AIM: To assess the feasibility, safety and efficacy of using a high-flow nasal cannula (HFNC) for stabilising very preterm infants after birth. METHODS: A prospective observational study included preterm infants born at 28 + 0 to 31 + 6 weeks' gestation between February 2021 and December 2022 at the General University Hospital in Prague. Following delayed cord clamping, HFNC was administered at a flow rate of 8 L/min through the infants' nostrils. Criteria for switching to continuous positive airway pressure (CPAP) or positive pressure ventilation (PPV) included persistent bradycardia in the first few minutes or low saturation of oxygen (SpO2) after 5 min, respectively. RESULTS: Of the 65 infants enrolled in the study, 56 (86%) were successfully stabilised exclusively using HFNC while 7 (11%) required PPV. Additionally, 52 (80%) infants achieved SpO2 > 80% at 5 min, and 54 (83%) infants were successfully treated with HFNC within the first 3 h of life. CONCLUSION: The primary use of HFNC seems to be an appropriate alternative to CPAP for the stabilisation of very premature infants after birth and subsequent transfer to the NICU. A randomised trial comparing HFNC and CPAP in the delivery room will enable to answer the questions raised in this study.
- MeSH
- Cannula * MeSH
- Humans MeSH
- Infant, Extremely Premature * MeSH
- Infant, Premature MeSH
- Infant, Newborn MeSH
- Oxygen Inhalation Therapy * instrumentation methods MeSH
- Prospective Studies MeSH
- Feasibility Studies MeSH
- Continuous Positive Airway Pressure MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Infant, Newborn MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Observational Study MeSH
Canalicular tumors of the salivary glands have recently emerged as an entity characterized by distinct morphology and recurrent HMGA2 gene rearrangement. In this study, we analyzed 40 cases intending to elucidate their features further. The monophasic or biphasic tumors exhibited a growth pattern of interconnected anastomosing trabeculae and canaliculi, accompanied by a classical pleomorphic adenoma in one-third of the cases. Invasive growth into surrounding adipose tissue was revealed in one case which was, therefore, diagnosed as epithelial-myoepithelial carcinoma. Although the tumor cells uniformly expressed HMGA2 protein in all cases, cytokeratin 7, S100 protein, and SOX10 displayed either diffuse positivity or highlighted the luminal and abluminal cell populations, respectively. Areas with morphological oncocytoid change and AR-immunopositivity of luminal cells were seen in 13/14 (93%) of tested biphasic cases. HMGA2 rearrangement was detected by RNA-sequencing in 30 cases. The most common alteration was an HMGA1::WIF1 fusion, but several novel or rare fusion partners were identified, including ARID2 , FHIT , MSRB3 and its antisense variant MSRB3-AS1 , IFNG-AS1 , and the long intergenic region LINC02389 . In addition, FISH revealed HGMA2 break-apart in the remaining 10 cases where targeted sequencing failed to detect any alteration or where RNA sequencing could not be performed. Notably, the loss of the 3'-untranslated region of HMGA2 emerges as the common denominator for the described rearrangements, possibly disrupting its negative regulation by small regulatory RNAs. Awareness of this lesion ensures appropriate diagnosis and clinical management, especially with regard to the possibility of malignant transformation described in this and previous studies.
- MeSH
- Adult MeSH
- Phenotype MeSH
- Genetic Predisposition to Disease MeSH
- Gene Rearrangement * MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Biomarkers, Tumor * genetics analysis MeSH
- Salivary Gland Neoplasms * genetics pathology chemistry MeSH
- Adenoma, Pleomorphic * genetics pathology chemistry MeSH
- HMGA2 Protein * genetics MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Intracellular trafficking involves an intricate machinery of motor complexes, including the dynein complex, to shuttle cargo for autophagolysosomal degradation. Deficiency in dynein axonemal chains, as well as cytoplasmic light and intermediate chains, have been linked with ciliary dyskinesia and skeletal dysplasia. The cytoplasmic dynein 1 heavy chain protein (DYNC1H1) serves as a core complex for retrograde trafficking in neuronal axons. Dominant pathogenic variants in DYNC1H1 have been previously implicated in peripheral neuromuscular disorders (NMD) and neurodevelopmental disorders (NDD). As heavy-chain dynein is ubiquitously expressed, the apparent selectivity of heavy chain dyneinopathy for motor neuronal phenotypes remains currently unaccounted for. Here, we aimed to evaluate the full DYNC1H1-related clinical, molecular and imaging spectrum, including multisystem features and novel phenotypes presenting throughout life. We identified 47 cases from 43 families with pathogenic heterozygous variants in DYNC1H1 (aged 0-59 years) and collected phenotypic data via a comprehensive standardized survey and clinical follow-up appointments. Most patients presented with divergent and previously unrecognized neurological and multisystem features, leading to significant delays in genetic testing and establishing the correct diagnosis. Neurological phenotypes include novel autonomic features, previously rarely described behavioral disorders, movement disorders and periventricular lesions. Sensory neuropathy was identified in nine patients (median age of onset 10.6 years), of which five were only diagnosed after the second decade of life, and three had a progressive age-dependent sensory neuropathy. Novel multisystem features included primary immunodeficiency, bilateral sensorineural hearing loss, organ anomalies and skeletal manifestations, resembling the phenotypic spectrum of other dyneinopathies. We also identified an age-dependent biphasic disease course with developmental regression in the first decade and, following a period of stability, neurodegenerative progression after the second decade of life. Of note, we observed several cases in whom neurodegeneration appeared to be prompted by intercurrent systemic infections with double-stranded DNA viruses (Herpesviridae) or single-stranded RNA viruses (Ross River fever, SARS-CoV-2). Moreover, the disease course appeared to be exacerbated by viral infections regardless of age and/or severity of neurodevelopmental disorder manifestations, indicating a role of dynein in anti-viral immunity and neuronal health. In summary, our findings expand the clinical, imaging and molecular spectrum of pathogenic DYNC1H1 variants beyond motor neuropathy disorders and suggest a life-long continuum and age-related progression due to deficient intracellular trafficking. This study will facilitate early diagnosis and improve counselling and health surveillance of affected patients.
- MeSH
- Cytoplasmic Dyneins * genetics MeSH
- Child MeSH
- Adult MeSH
- Phenotype MeSH
- Infant MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Neurodevelopmental Disorders genetics MeSH
- Infant, Newborn MeSH
- Child, Preschool MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Infant MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Infant, Newborn MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
STUDY OBJECTIVES: To assess the impact of the non-respiratory arousal burden at baseline polysomnography (PSG) on residual daytime sleepiness in positive airway pressure (PAP)-treated obstructive sleep apnea (OSA). METHODS: We included OSA patients from the European Sleep Apnea Database registry with available arousal data who had at least 2 treatment follow-up visits. The primary outcome was the Epworth Sleepiness Scale (ESS) score under PAP. The non-respiratory arousal ratio (NRAR) was defined as the ratio of non-respiratory to total arousals at baseline PSG. A linear mixed model tested the effect of NRAR tertiles on residual sleepiness. Baseline variables that differed significantly between groups were included as covariates. RESULTS: 800 patients with OSA (69.6 % male, mean age 57.1 ± 12.0 years, mean NRAR 0.22 ± 0.20) were evaluated during three follow up visits at a mean of 197.4, 499.3, and 731.6 days after PAP initiation. The interaction between time and NRAR tertile was statistically significant (F = 4.55, p = 0.001). The lowest NRAR tertile was associated with lower residual sleepiness over time compared to the highest NRAR tertile. The associations were independent of sex, comorbidities, body mass index, blood pressure, baseline apnea-hypopnea index, and baseline ESS score. CONCLUSIONS: NRAR at baseline PSG predicts residual sleepiness in PAP-treated OSA patients. The findings offer new insights into OSA phenotyping and have important implications for patient care.
- MeSH
- Arousal * physiology MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Sleep Apnea, Obstructive * therapy physiopathology complications MeSH
- Polysomnography * MeSH
- Disorders of Excessive Somnolence physiopathology MeSH
- Registries * MeSH
- Aged MeSH
- Sleepiness MeSH
- Continuous Positive Airway Pressure * MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Europe MeSH
Seizures elicited by corneal 6-Hz stimulation are widely acknowledged as a model of temporal lobe seizures. Despite the intensive research in rodents, no studies hint at this model in developing animals. We focused on seven age groups of both male and female rats. Biphasic pulses with 0.3 ms duration and current intensities from 20 to 80 mA were applied transcorneally for 3 s to calculate threshold intensities for individual age groups. Threshold stimulation intensity necessary for elicitation of clonic seizures was highly age- and sex-dependent. The highest threshold was observed in the youngest (15-day-old) group then it decreased to the age of 25 days and increased again up to adulthood. The threshold current tended to be lower in females of all age groups. The incidence of convulsive seizures increased with stimulation intensity up to postnatal day 25 in either sex. In rats of 31 days old and older convulsions occurred irregularly regardless of the stimulation current and sex. For subsequent analysis, the animals were categorized into two groups: juveniles, aged 15 to 25 days, and adolescents/adults, aged 31 days and older. Our statistical analyses revealed an increased risk of convulsions after the stimulation with higher intensities in juvenile but not adolescent/adult rats. Females tended to be more sensitive to the stimulation with lower currents than males. Seizure severity was higher in females 18- to 25-day old compared to males of the same age and the seizure duration increased with stimulation intensities in juvenile but not adolescent/adult animals. The data extend the use of the rat 6 Hz model to immature animals and may be useful as a model of pediatric temporal lobe seizures.
- MeSH
- Electric Stimulation * MeSH
- Rats MeSH
- Disease Models, Animal MeSH
- Cornea physiopathology pathology MeSH
- Age Factors MeSH
- Seizures * physiopathology etiology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Obstructive sleep apnea increases morbidity and mortality risks. The most common treatment is continuous positive airway pressure, with nasal mask usage being important, but not always optimal. While most research on treatment adherence focuses on the patient, the bed partner's involvement may be detrimental. Our study aim is to obtain a European-wide picture of the bed partner's attitude and support towards continuous positive airway pressure therapy, including effects on relationship satisfaction and intimacy. The English translation of a German bed partner questionnaire, assessing relationship satisfaction and three major components (general attitude, perceived mask looks, intimacy effects) was distributed within the European Sleep Apnea Database Network and translated in participating countries' local language. Data were collected for 2 years. In total, 10 European countries (13 sleep centres) participated with 1546 questionnaires. Overall, 91% of bed partners had a positive attitude towards continuous positive airway pressure therapy, 86% perceived mask looks not negative, 64% stated no negative intimacy effects. More specifically, 71% mentioned improved sleep quality, 68% supported nightly device usage. For 41% of bed partners, relationship satisfaction increased (no change for 47%). These results were significantly more pronounced in Eastern/Southern Europe compared with Middle Europe, especially regarding intimacy effects. However, increased continuous positive airway pressure therapy length affected attitude negatively. These results provide necessary information to improve treatment strategies by including educational couple-focused approaches. Among others, we revealed that negative intimacy effects are not considered a barrier to continuous positive airway pressure adherence. These results may inspire more research identifying regional gaps with need for treatment adjustments.
- MeSH
- Adult MeSH
- Interpersonal Relations MeSH
- Middle Aged MeSH
- Humans MeSH
- Sleep Apnea, Obstructive * therapy psychology MeSH
- Personal Satisfaction * MeSH
- Perception MeSH
- Surveys and Questionnaires MeSH
- Aged MeSH
- Sexual Partners psychology MeSH
- Continuous Positive Airway Pressure * MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Europe MeSH
Branchioma is an uncommon benign neoplasm with an adult male predominance, typically occurring in the lower neck region. Different names have been used for this entity in the past (ectopic hamartomatous thymoma, branchial anlage mixed tumor, thymic anlage tumor, biphenotypic branchioma), but currently, the term branchioma has been widely accepted. Branchioma is composed of endodermal and mesodermal lineage derivatives, in particular epithelial islands, spindle cells, and mature adipose tissue without preexistent thymic tissue or evidence of thymic differentiation. Twenty-three branchiomas were evaluated morphologically. Eighteen cases with sufficient tissue were assessed by immunohistochemistry, next-generation sequencing (NGS) using the Illumina Oncology TS500 panel, and fluorescence in situ hybridization (FISH) using an RB1 dual-color probe. All cases showed a biphasic morphology of epithelial and spindle cells with intermingled fatty tissue. Carcinoma arising in branchioma was detected in three cases. The neoplastic cells showed strong AE1/3 immunolabeling (100%), while the spindle cells expressed CD34, p63, and SMA (100%); AR was detected in 40-100% of nuclei (mean, 47%) in 14 cases. Rb1 showed nuclear loss in ≥ 95% of neoplastic cells in 16 cases (89%), while two cases revealed retained expression in 10-20% of tumor cell nuclei. NGS revealed a variable spectrum of likely pathogenic variants (n = 5) or variants of unknown clinical significance (n = 6). Loss of Rb1 was detected by FISH in two cases. Recent developments support branchioma as a true neoplasm, most likely derived from the rudimental embryological structures of endoderm and mesoderm. Frequent Rb1 loss by immunohistochemistry and heterozygous deletion by FISH is a real pitfall and potential confusion with other Rb1-deficient head and neck neoplasms (i.e., spindle cell lipoma), especially in small biopsy specimens.
- MeSH
- Branchioma * pathology MeSH
- Adult MeSH
- In Situ Hybridization, Fluorescence MeSH
- Humans MeSH
- Molecular Biology MeSH
- Thymus Neoplasms * MeSH
- Neoplasms, Glandular and Epithelial * MeSH
- Soft Tissue Neoplasms * pathology MeSH
- Retinal Neoplasms * MeSH
- Retinoblastoma * genetics pathology MeSH
- Thymoma * MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Ovarian carcinosarcoma, also referred as malignant mixed Mullerian tumour, is an uncommon, highly aggressive and malignant neoplasm which makes up 1 to 4% of all ovarian tumours. It is biphasic involving both malignant sarcomatous (mesenchymal) and carcinomatous (epithelial) cells. There are various subtypes such as serous and endometrioid. However, the mesenchymal part is sarcomatous. About 90% of cases of ovarian carcinosarcoma spread outside the ovary. The two most accepted theories of origin for carcinosarcoma of the ovary are the collision and conversion theories. A third theory is the combination theory. Prognosis remains poor even when still localised in the ovary. In the last few years, there has been no change in the survival rate. The median survival rate is lower than 2 years. Clinical features mainly include lower abdominal pain and a palpable abdominal mass. Ovarian carcinosarcoma remains poorly understood and understudied. Being a rare tumour, elaborate therapeutic consensus is not available for ovarian carcinosarcoma. The main treatment involves cytoreductive surgery and then chemotherapy. The type of chemotherapy, role of radiotherapy and novel therapies need to be further studied. The main objective of this article is to review the current literature on carcinosarcoma of the ovary.
BACKGROUND: The optimal energy protocol for direct current cardioversion of atrial fibrillation remains uncertain. The Rational vs Maximum Fixed Energy (PROTOCOLENERGY) randomized trial compared a stepwise escalating energy algorithm (RaA, 150 J, 360 J, and 360 J) with a maximum fixed energy algorithm (MfA, 3 x 360 J). METHODS: In a 1:1 randomized trial, 300 patients with atrial fibrillation received biphasic discharges via hand-held paddles in the anterolateral position. Primary endpoints were sinus rhythm at 1 minute and neurologic complications at 2 hours; secondary endpoints included sinus rhythm at 2 hours, skin changes and chest discomfort at 24 hours. RESULTS: Sinus rhythm at 1 minute was achieved in 92.7% of RaA and 94.0% of MfA patients (P = 0.643) and maintained at 2 hours in 91.3% of both groups. There were no neurologic complications. The protocols differed significantly after the first shock (72.7% in RaA vs 83.3% in MfA; P = 0.026) but equalized after subsequent maximum energy shocks. Fewer RaA patients experienced skin redness compared with MfA patients (19.3% vs 36.0%, P = 0.001), which was attributed to the lower initial 150-J shock and total energy delivered (r = 0.243, P < 0.0001). Chest discomfort at 24 hours was not different between groups (P = 0.378). In multivariate analysis, lower body mass index (P < 0.001, cutoff 29 to 34 kg/m2) was associated with cardioversion success after the initial 150-J shock. CONCLUSIONS: Both protocols showed similar high cumulative efficacy, but RaA with the initial 150-J shock proved to be beneficial in patients with body mass index less than 29 to 34 kg/m2 because of fewer skin complications. CLINICAL TRIAL REGISTRATION NO: NCT05148923.
- MeSH
- Algorithms * MeSH
- Electric Countershock * methods MeSH
- Atrial Fibrillation * therapy MeSH
- Middle Aged MeSH
- Humans MeSH
- Follow-Up Studies MeSH
- Aged MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Randomized Controlled Trial MeSH
- Comparative Study MeSH
BACKGROUND: During pulsed field ablation (PFA), electrode-tissue proximity optimizes lesion quality. A novel "single-shot" map-and-ablate spherical multielectrode PFA array catheter that is able to verify electrode-tissue contact was recently studied in a first-in-human trial of atrial fibrillation (AF). OBJECTIVE: The aim of this study was to report lesion durability data, safety, and 12-month effectiveness outcomes. METHODS: The spherical PFA catheter, an all-in-one mapping and ablation system, was used to render anatomy and to deliver biphasic pulses (ungated 1.7 kV pulses; ∼40 seconds/application). Ablation sites included pulmonary veins (PVs) and, in selected patients, posterior wall and mitral isthmus. Follow-up was invasive remapping at ∼3 months, electrocardiograms, Holter monitoring at 6 and 12 months, and symptomatic and scheduled transtelephonic monitoring. The primary and secondary efficacy end points were acute PV isolation (PVI), PVI durability, and atrial arrhythmia recurrence. RESULTS: In the 48-patient AF cohort (paroxysmal, 48%; persistent, 52%), lesion sets included PVI (n = 48; 1.2 applications/PV), posterior wall (n = 20; 3.6 applications/posterior wall), and mitral isthmus (n = 11; 2.9 applications/mitral isthmus). Lesions were acutely successful for all 187 of 187 PVs (100%), 20 of 20 posterior walls (100%), and 10 of 11 mitral isthmuses (91%). Pulse delivery time, left atrial catheter dwell time, and procedure time were 61.5 ± 32.8 seconds, 53.9 ± 26.5 minutes, and 87.8 ± 29.8 minutes, respectively. Remapping (43/48 patients [89.5%]) revealed that 158 of 169 PVs (93.5%) were durably isolated. The only complication was a drug-responsive pericarditis. The 1-year Kaplan-Meier estimates of freedom from atrial arrhythmia were 84.2% (paroxysmal AF) and 80.0% (persistent AF). CONCLUSION: The single-shot spherical array PFA catheter can safely achieve durable lesions, translating into good clinical efficacy.
- MeSH
- Time Factors MeSH
- Equipment Design MeSH
- Electrocardiography, Ambulatory methods MeSH
- Atrial Fibrillation * surgery physiopathology MeSH
- Catheter Ablation * methods instrumentation MeSH
- Middle Aged MeSH
- Humans MeSH
- Follow-Up Studies MeSH
- Heart Conduction System physiopathology MeSH
- Recurrence MeSH
- Aged MeSH
- Pulmonary Veins * surgery MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
