Severe Disease In Adults Research Articles

The Impact of Pulsed Electric Fields on Milk's Macro- and Micronutrient Profile: A Comprehensive Review.

Consumers around the world are attracted to products with beneficial effects on health. The stability, functionality, and integrity of milk constituents are crucial determinants of product quality in the dairy industry. Milk contains macronutrients and micronutrients that aid in a wide range of physiological functions in the human body. Deficiencies of these two types of nutrients can confine growth in children and increase the risk of several diseases in adults. The influence of pulsed electric fields (PEF) on milk has been extensively reviewed, mostly concentrating on the inactivation of microbes and enzymes for preservation purposes. Therefore, the information on the variations of milk macro- and micronutrients treated by PEF has yet to be elucidated and it is imperative as it may affect the functionality, stability, and integrity of the milk and dairy products. In this review, we describe in detail the introduction, types, and components of PEF, the inactivation mechanism of biological cells by PEF, as well as the effects of PEF on macro- and micronutrients in milk. In addition, we also cover the limitations that hinder the commercialization and integration of PEF in the food industry and the future outlook for PEF. The present review consolidates the latest research findings investigating the impact of PEF on the nutritional composition of milk. The assimilation of this valuable information aims to empower both industry professionals and consumers, facilitating a thorough understanding and meticulous assessment of the prospective adoption of PEF as an alternative technique for milk pasteurization.

Effectiveness of BNT162b2 COVID-19 vaccination in prevention of hospitalisations and severe disease in adults with SARS-CoV-2 Delta (B.1.617.2) and Omicron (B.1.1.529) variant between June 2021 and July 2022: A prospective test negative case-control study.

Whilst other studies have reported the effectiveness of mRNA vaccination against hospitalisation, including emergency department or intensive care admission, few have assessed effectiveness against other more clinically robust indices of COVID-19 severity. A prospective single-centre test-negative design case-control study of adults hospitalised with COVID-19 disease or other acute respiratory disease between 1 June 2021 and 20 July 2022. We assessed VE (vaccine effectiveness) against hospitalisation, length of stay [LOS] >3 days, WHO COVID Score >5 and supplementary oxygen FiO2 (fraction inspired oxygen) >28%, conducting regression analyses controlling for age, gender, index of multiple deprivation, Charlson comorbidity index, time, and community infection prevalence. 935 controls and 546 cases were hospitalised during the Delta period, with 721 controls and 372 cases hospitalised during the Omicron study period. Two-dose BNT162b2 was associated with VE 82.5% [95% confidence interval 76.2%-87.2%] against hospitalisation following Delta infection, 63.3% [26.9-81.8%], 58.5% [24.8-77.3%], and 51.5% [16.7-72.1%] against LOS >3 days, WHO COVID Score >5, and requirement for FiO2 >28% respectively. Three-dose BNT162b2 protection against hospitalisation with Omicron infection was 30.9% [5.9-49.3%], with sensitivity analyses ranging from 28.8-72.6%. Protection against LOS >3 days, WHO COVID Score >5 and requirement for FiO2 >28% was 56.1% [20.6-76.5%], 58.8% [31.2-75.8%], and 41.5% [-0.4-66.3%], respectively. In the UK, BNT162b2 was prioritised for high-risk individuals and those aged >75 years. In the latter group we found a higher estimate of VE against hospitalisation of 47.2% [16.8-66.6%]. BNT162b2 vaccination results in risk reductions for hospitalisation and multiple patient outcomes following Delta and Omicron COVID-19 infection, particularly in older adults. BNT162b2 remains effective against severe SARS-CoV-2 disease. AvonCAP is an investigator-led project funded under a collaborative agreement by Pfizer.

RSV Burden of Disease in Adults - a new threat

Abstract Respiratory syncytial virus (RSV) is responsible for lower respiratory tract infections across all age groups worldwide. Initial exposure to RSV in infants and young children can lead to severe bronchiolitis, which has the potential to be life-threatening. Among older children and healthy adults, recurrent upper respiratory tract infections caused by RSV are frequent, varying in intensity from asymptomatic infection to symptomatic upper respiratory tract disease. The presence of specific comorbidities (cardiopulmonary conditions, including COPD and CHF, and immunocompromising conditions) increases the likelihood of severe disease in adults (1). This editorial provides a review of the burden of RSV disease among adults, population groups at increased risk of developing severe RSV disease, the current status of surveillance systems and RSV prevention strategies in adults, including the use of RSV vaccines in adults, recently licensed for use.

Rates of respiratory syncytial virus (RSV)-associated hospitalization among adults with congestive heart failure-United States, 2015-2017.

BackgroundRespiratory syncytial virus (RSV) can cause severe disease in adults with cardiopulmonary conditions, such as congestive heart failure (CHF). We quantified the rate of RSV-associated hospitalization in adults by CHF status using population-based surveillance in the United States.MethodsPopulation-based surveillance for RSV (RSV-NET) was performed in 35 counties in seven sites during two respiratory seasons (2015–2017) from October 1–April 30. Adults (≥18 years) admitted to a hospital within the surveillance catchment area with laboratory-confirmed RSV identified by clinician-directed testing were included. Presence of underlying CHF was determined by medical chart abstraction. We calculated overall and age-stratified (<65 years and ≥65 years) RSV-associated hospitalization rates by CHF status. Estimates were adjusted for age and the under-detection of RSV. We also report rate differences (RD) and rate ratios (RR) by comparing the rates for those with and without CHF.Results2042 hospitalized RSV cases with CHF status recorded were identified. Most (60.2%, n = 1230) were ≥65 years, and 28.3% (n = 577) had CHF. The adjusted RSV hospitalization rate was 26.7 (95% CI: 22.2, 31.8) per 10,000 population in adults with CHF versus 3.3 (95% CI: 3.3, 3.3) per 10,000 in adults without CHF (RR: 8.1, 95% CI: 6.8, 9.7; RD: 23.4, 95% CI: 18.9, 28.5). Adults with CHF had higher rates of RSV-associated hospitalization in both age groups (<65 years and ≥65 years). Adults ≥65 years with CHF had the highest rate (40.5 per 10,000 population, 95% CI: 35.1, 46.6).ConclusionsAdults with CHF had 8 times the rate of RSV-associated hospitalization compared with adults without CHF. Identifying high-risk populations for RSV infection can inform future RSV vaccination policies and recommendations.

Effectiveness of BNT162b2 COVID-19 Vaccination in Prevention of Hospitalisations and Severe Disease in Adults with Delta (B.1.617.2) and Omicron (B.1.1.529) Variant SARS-CoV-2 Infection: A Prospective Test Negative Case-Control Study

Effectiveness of BNT162b2 COVID-19 Vaccination in Prevention of Hospitalisations and Severe Disease in Adults with Delta (B.1.617.2) and Omicron (B.1.1.529) Variant SARS-CoV-2 Infection: A Prospective Test Negative Case-Control Study

Severity of Disease Among Adults Hospitalized with Laboratory-Confirmed COVID-19 Before and During the Period of SARS-CoV-2 B.1.617.2 (Delta) Predominance - COVID-NET, 14 States, January-August 2021.

In mid-June 2021, B.1.671.2 (Delta) became the predominant variant of SARS-CoV-2, the virus that causes COVID-19, circulating in the United States. As of July 2021, the Delta variant was responsible for nearly all new SARS-CoV-2 infections in the United States.* The Delta variant is more transmissible than previously circulating SARS-CoV-2 variants (1); however, whether it causes more severe disease in adults has been uncertain. Data from the CDC COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), a population-based surveillance system for COVID-19-associated hospitalizations, were used to examine trends in severe outcomes in adults aged ≥18 years hospitalized with laboratory-confirmed COVID-19 during periods before (January-June 2021) and during (July-August 2021) Delta variant predominance. COVID-19-associated hospitalization rates among all adults declined during January-June 2021 (pre-Delta period), before increasing during July-August 2021 (Delta period). Among sampled nonpregnant hospitalized COVID-19 patients with completed medical record abstraction and a discharge disposition during the pre-Delta period, the proportion of patients who were admitted to an intensive care unit (ICU), received invasive mechanical ventilation (IMV), or died while hospitalized did not significantly change from the pre-Delta period to the Delta period. The proportion of hospitalized COVID-19 patients who were aged 18-49 years significantly increased, from 24.7% (95% confidence interval [CI]=23.2%-26.3%) of all hospitalizations in the pre-Delta period, to 35.8% (95% CI=32.1%-39.5%, p<0.01) during the Delta period. When examined by vaccination status, 71.8% of COVID-19-associated hospitalizations in the Delta period were in unvaccinated adults. Adults aged 18-49 years accounted for 43.6% (95% CI=39.1%-48.2%) of all hospitalizations among unvaccinated adults during the Delta period. No difference was observed in ICU admission, receipt of IMV, or in-hospital death among nonpregnant hospitalized adults between the pre-Delta and Delta periods. However, the proportion of unvaccinated adults aged 18-49 years hospitalized with COVID-19 has increased as the Delta variant has become more predominant. Lower vaccination coverage in this age group likely contributed to the increase in hospitalized patients during the Delta period. COVID-19 vaccination is critical for all eligible adults, including those aged <50 years who have relatively low vaccination rates compared with older adults.

Clinical outcomes of adults hospitalized for laboratory confirmed respiratory syncytial virus or influenza virus infection

Respiratory syncytial virus (RSV) can cause severe disease in adults, but far less is known than for influenza. The aim of our study was to compare the disease course of RSV infections with influenza infections among hospitalized adults. We retrieved clinical data from an ongoing surveillance of adults hospitalized with RSV or influenza virus infection in two acute care hospitals in North-Eastern Switzerland during the winter seasons 2017/2018 and 2018/2019. Our main analysis compared the odds between RSV and influenza patients for admission to an intensive care unit (ICU) or in-hospital death within 7 days after admission. There were 548 patients, of whom 79 (14.4%) had an RSV and 469 (85.6%) an influenza virus infection. Both groups were similar with respect to age, sex, smoking status, nutritional state, and comorbidities. More RSV patients had an infiltrate on chest radiograph on admission (46.4% vs 29.9%, p = .007). The proportion of patients with RSV who died or were admitted to ICU within seven days after admission was 19.0% compared to 10.2% in influenza patients (p = .024). In multivariable analysis, a higher leukocyte count (adjusted OR 1.07, 95% CI 1.02-1.13, p = .013) and the presence of a pneumonic infiltrate (aOR 3.41, 95% CI 1.93-6.02) significantly increased the risk for experiencing the adverse primary outcome while the effect of the underlying viral pathogen became attenuated (aOR 1.18, 95% CI 0.58-2.41, p = .0.655). Our results suggest that RSV is responsible for clinical courses at least as severe as influenza in adults. This supports the need for better guidance on diagnostic strategies as well as on preventive and therapeutic measures for hospitalized adults with RSV infection.

Taming a pandemic

Coronavirus One year after its emergence, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become so widespread that there is little hope of elimination. There are, however, several other human coronaviruses that are endemic and cause multiple reinfections that engender sufficient immunity to protect against severe adult disease. By making assumptions about acquired immunity from its already endemic relatives, Lavine et al. developed a model with which to analyze the trajectory of SARS-CoV-2 into endemicity. The model accounts for SARS-CoV-2's age-structured disease profile and assesses the impact of vaccination. The transition from epidemic to endemic dynamics is associated with a shift in the age distribution of primary infections to younger age groups, which in turn depends on how fast the virus spreads. Longer-lasting sterilizing immunity will slow the transition to endemicity. Depending on the type of immune response it engenders, a vaccine could accelerate establishment of a state of mild disease endemicity. Science , this issue p. [741][1] [1]: /lookup/doi/10.1126/science.abe6522

DiGeorge Syndrome and COVID-19 in Two Pediatric Patients

Immunocompromised patients, including those with primary immunodeficiency, may be expected to have more severe COVID-19 disease. However, the evidence is unclear as limited cases have been reported. Hispanic ethnicity and obesity also appear to confer risk of more severe disease in adults.

COVID-19 Severity in Hospitalized Pediatric Patients with Atopic Disease

Data from the Coronavirus-19 disease (COVID-19) pandemic suggests asthma is not a risk factor for severe disease in adults; it is unclear if this applies to pediatric patients. This study was undertaken to determine if pediatric patients with asthma or atopic disease had altered risk for severe disease when hospitalized with COVID-19. A retrospective chart review was performed of SARS-CoV-2 positive patients admitted to Nationwide Children’s Hospital from March 1 to July 31. Charts were evaluated for history of asthma or atopic disease (including asthma) and surrogate markers of COVID-19 severity, including ICU admission, supplemental oxygen requirement, and intubation. 49 patients were identified as positive for SARS-CoV-2, 22 of whom were admitted for COVID-19 related symptoms. Of the admitted patients, six patients (12%) had asthma and 18 (37%) atopic disease (including those with asthma). ICU admission rate for asthma versus non-asthma was 17% versus 12% (p=0.78) and for atopic versus non-atopic was 17% versus 6.4% (p=0.32), while supplemental oxygen rates were 17% versus 16% asthma versus non-asthma (p=0.98) and 22% versus 13% atopic versus non-atopic (p=0.43). Only two patients required intubation and both had atopic dermatitis. Two patients had Multisystem Inflammatory Syndrome in Children -- one with allergic rhinitis and atopic dermatitis, the other without any atopic disease. Markers of COVID-19 disease severity do not differ based on asthma or atopic status in pediatric patients. In children, like adults, the presence of asthma or atopy does not appear to alter the risk of severe COVID-19.

Immunological characteristics govern the transition of COVID-19 to endemicity.

We are currently faced with the question of how the severity of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may change in the years ahead. Our analysis of immunological and epidemiological data on endemic human coronaviruses (HCoVs) shows that infection-blocking immunity wanes rapidly but that disease-reducing immunity is long-lived. Our model, incorporating these components of immunity, recapitulates both the current severity of SARS-CoV-2 infection and the benign nature of HCoVs, suggesting that once the endemic phase is reached and primary exposure is in childhood, SARS-CoV-2 may be no more virulent than the common cold. We predict a different outcome for an emergent coronavirus that causes severe disease in children. These results reinforce the importance of behavioral containment during pandemic vaccine rollout, while prompting us to evaluate scenarios for continuing vaccination in the endemic phase.

Effects of family integrated care on refractory cancer-related pain receiving intrathecal morphine pump therapy: a cohort study.

Family integrated care (FIC), originating from the neonatal intensive care unit, has proved to be an effective therapy for the care of several diseases in adults. However, it is still unclear whether it is successful in the treatment of refractory cancer-related pain using an intrathecal morphine pump (IMP). A prospective study was performed to enroll patients with refractory cancer-related pain treated by IMP. Medical records, including demographic data, types of cancer, doses of opioids before the implantation, were gathered at baseline. Besides, numerical pain rating scales (NRS) were measured to assess the severity of pain. Karnofsky performance scores (KPS), self-rating anxiety scale (SAS) scores and selfrating depression scale (SDS) scores were used to assess the physical and psychological status of patients. Follow-up lasted for at least 12 months. The changes in NRS, KPS, SAS, and SDS scores were recorded, as well as adverse events and survival rates. Totally, 33 patients were enrolled and divided into traditional care groups and FIC groups. The results showed that the implantation of IMP relieved the pain in both groups. Moreover, patients in the FIC group had significantly more relief of pain than those in the traditional group (P=0.04). Similarly, KPS raised more, and scores of SAS and SDS decreased more in the FIC group. Besides, fewer adverse events occurred in the FIC group, but the survival rate showed no significant difference between the two groups. FIC enhances the effects of IMP on the relief of refractory cancer-related pain and improves the physical and psychological status of patients.

Compliance with Continuous Positive Airway Pressure in Patients with Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) is caused by upper airway obstruction during sleep and increases risk for stroke and cardiovascular morbidity. It is also related to excessive daytime sleepiness and cognitive dysfunction in affected adults. Additionally, OSA also affects children, manifesting as growth retardation and neurobehavioral abnormalities. Continuous positive airway pressure (CPAP) therapy is the treatment of choice for moderate to severe disease in adults and in some of the pediatric population. CPAP therapy reduces daytime sleepiness, improves quality of life, and reduces risk for cardiovascular morbidity and mortality in individuals with OSA. Although CPAP therapy is effective in these patients, it has significant limitations regarding compliance. Accordingly, the purpose of this review was to investigate factors impacting compliance with treatment including socioeconomic/demographic characteristics, nasal obstruction, previous upper airway surgery, severity of OSA, psychological factors, support/intervention of CPAP, and device-related factors. Additionally, factors associated with CPAP compliance in children are also discussed. Key words: Sleep apnea syndromes, Continuous positive airway pressure, Patient compliance

P0311INFECTION-RELATED GLOMERULONEPHRITIS IN ADULTS: TIME FOR A DEFINITIVE PARADIGM SHIFT?

Abstract Background and Aims The recent decades have witnessed significant changes in the epidemiology and clinical course of infection-related glomerulonephritis (IRGN). We analyzed the clinicopathological features and long-term outcome of adult patients with biopsy-proven IRGN followed in a large Italian referral centre. Method We included patients with biopsy-proven IRGN diagnosed from 2000 to 2018. Clinical and laboratory findings, histological features, possible risk factors and therapy were assessed for both renal and patient outcome. Results Forty-one patients met the inclusion criteria (male:female ratio 3:1, mean age 61±16 years). Smoke habit (47.2%), alcoholism (30.6%), and diabetes (27.5%) were the most common risk factors. The most frequently identified sites of infection were skin, lung and heart (Table 1). Staphylococci spp. accounted for 76.5% of positive cultures (Figure 1). Hypocomplementaemia emerged in 48.5% of cases. The most frequent histologic patterns were diffuse proliferative (56.0%) and membranoproliferative (29.3%) glomerulonephritis. Haemodialysis was required by 22.5% of patients at inception. Two thirds of patients developed chronic kidney disease; half of them reached end-stage renal disease (ESRD). By multivariate analysis ESRD was associated with diabetes (HR 13.7; 95% CI, 1.6-121.0; p=0.018), crescents (HR 25.2; 95% CI, 2.7-235.7; p=0.005), and interstitial fibrosis (HR 31.0; 95% CI, 3.3-287.3; p=0.003). Male gender (HR 12.7; 95% CI, 10.8-14.6; p=0.008) hypertension (HR 40.8; 95% CI, 38.6-43.1; p=0.001), gross haematuria (HR 11.8; 95% CI, 9.4-14.2; p=0.047), need for haemodialysis at onset (HR 16.3; 95% CI, 14.7-17.8; p&amp;lt;0.0001), and interstitial infiltrate (HR 13.3; 95% CI, 11.6-15.0; p=0.003) significantly affected survival. Corticosteroids did not affect prognosis. Conclusion While traditionally considered a “benign” disease with a favorable course in children, IRGN is a potentially severe disease in adults, particularly when a background of major comorbidities and older age are present. A significant proportion of patients does not recover renal function, with a remarkable risk of ESRD.

Exposure to secondhand tobacco smoke is associated with reduced muscle strength in US adults

Secondhand tobacco smoke (SHS) exposure is a well-established risk factor for several diseases in adults. Despite the evidence that active tobacco smoke is harmful for the muscles, the association between SHS and muscle strength is still uncertain.We analyzed data from 5390 nonsmoking U.S. adults aged >30 years who participated in the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Exposure to SHS was assessed with serum cotinine concentrations. Grip strength was measured using a Takei digital handgrip dynamometer, and combined grip strength was calculated as the sum of the largest reading from each hand. Median (interquartile range) serum cotinine and grip strength were 0.015 ng/mL (IQR 0.011-0.36) and 65.5 kg (IQR 53.4-86.4), respectively. After adjusting for sociodemographic, anthropometric, health-related behavioral, and clinical risk factors, the highest (0.047-9.9 ng/mL) vs lowest (≤0.011 ng/mL) quartile of serum cotinine was associated with a reduction in combined grip strength of 1.41 kg (95%CI: -2.58, -0.24), p-trend=0.02. These results were consistent across socio-demographic and clinical subgroups. In the US nonsmoking adult population, even low levels of exposure to passive smoking were associated with decreased grip strength. Despite great achievements in tobacco control, extending public health interventions to reduce SHS exposure is still needed.

Chicken ovalbumin upstream promoter-transcription factor II protects against cisplatin-induced acute kidney injury.

The chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) plays essential roles in organogenesis of embryos. Recently COUP-TFII is also implicated in several diseases in adults. Here we focus on the role of COUP-TFII in cisplatin-induced acute kidney injury (AKI). COUP-TFII was the most abundantly expressed in the kidney among organs. Male tamoxifen-inducible COUP-TFII-knockout mice or control mice were intraperitoneally treated with 30 mg/kg body weight of cisplatin at 12 weeks old to induce AKI. The kidney samples were subject to morphological studies, terminal deoxynucleotidyl transferase-mediated deoxyuridine nick-end labeling (TUNEL) assay, immunohistochemistry and RT-qPCR. Serum levels of creatinine, blood urea nitrogen (BUN) and tumor necrosis factor alpha (TNF-α) were measured. Administration of cisplatin induced a more severe AKI in adult COUP-TFII-knockout mice. An increase in dead cells in both the proximal tubules and thick ascending limb of Henle's loop (TAL) was observed in the knockout mouse kidney. The expression levels of COUP-TFII decreased in the TAL by cisplatin administration. There was no difference in the expression levels of transporter mRNAs responsible for cellular cisplatin uptake between control and knockout mouse kidney. COUP-TFII-knockout mice and COUP-TFII-depleted cells exhibited an elevation in TNF-α levels, suggesting the involvement of the TNF-α pathway. Chromatin immunoprecipitation showed that COUP-TFII was enriched in the potential binding site, suggesting that COUP-TFII might directly suppress the TNF-α gene at transcriptional level. These results indicate the involvement of COUP-TFII in the pathophysiology of AKI and COUP-TFII may be a potential therapeutic target for AKI.

Zika virus infection in the Veterans Health Administration (VHA), 2015-2016.

BackgroundZika virus (ZIKV) is an important flavivirus infection. Although ZIKV infection is rarely fatal, risk for severe disease in adults is not well described. Our objective was to describe the spectrum of illness in U.S. Veterans with ZIKV infection.MethodologyCase series study including patients with laboratory-confirmed or presumed positive ZIKV infection in all Veterans Health Administration (VHA) medical centers. Adjusted odds ratios of clinical variables associated with hospitalization and neurologic complications was performed.Principal findingsOf 1,538 patients tested between 12/2015-10/2016 and observed through 3/2017, 736 (48%) were RT-PCR or confirmed IgM positive; 655 (89%) were male, and 683 (93%) from VA Caribbean Healthcare System (VACHCS). Ninety-four (13%) were hospitalized, 91 (12%) in the VACHCS. Nineteen (3%) died after ZIKV infection. Hospitalization was associated with increased Charlson co-morbidity index (adjusted odds ratio [OR] 1.2; 95% confidence interval [CI], 1.1–1.3), underlying connective tissue disease (OR, 29.5; CI, 3.6–244.7), congestive heart failure (OR, 6; CI, 2–18.5), dementia (OR, 3.6; CI, 1.1–11.2), neurologic symptom presentation (OR, 3.9; CI, 1.7–9.2), leukocytosis (OR, 11.8; CI, 4.5–31), thrombocytopenia (OR, 7.8; CI, 3.3–18.6), acute kidney injury (OR, 28.9; CI, 5.8–145.1), or using glucocorticoids within 30 days of testing (OR, 13.3; CI 1.3–133). Patients presenting with rash were less likely to be hospitalized (OR, 0.29; CI, 0.13–0.66). Risk for neurologic complications increased with hospitalization (OR, 5.9; CI 2.9–12.2), cerebrovascular disease (OR 4.9; CI 1.7–14.4), and dementia (OR 2.8; CI 1.2–6.6).ConclusionOlder Veterans with multiple comorbidities or presenting with neurologic symptoms were at increased risk for hospitalization and neurological complications after ZIKV infection.

Long-term consequences of developmental vascular defects on retinal vessel homeostasis and function in a mouse model of Norrie disease.

Loss of Norrin signalling due to mutations in the Norrie disease pseudoglioma gene causes severe vascular defects in the retina, leading to visual impairment and ultimately blindness. While the emphasis of experimental work so far was on the developmental period, we focus here on disease mechanisms that induce progression into severe adult disease. The goal of this study was the comprehensive analysis of the long-term effects of the absence of Norrin on vascular homeostasis and retinal function. In a mouse model of Norrie disease retinal vascular morphology and integrity were studied by means of in vivo angiography; the vascular constituents were assessed in detailed histological analyses using quantitative retinal morphometry. Finally, electroretinographic analyses were performed to assess the retinal function in adult Norrin deficient animals. We could show that the primary developmental defects not only persisted but developed into further vascular abnormalities and microangiopathies. In particular, the overall vessel homeostasis, the vascular integrity, and also the cellular constituents of the vascular wall were affected in the adult Norrin deficient retina. Moreover, functional analyses indicated to persistent hypoxia in the neural retina which was suggested as one of the major driving forces of disease progression. In summary, our data provide evidence that the key to adult Norrie disease are ongoing vascular modifications, driven by the persistent hypoxic conditions, which are ineffective to compensate for the primary Norrin-dependent defects.

Dengue serotype-specific differences in clinical manifestation, laboratory parameters and risk of severe disease in adults, singapore.

Studies on serotype-specific features of dengue and disease severity on adults are limited. We prospectively recruited adult febrile patients without alternate diagnosis to dengue from April 2005 to December 2011. Outcomes were defined using both the World Health Organization (WHO) 1997 and 2009 criteria; Dengue hemorrhagic fever (DHF) and severe dengue (SD). Infecting serotype was identified in 469 dengue-confirmed patients comprising 22.0% dengue virus serotype 1 (DENV-1), 57.1% DENV-2, 17.1% DENV-3, and 3.8% DENV-4. Cases infected with DENV-1 were more likely to present with red eyes whereas presence of joint pain and lower platelet count was associated with DENV-2 cases. After adjusting for potential confounders, DENV-1 was associated with both DHF (adjusted Relative Risk [aRR] = 1.74) and SD (aRR = 2.1) whereas DENV-2 had a lower risk of DHF (aRR = 0.5). DENV-1 genotype 1 and DENV-2 cosmopolitan were the predominant genotypes identified. Infecting dengue serotype and possibly genotype may play an important role in disease severity among adult dengue patients in Singapore.

Leflunomide in addition to steroids improves proteinuria and renal function in adult Henoch‐Schoenlein nephritis with nephrotic proteinuria

Henoch-Schoenlein nephritis (HSPN) is a severe disease in adults and may cause renal insufficiency in a large portion of patients. But its rarity has led to lack of data. There are few controlled studies on therapy with immunosuppressants in HSPN adults. This study aims to evaluate the effect of leflunomide on HSPN adults with nephrotic proteinuria. We retrospectively studied 65 adult patients who had biopsy-proven HSPN with nephrotic proteinuria. Twenty-seven patients (Group P) only received steroids, and 38 (Group P + L) were treated with leflunomide in addition to steroids. The clinical features, laboratory data and pathological findings of both groups were analyzed. The two groups were well-matched at baseline. After 24 months of treatment, urinary protein excretion of both groups decreased significantly from the baseline, and the estimated glomerular filtration rate (eGFR) was higher in Group P + L. Four patients in Group P and three in Group P + L developed to end-stage renal disease at the most recent follow-up. Group P + L showed better renal outcome than Group P. The treatment group and the degree of mesangial hypercellularity were significantly related to renal prognosis. Leflunomide combined with steroids is effective for treating adult HSPN with nephrotic proteinuria.