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.

Quality of life of patients and caregivers affected by bronchopulmonary dysplasia: a systematic review.

PURPOSE: To synthesize evidence on the impact of bronchopulmonary dysplasia (BPD) on the Quality of Life (QoL) of affected individuals from three perspectives: (i) QoL of caregiver; (ii) caregiver's perception of BPD patient's QoL; and (iii) BPD patient's self-reported QoL. METHODS: Quantitative studies (case-control, cohort, and case series) on the QoL of BPD patients or their caregivers were considered. We conducted a systematic literature search of 6 databases (PubMed, Embase, World of Science, CINAHL, PsycINFO, and Chinese National Knowledge Infrastructure) for relevant studies. All databases were searched from the date of inception of the databases to 31 March 2022. Populations of interest were caregivers with preterm babies with BPD, or children/adults who were born premature and diagnosed with BPD. The main outcome measures were total and subdomain QoL scores, and factors affecting QoL. RESULTS: A total of 1078 articles were found; 10 were eligible for analysis, which included 247 caregivers and 1632 patients with BPD. The QoL of patients differed by domains-some were poorer or similar, but none of the QoL domains was better than QoL of healthy controls. Poor sleep and acute care needs of BPD patients negatively affected caregiver's QoL, while increasing illness acuity negatively affected the QoL of BPD patients. The QoL of BPD patients and their caregivers was most adversely affected during the immediate post-discharge period and tended to improve with time. The physical QoL of BPD patients was similar to that of preterm babies without BPD when assessed during late childhood and early adulthood. CONCLUSION: QoL assessment should be performed as an outcome measure and incorporated in the care plan for BPD patients and their caregivers. Systematic Review Registration PROSPERO CRD42021292253.

The Effect of a 20-Hour Baby-Friendly Hospital Initiative Training Program on Nurses' Breastfeeding Knowledge, Attitudes and Confidence, in a Tertiary Hospital in Singapore.

OBJECTIVE: The Baby-Friendly Hospital Initiative (BFHI) enables maternity units to be centers of breastfeeding support to increase breastfeeding rates. This study evaluates the impact of the 20-hour BFHI training course on nurses' breastfeeding knowledge, attitude, and confidence in breastfeeding practice in a tertiary hospital in Singapore. STUDY DESIGN: Seventeen sessions of the 20-hour BFHI training course were conducted by lactation consultants from 2010 to 2013 at the National University Hospital, Singapore. An anonymous self-administered survey on knowledge, attitude, and confidence in breastfeeding practices were distributed to nurses before (2009) and after (2014) the training courses to assess effectiveness of training. RESULTS: One-hundred forty nurses and one hundred forty-eight nurses participated in the surveys in 2009 and 2014, respectively. Majority were registered nurses who worked in the postnatal wards and the neonatal intensive care unit. After training, there were significant improvements for five of eight items in infant feeding knowledge, including greater awareness of the International Code of Marketing of Breastmilk Substitutes and medical contraindication for breastfeeding. Participants reported more confidence in assisting mothers on breastfeeding, 77.1 to 88.5% (p = 0.019); advising hand expressing breast milk, 75.7 to 86.5% (p = 0.012); and advising attachment to the breast, 75.7 to 89.2% (p = 0.004) in 2014 compared with 2009. However, despite having high levels of confidence, only about half the nurses reported being able to assist mothers in breastfeeding, mainly due to time constraints. CONCLUSION: Implementation of the 20-hour BFHI training program positively influenced nurses' breastfeeding knowledge, attitude, and confidence in breastfeeding practices. Hospital procedures and manpower requirements should be re-examined to overcome nursing constraints in providing breastfeeding help to postpartum mothers. KEY POINTS: · Nurses have low breastfeeding knowledge pretraining.. · The 20-hour BFHI training course is effective.. · Nurses have inadequate time to support breastfeeding..

Nocturnal hypoxaemia in interstitial lung disease: a systematic review.

BACKGROUND: Patients with interstitial lung disease (ILD) are at risk of developing nocturnal hypoxaemia due to ventilatory restriction and impaired gas exchange that worsen with supine posture and reduced ventilatory drive during sleep. This systematic review synthesised literature on the diagnostic evaluation, epidemiology, associations, management and prognosis of nocturnal hypoxaemia in ILD. METHODS: Ovid MEDLINE, Embase and CENTRAL databases were searched for eligible studies. Meta-analyses with subgroup analyses were conducted, where possible. RESULTS: Fifty-three studies were included (total participant number=2590). The most common definition for clinically significant nocturnal hypoxaemia was ≥10% of total sleep time with oxyhaemoglobin saturation <90%, with pooled prevalence of 37%. There were no significant differences in pooled prevalence according to ILD subtype and comorbid obstructive sleep apnoea status. Study heterogeneity precluded meta-analysis of associations and prognosis. Diffusing capacity for carbon monoxide (DLCO) and echocardiographic features for pulmonary hypertension were consistently associated with nocturnal hypoxaemia. There were inconsistent associations between nocturnal hypoxaemia with ILD subtype and severity. Multivariable analyses in most studies demonstrated significant associations of nocturnal hypoxaemia with survival. Two small short-term intervention studies demonstrated that supplemental oxygen of 1-3 L/min corrected nocturnal hypoxaemia, with improved heart rate control during in-laboratory observation and increased serum antioxidant levels after 1 month of therapy. CONCLUSION: Nocturnal hypoxaemia is common, associated with DLCO impairment and markers suggestive of pulmonary hypertension, and a potential prognostic factor in patients in ILD. There is a need to establish a consensus definition of nocturnal hypoxaemia and evaluate long-term effects of nocturnal supplemental oxygen in ILD.

Sources of Distress Experienced by Parents of Children with Chronic Kidney Disease on Dialysis: A Qualitative Systematic Review.

PROBLEM: Parents of children with chronic kidney disease face tremendous burdens of care, having to adopt dual roles as parents and informal healthcare providers, delivering home-based clinical care, despite lacking proper qualification and training. ELIGIBILITY CRITERIA: A systematic review of qualitative studies was conducted to identify sources of distress among parents caring for children with chronic kidney disease undergoing dialysis, excluding children who have had renal transplants. Guided by PRISMA guidelines, six electronic databases (PubMed, Embase, PsycINFO, Scopus, Cochrane, Google Scholar) were searched for relevant articles published in English. A three-step inductive thematic synthesis method outlined by Thomas and Harden (2018) was used to form descriptive themes and the Critical Appraisal Skill Program (CASP) qualitative checklist was utilised to appraise the quality of included articles. SAMPLE: A total of 23,129 title and abstracts were reviewed; 161 full texts were reviewed. Thirteen papers, with the experiences of 183 parents, met the inclusion criteria. Most included studies were conducted in Western countries, which may limit the applicability of this review to other countries. RESULTS: Five themes emerged: disease-related distress, personal struggles, family structure, lack of resources and unrealistic social expectations. CONCLUSION: Parents of children with chronic kidney disease undergoing dialysis experienced distress at multiple levels. IMPLICATION: Healthcare professionals caring for children with chronic kidney disease could screen parents early for distress, and refer them to relevant psychosocial and community services.

ASLAN003, a potent dihydroorotate dehydrogenase inhibitor for differentiation of acute myeloid leukemia.

Differentiation therapies achieve remarkable success in acute promyelocytic leukemia, a subtype of acute myeloid leukemia. However, excluding acute promyelocytic leukemia, clinical benefits of differentiation therapies are negligible in acute myeloid leukemia except for mutant isocitrate dehydrogenase 1/2. Dihydroorotate dehydrogenase catalyses the fourth step of the de novo pyrimidine synthesis pathway. ASLAN003 is a highly potent dihydroorotate dehydrogenase inhibitor that induces differentiation, as well as reduces cell proliferation and viability, of acute myeloid leukemia cell lines and primary acute myeloid leukemia blasts including in chemo-resistant cells. Apoptotic pathways are triggered by ASLAN003, and it also significantly inhibits protein synthesis and activates AP-1 transcription, contributing to its differentiation promoting capacity. Finally, ASLAN003 substantially reduces leukemic burden and prolongs survival in acute myeloid leukemia xenograft mice and acute myeloid leukemia patient-derived xenograft models. Notably, the drug has no evident effect on normal hematopoietic cells and exhibits excellent safety profiles in mice, even after a prolonged period of administration. Our results, therefore, suggest that ASLAN003 is an agent targeting dihydroorotate dehydrogenase with potential in the treatment of acute myeloid leukemia. ASLAN003 is currently being evaluated in phase 2a clinical trial in acute myeloid leukemia patients.

Breastfeeding in COVID-19: A Pragmatic Approach.

The novel coronavirus disease 2019 (COVID-19) pandemic has resulted in changes to perinatal and neonatal care, concentrating on minimizing risks of transmission to the newborn and health care staff while ensuring medical care is not compromised for both mother and infant. Current recommendations on infant care and feeding when mother has COVID-19 ranges from mother-infant separation and avoidance of human milk feeding, to initiation of early skin-to-skin contact and direct breastfeeding. Health care providers fearing risks of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) maternal-infant transmission may veer toward restricted breastfeeding practices. We reviewed guidelines and published literature and propose three options for infant feeding depending on various scenarios. Option A involves direct breastfeeding with the infant being cared for by the mother or caregiver. In option B, the infant is cared for by another caregiver and receives mother's expressed milk. In the third option, the infant is not breastfed directly and does not receive mother's expressed milk. We recommend joint decision making by parents and the health care team. This decision is also flexible as situation changes. We also provide a framework for counseling mothers on these options using a visual aid and a corresponding structured training program for health care providers. Future research questions are also proposed. We conclude that evidence and knowledge about COVID-19 and breastfeeding are still evolving. Our options can provide a quick and flexible reference guide that can be adapted to local needs. KEY POINTS: · SARS-CoV-2 is unlikely transmitted via human milk.. · A shared decision making on infant feeding is the preferred approach.. · Mothers can safely breastfeed with appropriate infection control measures..

ENL: structure, function, and roles in hematopoiesis and acute myeloid leukemia.

ENL/MLLT1 is a distinctive member of the KMT2 family based on its structural homology. ENL is a histone acetylation reader and a critical component of the super elongation complex. ENL plays pivotal roles in the regulation of chromatin remodelling and gene expression of many important proto-oncogenes, such as Myc, Hox genes, via histone acetylation. Novel insights of the key role of the YEATS domain of ENL in the transcriptional control of leukemogenic gene expression has emerged from whole genome Crisp-cas9 studies in acute myeloid leukemia (AML). In this review, we have summarized what is currently known about the structure and function of the ENL molecule. We described the ENL's role in normal hematopoiesis, and leukemogenesis. We have also outlined the detailed molecular mechanisms underlying the regulation of target gene expression by ENL, as well as its major interacting partners and complexes involved. Finally, we discuss the emerging knowledge of different approaches for the validation of ENL as a therapeutic target and the development of small-molecule inhibitors disrupting the YEATS reader pocket of ENL protein, which holds great promise for the treatment of AML. This review will not only provide a fundamental understanding of the structure and function of ENL and update on the roles of ENL in AML, but also the development of new therapeutic strategies.

Effectiveness of a Technology-Based Supportive Educational Parenting Program on Parental Outcomes (Part 1): Randomized Controlled Trial.

BACKGROUND: Transitioning into parenthood can be stressful for new parents, especially with the lack of continuity of care from health care professionals during the postpartum period. Short hospital stays limit the availability of support and time parents need to be well equipped with parenting and infant care skills. Poor parental adjustment may, in turn, lead to negative parental outcomes and adversely affect the child's development. For the family's future well-being, and to facilitate a smoother transition into parenthood, there is a need for easily accessible, technology-based educational programs to support parents during the crucial perinatal period. OBJECTIVE: This study aimed to examine the effectiveness of a technology-based supportive educational parenting program (SEPP) on parenting outcomes during the perinatal period in couples. METHODS: A randomized, single-blinded, parallel-armed, controlled trial was conducted. The study recruited 236 parents (118 couples) from an antenatal clinic of a tertiary hospital in Singapore. Eligible parents were randomly assigned to the intervention group (n=118) or the control group (n=118). The SEPP is based on Bandura's self-efficacy theory and Bowlby's theory of attachment. Components of the intervention include 2 telephone-based educational sessions (1 antenatal and 1 immediately postnatal) and a mobile health app follow-up for 1 month. The control group only received routine perinatal care provided by the hospital. Outcome measures including parenting self-efficacy (PSE), parental bonding, perceived social support, parenting satisfaction, postnatal depression (PND), and anxiety were measured using reliable and valid instruments. Data were collected over 6 months at 4 time points: during pregnancy (third trimester), 2 days postpartum, 1 month postpartum, and 3 months postpartum. Outcomes were standardized using baseline means and SDs. Linear mixed models were used to compare the groups for postpartum changes in the outcome variables. RESULTS: The intervention group showed significantly better outcome scores than the control group from baseline to 3 months postpartum for PSE (mean difference, MD, 0.37; 95% CI 0.06 to 0.68; P=.02), parental bonding (MD -1.32; 95% CI -1.89 to -0.75; P<.001), self-perceived social support (MD 0.69; 95% CI 0.18 to 1.19; P=.01), parenting satisfaction (MD 1.40; 95% CI 0.86 to 1.93; P<.001), and PND (MD -0.91; 95% CI -1.34 to -0.49; P<.001). Postnatal anxiety (PNA) scores of the intervention group were only significantly better after adjusting for covariates (MD -0.82; 95% CI -1.15 to -0.49; P<.001). CONCLUSIONS: The technology-based SEPP is effective in enhancing parental bonding, PSE, perceived social support and parental satisfaction, and in reducing PND and PNA. Health care professionals could incorporate it with existing hands-on infant care classes and routine care to better meet parents' needs and create positive childbirth experiences, which may in turn encourage parents to have more children. TRIAL REGISTRATION: ISRCTN Registry ISRCTN48536064; http://www.isrctn.com/ISRCTN48536064 (Archived by WebCite at http://www.webcitation.org/6wMuEysiO).

Identification of a novel ligand for the ATAD2 bromodomain with selectivity over BRD4 through a fragment growing approach.

ATAD2 is an ATPase that is overexpressed in a variety of cancers and associated with a poor patient prognosis. This protein has been suggested to function as a cofactor for a range of transcription factors, including the proto-oncogene MYC and the androgen receptor. ATAD2 comprises an ATPase domain, implicated in chromatin remodelling, and a bromodomain which allows it to interact with acetylated histone tails. Dissection of the functional roles of these two domains would benefit from the availability of selective, cell-permeable pharmacological probes. An in silico evaluation of the 3D structures of various bromodomains suggested that developing small molecule ligands for the bromodomain of ATAD2 is likely to be challenging, although recent reports have shown that ATAD2 bromodomain ligands can be identified. We report a structure-guided fragment-based approach to identify lead compounds for ATAD2 bromodomain inhibitor development. Our findings indicate that the ATAD2 bromodomain can accommodate fragment hits (Mr < 200) that yield productive structure-activity relationships, and structure-guided design enabled the introduction of selectivity over BRD4.

Trends in Post-Mastectomy Reconstruction in an Asian Population: A 12-Year Institutional Review.

Post-mastectomy breast reconstruction is an integral component of breast cancer treatment. It is often perceived that women in Asian countries have a lower rate of post-mastectomy reconstruction than Western populations. This study describes trends in timing and types of breast reconstruction performed in the largest healthcare provider in Singapore, over a period of 12 years. It also reports on the oncological outcomes and surgical safety. A retrospective review of all patients who underwent post-mastectomy reconstruction from January 2001 to December 2012 at the National Cancer Centre Singapore and Singapore General Hospital was performed. Six hundred and twenty post-mastectomy reconstructions were performed in 579 patients. The proportion of reconstructions increased from 4% in 2001 to 18% in 2012. Younger patients (<50 years old) and those with early stage cancer were more likely to undergo reconstruction. Immediate breast reconstruction was favored by more than 90% of patients. Postoperatively, 9% developed acute surgical complications that were treated surgically; 6% had additional surgery for late complications. Only 4% had delay of adjuvant chemotherapy. At median follow-up of 63 months (range 3-166), loco-regional recurrence was 4%, and distant metastases 8%. Post-mastectomy reconstruction for breast cancer is increasingly performed in our institution. Both younger age and lower stage disease were associated with choice for reconstruction in our study. Low rates of delay to adjuvant therapy were noted, and it may safely be offered to suitable women undergoing mastectomy.

Effectiveness of the 'Home-but not Alone' mobile health application educational programme on parental outcomes: a randomized controlled trial, study protocol.

AIMS: The aim of this study was to describe a study protocol that evaluates the effectiveness of the 'Home-but not Alone' educational programme delivered via a mobile health application in improving parenting outcomes. BACKGROUND: The development in mobile-based technology gives us the opportunity to develop an accessible educational programme that can be potentially beneficial to new parents. However, there is a scarcity of theory-based educational programmes that have incorporated technology such as a mobile health application in the early postpartum period. DESIGN: A randomized controlled trial with a two-group pre-test and post-test design. METHODS: The data will be collected from 118 couples. Eligible parents will be randomly allocated to either a control group (receiving routine care) or an intervention group (routine care plus access to the 'Home-but not Alone' mobile health application. Outcome measures comprise of parenting self-efficacy, social support, parenting satisfaction and postnatal depression. Data will be collected at the baseline (on the day of discharge) and at four weeks postpartum. DISCUSSION: This will be an empirical study that evaluates a theory-based educational programme delivered via an innovative mobile health application on parental outcomes. Results from this study will enhance parenting self-efficacy, social support and parenting satisfaction, which may then reduce parental risks of postnatal depression.

Selective insulin resistance in adipocytes.

Aside from glucose metabolism, insulin regulates a variety of pathways in peripheral tissues. Under insulin-resistant conditions, it is well known that insulin-stimulated glucose uptake is impaired, and many studies attribute this to a defect in Akt signaling. Here we make use of several insulin resistance models, including insulin-resistant 3T3-L1 adipocytes and fat explants prepared from high fat-fed C57BL/6J and ob/ob mice, to comprehensively distinguish defective from unaffected aspects of insulin signaling and its downstream consequences in adipocytes. Defective regulation of glucose uptake was observed in all models of insulin resistance, whereas other major actions of insulin such as protein synthesis and anti-lipolysis were normal. This defect corresponded to a reduction in the maximum response to insulin. The pattern of change observed for phosphorylation in the Akt pathway was inconsistent with a simple defect at the level of Akt. The only Akt substrate that showed consistently reduced phosphorylation was the RabGAP AS160 that regulates GLUT4 translocation. We conclude that insulin resistance in adipose tissue is highly selective for glucose metabolism and likely involves a defect in one of the components regulating GLUT4 translocation to the cell surface in response to insulin.

Novel systems for dynamically assessing insulin action in live cells reveals heterogeneity in the insulin response.

Regulated GLUT4 trafficking is a key action of insulin. Quantitative stepwise analysis of this process provides a powerful tool for pinpointing regulatory nodes that contribute to insulin regulation and insulin resistance. We describe a novel GLUT4 construct and workflow for the streamlined dissection of GLUT4 trafficking; from simple high throughput screens to high resolution analyses of individual vesicles. We reveal single cell heterogeneity in insulin action highlighting the utility of this approach - each cell displayed a unique and highly reproducible insulin response, implying that each cell is hard-wired to produce a specific output in response to a given stimulus. These data highlight that the response of a cell population to insulin is underpinned by extensive heterogeneity at the single cell level. This heterogeneity is pre-programmed within each cell and is not the result of intracellular stochastic events.

A Case of Inadequately Treated Bacterial Pneumonia Leading to Bronchopleural Fistula.

Bronchopulmonary fistula (BPF) is an abnormal connection between the pleural space and bronchial tree, potentially leading to fatal outcomes if untreated. While BPF commonly arises following lung surgery, it can also be linked to infections. This report details the case of a 47-year-old male with recent untreated bacterial pneumonia, who developed bilateral pneumothoraces with persistent air leaks, Pseudomonas and Aspergillus empyema, culminating in a right-sided BPF necessitating video-assisted thoracic surgery (VATS) decortication. The agenda of this presentation is to enhance early recognition of BPF, which can be presented subtly, to avert severe complications.

Familial occurrence of imperforate hymen in premature monozygotic twins and their mother: a case report and literature review.

Background: Imperforate hymen is an uncommon obstructive anomaly of the developing female reproductive tract. There are occasional case reports of imperforate hymen occurring in family clusters, suggesting a plausible familial mode of inheritance. We describe a set of monozygotic premature twins with imperforate hymen noted at birth, whose mother was diagnosed with the same condition as a teenager. We also elucidate the likely underlying mode of inheritance of imperforate hymen. Method: We utilized the CARE (Case Report) guideline in reporting the cases. Case presentation: These are monozygotic twins born prematurely at 30 weeks of gestation, noted at birth to have bulging cyst-like structures protruding from their vaginas. The twins were not dysmorphic and did not have any other congenital malformations. Over the next few weeks, these cyst-like structures (mucoceles) became less prominent. The genital anomaly was diagnosed as imperforate hymen. Their mother was also diagnosed with an imperforate hymen when she was 12 years old and was treated with hymenectomy. Discussion: This unique occurrence of imperforate hymen in a set of premature monozygotic twins and their mother suggests a plausible autosomal or X-linked dominant mode of inheritance. Given the role of genetic inheritance in imperforate hymen development, it is important to screen female relatives of an index case for this genital anomaly.

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.

High-flow nasal oxygen therapy compared with conventional oxygen therapy in hospitalised patients with respiratory illness: a systematic review and meta-analysis.

BACKGROUND: High-flow nasal oxygen therapy (HFNO) is used in diverse hospital settings to treat patients with acute respiratory failure (ARF). This systematic review aims to summarise the evidence regarding any benefits HFNO therapy has compared with conventional oxygen therapy (COT) for patients with ARF. METHODS: Three databases (Embase, Medline and CENTRAL) were searched on 22 March 2023 for studies evaluating HFNO compared with COT for the treatment of ARF, with the primary outcome being hospital mortality and secondary outcomes including (but not limited to) escalation to invasive mechanical ventilation (IMV) or non-invasive ventilation (NIV). Risk of bias was assessed using the Cochrane risk-of-bias tool (randomised controlled trials (RCTs)), ROBINS-I (non-randomised trials) or Newcastle-Ottawa Scale (observational studies). RCTs and observational studies were pooled together for primary analyses, and secondary analyses used RCT data only. Treatment effects were pooled using the random effects model. RESULTS: 63 studies (26 RCTs, 13 cross-over and 24 observational studies) were included, with 10 230 participants. There was no significant difference in the primary outcome of hospital mortality (risk ratio, RR 1.08, 95% CI 0.93 to 1.26; p=0.29; 17 studies, n=5887) between HFNO and COT for all causes ARF. However, compared with COT, HFNO significantly reduced the overall need for escalation to IMV (RR 0.85, 95% CI 0.76 to 0.95 p=0.003; 39 studies, n=8932); and overall need for escalation to NIV (RR 0.70, 95% CI 0.50 to 0.98; p=0.04; 16 studies, n=3076). In subgroup analyses, when considering patients by illness types, those with acute-on-chronic respiratory failure who received HFNO compared with COT had a significant reduction in-hospital mortality (RR 0.58, 95% CI 0.37 to 0.91; p=0.02). DISCUSSION: HFNO was superior to COT in reducing the need for escalation to both IMV and NIV but had no impact on the primary outcome of hospital mortality. These findings support recommendations that HFNO may be considered as first-line therapy for ARF. PROSPERO REGISTRATION NUMBER: CRD42021264837.