Early mortality in STXBP1-related disorders.

INTRODUCTION: Pathogenic variants in STXBP1 cause a spectrum of disorders mainly consisting of developmental and epileptic encephalopathy (DEE), often featuring drug-resistant epilepsy. An increased mortality risk occurs in individuals with drug-resistant epilepsy and DEE, with sudden unexpected death in epilepsy (SUDEP) often the major cause of death. This study aimed to identify the rate and causes of mortality in STXBP1-related disorders. METHODS: Through an international call, we analyzed data on individuals with STXBP1 pathogenic variants, who passed away from causes related to their disease. RESULTS: We estimated a mortality rate of 3.2% (31/966), based on the STXBP1 Foundation and the STXBP1 Global Connect registry. In total, we analyzed data on 40 individuals (23 males) harboring pathogenic STXBP1 variants, collected from different centers worldwide. They died at a median age of 13 years (range: 11 months-46 years). The most common cause of death was SUDEP (36%), followed by pulmonary infections and respiratory complications (33%). The incidence of SUDEP peaked in mid-childhood, while non-SUDEP causes were more frequent in early childhood or adulthood (p = 0.006). In the most severe phenotypes, death was related to non-SUDEP causes (p = 0.018). CONCLUSION: We found a mortality rate in STXBP1-related disorders similar to other DEEs, with an early age at death and SUDEP as well as pulmonary infections as the main cause of death. These findings assist in prognostic evaluation and genetic counseling for the families. They help to define the mortality risk of STXBP1-related disorders and implement preventative strategies.

Engagement, Acceptability, and Effectiveness of the Self-Care and Coach-Supported Versions of the Vira Digital Behavior Change Platform Among Young Adults at Risk for Depression and Obesity: Pilot Randomized Controlled Trial.

BACKGROUND: Adolescence and early adulthood are pivotal stages for the onset of mental health disorders and the development of health behaviors. Digital behavioral activation interventions, with or without coaching support, hold promise for addressing risk factors for both mental and physical health problems by offering scalable approaches to expand access to evidence-based mental health support. OBJECTIVE: This 2-arm pilot randomized controlled trial evaluated 2 versions of a digital behavioral health product, Vira (Ksana Health Inc), for their feasibility, acceptability, and preliminary effectiveness in improving mental health in young adults with depressive symptoms and obesity risk factors. METHODS: A total of 73 participants recruited throughout the United States were randomly assigned to use Vira either as a self-guided product (Vira Self-Care) or with support from a health coach (Vira+Coaching) for 12 weeks. The Vira smartphone app used passive sensing of behavioral data related to mental health and obesity risk factors (ie, activity, sleep, mobility, and language patterns) and offered users personalized insights into patterns of behavior associated with their daily mood. Participants completed self-reported outcome measures at baseline and follow-up (12 weeks). All study procedures were completed via digital communications. RESULTS: Both versions of Vira showed strong user engagement, acceptability, and evidence of effectiveness in improving mental health and stress. However, users receiving coaching exhibited more sustained engagement with the platform and reported greater reductions in depression (Cohen d=0.45, 95% CI 0.10-0.82) and anxiety (Cohen d=0.50, 95% CI 0.13-0.86) compared to self-care users. Both interventions also resulted in reduced stress (Vira+Coaching: Cohen d=-1.05, 95% CI -1.57 to --0.50; Vira Self-Care: Cohen d=-0.78, 95% CI -1.33 to -0.23) and were perceived as useful and easy to use. Coached users also reported reductions in sleep-related impairment (Cohen d=-0.51, 95% CI -1.00 to -0.01). Moreover, participants increased their motivation for and confidence in making behavioral changes, with greater improvements in confidence among coached users. CONCLUSIONS: An app-based intervention using passive mobile sensing to track behavior and deliver personalized insights into behavior-mood associations demonstrated feasibility, acceptability, and preliminary effectiveness for reducing depressive symptoms and other mental health problems in young adults. Future directions include (1) optimizing the interventions, (2) conducting a fully powered trial that includes an active control condition, and (3) testing mediators and moderators of outcome effects. TRIAL REGISTRATION: ClinicalTrials.gov NCT05638516; https://clinicaltrials.gov/study/NCT05638516.

Passively sensing smartphone use in teens with rates of use by sex and across operating systems.

Youth screen media activity is a growing concern, though few studies include objective usage data. Through the longitudinal, U.S.-based Adolescent Brain Cognitive Development (ABCD) Study, youth (mage = 14; n = 1415) self-reported their typical smartphone use and passively recorded three weeks of smartphone use via the ABCD-specific Effortless Assessment Research System (EARS) application. Here we describe and validate passively-sensed smartphone keyboard and app use measures, provide code to harmonize measures across operating systems, and describe trends in adolescent smartphone use. Keyboard and app-use measures were reliable and positively correlated with one another (r = 0.33) and with self-reported use (rs = 0.21-0.35). Participants recorded a mean of 5 h of daily smartphone use, which is two more hours than they self-reported. Further, females logged more smartphone use than males. Smartphone use was recorded at all hours, peaking on average from 8 to 10 PM and lowest from 3 to 5 AM. Social media and texting apps comprised nearly half of all use. Data are openly available to approved investigators ( https://nda.nih.gov/abcd/ ). Information herein can inform use of the ABCD dataset to longitudinally study health and neurodevelopmental correlates of adolescent smartphone use.

Language use in depressed and non-depressed mothers and their adolescent offspring.

BACKGROUND: Approximately 10% of mothers experience depression each year, which increases risk for depression in offspring. Currently no research has analysed the linguistic features of depressed mothers and their adolescent offspring during dyadic interactions. We examined the extent to which linguistic features of mothers' and adolescents' speech during dyadic interactional tasks could discriminate depressed from non-depressed mothers. METHODS: Computer-assisted linguistic analysis (Linguistic Inquiry and Word Count; LIWC) was applied to transcripts of low-income mother-adolescent dyads (N = 151) performing a lab-based problem-solving interaction task. One-way multivariate analyses were conducted to determine linguistic features hypothesized to be related to maternal depressive status that significantly differed in frequency between depressed and non-depressed mothers and higher and lower risk offspring. Logistic regression analyses were performed to classify between dyads belonging to the two groups. RESULTS: The results showed that linguistic features in mothers' and their adolescent offsprings' speech during problem-solving interactions discriminated between maternal depression status. Many, but not all effects, were consistent with those identified in previous research using primarily written text, highlighting the validity and reliability of language behaviour associated with depressive symptomatology across lab-based and natural environmental contexts. LIMITATIONS: Our analyses do not enable to ascertain how mothers' language behaviour may have influenced their offspring's communication patterns. We also cannot say how or whether these findings generalize to other contexts or populations. CONCLUSION: The findings extend the existing literature on linguistic features of depression by indicating that mothers' depression is associated with linguistic behaviour during mother-adolescent interaction.

Self-reported alcohol consumption during participation in a text messaging-based online drinking moderation platform.

BACKGROUND: Many individuals with excessive alcohol consumption desire moderation but do not seek formalized treatment. Commercially available, technology-assisted options are flexible and highly accessible, yet often not empirically validated. METHODS: Individuals desiring alcohol moderation (age 21+) self-selected to use Sunnyside®, a web application with tailored and adaptive text messaging. The evaluable dataset included 46,411 members who completed a baseline assessment, enrolled in the program, and tracked their drinking at least once. An adaptive and customizable weekly plan was generated from typical drinking patterns, goals, and weekly reported progress. Personalized daily messages included reminders for real-time drink tracking, plans, and available interactive messaging with peer coaches. Generalized mixed-effect growth models characterized change in drinks per week and daily drinking for 12 weeks after enrollment. Models allowed for nonlinear change and individual variability across members and weeks. RESULTS: A majority (64.3%) of members reported typically drinking 7 of 7 days per week at baseline. During tracking, drinks per week decreased most in the initial weeks and slowed thereafter, with an overall 33% reduction in weekly drink counts. More severe alcohol-use patterns and concern over drinking at baseline were associated with greater relative benefit. CONCLUSIONS: Drinking patterns appeared amenable to change during 12 weeks of daily drink tracking with Sunnyside®, a tailored web program to reduce drinking and improve overall wellness. Overall, the findings of this naturalistic study, one of the first of its kind, supplement data from randomized clinical trials and support the use of adaptive, technology-assisted tools for alcohol moderation.

Identifying Person-Specific Drivers of Depression in Adolescents: Protocol for a Smartphone-Based Ecological Momentary Assessment and Passive Sensing Study.

BACKGROUND: Adolescence is marked by an increasing risk of depression and is an optimal window for prevention and early intervention. Personalizing interventions may be one way to maximize therapeutic benefit, especially given the marked heterogeneity in depressive presentations. However, empirical evidence that can guide personalized intervention for youth is lacking. Identifying person-specific symptom drivers during adolescence could improve outcomes by accounting for both developmental and individual differences. OBJECTIVE: This study leverages adolescents' everyday smartphone use to investigate person-specific drivers of depression and validate smartphone-based mobile sensing data against established ambulatory methods. We describe the methods of this study and provide an update on its status. After data collection is completed, we will address three specific aims: (1) identify idiographic drivers of dynamic variability in depressive symptoms, (2) test the validity of mobile sensing against ecological momentary assessment (EMA) and actigraphy for identifying these drivers, and (3) explore adolescent baseline characteristics as predictors of these drivers. METHODS: A total of 50 adolescents with elevated symptoms of depression will participate in 28 days of (1) smartphone-based EMA assessing depressive symptoms, processes, affect, and sleep; (2) mobile sensing of mobility, physical activity, sleep, natural language use in typed interpersonal communication, screen-on time, and call frequency and duration using the Effortless Assessment of Risk States smartphone app; and (3) wrist actigraphy of physical activity and sleep. Adolescents and caregivers will complete developmental and clinical measures at baseline, as well as user feedback interviews at follow-up. Idiographic, within-subject networks of EMA symptoms will be modeled to identify each adolescent's person-specific drivers of depression. Correlations among EMA, mobile sensor, and actigraph measures of sleep, physical, and social activity will be used to assess the validity of mobile sensing for identifying person-specific drivers. Data-driven analyses of mobile sensor variables predicting core depressive symptoms (self-reported mood and anhedonia) will also be used to assess the validity of mobile sensing for identifying drivers. Finally, between-subject baseline characteristics will be explored as predictors of person-specific drivers. RESULTS: As of October 2023, 84 families were screened as eligible, of whom 70% (n=59) provided informed consent and 46% (n=39) met all inclusion criteria after completing baseline assessment. Of the 39 included families, 85% (n=33) completed the 28-day smartphone and actigraph data collection period and follow-up study visit. CONCLUSIONS: This study leverages depressed adolescents' everyday smartphone use to identify person-specific drivers of adolescent depression and to assess the validity of mobile sensing for identifying these drivers. The findings are expected to offer novel insights into the structure and dynamics of depressive symptomatology during a sensitive period of development and to inform future development of a scalable, low-burden smartphone-based tool that can guide personalized treatment decisions for depressed adolescents. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/43931.

Healthy and diabetic primary human osteoblasts exhibit varying phenotypic profiles in high and low glucose environments on 3D-printed titanium surfaces.

Background: The revolution of orthopedic implant manufacturing is being driven by 3D printing of titanium implants for large bony defects such as those caused by diabetic Charcot arthropathy. Unlike traditional subtractive manufacturing of orthopedic implants, 3D printing fuses titanium powder layer-by-layer, creating a unique surface roughness that could potentially enhance osseointegration. However, the metabolic impairments caused by diabetes, including negative alterations of bone metabolism, can lead to nonunion and decreased osseointegration with traditionally manufactured orthopedic implants. This study aimed to characterize the response of both healthy and diabetic primary human osteoblasts cultured on a medical-grade 3D-printed titanium surface under high and low glucose conditions. Methods: Bone samples were obtained from six patients, three with Type 2 Diabetes Mellitus and three without. Primary osteoblasts were isolated and cultured on 3D-printed titanium discs in high (4.5 g/L D-glucose) and low glucose (1 g/L D-Glucose) media. Cellular morphology, matrix deposition, and mineralization were assessed using scanning electron microscopy and alizarin red staining. Alkaline phosphatase activity and L-lactate concentration was measured in vitro to assess functional osteoblastic activity and cellular metabolism. Osteogenic gene expression of BGLAP, COL1A1, and BMP7 was analyzed using reverse-transcription quantitative polymerase chain reaction. Results: Diabetic osteoblasts were nonresponsive to variations in glucose levels compared to their healthy counterparts. Alkaline phosphatase activity, L-lactate production, mineral deposition, and osteogenic gene expression remained unchanged in diabetic osteoblasts under both glucose conditions. In contrast, healthy osteoblasts exhibited enhanced functional responsiveness in a high glucose environment and showed a significant increase in osteogenic gene expression of BGLAP, COL1A1, and BMP7 (p<.05). Conclusion: Our findings suggest that diabetic osteoblasts exhibit impaired responsiveness to variations in glucose concentrations, emphasizing potential osteoblast dysfunction in diabetes. This could have implications for post-surgery glucose management strategies in patients with diabetes. Despite the potential benefits of 3D printing for orthopedic implants, particularly for diabetic Charcot collapse, our results call for further research to optimize these interventions for improved patient outcomes.

Study Preregistration: Testing a Digital Suicide Risk Reduction Platform for Adolescents: A Pragmatic Randomized Controlled Trial.

Suicide is the second leading cause of death among adolescents, and rates of suicidal thoughts and behaviors (STBs) are climbing.1 Promising interventions such as dialectical behavior therapy (DBT) are available to treat suicidal youth, and new approaches may facilitate greater intervention engagement, adherence, and effectiveness.2 Digital tools (eg, personal smartphones) are a particularly promising avenue and could enhance existing, evidence-based interventions by providing new opportunities for assessment and intervention between sessions.

Identifying factors impacting missingness within smartphone-based research: Implications for intensive longitudinal studies of adolescent suicidal thoughts and behaviors.

Intensive longitudinal research-including experience sampling and smartphone sensor monitoring-has potential for identifying proximal risk factors for psychopathology, including suicidal thoughts and behaviors (STB). Yet, missing data can complicate analysis and interpretation. This study aimed to address whether clinical and study design factors are associated with missing data and whether missingness predicts changes in symptom severity or STB. Adolescents ages 13- to 18 years old (N = 179) reporting depressive, anxiety, and/or substance use disorders were enrolled; 65% reported current suicidal ideation and 29% indicated a past-year attempt. Passively acquired smartphone sensor data (e.g., global positioning system, accelerometer, and keyboard inputs), daily mood surveys, and weekly suicidal ideation surveys were collected during the 6-month study period using the effortless assessment research system smartphone app. First, acquisition of passive smartphone sensor data (with data on ∼80% of days across the whole sample) was strongly associated with survey data acquisition on the same day (∼44% of days). Second, STB and psychiatric symptoms were largely not associated with missing data. Rather, temporal features (e.g., length of time in study, weekends, and summer) explained more missingness of survey and passive smartphone sensor data. Last, within-participant changes in missing data over time neither followed nor predicted subsequent change in suicidal ideation and psychiatric symptoms. Findings indicate that considering technical and study design factors impacting missingness is critical and highlight several factors that should be addressed to maximize the validity of clinical interpretations in intensive longitudinal research. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The 2017 and 2022 ILAE epilepsy classification systems identify needs and opportunities in care: A paediatric hospital-based study.

OBJECTIVES: There is a paucity of studies reporting the epilepsy spectrum using the 2017 and 2022 ILAE classification systems in everyday clinical practice. To identify gaps and opportunities in care we evaluated a hospital-based cohort applying these epilepsy classification systems, including aetiology and co-morbidity, and the utility of molecular genetic diagnosis to identify available precision therapies. METHODS: Cross sectional retrospective study of all children with epilepsy (≤16 years) attending University Hospital Galway (2017-2022). Data collection and analysis of each case was standardised to ensure a systematic approach and application of the recent ILAE categorisation and terminology (2017 and 2022). Ethics approval was obtained. RESULTS: Among 356 children, epilepsy was classified as focal (46.1 %), generalised (38.8 %), combined (6.2 %), and unknown (9 %). Epilepsy syndrome was determined in 145/356 (40.7 %), comprising 24 different syndromes, most commonly SeLECTS (9 %), CAE (7 %), JAE (6.2 %) and IESS (5.9 %). New aetiology-specific syndromes were identified (e.g. CDKL5-DEE). Molecular diagnosis was confirmed in 19.9 % (n = 71) which encompassed monogenic (13.8 %) and chromosomopathy/CNV (6.2 %). There was an additional 35.7 % (n = 127) of patients who had a presumed genetic aetiology of epilepsy. Remaining aetiology included structural (18.8 %, n = 67), infectious (2 %, n = 7), metabolic (1.7 %, n = 6) and unknown (30.3 %, n = 108). Encephalopathy categorisation was determined in 182 patients (DE in 38.8 %; DEE in a further 11.8 %) associated with a range of co-morbidities categorised as global delay (29.2 %, n = 104), severe neurological impairment (16.3 %, n = 58), and ASD (14.6 %, n = 52). Molecular-based "precision therapy" was deemed available in 21/356 (5.9 %) patients, with "molecular precision" approach utilised in 13/356 (3.7 %), and some benefit noted in 6/356 (1.7 %) of overall cohort or 6/71 (8.5 %) of the molecular cohort. CONCLUSION: Applying the latest ILAE epilepsy classification systems allow comparison across settings and identifies a major neuro-developmental co-morbidity rate and a large genetic aetiology. We identified very few meaningful molecular-based disease modifying "precision therapies". There is a monumental gap between aetiological identification, and impact of meaningful therapies, thus the new 2017/2022 classification clearly identifies the major challenges in the provision of routine epilepsy care.

The effects of family support and smartphone-derived homestay on daily mood and depression among sexual and gender minority adolescents.

Sexual and gender minority (SGM) adolescents are at elevated risk for depression. This risk is especially pronounced among adolescents whose home environment is unsupportive or nonaffirming, as these adolescents may face familial rejection due to their identity. Therefore, it is critical to better understand the mechanisms underlying this risk by probing temporally sensitive associations between negative mood and time spent in potentially hostile home environments. The current study included adolescents (N = 141; 43% SGM; 13-18 years old), oversampled for depression history, who completed clinical interviews assessing lifetime psychiatric history and depression severity as well as self-report measures of social support. Participants also installed an app on their personal smartphones, which assessed their daily mood and geolocation-determined mobility patterns over a 6-month follow-up period. Over the 6-month follow-up period, SGM adolescents reported elevated depression severity and lower daily mood relative to non-SGM youth. Interestingly, SGM adolescents who reported low family support experienced lower daily mood than non-SGM adolescents, particularly on days when they spent more time at home. Current findings reinforce evidence for disparities in depression severity among SGM adolescents and highlight family support as a key factor. Specifically, more time spent in home environments with low family support was associated with worse mood among SGM adolescents. These results underscore the need for clinical interventions to support SGM youth, particularly interventions that focus on familial relationships and social support within the home environment. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The Google Health Digital Well-Being Study: Protocol for a Digital Device Use and Well-Being Study.

BACKGROUND: The impact of digital device use on health and well-being is a pressing question. However, the scientific literature on this topic, to date, is marred by small and unrepresentative samples, poor measurement of core constructs, and a limited ability to address the psychological and behavioral mechanisms that may underlie the relationships between device use and well-being. Recent authoritative reviews have made urgent calls for future research projects to address these limitations. The critical role of research is to identify which patterns of use are associated with benefits versus risks and who is more vulnerable to harmful versus beneficial outcomes, so that we can pursue evidence-based product design, education, and regulation aimed at maximizing benefits and minimizing the risks of smartphones and other digital devices. OBJECTIVE: The objective of this study is to provide normative data on objective patterns of smartphone use. We aim to (1) identify how patterns of smartphone use impact well-being and identify groups of individuals who show similar patterns of covariation between smartphone use and well-being measures across time; (2) examine sociodemographic and personality or mental health predictors and which patterns of smartphone use and well-being are associated with pre-post changes in mental health and functioning; (3) discover which nondevice behavior patterns mediate the association between device use and well-being; (4) identify and explore recruitment strategies to increase and improve the representation of traditionally underrepresented populations; and (5) provide a real-world baseline of observed stress, mood, insomnia, physical activity, and sleep across a representative population. METHODS: This is a prospective, nonrandomized study to investigate the patterns and relationships among digital device use, sensor-based measures (including both behavioral and physiological signals), and self-reported measures of mental health and well-being. The study duration is 4 weeks per participant and includes passive sensing based on smartphone sensors, and optionally a wearable (Fitbit), for the complete study period. The smartphone device will provide activity, location, phone unlocks and app usage, and battery status information. RESULTS: At the time of submission, the study infrastructure and app have been designed and built, the institutional review board of the University of Oregon has approved the study protocol, and data collection is underway. Data from 4182 enrolled and consented participants have been collected as of March 27, 2023. We have made many efforts to sample a study population that matches the general population, and the demographic breakdown we have been able to achieve, to date, is not a perfect match. CONCLUSIONS: The impact of digital devices on mental health and well-being raises important questions. The Digital Well-Being Study is designed to help answer questions about the association between patterns of smartphone use and well-being. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/49189.

The impact of screen use on sleep health across the lifespan: A National Sleep Foundation consensus statement.

OBJECTIVE: To achieve consensus on whether screen-based digital media (1) in general, (2) via prebedtime content, and (3) via prebedtime light impairs sleep health in (a) childhood, (b) adolescence, and (c) adulthood. Furthermore, to address whether employing behavioral strategies and interventions may reduce the potential negative effects of screens on sleep health. METHODS: The National Sleep Foundation convened a 16-person multidisciplinary expert panel ("Panel"). Panelists met virtually 5 times throughout 2023, during which they followed a modified Delphi RAND/UCLA Appropriateness Method to reach consensus. RESULTS: The Panel conducted a literature review starting with 2209 articles, narrowed down to 522 relevant empirical articles and 52 relevant review articles. The search was refined to include 35 experimental/intervention studies that examined whether there was a causal link between screen-based digital media and sleep. In addition, panelists reviewed 5 recent relevant systematic review articles. After reviewing the summarized current literature, panelists voted on 10 candidate statements about whether screen use impairs sleep health. The Panel met virtually to discuss the results of the first round of votes, which was then followed by a second round of voting, ultimately achieving consensus on 5 out of the 10 statements. CONCLUSIONS: The Panel achieved consensus that (1) in general, screen use impairs sleep health among children and adolescents, (2) the content of screen use before sleep impairs sleep health of children and adolescents, and (3) behavioral strategies and interventions may attenuate the negative effects of screen use on sleep health.

Fabrication of a Novel 3D Extrusion Bioink Containing Processed Human Articular Cartilage Matrix for Cartilage Tissue Engineering.

Cartilage damage presents a significant clinical challenge due to its intrinsic avascular nature which limits self-repair. Addressing this, our study focuses on an alginate-based bioink, integrating human articular cartilage, for cartilage tissue engineering. This novel bioink was formulated by encapsulating C20A4 human articular chondrocytes in sodium alginate, polyvinyl alcohol, gum arabic, and cartilage extracellular matrix powder sourced from allograft femoral condyle shavings. Using a 3D bioprinter, constructs were biofabricated and cross-linked, followed by culture in standard medium. Evaluations were conducted on cellular viability and gene expression at various stages. Results indicated that the printed constructs maintained a porous structure conducive to cell growth. Cellular viability was 87% post printing, which decreased to 76% after seven days, and significantly recovered to 86% by day 14. There was also a notable upregulation of chondrogenic genes, COL2A1 (p = 0.008) and SOX9 (p = 0.021), suggesting an enhancement in cartilage formation. This study concludes that the innovative bioink shows promise for cartilage regeneration, demonstrating substantial viability and gene expression conducive to repair and suggesting its potential for future therapeutic applications in cartilage repair.

Percutaneous thrombolysis via cholecystostomy catheter to dissolve biliary clots causing obstructive jaundice.

Haemobilia, or bleeding within the biliary tree, is rare. It can cause biliary obstruction secondary to blood clots. A comorbid 87-year-old was admitted to hospital with acute cholecystitis, choledocholithiasis, and an Escherichia coli bacteremia. He had a partial pancreatectomy and gastrojejunostomy 35 years prior for severe pancreatitis. He was treated with antibiotics and a percutaneous cholecystostomy. He developed atrial fibrillation and was subsequently commenced on warfarin. He re-presented 5 days after discharge with abdominal pain and fevers. Liver function tests revealed cholestasis and a supratherapeutic international normalised ratio. Imaging showed cholecystitis, biliary obstruction, and extensive biliary blood clots. He improved with antibiotics, vitamin K, and alteplase flushes through the percutaneous cholecystostomy. Repeat cholangiogram demonstrated dissolution of the biliary clots. Due to altered anatomy and comorbidities, alteplase flushes were utilized to relieve this patient's biliary obstruction. Thrombolytics may assist in treating biliary clots when first-line options are not possible or favourable.

Epileptic dyskinetic encephalopathy in KBG syndrome: Expansion of the phenotype.

KBG syndrome is characterised by developmental delay, dental (macrodontia of upper central incisors), craniofacial and skeletal anomalies. Since the identification of variants in the gene (ANKRD11) responsible for KBG syndrome, wider phenotypes are emerging. While there is phenotypic variability within many features of KBG syndrome, epilepsy is not usually markedly severe and movement disorders largely undocumented. Here we describe a novel early onset phenotype of dyskinetic epileptic encephalopathy in a male, who presented during infancy with a florid hyperkinetic movement disorder and developmental regression. Initially he had epileptic spasms and tonic seizures, and EEGs revealed a modified hypsarrhythmia. The epilepsy phenotype evolved to Lennox-Gastaut syndrome with seizures resistant to multiple anti-seizure therapies and the movement disorder evolved to choreoathetosis of limbs and head with oro-lingual dyskinesias. Previous extensive neurometabolic and imaging investigations, including panel-based exome sequencing were unremarkable. Later trio exome sequencing identified a de novo pathogenic heterozygous frameshift deletion of ANKRD11 (c.6792delC; p.Ala2265Profs*72). Review of the literature did not identify any individuals with such a hyperkinetic movement disorder presentation in combination with early-onset epileptic encephalopathy. This report expands the phenotype of ANKRD11-related KBG syndrome to include epileptic dyskinetic encephalopathy.

Laparoscopic partial splenectomy in distal pancreatectomy may preserve splenic function.

INTRODUCTION: Splenectomy is known to carry a risk of infection with encapsulated organisms and associated sepsis. Current Australian guidelines recommend intensive vaccination schedules and long-term antibiotic therapy. We postulate that in some clinical scenarios where distal pancreatectomy (DP) and splenectomy is being performed, a partial splenectomy is feasible. This may preserve splenic function and help retain immunocompetence. METHODS: Five patients underwent laparoscopic distal pancreatectomy with partial splenectomy (LDPPS). The DP is performed with proximal division and resection of the splenic artery and vein. The inferior portion of the spleen is removed en bloc with the distal pancreas with ligasure and linear cutting staplers. The line of demarcation on the spleen after the division of the splenic artery identifies the portion supplied by the short gastric vessels. Temporary clamping of the short gastrics during splenic parenchymal transection reduces blood loss. All operations were completed laparoscopically and within 4 h. RESULTS: The pathology of resected lesions includes a serous cystadenoma, a pseudocyst, an IPMN and two small medial pancreatic ductal adenocarcinomas. The benign lesions involved splenic vessels at the hilum, making Kimura or Warshaw procedures untenable. No patient required blood transfusion. One patient suffered a postoperative collection consistent with postoperative pancreatic fistula requiring a drain for 10 days. Follow-up ranged from 6 to 24 months. Following surgery, all patients had a perfused splenic remnant on imaging and benign blood films, which suggests retained splenic function. CONCLUSION: Preserving some spleen when performing distal pancreatectomy may provide long-term benefits for patients.

Full-body skin examination in screening for cutaneous malignancy: a focus on concealed sites and the practices of Australian dermatologists.

BACKGROUND: Full-body skin examination (FSE) is a vital practice in the diagnosis of cutaneous malignancy. Precisely how FSE should be conducted with respect to concealed site inclusion remains poorly elucidated. OBJECTIVE: To establish the approach of Australian dermatologists to concealed site examination (CSE). METHODS: A cross-sectional study was performed consisting of an online self-administered 11-question survey delivered to fellows of the Australasian College of Dermatologists. RESULTS: There were 237 respondents. Anogenitalia was the least often examined concealed site (4.6%), and 59.9, 32.9, and 14.3% reported always examining the scalp, breasts, and oral mucosa, respectively. Patient concern was the most frequently cited factor prompting examination, while many cited low incidence of pathology and limited chaperone availability as the main barriers to routine examination of these sites. CONCLUSION: Most Australian dermatologists do not routinely examine breasts, oral mucosal, or anogenital sites as part of an FSE. Emphasis should be made on identifying individual patient risk factors and education regarding self-examination of sensitive sites. A consensus approach to the conduct of the FSE, including concealed sites, is needed to better delineate clinician responsibilities and address medicolegal implications.