Prognostication for Patients Receiving Palliative Radiation Therapy.

Estimation of patient prognosis plays a central role in guiding decision making for the palliative management of metastatic disease, and a number of statistical models have been developed to provide survival estimates for patients in this context. In this review, we discuss several well-validated survival prediction models for patients receiving palliative radiotherapy to sites outside of the brain. Key considerations include the type of statistical model, model performance measures and validation procedures, studies' source populations, time points used for prognostication, and details of model output. We then briefly discuss underutilization of these models, the role of decision support aids, and the need to incorporate patient preference in shared decision making for patients with metastatic disease who are candidates for palliative radiotherapy.

Analysis of dose to the macula, optic disc, and lens in relation to vision toxicities - A retrospective study using COMS eye plaques.

PURPOSE: The aim of this study was to relate common toxicity endpoints with dose to the macula, optic disc, and lens for uveal melanoma patients treated with Iodine-125 Collaborative Ocular Melanoma Study (COMS) eye plaque brachytherapy. METHODS: A cohort of 52 patients treated at a single institution between 2005 and 2019 were retrospectively reviewed. Demographics, dosimetry, and clinical outcomes were recorded. Univariate, relative risk, and Kaplan-Meier analyses were performed to relate dose to toxicity endpoints including retinopathy, vision decline, and cataracts. RESULTS: By the end of follow up (Median = 3.6 years, Range = 0.4 - 13.5 years), 65 % of eyes sustained radiation retinopathy, 40 % demonstrated moderate vision decline (>5 Snellen lines lost), and 56 % developed cataracts. Significant (p < 0.05) risk estimates exist for retinopathy and VA decline for doses >52 Gy to the macula and >42 Gy to the optic disc. Moreover, dose to the lens > 16 Gy showed a significant risk for cataract formation. Kaplan-Meier analysis demonstrated significantly different incidence of radiation retinopathy for > 52 Gy to the macula and > 42 Gy to the optic disc. In addition, the Kaplan-Meier analysis showed significantly different incidence of cataract formation for patients with lens dose > 16 Gy. CONCLUSIONS: Dose-effect relationships exist for the macula and optic disc with respect to the loss of visual acuity and the development of retinopathy. To better preserve vision after treatment, further research is needed to reduce macula, optic disc, and lens doses while maintaining tumor control.

Teaching Smartphone Funduscopy with 20 Diopter Lens in Undergraduate Medical Education.

PURPOSE: To assess attitudes of pre-clinical undergraduate medical students toward learning smartphone funduscopy (SF) and its appropriateness as a teaching tool. PATIENTS AND METHODS: Second year medical students received instruction on direct ophthalmoscopy (DO) and SF; they were then paired with a peer and randomly assigned to perform DO or SF first. The SF technique involved freehand alignment of the axes of the smartphone camera with a condenser lens. Both techniques were done through a maximally dilated pupil. A questionnaire was completed to acquire data on baseline experience, performance of both examination techniques, attitudes, and appropriateness. Statistical significance testing and Bland-Altman analysis were used to determine differences between DO and SF, and a multivariable mixed regression model was fitted to identify any predictors for positive attitudes toward DO or SF. RESULTS: One hundred thirty-seven (137) individuals completed the study. A similar proportion of students could identify the optic nerve, macula, and vessels using DO and SF. However, self-reported quality scores were higher for DO for the optic nerve (p = 0.006) and macula (p = 0.08). The mean (standard deviation) attempts to identify these major structures were 2.7 (SD 2.3) for DO and 4.5 (SD 2.9) for SF (p < 0.001). Attitudes of students were consistently more positive toward DO across the five questions assessed. A small subset of students had equally positive attitudes toward DO and SF. Improved quality scores were predictive of positive attitudes for both DO and SF. Ultimately, 24% of students preferred SF over DO. CONCLUSION: Among inexperienced examiners of the fundus through a dilated pupil, SF is a non-inferior technique to DO in identifying structures. Despite overall favorable attitudes towards the more familiar DO, those students who quickly learned the SF technique had similar satisfaction scores. Teaching SF should be considered in undergraduate medical education.

Improved mobility performance with an artificial vision therapy system using a thermal sensor.

OBJECTIVE: To evaluate the benefit of integrating thermal imaging into an artificial vision therapy system, the Argus II retinal prosthesis, in simplifying a complex scene and improving mobility performance in the presence of other persons. APPROACH: Four Argus II retinal implant users were evaluated on two tasks: to locate and approach target persons in a booth, and to navigate a hallway while avoiding people. They completed the tasks using both the original Argus II system (the 'Argus II camera') and a thermal-integrated Argus II system (the 'thermal camera'). The safety and efficiency of their navigation were evaluated by their walking speed, navigation errors, and the number of collisions. MAIN RESULTS: Navigation performance was significantly superior when using the thermal camera compared to using the Argus II camera, including 75% smaller angle of deviation (p < 0.001), 48% smaller error of distance (p < 0.05), and 30% fewer collisions (p < 0.05). The thermal camera also brought the additional benefit of allowing the participants to perform the task in the dark as efficiently as in the light. More importantly, these benefits did not come at a cost of reduced walking speed. SIGNIFICANCE: Using the thermal camera in the Argus II system, compared to a visible-light camera, could improve the wearers' navigation performance by helping them better approach or avoid other persons. Adding the thermal camera to future artificial vision therapy systems may complement the visible-light camera and improve the users' mobility safety and efficiency, enhancing their quality of life.

Improved localisation and discrimination of heat emitting household objects with the artificial vision therapy system by integration with thermal sensor.

AIM: To demonstrate the potential clinically meaningful benefits of a thermal camera integrated with the Argus II, an artificial vision therapy system, for assisting Argus II users in localising and discriminating heat-emitting objects. METHODS: Seven blind patients implanted with Argus II retinal prosthesis participated in the study. Two tasks were investigated: (1) localising up to three heat-emitting objects by indicating the location of the objects and (2) discriminating a specific heated object out of three presented on a table. Heat-emitting objects placed on a table included a toaster, a flat iron, an electric kettle, a heating pad and a mug of hot water. Subjects completed the two tasks using the unmodified Argus II system with a visible-light camera and the thermal camera-integrated Argus II. RESULTS: Subjects more accurately localised heated objects displayed on a table (p=0.011) and discriminated a specific type of object (p=0.005) presented with the thermal camera integrated with the Argus II versus the unmodified Argus II camera. CONCLUSIONS: The thermal camera integrated with the artificial vision therapy system helps users to locate and differentiate heat-emitting objects more precisely than a visible light sensor. The integration of the thermal camera with the Argus II may have significant benefits in patients' daily life.

Hemifacial Spasm in an Argus II Retinal Prosthesis Patient.

Purpose: A 59-year-old man with retinitis pigmentosa, who received an Argus II retinal prosthesis in the left eye 3 years prior, presented with left-sided involuntary facial contractions that occurred only after turning on the Argus II device. Methods: A case report. Results: Given that this patient's reported and visualized lower eyelid twitching corresponds to the location of the external region of the implanted coil, we hypothesize that heat or wirelessly transmitted electrical signals from the external coil to the implanted coil may induce spasm of the facial nerve and thus play a role in hemifacial spasm onset. Conclusions: To our knowledge, this is the first report of hemifacial spasm associated with Argus II use.

Ultrasonic Aspiration for Debulking Infiltrative Masses of the Orbit.

PURPOSE: To demonstrate the utility of an ultrasonic aspirator (Sonopet, Stryker Corporation; Kalamazoo, MI) for debulking firm, soft tissue masses of the orbit. METHODS: Case series. The ultrasonic aspirator was used to debulk firm, soft tissue masses in 3 cases. The initial patient had a large orbitofacial mass extending to the inferior and lateral orbital apex secondary to IgG4 disease. The second patient had a lacrimal sac adenocarcinoma extending to the medial orbital apex. The third patient had a large orbital mass extending to the apex secondary to granulomatosis with polyangiitis. RESULTS: The ultrasonic aspirator facilitated debulking of infiltrative firm soft tissue masses of the orbit. The device's ability to emulsify, irrigate, and aspirate, along with its small footprint, facilitated precise sculpting and debulking to an extent which would have been difficult otherwise due to location. CONCLUSIONS: The ultrasonic aspirator allows precise sculpting of infiltrative firm soft tissue masses in the orbit and is particularly useful in cases with challenging anatomical access.

Floppy eyelid syndrome in stickler syndrome.

PURPOSE: To report the possible connection between Stickler syndrome and floppy eyelid syndrome. OBSERVATIONS: A 36-year-old man with genetically confirmed Stickler syndrome presented with prominent bilateral eyelid laxity consistent with floppy eyelid syndrome. He had a high-arched palate and reported years of apneic episodes during sleep consistent with obstructive sleep apnea (OSA). CONCLUSIONS AND IMPORTANCE: To our knowledge, there have been no prior reported cases of floppy eyelid syndrome in Stickler syndrome patients. However, many patients with Stickler syndrome have palate abnormalities, which are associated with a higher risk of OSA. Given the known association between floppy eyelid syndrome and OSA, this case highlights the potential role for the ophthalmologist in identifying these patients and referring them for a sleep study if floppy eyelid syndrome is identified.

Determining Subclinical Edema in Fuchs Endothelial Corneal Dystrophy: Revised Classification using Scheimpflug Tomography for Preoperative Assessment.

PURPOSE: To determine if Scheimpflug tomography can identify subclinical corneal edema in Fuchs endothelial corneal dystrophy (FECD), and to recommend a new classification of FECD for clinical practice and research. DESIGN: Cross-sectional study with follow-up of outcomes. PARTICIPANTS: Ninety-three eyes from 57 subjects with a range of severity of FECD and 74 eyes from 40 subjects with normal corneas. METHODS: Corneas were clinically assessed for FECD and corneal edema by using slit-lamp biomicroscopy, and categorized as having clinically definite edema (obvious visible edema), being suspicious for subclinical edema (possible corneal thickening without obvious edema on slit-lamp examination), or not having edema (no clinical suspicion of edema). Tomographic pachymetry and elevation maps derived from Scheimpflug images were evaluated by 3 masked observers for specific features believed to be consistent with corneal edema. FECD clinical disease course and outcomes were reviewed from the time of Scheimpflug image acquisition to the last available follow-up. MAIN OUTCOME MEASURES: Presence of tomographic features: (1) loss of parallel isopachs, (2) displacement of the thinnest point of the cornea, and (3) focal posterior corneal surface depression. Clinical outcomes included the change in central corneal thickness (CCT) and vision after endothelial keratoplasty (EK). RESULTS: The 3 specific tomographic features were all present in all FECD corneas with clinically definite edema (n = 15), in ≥81% of FECD corneas suspicious for subclinical edema (n = 16), in ≤42% of FECD corneas deemed not to have edema (n = 62), and in ≤5% of normal corneas (n = 74). Corneas suspicious for subclinical edema that subsequently underwent EK (n = 9) all had at least 2 of the tomographic features present before EK, and improvement in vision, CCT, and tomographic features after EK confirmed the presence of subclinical edema preoperatively. CONCLUSIONS: Subclinical corneal edema in FECD can be detected by Scheimpflug tomography. We recommend classifying FECD corneas as having clinically definite edema (based on slit-lamp examination), subclinical edema (based on tomographic features without clinically definite edema), or no edema (no tomographic or slit-lamp features of edema). This classification is independent of CCT and should be considered when evaluating FECD eyes for cataract surgery or EK.

Rationally designed peptide nanosponges for cell-based cancer therapy.

A novel type of supramolecular aggregate, named a "nanosponge" was synthesized through the interaction of novel supramolecular building blocks with trigonal geometry. The cholesterol-(K/D)nDEVDGC)3-trimaleimide unit consists of a trigonal maleimide linker to which homopeptides (either K or D) of variable lengths (n=5, 10, 15, 20) and a consensus sequence for executioner caspases (DEVDGC) are added via Michael addition. Upon mixing in aqueous buffer cholesterol-(K)nDEVDGC)3-trimaleimides and a 1:1 mixture of cholesterol-(K/D)nDEVDGC)3-trimaleimides form stable nanosponges, whereas cholesterol-(D)nDEVDGC)3-trimaleimide is unable to form supramolecular aggregates with itself. The structure of the novel nanosponges was investigated through explicit solvent and then coarse-grained molecular dynamics (MD) simulations. The nanosponges are between 80 nm and several micrometers in diameters and virtually non-toxic to monocyte/macrophage-like cells.

Chromosome X genomic and epigenomic aberrations and clinical implications in breast cancer by base resolution profiling.

AIM: Abnormal inactivation or loss of inactivated X chromosome (Xi) is implicated in women's cancer. However, the underlying mechanisms and clinical relevance are little known. MATERIALS & METHODS: High-throughput sequencing was conducted on breast cancer cell lines for copy number, RNA expression and 5'-methylcytosine in ChrX. The results were examined in primary breast tumors. RESULTS & CONCLUSION: Breast cancer cells demonstrated reduced or total loss of hemimethylation. Most cell lines lost part or one of X chromosomes. Cell lines without ChrX loss were more active in gene expression. DNA methylation was corroborated with Xi control lincRNA XIST. Similar transcriptome and DNA methylation changes were observed in primary breast cancer datasets with clinical phenotype associations. Dramatic genomic and epigenomic changes in ChrX may be used for potential diagnostic or prognostic markers in breast cancer.

Comparison of the behavior of CHO cells during cultivation in 24-square deep well microplates and conventional shake flask systems.

In biopharmaceutical production, the optimization of cell culture media and supplementation is a vital element of process development. Optimization is usually achieved through the screening of multiple media, feed and feeding strategies. However, most screening is performed in shake flasks, which makes the screening process very time consuming and inefficient. The use of small scale culture systems for the screening process can aid in the ability to screen multiple formulations during process development. In order to assess the suitability of 24 deep well (24DW) plates with the Duetz sandwich-covers as a small scale culture system for process development, we have tested growth and production performance of CHO cells in 24DW plates and conventional shake flask cultures. Multiple studies were performed to assess well-to-well and plate-to-plate variability in 24DW plates. Additional studies were performed to determine the applicability of 24DW plates for cell culture medium and supplement screening in batch and fed batch processes. Cultures in 24DW plates exhibited similar kinetics in growth, viability and protein production to those cultured in shake flasks, suggesting that 24DW plates with Duetz sandwich-covers can be effectively used for high throughput cell culture screening.

Compatibility of intravenous fosaprepitant with intravenous 5-HT3 antagonists and corticosteroids.

PURPOSE: Fosaprepitant dimeglumine for injection is the water-soluble phosphorylated prodrug of the neurokinin-1 receptor antagonist aprepitant. Both agents are approved (in combination with a 5-HT3 antagonist and a corticosteroid) for prevention of chemotherapy-induced nausea and vomiting. Because fosaprepitant is likely to be combined and stored in the same intravenous (IV) bag with 5-HT3 antagonists and corticosteroids, the in vitro compatibility of fosaprepitant with these agents and other IV diluents was assessed. METHODS: Fosaprepitant (1 mg/mL in 0.9 % sodium chloride injection solution) was combined in binary or tertiary fashion with therapeutic-dose preparations of a 5-HT3 antagonist (ondansetron, granisetron, palonosetron, or tropisetron) and/or a corticosteroid (dexamethasone sodium phosphate or methylprednisolone sodium succinate). For diluent compatibility assessment, fosaprepitant was also prepared 1 mg/mL in 0.9 % sodium chloride injection solution, water for injection, or 5 % dextrose injection solution. After 24-h storage under ambient conditions, samples were assayed for degradation. RESULTS: Fosaprepitant demonstrated compatibility when combined in the same IV infusion bag with common 5-HT3 antagonists and corticosteroids for storage and IV coadministration, with the exception of palonosetron (incompatible under all experimental conditions) and tropisetron (incompatible unless combined with a corticosteroid). No incompatibility was observed between fosaprepitant and any of the 3 diluents tested. CONCLUSIONS: Use of fosaprepitant in combination with other antiemetics may provide a flexible option for administration of antiemetics to patients receiving moderately or highly emetogenic chemotherapy.

Non-suicidal self-injury and suicidal behavior: prevalence, co-occurrence, and correlates of suicide among adolescents in Hong Kong.

BACKGROUND: Despite increasing concern over the prevalence of non-suicidal self-injury (NSSI) among adolescents, there is debate about its classification as a stand-alone psychiatric diagnosis. This study investigated the patterns, co-occurrence, and correlates of NSSI and other suicidal behaviors among a representative community sample of in-school adolescents. METHODS: A cross-sectional survey of 2,317 adolescents was conducted. Participants were asked to self-report NSSI, suicidal ideation, suicide attempt, and psychosocial conditions over the past 12 months. Logistic regression and cumulative logit modeling analyses were conducted to investigate the different and similar correlates among these self-harm behaviors. RESULTS: The age-standardized prevalence rates of NSSI among male and female adolescents were estimated to be 13.4 and 19.7 %, respectively, compared with 11.1 and 10.1 % for male and female suicide attempt. Only a small proportion engaged in NSSI exclusively in the past year. NSSI by burning or reckless and risky behaviors, frequent drinking, and sexual experience were associated with increasing severity level of suicidal behaviors among individuals with NSSI. CONCLUSIONS: NSSI is prevalent among in-school adolescents in Hong Kong. However, it co-occurs with suicidal ideation and suicide attempt. High lethality of NSSI, frequent drinking habit, and lifetime sexual experience are suggested to be indicators for screening potential suicide attempters among those having NSSI.

Generation of a packaging cell line for prolonged large-scale production of high-titer HIV-1-based lentiviral vector.

BACKGROUND: A stable packaging cell line facilitates large-scale lentivirus vector manufacture. However, it has been difficult to produce clinical-scale HIV-1-based lentiviral vectors using a packaging cell line, in part due to toxicity of packaging genes, and gene silencing that occurs during the long culture period necessary for sequential addition of packaging constructs. METHODS: To avoid these problems, we developed a three-level cascade gene regulation system designed to remove tetracycline transactivator (tTA) from cytomegalovirus immediate early promoter (CMV)-controlled expression to reduce cytotoxicity from constitutive expression of tTA and leaky expression of packaging genes. We also performed a one-step integration of the three packaging plasmids to shorten the culture time for clonal selection. RESULTS: Although leaky expression of p24 and vector production still occurred despite the three-level regulation system, little cytotoxicity was observed and producer cells could be expanded for large-scale production. Producer cells yielded remarkably stable vector production over a period greater than 11 days with the highest titer 3.5 x 10(7) transducing units (TU)/ml and p24 300 ng/ml, yielding 2.2 x 10(11) TU and 1.8 milligram (mg) p24 from one cell factory. No replication-competent lentivirus (RCL) was detected. Long-term analysis demonstrated that, although the cells are genetically stable, partial gene silencing occurs after 2-3 months in culture; however, the one-step construct integration allowed prolonged vector production before significant gene silencing. Concentrated vector resulted in 90% transduction in CD4+ lymphocytes at 20 TU per cell. CD34+ progenitor cells were transduced at 41-46% efficiency, and long-term initiating culture (LTC-IC) was transduced at 45-51%. CONCLUSIONS: These results demonstrate for the first time HIV-1-based lentiviral vector production on the large scale using a packaging cell line.

Acceptability and clinical performance of a copper-containing frameless IUCD in Hong Kong.

This is the first study conducted in Hong Kong to evaluate the acceptability and clinical performance of a copper-containing frameless intrauterine contraceptive device (IUCD; GyneFix/Ji Ni). Sixty-two women chose to use the frameless IUCD for contraception. A learning curve was demonstrated in the insertion technique of this new device. Pain associated with insertion was acceptable. No pregnancy was reported during the 1-year trial period. Objectively, the amount of menstrual loss did not change and dysmenorrhea improved, but the duration of menstrual flow was slightly prolonged during the use of this device. However, there was a 10.7% request rate for removal of the device because of its side effects. The expulsion rate during the first year was 5.3%, and the continuation rate at the end of the first year was 76.7%. It was found that 85% of the 40 subjects interviewed upon the completion of the 1-year trial period wished to replace the same device after the product expiration date and that 92.5% would recommend this device to their friends. In summary, the clinical performance of the frameless IUCD was comparable to its framed counterparts. The device was considered acceptable to a majority of the women.