Microcirculation-driven mitochondrion dysfunction during the progression of experimental sepsis.

Sepsis is accompanied by a less-known mismatch between hemodynamics and mitochondrial respiration. We aimed to characterize the relationship and time dependency of microcirculatory and mitochondrial functions in a rodent model of intraabdominal sepsis. Fecal peritonitis was induced in rats, and multi-organ failure (MOF) was evaluated 12, 16, 20, 24 or 28 h later (n = 8/group, each) using rat-specific organ failure assessment (ROFA) scores. Ileal microcirculation (proportion of perfused microvessels (PPV), microvascular flow index (MFI) and heterogeneity index (HI)) was monitored by intravital video microscopy, and mitochondrial respiration (OxPhos) and outer membrane (mtOM) damage were measured with high-resolution respirometry. MOF progression was evidenced by increased ROFA scores; microcirculatory parameters followed a parallel time course from the 16th to 28th h. Mitochondrial dysfunction commenced with a 4-h time lag with signs of mtOM damage, which correlated significantly with PPV, while no correlation was found between HI and OxPhos. High diagnostic value was demonstrated for PPV, mtOM damage and lactate levels for predicting MOF. Our findings indicate insufficient splanchnic microcirculation to be a possible predictor for MOF that develops before the start of mitochondrial dysfunction. The adequate subcellular compensatory capacity suggests the presence of mitochondrial subpopulations with differing sensitivity to septic insults.

Aromatase Inhibitors and Plasma Lipid Changes in Postmenopausal Women with Breast Cancer: A Systematic Review and Meta-Analysis.

Background: Women are typically diagnosed with estrogen receptor-positive breast cancer around the postmenopausal period when declining estrogen levels initiate changes in lipid profiles. Aromatase inhibitors (AI) are used to prevent the progression of cancer; however, a further reduction in estrogen levels may have detrimental effects on lipid levels, which was our working hypothesis. Methods: Our meta-analysis was conducted on the lipid profiles of postmenopausal breast cancer patients at baseline and at different treatment time points. Results: We identified 15 studies, including 1708 patients. Studies using anastrozole (ANA), exemestane (EXE), letrozole (LET), and tamoxifen (TMX) were involved. Subgroup analyses revealed that 3- and 12-month administrations of LET and EXE lead to negative changes in lipid profiles that tend to alter the lipid profile undesirably, unlike ANA and TMX. Conclusions: Our results suggest that, despite statistically significant results, EXE and LET may not be sufficient to cause severe dyslipidemia in patients without cardiovascular comorbidities according to the AHA/ACC Guideline on the Management of Blood Cholesterol. However, the results may raise the question of monitoring the effects of AIs in patients, especially those with pre-existing cardiovascular risk factors such as dyslipidemia.

A szegedi Sebészeti Mutéttani Intézet 25 éve •.

This publication was prepared on the occasion of the 25th anniversary of Professor Mihály Boros as the head of the Institute for Surgical Research, Szeged, and summarises the educational and research achievements between 1998-2023, with the intention to show the importance of combining pre-clinical and clinical surgery, surgical training and experimental surgical research.

Impairment of Mesenteric Perfusion as a Marker of Major Bleeding in Trauma Patients.

The majority of potentially preventable mortality in trauma patients is related to bleeding; therefore, early recognition and effective treatment of hemorrhagic shock impose a cardinal challenge for trauma teams worldwide. The reduction in mesenteric perfusion (MP) is among the first compensatory responses to blood loss; however, there is no adequate tool for splanchnic hemodynamic monitoring in emergency patient care. In this narrative review, (i) methods based on flowmetry, CT imaging, video microscopy (VM), measurement of laboratory markers, spectroscopy, and tissue capnometry were critically analyzed with respect to their accessibility, and applicability, sensitivity, and specificity. (ii) Then, we demonstrated that derangement of MP is a promising diagnostic indicator of blood loss. (iii) Finally, we discussed a new diagnostic method for the evaluation of hemorrhage based on exhaled methane (CH4) measurement. Conclusions: Monitoring the MP is a feasible option for the evaluation of blood loss. There are a wide range of experimentally used methodologies; however, due to their practical limitations, only a fraction of them could be integrated into routine emergency trauma care. According to our comprehensive review, breath analysis, including exhaled CH4 measurement, would provide the possibility for continuous, non-invasive monitoring of blood loss.

A Barrier to Defend - Models of Pulmonary Barrier to Study Acute Inflammatory Diseases.

Pulmonary diseases represent four out of ten most common causes for worldwide mortality. Thus, pulmonary infections with subsequent inflammatory responses represent a major public health concern. The pulmonary barrier is a vulnerable entry site for several stress factors, including pathogens such as viruses, and bacteria, but also environmental factors e.g. toxins, air pollutants, as well as allergens. These pathogens or pathogen-associated molecular pattern and inflammatory agents e.g. damage-associated molecular pattern cause significant disturbances in the pulmonary barrier. The physiological and biological functions, as well as the architecture and homeostatic maintenance of the pulmonary barrier are highly complex. The airway epithelium, denoting the first pulmonary barrier, encompasses cells releasing a plethora of chemokines and cytokines, and is further covered with a mucus layer containing antimicrobial peptides, which are responsible for the pathogen clearance. Submucosal antigen-presenting cells and neutrophilic granulocytes are also involved in the defense mechanisms and counterregulation of pulmonary infections, and thus may directly affect the pulmonary barrier function. The detailed understanding of the pulmonary barrier including its architecture and functions is crucial for the diagnosis, prognosis, and therapeutic treatment strategies of pulmonary diseases. Thus, considering multiple side effects and limited efficacy of current therapeutic treatment strategies in patients with inflammatory diseases make experimental in vitro and in vivo models necessary to improving clinical therapy options. This review describes existing models for studyying the pulmonary barrier function under acute inflammatory conditions, which are meant to improve the translational approaches for outcome predictions, patient monitoring, and treatment decision-making.

A Porcine Sepsis Model With Numerical Scoring for Early Prediction of Severity.

Introduction: Sepsis can lead to organ dysfunctions with disturbed oxygen dynamics and life-threatening consequences. Since the results of organ-protective treatments cannot always be transferred from laboratory models into human therapies, increasing the translational potential of preclinical settings is an important goal. Our aim was to develop a standardized research protocol, where the progression of sepsis-related events can be characterized reproducibly in model experiments within clinically-relevant time frames. Methods: Peritonitis was induced in anesthetized minipigs injected intraperitoneally with autofeces inoculum (n = 27) or with saline (sham operation; n = 9). The microbial colony-forming units (CFUs) in the inoculum were retrospectively determined. After awakening, clinically relevant supportive therapies were conducted. Nineteen inoculated animals developed sepsis without a fulminant reaction. Sixteen hours later, these animals were re-anesthetized for invasive monitoring. Blood samples were taken to detect plasma TNF-α, IL-10, big endothelin (bET), high mobility group box protein1 (HMGB1) levels and blood gases, and sublingual microcirculatory measurements were conducted. Hemodynamic, respiratory, coagulation, liver and kidney dysfunctions were detected to characterize the septic status with a pig-specific Sequential Organ Failure Assessment (pSOFA) score and its simplified version (respiratory, cardiovascular and renal failure) between 16 and 24 h of the experiments. Results: Despite the standardized sepsis induction, the animals could be clustered into two distinct levels of severity: a sepsis (n = 10; median pSOFA score = 2) and a septic shock (n = 9; median pSOFA score = 8) subgroup at 18 h of the experiments, when the decreased systemic vascular resistance, increased DO2 and VO2, and markedly increased ExO2 demonstrated a compensated hyperdynamic state. Septic animals showed severity-dependent scores for organ failure with reduced microcirculation despite the adequate oxygen dynamics. Sepsis severity characterized later with pSOFA scores was in correlation with the germ count in the induction inoculum (r = 0.664) and CFUs in hemocultures (r = 0.876). Early changes in plasma levels of TNF-α, bET and HMGB1 were all related to the late-onset organ dysfunctions characterized by pSOFA scores. Conclusions: This microbiologically-monitored, large animal model of intraabdominal sepsis is suitable for clinically-relevant investigations. The methodology combines the advantages of conscious and anesthetized studies, and mimics human sepsis and septic shock closely with the possibility of numerical quantification of host responses.

Out-of-hospital pediatric sudden cardiac arrest and inherited arrhythmia syndromes in Hungary. / Gyermekkori, kórházon kívüli hirtelen szívmegállás és öröklodo arrhythmiaszindrómák Magyarországon.

Összefoglaló. Bevezetés: A gyermekkori hirtelen szívmegállás ritka, de egy részük megelozheto lehetne. Célkituzés: Vizsgálatunk célja az volt, hogy a Magyarországon eloforduló, kórházon kívüli gyermekkori szívmegállás gyakoriságát és hátterében az öröklodo arrhythmiaszindrómák jelentoségét megbecsüljük. Módszer: Három megközelítést alkalmaztunk. Elemeztük 1) az Országos Mentoszolgálat 2012. január 1. és 2015. június 30. közötti eseteinek Utstein-adatlapjait, 2) az Országos Gyermekszív Központba hirtelen szívmegállás miatt 2000. január 1. és 2021. augusztus 11. között felvett, valamint 3) az öröklött arrhythmiaszindróma gyanúja miatt 2015. október 1. és 2021. augusztus 11. között gondozásba vett gyermekek adatait. Eredmények: 1) A vizsgált 3,5 év alatt 373 gyermekkori keringésmegálláshoz riasztották a mentoket. Az Utstein-adatlapok alapján vélhetoen 84 esetben (≈24/év) állhatott cardialis ok a háttérben. A reanimáció az esetek 20%-ában volt sikeres. 2) A vizsgált közel 21 évben 24 gyermek (≈1/év) került felvételre elozmény nélküli hirtelen szívmegállást követoen a tercier országos központba. Hátterükben 11/24 (46%) esetben öröklött arrhythmiaszindróma, 4/24 (16%) esetben strukturális szívbetegség igazolódott. 9/24 (38%) esetben az ok nem volt tisztázható. 3) A vizsgált közel 6 évben 73 gyermeknél (≈12/év) történt genetikai vizsgálat öröklodo arrhythmiaszindróma gyanúja miatt: tünetek nélküli kóros EKG: n = 23, családszurés: n = 21, syncope: n = 15, sikeres újraélesztést követoen: n = 14. Egyértelmu patológiás mutáció 29 (≈5/év), ismeretlen jelentoségu variáns 15 esetben igazolódott. Következtetés: Az Országos Mentoszolgálat adatai alapján Magyarországon évente kb. 20-25 gyermeknél következik be kórházon kívüli hirtelen szívmegállás. Ezen esetek körülbelül egyötödében sikeres az újraélesztés, és a túlélo betegek egyötöde gyógyul súlyos szövodmények, neurológiai károsodás nélkül és kerül az Országos Gyermekszív Központba további ellátásra (a gyermekkori szívmegállások 5%-a). Ezen betegek közel felénél utólag öröklött arrhythmiaszindróma igazolható. Öröklodo arrhythmiaszindróma miatt az országos központban gondozásba kerülo gyermekek egyötödét ismerik fel hirtelen szívmegállást követoen. Orv Hetil. 2022; 163(12): 473-477. INTRODUCTION: The incidence of pediatric out-of-hospital sudden cardiac arrest is low, but a part of them could be preventable. OBJECTIVE: Aim of our study was to assess the pediatric cardiac arrest in Hungary and the magnitude of inherited cardiac arrhythmias in the background. METHOD: Three methods were used. 1) Utstein data sheets of the National Ambulance Service between 01. 01. 2012 and 30. 06. 2015. 2) Records of admissions to the national tertiary pediatric heart centre, due to out-of-hospital pediatric sudden cardiac arrest between 01. 01. 2000 - 11. 08. 2021. and 3) Results of genetic testing in patients with suspicion of inherited arrhythmia syndromes between 01. 10. 2015 - 11. 08. 2021 were analysed retrospectively. RESULTS: 1) Ambulance was called to 373 paediatric cardiac arrests during the study period of 3.5 years. Primary cardiac origin was presumed in 84 cases (≈24/year) on the basis of Utstein data sheets. Reanimation was successful in 20%. 2) 24 children (≈1/year) were admitted to the national pediatric heart centre after out-of-hospital sudden cardiac arrest during the study period of 21 years. Inherited arrhythmia syndromes in 11/24 (46%), structural heart disease in 4/24 (16%) cases could be identified, but etiology remained unclear in the rest 9/24 (38%). 3) Suspicion of inherited arrhythmia syndrome emerged in 73 children in 6 years of the study (≈12/year) and it was based on pathological ECG: n = 23, family screening: n = 21, syncope: n = 15, successful reanimation: n = 14. Genetic testing revealed pathological variation in 29 cases (≈5/year), variant of unknown significance in 15 cases. CONCLUSION: 20-25 children have out-of-hospital cardiac arrest annually in Hungary based on data from the National Ambulance Service. Reanimation is successful in one fifth of the cases. One fifth of these surviving children had no severe complications and neurological deficit and they were admitted to the national pediatric heart centre for further diagnosis and treatment (5% of pediatric cardiac arrest). Inherited arrhythmia syndrome could be identified in the background in half of these admissions. One fifth of children checked up and followed for inherited arrhythmia syndrome in the national centre were diagnosed after sudden cardiac arrest. Orv Hetil. 2022; 163(12): 473-477.

Characterization of technical skill progress in a standardized rabbit model for training in laparoscopic duodenal atresia repair.

BACKGROUND: Laboratory skills training is an essential step before conducting minimally invasive surgery in clinical practice. Our main aim was to develop an animal model for training in clinically highly challenging laparoscopic duodenal atresia repair that could be useful in establishing a minimum number of repetitions to indicate safe performance of similar interventions on humans. MATERIALS AND METHODS: A rabbit model of laparoscopic duodenum atresia surgery involving a diamond-shaped duodeno-duodenostomy was designed. This approach was tested in two groups of surgeons: in a beginner group without any previous clinical laparoscopic experience (but having undergone previous standardized dry-lab training, n = 8) and in an advanced group comprising pediatric surgery fellows with previous clinical experience of laparoscopy (n = 7). Each participant performed eight interventions. Surgical time, expert assessment using the Global Operative Assessment of Laparoscopic Skills (GOALS) score, anastomosis quality (leakage) and results from participant feedback questionnaires were analyzed. RESULTS: Participants in both groups successfully completed all eight surgeries. The surgical time gradually improved in both groups, but it was typically shorter in the advanced group than in the beginner group. The leakage rate was significantly lower in the advanced group in the first two interventions, and it reached its optimal level after five operations in both groups. The GOALS and participant feedback scores showed gradual increases, evident even after the fifth surgery. CONCLUSIONS: Our data confirm the feasibility of this advanced pediatric laparoscopic model. Surgical time, anastomosis quality, GOALS score and self-assessment parameters adequately quantify technical improvement among the participants. Anastomosis quality reaches its optimal value after the fifth operation even in novice, but uniformly trained surgeons. A minimum number of wet-lab operations can be determined before surgery can be safely conducted in a clinical setting, where the development of further non-technical skills is also required.

Students in Danger: Binge Drinking Behaviour and Associated Factors in Hungary.

INTRODUCTION: Among young adults, high rates of binge drinking were observed in certain European countries. Binge drinking is associated with several health problems (unplanned pregnancy, HIV infections, problems with memory, and injuries). The aim of this questionnaire-based study was to measure the frequency of binge drinking and its association with sociodemographic, familial, lifestyle factors and school performance among secondary and university students (n=2449) in Csongrád County, Hungary. METHODS: In this cross-sectional study the students' sociodemographic data, parents' educational and economic level, and students' academic performance and self-reported use of tobacco, drugs, and alcohol were collected by a questionnaire. Descriptive statistics and multivariable binary logistic regression analyses were applied using SPSS 24.0 software. RESULTS: Altogether 2449 Hungarian secondary school students and university students participated in the study. Nearly one-third of the students were classified as binge drinkers, significantly more male university students. Tobacco or illicit drug use resulted in higher odds of being a binge drinker in both subgroups. Poor school performance and binge drinking were significantly correlated especially among secondary school students. CONCLUSIONS: Targeting alcohol, tobacco, and illicit drug use together, including education, parent interventions, and public health policies, are crucial in the prevention of possible serious consequences.

The microbial composition of the initial insult can predict the prognosis of experimental sepsis.

We hypothesized that the composition of sepsis-inducing bacterial flora influences the course of fecal peritonitis in rodents. Saline or fecal suspensions with a standardized dose range of bacterial colony-forming units (CFUs) were injected intraperitoneally into Sprague-Dawley rats. The qualitative composition of the initial inoculum and the ascites was analyzed separately by MALDI-TOF mass spectrometry. Invasive monitoring was conducted in separate anesthetized groups (n = 12-13/group) after 12, 24, 48 and 72 h to determine rat-specific organ failure assessment (ROFA) scores. Death and ROFA scores peaked at 24 h. At this time, 20% mortality occurred in animals receiving a monomicrobial E. coli suspension, and ROFA scores were significantly higher in the monomicrobial subgroup than in the polymicrobial one (median 6.5; 5.0-7.0 and 5.0; 4.75-5.0, respectively). ROFA scores dropped after 48 h, accompanied by a steady decrease in ascites CFUs and a shift towards intra-abdominal monomicrobial E. coli cultures. Furthermore, we found a relationship between ascites CFUs and the evolving change in ROFA scores throughout the study. Hence, quantitatively identical bacterial loads with mono- or polymicrobial dominance lead to a different degree of sepsis severity and divergent outcomes. Initial and intraperitoneal microbiological testing should be used to improve translational research success.

Kynurenic Acid and Its Synthetic Derivatives Protect Against Sepsis-Associated Neutrophil Activation and Brain Mitochondrial Dysfunction in Rats.

Background and Aims: The systemic host response in sepsis is frequently accompanied by central nervous system (CNS) dysfunction. Evidence suggests that excessive formation of neutrophil extracellular traps (NETs) can increase the permeability of the blood-brain barrier (BBB) and that the evolving mitochondrial damage may contribute to the pathogenesis of sepsis-associated encephalopathy. Kynurenic acid (KYNA), a metabolite of tryptophan catabolism, exerts pleiotropic cell-protective effects under pro-inflammatory conditions. Our aim was to investigate whether exogenous KYNA or its synthetic analogues SZR-72 and SZR-104 affect BBB permeability secondary to NET formation and influence cerebral mitochondrial disturbances in a clinically relevant rodent model of intraabdominal sepsis. Methods: Sprague-Dawley rats were subjected to fecal peritonitis (0.6 g kg-1 ip) or a sham operation. Septic animals were treated with saline or KYNA, SZR-72 or SZR-104 (160 µmol kg-1 each ip) 16h and 22h after induction. Invasive monitoring was performed on anesthetized animals to evaluate respiratory, cardiovascular, renal, hepatic and metabolic parameters to calculate rat organ failure assessment (ROFA) scores. NET components (citrullinated histone H3 (CitH3); myeloperoxidase (MPO)) and the NET inducer IL-1ß, as well as IL-6 and a brain injury marker (S100B) were detected from plasma samples. After 24h, leukocyte infiltration (tissue MPO) and mitochondrial complex I- and II-linked (CI-CII) oxidative phosphorylation (OXPHOS) were evaluated. In a separate series, Evans Blue extravasation and the edema index were used to assess BBB permeability in the same regions. Results: Sepsis was characterized by significantly elevated ROFA scores, while the increased BBB permeability and plasma S100B levels demonstrated brain damage. Plasma levels of CitH3, MPO and IL-1ß were elevated in sepsis but were ameliorated by KYNA and its synthetic analogues. The sepsis-induced deterioration in tissue CI-CII-linked OXPHOS and BBB parameters as well as the increase in tissue MPO content were positively affected by KYNA/KYNA analogues. Conclusion: This study is the first to report that KYNA and KYNA analogues are potential neuroprotective agents in experimental sepsis. The proposed mechanistic steps involve reduced peripheral NET formation, lowered BBB permeability changes and alleviation of mitochondrial dysfunction in the CNS.

COVID-19 in Pregnancy: Occupations With Higher Density of Population Exposure Associated With More Severe Disease.

OBJECTIVE: To define the symptomatology of SARS-CoV-2 infection in pregnancy and associations between occupation, sociodemographic factors, and comorbidities with the severity of COVID-19 disease in pregnancy in all trimesters, regardless of hospitalization. METHODS: We studied a retrospective cohort of a public health surveillance sample of persons with COVID-19 infection diagnosed during pregnancy. Data was collected March 2020 to August 2020 regarding symptoms, disease severity, comorbidities, obstetric history, and occupation. RESULTS: One hundred sixty-three individuals were identified. Constitutional (64%) and lower respiratory symptoms (61%) were most common. Seventeen individuals (13.6%) were hospitalized, and one person (0.7%) died due to COVID-19. Risk factors for severe disease were age and an occupation that had high intensity exposure to people. CONCLUSIONS: Occupational exposure is a risk factor for severe COVID-19 disease in pregnancy, justifying policy measures to ensure protection of this vulnerable population.

Orally Administered Probiotics Decrease Aggregatibacter actinomycetemcomitans but Not Other Periodontal Pathogenic Bacteria Counts in the Oral Cavity: A Systematic Review and Meta-Analysis.

Introduction: At the initial part of the gastrointestinal tract, multiple tissues serve the normal function of food delivery. Periodontal structures are integral elements of these. When they deteriorate, it is extremely challenging to regenerate and reconstruct them. The conventional intervention for periodontal disease is scaling and root planning with the aim of reducing pathogenic bacteria. However, periodontal pathogens can rapidly recolonize treated areas. Probiotics have been proposed as novel tools for managing oral health by suppressing pathogenic bacteria through their anti-inflammatory effect, but the available data are controversial. Aim: Therefore, we performed a meta-analysis to study the effect of probiotics on periodontal pathogenic bacteria. Methods: The study was registered in PROSPERO under registration number CRD42018094903. A comprehensive literature search from four electronic databases (PubMed, Cochrane CENTRAL, Embase, and Web of Science) yielded nine eligible records for statistical analysis. Studies measuring bacterial counts in saliva and supra- and subgingival plaque were included. Bacterial counts were analyzed using standard mean difference (SMD) and by a random effects model with the DerSimonian-Laird estimation. Results: The results showed a significant decrease in the overall count of Aggregatibacter actinomycetemcomitans in the probiotic-treated group compared to the control at 4 weeks (SMD: -0.28; 95% CI: -0.56--0.01; p = 0.045) but not later. Analyzing the bacterial counts in subgroups, namely, in saliva and supra- and subgingival plaque, separately, yielded no significant difference. Probiotics had no significant effect on the overall count of Porphyromonas gingivalis at 4 weeks (SMD: -0.02; 95% CI: -0.35-0.31; p = 0.914) or later. Subgroup analysis also revealed no significant difference between treatment and control groups nor did probiotics significantly decrease the overall and subgroup bacterial counts of Prevotella intermedia, Tannerella forsythia, and Fusobacterium nucleatum. Conclusion: Our data support the beneficial effect of probiotics in reducing A. actinomycetemcomitans counts, but not of other key periodontal pathogenic bacteria in periodontal disease patients. However, due to the complex mechanism associated with periodontal disease and the limitations of the available studies, there is a further need for well-designed randomized clinical trials to assess the efficacy of probiotics.

Cross-modality imaging of bisphosphonate-treated murine jawbones.

In this proof-of-principle study, we established and implemented a cross-modality imaging (CMI) pipeline to characterize and compare bisphosphonate (BIS)-treated jawbones of Sprague-Dawley rats after tooth extraction after physical therapies (photobiomodulation and extracorporeal shockwave therapy (PBMT and ESWT)). We showcase the feasibility of such a CMI approach and its compatibility across imaging modalities to probe the same region of interest (ROI) of the same jawbone. Jawbones were imaged in toto in 3D using micro-Computed Tomography to identify ROIs for subsequent sequential 2D analysis using well-established technologies such as Atomic Force Microscopy and Scanning Electron Microscopy, and recent imaging approaches in biomedical settings, such as micro-X-Ray Fluorescence Spectroscopy. By combining these four modalities, multiscale information on the morphology, topography, mechanical stiffness (Young's modulus), and calcium, zinc and phosphorus concentrations of the bone was collected. Based on the CMI pipeline, we characterized and compared the jawbones of a previously published clinically relevant rat model of BIS-related osteonecrosis of the jawbone (BRONJ) before and after treatment with BISs, PBMT and ESWT. While we did not find that physical therapies altered the mechanical and elemental jawbone parameters with significance (probably due to the small sample size of only up to 5 samples per group), both ESWT and PBMT reduced pore thicknesses and bone-to-enamel distances significantly compared to the controls. Although focused on BIS-treated jawbones, the established CMI platform can be beneficial in the study of bone-related diseases in general (such as osteoarthritis or -porosis) to acquire complementary hallmarks and better characterize disease status and alleviation potentials.

Supraventricular tachycardias in neonates and infants: factors associated with fatal or near-fatal outcome.

Prognosis of supraventricular tachycardias in neonates and infants is thought to be excellent with rare fatal outcomes. Nevertheless, initial management can be challenging. The aim of this study was to perform a retrospective analysis in neonates/infants with non-pos-toperative supraventricular tachycardias regarding risk factors for clinical outcome and type of antiarrhythmic drug therapy. The data of 157 patients aged < 1 year who presented between 2000 and 2015 with symptomatic tachycardias were retrospectively reviewed. Pharmacological therapy was successful in 151 patients (96%); 1 patient (1%) required catheter ablation and 5 patients (3%) died (1 death linked to hemodynamical reasons after effective arrhythmia control). Serious complications following acute medical therapy occurred in 4 patients of survivors. Patients with complications or death had a lower bodyweight, more frequent intrauterine tachycardia, transplacental therapy, urgent caesarian section, higher PRISM II score, longer period to control tachycardia, more frequent proarrhythmia, and major adverse event-defined as life-threatening event without a documented new arrhythmia-compared to the group without complications. There was no significant difference between the groups regarding prematurity, structural heart disease, and type of tachycardia. Proarrhythmia occurred in 6 cases and was related to intravenous drug use with class IC antiarrhythmics in 3/6 cases, digoxin in 2/6 cases, and amiodarone in 1/6 cases. ECG signs of impending proarrhythmia without new-onset arrhythmia requiring cessation of therapy were detected in 6 patients.Conclusion: Although rare, non-post-operative supraventricular tachycardia in neonates and infants might be a serious disease. Acute intravenous pharmacological treatment to control tachycardia might pose a risk for fatal or near-fatal outcome. Detection of proarrhythmia related to class IC antiarrhythmics in neonates might be especially difficult and requires alertness. What is Known • Prognosis of supraventricular tachycardias in children are thought to be excellent with fatal outcomes being rare. • Mortality is increased in the very young and in those with structural heart disease. What is New • Complicated outcome of non-post-operative supraventricular tachycardias in neonates is associated with lower bodyweight, age, prenatal tachycardia, higher PRISM II score, longer period to control tachycardia, and proarrhythmia. • Detection of class IC proarrhythmic effect is especially difficult in neonates because of their narrow QRS and warrants alertness.

Frequency of syncope as a presenting symptom in channelopathies diagnosed in childhood. Can the multivariable EGSYS score unmask these children?

Pediatric syncope raises cardiac etiology concern as it might be the first sign of life-threatening arrhythmia syndromes. Our aim was to study the incidence of syncope as the presenting symptom in children with arrhythmia syndromes, and if known, warning signs are helpful to reveal the arrhythmic origin. All data on children with channelopathy was followed by a tertiary pediatric cardiac center between 2000 and 2018 and data were reviewed retrospectively. Forty-eight patients were enrolled, representing long QT syndrome (n = 39), catecholaminergic polymorphic ventricular tachycardia (n = 5), and Brugada syndrome (n = 4). Presenting symptoms were syncope in 13 cases [27%] (including 7 initially mislabeled as epilepsy) and sudden cardiac arrest (SCA) in 9 cases [19%]. In the rest of the group, the concern for arrhythmic etiology was raised by either an abnormal ECG during sports medicine screening (n = 13) [27%] or a positive family history of channelopathy (n = 13) [27%]. None of the patients presenting with SCA had a prior syncopal history. Six patients presenting with syncope and afterward treated with ICD had an appropriate shock. Description of witnessed syncope was available in eight out of thirteen children presenting with syncope. Multivariable EGSYS score suggested cardiac origin (≥ 3 points) in 7 out of 8 (88%) patients.Conclusions: Syncope was a relatively uncommon presenting symptom of channelopathies in this sample and did not always precede sudden cardiac arrests. However, we found that multivariable EGSYS score can identify syncope of arrhythmic origin, raising suspicion for pediatric channelopathies even in patients previously misdiagnosed with epilepsy. What is known: • Cardiac syncope is rare in children but can be the first sign of a potentially fatal primary arrhythmia syndrome and is frequently misdiagnosed as atypical/therapy-resistant epilepsy. • Multivariate EGSYS score is effective to diagnose cardiac syncope in adults. What is new: • Cardiac syncope as a presenting symptom is not common in children with cardiac channelopathies and is not often present before sudden cardiac arrest. • Multivariable EGSYS score might identify cardiac syncope in children with a hereditary and secondary channelopathy.

Clinical aspects and therapeutic possibilities of neurogenic bladder / A neurogén húgyhólyag klinikuma és terápiás lehetoségei.

Összefoglaló. Az alsó húgyutak fo funkciója a vizelet tárolása és ürítése, amely muködések zavara az úgynevezett alsó húgyúti tünetegyüttes kialakulásához vezet, ami a kiváltó októl függoen vizeletürítési zavarral és vizeletretencióval is járhat. Kezeletlen esetekben a felso húgyutak károsodása következik be a magas hólyagnyomás által kiváltott vesicoureteralis reflux következtében, amely ureter- és veseüregrendszeri tágulat kialakulására, illetve fertozésekre és koképzodésre hajlamosít. A vizelettárolási/vizeletürítési zavarokat három fo csoportba sorolhatjuk, úgymint stressz- (terheléses) inkontinencia , hiperaktív hólyag (nedves/száraz) és neurogén hólyag. A jelen összefoglaló közlemény tárgyát képezo neurogén hólyag egy gyujtofogalom, mely magában foglal minden, releváns neurológiai kórkép talaján kialakult vizelettárolási és vizeletürítési zavart. Mivel a húgyhólyag mellett a záróizomzat és a hátsó húgycso is érintett, ezt a kórképet napjainkban "neurogén alsó húgyúti diszfunkció" elnevezéssel is szokás illetni. A kórállapotot a neurológiai diszfunkciók széles spektruma okozhatja, kezdve a helyi funkcionális zavartól a helyi idegi sérülésen át a felso és alsó motoneuron-sérülésig vagy a centrális degeneratív folyamatokig. Az eltéro etiológia ellenére a klinikai tünetek rendszerint két alapveto klinikai típusban manifesztálódhatnak: túlmuködo (fokozott detrusorkontraktilitást okozó automata) hólyag vagy alulmuködo hólyag formájában. Tekintettel a neurogén alsó húgyúti diszfunkció következtében létrejövo felso húgyúti komplikációkra, a közlemény egyik célja a betegség diagnózisát segíto algoritmus bemutatása a legújabb nemzetközi szakirodalmi ismeretek alapján. A neurogén hólyag kezelése jobbára nem terjedhet ki a kiváltó ok kezelésére, ezért a jelen összefoglaló másik célja azon gyógyszeres és invazív terápiás beavatkozások összefoglalása, melyek a felso húgyutak védelmét szolgálják az alacsony hólyagnyomás fenntartása révén. Orv Hetil. 2021; 162(4): 135-143. Summary. Storage and urination are the main functions of the lower urinary tract and its lesions lead to the so-called lower urinary tract syndrome causing either urinary incontinence or retention. In untreated cases, the upper urinary tract becomes injured via a vesicoureteral reflux resulting from increased bladder pressure and resultant dilations of the ureter and the renal pelvis which predispose to infection and stone formation. Lower urinary tract storage/urination disorders can be classified as stress incontinence, hyperactive bladder (wet/dry) and neurogenic bladder. Neurogenic bladder which is the subject of this review, is a collective term that encompasses all urinary storage and emptying disorders which develop on the basis of neurological diseases. Being not only the bladder, but also the sphincter and posterior urethra (generally termed as the "bladder outlet") affected, nowadays this condition is referred to as "neurogenic lower urinary tract dysfunction". A wide range of neurological dysfunctions could contribute to the development of this condition, ranging from local dysfunction (autonomic dysreflexia) or local nerve injury to upper/lower motoneuron injury or central degenerative processes. Regardless of the diverse etiology, the clinical symptoms eventually manifest in two major forms, i.e., overacting (automatic bladder with increased detrusor contractility) and underactive bladder. Considering the severity of complication occurring in the upper urinary tract in response to the pathophysiological changes in the lower urinary tract, one of the aims of this paper was to present an algorithm aiming to build up a state of the art diagnosis of the disease based on current international literature data. Since treatment of the neurogenic bladder usually can not target elimination of the underlying cause, the other goal of the present paper is to summarize the pharmacological treatment regimen and invasive therapeutic interventions that protect the upper urinary tract by maintaining low pressure values in the bladder. Orv Hetil. 2021; 162(4): 135-143.

Characterization of community-wide transmission of SARS-CoV-2 in congregate living settings and local public health-coordinated response during the initial phase of the COVID-19 pandemic.

BACKGROUND: Clusters of COVID-19 cases amplify the pandemic and are critical targets for intervention, but comprehensive cluster-level data are not collected systematically by federal or most state public health entities. This analysis characterizes COVID-19 clusters among vulnerable populations housed in congregate living settings across an entire community and describes early mitigation efforts. METHODS: The Cuyahoga County Board of Health identified and interviewed COVID-19 cases and exposed contacts, assessing possible connections to congregate living facilities within its jurisdiction from March 7, 2020, to May 15, 2020, during the first phase of the pandemic, while state of Ohio stay-at-home orders were in effect. A multi-disciplinary team-based response network was mobilized to support active case finding and develop facility-focused containment strategies. RESULTS: We identified a cascade of 45 COVID-19 clusters across community facilities (corrections, nursing, assisted living, intermediate care, extended treatment, shelters, group homes). Attack rates were highest within small facilities (P < .01) and large facilities requiring extensive support to implement effective containment measures. For 25 clusters, we identified an index case who frequently (88%) was a healthcare worker. Engagement of clinical, community, and government partners through public health coordination efforts created opportunities to rapidly develop and coordinate effective response strategies to support the facilities facing the dawning impact of the pandemic. CONCLUSIONS: Active cluster investigations can uncover the dynamics of community transmission affecting both residents of congregate settings and their caregivers and help to target efforts toward populations with ongoing challenges in access to detection and control resources.