BACKGROUND: Hereditary angio-oedema (HAE) is manifested by repeated episodes of localised subcutaneous or sub-mucosal oedema. Symptoms are extremely variable in frequency, localisation, and severity. Atypical or mild clinical symptoms of the disease may lead to erroneous diagnosis, causing diagnostic delay. The goal of this study was to assess how diagnostic delay has changed over 33 years at a single referral centre. METHODS: We analysed diagnostic delay and first symptoms of HAE in patients who were diagnosed at an immunology department between 1980 and 2013. Patient's records were analysed. RESULTS: The median diagnostic delay in 77 HAE type 1 and 2 patients was seven (range, 0-42) years. The difference observed in diagnostic delay between probands (18 [0-42] years) and others (1 [0-37] year) was significant (p<0.001). Our data show a significant negative correlation between the length of diagnostic delay and the year of diagnosis in our group of patients (p=0.024). The median age of first symptoms among all HAE patients (N=64) was 17 (1-40) years. The first symptoms of HAE in 64 patients were analysed. Twenty-six patients had abdominal, seventeen peripheral, five facial, two urogenital, and three had laryngeal oedema as the first manifestation of the disease. The last death that was attributed to HAE was in 1977. CONCLUSIONS: Our observations demonstrate improved awareness of HAE among physicians, as documented by the significant decrease in diagnostic delay. It is believed that earlier treatment will improve patient quality of life and life expectancy.

• Klíčová slova
• Diagnostic delay, First symptoms, Hereditary angio-oedema,
• MeSH
• dítě MeSH
• dospělí MeSH
• hereditární angioedémy diagnóza   genetika   mortalita   MeSH
• inhibiční protein komplementu C1 MeSH
• kojenec MeSH
• komplement C1 - inaktivátory analýza   genetika   MeSH
• kvalita života MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nefelometrie a turbidimetrie MeSH
• opožděná diagnóza statistika a číselné údaje   MeSH
• předškolní dítě MeSH
• retrospektivní studie MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• inhibiční protein komplementu C1 MeSH
• komplement C1 - inaktivátory MeSH
• SERPING1 protein, human MeSH Prohlížeč

BACKGROUND: Early diagnosis and treatment of patients with multiple sclerosis (MS) are associated with better outcomes; however, diagnostic delays remain a major problem. OBJECTIVE: Describe the prevalence, determinants and consequences of delayed diagnoses. METHODS: This single-centre ambispective study analysed 146 adult relapsing-remitting MS patients (2016-2021) for frequency and determinants of diagnostic delays and their associations with clinical, cognitive, imaging and biochemical measures. RESULTS: Diagnostic delays were identified in 77 patients (52.7%), including 42 (28.7%) physician-dependent cases and 35 (24.0%) patient-dependent cases. Diagnosis was delayed in 22 (15.1%) patients because of misdiagnosis by a neurologist. A longer diagnostic delay was associated with trends towards greater Expanded Disability Status Scale (EDSS) scores (B = 0.03; p = 0.034) and greater z-score of the blood neurofilament light chain (B = 0.35; p = 0.031) at the time of diagnosis. Compared with patients diagnosed at their first clinical relapse, patients with a history of >1 relapse at diagnosis (n = 63; 43.2%) had a trend towards greater EDSS scores (B = 0.06; p = 0.006) and number of total (B = 0.13; p = 0.040) and periventricular (B = 0.06; p = 0.039) brain lesions. CONCLUSION: Diagnostic delays in MS are common, often determined by early misdiagnosis and associated with greater disease burden.

• Klíčová slova
• Delayed diagnosis, brain lesion, cerebrospinal fluid, disability, magnetic resonance imaging, misdiagnosis, multiple sclerosis, neurofilament,
• MeSH
• dospělí MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mozek patologie   MeSH
• opožděná diagnóza MeSH
• prevalence MeSH
• recidiva MeSH
• relabující-remitující roztroušená skleróza * diagnóza   epidemiologie   patologie   MeSH
• roztroušená skleróza * diagnóza   epidemiologie   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: The classical clinical manifestation of untreated immunoglobulin deficiency comprises predominantly recurrent and complicated respiratory tract infections. Before the 1980s, little was known about the clinical manifestation of immunodeficiency in the general medical population, and also the availability of serum immunoglobulin laboratory determination was not sufficient, leading to a significant diagnostic delay. METHODS: We have analysed the diagnostic delay and referral diagnoses in patients in whom any form of primary hypogammaglobulinaemia had been diagnosed at our department, which was established in 1981. RESULTS: Comparing the diagnostic delay in the 1980s (19 patients, median 5.5 years), the 1990s (37 patients, median 3.5 years) and the years 2001-2008 (33 patients, median 1 year), a significant decrease was observed (p < 0.05, Spearman's correlation coefficient). Also, the median number of pneumonia episodes during the diagnostic delay decreased from 5 in the 1980s, to 1 in the 1990s and to 0 in the period of 2001-2008 (p < 0.05, Spearman's correlation coefficient). While in the 1980s 17 of the 19 patients had pneumonia in their past history, in the period of 2001-2008 only 13 of the 33 patients were concerned. CONCLUSIONS: Our observation documents improved awareness of immunodeficiencies among physicians. It is supposed that earlier diagnosis will prevent complications, improve the quality of life and even survival of hypogammaglobulinaemic patients.

• MeSH
• agamaglobulinemie komplikace   diagnóza   epidemiologie   MeSH
• běžná variabilní imunodeficience komplikace   diagnóza   epidemiologie   MeSH
• časové faktory MeSH
• chybná diagnóza statistika a číselné údaje   MeSH
• konziliární vyšetření a konzultace statistika a číselné údaje   MeSH
• lidé MeSH
• pneumonie diagnóza   epidemiologie   etiologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH

PURPOSE: Narcolepsy type-1 (NT1) is a rare chronic neurological sleep disorder with excessive daytime sleepiness (EDS) as usual first and cataplexy as pathognomonic symptom. Shortening the NT1 diagnostic delay is the key to reduce disease burden and related low quality of life. Here we investigated the changes of diagnostic delay over the diagnostic years (1990-2018) and the factors associated with the delay in Europe. PATIENTS AND METHODS: We analyzed 580 NT1 patients (male: 325, female: 255) from 12 European countries using the European Narcolepsy Network database. We combined machine learning and linear mixed-effect regression to identify factors associated with the delay. RESULTS: The mean age at EDS onset and diagnosis of our patients was 20.9±11.8 (mean ± standard deviation) and 30.5±14.9 years old, respectively. Their mean and median diagnostic delay was 9.7±11.5 and 5.3 (interquartile range: 1.7-13.2 years) years, respectively. We did not find significant differences in the diagnostic delay over years in either the whole dataset or in individual countries, although the delay showed significant differences in various countries. The number of patients with short (≤2-year) and long (≥13-year) diagnostic delay equally increased over decades, suggesting that subgroups of NT1 patients with variable disease progression may co-exist. Younger age at cataplexy onset, longer interval between EDS and cataplexy onsets, lower cataplexy frequency, shorter duration of irresistible daytime sleep, lower daytime REM sleep propensity, and being female are associated with longer diagnostic delay. CONCLUSION: Our findings contrast the results of previous studies reporting shorter delay over time which is confounded by calendar year, because they characterized the changes in diagnostic delay over the symptom onset year. Our study indicates that new strategies such as increasing media attention/awareness and developing new biomarkers are needed to better detect EDS, cataplexy, and changes of nocturnal sleep in narcolepsy, in order to shorten the diagnostic interval.

• Klíčová slova
• cataplexy, diagnostic delay, machine learning, misdiagnosis, symptom onset,
• Publikační typ
• časopisecké články MeSH

This study aimed to define the differences in growth characteristics in the three most frequent causes of growth retardation - growth hormone deficiency, hypothyreosis and constitutional delay of growth and development - in order to provide diagnostic means for distinguishing these disorders. The study included 166 children with growth disorders aged 4-18 years. The height for age, the bone age using the TW3 method, the predicted height as the target height and the current prediction using the TW3 method were studied. For bone age, the radius, ulna and short bones compartment (RUS) and carpal bones (CARP) were evaluated separately and the difference in their delay in relation to chronological age (ΔBA_RUS_CARP) was determined. The relationship of the studied variables with sex and the underlying diagnosis was tested and the relationship of hypothyreosis and growth data was estimated. The model was tested on the growth data of 104 randomly selected patients with a growth disorder. The largest significant distinction was demonstrated by the difference ΔBA_RUS_CARP in hypothyreosis. The created linear regression model was highly statistically significant (χ2 = 19.4, p < 0.0001) and showed high selectivity (0.609, 95% CI 0.409; 0.808) as well as high specificity (0.864, 95% CI 0.781; 0.946). The clinical validity of the model demonstrated a 61% predictive value for the detection and an 81% successful specification of hypothyreosis. The study demonstrated the possibility of distinguishing suspected hypothyreosis from other causes of growth retardation based on differences in severity of the ossification delay in skeletal compartments of the hand.

• Klíčová slova
• Bone age, Constitutional delay of growth and development, Diagnostic model, Growth hormone deficiency, Short stature,
• MeSH
• biologické modely MeSH
• diferenciální diagnóza MeSH
• dítě MeSH
• hypotyreóza diagnóza   patologie   MeSH
• kosti zápěstní patologie   MeSH
• lidé MeSH
• lidský růstový hormon nedostatek   MeSH
• lineární modely MeSH
• mladiství MeSH
• poruchy růstu diagnóza   patologie   MeSH
• předškolní dítě MeSH
• radius patologie   MeSH
• tělesná výška MeSH
• ulna patologie   MeSH
• určení kostního věku MeSH
• vývoj kostí MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• lidský růstový hormon MeSH

BACKGROUND: Melanoma is a malignant skin disease. The tumor development is caused by an uncontrollable proliferation of melanocytes. The most common occurrence is on the skin, but melanoma may also develop on the mucous membrane, meninges, and eyes. Some melanomas develop from melanocytic nevus. Acral lentiginous melanoma occurs on palms, feet, fingers and under nails, and is the most common type of melanoma for phototype VI. The most important factor for successful treatment of malignant melanoma is an early detection, excision of the primary tumor and histological staging. Surgical treatment of an early-stage melanoma is a key to successful therapy; however, many patients (mostly men) do not seek medical attention before it istoo late. CASE REPORT: This case study presents a 59-year-old patient, who suffers from white coat syndrome and whose finger was amputated for alleged gangrene. Subsequently, brownish black nodules appeared across his arm. Histological examination proved metastases of malignant melanoma. It was only at this phase, when the patient admitted a nevus at the tip of his amputated finger, from which ulceration and gangrene gradually emerged. CONCLUSION: This case demonstrates a combination of multiple unfavorable factors, which led to delayed diagnosis and therapy.

• MeSH
• chybná diagnóza * MeSH
• gangréna etiologie   MeSH
• lentigo maligna kůže diagnóza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory kůže diagnóza   MeSH
• opožděná diagnóza škodlivé účinky   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• kazuistiky MeSH

This narrative review summarizes and discusses the implications of the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 and the upcoming International Classification of Diseases (ICD)-11 classification systems on the prevalence of bipolar disorder and on the validity of the DSM-5 diagnosis of bipolar disorder according to the Robin and Guze criteria of diagnostic validity. Here we review and discuss current data on the prevalence of bipolar disorder diagnosed according to DSM-5 versus DSM-IV, and data on characteristics of bipolar disorder in the two diagnostic systems in relation to extended Robin and Guze criteria: 1) clinical presentation, 2) associations with para-clinical data such as brain imaging and blood-based biomarkers, 3) delimitation from other disorders, 4) associations with family history / genetics, 5) prognosis and long-term follow-up, and 6) treatment effects. The review highlights that few studies have investigated consequences for the prevalence of the diagnosis of bipolar disorder and for the validity of the diagnosis. Findings from these studies suggest a substantial decrease in the point prevalence of a diagnosis of bipolar with DSM-5 compared with DSM-IV, ranging from 30-50%, but a smaller decrease in the prevalence during lifetime, corresponding to a 6% reduction. It is concluded that it is likely that the use of DSM-5 and ICD-11 will result in diagnostic delay and delayed early intervention in bipolar disorder. Finally, we recommend areas for future research.

• Klíčová slova
• Bipolar disorder;DSM-5;ICD-11;Validity of diagnosis;Diagnostic delay;Delayed early intervention,
• MeSH
• bipolární porucha * diagnóza   epidemiologie   MeSH
• Diagnostický a statistický manuál mentálních poruch MeSH
• lidé MeSH
• mezinárodní klasifikace nemocí MeSH
• opožděná diagnóza MeSH
• prevalence MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Minimal residual disease (MRD) at the end of induction therapy is important for risk stratification of acute lymphoblastic leukaemia (ALL), but bone marrow (BM) aspiration is often postponed or must be repeated to fulfil qualitative and quantitative criteria for morphological assessment of haematological remission and/or MRD analysis. The impact of BM aspiration delay on measured MRD levels and resulting risk stratification is currently unknown. We analysed paired MRD data of 289 paediatric ALL patients requiring a repeat BM aspiration. MRD levels differed in 108 patients (37%) with a decrease in the majority (85/108). This would have resulted in different risk group allocation in 64 of 289 patients (23%) when applying the ALL-Berlin-Frankfurt-Münster 2000 criteria. MRD change was associated with the duration of delay; 40% of patients with delay ≥7 days had a shift to lower MRD levels compared to only 18% after a shorter delay. Patients MRD-positive at the original but MRD-negative at the repeat BM aspiration (n = 50) had a worse 5-year event-free survival than those already negative at first aspiration (n = 115) (86 ± 5% vs. 94 ± 2%; P = 0·024). We conclude that BM aspirations should be pursued as scheduled in the protocol because delayed MRD sampling at end of induction may result in false-low MRD load and distort MRD-based risk assessment.

• Klíčová slova
• Paediatric acute lymphoblastic leukaemia, bone marrow aspiration delay, minimal residual disease, risk stratification, treatment outcome,
• MeSH
• akutní lymfatická leukemie diagnóza   patologie   MeSH
• časové faktory MeSH
• chybná diagnóza prevence a kontrola   MeSH
• dítě MeSH
• hodnocení rizik MeSH
• indukce remise MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• opožděná diagnóza MeSH
• předškolní dítě MeSH
• reziduální nádor diagnóza   patologie   MeSH
• tenkojehlová biopsie MeSH
• vyšetřování kostní dřeně metody   MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The primary aim of the research was to find the delay between the first symptoms of an autistic disorder being recognized by parents and diagnosis in our centre. A secondary objective was to evaluate the number of contacts with professionals (physicians, teachers, and speech therapists) in which parents pointed out special manifestations seen in children and, in spite of that, the children were not referred to a specialist. A retrospective study assessed 204 children (59 girls, 145 boys) in total; 126 children (39 girls, 87 boys) with childhood autism (CHA), 57 (17 girls, 40 boys) with atypical autism (AA), and 21 (3 girls, 18 boys) with Asperger's syndrome (AS). The mean age at appearance of the first signs was 29.7 months (range 0-70, median 30+/-17.0) in N=201, and the average age at diagnosis was 81.5 months (range 13-276, median 69.5+/-45.2) in N=204. The mean delay in making a diagnosis was 51.3 months (range 0-246, median 39+/-40.9) in N=201. The delay in diagnosis is shortest in patients with AA (a mean period of 44.4 months = 3 years and 8 months), longer in CHA patients (49.5 months = 4 years and 2 months), and longest in patients with AS (80.8 months = 6 years and 9 months). A statistically significant difference in the period to diagnosis was found between CHA and AS patients (p=0.023) and between AA and AS patients (p=0.019). The mean number of visits to physicians and other specialists before referring to a specialized centre for diagnosis in N=133 was 2.4 (range 1-5, median 2+/-0.9). The diagnosis of autism is made late and early educational and behavioural interventions cannot be initiated.

• MeSH
• autistická porucha klasifikace   diagnóza   MeSH
• časná diagnóza MeSH
• časové faktory MeSH
• chybná diagnóza statistika a číselné údaje   MeSH
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• konziliární vyšetření a konzultace statistika a číselné údaje   MeSH
• kvalita zdravotní péče * MeSH
• lidé MeSH
• mladiství MeSH
• předškolní dítě MeSH
• raná péče normy   MeSH
• rodiče MeSH
• sexuální faktory MeSH
• věkové faktory MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive deterioration of upper and lower motor neurons. A definitive diagnostic test or biomarker for ALS is currently unavailable, leading to a diagnostic delay following the onset of initial symptoms. Our study focused on cerebrospinal fluid (CSF) concentrations of clusterin, tau protein, phosphorylated tau protein, and beta-amyloid1-42 in ALS patients and a control group. METHODS: Our study involved 54 ALS patients and 58 control subjects. Among the ALS patients, 14 presented with bulbar-onset ALS, and 40 with limb-onset ALS. We quantified biomarker levels using enzyme-linked immunosorbent assay (ELISA) and compared the results using the Mann-Whitney U-test. RESULTS: Significant elevations in neurodegenerative markers, including tau protein (p < 0.0001), phosphorylated tau protein (p < 0.0001), and clusterin (p = 0.038), were observed in ALS patients compared to controls. Elevated levels of tau protein and phosphorylated tau protein were also noted in both bulbar and limb-onset ALS patients. However, no significant difference was observed for beta-amyloid1-42. ROC analysis identified tau protein (AUC = 0.767) and p-tau protein (AUC = 0.719) as statistically significant predictors for ALS. CONCLUSION: Our study demonstrates that neurodegenerative marker levels indicate an ongoing neurodegenerative process in ALS. Nonetheless, the progression of ALS cannot be predicted solely based on these markers. The discovery of a specific biomarker could potentially complement existing diagnostic criteria for ALS.

• Klíčová slova
• Amyotrophic lateral sclerosis, Biomarkers, Cerebrospinal fluid,
• MeSH
• amyotrofická laterální skleróza * diagnóza   MeSH
• biologické markery MeSH
• klusterin MeSH
• lidé MeSH
• opožděná diagnóza MeSH
• proteiny tau MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery MeSH
• klusterin MeSH
• proteiny tau MeSH