A threshold for mitotic activity and post-surgical residual volume defines distinct prognostic groups for astrocytoma IDH-mutant.

AIMS: The distinction between CNS WHO grade 2 and grade 3 is instrumental in choosing between observational follow-up and adjuvant treatment for resected astrocytomas IDH-mutant. However, the criteria of CNS WHO grade 2 vs 3 have not been updated since the pre-IDH era. METHODS: Maximal mitotic activity in consecutive high-power fields corresponding to 3 mm2 was examined for 118 lower-grade astrocytomas IDH-mutant. The prognostic value for time-to-treatment (TTT) and overall survival (OS) of mitotic activity and other putative prognostic factors (including age, performance status, pre-surgical tumour volume, multilobar involvement, post-surgical residual tumour volume and midline involvement) was assessed for tumours with ATRX loss and the absence of CDKN2A homozygous deletion or CDK4 amplification, contrast enhancement, histological necrosis and microvascular proliferation. RESULTS: Seventy-one per cent of the samples had <6 mitoses per 3 mm2 . Mitotic activity, residual volume and multilobar involvement were independent prognostic factors of TTT. The threshold of ≥6 mitoses per 3 mm2 identified patients with a shorter TTT (median 18.5 months). A residual volume ≥1 cm3 also identified patients with a shorter TTT (median 24.5 months). The group defined by <6 mitoses per 3 mm2 and a residual volume <1 cm3 had the longest TTT (median 73 months) and OS (100% survival at 7 years). These findings were confirmed in a validation cohort of 52 tumours. CONCLUSIONS: Mitotic activity and post-surgical residual volume can be combined to evaluate the prognosis for patients with resected astrocytomas IDH-mutant. Patients with <6 mitoses per 3 mm2 and a residual volume <1 cm3 were the best candidates for observational follow-up.

Radiotherapy for newly diagnosed primary central nervous system lymphoma: role and perspective.

Whole brain radiotherapy (WBRT) has long been a key treatment of newly diagnosed primary central nervous system lymphoma (PCNSL). In the 1990s, the addition of high dose Methotrexate-based induction chemotherapy (HD MTX-based CT) has enabled a drastic improvement in PCNSL patients outcome. However, combined treatment has led to radiation-induced delayed neurotoxicity, especially in older patients. Alternative treatment strategies have been assessed to improve the efficacy and neurotoxicity ratio. Nowadays, in the elderly patients WBRT is widely omitted or deferred, and in younger patients WBRT is challenged by high dose chemotherapy with autologous stem cell transplant (HCT-ASCT) for consolidation treatment after HD MTX-based CT. In this setting, this review is addressed to clinicians with the aim to summarize the role of WBRT in the treatment of newly diagnosed PCNSL and its perspectives.

A role for the OsHKT 2;1 sodium transporter in potassium use efficiency in rice.

Increasing the potassium use efficiency (KUE) of crops is important for agricultural sustainability. However, a greater understanding of this complex trait is required to develop new, high-KUE cultivars. To this end, a genome-wide association study (GWAS) was applied to diverse rice (Oryza sativa L.) genotypes grown under potassium-stressed and -replete conditions. Using high-stringency criteria, the genetic architecture of KUE was uncovered, together with the breadth of physiological responses to low-potassium stress. Specifically, three quantitative trait loci (QTLs) were identified, which contained >90 candidate genes. Of these, the sodium transporter gene OsHKT2;1 emerged as a key factor that impacts on KUE based on (i) the correlation between shoot Na+ and KUE, and (ii) higher levels of HKT2;1 expression in high-KUE lines.

Peritoneal dialysis in patients with failed kidney transplant: Single centre experience.

AIM: To determine if patients with failing kidney transplants who opt to have peritoneal dialysis (PD) have poor short-term PD technique survival and increased rates of peritonitis. METHODS: We performed a retrospective analysis comparing 50 consecutive patients starting PD after a failed kidney transplant to 93 incident patients starting PD (matching for age, gender, diabetes causing renal failure, ethnicity and year of starting PD). RESULTS: The mean follow-up period was 26 months. PD technique survival was lower for the post-transplant cohort. However, this did not appear to be related to PD peritonitis risk; infection rate was lower in the post-transplant group albeit not statistically significant (1 in 23.6 patient months vs 1 in 22.5 patient months). There were no differences in the proportion of Gram positive: Gran negative: Culture Negative infections. The only fungal peritonitis occurred in a Control patient. Results of baseline Peritoneal Equilibration Tests were not different; D/Pcr was 0.69 for post-TP versus 0.64 for Control (P = ns), and net UF was 250 mL for post-TP versus 310 mL for Control (P = ns). PET results after 12 months were also similar. CONCLUSION: Our study found a small but significantly higher rate of PD technique failure in the post-transplant cohort, but this did not appear to be related to peritonitis rates or peritoneal membrane function. Further studies are required to explore reasons for PD technique failure in patients who have had kidney transplant, but our study supports the use of PD in selected patient from this cohort.

Survival Outcomes Associated With First-Line Procarbazine, CCNU, and Vincristine or Temozolomide in Combination With Radiotherapy in IDH-Mutant 1p/19q-Codeleted Grade 3 Oligodendroglioma.

PURPOSE: Patients with IDH-mutant 1p/19q-codeleted grade 3 oligodendroglioma (O3IDHmt/Codel) benefit from adding alkylating agent chemotherapy to radiotherapy (RT). However, the optimal chemotherapy regimen between procarbazine, 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), and vincristine (PCV) and temozolomide (TMZ) remains unclear given the lack of randomized trial data comparing both regimens. METHODS: The objective was to assess the overall survival (OS) and progression-free survival (PFS) associated with first-line PCV/RT versus TMZ/RT in patients newly diagnosed with O3IDHmt/Codel. We included patients with histologically proven O3IDHmt/Codel (according to WHO criteria) from the French national prospective cohort Prise en charge des OLigodendrogliomes Anaplasiques (POLA). All tumors underwent central pathological review. OS and PFS from surgery were estimated using the Kaplan-Meier method and Cox regression model. RESULTS: 305 newly diagnosed patients with O3IDHmt/Codel treated with RT and chemotherapy between 2008 and 2022 were included, of which 67.9% of patients (n = 207) were treated with PCV/RT and 32.1% with TMZ/RT (n = 98). The median follow-up was 78.4 months (IQR, 44.3-102.7). The median OS was not reached (95% CI, Not reached [NR] to NR) in the PCV/RT group and was 140 months (95% CI, 110 to NR) in the TMZ/RT group (log-rank P = .0033). On univariable analysis, there was a significant difference in favor of PCV/RT in both 5-year (PCV/RT: 89%, 95% CI, 85 to 94; TMZ/RT: 75%, 95% CI, 66 to 84) and 10-year OS (PCV/RT: 72%, 95% CI, 61 to 85; TMZ/RT: 60%, 95% CI, 49 to 73), which was confirmed using the multivariable Cox model adjusted for age, type of surgery, gender, Eastern Cooperative Oncology Group performance status, and CDKN2A homozygous deletion (hazard ratio, 0.53 for PCV/RT, 95% CI, 0.30 to 0.92, P = .025). CONCLUSION: In patients with newly diagnosed O3IDHmt/Codel from the POLA cohort, first-line PCV/RT was associated with better OS outcomes compared with TMZ/RT. Our data suggest that the improved safety profile associated with TMZ comes at the cost of inferior efficacy in this population. Further investigation using prospective randomized studies is warranted.

Safety of video-based telemedicine compared to in-person triage in emergency ophthalmology during COVID-19.

BACKGROUND: the need for social distancing midst the COVID-19 pandemic has forced ophthalmologists to innovate with telemedicine. The novel process of triaging emergency ophthalmology patients via videoconsultations should reduce hospital attendances. However, the safety profile of such services were unknown. METHODS: in this retrospective cohort study, we reviewed case notes of 404 adults who used our videoconsultation service from 20/04/2020 to 03/05/2020. We compared these to 451 patient who attended eye casualty in person at the same time who were deemed not to require same day ophthalmic examination. FINDINGS: patients seen by videoconsultations tended to be younger (Median = 43 years, Inter-quartile range = 27 vs Median= 49 years, Inter-quartile range = 28)'. More males used the face-to-face triage (55%) while more females used videoconsultation (54%)%. Fewer patients seen by videoconsultations required specialist review compared to face-face triage [X 2 (1, N = 854) = 128.02, p<0.001)]. 35.5% of the patients initially seen by videoconsultation had unplanned reattendance within 1 month, compared to 15.7% in the group initially seen in person. X 2 (1, N = 234) = 7.31, p = 0.007). The rate of actual harm was no different (at 0% for each method), with perfect inter-grader correlation when graded independently by two senior ophthalmologists. 97% of patients seen on the video platform surveyed were satisfied with their care. INTERPRETATION: we demonstrate comparable patient safety of videoconsultations at one-month follow-up to in person review. The service is acceptable to patients and reduces the risk of COVID-19 transmission. We propose that videoconsultations are effective and desirable as a tool for triage in ophthalmology. FUNDING: the research supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology who fund PT and DS's time to conduct research. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.

Creating the Moorfields' virtual eye casualty: video consultations to provide emergency teleophthalmology care during and beyond the COVID-19 pandemic.

BACKGROUND: The COVID-19 crisis forced hospitals in the UK dramatically to reduce outpatient activity. To provide continuity of care and to assist patients reluctant or unable to leave their homes, video consultations were rapidly implemented across routine and emergency ophthalmology services. OBJECTIVE: To describe the deployment and scaling to a large volume of teleophthalmology using a video consultation platform 'Attend Anywhere' in Moorfields Eye Hospital's accident and emergency (A&E) department (London, UK). METHOD: Patient satisfaction, waiting time, consultation duration, outcome and management were audited following the launch of the new virtual A&E service. RESULTS: In the 12 days following the service launch, 331 patients were seen by video consultation. 78.6% of patients (n=260) were determined not to need hospital A&E review and were managed with advice (n=126), remote prescription (n=57), general practitioner referral (n=27), direct referral to hospital subspecialty services (n=26) or diversion to a local eye unit (n=24). Mean patient satisfaction was 4.9 of 5.0 (n=62). The mean consultation duration was 12 min (range 5-31 min) and the wait time was 6 min (range 0-37 min). CONCLUSION: Video consultations showed greater than expected usefulness in the remote management of eye disease and supported a substantial reduction in the number of people visiting the hospital.

Initial surgical resection and long time to occurrence from initial diagnosis are independent prognostic factors in resected recurrent IDH wild-type glioblastoma.

OBJECTIVE: IDH wild-type glioblastoma is the most common and aggressive primary brain cancer in adults. At tumor recurrence, treatment decision-making is not standardized; several options include second surgery, reirradiation, and a second line of chemotherapy. In this retrospective monocentric study conducted at the era of WHO 2016 classification, we investigated IDH wild-type glioblastoma patients below the age of 70 to see (i) the clinical benefit of second surgery at recurrence and (ii) the prognostic factors in resected recurrent glioblastoma patients. METHODS: 229 newly diagnosed IDH wild-type glioblastoma patients below the age of 70 treated with the standard of care (SOC) were enrolled in the current study and stratified into two subgroups according to treatment at recurrence: re-resection and no re-resection. RESULTS: All experienced tumor recurrence with a median progression-free survival of 11 months. 25 % of patients were reoperated. Patients reoperated at recurrence had longer post-progression median overall survival compared to their non-reoperated counterparts (14 versus 9 months, p < .05). Initial surgical resection and a long time from the initial diagnosis to the first recurrence were independent prognostic factors for good outcomes in resected recurrent IDH-wild-type glioblastoma patients; however, tumor size before and after surgery did not impact post-surgical survival. CONCLUSION: Our study supports surgical resection at recurrence as therapeutic in IDH wild-type glioblastoma patients aged below 70 and in good clinical condition regardless of preoperative tumor size, particularly in patients who experienced a longer time before first recurrence and surgery at initial diagnosis. Further prospective and larger studies are warranted to validate our findings.

Medulloblastoma: optimizing care with a multidisciplinary approach.

Medulloblastoma is a malignant tumor of the cerebellum and the most frequent malignant brain tumor in children. The standard of care consists of maximal resection surgery, followed by craniospinal irradiation and chemotherapy. Such treatment allows long-term survival rates of nearly 70%; however, there are wide disparities among patient outcomes, and in any case, major long-term morbidity is observed with conventional treatment. In the last two decades, the molecular understanding of medulloblastoma has improved drastically, allowing us to revolutionize our understanding of medulloblastoma pathophysiological mechanisms. These advances led to an international consensus in 2010 that defined four prognostic molecular subgroups named after their affected signaling pathways, that is, WNT, SHH, Group 3 and Group 4. The molecular understanding of medulloblastoma is starting to translate through to clinical settings due to the development of targeted therapies. Moreover, recent improvements in radiotherapy modalities and the reconsideration of craniospinal irradiation according to the molecular status hold promise for survival preservation and the reduction of radiation-induced morbidity. This review is an overview of the current knowledge of medulloblastoma through a molecular approach, and therapeutic prospects currently being developed in surgery, radiotherapy and targeted therapies to optimize the treatment of medulloblastoma with a multidisciplinary approach will also be discussed.

Assessment of a Dedicated Transplant Low Clearance Clinic and Patient Outcomes on Dialysis After Renal Allograft Loss at 2 UK Transplant Centers.

BACKGROUND: Low clearance transplant clinics (LCTCs) are recommended for the management of recipients with a failing kidney transplant (RFKT) but data to support their use is limited. We conducted a retrospective study to assess management of RFKT at 2 transplant centers, 1 with a LCTC (center A) and 1 without (center B). METHODS: Patients who transitioned to an alternative form of renal replacement therapy (RRT) between January 1, 2012, and November 30, 2016, were included. Patients with graft failure within a year of transplantation or due to an unpredictable acute event were excluded. Clinical data were collected after review of medical records. RESULTS: One hundred seventy-nine patients (age, 48.6 ± 13.4 years, 99 [55.3%] male, and mean transplant duration 10.3 ± 7.8 years) were included. RRT counseling occurred in 79 (91%) and 68 (74%) patients at centers A and B (P = 0.003), at median 135 (61-319) and 133 (69-260) days before dialysis after graft loss (P = 0.92). Sixty-one (34.1%) patients were waitlisted for retransplantation; 18 (32.7%) nonwaitlisted patients were still undergoing workup at center A compared with 37 (58.7%) at center B (P = 0.028). Preemptive retransplantation occurred in 4 (4.6%) and 5 (5.4%) patients at centers A and B (P = 0.35). At 1 year after initiation of dialysis after graft loss, 11 (15.3%) and 11 (17.2%) patients were retransplanted (P = 0.12), and mortality was 6.6% overall. CONCLUSIONS: A dedicated LCTC improved RRT counseling and transplant work-up but did not lead to improved rates of retransplantation. Earlier consideration of retransplantation in LCTCs is required to improve RFKT outcomes.

Chemical reactions at the graphitic step-edge: changes in product distribution of catalytic reactions as a tool to explore the environment within carbon nanoreactors.

A series of explorative cross-coupling reactions have been developed to investigate the local nanoscale environment around catalytically active Pd(ii)complexes encapsulated within hollow graphitised nanofibers (GNF). Two new fullerene-containing and fullerene-free Pd(ii)Salen catalysts have been synthesised, and their activity and selectivity towards different substrates has been explored in nanoreactors. The catalysts not only show a significant increase in activity and stability upon heterogenisation at the graphitic step-edges inside the GNF channel, but also exhibit a change in selectivity affected by the confinement which alters the distribution of isomeric products of the reaction. Furthermore, the observed selectivity changes reveal unprecedented details regarding the location and orientation of the catalyst molecules inside the GNF nanoreactor, inaccessible by any spectroscopic or microscopic techniques, thus shedding light on the precise reaction environment inside the molecular catalyst-GNF nanoreactor.

An interprofessional induction to hand surgery.

BACKGROUND: Hand surgery is a multidisciplinary specialty and health care professionals require effective training. An interprofessional induction for hand trauma co-ordinators (HTCs), core trainees (CTs) and specialty trainees (STs) was designed. The primary aim of our study was to determine any improvement in participants' knowledge. Our secondary aim was to assess participants' responses to the interprofessional aspect of the induction, and to gather general feedback. METHODS: Validated multiple-choice questionnaires (MCQs) were distributed to 18 participants before and after induction. Score improvement was analysed for significance with a Student's t-test. Feedback was obtained with validated questionnaires using Likert-scale answers, Yes/No answers and qualitative free-text answers. RESULTS/FINDINGS: Overall, the MCQ scores significantly improved by 3.8/16 points (p < 0.0001). HTC, CT and ST scores improved by 4.3 points (p < 0.05), 3.8 points (p < 0.0005) and 3.6 points (p < 0.005), respectively. The educational content and presentation of the sessions were rated as 4.44/5 and 4.50/5, respectively. Participants appreciated the interdisciplinary aspect of the induction and thought it improved interprofessional teamworking (83%) and patient care (89%), but needed more time to cover topics. DISCUSSION: Our study shows that our interprofessional induction significantly improved the knowledge of participants from all levels of experience within the MDT, whilst developing interprofessional collaboration to promote safe and effective care for patients. This study is of interest to specialties working within a multidisciplinary team environment. Hand surgery is a multidisciplinary speciality and health care professionals require effective training.

Establishing likelihood ratios for patterned garment comparisons from seam measurement data.

It is often challenging to ascribe an objective measure of confidence for identifications based on surveillance imagery from a crime scene. The present work seeks to address this deficiency in the case of garment comparison evidence by developing a quantitative method for establishing a conservative lower bound on the likelihood ratio (LR) for identifications involving patterned garments. The method is based on statistical analysis of pattern offset measurements taken from a sample of garments of the same type (manufacturer, style, and size) as the seized evidence. The developed analysis framework was demonstrated on different types of garments over a range of modeled surveillance imaging scenarios with variable image quality; the lower bounds on the LRs ranged from approximately 10-1 to over 400-1. The statistical model was tested and validated through a large-scale empirical study involving both simulated and human observer-performed garment comparisons.

Single KTP nanocrystals as second-harmonic generation biolabels in cortical neurons.

We report an efficient colloidal synthesis of KTiOPO4 (KTP) nanocrystals with excellent crystallinity and the direct observation of optical second-harmonic generation (SHG) from discrete KTP nanocrystals in neurons cultured from mammalian brain cortex. Direct internalization and monitoring of these nanoparticles was successfully achieved without limitations from cytotoxicity, bleaching and blinking emission.