Clinical Severity Parameters Research Articles

Clinical characteristics, laboratory features and genetic profile of hemoglobin E (HBB:c.79 G > A)/β (nucleotide -28 A > G) (HBB:c.-78 A > G) -thalassemia subjects identified from community- and hospital-recruited cohorts

Despite several existing laboratory-based studies of hemoglobin (Hb) E (HBB:c.79 G > A)/ β (nucleotide (NT) -28 A > G) (HBB:c.-78 A > G) -thalassemia, no reports have ever provided clinical severity information as well as dependency of blood transfusion. Previously, a comparative study of community- and hospital-recruited Hb E/β-thalassemia subjects was conducted in the lower northern Thailand between June 2020 and December 2021. A mobile medical team visited each community hospital on-site, collecting clinical severity parameters, and conducting Hb and DNA analyses. The control included Hb E/β-thalassemia patients undergoing transfusions. Subgroup study of adult Hb E/β (NT -28 A > G) -thalassemia subjects was subsequently conducted. Additional pediatric individuals were recruited from prenatal diagnosis databases. Twenty adult and nine pediatric subjects were enrolled; all were classified as having mild disease severity. Twenty-two individuals (75.9 %) were asymptomatic. Six adults (20.7 %) required blood transfusion. The mean Hb level of subjects without transfusion (23 [79.3 %]) was 10.77 ± 1.10 g/dL. Hb analysis revealed a distinct EFA pattern with low Hb F fraction. The positive impact of genetic modifiers could not be statistically demonstrated except rs7482144-XmnI. These findings could provide essential information for parents carrying fetuses with Hb E/β (NT -28 A > G) -thalassemia.

Quantitative T2 Mapping of Acute Pancreatitis.

Quantification of the T2 signal by means of T2 mapping in acute pancreatitis (AP) has the potential to quantify the parenchymal edema. Quantitative T2 mapping may overcome the limitations of previously reported scoring systems for reliable assessment of AP. To evaluate MR-derived pancreatic T2 mapping values in AP and correlate them with markers of disease severity. Prospective single-center study. 76 adults with AP (20-91 years, females/males: 39/37). Fat suppressed multiecho spin-echo prototype sequence to quantify T2 signal at 3T MRI. The severity of AP was assessed clinically, biologically, and by contrast-enhanced CT (CECT) performed 48-72 hours after symptom onset. MRI was then performed ≤24 hours after CT. Two readers blinded to any clinical information independently evaluated the T2 values by placing three regions of interest inside the pancreatic head, body, and tail on the T2 mapping MR sequence. Results were compared with corresponding CECT images as the standard and clinical severity parameters, using the length of hospital stay as our primary endpoint. Continuous variables were compared using the Spearman's rank correlation coefficient, analysis of variance (ANOVA) or Student's t-test. T2 values significantly correlated with the length of hospital stay (rs (74) = 0.29), CT severity index (CTSI) (rs (73) = 0.61; CTSI 0-3: 72 ± 14 msec, CTSI 4-10: 88 ± 15), intensive care unit (ICU) admission (t(2.77) = -3.41) and presence of organ failure (t(6.72) = -3.42), whereas the CTSI and Ranson score were not significantly related with ICU admission (CTSI: P = 0.24; Ranson score: P = 0.24) and organ failure (CTSI: P = 0.11; Ranson score P = 0.11). T2 mapping correlates with AP severity parameters and is useful for assessing the severity of AP with higher sensitivity than the usual clinical and radiological scoring systems. 1 TECHNICAL EFFICACY: Stage 2.

Immunoglobulin free light chains in severe asthma patient: Could they be a new biomarker?

Increasing evidence is available about the presence of increased serum concentration of immunoglobulin (Ig) free light chains (FLCs) in both atopic and non-atopic inflammatory diseases, including severe asthma, providing a possible new biomarker of disease. We analyzed clinical and laboratory data, including FLCs, obtained from a cohort of 79 asthmatic subjects, clinically classified into different GINA steps. A control group of 40 age-matched healthy donors (HD) was considered. Particularly, HD have been selected according to the absence of monoclonal components (in order to exclude paraproteinemias), were tested for total IgE (that were in the normal ranges) and were negative for aeroallergens specific IgE. Moreover, no abnormality of common inflammatory markers (i.e., erythrocyte sedimentation rate and C-reactive protein) was detectable. FLC-k levels were significantly increased in the asthmatic population, compared to the control group. Despite the absence of statistically significant differences in FLC-λ levels, the FLC-k/FLC-λ ratio displayed remarkable differences between the two groups. A positive correlation between FLC-κ and FLC-λ levels was found. FLC- λ level displayed a significant negative correlation with the FEV1 value. Moreover, the FLC-κ /FLC- λ ratio was negatively correlated with the SNOT-22 score and a positive correlation was observed between FLCs and Staphylococcus Aureus IgE enterotoxins sensitization. Our findings confirmed the role of FLCs in asthma as a potential biomarker in an inflammatory disease characterized by different endotypes and phenotypes. In particular, FLC-κ and FLC-k/FLC-λ ratio could be a qualitative indicator for asthma, while FLC-λ levels could be a quantitative indicator for clinical severity parameters.

Scottish Index of Multiple Deprivation (SIMD) indicators as predictors of mortality among patients hospitalised with COVID-19 disease in the Lothian Region, Scotland during the first wave: a cohort study

BackgroundSars-CoV-2, the causative agent of COVID-19, has led to more than 226,000 deaths in the UK and multiple risk factors for mortality including age, sex and deprivation have been identified. This study aimed to identify which individual indicators of the Scottish Index of Multiple Deprivation (SIMD), an area-based deprivation index, were predictive of mortality.MethodsThis was a prospective cohort study of anonymised electronic health records of 710 consecutive patients hospitalised with Covid-19 disease between March and June 2020 in the Lothian Region of Southeast Scotland. Data sources included automatically extracted data from national electronic platforms and manually extracted data from individual admission records. Exposure variables of interest were SIMD quintiles and 12 indicators of deprivation deemed clinically relevant selected from the SIMD. Our primary outcome was mortality. Age and sex adjusted univariable and multivariable analyses were used to determine measures of association between exposures of interest and the primary outcome.ResultsAfter adjusting for age and sex, we found an increased risk of mortality in the more deprived SIMD quintiles 1 and 3 (OR 1.75, CI 0.99–3.08, p = 0.053 and OR 2.17, CI 1.22–3.86, p = 0.009, respectively), but this association was not upheld in our multivariable model containing age, sex, Performance Status and clinical parameters of severity at admission. Of the 12 pre-selected indicators of deprivation, two were associated with greater mortality in our multivariable analysis: income deprivation rate categorised by quartile (Q4 (most deprived): 2.11 (1.20–3.77) p = 0.011)) and greater than expected hospitalisations due to alcohol per SIMD data zone (1.96 (1.28–3.00) p = 0.002)).ConclusionsSIMD as an aggregate measure of deprivation was not predictive of mortality in our cohort when other exposure measures were accounted for. However, we identified a two-fold increased risk of mortality in patients residing in areas with greater income-deprivation and/or number of hospitalisations due to alcohol. In areas where aggregate measures fail to capture pockets of deprivation, exploring the impact of specific SIMD indicators may be helpful in targeting resources to residents at risk of poorer outcomes from Covid-19.

Anti-SARS-CoV-2 Seroconversion in COVID-19 Convalescent Kidney Transplant Recipients Compared with Non-transplanted Patients

Objective: Due to immunosuppression, kidney transplant recipients (KTRs) might have lower seroconversion after COVID-19 than non-KTRs. Thus, we aimed to evaluate the seroconversion rate after COVID-19 between KTRs and non-KTRs. Methods: This cohort study enrolled three non-paired groups of patients with COVID-19: 601 KTRs, 211 healthcare workers (HCWs), and 170 non-transplanted inhabitants (INHs) in a countryside city in Brazil. The anti-severe acute respiratory syndrome coronavirus 2 nucleocapsid antibody was assessed 14 days after diagnosis. The primary outcome was seroconversion. Results: The KTRs were older, had more comorbidities and severe COVID-19. Compared to HCWs and INHs, admission to the intensive care unit (ICU; 44.9% vs. 0% vs. 1.8%, p<0.001), mechanical ventilation requirement (32.3% vs. 0% vs. 1.8%, p<0.001), and death (28.8% vs. 0% vs. 1.2%, p<0.001) were significantly higher in KTRs. Seroconversion did not differ between the groups: 76.2% in KTRs, 74.9% in HCWs, and 82.2% in INHs (p=0.35). In a group-adjusted multivariable logistic regression, while a short period between infection and blood sample collection reduced the probability of seroconversion (adjusted odds ratio [aOR]=0.986), the presence of fever (aOR=1.737, p=0.017), cough (aOR=1.785, p=0.005), and requirement for ventilatory support (OR=1.981, p=0.017) increased the risk. Conclusions: Clinical severity, mechanical ventilation requirement and death by COVID-19 were significantly higher among the KTRs. However, among the survivors, KTRs had a similar seroconversion prevalence associated with clinical severity parameters and a shorter time of blood sample collection.

Complement activation profiles in anti-acetylcholine receptor positive myasthenia gravis.

Complement component 5 (C5) targeting therapies are clinically beneficial in patients with acetylcholine receptor antibody+ (AChR-Ab+ ) generalized myasthenia gravis (MG). That clearly implicates antibody-mediated complement activation in MG pathogenesis. Here, classical and alternative complement pathways were profiled in patients from different MG subgroups. In a case-control study, concentrations of C3a, C5a and sC5b9 were simultaneously quantified, indicating general activation of the complement system, whether via the classical and lectin pathways (C4a) or the alternative pathway (factors Ba and Bb) in MG patients with AChR or muscle-specific kinase antibodies (MuSK-Abs) or seronegative MG compared to healthy donors. Treatment-naïve patients with AChR-Ab+ MG showed substantially increased plasma levels of cleaved complement components, indicating activation of the classical and alternative as well as the terminal complement pathways. These increases were still present in a validation cohort of AChR-Ab+ patients under standard immunosuppressive therapies; notably, they were not evident in patients with MuSK-Abs or seronegative MG. Neither clinical severity parameters (at the time of sampling or 1 year later) nor anti-AChR titres correlated significantly with activated complement levels. Markers indicative of complement activation are prominently increased in patients with AChR-Ab MG despite standard immunosuppressive therapies. Complement inhibition proximal to C5 cleavage should be explored for its potential therapeutic benefits in AChR-Ab+ MG.

Short- and long-interval intracortical inhibition in EPM1 is related to genotype.

Progressive myoclonic epilepsy type 1 (EPM1) is caused by biallelic alterations in the CSTB gene, most commonly dodecamer repeat expansions. Although transcranial magnetic stimulation (TMS)-induced long-interval intracortical inhibition (LICI) was previously reported to be normal in EPM1, short-interval intracortical inhibition (SICI) was reduced. We explored the association between these measures and the clinical and genetic features in a separate group of patients with EPM1. TMS combined with electromyography was performed under neuronavigation. LICI was induced with an inter-stimulus interval (ISI) of 100 ms, and SICI with ISIs of 2 and 3ms, and their means (mSICIs) were expressed as the ratio of conditioned to unconditioned stimuli. LICI and mSICI were compared between patients and controls. Nonparametric correlation was used to study the association between inhibition and parameters of clinical severity, including the Unified Myoclonus Rating Scale (UMRS); among patients with EPM1 due to biallelic expansion repeats, also the association with the number of repeats was assessed. The study protocol was completed in 19 patients (15 with biallelic expansion repeats and 4 compound heterozygotes), and 7 healthy, age- and sex-matched control participants. Compared to controls, patients demonstrated significantly less SICI (median mSICI ratio 1.18 vs 0.38; p < .001). Neither LICI nor SICI was associated with parameters of clinical severity. In participants with biallelic repeat expansions, the number of repeats in the more affected allele (greater repeat number [GRN]) correlated with LICI (rho=0.872; p < .001) and SICI (rho=0.689; p=.006). Our results strengthen the finding of deranged γ-aminobutyric acid (GABA)ergic inhibition in EPM1. LICI and SICI may have use as markers of GABAergic impairment in future trials of disease-modifying treatment in this condition. Whether a higher number of expansion repeats leads to greater GABAergic impairment warrants further study.

Impact of metabolic syndrome and its components on clinical severity and long-term prognosis in patients with premature myocardial infarction

Abstract Background Metabolic syndrome (MetS) is involved in the occurrence, development and prognosis of cardiovascular diseases, especially acute myocardial infarction (AMI). In recent years, the trend of AMI at a younger age has gradually attracted people's attention. Relevant studies have confirmed that MetS affects the prognosis of people aged ≥45 with AMI. However, there is still a lack of research on MetS in people with premature myocardial infarction (PMI). Purpose To explore the impact of MetS and its components on clinical severity and long-term prognosis in PMI patients. Methods 772 Patients with AMI who aged ≤45 years old from 2015 to 2020 in a hospital were enrolled. The patients were divided into MetS group (n=417) and non-MetS group (n=355) according to the criteria proposed by NCEP ATP III in 2005 (Any 3 of the following 5): 1) Hypertension: BP ≥130/85 mmHg or consistent hypertensive patients undergoing treatment; 2) Hypertriglyceridemia: fasting plasma triglyceride ≥1.7 mmol/L; 3) Fasting HDL-C &amp;lt;1.0 mmol/L in men and &amp;lt;1.3 mmol/L in women. 4) Hyperglycemia: fasting blood glucose level ≥6.1 mmol/L or known diabetic patients undergoing treatment; 5) Central obesity: BMI ≥28.0 kg/m2. Patients were followed for median of 42 months for major adverse cardiovascular events (MACE). The parameters of clinical severity were compared using logistic regression analysis. Cox regression were used to analyze the relationship between MetS and its components and prognosis. Results A total of 772 patients were included in the analysis. Hyperglycemia was associated with multi-vessel disease (OR=1.700, 95% CI 1.172–2.464, P=0.005) and Syntax score ≥33 (OR=2.736, 95% CI 1.241–6.032, P=0.013).Increased MACE were observed in the MetS group (17.9% vs 10.3%, P=0.004) after 42 months follow-up. The Kaplan-Meier curve also showed significant differences (P&amp;lt;0.001). MetS was an independent risk factor for MACE (HR=2.181, 95% CI 1.392–3.418, P=0.001). Of each component of the definition, BMI ≥28.0 kg/m2 (HR=2.047, 95% CI 1.229–3.410, P=0.006) and hyperglycemia (HR=2.911, 95% CI 1.850–4.580, P&amp;lt;0.001) were independent risk factors for MACE. Conclusions In patients with PMI, (1) hyperglycemia usually indicates more severe lesions; (2) MetS as a whole was an independent risk factor for MACE; (3) Of each component of the MetS, BMI ≥28.0 kg/m2 and hyperglycemia were associated with MACE. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): This research was supported by the Key Project of Scientific and Technological Support Plan of Tianjin in 2020

EVALUATION OF SERUM VITAMIN D3 [1.25 (OH) 2] LEVELS IN PATIENTS WITH ORAL LICHEN PLANUS AND ITS ASSOCIATION WITH DISEASE

<h3>Objectives</h3> To evaluate the serum levels of vitamin D3 (VD3) in patients with oral lichen planus (OLP) and its relationship with the severity of this pathology. <h3>Study Design</h3> This observational study was composed of patients diagnosed with OLP according to the criteria of the American Academy of Oral and Maxillofacial Pathology. Clinical-demographic data of the patients were collected, and a serologic exam was requested to assess the levels of VD3, which subsequently related to clinical parameters of severity: clinical type, symptoms, and response to corticosteroid therapy. The statistical analysis was descriptive, and chi-square test was used. <h3>Results</h3> The analysis of 34 patients with OLP revealed a predominance of females (<i>n</i> = 29; 85.2%) with a mean age of 47.5 (±14.6) years. VD3 deficiency (<30 ng/mL) was detected in 24 patients (70.5%) and, when compared to the milder forms of the disease, most were of the erosive type (<i>P</i> = .02) and with a negative response to corticotherapy (<i>P</i> < .001). In patients with painful symptoms, although there was no significant difference (<i>P</i> = .2), a predominance of deficient levels of VD3 was detected (80.9%). <h3>Conclusions</h3> The results of this study demonstrate that VD3 deficiency was more frequent in the most severe forms of OLP.

Impact of Metabolic Syndrome and Its Components on Clinical Severity and Long-Term Prognosis in Patients With Premature Myocardial Infarction.

BackgroundThe effects of metabolic syndrome (MS) on premature myocardial infarction (PMI) are not clear to date. This study aimed to investigate the impact of MS and its components on clinical severity and long-term prognosis in patients with PMI.MethodsWe enrolled 772 patients aged ≤45 years old who were diagnosed with acute myocardial infarction (AMI) at our hospital consecutively between 2015 and 2020. The patients were divided into an MS group and non-MS group. The parameters of clinical severity were compared using regression analysis. Patients were followed for median of 42 months for major adverse cardiovascular events (MACE).ResultsHyperglycemia was associated with multi-vessel disease [odds ratio(OR)=1.700, 95% confidence interval (CI)=1.172-2.464, P=0.005] and Syntax score ≥33 (OR=2.736, 95% CI=1.241-6.032, P=0.013). Increased MACE were observed in the MS group(17.9% vs 10.3%, P=0.004).The Kaplan-Meier curve also showed significant differences (P< 0.001). MS was an independent risk factor for MACE. Of each component of MS, BMI ≥28 kg/m2 (hazard ratio [HR]=2.022, 95% CI =1.213-3.369, P=0.007] and hyperglycemia (HR=2.904, 95% CI=1.847-4.567, P<0.001) were independent risk factors for MACE.ConclusionsIn patients with PMI, 1) hyperglycemia usually indicates more severe lesions; 2) MS as a whole was an independent risk factor for MACE; 3) BMI ≥28.0 kg/m2 and hyperglycemia were associated with MACE.

Systemic-pulmonary collateral supply associated with clinical severity of chronic thromboembolic pulmonary hypertension: a study using intra-aortic computed tomography angiography

ObjectivesTo assess whether systemic-pulmonary collaterals are associated with clinical severity and extent of pulmonary perfusion defects in chronic thromboembolic pulmonary hypertension (CTEPH).MethodsThis prospective study was approved by a local ethics committee. Twenty-four patients diagnosed with inoperable CTEPH were enrolled between July 2014 and February 2017. Systemic-pulmonary collaterals were detected using pulmonary vascular enhancement on intra-aortic computed tomography (CT) angiography. The pulmonary enhancement parameters were calculated, including (1) Hounsfield unit differences (HUdiff) between pulmonary trunks and pulmonary arteries (PAs) or veins (PVs), namely HUdiff-PA and HUdiff-PV, on the segmental base; (2) the mean HUdiff-PA, mean HUdiff-PV, numbers of significantly enhanced PAs and PVs, on the patient base. Pulmonary perfusion defects were recorded and scored using the lung perfused blood volume (PBV) based on intravenous dual-energy CT (DECT) angiography. Pearson’s or Spearman’s correlation coefficients were used to evaluate correlations between the following: (1) segment-based intra-aortic CT and intravenous DECT parameters (2) patient-based intra-aortic CT parameters and clinical severity parameters or lung PBV scores. Statistical significance was set at p < 0.05.ResultsSegmental HUdiff-PV was correlated with the segmental perfusion defect score (r = 0.45, p < 0.01). The mean HUdiff-PV was correlated with the mean pulmonary arterial pressure (PAP) (r = 0.52, p < 0.01), cardiac output (rho = − 0.41, p = 0.05), and lung PBV score (rho = 0.43, p = 0.04). And the number of significantly enhanced PVs was correlated with the mean PAP (r = 0.54, p < 0.01), pulmonary vascular resistance (r = 0.54, p < 0.01), and lung PBV score (rho = 0.50, p = 0.01).ConclusionsPV enhancement measured by intra-aortic CT angiography reflects clinical severity and pulmonary perfusion defects in CTEPH.Key Points• Intra-aortic CT angiography demonstrated heterogeneous enhancement within the pulmonary vasculature, showing collaterals from the systemic arteries to the pulmonary circulation in CTEPH.• The degree of systemic-pulmonary collateral development was significantly correlated with the clinical severity of CTEPH and may be used to evaluate disease progression.• The distribution of systemic-pulmonary collaterals is positively correlated with perfusion defects in the lung segments in CTEPH.

Parenchymal involvement on CT pulmonary angiography in SARS-CoV-2 Alpha variant infection and correlation of COVID-19 CT severity score with clinical disease severity and short-term prognosis in a UK cohort

AIMTo determine if there is a difference in radiological, biochemical, or clinical severity between patients infected with Alpha-variant SARS-CoV-2 compared with those infected with pre-existing strains, and to determine if the computed tomography (CT) severity score (CTSS) for COVID-19 pneumonitis correlates with clinical severity and can prognosticate outcomes.MATERIALS AND METHODSBlinded CTSS scoring was applied to 137 hospital patients who had undergone both CT pulmonary angiography (CTPA) and whole-genome sequencing of SARS-CoV-2 within 14 days of CTPA between 1/12/20–5/1/21.RESULTSThere was no evidence of a difference in imaging severity on CTPA, viral load, clinical parameters of severity, or outcomes between Alpha and preceding variants. CTSS on CTPA strongly correlates with clinical and biochemical severity at the time of CTPA, and with patient outcomes. Classifying CTSS into a binary value of “high” and “low”, with a cut-off score of 14, patients with a high score have a significantly increased risk of deterioration, as defined by subsequent admission to critical care or death (multivariate hazard ratio [HR] 2.76, p<0.001), and hospital length of stay (17.4 versus 7.9 days, p<0.0001).CONCLUSIONThere was no evidence of a difference in radiological severity of Alpha variant infection compared with pre-existing strains. High CTSS applied to CTPA is associated with increased risk of COVID-19 severity and poorer clinical outcomes and may be of use particularly in settings where CT is not performed for diagnosis of COVID-19 but rather is used following clinical deterioration.

Long-term infant outcomes after hyperbaric oxygen treatment for acute carbon monoxide poisoning during pregnancy.

Carbon monoxide (CO) poisoning in pregnant women is linked to foetal mortality of 36-67%. This study assessed long-term fetal outcomes following hyperbaric oxygen treatment (HBOT) for acute CO poisoning in pregnant women. The effects of clinical severity parameters and pregnancy trimester were also analysed. A retrospective review of 28 pregnant patients who received HBOT for acute CO poisoning between January 2013-June 2016 was made. Adverse events, birth week, birth weight-height, birth complications, and the age of crawling, walking independently, talking (first words) of their children were recorded. Twenty-eight singleton pregnancies were included. One fetus was dead before HBOT. Three adverse events were reported: abortion, premature birth, and limb malformation. All remaining patients (n = 24) delivered healthy term infants and reported normal neurophysiological development. At final interview the median age of babies was 34 (8-44) months and none had any diagnosed disease. There was no relationship between clinical severity parameters and long-term outcomes. However, the pregnancy trimester at the time of CO poisoning had a significant relationship to birth weight (P = 0.029). Also, the week of pregnancy at the time of the incident correlated with the age of walking independently (P = 0.043, r = 0.436). This is the largest relevant series and longest follow-up to date. Adverse outcomes were likely incidental because the mothers' medical histories revealed alternative aetiologies. There was no definite evidence of fetal morbidity or mortality after HBOT in this study. HBOT may improve long-term fetal outcomes after in-utero CO poisoning without complications.

Retinal Microcirculation as a Correlate of a Systemic Capillary Impairment After Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), affects the pulmonary systems via angiotensin-converting enzyme-2 (ACE-2) receptor, being an entry to systemic infection. As COVID-19 disease features ACE-2 deficiency, a link to microcirculation is proposed. Optical coherence tomography angiography (OCT-A) enables non-invasive analysis of retinal microvasculature. Thus, an impaired systemic microcirculation might be mapped on retinal capillary system. As recent OCT-A studies, analyzing microcirculation in two subdivided layers, yielded contrary results, an increased subdivision of retinal microvasculature might offer an even more fine analysis. The aim of the study was to investigate retinal microcirculation by OCT-A after COVID-19 infection in three subdivided layers (I). In addition, short-term retinal affections were monitored during COVID-19 disease (II). Considering (I), a prospective study (33 patientspost−COVID and 28 controls) was done. Macula and peripapillary vessel density (VD) were scanned with the Spectralis II. Macula VD was measured in three layers: superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP). Analysis was done by the EA-Tool, including an Anatomical Positioning System and an analysis of peripapillary VD by implementing Bruch's membrane opening (BMO) landmarks. Overall, circular (c1, c2, and c3) and sectorial VD (s1-s12) was analyzed. Considering (II), in a retrospective study, 29 patients with severe complications of COVID-19 infection, hospitalized at the intensive care unit, were monitored for retinal findings at bedside during hospitalization. (I) Overall (p = 0.0133) and circular (c1, p = 0.00257; c2, p = 0.0067; and c3, p = 0.0345). VD of the ICP was significantly reduced between patientspost−COVID and controls, respectively. Overall (p = 0.0179) and circular (c1, p = 0.0189) peripapillary VD was significantly reduced between both groups. Subgroup analysis of hospitalized vs. non-hospitalized patientspost−COVID yielded a significantly reduced VD of adjacent layers (DCP and SVP) with increased severity of COVID-19 disease. Clinical severity parameters showed a negative correlation with VD (ICP) and peripapillary VD. (II) Funduscopy yielded retinal hemorrhages and cotton wool spots in 17% of patients during SARS-CoV-2 infection. As VD of the ICP and peripapillary regions was significantly reduced after COVID-19 disease and showed a link to clinical severity markers, we assume that the severity of capillary impairment after COVID-19 infection is mapped on retinal microcirculation, visualized by non-invasive OCT-A.

The effect of the COVID-19 lockdown on children with asthma-related symptoms: A tertiary care center experience.

BackgroundAcute asthma exacerbations are a common cause for emergency department (ED) visits and hospitalizations in children. Since the outbreak of coronavirus disease 2019 (COVID‐19) and the education system closure/total lockdown in Israel on March 2020, we have noticed a decrease in pediatric ED visits and an increase in hospitalizations of asthma exacerbations.Objectiveto examine the patterns of ED visits for asthma exacerbations during COVID‐19 outbreak, in comparison to the previous year.MethodsA retrospective study comparing asthma related ED visits and hospitalizations among children aged 2–18 years at a tertiary center in southern Israel. Three time periods were selected: 2020 A (prelockdown, 2/1/20 to 3/14/20), 2020 B (lockdown, 3/15/20 to 5/15/20) and 2020 C (postlockdown, 5/16/20 to 6/30/20) and compared to the three parallel time periods in 2019. Data regarding demographics, number of ED visits and clinical severity parameters were collected and analyzed.ResultsFive hundred and twelve children visited the ED for asthma exacerbation: 273 children during 2019 and 239 children during 2020. Lockdown period in 2020 revealed significantly fewer ED visits per day compared to the parallel calendar period in 2019 (1.8 vs. 1.43, p < .001). Significantly higher hospitalization rate (47.1% vs. 33.7%, p = .05) and longer length of stay (3.15 vs. 1.9 days, p = .03) were observed during the lockdown.ConclusionLockdown is associated with fewer ED visits for asthma exacerbation, probably due to; reduced exposure to viral infections and environmental allergens, decreased availability of primary physicians and families' reluctance to arrive to the ED. ED visits during lockdown were characterized by higher hospitalization rate and longer LOS.

Acquired decrease of the C3b/C4b receptor (CR1, CD35) and increased C4d deposits on erythrocytes from ICU COVID-19 patients

In order to study the mechanisms of COVID-19 damage following the complement activation phase occurring during the innate immune response to SARS-CoV-2, CR1 (the regulating complement activation factor, CD35, the C3b/C4b receptor), C4d deposits on Erythrocytes (E), and the products of complement activation C3b/C3bi, were assessed in 52 COVID-19 patients undergoing O2 therapy or assisted ventilation in ICU units in Rheims France. An acquired decrease of CR1 density on E from COVID-19 patients was observed (Mean = 418, SD = 162, N = 52) versus healthy individuals (Mean = 592, SD = 287, N = 400), Student’s t-test p < 10−6, particularly among fatal cases, and in parallel with several parameters of clinical severity. Large deposits of C4d on E in patients were well above values observed in normal individuals, mostly without concomitant C3 deposits, in more than 80% of the patients. This finding is reminiscent of the increased C4d deposits on E previously observed to correlate with sub endothelial pericapillary deposits in organ transplant rejection, and with clinical SLE flares. Conversely, significant C3 deposits on E were only observed among ¼ of the patients. The decrease of CR1/E density, deposits of C4 fragments on E and previously reported detection of virus spikes or C3 on E among COVID-19 patients, suggest that the handling and clearance of immune complex or complement fragment coated cell debris may play an important role in the pathophysiology of SARS-CoV-2. Measurement of C4d deposits on E might represent a surrogate marker for assessing inflammation and complement activation occurring in organ capillaries and CR1/E decrease might represent a cumulative index of complement activation in COVID-19 patients.Taken together, these original findings highlight the participation of complement regulatory proteins and indicate that E are important in immune pathophysiology of COVID-19 patients. Besides a potential role for monitoring the course of disease, these observations suggest that novel therapies such as the use of CR1, or CR1-like molecules, in order to down regulate complement activation and inflammation, should be considered.

Optical coherence tomography to measure the progression of myelopathy in adrenoleukodystrophy.

ObjectiveTo prospectively determine the value of optical coherence tomography (OCT) as a surrogate outcome measure for the progression of myelopathy in males with adrenoleukodystrophy.MethodsRetinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) thickness were measured at baseline, 1‐ and 2‐year follow‐up in patients and age‐matched controls. We assessed the severity of myelopathy with clinical parameters: Expanded Disability Status Scale (EDSS), Severity Scoring system for Progressive Myelopathy (SSPROM), and timed up‐and‐go. Linear mixed model analysis was used to compare changes in retinal layer thickness of patients to controls. In addition, we correlated changes in retinal layer thickness with changes in clinical parameters.ResultsLongitudinal data were available for 28 patients and 29 controls. Peripapillary RNFL (pRNFL) thickness decreased significantly in patients compared to controls (−1.75µm, p = 0.001), whereas change in macular GCL and RNFL was not different between groups. Analysis of the symptomatic subgroup showed that, apart from a similar decrease in pRNFL thickness, GCL thickness decreased significantly (−0.55 µm, p = 0.014). There were moderately strong correlations between changes in retinal layer thickness and changes in clinical parameters of severity of myelopathy.InterpretationThis prospective study demonstrates the potential of OCT‐measured retinal neurodegeneration as a surrogate outcome measure for the progression of myelopathy in adrenoleukodystrophy. As differences were small, our findings need to be confirmed with longer follow‐up and/or in a larger patient sample.

Plasma NfL and GFAP as biomarkers of spinal cord degeneration in adrenoleukodystrophy.

ObjectiveTo explore the potential of neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) as biomarkers of spinal cord degeneration in adrenoleukodystrophy, as objective treatment‐outcome parameters are needed.MethodsPlasma NfL and GFAP levels were measured in 45 male and 47 female ALD patients and compared to a reference cohort of 73 healthy controls. For male patients, cerebrospinal fluid (CSF) samples (n = 33) and 1‐year (n = 39) and 2‐year (n = 18) follow‐up data were also collected. Severity of myelopathy was assessed with clinical parameters: Expanded Disability Status Scale (EDSS), Severity Scoring system for Progressive Myelopathy (SSPROM), and timed up‐and‐go.ResultsNfL and GFAP levels were higher in male (P < 0.001, effect size (partial ƞ2) NfL = 0.49, GFAP = 0.13) and female (P < 0.001, effect size NfL = 0.19, GFAP = 0.23) patients compared to controls; levels were higher in both symptomatic and asymptomatic patients. In male patients, NfL levels were associated with all three clinical parameters of severity of myelopathy (EDSS, SSPROM, and timed up‐and go), while GFAP in male and NfL and GFAP in female patients were not. Changes in clinical parameters during follow‐up did not correlate with (changes in) NfL or GFAP levels. Plasma and CSF NfL were strongly correlated (r = 0.60, P < 0.001), but plasma and CSF GFAP were not (r = 0.005, P = 0.98).InterpretationOur study illustrates the potential of plasma NfL as biomarker of spinal cord degeneration in adrenoleukodystrophy, which was superior to plasma GFAP in our cohort.

Optical coherence tomography shows neuroretinal thinning in myelopathy of adrenoleukodystrophy

BackgroundProgressive myelopathy is the main cause of disability in adrenoleukodystrophy (ALD). Development of therapies is hampered by a lack of quantitative outcome measures. In this study, we investigated whether myelopathy in ALD is associated with retinal neurodegeneration on optical coherence tomography (OCT), which could serve as a surrogate outcome measure.MethodsSixty-two patients (29 men and 33 women) and 70 age-matched and sex-matched controls (33 men and 37 women) were included in this cross-sectional study. We compared retinal nerve fiber layer (RNFL), ganglion cell layer (GCL) and peripapillary retinal nerve fiber layer (pRNFL) thickness between ALD patients and controls. In addition, we correlated these OCT measurements with clinical parameters of severity of myelopathy.ResultsPatients had significantly thinner RNFL (male group, p < 0.05) and pRNFL superior and temporal quadrant [both male (p < 0.005) and female (p < 0.05) groups] compared to controls. Comparing three groups (symptomatic patients, asymptomatic patients and controls), there were significant differences in RNFL thickness (total grid and peripheral ring) in the male group (p ≤ 0.002) and in pRNFL thickness (superior and temporal quadrant) in both male (p ≤ 0.02) and the female (p ≤ 0.02) groups. Neuroretinal layer thickness correlated moderately with severity of myelopathy in men (correlation coefficients between 0.29–0.55, p < 0.02), but not in women.ConclusionsThese results suggest that neurodegeneration of the spinal cord in ALD is reflected in the retina of patients with ALD. Therefore, OCT could be valuable as an outcome measure for the myelopathy of ALD. Additional longitudinal studies are ongoing.

Diaphragmatic thickness in chronic obstructive lung disease and relationship with clinical severity parameters

Background/aimSonographic assessment of diaphragm structure and function would be a useful clinical tool in patients with chronic obstructive pulmonary disease (COPD). Our aim was to determine the muscle thickness of the diaphragm and the usefulness of clinical practice in patients with COPD.Materials and methodsThe diaphragmatic thickness of 34 COPD patients and 34 healthy subjects was measured during tidal volume (Tmin) and deep inspiration (Tmax) on both sides using a B-mode ultrasound. The body mass index and the modified Medical Research Council (mMRC) index values were reported.ResultsThere was no correlation among TminR (P = 0.134), TminL (P = 0.647), TmaxR (P = 0.721), and TmaxL (P = 0.905) between the patients with COPD and the control group. There was also no significant difference between diaphragmatic thickness and COPD severity, respiratory function (P = 0.410), and frequency of exacerbations (P = 0.881) and mMRC (P = 0.667). ConclusionDiaphragmatic dysfunction in COPD is related to mobility restriction rather than muscle thickness.