Multiplexed RNA profiling by regenerative catalysis enables blood-based subtyping of brain tumors.

Current technologies to subtype glioblastoma (GBM), the most lethal brain tumor, require highly invasive brain biopsies. Here, we develop a dedicated analytical platform to achieve direct and multiplexed profiling of circulating RNAs in extracellular vesicles for blood-based GBM characterization. The technology, termed 'enzyme ZIF-8 complexes for regenerative and catalytic digital detection of RNA' (EZ-READ), leverages an RNA-responsive transducer to regeneratively convert and catalytically enhance signals from rare RNA targets. Each transducer comprises hybrid complexes - protein enzymes encapsulated within metal organic frameworks - to configure strong catalytic activity and robust protection. Upon target RNA hybridization, the transducer activates directly to liberate catalytic complexes, in a target-recyclable manner; when partitioned within a microfluidic device, these complexes can individually catalyze strong chemifluorescence reactions for digital RNA quantification. The EZ-READ platform thus enables programmable and reliable RNA detection, across different-sized RNA subtypes (miRNA and mRNA), directly in sample lysates. When clinically evaluated, the EZ-READ platform established composite signatures for accurate blood-based GBM diagnosis and subtyping.

Incorporating transitional palliative care in a bone marrow transplant unit by serious illness conversation: a case report.

Background: Transplant professionals are specialized in providing lifesaving organs to patients in whom organ failure including bone marrow, in a way that gives strong hope to patients and families. We should be aware of that patients with advanced medical conditions must have an advanced care planning (ACP) in place, though it is difficult to balance possible outcomes and hope. Case Description: This case report showed our serious illness conversation program (SICP) could transit gradually a patient with bone marrow transplant (BMT) and palliative care (PC) needs to hospice care. Initially, she had difficulty in accepting the relapse of her hematological disease, with the main focus on disease treatment and blood parameters. After the transition, this patient's symptoms got better, she felt more stable emotionally, her muscle strength improved, and her hope was reignited because she wanted to go to her daughter's wedding. All these have been facilitated by the PC team. Conclusions: In this case, use of SIC can be regarded as a tool to facilitate better communication and so lead to faster and smoother transition to PC and subsequently hospice care. The use of chemotherapy (e.g., vidaza), on the other hand, had important palliative roles including for symptom control, maintaining patient's mobility and quality of life. Despite her condition being gradually deteriorated, her grief could be largely resolved if most of the wishes fulfilled.

Supportive care and symptom management in patients with advanced hematological malignancies: a literature review.

BACKGROUND AND OBJECTIVE: Recent advances have led to cure or long-term disease control for patients with hematological malignancy (HM). Unfortunately, some of them still have poor prognoses and are often associated with significant symptom burden and poor quality of life for patients and families. These patients usually require supportive care including red blood cell and platelet transfusion, due to disease itself and the oncological treatment, apart from their symptom management. However, there is currently lack of the literatures review in these aspects. The objective of this review is to summarize practical supportive care recommendations for physicians or nurses practicing in palliative care (PC)/hematology-oncology unit, starting with core approaches in use of blood products for anemia and thrombocytopenia, management of tumor lysis syndrome, PC and oncology nursing care. METHODS: Evidence for this review was obtained from a search of the Cochrane database, PubMed, guidelines of European Society of Medical Oncology, British society of Hematology, American Society of Clinical Oncology, National Comprehensive Cancer Network and peer-reviewed journal articles. KEY CONTENT AND FINDINGS: For asymptomatic cancer patients who are anaemic, a threshold of haemoglobin level of 7 g/dL is considered to be safe and generally favored for blood transfusion. 'Single-unit' red cell transfusion is safer and at least as effective as 'double-unit' transfusion. Prophylactic platelet transfusion should be given to stable patients without bleeding and with platelet count less than 10×109/L. In febrile patients, the threshold is lifted to 20×109/L. There are also recommendations for the use of blood products during COVID-19 pandemic. In general, HM patients were more prone to painful infections when compared with solid cancer patients. Thus, antibiotics to treat underlying infections should be applied whenever possible and as required to control pain. CONCLUSIONS: This narrative review showed the recent literatures in the supportive care and symptom management of advanced HM patients. However, it is limited by some of the 'evidence-based' recommendations for interventions (including symptom management) based on early phase of HM populations rather than those receiving end-of-life care.

Safety and tolerability of subcutaneous trastuzumab and intravenous pertuzumab as adjuvant treatment for HER2 positive breast cancer: a pilot study.

BACKGROUND: Subcutaneous (SC) trastuzumab is similar to intravenous trastuzumab in terms of pharmacokinetics, efficacy and tolerability. The use of dual anti-HER2 agents trastuzumab and pertuzumab has become the new standard for node-positive HER2-positive breast cancers at adjuvant setting, but the safety and tolerability of combining SC trastuzumab and intravenous pertuzumab is not well studied. METHODS: This was a prospective single-arm pilot study with locally advanced HER2-positive breast cancer who received adjuvant SC trastuzumab and intravenous pertuzumab after standard anti-HER2 treatment with chemotherapy. Primary outcomes included adverse events (AEs), severe AEs and cardiac AEs. Secondary outcome was invasive disease-free survival (iDFS). RESULTS: With a median follow-up of 21.7 months, 20 patients were enrolled. One patient (5%) developed asymptomatic drop in left ventricular ejection fraction from 69% to 53%. Two patients (10%) developed grade 1 injection site reaction related to SC trastuzumab. There were no grade 2 or above AEs. All AEs were transient. No new AEs were observed. The 1-year iDFS was 90% (95% CI 0.656 to 0.974). CONCLUSIONS: Combination of SC trastuzumab and intravenous pertuzumab for HER2-positive breast cancer is a safe and well-tolerated option in adjuvant setting.

Impact of enhanced haematology palliative care services in patients with myelodysplastic syndrome and acute myeloid leukaemia: study protocol for a randomized controlled trial.

BACKGROUND: Patients with acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) suffer from a significant symptom burden and psychological, spiritual, social needs comparable to patients with solid metastatic malignancy. Referral to palliative care services for these haematological patients remains limited or often confined to the last days of life. We pioneered a palliative care (PC) program integrated with standard haematological care. The purpose of this trial will study the interventions by the PC team and preliminary results in the clinical outcomes. METHODS: This project is a non-blinded, randomized, controlled trial. In this study, we examine the clinical outcomes of the integrated PC program for MDS/AML patients when the 2nd lines disease treatment failed and in the presence of prognostic indicators. In group 1, patients will receive standard haematological care associated with PC (i.e., intervention group). In contrast, in group 2, patients will receive standard haematological care only (i.e., control group) with PC service only on a request basis. Patients who join the program would have to complete a standardized questionnaire to assess their quality of life and their psychological and physical symptoms. RESULTS: This is to exam the impact of the early integrated palliative care with enhanced psychosocial interventions to both advanced MDS/AML patients and their primary family members in Hong Kong. DISCUSSION: This protocol will not display any result. If future results demonstrate that the enhanced PC interventions are effective, they will provide a quality treatment plan for patients with MDS/AML. TRIAL REGISTRATION: The Hong Kong University/Hospital Authority Hong Kong West Institutional Review Board (HKU/HA HKW IRB). The registration number is UW 19-824.

Early integrated palliative care for haematology cancer patients-the impact on symptom burden in Hong Kong.

BACKGROUND: Evidence showed that early palliative care could have many benefits in clinical outcomes for patients living with advanced medical illnesses. In fact, most of these studies have not involved patients with advanced haematologic cancer (HC), which are known to be associated with significant physical and psychological symptoms. In Hong Kong, an Early Integrated Palliative Care (EIPC) collaboration involving both Heamatology unit of Queen Mary Hospital (QMH) and the Palliative Medical Unit of Grantham Hospital (GH) has been started since early 2018 as a better way to improve the service gap. The HC patients failed 2 or more lines of cancer treatment are identified during the joint round and hematology clinic. Some of these patients will be referred to our PC services. Our joint PC clinic has multidisciplinary input from palliative care physicians, hematologists, and clinical psychologists. The clinic program is well coordinated and structured. The HC patients are initially seen by the parent team for disease treatment and then by GH PC team for symptom control and psychosocial care. METHODS: This was a retrospective study with a review of the clinical charts and electronic healthcare records of all patients who attended the Hematology PC clinic from June 2018 to September 2020. For the inclusion criteria, patients were found eligible if they had prospectively completed Edmonton Symptom Assessment Scale (ESAS) assessments for at least the initial and follow-up visits within a range of ≥7 days and ≤60 days of the first visit. RESULTS: Thirty-eight patients ultimately agreed to the referral. The mean age was 70.5 (12.5) years old. Twenty-five patients (66%) had myelodysplastic syndrome (MDS); 10 (26%) had acute myeloid leukemia (AML). Around 50-60% of patients reported significant symptoms of fatigue, anxiety, drowsiness, and anorexia; 42% of patients had significantly depressed moods while 37% had pain. There were significant symptom improvements for pain, depression, and anxiety after follow-up visits. CONCLUSIONS: The study showed that our EIPC program resulted in a significant reduction in some of the important symptom item scores, including pain, anorexia, anxiety, and depression, after the follow-up visits.

Roles of specific drug therapies for severe pulmonary arterial hypertension in palliative care: a case report.

Pulmonary arterial hypertension (PAH) is an uncommon but potentially life-threatening illness. The elevated pulmonary arterial blood pressure will lead to right heart failure and even cardiopulmonary collapse if it is severe. Apart from general supportive measures, pulmonary hypertension-specific therapies (PHST) are available to slow down disease progression, but they are not curative. According to previous studies, many patients with severe PAH often had significant physical symptoms and psychological distress for both themselves and their families at the end of life. Moreover, they would have repeated admissions due to physical deterioration and decline in functioning associated with worsening in cardiac function. Some of these patients might suffer from unnecessary aggressive interventions and resuscitation because of lack of advance care planning discussion. As such, Palliative Care (PC) would be an important element as part of the overall management. Hereby, we reported a patient with severe PAH and schizoaffective disorder achieved good outcome from the use of combination PHST and PC input. Her physical and psychosocial needs could be addressed well by PC team. This case report showed the collaborative work between PC and parent teams. While parent team was able to manage the medical conditions related to PAH, however the physical and psychosocial needs should be addressed by PC team. More importantly, the PC team has essential roles of providing advance care planning discussions with the patient and help to reduce unnecessary interventions. Furthermore, PC would coordinate the community service to support her while staying at home. Roles of PHST will also be discussed in this case. Clinicians must take into account possible hemodynamic effects of any palliative intervention for PAH.

Impact of structured advance care planning program on patients' wish items and healthcare utilization.

BACKGROUND: Structured advance care planning (ACP) program is an important service in the end-of-life care for patients with advanced medical illness. We pioneered a structured and coordinated ACP program for patients with advanced malignancies and end-stage organ failure in Hong Kong. This study investigated the impact of a structured ACP program on the concordance rate for patients' final wishes, patient/family satisfaction, and the number of acute admissions (AA) and length of stay (LOS) in hospital. METHODS: Patients with advanced malignancy or end-stage organ failure who were able to complete ACP forms during the current admission to medical units were recruited. Patients who could not complete ACP forms or <18 years of age were excluded. The ACP program comprised the following components: (I) baseline education (workshop/role play) in ACP sessions for linked nurses of different medical units; (II) structured ACP discussions with recruited patients and their proxies during admission, after any change in clinical status, and also at monthly intervals; (III) formal structured review of patients' goals at regular team meetings; (IV) "flagging" of advance directive (AD) in hospital computer system and (V) feedback to linked nurse on the congruence of care. Mentally competent patients who did not receive ACP and matched for disease and demographics were selected as controls in a 1:2.5 ratio. RESULTS: Two hundred forty-three patients were included for analysis between August 2016 and July 2017, of which 69 patients joined the ACP program and 174 of them did not. Two hundred and one patients (83%) had advanced cancer. All had done do-not-attempt-cardiopulmonary-resuscitation (DNACPR) order in the ACP group. The concordance rates for patients' wishes on quality of life, end-of-life and funeral arrangements were 95%, 100% and 100% respectively. Over 70% of patients and their families (N=10) showed satisfaction with the program. The ACP group also had lower mean AA and shorter LOS (0.78±0.23 vs. 1.2±0.8 episode/patient, 4.6±1.7 vs. 7.5±2.5 days, P=0.037 and P=0.023 respectively) in the last 3 months of life compared with the non-ACP group. CONCLUSIONS: This ACP program achieved high concordance rate for patients' wish items and reduced healthcare utilization.

Microhexagon gradient array directs spatial diversification of spinal motor neurons.

Motor neuron diversification and regionalization are important hallmarks of spinal cord development and rely on fine spatiotemporal release of molecular cues. Here, we present a dedicated platform to engineer complex molecular profiles for directed neuronal differentiation. Methods: The technology, termed microhexagon interlace for generation of versatile and fine gradients (microHIVE), leverages on an interlocking honeycomb lattice of microstructures to dynamically pattern molecular profiles at a high spatial resolution. By packing the microhexagons as a divergent, mirrored array, the platform not only enables maximal mixing efficiency but also maintains a small device footprint. Results: Employing the microHIVE platform, we developed optimized profiles of growth factors to induce rostral-caudal patterning of spinal motor neurons, and directed stem cell differentiation in situ into a spatial continuum of different motor neuron subtypes. Conclusions: The differentiated cells showed progressive RNA and protein signatures, consistent with that of representative brachial, thoracic and lumbar regions of the human spinal cord. The microHIVE platform can thus be utilized to develop advanced biomimetic systems for the study of diseases in vitro.

Broadband focusing grating couplers for suspended-membrane waveguides.

We propose and demonstrate broadband focusing grating couplers for suspended-membrane waveguides on silicon-on-insulator both in near-infrared (near-IR) and in mid-IR wavelength range. Finite-difference time-domain simulation predicts ∼100 nm 3 dB bandwidth with -1.7 dB coupling efficiency for an apodized grating in near-IR. -3.5 dB maximum coupling efficiency and ∼90 nm 3 dB bandwidth are realized experimentally. In mid-IR, -5.5 dB maximum coupling efficiency from a uniform focusing grating is measured at 2.75 µm, and ∼500 nm 3 dB bandwidth is predicted theoretically.

Tunable integrated variable bit-rate DPSK silicon receiver.

We integrate a wavelength-tunable microring resonator with a monolithic Ge-on-Si photodetector for use as a variable bit-rate silicon receiver. The integrated receiver has a responsivity of 0.7 A/W. We achieved error-free operation for a wide range of bit rates from 5 Gb/s to 12.5 Gb/s. The wavelength tuning was realized by a TiN-based thermal heater, which enabled tuning of up to ~1 free spectral range.

Demodulation of 20 Gbaud/s differential quadrature phase-shift keying signals using wavelength-tunable silicon microring resonators.

We experimentally demonstrate a demodulation scheme for 20 Gbaud/s nonreturn-to-zero differential quadrature phase-shift keying signals using a silicon microring resonator. Either the I or Q channel can be selected by electrical tuning using the carrier depletion effect. Error-free (bit error rate <10(-9)) operations can be achieved for both the I and Q channels with ~1.5 dB power penalty compared with a commercial 20 GHz Mach-Zehnder delay interferometer. The tuning range of the ring resonator can be up to 60 GHz, which enables operation over a wide range of data rates.

Psychosocial factors influencing the practice of preventive behaviors against the severe acute respiratory syndrome among older Chinese in Hong Kong.

OBJECTIVE: This study explored psychosocial factors that influenced the practice of preventive behaviors against the severe acute respiratory syndrome (SARS) among older adults. METHOD: A total of 354 older Chinese were telephone interviewed during the outbreak of SARS in Hong Kong. They were asked about their perceived health threats, efficacy beliefs, and the practice of SARS preventive behaviors. RESULTS: Only 40.7% of the elderly participants practiced the recommended SARS preventive behaviors. Elderly participants who perceived greater personal vulnerability to the disease, who possessed greater self-efficacy, who had greater confidence in local health authorities, and who had lower educational attainment were more likely to adopt the suggested SARS preventive behaviors. DISCUSSION: This study supported the conceptual framework that specified perceived health threats and efficacy beliefs as the two core dimensions of motivating factors in adopting SARS preventive behaviors.

Practice of habitual and volitional health behaviors to prevent severe acute respiratory syndrome among Chinese adolescents in Hong Kong.

PURPOSE: To explore factors relating to the practice of habitual and volitional health behaviors against the severe acute respiratory syndrome (SARS) among Chinese adolescents in Hong Kong. METHODS: A community telephone survey was conducted with 230 Chinese adolescents. Random-digit dialing of the local residential telephone directory was used to select respondents, who were asked to provide information on their practice of SARS preventive health behaviors and associated factors as specified by the Health Belief Model. These factors included perceived threat of SARS, perceived benefits and barriers in practicing SARS preventive health behaviors, cues to action, knowledge of SARS, and self-efficacy. Hierarchical regression analyses were conducted to determine salient correlates of habitual and volitional health behaviors against SARS. RESULTS: About 54.8% of respondents reported practicing all three recommended habitual health behaviors. Another 47.8% indicated consistent practice of volitional health behavior of facemask-wearing to prevent SARS. Results of hierarchical regression analyses showed that habitual health behaviors against SARS were related to perceived health threat and environmental cues. For facemask-wearing, salient correlates were environmental cues, rates of SARS habitual health behaviors, younger age, and perceived health threat. CONCLUSIONS: The Health Belief Model is useful in understanding Chinese adolescents' practice of health behaviors, especially volitional health behaviors.

Factors influencing the wearing of facemasks to prevent the severe acute respiratory syndrome among adult Chinese in Hong Kong.

BACKGROUND: The global outbreak of the severe acute respiratory syndrome (SARS) in 2003 has been an international public health threat. Quick diagnostic tests and specific treatments for SARS are not yet available; thus, prevention is of paramount importance to contain its global spread. This study aimed to determine factors associating with individuals' practice of the target SARS preventive behavior (facemask wearing). METHODS: A total of 1329 adult Chinese residing in Hong Kong were surveyed. The survey instrument included demographic data, measures on the five components of the Health Belief Model, and the practice of the target SARS preventive behavior. Logistic regression analyses were conducted to determine rates and predictors of facemask wearing. RESULTS: Overall, 61.2% of the respondents reported consistent use of facemasks to prevent SARS. Women, the 50-59 age group, and married respondents were more likely to wear facemasks. Three of the five components of the Health Belief Model, namely, perceived susceptibility, cues to action, and perceived benefits, were significant predictors of facemask-wearing even after considering effects of demographic characteristics. CONCLUSIONS: The Health Belief Model is useful in identifying determinants of facemask wearing. Findings have significant implications in enhancing the effectiveness of SARS prevention programs.

Coming out experiences and psychological distress of Chinese homosexual men in Hong Kong.

This study adopted a cognitive-behavioral conceptual framework based on the Theory of Reasoned Action (TRA) in understanding coming out experiences and psychological distress of 187 Chinese gay men. Results showed that participants' coming out experiences were characterized by same-sex sexual fantasy at teenage years, followed by awareness of homosexual tendency, same-sex sexual contact, and then self-identification and disclosure of homosexual orientation in young adulthood. Regarding targets of disclosure, participants tended to disclose their sexual orientation to their gay friends first, followed by heterosexual friends, siblings, parents, and coworkers. This study also supported the extension of the TRA conceptual framework to Chinese societies. Results showed that a low level of psychological distress in Chinese gay men was linked to their coming out experiences, which were in turn related to TRA components of involvement and identification with gay communities and positive attitudes toward coming out. Limitations and implications were also discussed.