Evaluating compliance with the care standard of proactively assessing bone health in patients with diabetes: a pilot audit of practice across Asia by the Asia Pacific Consortium on Osteoporosis (APCO).

This pilot audit explored how bone health is assessed patients with diabetes in diverse centres across Asia. Only 343 of 1092 (31%) audited patients had a bone health assessment, 27% of whom were diagnosed with osteoporosis. Quality improvement strategies are needed to address gaps in patient care in this area. PURPOSE: The Asia Pacific Consortium on Osteoporosis (APCO) Framework outlines clinical standards for assessing and managing osteoporosis. A pilot audit evaluated adherence to clinical standard 4, which states that bone health should be assessed in patients with conditions associated with bone loss and/or increased fracture risk; this report summarises the audit findings in patients with diabetes. A secondary aim was to assess the practicality and real-world use of the APCO bone health audit tool kit. METHODS: Eight centres across Asia participated in the pilot audit, selecting diabetes as the target group. Participants reviewed their practice records for at least 20 consecutively treated patients with the target condition. Questions covered routine investigations, bone health assessment, osteoporosis diagnosis, and patient referral pathways. Data were summarised descriptively. RESULTS: The participants represented public hospitals, university medical centres, and private clinics from India, Malaysia, Pakistan, Singapore, Taiwan, and Vietnam that see an estimated total of 95,000 patients with diabetes per year. Overall, only 343 of 1092 audited patients (31%) had a bone health assessment. Osteoporosis was subsequently diagnosed in 92 of 343 (27%) patients. CONCLUSION: Bone health was not assessed in most patients with diabetes. The results provide insight into current practices across diverse Asian centres and demonstrate the practical value of the audit tool kit. Participant feedback has been used to improve the tool kit. Results of this pilot audit are being used in the respective centres to inform quality improvement projects needed to overcome the gap in patient care.

Healthy Eating Report Card for Pre-school Children in Hong Kong.

INTRODUCTION: This study aimed to develop the Healthy Eating Report Card for Pre-school Children in Hong Kong for evaluating the prevalence of healthy eating behaviours and favourable family home food environments (FHFEs) among pre-school children in Hong Kong. METHODS: In this cross-sectional study, 538 parent-child dyads from eight kindergartens in Hong Kong were recruited. Parents or guardians completed a questionnaire comprising Report Card items. The Report Card included two indicators of Children's Eating Behaviours (ie, Children's Dietary Patterns and Children's Mealtime Behaviours) and three indicators of FHFEs (ie, Parental Food Choices and Preparation, Avoidance of Unhealthy Foods, and Family Mealtime Environments). Each indicator and its specific items were assigned a letter grade representing the percentage of participants achieving the predefined benchmarks. The grades were defined as A (≥80%, Excellent); B (60%-79%, Good); C (40%-59%, Fair); D (20%-39%, Poor); and F (<20%, Very poor). Plus (+) and minus (-) signs were used to indicate the upper or lower 5% of each grade. RESULTS: Overall, Children's Eating Behaviours were classified as Fair (average grade of 'C'), whereas FHFEs were classified as Good (average grade of 'B'). The sub-grades ranged from 'C' to 'A-', as follows: Children's Dietary Patterns, 'C+'; Children's Mealtime Behaviours, 'C'; Parental Food Choices and Preparation, 'C+'; Avoidance of Unhealthy Foods, 'B'; and Family Mealtime Environments, 'A-'. CONCLUSION: The findings highlight areas for improvement in healthy eating among children. The Healthy Eating Report Card could offer novel insights into intervention tools that promote healthy eating.

PRMT1 promotes epigenetic reprogramming associated with acquired chemoresistance in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) carries a dismal prognosis due to therapeutic resistance. We show that PDAC cells undergo global epigenetic reprogramming to acquire chemoresistance, a process that is driven at least in part by protein arginine methyltransferase 1 (PRMT1). Genetic or pharmacological PRMT1 inhibition impairs adaptive epigenetic reprogramming and delays acquired resistance to gemcitabine and other common chemo drugs. Mechanistically, gemcitabine treatment induces translocation of PRMT1 into the nucleus, where its enzymatic activity limits the assembly of chromatin-bound MAFF/BACH1 transcriptional complexes. Cut&Tag chromatin profiling of H3K27Ac, MAFF, and BACH1 suggests a pivotal role for MAFF/BACH1 in global epigenetic response to gemcitabine, which is confirmed by genetically silencing MAFF. PRMT1 and MAFF/BACH1 signature genes identified by Cut&Tag analysis distinguish gemcitabine-resistant from gemcitabine-sensitive patient-derived xenografts of PDAC, supporting the PRMT1-MAFF/BACH1 epigenetic regulatory axis as a potential therapeutic avenue for improving the efficacy and durability of chemotherapies in patients of PDAC.

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.

A clinico-radiological review of chronic non-bacterial osteomyelitis in paediatrics, adolescents, and adults: demystifying a forgotten differential.

Chronic non-bacterial osteomyelitis (CNO), also known as non-bacterial osteitis, is a chronic autoinflammatory disease of unknown aetiology that primarily occurs in the paediatric population, although rare cases of adult-onset disease also exist. CNO has non-specific clinical and radiological presentations, and the affected population often present with bone pain of insidious onset secondary to sterile bony inflammation that can be associated with swelling, focal tenderness, and warmth at the affected sites. The pattern of bony involvement appears to be dependent on the age of onset, with adults frequently having axial skeletal lesions and children and adolescents often being affected in the appendicular skeletal sites. CNO is a diagnosis of exclusion, and imaging is heavily relied on to identify and characterise the bony lesions in addition to exclude diseases that can mimic CNO. Magnetic resonance imaging is often the reference standard with biochemical and histopathological findings being complementary. Although combining imaging methods can be used to facilitate the diagnosis, a single technique could be adequate depending on the clinical picture. Given the relatively rare incidence of CNO, limited awareness of the disease among care providers, and its similarity in clinical and radiological presentation to various bony diseases, there are often long delays in diagnosis, with adults being unfavourably affected compared to paediatrics and adolescents. This review of CNO will describe the condition, overview its clinical presentation, highlight the radiological features, and emphasise clinical pearls that can aid in diagnosis and ruling out the mimics.

Factors Influencing the Utilisation of Mammography Among Ethnic Minorities: A Framework-Driven Systematic Review and Meta-Analysis.

Ethnic minority women experience disparities in mammography screening utilisation and breast cancer outcomes. This systematic review and meta-analysis synthesised multidomain and multilevel factors that intersect to influence the utilisation of mammography among ethnic minorities. A literature search was conducted in five databases (PubMed, Ovid MEDLINE, EMBASE, CINAHL, and PsycINFO) from inception to May 2022. Guided by the National Institute on Minority Health and Health Disparity research framework, the retrieved data were synthesised using narrative summaries and meta-analyses. Among the 27 studies, most (n = 24) reported individual, interpersonal, and community factors in the health care system domain. In the sociocultural domain, interpersonal and societal (n = 8) factors, such as modesty and karma beliefs, were less frequently identified than individual (n = 20) factors in relation to acculturation. Only individual-level factors were reported for the biological and physical/built environment (e.g., rural residence) domains. In the behavioural domain, cancer screening behaviours had a high combined prediction ability (odds ratio = 18.23; I2 = 23%), whereas interpersonal (e.g., family obligations) and community (e.g., neighbourhood violence) factors discouraged mammography screening. Special focus should be given to ethnic minority women, especially those living in rural areas, those with considerable family obligations, and those who have suffered from violence and other life pressures, to increase their access to mammography services. Multidomain and multilevel efforts, culturally appropriate strategies, and equity-advancing policies such as geographic access and insurance coverage would help to mitigate the ethnic disparities in mammography screening.

Transhepatic versus transperitoneal approach in percutaneous cholecystostomy: a meta-analysis.

AIM: To determine whether the transhepatic or transperitoneal approach is the optimal percutaneous cholecystostomy approach. MATERIALS AND METHODS: A systematic review and meta-analysis was undertaken in which the Medline, EMBASE, and PubMed databases were searched for studies that compared both approaches in patients undergoing percutaneous cholecystostomy. Statistical analysis of dichotomous variables was carried out using odds ratio as the summary statistic. RESULTS: Four studies totalling 684 patients (396 [58%] males, mean age 74 years) who had undergone percutaneous cholecystostomy via the transhepatic (n=367) and transperitoneal (n=317) approach were analysed. Although the overall risk of bleeding was low (4.1%), it was significantly higher in the transhepatic approach compared with the transperitoneal approach (6.3% versus 1.6% respectively, odds ratio = 4.02 [1.56, 10.38]; p=0.004). There were no significant differences in pain, bile leak, tube-related complications, wound infection, or abscess formation between the approaches. CONCLUSION: Percutaneous cholecystostomy can be performed safely and successfully via the transhepatic and transperitoneal approaches. Although the overall rate of bleeding was significantly higher with the transhepatic approach, there were confounding factors due to technical differences between the studies. The small number of the included studies, in addition to variability of the definitions of outcomes, imposed other limitations. Further large-volume cases series and ideally a randomised trial with well-defined outcomes are required to confirm these findings.

Single-centre experience with peptide receptor radionuclide therapy for neuroendocrine tumours (NETs): results using a theranostic molecular imaging-guided approach.

AIM: To summarise our centre's experience managing patients with neuroendocrine tumours (NETs) in the first 5 years after the introduction of peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-DOTA-octreotate (LUTATE). The report emphasises aspects of the patient management related to functional imaging and use of radionuclide therapy. METHODS: We describe the criteria for treatment with LUTATE at our centre, the methodology for patient selection, and the results of an audit of clinical measures, imaging results and patient-reported outcomes. Subjects are treated initially with four cycles of ~ 8 GBq of LUTATE administered as an outpatient every 8 weeks. RESULTS: In the first 5 years offering LUTATE, we treated 143 individuals with a variety of NETs of which approx. 70% were gastroentero-pancreatic in origin (small bowel: 42%, pancreas: 28%). Males and females were equally represented. Mean age at first treatment with LUTATE was 61 ± 13 years with range 28-87 years. The radiation dose to the organs considered most at risk, the kidneys, averaged 10.6 ± 4.0 Gy in total. Median overall survival (OS) from first receiving LUTATE was 72.5 months with a median progression-free survival (PFS) of 32.3 months. No evidence of renal toxicity was seen. The major long-term complication seen was myelodysplastic syndrome (MDS) with a 5% incidence. CONCLUSIONS: LUTATE treatment for NETs is a safe and effective treatment. Our approach relies heavily on functional and morphological imaging informing the multidisciplinary team of NET specialists to guide appropriate therapy, which we suggest has contributed to the favourable outcomes seen.

Osteoarthritis year in review 2022: Genetics, genomics and epigenetics.

This "year in review" provides a summary of the research findings on the topic of genetics, genomics and epigenetics for osteoarthritis (OA) between Mar 2021-Apr 2022. A search routine of the literature in PubMed for the keyword, osteoarthritis, together with topics on genetics, genomics, epigenetics, polymorphism, Deoxyribonucleic acid (DNA) methylation, noncoding RNA, lncRNA, proteomics, and single cell RNA sequencing, returned key research articles and relevant reviews. Following filtering of duplicates across search routines, 695 unique research articles and 112 reviews were identified. We manually curated these articles and selected 90 as references for this review. However, we were unable to refer to all these articles, and only used selected articles to highlight key outcomes and trends. The trend in genetics is on the meta-analysis of existing cohorts with comparable genetic and phenotype characterization of OA; in particular, clear definition of sub phenotypes to enhance the genetic power. Further, many researchers are realizing the power of big data and multi-omics approaches to gain molecular insights for OA, and this has opened innovative approaches to include transcriptomics and epigenetics data as quantitative trait loci (QTLs). Given that most of the genetic loci for OA are not located within coding regions of genes, implying the impact is likely to be on gene regulation, epigenetics is a hot topic, and there is a surge in studies relating to the role of miRNA and long non-coding RNA on cartilage biology and pathology. The findings are exciting and new insights are provided in this review to summarize a year of research and the road map to capture all new innovations to achieve the desired goal in OA prevention and treatment.

SARS-CoV-2 and male infertility: from short- to long-term impacts.

PURPOSE: The coronavirus 2019 (COVID-19) pandemic-caused by a new type of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-has posed severe impacts on public health worldwide and has resulted in a total of > 6 million deaths. Notably, male patients developed more complications and had mortality rates ~ 77% higher than those of female patients. The extensive expression of the SARS-CoV-2 receptor and related proteins in the male reproductive tract and the association of serum testosterone levels with viral entry and infection have brought attention to COVID-19's effects on male fertility. METHODS: The peer-reviewed articles and reviews were obtained by searching for the keywords SARS-CoV-2, COVID-19, endocrine, spermatogenesis, epididymis, prostate, and vaccine in the databases of PubMed, Web of Science and Google Scholar from 2020-2022. RESULTS: This review summarizes the effects of COVID-19 on the male reproductive system and investigates the impact of various types of SARS-CoV-2 vaccines on male reproductive health. We also present the underlying mechanisms by which SARS-CoV-2 affects male reproduction and discuss the potentially harmful effects of asymptomatic infections, as well as the long-term impact of COVID-19 on male reproductive health. CONCLUSION: COVID-19 disrupted the HPG axis, which had negative impacts on spermatogenesis and the epididymis, albeit further investigations need to be performed. The development of vaccines against various SARS-CoV-2 variations is important to lower infection rates and long-term COVID risks.

Spontaneously evolved progenitor niches escape Yap oncogene addiction in advanced pancreatic ductal adenocarcinomas.

Lineage plasticity has been proposed as a major source of intratumoral heterogeneity and therapeutic resistance. Here, by employing an inducible genetic engineered mouse model, we illustrate that lineage plasticity enables advanced Pancreatic Ductal Adenocarcinoma (PDAC) tumors to develop spontaneous relapse following elimination of the central oncogenic driver - Yap. Transcriptomic and immunohistochemistry analysis of a large panel of PDAC tumors reveals that within high-grade tumors, small niches of PDAC cells gradually evolve to re-activate pluripotent transcription factors (PTFs), which lessen their dependency on Yap. Comprehensive Cut&Tag analysis demonstrate that although acquisition of PTF expression is coupled with the process of epithelial-to-mesenchymal transition (EMT), PTFs form a core transcriptional regulatory circuitry (CRC) with Jun to overcome Yap dependency, which is distinct from the classic TGFb-induced EMT-TF network. A chemical-genetic screen and follow-up functional studies establish Brd4 as an epigenetic gatekeeper for the PTF-Jun CRC, and strong synergy between BET and Yap inhibitors in blocking PDAC growth.

Implementation of ovarian tissue cryopreservation in Hong Kong.

INTRODUCTION: Worldwide, >130 babies have been born from ovarian tissue cryopreservation (OTC) and ovarian tissue transplantation (OTT). Ovarian tissue cryopreservation can improve quality of life among young female cancer survivors. Here, we assessed the feasibility of OTC and subsequent OTT in Hong Kong via xenografts in nude mice. METHODS: This pilot study was conducted in a university-affiliated tertiary hospital. Fifty-two ovarian tissues were collected from 12 patients aged 29 to 41 years during ovarian surgery, then engrafted into 34 nude mice. The efficacies of slow freezing and vitrification were directly compared. In Phase I, non-ovariectomised nude mice underwent ovarian tissue engraftment. In Phase II, ovariectomised nude mice underwent ovarian tissue engraftment, followed by gonadotrophin administration to promote folliculogenesis. Ovarian tissue viability was assessed by gross anatomical, histological, and immunohistochemical examinations before and after OTC. Follicular density and morphological integrity were also assessed. RESULTS: After OTC and OTT, grafted ovarian tissues remained viable in nude mice. Primordial follicles were observed in thawed and grafted ovarian tissues, indicating that the cryopreservation and transplantation protocols were both effective. The results were unaffected by gonadotrophin stimulation. CONCLUSION: This study demonstrated the feasibility of OTC in Hong Kong as well as primordial follicle viability after OTC and OTT in nude mice. Ovarian tissue cryopreservation is ideal for patients who cannot undergo the ovarian stimulation necessary for oocyte or embryo freezing as well as prepubertal girls (all ineligible for oocyte freezing). Our findings support the clinical implementation of OTC and subsequent OTT in Hong Kong.

A systematic review and meta-analysis of the role of doxycycline in chronic rhinosinusitis.

OBJECTIVE: The objective of this systematic review and meta-analysis was to evaluate the role of doxycycline in the management of chronic rhinosinusitis. METHOD: This was a systematic review using Ovid Medline, Cinahl, Scopus and Cochrane and was limited to meta-analyses, systematic reviews and randomised, clinical trials. A combination of the following search terms was used: 'sinusitis', 'nasal polyps', 'doxycycline' and 'tetracycline'. Raw means and standard deviations were extracted from the included studies. The meta-analysis was performed using mean differences of pre- versus post-doxycycline treatment. RESULTS: A total of 279 studies were screened, of which 5 studies met the criteria (all randomised, controlled trials published between 2010 and 2021). The interventions, endpoints and measured outcomes varied across all studies. Meta-analysis performed on pre- versus post-doxycycline treatment for Sino-Nasal Outcome Test-22, nasal polyp scores and symptom scores did not yield statistically significant results. CONCLUSION: This review identified a small number of high-quality studies on the use of doxycycline in chronic rhinosinusitis. There does not seem to be convincing evidence for the routine use of doxycycline in patients with chronic rhinosinusitis. Further research may try to identify certain phenotypes of chronic rhinosinusitis that may better respond to doxycycline.

Imaging the acute abdomen in pregnancy: a radiological decision-making tool and the role of MRI.

Acute abdominal pain in pregnancy poses a significant diagnostic challenge. The differential diagnosis is wide, clinical assessment is difficult, and the use of conventional imaging methods is restricted due to risks to the fetus. This can lead to delay in diagnosis, which increases the risk of maternal and fetal harm. Imaging techniques not involving ionising radiation are preferred. Sonography remains first line, but anatomical visualisation can be limited due to displacement of adjacent structures by the gravid uterus. MRI provides excellent cross-sectional soft-tissue assessment of the abdomen and pelvis, and no study to date has demonstrated significant deleterious effects to the fetus at any gestation; however, there remains a theoretical risk of tissue heating by radiofrequency pulses, and there must be consideration of benefit versus potential risk for any use of magnetic resonance imaging (MRI) in pregnancy. With a limited protocol of sequences, a broad spectrum of pathologies can be evaluated. Computed tomography carries the highest exposure of ionising radiation to the fetus, but may be necessary, particularly in cases of trauma. The patient must be kept informed and any potential risks to the patient and fetus should be clearly explained. We present a radiological decision-making tool to guide choice of imaging and best establish the underlying diagnosis in the acute pregnant abdomen. In addition, using illustrative examples from our practice at a large tertiary centre, we review the advantages and disadvantages of each imaging method, with particular focus on the utility of MRI.