, delayed, and accelerated GE.