Addressing the risk and management of cardiometabolic complications in prostate cancer patients on androgen deprivation therapy and androgen receptor axis-targeted therapy: consensus statements from the Hong Kong Urological Association and the Hong Kong Society of Uro-Oncology.

Background: Androgen deprivation therapy (ADT) is the foundational treatment for metastatic prostate cancer (PCa). Androgen receptor (AR) axis-targeted therapies are a new standard of care for advanced PCa. Although these agents have significantly improved patient survival, the suppression of testosterone is associated with an increased risk of cardiometabolic syndrome. This highlights the urgency of multidisciplinary efforts to address the cardiometabolic risk of anticancer treatment in men with PCa. Methods: Two professional organizations invited five urologists, five clinical oncologists, and two cardiologists to form a consensus panel. They reviewed the relevant literature obtained by searching PubMed for the publication period from April 2013 to April 2023, to address three discussion areas: (i) baseline assessment and screening for risk factors in PCa patients before the initiation of ADT and AR axis-targeted therapies; (ii) follow-up and management of cardiometabolic complications; and (iii) selection of ADT agents among high-risk patients. The panel convened four meetings to discuss and draft consensus statements using a modified Delphi method. Each drafted statement was anonymously voted on by every panelist. Results: The panel reached a consensus on 18 statements based on recent evidence and expert insights. Conclusion: These consensus statements serve as a practical recommendation for clinicians in Hong Kong, and possibly the Asia-Pacific region, in the management of cardiometabolic toxicities of ADT or AR axis-targeted therapies in men with PCa.

Knowledge, attitudes and intention on fertility preservation among breast cancer patients.

Breast cancer is the most common cancer in reproductive age women. The aim of this study is to assess the knowledge, attitude and intention on fertility preservation among women diagnosed to have breast cancer. This is a multi-centre cross-sectional questionnaire study. Reproductive age women diagnosed with breast cancer attending Oncology, Breast Surgery and Gynaecology Clinics and support groups were invited to participate. Women filled in paper or electronic form of the questionnaire. 461 women were recruited and 421 women returned the questionnaire. Overall, 181/410 (44.1%) women had heard of fertility preservation. Younger age and higher education level were significantly associated with increased awareness of fertility preservation. Awareness and acceptance of the different fertility preservation methods in reproductive age women with breast cancer was suboptimal. However, 46.1% women felt that their fertility concerns affected their decision for cancer treatment in some way.

Highly Ordered Supramolecular Materials of Phase-Separated Block Molecules for Long-Range Exciton Transport.

Efficient energy transport over long distances is essential for optoelectronic and light-harvesting devices. Although self-assembled nanofibers of organic molecules are shown to exhibit long exciton diffusion lengths, alignment of these nanofibers into films with large, organized domains with similar properties remains a challenge. Here, it is shown how the functionalization of C3 -symmetric carbonyl-bridged triarylamine trisamide (CBT) with oligodimethylsiloxane (oDMS) side chains of discrete length leads to fully covered surfaces with aligned domains up to 125 × 70 µm2 in which long-range exciton transport takes place. The nanoscale morphology within the domains consists of highly ordered nanofibers with discrete intercolumnar spacings within a soft amorphous oDMS matrix. The oDMS prevents bundling of the CBT fibers, reducing the number of defects within the CBT columns. As a result, the columns have a high degree of coherence, leading to exciton diffusion lengths of a few hundred nanometers with exciton diffusivities (≈0.05 cm2 s-1 ) that are comparable to those of a crystalline tetracene. These findings represent the next step toward fully covered surfaces of highly aligned nanofibers through functionalization with oDMS.

Post-radiation primary hypothyroidism in patients with head and neck cancer: External validation of thyroid gland dose-volume constraints with long-term endocrine outcomes.

BACKGROUND: Post-radiation primary hypothyroidism is a common late complication in head and neck cancer (HNC) survivors. No radiation dose-volume constraint of the thyroid gland has been externally validated for predicting long-term thyroid function outcomes. MATERIALS AND METHODS: This external validation study evaluated the diagnostic properties of 22 radiation dose-volume constraints of the thyroid gland proposed in the literature. Radiation dosimetric data from 488 HNC patients who underwent neck irradiation from January 2013 to December 2015 at two tertiary oncology centers were reviewed. The diagnostic metrics of candidate constraints were computed by inverse probability of censoring weighting and compared using time-dependent receiver operating characteristic (ROC) curves with death designated as a competing event. Multivariable regression analyses were performed using the Fine-Gray sub-distribution hazard model. RESULTS: Over a median follow-up period of 6.8 years, 205 (42.0 %) patients developed post-radiation primary hypothyroidism. The thyroid volume spared from 60 Gy (VS60) had the largest area under ROC curve of 0.698 at 5 years after radiotherapy. Of all evaluated constraints, VS60 at a cutoff value of 10 cc had the highest F-score of 0.53. The 5-year hypothyroidism risks of patients with thyroid VS60 ≥ 10 cc and < 10 cc were 14.7 % and 38.2 %, respectively (p < 0.001). The adjusted sub-hazard ratio for post-radiation primary hypothyroidism for VS60 < 10 cc was 1.87 (95 % confidence interval, 1.22-2.87; p < 0.001). CONCLUSION: Thyroid VS60 is the best radiation dose-volume parameter to predict the long-term risk of primary hypothyroidism in patients with HNC who underwent neck irradiation. VS60 ≥ 10 cc is a robust constraint that limits the 5-year primary hypothyroidism risk to less than 15 % and should be routinely employed during radiotherapy optimization.

Genetic Testing and Its Clinical Application in Prostate Cancer Management: Consensus Statements from the Hong Kong Urological Association and Hong Kong Society of Uro-Oncology.

Background: In recent years, indications for genetic testing in prostate cancer (PC) have expanded from patients with a family history of prostate and/or related cancers to those with advanced castration-resistant disease, and even to early PC patients for determination of the appropriateness of active surveillance. The current consensus aims to provide guidance to urologists, oncologists and pathologists working with Asian PC patients on who and what to test for in selected populations. Methods: A joint consensus panel from the Hong Kong Urological Association and Hong Kong Society of Uro-Oncology was convened over a series of 5 physical and virtual meetings. A background literature search on genetic testing in PC was performed in PubMed, ClinicalKey, EBSCOHost, Ovid and ProQuest, and three working subgroups were formed to review and present the relevant evidence. Meeting agendas adopted a modified Delphi approach to ensure that discussions proceed in a structured, iterative and balanced manner, which was followed by an anonymous voting on candidate statements. Of 5 available answer options, a consensus statement was accepted if ≥ 75% of the panelists chose "Accept Completely" (Option A) or "Accept with Some Reservation" (Option B). Results: The consensus was structured into three parts: indications for testing, testing methods, and therapeutic implications. A list of 35 candidate statements were developed, of which 31 were accepted. The statements addressed questions on the application of PC genetic testing data and guidelines to Asian patients, including patient selection for germline testing, selection of gene panel and tissue sample, provision of genetic counseling, and use of novel systemic treatments in metastatic castration-resistant PC patients. Conclusion: This consensus provides guidance to urologists, oncologists and pathologists working with Asian patients on indications for genetic testing, testing methods and technical considerations, and associated therapeutic implications.

Tuning the donor-acceptor interactions in phase-segregated block molecules.

The assembly of donor-acceptor molecules via charge transfer (CT) interactions gives rise to highly ordered nanomaterials with appealing electronic properties. Here, we present the synthesis and bulk co-assembly of pyrene (Pyr) and naphthalenediimide (NDI) functionalized oligodimethylsiloxanes (oDMS) of discrete length. We tune the donor-acceptor interactions by connecting the pyrene and NDI to the same oligomer, forming a heterotelechelic block molecule (NDI-oDMSPyr), and to two separate oligomers, giving Pyr and NDI homotelechelic block molecules (Pyr-oDMS and NDI-oDMS). Liquid crystalline materials are obtained for binary mixtures of Pyr-oDMS and NDI-oDMS, while crystallization of the CT dimers occurred for the heterotelechelic NDI-oDMS-Pyr block molecule. The synergy between crystallization and phase-segregation coupled with the discrete length of the oDMS units allows for perfect order and sharp interfaces between the insulating siloxane and CT layers composed of crystalline CT dimers. We were able to tune the lamellar domain spacing and donor-acceptor CT interactions by applying pressures up to 6 GPa on the material, making the system promising for soft-material nanotechnologies. These results demonstrate the importance of the molecular design to tune the CT interactions and stability of a CT material.

MC3R links nutritional state to childhood growth and the timing of puberty.

The state of somatic energy stores in metazoans is communicated to the brain, which regulates key aspects of behaviour, growth, nutrient partitioning and development1. The central melanocortin system acts through melanocortin 4 receptor (MC4R) to control appetite, food intake and energy expenditure2. Here we present evidence that MC3R regulates the timing of sexual maturation, the rate of linear growth and the accrual of lean mass, which are all energy-sensitive processes. We found that humans who carry loss-of-function mutations in MC3R, including a rare homozygote individual, have a later onset of puberty. Consistent with previous findings in mice, they also had reduced linear growth, lean mass and circulating levels of IGF1. Mice lacking Mc3r had delayed sexual maturation and an insensitivity of reproductive cycle length to nutritional perturbation. The expression of Mc3r is enriched in hypothalamic neurons that control reproduction and growth, and expression increases during postnatal development in a manner that is consistent with a role in the regulation of sexual maturation. These findings suggest a bifurcating model of nutrient sensing by the central melanocortin pathway with signalling through MC4R controlling the acquisition and retention of calories, whereas signalling through MC3R primarily regulates the disposition of calories into growth, lean mass and the timing of sexual maturation.

Highly Ordered 2D-Assemblies of Phase-Segregated Block Molecules for Upconverted Linearly Polarized Emission.

Materials based on the laminar ordering of self-assembled molecules have a unique potential for applications requiring efficient energy migration through densely packed chromophores. Here, employing molecular assemblies of coil-rod-coil block molecules for triplet-triplet annihilation upconversion (TTA-UC) based on triplet energy migration with linearly polarized emission is reported. By covalently attaching discrete-length oligodimethylsiloxane (oDMS) to 9,10-diphenylanthracene (DPA), highly ordered 2D crystalline DPA sheets separated by oDMS layers are obtained. Transparent films of this material doped with small amounts of triplet sensitizer PtII octaethylporphyrin show air-stable TTA-UC under non-coherent excitation. Upon annealing, an increase in TTA-UC up to two orders of magnitude is observed originating from both an improved molecular ordering of DPA and an increased dispersion of the sensitizer. The molecular alignment in millimeter-sized domains leads to upconverted linearly polarized emission without alignment layers. By using a novel technique, upconversion imaging microscopy, the TTA-UC intensity is spatially resolved on a micrometer scale to visually demonstrate the importance of molecular dispersion of sensitizer molecules for efficient TTA-UC. The reported results are promising for anti-counterfeiting and 3D night-vision applications, but also exemplify the potential of discrete oligodimethylsiloxane functionalized chromophores for highly aligned and densely packed molecular materials.

One-Pot Synthesis of ABCDE Multiblock Copolymers with Hydrophobic, Hydrophilic, and Semi-Fluorinated Segments.

The scope and accessibility of sequence-controlled multiblock copolymers is demonstrated by direct "in situ" polymerization of hydrophobic, hydrophilic and fluorinated monomers. Key to the success of this strategy is the ability to synthesize ABCDE, EDCBA and EDCBABCDE sequences with high monomer conversions (>98 %) through iterative monomer additions, yielding excellent block purity and low overall molar mass dispersities (Ð<1.16). Small-angle X-ray scattering showed that certain sequences can form well-ordered mesostructures. This synthetic approach constitutes a simple and versatile platform for expanding the availability of tailored polymeric materials from readily available monomers.

Amplifying (Im)perfection: The Impact of Crystallinity in Discrete and Disperse Block Co-oligomers.

Crystallinity is seldomly utilized as part of the microphase segregation process in ultralow-molecular-weight block copolymers. Here, we show the preparation of two types of discrete, semicrystalline block co-oligomers, comprising an amorphous oligodimethylsiloxane block and a crystalline oligo-l-lactic acid or oligomethylene block. The self-assembly of these discrete materials results in lamellar structures with unforeseen uniformity in the domain spacing. A systematic introduction of dispersity reveals the extreme sensitivity of the microphase segregation process toward chain length dispersity in the crystalline block.

[Cisplatin-induced hearing loss in children in relation to eye color]. / Cisplatininduzierte Hörstörungen bei Kindern in Abhängigkeit von der Pigmentierung der Iris.

BACKGROUND: Cisplatin is commonly used as a chemotherapeutic agent in the treatment of solid tumors. Ototoxicity is an important side-effect. Melanin in the inner ear either plays an otoprotective role or has a negative influence on hearing. The concentration of cochlear melanin correlates with its concentration in the iris. PATIENTS AND METHODS: We retrospectively examined 65 children (37 males, 28 females, average age 7.5 years) treated with cisplatin at the University Clinic of Muenster, Germany. We checked whether their eye color could be inferred from the prevalence and extent of cisplatin-induced hearing loss. RESULTS: We found a hearing loss of >20 dB in 29 light-eyed and in 21 dark-eyed patients. Seven light-eyed and eight dark-eyed patients did not suffer from hearing impairment. Using the chi(2)-test on these four parameters, we found no significant connection between iris pigmentation and the prevalence or extent of hearing loss, although light-eyed children (80.6%) suffered more from hearing loss than dark-eyed children (72.4%). After the end of therapy with cisplatin, the prevalence of hearing loss was 83.3% in children up to 6 years and 71.4% in children older than 6 years. The average cumulative dose of cisplatin was 372 mg/m(2) of body surface in children with hearing loss, compared to 390 mg/m(2) in children without hearing loss. CONCLUSION: We found no significant correlation between iris pigmentation (eye color) and hearing loss. Cisplatin-induced hearing loss occurs frequently and requires repeated monitoring.

Long-term outcome of anorectal malformations: the patient perspective.

To assess the long-term outcome of surgery for anorectal malformations (ARM) from the patient's perspective. One hundred and sixty seven children were operated for ARM between 1982 and 2000. Disease impact questionnaires to assess both clinical and psychological outcomes were sent to 137 eligible families. Statistical analysis was performed using SPSS version 11.5. The response rate was 61% (n=84). Sixty six percent had soiling. There was no significant difference in the incidence of soiling between genders or between the younger child and adolescent. Soiling was significantly increased in high (86%) and intermediate (79%) compared to low (43%) malformation (P=0.001). Constipation was seen in 62% and abdominal pain in 49%, with no significant difference between malformation levels. Overall, 71% had associated anomalies. Although 44% had a documented urological abnormality, clinical significant problems were seen in only 30%. Eighty percent of the children had one or more behavioural problems and 15% expressed suicidal thoughts. ARM had a negative impact on the social life of the child in 52% and on family functioning in 50%. Soiling (P=0.000), presence of associated anomalies (P=0.001), constipation (P=0.005), level of ARM (P=0.015) and abdominal pain (P=0.039) correlated significantly with psychosocial morbidity. Despite these findings, 62% of adolescents and 71% of children below 12 years with their parents reported above average global hopefulness score, remaining hopeful for the future. Children with ARM have ongoing physical and social morbidity, indicating the need for continuing multidisciplinary review and support to optimise their quality of life.

Laser Doppler imaging of paediatric burns: burn wound outcome can be predicted independent of clinical examination.

This study sought to assess the validity of independent, blinded reporting of Laser Doppler Imaging (LDI) prediction of burn wound outcome in children. Two experienced paediatric burn consultants were invited to report on LDI scans performed routinely within 3 days of burn. They were provided with the LDI flux image, a low-resolution colour digital photograph of the burnt area and a basic history. Report predictions were correlated with outcome. Reports were compiled on 50 scans performed on 31 patients at a mean of 54h post burn. Of the 100 reports generated, mean correlation with outcome was 97%. If the LDI predicted a deep burn, it was always correct. Non-correlations were due to a number of factors including inadequate scanning of the affected area, excessive movement and residual wound debris. Accurate prediction of burn wound outcome could be made via the standard information generated by LDI and appeared more reliable than clinical prediction. The correlation improved with increasing experience with LDI.

Incremental nonlinear dimensionality reduction by manifold learning.

Understanding the structure of multidimensional patterns, especially in unsupervised cases, is of fundamental importance in data mining, pattern recognition, and machine learning. Several algorithms have been proposed to analyze the structure of high-dimensional data based on the notion of manifold learning. These algorithms have been used to extract the intrinsic characteristics of different types of high-dimensional data by performing nonlinear dimensionality reduction. Most of these algorithms operate in a "batch" mode and cannot be efficiently applied when data are collected sequentially. In this paper, we describe an incremental version of ISOMAP, one of the key manifold learning algorithms. Our experiments on synthetic data as well as real world images demonstrate that our modified algorithm can maintain an accurate low-dimensional representation of the data in an efficient manner.

Colonic duplication: diagnostic dilemma.

Colonic duplication is a rare congenital anomaly which presents as a diagnostic and therapeutic challenge. We report a 5-year-old boy with colonic duplication who required multiple hospital admissions, multiple diagnostic tests, and evaluation by various clinical specialists before the diagnosis was made intraoperatively. He was known to have left renal hypoplasia, low spinal abnormalities, hypoplasia of the left hemipelvis, and mild hypoplasia of the left lower limb, all of which were considered to be a variant of caudal regression syndrome.

Recurrent parotitis of childhood.

BACKGROUND: Recurrent parotitis (RP) of childhood is a rare condition of unknown aetiology, probably immunologically mediated. OBJECTIVE: To review the clinical presentation, diagnosis and management of RP of childhood. METHODS: Retrospective study from 1983 to 2004 of children diagnosed with RP of childhood at a tertiary children's hospital. RESULTS: We identified 53 children, 37 (70%) male and 16 (30%) female. The age of onset was biphasic, with peaks at 2-5 years of age and at 10 years. The commonest symptoms were swelling (100%), pain (92.5%) and fever (41.5%). Symptoms usually lasted 2-7 days with a median of 3 days. The mean frequency was 8 episodes per year. The diagnosis was often delayed, >1 year in 70% of patients, maximum 8 years. The most common diagnoses, before the definitive diagnosis of RP, were mumps (21%), 'infection' (15%) and stones (11%). Sialogram (57%) and/or ultrasound (41%) showed sialectasis in 81% of patients. Over half the patients (54%) were given antibiotics at least once to treat the parotitis. Two children had hypogammablobulinaemia, one child had human immunodeficiency virus infection, and one child had Sjogren's syndrome. Two children had high titre antinuclear antibodies. CONCLUSIONS: Recurrent parotitis had a biphasic age distribution. The major clinical features that distinguish it from other causes of parotid swelling are the lack of pus and recurrent episodes. A clinical diagnosis can often be confirmed by ultrasound. Antibiotics do not have a role in treatment. Affected children should be screened for Sjogren's syndrome and immune deficiency.

Biliary dyskinesia: is the problem with Oddi?

We report our experience of cholecystectomy for treating symptoms suggestive of biliary disease in association with a decreased gallbladder ejection fraction (GBEF) but without evidence of cholelithiasis. Five children with normal biliary ultrasounds were evaluated between January 1990 and December 2000 for recurrent upper abdominal pain. Based on a cholecystokinin (CCK)-provoked GBEF of less than 50% and the absence of any other gastrointestinal pathology, patients underwent cholecystectomy with operative cholangiography for presumed biliary dyskinesia. Pathological examination demonstrated chronic inflammation in all cases. Two patients had complete resolution of their symptoms, but three had persistent pain following surgery. Biliary dyskinesia seems an uncommon cause of persistent abdominal pain in childhood. Cholecystectomy was not always effective in relieving symptoms. Biliary scintigraphy with CCK provocation should not be used as the sole criterion for cholecystectomy. Sphincteric manometry may be valuable in the assessment of this small group of patients to avoid inappropriate intervention. The future perhaps lies in better understanding of the physiological action and pharmacological control of the sphincter of Oddi.

Simultaneous feature selection and clustering using mixture models.

Clustering is a common unsupervised learning technique used to discover group structure in a set of data. While there exist many algorithms for clustering, the important issue of feature selection, that is, what attributes of the data should be used by the clustering algorithms, is rarely touched upon. Feature selection for clustering is difficult because, unlike in supervised learning, there are no class labels for the data and, thus, no obvious criteria to guide the search. Another important problem in clustering is the determination of the number of clusters, which clearly impacts and is influenced by the feature selection issue. In this paper, we propose the concept of feature saliency and introduce an expectation-maximization (EM) algorithm to estimate it, in the context of mixture-based clustering. Due to the introduction of a minimum message length model selection criterion, the saliency of irrelevant features is driven toward zero, which corresponds to performing feature selection. The criterion and algorithm are then extended to simultaneously estimate the feature saliencies and the number of clusters.

Small bowel perforation in the premature neonate: congenital or acquired?

To determine the potential aetiological factors of small bowel perforation in the premature neonate, we performed a retrospective chart review of those neonates with spontaneous intestinal perforation (SIP) of the small bowel seen in our tertiary paediatric hospital between January 1980 and December 2000. Data were collected on gestational feto-maternal health, medical interventions prior to perforation and the subsequent operative and laboratory findings. There were 23 patients with SIP of the small bowel over the 21-year review; 65% were male. There were 7 twin pregnancies but no cases linked to maternal drug abuse. The median gestational age was 27 weeks, the median birth weight 973 g, 19 neonates required ventilation, 15 steroids and 13 indomethacin. The median age at diagnosis was 7 days, heralded by rapid development of abdominal distension in 22 patients. Surgical intervention in addition to insertion of a peritoneal drain was required in 19 patients. Positive microbiological cultures of blood or peritoneal fluid at operation were documented in 8 patients; 5 grew Staphylococcus epidermidis and 4 Candida species. Perforations were located in the ileum in 20 and the jejunum in 1. Deficiency of the muscularis propria was found in 6 patients. Of the 6 deaths, 2 neonates had significant co-morbidity in addition to extreme prematurity. Small bowel SIP occurs in the premature neonate after the first week of life and usually presents with abdominal distension. Putative risk factors identified included twin gestation, neonatal ventilation, use of steroids and indomethacin, infection with Staphylococcus epidermidis and Candida species and deficiency of enteric smooth muscle.