The incremental yield of prenatal exome sequencing over chromosome microarray for congenital heart abnormalities: A systematic review and meta-analysis.

OBJECTIVES: To determine the incremental yield of prenatal exome sequencing (PES) over standard testing in fetuses with an isolated congenital heart abnormality (CHA), CHA associated with extra-cardiac malformations (ECMs) and CHA dependent upon anatomical subclassification. METHODS: A systematic review of the literature was performed using MEDLINE, EMBASE, Web of Science and grey literature January 2010-February 2023. Studies were selected if they included greater than 20 cases of prenatally diagnosed CHA when standard testing (QF-PCR/chromosome microarray/karyotype) was negative. Pooled incremental yield was determined. PROSPERO CRD 42022364747. RESULTS: Overall, 21 studies, incorporating 1957 cases were included. The incremental yield of PES (causative pathogenic and likely pathogenic variants) over standard testing was 17.4% (95% CI, 13.5%-21.6%), 9.3% (95% CI, 6.6%-12.3%) and 35.9% (95% CI, 21.0%-52.3%) for all CHAs, isolated CHAs and CHAs associated with ECMs. The subgroup with the greatest yield was complex lesions/heterotaxy; 35.2% (95% CI 9.7%-65.3%). The most common syndrome was Kabuki syndrome (31/256, 12.1%) and most pathogenic variants occurred de novo and in autosomal dominant (monoallelic) disease causing genes (114/224, 50.9%). CONCLUSION: The likelihood of a monogenic aetiology in fetuses with multi-system CHAs is high. Clinicians must consider the clinical utility of offering PES in selected isolated cardiac lesions.

COVID-19 vaccination and transmission patterns among pregnant and postnatal women during the fifth wave of COVID-19 in a tertiary hospital in Hong Kong.

INTRODUCTION: Vaccination is a key strategy to control the coronavirus disease 2019 (COVID-19) pandemic. Safety concerns strongly influence vaccine hesitancy. Disease transmission during pregnancy could exacerbate risks of preterm birth and perinatal mortality. This study examined patterns of vaccination and transmission among pregnant and postnatal women during the fifth wave of COVID-19 in Hong Kong. METHODS: The Antenatal Record System and Clinical Management System of the Hospital Authority was used to retrieve information concerning the demographic characteristics, vaccination history, COVID-19 status, and obstetric outcomes of women who were booked for delivery at Queen Mary Hospital in Hong Kong and had attended the booking antenatal visit from 1 July 2021 to 30 June 2022. RESULTS: Among 2396 women in the cohort, 2006 (83.7%), 1843 (76.9%), and 831 (34.7%) had received the first, second, and third doses of COVID-19 vaccine, respectively. Among 1012 women who had received the second dose, 684 (67.6%) women were overdue for their third dose. There were 265 (11.1%) reported COVID-19 cases. Women aged 20 to 29 years had a low vaccination rate but the highest disease rate (19.1%). The disease rate was more than tenfold higher in women who had no (20.3%) or incomplete (18.8%) vaccination, compared with women who had complete vaccination (2.1%; P<0.001). CONCLUSION: Acceptance of COVID-19 vaccination was low in pregnant women. Urgent measures are needed to promote vaccination among pregnant women before the next wave of COVID-19.

The role of high-risk HPV testing in cervical cancer surveillance.

OBJECTIVES: While high-risk HPV (hrHPV) testing is not formally recommended as a surveillance modality in patients with a history of cervical cancer, it is often performed in routine practice. It is unclear whether the presence of hrHPV infection after cervical cancer treatment is associated with recurrent disease. METHODS: Patients with a cervical cancer diagnosis who were seen in a single institution between May 2012 and December 2019 were retrospectively identified. Squamous cell, adenocarcinoma, adenosquamous, and neuroendocrine histologies were included. Those with cancer progression within 3 months of treatment or < 1 year of documented surveillance were excluded. Patients who had hrHPV testing performed were included in the primary outcome analysis. RESULTS: Of the 262 patients meeting inclusion criteria, 58 (22%) recurrences were diagnosed, and recurrence was most commonly detected by a surveillance imaging study (71%). Among the 169 patients that were tested for hrHPV during the surveillance period, 41 (24%) had at least one positive hrHPV test. Recurrent disease was diagnosed in 24 (14%). Of the 24 patients with recurrent disease, 5 (21%) had at least one positive hrHPV test during surveillance, versus 36 (24%) of 145 patients without recurrent disease (p = 0.67). No recurrences were detected by hrHPV testing. CONCLUSIONS: Positive hrHPV testing in the surveillance setting was not associated with cervical cancer recurrence but did lead to additional studies and procedures. Our findings do not support the routine use of hrHPV testing for the evaluation of cervical cancer recurrence.

Impact of seed-applied pesticides on rhizobial survival and legume nodulation.

AIMS: Compatibility of seed-applied pesticides and rhizobial inoculants is an important consideration for farmers when sowing legumes. Some of the seed-applied pesticides may influence rhizobial growth and nodulation, but there is currently little available information on the potential inhibitory effects. Therefore, common seed fungicidal and insecticidal treatments were assessed to determine adverse impacts on rhizobial inoculants both in vitro, on treated seed, and in the field. METHODS AND RESULTS: Initially, the in vitro toxicity of the seed-applied fungicides Thiram 600, P-Pickel T (PPT), their active ingredients (thiram and thiabendazole) and the insecticide Gaucho to rhizobia was measured with filter discs containing varying concentrations of the pesticides. Pea and chickpea seed was then coated with the same pesticides and inoculated with rhizobia in different inoculant substrates to determine bacterial survival and nodulation. Finally, a field trial using the fungicide PPT and commercial inoculants was conducted. Some seed fungicide treatments were found to be inhibitory to rhizobia and reduce nodulation under monoxenic conditions and in the field. SIGNIFICANCE AND IMPACT OF THE STUDY: These data provide more detailed information on the compatibility of specific rhizobial inoculants with common seed-applied pesticides. This research will provide information on the compatibility of rhizobia and seed-applied pesticides, and assist farmers to select sowing practices which reduce the risk of crop nodulation failures.

[An epidemiologic study of pelvic organ prolapse in urban Chinese women: a population-based sample in China].

Objective: This study aimed to assess the prevalence and factors associated with pelvic organ prolapse (POP) in a representative sample of Chinese urban women. Methods: A total of 29613 Chinese urban women were recruited to this cross-sectional study between February 2014 and March 2016. The prevalence of POP, defined as any stage Ⅱ or higher POP resulting in symptoms, was assessed using questionnaires and physical examinations. Multivariable logistic regression was used to assess factors associated with POP. Results: 2 864 of 29 613 women (9.67%) had POP. The prevalence of POP increased with age ranging from 1.23% (82/6 646) of women aged between 20 and 29 years to 26.11% (727/2 784) for those aged 70 years or older (P<0.000 1). Overweight and obese women were more likely to have POP than normal weight women [AOR=1.56, 95%CI 1.42-1.72 vs AOR=1.74, 95%CI 1.48-2.03]. In the multivariate analysis, the independent risk factors were cough (AOR=1.70, 95%CI 1.44-2.02), constipation (AOR=2.05, 95%CI 1.82-2.32), physical disease (AOR=1.27, 95%CI 1.15-1.41), and gynecological diseases (AOR=2.08, 95%CI 1.89-2.29). Nulliparous (AOR=0.12, 95%CI 0.06-0.22) and caesarean section (CS) (AOR=0.55, 95%CI 0.47-0.64) were protective factors for POP. Conclusions: POP affects nearly 10% of women in Chinese urban region. The prevalence of POP increases significantly with age. The independent risk factors for POP are body mass index, cough, constipation, physical disease and gynecological diseases. Nulliparous and CS are protective factors for POP.

Repeatability of vessel density measurement in human skin by OCT-based microangiography.

PURPOSE: To investigate the repeatability of vessel density measurement at human arm skin in healthy subjects with OCT-based microangiography (OMAG). METHODS: Four locations including volar wrist, volar forearm, shoulder, and volar upper arm were scanned using an optimized swept source OCT system, working at center wavelength of 1300 nm and A-line rate of 100 kHz. Three scans were acquired at each location at the same visit. Vascular images of papillary dermis, reticular dermis, and the whole dermis layer were generated with OMAG processing and automatic segmentation algorithms. The vessel density (VD) of each layer was calculated based on vascular images, and the repeatability of the VD at the same physiological location was thereafter assessed. RESULTS: Fifteen healthy volunteers were included. High repeatability of VD was found for wrist, forearm, shoulder, and upper arm (coefficient of variation (CV)=2.4, 2.7, 2.7, 2.0, and intraclass correlation coefficient (ICC)=0.906, 0.854, 0.943, 0.916 respectively). The VD measurements showed no significant difference between the four locations in any of the three layers, ie papillary layer (P=.1063), reticular layer (P=.3371), and whole dermis layer (P=.3233). CONCLUSION: Quantification of VD by using OCT/OMAG is repeatable when imaging skin tissue beds in healthy individuals.

Pathological outcome for Chinese patients with low-risk prostate cancer eligible for active surveillance and undergoing radical prostatectomy: comparison of six different active surveillance protocols.

INTRODUCTION: Active surveillance is one of the therapeutic options for the management of patients with low-risk prostate cancer. This study compared the performance of six different active surveillance protocols for prostate cancer in the Chinese population. METHODS: Patients who underwent radical prostatectomy for prostate cancer from January 1998 to December 2012 at a university teaching hospital in Hong Kong were reviewed. Six active surveillance protocols were applied to the cohort. Statistical analyses were performed to compare the probabilities of missing unfavourable pathological outcome. The sensitivity and specificity of each protocol in identifying low-risk disease were compared. RESULTS: During the study period, 287 patients were included in the cohort. Depending on different active surveillance protocols used, extracapsular extension, seminal vesicle invasion, pathological T3 disease, and upgrading of Gleason score were present on final pathology in 3.3%-17.1%, 0%-3.3%, 3.3%-19.1%, and 20.6%-34.5% of the patients, respectively. The University of Toronto protocol had a higher rate of extracapsular extension at 17.1% and pathological T3 disease at 19.1% on final pathology than the more stringent protocols from John Hopkins (3.3% extracapsular extension, P=0.05 and 3.3% pathological T3 disease, P=0.03) and Prostate Cancer Research International: Active Surveillance (PRIAS; 8.0% pathological T3 disease, P=0.04). The Royal Marsden protocol had a higher rate of upgrading of Gleason score at 34.5% compared with the more stringent protocol of PRIAS at 20.6% (P=0.04). The specificities in identifying localised disease and low-risk histology among different active surveillance protocols were 59%-98% and 58%-94%, respectively. The John Hopkins active surveillance protocol had the highest specificity in both selecting localised disease (98%) and low-risk histology (94%). CONCLUSIONS: Active surveillance protocols based on prostate-specific antigen and Gleason score alone or including Gleason score of 3+4 may miss high-risk disease and should be used cautiously. The John Hopkins and PRIAS protocols are highly specific in identifying localised disease and low-risk histology.

Partial nephrectomy for T1 renal cancer can achieve an equivalent oncological outcome to radical nephrectomy with better renal preservation: the way to go.

INTRODUCTION: Patients who undergo partial nephrectomy have been shown to be at decreased risk of renal impairment compared with radical nephrectomy. We examined the oncological outcome of patients in our centre who underwent partial or radical nephrectomy for T1 renal cancer (7 cm or smaller), and compared the likelihood of developing chronic kidney disease. METHODS: This historical cohort study with internal comparison was conducted in a tertiary hospital in Hong Kong. A cohort of 86 patients with solitary T1 renal cancer and a normal contralateral kidney who underwent radical (38 patients) or partial (48 patients) nephrectomy between January 2005 and December 2010 was included. The overall and cancer-free survival, change in glomerular filtration rate, and new onset of chronic kidney disease were compared between the radical and partial nephrectomy groups. RESULTS: A total of 32 (84%) radical nephrectomy patients and 43 (90%) partial nephrectomy patients were alive by 31 December 2012. The mean follow-up was 43.5 (standard deviation, 22.4) months. There was no significant difference in overall survival (P=0.29) or cancer-free survival (P=0.29) between the two groups. Both groups enjoyed good oncological outcome with no recurrence in the partial nephrectomy group. Overall, 18 (21%) patients had pre-existing chronic kidney disease. The partial nephrectomy group had a significantly smaller median reduction in glomerular filtration rate (12.6% vs 35.4%; P<0.001), and radical nephrectomy carried a significantly higher risk of developing chronic kidney disease (hazard ratio=5.44; 95% confidence interval, 1.26-23.55; P=0.02). CONCLUSIONS: Compared with radical nephrectomy, partial nephrectomy can prevent chronic kidney disease and still achieve an excellent oncological outcome for T1 renal tumours, in particular T1a tumours and tumours with a low R.E.N.A.L. score.

Anorexia nervosa and body dysmorphic disorder are associated with abnormalities in processing visual information.

BACKGROUND: Anorexia nervosa (AN) and body dysmorphic disorder (BDD) are characterized by distorted body image and are frequently co-morbid with each other, although their relationship remains little studied. While there is evidence of abnormalities in visual and visuospatial processing in both disorders, no study has directly compared the two. We used two complementary modalities--event-related potentials (ERPs) and functional magnetic resonance imaging (fMRI)--to test for abnormal activity associated with early visual signaling. METHOD: We acquired fMRI and ERP data in separate sessions from 15 unmedicated individuals in each of three groups (weight-restored AN, BDD, and healthy controls) while they viewed images of faces and houses of different spatial frequencies. We used joint independent component analyses to compare activity in visual systems. RESULTS: AN and BDD groups demonstrated similar hypoactivity in early secondary visual processing regions and the dorsal visual stream when viewing low spatial frequency faces, linked to the N170 component, as well as in early secondary visual processing regions when viewing low spatial frequency houses, linked to the P100 component. Additionally, the BDD group exhibited hyperactivity in fusiform cortex when viewing high spatial frequency houses, linked to the N170 component. Greater activity in this component was associated with lower attractiveness ratings of faces. CONCLUSIONS: Results provide preliminary evidence of similar abnormal spatiotemporal activation in AN and BDD for configural/holistic information for appearance- and non-appearance-related stimuli. This suggests a common phenotype of abnormal early visual system functioning, which may contribute to perceptual distortions.

Hospital Authority audit of the outcome of endoscopic resection of superficial upper gastro-intestinal lesions in Hong Kong.

OBJECTIVES: To review the short-term outcome of endoscopic resection of superficial upper gastro-intestinal lesions in Hong Kong. DESIGN: Historical cohort study. SETTING: All Hospital Authority hospitals in Hong Kong. PATIENTS: This was a multicentre retrospective study of all patients who underwent endoscopic resection of superficial upper gastro-intestinal lesions between January 2010 and June 2013 in all government-funded hospitals in Hong Kong. MAIN OUTCOME MEASURES: Indication of the procedures, peri-procedural and procedural parameters, oncological outcomes, morbidity, and mortality. RESULTS: During the study period, 187 lesions in 168 patients were resected. Endoscopic mucosal resection was performed in 34 (18.2%) lesions and endoscopic submucosal dissection in 153 (81.8%) lesions. The mean size of the lesions was 2.6 (standard deviation, 1.8) cm. The 30-day morbidity rate was 14.4%, and perforations and severe bleeding occurred in 4.3% and 3.2% of the patients, respectively. Among patients who had dysplasia or carcinoma, R0 resection was achieved in 78% and the piecemeal resection rate was 11.8%. Lateral margin involvement was 14% and vertical margin involvement was 8%. Local recurrence occurred in 9% of patients and 15% had residual disease. The 2-year overall survival rate and disease-specific survival rate was 90.6% and 100%, respectively. CONCLUSION: Endoscopic mucosal resection and endoscopic submucosal dissection were introduced in low-to-moderate-volume hospitals with acceptable morbidity rates. The short-term survival was excellent. However, other oncological outcomes were higher than those observed in high-volume centres and more secondary procedures were required.

It's time to regulate - The importance of accurate surgical-grade tourniquet autoregulation in blood flow restriction exercise applications.

OBJECTIVE: Evaluate the efficacy of five common blood flow restriction (BFR) systems to accurately maintain and autoregulate BFR pressure in the tourniquet cuff near target pressure throughout exercise. DESIGN: Randomised crossover design. SETTING: Laboratory. PARTICIPANTS: 15 healthy individuals. OUTCOME MEASURES: 1) Percentage of total BFR time that surgical-grade tourniquet autoregulation, defined as automatic and rapid self-regulation of cuff pressure to within ±15 mmHg of initial target pressure within 1 s in the presence of transient pressure changes associated with exercise, was provided; 2) pressure change in the BFR cuff throughout exercise, by comparing the initial target pressure to the measured pressure at completion of BFR exercise. RESULTS: One BFR system could provide surgical-grade tourniquet autoregulation for the whole duration (100 ± 0%) of the BFR exercise in all subjects. In two of the five BFR systems evaluated, measured cuff pressure at the end of exercise was not different (p < 0.05) to the initial target pressure. CONCLUSIONS: Surgical-grade tourniquet autoregulation is important to consistently and reliably apply a targeted BFR pressure stimulus. This may allow BFR methodology and protocols to be accurately implemented and controlled so that the results can be more meaningfully compared, leading to the potential optimization of applications.

A rare partnership: patient community and industry collaboration to shape the impact of real-world evidence on the rare disease ecosystem.

People with rare lysosomal storage diseases face challenges in their care that arise from disease complexity and heterogeneity, compounded by many healthcare professionals being unfamiliar with these diseases. These challenges can result in long diagnostic journeys and inadequate care. Over 30 years ago, the Rare Disease Registries for Gaucher, Fabry, Mucopolysaccharidosis type I and Pompe diseases were established to address knowledge gaps in disease natural history, clinical manifestations of disease and treatment outcomes. Evidence generated from the real-world data collected in these registries supports multiple stakeholders, including patients, healthcare providers, drug developers, researchers and regulators. To maximise the impact of real-world evidence from these registries, engagement and collaboration with the patient communities is essential. To this end, the Rare Disease Registries Patient Council was established in 2019 as a partnership between the Rare Disease Registries and global and local patient advocacy groups to share perspectives on how registry data are used and disseminated. The Patient Council has resulted in a number of patient initiatives including patient representation at Rare Disease Registries advisory boards; development of plain language summaries of registry publications to increase availability of real-world evidence to patient communities; and implementation of digital innovations such as electronic patient-reported outcomes, and patient-facing registry reports and electronic consent (in development), all to enhance patient engagement. The Patient Council is building on the foundations of industry-patient advocacy group collaboration to fully integrate patient communities in decision-making and co-create solutions for the rare disease community.

[Genotype-phenotype analysis of Fabry disease caused by GLA gene variation in a pedigree].

Objective: To investigate the clinical phenotype and genetic characteristics of patients with Fabry disease caused by a GLA variant, IVS4+919G>A. Methods: It was a prospective study. Fabry disease screening was conducted among high-risk population in Ninghai from October 2021 to August 2023. Those children with decreased α-galactosidase enzyme activity<2.40 µmol/(L·h) or elavated Lyso-GL-3 level>1.10 µg/L in dried blood spot (DBS) method underwent GLA genetic testing for diagnosis confirmation. Meanwhile, family screening was carried out. A proband and his family members diagnosed with Fabry disease were research subjects. The clinical and genetic characteristics of patients with Fabry disease caused by the GLA variant (IVS4+919G>A) were analyzed. Results: The female proband aged 9.8 years with pain in both lower limbs as the initial symptom was found to have a heterozygous GLA variant IVS4+919G>A among 102 patients. In family screening, there were 4 family members (proband's father, elder sister, elder male cousin and elder female cousin) with Fabry disease and a family member (proband's fifth aunt) with a GLA variant. Among these 4 diagnosed family members, the elder male cousin of the proband, a boy aged 13.2 years had a heterozygous GLA variant, IVS4+919G>A with intermittent pain in both lower limbs as the initial symptom. The proband's father had knee joint pain. The proband's elder sister had decreased vision and his elder female cousin had no obvious symptoms. The proband's fifth aunt with a GLA variant had decreased vision. Conclusions: High-risk screening in children and family screening are helpful for early diagnosis and treatment of Fabry disease. Neuropathic pain may be a early symptom in children with Fabry disease caused by the GLA variant, IVS4+919G>A.

Effects of short-course oral corticosteroid therapy in early dengue infection in Vietnamese patients: a randomized, placebo-controlled trial.

BACKGROUND: Patients with dengue can experience a variety of serious complications including hypovolemic shock, thrombocytopenia, and bleeding. These problems occur as plasma viremia is resolving and are thought to be immunologically mediated. Early corticosteroid therapy may prevent the development of such complications but could also prolong viral clearance. METHODS: We performed a randomized, placebo-controlled, blinded trial of low-dose (0.5 mg/kg) or high-dose (2 mg/kg) oral prednisolone therapy for 3 days in Vietnamese patients aged 5-20 years admitted with dengue and fever for ≤72 hours, aiming to assess potential harms from steroid use during the viremic phase. Intention-to-treat analysis was performed using linear trend tests with a range of clinical and virological endpoints specified in advance. In addition to recognized complications of dengue, we focused on the are under the curve for serial plasma viremia measurements and the number of days after enrollment to negative viremia and dengue nonstructural protein 1 status. RESULTS: Between August 2009 and January 2011, 225 participants were randomized to 1 of the 3 treatment arms. Baseline characteristics were similar across the groups. All patients recovered fully and adverse events were infrequent. Aside from a trend toward hyperglycemia in the steroid recipients, we found no association between treatment allocation and any of the predefined clinical, hematological, or virological endpoints. CONCLUSIONS: Use of oral prednisolone during the early acute phase of dengue infection was not associated with prolongation of viremia or other adverse effects. Although not powered to assess efficacy, we found no reduction in the development of shock or other recognized complications of dengue virus infection in this study.

Low prevalence of major depressive disorder in Taiwanese adults: possible explanations and implications.

BACKGROUND: This study examined the prevalence of major depressive disorder (MDD), and the correlations and co-morbid conditions associated with MDD, in the adult Taiwanese population, which a previous estimate in the 1980s had found to be at the lower end of the spectrum worldwide. Possible explanations for the reported low prevalence of MDD were evaluated. METHOD: As part of a survey of common psychiatric disorders in a nationally representative sample of individuals aged ≥ 18 years who were non-institutionalized civilians in Taiwan, a face-to-face interview using the paper version of the World Mental Health Survey of the World Health Organization (WHO) Composite International Diagnostic Interview (WMH-CIDI) was conducted between 2003 and 2005. Functional impairment and help-seeking behaviors were compared between Taiwanese subjects with MDD and their counterparts in the USA. RESULTS: Among the 10 135 respondents, the lifetime prevalence of MDD was 1.20% [standard error (S.E.)=0.2%]. Individuals who were divorced or widowed, aged ≤ 40 years, and female were at increased risk, whereas rural residents were at lower risk for MDD. The proportion of MDD cases co-morbid with other psychiatric disorders in this study was much lower than in the US study. Only one-third of Taiwanese individuals with MDD sought help despite having twice the number of lost workdays compared with the US sample. CONCLUSIONS: Despite the low prevalence of MDD in Taiwanese adults, the pattern of low help-seeking behavior and profound functional impairment indicates much room for improvement in the early detection of and intervention in major depression in this population.