Over- and underreporting of seizures: How big is the problem?

OBJECTIVE: Clinical decisions on managing epilepsy patients rely on patient accuracy regarding seizure reporting. Studies have noted disparities between patient-reported seizures and electroencephalographic (EEG) findings during video-EEG monitoring periods, chiefly highlighting underreporting of seizures, a well-recognized phenomenon. However, seizure overreporting is a significant problem discussed within the literature, although not in such a large cohort. Our aim is to quantify the over- and underreporting of seizures in a large cohort of ambulatory EEG patients. METHODS: We performed a retrospective data analysis on 3407 patients referred to a diagnostic service for ambulatory video-EEG between 2020 and 2022. Both patient-reported events and events discovered on review of the video-EEG were analyzed and classified as epileptic, psychogenic (typically clinical motor events, without accompanying EEG change), or noncorrelated events (NCEs; without perceivable clinical or EEG change). Events were analyzed by state of arousal and indication for referral. Subgroup analysis was performed in patients with focal and generalized epilepsies. RESULTS: A total of 21 024 events were recorded by 3407 patients. Fifty-eight percent of reported events were NCEs, whereas 27% of all events were epileptic. Sixty-four percent of epileptic seizures were not reported by the patient but discovered by the clinical service on review of the recording. NCEs were in the highest proportion in the awake and drowsy arousal states and were the most common event type for the majority of referral indications. Subgroup analysis found a significantly higher proportion of NCEs in the patients with focal epilepsy (23%) compared to generalized epilepsy (10%; p < .001, chi-squared proportion test). SIGNIFICANCE: Our results reaffirm the phenomenon of underreporting and highlight the prevalence of overreporting. Overreporting likely represents irrelevant symptoms or electrographic discharges not represented on scalp electrodes, identification of which has important clinical relevance. Future studies should analyze events by risk factors to elucidate relationships clinicians can use and investigate the etiology of NCEs.

Prediction of 30-day and 1-year postoperative complications after balloon-assisted kyphoplasty in the elderly using the Risk Analysis Index.

OBJECTIVE: Vertebral compression fracture (VCF) is the most prevalent fragility fracture. When conservative management fails, patients may undergo balloon-assisted kyphoplasty (BAK). In BAK, an expandable balloon preforms a cavity in the fractured vertebra before injection of bone cement. The aim of this study was to compare outcomes in patients stratified by age and frailty assessed by the Risk Analysis Index (RAI). METHODS: A retrospective analysis of 334 BAK procedures (280 patients) for osteoporotic VCFs at a single institution was performed (2015-2022). Patients with at least 1 year of follow-up were eligible for inclusion. Patient demographics were recorded, including age, sex, BMI, RAI score, tobacco and steroid use, osteoporosis treatments, and bone density. Patients who underwent outpatient surgery were identified, and length of stay (LOS) was obtained for admitted patients. The rates of additional VCFs after kyphoplasty, 30-day and 1-year postoperative complications, and reoperation were identified. RESULTS: The overall rates of additional VCFs, 30-day postoperative complications, 1-year postoperative complications, and reoperation were 16.2%, 5.1%, 12.0%, and 6.3%, respectively. Patients were stratified by age: nonelderly (< 80 years; 220 patients, 263 treated vertebrae) and elderly (≥ 80 years; 60 patients, 71 treated vertebrae). There were no differences in sex (p = 0.593), tobacco use (p = 0.973), chronic steroid use (p = 0.794), treatment for osteoporosis (p = 0.537), bone density (p = 0.056), outpatient procedure (p = 0.273), and inpatient LOS (p = 0.661) between both groups. There were also no differences in the development of additional VCFs (p = 0.862) at an adjacent level (p = 0.739) or remote level (p = 0.814), 30-day and 1-year postoperative complications (p = 0.794 and p = 0.560, respectively), and reoperation rates (p = 0.420). Patients were then analyzed by RAI: nonfrail (RAI score < 30; 203 patients, 243 treated vertebrae) and frail (RAI score ≥ 31; 77 patients, 91 treated vertebrae). There were no differences in tobacco use (p = 0.959), chronic steroid use (p = 0.658), treatment for osteoporosis (p = 0.560), bone density (p = 0.339), outpatient procedure (p = 0.241), inpatient LOS (p = 0.570), and development of additional VCFs (p = 0.773) at an adjacent level (p = 0.390) or remote level (p = 0.689). However, rates of 30-day and 1-year postoperative complications in frail patients more than doubled in comparison with nonfrail patients (p = 0.031 and p = 0.007, respectively), and frail patients trended toward reoperation (p = 0.097). CONCLUSIONS: BAK is a safe treatment in the elderly, and age alone should not be used as an exclusion criterion during patient selection. Frailty, which can be assessed reliably using the RAI, may serve as a better predictor for postoperative complications and reoperation following BAK.

IL-2RαKO mice exhibit maternal microchimerism and reveal nuclear localization of IL-2Rα in lymphoid and non-lymphoid cells.

IL-2Rα KO mice have been instrumental to discovering the immunoregulatory properties of IL-2Rα. While initially thought of only as a stimulatory cytokine, IL-2 and IL-2Rα knock out (KO) mice revealed that this cytokine-receptor system controls immune responses through restimulation-induced cell death and by promoting the survival of T regulatory cells. Although described mostly in the context of lymphocytes, recent studies by our laboratory showed that IL-2R is expressed in smooth muscle cells. Given this finding, we sought to use IL-2Rα knock mice to determine the function of this receptor in vascular smooth muscle cells. Surprisingly, we found that IL-2Rα knock out vascular smooth muscle cells had detectable IL-2Rα. Further studies suggested that the source of IL-2Rα protein was likely maternal heterozygous cells present in KO offspring due to maternal microchimerism. Because the KO was generated by using a neomycin resistance gene insert, we treated cells with G418 and were able to eliminate the majority of IL-2Rα expressing cells. This elimination revealed that IL-2Rα KO vascular smooth muscle cells exhibited increased proliferation, decreased size, and hypodiploid DNA content when compared to wildtype cells. Our findings suggest that the phenotype of complete IL-2Rα loss is more severe than demonstrated by IL-2Rα KO mice, and that IL-2Rα plays a here-to-fore unrecognized role in regulating cell proliferation in non-lymphoid cells.

Comparing bone shape models from deep learning processing of magnetic resonance imaging to computed tomography-based models.

Background: The purpose of this study was to develop a deep learning approach to automatically segment the scapular bone on magnetic resonance imaging (MRI) images and to compare the accuracy of these three-dimensional (3D) models with that of 3D computed tomography (CT). Methods: Fifty-five patients with high-resolution 3D fat-saturated T2 MRI were retrospectively identified. The underlying pathology included rotator cuff tendinopathy and tears, shoulder instability, and impingement. Two experienced musculoskeletal researchers manually segmented the scapular bone. Five cross-validation training and validation splits were generated to independently train two-dimensional (2D) and 3D models using a convolutional neural network approach. Model performance was evaluated using the Dice similarity coefficient (DSC). All models with DSC > 0.70 were ensembled and used for the test set, which consisted of four patients with matching high-resolution MRI and CT scans. Clinically relevant glenoid measurements, including glenoid height, width, and retroversion, were calculated for two of the patients. Paired t-tests and Wilcoxon signed-rank tests were used to compare the DSC of the models. Results: The 2D and 3D models achieved a best DSC of 0.86 and 0.82, respectively, with no significant difference observed. Augmentation of imaging data significantly improved 3D but not 2D model performance. In comparing clinical measurements of 3D MRI and CT, there was a mean difference ranging from 1.29 mm to 3.46 mm and 0.05° to 7.47°. Conclusion: We have presented a fully automatic, deep learning-based strategy for extracting scapular shape from a high-resolution MRI scan. Further developments of this technology have the potential to allow for surgeons to obtain all clinically relevant information from MRI scans and reduce the need for multiple imaging studies for patients with shoulder pathology.

MMD collaborates with ACSL4 and MBOAT7 to promote polyunsaturated phosphatidylinositol remodeling and susceptibility to ferroptosis.

Ferroptosis is a form of regulated cell death with roles in degenerative diseases and cancer. Excessive iron-catalyzed peroxidation of membrane phospholipids, especially those containing the polyunsaturated fatty acid arachidonic acid (AA), is central in driving ferroptosis. Here, we reveal that an understudied Golgi-resident scaffold protein, MMD, promotes susceptibility to ferroptosis in ovarian and renal carcinoma cells in an ACSL4- and MBOAT7-dependent manner. Mechanistically, MMD physically interacts with both ACSL4 and MBOAT7, two enzymes that catalyze sequential steps to incorporate AA in phosphatidylinositol (PI) lipids. Thus, MMD increases the flux of AA into PI, resulting in heightened cellular levels of AA-PI and other AA-containing phospholipid species. This molecular mechanism points to a pro-ferroptotic role for MBOAT7 and AA-PI, with potential therapeutic implications, and reveals that MMD is an important regulator of cellular lipid metabolism.

Ambulatory video EEG extended to 10 days: A retrospective review of a large database of ictal events.

OBJECTIVE: This work aims to determine the ambulatory video electroencephalography monitoring (AVEM) duration and number of captured seizures required to resolve different clinical questions, using a retrospective review of ictal recordings. METHODS: Patients who underwent home-based AVEM had event data analyzed retrospectively. Studies were grouped by clinical indication: differential diagnosis, seizure type classification, or treatment assessment. The proportion of studies where the conclusion was changed after the first seizure was determined, as was the AVEM duration needed for at least 99% of studies to reach a diagnostic conclusion. RESULTS: The referring clinical question was not answered entirely by the first event in 29.6% (n = 227) of studies. Diagnostic and classification indications required a minimum of 7 days for at least 99% of studies to be answered, whilst treatment-assessment required at least 6 days. CONCLUSIONS: At least 7 days of monitoring, and potentially multiple events, are required to adequately answer these clinical questions in at least 99% of patients. The widely applied 72 h or single event recording cut-offs may be inadequate to adequately answer these three indications in a substantial proportion of patients. SIGNIFICANCE: Extended duration of monitoring and capturing multiple events should be considered when attempting to capture seizures on video-EEG.

Rates of event capture of home video EEG.

OBJECTIVE: Recording electrographic and behavioral information during epileptic and other paroxysmal events is important during video electroencephalography (EEG) monitoring. This study was undertaken to measure the event capture rate of an home service operating across Australia using a shoulder-worn EEG device and telescopic pole-mounted camera. METHODS: Neurologist reports were accessed retrospectively. Studies with confirmed events were identified and assessed for event capture by recording modality, whether events were reported or discovered, and physiological state. RESULTS: 6,265 studies were identified, of which 2,788 (44.50%) had events. A total of 15,691 events were captured, of which 77.89% were reported. The EEG amplifier was active for 99.83% of events. The patient was in view of the camera for 94.90% of events. 84.89% of studies had all events on camera, and 2.65% had zero events on camera (mean = 93.66%, median = 100.00%). 84.42% of events from wakefulness were reported, compared to 54.27% from sleep. CONCLUSIONS: Event capture was similar to previously reported rates from home studies, with higher capture rates on video. Most patients have all events captured on camera. SIGNIFICANCE: Home monitoring is capable of high rates of event capture, and the use of wide-angle cameras allows for all events to be captured in the majority of studies.

Egg-laying and locomotory screens with C. elegans yield a nematode-selective small molecule stimulator of neurotransmitter release.

Nematode parasites of humans, livestock and crops dramatically impact human health and welfare. Alarmingly, parasitic nematodes of animals have rapidly evolved resistance to anthelmintic drugs, and traditional nematicides that protect crops are facing increasing restrictions because of poor phylogenetic selectivity. Here, we exploit multiple motor outputs of the model nematode C. elegans towards nematicide discovery. This work yielded multiple compounds that selectively kill and/or immobilize diverse nematode parasites. We focus on one compound that induces violent convulsions and paralysis that we call nementin. We find that nementin stimulates neuronal dense core vesicle release, which in turn enhances cholinergic signaling. Consequently, nementin synergistically enhances the potency of widely-used non-selective acetylcholinesterase (AChE) inhibitors, but in a nematode-selective manner. Nementin therefore has the potential to reduce the environmental impact of toxic AChE inhibitors that are used to control nematode infections and infestations.

Accelerated corneal collagen cross-linking in progressive keratoconus: Five-year results and predictors of visual and topographic outcomes.

Purpose: To analyze the 5-year results of accelerated corneal collagen crosslinking (CXL) for progressive keratoconus and identify preoperative characteristics predictive of visual and topographic outcomes. Methods: A prospective interventional case series. Nineteen eyes of 19 patients receiving accelerated CXL with settings of 18 mW/cm2 for 5 min were included. Clinical and topographic parameters were assessed. Linear regression and logistic regression were used to compare the R2 and odds ratio (OR), respectively, between baseline characteristics and postoperative outcomes. Results: Corrected distance visual acuity (CDVA) remained stable from 0.28 ± 0.21 to 0.25 ± 0.18 logMAR (P = 0.486). The mean cylindrical refraction was stable (P = 0.119). The maximal keratometry (Kmax) decreased from 61.99 ± 10.37 to 59.25 ± 7.75 D (P < 0.001), flattening in the flattest and steepest meridians and mean keratometry were also observed (P ≤ 0.040). The mean anterior elevation at the apex reduced from 21.42 ± 16.69 to 18.53 ± 12.74 µm (P = 0.013) and changes in posterior elevation were non-significant (P = 0.629). Preoperative Kmax best predicted the postoperative change in Kmax (R2 = 0.55, P < 0.001) compared to the other baseline characteristics (P ≤ 0.028), whereas preoperative CDVA was the only significant predictor of postoperative change in CDVA (R2 = 0.41, P = 0.003). Accelerated CXL is less likely to fail in eyes with a steeper preoperative Kmax (OR = 0.74, P = 0.040) or greater posterior elevation at the apex (OR = 0.91, P = 0.042). Conclusion: Kmax significantly decreased following accelerated CXL. Eyes with worse preoperative CDVA and higher Kmax were more likely to have an improvement in visual acuity and corneal flattening.

Discovery of Potent and Orally Bioavailable Pyridine N-Oxide-Based Factor XIa Inhibitors through Exploiting Nonclassical Interactions.

Activated factor XI (FXIa) inhibitors are promising novel anticoagulants with low bleeding risk compared with current anticoagulants. The discovery of potent FXIa inhibitors with good oral bioavailability has been challenging. Herein, we describe our discovery effort, utilizing nonclassical interactions to improve potency, cellular permeability, and oral bioavailability by enhancing the binding while reducing polar atoms. Beginning with literature-inspired pyridine N-oxide-based FXIa inhibitor 1, the imidazole linker was first replaced with a pyrazole moiety to establish a polar C-H···water hydrogen-bonding interaction. Then, structure-based drug design was employed to modify lead molecule 2d in the P1' and P2' regions, with substituents interacting with key residues through various nonclassical interactions. As a result, a potent FXIa inhibitor 3f (Ki = 0.17 nM) was discovered. This compound demonstrated oral bioavailability in preclinical species (rat 36.4%, dog 80.5%, and monkey 43.0%) and displayed a dose-dependent antithrombotic effect in a rabbit arteriovenous shunt model of thrombosis.

CFTR interactome mapping using the mammalian membrane two-hybrid high-throughput screening system.

Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is a chloride and bicarbonate channel in secretory epithelia with a critical role in maintaining fluid homeostasis. Mutations in CFTR are associated with Cystic Fibrosis (CF), the most common lethal autosomal recessive disorder in Caucasians. While remarkable treatment advances have been made recently in the form of modulator drugs directly rescuing CFTR dysfunction, there is still considerable scope for improvement of therapeutic effectiveness. Here, we report the application of a high-throughput screening variant of the Mammalian Membrane Two-Hybrid (MaMTH-HTS) to map the protein-protein interactions of wild-type (wt) and mutant CFTR (F508del), in an effort to better understand CF cellular effects and identify new drug targets for patient-specific treatments. Combined with functional validation in multiple disease models, we have uncovered candidate proteins with potential roles in CFTR function/CF pathophysiology, including Fibrinogen Like 2 (FGL2), which we demonstrate in patient-derived intestinal organoids has a significant effect on CFTR functional expression.

Demographic and technological factors influencing virtual seizure clinic visit satisfaction before and during the Covid-19 pandemic in rural Hawaii.

BACKGROUND: Telemedicine clinic visits traditionally originated from spoke clinic sites, but recent trends have favored home-based telemedicine, particularly in the time of Covid-19. Our study focused on identification of barriers and factors influencing perceptions of care with use of home-based telemedicine in patients with seizures living in rural Hawaii. We additionally compared characteristics of patients using telemedicine versus in-person clinic visits prior to the Covid-19 pandemic. METHODS: For the retrospective portion of our study, we queried charts of adult outpatients treated by the two full-time epileptologists at a Level 4 epilepsy center accredited by the National Association of Epilepsy Centers between November 2018 and December 2019. We included patients who live on the neighbor islands of Hawaii but not on Oahu, i.e., patients who would require air travel to see an epileptologist. There had been no set protocol at the epilepsy center for telemedicine referral; our practice had been to offer telemedicine visits to all neighbor island patients when felt to be appropriate. We collected demographic and clinic visit data. For the prospective portion we surveyed neighbor island patients or their caregivers, seen via home-based telemedicine between March 2020 and December 2020. We obtained verbal consent for study participation. Survey questions addressed satisfaction with clinical care, visit preferences, and potential barriers to care. RESULTS: In a 14-month period prior to the Covid-19 pandemic, 75 (61%) neighbor island patients were seen exclusively in-person in seizure clinic while 47 (39%) had at least one telemedicine visit. 39% of patients seen only in-person were female whereas 38% of patients seen by telemedicine were female. Patients seen in-person had an older median age (47.2 years) compared to those seen at least once by telemedicine (42.4 years). The no-show rate was 13% for in-person visits versus 4% for telemedicine visits. Among patients seen in person, 17% were Asian, 32% Native Hawaiian, and 47% White, whereas patients seen by telemedicine were 15% Asian, 23% Native Hawaiian, and 57% White. Patients who were seen in person lived in zip codes with median household income of $68,516 and patients who were seen by telemedicine lived in zip codes with median household income of $67,089. Patients who were seen in person lived in zip codes in which 78% of the population had access to broadband internet, whereas patients who were seen by telemedicine lived in zip codes in which 79% of the population had access to broadband internet. During the Covid-19 pandemic, we surveyed 47 consecutive patients seen by telemedicine, 45% female with median age of 33 years. Telemedicine connection was set up by the patient in 74% of cases, or by the patient's mother (15%), other family member (9%), or other caregiver (2 %). Median patient satisfaction score was 5 ("highly satisfied") on a 5-point Likert scale with mean score of 4.6. Telemedicine visit was done using a smartphone by 62% of patients, a computer by 36% of patients, and a tablet by 2% of patients. A home WiFi connection was used in 83% of patients. CONCLUSIONS: Home-based telemedicine visits provide a high-satisfaction method for seizure care delivery despite some obstacles. Demographic disparities may be an obstacle to telemedicine care and seem to relate to race and possibly age, rather than to sex/gender, household income, or access to broadband internet. Additionally, despite high satisfaction overall, more patients felt the physical exam was superior at in-person clinic visits and more patients expressed a preference for in-person visits. During the Covid-19 pandemic when there may be barriers to in-person clinic visits, home-based telemedicine is a feasible alternative.

Chemical Genetics Screen Identifies COPB2 Tool Compounds That Alters ER Stress Response and Induces RTK Dysregulation in Lung Cancer Cells.

Activating mutations in the epidermal growth factor receptor (EGFR) are common driver mutations in non-small cell lung cancer (NSCLC). First, second and third generation EGFR tyrosine kinase inhibitors (TKIs) are effective at inhibiting mutant EGFR NSCLC, however, acquired resistance is a major issue, leading to disease relapse. Here, we characterize a small molecule, EMI66, an analog of a small molecule which we previously identified to inhibit mutant EGFR signalling via a novel mechanism of action. We show that EMI66 attenuates receptor tyrosine kinase (RTK) expression and signalling and alters the electrophoretic mobility of Coatomer Protein Complex Beta 2 (COPB2) protein in mutant EGFR NSCLC cells. Moreover, we demonstrate that EMI66 can alter the subcellular localization of EGFR and COPB2 within the early secretory pathway. Furthermore, we find that COPB2 knockdown reduces the growth of mutant EGFR lung cancer cells, alters the post-translational processing of RTKs, and alters the endoplasmic reticulum (ER) stress response pathway. Lastly, we show that EMI66 treatment also alters the ER stress response pathway and inhibits the growth of mutant EGFR lung cancer cells and organoids. Our results demonstrate that targeting of COPB2 with EMI66 presents a viable approach to attenuate mutant EGFR signalling and growth in NSCLC.

Management of Hematologic Adverse Events Associated With Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors target suppressor receptors, including cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1), and programmed cell death ligand 1 (PD-L1). The activated T cells are not antigen specific; therefore, the blockade of the immune checkpoint may result in the development of autoimmune adverse events. The most common immune-related adverse events (irAEs) are rash, colitis, and endocrinopathies. However, irAEs that affect the hematologic system are rare and can affect red blood cells (e.g., autoimmune hemolytic anemia), white blood cells, and platelets (e.g., immune thrombocytopenia). Usually one cell line is affected; however, in some cases, multiple cell lines can be affected. Other changes in the hematologic system can also be affected (e.g., cryoglobulinemia, cytokine release syndrome). Due to the rarity and lack of recognition of these AEs, the timing, spectrum of events, and clinical presentation are poorly understood. Management of hematologic irAEs usually involves the use of steroids; however, other agents (e.g., IVIG, cyclosporine, rituximab) or procedures (e.g., plasma exchange, transfusions) can also be used.

Receptor tyrosine kinases and cancer: oncogenic mechanisms and therapeutic approaches.

Receptor tyrosine kinases (RTKs) are transmembrane receptors of great clinical interest due to their role in disease, notably cancer. Since their discovery, several mechanisms of RTK dysregulation have been identified, resulting in multiple cancer types displaying 'oncogenic addiction' to RTKs. As a result, RTKs have represented a major class for targeted therapeutics over the past two decades, with numerous small molecule-based tyrosine kinase inhibitor (TKI) therapeutics having been developed and clinically approved for several cancers. However, many of the current RTK inhibitor treatments eventually result in the rapid development of acquired resistance and subsequent tumor relapse. Recent technological advances and tools are being generated for the identification of novel RTK small molecule therapeutics. These newer technologies will be important for the identification of diverse types of RTK inhibitors, targeting both the receptors themselves as well as key cellular factors that play important roles in the RTK signaling cascade.

Evaluation of Meibomian Gland Dysfunction Among Ophthalmic Healthcare Workers.

PURPOSE: To evaluate the prevalence of meibomian gland dysfunction (MGD) among ophthalmic healthcare workers. SETTING: A tertiary ophthalmic center. DESIGN: Prospective, observational study. METHODS: Forty-four volunteer ophthalmologists and ophthalmic nurses were recruited. Information including demographics, contact lens wear, history of refractive surgery and symptom score based on Standardized Patient Evaluation of Eye Dryness (SPEED) II Questionnaire for Dry Eye Disease/Ocular Surface Disease were recorded. Lipid layer thickness (LLT), meibomian glands dropout and dilation grades, and proportion of partial blinking were evaluated using an ocular surface interferometer with dynamic meibomian imaging (LipiView, Johnson & Johnson). Based on the chance of MGD, meibomian gland dropout and dilation, selected subjects also underwent treatment with a thermal pulsation system (LipiFlow, Johnson & Johnson) in one or both eyes. RESULTS: Eighty-eight eyes of 44 volunteers were evaluated during the study period. The mean LLT was 60.0nm. Twenty-seven (61.4%) subjects had a 90% or high chance of MGD and their mean lower lid meibomian gland dropout and dilation grades were 1.2 and 1.7, respectively. Twenty-eight eyes of 16 volunteers received treatment with the thermal pulsation system. Following treatment, the mean LLT improved from 50.3nm to 61.0nm (Wilcoxon's signed rank test, p=0.001). CONCLUSION: Despite being more knowledgeable to MGD and more accessible to treatment, MGD is a highly prevalent condition among ophthalmic healthcare workers, with a 61.4% prevalence among the recruited subjects. This is similar to reported prevalence in Asian populations of up to 74.5%. Targeted therapy based on dynamic meibomian imaging is effective in improving both objective and subjective measures of MGD.

Metastatic Melanoma With Leptomeningeal Disease.

Leptomeningeal disease in patients with melanoma historically portends a grim prognosis, with median survival measured in weeks to months. The advent of effective immunotherapy and targeted agents may modify the outcome of such patients. This case report describes a 43-year-old patient diagnosed with stage IIIa BRAF-positive cutaneous melanoma in 2012 who subsequently developed leptomeningeal involvement as her sole site of melanotic metastasis. She received multiple systemic therapies and radiotherapy and survived 2.5 years after her diagnosis with central nervous system involvement. This case report highlights the importance of a multidisciplinary team and the advent of effective agents, which offers the potential for significantly improved outcomes for patients with metastatic melanoma involving the central nervous system.

Ophthalmology in the time of COVID-19: experience from Hong Kong Eye Hospital.

AIM: To review international guidelines and to share our infection control experience during the coronavirus disease 2019 (COVID-19) pandemic at a tertiary eye centre in Hong Kong. METHODS: Infection control guidelines and recommendations from international ophthalmological bodies are reviewed and discussed. The measures at our hospital were drawn up as per international and local health authorities' guidelines and implemented with the collaboration of doctors, nurses and administrative staff. RESULTS: The aims of our infection control measures are to 1) minimize cross-infection within the hospital; 2) protect and support hospital staff; 3) ensure environmental control. To minimize the risk of cross-infection, outpatient attendance and elective surgery have been reduced by 40%, and general anesthesia procedures were reduced by 90%. Patients entering the hospital are screened for fever, travel history, contact and cluster history, and COVID-19 related symptoms. To protect and support hospital staff, we ensure provision of adequate personal protective equipment (PPE) and provide clear guidelines on the level of PPE needed, depending on the clinical situation. Other protective measures include provision of work uniforms, easy access to alcohol-based hand rub, opening new lunch areas, implementation of self-monitoring and self-reporting systems, and communication via online education and updates. Finally, environmental control is achieved by ensuring regular disinfection of the hospital premise, enhancing ventilation, and usage of disposable ophthalmic instruments. CONCLUSION: Our multi-pronged approach to infection control is, so far, successful in minimizing infection risks, while allowing the maintenance of essential ophthalmic services.

Natural history of the social millipede Brachycybe lecontii Wood, 1864.

The millipede Brachycybe lecontii Wood, 1864 is a fungivorous social millipede known for paternal care of eggs and forming multi-generational aggregations. We investigated the life history, paternal care, chemical defence, feeding and social behaviour of B. lecontii and provided morphological and anatomical descriptions, using light and scanning electron microscopy. Based on observations of B. lecontii from 13 locations throughout its distribution, we report the following natural history aspects. The oviposition period of B. lecontii lasted from mid-April to late June and the incubation period lasted 3-4 weeks. Only males cared for the eggs and subsequent care of juveniles was not observed. In one case, the clutches of two males became combined and they were later cared for by only one of the males. The defensive compound of B. lecontii is stored in large glands occupying a third of the paranotal volume and were observed only in stadia II millipedes and older. We observed B. lecontii feeding on fungi of the order Polyporales and describe a cuticular structure on the tip of the labrum that may relate to fungivory. We found that their stellate-shaped aggregations (pinwheels) do not form in the absence of fungus and suggest the aggregation is associated with feeding. We describe and illustrate a previously undescribed comb-like structure on the tibia and tarsi of the six anterior-most leg-pairs and measure the colour and spectral reflectance of the B. lecontii exoskeleton.