Phosphofurin acidic cluster sorting protein 2 (PACS2) plays a vital role in maintaining cellular homeostasis by regulating protein trafficking between cellular membranes. This function impacts crucial processes like apoptosis, mitochondria-endoplasmic reticulum interaction, and subsequently Ca2+ flux, lipid biosynthesis, and autophagy. Missense mutations, particularly E209K and E211K, are linked to developmental and epileptic encephalopathy-66 (DEE66), known as PACS2 syndrome. Individuals with this syndrome exhibit neurodevelopmental delay, seizures, facial dysmorphism, hypotonia, and delayed motor skills.Understanding the impact of these missense mutations on molecular processes is crucial. Studies suggest that E209K mutation decreases phosphorylation, increases the survival time of protein, and modifies protein-protein interaction, consequently leading to disruption of calcium flux and lower resistance to apoptosis induction. Unfortunately, to date, only a limited number of research groups have investigated the effects of mutations in the PACS2 gene. Current research on PACS2 syndrome is hampered by the lack of suitable models. While in vitro models using transfected cell lines offer insights, they cannot fully capture the disease's complexity.To address this, utilizing cells from individuals with PACS2 syndrome, specifically induced pluripotent stem cells (iPSCs), holds promise for understanding phenotypic diversity and developing personalized therapies. However, iPSC models may not fully capture tissue-specific effects of the E209K/E211K mutation. In vivo studies using animal models, particularly mice, could overcome these limitations.This review summarizes current knowledge about PACS2 structure and functions, explores the cellular consequences of E209K and E211K mutations, and highlights the potential of iPSC and mouse models in advancing our understanding of PACS2 syndrome.

• MeSH
• indukované pluripotentní kmenové buňky metabolismus   MeSH
• lidé MeSH
• missense mutace * MeSH
• mutace MeSH
• vezikulární transportní proteiny * genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND CONTEXT: Spondylodiscitis management presents significant clinical challenges, particularly in critically ill patients, where the risks and benefits of surgical intervention must be carefully balanced. The optimal timing of surgery in this context remains a subject of debate. PURPOSE: This study aims to evaluate the effectiveness of early surgery versus delayed surgery or conservative management in critically ill patients with de novo pyogenic spondylodiscitis. STUDY DESIGN/SETTING: This is an international, multicenter retrospective cohort study involving 24 centers, primarily in Europe. PATIENT SAMPLE: The study included 192 critically ill patients (65.63% male) with a median age of 69 years, all severely affected by pyogenic spondylodiscitis characterized by an initial CRP level >200 mg/l or the presence of two out of four Systemic Inflammatory Response Syndrome criteria upon admission. OUTCOME MEASURES: The primary outcome was 30-day mortality. Secondary outcomes included length of ICU stay, length of hospital stay, and relapse rates of spondylodiscitis. METHODS: Patients were divided into three groups: early surgery (within three days of admission), delayed surgery (after three days of admission), and conservative therapy. Propensity score matching and multivariate regression analyses were performed to adjust for baseline differences and assess the impact of treatment modalities on mortality and other clinical outcomes. RESULTS: Delayed surgery was associated with significantly lower 30-day mortality (4.05%) compared to early surgery (27.85%) and conservative therapy (27.78%) (p<.001). Delayed surgery also resulted in shorter hospital stays (42.76 days) compared to conservative therapy (55.53 days) and early surgery (26.33 days) (p<.001), and shorter ICU stays (4.52 days) compared to conservative therapy (16.48 days) and early surgery (7.92 days) (p<.001). The optimal window for surgery, minimizing mortality, was identified as ten to fourteen days postadmission (p=.02). Risk factors for increased mortality included age (p<.05), multiple organ failure (p<.05), and vertebral body destruction (p<.05), whereas delayed surgery (p<.05) and the presence of an epidural abscess were associated with reduced mortality (p<.05). CONCLUSIONS: Delayed surgery, optimally between 10 to 14 days postadmission, was associated with lower mortality in critically ill spondylodiscitis patients. These findings highlight the potential benefits of considering surgical timing to improve patient outcomes.

• MeSH
• antibakteriální látky terapeutické užití   MeSH
• délka pobytu MeSH
• discitida * terapie   mortalita   chirurgie   mikrobiologie   MeSH
• konzervativní terapie MeSH
• kritický stav MeSH
• lidé středního věku MeSH
• lidé MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

PURPOSE: High-dose intravenous glucocorticoids are the standard first-line treatment in active, moderate to severe and severe thyroid eye disease (TED). We evaluate the usefulness of clinical activity score (CAS) and thyroid-stimulating immunoglobulin (TSI) as predictors and/or post-treatment markers of corticoresistance in patients with TED and the effect of rituximab in second-line treatment. METHODS: We enrolled 236 patients with an active TED into this retrospective single-tertiary-center cohort study. All patients were initially treated with high-dose systemic glucocorticoids. Rituximab was later administered to 29 of 42 corticoresistant patients. RESULTS: The CAS of the corticoresistant patients was significantly higher both before (p = 0.0001) and after (p = <0.0001) first-line treatment compared to the corticosensitive group. ROC analysis established the cut-point value as CAS ≥ 2.5 with a sensitivity of 96.3%, specificity of 57.5% and area under the curve of 82.8%. In 22 patients treated with rituximab, CAS gradually decreased to zero values without reactivation during extended follow-up. There was no difference in the TSI of corticosensitive and corticoresistant patients before or after first-line therapy. CONCLUSION: CAS ≥ 2, after first-line treatment, could be used as a corticoresistance marker. Corticoresistant patients should be subject to long-term follow-up for early detection of reactivation to reduce the delay to second-line treatment. Rituximab is a well-tolerated choice of second-line treatment and has a long-lasting effect on disease activity. Although TSI is a valuable biomarker of Graves' disease and TED activity, according to our results, TSI cannot be used as a marker of corticoresistance.

• MeSH
• dospělí MeSH
• glukokortikoidy terapeutické užití   MeSH
• Gravesova oftalmopatie * farmakoterapie   krev   MeSH
• imunoglobuliny stimulující tyreoideu krev   MeSH
• imunologické faktory terapeutické užití   MeSH
• léková rezistence * MeSH
• lidé středního věku MeSH
• lidé MeSH
• retrospektivní studie MeSH
• rituximab * terapeutické užití   MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: Late capsular bag distension syndrome (CBS) is a rare complication of the ^lcataract surgery. AIM: The aim is to present 9 cases with delayed presentation and describe their successful management with surgical approach. METHOD: A two-year retrospective review of 9 cases was undertaken. Anterior segment optical coherence tomography (AS-OCT) was used to confirm this diagnosis. Aspiration of the milky fluid with 26 gauge needle followed by capsular bag lavage was performed and aspirated fluid was examined. RESULTS: Patients showed signs of late CBS 6,56 ± 1,94 years after uncomplicated phacoemulsification with intraocular lens (IOL) implantation into the capsular bag. All 9 patients presented with a turbid fluid collection within the distended capsular bag. AS-OCT showed a hyper-reflective material in the space between the IOL and distended posterior capsule. CONCLUSION: Awareness of the manifestations of CBS and choice of the correct imaging modality may lead to regular diagnosis and successful treatment. Management with aspiration of the milky fluid and lavage of the capsular bag is technically safe and effective procedure. It has the advantage of microbial testing of the fluid. AS-OCT is useful tool to differentiate this condition clearly from IOL opacification and posterior capsule opacification.

• MeSH
• fakoemulzifikace * MeSH
• implantace nitrooční čočky * MeSH
• lidé středního věku MeSH
• lidé MeSH
• nemoci oční čočky diagnóza   etiologie   chirurgie   MeSH
• optická koherentní tomografie * MeSH
• pooperační komplikace * MeSH
• pouzdro oční čočky * chirurgie   diagnostické zobrazování   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• syndrom MeSH
• zraková ostrost fyziologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: A third of endovascularly treated patients with stroke experience incomplete reperfusion (expanded Thrombolysis in Cerebral Infarction [eTICI] <3), and the natural evolution of this incomplete reperfusion remains unknown. We systematically reviewed the literature and performed a meta-analysis on the natural evolution of incomplete reperfusion after endovascular therapy. METHODS: A systematic review of MEDLINE, Embase, and PubMed up until March 1, 2024, using a predefined strategy. Only full-text English-written articles reporting rates of either favorable (ie, delayed reperfusion (DR) or no new infarct) or unfavorable progression (ie, persistent perfusion deficit or new infarct) of incompletely reperfused tissue were included. The primary outcome was the rate of DR and its association with functional independence (modified Rankin Scale score, 0-2) at 90 days postintervention. Pooled odds ratios with 95% CIs were calculated using a random-effects model. RESULTS: Six studies involving 950 patients (50.7% female; median age, 71 years; interquartile range, 60-79) were included. Four studies assessed the evolution of incomplete reperfusion on magnetic resonance imaging perfusion imaging, while 2 studies used diffusion-weighted imaging and noncontrast computed tomography imaging, where new infarct was used to denote unfavorable progression. Five studies defined incomplete reperfusion as eTICI 2b50 or 2c. DR occurred in 41% (interquartile range, 33%-51%) of cases 24 hours postintervention. Achieving DR was associated with a higher likelihood of functional independence at 90 days (odds ratio, 2.5 [95% CI, 1.9-3.4]). CONCLUSIONS: Nearly half of eTICI <3 patients achieve DR, leading to favorable clinical outcomes. This subgroup may derive limited or potentially harmful effects from pursuing additional reperfusion strategies (eg, intra-arterial lytics or secondary thrombectomy). Accurately predicting the evolution of incomplete reperfusion could optimize patient selection for adjunctive reperfusion strategies at the end of an intervention. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT05499832.

• MeSH
• endovaskulární výkony * metody   MeSH
• ischemická cévní mozková příhoda * chirurgie   diagnostické zobrazování   terapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• reperfuze metody   MeSH
• senioři MeSH
• trombolytická terapie metody   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• systematický přehled MeSH

BACKGROUND: Postoperative nausea and vomiting (PONV) in pediatric patients is a common and clinically significant postoperative complication. The incidence of PONV has not been extensively studied in large pediatric cohorts. Furthermore, in 2020, the Fourth Consensus Guidelines for the management of PONV were published. However, the association between perioperative factors and adherence to these guidelines remains unclear. This study aims to assess both the incidence of PONV and guideline adherence within a large and diverse pediatric population. METHODS: We conducted a retrospective observational study at a large tertiary medical center, including pediatric patients (≤18 years) who underwent surgery between September 2020 and March 2023. We conducted a retrospective analysis of data from our electronic health records, focusing on patient demographics, surgical details, anesthesia details, and prophylaxis for PONV. We calculated the incidence of PONV and used multivariable logistic regression to identify the predictors of guideline adherence. RESULTS: The cohort included 3772 patients with a median (interquartile range [IQR]) age of 9.21 (3.55-14.68) years. The incidence (95% confidence intervals) of early PONV was 1.0% (0.7-1.4) and 3.8% (3.2-4.5) for delayed PONV. Adherence to the fourth consensus guidelines for PONV management was observed in 32.5% (31.0-34.0) of cases. A high risk of PONV was identified in 55.9% (54.3-57.5) of the patients. The most common number of PONV risk factors was 3, observed in 1151 patients (30.5% [29.1-32.0]). Significant predictors of guideline adherence included the intraoperative use of long-acting opioids (odds ratio [OR], 2.711, P < .001) and age ≥3 years (OR, 2.074, P < .001). Nonadherence was associated with a higher incidence of PONV at 24 hours postsurgery (4.4% (3.6-5.2) vs 2.7% (1.9-3.8), P = .012). Factors such as specific high PONV risk surgeries ( P = .001), maintenance with inhalational agents solely ( P = .017), and neostigmine use ( P < .001) were also all statistically significant. CONCLUSIONS: Our study revealed a lower-than-expected incidence of PONV in pediatric patients, highlighting the need for standardized definitions and improved reporting. Adherence to PONV guidelines was suboptimal, emphasizing the need for better implementation strategies.

• MeSH
• antiemetika terapeutické užití   MeSH
• dítě MeSH
• dodržování směrnic * normy   MeSH
• incidence MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• pooperační nevolnost a zvracení * epidemiologie   diagnóza   prevence a kontrola   MeSH
• předškolní dítě MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• směrnice pro lékařskou praxi jako téma normy   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH

Hand and foot osteosarcoma represents ~1% of all diagnosed cases of osteosarcoma. The rarity of osteosarcoma of the hand and foot leads to frequent misdiagnosis, delayed diagnosis or incorrect treatments, which can lead to fatal consequences. Typically, salvaging the affected limb is the treatment of choice, and with the use of chemotherapy, 60-65% of patients with osteosarcoma can be treated without amputation. Due to its rarity, misdiagnosis and treatment delays are common, yet detailed reviews and analyses of such cases are limited. The present retrospective cohort study aimed to review and analyze cases of osteosarcoma located in the hand and foot. From January 2007 to January 2019, 11 patients were treated at the Masaryk Memorial Cancer Institute Sarcoma Center (Brno, Czechia), 5 cases affected the hand and 6 affected the foot. A total of 6 male patients and 5 female patients, with a mean age of 30.9±16.74 years, were diagnosed with hand or foot osteosarcoma. The mean follow-up period was 90.36±66.14 months. The mean tumor size detected during diagnosis was 4.29±1.81 cm. Osteoblastic osteosarcoma was the most common histopathological type, accounting for 4 cases (33.4%). A majority of the osteosarcomas were identified as high grade (81.8%). A total of 5 patients experienced misdiagnoses following their initial biopsy, with 2 patients initially receiving treatment outside the Masaryk Memorial Cancer Institute Sarcoma Center. The most frequently encountered misdiagnosis was giant-cell tumor of the bone. A total of 3 patients underwent limb amputation and 2 patients developed lung metastasis and succumbed to the disease. The disease-free survival period and overall survival rate were calculated using Kaplan-Meier survival analysis. The mean disease-free survival period was 82.83±60.05 months, while the overall survival rate was 72%, with a mean survival time of 90.36±56.73 months. In summary, an examination of a case series involving 11 patients diagnosed with osteosarcoma of the hand and foot was conducted. The treatment approach, clinical characteristics and patient outcomes were described. A total of four case studies of patients with osteosarcoma in the hand or foot were presented. Misdiagnosis of this disease may result in the inappropriate treatment being administered to patients, therefore, the correct and rapid diagnosis of disease is necessary for effective treatment of hand and foot osteosarcomas.

• Publikační typ
• časopisecké články MeSH

Pseudohypoaldosteronism type 2 (PHA2) is a rare inherited condition of altered tubular salt handling. It is characterized by the specific constellation of hyperkalaemic hyporeninemic hypertension, hyperchloremic metabolic acidosis and hypercalciuria. Molecular genetic testing confirms the diagnosis in the majority of cases. Thiazides constitute effective treatment. Due to its rarity, the diagnosis is often delayed. We here present two children with PHA2, who were initially treated with fludrocortisone and bicarbonate complicated mainly by exacerbation of their hypertension. Discontinuation of their previous therapy and commencement of thiazide diuretics led to normalisation of their blood pressure and electrolyte and acid-base status.

• MeSH
• acidóza * diagnóza   etiologie   MeSH
• dítě MeSH
• fludrokortison terapeutické užití   MeSH
• hyperkalemie diagnóza   etiologie   genetika   krev   MeSH
• hypertenze * diagnóza   etiologie   farmakoterapie   genetika   MeSH
• inhibitory symportérů pro chlorid sodný terapeutické užití   MeSH
• krevní tlak MeSH
• lidé MeSH
• pseudohypoaldosteronismus * genetika   diagnóza   patofyziologie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

BACKGROUND AND AIM: Diabetes has been shown in last decades to be associated with a significantly higher mortality among patients with ST-segment elevation myocardial infarction (STEMI) treated with primary PCI (PPCI). Therefore, the aim of current study was to evaluate the impact of diabetes on times delays, reperfusion and mortality in a contemporary STEMI population undergoing PPCI, including treatment during the COVID pandemic. METHODS AND RESULTS: The ISACS-STEMI COVID-19 is a large-scale retrospective multicenter registry involving PPCI centers from Europe, Latin America, South-East Asia and North-Africa, including patients treated from 1st of March until June 30, 2019 and 2020. Primary study endpoint of this analysis was in-hospital mortality. Secondary endpoints were postprocedural TIMI 0-2 flow and 30-day mortality. Our population is represented by 16083 STEMI patients. A total of 3812 (23,7 %) patients suffered from diabetes. They were older, more often males as compared to non-diabetes. Diabetic patients were less often active smokers and had less often a positive family history of CAD, but they were more often affected by hypertension and hypercholesterolemia, with higher prevalence of previous STEMI and previous CABG. Diabetic patients had longer ischemia time, had more often anterior MI, cardiogenic shock, rescue PCI and multivessel disease. They had less often out-of-hospital cardiac arrest and in-stent thrombosis, received more often a mechanical support, received less often a coronary stent and DES. Diabetes was associated with a significantly impaired postprocedural TIMI flow (TIMI 0-2: 9.8 % vs 7.2 %, adjusted OR [95 % CI] = 1.17 [1.02-1.38], p = 0.024) and higher mortality (in-hospital: 9.1 % vs 4.8 %, Adjusted OR [95 % CI] = 1.70 [1.43-2.02], p < 0.001; 30-day mortality: 10.8 % vs 6 %, Adjusted HR [95 % CI] = 1.46 [1.26-1.68], p < 0.001) as compared to non-diabetes, particularly during the pandemic. CONCLUSIONS: Our study showed that in a contemporary STEMI population undergoing PPCI, diabetes is significantly associated with impaired epicardial reperfusion that translates into higher in-hospital and 30-day mortality, particularly during the pandemic.

• MeSH
• čas zasáhnout při rozvinutí nemoci MeSH
• časové faktory MeSH
• COVID-19 * mortalita   epidemiologie   MeSH
• diabetes mellitus * mortalita   diagnóza   epidemiologie   MeSH
• hodnocení rizik MeSH
• infarkt myokardu s elevacemi ST úseků * mortalita   terapie   diagnóza   MeSH
• koronární angioplastika * mortalita   škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mortalita v nemocnicích MeSH
• registrace MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

OBJECTIVE: Ischemic complications account for significant patient morbidity following aneurysmal subarachnoid hemorrhage (aSAH). The Prevention and Treatment of Vasospasm with Clazosentan (REACT) study was designed to assess the safety and efficacy of clazosentan, an endothelin receptor antagonist, in preventing clinical deterioration due to delayed cerebral ischemia (DCI) in patients with aSAH. METHODS: REACT was a prospective, multicenter, randomized, double-blind, phase 3 study. Eligible patients had aSAH secured by surgical clipping or endovascular coiling, and had presented with thick and diffuse clot on admission CT scan. Patients were randomized (1:1 ratio) to 15 mg/hour intravenous clazosentan or placebo within 96 hours of the aSAH for up to 14 days, in addition to standard of care treatment including oral or intravenous nimodipine. The primary efficacy endpoint was the occurrence of clinical deterioration due to DCI up to 14 days after initiation of the study drug. The main secondary endpoint was the occurrence of clinically relevant cerebral infarction at day 16 after study drug initiation. Other secondary endpoints included clinical outcome assessed on the modified Rankin Scale (mRS) and the Glasgow Outcome Scale-Extended (GOSE) at week 12 post-aSAH. Imaging and clinical endpoints were centrally adjudicated. RESULTS: A total of 409 patients were randomized between February 2019 and May 2022 across 74 international sites. Three patients did not start study treatment and were not included in the analysis set. The occurrence of clinical deterioration due to DCI was 15.8% (32/202 patients) in the clazosentan group and 17.2% (35/204 patients) in the placebo group, and the difference was not statistically significant (relative risk reduction [RRR] 7.2%, 95% CI -42.6% to 39.6%, p = 0.734). A nonsignificant RRR of 34.1% (95% CI -21.3% to 64.2%, p = 0.177) was observed in clinically relevant cerebral infarcts treated with clazosentan (7.4%, 15/202) versus placebo (11.3%, 23/204). Rescue therapy was less frequently needed for patients treated with clazosentan compared to placebo (10.4%, 21/202 vs 18.1%, 37/204; RRR 42.6%, 95% CI 5.4%-65.2%). A nonsignificant relative risk increase of 25.4% (95% CI -10.7% to 76.0%, p = 0.198) was reported in the risk of poor GOSE and mRS scores with clazosentan (24.8%, 50/202) versus placebo (20.1%, 41/204) at week 12 post-aSAH. Treatment-emergent adverse events were similar to those reported previously. CONCLUSIONS: Clazosentan administered for up to 14 days at 15 mg/hour had no significant effect on the occurrence of clinical deterioration due to DCI. Clinical trial registration no.: NCT03585270 (ClinicalTrials.gov) EU clinical trial registration no.: 2018-000241-39 (clinicaltrialsregister.eu).

• MeSH
• dioxany * terapeutické užití   škodlivé účinky   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• intrakraniální vazospazmus etiologie   prevence a kontrola   farmakoterapie   diagnostické zobrazování   MeSH
• ischemie mozku * prevence a kontrola   etiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• prospektivní studie MeSH
• pyridiny * terapeutické užití   škodlivé účinky   aplikace a dávkování   MeSH
• pyrimidiny * terapeutické užití   škodlivé účinky   aplikace a dávkování   MeSH
• senioři MeSH
• subarachnoidální krvácení * komplikace   diagnostické zobrazování   MeSH
• sulfonamidy * terapeutické užití   škodlivé účinky   aplikace a dávkování   MeSH
• tetrazoly * terapeutické užití   škodlivé účinky   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH