Efficacy of Traditional Acupuncture Compared to Biofeedback Therapy in Fecal Incontinence: A Randomized Controlled Trial.

BACKGROUND: Fecal incontinence has a devastating impact on quality of life and imposes a substantial socioeconomic burden. Best medical therapy including biofeedback therapy improves mild symptoms, with minimal impact on moderate to severe symptoms. Surgical management for incontinence carries a degree of morbidity resulting in low uptake and acceptability. While acupuncture is common practice in Singapore for numerous medical conditions, its role in fecal incontinence is relatively novel. In our local context, however, acupuncture is accessible, inexpensive, and potentially well-accepted as a treatment strategy. OBJECTIVE: To determine the effectiveness of Traditional Chinese Medicine acupuncture, compared to biofeedback therapy in the treatment of fecal incontinence. The secondary aim is to investigate the differences in quality of life following treatment. DESIGN: Randomized controlled trial. SETTING: Prospective, single institution study. PATIENTS: Patients with ≥2 episodes of fecal incontinence/week, or St Mark's incontinence score of ≥5 were recruited. Patients were randomized into biofeedback therapy which included 3 sessions over 10 weeks, or 30 sessions of acupuncture over 10 weeks. MAIN OUTCOME MEASURES: Incontinence episodes, St. Mark's Score and Fecal Incontinence Quality of Life scale. RESULTS: Eighty-five patients were randomized into biofeedback therapy (n=46) or acupuncture (n = 39). Demographics and baseline clinical characteristics were not different (p > 0.05). Overall median incontinence episodes were reduced in both, with the acupuncture arm reporting significantly fewer at week 15 (p < 0.001). Acupuncture also improved quality of life, with improvement in lifestyle, coping, depression, and embarrassment at week 15 (p < 0.05). While the St. Mark's score was significantly reduced in both arms at week 15 (p < 0.001), the acupuncture arm's score was significantly lower (p = 0.002). LIMITATIONS: Longer follow-up required. CONCLUSIONS: Acupuncture is clinically effective and improves quality of life in patients with fecal incontinence. See Video Abstract. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov: NCT04276350.

Immunogenicity of a Third Dose of BNT162b2 to Ancestral Severe Acute Respiratory Syndrome Coronavirus 2 and the Omicron Variant in Adults Who Received 2 Doses of Inactivated Vaccine.

BACKGROUND: Limited data exist on antibody responses to mixed vaccination strategies that involve inactivated coronavirus disease 2019 (COVID-19) vaccines, particularly in the context of emerging variants. METHODS: We conducted an open-label trial of a third vaccine dose of a messenger RNA (mRNA) vaccine (BNT162b2, Fosun Pharma/BioNTech) in adults aged ≥30 years who had previously received 2 doses of inactivated COVID-19 vaccine. We collected blood samples before administering the third dose and 28 days later and tested for antibodies to the ancestral virus using a binding assay (enzyme-linked immunosorbent assay [ELISA]), a surrogate virus neutralization test (sVNT), and a live virus plaque reduction neutralization test (PRNT). We also tested for antibodies against the Omicron variant using live-virus PRNT. RESULTS: In 315 participants, a third dose of BNT162b2 substantially increased antibody titers on each assay. Mean ELISA levels increased from an optical density of 0.3 to 2.2 (P < .001), and mean sVNT levels increased from an inhibition of 17% to 96% (P < .001). In a random subset of 20 participants, the geometric mean PRNT50 titers rose substantially, by 45-fold from day 0 to day 28 against the ancestral virus (P < .001) and by 11-fold against the Omicron variant (P < .001). In daily monitoring, post-vaccination reactions subsided within 7 days for more than 99% of participants. CONCLUSIONS: A third dose of COVID-19 vaccine with an mRNA vaccine substantially improved antibody levels against the ancestral virus and the Omicron variant with a well-tolerated safety profile in adults who had received 2 doses of inactivated vaccine 6 months earlier. CLINICAL TRIALS REGISTRATION: NCT05057182.

Surgical and short-term oncological safety of total neoadjuvant therapy in high-risk locally advanced rectal cancer.

BACKGROUND: Management for locally advanced rectal cancer (LARC) conventionally comprises long-course chemoradiotherapy (LCCRT), total mesorectal excision (TME), and adjuvant chemotherapy. However, the RAPIDO study published in 2021 showed that total neoadjuvant therapy (TNT) led to better oncological outcomes without increased toxicity. We review the surgical and short-term oncological outcomes of patients with high-risk LARC who underwent TNT or LCCRT before TME. METHODS: Patients with high-risk LARC who underwent TNT or LCCRT before TME between 2021 and 2022 were reviewed. RESULTS: Thirty-five patients (66%) had TNT as per RAPIDO whilst 18 underwent LCCRT. Median follow-up was 16 months (range 5-25). Of the patients who had TNT, median age was 65 years old (range 44-79), 34 (97%) had clinical Stage 3 LARC and median height FAV was 5 cm (range 0.5-14). Nine (26%) required a dose delay/reduction due to treatment toxicity. Seven (50%) showed resolution of previously enlarged lateral nodes. Three (9%) had pathological complete response. Postoperative major morbidity was 23%, of which 4 patients required a reoperation. Six (17%) patients had disease-related treatment failure, with two having disease progression during TNT, two developed local recurrence, and two developed distal metastasis following surgery. Median duration to surgery following completion of chemotherapy was significantly shorter with TNT (36 days versus 74 days) (P < 0.001). There were no other significant differences in outcomes. CONCLUSION: TNT is clinically safe in high-risk LARC patients with no significant difference to surgical and short-term oncological outcomes compared to LCCRT, although a higher incidence of early surgical morbidity was observed.

Colorimetric CO2 Detector to Improve Effective Mask Ventilations in Very Preterm Infants: A Pilot Randomized Controlled Study.

INTRODUCTION: End-tidal CO2 (ETCO2) detector is currently recommended for confirmation of endotracheal tube placement during neonatal resuscitation. Whether it is feasible to use ETCO2 detectors during mask ventilation to reduce risk of bradycardia and desaturations, which are associated with increased risk of death in preterm babies, is unknown. METHODS: This is a pilot randomized controlled trial (NCT04287907) involving newborns 24 + 0/7 to 32 + 0/7 weeks gestation who required mask ventilation at birth. Infants were randomized into groups with or without colorimetric ETCO2 detectors. Combined duration of any bradycardia (<100 bpm) and time below prespecified target oxygen saturation (SpO2) as measured by pulse oximetry were compared. RESULTS: Fifty participants were randomized, 47 with outcomes analysed (2 incomplete data, 1 postnatal diagnosis of trachea-oesophageal fistula). Mean gestational age and birthweight were 28.5 ± 1.9 versus 29.4 ± 1.6 weeks (p = 0.1) and 1,252.7 ± 409.7 g versus 1,334.6 ± 369.1 g (p = 0.5) in the intervention and control arm, respectively. Mean combined duration of bradycardia and desaturation was 276.7 ± 197.7 s (intervention) and 322.7 ± 277.7 s (control) (p = 0.6). Proportion of participants with any bradycardia or desaturation at 5 min were 38.1% (intervention) and 56.5% (control) (p = 0.2). No chest compressions, epinephrine administration, or death occurred in the delivery room. CONCLUSION: This pilot study demonstrates the feasibility of a trial to evaluate colorimetric ETCO2 detectors during mask ventilation of very preterm infants to reduce bradycardia and low SpO2. Further assessment with a larger population will be required to determine if ETCO2 detector usage at resuscitation reduces risk of adverse outcomes, including death and disability, in very preterm infants.

Comparative antibody and cell-mediated immune responses, reactogenicity, and efficacy of homologous and heterologous boosting with CoronaVac and BNT162b2 (Cobovax): an open-label, randomised trial.

BACKGROUND: Few trials have compared homologous and heterologous third doses of COVID-19 vaccination with inactivated vaccines and mRNA vaccines. The aim of this study was to assess immune responses, safety, and efficacy against SARS-CoV-2 infection following homologous or heterologous third-dose COVID-19 vaccination with either one dose of CoronaVac (Sinovac Biotech; inactivated vaccine) or BNT162b2 (Fosun Pharma-BioNTech; mRNA vaccine). METHODS: This is an ongoing, randomised, allocation-concealed, open-label, comparator-controlled trial in adults aged 18 years or older enrolled from the community in Hong Kong, who had received two doses of CoronaVac or BNT162b2 at least 6 months earlier. Participants were randomly assigned, using a computer-generated sequence, in a 1:1 ratio with allocation concealment to receive a (third) dose of CoronaVac or BNT162b2 (ancestral virus strain), stratified by types of previous COVID-19 vaccination (homologous two doses of CoronaVac or BNT162b2). Participants were unmasked to group allocation after vaccination. The primary endpoint was serum neutralising antibodies against the ancestral virus at day 28 after vaccination in each group, measured as plaque reduction neutralisation test (PRNT50) geometric mean titre (GMT). Surrogate virus neutralisation test (sVNT) mean inhibition percentage and PRNT50 titres against omicron BA.1 and BA.2 subvariants were also measured. Secondary endpoints included geometric mean fold rise (GMFR) in antibody titres; incidence of solicited local and systemic adverse events; IFNγ+ CD4+ and IFNγ+ CD8+ T-cell responses at days 7 and 28; and incidence of COVID-19. Within-group comparisons of boost in immunogenicity from baseline and between-group comparisons were done according to intervention received (ie, per protocol) by paired and unpaired t test, respectively, and cumulative incidence of infection was compared using Kaplan-Meier curves and a proportional hazards model to estimate hazard ratio. The trial is registered with ClinicalTrials.gov, NCT05057169. FINDINGS: We enrolled participants from Nov 12, 2021, to Jan 27, 2022. We vaccinated 219 participants who previously received two doses of CoronaVac, including 101 randomly assigned to receive CoronaVac (CC-C) and 118 randomly assigned to receive BNT162b2 (CC-B) as their third dose; and 232 participants who previously received two doses of BNT162b2, including 118 randomly assigned to receive CoronaVac (BB-C) and 114 randomly assigned to receive BNT162b2 (BB-B) as their third dose. The PRNT50 GMTs on day 28 against ancestral virus were 109, 905, 92, and 816; against omicron BA.1 were 9, 75, 8, and 86; and against omicron BA.2 were 6, 80, 6, and 67 in the CC-C, CC-B, BB-C, and BB-B groups, respectively. Mean sVNT inhibition percentages on day 28 against ancestral virus were 83%, 96%, 87%, and 96%; against omicron BA.1 were 15%, 58%, 19%, and 69%; and against omicron BA.2 were 43%, 85%, 50%, and 90%, in the CC-C, CC-B, BB-C, and BB-B groups, respectively. Participants who had previously received two doses of CoronaVac and a BNT162b2 third dose had a GMFR of 12 (p<0·0001) compared with those who received a CoronaVac third dose; similarly, those who had received two doses of BNT162b2 and a BNT162b2 third dose had a GMFR of 8 (p<0·0001). No differences in CD4+ and CD8+ T-cell responses were observed between groups. We did not identify any vaccination-related hospitalisation within 1 month after vaccination. We identified 58 infections when omicron BA.2 was predominantly circulating, with cumulative incidence of 15·3% and 15·4% in the CC-C and CC-B groups, respectively (p=0·93), and 16·7% and 14·0% in the BB-C and BB-B groups, respectively (p=0·56). INTERPRETATION: Similar levels of incidence of, presumably, omicron BA.2 infections were observed in each group despite very weak antibody responses to BA.2 in the recipients of a CoronaVac third dose. Further research is warranted to identify appropriate correlates of protection for inactivated COVID-19 vaccines. FUNDING: Health and Medical Research Fund, Hong Kong. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Clinical patterns and management of primary mucosal melanoma: a single centre experience.

BACKGROUND: Primary mucosal melanomas (MM) are rare neoplasms arising from melanocytes in mucosal membranes. Delayed diagnosis and aggressive disease biology contribute to a poorer prognosis. The clinical patterns of MMs treated in a large tertiary centre, and the differences between MMs in the head and neck versus other anatomical sites are described. METHODS: A retrospective review of 43 patients diagnosed with MM in the head and neck, urogenital, esophageal and anorectal sites from 1993 to 2015 was conducted. RESULTS: Distribution of head and neck, urogenital and gastrointestinal MM were 42, 30 and 28% respectively. Disease extent was local in 44%, regional in 40% and distal in 12% at diagnosis. Head and neck MMs were more likely to be diagnosed at an earlier stage as compared to other sites (P = 0.04). Surgery was performed with curative intent in 72%, while 2% had palliative surgery for symptom control. Of the remaining patients who did not undergo surgery, four had palliative chemotherapy and/or radiotherapy. Median disease-free survival was 13 months (1-179 months). There was a significantly longer time to locoregional recurrence in head and neck MM (16 months) compared to other sites (11 months) (P = 0.03). The 2-year overall survival was also significantly higher in head and neck MM (P = 0.003). CONCLUSION: MM of the head and neck is diagnosed at an earlier stage and associated with a longer time to locoregional recurrence. Surgical resection is the mainstay of treatment and may offer long-term survival benefit in selected patients.