Pathological sequelae of long-haul COVID.

The world continues to contend with successive waves of coronavirus disease 2019 (COVID-19), fueled by the emergence of viral variants. At the same time, persistent, prolonged and often debilitating sequelae are increasingly recognized in convalescent individuals, named 'post-COVID-19 syndrome' or 'long-haul COVID'. Clinical symptomatology includes fatigue, malaise, dyspnea, defects in memory and concentration and a variety of neuropsychiatric syndromes as the major manifestations, and several organ systems can be involved. The underlying pathophysiological mechanisms are poorly understood at present. This Review details organ-specific sequelae of post-COVID-19 syndromes and examines the underlying pathophysiological mechanisms available so far, elaborating on persistent inflammation, induced autoimmunity and putative viral reservoirs. Finally, we propose diagnostic strategies to better understand this heterogeneous disorder that continues to afflict millions of people worldwide.

Half of US population exposed to adverse lead levels in early childhood.

SignificanceConsiderable effort is expended to protect today's children from lead exposure, but there is little evidence on the harms past lead exposures continue to hold for yesterday's children, who are victims of what we term legacy lead exposures. We estimate that over 170 million Americans alive today were exposed to high-lead levels in early childhood, several million of whom were exposed to five-plus times the current reference level. Our estimates allow future work to plan for the health needs of these Americans and to inform estimation of the true contributions of lead exposure to population health. We estimate population-level effects on IQ loss and find that lead is responsible for the loss of 824,097,690 IQ points as of 2015.

Patient-reported symptoms before adjuvant locoregional radiotherapy for breast cancer: triple-negative histology impacts the symptom burden.

BACKGROUND: Multimodal breast cancer treatment may cause side effects reflected in patient-reported outcomes and/or symptom scores at the time of treatment planning for adjuvant radiotherapy. In our department, all patients have been assessed with the Edmonton Symptom Assessment System (ESAS; a questionnaire addressing 11 major symptoms and wellbeing on a numeric scale of 0-10) at the time of treatment planning since 2016. In this study, we analyzed ESAS symptom severity before locoregional radiotherapy. PATIENTS AND METHODS: Retrospective review of 132 patients treated between 2016 and 2021 (all comers in breast-conserving or post-mastectomy settings, different radiotherapy fractionations) was performed. All ESAS items and the ESAS point sum were analyzed to identify subgroups with higher symptom burden and thus need for additional care measures. RESULTS: The biggest patient-reported issues were fatigue, pain, and sleep problems. Patients with triple negative breast cancer reported a higher symptom burden (mean 30 versus 20, p = 0.038). Patients assigned to adjuvant endocrine therapy had the lowest point sum (mean 18), followed by those on Her-2-targeting agents without chemotherapy (mean 19), those on chemotherapy with or without other drugs (mean 26), and those without systemic therapy (mean 41), p = 0.007. Those with pathologic complete response after neoadjuvant treatment had significantly lower anxiety scores (mean 0.7 versus 1.8, p = 0.03) and a trend towards lower depression scores, p = 0.09. CONCLUSION: Different surgical strategies, age, and body mass index did not impact on ESAS scores, while the type of adjuvant systemic therapy did. The effect of previous neoadjuvant treatment and unfavorable tumor biology (triple negative) emerged as important factors associated with symptom burden, albeit in different domains. ESAS data may facilitate identification of patients who should be considered for additional supportive measures to alleviate specific symptoms.

Ambient pollen exposure and pollen allergy symptom severity in the EPOCHAL study.

BACKGROUND: Ambient pollen exposure causes nasal, ocular, and pulmonary symptoms in allergic individuals, but the shape of the exposure-response association is not well characterized. We evaluated this association and determined (1) whether symptom severity differs between subpopulations; (2) how the association changes over the course of the pollen season; and (3) which pollen exposure time lags affect symptoms. METHODS: Adult study participants (n = 396) repeatedly scored severity of nasal, ocular, and pulmonary allergic symptoms, resulting in three composite symptom scores. We calculated hourly individually relevant pollen exposure to seven allergenic plants (alder, ash, birch, hazel, grasses, mugwort, and ragweed) considering personal sensitization and exposure time lags of up to 96 h. We fitted generalized additive mixed models, with a random personal intercept, adjusting for weather and air pollution as potential time-varying confounders. RESULTS: We identified a clear nonlinear positive association between pollen exposure and ocular and nasal symptom severity in the pollen allergy group: Symptom severity increased steeply with increasing exposure initially, but attenuated beyond approximately 80 pollen/m3. We found no evidence of an exposure threshold, below which no symptoms occur. While recent pollen exposure in the last approximately 5 h affected symptoms most, associations lingered for up to 60 h. Grass pollen exposure (compared to tree pollen) and younger age (18-30 years, as opposed to 30-65 years) were both associated with higher nasal and ocular symptom severity. CONCLUSIONS: The lack of a threshold and attenuated dose-response curve may have implications for pollen warning systems, which may be revised to include multiday pollen concentrations in the future.

MRI-based radiomic features of the urinary bladder wall identify patients with moderate-to-severe international prostate symptom score.

BACKGROUND: The International Prostate Symptom Score (IPSS) is a patient-reported measurement to assess the lower urinary tract symptoms of bladder outlet obstruction. Bladder outlet obstruction induces molecular and morphological alterations in the urothelium, suburothelium, detrusor smooth muscle cells, detrusor extracellular matrix, and nerves. We sought to analyze MRI-based radiomics features of the urinary bladder wall and their association with IPSS. METHOD: In this retrospective study, 87 patients who had pelvic MRI scans were identified. A biomarker discovery approach based on the optimal biomarker (OBM) method was used to extract features of the bladder wall from MR images, including morphological, intensity-based, and texture-based features, along with clinical variables. Mathematical models were created using subsets of features and evaluated based on their ability to discriminate between low and moderate-to-severe IPSS (less than 8 vs. equal to or greater than 8). RESULTS: Of the 7,666 features per patient, four highest-ranking optimal features were derived (all texture-based features), which provided a classification accuracy of 0.80 with a sensitivity, specificity, and area under the receiver operating characteristic curve of 0.81, 0.81, and 0.87, respectively. CONCLUSION: A highly independent set of urinary bladder wall features derived from MRI scans were able to discriminate between patients with low vs. moderate-to-severe IPSS with accuracy of 80%. Such differences in MRI-based properties of the bladder wall in patients with varying IPSS's might reflect differences in underlying molecular and morphological alterations that occur in the setting of chronic bladder outlet obstruction.

Implementing a nurse-led screening clinic for symptom distress with community-based referral for cancer survivors: A feasibility study.

INTRODUCTION: This prospective, single-arm, pragmatic implementation study evaluated the feasibility of a nurse-led symptom-screening program embedded in routine oncology post-treatment outpatient clinics by assessing (1) the acceptance rate for symptom distress screening (SDS), (2) the prevalence of SDS cases, (3) the acceptance rate for community-based psychosocial support services, and (4) the effect of referred psychosocial support services on reducing symptom distress. METHODS: Using the modified Edmonton Symptom Assessment System (ESAS-r), we screened patients who recently completed cancer treatment. Patients screening positive for moderate-to-severe symptom distress were referred to a nurse-led community-based symptom-management program involving stepped-care symptom/psychosocial management interventions using a pre-defined triage system. Reassessments were conducted at 3-months and 9-months thereafter. The primary outcomes included SDS acceptance rate, SDS case prevalence, intervention acceptance rate, and ESAS-r score change over time. RESULTS: Overall, 2988/3742(80%) eligible patients consented to SDS, with 970(32%) reporting ≥1 ESAS-r symptom as moderate-to-severe (caseness). All cases received psychoeducational material, 673/970(69%) accepted psychosocial support service referrals. Among 328 patients completing both reassessments, ESAS-r scores improved significantly over time (p < 0.0001); 101(30.8%) of patients remained ESAS cases throughout the study, 112(34.1%) recovered at 3-month post-baseline, an additional 72(22%) recovered at 9-month post-baseline, while 43(12.2%) had resumed ESAS caseness at 9-month post-baseline. CONCLUSION: Nurse-led SDS programs with well-structured referral pathways to community-based services and continued monitoring are feasible and acceptable in cancer patients and may help in reducing symptom distress. We intend next to develop optimal strategies for SDS implementation and referral within routine cancer care services.

Acceptability and usefulness of the EORTC 'Write In three Symptoms/Problems' (WISP): a brief open-ended instrument for symptom assessment in cancer patients.

BACKGROUND: The use of open-ended questions supplementing static questionnaires with closed questions may facilitate the recognition of symptoms and toxicities. The open-ended 'Write In three Symptoms/Problems (WISP)' instrument permits patients to report additional symptoms/problems not covered by selected EORTC questionnaires. We evaluated the acceptability and usefulness of WISP with cancer patients receiving active and palliative care/treatment in Austria, Chile, France, Jordan, the Netherlands, Norway, Spain and the United Kingdom. METHODS: We conducted a literature search on validated instruments for cancer patients including open-ended questions and analyzing their responses. WISP was translated into eight languages and pilot tested. WISP translations were pre-tested together with EORTC QLQ-C30, QLQ-C15-PAL and relevant modules, followed by patient interviews to evaluate their understanding about WISP. Proportions were used to summarize patient responses obtained from interviews and WISP. RESULTS: From the seven instruments identified in the literature, only the free text collected from the PRO-CTAE has been analyzed previously. In our study, 161 cancer patients participated in the pre-testing and interviews (50% in active treatment). Qualitative interviews showed high acceptability of WISP. Among the 295 symptoms/problems reported using WISP, skin problems, sore mouth and bleeding were more prevalent in patients in active treatment, whereas numbness/tingling, dry mouth and existential problems were more prevalent in patients in palliative care/treatment. CONCLUSIONS: The EORTC WISP instrument was found to be acceptable and useful for symptom assessment in cancer patients. WISP improves the identification of symptoms/problems not assessed by cancer-generic questionnaires and therefore, we recommend its use alongside the EORTC questionnaires.

Undergoing Lung Surgery (PSA-Lung) was appropriate for symptom assessment after discharge.

PURPOSE: To examine whether a 7-day or 24-h recall period of Perioperative Symptom Assessment for Patients Undergoing Lung Surgery (PSA-Lung) was appropriate for symptom assessment after discharge. METHODS: A total of 377 patients were recruited in a cohort study of patients who underwent lung surgery. We measured patient symptoms daily and weekly using the two recall period versions of the PSA-Lung scale, respectively. The psychometric properties of both versions were calculated. Spearman rank correlation coefficients and kappa (k) coefficients were used to measure the association between items score measured by the two version scales each week. Cohen's d effect size and mixed linear model were used to measure responsiveness to change over time. RESULTS: Spearman rank correlation coefficients between the symptom scores generated by the 7-day and 24-h versions (range 0.48-0.77; all P < 0.05). The correlations increased in patients in stable condition (weekly symptom change < 2). Cronbach's α coefficients for both ratings were > 0.87 and both had good test-retest reliability. The longitudinal analysis and Cohen's d effect sizes showed that both ratings had good ability to detect changes in all items. CONCLUSION: The 7-day retrospective scale was as effective as the 24-h retrospective scale in terms of psychometric performance. In the stage where the patient's symptoms change rapidly, it is recommended to use the 24-h retrospective scale for symptom monitoring. On the contrary, in a stable state, it can be considered to use the 7-day retrospective scale for monitoring to reduce the patient's burden.

A comparison of the prevalence of dry mouth and other symptoms using two different versions of the Edmonton Symptom Assessment System on an inpatient palliative care unit.

BACKGROUND: Symptom assessment is key to effective symptom management and palliative care for patients with advanced cancer. Symptom prevalence and severity estimates vary widely, possibly dependent on the assessment tool used. Are symptoms specifically asked about or must the patients add them as additional symptoms? This study compared the prevalence and severity of patient-reported symptoms in two different versions of a multi-symptom assessment tool. In one version, three symptoms dry mouth, constipation, sleep problems were among those systematically assessed, while in the other, these symptoms had to be added as an "Other problem". METHODS: This retrospective cross-sectional study included adult patients with advanced cancer at an inpatient palliative care unit. Data were collected from two versions of the Edmonton Symptom Assessment System (ESAS): modified (ESAS-m) listed 11 symptoms and revised (ESAS-r) listed 9 and allowed patients to add one "Other problem". Seven similar symptoms were listed in both versions. RESULTS: In 2013, 184 patients completed ESAS-m, and in 2017, 156 completed ESAS-r. Prevalence and severity of symptoms listed in both versions did not differ. In ESAS-m, 83% reported dry mouth, 73% constipation, and 71% sleep problems, but on ESAS-r, these symptoms were reported by only 3%, 15% and < 1%, respectively. Although ESAS-r severity scores for these three symptoms were higher than on ESAS-m, differences did not reach statistical significance. CONCLUSION: We identified significant differences in patient symptom reporting based on whether symptoms like dry mouth, obstipation and sleep problems were specifically assessed or had to be added by patients as an "Other problem".

WeChat assisted electronic symptom measurement for patients with adenomyosis.

PURPOSE: Symptom assessment is central to appropriate adenomyosis management. Using a WeChat mini-program-based portal, we aimed to establish a valid symptom assessment scale of adenomyosis (AM-SAS) to precisely and timely identify needs of symptom management and ultimately, to alert disease recurrence. METHODS: A combination of intensive interviews of patients with adenomyosis and natural language processing on WeChat clinician-patient group communication was used to generate a pool of symptom items-related to adenomyosis. An expert panel shortened the list to form the provisional AM-SAS. The AM-SAS was built in a Wechat mini-programmer and sent to patients to exam the psychotically validity and clinical applicability through classic test theory and item response theory. RESULTS: Total 338 patients with adenomyosis (29 for interview, 179 for development, and 130 for external validation) and 86 gynecologists were included. The over 90% compliance to the WeChat-based symptom evaluate. The AM-SAS demonstrated the uni-dimensionality through Rasch analysis, good internal consistency (all Cronbach's alphas above 0.8), and test-retest reliability (intraclass correlation coefficients ranging from 0.65 to 0.84). Differences symptom severity score between patients in the anemic and normal hemoglobin groups (3.04 ± 3.17 vs. 5.68 ± 3.41, P < 0.001). In external validation, AM-SAS successfully detected differences in symptom burden and physical status between those with or without relapse. CONCLUSION: Electronic PRO-based AM-SAS is a valuable instrument for monitoring AM-related symptoms. As an outcome measure of multiple symptoms in clinical trials, the AM-SAS may identify patients who need extensive care after discharge and capture significant beneficial changes of patients may have been overlooked. TRIAL REGISTRATION: This trial was approved by the institutional review board of the Chongqing Medical University and three participating hospitals (Medical Ethics Committee of Nanchong Central Hospital, Medical Ethics Committee of Affiliated Hospital of Southwest Medical University, and Medical Ethics Committee of Haifu Hospital) and registered in the Chinese Clinical Trial Registry (registration number ChiCTR2000038590), date of registration was 26/10/2020.

Effect of Education on Symptom Management and Control in Cancer Patients Receiving Palliative Care.

OBJECTIVE: This study aims to investigate the effect of an educational intervention on cancer patients receiving palliative care and their caregivers concerning symptom management and family needs. METHODS: This study involved 120 participants-60 cancer patients and their respective caregivers-divided into intervention and control groups. Over a 2-week period, the intervention group received a comprehensive educational program focusing on symptom management, while the control group did not receive any educational intervention. The Edmonton Symptom Assessment System (ESAS) and Palliative Performance Scale (PPS) were used to assess patients' symptoms, their intensity, and performance, while the Family Need Scale (FNS) was utilized to evaluate caregivers' needs. These assessments were conducted at the beginning and end of the study. Primary outcomes focused on symptom assessment using ESAS and PPS, along with evaluating caregivers' needs through FNS. Secondary outcomes involved assessing participant satisfaction with the intervention. RESULTS: At the end of the study, comparing initial and second evaluations, both ESAS and PPS scores significantly increased in the intervention and control groups (p = .003, p = .002, respectively). Additionally, a statistically significant decrease in the severity of symptoms, except for lethargy/hypokinesis, was observed in the intervention group compared to the control group. The FNS scale indicated that family needs satisfaction was higher in the intervention group compared to the control group. The data obtained demonstrated that there was a reduction the pain, fatigue, depression, anxiety, drowsiness, and shortness of breath levels in the intervention group compared to the control group, but there was no significant difference other than these symptoms. CONCLUSIONS: The educational intervention positively impacted symptom management and family needs. Optimizing symptom control would greatly benefit palliative care patients and their caregivers.

Pre-hospital symptom clusters and symptom network analysis in decompensated cirrhotic patients: A cross-sectional study.

AIMS: To generate pre-hospital symptom networks, explore core, bridge and sentinel symptoms, identify pre-hospital symptom clusters and analyse relationship between influencing factors and symptom clusters in decompensated cirrhosis patients. DESIGN: A cross-sectional study design using the Strengthening the Reporting of Observational Studies in Epidemiology checklist. METHODS: Demographical, physiological, psychological and sociological characteristics and the pre-hospital symptoms of 292 decompensated cirrhotic patients were collected from October 2021 to March 2023 in China. Frequencies, percentages, means, standard deviations, independent samples t-tests, one-way analysis of variance, exploratory factor analysis, multiple stepwise regression analysis and network analysis were used for data analysis. RESULTS: 'I don't look like myself' and itching were core and bridge symptoms, while bloating and lack of energy were sentinel symptoms in decompensated cirrhotic patients. Monthly family income, anxiety, depression, social support and disease duration influenced the neuropsychological symptom cluster, with worrying as the strongest predictor symptom. Influential factors for cirrhosis-specific symptom cluster included Child-Pugh class, monthly family income, disease duration, anxiety and depression, with itching being the strongest predictor symptom. Monthly family income, disease duration and depression were influential factors for gastrointestinal symptom cluster, with loss of appetite as the strongest predictor symptom. CONCLUSIONS: Neuropsychological, cirrhosis-specific and gastrointestinal symptom clusters were formed in decompensated cirrhotic patients. Through network analysis, direct connections between symptoms, symptom clusters and their influencing factors were revealed, thereby offering clinicians a foundation for effectively managing patients' pre-hospital symptoms. IMPACT: Decompensated cirrhosis patients commonly have multiple symptoms, while the management of pre-hospital symptoms is often suboptimal. This study identified neuropsychological, cirrhosis-specific, gastrointestinal symptom clusters and recognized core, bridge and sentinel symptoms in these patients. It also revealed the most prominent symptoms within each cluster. This provides insight into the hierarchy of symptoms, improving symptom management in decompensated cirrhosis. PATIENT AND PUBLIC INVOLVEMENT: There was no patient or public involvement.

Exploring symptom clusters in Chinese patients with peritoneal dialysis: a network analysis.

BACKGROUND: In recent years, the research on symptom management in peritoneal dialysis (PD) patients has shifted from a single symptom to symptom clusters and network analysis. This study collected and evaluated unpleasant symptoms in PD patients and explored groups of symptoms that may affect PD patients with a view to higher symptom management. METHODS: The symptoms of PD patients were measured using the modified Dialysis Symptom Index. The symptom network and node characteristics were assessed by network analysis, and symptom clusters were explored by factor analysis. RESULTS: In this study of 602 PD patients (mean age 47.8 ± 16.8 years, 47.34% male), most had less than 2 years of dialysis experience. Five symptom clusters were obtained from factor analysis, which were body symptom cluster, gastrointestinal symptom cluster, mood symptom cluster, sexual disorder symptom cluster, and skin-sleep symptom cluster. Itching and decreased interest in sex may be sentinel symptoms, and being tired or lack of energy and feeling anxious are core symptoms in PD patients. CONCLUSIONS: This study emphasizes the importance of recognizing symptom clusters in PD patients for better symptom management. Five clusters were identified, with key symptoms including itching, decreased interest in sex, fatigue, and anxiety. Early intervention focused on these symptom clusters in PD patients holds promise for alleviating the burden of symptoms.

Assessment of emotional distress in palliative care: Edmonton Symptom Assessment System-revised (ESAS-r) vs Distress Thermometer.

OBJECTIVES: To evaluate the sensitivity and specificity of the Distress Thermometer (DT) as a screening tool for emotional distress in oncological palliative care patients and to compare the DT with the Edmonton Symptom Assessment System-revised (ESAS-r) and the gold standard to determine the most appropriate assessment method in palliative psychological care. METHODS: Data were collected from psychological screening tests (ESAS-r and DT), and clinical interviews (gold standard) were conducted by a clinical psychologist specialist in palliative oncology from January 2021 to January 2022 in an oncology palliative care service. RESULTS: The sample consisted of 356 first-time patients with a diagnosis of advanced cancer in palliative care. The most frequently reported oncological diagnoses were gastrointestinal tract (49.3%) and breast (18.3%). Most patients were female (n = 206; 57.9%), 60.4% were married/with a partner, 55.4% had between 6 and 9 years of schooling, and a median age of 57 (range, 46-65) years. The cutoff of the DT was 5, with a sensitivity of 75.88% and specificity of 54.3%. Emotional problems (sadness and nervousness) had a greater area under the curve (AUC) when measured using the DT than the ESAS-r; however, only in the case of the comparative sadness and discouragement was the difference between the AUC marginally significant. SIGNIFICANCE OF RESULTS: The use of the DT as a screening tool in oncological palliative care is more effective in the evaluation of psychological needs than the ESAS-r. The DT, in addition to evaluation by an expert psychologist, allows for a more comprehensive identification of signs and symptoms to yield an accurate mental health diagnosis based on the International Classification of Diseases-11th Revision and/or Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition.

Symptom Assessment Following Surgery for Lung Cancer: A Canadian Population-based Retrospective Cohort Study.

OBJECTIVE: To conduct a population-level analysis of temporal trends and risk factors for high symptom burden in patients receiving surgery for non-small cell lung cancer (NSCLC). BACKGROUND: A population-level overview of symptoms after curative intent surgery is necessary to inform decision making and supportive care for patients with lung cancer. METHODS: Retrospective cohort study of patients receiving surgery for stages I to III NSCLC between January 2007 and September 2018. Prospectively collection Edmonton Symptom Assessment System (ESAS) scores, linked to provincial administrative data, were used to describe the prevalence, trajectory, and predictors of moderate-to-severe symptoms in the year following surgery. RESULTS: A total of 5350 patients, with 28,490 unique ESAS assessments, were included in the analysis. Moderate-to-severe tiredness (68%), poor wellbeing (63%), and shortness of breath (60%) were the most common symptoms reported. The rise and fall in the proportion of patients experiencing moderate-to-severe symptoms after surgery coincided with the median time to first (58 days, interquartile range: 47-72) and last cycle of chemotherapy (140 days, interquartile range: 118-168), respectively. There was eventual stabilization, albeit above the preoperative baseline, within 6 to 7 months after surgery. Female sex (relative risk [RR] 1.09- 1.26), lower income (RR 1.08-1.23), stage III disease (RR 1.15-1.43), adjuvant therapy (RR 1.09-1.42), chemotherapy within 2 weeks of an ESAS assessment (RR 1.14-1.73), and pneumonectomy (RR 1.05-1.15) were associated with moderate-to-severe symptoms following surgery. CONCLUSIONS: Knowledge of population-level prevalence, trajectory, and predictors of moderate-to-severe symptoms after surgery for NSCLC can be used to facilitate shared decision making and improve symptom management throughout the course of illness.

Time Series Transcriptomic Analysis of Bronchoalveolar Lavage Cells from Piglets Infected with Virulent or Low-Virulent Porcine Reproductive and Respiratory Syndrome Virus 1.

Porcine reproductive and respiratory syndrome virus (PRRSV) has evolved to escape the immune surveillance for a survival advantage leading to a strong modulation of host's immune responses and favoring secondary bacterial infections. However, limited data are available on how the immunological and transcriptional responses elicited by virulent and low-virulent PRRSV-1 strains are comparable and how they are conserved during the infection. To explore the kinetic transcriptional signature associated with the modulation of host immune response at lung level, a time-series transcriptomic analysis was performed in bronchoalveolar lavage cells upon experimental in vivo infection with two PRRSV-1 strains of different virulence, virulent subtype 3 Lena strain or the low-virulent subtype 1 3249 strain. The time-series analysis revealed overlapping patterns of dysregulated genes enriched in T-cell signaling pathways among both virulent and low-virulent strains, highlighting an upregulation of co-stimulatory and co-inhibitory immune checkpoints that were disclosed as Hub genes. On the other hand, virulent Lena infection induced an early and more marked "negative regulation of immune system process" with an overexpression of co-inhibitory receptors genes related to T-cell and NK cell functions, in association with more severe lung lesion, lung viral load, and BAL cell kinetics. These results underline a complex network of molecular mechanisms governing PRRSV-1 immunopathogenesis at lung level, revealing a pivotal role of co-inhibitory and co-stimulatory immune checkpoints in the pulmonary disease, which may have an impact on T-cell activation and related pathways. These immune checkpoints, together with the regulation of cytokine-signaling pathways, modulated in a virulence-dependent fashion, orchestrate an interplay among pro- and anti-inflammatory responses. IMPORTANCE Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the major threats to swine health and global production, causing substantial economic losses. We explore the mechanisms involved in the modulation of host immune response at lung level performing a time-series transcriptomic analysis upon experimental infection with two PRRSV-1 strains of different virulence. A complex network of molecular mechanisms was revealed to control the immunopathogenesis of PRRSV-1 infection, highlighting an interplay among pro- and anti-inflammatory responses as a potential mechanism to restrict inflammation-induced lung injury. Moreover, a pivotal role of co-inhibitory and co-stimulatory immune checkpoints was evidenced, which may lead to progressive dysfunction of T cells, impairing viral clearance and leading to persistent infection, favoring as well secondary bacterial infections or viral rebound. However, further studies should be conducted to evaluate the functional role of immune checkpoints in advanced stages of PRRSV infection and explore a possible T-cell exhaustion state.

Closing the Loop: Re-engineering the Assessment and Tracking of Symptoms in Primary Care.

Reliable systems that track the continuation, progression, or resolution of a patient's symptoms over time are essential for reliable diagnosis and ensuring that patients harboring more worrisome diagnoses are safely followed up. Given their first-contact role and increasing stresses on busy primary care clinicians and practices, new processes that make these tasks easier rather than creating more work for busy clinicians are especially needed.Some symptoms are sufficiently worrisome that they demand an urgent diagnosis and treatment while others result in a differential that can be more safely explored over time, or less differentiated and worrisome that they are best managed with the "test of time" to see if they resolve, worsen, or evolve into symptoms that are more worrisome. Regardless, it is essential that clinicians are able to reliably track symptoms over time, yet this capacity is rarely available or explicit. Working with systems engineers, we are developing prototypes for such systems and are working on their implementation and evaluation. In this commentary, we describe approaches to this essential, but underappreciated, problem in primary care.

Feasibility of three times weekly symptom screening in pediatric cancer patients.

OBJECTIVE: Primary objective was to determine the feasibility of three times weekly symptom reporting by pediatric cancer patients for eight weeks. METHODS: We included English-speaking patients 8-18 years of age with cancer. Patients were sent reminders by text or email to complete Symptom Screening in Pediatrics Tool (SSPedi) three times weekly for eight weeks. When patients reported at least one severely bothersome symptom, the symptom report was emailed to the primary healthcare team. Patient-reported outcomes were obtained at baseline, week 4 ± 1 and week 8 ± 1. Symptom documentation, intervention provision for symptoms and unplanned healthcare encounters were determined by chart review at weeks 4 and 8. The primary endpoint was feasibility, defined as at least 75% patients achieving adherence with at least 60% of SSPedi evaluations. We planned to enroll successive cohorts until this threshold was met. RESULTS: Two cohorts consisting of 30 patients (cohort 1 (n = 20) and cohort 2 (n = 10)) were required to meet the feasibility threshold. In cohort 1, 11/20 (55%) met the SSPedi completion threshold. Interventions applied after cohort 1 included engaging parents to facilitate pediatric patient self-report, offering mechanisms to remember username and password and highlighting potential benefits of symptom feedback to clinicians. In cohort 2, 9/10 (90%) met the SSPedi completion threshold and thus feasibility was met. Patient-reported outcomes and chart review outcomes were obtained for all participants in cohort 2. CONCLUSIONS: Three times weekly symptom reporting by pediatric patients with cancer for eight weeks was feasible. Mechanisms to enhance three times weekly symptom reporting were identified and implemented. Future studies of longitudinal symptom screening can now be planned.

Current Therapeutic Options in Aortic Stenosis.

Aortic stenosis is the most common valvular disease requiring valve replacement. Valve replacement therapies have undergone progressive evolution since the 1960s. Over the last 20 years, transcatheter aortic valve replacement has radically transformed the care of aortic stenosis, such that it is now the treatment of choice for many, particularly elderly, patients. This review provides an overview of the pathophysiology, presentation, diagnosis, indications for intervention, and current therapeutic options for aortic stenosis.

Pathophysiology and Therapeutic Approaches to Acute Decompensated Heart Failure.

Acute decompensated heart failure (ADHF) is one of the leading admission diagnoses worldwide, yet it is an entity with incompletely understood pathophysiology and limited therapeutic options. Patients admitted for ADHF have high in-hospital morbidity and mortality, as well as frequent rehospitalizations and subsequent cardiovascular death. This devastating clinical course is partly due to suboptimal medical management of ADHF with persistent congestion upon hospital discharge and inadequate predischarge initiation of life-saving guideline-directed therapies. While new drugs for the treatment of chronic HF continue to be approved, there has been no new therapy approved for ADHF in decades. This review will focus on the current limited understanding of ADHF pathophysiology, possible therapeutic targets, and current limitations in expanding available therapies in light of the unmet need among these high-risk patients.