Singlet oxygen-based photoelectrochemical detection of miRNAs in prostate cancer patients' plasma: A novel diagnostic tool for liquid biopsy.

Dysregulation of miRNA expression occurs in many cancers, making miRNAs useful in cancer diagnosis and therapeutic guidance. In a clinical context using methods such as polymerase chain reaction (PCR), the limited amount of miRNAs in circulation often limits their quantification. Here, we present a PCR-free and sensitive singlet oxygen (1O2)-based strategy for the detection and quantification of miRNAs in untreated human plasma from patients diagnosed with prostate cancer. A target miRNA is specifically captured by functionalised magnetic beads and a detection oligonucleotide probe in a sandwich-like format. The formed complex is concentrated at the sensor surface via magnetic beads, providing an interface for the photoinduced redox signal amplification. The detection oligonucleotide probe bears a molecular photosensitiser, which produces 1O2 upon illumination, oxidising a redox reporter and creating a redox cycling loop, allowing quantification of pM level miRNA in diluted human plasma within minutes after hybridisation and without target amplification.

EFAS/EAN survey on the influence of the COVID-19 pandemic on European clinical autonomic education and research.

PURPOSE: To understand the influence of the coronavirus disease 2019 (COVID-19) pandemic on clinical autonomic education and research in Europe. METHODS: We invited 84 European autonomic centers to complete an online survey, recorded the pre-pandemic-to-pandemic percentage of junior participants in the annual congresses of the European Federation of Autonomic Societies (EFAS) and European Academy of Neurology (EAN) and the pre-pandemic-to-pandemic number of PubMed publications on neurological disorders. RESULTS: Forty-six centers answered the survey (55%). Twenty-nine centers were involved in clinical autonomic education and experienced pandemic-related didactic interruptions for 9 (5; 9) months. Ninety percent (n = 26/29) of autonomic educational centers reported a negative impact of the COVID-19 pandemic on education quality, and 93% (n = 27/29) established e-learning models. Both the 2020 joint EAN-EFAS virtual congress and the 2021 (virtual) and 2022 (hybrid) EFAS and EAN congresses marked higher percentages of junior participants than in 2019. Forty-one respondents (89%) were autonomic researchers, and 29 of them reported pandemic-related trial interruptions for 5 (2; 9) months. Since the pandemic begin, almost half of the respondents had less time for scientific writing. Likewise, the number of PubMed publications on autonomic topics showed the smallest increase compared with other neurological fields in 2020-2021 and the highest drop in 2022. Autonomic research centers that amended their trial protocols for telemedicine (38%, n = 16/41) maintained higher clinical caseloads during the first pandemic year. CONCLUSIONS: The COVID-19 pandemic had a substantial negative impact on European clinical autonomic education and research. At the same time, it promoted digitalization, favoring more equitable access to autonomic education and improved trial design.

Extraperitoneal robot-assisted radical prostatectomy with the Hugo™ RAS system: initial experience of a tertiary center with a high background in extraperitoneal laparoscopy surgery.

PURPOSE: The Hugo™ RAS system is a novel robotic platform with innovative features. However, there are currently no available data on extraperitoneal robot-assisted radical prostatectomy (RARP) performed using this system. The objective of this study is to describe the surgical setup and assess the safety and feasibility of the extraperitoneal approach in robotic radical prostatectomy with the Hugo™ RAS system. METHODS: Sixteen consecutive patients diagnosed with localized prostate cancer underwent extraperitoneal RARP ± lymph node dissection at our institution, between March and May 2023. All RARP procedures were performed extraperitoneal with a modular four-arm configuration. The focus was to describe the operative room setup, trocar placement, tilt and docking angles and evaluate the safety and feasibility of this approach with this robotic platform. Secondary outcomes recorded included, total operative time, console time, estimated bleeding, intra- and postoperative complications, and length of stay after surgery. A descriptive analysis was conducted. RESULTS: We report on the first sixteen cases of extraperitoneal robot-assisted radical prostatectomy performed with the new Hugo™ RAS system. All procedures were completed, without the need for conversion or placement of additional ports. No intraoperative complications or major technical failures that would prevent the completion of surgery were recorded. The median operative time was 211 min (IQR 180-277), and the median console time was 152 min (IQR 119-196). The mean docking time was 4.6 min (IQR 4.1-5.2). The median estimated blood loss and the median time to remove the vesical catheter were 200 mL (IQR 150-400) and 8 days (IQR 7-8), respectively. The median length of stay was 2 days (IQR 2-2). Only one minor complication was registered in the first 30 days. CONCLUSION: This study provides evidence of the safety and feasibility of the extraperitoneal approach in RARP with the Hugo™ RAS system. The description of the surgical setup in terms of trocar placement, arm-cart disposition, tilt and docking angles offers valuable information for surgeons interested in adopting this surgical approach with the Hugo™ RAS platform.

Augenblickdiagnose in neurology: Revisiting 'diagnosis in the blink of an eye'.

BACKGROUND AND PURPOSE: The art of diagnosis in clinical neurology requires attentive listening and careful observation. In certain situations, a fragment of the history or a physical sign may be so distinctive that it allows clinicians to evoke a specific diagnosis. This quick mental process was previously referred to as 'Augenblickdiagnose' ('diagnosis in the blink of an eye') in a seminal paper by Dr. William Campbell in 1998. We aimed to revisit this concept by providing additional clinical vignettes. METHODS: The authors wrote clinical vignettes using examples from their own clinical practice and performed a non-systematic review of influential neurology textbooks using the words 'pathognomonic' and 'highly suggestive'. RESULTS: Twenty examples from various fields of neurology are presented in a table, stratified by major fields of neurology. A short educational reflection is provided for each diagnosis considered. CONCLUSION: 'Augenblickdiagnose' is an engaging teaching resource that also contributes to 'neurophilia', that is, a fascination for neurology, perhaps increasingly in today's modern neurology practice. However, multiple cognitive biases underlying mental shortcuts may lead to an incorrect diagnosis. It is important to stress that good clinical practice in neurology requires taking a thorough history and performing a careful neurological examination.

Association of the Calcification Score of the Abdominal Aorta, Common Iliac, and Renal Arteries with Outcomes in Living Kidney Donors.

BACKGROUND: Vascular calcification is an ever-more-common finding in protocoled pre-transplant imaging in living kidney donors. We intended to explore whether a connection could be found between the Agatston calcification score, prior to kidney donation, and post-donation renal function. METHODS: This is a retrospective analysis of 156 living kidney donors who underwent living donor nephrectomy between January 2010 and December 2016. We quantified the total calcification score (TCaScore) by calculating the Agatston score for each vessel, abdominal aorta, common iliac, and renal arteries. Donors were placed into two different groups based on their TCaScore: <100 TCaScore group and ≥100 TCaScore group. The relationship between TCaScore, 1-year eGFR, proteinuria, and risk of 1 measurement of decreased renal function (eGFR < 60 mL/min/1.73 m2) over 5 years of follow-up was investigated. RESULTS: The ≥100 TCaScore group consisted of 29 (19%) donors, with a median (interquartile range) calcification score of 164 (117-358). This group was significantly older, 56.7 ± 6.9 vs. 45.5 ± 10.6 (p < 0.001), had a higher average BMI (p < 0.019), and had a lower preoperative eGFR (p < 0.014). The 1-year eGFR was similarly diminished, 69.9 ± 15.7 vs. 76.3 ± 15.5 (p < 0.048), while also having an increased risk of decreased renal function during the follow-up, 22% vs. 48% (p < 0.007). CONCLUSIONS: Our study, through univariate analyses, found a relationship between a TCaScore > 100, lower 1-year eGFR, and decreased renal function in 5 years. However, a higher-than-expected vascular calcification should not be an excluding factor in donors, although they may require closer monitoring during follow-up.

Two-Stage Framework for Faster Semantic Segmentation.

Semantic segmentation consists of classifying each pixel according to a set of classes. Conventional models spend as much effort classifying easy-to-segment pixels as they do classifying hard-to-segment pixels. This is inefficient, especially when deploying to situations with computational constraints. In this work, we propose a framework wherein the model first produces a rough segmentation of the image, and then patches of the image estimated as hard to segment are refined. The framework is evaluated in four datasets (autonomous driving and biomedical), across four state-of-the-art architectures. Our method accelerates inference time by four, with additional gains for training time, at the cost of some output quality.

Impact of the COVID-19 pandemic on clinical autonomic practice in Europe A survey of the European Academy of Neurology (EAN) and the European Federation of Autonomic Societies (EFAS).

OBJECTIVE: To investigate the impact of the coronavirus-disease-2019 (COVID-19) pandemic on European clinical autonomic practice. METHODS: Eighty-four neurology-driven or interdisciplinary autonomic centers in 22 European countries were invited to fill in a web-based survey between September and November 2021. RESULTS: Forty-six centers completed the survey (55%). During the first pandemic year, the number of performed tilt-table tests, autonomic outpatient and inpatient visits decreased respectively by 50%, 45% and 53%, and every-third center reported major adverse events due to postponed examinations or visits. The most frequent newly-diagnosed or worsened cardiovascular autonomic disorders after COVID-19 infection included postural orthostatic tachycardia syndrome (POTS), orthostatic hypotension, and recurrent vasovagal syncope, deemed likely related to the infection by ≥50% of the responders. Forty-seven percent of the responders also reported about people with new-onset of orthostatic intolerance, but negative tilt-table findings, and 16% about people with psychogenic pseudosyncope after COVID-19. Most patients were treated non-pharmacologically and symptomatic recovery at follow-up was observed in ≥45% of cases. By contrast, low frequencies of newly-diagnosed cardiovascular autonomic disorders following COVID-19 vaccination were reported, most frequently POTS and recurrent vasovagal syncope, and most of the responders judged a causal association unlikely. Non-pharmacological measures were the preferred treatment choice, with 50-100% recovery rates at follow-up. CONCLUSIONS: Cardiovascular autonomic disorders may develop or worsen following a COVID-19 infection, while the association with COVID-19 vaccines remains controversial. Despite the severe pandemic impact on European clinical autonomic practice, a specialized diagnostic work-up was pivotal to identify non-autonomic disorders in people with post-COVID-19 orthostatic complaints.

Sapheno-Cavernous Shunt: A Vascular Approach In The Treatment Of Ischemic Priapism.

Priapism is an urologic emergency defined as an erection that persists for more than 4 hours and is unrelated or lasts beyond sexual stimulation. Ischemic priapism, caused by prolonged venous occlusion within the corporal bodies, works as a compartment syndrome that requires prompt resolution in order to preserve erectile function. We present two cases of ischemic priapism refractory to conventional treatment that were treated with the help of vascular surgeons. In both cases a sapheno-cavernous shunt was effective in achieving detumescence and erectile function recovery. Despite rarely described in literature, this can be a safe and effective technique in the treatment of ischemic priapism.

Clinical presentation and management strategies of cardiovascular autonomic dysfunction following a COVID-19 infection - A systematic review.

BACKGROUND: Cardiovascular autonomic dysfunction may reportedly occur after a coronavirus-disease-2019 (COVID-19) infection, but the available evidence is scattered. Here we sought to understand the acute and mid-term effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on cardiovascular autonomic function. METHODS: We performed a systematic PubMed, Embase, Web of Science, medRxiv, and bioRxiv search for cases of cardiovascular autonomic dysfunction during an acute SARS-CoV-2 infection or post-COVID-19 condition. The clinical-demographic characteristics of individuals in the acute versus post-COVID-19 phase were compared. RESULTS: We screened 6470 titles and abstracts. Fifty-four full-length articles were included in the data synthesis. One-hundred and thirty-four cases were identified: 81 during the acute SARS-CoV-2 infection (24 thereof diagnosed by history) and 53 in the post-COVID-19 phase. Post-COVID-19 cases were younger than those with cardiovascular autonomic disturbances in the acute SARS-CoV-2 phase (42 vs. 51 years old, p = 0.002) and were more frequently women (68% vs. 49%, p = 0.034). Reflex syncope was the most common cardiovascular autonomic disorder in the acute phase (p = 0.008) and postural orthostatic tachycardia syndrome (POTS) the most frequent diagnosis in individuals with post-COVID-19 orthostatic complaints (p < 0.001). Full recovery was more frequent in individuals with acute versus post-COVID-19 onset of cardiovascular autonomic disturbances (43% vs. 15%, p = 0.002). CONCLUSIONS: There is evidence from the scientific literature about different types of cardiovascular autonomic dysfunction developing during and after COVID-19. More data about the prevalence of autonomic disorders associated with a SARS-CoV-2 infection are needed to quantify its impact on human health.

CT volumetry performs better than nuclear renography in predicting estimated renal function one year after living donation.

The evaluation of split renal function (SRF) is a critical issue in living kidney donations and can be evaluated using nuclear renography (NR) or computerized tomography (CT), with unclear comparative advantages. We conducted this retrospective study in 193 donors to examine the correlation of SRF assessed by NR and CT volumetry and compared their ability to predict remaining donor renal function at 1 year, through multiple approaches. A weak correlation between imaging techniques for evaluating the percentage of the remaining kidney volume was found in the global cohort, with an R2 = 0.15. However, the Bland-Altman plot showed an acceptable agreement (95% of the difference between techniques falling within - 8.51 to 6.11%). The predicted and observed eGFR one year after donation were calculated using the CKD-EPI, and CG/BSA equations. CT volume showed a better correlation than NR for both formulas (adjusted R2 of 0.42. and 0.61 vs 0.37 and 0.61 for CKD-EPI and CG/ BSA equations, respectively). In non-nested modeling tests, CT volumetry was significantly superior to NR for both equations. CT volumetry performed better than NR in predicting the estimated renal function of living donors at 1-year, independently from the eGFR equation.

Clinical autonomic nervous system laboratories in Europe: A joint survey of the European Academy of Neurology and the European Federation of Autonomic Societies: A joint survey of the European Academy of Neurology and the European Federation of Autonomic Societies.

BACKGROUND AND PURPOSE: Disorders of the autonomic nervous system (ANS) are common conditions, but it is unclear whether access to ANS healthcare provision is homogeneous across European countries. The aim of this study was to identify neurology-driven or interdisciplinary clinical ANS laboratories in Europe, describe their characteristics and explore regional differences. METHODS: We contacted the European national ANS and neurological societies, as well as members of our professional network, to identify clinical ANS laboratories in each country and invite them to answer a web-based survey. RESULTS: We identified 84 laboratories in 22 countries and 46 (55%) answered the survey. All laboratories perform cardiovascular autonomic function tests, and 83% also perform sweat tests. Testing for catecholamines and autoantibodies are performed in 63% and 56% of laboratories, and epidermal nerve fiber density analysis in 63%. Each laboratory is staffed by a median of two consultants, one resident, one technician and one nurse. The median (interquartile range [IQR]) number of head-up tilt tests/laboratory/year is 105 (49-251). Reflex syncope and neurogenic orthostatic hypotension are the most frequently diagnosed cardiovascular ANS disorders. Thirty-five centers (76%) have an ANS outpatient clinic, with a median (IQR) of 200 (100-360) outpatient visits/year; 42 centers (91%) also offer inpatient care (median 20 [IQR 4-110] inpatient stays/year). Forty-one laboratories (89%) are involved in research activities. We observed a significant difference in the geographical distribution of ANS services among European regions: 11 out of 12 countries from North/West Europe have at least one ANS laboratory versus 11 out of 21 from South/East/Greater Europe (p = 0.021). CONCLUSIONS: This survey highlights disparities in the availability of healthcare services for people with ANS disorders across European countries, stressing the need for improved access to specialized care in South, East and Greater Europe.

Vasculitic peripheral neuropathy in deficiency of adenosine deaminase 2.

Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive inflammatory vasculopathy characterized by systemic vasculitis, early-onset stroke and livedo racemosa. We report a family cohort of 3 patients with ADA2 compound heterozygous mutation p.[Thr360Ala] and [Gly383Ser]. Two of them had progressive involvement of the peripheral nervous system in the fourth decade, both after stroke. In one patient, clinical and neurophysiological studies showed progression of mononeuritis multiplex to chronic axonal sensorimotor polyneuropathy, nerve biopsy had features of small vessel vasculitic neuropathy, and muscle biopsy disclosed neurogenic atrophy with reinnervation. The second patient presented with progressive sensory symptoms of the lower limbs and chronic axonal sensorimotor polyneuropathy in nerve conduction studies. These two patients had absent plasma ADA2 activity. The third patient had no neurological affection despite low, but not absent, plasma ADA2 activity. Patients were started on a tumor necrosis factor (TNF) inhibitor, which has presumed benefits for the vasculitic phenotype of DADA2.

Primary intraventricular haemorrhage: the role of frontal minicraniotomy and external ventricular drainage.

Primary intraventricular haemorrhage (PIVH) is an uncommon type of intracerebral haemorrhage, accounting for only 0.31% of all strokes and 3.1% of all intracerebral haemorrhages. Due to the low incidence of PIVH, little is known about its clinical characteristics, risk factors, aetiologies, prognosis and treatment. Acute hydrocephalus is common and is associated with a poor prognosis. External ventricular drainage (EVD) could promptly reduce intracranial pressure by diverting cerebrospinal fluid and intraventricular blood; however, the incidence of complications such as central nervous system infection, catheter occlusion and rebleeding are relatively common. Despite being an invasive procedure, frontal minicraniotomy is an available therapeutic option to avoid complications of EVD. The authors report a case of a PIVH managed with frontal minicraniotomy and perform a literature review about epidemiological data, clinical features and treatment of PIVH.