Cycle threshold (Ct)values of SARS-CoV2 vary with the type of symptoms and comorbidities of the patients.

BACKGROUND: Literature depicts no association of cycle threshold values for SARS-CoV-2 with the patient's demographics or clinical history. However, the severity of the COVID-19 symptoms showed some associations with Ct values in previous studies. We aimed to study the relationship of Ct values with type of the symptoms and comorbidities of the patients. METHODS AND RESULTS: We examined the individuals (n = 8660) that consulted a private diagnostic center for COVID-19 testing. Nasopharyngeal samples were collected from the patients and SARS-CoV-2 was detected by RT-PCR assays using Sansure Biotech kit. Clinical and demographic information was collected by the attending healthcare professional. The differences between groups were analyzed by t-test (unpaired). P-values < 0.05 were considered statistically significant. We found that the mean age of asymptomatic patients (41.47 ± 17.01 years) and symptomatic patients (47.75 ± 17.51) varies significantly (p value < 0.0001). Among the most prevalent symptoms were fever (77.74%) and cough (66.46%). The Ct values of COVID-19 patients with symptoms (25.70 for Orf1ab, 24.25 for N gene) were significantly lower than the Ct values of the patients without symptoms (28.99 for Orf1ab, 28.17 for N gene) (p value < 0.0001). Patients having co-occurrence of cough with fever (24.67 for Orf1ab, 22.86 for N gene) and solely fever (25.12 for Orf1ab, 24.01 for N gene) showed significantly lower Ct values than the patients without symptoms (28.99 for Orf1ab, 28.17 for N gene, p value < 0.0001). However, this difference was independent of patients sex and dependent upon patient's age and SARS-CoV-2 detected gene. The most prevalent comorbidities among COVID-19 patients were blood pressure (64.7%) and diabetes (50.5%). The patients having blood pressure and diabetes together showed significantly lower Ct values (23.37 for Orf1ab, 23.33 for N gene) than patients without comorbidities (27.65 for Orf1ab, 26.75 for N gene, p value < 0.001). CONCLUSION: We conclude that the Ct values of the SARS-CoV-2 detected gene (either Orf1ab or N) is associated with the types of symptoms and comorbidities of the COVID-19 patients. Furthermore, the relationship between Ct values and symptomology or comorbidity of the patients is independent of patient's sex but dependent upon patient's age and SARS-CoV-2 detected gene.

COVID-19 second wave and clinical characteristics of cases in Uganda: A retrospective cross-sectional survey of confirmed SARS-CoV-2 cases, March-June 2021.

We conducted a retrospective cross-sectional population-based survey among recovered COVID-19 cases in Uganda to establish the case presentations of the second wave SARS-CoV-2 infections. We interviewed 1,120 recovered COVID-19 cases from 10 selected districts in Uganda. We further conducted 38 key informant interviews with members of the COVID-19 District Taskforce and 19 in-depth interviews among COVID-19 survivors from March to June 2021. Among them, 62% were aged 39 years and below and 51.5% were female with 90.9% under home-based care management. Cases were more prevalent among businesspeople (25.9%), students (16.2%), farmers (16.1%), and health workers (12.4%). Being asymptomatic was found to be associated with not seeking healthcare (APR 2, P < 0.001). The mortality rate was 3.6% mostly among the elderly (6.3%) and 31.3% aged 40 years and above had comorbidities of high blood pressure, diabetes, and asthma. Being asymptomatic, or under home-based care management (HBCM), working/operating/studying at schools, and not being vaccinated were among the major drivers of the second wave of the resurgence of COVID19 in Uganda. Managing future COVID-19 waves calls for proactive efforts for improving homebased care services, ensuring strict observation of SOPs in schools, and increasing the uptake of COVID-19 vaccination.

Challenge of post-COVID era: management of cardiovascular complications in asymptomatic carriers of SARS-CoV-2.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), a highly pathogenic member of family coronaviridae, has caused an exponentially growing global pandemic termed as the coronavirus disease 2019 (COVID-19) with more than 12 million cases worldwide till date. This deadly disease has average fatality rate of 6.5% and even higher among elderly patients and patients with comorbidities. SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE-2) as the entry receptor into host cell. ACE-2, a type-I transmembrane metallocarboxypeptidase, is a critical regulator of the renin-angiotensin system. The entry of SARS-CoV-2 within host cells results in a reduced availability of ACE-2 on the host cell surface followed by significant downregulation of ACE-2 gene expression. As ACE-2 is a well-known cardio-protective molecule, its downregulation could result in severe cardiac disorders. This review deals with a challenging aspect of SARS-CoV-2 infected patients who are asymptomatic or have mild syndromes similar to influenza infections. These patients are proving to be the Achilles' heel to combat COVID-19 mainly in developing countries of South Asia, where the average number of tests conducted per million individuals is considerably low. Consequently, there is high possibility that individuals with negligible respiratory trouble will not be tested for SARS-CoV-2. Hence, a huge percentage of the population have the risk of developing cardiovascular disorders as a bystander effect of viral infection apart from being potential reservoir of disease transmission. Based on available demographic as well as molecular data, this review predicts a huge spike in cardiovascular disorders among this undetected reservoir in post COVID-19 era.

Diagnostic performance of a novel digital immunoassay (RapidTesta SARS-CoV-2): A prospective observational study with nasopharyngeal samples.

INTRODUCTION: Digital immunoassays are generally regarded as superior tests for the detection of infectious disease pathogens, but there have been insufficient data concerning SARS-CoV-2 immunoassays. METHODS: We prospectively evaluated a novel digital immunoassay (RapidTesta SARS-CoV-2). Two nasopharyngeal samples were simultaneously collected for antigen tests and Real-time RT-PCR. RESULTS: During the study period, 1127 nasopharyngeal samples (symptomatic patients: 802, asymptomatic patients: 325) were evaluated. For digital immunoassay antigen tests, the sensitivity was 78.3% (95% CI: 67.3%-87.1%) and the specificity was 97.6% (95% CI: 96.5%-98.5%). When technicians visually analyzed the antigen test results, the sensitivity was 71.6% (95% CI: 59.9%-81.5%) and the specificity was 99.2% (95% CI: 98.5%-99.7%). Among symptomatic patients, the sensitivity was 89.4% (95% CI; 76.9%-96.5%) with digital immunoassay antigen tests, and 85.1% (95% CI; 71.7%-93.8%) with visually analyzed the antigen test, respectively. CONCLUSIONS: The sensitivity of digital immunoassay antigen tests was superior to that of visually analyzed antigen tests, but the rate of false-positive results increased with the introduction of a digital immunoassay device.

Role of Asymptomatic COVID-19 Cases in Viral Transmission: Findings From a Hierarchical Community Contact Network Model.

As part of ongoing efforts to contain the coronavirus disease (COVID-19) pandemic, understanding the role of asymptomatic patients in the transmission system is essential for infection control. However, the optimal approach to risk assessment and management of asymptomatic cases remains unclear. This study proposed a Susceptible, Exposed, Infectious, No symptoms, Hospitalized and reported, Recovered, Death (SEINRHD) epidemic propagation model. The model was constructed based on epidemiological characteristics of COVID-19 in China and accounting for the heterogeneity of social contact networks. The early community outbreaks in Wuhan were reconstructed and fitted with the actual data. We used this model to assess epidemic control measures for asymptomatic cases in three dimensions. The impact of asymptomatic cases on epidemic propagation was examined based on the effective reproduction number, abnormally high transmission events, and type and structure of transmission. Management of asymptomatic cases can help flatten the infection curve. Tracing 75% of the asymptomatic cases corresponds to a 32.5% overall reduction in new cases (compared with tracing no asymptomatic cases). Regardless of population-wide measures, household transmission is higher than other types of transmission, accounting for an estimated 50% of all cases. The magnitude of tracing of asymptomatic cases is more important than the timing; when all symptomatic patients were traced, tested, and isolated in a timely manner, the overall epidemic was not sensitive to the time of implementing the measures to trace asymptomatic patients. Disease control and prevention within families should be emphasized during an epidemic. Note to Practitioners-This article addresses the urgent need to assess the risk of another COVID-19 outbreak caused by asymptomatic cases and to find the optimal, most practical approach to asymptomatic case management. Previous studies mostly focused on the clinical and statistical characteristics of asymptomatic cases; few have evaluated the impact of asymptomatic case measures using mathematical modeling at the community scale. This study proposed a Susceptible, Exposed, Infectious, No symptoms, Hospitalized and reported, Recovered, Death (SEINRHD) propagation model based on local community structures and social contact networks, according to the development characteristics and trend of COVID-19 in a Chinese community. The conclusion provides theoretical support for emergency work of relevant departments in different periods of an epidemic. In the early stages of the epidemic, timely detection and isolation of symptomatic patients should be a priority. Where there are surplus resources for epidemic prevention, the authorities should consider increasing the proportion of asymptomatic patients being traced. Epidemic prevention measures among family members should be a primary focus of attention. This combination of strategies can help reduce the rate of viral transmission and result in extinguishing the epidemic.

Response System for and Epidemiological Features of COVID-19 in Gyeongsangnam-do Province in South Korea.

BACKGROUND: The South Korean government has been combating the coronavirus disease 2019 (COVID-19) outbreak using public information and extensive viral screening. We describe the application of the Korean response system in Gyeongsangnam-do province and outline the epidemiological features of COVID-19 in the cohort. METHODS: A Rapid Response Team tracked the patients' activities and identified close contacts. A Patient Management Team made decisions regarding the severity of illness, hospital allocation depending on severity, and time of discharge. A national medical center with 155 beds and 4 university-affiliated hospitals with 48 negative-pressure isolation rooms were dedicated for patients with COVID-19. RESULTS: As of 15 April, 17 400 residents were tested, of whom 111 were confirmed positive cases. Of the 111 patients, 78 were cured and discharged, 2 recovered after mechanical ventilation, and none died. One healthcare worker at the national center tested positive for SARS-CoV-2. All 412 staff members at the center were tested, but there were no additional infections. Cough (30.0%) was the most common initial symptom, whereas anosmia and ageusia were the first symptoms in 14.7% and 15.7% of the patients, respectively. Overall, 25 patients (22.5%) reported having no symptoms at admission and 7 (6.3%) remained asymptomatic at discharge. CONCLUSIONS: A response system that enabled the early detection of COVID-19 cases, including asymptomatic and presymptomatic cases, and timely quarantine of these patients and their contacts, along with efficient allocation of medical resources, was the key to curbing the COVID-19 outbreak in Gyeongsangnam-do Province.

Virological and immunological features of SARS-COV-2 infected children with distinct symptomatology.

BACKGROUND: Although SARS-CoV-2 immunizations have started in most countries, children are not currently included in the vaccination programs; thus, it remains crucial to define their anti-SARS-CoV-2 immune response in order to minimize the risk for other epidemic waves. This study sought to provide a description of the virology ad anti-SARS-CoV-2 immunity in children with distinct symptomatology. METHODS: Between March and July 2020, we recruited 15 SARS-CoV-2 asymptomatic (AS) and 51 symptomatic (SY) children, stratified according to WHO clinical classification. We measured SARS-CoV-2 viral load using ddPCR and qPCR in longitudinally collected nasopharyngeal swab samples. To define anti-SARS-CoV-2 antibodies, we measured neutralization activity and total IgG load (DiaSorin). We also evaluated antigen-specific B and CD8+T cells, using a labeled S1+S2 protein and ICAM expression, respectively. Plasma protein profiling was performed with Olink. RESULTS: Virological profiling showed that AS patients had lower viral load at diagnosis (p = .004) and faster virus clearance (p = .0002) compared with SY patients. Anti-SARS-CoV-2 humoral and cellular response did not appear to be associated with the presence of symptoms. AS and SY patients showed similar titers of SARS-CoV-2 IgG, levels of neutralizing activity, and frequency of Ag-specific B and CD8+ T cells, whereas pro-inflammatory plasma protein profile was found to be associated with symptomatology. CONCLUSION: We demonstrated the development of anti-SARS-CoV-2 humoral and cellular response with any regard to symptomatology, suggesting the ability of both SY and AS patients to contribute toward herd immunity. The virological profiling of AS patients suggested that they have lower virus load associated with faster virus clearance.

Viral Replication and Antibody Kinetics in the Recognition of Asymptomatic COVID-19 Patients.

Following the discovery of COVID-19 disease caused by the SARS-CoV-2 coronavirus, different studies have been carried out to recognize the stages of the disease and the methods of achieving correct diagnosis. Investigations of cases and their contacts have revealed different degrees in the symptomatology of the disease, with asymptomatic patients gaining relevance because of the controversy regarding their role in the spread of the disease. Recognition and assessment of asymptomatic patients is essential to carry out containment actions such as public health measures for affected patients and contacts. In this review, we assess the diagnostic aspects of asymptomatic patients according to the available evidence of people with COVID-19.

Comparison of COVID-19 disease between young and elderly patients: Hidden viral shedding of COVID-19.

OBJECTIVES: The symptoms of Coronavirus disease 2019 (COVID-19) vary among patients. The aim of this study was to investigate the clinical manifestation and disease duration in young versus elderly patients. METHODS: We retrospectively analyzed 187 patients (87 elderly and 100 young patients) with confirmed COVID-19. The clinical characteristics and chest computed tomography (CT) extent as defined by a score were compared between the two groups. RESULTS: The numbers of asymptomatic cases and severe cases were significantly higher in the elderly group (elderly group vs. young group; asymptomatic cases, 31 [35.6%] vs. 10 [10%], p < 0.0001; severe cases, 25 [28.7%] vs. 8 [8.0%], p = 0.0002). The proportion of asymptomatic patients and severe patients increased across the 10-year age groups. There was no significant difference in the total CT score and number of abnormal cases. A significant positive correlation between the disease duration and patient age was observed in asymptomatic patients (ρ = 0.4570, 95% CI 0.1198-0.6491, p = 0.0034). CONCLUSIONS: Although the extent of lung involvement did not have a significant difference between the young and elderly patients, elderly patients were more likely to have severe clinical manifestations. Elderly patients were also more likely to be asymptomatic and a source of COVID-19 viral shedding.

Comparison of shoulder muscle strength, cross-sectional area, acromiohumeral distance, and thickness of the supraspinatus tendon between symptomatic and asymptomatic patients with rotator cuff tears.

BACKGROUND: The purpose of this study was to demonstrate the differences in shoulder muscle strength, cross-sectional area of the rotator cuff muscles, acromiohumeral distance, and supraspinatus tendon thickness between symptomatic and asymptomatic patients with rotator cuff tears. METHODS: Thirty-two symptomatic patients and 23 asymptomatic patients with rotator cuff tears participated in this study. Data of the patients with any type of tear and supraspinatus tear were analyzed. We evaluated the isometric torque, cross-sectional area of the rotator cuff muscles, supraspinatus tendon thickness, acromiohumeral distance, range of motion, and Western Ontario Rotator Cuff Index. RESULTS: Asymptomatic patients showed greater isometric torque of shoulder abduction and internal rotation than symptomatic patients with any type of tear (P ≤ .01). Asymptomatic patients also demonstrated greater cross-sectional area of the supraspinatus (P < .01); however, there was no significant difference in the cross-sectional area of the other cuff muscles. There was also no significant difference in the supraspinatus tendon thickness (P = .10). The acromiohumeral distance at 90° of shoulder abduction was larger (P = .04) in asymptomatic patients. Additionally, similar tendencies were observed in the results of patients with supraspinatus tears, except for the isometric torque of shoulder external rotation. This torque was greater (P < .01) in asymptomatic patients. CONCLUSION: Asymptomatic patients showed greater shoulder range of motion, muscle strength of shoulder abduction and internal rotation, small occupation ratio of supraspinatus tendon thickness as a percentage of acromiohumeral distance, and large cross-sectional area of supraspinatus.

Duration of asymptomatic status and outcomes following carotid endarterectomy and carotid artery stenting in the Carotid Revascularization Endarterectomy vs Stenting Trial.

BACKGROUND: Most carotid revascularization studies define asymptomatic as symptom-free for more than 180 days; however, it is unknown if intervention carries similar risk among those currently asymptomatic but with previous symptoms (PS) vs those who were always asymptomatic (AA). METHODS: We compared the periprocedural and 4-year risks of PS vs AA patients in the Carotid Revascularization Endarterectomy vs Stenting Trial (CREST) randomized to carotid endarterectomy (CEA) or carotid artery stenting (CAS)/angioplasty. Proportional hazards models adjusting for age, sex, and treatment were used to assess the risk of periprocedural stroke and/or death (S+D; any S+D during periprocedural period), stroke and death at 4 years (any S+D within the periprocedural period and ipsilateral stroke out to 4 years) and the primary end point at 4 years (any stroke, death, and myocardial infarction within the periprocedural period and ipsilateral stroke out to 4 years). Analysis was performed pooling the CEA-treated and CAS-treated patients, and separately for each treatment. RESULTS: Of 1181 asymptomatic patients randomized in CREST, 1104 (93%) were AA and 77 (7%) were PS. There was no difference in risk when comparing the AA and PS cohorts in the pooled CAS+CEA population for periprocedural S+D (2.0% vs 1.3%), S+D at 4 years (3.6% vs 3.2%), or the primary end point (5.2% vs 5.8%). There were also no differences among those assigned to CEA (periprocedural S+D, 1.5% vs 0%; S+D at 4 years, 2.7% vs 0%; or primary end point, 5.1% vs 2.4%) or CAS (periprocedural S+D, 2.5% vs 2.8%; S+D at 4 years, 4.4% vs 6.9%; or primary end point, 5.3% vs 9.8%) when analyzed separately. CONCLUSIONS: In CREST, only a small minority of asymptomatic patients had previous ipsilateral symptoms. The outcomes of periprocedural S+D, periprocedural S+D, and ipsilateral stroke up to 4 years, and the primary end point did not differ for AA patients compared with PS patients.

Inflammatory profile in X-linked adrenoleukodystrophy patients: Understanding disease progression.

X-linked adrenoleukodystrophy (X-ALD) is an inherited disease characterized by progressive inflammatory demyelization in the brain, adrenal insufficiency, and an abnormal accumulation of very long chain fatty acids (VLCFA) in tissue and body fluids. Considering that inflammation might be involved in pathophysiology of X-ALD, we aimed to investigate pro- and anti-inflammatory cytokines in plasma from three different male phenotypes (CCER, AMN, and asymptomatic individuals). Our results showed that asymptomatic patients presented increased levels of pro-inflammatory cytokines IL-1ß, IL-2, IL-8, and TNF-α and the last one was also higher in AMN phenotype. Besides, asymptomatic patients presented higher levels of anti-inflammatory cytokines IL-4 and IL-10. AMN patients presented higher levels of IL-2, IL-5, and IL-4. We might hypothesize that inflammation in X-ALD is related to plasmatic VLCFA concentration, since there were positive correlations between C26:0 plasmatic levels and pro-inflammatory cytokines in asymptomatic and AMN patients and negative correlation between anti-inflammatory cytokine and C24:0/C22:0 ratio in AMN patients. The present work yields experimental evidence that there is an inflammatory imbalance associated Th1, (IL-2, IL-6, and IFN-γ), Th2 (IL-4 and IL-10), and macrophages response (TNF-α and IL-1ß) in the periphery of asymptomatic and AMN patients, and there is correlation between VLCFA plasmatic levels and inflammatory mediators in X-ALD. Furthermore, we might also speculate that the increase of plasmatic cytokines in asymptomatic patients could be considered an early biomarker of brain damage and maybe also a predictor of disease progression.

High prevalence of dengue antibodies and the arginine variant of the FcγRIIa polymorphism in asymptomatic individuals in a population of Minas Gerais State, Southeast Brazil.

Dengue is the most prevalent arthropod-borne viral illness in humans worldwide. Single-nucleotide polymorphisms (SNPs) in genes involved in the immune response, such as dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), IgG Fc receptor II-A (FcγRIIa), vitamin D receptor (VDR), and tumor necrosis factor alpha (TNF-α), were previously reported to be associated with susceptibility to dengue disease in different human populations. Therefore, due to the relevant association of host immune and genetic status with disease susceptibility/severity of dengue, this work aims to verify the frequency of anti-dengue virus antibodies and some dengue-associated risk SNPs in a population in Minas Gerais State, Southeast Brazil. A total of 1560 individuals were genotyped for polymorphisms in DC-SIGN (rs4804803), FcγRIIa (rs1801274), VDR (rs7975232), and TNF-α (rs1800629). The presence of anti-dengue antibodies (IgM and/or IgG) in these samples was also assayed. Anti-dengue antibodies were detected at an overall frequency of 16.86%, indicating a virus infection in asymptomatic individuals. The genotypic frequencies of all SNPs studied did not differ between the asymptomatic and control groups. Regarding the allelic frequencies of the four SNPs analyzed, a higher frequency was detected of the G allele of FcγRIIa/rs1801274 in the asymptomatic individuals when compared to that in the control group (p = 0.03). Therefore, the results showed a high prevalence of asymptomatic individuals in Minas Gerais State, with a potential association between the presence of the G allele of FcγRIIa/rs1801274 and protection against symptomatic disease.

Prevalence of signs of celiac axis compression by the median arcuate ligament on computed tomography angiography in asymptomatic patients.

OBJECTIVE: The increasing use of computed tomography (CT) angiography has led to more frequent diagnoses of celiac artery compression (CAC) by the median arcuate ligament (MAL). The signs of CAC by the MAL have been described as stenosis and a hook or J appearance on sagittal views. The importance of the "hook signal," however, has not been documented by studies of the normal anatomy of the celiac axis. METHODS: CT angiography images of 344 completely asymptomatic, live kidney donors (without history of chronic abdominal pain or weight loss) were reviewed. The angle of emergence (AE) of the celiac axis from the aorta and the angle of upward or downward shifting of the celiac axis before its first branch (fold angle [FA]) were measured. Weight, height, and body mass index were obtained from our electronic database, and correlations with the angles measured were tested. The occurrence of stenosis >50% at the origins of the celiac axis was also determined in the sample. RESULTS: Measurements were possible in 321 cases. The celiac axis was found to leave the aorta at an angle of <90 degrees in all patients (AE range, 7-83 degrees) and <45 degrees in 292 (90%) patients. The FA ranged from 66 to 208 degrees. Before the first branch, the celiac trunk shifted upward in 306 (95%) patients, remained straight in just one of them, and shifted downward in 14 (4%). The AE was positively correlated with weight in women. The FA was negatively correlated with weight in men and women. Body mass index was positively correlated with AE and negatively correlated with FA in both men and women. In 11 cases (3.4%), stenosis >50% was found at the origin of the celiac axis. In only two patients, the celiac axis had an upward slope after the stenosis, which could be interpreted as a hook shape. CONCLUSIONS: The normal anatomy of the celiac axis, when seen on CT angiography images, demonstrates that it exits the aorta downward and then shifts upward. This hook or J shape should not be interpreted as resulting from external compression. CAC by the MAL occurs in 3.42% of the normal asymptomatic population; a hook or J shape is not visible in most cases in that subgroup.

Coronary computed tomography angiography in the evaluation of intermediate risk asymptomatic individuals.

Cardiovascular disease is still one of the main causes of death and an early identification of coronary artery disease (CAD) remains the primary step in clinical management of patients with cardiovascular risk factor. Coronary computed tomography angiography (CCTA) has shown high sensitivity in CAD detection and could be helpful as screening method. The purpose of this study was to assess the prevalence of coronary artery disease detected by CCTA in asymptomatic patients with an intermediate risk of CAD. MATERIALS AND METHODS: We retrospectively selected 185 asymptomatic patients with an intermediate Framingan Risk Score (mean age was 62.3 ± 12.4 years); all patients underwent CCTA, using 640-slice CT. RESULTS: Atherosclerotic plaques were present in 112 out of 185 patients (60.5%); 56 subjects (30.2%) had mild stenosis, 49 (26.5%) moderate stenosis, only 3 patients (1.6%) had severe stenosis and in 4 cases (2.2%) the "blooming effect" did not allow for evaluation of the degree of stenosis. Among the positive cases, a high number of patients (44.6%) [50] showed coronary artery disease in one vessel, 33 patients (29.4%) in two vessels, 22 patients (19.6%) in three vessels and 5 patients in four vessels or more (4.5%). Patients with moderate stenosis were older, had hypertension in most cases, higher total cholesterol levels and more often were smokers. The radiation dose (mSv) dispensed to the patients was 3.7 ± 1.6 mSv. CONCLUSION: High prevalence of coronary stenosis detected by low-dose CCTA in patients not properly classified by the traditional methods of risk stratification commonly used in clinical practice emphasizes the need to extend the risk stratification to other diagnostic tools with higher capability to detect CAD.

Distribution and Quantitative Estimates of Variant Creutzfeldt-Jakob Disease Prions in Tissues of Clinical and Asymptomatic Patients.

In the United-Kingdom, ≈1 of 2,000 persons could be infected with variant Creutzfeldt-Jakob disease (vCJD). Therefore, risk of transmission of vCJD by medical procedures remains a major concern for public health authorities. In this study, we used in vitro amplification of prions by protein misfolding cyclic amplification (PMCA) to estimate distribution and level of the vCJD agent in 21 tissues from 4 patients who died of clinical vCJD and from 1 asymptomatic person with vCJD. PMCA identified major levels of vCJD prions in a range of tissues, including liver, salivary gland, kidney, lung, and bone marrow. Bioassays confirmed that the quantitative estimate of levels of vCJD prion accumulation provided by PMCA are indicative of vCJD infectivity levels in tissues. Findings provide critical data for the design of measures to minimize risk for iatrogenic transmission of vCJD.

Impact of sex and age on carotid plaque instability in asymptomatic patients-results from the Munich Vascular Biobank.

BACKGROUND: It is still a controversial issue whether carotid endarterectomy (CEA) for asymptomatic carotid stenosis is superior to best medical treatment. The aim of this study was therefore to analyze the impact of sex and age on carotid plaque instability in asymptomatic patients undergoing CEA. PATIENTS AND METHODS: Atherosclerotic plaques from 465 asymptomatic patients with high-grade carotid artery stenosis (2004 - 2013) at the Munich Vascular Biobank were analyzed. Ascertainment of lesion stability/instability was performed on formalin-fixed paraffin-embedded tissue samples using hematoxylin-eosin and elastic van Gieson staining. Unstable plaques were considered lesions with a fibrous cap < 200 µm overlaying lipid-rich atheroma. RESULTS: The average age of the patients was 69.3 ± 8.2 years. Independent of age, asymptomatic men had in total more frequently unstable plaques in contrast to women (41 % versus 52%, p = 0.042). No differences were found in plaque instability between age-related quartiles (< 65, 65- 69, 70 - 74, > 74 years) for female sex (p = 0.422). In men, a continuous increase in plaque instability with age was observed, without achieving statistical significance (p = 0.125). The greatest differences between male and female sex were found in the last quartile (> 74 years), without achieving statistical significance (p = 0.053). The chance of unstable carotid plaques in men was significantly higher than in women (OR = 1.562, p = 0.040). The probability of age-associated quartiles related to the first quartile demonstrated significant increase in plaque instability in the group of 65- to 69-year-old patients (OR 1.867, p = 0.024) and for patients older than 74 years (OR 1.740, p = 0.040). CONCLUSIONS: Asymptomatic men had in total more frequently unstable plaques in contrast to women. Thus, male sex seems to be an additional risk factor for ischemic stroke.

Late diagnosis of HIV infection in asymptomatic patients.

Recent findings from the START Trial provided evidence that early initiation of antiretroviral treatment should be implemented as the global standard of care. However, a large proportion of patients are still being diagnosed in late stages. Our objective was to evaluate the temporal trend in the CD4+ cell count at diagnosis during a 13 year period and the factors associated with late HIV diagnosis in asymptomatic individuals tested in the Centre for Prevention, Counselling and Diagnosis of our hospital. It was a retrospective study including all asymptomatic patients with new diagnosis of HIV infection. Very late presenters (VLP) were defined as those with CD4+ counts < 200 and late presenters (LP) with CD4+ < 350 cell/mm3. We also evaluated the proportion of patients diagnosed with CD4+ cell counts below 500 cell/mm3. Between January 2002 and December 2014, 20 263 patients were tested for HIV, 1104 with a positive result of whom 995 asymptomatic individuals were included. Overall, median CD4+ count was 372 cells/mm3 and HIV-RNA 31 145 copies/ml. There was no evidence that the CD4+ count at diagnosis progressively increased over time, nor that the proportion of VLP and LP decreased. In a multivariate model older age, heterosexual transmission and intravenous drug use remained as independent factors associated with LP. In conclusion, late diagnosis of HIV infection remains prevalent among asymptomatic patients, highlighting the need to continue implementing strategies towards early diagnosis.

Alteration or adaptation, the two roads for human gastric mucin glycosylation infected by Helicobacter pylori.

Helicobacter pylori is a Gram-negative bacterium that colonizes the mucus niche of the gastric mucosa and infects more than half of the world's human population. Chronic infection may cause gastritis, duodenal ulcer, intestinal metaplasia or gastric cancer. In the stomach, H. pylori interacts with O-glycans of gastric mucins but the mechanism by which the bacteria succeed in altering the mucosa remains mainly unknown. To better understand the physiopathology of the infection, inhibitory adhesion assays were performed with various O-glycans expressed by human gastric mucins, and topographic expression of gastric mucins MUC5AC and MUC6 was analyzed for healthy uninfected individuals, for infected asymptomatic individuals and for patients infected by H. pylori and having the incomplete type of intestinal metaplasia. The glycosylation of the gastric mucosa of asymptomatic individuals infected by H. pylori was determined and compared with the glycosylation pattern found for patients with the incomplete type of intestinal metaplasia. Results show that H. pylori manages to modulate host's glycosylation during the course of infection in order to create a favorable niche, whereas asymptomatic infected individuals seem to counteract further steps of infection development by adapting their mucus glycosylation.

WFUMB Review Paper. Incidental Findings in Otherwise Healthy Subjects, How to Manage: Liver.

An incidental focal liver lesion (IFLL) is defined as a hepatic lesion identified in a patient imaged for an unrelated reason. They are frequently encountered in daily practice, sometimes leading to unnecessary, invasive and potentially harmful follow-up investigations. The clinical presentation and the imaging aspects play an important role in deciding if, and what further evaluation, is needed. In low-risk patients (i.e., without a history of malignant or chronic liver disease or related symptoms), especially in those younger than 40 years old, more than 95% of IFLLs are likely benign. Shear Wave liver Elastography (SWE) of the surrounding liver parenchyma should be considered to exclude liver cirrhosis and for further risk stratification. If an IFLL in a low-risk patient has a typical appearance on B-mode ultrasound of a benign lesion (e.g., simple cyst, calcification, focal fatty change, typical hemangioma), no further imaging is needed. Contrast-Enhanced Ultrasound (CEUS) should be considered as the first-line contrast imaging modality to differentiate benign from malignant IFLLs, since it has a similar accuracy to contrast-enhanced (CE)-MRI. On CEUS, hypoenhancement of a lesion in the late vascular phase is characteristic for malignancy. CE-CT should be avoided for characterizing probable benign FLL and reserved for staging once a lesion is proven malignant. In high-risk patients (i.e., with chronic liver disease or an oncological history), each IFLL should initially be considered as potentially malignant, and every effort should be made to confirm or exclude malignancy. US-guided biopsy should be considered in those with unresectable malignant lesions, particularly if the diagnosis remains unclear, or when a specific tissue diagnosis is needed.