Minor Abnormalities Research Articles

Neurological soft signs and cognitive performance in early childhood.

Neurological soft signs (NSSs), minor neurological abnormalities, have been implicated as risk factors for poor cognitive performance in small-scale studies. Here we investigate the associations between NSSs and multiple domains of cognitive performance in a large, population-based cohort and evaluate sex differences in these associations. We analyzed data from 35,710 seven-year-old children in the Collaborative Perinatal Project to study the association between the number of NSSs and cognitive test scores using multiple linear regression models adjusting for risk factors for brain injury and aberrant neurodevelopment. NSSs were associated with lower scores on all domains of cognitive performance. Each additional soft sign was associated with lower full-scale IQ (b = -4.83, 95% CI [-5.06, -4.60]), performance IQ (b = -4.28, 95% CI [-4.54, -4.02]), and verbal IQ scores (b = -4.53, 95% CI [-4.76, -4.30]), as well as arithmetic (b = -4.06, 95% CI [-4.26, -3.85]), spelling (b = -3.53, 95% CI [-3.75, -3.30]), and reading (b = -4.00, 95% CI [-4.26, -3.75]) scores on the Wide Range Achievement Test (WRAT). Only one sex difference was observed: The association between NSS and the WRAT spelling test was somewhat stronger in girls (b = -4.01, 95% CI [-4.26, -3.36]) than in boys (b = -3.53, 95% CI [-3.75, -3.30]). There is an association between NSSs and poor cognitive performance that is not attributable to established risk factors for brain injury and aberrant neurodevelopment. Further research is needed to investigate the mechanisms underlying this association and to determine if interventions targeting NSS in children might have beneficial effects on neurocognitive development. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

ABNORMAL TREC RESULTS ON THE OHIO NEWBORN SCREEN IN CHILDREN WITH CARTILAGE-HAIR HYPOPLASIA

Introduction While newborn screening (NBS) using T-cell receptor excision circle (TREC) analysis was introduced primarily to screen for severe combined immunodeficiency (SCID), it also identifies T-cell lymphopenia or low naive T-cell numbers due to other etiologies. Cartilage-hair hypoplasia (CHH) is an autosomal recessive disorder caused by mutations in the RMRP gene that result in short limbed skeletal dysplasia and a range of immunologic deficits involving both cellular and humoral immune function. The immune defect can range from minor abnormalities to a SCID phenotype. Methods We analyzed the NBS TREC results performed in Ohio between July 2013 and July 2018. We reviewed the results of the immunologic workup in patients with abnormal TREC results who were later confirmed to have CHH. Results A total of 693,706 unique infants had NBS performed between July 2013 and July 2018, with 192 (0.027%) having abnormal TREC results. Eight infants with abnormal TREC results were diagnosed with CHH. This included 6 cases of non-SCID T-cell lymphopenia and 2 children with SCID phenotypes. In the children with abnormal screening and a diagnosis of CHH, the absolute CD4 lymphocyte counts on initial immunophenotyping ranged from 76 – 757 cells/mm3 (median = 552 cells/mm3). The two CHH patients with SCID received bone marrow transplants. Conclusions CHH is a rare genetic disorder associated with widely varying levels of T-cell lymphopenia ranging from clinically insignificant to SCID. The T-cell lymphopenia may cause an abnormal result on the NBS TREC analysis, allowing for early diagnosis of a significant immunodeficiency and institution of life-saving therapies.

The Effect of Morinda citrifolia L. Fruit Extract Supplemented in to Diluent Tris-Egg Yolk Toward the Abnormality of Goat’s Spermatozoa after Freezing at -80°C

The aim of this research is to know the effect of diluent Tris-egg yolk medium added with Morinda citrifolia L. extract towards the sperms abnormality after storage at -80°C for 24 hours. The extracts added in diluent Tris-egg yolk medium were 0% (P 0 ), 10% (P 1 ), 20% (P 2 ), and 30% (P 3 ). The result showed that the percentage of sperms abnormality in P 0 , P 1 , P 2 , and P 3 were respectively 8.67%, 6.67%, 5.67%, and 10%. P 2 was the lowest percentage, while P 3 was the highest percentage of sperms abnormality. In addition, this research found twelve kinds of sperms abnormality divided into categories: major abnormality included the broke tail, absent head, detached head, dag defect, tapered head, proximal droplet, round head and abaxial; and minor abnormality included the coiled tail, shoe hook tail, bent tail, and distal droplet. It has been concluded that the allotment of 20% Morinda citrifolia L. extracts in Tris-egg yolk medium able to maintain the sperm morphology at -80°C storage for 24 hours. Keywords: goat, Morinda citrifolia L., post-thawing, spermatozoa.

Clinical and pathological features of anti-neutrophil cytoplasmic antibody-associated vasculitis in patients with minor urinary abnormalities.

Kidney biopsy is the gold standard for diagnosis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), but it is unknown whether vasculitis can be detected from AAV patients with minor urinary abnormalities. Ninety ANCA-positive patients undergoing kidney biopsy were evaluated retrospectively after being divided into two groups, which were group A (minor urinary abnormalities with both proteinuria <0.5 g/day and red blood cells ≤5/high power field) and group B (major urinary abnormalities except group A). Thirteen patients were included in group A and 77 patients were in group B. Crescentic glomeruli were detected less frequently in group A than in group B (61.5% vs. 92.2%, P < 0.01). The percentage of crescentic glomeruli relative to total glomeruli was significantly lower in group A than in group B (median [interquartile range]; 2.7% [0-5.2%] vs. 27.3% [8.1-56.1%], P < 0.01). Vasculitis of the small renal arteries was detected more frequently in group A than in group B without significant difference (30.8% vs. 19.5%, P = 0.46). Overall renal vasculitis (crescentic glomeruli and/or small renal artery vasculitis) was detected less frequently in group A than in group B (69.2% vs. 92.2%, P = 0.03). These findings indicate that renal biopsy can be a useful tool for histological diagnosis of ANCA-associated vasculitis in ANCA-positive patients with minor urinary abnormalities, even though the rate of renal vasculitis to the total number of glomeruli sampled is lower in patients with minor urinary abnormalities than patients with major abnormalities.

Enhanced angiotensinogen expression in neonates during kidney development

We recently demonstrated that preterm neonates have higher urinary angiotensinogen (AGT) levels than full-term neonates. Here, we tested the hypothesis that enhanced neonatal AGT expression is associated with intrarenal renin-angiotensin system (RAS) status during kidney development. We prospectively recruited neonates born at our hospital and healthy children with minor glomerular abnormalities between April 2013 and March 2017. We measured neonatal plasma and urinary AGT levels at birth and 1 year later and assessed renal AGT expression in kidney tissues from neonates and healthy children using immunohistochemical (IHC) analysis. Fifty-four neonates and eight children were enrolled. Although there were no changes in plasma AGT levels, urinary AGT levels were significantly decreased 1 year after birth. Urinary AGT levels at birth were inversely correlated with gestational age, and urinary AGT levels at birth and 1 year later were inversely correlated with estimated glomerular filtration rate 1 year after birth. IHC analysis showed that renal AGT expression in neonates was higher than that in healthy children and inversely correlated with gestational age. Enhanced AGT expression and urinary AGT excretion may reflect intrarenal RAS activation associated with kidney development in utero.

Clinical performance of the Cobas 4800 HPV test and the Aptima HPV assay in the management of women referred to colposcopy with minor cytological abnormalities.

The aim of this study was to evaluate the clinical performance of the Cobas 4800 HPV test and the Aptima HPV assay for the detection of CIN2+ disease in women referred to colposcopy with minor cytological abnormalities. ThinPrep liquid-based cytology samples were collected from 562 women referred to colposcopy with minor cytological abnormalities. HPV testing by both assays was performed on these samples. Clinical performances for detection of histologically diagnosed CIN2+ and CIN3+ were calculated. HPV prevalence by the Cobas 4800 HPV test was 58.2% and 53.0% women tested positive with the Aptima HPV assay in the entire study population. The Aptima HPV assay and the Cobas 4800 HPV test displayed equivalent sensitivity of 90.2% (95%CI, 83.4-94.9) for the detection of CIN2+ disease. However, the Aptima HPV assay displayed greater specificity of 61.0% (95% CI, 54.0-68.0) when compared to the Cobas 4800 HPV test 53.0% (95% CI, 46.0-60.0), and this was significantly higher (P = .0004). The Aptima HPV assay also displayed higher specificity 76.5% (95% CI, 66.0-85.0) in the ASCUS category in comparison to the Cobas 4800 HPV test 65.0% (95% 54.0-75.0) which was statistically significant (P = .004). Both the tests displayed similar sensitivity. However, the Aptima HPV assay was significantly more specific in the identification of women with CIN2+ disease in a colposcopy referral population.

Prognostic impact of myocardial perfusion single photon emission computed tomography in patients with major extracardiac findings by computed tomography for attenuation correction

BackgroundAttenuation correction computed tomography (CT) contributes to an improvement in the diagnostic accuracy of myocardial perfusion imaging (MPI) by single photon emission tomography (SPECT). The aim of this study was to explore the prognosis of patients with major findings by CT according to the results of MPI. Methods and Results1506 patients who underwent MPI by SPECT were retrospectively included. Attenuation correction CT images were systematically analyzed for major and minor abnormalities. 830 (55.1%) and 212 (14.1%) patients had minor and major extracardiac findings, respectively. Among patients with major extracardiac findings, the abnormality was previously unknown in 113 (53.3%) patients. 90 (41.9%) had abnormal MPI, 73 (34.4%) had a myocardial infarction scar, 55 (25.9%) had myocardial ischemia, and 38 (17.7%) patients had both myocardial infarction scar and myocardial ischemia. Among the 201 patients available for survival analysis, there were 67 (31.2%) deaths over a follow-up period of 3.2±1.3 years. There was no significant impact on survival arising from MPI, whatever the result. The results were the same among the 103 patients with previously unknown major extracardiac findings. ConclusionExtracardiac findings by CT during MPI are frequent. Patients with major extracardiac findings have a poor mid-term outcome, whatever the results of the myocardial perfusion imaging. Extracardiac findings should be systematically checked when attenuation correction CT is performed.

PIN21 - ECONOMIC BURDEN OF CERVICAL SCREENING AND TREATMENT OF HPV-RELATED CERVICAL LESIONS AND CANCERS IN EUROPE

Cervical cancer is the sixth leading cancer among European women. Country-specific data on costs of management of HPV-related cervical lesions and cancers are important for decision-makers to determine the value of public health interventions including screening and vaccination. We compiled published information on screening and management costs of HPV-related cervical diseases in Europe. PubMed/EMBASE were systematically searched for cost-of-illness studies, published from February 2013–October 2017, reporting on country-level economic burden of screening, diagnosis, treatment, and follow-up of HPV-related cervical lesions (intraepithelial neoplasia, adenocarcinoma in situ and minor cytological abnormalities) and cancers among the general European population. Key exclusion criteria were limited age range (<25 or >45 years only), not English, and patient or regional level data only. Data extracted included, costing year, sources and types of costs and population information. Out of 2,625 studies screened, five (from Belgium, Finland, Poland and Sweden) met the inclusion criteria; only one estimated indirect costs. Annual direct costs of cervical cancer screening were 22.6€ million in Belgium, 30.7€ million in Finland 45.9zl (11.2€) million in Poland, and 49.8€ million in Sweden. Women aged 25-44 years represented 40% (22.4€ million) of the screening costs in Finland. Annual direct costs of diagnosis and treatment of cervical lesions were 6.8€ million in Finland, 69.0zl (16.8€) million in Poland, and 5.2€ million in Sweden. Annual direct costs of diagnosis and treatment of cervical cancer were 3.6€ million in Finland, 52.4zl (12.8€) million in Poland, and €18.1 million in Sweden. In Sweden, indirect costs (productivity losses) were 18.1€, 0.8€ and 4.8€.million for screening, management of cervical lesions and cancers, respectively. Although majority of costs associated with cervical cancer detection and treatment in developed countries are attributable to cervical cancer screening, follow up of abnormal cytology results to prevent disease progression consumes substantial healthcare resources.

Probabilistic Damage Detection of Long-Span Bridges Using Measured Modal Frequencies and Temperature

This paper aims to develop a new probabilistic monitoring-based framework for damage detection of long-span bridges, by eliminating the temperature effects from the measured modal frequencies, probabilistic modeling of modal frequencies using kernel density estimate, and detection damage using the control chart. A methodology is presented to address the issue of modal frequencies' non-normal distribution, which has been neglected in the past studies using the control chart to detect the modal frequencies' abnormality caused by structural damages. The efficiency of the proposed framework is validated through a case study of long-term monitoring data of a long-span suspension bridge. The results show that after elimination of the temperature effects, the selected modal frequencies are not normally distributed, while the Q statistics transferred from the modal frequencies follow the standard normal distribution. The abnormality of modal frequencies can be detected when the data points of the Q statistics exceed the limits of the control chart. Further, the control chart has sufficient sensitivity and thus can be used to detect minor abnormalities of the prototype bridge's modal frequencies. It is concluded that the proposed probabilistic monitoring-based framework offers an effective technique for structural health monitoring of long-span bridges.

Loss of hepatocyte β-catenin protects mice from experimental porphyria-associated liver injury

Porphyrias result from anomalies of heme biosynthetic enzymes and can lead to cirrhosis and hepatocellular cancer. In mice, these diseases can be modeled by administration of a diet containing 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), which causes accumulation of porphyrin intermediates, resulting in hepatobiliary injury. Wnt/β-catenin signaling has been shown to be a modulatable target in models of biliary injury; thus, we investigated its role in DDC-driven injury. β-Catenin (Ctnnb1) knockout (KO) mice, Wnt co-receptor KO mice, and littermate controls were fed a DDC diet for 2 weeks. β-Catenin was exogenously inhibited in hepatocytes by administering β-catenin dicer-substrate RNA (DsiRNA), conjugated to a lipid nanoparticle, to mice after DDC diet and then weekly for 4 weeks. In all experiments, serum and livers were collected; livers were analyzed by histology, western blotting, and real-time PCR. Porphyrin was measured by fluorescence, quantification of polarized light images, and liquid chromatography-mass spectrometry. DDC-fed mice lacking β-catenin or Wnt signaling had decreased liver injury compared to controls. Exogenous mice that underwent β-catenin suppression by DsiRNA during DDC feeding also showed less injury compared to control mice receiving lipid nanoparticles. Control livers contained extensive porphyrin deposits which were largely absent in mice lacking β-catenin signaling. Notably, we identified a network of key heme biosynthesis enzymes that are suppressed in the absence of β-catenin, preventing accumulation of toxic protoporphyrins. Additionally, mice lacking β-catenin exhibited fewer protein aggregates, improved proteasomal activity, and reduced induction of autophagy, all contributing to protection from injury. β-Catenin inhibition, through its pleiotropic effects on metabolism, cell stress, and autophagy, represents a novel therapeutic approach for patients with porphyria. Porphyrias are disorders resulting from abnormalities in the steps that lead to heme production, which cause build-up of toxic by-products called porphyrins. Liver is commonly either a source or a target of excess porphyrins, and complications can range from minor abnormalities to liver failure. In this report, we inhibited Wnt/β-catenin signaling in an experimental model of porphyria, which resulted in decreased liver injury. Targeting β-catenin affected multiple components of the heme biosynthesis pathway, thus preventing build-up of porphyrin intermediates. Our study suggests that drugs inhibiting β-catenin activity could reduce the amount of porphyrin accumulation and help alleviate symptoms in patients with porphyria.

Exercise recommendations in patients with valvular heart disease.

Valvular heart disease affects 1%-2% of young individuals, many of whom aspire to partake in competitive sport or high intensity recreational exercise. There are limited reports on the impact of intensive physical activity on the progression of valvular heart disease; therefore, current recommendations are based on consensus opinion. The management of exercising individuals with valvular heart disease requires a structured approach that incorporates several key factors including symptomatic status, functional capacity, type and nature of the valvular lesion, impact on ventricular structure and function and effect on pulmonary artery pressure. Asymptomatic individuals with minor valvular abnormalities may engage in all forms of competitive sport, whereas those with lesions of moderate severity may exercise intensively if an exercise stress test tailored to the relevant physical activity reveals good functional capacity without myocardial ischaemia, haemodynamic disturbances or arrhythmia. Symptomatic athletes and those with severe valvular heart disease, impaired ventricular function, pulmonary hypertension and arrhythmias should refrain from most competitive sports. Athletes with a bicuspid aortic valve and aortic root diameter >40 mm should avoid sport with a strong isometric component even with minimal valvular dysfunction. There is an association between mitral valve prolapse and sudden cardiac death in the general population; however, there is limited evidence of increased risk with competitive sport. Athletes undergoing corrective surgery may return to exercise after 3 months if ventricular function and exercise capacity are preserved. Individuals anticoagulated for mechanical bioprosthetic valves should avoid contact or collision sport to minimise the risk of bleeding.

Clonal architecture in patients with myelodysplastic syndromes and double or minor complex abnormalities: Detailed analysis of clonal composition, involved abnormalities, and prognostic significance.

The study analyzes the clonal architecture and the abnormalities involved in a series of 191 patients with myelodysplastic syndromes (MDS) and 2-3 clonal abnormalities. All patients were extracted from an international database. The patients were classified into six clonal subtypes (2A-3C) based on the number of abnormalities and the presentation of unrelated clones (UC) and/or a clonal evolution. UC were detected in 23/191 patients (12%). The composition of UC showed great variability. The only recurrent combination of abnormalities was del(5q) and + 8 in 8 of 23 patients (35%). In patients with clonal evolution, the clone size of the primary and secondary clone varied: Patients with -7 and + 8 in the primary clone showed a larger primary and a smaller secondary clone (-7: median 74% vs 10%; +8 73% vs 18%) while patients with del(5q) in the primary clone showed a smaller primary and a larger secondary clone (33% vs 61%). Univariate and multivariate analyses showed no significant differences regarding overall or AML-free survival between the clonal subtypes. Only the subtype 3C (3 abnormalities and clonal evolution) was an independent risk factor for developing AML (Hazard Ratio 5.5 as compared to subtype 2A, P < .05). Finally, our study confirms that the number of abnormalities clearly defines a significant risk factor for overall- as well as AML-free survival. Importantly, in patients with more than one clone, the calculation of the number of abnormalities in the entire sample instead of the number of abnormalities per clone allows a higher prognostic accuracy.

Court “Monsters”: Deformity in the Western European Royal Courts between 1500 and 1700

ABSTRACT Whereas early modern monstrosity generally has enjoyed in-depth historical investigation, the presence of so-called monsters at the European royal courts has been somewhat overlooked. By using a severity continuum of deformity and a subcontinuum of emancipation as a framework, this article addresses three specific questions regarding court monstrosity: Why did such individuals reside at court? What role did they have within the court? How were they perceived and treated by other courtiers? The article will first address those who belonged at the less severe end of the severity continuum but whose relatively minor abnormalities nevertheless rendered them wondrous—courtly dwarfs and giants. This is followed by an examination of two of the more unusual types of deformities belonging to the more severe end of the continuum—people with hirsutism and conjoined twins.

Growth Hormone Treatment for Patients with Noonan Syndrome.

Noonan syndrome (NS) is a genetic disorder, which can present clinically with a variable phenotype. Proportional post natal short stature is a common manifestation of NS, with the majority of affected patients having an adult height below the third percentile. Some investigators have reported minor abnormalities in GH secretion and/or action, suggesting that recombinant growth hormone (rhGH) therapy may be useful for the treatment of their short stature. Our review of the literature regarding rhGH therapy in children with NS indicates that this therapy improves height velocity, but relatively few controlled clinical trials reporting adult height are available. rhGH treatment does not appear to be associated with adverse effects in these patients, but data on the possible development of malignancy during treatment are somewhat limited. Therefore, we believe that there is a need for large controlled clinical trials in patients with this condition, in order to accurately assess the effects of rhGH therapy over adult height.

P2476What are the causes of a suboptimal FFR after coronary stent deployment? Insights from a consecutive series using OCT imaging

AIMS Fractional flow reserve (FFR) can be used to detect a suboptimal result after percutaneous coronary intervention (PCI). A lower post-procedure FFR (<0.90) has been shown to be associated with adverse clinical outcomes at follow-up. This pilot study aimed to understand the mechanisms resulting in a suboptimal FFR and whether optical coherence tomography (OCT)-guided optimisation could improve final FFR. METHODS AND RESULTS Thirty-five patients undergoing complex PCI were prospectively enrolled. After stenting and post-dilatation, OCT and pressure wire were performed. An FFR threshold <0.90 after PCI was defined as suboptimal and mandated further PCI optimisation. A satisfactory post-PCI FFR (predefined as ≥0.90) was achieved immediately after conventional PCI in 14 patients (40%) and in this group no further treatment was performed. Minor abnormalities (stent malapposition of 200-500 µm) were observed with OCT in three of these patients. Suboptimal functional results after conventional stenting (predefined as an FFR <0.90) were found in 21 patients (60%). In thirteen out of these 21 patients (61.9%), OCT demonstrated a suboptimal stent result. Subsequent OCT-guided optimisation was performed resulting in a higher final FFR (increase from 0.80±0.02 to 0.88±0.01; p=0.008). CONCLUSIONS Despite a satisfactory angiographic result, a suboptimal functional result is evident in a substantial proportion of patients undergoing complex PCI. Implementation of an OCT-guided PCI optimisation protocol may reveal potentially treatable causes, allowing optimisation of the post-PCI functional result.

Renal expression of trefoil factor 3 mRNA in association with tubulointerstitial fibrosis in IgA nephropathy.

ABSTRACTAimTrefoil factor 3 (TFF3) is a small peptide that is involved in mucosal protection. TFF3 is widely expressed in multiple tissues including kidney tissue. Previous studies have reported that the levels of urinary TFF3 are significantly increased in patients with chronic kidney disease. The aim of this study is to detect the TFF3 mRNA in kidney and elucidate the relationship between renal TFF3 mRNA and tubulointerstitial fibrosis in IgA nephropathy (IgAN).MethodsWe investigated the renal mRNA expression of TFF3 by real‐time PCR analysis in biopsy specimens from patients with IgAN, other glomerulonephritis (OGN) and minor glomerular abnormalities (MGA). We also determined the renal localization of TFF3 and the levels of urinary TFF3 by immunostaining and ELISA, respectively.ResultsThe renal TFF3 mRNA expression was significantly associated with the urinary TFF3 secretion and the tubulointerstitial fibrosis score in the IgAN group alone. Immunostaining of the renal specimen of IgAN patients revealed that TFF3 is located in the renal tubular epithelial cells. The locations were almost the same as those that showed uromodulin positivity; specifically, the thick ascending limb (TAL) of the loop of Henle and the early portion of the distal tubule. The urinary TFF3 levels were positively correlated with the levels of urinary biomarkers of tubulointerstitial injury in such patients.ConclusionRenal TFF3 mRNA is associated with renal tubulointerstitial fibrosis in IgAN patients. The TFF3 located in the renal tubular epithelial cells may play a role in the progression of tubulointerstitial fibrosis in IgAN patients.

Value of HPV 16/18 Genotyping and p16/Ki-67 Dual Staining to Predict Progression to HSIL/CIN2+ in Negative Cytologies From a Colposcopy Referral Population.

To assess the prognostic value of human papillomavirus (HPV) 16/18 genotyping and p16/Ki-67 dual staining cytology in high-risk HPV (hrHPV)-positive women with no lesion or minor abnormalities. We evaluated progression to high-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grades 2 to 3 or cervical cancer (HSIL/CIN2+), persistence/regression of hrHPV infection in women referred to colposcopy showing hrHPV infection, histology diagnosis different from HSIL/CIN2+, and negative cytology. HPV 16/18 genotyping and dual staining were performed in liquid-based cytologic specimens obtained on the first visit. Progression was observed in 16 (8.0%) of 200 women. Those with HPV 16/18 infection had an increased risk of progression compared with women infected by other hrHPV types, and they also showed more persistence. However, no association was observed between progression or persistence and the result of the dual staining. HPV 16/18-positive women with no lesions or minor abnormalities are at high risk of progression to HSIL/CIN2+ and hrHPV persistence.

Prevalence of middle ear abnormalities from otitis media in relation with pneumococcal vaccine use in the Inuit population of Nunavik, province of Quebec, Canada

BackgroundOtitis media (OM) constitutes an important public health problem in the Inuit population of Nunavik, Northern Quebec. One of the objectives of the childhood pneumococcal vaccination program is to reduce OM burden. The program was implemented in 2002, and 7-, 10-, and 13-valent conjugate vaccines were used sequentially, with doses offered at 2, 4, 6 and 12–18 months, respectively. ObjectiveTo assess the prevalence of middle ear abnormalities at age 5 years in relation with exposure to different pneumococcal conjugate vaccines. MethodsImmunization cards and audiology screening tests at age 5 years of children born in 1994–2010 were reviewed. Children were classified according to the vaccine schedule recommended for their birth cohort or to the vaccines they actually received. Log-linked binomial regression models were used to assess the relative abnormalities risk according to different vaccination schedules. ResultsAmong 3517 children with complete documentation, the prevalences of minor and major abnormalities were 29% and 18%, respectively. Minor abnormalities frequency was higher in unvaccinated children (34%) and lower in children vaccinated with PCV7 (22%), PCV7 + PCV10 (17%), PCV10 (15%) and PCV10 + PCV13 (18%). No substantial differences among vaccine schedules were observed for major abnormalities. ConclusionsPneumococcal conjugate vaccination was associated with a decreased frequency of middle ear abnormalities although no effect was seen for major abnormalities which may be trigger by OM with early onset.Clinicaltrials.gov registration number: NCT01694329

Spontaneous remission of adult-onset minimal change nephrotic syndrome associated with influenza B infection: a case report

BackgroundWhile the majority of adult-onset minimal change nephrotic syndrome (MCNS) is a primary or an idiopathic form of disease, it can also occur as a secondary form. Reports on the spontaneous remission of MCNS are rare since the condition is typically treated with corticosteroids. We herein describe the spontaneous remission of adult-onset MCNS in a patient who developed nephrotic syndrome after type B influenza infection.Case presentationA 50-year-old woman experienced fever, cough, malaise, and low back pain, which had persisted for 6 days before she presented to our hospital, and edema of the face and limbs, which had persisted for 5 days before her presentation. She was diagnosed with type B influenza infection and later exhibited an exacerbation of facial edema, decreased urine output, and a high level of proteinuria. She was referred to our department after the diagnosis of nephrotic syndrome. On admission, her proteinuria level was 20.88 g/gCr and her selectivity index value was 0.13. The examination of a kidney biopsy specimen obtained on the fourth day of hospitalization under a light microscope revealed minor abnormalities. An immunofluorescence showed only nonspecific granular IgM deposits in the mesangium. Electron microscopy showed extensive foot process effacement without any immune complex deposits. Based on these findings, the patient was diagnosed with MCNS. After admission, the proteinuria decreased to 0.06 g/gCr with rest and sodium restriction (6 g/day) alone; a complete remission from nephrotic syndrome was observed at approximately 2 weeks after the onset of symptoms. There have been no signs of recurrence of nephrotic syndrome in the one years since.ConclusionWe experienced a rare case in which spontaneous remission of MCNS occurred within a short period of 2 weeks after influenza B infection. When patients present with nephrotic syndrome after an infection, it is necessary to consider MCNS in the differential diagnosis, which also includes post-infectious glomerulonephritis and the acute exacerbation of IgA nephropathy.

Should 45,X/46,XY boys with no or mild anomaly of external genitalia be investigated and followed up?

Few studies of patients with a 45,X/46,XY mosaicism have considered those with normal male phenotype. The purpose of this study was to evaluate the clinical outcome of 45,X/46,XY boys born with normal or minor abnormalities of external genitalia, notably in terms of growth and pubertal development. Retrospective longitudinal study of 40 patients followed between 1982 and 2017 in France. Twenty patients had a prenatal diagnosis, whereas 20 patients had a postnatal diagnosis, mainly for short stature. Most patients had stunted growth, with abnormal growth spurt during puberty and a mean adult height of 158 ± 7.6 cm, i.e. -2.3 DS with correction for target height. Seventy percent of patients presented Turner-like syndrome features including cardiac (6/23 patients investigated) and renal malformations (3/19 patients investigated). Twenty-two patients had minor abnormalities of external genitalia. One patient developed a testicular embryonic carcinoma, suggesting evidence of partial gonadal dysgenesis. Moreover, puberty occurred spontaneously in 93% of patients but 71% (n = 5) of those evaluated at the end of puberty presented signs of declined Sertoli cell function (low inhibin B levels and increased FSH levels). This study emphasizes the need to identify and follow-up 45,X/46,XY patients born with normal male phenotype until adulthood, as they present similar prognosis than those born with severe genital anomalies. Currently, most patients are diagnosed in adulthood with azoospermia, consistent with our observations of decreased testicular function at the end of puberty. Early management of these patients may lead to fertility preservation strategies.