Difference In Clinical Severity Research Articles

Independent COL17A1 Variants in Cats with Junctional Epidermolysis Bullosa.

Epidermolysis bullosa (EB), characterized by defective adhesion of the epidermis to the dermis, is a heterogeneous disease with many subtypes in human patients and domestic animals. We investigated two unrelated cats with recurring erosions and ulcers on ear pinnae, oral mucosa, and paw pads that were suggestive of EB. Histopathology confirmed the diagnosis of EB in both cats. Case 1 was severe and had to be euthanized at 5 months of age. Case 2 had a milder course and was alive at 11 years of age at the time of writing. Whole genome sequencing of both affected cats revealed independent homozygous variants in COL17A1 encoding the collagen type XVII alpha 1 chain. Loss of function variants in COL17A1 lead to junctional epidermolysis bullosa (JEB) in human patients. The identified splice site variant in case 1, c.3019+1del, was predicted to lead to a complete deficiency in collagen type XVII. Case 2 had a splice region variant, c.769+5G>A. Assessment of the functional impact of this variant on the transcript level demonstrated partial aberrant splicing with residual expression of wildtype transcript. Thus, the molecular analyses provided a plausible explanation of the difference in clinical severity between the two cases and allowed the refinement of the diagnosis in the affected cats to JEB. This study highlights the complexity of EB in animals and contributes to a better understanding of the genotype-phenotype correlation in COL17A1-related JEB.

Coexistence of Multiple Myositis-Specific Antibodies in Patients with Idiopathic Inflammatory Myopathies

The mutual exclusivity of myositis-specific antibodies (MSAs) has been reported before, but the coexistence of 2 or more MSAs was still found in a few case reports. This study aims to confirm the existence and prevalence of double MSAs in patients with idiopathic inflammatory myopathy (IIM) and to clarify the clinical features of these patients. One hundred fifty-one patients with IIM diagnosed from 1 July 2018 to 31 July 2022, at National Cheng Kung University Hospital, Taiwan, were enrolled and divided into two groups, patients with ≤1 MSA (n = 128, 84.8%) and those with ≥2 MSAs (n = 23, 15.2%) according to the initial serology results. After being re-examined by ANA-IIF assay, 8 out of 23 patients were confirmed to have ≥2 MSAs. The demographic data and clinical features were presented. The prevalence of double-positive MSAs among IIM was 5.3% in this cohort. The coexistence of two MSAs in an IIM patient does exist but is rare. Patients with two MSAs belonging to two distinct IIM subtypes presented clinical features skewed to one subtype instead of "mixed phenotypes". No apparent difference in clinical severity was found between patients with ≥2 MSAs and ≤1 MSA. Longer follow-ups and more studies are required to characterize the patients of IIM with ≥2 MSAs.

Childhood Multisystem Inflammatory Syndrome With Prominent Neurological Involvement

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen that causes coronavirus disease 2019 (COVID-19), which was declared a pandemic on March 11, 2020, by the World Health Organization.1 The difference in clinical severity between adults and children may be due to the differences in renin-angiotensin system receptors and altered inflammatory pathogen responses.2

Hand, foot and mouth disease in southern Vietnam during 2015–2018

Background: Hand, foot and mouth disease (HFMD) continues to challenge Asia with pandemic potential. In Vietnam, there have been two major outbreaks occurring during 2011–2012 (>200,000 hospitalizations and >200 deaths) and more recently in 2018 (>130,000 hospitalizations and 17 deaths). Given the high burden and the complex epidemic dynamics of HFMD, synthesizing its clinical and epidemiological data remains essential to inform the development of appropriate interventions and design public health measures. Methods and materials: Methodology/principal findings: We report the results of a hospital-based study conducted during 2015–2018, covering the severe HFMD outbreak recently documented in Vietnam in 2018. The study was conducted at three major hospitals responsible for receiving HFMD patients from southern Vietnam with a population of over 40 million. A total of 19 enterovirus serotypes were detected in 1196 HFMD patients enrolled in the clinical study during 2015–2018, with enterovirus A71 (EV-A71), coxsackievirus A6 (CV-A6), CV-A10 and CV-A16 being the major causes. Despite the emergence of coxsackieviruses, EV-A71 remains the leading cause of severe HFMD in Vietnam. EV-A71 was consistently detected at a higher frequency during the second half of the years. Results: The emergence of EV-A71 subgenogroup C4 in late 2018 was preceded by its low activity during 2017–early 2018. Compared with EV-A71 subgenogroup B5, C4 was more likely to be associated with severe HFMD, representing the first report demonstrating the difference in clinical severity between subgenogroup C4 and B5, the two predominant EV-A71 subgenogroups causing HFMD worldwide. Conclusion: Conclusion/significance: Our data have provided significant insights into important aspects of HFMD over six years (2013–2018) in Vietnam, and emphasize active surveillance for pathogen circulation remains essential to inform the local public health authorities in the development of appropriate intervention strategies to reduce the burden of this emerging infections. Multivalent vaccines are urgently needed to control HFMD.

Clinical impact of respiratory virus in pulmonary exacerbations of children with Cystic Fibrosis

Cystic Fibrosis (CF) is a genetic, multisystemic, progressive illness that causes chronic suppurative lung disease. A major cause of morbimortality in this condition are pulmonary exacerbations. Although classically attributed to bacterial infections, respiratory virus have been increasingly recognized in its ethiopathogeny. Nasopharyngeal swab samples were collected from children < 18 years old with CF in Rio de Janeiro, Brazil, with pulmonary exacerbation criteria. Samples were submitted to RT-PCR for Adenovirus, Influenza A and B, Parainfluenza Virus, Respiratory Syncytial Virus (RSV), Metapneumovirus and Rhinovirus. Virus positive and virus negative groups were compared in regards to clinical presentation, severity of exacerbation and bacterial colonization. Out of 70 samples collected from 48 patients, 35.7% were positive for respiratory viruses. Rhinovirus were the most common (28% of all positive samples), followed by RSV. The virus positive group was associated with change in sinus discharge (p = 0.03). Considering only patients younger than five years old, positive virus detection was also associated with fever (p = 0.01). There was no significant difference in clinical severity or in bacterial colonization between virus positive and negative groups. Prospective studies are still needed to assess the long term impact of viral infections in patients with CF, and their interaction with the bacterial microbiome in these patients.

Clinical, etiological and epidemiological investigations of hand, foot and mouth disease in southern Vietnam during 2015 - 2018.

Hand, foot and mouth disease (HFMD) continues to challenge Asia with pandemic potential. In Vietnam, there have been two major outbreaks occurring during 2011–2012 (>200,000 hospitalizations and >200 deaths) and more recently in 2018 (>130,000 hospitalizations and 17 deaths). Given the high burden and the complex epidemic dynamics of HFMD, synthesizing its clinical and epidemiological data remains essential to inform the development of appropriate interventions and design public health measures. We report the results of a hospital-based study conducted during 2015–2018, covering the severe HFMD outbreak recently documented in Vietnam in 2018. The study was conducted at three major hospitals responsible for receiving HFMD patients from southern Vietnam with a population of over 40 million. A total of 19 enterovirus serotypes were detected in 1196 HFMD patients enrolled in the clinical study during 2015–2018, with enterovirus A71 (EV-A71), coxsackievirus A6 (CV-A6), CV-A10 and CV-A16 being the major causes. Despite the emergence of coxsackieviruses, EV-A71 remains the leading cause of severe HFMD in Vietnam. EV-A71 was consistently detected at a higher frequency during the second half of the years. The emergence of EV-A71 subgenogroup C4 in late 2018 was preceded by its low activity during 2017–early 2018. Compared with EV-A71 subgenogroup B5, C4 was more likely to be associated with severe HFMD, representing the first report demonstrating the difference in clinical severity between subgenogroup C4 and B5, the two predominant EV-A71 subgenogroups causing HFMD worldwide. Our data have provided significant insights into important aspects of HFMD over four years (2015–2018) in Vietnam, and emphasize active surveillance for pathogen circulation remains essential to inform the local public health authorities in the development of appropriate intervention strategies to reduce the burden of this emerging infections. Multivalent vaccines are urgently needed to control HFMD.

Macrolide-Resistant Mycoplasma pneumoniae Infections in Pediatric Community-Acquired Pneumonia.

A high prevalence rate of macrolide-resistant Mycoplasma pneumoniae (MRMP) has been reported in Asia. We performed a systematic review and meta-analysis to investigate the effect of macrolide resistance on the manifestations and clinical judgment during M. pneumoniae infections. We found no difference in clinical severity between MRMP and macrolide-sensitive Mycoplasma pneumoniae (MSMP) infections. However, in the pooled data, patients infected with MRMP had a longer febrile period (1.71 days), length of hospital stay (1.61 day), antibiotic drug courses (2.93 days), and defervescence time after macrolide treatment (2.04 days) compared with patients infected with MSMP. The risk of fever lasting for >48 hours after macrolide treatment was also significantly increased (OR 21.24), and an increased proportion of patients was changed to second-line treatment (OR 4.42). Our findings indicate diagnostic and therapeutic challenges after the emergence of MRMP. More precise diagnostic tools and clearly defined treatment should be appraised in the future.

Clinical characteristics and outcomes of methamphetamine-associated versus non-methamphetamine intracerebral hemorrhage

Methamphetamine use has emerged as a risk factor for intracerebral hemorrhage (ICH). We aim to investigate the clinical characteristics and outcomes of methamphetamine-associated ICH (Meth-ICH) versus Non-Meth-ICH. Patients with ICH between January 2011 and December 2017 were studied. Meth-ICH and Non-Meth-ICH were defined by history of abuse and urine drug screen (UDS). The clinical features of the 2 groups were explored. Among the 677 consecutive patients, 61 (9.0%) were identified as Meth-ICH and 350 as Non-Meth ICH. Meth-ICH was more common in Hispanics (14.6%) and Whites (10.1%) as compared to Asians (1.2%). Patients with Meth-ICH were more often younger (51.2 vs. 62.2 years, p < 0.001), male (77.0% vs. 61.4.0%, p < 0.05), and smokers (44.3% vs. 13.4%, p < 0.001). Non-Meth-ICH was more likely to have history of hypertension (72.61% v. 59%, p < 0.05) or antithrombotic use (10.9% vs. 1.6%, p < 0.05). There was no significant difference in clinical severity, hospital length of stay (LOS), rate of functional independence (29.5% vs. 25.7%, p = 0.534), or mortality (18.0% vs. 24.6%, p = 0.267) between the 2 groups. Methamphetamine use was not an independent predictor of poor outcome. Despite difference in demographics, Meth-ICH is similar to Non-Meth ICH in hospital course and outcome.

The effect of RAS blockers on the clinical characteristics of COVID-19 patients with hypertension.

BackgroundCoronavirus disease 2019 (COVID-19), caused by a novel coronavirus (designated as SARS-CoV-2) has become a pandemic worldwide. Based on the current reports, hypertension may be associated with increased risk of sever condition in hospitalized COVID-19 patients. Angiotensin-converting enzyme 2 (ACE2) was recently identified to functional receptor of SARS-CoV-2. Previous experimental data revealed ACE2 level was increased following treatment with ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). Currently doctors concern whether these commonly used renin-angiotensin system (RAS) blockers-ACEIs/ARBs may increase the severity of COVID-19.MethodsWe extracted data regarding 50 hospitalized hypertension patients with laboratory confirmed COVID-19 in the Renmin Hospital of Wuhan University from Feb 7 to Mar 03, 2020. These patients were grouped into RAS blockers group (Group A, n=20) and non-RAS blockers group (Group B, n=30) according to the basic blood pressure medications. All patients continued to use pre-admission antihypertensive drugs. Clinical severity (symptoms, laboratory and chest CT findings, etc.), clinical course, and short time outcome were analyzed after hospital admission.ResultsTen (50%) and seventeen (56.7%) of the Group A and Group B participants were males (P=0.643), and the average age was 52.65±13.12 and 67.77±12.84 years (P=0.000), respectively. The blood pressure of both groups was under effective control. There was no significant difference in clinical severity, clinical course and in-hospital mortality between Group A and Group B. Serum cardiac troponin I (cTnI) (P=0.03), and N-terminal (NT)-pro hormone BNP (NT-proBNP) (P=0.04) showed significant lower level in Group A than in Group B. But the patients with more than 0.04ng/mL or elevated NT-proBNP level had no statistical significance between the two groups. In patients over 65 years or under 65 years, cTnI or NT-proBNP level showed no difference between the two groups.ConclusionsWe observed there was no obvious difference in clinical characteristics between RAS blockers and non-RAS blockers groups. These data suggest ACEIs/ARBs may have few effects on increasing the clinical severe conditions of COVID-19.

Influenza B associated paediatric acute respiratory infection hospitalization in central vietnam.

BackgroundInfluenza B is one of the major etiologies for acute respiratory infections (ARI) among children worldwide; however, its clinical‐epidemiological information is limited. We aimed to investigate the hospitalization incidence and clinical‐epidemiological characteristics of influenza B‐associated paediatric ARIs in central Vietnam.MethodsWe collected clinical‐epidemiological information and nasopharyngeal swabs from ARI children hospitalized at Khanh Hoa General Hospital, Nha Trang, Vietnam from February 2007 through June 2013. Nasopharyngeal samples were screened for 13 respiratory viruses using Multiplex‐PCRs. Influenza B‐confirmed cases were genotyped by Haemagglutinin gene sequencing. We analyzed the clinical‐epidemiological characteristics of influenza B Lineages (Victoria/Yamagata) and WHO Groups.ResultsIn the pre‐A/H1N1pdm09 period, influenza B‐associated ARI hospitalization incidence among children under five was low, ranging between 14.7 and 80.7 per 100 000 population. The incidence increased to between 51.4 and 330 in the post‐A/H1N1pdm09. Influenza B ARI cases were slightly older with milder symptoms. Both Victoria and Yamagata lineages were detected before the A/H1N1pdm09 outbreak; however, Victoria lineage became predominant in 2010‐2013 (84% Victoria vs 16% Yamagata). Victoria and Yamagata lineages did not differ in demographic and clinical characteristics. In Victoria lineage, Group1 ARI cases were clinically more severe compared to Group5, presenting a greater proportion of wheeze, tachypnea, and lower respiratory tract infection.ConclusionsThe current results highlight the increased incidence of influenza B‐related ARI hospitalization among children in central Vietnam in the post‐A/H1N1pdm09 era. Furthermore, the difference in clinical severity between Victoria lineage Group1 and 5 implies the importance of influenza B genetic variation on clinical presentation.

Clinical and virological analysis of epidemic keratoconjunctivitis caused by adenovirus type 54 in a regional ophthalmic clinic in Kyushu, Japan.

BackgroundHuman adenovirus type 54 (HAdV-54) is a novel type of adenovirus that belongs to species D and has thus far been detected only in Japan in patients with epidemic keratoconjunctivitis (EKC). There was a large nationwide outbreak of HAdV-54 EKC from 2015 to 2016 in Japan. The clinical characteristics of an outbreak of HAdV-54 conjunctivitis treated in a regional ophthalmic clinic in Fukuoka, Japan, in 2016 were analyzed.Patients and methodsA consecutive series of 55 cases diagnosed clinically as EKC confirmed by HAdV-54 detection from conjunctival scrapings by polymerase chain reaction (PCR) method between 17 June 2016 and 29 August 2016 were enrolled. Viral DNA copies were counted by real-time PCR method. The clinical findings were recorded at the first visit to the clinic and evaluated.ResultsIn the analysis of the relationship between mean clinical score groups and several factors, such as days after onset, sex, HAdV DNA number on a logarithmic scale, and age, most factors did not show a significant difference in clinical score between groups. However, mean clinical score of cases aged <23 years was significantly higher than that of cases aged ≥23 years (P<0.01). The correlation coefficient between DNA copies on a logarithmic scale and clinical score was 0.280, and a significant correlation was observed (P<0.05). Multiple subepithelial corneal infiltrates (MSI) were observed in 24 out of 31 cases (77%).ConclusionThese results suggested that the clinical features in the early phase of HAdV-54 keratoconjunctivitis were milder but the rate of MSI observed in the late phase was higher than those in previous epidemics of several HAdV types. The significant difference in clinical severity between age groups might be a virological characteristic of HAdV-54.

Blood pressure differences between patients with lacunar and nonlacunar infarcts.

BackgroundElevated blood pressure is frequently seen in acute stroke, and patients with lacunar and nonlacunar infarcts may have different underlying mechanisms for increase in blood pressure. The impact of hypertension as a risk factor may also vary. The aims of the present study were to investigate blood pressure in patients presenting with lacunar syndromes but with different anatomical subtypes of stroke, to explore the impact of subtype on blood pressure, and to identify stroke-related factors associated with hypertension.MethodsConsecutive patients presenting with an acute lacunar syndrome were enrolled. Patients were classified into a lacunar or nonlacunar group based on radiological verified infarcts. Blood pressure was measured. Between-group differences were analyzed by χ2-test, t-test, and Mann–Whitney U test, as appropriate. We performed linear regression to analyze the association between blood pressure and lacunar infarct, and multiple linear regression to adjust for other covariates.ResultsOne hundred thirteen patients were included. Seventy five percent had lacunar and 25% nonlacunar infarcts. There was no significant difference in clinical severity between the two groups. In the linear regression model, we found a significant association between blood pressure and lacunar infarct. No other factor was significantly associated with blood pressure in the two groups.ConclusionsLacunar infarcts may be independently associated with higher blood pressure compared to nonlacunar infarcts with the same clinical severity. Blood pressure differences between different subtypes of stroke may not be related to clinical severity but to the underlying cause of stroke.

Significantly Higher Cytokine and Chemokine Levels in Patients with Japanese Spotted Fever than in Those with Tsutsugamushi Disease

Tetracyclines are administered to cure Japanese spotted fever (JSF) and tsutsugamushi disease (TD). It is generally said that the clinical course of JSF is worse than that of TD despite antibiotic treatment. The precise mechanism underlying the more severe clinical course of JSF is not fully understood. We therefore examined whether the differential cytokine profile between these two infectious diseases contributes to the difference in clinical severity. The serum concentrations of various cytokines (tumor necrosis factor alpha [TNF-α], interleukin-6 [IL-6], and gamma interferon [IFN-γ]) and chemokines (IL-8, interferon-inducible protein 10 [IP-10], monocyte chemoattractant protein 1 [MCP-1], macrophage inflammatory protein 1α [MIP-1α], MIP-1β, and eotaxin) were measured in 32 TD and 21 JSF patients. The results showed that serum levels of TNF-α in the acute phases of TD and JSF were significantly increased, with a higher concentration of TNF-α in patients with JSF (mean, 39.9 pg/ml) than in those with TD (mean, 13.8 pg/ml). Comparatively higher levels of other cytokines and chemokines (IL-6, IFN-γ, IL-8, IP-10, MCP-1, MIP-1α, and MIP-1β) were also observed in the acute phase of JSF. The clinical severity score (3.67 ± 1.71) of JSF patients was higher than that of TD patients (1.47 ± 0.77). Our findings revealed that the cytokine and chemokine levels in the acute phase of JSF were significantly higher than those in the acute phase of TD. The differential cytokine levels may be related to the difference in clinical severity between JSF and TD.

Prevalence of human rhinovirus in children admitted to hospital with acute lower respiratory tract infections in Changsha, China

Human rhinovirus (HRV) is a causative agent of acute respiratory tract infections. This study analyzed the prevalence and clinical characteristics of three HRV groups (HRV‐A, ‐B, and ‐C) among 1,165 children aged 14 years or younger who were hospitalized with acute lower respiratory tract infection in China. PCR or reverse transcription‐PCR was performed to detect 14 respiratory viruses in nasopharyngeal aspirates collected from September 2007 to August 2008 in Changsha, China. HRV was detected in 202 (17.3%) of the 1,165 children; 25.3% of the HRV‐positive children were 13–36 months of age (χ2 = 22.803, P = 0.000). HRV was detected year round and peaked between September and December. Fifty‐three percent of the HRV‐positive samples were also positive for other respiratory viruses; respiratory syncytial virus (RSV) was the most common secondary virus. Phylogenetic analysis using the VP4/VP2 region grouped the HRV‐positive strains as follows: 101 HRV‐A (50.0%), 21 HRV‐B (10.4%), and 80 HRV‐C (39.6%). HRV‐A infections occurred predominantly in spring and autumn, and the peak prevalence of HRV‐C was in early winter and late autumn. HRV‐B infections were less common in spring (χ2 = 31.914, P = 0.000). No significant difference in clinical severity or presentation was found between patients with HRV single infection and HRV co‐detections. Furthermore, the clinical characterizations did not differ among the three HRV species. These results suggest that HRV‐C is an important viral agent along with HRV‐A and HRV‐B and that among hospitalized children with acute lower respiratory tract infection in China, the three HRV genotypes have similar clinical characteristics. J. Med. Virol. 86:1983–1989, 2014. © 2014 Wiley Periodicals, Inc.

Differing Epidemiological Dynamics of Influenza B Virus Lineages in Guangzhou, Southern China, 2009-2010

The epidemiological and evolutionary dynamics of the two cocirculating lineages of influenza B virus, Victoria and Yamagata, are poorly understood, especially in tropical or subtropical areas of Southeast Asia. We performed a phylogenetic analysis of the hemagglutinin (HA) and neuraminidase (NA) sequences of influenza B viruses isolated in Guangzhou, a southern Chinese city, during 2009 to 2010 and compared the demographic and clinical features of infected patients. We identified multiple viral introductions of Victoria strains from both Chinese and international sources, which formed two phylogenetically and antigenically distinct clades (Victoria 1 and 2), some of which persisted between seasons. We identified one dominant Yamagata introduction from outside China during 2009. Our phylogenetic analysis reveals the occurrence of reassortment events among the Victoria and Yamagata lineages and also within the Victoria lineage. We found no significant difference in clinical severity by influenza B lineage, with the exceptions that (i) the Yamagata lineage infected older people than either Victoria lineage and (ii) fewer upper respiratory tract infections were caused by the Victoria 2 than the Victoria 1 clade. Overall, our study reveals the complex epidemiological dynamics of different influenza B lineages within a single geographic locality and has implications for vaccination policy in southern China.

Anti-KCNQ1 K+ channel autoantibodies increase IKs current and are associated with QT interval shortening in dilated cardiomyopathy

Autoimmune-associated proarrhythmia in dilated cardiomyopathy (DCM) is poorly understood. Given the significance of KCNQ1 potassium channels in heart rhythm disorders, we hypothesized that circulating anti-KCNQ1 autoantibodies directly modulate cardiac electrophysiology in DCM patients. The purpose of this pilot study was to characterize ion channel autoantibodies in DCM targeting the cardiac repolarizing K(+) current, IKs, and the underlying KCNQ1 potassium channel. One hundred and fifty DCM patients were screened for anti-KCNQ1 autoantibodies using an enzyme-linked immunosorbent assay. Autoantibodies targeting the extracellular pore domain of the KCNQ1 channel were detected in 6% of study patients. Seropositive individuals exhibited significantly shorter corrected QT intervals when compared with seronegative patients (371 ± 39.9 ms vs. 408 ± 47.9 ms; P = 0.036). There was no difference in clinical severity of heart failure between groups. The functional significance of anti-KCNQ1 antibodies was determined in human embryonic kidney 293 cells expressing KCNQ1/KCNE1 using the whole-cell patch clamp technique. IKs recordings demonstrated a 2.7-fold increase in mean current density on exposure to patients' sera containing anti-KCNQ1 antibodies in contrast to seronegative controls (8.74 ± 1.44 pA/pF vs. 3.26 ± 0.36 pA/pF; P = 0.003). IKs enhancement was not associated with increased KCNQ1 protein levels or altered cell surface expression of the channel. Anti-KCNQ1 autoantibodies found in a subgroup of DCM patients are associated with QT interval shortening and increased IKs current.

Mosaic 18q21.2 deletions including the TCF4 gene: A clinical report

Pitt-Hopkins syndrome (PTHS) is characterized by distinctive facial dysmorphism, profound intellectual disability, and the possible occurrence of epilepsy and breathing anomalies. It is caused by haploinsufficiency of the TCF4 gene. No significant difference in clinical severity has been reported to date between PTHS patients carrying 18q21 deletions including the TCF4 gene, and those harboring TCF4 point mutations, suggesting a lack of genotype/phenotype correlation. Moreover, the size of 18q21 deletions including the TCF4 gene does not appear to have a significant effect on the phenotypic severity, suggesting that TCF4 haploinsufficiency is the most important prognostic factor in 18q deletions. We describe two unrelated patients presenting with clinical features reminiscent of PTHS and carrying mosaic interstitial 18q21 deletions characterized by array comparative genomic hybridization. One of the patients presented the lowest level of mosaic 18q21 deletion reported to date (5-10%). Our report and a review of the literature show that the mosaic status does not appear to have a significant effect on the clinical severity of 18q21 deletions, which are associated with a poor neurological outcome, whereas a mosaic TCF4 point mutation can result in a significantly milder phenotype. Malformations of internal organs are currently considered to be rare in PTHS. The patients described here had visceral anomalies, suggesting that a full morphological assessment, including heart and abdominal ultrasound scans, should be performed systematically in PTHS patients.

C.P.1 Central core disease with a novel RYR1 mutation in a Korean family

Central core disease (CCD) is a form of myopathy inherited autosomal dominantly. It is caused by mutations in RYR1 and allelic to malignant hyperthermia. The diagnosis is established by characteristic muscle pathology and the identification of mutation. Here we report clinical and pathological features of a Korean family with CCD carrying a novel RYR1 mutation. A 15-year-old boy presented with slowly progressive weakness of bilateral legs since school age. The boy could not run and had difficulty in climbing stairs. His muscle weakness slowly progressed and he now has difficulty in rising up from a chair. His mother and sister had markedly milder proximal leg weakness. Diffuse muscle atrophy was noted especially in lower extremities. Muscle power examination disclosed predominantly proximal leg weakness. Serum creatine kinase was within normal limits, and needle electromyography showed active myopathic pattern. Muscle biopsy revealed multiple peripheral and central cores in muscle fibers devoid of oxidative enzyme activities. All the muscle fibers were of type 1. Sequence analysis of RYR1 disclosed a novel mutation in exon 101 (c.14590T>C[p.Tyr4864His]). None of the affected members showed facial muscle weakness or skeletal deformities, although it is said to be frequently accompanied in CCD. Marked difference in clinical severity is noted between proband and his mother; this kind of intrafamilial phenotypic variability had previously been reported in CCD. It has been known that mutations at C-terminal of RYR1 are associated with severe clinical phenotype and clearly demarcated central cores, while mutations outside the C-terminal show milder clinical phenotype and atypical cores in their muscle fiber. Interestingly, the mutation identified in this family is at C-terminal region, all the affected members showed mild phenotype of later-onset and atypical cores inexplicitly ovoid with indistinct borders in the subsarcolemmal areas.

Influence of systemic antibiotics on the treatment of dogs with generalized demodicosis

Canine generalized demodicosis (CGD) is a skin disease with distinct breed predispositions. Secondary bacterial infections are common. Dogs typically receive miticidal therapy in combination with antibacterial treatment. Whether antibiotics influence the duration of acaricidal therapy is unknown at the moment. There is also debate over how common short-tailed Demodex mites occur in demodicosis. This study evaluated the influence of systemic antibiotics on the course of CGD, the occurrence of short-tailed Demodex mites in demodectic dogs and the influence of furunculosis on treatment outcome. Breed predispositions for CGD in Moscow were identified. Fifty-eight dogs were randomly distributed in two groups. Both were treated with ivermectin 600mcg/kg q24h orally and benzoyl peroxide shampoo weekly. The dogs in one group (AB) were additionally treated with systemic antibiotics for at least 1 month, dogs in the other group (NAB) were not. Monthly examinations, skin scrapings and impression smears were performed. Prior to the study there was no difference in clinical severity, presence of pyoderma and mite numbers between groups. There was no significant difference in duration until first negative skin scrapings and resolution of bacterial infection. In dogs with furunculosis the number of the mites was significantly higher than in dogs without furunculosis but the duration until microscopic remission albeit longer, was not significantly different. Short-tailed Demodex mites were found in 25% of the cases. Pugs and English Bulldogs were predisposed. Based on these results, systemic antibiotics may not impact as much as previously thought on the actual success of CGD treatment.

Nonthymoma early-onset- and late-onset-generalized myasthenia gravis—A retrospective hospital-based study

Objective Acquired myasthenia gravis (MG) is predominantly due to nicotinic acetylcholine receptor (AChR) autoantibodies (Ab). Differences between nonthymoma early-onset and late-onset MG were reported. We studied the clinical and serological characteristics of nonthymoma AChR Ab-positive-generalized MG patients. Patients and methods Chinese AChR Ab-positive-generalized MG patients who had generalized disease for 3 years or longer were studied. Results Among 41 such patients, 25 (61%) were female. The mean onset age was 43.5 years (range 9–78 years) and the mean follow-up duration was 7.8 years (range 3–20 years). Sixteen (39%) patients had late-onset disease (onset age ≥50 years). Compared to early-onset patients (onset age <50 years), late-onset patients were characterized by male predominance ( p = 0.002), absence of thymic lymphofollicular hyperplasia ( p = 0.036), and a higher striated muscle Ab seropositivity rate (94% versus 4%, p < 0.001). Although there was no statistically significant difference in clinical severity and outcome or response to treatment between late-onset and early-onset patients, 50% and 75% of late-onset patients had moderate or severe disease at onset and worst status, respectively, compared to 28% and 52% for early-onset patients at onset and worst status, respectively. Also 63% of late-onset patients had disease progressed within first 3 years compared to only 40% of early-onset patients did. Conclusion Nonthymoma late-onset-generalized MG patients were common among Hong Kong Chinese, with a statistically non-significant trend that it was clinically more severe than early-onset MG but with similar clinical outcome or response to treatment; >90% of these patients were seropositive for striated muscle Ab.