Background
Lemierre syndrome is characterized by head/neck vein thrombosis and septic embolism usually complicating an acute oropharyngeal bacterial infection in adolescents and young adults. We ...described the course of Lemierre syndrome in the contemporary era.
Methods
In our individual‐level analysis of 712 patients (2000–2017), we included cases described as Lemierre syndrome if these criteria were met: (i) primary site of bacterial infection in the head/neck; (ii) objectively confirmed local thrombotic complications or septic embolism. The study outcomes were new or recurrent venous thromboembolism or peripheral septic lesions, major bleeding, all‐cause death and clinical sequelae.
Results
The median age was 21 (Q1–Q3: 17–33) years, and 295 (41%) were female. At diagnosis, acute thrombosis of head/neck veins was detected in 597 (84%) patients, septic embolism in 582 (82%) and both in 468 (80%). After diagnosis and during in‐hospital follow‐up, new venous thromboembolism occurred in 34 (5.2%, 95% CI 3.8–7.2%) patients, new peripheral septic lesions became evident in 76 (11.7%; 9.4–14.3%). The rate of either was lower in patients who received anticoagulation (OR: 0.59; 0.36–0.94), higher in those with initial intracranial involvement (OR: 2.35; 1.45–3.80). Major bleeding occurred in 19 patients (2.9%; 1.9–4.5%), and 26 died (4.0%; 2.7–5.8%). Clinical sequelae were reported in 65 (10.4%, 8.2–13.0%) individuals, often consisting of cranial nerve palsy (n = 24) and orthopaedic limitations (n = 19).
Conclusions
Patients with Lemierre syndrome were characterized by a substantial risk of new thromboembolic complications and death. This risk was higher in the presence of initial intracranial involvement. One‐tenth of survivors suffered major clinical sequelae.
Elevated neural plasticity during development contributes to dramatic improvements in perceptual, motor, and cognitive skills. However, malleable neural circuits are vulnerable to environmental ...influences that may disrupt behavioral maturation. While these risks are well-established prior to sexual maturity (i.e., critical periods), the degree of neural vulnerability during adolescence remains uncertain. Here, we induce transient hearing loss (HL) spanning adolescence in gerbils, and ask whether behavioral and neural maturation are disrupted. We find that adolescent HL causes a significant perceptual deficit that can be attributed to degraded auditory cortex processing, as assessed with wireless single neuron recordings and within-session population-level analyses. Finally, auditory cortex brain slices from adolescent HL animals reveal synaptic deficits that are distinct from those typically observed after critical period deprivation. Taken together, these results show that diminished adolescent sensory experience can cause long-lasting behavioral deficits that originate, in part, from a dysfunctional cortical circuit.
Autosomal recessive congenital ichthyosis (ARCI) represents a heterogeneous group of rare disorders of cornification with 3 major subtypes: harlequin ichthyosis (HI), lamellar ichthyosis (LI) and ...congenital ichthyosiform erythroderma (CIE). A 4th subtype has also been proposed: pleomorphic ichthyosis (PI), characterized by marked skin changes at birth and subsequently mild symptoms. In nationwide screenings of suspected cases of ARCI in Denmark and Sweden, we identified 132 patients (age range 0.1-86 years) classified as HI (n = 7), LI (n = 70), CIE (n = 17) and PI (n = 38). At birth, a collodion membrane or similar severe hyperkeratosis was reported in almost all patients with HI and LI, and in nearly half of patients with CIE and PI. Persistent ectropion was more common in HI (85%) and LI (57%), than in CIE (35%) and PI (5%). Anhidrosis was a frequent problem in all 4 groups (58-100%). A scoring (0-4) of ichthyosis/ery-thema past infancy showed widely different mean values in the subgroups: HI (3.2/3.1), LI (2.4/0.6), CIE (1.8/1.6), PI (1.1/0.3). Novel or recurrent mutations were found in 113 patients: TGM1 (n = 56), NIPAL4 (n = 15), ALOX12B (n = 15), ABCA12 (n = 8), ALOXE3 (n = 9), SLC27A4 (n = 5), CYP4F22 (n = 3), PNPLA1 (n = 1) and ABHD5 (n = 1). In conclusion, by performing a deep phenotyping and gene screening, ARCI can be definitely diagnosed in 85% of cases in Scandinavia, with a prevalence of 1:100,000 and > 8 different aetiologies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background
Epidermolysis bullosa simplex (EBS) is the most common type of EB, a group of rare genodermatoses. Affected individuals suffer from skin blistering and report a high disease burden. In ...some EBS subtypes, plantar keratoderma (PK) has been described.
Objectives
This study investigated the presence and correlation of PK with body mass index, pain and mobility in EBS.
Methods
Individuals (n = 157) with genetically characterized EBS were included in this retrospective cohort study, and clinical data were collected over 16 years (referral patients to the largest German EB centre). Descriptive statistics and mixed linear models were used to assess correlations.
Results
PK was found in 75.8% of patients beginning at a mean age of 4.3 years. Both focal and diffuse PK were observed, and 60% of adults with localized and severe EBS were preobese or obese, with ˜30% of patients reporting severely reduced mobility. The presence of PK, especially diffuse PK, correlated significantly with local infections, obesity, pain and requirement of a wheelchair.
Conclusion
Along with treating skin fragility and blistering, PK should be considered a potential marker of increased morbidity and may represent a target of EBS therapy development.
Background
Non‐syndromic congenital ichthyosis describes a heterogeneous group of hereditary skin disorders associated with erythroderma and scaling at birth. Although both severe and mild courses ...are known, the prediction of the natural history in clinical practice may be challenging.
Objectives
To determine clinical course and genotype‐phenotype correlations in children affected by non‐syndromic congenital ichthyosis in a case series from south‐western Germany.
Methods
We performed a retrospective observational study of 32 children affected by non‐syndromic congenital ichthyoses seen in our genodermatosis clinic between 2011 and 2020. Follow‐ups included assessment of weight and severity of skin involvement utilizing a modified Ichthyosis Area Severity Index (mIASI). mIASI was calculated as a sum comprising the previously published IASI score and an additional novel score to evaluate palmoplantar involvement. Linear regression was assessed using Pearson correlation, and statistical analysis was performed using the Wilcoxon–Mann–Whitney test.
Results
This study included 23 patients with autosomal recessive congenital ichthyosis, seven with keratinopathic ichthyosis and two with harlequin ichthyosis. Cutaneous manifestations improved in more than 70% of the children during the follow‐up. Especially in patients with mutations in ALOXE3 and ALOX12B, mIASI scores dropped significantly. The most common phenotype observed in this study was designated ′mild fine scaling ichthyosis′. Severe palmoplantar involvement occurred in patients with KRT1 and ABCA12 mutations; most patients demonstrated hyperlinearity as a sign of dryness and scaling. Weight was mainly in the normal range and negatively correlated with the severity of skin involvement.
Conclusions
Congenital ichthyosis that self‐improves and evolves with mild fine scaling ichthyosis was the most common phenotype observed in our patients. This type might be underdiagnosed if the genetic diagnosis is not performed in the first year of life. mIASI is an easy and fast instrument for scoring disease severity and adding additional points for palmoplantar involvement might be valuable.
Twenty-six families with keratinopathic ichthyoses (epidermolytic ichthyosis, superficial epidermolytic ichthyosis or congenital reticular ichthyosiform erythroderma) were studied. Epidermolytic ...ichthyosis is caused by mutations in the genes KRT1 or KRT10, mutations in the gene KRT2 lead to superficial epidermolytic ichthyosis, and congenital reticular ichthyosiform erythroderma is caused by frameshift mutations in the genes KRT10 or KRT1, which lead to the phenomenon of revertant mosaicism. In this study mutations were found in KRT1, KRT2 and KRT10, including 8 mutations that are novel pathogenic variants. We report here the first case of a patient with congenital reticular ichthyosiform erythroderma carrying a mutation in KRT10 that does not lead to an arginine-rich reading frame. Novel clinical features found in patients with congenital reticular ichthyosiform erythroderma are described, such as mental retardation, spasticity, facial dysmorphisms, symblepharon and malposition of the 4th toe.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Objective To evaluate the usefulness and accuracy of fine‐needle aspiration cytology (FNAC) in the diagnosis of parotid gland masses.
Study Design Retrospective chart review of patients undergoing ...FNAC.
Methods Between January 1990 and December 1998, 410 parotid glands were resected at the Department of Otorhinolaryngology–Head and Neck Surgery at the University of Berne, Inselpital (Berne, Switzerland). Included in the study were 228 cases with preoperative FNAC. In a retrospective study the results of FNAC were analyzed and compared with the corresponding histopathological diagnosis.
Results Histological evaluation revealed 65 malignant tumors and 163 benign lesions (150 neoplasms and 13 nonneoplastic lesions). The cytological findings were nondiagnostic in 13 (5.7%), true‐negative in 146 (64%), true‐positive in 39 (17%), false‐negative in 22 (9.8%) and false‐positive in 8 (4.5%) cases in detecting malignant tumors. Nineteen of 39 (49%) malignant tumors (true‐positive) and 123 of 146 (84%) benign lesions (true‐negative) were classified accurately. The accuracy, sensitivity, and specificity were 86%, 64%, and 95% respectively.
Conclusions Fine‐needle aspiration cytology is a valuable adjunct to preoperative assessment of parotid masses. Preoperative recognition of malignant tumors may help prepare both the surgeon and patient for an appropriate surgical procedure.
Summary
Background
Autosomal recessive congenital ichthyosis (ARCI) is a genetically heterogeneous group of rare Mendelian skin disorders characterized by cornification and differentiation defects of ...keratinocytes. Mutations in nine genes including PNPLA1 are known to cause nonsyndromic forms of ARCI. To date, only 10 distinct pathogenic mutations in PNPLA1 have been reported.
Objectives
To identify new causative PNPLA1 mutations.
Methods
We screened genetically unresolved cases, including our ARCI collection, comprising more than 700 families. Screening for mutations was performed either by direct Sanger sequencing or in combination with a multigene panel, followed by sequence and mutation analysis.
Results
Here we report on 16 novel mutations present in patients from 17 families. While all previously reported mutations and most of our novel mutations are located within the core patatin domain, we report five novel PNPLA1 mutations that are downstream of this domain. Thus, as recently described for PNPLA2, we hypothesize that a region larger than the core domain is required for full enzymatic activity of PNPLA1 in human skin barrier formation.
Conclusions
We estimate the frequency of PNPLA1 mutations among patients with ARCI to be around 3%. Most of our patients were born as collodion babies and showed a relatively mild ichthyosis phenotype. In four unrelated patients we observed a cyclic scaling course, which seems to be a potential phenotypic variation in a small percentage of patients with PNPLA1 mutations. The variability of the clinical manifestations and the lack of typical clinical features are specific for patients with PNPLA1 mutations, and emphasize the importance of DNA sequencing for differential diagnosis of ARCIs.
What's already known about this topic?
Only five reports with 10 distinct PNPLA1 mutations causing autosomal recessive congenital ichthyosis (ARCI) have been described.
Relatively little is known about the type and localization of mutations in PNPLA1 that cause ARCI.
What does this study add?
This is the first comprehensive series of PNPLA1 mutations, from 18 patients with autosomal recessive congenital ichthyosis.
The results of this study provide important conclusions about the localization of disease‐causing mutations in PNPLA1 and the resulting phenotype, including clinical variations.
What is the translational message?
Multigene panels and knowledge about causative PNPLA1 mutations will lead to progress in deciphering the function of PNPLA1.
This might facilitate diagnosis and provide a basis for novel therapeutic strategies in patients with PNPLA1 mutations.
Respond to this article
Linked Comment: Uitto et al. Br J Dermatol 2017; 177:342–343
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