Distinct spatiotemporal atrophy patterns in corticobasal syndrome are associated with different underlying pathologies.

Objective: To identify imaging subtypes of the cortico-basal syndrome (CBS) based solely on a data-driven assessment of MRI atrophy patterns, and investigate whether these subtypes provide information on the underlying pathology. Methods: We applied Subtype and Stage Inference (SuStaIn), a machine learning algorithm that identifies groups of individuals with distinct biomarker progression patterns, to a large cohort of 135 CBS cases (52 had a pathological or biomarker defined diagnosis) and 252 controls. The model was fit using volumetric features extracted from baseline T1-weighted MRI scans and validated using follow-up MRI. We compared the clinical phenotypes of each subtype and investigated whether there were differences in associated pathology between the subtypes. Results: SuStaIn identified two subtypes with distinct sequences of atrophy progression; four-repeat-tauopathy confirmed cases were most commonly assigned to the Subcortical subtype (83% of CBS-PSP and 75% of CBS-CBD), while CBS-AD was most commonly assigned to the Fronto-parieto-occipital subtype (81% of CBS-AD). Subtype assignment was stable at follow-up (98% of cases), and individuals consistently progressed to higher stages (100% stayed at the same stage or progressed), supporting the model's ability to stage progression. Interpretation: By jointly modelling disease stage and subtype, we provide data-driven evidence for at least two distinct and longitudinally stable spatiotemporal subtypes of atrophy in CBS that are associated with different underlying pathologies. In the absence of sensitive and specific biomarkers, accurately subtyping and staging individuals with CBS at baseline has important implications for screening on entry into clinical trials, as well as for tracking disease progression.

Comparison of United Kingdom and United States screening criteria for detecting retinopathy of prematurity in Hong Kong.

INTRODUCTION: We examined whether the United Kingdom (UK) or the United States (US) screening criteria are more appropriate for retinopathy of prematurity (ROP) screening in Hong Kong, in terms of sensitivity for detecting type 1 ROP and the number of infants requiring screening. METHODS: In this retrospective cohort study, we reviewed the medical records of all infants who underwent ROP screening from 2009 to 2018 at a tertiary hospital in Hong Kong. During this period, all infants born at gestational age (GA) ≤31 weeks and 6 days or birth weight (BW) <1501 g (ie, the UK screening criteria) underwent ROP screening. We determined the number of infants requiring screening and the number of type 1 ROP cases that would have been missed if the US screening criteria (GA ≤30 weeks & 0 days or BW ≤1500 g) had been used. RESULTS: Overall, 796 infants were screened using the UK screening criteria. If the US screening criteria had been used, the number of infants requiring screening would have decreased by 21.1%; all type 1 ROP cases would have been detected (38/38, 100% sensitivity). Of the 168 infants who would not have been screened using the US screening criteria, only four of them (2.4%) had developed ROP (all maximum stage 1 only). CONCLUSION: In our population, the use of the US screening criteria could reduce the number of infants screened without compromising sensitivity for the detection of type 1 ROP requiring treatment. We suggest narrowing the GA criterion for consistency with the US screening criteria during ROP screening in Hong Kong.

Gender representation in editorial boards of international general surgery journals.

BACKGROUND: Despite women constituting over half of new doctors, gender disparity remains an issue. Surgery has shown particularly slow progress towards gender parity. This study aimed to quantify gender representation within editorial boards of the highest ranking international general surgery journals. METHODS: Surgical journals were collated using two indices: SCImago Journal Rank (SJR) and Journal Impact Factor (JIF). Non-general surgery journals were excluded. Journals were contacted, requesting gender editorial team demographics. Editorial board data were collected via journal websites on 28 November 2019. RESULTS: The top 25 general surgery journals according to SJR and JIF ranking methods were determined, identifying 28 unique journals. Editorial board data were publicly available for 27 of these 28 surgical journals, and were examined. Women accounted for 20.2 per cent (568 of 2816) of total editorial board positions. Women constituted 11 per cent (4 of 36) of editor-in-chief positions, 32 per cent (29 of 92) of deputy editors, and 19.1 per cent (369 of 1935) of general editorial board positions. CONCLUSION: The findings demonstrate gender disparity within editorial boards of the most prominent general surgery journals.

Epidemiology of myopia and prevention of myopia progression in children in East Asia: a review.

INTRODUCTION: Myopia (short-sightedness) exhibits high prevalence in East Asia. Methods to mitigate myopia progression are important in preventing the vision-threatening complications associated with high myopia. In this review, we examine the regional epidemiology of myopia and provide updated evidence regarding interventions to slow myopia progression in children. METHODS: We performed a literature search using PubMed from the date of inception through 25 June 2018. Studies involving myopia epidemiology and control of myopia progression were selected; only studies published in English were reviewed. Preference was given to prospective studies, as well as those conducted in Hong Kong or East Asia. RESULTS: Atropine eye drops and pirenzepine eye gel are highly effective for controlling myopia progression in children. Orthokeratology, peripheral defocus contact lenses, bifocal or progressive addition spectacles, and increased involvement in outdoor activities are also effective for controlling myopia progression; however, myopia undercorrection and single vision contact lenses are ineffective. CONCLUSION: Although various methods are effective for controlling myopia progression in children, no curative remedy exists for myopia. Health care professionals should be aware of the available methods, as well as their risks and benefits. Treatment should be individualised and based on the preferences of the patient's family, after full discussion of the risks and benefits of each modality.

Expectations of outcomes in patients with colorectal cancer.

BACKGROUND: Understanding patients' expectations of their treatment is critical to ensure appropriate treatment decisions, and to explore how expectations influence coping, quality of life and well-being. This study aimed to examine these issues related to treatment in patients with colorectal cancer. METHODS: A literature search from January 1946 to September 2016 was performed to identify available data regarding patients' expectations of outcomes following colorectal cancer treatment. A narrative synthesis of the evidence was planned. RESULTS: Of 4337 items initially identified, 20 articles were included in the review. In studies presenting data on overall and short-term survival, patients considerably overestimated prognosis. Patients also had unrealistic expectations of the negative aspects of chemotherapy and stomas. There was marked discordance between patients' and clinicians' expectations regarding chemotherapy, end-of-life care, bowel function and psychosocial outcomes. Level of education was the most consistent factor influencing the accuracy of patients' expectations. CONCLUSION: Patients with colorectal cancer frequently have unrealistic expectations of treatment. Marked disparities exist between patients' and clinicians' expectations of outcomes.

Impact of a National Controlled Donation After Circulatory Death (DCD) Program on Organ Donation in the United Kingdom: A 10-Year Study.

Organ transplantation is the most successful treatment for some forms of organ failure, yet a lack of organs means many die on the waiting list. In the United Kingdom, the Organ Donation Taskforce was set up to identify barriers to organ donation and in 2008 released its first report (Organ Donation Taskforce Report; ODTR). This study assesses the success since the ODTR and examines the impact of the United Kingdom's controlled donation after circulatory death (DCD) program and the controversies surrounding it. There were 12 864 intended donation after brain death (DBD) or DCD donors from April 2004 to March 2014. When the 5 years preceding the ODTR was compared to the 5 years following, intended DCD donors increased 292% (1187 to 4652), and intended DBD donors increased 11% (3327 to 3698). Organs retrieved per intended DBD donor remained static (3.30 to 3.26), whereas there was a decrease in DCD (1.54 to 0.99) due to a large rise in donors who did not proceed to donation (325 to 2464). The majority of DCD donors who proceeded did so within 30 min from time of withdrawal. Our study suggests further work on converting eligible referrals to organ donation and exploring methods of converting DCD to DBD donors.

Dnmt3a regulates T-cell development and suppresses T-ALL transformation.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematopoietic neoplasm resulting from the malignant transformation of T-cell progenitors, and comprises ~15% and 25% of pediatric and adult ALL cases, respectively. It is well-established that activating NOTCH1 mutations are the major genetic lesions driving T-ALL in most patients, but efforts to develop targeted therapies against this pathway have produced limited success in decreasing leukemic burden and come with significant clinical side effects. A finer detailed understanding of the genetic and molecular mechanisms underlying T-ALL is required identify patients at increased risk for treatment failure and the development of precision medicine strategies. Generation of genetic models that more accurately reflect the normal developmental history of T-ALL are necessary to identify new avenues for treatment. The DNA methyltransferase enzyme DNMT3A is also recurrently mutated in T-ALL patients, and we show here that inactivation of Dnmt3a combined with Notch1 gain-of-function leads to an aggressive T-ALL in mouse models. Moreover, conditional inactivation of Dnmt3a in mouse hematopoietic cells leads to an accumulation of immature progenitors in the thymus, which are less apoptotic. These data demonstrate that Dnmt3a is required for normal T-cell development, and acts as a T-ALL tumor suppressor.

Grandparents of children with cancer: Quality of life, medication and hospitalizations.

BACKGROUND: Grandparents can play a crucial role of providing emotional and practical support for families facing childhood cancer. Yet, many have their own healthcare needs. This controlled study systematically assesses the impact of childhood cancer on grandparents' quality of life (QOL). Our objective was to compare QOL in grandparents of children with and without cancer and to identify factors associated with grandparents' QOL. PROCEDURE: Grandparents (N = 222) completed two patient-reported outcome (PRO) measures assessing QOL: EQ-5D-5L and WHOQOL-BREF. Secondary endpoints included sleep, medications and hospitalizations. We used independent samples t-tests and multivariate linear regression to assess between-group differences and identify predictors. RESULTS: Grandparents of children with cancer (n = 89) reported significantly worse QOL than controls (n = 133) [mean WHOQOL-BREF score: 75.6 (SD = 17.6) vs. 81.5 (15.6), P = 0.007; mean EQ-5D-5L index value: 0.777 (0.20) vs. 0.874 (0.14), P < 0.001)]. They also reported more problems with anxiety and depression (47.2 vs. 21.8%, P < 0.001) and pain (64.8 vs. 49.6%, P = 0.031). Grandparents of children with cancer reported taking longer to fall asleep [mean: 30.4 min (55.6) vs. 18.2 (20.2), P = 0.011] and taking more medications in the last 4 weeks [mean: 2.9 (SD = 3.8) vs. 1.8 (SD = 2.3), P = 0.012]. Hospitalizations were comparable across groups. Grandmothers, those living in urban locations, and retired/unemployed grandparents experienced reduced QOL. CONCLUSIONS: Grandparents are significantly affected by childhood cancer. The impact appears across many domains of life and results in meaningful QOL differences. Given that four or more individuals may be affected per child, and that grandparent well-being can influence the whole family, interventions targeting at-risk grandparents are needed.

Depression and anxiety in dry eye disease: a systematic review and meta-analysis.

AimTo evaluate the association of dry eye disease (DED) with depression and anxiety.Patients and methodsWe conducted a systematic review and meta-analysis of studies that reported the prevalence, incidence and/or severity grading of depression and/or anxiety in DED patients and healthy controls. We searched MEDLINE, EMBASE, PsycINFO, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform for relevant studies.ResultsTwenty-two eligible studies consisted of 2 980 026 patients were analyzed. DED was associated with an increased prevalence of depression (summary odds ratio (OR)=2.92, 95% CI: 2.13-4.01, P<0.00001) and anxiety (OR=2.80, 95% CI: 2.61-3.02, P<0.00001). The depression score (standardized mean difference (SMD)=0.81, 95% CI: 0.48-1.15, P<0.00001) and anxiety score (SMD=0.37, 95% CI: 0.10-0.64, P=0.007) were higher in DED patients than in controls. Subgroup analyses revealed that the prevalence and severity of depression are greatest in primary Sjogren's syndrome patients. No study reported the incidence.ConclusionDepression and anxiety are more prevalent in DED patients than in controls. Among patients with DED, those suffering from primary Sjogren's syndrome have higher prevalence and severity of depression.

The management of the surgical complications of HELLP syndrome.

INTRODUCTION: Complications from HELLP (Haemolysis, Elevated Liver enzymes and Low Platelet) syndrome may present as an emergency to any surgeon. We review the ten-year experience of a tertiary hepatobiliary centre managing HELLP patients. Three selected cases are described to highlight our management strategy and a systematic review of the recent literature is presented. METHODS: All patients with HELLP syndrome were identified from a prospectively maintained database and their details collated. Subsequently, a detailed search of PubMed was carried out to identify all case series of HELLP syndrome in the literature in the English language since 1999. RESULTS: On review of 1,002 cases, 10 patients were identified with surgical complications of HELLP syndrome. Seven of these patients had a significant liver injury. Only three of these required surgical intervention for liver injury although four other patients required surgical intervention for other complications. There was no maternal mortality in this series. Review of the literature identified 49 cases in 31 publications. The management approaches of these patients were compared with ours. CONCLUSIONS: We have presented a large series of patients with surgical complications resulting from HELLP syndrome managed without maternal mortality. This review has confirmed that haemodynamically stable patients with HELLP syndrome associated hepatic rupture can be conservatively treated successfully. However, in unstable patients, perihepatic packing and transfer to a specialist liver unit is recommended.

Outcome of polypoidal choroidal vasculopathy at 1 year by combined therapy of photodynamic therapy with ranibizumab and predictive factors governing the outcome.

AIM: To report the visual outcome of polypoidal choroidal vasculopathy receiving combined treatment with photodynamic therapy using Visudyne and intravitreal ranibizumab injections, and to analyze the predictive factors of visual outcome at 1 year post treatment. METHODS: Seventy-four consecutive patients with newly diagnosed polypoidal choroidal vasculopathy were treated with photodynamic therapy using Visudyne and three loading doses of intravitreal ranibizumab. The final visual outcome and polyp eradication rate at 1 year were reported. A stepwise regression model was used to estimate the baseline clinical factors predictive of better visual outcome and polyp eradication. RESULTS: Visual acuities at 12-months follow-up improved significantly compared with baseline from 0.828 logMAR to 0.728 logMAR (P=0.026). The mean foveal thickness decreased from 380±175 to 278±117 µm. In all 29.7% of eyes improved at least by 0.3 logMAR, and 55.4% remained stable in visual acuity with less than 0.3 logMAR change. Overall, 85% of eyes achieved at least stable vision, 20.2% (15/74) cases achieved polyp eradication on angiogram, and 60.8% (45/74) achieved polyp size reduction on angiogram at 1 year. Regarding predictive factors, the baseline visual acuity (P=0.003), no foveal involvement by abnormal choroidal vasculature (P<0.0001), absence of hard exudates (0.001) or subretinal fluid (<0.0001) are important clinical factors affecting the final visual outcome. CONCLUSIONS: Combination therapy with photodynamic therapy using Visudyne and three loading doses of intravitreal ranibizumab injections resulted in 85% success rate on visual stabilization and 81% success rate in polypoidal lesion control.

Variation in referral practice for patients with colorectal cancer liver metastases.

BACKGROUND: Half of patients with colorectal cancer develop liver metastases. There remains great variability between hospitals in rates of liver resection for colorectal cancer liver metastases (CLM). This study aimed to determine how many patients with potentially resectable CLM are not seen by specialist liver surgeons. METHODS: Patients presenting with new CLM in a cancer network consisting of a tertiary centre and seven attached hospitals were studied prospectively over 12 months. Data were collected retrospectively for patients who did not have a complete data set. Outcomes for patients referred to the liver tertiary centre were collated. The radiology of tumours deemed inoperable by the local colorectal specialist teams was reviewed by specialist liver surgeons and radiologists. RESULTS: In total, 631 patients with CLM were assessed. Prospective data were complete for 241 patients, and 64 (26.6 per cent) of these were referred to the specialist liver team for consideration of resection. No decision was documented for 16 patients (6.6 per cent). Of those not referred, 30 (18.6 per cent) were deemed unfit or refused and 131 (81.4 per cent) were thought inoperable. Referral rates varied between hospitals (13-43.6 per cent). Of 131 patients deemed fit but inoperable by the colorectal specialist teams, 38 (29.0 per cent) were deemed operable and 20 (15.3 per cent) had equivocal imaging when assessed retrospectively by liver specialists. In total, 142 of the 631 patients were referred to liver specialists for consideration of treatments, and 107 (75.4 per cent) treated with curative intent. CONCLUSION: A considerable number of patients with potentially resectable CLM are not assessed by specialist liver teams. Improved referral rates could greatly improve resection rates for CLM, which may improve outcomes for patients with colorectal cancer.