Ultrasound Tonsillectomy

Автора представя своя пет годишен опит от приложението на ултразвуковия хармоничен скалпел за извършване на тонзилектомия сравнявайки го с класическата студена дисекция.В изследванията са включени 312 пациенти оперирани с ултразвуковия хармоничен скалпел и 64 със студена дисекция във възрастовата граница от 7 до 45 години. Хирургическата ефикасност на метода се отчита въз основа на следните параметри: Оперативно време, интраоперативно кървене, следоперативно кървене, следоперативна болка, хранене и двигателна активност.Резултатите показаха значителна разлика в полза на ултразвуковата тонзилектомия по отношение на оперативното време, интраоперативното кървене, следоперативното кървене и следоперативната болка в първия следоперативен ден, при приблизително еднакви резултати по отношение на другите показатели.Автора препоръчва ултразвуковата тонзилектомия като ефикасен, практичен, сигурен, и модерен оперативен метод, които трябва да бъде популяризиран.The author presents his 5 year experience with the use of Ultrasound Harmonic Scalpel(UHS) for tonsillectomy compared to traditional cold steel dissection.The study recruited 312 patients that underwent surgery with the UHS and 64 patients that were subject to cold steel dissection with their age ranging between 7 and 45 years. Surgical efficacy of the of the method was assessed using the following parameters: Surgery duration, intraoperative bleeding, postoperative bleeding, postoperative pain, feeding and muscle activity.The results show a significant difference and clear advantage of ultrasound tonsillectomy in surgery duration, intraoperative bleeding, postoperative bleeding and postoperative pain in the first day after surgery with comparatively equal results regarding the rest of the studied parameters.The Author recommends the Ultrasound Harmonic Tonsillectomy as effective, practical, reliable and modern surgical technique which needs to be made more popular

Plasma proteomic signature predicts who will get persistent symptoms following SARS-CoV-2 infection

BACKGROUND: The majority of those infected by ancestral Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) during the UK first wave (starting March 2020) did not require hospitalisation. Most had a short-lived mild or asymptomatic infection, while others had symptoms that persisted for weeks or months. We hypothesized that the plasma proteome at the time of first infection would reflect differences in the inflammatory response that linked to symptom severity and duration. METHODS: We performed a nested longitudinal case-control study and targeted analysis of the plasma proteome of 156 healthcare workers (HCW) with and without lab confirmed SARS-CoV-2 infection. Targeted proteomic multiple-reaction monitoring analysis of 91 pre-selected proteins was undertaken in uninfected healthcare workers at baseline, and in infected healthcare workers serially, from 1 week prior to 6 weeks after their first confirmed SARS-CoV-2 infection. Symptom severity and antibody responses were also tracked. Questionnaires at 6 and 12 months collected data on persistent symptoms. FINDINGS: Within this cohort (median age 39 years, interquartile range 30-47 years), 54 healthcare workers (44% male) had PCR or antibody confirmed infection, with the remaining 102 (38% male) serving as uninfected controls. Following the first confirmed SARS-CoV-2 infection, perturbation of the plasma proteome persisted for up to 6 weeks, tracking symptom severity and antibody responses. Differentially abundant proteins were mostly coordinated around lipid, atherosclerosis and cholesterol metabolism pathways, complement and coagulation cascades, autophagy, and lysosomal function. The proteomic profile at the time of seroconversion associated with persistent symptoms out to 12 months. Data are available via ProteomeXchange with identifier PXD036590. INTERPRETATION: Our findings show that non-severe SARS-CoV-2 infection perturbs the plasma proteome for at least 6 weeks. The plasma proteomic signature at the time of seroconversion has the potential to identify which individuals are more likely to suffer from persistent symptoms related to SARS-CoV-2 infection. FUNDING INFORMATION: The COVIDsortium is supported by funding donated by individuals, charitable Trusts, and corporations including Goldman Sachs, Citadel and Citadel Securities, The Guy Foundation, GW Pharmaceuticals, Kusuma Trust, and Jagclif Charitable Trust, and enabled by Barts Charity with support from University College London Hospitals (UCLH) Charity. This work was additionally supported by the Translational Mass Spectrometry Research Group and the Biomedical Research Center (BRC) at Great Ormond Street Hospital

Operation Moonshot: rapid translation of a SARS-CoV-2 targeted peptide immunoaffinity liquid chromatography-tandem mass spectrometry test from research into routine clinical use

OBJECTIVES: During 2020, the UK's Department of Health and Social Care (DHSC) established the Moonshot programme to fund various diagnostic approaches for the detection of SARS-CoV-2, the pathogen behind the COVID-19 pandemic. Mass spectrometry was one of the technologies proposed to increase testing capacity. METHODS: Moonshot funded a multi-phase development programme, bringing together experts from academia, industry and the NHS to develop a state-of-the-art targeted protein assay utilising enrichment and liquid chromatography tandem mass spectrometry (LC-MS/MS) to capture and detect low levels of tryptic peptides derived from SARS-CoV-2 virus. The assay relies on detection of target peptides, ADETQALPQRK (ADE) and AYNVTQAFGR (AYN), derived from the nucleocapsid protein of SARS-CoV-2, measurement of which allowed the specific, sensitive, and robust detection of the virus from nasopharyngeal (NP) swabs. The diagnostic sensitivity and specificity of LC-MS/MS was compared with reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) via a prospective study. RESULTS: Analysis of NP swabs (n=361) with a median RT-qPCR quantification cycle (Cq) of 27 (range 16.7-39.1) demonstrated diagnostic sensitivity of 92.4% (87.4-95.5), specificity of 97.4% (94.0-98.9) and near total concordance with RT-qPCR (Cohen's Kappa 0.90). Excluding Cq>32 samples, sensitivity was 97.9% (94.1-99.3), specificity 97.4% (94.0-98.9) and Cohen's Kappa 0.95. CONCLUSIONS: This unique collaboration between academia, industry and the NHS enabled development, translation, and validation of a SARS-CoV-2 method in NP swabs to be achieved in 5 months. This pilot provides a model and pipeline for future accelerated development and implementation of LC-MS/MS protein/peptide assays into the routine clinical laboratory

Metabolite and lipoprotein profiles reveal sex-related oxidative stress imbalance in de novo drug-naive Parkinson's disease patients

Parkinson’s disease (PD) is the neurological disorder showing the greatest rise in prevalence from 1990 to 2016. Despite clinical definition criteria and a tremendous effort to develop objective biomarkers, precise diagnosis of PD is still unavailable at early stage. In recent years, an increasing number of studies have used omic methods to unveil the molecular basis of PD, providing a detailed characterization of potentially pathological alterations in various biological specimens. Metabolomics could provide useful insights to deepen our knowledge of PD aetiopathogenesis, to identify signatures that distinguish groups of patients and uncover responsive biomarkers of PD that may be significant in early detection and in tracking the disease progression and drug treatment efficacy. The present work is the first large metabolomic study based on nuclear magnetic resonance (NMR) with an independent validation cohort aiming at the serum characterization of de novo drug-naive PD patients. Here, NMR is applied to sera from large training and independent validation cohorts of German subjects. Multivariate and univariate approaches are used to infer metabolic differences that characterize the metabolite and the lipoprotein profiles of newly diagnosed de novo drug-naive PD patients also in relation to the biological sex of the subjects in the study, evidencing a more pronounced fingerprint of the pathology in male patients. The presence of a validation cohort allowed us to confirm altered levels of acetone and cholesterol in male PD patients. By comparing the metabolites and lipoproteins levels among de novo drug-naive PD patients, age- and sex-matched healthy controls, and a group of advanced PD patients, we detected several descriptors of stronger oxidative stress

Heterogeneity of prodromal Parkinson symptoms in siblings of Parkinson disease patients

A prodromal phase of Parkinson’s disease (PD) may precede motor manifestations by decades. PD patients’ siblings are at higher risk for PD, but the prevalence and distribution of prodromal symptoms are unknown. The study objectives were (1) to assess motor and non-motor features estimating prodromal PD probability in PD siblings recruited within the European PROPAG-AGEING project; (2) to compare motor and non-motor symptoms to the well-established DeNoPa cohort. 340 PD siblings from three sites (Bologna, Seville, Kassel/Goettingen) underwent clinical and neurological evaluations of PD markers. The German part of the cohort was compared with German de novo PD patients (dnPDs) and healthy controls (CTRs) from DeNoPa. Fifteen (4.4%) siblings presented with subtle signs of motor impairment, with MDS-UPDRS-III scores not clinically different from CTRs. Symptoms of orthostatic hypotension were present in 47 siblings (13.8%), no different to CTRs (p = 0.072). No differences were found for olfaction and overall cognition; German-siblings performed worse than CTRs in visuospatial-executive and language tasks. 3/147 siblings had video-polysomnography-confirmed REM sleep behavior disorder (RBD), none was positive on the RBD Screening Questionnaire. 173/300 siblings had <1% probability of having prodromal PD; 100 between 1 and 10%, 26 siblings between 10 and 80%, one fulfilled the criteria for prodromal PD. According to the current analysis, we cannot confirm the increased risk of PD siblings for prodromal PD. Siblings showed a heterogeneous distribution of prodromal PD markers and probability. Additional parameters, including strong disease markers, should be investigated to verify if these results depend on validity and sensitivity of prodromal PD criteria, or if siblings’ risk is not elevated

A geroscience approach for Parkinson's disease: Conceptual framework and design of PROPAG-AGEING project

Advanced age is the major risk factor for idiopathic Parkinson's disease (PD), but to date the biological relationship between PD and ageing remains elusive. Here we describe the rationale and the design of the H2020 funded project “PROPAG-AGEING”, whose aim is to characterize the contribution of the ageing process to PD development. We summarize current evidences that support the existence of a continuum between ageing and PD and justify the use of a Geroscience approach to study PD. We focus in particular on the role of inflammaging, the chronic, low-grade inflammation characteristic of elderly physiology, which can propagate and transmit both locally and systemically. We then describe PROPAG-AGEING design, which is based on the multi-omic characterization of peripheral samples from clinically characterized drug-naïve and advanced PD, PD discordant twins, healthy controls and "super-controls", i.e. centenarians, who never showed clinical signs of motor disability, and their offspring. Omic results are then validated in a large number of samples, including in vitro models of dopaminergic neurons and healthy siblings of PD patients, who are at higher risk of developing PD, with the final aim of identifying the molecular perturbations that can deviate the trajectories of healthy ageing towards PD development

Early downregulation of hsa-miR-144-3p in serum from drug-naïve Parkinson’s disease patients

Advanced age represents one of the major risk factors for Parkinson’s Disease. Recent biomedical studies posit a role for microRNAs, also known to be remodelled during ageing. However, the relationship between microRNA remodelling and ageing in Parkinson’s Disease, has not been fully elucidated. Therefore, the aim of the present study is to unravel the relevance of microRNAs as biomarkers of Parkinson’s Disease within the ageing framework. We employed Next Generation Sequencing to profile serum microRNAs from samples informative for Parkinson’s Disease (recently diagnosed, drug-naïve) and healthy ageing (centenarians) plus healthy controls, age-matched with Parkinson’s Disease patients. Potential microRNA candidates markers, emerging from the combination of differential expression and network analyses, were further validated in an independent cohort including both drug-naïve and advanced Parkinson’s Disease patients, and healthy siblings of Parkinson’s Disease patients at higher genetic risk for developing the disease. While we did not find evidences of microRNAs co-regulated in Parkinson’s Disease and ageing, we report that hsa-miR-144-3p is consistently down-regulated in early Parkinson’s Disease patients. Moreover, interestingly, functional analysis revealed that hsa-miR-144-3p is involved in the regulation of coagulation, a process known to be altered in Parkinson’s Disease. Our results consistently show the down-regulation of hsa-mir144-3p in early Parkinson’s Disease, robustly confirmed across a variety of analytical and experimental analyses. These promising results ask for further research to unveil the functional details of the involvement of hsa-mir144-3p in Parkinson’s Disease

Obstructive sleep apnea in children

Обструктивното нарушение на дишането по време на сън се среща често при децата. От 3 до 12% от децата хъркат докато обструктивната сънна апнея засяга 08. До 2% от децата. По-голямата част от тези деца имат леки симптоми и могат да превъзмогнат това състояние. Последствията от нелекуваната обструктивна сънна апнея включват забавен растеж, напикаване, разстройство на вниманието, поведенчески проблеми, лош успех в училище, сърдечни заболявания. Най-често етиологията наобструктивната сънна апнея е аденотонзиларната хипертрофия. Клиничната диагноза на обструктивната сънна апнея е надеждна. Една внимателна анамнеза и обективен преглед обикновено са достатъчни дали има обструкция и апнея през нощта. Допълнителни изследвания като полис-омнография са полезни за документация на заболяването. Лечението на обструктивната сънна апнея е хирургическо. По-голямата част от децата с обструкция имат драматично подобрение след тонзелектомия и аденотомия. Понякога допълнителните процедури, включително увулопалатофарингопластика и трахеотомия са необходими.Obstructive sleep-disordered breathing is common in children. From 3 percent to 12 percent of children snore, while obstructive sleep apnea syndrome affects 0.8 percent to 2 percent of children. The majority of these children have mild symptoms, and many outgrow the condition. Consequences of untreated obstructive sleep apnea include failure to thrive, enuresis, attention-deficit disorder, behavior problems, poor academic performance, and cardiopulmonary disease. The most commonetiology of obstructive sleep apnea is adenotonsillar hypertrophy. Clinical diagnosis of obstructive sleep apnea is reliable; A careful history and physical examination are usually sufficient to determine if obstruction and apnea are present at night. Additional studies such as polysomnography are helpful for documentation of the disorder. The treatment of obstructiveapnea, is surgical. The vast majority of children with obstruction have dramatic resolution of their obstruction following a tonsillectomy and adenoidectomy. Occasionally additional procedures including uvulopalatopharyngoplasty and tracheotomy are needed

Melanoma malignum of the extermal auditory canal

Представя се рядък случай с малигнен меланом на външния слухов канал при 21-годишен пациент. След патохистологична верификация на заболяването се престъпи към хирургическо лечение, включващо широка ексцизия на тумора на 2 см в здраво, трепанация на подлежаща кост, профилактична селективна шийна дисекция от страната на процеса и следоперативна полихимиотерапия. Една година след лечението пациентът е без данни за рецидив и метастази.Authors are presenting a rare case of 21-years old patient with Melanoma malignum of the external auditory canal. After histological verification of the disease surgical treatment has been undertaken including wide excision (margins of 2 cm), trepanation of the side of the underlying bone, prophylactic cervical lymph node dissection on the side of the process and postoperative polychemotherapy. One year after the treatment the patient is with no evidence for relapse or metastase

'The long tail of Covid-19' - The detection of a prolonged inflammatory response after a SARS-CoV-2 infection in asymptomatic and mildly affected patients [version 1; peer review: awaiting peer review]

‘Long Covid’, or medical complications associated with post SARS-CoV-2 infection, is a significant post-viral complication that is being more and more commonly reported in patients. Therefore, there is an increasing need to understand the disease mechanisms, identify drug targets and inflammatory processes associated with a SARS-CoV-2 infection. To address this need, we created a targeted mass spectrometry based multiplexed panel of 96 immune response associated proteins. We applied the multiplex assay to a cohort of serum samples from asymptomatic and moderately affected patients. All patients had tested positive for a SARS-CoV-2 infection by PCR and were determined to be subsequently positive for antibodies. Even 40-60 days post-viral infection, we observed a significant remaining inflammatory response in all patients. Proteins that were still affected were associated with the anti-inflammatory response and mitochondrial stress. This indicates that biochemical and inflammatory pathways within the body can remain perturbed long after SARS-CoV-2 infections have subsided even in asymptomatic and moderately affected patients