Longitudinal assessment of ventricular volume trajectories in early-stage schizophrenia: evidence of both enlargement and shrinkage.

BACKGROUND: Lateral ventricular enlargement represents a canonical morphometric finding in chronic patients with schizophrenia; however, longitudinal studies elucidating complex dynamic trajectories of ventricular volume change during critical early disease stages are sparse. METHODS: We measured lateral ventricular volumes in 113 first-episode schizophrenia patients (FES) at baseline visit (11.7 months after illness onset, SD = 12.3) and 128 age- and sex-matched healthy controls (HC) using 3T MRI. MRI was then repeated in both FES and HC one year later. RESULTS: Compared to controls, ventricular enlargement was identified in 18.6% of patients with FES (14.1% annual ventricular volume (VV) increase; 95%CI: 5.4; 33.1). The ventricular expansion correlated with the severity of PANSS-negative symptoms at one-year follow-up (p = 0.0078). Nevertheless, 16.8% of FES showed an opposite pattern of statistically significant ventricular shrinkage during ≈ one-year follow-up (-9.5% annual VV decrease; 95%CI: -23.7; -2.4). There were no differences in sex, illness duration, age of onset, duration of untreated psychosis, body mass index, the incidence of Schneiderian symptoms, or cumulative antipsychotic dose among the patient groups exhibiting ventricular enlargement, shrinkage, or no change in VV. CONCLUSION: Both enlargement and ventricular shrinkage are equally present in the early stages of schizophrenia. The newly discovered early reduction of VV in a subgroup of patients emphasizes the need for further research to understand its mechanisms.

Azithromycin promotes proliferation, and inhibits inflammation in nasal epithelial cells in primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) is a genetic disorder associated with recurrent and chronic respiratory infections due to functional defects of motile cilia. In this study, we aimed to elucidate inflammatory and proliferative responses in PCD respiratory epithelium and evaluate the effect of Azithromycin (AZT) on these responses. Airway basal cells (BCs) were isolated from nasal samples of Wild-type (WT) epitope of healthy donors and PCD donors with bi-allelic mutations in DNAH5, DNAH11 and CCDC39. Cells were expanded in vitro and stimulated with either Lipopolysaccharide (LPS) or vehicle control. Post stimulation, cells were treated with either Azithromycin (AZT) or vehicle control. Cell proliferation was imaged in real-time. Separately, BCs from the same donors were expanded and grown at an air-liquid interface (ALI) to generate a multi-ciliated epithelium (MCE). Once fully mature, cells were stimulated with LPS, AZT, LPS + AZT or vehicle control. Inflammatory profiling was performed on collected media by cytokine Luminex assay. At baseline, there was a significantly higher mean production of pro-inflammatory cytokines by CCDC39 BCs and MCEs when compared to WT, DNAH11 and DNAH5 cells. AZT inhibited production of cytokines induced by LPS in PCD cells. Differences in cell proliferation were noted in PCD and this was also corrected with AZT treatment.

Clostridioides difficile infections were predominantly driven by fluoroquinolone-resistant Clostridioides difficile ribotypes 176 and 001 in Slovakia in 2018-2019.

AIM: To investigate the epidemiology of Clostridioides difficile infection (CDI) in Slovakian hospitals after the emergence of ribotype 176 (027-like) in 2016. METHODS: Between 2018 and 2019, European Centre for Disease Control and Prevention CDI surveillance protocol v2.3 was applied to 14 hospitals, with additional data collected on recent antimicrobial use and the characterization of C. difficile isolates. RESULTS: The mean hospital incidence of CDI was 4.1 cases per 10,000 patient bed-days. One hundred and five (27.6%) in-hospital deaths were reported among the 381 cases. Antimicrobial treatment within the previous 4 weeks was recorded in 90.5% (333/368) of cases. Ribotype (RT)176 was detected in 50% (n=185/370, 14 hospitals) and RT001 was detected in 34.6% (n=128/370,13/14 hospitals) of cases with RT data. Overall, 86% (n=318/370) of isolates were resistant to moxifloxacin by Thr82Ile in GyrA (99.7%). Multi-locus variable tandem repeat analysis showed clonal relatedness of predominant RTs within and between hospitals. Seven of 14 sequenced RT176 isolates and five of 13 RT001 isolates showed between zero and three allelic differences by whole-genome multi-locus sequence typing. The majority of sequenced isolates (24/27) carried the erm(B) gene and 16/27 also carried the aac(6')-aph(2'') gene with the corresponding antimicrobial susceptibility phenotypes. Nine RT176 strains carried the cfr(E)gene and one RT001 strain carried the cfr(C) gene, but without linezolid resistance. CONCLUSIONS: The newly-predominant RT176 and endemic RT001 are driving the epidemiology of CDI in Slovakia. In addition to fluoroquinolones, the use of macrolide-lincosamide-streptogramin B antibiotics can represent another driving force for the spread of these epidemic lineages. In C. difficile, linezolid resistance should be confirmed phenotypically in strains with detected cfr gene(s).

mHealth intervention delivered in general practice to increase physical activity and reduce sedentary behaviour of patients with prediabetes and type 2 diabetes (ENERGISED): rationale and study protocol for a pragmatic randomised controlled trial.

BACKGROUND: The growing number of patients with type 2 diabetes and prediabetes is a major public health concern. Physical activity is a cornerstone of diabetes management and may prevent its onset in prediabetes patients. Despite this, many patients with (pre)diabetes remain physically inactive. Primary care physicians are well-situated to deliver interventions to increase their patients' physical activity levels. However, effective and sustainable physical activity interventions for (pre)diabetes patients that can be translated into routine primary care are lacking. METHODS: We describe the rationale and protocol for a 12-month pragmatic, multicentre, randomised, controlled trial assessing the effectiveness of an mHealth intervention delivered in general practice to increase physical activity and reduce sedentary behaviour of patients with prediabetes and type 2 diabetes (ENERGISED). Twenty-one general practices will recruit 340 patients with (pre)diabetes during routine health check-ups. Patients allocated to the active control arm will receive a Fitbit activity tracker to self-monitor their daily steps and try to achieve the recommended step goal. Patients allocated to the intervention arm will additionally receive the mHealth intervention, including the delivery of several text messages per week, with some of them delivered just in time, based on data continuously collected by the Fitbit tracker. The trial consists of two phases, each lasting six months: the lead-in phase, when the mHealth intervention will be supported with human phone counselling, and the maintenance phase, when the intervention will be fully automated. The primary outcome, average ambulatory activity (steps/day) measured by a wrist-worn accelerometer, will be assessed at the end of the maintenance phase at 12 months. DISCUSSION: The trial has several strengths, such as the choice of active control to isolate the net effect of the intervention beyond simple self-monitoring with an activity tracker, broad eligibility criteria allowing for the inclusion of patients without a smartphone, procedures to minimise selection bias, and involvement of a relatively large number of general practices. These design choices contribute to the trial's pragmatic character and ensure that the intervention, if effective, can be translated into routine primary care practice, allowing important public health benefits. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05351359, 28/04/2022).

ChildTalks+: a study protocol of a pre-post controlled, paired design study on the use of preventive intervention for children of parents with a mental illness with focus on eating disorders.

BACKGROUND: Children of parents with a mental illness are at high risk of developing a mental disorder as a result of transgenerational transmission. Without effective intervention, they could form the next generation of psychiatric patients. ChildTalks+ is a preventive intervention involving four structured psychoeducational sessions designed for parents affected by a mental disorder and their children. Its aim is to reduce the risk of mental disorders in children of parents with mental illness. This study draws on our clinical practice and involves a group of patients with eating disorders. The aim of the project, which will run in the Czech Republic, is to evaluate the effectiveness of ChildTalks+ methodology. METHODS: ChildTalks+ therapists (professionals from health, social, and educational facilities) will recruit 66 families where a parent is treated for a mental disorder and the family includes children aged 6-18. Paired allocation into an intervention group (N = 33) and a control group (N = 33) will be based on the number of risk factors identified in the family. Both groups will complete questionnaires at the baseline, post-test, and follow-up assessments after six and 12 months. The intervention group will receive the ChildTalks+ intervention within 2 months of the baseline assessment; the control group after the last assessment. Questionnaires will be completed by parents and children aged 12+ and, in two cases, 15+ years. Quantitative data will be supplemented with qualitative data from ChildTalks+ therapists working with patients with eating disorders. DISCUSSION: The ChildTalks+ intervention is expected to strengthen parenting competencies and family protective factors, improve family communication, increase awareness of parental mental health issues, and improve the wellbeing of children of parents with mental illness with long-term sustainable outcomes. The study should contribute to the evidence base for the ChildTalks+ program and help identify key themes in the implementation of similar preventive interventions. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05554458. Registered 26 September 2022. Retrospectively registered.

Long-term effect of transcranial direct current stimulation in the treatment of chronic tinnitus: A randomized, placebo-controlled trial.

Introduction: Tinnitus is an intrusive and chronic illness affecting a significant portion of the population, decreasing affected individuals' quality of life and socioeconomic functioning. Transcranial Direct Current Stimulation (tDCS) is a non-invasive neuromodulatory method utilizing weak electrical currents to elicit short and long-term central nervous system changes. Several studies have proven its effect on tinnitus. We aimed to broaden the knowledge and provide data on the effect and its retention. Methods: In the randomized, double-blinded, sham-controlled trial, 39 patients (active n = 19, sham n = 20) underwent bifrontal tDCS (anode over right dorsolateral prefrontal cortex (DLPFC), cathode left DLPFC, current of 1.5 mA, 20 min, 6 sessions in 2 weeks). Tinnitus Functional Index (TFI), Iowa Tinnitus Handicap Questionnaire (ITHQ), Beck Anxiety Inventory (BAI), Zung Self-Rating Depression Scale (SDS), and WHO-Quality of Life-BREF were employed in 4 evaluation points, including the follow-ups of 6 weeks and 6 months. Results: We reached a delayed, significant long-term improvement (p < 0.05) in auditory difficulties associated with tinnitus and noticed it even after 6 months compared to placebo. We also reached a short-term, negative effect in the psychological domain of WHO-Quality of Life-BREF (p < 0.05). Not all subdomains of TFI and ITHQ reached statistical significance during the data analysis, even though specific positive trends were noticed. Conclusion: We proved partial, positive, long-term effects of tDCS on tinnitus and short-term, negative, transient effect on a specific aspect of the general quality of life. We expanded upon the results of previous trials and provided data concerning the longevity and the precise effect of multiple sessions, bifrontal DLPFC tDCS. Our sample size (n = 39) was limited, which might have contributed to the lesser statistical power of the analyzed items. Clinical trial registration: [www.ClinicalTrials.gov], identifier [NCT05437185].

Thermal quantitative sensory testing as a screening tool for cardiac autonomic neuropathy in patients with diabetes mellitus.

INTRODUCTION: Electrophysiological diagnosis of cardiac autonomic neuropathy (CAN) is based on the evaluation of cardiovascular autonomic reflex tests (CARTs). CARTs are relatively time consuming and must be performed under standardized conditions. This study aimed to determine whether thermal quantitative sensory testing (TQST) can be used as a screening tool to identify patients with diabetes at a higher risk of CAN. METHODS: Eighty-five patients with diabetes and 49 healthy controls were included in the study. Neurological examination, CARTs, TQST, biochemical analyses, and neuropathy symptom questionnaires were performed. RESULTS: CAN was diagnosed in 46 patients with diabetes (54%). CAN-positive patients with diabetes had significantly higher warm detection thresholds (WDT) and significantly lower cold detection thresholds (CDT) in all tested regions (thenar, tibia, and the dorsum of the foot). CDT on the dorsum < 21.8°C in combination with CDT on the tibia < 23.15°C showed the best diagnostic ability in CAN prediction, with 97.4 % specificity, 60.9% sensitivity, 96.6% positive predictive value, and 67.3% negative predictive value. CONCLUSION: TQST can be used as a screening tool for CAN before CART.

Pregnancy-induced brain magnetic resonance imaging changes in women with multiple sclerosis.

BACKGROUND AND PURPOSE: The effect of pregnancy on brain changes and radiological disease activity in women with multiple sclerosis (MS) is not well understood. This study was undertaken to describe the dynamics of lesion activity and brain volume changes during the pregnancy and postpartum periods. METHODS: This observational study of 62 women with relapsing-remitting MS included magnetic resonance imaging (221 scans) as well as clinical visits at baseline (<24 and >6 months before pregnancy), prepregnancy (<6 months before pregnancy), postpartum (<3 months after delivery), and follow-up (>12 and <24 months after delivery) periods. RESULTS: The majority of women had a mild disability and a short disease duration (median = 5.5 years). Eighteen (29.0%) women had a relapse during the year preceding pregnancy onset, nine (14.5%) during pregnancy, and 20 (32.3%) in the year following delivery. Disability status remained unchanged during follow-up. Women in the postpartum period (n = 62) had higher T2 lesion volume (median = 1.18 ml vs. 0.94 ml), greater annualized T2 lesion volume increase (0.23 ml vs. 0.0 ml), lower brain parenchymal fraction (85.6% vs. 86.4%), and greater annualized brain volume loss (-1.74% vs. -0.16%) compared with the prepregnancy period (all p < 0.001). At 12-24 months after delivery, women (n = 41) had higher T2 lesion volume (1.16 ml vs. 1.0 ml) and lower brain parenchymal fraction (86.0% vs. 86.5%) compared to the prepregnancy period (both p < 0.001). CONCLUSIONS: The postpartum period was associated with an increase in T2 lesion volume and accelerated brain volume loss in a considerable proportion of women. This should be considered in treatment decision-making and designing clinical trials.

Severely disabled multiple sclerosis patients can achieve the performance of healthy subjects after expiratory muscle strength training.

BACKGROUND: The efficacy of expiratory muscle strength training (EMST) in patients with multiple sclerosis (MS) is controversial. The current study's primary objective was to test the effects of a progressive and intensive 12 week home based EMST program on expiratory muscle strength and voluntary cough strength. The secondary objective was to determine the retention of EMST benefits. METHODS: Thirty-five severely disabled MS patients (relapsing-remitting MS, n = 15; primary progressive MS, n = 5; secondary progressive MS, n = 15) with Expanded Disability Status Scale (EDSS) 5.0 - 7.0 were included in the study. Within 36 weeks, patients completed 12 weeks of a non-training period, 12 weeks of EMST and 12 weeks of a detraining period. Maximal expiratory pressure (PEmax) and voluntary peak cough flow (vPCF) were assessed 4 times: at week 0 (baseline), week 12 (pre-training), week 24 (post-training), and week 36 (post-detraining). MS patients included in the study were compared to age- and sex-matched healthy subjects. In the healthy controls, the PEmax and vPCF were assessed once to obtain normative data. RESULTS: Twenty-six patients completed the training period (mean age 52.7 ± 10.2, EDSS 5.9 ± 0.6) and were compared to 26 sex- and age-matched healthy subjects (mean age 53.5 ± 5.8). Patients with MS had a lower PEmax (p = 0.002) and vPCF (p = 0.022) at baseline than the healthy control group. In training period, the PEmax and vPCF increased (p = 0.0000; effect size: d = 0.94 and p = 0.0036; d = 0.57 respectively) in comparison with the non-training period (p = 0.0692; d = -0.36 and p = 0.5810; d = 0.11 respectively). Following the 12 weeks detraining period, the PEmax and vPCF declined but remained 16.7% and 5.5% respectively above the pre-training values. No differences were observed in the PEmax and vPCF between the MS group at the post-training and post-detraining timepoint and the healthy control group normative values. CONCLUSIONS: EMST improves expiratory muscle strength and voluntary cough strength in severely disabled MS patients.

Evaluation of a Clinical Index as a Predictive Tool for Primary Ciliary Dyskinesia.

BACKGROUND: In primary ciliary dyskinesia (PCD) there is no single diagnostic test. Different predictive tools have been proposed to guide referral of high-risk patients for further diagnostic workup. We aimed to test clinical index (CI) on a large unselected cohort and compare its characteristics with other widely used tools-PICADAR and NA-CDCF. METHODS: CI, PICADAR, and NA-CDCF scores were calculated in 1401 patients with suspected PCD referred to our center. Their predictive characteristics were analyzed using receiver operating characteristics (ROC) curves and compared to each other. Nasal nitric oxide (nNO) was measured in 569 patients older than 3 years. RESULTS: PCD was diagnosed in 67 (4.8%) patients. CI, PICADAR, and NA-CDCF scores were higher in PCD than in nonPCD group (all p < 0.001). The area under the ROC curve (AUC) for CI was larger than for NA-CDCF (p = 0.005); AUCPICADAR and AUCNA-CDCF did not differ (p = 0.093). An overlap in signs and symptoms among tools was identified. PICADAR could not be assessed in 86 (6.1%) patients without chronic wet cough. For CI laterality or congenital heart defects assessment was not necessary. nNO further improved predictive power of all three tools. CONCLUSION: CI is a feasible predictive tool for PCD that may outperform PICADAR and NA-CFCD.

Microarray and qPCR Analysis of Mitochondrial Metabolism Activation during Prenatal and Early Postnatal Development in Rats and Humans with Emphasis on CoQ10 Biosynthesis.

At the end of the mammalian intra-uterine foetal development, a rapid switch from glycolytic to oxidative metabolism must proceed. Using microarray techniques, qPCR, enzyme activities and coenzyme Q content measurements, we describe perinatal mitochondrial metabolism acceleration in rat liver and skeletal muscle during the perinatal period and correlate the results with those in humans. Out of 1546 mitochondrial genes, we found significant changes in expression in 1119 and 827 genes in rat liver and skeletal muscle, respectively. The most remarkable expression shift occurred in the rat liver at least two days before birth. Coenzyme Q-based evaluation in both the rat model and human tissues showed the same trend: the total CoQ content is low prenatally, significantly increasing after birth in both the liver and skeletal muscle. We propose that an important regulator of rat coenzyme Q biosynthesis might be COQ8A, an atypical kinase involved in the biosynthesis of coenzyme Q. Our microarray data, a total of 16,557 RefSeq (Entrez) genes, have been deposited in NCBI's Gene Expression Omnibus and are freely available to the broad scientific community. Our microarray data could serve as a suitable background for finding key factors regulating mitochondrial metabolism and the preparation of the foetus for the transition to extra-uterine conditions.

A Real-World Study on the Use of the Alcohol Use Disorders Identification Test (AUDIT) in Men Admitted to a Psychiatric Hospital.

BACKGROUND This real-world study aimed to investigate the use of the Alcohol Use Disorders Identification Test (AUDIT) in men admitted to a psychiatric hospital. MATERIAL AND METHODS The AUDIT questionnaire (10 items) was consecutively administered for a period of 3 years to male patients admitted to a psychiatric hospital (n=636). Laboratory blood tests of biochemical parameters were measured as biomarkers of alcohol consumption. Data were evaluated using linear models with mixed effects in the case of continuous dependent variables and logistic regression models with mixed effects in the case of categorical dependent variables. RESULTS We found that 45.3% of the patients had a high risk of alcohol consumption or alcohol dependence and 54.7% had a low risk of alcohol consumption. The ICD-10 diagnoses of alcohol-related disorders (F1x), psychotic disorders (F2x), affective disorders (F3x), neurotic and psychosomatic disorders (F4x) were statistically significantly associated with total AUDIT score (P<0.001). There was a statistically significant association between the total AUDIT score and length of hospitalization (P=0.004) and the incidence of suicidal thoughts (P=0.003). Plasma concentrations of alanine aminotransferase (P=0.005), aspartate aminotransferase (P<0.001), gamma glutamyltransferase (P=0.001), total cholesterol (P=0.027) and mean corpuscular value of erythrocytes (P<0.001) were statistically significantly increased with a higher AUDIT score. CONCLUSIONS This real-world study showed that the AUDIT questionnaire evaluated the severity of disorders caused by alcohol and their impact on comorbid mental disorders. These results may be helpful in improving targeted interventions in this group of patients.

Semen analysis and treatment risk factors in long-term survivors of childhood cancer.

The objective of this study was to compare semen quality (sperm density, progressive motility and spermia) between long-term childhood cancer survivors and a control group of males. The second objective was to correlate the semen analysis of the survivors with cancer treatment and endocrine status. The semen quality of 143 survivors (median age, 23.6 years) was compared to 200 men (median age, 27.9 years) who had not been diagnosed with cancer. The cancer-related risk factors and gonadotrophin levels were compared. Overall, 65% of the survivors had abnormal semen analysis compared to 26.5% of the controls (p < 0.0001). Survivors with nonaspermia had lower sperm density than the controls (p < 0.001). Other observed correlations were not significant. Survivors who were treated with alkylating agents were more likely to have abnormal semen analysis (p < 0.008). Follicle-stimulating hormone and luteinising hormone levels were significantly elevated (p < 0.0001) in survivors with abnormal semen analysis. The semen quality parameters, except for low sperm density, did not differ in survivors with nonaspermia compared to the controls. The risk factors included treatment with alkylating agents. Elevated gonadotrophin levels correlated with abnormal semen analysis. All cancer survivors should be made aware of the possibility of suffering from cancer treatment-related infertility.

The molecular epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) in the Czech Republic.

OBJECTIVES: To gain data on the current molecular epidemiology and resistance of MRSA in the Czech Republic. METHODS: Between September 2017 and January 2018, a total of 441 single-patient MRSA isolates were collected from 11 Czech hospitals and analysed by spa typing, SCCmec typing, antibiotic susceptibility testing, detection of the PVL toxin and the arcA gene. RESULTS: Of all MRSA isolates, 81.41% (n = 359) belonged to the CC5-MRSA clone represented by the spa types t003 (n = 136), t586 (n = 92), t014 (n = 81), t002 (n = 20) and other spa types (n = 30); a majority of the CC5 isolates (n = 348, 96.94%) carried SCCmec type II. The occurrence of CC5-MRSA was more likely in older inpatients and associated with a healthcare origin (P < 0.001). The CC5-MRSA isolates were resistant to more antimicrobial drugs compared with the other MRSAs (P < 0.001). Interestingly, t586 was detected in blood samples more often than the other spa types and, contrary to other spa types belonging to CC5-MRSA, t586 was not associated with patients of advanced age. Other frequently found lineages were CC8 (n = 17), CC398 (n = 11) and CC59 (n = 10). The presence of the PVL was detected in 8.62% (n = 38) of the MRSA isolates. CONCLUSIONS: The healthcare-associated CC5-MRSA-II lineage (t003, t586, t014) was found to be predominant in the Czech Republic. t586 is a newly emerging spa type in the Czech Republic, yet reported rarely in other countries. Our observations stress the need for MRSA surveillance in the Czech Republic in order to monitor changes in MRSA epidemiology.

Fidaxomicin versus metronidazole, vancomycin and their combination for initial episode, first recurrence and severe Clostridioides difficile infection - An observational cohort study.

PURPOSE: We aimed to evaluate the efficacy of different antibiotic regimens for the treatment of Clostridioides difficile infection (CDI) with regard to the CDI episode number and disease severity. METHODS: An observation cohort study included 271 CDI patients hospitalised between 2013-2016. Univariate logistic regression was used to evaluate the association between patients' clinical outcome (sustained clinical cure or recurrence) in a 60-day follow-up and the antibiotic regimen used (oral metronidazole, oral vancomycin, combination of oral vancomycin and metronidazole, oral fidaxomicin). Subgroup analyses, based on CDI episode number and severity, were performed. RESULTS: In the overall population, fidaxomicin was superior to metronidazole, vancomycin or their combination, for a sustained clinical response and in the prevention of recurrent CDI (rCDI). In the subgroup analyses, fidaxomicin was superior to vancomycin or metronidazole for a sustained clinical response and in the prevention of rCDI in the initial episode, first recurrence and non-severe cases. In the oral treatment of severe CDI, fidaxomicin had a similar treatment outcome to vancomycin and none of the antibiotic treatments were superior in the prevention of rCDI. Fidaxomicin, vancomycin, or a combination of metronidazole and vancomycin, had similar outcomes for sustained clinical response and prevention of rCDI in patients with multiple rCDI. CONCLUSION: Fidaxomicin was superior to metronidazole or vancomycin for the treatment of the initial episode, first recurrence, and non-severe CDI.

Biopsy of lung lesions under CT control.

OBJECTIVES: With the increasing number of detected lung nodules and the need for morphological verification, the number of CT- controlled biopsies is increasing. The aim of this study was to assess the risks and benefits of these biopsies. METHODS: This is a prospective and observational study. We evaluated 101 punctures performed on a group of 90 consecutive patients in the Department of Radiology. RESULTS: In patients with a mean age of 66 years, with mostly accidentally detected lung nodules, we observed complications 38 times. The most common were minor pneumothoraxes or insignificant bleedings. In 6 patients, the complications were more serious, 5 times the pneumothoraxes required chest drainage, once massive hemoptysis was recorded. The lesions were successfully biopsied 78 times, the target was missed 23 times. The diagnosis of lung cancer (LC) was confirmed in 60 patients, 49 LCs were verified by puncture under CT control. 42% (25/60) of patients with LC were diagnosed in TNM stages I and II. 23% (14/60) of patients with LC were treated surgically. The remaining 30 patients most often suffered from lung metastazes (13/30), in 8 of them an inflammatory lung disease was diagnosed. 69 patients underwent bronchoscopy, in only 19% (13/69) it contributed to the diagnosis. In a model "screening like" group of 49 patients with only randomly detected lung deposits, we diagnosed LC in 76% (37/49). 49% (18/37) were in TNM stage I and II, 11 were treated surgically. CONCLUSIONS: CT-controlled biopsy of lung lesions is an effective and safe diagnostic method.

Older age is a protective factor for academic achievements irrespective of treatment modalities for posterior fossa brain tumours in children.

The treatment of children with posterior fossa brain tumours (PFBT) impacts their long term functional and imaging outcomes. This study aimed to evaluate academic achievement correlated with long-term sequelae after different PFBT treatment modalities. The study cohort consisted of 110 survivors (median age at diagnosis 10.1 years and median time of follow up 13.2 years) who completed hearing questionnaires, neurological assessment and MRI of the brain ≥5 years after the end of treatment. There were three treatment groups. A cisplatin group which underwent cisplatin chemotherapy, radiotherapy and surgery (medulloblastoma N = 40), a radiotherapy group which underwent radiotherapy and surgery (astrocytoma/ependymoma N = 30), and a surgery group (astrocytoma N = 40). Academic achievement was correlated to the age at diagnosis, ototoxicity, Karnofsky score (KS), and MRI findings (Fazekas Score (FS)- treatment related parenchymal changes). For a modelled age at diagnosis of five years, the cisplatin group had lower academic achievements compared to the radiotherapy (p = 0.028) and surgery (p = 0.014) groups. Academic achievements evaluated at a modelled age of 10 years at diagnosis did not significantly differ among the treatment groups. The cisplatin group exhibited a higher occurrence of ototoxicity than the radiotherapy (p<0.019) and surgery groups (p<0.001); however, there was no correlation between ototoxicity and academic achievements (p = 0.722) in older age at diagnosis. The radiotherapy group exhibited lower KS than the surgery group (p<0.001). KS significantly influenced academic achievements in all groups (p<0.000). The cisplatin group exhibited higher FS than the surgery group (p<0.001) while FS did not correlate with academic achievement (p = 0.399). Older age is a protective factor for academic achievements irrespective of a treatment modality.

The association of a reduced susceptibility to moxifloxacin in causative Clostridium (Clostridioides) difficile strain with the clinical outcome of patients.

OBJECTIVES: To investigate the relationship between Clostridium (Clostridioides) difficile strain characteristics and C. difficile infection (CDI) outcome. METHODS: Between October and December 2017, 16 hospitals collected epidemiological data according to the European Centre for Disease Prevention and Control (ECDC) surveillance protocol for CDI. C. difficile isolates were characterized by ribotyping, toxin genes detection and antibiotic susceptibility testing to metronidazole, vancomycin and moxifloxacin. RESULTS: The overall mean CDI incidence density was 4.5 [95% CI 3.6-5.3] cases per 10,000 patient-days. From the 433 CDI cases, 330 (76.2%) were healthcare-associated, 52 (12.0%) cases were community-associated or of unknown origin and 51 (11.8%) CDI cases recurrent; a complicated course of CDI was reported in 65 cases (15.0%). Eighty-eight (20.3%) of patients died and 59 of them within 30 days after the CDI diagnosis. From the 379 C. difficile isolates, the most prevalent PCR ribotypes were 001 (n = 127, 33.5%) and 176 (n = 44, 11.6%). A total of 186 (49.1%) isolates showed a reduced susceptibility to moxifloxacin (> 4 mg/L) and 96.4% of them had Thr82Ile in the GyrA. Nineteen isolates revealed reduced susceptibility to metronidazole and two isolates to vancomycin (> 2 mg/L). A fatal outcome was associated with a reduced susceptibility to moxifloxacin, the advanced age of the patients and a complicated course of CDI (p<0.05). No association between ribotype, binary toxin and a reduced susceptibility to moxifloxacin and complicated course or recurrent CDI was found. CONCLUSIONS: A reduced susceptibility to moxifloxacin, in causative C. difficile strains was associated with fatal outcome of the patients, therefore it is an important marker in surveillance of CDI.

Serum mannose-binding lectin (MBL) concentrations are reduced in non-pregnant women with previous adverse pregnancy outcomes.

Mannose-binding lectin (MBL) is an important component of the innate immunity, and it is responsible not only for opsonization of micro-organisms, but also for efferocytosis. The aim of this study was to investigate whether MBL concentrations and lectin complement pathway activity are altered in non-pregnant women with previous adverse pregnancy outcomes. Patients were divided into four groups on the basis of their history of pregnancy complications, including control patients who had uncomplicated pregnancies and term deliveries (control, n = 33), and three groups of patients with a history of pregnancy complications, including preterm labour (n = 29), recurrent miscarriage (n = 19) or unexplained intrauterine foetal death (IUFD; n = 17). All women enrolled in the study had an interval of three to six months following their previous pregnancy, and they agreed to have a blood sample taken. We found significantly higher MBL concentrations and functional activity of the lectin complement pathway in healthy controls who had previous uneventful term pregnancies (1341 ng/mL; activity 100% (IQR: 62%-100%)), compared to women with the history of IUFD (684 ng/mL, P = .008; activity 8.5% (IQR: 0%-97.8%), P = .011), recurrent miscarriage (524 ng/mL, P = .022; activity 44% (IQR: 4%-83%), P = .011) or preterm labour (799 ng/mL, P = .022; activity 62.5% (IQR: 0%-83%), P = .003). Our results suggest that inadequate function of the complement lectin pathway is associated with a higher risk of preterm labour, recurrent miscarriage and unexplained intrauterine foetal death.

Validity of six consumer-level activity monitors for measuring steps in patients with chronic heart failure.

INTRODUCTION: Although numerous activity trackers have been validated in healthy populations, validation is lacking in chronic heart failure patients who normally walk at a slower pace, making it difficult for researchers and clinicians to implement activity monitors during physical activity interventions. METHODS: Six consumer-level activity monitors were validated in a 3-day field study in patients with chronic heart failure and healthy individuals under free living conditions. Furthermore, the same devices were evaluated in a lab-based study during treadmill walking at speeds of 2.4, 3.0, 3.6, and 4.2 km·h-1. Concordance correlation coefficients (CCC) were used to evaluate the agreement between the activity monitors and the criterion, and mean absolute percentage errors (MAPE) were calculated to assess differences between each device and the criterion (MAPE <10% was considered as a threshold for validity). RESULTS: In the field study of healthy individuals, all but one of the activity monitors showed a substantial correlation (CCC ≥0.95) with the criterion device and MAPE <10%. In patients with heart failure, the correlation of only two activity monitors (Garmin vívofit 3 and Withings Go) was classified as at least moderate (CCC ≥0.90) and none of the devices had MAPE <10%. In the lab-based study at speeds 4.2 and 3.6 km·h-1, all activity monitors showed substantial to almost perfect correlations (CCC ≥0.95) with the criterion and MAPE in the range 1%-3%. However, at slower speeds of 3.0 and 2.4 km·h-1, the accuracy of all devices substantially deteriorated: their correlation with the criterion decreased below 90% and their MAPE increased to 4-8% and 10-45%, respectively. CONCLUSIONS: Even though none of the tested activity monitors fall within arbitrary thresholds for validity, most of them perform reasonably well enough to be useful tools that clinicians can use to simply motivate chronic heart failure patients to walk more.