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Angina is a significant contributor to disability and impairment in quality of life in patients with chronic coronary syndromes (CCS). An elevated heart rate (HR) may trigger myocardial ischemia by increasing oxygen consumption and decreasing the diastolic time, compromising the coronary flow. HR-lowering strategies offer symptom control and prevent cardiovascular events in subgroups of patients with CCS. However, the best therapeutic approach to achieve the desired HR in patients with CCS can be challenging based on efficacy and tolerability. Guidelines usually propose β-blockers and/or non-dihydropyridine calcium channel blockers (CCB) for angina patients with elevated HR. Nonetheless, there is no clear evidence of greater antianginal efficacy of this strategy versus an alternative HR-lowering agent. Ivabradine reduces the HR by blocking the If current in the sinoatrial node without affecting myocardial contractility or vascular tone. The magnitude of the HR reduction by ivabradine is proportional to the initial HR, which decreases the risk of significant bradycardia. Ivabradine increases the diastolic time and the coronary flow reserve to a greater extent than β-blockers and favors collateralization, improving the regional blood flow. We present two clinical cases of patients with symptomatic CCS in whom HR control with ivabradine was fundamental for symptom control and improvement in left ventricular (LV) function. An earlier combination of ivabradine plus β-blockers would have provided more rapid symptom control and improved LV function in the first case. In the second case, the primary mechanism responsible for angina was most likely a coronary vasomotor abnormality, in which the use of β-blockers aggravated the discomfort. The combination of a dihydropyridine CCB plus ivabradine was highly influential in symptom control. Due to its effects beyond HR reduction and good tolerability, ivabradine should be considered an essential ally in managing patients with angina and high HR with or without LV dysfunction.

Background Antigen testing offers rapid and inexpensive testing for SARS-CoV-2 but concerns regarding performance, especially sensitivity, remain. Limited data exists for use of antigen testing in asymptomatic patients; thus, performance and reliability of antigen testing remains unclear. Methods 148 symptomatic and 144 asymptomatic adults were included. A nasal swab was collected for testing by Quidel Sofia SARS IFA (Sofia) as point of care. A nasopharyngeal swab was also collected and transported to the laboratory for testing by Cepheid Xpert Xpress SARS-CoV-2/Flu/RSV RT-PCR (Cepheid). Results Overall, Sofia had good agreement with Cepheid (> 95%) in adults, however was less sensitive. Sofia had a sensitivity of 87.8% and 33.3% for symptomatic and asymptomatic patients, respectively. Among symptomatic patients, testing > 5 days post symptom onset resulted in lower sensitivity (82%) when compared with testing within 5 days of symptom onset (90%). Of the four Sofia false-negative results in the asymptomatic cohort, 50% went on to develop COVID-19 disease within 5 days of testing. Specificity in both symptomatic and asymptomatic cohorts was 100%. Conclusions Sofia has acceptable performance in symptomatic adults when tested 5 days of symptom onset and asymptomatic patients.

Objective: To investigate possible differences between laboratory profiles of symptomatic and asymptomatic patients. There are different of them available for COVID-19 diagnoses and surveillance, so this research was to evaluate the positive agreement the diagnostic methods. Methods: For symptomatic patients swab samples from nasal and oral mucosal were collected between first and second week after symptoms onset, to perform RT-PCR, blood samples were collected 7 days after to perform antibody detection test. For asymptomatic patients, only antibody detection was performed to confirm the infection. We investigated specific humoral immune response for symptomatic and asymptomatic patients and also analyzed the positivity index and kappa agreement between immunochromatographic and ELISA assays. Results: Most symptomatic patients presented negative RT-PCR with IgM and IgA detection. Symptomatic and asymptomatic patients have presented elevated IgM and IgA immunoglobulins, being this detection higher in symptomatic patients. The positivity index for immunochromatographic was higher than ELISA and there was no kappa agreement between IgM and IgA detection between these two methods. Conclusion: Symptomatic patients presented higher amounts of IgM and IgA than asymptomatic, suggesting a relation between antibody quantity and severity of disease. We verified no agreement between IgM and IgA detection, and observed higher positivity index for IMMUNO when compared to ELISA. The different kinetics may cause a variation in their detection. Also, many different virus proteins can be used as antigens in these methods, being able of altering their sensibility and specificity.

Background Intestinal parasitic infections are amongst the most common infections worldwide and have been identified as one of the most significant causes of morbidity and mortality among disadvantaged populations. This comparative cross-sectional study was conducted to assess the prevalence of intestinal protozoan infections and to identify the significant risk factors associated with intestinal parasitic infections in Laghouat province, Southern Algeria. Methods A comparative cross-sectional study was conducted, involving 623 symptomatic and 1654 asymptomatic subjects. Structured questionnaires were used to identify environmental, socio demographic and behavioral factors. Stool specimens were collected and examined using direct wet mount, formalin-ether concentration, xenic in vitro culture and staining methods. Results A highly significant difference of prevalence was found between symptomatic (82.3%) and asymptomatic subjects (14.9%), with the majority attributable to protozoan infection. The most common species in the symptomatic subjects were Blastocystis spp. (43.8%), E. histolytica/dispar (25.4%) and Giardia intestinalis (14.6%) and more rarely Enterobius vermicularis (02.1%), Teania spp. (0.6%) and Trichuris trichiura (0.2%), while in asymptomatic population Blastocystis spp. (8%), Entamoeba coli (3.3%) and Entamoeba histolytica/dispar (2.5%) were the most common parasites detected with no case of helminth infection. Multivariate log-linear analysis showed that contact with animals was the main risk factor for transmission of these protozoa in both populations. Furthermore, living in rural areas was significantly associated with combined protozoan infection in the asymptomatic population, whereas, in the symptomatic population an increasing trend of protozoan infection was detected in the hot season. In addition, Blastocystis spp. and G. intestinalis infection were found to be associated with host sex and contact with animals across the study period. Conclusions Based on these results, several strategies are recommended in order to effectively reduce these infections including good animal husbandry practices, health education focused on good personal hygiene practices and adequate sanitation.

Background Guidelines for urgent investigation of colorectal cancer (CRC) are based on age and symptom-based criteria. This study aims to compare the diagnostic value of clinical features and faecal immunochemical test (FIT) results to identify those at a higher risk of CRC, thereby facilitating effective triage of patients. Methods We undertook a review of all patients referred for investigation of CRC at our centre between September 2016 and June 2018. Patients were identified using a prospectively recorded local database. We performed a logistic regression analysis of factors associated with a diagnosis of CRC. Results One-thousand-and-seven-hundred-eighty-four patients with FIT results were included in the study. Change in bowel habit (CIBH) was the most common referring clinical feature (38.3%). Patients diagnosed with CRC were significantly older than those without malignancy (74.0 years vs 68.9 years, p = 0.0007). Male patients were more likely to be diagnosed with CRC than females (6.5% vs 2.5%, Chi-squared 16.93, p

A model of a COVID-19 epidemic is used to predict the effectiveness of vaccination in the US. The model incorporates key features of COVID-19 epidemics: asymptomatic and symptomatic infectiousness, reported and unreported cases data, and social measures implemented to decrease infection transmission. The model analyzes the effectiveness of vaccination in terms of vaccination efficiency, vaccination scheduling, and relaxation of social measures that decrease disease transmission. The model demonstrates that the subsiding of the epidemic as vaccination is implemented depends critically on the scale of relaxation of social measures that reduce disease transmission.

Background In December 2019 an outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 was first observed in Wuhan, China. The virus has spread rapidly throughout the world creating a pandemic scenario. Several risk factors have been identified, such as age, sex, concomitant diseases as well as viral load. A key point is the role of asymptomatic people in spreading SARS-CoV-2. An observational study in Southern Italy was conducted in order to elucidate the possible role of asymptomatic individuals related to their viral loads in the transmission of the virus within two nursing facilities. Methods Oro-nasopharyngeal swabs from 179 nursing health care workers and patients were collected. SARS-CoV-2 RT-qPCR was performed and viral loads were calculated by using standard curve. A statistical correlation between viral loads, the presence/absence of symptoms, age and sex variables was investigated. Results SARS-CoV-2 was confirmed in the 50.8 % (n = 91) of the cases. Median age of positive individuals resulted higher than negative ones. Over 65 year as well as female individuals showed higher susceptibility to SARS-CoV-2 infection, OR = 3.93 and 2.86, respectively. Among 91 tested positive, the 70.3 % was symptomatic while the 29.7 % was asymptomatic. Median viral loads of asymptomatic individuals were found statistically significant higher than symptomatic ones (p = 0.001), while no influence was observed in age and sex variables. The presence of comorbidities was 8.9 folds higher in patients who showed and developed symptoms compared to non-symptomatic ones. Moreover, higher viral loads were found in patients who remained asymptomatic than pre-symptomatic (p = 0.022). Conclusions A range from 9.2 to 69 % of confirmed SARS-CoV-2 cases remains asymptomatic, moreover, sporadic transmissions from asymptomatic people are reported, that makes their involvement an important issue to take into account in the spreading control of the virus. An asymptomatic clinical course was observed in the 29.7 % of positive individuals, moreover, median viral loads resulted to be statistically significant when compared to symptomatic ones. Surely, such a relevant frequency should not be ignored in relation to the spread of the disease in an environment which has not only important intrinsic (age, sex, concomitant diseases) but also extrinsic factors such as high population density and close contacts.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread globally and is a major public health issue. Procedures that have been established to decrease the spread of the virus depend on the careful and precise detection of infected individuals using quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). There have been many ambiguous concerns among the public regarding the severity of infection and its connection with the Cycle threshold (Ct) value and there was forceful need to inform the values to the public especially those with symptoms. The main objective of this study was to determine the association between the E (Envelop) gene Ct values of the symptomatic and asymptomatic COVID 19 patients. The study was conducted at the Virus Research and Diagnostic Laboratory (VRDL), Jagdalpur, Chhattisgarh. Between March 2020 and June 2020, samples were collected from the Bastar region as per the Indian Council of Medical Research (ICMR) guidelines. A total of 29228 clinical samples were tested by qRT-PCR targeting the E and RdRp (RNA-dependant RNA polymerase) genes as well as the ORF (open reading frame) gene that encode polyproteins of SARS-CoV-2. Of the 29228 samples tested, 75 were tested positive and 29153 were tested negative. In addition, the Ct values varied between the symptomatic and asymptomatic patients. It was observed that, the Ct values ranged from 15 to 32 in the asymptomatic patients and between 13 to 34 in the symptomatic patients. E gene Ct value analysis showed no significant difference between the asymptomatic and symptomatic COVID-19 patients. Thus, we observed that there was no association between the Ct values of symptomatic and asymptomatic patients of COVID-19.

CT colonography has emerged as the investigation of choice for suspected colorectal cancer in patients when a colonoscopy in incomplete, is deemed high risk or is declined because of patient preference. Unlike a traditional colonoscopy, it frequently reveals extracolonic as well as colonic findings. Our study aimed to determine the prevalence, characteristics and potential significance of extracolonic findings on CT colonography within our own institution. A retrospective review was performed of 502 patients who underwent CT colonography in our institution between January 1, 2010 and January 4, 2015. Of 502 patients, 60.63% had at least one extracolonic finding. This was close to other similar-sized studies (Kumar et al. Radiology 236(2):519-526, 2005). However, our rate of E4 findings was significantly higher than that reported in larger studies at 5.3%(Pooler et al. AJR 206:313-318, 2016). The difference may be explained by our combination of symptomatic/screening patients or by the age and gender distribution of our population. Our study lends support to the hypothesis that CT colonography may be particularly useful in identifying clinically significant extracolonic findings in symptomatic patients. CT colonography may allow early identification of extracolonic malignancies and life-threatening conditions such as an abdominal aortic aneurysm at a preclinical stage when they are amenable to medical or surgical intervention. However, extracolonic findings may also result in unnecessary investigations for subsequently benign findings.

Highlights • Serum IgG antibody responses developed in 95% of mildly symptomatic individuals by day 14 and all subjects had seroconverted by day 30. • Serum IgM and IgA antibody responses were lower and less frequent than corresponding IgG responses, and peaked and declined earlier 100% of mild symptomatic individuals developed an IgG antibody response by day 30. • Fewer than 45% of asymptomatic infected individuals had seroconverted by day 30 post-PCR diagnosis. • Impact on modeling of herd immunity., Objectives Studies on serologic responses following COVID-19 have been published primarily in individuals who are moderately or severely symptomatic, but there are few data from individuals who are mildly symptomatic or asymptomatic. Methods We measured IgG, IgM, and IgA to the receptor-binding domain of SARS-CoV-2 by ELISA in mildly symptomatic (n = 108) and asymptomatic (n = 63) on days 1, 7, 14, and 30 following RT-PCR confirmation in Bangladesh, and compared with pre-pandemic samples, including healthy controls (n = 73) and individuals infected with other viruses (n = 79). Results Mildly symptomatic individuals developed IgM and IgA responses by day 14 in 72% and 83% of individuals, respectively, while 95% of individuals developed IgG response, and rose to 100% by day 30. In contrast, individuals infected with SARS-CoV-2 but who remained asymptomatic developed antibody responses significantly less frequently, with only 20% positive for IgA and 22% positive for IgM by day 14, and 45% positive for IgG by day 30 after infection. Conclusions These results confirm immune responses are generated following COVID-19 who develop a mildly symptomatic illness. However, those with the asymptomatic infection do not respond or have lower antibody levels. These results will impact modeling needed for determining herd immunity generated by natural infection or vaccination.

Objectives:Evaluate the relevance of the coronavirus disease 2019 (COVID-19) positive case detection policy or model implemented by the Ministry of Public Health (MPH) of Ecuador and to compare it with the experiences of other countries.Methods:Data contained the daily reports publicized by the MPH. The formulations were carried out under the Conditioned Probability modality applying Bayes’ Theorem. All the COVID-19 tests applied in relation to the confirmed cases per million inhabitants were considered to obtain their level of positivity, and compared with the experience of Iceland and South Korea.Results:The probability of detecting positive cases of COVID-19 in Ecuador was higher than Iceland and South Korea, because the diagnostic tests were aimed at symptomatic patients, without identifying asymptomatic or mild symptomatic, who play an important role in the transmission of the disease. In addition, many symptomatic patients were examined but will remain undiagnosed due to the unavailability of tests and the low quality of many of them.Conclusions:The daily reports on the behavior of the COVID-19 issued by the Ecuadorian government do not adequately represent the growth in the number of those infected each day, nor the actual behavior of the epidemic, affecting possible control measures.

Background: This study aims to investigate the association of lipid ratios with intracranial atherosclerotic stenosis (ICAS) in a Chinese population.Methods: This cross-sectional study included 658 consecutive patients with ischemic stroke. Intracranial and extracranial arteries were evaluated for atherosclerotic stenosis using digital subtraction angiography or computed tomography angiography. Lipid ratios [total cholesterol (TC)/high-density lipoprotein-cholesterol (HDL-C), triglycerides (TG)/HDL-C, low-density lipoprotein-cholesterol (LDL-C)/HDL-C, non-high-density lipoprotein-cholesterol (non-HDL-C)/HDL-C, remnant cholesterol (RC)/HDL-C, apolipoprotein B (apo B)/apolipoprotein A-I (apo A-I), and apo B/HDL-C] were calculated.Results: The TC/HDL-C, LDL-C/HDL-C, RC/HDL-C, non-HDL-C/HDL-C, apo B/HDL-C and apo B/apo A-I ratios (all P Conclusion: The TC/HDL-C, LDL-C/HDL-C, RC/HDL-C, non-HDL-C/HDL-C apo B/HDL-C, and apo B/apo A-I ratios were significantly related to ICAS risk. Compared with the other variables tested, the apo B/apo A-I ratio appeared to be a better discriminator for identifying ICAS risk in stroke patients.

Introduction Currently, 15–20% of individuals with coronary artery disease (chronic coronary syndrome [CCS]) or peripheral artery disease (PAD) receiving routine treatment experience cardiovascular events (CVEs) within 3–4 years. Using PICOSTEPS (Patients-Intervention-Comparators-Outcomes-Setting-Time-Effects-Perspective-Sensitivity analysis) reporting, we evaluated the cost-effectiveness of recently approved rivaroxaban 2.5 mg twice daily in combination with acetylsalicylic acid 100 mg daily (RIV + ASA) for the prevention of CVEs among Finns with CCS or symptomatic PAD. Methods Myocardial infarction, ischemic stroke, intracranial hemorrhage, acute limb ischemia, amputations, major extracranial bleeding, venous thromboembolism, and cardiovascular deaths were modeled in a Markov model examining a cohort of patients with CCS or symptomatic PAD. Relative effects of the intervention (RIV + ASA) and comparator (ASA) were based on the COMPASS trial. The primary outcome was 3%/year discounted incremental cost-effectiveness ratio (ICER), defined as cost (2019 euros) per quality-adjusted life year (QALY) gained in the Finnish setting over a lifetime horizon. In addition to nonfatal and fatal CVEs, the effects factored Finnish non-CVE mortality, quality of life, and direct costs from a public payer perspective. Disaggregated costs and QALYs, costs per life year gained (LYG), and ischemic strokes avoided, net monetary benefit (NMB), expected value of perfect information (EVPI), economic value-added (EVA), cost-effectiveness table, and acceptability frontier were examined. Probabilistic and deterministic sensitivity analyses were conducted. Results In the deterministic comparison with ASA over a lifetime horizon, RIV + ASA resulted in a benefit of 0.404 QALYs and 0.474 LYGs for an additional cost of €3241, resulting in an ICER of €8031/QALY. The probabilistic ICER was €4313/QALY (EVPI €1829/patient). RIV + ASA had positive NMB (€8791/patient), low EVPI (€88/patient), high EVA (€8703/patient), and 91% probability of cost-effectiveness using the willingness-to-pay of €25,254/QALY. The primary result was conservative and robust for RIV + ASA. Conclusion RIV + ASA was a cost-effective treatment alternative compared with ASA in patients with CCS or symptomatic PAD in Finland. Electronic supplementary material The online version of this article (10.1007/s12325-020-01398-8) contains supplementary material, which is available to authorized users., Plain Language Summary Finland lacks published evidence on the cost-effectiveness of approved interventions for the prevention of cardiovascular events among individuals with chronic coronary syndrome (stable coronary artery disease) or symptomatic peripheral artery disease at risk of cardiovascular complications. Rivaroxaban 2.5 mg twice daily plus acetylsalicylic acid 100 mg once daily is indicated and reimbursed in Finland for the prevention of cardiovascular events for patients with stable coronary artery disease or symptomatic peripheral artery disease. We assessed the effectiveness and costs of treatment with rivaroxaban plus acetylsalicylic acid in comparison with treatment with acetylsalicylic acid. That is, we examined whether rivaroxaban is cost-effective when prescribed in combination with acetylsalicylic acid. Cardiovascular events with their associated costs and impact on quality of life were modeled over the lifetime of patients. The main effectiveness outcome was quality-adjusted life years (modeled survival multiplied by the expected quality of life), and costs included those relevant to the Finnish public payer in 2019. Extensive sensitivity analyses were carried out to evaluate the impacts of different model inputs and rationale. Rivaroxaban plus acetylsalicylic acid had high probability of being cost-effective, compared with acetylsalicylic acid. By valuing quality-of-life benefit with a plausible willingness-to-pay, net cost savings of €8791 per patient could be gained or economic value added by €8703 per patient if rivaroxaban was used. Electronic supplementary material The online version of this article (10.1007/s12325-020-01398-8) contains supplementary material, which is available to authorized users.

Aim The long-term value of coronary artery calcium (CAC) scanning has not been studied extensively in symptomatic patients, but was evaluated by us in 644 consecutive patients referred for stable chest pain. Methods We excluded patients with a history of cardiovascular disease and with a CAC score of zero. CAC scanning was done with a 16-row MDCT scanner. Endpoints were: (a) overall mortality, (b) mortality or non-fatal myocardial infarction and (c) the composite of mortality, myocardial infarction or coronary revascularisation. Revascularisations within 1 year following CAC scanning were not considered. Results The mean age of the 320 women and 324 men was 63 years. Follow-up was over 8 years. There were 58 mortalities, while 22 patients suffered non-fatal myocardial infarction and 24 underwent coronary revascularisation, providing 104 combined endpoints. Cumulative 8‑year survival was 95% with CAC score 100 and 100 and ≥400 units was 2.6 [95% confidence interval (CI) 1.23–5.54], and 4.6 (95% CI 2.1–9.47) respectively. After correction for clinical risk factors, CAC score remained independently associated with increased risk of cardiac events. Conclusions Risk increased with increasing CAC score. Patients with CAC >100 or ≥400 Agatston units were at increased risk of major adverse cardiac events and are eligible for preventive measures. CAC scanning provided incremental prognostic information to guide the choice of diagnostic and therapeutic options in many subjects evaluated for chest pain.

Neuromyelitis optica spectrum disorders (NMOSD) are a group of autoimmune inflammatory conditions that primarily target the optic nerves, spinal cord, brainstem, and occasionally the cerebrum. NMOSD is characterized by recurrent attacks of visual, motor, and/or sensory dysfunction that often result in severe neurological deficits. In recent years, there has been a significant progress in relapse treatment and prevention but the residual disability per attack remains high. Although symptomatic and restorative research has been limited in NMOSD, some therapeutic approaches can be inferred from published case series and evidence from multiple sclerosis literature. In this review, we will discuss established and emerging therapeutic options for symptomatic treatment and restoration of function in NMOSD. We highlight NMOSD-specific considerations and identify potential areas for future research. The review covers pharmacologic, non-pharmacologic, and neuromodulatory approaches to neuropathic pain, tonic spasms, muscle tone abnormalities, sphincter dysfunction, motor and visual impairment, fatigue, sleep disorders, and neuropsychological symptoms. In addition, we briefly discuss remyelinating agents and mesenchymal stem cell transplantation in NMOSD., Open access funding provided by the Guthy-Jackson Charitable Foundation

International audience; The development of new possible treatments for C9orf72-related ALS and the possibility of early identification of subjects genetically at risk of developing the disease is creating a critical need for biomarkers to track neurodegeneration that could be used as outcome measures in clinical trials. Current candidate biomarkers in C9orf72-ALS include neuropsychology tests, imaging, electrophysiology as well as different circulating biomarkers. Neuropsychology tests show early executive and verbal function involvement both in symptomatic and asymptomatic mutation carriers. At brain MRI, C9orf72-ALS patients present diffuse white and grey matter degeneration, which are already identified up to 20 years before symptom onset and that seem to be slowly progressive over time, while regions of altered connectivity at fMRI and of hypometabolism at [18F]FDG PET have been described as well. At the same time, spinal cord MRI has also shown progressive decrease of FA in the cortico-spinal tract over time. On the side of wet biomarkers, neurofilament proteins are increased both in the CSF and serum just before symptom onset and tend to slowly increase over time, while poly(GP) protein can be detected in the CSF and probably used as target engagement marker in clinical trials.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Understanding the influence of mutations in the SARS-CoV-2 gene on clinical outcomes is critical for treatment and prevention. Here, we analyzed all high-coverage complete SARS-CoV-2 sequences from GISAID database from January 1, 2020, to January 1, 2021, to mine the mutation hotspots associated with clinical outcome and developed a model to predict the clinical outcome in different epidemic strains. Exploring the cause of mutation based on RNA-dependent RNA polymerase (RdRp) and RNA-editing enzyme, mutation was more likely to occur in severe and mild cases than in asymptomatic cases, especially A > G, C > T, and G > A mutations. The mutations associated with asymptomatic outcome were mainly in open reading frame 1ab (ORF1ab) and N genes; especially R6997P and V30L mutations occurred together and were correlated with asymptomatic outcome with high prevalence. D614G, Q57H, and S194L mutations were correlated with mild and severe outcome with high prevalence. Interestingly, the single-nucleotide variant (SNV) frequency was higher with high percentage of nt14408 mutation in RdRp in severe cases. The expression of ADAR and APOBEC was associated with clinical outcome. The model has shown that the asymptomatic percentage has increased over time, while there is high symptomatic percentage in Alpha, Beta, and Gamma. These findings suggest that mutation in the SARS-CoV-2 genome may have a direct association with clinical outcomes and pandemic. Our result and model are helpful to predict the prevalence of epidemic strains and to further study the mechanism of mutation causing severe disease.

COVID-19 is a disease that is caused by a highly transmissible and pathogenic novel coronavirus: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). All of the COVID-19 positive cases in Bhutanese travellers returning via the Phuentsholing point of entry, the local population, and Indian nationals were isolated in the Phuentsholing COVID-19 isolation ward, Bhutan. This study aimed to identify the risk factors for developing symptoms among COVID-19 positive patients in this ward. A retrospective cohort study was conducted using the data regarding COVID-19 positive cases in the Phuentsholing COVID-19 isolation ward from 28 May 2020 to 31 May 2021. The Cox proportional hazards regression model was used to identify the risk factors of developing COVID-19 symptoms. There were 521 patients in the study, 368 (70.6%) were males and 153 (29.4%) were females. The mean age was 32 years (with a range of 1–78 years), and 290 (56.0%) reported at least one symptom. The median length of isolation was eight days (with a range of 3–48 days). The common symptoms were: cough (162, 31.0%), fever (135, 26.0%), and headache (101, 19.0%). In the multivariable Cox regression, vaccinated patients were 77.0% (p = 0.047) less likely to develop symptoms compared to those who were not vaccinated. The front line workers and the mini-dry port (MDP) workers were 15 (p = 0.031) and 41 (p &lt, 0.001) times more likely to be symptomatic compared to returning travellers. The young and economically active population group was most commonly affected by COVID-19. The presence of risk factors, such as being front line workers, MDP workers, or not being vaccinated against COVID-19, meant that patients had a higher probability of developing symptoms of COVID-19.

Purpose: This real-world study evaluated the effectiveness of different inhalation therapies in patients with symptomatic chronic obstructive pulmonary disease (COPD) in China and also explored the relevant factors that influence the effectiveness of inhalation therapy.Patients and Methods: We conducted a multicenter prospective longitudinal study that was carried out in 12 hospitals in China from December 2016 to June 2021. A face-to-face interview was conducted to collect data. Baseline data were collected at the first visit. Minimum clinically important difference (MCID) was defined as attaining a COPD assessment test (CAT) decrease ≥2. We mainly assessed the MCID and the incidence of exacerbations at the 6 months follow-up.Results: In 695 patients, the mean age was 62.5 ± 8.2 years, with a mean CAT score of 15.1 ± 6.0. Overall, 341 (49.1%) patients attained the MCID of CAT and the incidence of exacerbation during follow-up was 22.3%. Females were significantly more likely to attain MCID than male in COPD patients (adjusted odd ratio (aOR) = 1.93, adjusted 95% confidence interval (a95%CI) = 1.09–3.42, p = 0.024). Patients treated with LABA/LAMA or ICS/LABA/LAMA (ICS, inhaled corticosteroid; LABA, long-acting β2-agonist; LAMA, long-acting muscarinic antagonist) were more likely to attain MCID than patients treated with LAMA (aOR = 3.97, a95%CI = 2.48–6.35, p < 0.001; aOR = 3.17, a95%CI = 2.09–4.80, p < 0.001, respectively). Patients treated with LABA/LAMA had a higher incidence of severe exacerbation than patients treated with ICS/LABA/LAMA (aOR = 1.95, a95%CI = 1.04–3.66, p = 0.038).Conclusion: The incidence of MCID in symptomatic COPD patients treated with inhalation therapy was nearly 50%. Patients treated with LABA/LAMA or ICS/LABA/LAMA were more likely to attain MCID than patients treated with LAMA. Patients treated with LABA/LAMA had a higher incidence of severe exacerbations than with ICS/LABA/LAMA.

Central venous catheters (CVC) are widely used in critically ill patients given their benefits in monitoring vital signs, treatment administration, and renal replacement therapy in intensive care unit (ICU) patients, but these catheters have the potential to induce symptomatic catheter-related venous thrombosis (CRVT). This study reported the rate of symptomatic CRVT in ICU patients receiving CVC and analyzed the disease-related risk factors for symptomatic CRVT in ICU patients. A retrospective analysis was performed on the consecutive ICU 1643 critically ill patients with CVCs inserted from January 2015 to December 2019. Symptomatic CRVT was confirmed by ultrasound. CVCs were divided into 2 groups based on the presence of symptomatic CRVT, and the variables were extracted from the electronic medical record system. Logistic univariate and multivariate regression analyses were used to determine the disease-related risk factors of symptomatic CRVT. A total of 209 symptomatic CRVT events occurred among 2114 catheters. The rate of CRVT was 9.5 per 1000 catheter days. Univariate analysis revealed that trauma, major surgery, heart failure, respiratory failure, and severe acute pancreatitis were risk factors for symptomatic CRVT in the ICU. Multivariate analysis showed that trauma (odds ratio [OR], 2.046; 95% confidence interval [CI] [1.325–3.160], P = .001), major surgery (OR, 2.457; 95% CI [1.641–3.679], P = .000), and heart failure (OR, 2.087; 95% CI [1.401–3.111], P = .000) were independent disease-related risk factors for symptomatic CRVT in ICU. The C-statistic for this model was 0.61 (95% CI [0.57–0.65], P = .000). The incidence rate of symptomatic CRVT in the ICU population was 9.5 per 1000 catheter days. Trauma, major surgery, and heart failure are independent disease-related risk factors of symptomatic CRVT.

Background and Objective: Sacubitril/valsartan (SV) is an angiotensin receptor-neprilysin inhibitor that works by inhibiting the neprilysin enzyme as well as blocking angiotensin receptors. The benefits of using SV in congestive heart failure patients has been demonstrated in several clinical trials; however, limited data are available for dogs with heart failure. The aim of this study was to investigate the short-term effects of SV in comparison with ramipril in the standard therapy of symptomatic dogs suffering from myxomatous mitral valve disease (MMVD).Methods: In this prospective, randomized, single-blind study, 21 dogs with MMVD stage C were randomly assigned to received SV (20 mg/kg orally twice a day) or ramipril (0.125 mg/kg, orally once a day) in addition to pimobendan and furosemide. Echocardiography, electrocardiography, blood pressure, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and urinary aldosterone per creatinine ratio were obtained at baseline (D0) and at follow-up (4 weeks).Results: When comparing the percent change from baseline between groups, the left atrium to aortic root ratio (LA/Ao) and left ventricular internal diameter diastole normalized to body weight (LVIDDN) were significantly reduced in the SV group (P < 0.001 and P < 0.01, respectively). The end-diastolic volume index (EDVI), end-systolic volume index (ESVI), and stroke volume were lower in the SV group (P < 0.001, P < 0.05, and P < 0.01, respectively). No changes were observed between groups for NTproBNP, blood pressure, ECG parameters, and urinary aldosterone per creatinine ratio.Conclusion: The current study suggested that the short-term effects of SV can reverse myocardial remodeling, as inferred from several echocardiographic indices (i.e., the reduction in LA/Ao, LVIDDN, EDVI and ESVI) in dogs with MMVD stage C. These findings would support the use of SV in clinically symptomatic heart failure in dogs.

Background Valproate-induced hypothyroidism is a rare condition and has been considered asymptomatic. Here, we report a case of bipolar I disorder who developed symptomatic valproate-induced hypothyroidism. Case presentation A 44-year-old woman with bipolar I disorder complained of severe fatigue after starting valproate. She showed a hormonal pattern of central hypothyroidism. Thyroid autoantibodies were negative, and no pituitary abnormality was seen on magnetic resonance imaging. After stopping valproate, her severe fatigue rapidly improved with normalizing thyroid function. Conclusions Our case suggests that valproate-induced hypothyroidism should be considered when patients complain of excessive fatigue under treatment with valproate.

Larval form of Taenia solium causes cysticercosis that commonly involves the central nervous system. Other sites of manifestation are eye, gastrointestinal system, skeletal muscles and subcutaneous tissues. Isolated muscular involvement is rare with only a handful of cases reported in the literature. We present this case of an isolated symtomatic hand swelling due to Myocysticercosis which pose diagnostic dilemma. This should be considered in differential diagnosis in our developing nation and especially in endemic region. High resolution ultrasound of the hand (thenar region) helped in the diagnosis and is often diagnostic like in our case. The treatment of choice of an isolated symptomatic lesion without involvement of central nervous system is surgical excision which we did followed by short course of antiheminthic and anti-inflammatory medication for two weeks.

N-methyl-D-aspartate receptor (NMDAR) encephalitis presents with multiple symptoms including memory loss, seizure, psychosis, aphasia, altered mentality, dyskinesia, autonomic dysfunction, and central hypoventilation. While immunotherapy protocols are improving, morbidity and mortality in the disease largely depend on supportive care to control intractable symptoms. However, no prospective or controlled trials have been conducted on immunotherapy or supportive care principles in the disease. Thus, this study discusses and shares experience and ideas for symptomatic care of NMDAR encephalitis.

Although Alzheimer’s disease (AD) is the world’s leading cause of dementia and the population of patients with AD continues to grow, no new therapies have been approved in more than a decade. Many clinical trials of single-agent therapies have failed to affect disease progression or symptoms compared with placebo. The complex pathophysiology of AD may necessitate combination treatments rather than monotherapy. The goal of this narrative literature review is to describe types of combination therapy, review the current clinical evidence for combination therapy regimens (both symptomatic and disease-modifying) in the treatment of AD, describe innovative clinical trial study designs that may be effective in testing combination therapy, and discuss the regulatory and drug development landscape for combination therapy. Successful combination therapies in other complex disorders, such as human immunodeficiency virus, may provide useful examples of a potential path forward for AD treatment.

This was a cross-sectional, observational study.The main objectives of this study were to observe the prevalence of a true L6 among patients with symptomatic adult spinal degeneration, and to evaluate similarities of their radiographic spinopelvic parameters to L5 patients.Spinopelvic parameter values used for diagnosis and surgical planning are different between individuals with 5 or 6 lumbar vertebrae. The difference has not been studied in patients with symptomatic spinal degenerative conditions.A total of 775 consecutive symptomatic patients with degenerative spinal disorders were classified as having 5 or 6 lumbar vertebrae in full spine radiographs. Pelvic incidence minus lumbar lordosis (PI-LL), sagittal vertical axis (SVA), pelvic tilt, and T1 pelvic angle were measured in 3 groups: sacral (L5 and L6s) and L6 upper endplate (L6e). Oswestry Disability Index (ODI) was obtained.In total, 715 (92.3%) patients had L5 and 60 (7.7%) had L6. LL values were comparable between the L5 and L6s (P=0.355) and SVA between all groups (P=0.869). Only SVA had excellent concordance correlation (ρc=0.91) between the L6s and L6e groups. PI-LL had significantly different values (P0.001 all groups) and distributions between L5 and L6s (P=0.038), and L6s and L6e (P0.001) groups. In patients with severe disability (ODI40%) the parameters that deteriorate with increasing degeneration (pelvic tilt, T1 pelvic angle, SVA, LL, PI-LL) were not significantly different between L5 and L6s groups unlike patients with ODI40% while PI remained similarly different (P0.001). PI and LL had a multivariate relationship in L6 patients computable as regression model equation: PI (sacrum)=-0.92×LL (L6e)+0.91×LL (sacrum) +1.11×PI (L6e)+10.81 (R=0.88).L6 variant is fairly common. The radiographic L6 parameters were different from L5 except for SVA and values of patients with severe disability measured from sacrum. PI and LL have a mathematic relationship in L6 patients. The cutoff values for radiographic modifiers need further studies combining radiology and clinical outcome.Level III.

Background: Tandem spinal stenosis (TSS) is a rare presentation leading to combined clinical features of upper motor neuron and lower motor neuron lesion which includes intermittent neurogenic claudication with or without neurological deficit, progressive gait imbalance and gait disturbances. In literature, there is controversy whether stage surgery or single-stage surgery should be done. Materials and Methods: From June 2009 to November 2016 in a series of 1381 patients who underwent surgery for various degenerative spinal conditions, 82 patients were diagnosed with having symptomatic TSS with an incidence of 5.93%. All patients diagnosed with TSS underwent single-stage surgical intervention by one surgical team. The perioperative factors were recorded for each patient. All patients were evaluated preoperatively and postoperatively at each followup with the modified Japanese Orthopaedic Association (mJOA) score, Nurick's grading, Oswestry disability index (ODI) and Cooper scale. Results: In this study, 82 patients including 70 males and 12 females underwent simultaneous surgical intervention for symptomatic TSS. The mean age of patients was 61.78 ± 10.48 years. There was a significant improvement in mJOA score, Nuricks grading, ODI and Coopers scale postoperatively as compared to preoperative values (P < 0.05). Conclusion: Symptomatic TSS can be safely managed by single-stage surgical intervention with good postoperative results or without a significant increase in complication rates. Single-stage surgical intervention helps to relieve the symptoms of both cervical and lumbar spinal cord compression, avoids the risk of repeated anesthesia, reduce the duration of surgery, repeated hospitalization hence, reducing the cost for hospitalization and also reducing the rehabilitation, recuperation time and early functional recovery justifies single-stage surgical intervention.

Background This review compares the outcomes and complication rates of three surgical strategies used for the management of symptomatic os acromiale. The purpose of this study was to help guide best practice recommendations. Methods A systematic review of nine prospective studies, seven retrospective studies, and three case studies published across ten countries between 1993 and 2018 was performed. Adult patients (i.e., ≥ 18 years of age) with a symptomatic os acromiale that failed nonoperative management were included in this review. Surgical techniques utilized within the included studies include excision, acromioplasty, and open reduction and internal fixation (ORIF). The primary outcomes of interest included patient satisfaction. Range of motion and several standardized outcome measurement tools were also included in the final analysis. Results Patient satisfaction was highest in the excision and ORIF groups, with 92% and 82% of patients reporting good to excellent postoperative results, respectively, compared to 63% in the acromioplasty group. All three patient groups experienced improvements in postoperative outcomes (i.e., active range of motion and patient-reported outcome scores). The excision group experienced a complication rate of 1%, while the acromioplasty group experienced a complication rate of 11% and the ORIF group a rate of 67%. Conclusion This study reports on the largest sample of patients who underwent surgical treatment for a symptomatic os acromiale. We have demonstrated that excision of the os with meticulous repair of the deltoid resulted in the best clinical outcomes with the least complications. In healthy adult patients with a large os fragment and a normal rotator cuff, surgical fixation may provide increased preservation of deltoid function while offering good to excellent patient satisfaction. However, patients must be informed that a second procedure may be required to remove symptomatic hardware.

Background A higher risk of shoulder injury in the athletic and non-athletic population is frequently associated with strength deficits. Therefore, shoulder strength assessment can be clinically useful to identify and to quantify the magnitude of strength deficit. Thus, the aim of this study was to evaluate the validity and reliability of a DiCI (a new hand-held dynamometer) for the measurement of shoulder flexion and abduction strength in asymptomatic and symptomatic subjects. Methods Forty-three recreational athletes (29 males and 14 females; age: 22.1 ± 0.47 years; body mass: 68.7 ± 13.1 kg; height = 173.3 ± 9.7 cm) and 40 symptomatic subjects (28 males and 12 females; age: 49.9 ± 8.1 years; body mass: 70.6 ± 14.3 kg; height = 171.7 ± 9.0 cm) completed shoulder flexion and abduction strength tests in two identical sessions one-week apart. Both types of movement were evaluated at 45º and 90º. Results Relative reliability analysis showed excellent intra-class correlation coefficients (ICC) for all evaluated movements (ICC range = 0.90 to 0.99). Absolute reliability analysis showed a standard error of measurement (SEM) ranging from 1.36% to 2.25%, and minimal detectable change (MDC) ranging from 3.93% to 6.25%. In conclusion, the DiCI is a valid and reliable device for assessing shoulder strength both in recreational athletes and in subjects with restricted mobility and loss of strength.

The introduction of immune checkpoint blockade (ICB) and BRAF-MEK inhibitors has substantially improved outcomes in patients with metastatic melanoma. However, several challenging factors may hinder the efficacy of ICB in patients with symptomatic intracranial metastatic melanoma who are immunosuppressed due to the use of steroids prior to the administration of ICB. This has resulted in the exclusion of patients treated with high dose steroid at baseline from the majority of ICB clinical trials. In addition, despite the high efficacy of BRAF-MEK inhibitors in BRAF-mutant intracranial metastatic melanoma, most tumors will eventually progress. This demonstrates a gap in addressing the best management in such patients. Here, we present a case demonstrating our approach in this patient population., Tweetable abstract Management of symptomatic BRAF-mutated intracranial melanoma.

Background COVID-19 is associated with both venous and arterial thrombotic complications. While prophylactic anticoagulation is now widely recommended for hospitalized patients with COVID-19, the effectiveness and safety of thromboprophylaxis in outpatients with COVID-19 has not been established. Study Design PREVENT-HD is a double-blind, placebo-controlled, pragmatic, event-driven phase 3 trial to evaluate the efficacy and safety of rivaroxaban in symptomatic outpatients with laboratory-confirmed COVID-19 at risk for thrombotic events, hospitalization, and death. Several challenges posed by the pandemic have necessitated innovative approaches to clinical trial design, start-up, and conduct. Participants are randomized in a 1:1 ratio, stratified by time from COVID-19 confirmation, to either rivaroxaban 10 mg once daily or placebo for 35 days. The primary efficacy end point is a composite of symptomatic venous thromboembolism, myocardial infarction, ischemic stroke, acute limb ischemia, non-central nervous system systemic embolization, all-cause hospitalization, and all-cause mortality. The primary safety end point is fatal and critical site bleeding according to the International Society on Thrombosis and Haemostasis definition. Enrollment began in August 2020 and is expected to enroll approximately 4,000 participants to yield the required number of end point events. Conclusions PREVENT-HD is a pragmatic trial evaluating the efficacy and safety of the direct oral anticoagulant rivaroxaban in the outpatient setting to reduce major venous and arterial thrombotic events, hospitalization, and mortality associated with COVID-19.

SARS-CoV-2 infection has generated the biggest pandemic since the influenza outbreak of 1918–1919. One clear difference between these pandemics has been the ability to test for the presence of the virus or for evidence of infection. This review examined the performance characteristics of sample types via PCR detection of the virus, of antibody testing, of rapid viral antigen detection kits and computerised tomography (CT) scanning. It was found that combined detection approaches, such as the incorporation of CT scans, may reduce the levels of false negatives obtained by PCR detection in both symptomatic and asymptomatic patients, while sputum and oral throat washing sample types should take precedence over swabbing when available. Rt-PCR assays for detection of the virus remain the gold-standard method for SARS-CoV-2 diagnosis and can be used effectively on pooled samples for widespread screening. The novel Oxford antibody assay was found to have the highest sensitivity and specificity of four currently available commercial antibody kits but should only be used during a specific timeframe post-symptom onset. Further research into transmission modes between symptomatic and asymptomatic patients is needed. Analysis of the performance characteristics of different sampling and detection methods for SARS-CoV-2 showed that timing of sampling and testing methods used can greatly influence the rate of false-positive and false-negative test results, thereby influencing viral spread.

Introduction Subclavian steal syndrome (SSS) is the hemodynamic phenomenon of blood flow reversal in the vertebral artery due to significant stenosis or occlusion of the proximal ipsilateral subclavian artery. Materials and methods Four patients with subclavian steal syndrome were treated in our center. Percutaneous radial approach was used for angioplasty, primary stenting of subclavian artery was performed, surgical techniques in particular carotid-subclavian bypass and carotid-subclavian transposition were used. Results We report the cases of four patients, three of which are male, with an average age of 60 years. All of them were symptomatic. Diagnosis was made by duplex ultrasound, supplemented by CT-angiography and arteriography. Endovascular treatment was attempted in all four patients, which was successful in two patients, who underwent primary stenting, and failed for the two others, for whom surgical treatment was considered. One had a subclavio-carotid bypass graft with a polytetrafluorethylene (PTFE) prosthesis and the other had a subclavio-carotid transposition. The technical results were satisfactory in all patients with symptoms resolution. The postoperative evolution was without notable complications and the postoperative checkups were satisfactory. Discussion There are excellent screening tools and effective medical therapies which can be instituted if the SSS is diagnosed early. When the need for revascularization arises, percutaneous modalities are favored given their proven long-term efficacy, decreased morbidity and mortality, and cost-effectiveness. Nevertheless, large, prospective, randomized and controlled trials are needed to compare the long-term patency rates between the endovascular and surgical techniques., Highlights • SSS is caused by the reversal of blood flow in the vertebral artery. • Doppler ultrasound is the ultimate screening tool for diagnosis. • Treatment of symptomatic SSS is always indicated. • Endovascular approach is the first-line treatment.

Early detection of infections is crucial to limit the spread of coronavirus 2019 disease (COVID-19). Here, we develop a flow cytometry-based assay to detect SARS-CoV-2 Spike protein (S protein) antibodies in COVID-19 patients. The assay detects specific IgM, IgA and IgG in COVID-19 patients and also the acquisition of all IgG subclasses, with IgG1 being the most dominant. The antibody response is significantly higher at a later stage of the infection. Furthermore, asymptomatic COVID-19 patients also develop specific IgM, IgA and IgG, with IgG1 as the most dominant subclass. Although the antibody levels are lower in asymptomatic infections, the assay is highly sensitive and detect 97% of asymptomatic infections. These findings demonstrate that the assay can be used for serological analysis of symptomatic infections, and also asymptomatic infections, which may, otherwise, go undetected., Graphical Abstract, Highlights Flow cytometry assay detects specific antibodies in symptomatic COVID-19 patients. Asymptomatic COVID-19 patients also develop specific antibodies. IgG1 is the dominant IgG subclass in both symptomatic and asymptomatic patients. The assay is highly sensitive and detects 97% of asymptomatic infections., Using a flow cytometry-based assay, Goh et al. finds specific antibodies in symptomatic COVID-19 patients’ plasma samples. IgG1 is the most dominant IgG subclass. Despite lower antibody levels, the assay detects 97% of asymptomatic infections, suggesting the feasibility of the assay to detect asymptomatic infections, which may otherwise go undetected.

Background: The correlation of SARS-CoV-2 viral load with disease severity in different population subsets is still elusive. There is a scarcity of literature regarding this aspect in Indian Population. Aim: To study retrospectively the risk factors and the role of viral load with disease severity among different age groups of North Indian population. Methods: Here we quantified the viral load of 239 positive participants and collected data retrospectively from April 2020 to May 2020 and categorised the patients as per disease severity and population subsets. Results: Asymptomatic patients were found to have higher viral load than the symptomatic patients, though the difference was not found to be statistically significant. The logistic regression analysis showed that contact with laboratory confirmed cases, SARI and ILI were independent risk factors for acquiring COVID-19 infection. Conclusion: SARS-CoV-2 viral load is not significantly associated with disease severity among different population subsets. However, there is a need to carry out more studies with a larger number of patients to validate and confirm the above findings.

Purpose: The COVID-19 pandemic has led to over 92 million cases and 1.9 million deaths worldwide since its outbreak. Public health responses have focused on identifying symptomatic individuals to halt spread. However, evidence is accruing that asymptomatic individuals are infectious and contributing to this global pandemic. Methods: Observational data of 320 index cases and their 1289 positive contacts from the National COVID-19 Database in Bahrain were used to analyze symptoms, infectivity rate and PCR Cycle threshold (Ct) values. Results: No significant difference (p = 1.0) in proportions of symptomatic (n = 160; 50.0%) and asymptomatic index cases (n = 160; 50.0%) were seen; however, SARS-CoV-2 positive contact cases were predominantly asymptomatic (n = 1127, 87.4%). Individuals aged 0−19 years constituted a larger proportion of positive contact cases (20.8%) than index cases (4.7%; p

Background The relative contributions of asymptomatic, presymptomatic, and symptomatic transmission of severe acute respiratory syndrome coronavirus 2 have not been clearly measured, although control measures may differ in response to the risk of spread posed by different types of cases. Methods We collected detailed information on transmission events and symptom status based on laboratory-confirmed patient data and contact tracing data from 4 provinces and 1 municipality in China. We estimated the variation in risk of transmission over time and the severity of secondary infections by symptomatic status of the infector. Results There were 393 symptomatic index cases with 3136 close contacts and 185 asymptomatic index cases with 1078 close contacts included in the study. The secondary attack rates among close contacts of symptomatic and asymptomatic index cases were 4.1% (128 of 3136) and 1.1% (12 of 1078), respectively, corresponding to a higher transmission risk from symptomatic cases than from asymptomatic cases (odds ratio, 3.79; 95% confidence interval, 2.06–6.95). Approximately 25% (32 of 128) and 50% (6 of 12) of the infected close contacts were asymptomatic from symptomatic and asymptomatic index cases, respectively, while more than one third (38%) of the infections in the close contacts of symptomatic cases were attributable to exposure to the index cases before symptom onset. Conclusions Asymptomatic and presymptomatic transmissions play an important role in spreading infection, although asymptomatic cases pose a lower risk of transmission than symptomatic cases. Early case detection and effective test-and-trace measures are important to reduce transmission.

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.

Objective: To access the feasibility of palliative cystoprostatectomy/pelvic exenteration in patients with bladder/rectal invasion due to prostate cancer (PC). Patients and methods: Twenty-five men with cT4 PC were retrospectively identified in the institutional databases of six tertiary referral centers in the last decade. Local invasion was documented by CT or MRI scans and was confirmed by urethrocystoscopy. Oncological therapies, local symptoms, previous local treatments, time from diagnosis to intervention and type of surgical procedure were recorded. Patients were divided into groups: ADT group (12 pts) and 13 pts without any history of previous local/systemic treatments for PCa (nonADT groups). Perioperative complications were classified using the Clavien–Dindo system. Overall survival (OS) was defined as the time from surgery to death from any cause. A Cox regression analysis, stratified for ISUP score and previous hormonal treatment (ADT) was also performed for survival analysis. Results: Ileal conduit was the main urinary diversion in both cohorts. For the entire cohort, complication rate was 44%. No significant differences regarding perioperative complications and complication severity between both subgroups were observed (p = 0.2). Median follow-up was 15months (range 3–41) for the entire cohort with a median survival of 15months (95% CI 10.1–19.9). In Cox regression analysis stratified for ISUP score, no statistically significant differences in OS in patients with and without previous ADT before cystectomy or exenteration were observed (HR 3.26, 95% CI 0.62–17.23, p = 0.164). Conclusion: Palliative cystoprostatectomy and pelvic exenteration represent viable treatment options associated with acceptable morbidity and good short-term survival outcome.

Purpose: The aim of this study is to determine the proportion of maternal hydronephrosis and symptomatic cases requiring treatment in pregnant women without ureteral stones and the characteristics of these cases. Materials and methods: Between February 2018 and April 2019, all pregnant women followed for pregnancy in obstetrics and outpatient policlinic were evaluated prospectively. Maternal hydronephrosis rate, degree of hydronephrosis and side, symptomatic hydronephrosis rate, maximum renal anteroposterior diameter of renal pelvis and visual analogue scale were detected. Symptomatic patients were treated conservatively or surgically. Findings in both treatment groups were analyzed by t-test or Chi-squared test. Pearson or Spermean’s tests were used for correlation analyzes. Results: A total of 1026 pregnant women aged 18-45 (27.7 ± 5.2 years) were followed prospectively. The rate of maternal hydronephrosis was 28.7% and the rate of symptomatic hydronephrosis was 4.7%. Of the patients with symptomatic hydronephrosis, 73.4% (3.5% of total) were treated conservatively and 26.5% (1.3% of total) were treated surgically. There was a positive correlation between hydronephrosis and gestational week (p < 0.001), visual analogue scale (p < 0.001) and hematuria (p < 0.05). There was a negative correlation between hydronephrosis and maternal age (p < 0.05) and number of pregnancies (p < 0,001). The anteroposterior diameter of renal pelvis (p < 0.001), visual analogue scale (p < 0.05) and fetal body weight values (p < 0.05) on the right side were higher in the surgical treatment group than the conservative group. Conclusions: The majority of cases with maternal hydronephrosis in pregnant women without ureteral stones are asymptomatic. Most symptomatic cases can also be treated conservatively. In cases requiring surgical treatment (1.3%), fetal body weight, visual analogue scale and anteroposterior renal pelvis diameter are higher.

Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS; the most common phenotype of corticobasal degeneration) are tauopathies with a relentless course, usually starting in the mid-60s and leading to death after an average of 7 years. There is as yet no specific or disease-modifying treatment. Clinical deficits in PSP are numerous, involve the entire neuraxis, and present as several discrete phenotypes. They center on rigidity, bradykinesia, postural instability, gait freezing, supranuclear ocular motor impairment, dysarthria, dysphagia, incontinence, sleep disorders, frontal cognitive dysfunction, and a variety of behavioral changes. CBS presents with prominent and usually asymmetric dystonia, apraxia, myoclonus, pyramidal signs, and cortical sensory loss. The symptoms and deficits of PSP and CBS are amenable to a variety of treatment strategies but most physicians, including many neurologists, are reluctant to care for patients with these conditions because of unfamiliarity with their multiplicity of interacting symptoms and deficits. CurePSP, the organization devoted to support, research, and education for PSP and CBS, created its CurePSP Centers of Care network in North America in 2017 to improve patient access to clinical expertise and develop collaborations. The directors of the 25 centers have created this consensus document outlining best practices in the management of PSP and CBS. They formed a writing committee for each of 12 sub-topics. A 4-member Steering Committee collated and edited the contributions. The result was returned to the entire cohort of authors for further comments, which were considered for incorporation by the Steering Committee. The authors hope that this publication will serve as a convenient guide for all clinicians caring for patients with PSP and CBS and that it will improve care for patients with these devastating but manageable disorders.

Background The year 2020 was the year of the global COVID-19 pandemic. The severity of the situation has become so substantial that many or even most of the patients with mild to moderate symptoms had to self-isolate without specific medical treatments or even without being tested for COVID-19. Many patients joined internet membership groups to exchange information and support each other. Objective Our goal is to determine the benefits and limits of using social media to understand the symptoms of patients with suspected COVID-19 with mild to moderate symptoms and, in particular, their symptoms of anosmia (loss of the sense of smell) and ageusia (loss of the sense of taste). The voluntary reports on an internet website of a membership group will be the platform of the analyses. Methods Posts and comments of members of an internet group known as COVID-19 Smell and Taste Loss, founded on March 24, 2020, to support patients with suspected COVID-19 were collected and analyzed daily. Demographic data were collected using the software mechanism called Group Insights on the membership group website. Results Membership groups on social media have become rare sources of support for patients with suspected COVID-19 with mild to moderate symptoms. These groups provided mental support to their members and became resources for information on COVID-19 tests and medicines or supplements. However, the membership was voluntary, and often the members leave without notification. It is hard to be precise from the free voluntary reports. The number of women in the group (6995/9227, 75.38% as of October 12, 2020) was about three times more than men (2272/9227, 24.62% as of October 12, 2020), and the peak age of members was between 20-40 years in both men and women. Patients who were asymptomatic other than the senses comprised 14.93% (53/355) of the total patients. Recovery of the senses was higher in the patients who were asymptomatic besides having anosmia and ageusia. Most (112/123, 91.06%) patients experienced other symptoms first and then lost their senses, on average, 4.2 days later. Patients without other symptoms tended to recover earlier (P=.02). Patients with anosmia and ageusia occasionally reported distorted smell and taste (parosmia and dysgeusia) as well as experiencing or perceiving the smell and taste without the sources of the smell or taste (phantosmia and phantogeusia). Conclusions Our analysis of the social media database of suspected COVID-19 patients’ voices demonstrated that, although accurate diagnosis of patients is not always obtained with social media–based analyses, it may be a useful tool to collect a large amount of data on symptoms and the clinical course of worldwide rapidly growing infectious diseases.

BackgroundCoronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic. Based on symptoms, COVID-19 cases can be classified as symptomatic or asymptomatic. However, there is limited information about the differences between COVID-19 patients with and without pneumonia. Our study aimed to further discuss the spectrum and clinical characteristics of symptomatic and asymptomatic COVID-19 patients with and without pneumonia. MethodsIn China, all COVID-19 cases are hospitalized in designated hospitals until two continuous negative oropharyngeal swabs obtained, which allows the professional monitoring of symptoms and clinical characteristics. We stratified all COVID-19 cases in our database, and evaluated clinical characteristics in different COVID-19 subgroups (symptomatic with pneumonia, symptomatic without pneumonia, asymptomatic with pneumonia and asymptomatic without pneumonia). ResultsAccording to symptoms and laboratory and radiologic findings, COVID-19 cases were defined as symptomatic with pneumonia, symptomatic without pneumonia, asymptomatic with pneumonia or asymptomatic without pneumonia. There were differences in the clinical characteristics and prognosis among the four groups. Both noninvasive (18, 4.2%) and invasive mechanical ventilation (11, 2.6%) were applied in only the symptomatic with pneumonia group. Likewise, extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT) were applied in only the symptomatic with pneumonia group. There were no differences in the durations of viral shedding and hospitalization among the four groups.ConclusionWe have defined a comprehensive spectrum of COVID-19 with and without pneumonia. The symptomatic with pneumonia group consumed more medical resources than the other groups, and extra caution and monitoring should be applied in this group. The asymptomatic COVID-19 group had a similar viral shedding duration as the symptomatic COVID-19 group.Trial registrationNot available

In this report, we present the case of a COVID-19-positive patient whose symptomatic inflammatory abdominal aortic aneurysm was successfully treated with endovascular aortic repair at our institution. We discuss the reasoning behind the type of therapy used and the various lessons learned. Based on our experience with this patient, we recommend an endovascular approach for similar COVID-19 patients and suggest a prophylactic dose of enoxaparin (Lovenox; 40 mg daily) postoperatively for 14 days.

Background The immune mechanisms that determine whether a Plasmodium falciparum infection would be symptomatic or asymptomatic are not fully understood. Several studies have been carried out to characterize the associations between disease outcomes and leucocyte numbers. However, the majority of these studies have been conducted in adults with acute uncomplicated malaria, despite children being the most vulnerable group. Methods Peripheral blood leucocyte subpopulations were characterized in children with acute uncomplicated (symptomatic; n = 25) or asymptomatic (n = 67) P. falciparum malaria, as well as malaria-free (uninfected) children (n = 16) from Obom, a sub-district of Accra, Ghana. Leucocyte subpopulations were enumerated by flow cytometry and correlated with two measures of parasite load: (a) plasma levels of P. falciparum histidine-rich protein 2 (PfHRP2) as a proxy for parasite biomass and (b) peripheral blood parasite densities determined by microscopy. Results In children with symptomatic P. falciparum infections, the proportions and absolute cell counts of total (CD3 +) T cells, CD4 + T cells, CD8 + T cells, CD19 + B cells and CD11c + dendritic cells (DCs) were significantly lower as compared to asymptomatic P. falciparum-infected and uninfected children. Notably, CD15 + neutrophil proportions and cell counts were significantly increased in symptomatic children. There was no significant difference in the proportions and absolute counts of CD14 + monocytes amongst the three study groups. As expected, measures of parasite load were significantly higher in symptomatic cases. Remarkably, PfHRP2 levels and parasite densities negatively correlated with both the proportions and absolute numbers of peripheral leucocyte subsets: CD3 + T, CD4 + T, CD8 + T, CD19 + B, CD56 + NK, γδ + T and CD11c + cells. In contrast, both PfHRP2 levels and parasite densities positively correlated with the proportions and absolute numbers of CD15 + cells. Conclusions Symptomatic P. falciparum infection is correlated with an increase in the levels of peripheral blood neutrophils, indicating a role for this cell type in disease pathogenesis. Parasite load is a key determinant of peripheral cell numbers during malaria infections.

Reproduction is a crucial issue at the present stage in the pig husbandry development. Infertility of breeding sows leads to excessive use of feed, increased costs associated with failed inseminations, insufficient breed and early culling of sows. Aim of the research.Study of infertility types and prevention of postpartum diseases in sows in order to develop methods to control them. Methods.A two-stage experiment was carried out in 2019–2020 at the LLC "Ryasnyanske" farm in Sumy region, Ukraine. The first stage involved development of a method for prevention and control of infertility in sows. The second stage focused on the method of postpartum pathology prevention. Results.The conducted research established that surfagon and vitamins manifested the highest efficiency in case of alimentary infertility as they increased fertilization by 20.8 %. In terms of symptomatic infertility, the best results were achieved through a combined use of surfagon and gonadotropic hormone for both primary and multiple fertilization of sows, especially considering extremely low values in the control group - 15 % and 6.5 % of piglets, respectively. Aminazine proved to be the most effective remedy for immune infertility, the obtained results were 17.2 % higher than in the control group. Surfagon at a dose of 5 ml together with estrofan twice a day fully prevented inflammatory postpartum pathologies in sows. Conclusions.Pathologies of the reproductive organs in sows are widespread at pork-producing farms. Individual use of surfagon was justified for treatment of alimentary, symptomatic and immune infertility of sows and prevention of postpartum pathologies. A combined use of tissue therapy and biologically active drugs proved to be the most effective. The treatment regimens described above reduce infertility and prevent postpartum pathologies in sows.

Purpose: The purpose of this study was to compare the diagnostic performance of breast lesions between deep learning-based computer-aided diagnosis (deep learning-based CAD) system and experienced radiologists and to compare the performance between symptomatic and asymptomatic patients. Methods: From January to December 2018, a total of 451 breast lesions in 389 consecutive patients were examined (mean age 46.86 ± 13.03 years, range 19-84 years) by both ultrasound and deep learning-based CAD system, all of which were biopsied, and the pathological results were obtained. The lesions were diagnosed by two experienced radiologists according to the fifth edition Breast Imaging Reporting and Data System (BI-RADS). The final deep learning-based CAD assessments were dichotomized as possibly benign or possibly malignant. The diagnostic performances of the radiologists and deep learning-based CAD were calculated and compared for asymptomatic patients and symptomatic patients. Results: There were 206 asymptomatic screening patients with 235 lesions (mean age 45.06 ± 10.90 years, range 21-73 years) and 183 symptomatic patients with 216 lesions (mean age 50.03 ± 14.97 years, range 19-84 years). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy and area under the receiver operating characteristic curve (AUC) of the deep learning-based CAD in asymptomatic patients were 93.8, 83.9, 75.0, 96.3, 87.2, and 0.89%, respectively. In asymptomatic patients, the specificity (83.9 vs. 66.5%, p < 0.001), PPV (75.0 vs. 59.4%, p = 0.013), accuracy (87.2 vs. 76.2%, p = 0.002) and AUC (0.89 to 0.81, p = 0.0013) of CAD were all significantly higher than those of the experienced radiologists. The sensitivity (93.8 vs. 80.0%), specificity (83.9 vs. 61.8%,), accuracy (87.2 vs. 73.6%) and AUC (0.89 vs. 0.71) of CAD were all higher for asymptomatic patients than for symptomatic patients. If the BI-RADS 4a lesions diagnosed by the radiologists in asymptomatic patients were downgraded to BI-RADS 3 according to the CAD, then 54.8% (23/42) of the lesions would avoid biopsy without missing the malignancy. Conclusion: The deep learning-based CAD system had better performance in asymptomatic patients than in symptomatic patients and could be a promising complementary tool to ultrasound for increasing diagnostic specificity and avoiding unnecessary biopsies in asymptomatic screening patients.

The current outbreak of coronavirus disease 2019 (COVID-19) has been defined as a pandemic by the World Health Organization. We aimed to evaluate the clinical features and virological course of non-severe COVID-19 patients with or without symptoms who were admitted to a Chinese cabin hospital. In this retrospective single center study, we reviewed 252 laboratory-confirmed COVID-19 patients treated at one temporary cabin hospital in Wuhan, China. Demographic, clinical, serial chest computed tomography (CT), and serial viral test data were compared between asymptomatic and symptomatic patients. The association between clinical features and symptomatic status or patient referral status was analyzed. Among all 252 patients, 74 (29.4%) were asymptomatic and 138 (54.76%) had more than two family members who developed COVID-19. The probability for family clustering was similar between asymptomatic and symptomatic patients (59.70 vs. 61.64%, P = 0.79). Asymptomatic patients and symptomatic patients were equally likely to reach a virus-free state during their stay at the cabin hospital (93.15 vs. 86.44%, P = 0.13). The initial chest CT screening showed that 81 (32.1%) patients had no visible pneumonia, 52 (20.6%) had unilateral pneumonia, and 119 (47.2%) had bilateral pneumonia. Symptomatic patients had a higher chance to have bilateral pneumonia (P < 0.0001) and were less likely to show improvement on the follow-up CT scan (P = 0.0002). In total, 69 (27.4%) patients were referred to the designated hospital and only 23 (9.1%) patients were referred due to the progression of pneumonia. Non-severe COVID-19 patients can transmit the disease regardless of their symptomatic status. It is highly recommended that asymptomatic patients be identified and quarantined to eliminate the transmission of COVID-19.

Background The Phase III PINNACLE studies assessed the efficacy and safety of glycopyrrolate/formoterol fumarate metered dose inhaler (GFF MDI), a dual long-acting bronchodilator for chronic obstructive pulmonary disease (COPD). Here we present a pre-specified pooled analysis of PINNACLE-1, PINNACLE-2, and PINNACLE-4. Methods PINNACLE-1, -2, and -4 were multicenter, double-blind, randomized controlled trials that enrolled patients with moderate-to-very severe COPD, with no requirement for exacerbation history or a high symptom burden. Patients received GFF MDI 18/9.6 μg, glycopyrrolate (GP) MDI 18 μg, formoterol fumarate (FF) MDI 9.6 μg, or placebo MDI, twice-daily for 24 weeks. The primary endpoint of the pooled analysis was the change from baseline in morning pre-dose trough forced expiratory volume in 1 s (FEV1) at week 24. Secondary endpoints included COPD exacerbations and clinically important deterioration (CID). Adverse events were also assessed. Results The pooled intent-to-treat population included 4983 patients; of these, 61.9% had a COPD assessment test (CAT) score ≥15, and 25.0% had experienced ≥1 moderate/severe exacerbation in the past year. At week 24, GFF MDI improved morning pre-dose trough FEV1 versus GP MDI (least squares mean [LSM] difference [95% confidence interval (CI)]: 59 mL [43, 75]), FF MDI (65 mL [48, 81]), and placebo MDI (146 mL [125, 166]); all p p = 0.0168), 15% (p = 0.0628), and 28% (p = 0.0012) compared with GP MDI, FF MDI, and placebo MDI, respectively. In general, exacerbation risk reduction with GFF MDI versus comparators was greater in subgroups of symptomatic patients (CAT ≥15) and those who had an exacerbation history, than in the pooled intent-to-treat population. The risk of CID was also lower with GFF MDI versus GP MDI (23% decrease), FF MDI (17%), and placebo MDI (49%); all p Conclusions This pooled analysis of the PINNACLE studies demonstrated that GFF MDI improved lung function and reduced the risk of exacerbations compared with monocomponents and placebo in patients with COPD. Exacerbation reductions with GFF MDI versus comparators were generally greater in patients with higher symptom burden and those with exacerbation history. Trial registration ClinicalTrials.gov NCT01854645, NCT01854658, and NCT02343458. Registered 13 May 2013 (NCT01854645, NCT01854658) and 6 January 2015 (NCT02343458).

Background Schmorls node (SN) are mostly asymptomatic and incidental findings on MRI. However, sometimes they present like acute onset low back pain or acute exacerbation of chronic back pain after minor trauma. Case presentation We present rare case of symptomatic infected SN in 67 years female patient presented with complains of low back pain radiating to right buttock. After initial conservative treatment failed subsequent imaging showed significant increase in size of lesion with focal signal changes in disc space gave suspicion of underlying secondary pathology. Patient operated for complete excision of lesion. Histopathological report was suggestive of pyogenic vertebral osteomyelitis. Patient improved well postoperatively. Conclusion Most of the time acute SN responds well to conservative treatment; however rapid deterioration of symptoms or persistent severe pain should give suspicion of underlying secondary pathology.