Non-terminally exhausted tumor-resident memory HBV-specific T cell responses correlate with relapse-free survival in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) often develops following chronic hepatitis B virus (HBV) infection and responds poorly to immune checkpoint blockade. Here, we examined the antigen specificities of HCC-infiltrating T cells and their relevance to tumor control. Using highly multiplexed peptide-MHC tetramer staining of unexpanded cells from blood, liver, and tumor tissues from 46 HCC patients, we detected 91 different antigen-specific CD8+ T cell populations targeting HBV, neoantigen, tumor-associated, and disease-unrelated antigens. Parallel high-dimensional analysis delineated five distinct antigen-specific tissue-resident memory T (Trm) cell populations. Intratumoral and intrahepatic HBV-specific T cells were enriched for two Trm cell subsets that were PD-1loTOXlo, despite being clonally expanded. High frequencies of intratumoral terminally exhausted T cells were uncommon. Patients with tumor-infiltrating HBV-specific CD8+ Trm cells exhibited longer-term relapse-free survival. Thus, non-terminally exhausted HBV-specific CD8+ Trm cells show hallmarks of active involvement and effective antitumor response, implying that these cells could be harnessed for therapeutic purposes.

A structural basis of T cell cross-reactivity to native and spliced self-antigens presented by HLA-DQ8.

Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease that has a strong HLA association, where a number of self-epitopes have been implicated in disease pathogenesis. Human pancreatic islet-infiltrating CD4+ T cell clones not only respond to proinsulin C-peptide (PI40-54; GQVELGGGPGAGSLQ) but also cross-react with a hybrid insulin peptide (HIP; PI40-47-IAPP74-80; GQVELGGG-NAVEVLK) presented by HLA-DQ8. How T cell receptors recognize self-peptide and cross-react to HIPs is unclear. We investigated the cross-reactivity of the CD4+ T cell clones reactive to native PI40-54 epitope and multiple HIPs fused at the same N-terminus (PI40-54) to the degradation products of two highly expressed pancreatic islet proteins, neuropeptide Y (NPY68-74) and amyloid polypeptide (IAPP23-29 and IAPP74-80). We observed that five out of the seven selected SKW3 T cell lines expressing TCRs isolated from CD4+ T cells of people with T1D responded to multiple HIPs. Despite shared TRAV26-1-TRBV5-1 gene usage in some T cells, these clones cross-reacted to varying degrees with the PI40-54 and HIP epitopes. Crystal structures of two TRAV26-1+-TRBV5-1+ T cell receptors (TCRs) in complex with PI40-54 and HIPs bound to HLA-DQ8 revealed that the two TCRs had distinct mechanisms responsible for their differential recognition of the PI40-54 and HIP epitopes. Alanine scanning mutagenesis of the PI40-54 and HIPs determined that the P2, P7, and P8 residues in these epitopes were key determinants of TCR specificity. Accordingly, we provide a molecular basis for cross-reactivity towards native insulin and HIP epitopes presented by HLA-DQ8.

Carriers, Quasi-particles, and Collective Excitations in Halide Perovskites.

Halide perovskites (HPs) are potential game-changing materials for a broad spectrum of optoelectronic applications ranging from photovoltaics, light-emitting devices, lasers to radiation detectors, ferroelectrics, thermoelectrics, etc. Underpinning this spectacular expansion is their fascinating photophysics involving a complex interplay of carrier, lattice, and quasi-particle interactions spanning several temporal orders that give rise to their remarkable optical and electronic properties. Herein, we critically examine and distill their dynamical behavior, collective interactions, and underlying mechanisms in conjunction with the experimental approaches. This review aims to provide a unified photophysical picture fundamental to understanding the outstanding light-harvesting and light-emitting properties of HPs. The hotbed of carrier and quasi-particle interactions uncovered in HPs underscores the critical role of ultrafast spectroscopy and fundamental photophysics studies in advancing perovskite optoelectronics.

Human T cells recognize HLA-DP-bound peptides in two orientations.

Human leukocyte antigen (HLA) molecules present small peptide antigens to T cells, thereby allowing them to recognize pathogen-infected and cancer cells. A central dogma over the last 50+ y is that peptide binding to HLA molecules is mediated by the docking of side chains of particular amino acids in the peptide into pockets in the HLA molecules in a conserved N- to C-terminal orientation. Whether peptides can be presented in a reversed C- to N-terminal orientation remains unclear. Here, we performed large-scale identification of peptides bound to HLA-DP molecules and observed that in addition to peptide binding in an N- to C-terminal orientation, in 9 out of 14 HLA-DP allotypes, reverse motifs are found, compatible with C- to N-terminal peptide binding. Moreover, we isolated high-avidity human cytomegalovirus (CMV)-specific HLA-DP-restricted CD4+ T cells from the memory repertoire of healthy donors and demonstrate that such T cells recognized CMV-derived peptides bound to HLA-DPB1*01:01 or *05:01 in a reverse C- to N-terminal manner. Finally, we obtained a high-resolution HLA-DPB1*01:01-CMVpp65(142-158) peptide crystal structure, which is the molecular basis for C- to N-terminal peptide binding to HLA-DP. Our results point to unique features of HLA-DP molecules that substantially broaden the HLA class II bound peptide repertoire to combat pathogens and eliminate cancer cells.

Making and Breaking of Exciton Cooling Bottlenecks in Halide Perovskite Nanocrystals.

Harnessing quantum confinement (QC) effects in semiconductors to retard hot carrier cooling (HCC) is an attractive approach for enabling efficient hot carrier extraction to overcome the Shockley-Queisser limit. However, there is a debate about whether halide perovskite nanocrystals (PNCs) can effectively exploit these effects. To address this, we utilized pump-probe and multipulse pump-push-probe spectroscopy to investigate HCC behavior in PNCs of varying sizes and cation compositions. Our results validate the presence of an intrinsic phonon bottleneck with clear manifestations of QC effects in small CsPbBr3 PNCs exhibiting slower HCC rates compared to those of larger PNCs. However, the replacement of inorganic Cs+ with organic cations suppresses this intrinsic bottleneck. Furthermore, PNCs exhibit distinct size-dependent HCC behavior in response to changes in the cold carrier densities. We attribute this to the enhanced exciton-exciton interactions in strongly confined PNCs that facilitate Auger heating. Importantly, our findings dispel the existing controversy and provide valuable insights into design principles for engineering QC effects in PNC hot carrier applications.

A multimodal atlas of hepatocellular carcinoma reveals convergent evolutionary paths and 'bad apple' effect on clinical trajectory.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is a highly fatal cancer characterized by high intra-tumor heterogeneity (ITH). A panoramic understanding of its tumor evolution, in relation to its clinical trajectory, may provide novel prognostic and treatment strategies. METHODS: Through the Asia-Pacific Hepatocellular Carcinoma trials group (NCT03267641), we recruited one of the largest prospective cohorts of patients with HCC, with over 600 whole genome and transcriptome samples from 123 treatment-naïve patients. RESULTS: Using a multi-region sampling approach, we revealed seven convergent genetic evolutionary paths governed by the early driver mutations, late copy number variations and viral integrations, which stratify patient clinical trajectories after surgical resection. Furthermore, such evolutionary paths shaped the molecular profiles, leading to distinct transcriptomic subtypes. Most significantly, although we found the coexistence of multiple transcriptomic subtypes within certain tumors, patient prognosis was best predicted by the most aggressive cell fraction of the tumor, rather than by overall degree of transcriptomic ITH level - a phenomenon we termed the 'bad apple' effect. Finally, we found that characteristics throughout early and late tumor evolution provide significant and complementary prognostic power in predicting patient survival. CONCLUSIONS: Taken together, our study generated a comprehensive landscape of evolutionary history for HCC and provides a rich multi-omics resource for understanding tumor heterogeneity and clinical trajectories. IMPACT AND IMPLICATIONS: This prospective study, utilizing comprehensive multi-sector, multi-omics sequencing and clinical data from surgically resected hepatocellular carcinoma (HCC), reveals critical insights into the role of tumor evolution and intra-tumor heterogeneity (ITH) in determining the prognosis of HCC. These findings are invaluable for oncology researchers and clinicians, as they underscore the influence of distinct evolutionary paths and the 'bad apple' effect, where the most aggressive tumor fraction dictates disease progression. These insights not only enhance prognostic accuracy post-surgical resection but also pave the way for personalized treatment strategies tailored to specific tumor evolutionary and transcriptomic profiles. The coexistence of multiple subtypes within the same tumor prompts a re-appraisal of the utilities of depending on single samples to represent the entire tumor and suggests the need for clinical molecular imaging. This research thus marks a significant step forward in the clinical understanding and management of HCC, underscoring the importance of integrating tumor evolutionary dynamics and multi-omics biomarkers into therapeutic decision-making. CLINICAL TRIAL NUMBER: NCT03267641 (Observational cohort).

MOrgAna: accessible quantitative analysis of organoids with machine learning.

Recent years have seen a dramatic increase in the application of organoids to developmental biology, biomedical and translational studies. Organoids are large structures with high phenotypic complexity and are imaged on a wide range of platforms, from simple benchtop stereoscopes to high-content confocal-based imaging systems. The large volumes of images, resulting from hundreds of organoids cultured at once, are becoming increasingly difficult to inspect and interpret. Hence, there is a pressing demand for a coding-free, intuitive and scalable solution that analyses such image data in an automated yet rapid manner. Here, we present MOrgAna, a Python-based software that implements machine learning to segment images, quantify and visualize morphological and fluorescence information of organoids across hundreds of images, each with one object, within minutes. Although the MOrgAna interface is developed for users with little to no programming experience, its modular structure makes it a customizable package for advanced users. We showcase the versatility of MOrgAna on several in vitro systems, each imaged with a different microscope, thus demonstrating the wide applicability of the software to diverse organoid types and biomedical studies.

Bridging science and accessibility: a tactile journey from gluten through to coeliac disease.

As part of the Monash Sensory Science Exhibition, our team guided participants through a multisensory journey unraveling coeliac disease development and pathology. Through tactile and sensory exhibits, we showed how benign dietary gluten can be transformed into a harmful entity for the 1 in 70 Australians with this illness. In contrast to the common misconception of coeliac disease as a food allergy, our exhibits revealed its closer association with autoimmune diseases such as type 1 diabetes, involving genetic susceptibility linked to specific human leukocyte antigens, crucial antigen-specific T- and B-cell responses and autoantibody production. Tactile models underscored the severe consequences of the proinflammatory immune response to gluten on patient health and quality of life. This educational event affirmed to us the value and importance of fostering inclusivity in science education.

Nonclassical Crystal Growth of Supramolecular Polymers in Aqueous Medium.

A mechanistic understanding of the principles governing the hierarchical organization of supramolecular polymers offers a paradigm for tailoring synthetic molecular architectures at the nano to micrometric scales. Herein, the unconventional crystal growth mechanism of a supramolecular polymer of superbenzene(coronene)-diphenylalanine conjugate (Cr-FFOEt ) is demonstrated. 3D electron diffraction (3D ED), a technique underexplored in supramolecular chemistry, is effectively utilized to gain a molecular-level understanding of the gradual growth of the initially formed poorly crystalline hairy, fibril-like supramolecular polymers into the ribbon-like crystallites. The further evolution of these nanosized flat ribbons into microcrystals by oriented attachment and lateral fusion is probed by time-resolved microscopy and electron diffraction. The gradual morphological and structural changes reveal the nonclassical crystal growth pathway, where the balance of strong and weak intermolecular interactions led to a structure beyond the nanoscale. The role of distinct π-stacking and H-bonding interactions that drive the nonclassical crystallization process of Cr-FFOEt supramolecular polymers is analyzed in comparison to analogous molecules, Py-FFOEt and Cr-FF forming helical and twisted fibers, respectively. Furthermore, the Cr-FFOEt crystals formed through nonclassical crystallization are found to improve the functional properties.

Identification of Genetic Variants in Progressive Supranuclear Palsy in Southeast Asia.

BACKGROUND: Progressive supranuclear palsy (PSP) is largely a sporadic disease with few reported familial cases. Genome-wide association studies (GWAS) in sporadic PSP in Caucasian populations have identified MAPT as the most commonly associated genetic risk locus with the strongest effect size. At present there are limited data on genetic factors associated with PSP in Asian populations. OBJECTIVES: Our goal was to investigate the genetic factors associated with PSP in Southeast Asian PSP patients. METHODS: Next-generation sequencing (whole-exome, whole-genome and targeted sequencing) was performed in two Asian cohorts, comprising 177 PSP patients. RESULTS: We identified 17 pathogenic or likely pathogenic variants in 16 PSP patients (9%), eight of which were novel. The most common relevant genetic variants identified were in MAPT, GBA1, OPTN, SYNJ1, and SQSTM1. Other variants detected were in TBK1, PRNP, and ABCA7-genes that have been implicated in other neurodegenerative diseases. Eighteen patients had a positive family history, of whom two carried pathogenic MAPT variants, and one carried a likely pathogenic GBA1 variant. None of the patients had expanded repeats in C9orf72. Furthermore, we found 16 different variants of uncertain significance in 21 PSP patients in PSEN2, ABCA7, SMPD1, MAPT, ATP13A2, OPTN, SQSTM1, CYLD, and BSN. CONCLUSIONS: The genetic findings in our PSP cohorts appear to be somewhat distinct from those in Western populations, and also suggest an overlap of the genetic architecture between PSP and other neurodegenerative diseases. Further functional studies and validation in independent Asian cohorts will be useful for improving our understanding of PSP genetics and guiding genetic screening strategies in these populations. © 2024 International Parkinson and Movement Disorder Society.

Dexmedetomidine for analgesia and sedation in newborn infants receiving mechanical ventilation.

BACKGROUND: Dexmedetomidine is a selective alpha-2 agonist with minimal impact on the haemodynamic profile. It is thought to be safer than morphine or stronger opioids, which are drugs currently used for analgesia and sedation in newborn infants. Dexmedetomidine is increasingly being used in children and infants despite not being licenced for analgesia in this group. OBJECTIVES: To determine the overall effectiveness and safety of dexmedetomidine for sedation and analgesia in newborn infants receiving mechanical ventilation compared with other non-opioids, opioids, or placebo. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, and two trial registries in September 2023. SELECTION CRITERIA: We planned to include randomised controlled trials (RCTs) and quasi-RCTs evaluating the effectiveness of dexmedetomidine compared with other non-opioids, opioids, or placebo for sedation and analgesia in neonates (aged under four weeks) requiring mechanical ventilation. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were level of sedation and level of analgesia. Our secondary outcomes included days on mechanical ventilation, number of infants requiring additional medication for sedation or analgesia (or both), hypotension, neonatal mortality, and neurodevelopmental outcomes. We planned to use GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We identified no eligible studies for inclusion. We identified four ongoing studies, two of which appear to be eligible for inclusion; they will compare dexmedetomidine with fentanyl in newborn infants requiring surgery. We listed the other two studies as awaiting classification pending assessment of full reports. One study will compare dexmedetomidine with morphine in asphyxiated newborns undergoing hypothermia, and the other (mixed population, age up to three years) will evaluate dexmedetomidine versus ketamine plus dexmedetomidine for echocardiography. The planned sample size of the four studies ranges from 40 to 200 neonates. Data from these studies may provide some evidence for dexmedetomidine efficacy and safety. AUTHORS' CONCLUSIONS: Despite the increasing use of dexmedetomidine, there is insufficient evidence supporting its routine use for analgesia and sedation in newborn infants on mechanical ventilation. Furthermore, data on dexmedetomidine safety are scarce, and there are no data available on its long-term effects. Future studies should address the efficacy, safety, and long-term effects of dexmedetomidine as a single drug therapy for sedation and analgesia in newborn infants.

Evaluation of the microbiological efficacy of cleaning agents for tracheostomy inner cannulas.

PURPOSE: Biofilms are a significant cause of morbidity in patients with indwelling medical devices. Biofilms pose a potential risk with reusable inner cannulas by increasing the risk of infections. Effective decontamination is thus vital in decreasing bioburden. The current guidelines for cleaning inner cannulas are varied, with multiple techniques being recommended, which are not supported by strong evidence. This randomized, controlled, cross-over study attempted to enumerate the bacterial count of inner cannulas used in tracheostomy patients (n = 60) pre-and post-decontamination with detergent (A) or sterile water (B). MATERIALS AND METHODS: The patients were randomly allocated to sequence A > B or B > A in 1:1 fashion. The saline flushing of the inner cannulas was plated on trypticase soy agar with 5 % sheep blood to enumerate the bacterial count. RESULTS: The mean ratio [Log (CFU)post/Log (CFU)pre]A/[Log (CFU)post/Log (CFU)pre]B based on 53 samples was 0.918 ± 0.470, two-sided 90 % confidence interval (CI) 0.812, 1.024. The equivalence criterion was met as the mean ratio after cleaning fell within the equivalence region of 0.8 and 1.25. CONCLUSION: This study demonstrated the microbiological efficacy of both detergent and sterile water in the decontamination of inner cannulas, and that sterile water was not less effective than detergent in reducing the bacterial load for safe re-use of inner cannulas. This has the potential to promote cost savings for patients with tracheostomy, both in the hospital and the community. The study findings may also be relevant in formulating tracheostomy care policies.

Low Dietary Diversity and Low Haemoglobin Status in Ghanaian Female Boarding and Day Senior High School Students: A Cross-Sectional Study.

Background and Objectives: Anaemia is one of the most common forms of malnutrition globally, with most anaemia cases related to micronutrient deficiency. Diets with higher dietary diversity scores (DDS) are usually nutritionally diverse and could positively impact micronutrient status, including haemoglobin (Hb) concentration improvement. The study aimed to determine DDS and its association with the Hb concentration of Boarding and Day adolescent Senior High School students in Ghana. Materials and Methods: A semi-structured and three 24 h dietary recalls were used to obtain the participants' demographic and diet intake data, respectively. Hb concentration was assessed using a validated portable haemoglobinometer. DDS was evaluated using the Minimum Dietary Diversity for Women (MDD-W) approach. Results: A significant difference in the DDS between Boarding and Day students existed. Only 22% of the Boarding students had adequate dietary diversity, whereas 64% of the Day students had adequate dietary diversity. A significantly smaller proportion of the Boarding students consumed nuts and seeds, dairy, flesh foods, eggs, vitamin A-rich vegetables and fruits, other vegetables, and other fruits compared to Day students (p < 0.05, all). No significant difference (p = 0.925) in mean (±SD) Hb concentrations between Boarding (11.9 ± 1.1 g/dL) and Day (11.9 ± 1.1 g/dL) students was found. Additionally, no significant correlation between mean DDS and Hb concentration (p = 0.997) was recorded. Using Hb < 12 g/dL as the determination of anaemia, 55.1% Boarding and 57.8% Day students had anaemia. Conclusions: Low dietary diversity in Boarding students highlighted inadequate nutrition provided by school meals. Strategies to increase meal diversity should be prioritised by stakeholders in Ghana's educational sector.

Enzyme-Triggered Assembly of Glycan Nanomaterials.

A comprehensive molecular understanding of carbohydrate aggregation is key to optimize carbohydrate utilization and to engineer bioinspired analogues with tailored shapes and properties. However, the lack of well-defined synthetic standards has substantially hampered advances in this field. Herein, we employ a phosphorylation-assisted strategy to synthesize previously inaccessible long oligomers of cellulose, chitin, and xylan. These oligomers were subjected to enzyme-triggered assembly (ETA) for the on-demand formation of well-defined carbohydrate nanomaterials, including elongated platelets, helical bundles, and hexagonal particles. Cryo-electron microscopy and electron diffraction analysis provided molecular insights into the aggregation behavior of these oligosaccharides, establishing a direct connection between the resulting morphologies and the oligosaccharide primary sequence. Our findings demonstrate that ETA is a powerful approach to elucidate the intrinsic aggregation behavior of carbohydrates in nature. Moreover, the ability to access a diverse array of morphologies, expanded with a non-natural sequence, underscores the potential of ETA, coupled with sequence design, as a robust tool for accessing programmable glycan architectures.

Insights to Carrier-Phonon Interactions in Lead Halide Perovskites via Multi-Pulse Manipulation.

A fundamental understanding of the hot-carrier dynamics in halide perovskites is crucial for unlocking their prospects for next generation photovoltaics. Presently, a coherent picture of the hot carrier cooling process remains patchy due to temporally overlapping contributions from many-body interactions, multi-bands, band gap renormalization, Burstein-Moss shift etc. Pump-push-probe (PPP) spectroscopy recently emerges as a powerful tool complementing the ubiquitous pump-probe (PP) spectroscopy in the study of hot-carrier dynamics. However, limited information from PPP on the initial excitation density and carrier temperature curtails its full potential. Herein, this work bridges this gap in PPP with a unified model that retrieves these essential hot carrier metrics like initial carrier density and carrier temperature under the push conditions, thus permitting direct comparison with traditional PP spectroscopy. These results are well-fitted by the phonon bottleneck model, from which the longitudinal optical phonon scattering time τLO , for MAPbBr3 and MAPbI3 halide perovskite thin film samples are determined to be 240 ± 10 and 370 ± 10 fs, respectively.

Multi-region sampling with paired sample sequencing analyses reveals sub-groups of patients with novel patient-specific dysregulation in Hepatocellular Carcinoma.

BACKGROUND: Conventional differential expression (DE) testing compares the grouped mean value of tumour samples to the grouped mean value of the normal samples, and may miss out dysregulated genes in small subgroup of patients. This is especially so for highly heterogeneous cancer like Hepatocellular Carcinoma (HCC). METHODS: Using multi-region sampled RNA-seq data of 90 patients, we performed patient-specific differential expression testing, together with the patients' matched adjacent normal samples. RESULTS: Comparing the results from conventional DE analysis and patient-specific DE analyses, we show that the conventional DE analysis omits some genes due to high inter-individual variability present in both tumour and normal tissues. Dysregulated genes shared in small subgroup of patients were useful in stratifying patients, and presented differential prognosis. We also showed that the target genes of some of the current targeted agents used in HCC exhibited highly individualistic dysregulation pattern, which may explain the poor response rate. DISCUSSION/CONCLUSION: Our results highlight the importance of identifying patient-specific DE genes, with its potential to provide clinically valuable insights into patient subgroups for applications in precision medicine.

Paediatric ventriculoperitoneal shunt failures: 12-year experience from a Singapore children's hospital.

PURPOSE: Cerebrospinal fluid (CSF) shunt failures in children are devastating. The primary aims of this study are to, firstly, review our institutional series of ventriculoperitoneal shunt (VPS) insertions and identify factors associated with shunt failure. METHODS: This is a single-institution, retrospective study conducted over a 12-year period. All patients under 18 years old with VPS inserted were included. Variables of interest such as patient characteristics, hydrocephalus aetiology, shunt implant details, and outcomes were subjected to statistical analyses. RESULTS: A total of 214 VPS patients were selected for this study. The mean age at VPS insertion was 6 months with a mean follow-up duration of 44 months. The most common type of hydrocephalus was obstructive (n = 142, 66.4%), and the most frequent aetiology was tumour-related (n = 66, 30.8%). The 30-day shunt failure rate was 9.3%: 9 infections (4.2%), 7 occlusions (3.3%), and 4 others (1.9%). After multivariable analysis, only recent central nervous system (CNS) infection prior to VPS insertion remained significant (OR 15.4 (1.3-175), p = 0.028). CONCLUSION: This is the first, large-scale local study focused on the shunt failure in Singaporean children. Significant findings in our study demonstrate that recently treated CNS infection is a factor associated with 30-day shunt failure while the values of CSF constituents were not contributory.

Closure intracranial pressure as a determinant of surgical decompression adequacy in spontaneous supratentorial intracerebral haematoma: a multicentre observational study.

PURPOSE: Despite significant advances, the literature on the optimal surgical treatment for spontaneous supratentorial intracerebral haematoma (ICH) remains lacking. Intraoperative ICP measured on closure (closure ICP) was reported to be a potential marker of adequate decompression in various neurosurgical conditions. We hypothesize that closure ICP also correlates with outcomes in ICH. METHODS: A multicentre retrospective study of 203 decompressive surgeries performed for ICHs was conducted (clot evacuation with either craniectomy or craniotomy). Receiver operating characteristic analysis on closure ICP was performed and an optimal threshold of 5 separated the patients into inadequate (iICP; ICP > 5 mmHg) and good decompression (gICP; ICP ≤ 5 mmHg). Postoperative ICP control, modified Rankin scale (mRS) and mortality were reported. RESULTS: There were 85 patients in the iICP and 118 patients in the gICP group respectively. The mean age, median preoperative Glasgow coma scale, ICH laterality, location, and volume were similar. After multivariable analysis, the need for (OR 2.55 [1.31-4.97]) and the duration of postoperative hyperosmolar therapy (iICP: 3 days, gICP: 1 day; p = 0.045), and repeat surgery for refractory ICP (OR 5.80 [1.53-22]) were more likely in the iICP group. The likelihood of mRS improvement at 1-year follow up was significantly worse in the iICP group (OR 0.38 [0.17-0.83], p = 0.015). CONCLUSION: Closure ICP is an objective and reproducible surgical target. When planning for surgical decompression, obtaining closure ICP of ≤ 5 mmHg is potentially able to improve postoperative ICP management and optimise functional recovery in a well selected patient population.

Outcomes of decompressive craniectomy for large territory cerebral infarction with and without prior reperfusion: a multicentre retrospective review.

PURPOSE: Reperfusion therapy has greatly improved outcomes of ischaemic stroke but remains associated with haemorrhagic conversion and early deterioration in a significant proportion of patients. Outcomes in terms of function and mortality are mixed and the evidence for decompressive craniectomies (DC) in this context remains sparse. We aim to investigate the clinical efficacy of DC in this group of patients compared to those without prior reperfusion therapy. METHODS: A multicentre retrospective study was conducted between 2005 and 2020, and all patients with DC for large territory infarctions were included. Outcomes in terms of inpatient and long-term modified Rankin scale (mRS) and mortality were assessed at various time points and compared using both univariable and multivariable analyses. Favourable mRS was defined as 0-3. RESULTS: There were 152 patients included in the final analysis. The cohort had a mean age of 57.5 years and median Charlson comorbidity index of 2. The proportion of preoperative anisocoria was 15.1%, median preoperative Glasgow coma scale was 9, the ratio of left-sided stroke was 40.1%, and ICA infarction was 42.8%. There were 79 patients with prior reperfusion and 73 patients without. After multivariable analysis, the proportion of favourable 6-month mRS (reperfusion, 8.2%; no reperfusion, 5.4%) and 1-year mortality (reperfusion, 26.7%; no reperfusion, 27.3%) were similar in both groups. Subgroup analysis of thrombolysis and/or thrombectomy against no reperfusion was also unremarkable. CONCLUSION: Reperfusion therapy prior to DC performed for large territory cerebral infarctions does not affect the functional outcome and mortality in a well-selected patient population.

A systematic scoping review of reflective writing in medical education.

BACKGROUND: Reflective writing (RW) allows physicians to step back, review their thoughts, goals and actions and recognise how their perspectives, motives and emotions impact their conduct. RW also helps physicians consolidate their learning and boosts their professional and personal development. In the absence of a consistent approach and amidst growing threats to RW's place in medical training, a review of theories of RW in medical education and a review to map regnant practices, programs and assessment methods are proposed. METHODS: A Systematic Evidence-Based Approach guided Systematic Scoping Review (SSR in SEBA) was adopted to guide and structure the two concurrent reviews. Independent searches were carried out on publications featured between 1st January 2000 and 30th June 2022 in PubMed, Embase, PsychINFO, CINAHL, ERIC, ASSIA, Scopus, Google Scholar, OpenGrey, GreyLit and ProQuest. The Split Approach saw the included articles analysed separately using thematic and content analysis. Like pieces of a jigsaw puzzle, the Jigsaw Perspective combined the themes and categories identified from both reviews. The Funnelling Process saw the themes/categories created compared with the tabulated summaries. The final domains which emerged structured the discussion that followed. RESULTS: A total of 33,076 abstracts were reviewed, 1826 full-text articles were appraised and 199 articles were included and analysed. The domains identified were theories and models, current methods, benefits and shortcomings, and recommendations. CONCLUSIONS: This SSR in SEBA suggests that a structured approach to RW shapes the physician's belief system, guides their practice and nurtures their professional identity formation. In advancing a theoretical concept of RW, this SSR in SEBA proffers new insight into the process of RW, and the need for longitudinal, personalised feedback and support.