{ "items": [ "\n\n
PURPOSE: Radical prostatectomy (RP) is a common treatment for prostate cancer, but a fraction of patients may experience PSA recurrence after surgery, manifesting as an elevation in prostate specific antigen (PSA). Vast literature has reported different prognostic factors for PSA recurrence without reaching a consensus. This retrospective study investigated the efficacy of a new indicator in predicting PSA recurrence in patients after RP. PATIENTS AND METHODS: From October 2000 to December 2015, 102 PCa patients who underwent laparoscopic prostatectomy in the Urology Department of Peking Union Medical College Hospital were analyzed. We calculated PSApostd3/PSApre, defined as the ratio of the PSA on day 3 postop as the numerator and the pre-operative PSA as the denominator, in these patients to represent PSA decrement after surgery, and investigated its relationship with PSA recurrence during follow-up. RESULTS: The receiver operating characteristic (ROC) curve of PSApostd3/PSApre derived a cut-off at 0.453 (sensitivity=0.704, specificity=0.853, P<0.0001), suggesting an increased risk of PSA recurrence in patients whose PSA on day 3 postop did not decrease to approximately half of their preoperative levels. Among several factors, PSApostd3/PSApre (P<0.0001), pathological T stage (P=0.042) and Gleason Grade (P=0.021) were determined to be significantly associated with PSA recurrence by Fisher's exact test, while only PSApostd3/PSApre (P<0.001) was significantly related to PSA recurrence-free survival (PRFS) by multivariate logistic regression analysis. CONCLUSION: These results imply that PSApostd3/PSApre could provide substantial information for PSA recurrence prediction in patients after RP.
\n \n\n \n \nOBJECTIVE: To characterize the patterns of brain atrophy and perfusion as measured by arterial spin labeling (ASL)-MRI, in amyotrophic lateral sclerosis (ALS) patients with varying levels of cognitive deficit, including ALS with frontotemporal dementia (FTD). METHODS: A total of 55 ALS patients and 20 healthy controls (HCs) were included, and all participants underwent neuropsychological assessments and MRI scans. According to their cognitive performance, ALS patients were further subclassified into ALS with normal cognition (ALS-Cn, n\u2009=\u200927), ALS with cognitive impairment (ALS-Ci, n\u2009=\u200917), and ALS-FTD (n\u2009=\u200911). Voxel-based comparisons of gray matter (GM) changes and cerebral blood flow (CBF) were conducted among the subgroups. RESULTS: The whole-brain comparisons of GM changes and CBF among ALS-Ci, ALS-Cn, and HCs were not significantly different. However, the ALS-FTD patients demonstrated a similar pattern of GM loss and hypoperfusion with more significant alterations in the left frontal and temporal lobe compared with the HCs, ALS-Cn, and ALS-Ci patients. Decreased CBF was found in many of the same brain areas wherein structural alterations occurred, although isolated GM loss and hypoperfusion were also observed. In addition, for both GM and CBF abnormalities, a similar pattern of changes was found in the comparisons of ALS-FTD vs. ALS-Ci, ALS-FTD vs. ALS-Cn, and ALS-FTD vs. HCs, with the differences being most significant between ALS-FTD and HCs. CONCLUSION: The cognitive status of ALS patients is associated with different patterns of GM changes and cerebral perfusion. ASL-MRI might be a useful tool with which to investigate the pathological burden of ALS and to disclose the early signature of possible cognitive impairment.
\n \n\n \n \nTo compare the accuracy of magnetic resonance-guided prostate biopsy (MR-GPB) and template-guided transperineal prostate saturation biopsy (TTPSB).A total of 219 patients with elevated prostate-specific antigen, abnormal digital rectal examination or ultrasound findings were enrolled. All patients underwent multiparametric magnetic resonance image (mpMRI). Patients with a Prostate Imaging Reporting and Data System (PI-RADS) score of 3 to 5 underwent MR-GPB using 2 to 5 biopsy cores and then immediately underwent an 11-region TTPSB. Patients with a PI-RADS score of 1 to 2 underwent TTPSB alone. We compared the detection rates for any cancer, clinically significant prostate cancer (csPCA), and the spatial distribution of missed csPCA lesions.Among the 219 cases, 66 (30.1%) had a PI-RADS score of 1 to 2 on mpMRI. The detection rate of TTPSB in these patients was 9.1% (6/66). In total, detection rates for any cancer and csPCA were 48.9% (107/219) and 42.9% (94/219), respectively. Detection rates for any cancer (TTPSB 87/219, 39.7%; MR-GPB76/219, 34.7%, P\u200a=\u200a.161) and csPCA (TTPSB 76/219, 34.7%; MR-GPB 72/219, 32.9%, P\u200a=\u200a.636) did not significantly differ between the 2 groups. The csPCA lesions missed by MR-GPB were most commonly located on the left (8.5%, 8/94) and right (9.6%, 9/94) sides of the urethra.MR-GPB can reduce the rate of unnecessary prostate biopsies by approximately 30% and exhibits an efficacy comparable to TTPSB for the detection of any cancer and csPCA. Nevertheless, approximately 1/4 of csPCAs were missed by MR-GPB and were most commonly located on both sides of the urethra.
\n \n\n \n \nThis paper presents a deep learning system applied for detecting anomalies from respiratory sound recordings. Our system initially performs audio feature extraction using Continuous Wavelet transformation. This transformation converts the respiratory sound input into a two-dimensional spectrogram where both spectral and temporal features are presented. Then, our proposed deep learning architecture inspired by the Inception-residual-based backbone performs the spatio-temporal-focusing and multi-head attention mechanism to classify respiratory anomalies. In this work, we evaluate our proposed models on the benchmark SPRSound (The Open-Source SJTU Paediatric Respiratory Sound) database proposed by the IEEE BioCAS 2023 challenge. As regards the Score computed by an average between the average score and harmonic score, our robust system has achieved Top-1 performance with Scores of 0.810, 0.667, 0.744, and 0.608 in Tasks 1-1, 1-2, 2-1, and 2-2, respectively.
\n \n\n \n \nAge-related macular degeneration (AMD) is the leading cause of irreversible vision loss among the elderly in the developed world. Whilst AMD is a multifactorial disease, the involvement of the complement system in its pathology is well documented, with single-nucleotide polymorphisms (SNPs) in different complement genes representing an increased risk factor. With several complement inhibitors explored in clinical trials showing limited success, patients with AMD are still without a reliable treatment option. This indicates that there is still a gap of knowledge in the functional implications and manipulation of the complement system in AMD, hindering the progress towards translational treatments. Since the discovery of the CRISPR/Cas system and its development into a powerful genome engineering tool, the field of molecular biology has been revolutionised. Genetic variants in the complement system have long been associated with an increased risk of AMD, and a variety of haplotypes have been identified to be predisposing/protective, with variation in complement genes believed to be the trigger for dysregulation of the cascade leading to inflammation. AMD-haplotypes (SNPs) alter specific aspects of the activation and regulation of the complement cascade, providing valuable insights into the pathogenic mechanisms of AMD with important diagnostic and therapeutic implications. The effect of targeting these AMD-related SNPs on the regulation of the complement cascade has been poorly explored, and the CRISPR/Cas system provides an ideal tool with which to explore this avenue. Current research concentrates on the association events of specific AMD-related SNPs in complement genes without looking into the effect of targeting these SNPs and therefore influencing the complement system in AMD pathogenesis. This review will explore the current understanding of manipulating the complement system in AMD pathogenesis utilising the genomic manipulation powers of the CRISPR/Cas systems. A number of AMD-related SNPs in different complement factor genes will be explored, with a particular emphasis on factor H (CFH), factor B (CFB), and complement C3 (C3).
\n \n\n \n \nBackground/aimsTo investigate the clinical effectiveness of adjunctive triamcinolone acetonide (TA) given at the time of vitreoretinal surgery following open globe trauma (OGT).MethodsA phase 3, multicentre, double-masked randomised controlled trial of patients undergoing vitrectomy following OGT comparing adjunctive TA (intravitreal and subtenons) against standard care (2014-2020). The primary outcome was the proportion of patients with at least 10 Early Treatment Diabetic Retinopathy Study (ETDRS) letter improvement in corrected visual acuity (VA) at 6 months. Secondary outcomes included: change in ETDRS, retinal detachment (RD) secondary to PVR, retinal reattachment, macular reattachment, tractional RD, number of operations, hypotony, elevated intraocular pressure and quality of life.Results280 patients were randomised over 75 months, of which 259 completed the study. 46.9% (n=61/130) of patients in the treatment group had a 10-letter improvement in VA compared with 43.4% (n=56/129) of the control group (difference 3.5% (95% CI -8.6% to 15.6%), OR=1.03 (95% CI 0.61 to 1.75), p=0.908)). Secondary outcome measures also failed to show any treatment benefit. For two of the secondary outcome measures, stable complete retinal and macular reattachment, outcomes were worse in the treatment group compared with controls, respectively, 51.6% (n=65/126) vs 64.2% (n=79/123), OR=0.59 (95% CI 0.36 to 0.99), and 54.0% (n=68/126) vs 66.7% (n=82/123), OR=0.59 (95% CI 0.35 to 0.98), for TA vs control.ConclusionThe use of combined intraocular and sub-Tenons capsule TA is not recommended as an adjunct to vitrectomy surgery following OGT.Trial registration numberNCT02873026.
\n \n\n \n \nINTRODUCTION: Molecular confirmation of pathogenic sequence variants in the CHM gene is required prior to enrolment in retinal gene therapy clinical trials for choroideremia. Individuals with mild choroideremia have been reported. The molecular basis of genotype-phenotype associations is of clinical relevance since it may impact on selection for retinal gene therapy. METHODS AND MATERIALS: Genetic testing and RNA analysis were undertaken in a patient with mild choroideremia to confirm the pathogenicity of a novel intronic variant in CHM and to explore the mechanism underlying the mild clinical phenotype. RESULTS: A 42-year-old male presented with visual field loss. Fundoscopy and autofluorescence imaging demonstrated mild choroideremia for his age. Genetic analysis revealed a variant at a splice acceptor site in the CHM gene (c.1350-3C\u2009>\u2009G). RNA analysis demonstrated two out-of-frame transcripts, suggesting pathogenicity, without any detectable wildtype transcripts. One of the two out-of-frame transcripts is present in very low levels in healthy controls. DISCUSSION: Mild choroideremia may result from\u2009+3 or -3 splice site variants in CHM. It is presumed that the resulting mRNA transcripts may be partly functional, thereby preventing the development of the null phenotype. Choroideremia patients with such variants may present challenges for gene therapy since there may be residual transcript activity which could result in long-lasting visual function which is atypical for this disease.
\n \n\n \n \nABSTRACT\nPatched 1 (PTCH1) is the primary receptor for the sonic hedgehog (SHH) ligand and negatively regulates SHH signalling, an essential pathway in human embryogenesis. Loss-of-function mutations in PTCH1 are associated with altered neuronal development and the malignant brain tumour medulloblastoma. As a result of differences between murine and human development, molecular and cellular perturbations that arise from human PTCH1 mutations remain poorly understood. Here, we used cerebellar organoids differentiated from human induced pluripotent stem cells combined with CRISPR/Cas9 gene editing to investigate the earliest molecular and cellular consequences of PTCH1 mutations on human cerebellar development. Our findings demonstrate that developmental mechanisms in cerebellar organoids reflect in vivo processes of regionalisation and SHH signalling, and offer new insights into early pathophysiological events of medulloblastoma tumorigenesis without the use of animal models.
\n \n\n \n \nSleep restriction therapy is a behavioural component within cognitive behavioural therapy for insomnia and is an effective standalone treatment for insomnia, but its effect on depressive symptoms remains unclear. This review aimed to synthesise and evaluate the impact of single-component sleep restriction therapy on depressive symptoms relative to a control intervention. We searched electronic databases and sleep-related journals for randomised controlled trials and uncontrolled clinical trials, published from 1 January 1986 until 19 August 2023, that delivered sleep restriction therapy to adults with insomnia. Random-effects meta-analysis of standardised mean differences and Cochrane risk of bias assessment were performed on randomised controlled trials, while uncontrolled clinical trials were discussed narratively. The meta-analysis was pre-registered on PROSPERO (ID: CRD42020191803). We identified seven randomised controlled trials (N\u2009=\u20091102) and two uncontrolled clinical trials (N\u2009=\u200922). Findings suggest that sleep restriction therapy is associated with a medium effect for improvement in depressive symptoms at post-treatment (Nc \u2009=\u20096, g\u2009=\u2009-0.45 [95% confidence interval\u2009=\u2009-0.70 to -0.21], p\u2005
\n \n\n \n \nShortages in the physician anaesthesia workforce have led to proposals to introduce new staff groups, notably in the UK\u00a0National Health Service (NHS) Anaesthesia Associates (AAs) who have shorter training periods than doctors and could potentially contribute to workflow efficiencies in several ways. We analysed the economic viability of the most efficient staffing model, previously endorsed by both the UK Royal College of Anaesthetists and the Association of Anaesthetists, wherein one physician supervises two AAs across two operating lists (1:2 model). For this model to be economically rational (something which neither national organisation considered), the employment cost of the two AAs should be equal to or less than that of a single supervisor physician (i.e. AAs should be paid <50% of the supervisor's salary). As the supervisor can be an autonomous specialty and specialist (SAS) doctor, this sets the economically viable AA salary envelope at less than \u00a340,000 per year. However, we report that actual advertised AA salaries greatly exceed this, with even student AAs paid up to \u00a348,472. Economically, one way to justify such salaries is for AAs to become autonomous such that they eventually replace SAS doctors at a lower cost. We discuss some other options that might increase AA productivity to justify these salaries (e.g. \u22651:3 staffing ratios), but the medico-political consequences of each of them are also profound. Alternatively, the AA programme should be terminated as economically nonviable. These results have implications for any country seeking to introduce new models of working in anaesthesia.
\n \n\n \n \nAbstract\nBackground\nHealthcare systems are operating under substantial pressures, and often simply cannot provide the standard of care they aspire to within the available resources. Organisations, managers, and individual clinicians make constant adaptations in response to these pressures, which are typically improvised, highly variable and not coordinated across clinical teams. The purpose of this study was to identify and describe the types of everyday pressures experienced by surgical teams and the adaptive strategies they use to respond to these pressures.\n\nMethods\nWe conducted interviews with 20 senior multidisciplinary healthcare professionals from surgical teams in four major hospitals in the United Kingdom. The interviews explored the types of everyday pressures staff were experiencing, the strategies they use to adapt, and how these strategies might be taught to others.\n\nResults\nThe primary pressures described by senior clinicians in surgery were increased numbers and complexity of patients alongside shortages in staff, theatre space and post-surgical beds. These pressures led to more difficult working conditions (e.g. high workloads) and problems with system functioning such as patient flow and cancellation of lists. Strategies for responding to these pressures were categorised into increasing or flexing resources, controlling and prioritising patient demand and strategies for managing the workload (scheduling for efficiency, communication and coordination, leadership, and teamwork strategies).\n\nConclusions\nTeams are deploying a range of strategies and making adaptations to the way care is delivered. These findings could be used as the basis for training programmes for surgical teams to develop coordinated strategies for adapting under pressure and to assess the impact of different combinations of strategies on patient safety and surgical outcomes.\n
\n \n\n \n \nThe accuracy of actigraphy for sleep staging is assumed to be poor, but examination is limited. This systematic review aimed to assess the performance of actigraphy in sleep stage classification of adults. A systematic search was performed using MEDLINE, Web of Science, Google Scholar, and Embase databases. We identified eight studies that compared sleep architecture estimates between wrist-worn actigraphy and polysomnography. Large heterogeneity was found with respect to how sleep stages were grouped, and the choice of metrics used to evaluate performance. Quantitative synthesis was not possible, so we performed a narrative synthesis of the literature. From the limited number of studies, we found that actigraphy-based sleep staging had some ability to classify different sleep stages compared with polysomnography.
\n \n\n \n \nBackground and Objectives: The global outbreak caused by the SARS-CoV-2 pandemic disrupted healthcare worldwide, impacting the organization of intensive care units and surgical care units. This study aimed to document the daily neurosurgical activity in Alsace, France, one of the European epicenters of the pandemic, and provide evidence of the adaptive strategies deployed during such a critical time for healthcare services. Materials and Methods: The multicentric longitudinal study was based on a prospective cohort of patients requiring neurosurgical care in the Neurosurgical Departments of Alsace, France, between March 2020 and March 2022. Surgical activity was compared with pre-pandemic performances through data obtained from electronic patient records. Results: A total of 3842 patients benefited from care in a neurosurgical unit during the period of interest; 2352 of them underwent surgeries with a wide range of pathologies treated. Surgeries were initially limited to neurosurgical emergencies only, then urgent cases were slowly reinstated; however, a significant drop in surgical volume and case mix was noticed during lockdown (March\u2013May 2020). The crisis continued to impact surgical activity until March 2022; functional procedures were postponed, though some spine surgeries could progressively be performed starting in October 2021. Various social factors, such as increased alcohol consumption during the pandemic, influenced the severity of traumatic pathologies. The progressive return to the usual profile of surgical activity was characterized by a rebound of oncological interventions. Deferrable procedures for elective spinal and functional pathologies were the most affected, with unexpected medical and social impacts. Conclusions: The task shifting and task sharing approaches implemented during the first wave of the pandemic supported the reorganization of neurosurgical care in its aftermath and enabled the safe and timely execution of a broad spectrum of surgeries. Despite the substantial disruption to routine practices, marked by a significant reduction in elective surgical volumes, comprehensive records demonstrate the successful management of the full range of neurosurgical pathologies. This underscores the efficacy of adaptive strategies in navigating the challenges imposed by the largest healthcare crisis in recent history. Those lessons will continue to provide valuable insights and guidance for health and care managers to prepare for future unpredictable scenarios.
\n \n\n \n \nAbstractMelanopsin\u2010expressing ganglion cells have been proposed as the photoreceptors mediating non\u2010rod, non\u2010cone ocular responses to light. Here we use the aged (approximately 2\u2003years) rodless and coneless (rd/rd cl) mouse to assess the impact of progressive inner retinal cell loss on melanopsin expression, circadian entrainment and pupillary constriction. Aged rd/rd cl mice show substantial transneuronal retinal degeneration leaving only the ganglion cell layer and little of the inner nuclear layer. Despite this loss, quantitative reverse transcriptase\u2010polymerase chain reaction showed normal levels of melanopsin expression, and immunocytochemistry demonstrated both the presence and normal cellular appearance of these cells. Furthermore, the optic nerves of the two genotypes (rd/rd cl and +/+) were not obviously different in animals older than 2\u2003years. However, this massive level of retinal degeneration left both pupillary and circadian responses to light intact, even in rd/rd cl mice older than 2\u2003years. Our data provide the first positive correlation between the persistence of melanopsin\u2010expressing cells and the maintenance of both circadian and pupillary responses to light in the absence of rods and cones. These findings, together with recent studies on melanopsin knockout mice, are consistent with the hypothesis that melanopsin\u2010expressing ganglion cells are photosensitive and mediate a range of irradiance\u2010detection tasks.
\n \n\n \n \nA rare type of rodent retinal ganglion cell expresses melanopsin (Opn4), the majority of which project to the suprachiasmatic nuclei. Many of these cells are directly light sensitive and appear to regulate the circadian system in the absence of rod and cone photoreceptors. However, the rodent retina contains no overt regions of specialization, and the different ganglion cell types are hard to distinguish. Consequently, attempts to distinguish the distribution of melanopsin ganglion cells in relation to regions of retinal specialization or subtype have proved problematic. Retinal cells with a common function tend to be regularly distributed. In this study, we isolate cat melanopsin and label melanopsin expressing cells usingin situhybridization. The labelled cells were all confined to the ganglion cell layer, their density was low, and their distribution was random. Melanopsin containing cells showed no clear center-to-periphery gradient in their distribution and were comprised of a relatively uniform cellular population.
\n \n\n \n \nAging causes anatomical and functional changes in visual and circadian systems. In wild type mice rods, cones, and photosensitive retinal ganglion cells (pRGCs) decline with age. In rd/rd cl mice, the early loss of rods and cones is followed by protracted transneuronal loss of inner retinal neurons as well as the pRGCs. Here we use Fos induction to study the light input pathway to the suprachiasmatic nuclei (SCN), the intergeniculate leaflets (IGL) and ventral lateral geniculate nuclei (vLGN) of old (~700 days) and young (~150 days) wild type and rd/rd cl mice. Cholera toxin tracing was used in parallel to study the anatomy of this pathway. We find that aging rather than retinal degeneration is a more important factor in reducing light input to the SCN, causing both a reduction in Fos expression and retinal afferents. Furthermore, we show light-induced Fos within the vLGN and IGL is predominantly subserved by rods and cones, and once again aging reduces the amplitude of this response. \u00a9 2012 Elsevier Inc.
\n \n\n \n \n