INTRODUCTION: The use of signal dogs for cancer detection is not yet routinely performed,but dogs and their powerful olfactory system have proven to be a unique and valuable tool for many lineages and are beginning to be incorporated into medical practice. This method has great advantages; the dog can detect a tumour in the human body already in preclinical stages, when the patient has no symptoms yet. The identification of cancer biomarkers to enable early diagnosis is a need for many types of cancer, whose prognosis is strongly dependent on the stage of the disease. However, this method also has its various pitfalls that must be taken into account. AIM: The aim of the study was to identify and highlight the factors that affect the level of detection accuracy, but also the conditions associated with olfactometric diagnosis. METHODS: The study included 48 dogs and 48 handlers, that were part of the training between 2016 and 2023.All those who started olfactometry training and remained in training for at least one year were included in the study. The dogs ranged in age from 8 months to 12 years and were of different races and sexes. After long-term observation, a qualitative analysis was performed and factors that may play a role in the early detection of the disease were listed. RESULTS: The results of the search for the different factors have been compiled into two groups, focussing on the actual handling of the patient biological sample from collection, processing, storage until transport, preparation of the sample,and detection. Focus on the actual work and behaviour of the dog and handler. CONCLUSION: There are many factors; however, it is worth addressing them because the canine sense of smell is one of the possible uses as a diagnostic method.

• Publication type
• Journal Article MeSH

Juxtaglomerular cell tumor (JxGCT) is a rare type of renal neoplasm demonstrating morphologic overlap with some mesenchymal tumors such as glomus tumor (GT) and solitary fibrous tumor (SFT). Its oncogenic drivers remain elusive, and only a few cases have been analyzed with modern molecular techniques. In prior studies, loss of chromosomes 9 and 11 appeared to be recurrent. Recently, whole-genome analysis identified alterations involving genes of MAPK-RAS pathway in a subset, but no major pathogenic alterations have been discovered in prior whole transcriptome analyses. Considering the limited understanding of the molecular features of JxGCTs, we sought to assess a collaborative series with a multiomic approach to further define the molecular characteristics of this entity. Fifteen tumors morphologically compatible with JxGCTs were evaluated using immunohistochemistry for renin, single-nucleotide polymorphism array (SNP), low-pass whole-genome sequencing, and RNA sequencing (fusion assay). In addition, methylation analysis comparing JxGCT, GT, and SFT was performed. All cases tested with renin (n=11) showed positive staining. Multiple chromosomal abnormalities were identified in all cases analyzed (n=8), with gains of chromosomes 1p, 10, 17, and 19 and losses of chromosomes 9, 11, and 21 being recurrent. A pathogenic HRAS mutation was identified in one case as part of the SNP array analysis. Thirteen tumors were analyzed by RNA sequencing, with 2 revealing in-frame gene fusions: TFG::GPR128 (interpreted as stochastic) and NAB2::STAT6 . The latter, originally diagnosed as JxGCT, was reclassified as SFT and excluded from the series. No fusions were detected in the remaining 11 cases; of note, no case harbored NOTCH fusions previously described in GT. Genomic methylation analysis showed that JxGCT, GT, and SFT form separate clusters, confirming that JxGCT represents a distinct entity (ie, different from GT). The results of our study show that JxGCTs are a distinct tumor type with a recurrent pattern of chromosomal imbalances that may play a role in oncogenesis, with MAPK-RAS pathway activation being likely a driver in a relatively small subset.

• MeSH
• Adult MeSH
• Epigenesis, Genetic MeSH
• Epigenomics MeSH
• Gene Fusion * MeSH
• Genetic Predisposition to Disease MeSH
• Genomics MeSH
• Immunohistochemistry MeSH
• Polymorphism, Single Nucleotide MeSH
• Juxtaglomerular Apparatus pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• DNA Methylation MeSH
• Biomarkers, Tumor * genetics   MeSH
• Kidney Neoplasms * genetics   pathology   chemistry   MeSH
• Whole Genome Sequencing MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

Gambling encompasses a wide variety of activities, and the structural characteristics of each form contribute to its potential risk. However, the literature does not fully agree on the risk levels of certain gambling forms. In this study, we classify less risky gambling forms (soft forms) based on public perceptions of their riskiness. We examine the link between gambling experience and problem gambling prevalence. A survey was conducted in a model region of the Czech Republic, a post-socialist country with high gambling availability, with N = 2,498 respondents. A typology of gambling forms (lotteries, betting, and casino games) was created based on perceived risk similarities. Lotteries are the most frequently played gambling form, with 86.3% reporting lifetime participation. Among those who exclusively engage in lottery-type forms, 15 percentage points more women than men participated in the last year, and the gap widens to 31 points over a lifetime. Forms of gambling perceived as more risky show a lower proportion of non-problem gamblers, both for recent and lifetime participation. Furthermore, individuals who gambled within the past month or year are at higher risk of developing gambling problems compared to those whose gambling experiences were less recent.

• MeSH
• Adult MeSH
• Gambling * psychology   classification   epidemiology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Behavior, Addictive * psychology   epidemiology   classification   MeSH
• Prevalence MeSH
• Surveys and Questionnaires MeSH
• Risk-Taking * MeSH
• Risk Factors MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH

OBJECTIVE: We comprehensively characterized a large pediatric cohort with focal cortical dysplasia (FCD) type 1 to expand the phenotypic spectrum and to identify predictors of postsurgical outcomes. METHODS: We included pediatric patients with histopathological diagnosis of isolated FCD type 1 and at least 1 year of postsurgical follow-up. We systematically reanalyzed clinical, electrophysiological, and radiological features. The results of this reanalysis served as independent variables for subsequent statistical analyses of outcome predictors. RESULTS: All children (N = 31) had drug-resistant epilepsy with varying impacts on neurodevelopment and cognition (presurgical intelligence quotient [IQ]/developmental quotient scores = 32-106). Low presurgical IQ was associated with abnormal slow background electroencephalographic (EEG) activity and disrupted sleep architecture. Scalp EEG showed predominantly multiregional and often bilateral epileptiform activity. Advanced epilepsy magnetic resonance imaging (MRI) protocols identified FCD-specific features in 74.2% of patients (23/31), 17 of whom were initially evaluated as MRI-negative. In six of eight MRI-negative cases, fluorodeoxyglucose-positron emission tomography (PET) and subtraction ictal single photon emission computed tomography coregistered to MRI helped localize the dysplastic cortex. Sixteen patients (51.6%) underwent invasive EEG. By the last follow-up (median = 5 years, interquartile range = 3.3-9 years), seizure freedom was achieved in 71% of patients (22/31), including seven of eight MRI-negative patients. Antiseizure medications were reduced in 21 patients, with complete withdrawal in six. Seizure outcome was predicted by a combination of the following descriptors: age at epilepsy onset, epilepsy duration, long-term invasive EEG, and specific MRI and PET findings. SIGNIFICANCE: This study highlights the broad phenotypic spectrum of FCD type 1, which spans far beyond the narrow descriptions of previous studies. The applied multilayered presurgical approach helped localize the epileptogenic zone in many previously nonlesional cases, resulting in improved postsurgical seizure outcomes, which are more favorable than previously reported for FCD type 1 patients.

• MeSH
• Child MeSH
• Electroencephalography * methods   MeSH
• Epilepsy MeSH
• Focal Cortical Dysplasia MeSH
• Cohort Studies MeSH
• Infant MeSH
• Humans MeSH
• Magnetic Resonance Imaging * MeSH
• Malformations of Cortical Development, Group I * surgery   complications   diagnostic imaging   MeSH
• Malformations of Cortical Development surgery   complications   diagnostic imaging   MeSH
• Adolescent MeSH
• Positron-Emission Tomography MeSH
• Child, Preschool MeSH
• Drug Resistant Epilepsy * surgery   diagnostic imaging   physiopathology   MeSH
• Treatment Outcome MeSH
• Check Tag
• Child MeSH
• Infant MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Microbiology reference laboratories perform a crucial role within public health systems. This role was especially evident during the COVID-19 pandemic. In this Viewpoint, we emphasise the importance of microbiology reference laboratories and highlight the types of digital data and expertise they provide, which benefit national and international public health. We also highlight the value of surveillance initiatives among collaborative international partners, who work together to share, analyse, and interpret data, and then disseminate their findings in a timely manner. Microbiology reference laboratories have substantial impact at regional, national, and international levels, and sustained support for these laboratories is essential for public health in both pandemic and non-pandemic times.

• MeSH
• COVID-19 * epidemiology   MeSH
• Communicable Diseases MeSH
• Laboratories * economics   MeSH
• Humans MeSH
• Microbiology MeSH
• Pandemics MeSH
• SARS-CoV-2 MeSH
• Public Health MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

PURPOSE: Missense de novo variants in CACNA1G, which encodes the Cav3.1 T-type calcium channel, have been associated with a severe, early-onset form of cerebellar disorder with neurodevelopmental deficits (SCA42ND). We explored a large series of pediatric cases carrying heterozygous variants in CACNA1G to further characterize genotype-phenotype correlations in SCA42ND. METHODS: We describe 19 patients with congenital CACNA1G-variants, including 6 new heterozygotes of the recurrent SCA42ND variants, p.(Ala961Thr) and p.(Met1531Val), and 8 unreported variants, including 7 missense variants, mainly de novo. We carried out genetic and structural analyses of all variants. Patch-clamp recordings were performed to measure their channel activity. RESULTS: We provide a consolidated clinical description for the patients carrying p.(Ala961Thr) and p.(Met1531Val). The new variants associated with the more severe phenotypes are found in the Cav3.1 channel intracellular gate. Calcium currents of these Cav3.1 variants showed slow inactivation and deactivation kinetics and an increase in window current, supporting a gain of channel activity. On the contrary, the p.(Met197Arg) variant (IS4-S5 loop) resulted in a loss of channel activity. CONCLUSION: This detailed description of several de novo missense pathogenic variants in CACNA1G, including 13 previously reported cases, supports a clinical spectrum of congenital CACNA1G syndrome beyond spinocerebellar ataxia.

• MeSH
• Child MeSH
• Phenotype * MeSH
• Genetic Association Studies MeSH
• Heterozygote MeSH
• Infant MeSH
• Humans MeSH
• Mutation, Missense * genetics   MeSH
• Adolescent MeSH
• Neurodevelopmental Disorders * genetics   pathology   MeSH
• Child, Preschool MeSH
• Calcium Channels, T-Type * genetics   metabolism   MeSH
• Check Tag
• Child MeSH
• Infant MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

BACKGROUND AND OBJECTIVES: Enhanced Recovery After Surgery (ERAS) guidelines for Radical Cystectomy (RC) were published over ten years ago. Aim of this systematic review is to update ERAS recommendations for patients undergoing RC and to give an expert opinion on the relevance of each single ERAS item. METHODS: A systematic review was performed to identify the impact of each single ERAS item on RC outcomes. Embase and Medline (through Pubmed) were searched systematically. Relevant articles were selected and graded. For each ERAS item, a level of evidence was determined. An e-Delphi consensus was then performed amongst an international panel with renowned experience in RC to provide recommendations based on expert opinion. KEY FINDINGS AND LIMITATIONS: Preoperative medical optimization and avoiding bowel preparation are highly recommended. Robotic-assisted RC with intracorporeal urinary diversion is moderately recommended and can help in applying other ERAS items, such as early mobilization. Medical thromboprophylaxis should be administered and nasogastric tube should be removed at the end of surgery. Perioperative fluid restriction as well as opioid-sparing anesthesia protocols should be implemented. Generally, consensus was reached on most ERAS items, with the exception of epidural anesthesia (no consensus), resection site drainage (consensus against), and type of urinary drainage. Limitations include the lack of a multidisciplinary approach to the present consensus, giving however a highly specialized surgical opinion on ERAS. CONCLUSIONS: and clinical implications: The current study updates ERAS recommendations for patients undergoing RC and suggests application of ERAS by a panel of experts in the field.

• MeSH
• Early Ambulation MeSH
• Surgeons MeSH
• Cystectomy * methods   MeSH
• Urinary Diversion methods   MeSH
• Humans MeSH
• Urinary Bladder Neoplasms surgery   MeSH
• Robotic Surgical Procedures MeSH
• Practice Guidelines as Topic MeSH
• Enhanced Recovery After Surgery * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Systematic Review MeSH

PURPOSE: The study sought to understand the experiences of working age adults with myeloma and their partner/family members, living in Czechia, Germany, and Poland. METHODS: Qualitative interviews were conducted with 36 working age adults living with myeloma, and three family members. Data were collected from May to October 2022. Thematic analysis was applied to the data. RESULTS: Healthcare and state support within each country are described. The degree of work engagement was informed by patients' symptom burden, treatment needs, state financial aid, and family/financial obligations. Many did not conceptualise their status as involving 'return to work' as they had continued to be engaged with their jobs throughout. For some, remote working enabled them to manage treatments/side-effects and their job, while avoiding infection. In some cases, patients did not tell their employer or colleagues about their illness, for fear of discrimination. CONCLUSION: While experiences varied between countries, common across accounts was a struggle to balance ongoing treatments with employment, at a time when participants were expected to finance their own households and maintain their income and roles. Implications for Cancer Survivors To improve quality of life, clinical discussions around treatment decision-making should take into account patients' attitudes/approach to work, type of work engaged in, and other activities considered important to them. European Union and national cancer plans should set out optimum standards for employers, to ensure an equitable benchmark for how employees are supported. Such approaches would improve legal protections and better enforcement of employer policies to accommodate patients' limitations in the workplace.

• MeSH
• Adult MeSH
• Quality of Life * MeSH
• Qualitative Research MeSH
• Middle Aged MeSH
• Humans MeSH
• Multiple Myeloma * psychology   therapy   epidemiology   mortality   MeSH
• Cancer Survivors * psychology   statistics & numerical data   MeSH
• Interviews as Topic MeSH
• Employment * statistics & numerical data   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH
• Germany MeSH
• Poland MeSH

BACKGROUND: Charcot-Marie-Tooth is the most common inherited neuromuscular disorder. Rarely, it can be associated with heart failure and various arrhythmic disturbances. This case illustrates the challenges of making decisions to prevent sudden cardiac death in a patient with Charcot-Marie-Tooth disease. CASE SUMMARY: A 69-year-old male with a history of Type 1A Charcot-Marie-Tooth disease was admitted due to repetitive runs of ventricular tachycardia. Twelve-lead electrocardiogram, echocardiography, selective coronary angiography, and cardiac magnetic resonance did not clarify the cause of the electrical storm. As conservative therapy was not successful, radiofrequency ablation was chosen to treat the electrical storm. After this procedure, implantable cardioverter defibrillator (ICD) was implanted. The follow-up revealed severe perforation by the ventricular lead. An extraction was performed with no complications and a new lead was immediately implanted. The patient remains asymptomatic. Three episodes of non-sustained ventricular tachycardia were recorded during the last follow-up. DISCUSSION: This case illustrates the challenges of making decisions to prevent sudden cardiac death in a patient with Charcot-Marie-Tooth disease after successful ablation for electrical storm. Due to a lack of evidence, atypical origin of arrhythmia, and clinical presentation, we did not consider this as idiopathic arrhythmia and decided to implant an ICD, which was complicated by severe perforation by the lead. Specific recommendations for preventing sudden cardiac death in rare cardiac conditions, such as Charcot-Marie-Tooth disease, still need to be refined.

• Publication type
• Journal Article MeSH
• Case Reports MeSH

BACKGROUND: Widespread use of pneumococcal conjugate vaccines (PCVs) has reduced vaccine-type invasive pneumococcal disease (IPD). We describe the serotype distribution of IPD after extensive use of ten-valent PCV (PCV10; Synflorix, GSK) and 13-valent PCV (PCV13; Prevenar 13, Pfizer) globally. METHODS: IPD data were obtained from surveillance sites participating in the WHO-commissioned Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project that exclusively used PCV10 or PCV13 (hereafter PCV10 and PCV13 sites, respectively) in their national immunisation programmes and had primary series uptake of at least 70%. Serotype distribution was estimated for IPD cases occurring 5 years or more after PCV10 or PCV13 introduction (ie, the mature period when the serotype distribution had stabilised) using multinomial Dirichlet regression, stratified by PCV product and age group (<5 years, 5-17 years, 18-49 years, and ≥50 years). FINDINGS: The analysis included cases occurring primarily between 2015 and 2018 from 42 PCV13 sites (63 362 cases) and 12 PCV10 sites (6806 cases) in 41 countries. Sites were mostly high income (36 [67%] of 54) and used three-dose or four-dose booster schedules (44 [81%]). At PCV10 sites, PCV10 serotypes caused 10·0% (95% CI 6·3-12·9) of IPD cases in children younger than 5 years and 15·5% (13·4-19·3) of cases in adults aged 50 years or older, while PCV13 serotypes caused 52·1% (49·2-65·4) and 45·6% (40·0-50·0), respectively. At PCV13 sites, PCV13 serotypes caused 26·4% (21·3-30·0) of IPD cases in children younger than 5 years and 29·5% (27·5-33·0) of cases in adults aged 50 years or older. The leading serotype at PCV10 sites was 19A in children younger than 5 years (30·6% [95% CI 18·2-43·1]) and adults aged 50 years or older (14·8% [11·9-17·8]). Serotype 3 was a top-ranked serotype, causing about 9% of cases in children younger than 5 years and 14% in adults aged 50 years or older at both PCV10 and PCV13 sites. Across all age and PCV10 or PCV13 strata, the proportion of IPD targeted by higher-valency PCVs beyond PCV13 was 4·1-9·7% for PCV15, 13·5-36·0% for PCV20, 29·9-53·8% for PCV21, 15·6-42·0% for PCV24, and 31·5-50·1% for PCV25. All top-ten ranked non-PCV13 serotypes are included in at least one higher-valency PCV. INTERPRETATION: The proportion of IPD due to serotypes included in PCVs in use was low in mature PCV10 and PCV13 settings. Serotype distribution differed between PCV10 and PCV13 sites and age groups. Higher-valency PCVs target most remaining IPD and are expected to extend impact. FUNDING: Bill & Melinda Gates Foundation as part of the WHO Pneumococcal Vaccines Technical Coordination Project.

• MeSH
• Global Health MeSH
• Child MeSH
• Adult MeSH
• Infant MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Immunization Programs MeSH
• Pneumococcal Infections * prevention & control   epidemiology   microbiology   MeSH
• Pneumococcal Vaccines * administration & dosage   MeSH
• Child, Preschool MeSH
• Aged MeSH
• Serogroup * MeSH
• Streptococcus pneumoniae * classification   immunology   MeSH
• Vaccines, Conjugate administration & dosage   MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Infant MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Child, Preschool MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH