Low Lymphocyte Count Research Articles

Epidemiological, Clinical, and Laboratory Findings of 235 Hospitalized COVID-19 Adult Patients (Survivors and Non-Survivors) at Sohar Hospital in Oman.

The aim of this study was to describe the epidemiological and clinical characteristics and laboratory findings of coronavirus disease 2019 (COVID-19) patients at the Sohar Hospital, Sohar, Oman. This retrospective study of admitted COVID-19 patients at Sohar Hospital in Oman was carried out from March to October 2020. Demographics and laboratory data of 19 tests for 235 COVID-19 patients, of which 202 were survivors and 33 were non-survivors, were collected from the hospital information system after ethics approval. Thirteen factors were significantly correlated with in-hospital mortality, including older age, having chronic disease, high neutrophil count, high troponin T, high creatinine, low albumin (p < 0.0001), high white blood cell (WBC) count, low hemoglobin, high D-dimer (p < 0.001), high C-reactive protein (CRP) (p < 0.002), low lymphocyte count (p < 0.003), high alkaline phosphatase (ALP) enzyme (p < 0.007) and high ferritin (p < 0.045). The most common laboratory blood test abnormalities that were highly correlated with mortality were increased values of CRP (100% of non-survivors), D-dimer (94.1% of non-survivors), ferritin (88.2% of non-survivors), and troponin T (85% of non-survivors) and reduced lymphocyte count (73.9% of non-survivors). These findings could help in categorizing COVID-19 patients for risk-based assessment and early identification of patients with poor prognosis.

The immunological response of Egyptians to coronavirus disease-19 infection: a cohort study of lymphocyte populations and peripheral blood counts

Background The worldwide pandemic of COVID-19 infection that started in 2019 still lays its shadows over all populations of the world. COVID-19 infection presented with a spectrum of symptoms that varied from wave to wave, and also led to a wide number of long-term sequelae. Many immune system cells and cytokines were implicated in COVID-19 pathophysiology. Thus, many immuno-modulator and immuno-suppressive drugs were used in the management of severe cases. Lymphocytes are the key players of immune system, the change in their count and different subsets is expected to vary with COVID-19 infection. Objective The current study aimed to evaluate the role of peripheral blood lymphocyte subsets in predicting the outcome of COVID-19 patients and to investigate their correlation with different clinical and laboratory variables. Materials and methods The study included 64 patients hospitalized with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). They were stratified according to in-hospital mortality into survivors and nonsurvivors. Demographic, clinical and laboratory data were collected. Flowcytometric evaluation of lymphocyte subsets was done on admission. Results and conclusion Nonsurvivors showed lower relative lymphocyte count, higher absolute neutrophil count, and higher neutrophil to lymphocyte ratio (NLR) compared with survivors (P = 0.034, 0.006, 0.011; respectively). NLR at a cut off 15.3 had a sensitivity of 70.59% and specificity of 61.29% for predicting mortality in COVID-19 patients. The relative and absolute counts of lymphocyte subsets did not show a statistically significant difference between the two groups. Platelet count showed statistically significant positive correlation with absolute counts of total T lymphocytes, T helper, T cytotoxic, and B lymphocytes. The platelet to lymphocyte ratio (PLR), NLR and D-dimer results were negatively correlated with the total T lymphocytes, T helper, T cytotoxic, naïve T cytotoxic and B lymphocyte absolute counts. The NLR, absolute neutrophil count and platelet count may serve as adjuvant predictors of survival in COVID-19 disease. Although lymphocyte subsets did not differ statistically across survival groups, their correlation with other possible prognostic markers may justify further investigation on their role in COVID-19 pathophysiology.

Characteristics of COVID-19 Infections and Severe Outcomes in a Multinational Study in Latin America During the Circulation Period of the Delta Variant in the Pediatric Population

Abstract Background SARS-CoV-2 infection had specific characteristics in the pediatric population described in previous studies. These clinical features included specific COVID-19 presentation, antibiotic usage, and predictors of disease severity. In addition to patient related factors, external influences could affect COVID-19 outcomes. The features of children with COVID-19 of five Latin American countries were described. Study participants were members of the Prevencionistas e Infectólogos para Cáncer Pediátrico en América Latina (PRINCIPAL) Network of the Global Infectious Diseases Program at St Jude Children's Research Hospital. This study aims to analyze the differences between patients with non-severe and severe disease when the circulation of the Delta variant was predominant, and few children had received SARS-CoV-2 vaccines. Methods This is a retrospective, observational, multinational study that included children with a confirmed diagnosis of COVID-19 between January 2021 and January 2022. Epidemiological, clinical, and treatment characteristics are described and compared between patients with severe and non-severe disease. Frequencies and percentages are presented as well as median and interquartile ranges (IQR). Comparisons were made using the chi-squared test for proportions and the Wilcoxon test for nonparametric quantitative variables. Results 745 patients were included. Patients had a median age of 51 (13-139) months, 194 (26%) had comorbidities, and 701 (94%) presented with symptomatic disease. Fever was present in 524 (74.8%) patients, respiratory symptoms in 550 (78.5%), followed by gastrointestinal manifestations in 218 (31.1%). X-ray findings were abnormal in 175/362 patients, with interstitial infiltrates being the most common finding, 123 (70.7%). Almost a third of patients (29%) received an antibiotic; ceftriaxone was most frequently prescribed in 123/216 cases. Of 745 patients, 526 (70.8%) were hospitalized, of which 165 (31.4%) required PICU admission. Patients presenting with severe disease and requiring PICU admission we more likely to have a comorbidity, 128 (22%) vs. 66 (40%), p&amp;lt;0.001. Mucocutaneous findings or adenitis were more frequently described in severe cases, 19 (11.5) vs. 18 (5.0%), p=0.007. Regarding laboratory results, low lymphocytes 2445 vs. 1676 (p&amp;lt;0.001) and low platelets 294,000 vs. 250,000 (p=0.0002) were most common in patients with severe disease. The proportion of patients with lymphocytopenia was also higher in those with severe disease, 39% vs. 52% p= 0.010. Not surprisingly, antibiotic usage (broad and narrow spectrum) was higher in patients admitted to the PICU (32 vs. 16.5%) p=0.001, despite no significant difference in the frequency of bacterial coinfection (5.56% vs. 9.7% p=0.081) when compared to patients with non-severe disease. Specific treatment strategies were more frequent in PICU patients (39.1% vs. 72.1%) p&amp;lt;0.001, and steroids were the most frequently used drug, 35.2% vs. 70.7% (p&amp;lt;0.001). Table 1. Conclusions Regardless of the variant, COVID-19 is an important cause of hospitalization in children. Fever, respiratory and gastrointestinal symptoms are the most frequent manifestations in children. Despite the low frequency of bacterial coinfection, a high proportion of antibiotic usage is described. Compared to recent publications, mucocutaneous involvement, lower lymphocyte and platelet counts, and higher inflammatory markers were more frequently found in admissions to the PICU. Currently, with higher vaccine coverage and more comprehensive knowledge of the disease, optimization of pediatric COVID-19 management is expected, especially concerning antibiotic use. It is essential to continue multicenter surveillance of the behavior of COVID-19 in the pediatric population.

A Comparison of Haematological and Biochemical Profiles between Intrauterine Growth Restriction and Normal Piglets at 72 Hours Postpartum.

Intrauterine growth restriction in piglets has been a problem in the pig industry due to genetic selection based on hyperprolificacy. This has led to an increase in the number of underweight piglets and a worsening of the survival rate. The goal of this study was to enhance the knowledge of differences between normal and IUGR piglets a few hours after birth in terms of haematological variables, biochemical parameters, and immunoglobulin levels. Two groups of 20 piglets each were assessed. The control group (N) was made up of piglets with weights greater than 1500 g, and the IUGR group consisted of piglets weighing 500-1000 g and with at least two IUGR features. Blood samples were collected 72 h after birth for analysis of the red and white blood cell parameters, reticulocyte indices, platelet indices, biochemical parameters, and immunoglobulin levels. Alterations in red blood cells and reticulocytes, a lower lymphocyte count, hyperinsulinemia, and high oxidative stress were observed in IUGR piglets (p < 0.05). In contrast, differences were not observed (p > 0.05) in the serum immunoglobulin level. It can be concluded that the haematological and biochemical differences in IUGR piglets with respect to normal-weight piglets are present at birth indicating possible alterations in immunity, metabolism, and redox status; therefore, IUGR piglets could be more vulnerable to illness and future disorders, such as metabolic syndrome.

Prognostic significance of peripheral neutrophils and lymphocytes in early untreated Parkinson’s disease: an 8-year follow-up study

BackgroundTo explore whether peripheral blood neutrophils and lymphocytes are associated with longitudinal motor and cognitive decline in patients with early Parkinson’s disease (PD) and, to uncover the disease-specific mechanisms underlying...

Frequency and risk factors of rebound after fingolimod discontinuation – A retrospective study

BackgroundFingolimod (FTY) rebound, a phenomenon of unexpectedly severe disease activity following FTY discontinuation, has been reported to occur in 5–43 % of patients. Only a few larger cohorts have been analyzed. We aimed to determine the frequency and risk factors of FTY rebound in our hospital district in Southern Finland with a population of 1.7 million. MethodsWe searched the Finnish MS-register for patients who were previous or current users of FTY for at least 6 months by November 2020. We assessed medical records and collected basic demographic data for the whole cohort. Criteria for a rebound were: (i) the most severe relapse in patient's history and an increase of at least 2 EDSS points during the relapse occurring within 6 months from FTY cessation, or (ii) more than one relapse within 6 months after FTY discontinuation, this being the highest relapse rate observed during the patient's lifetime. ResultsAmong 3496 MS patients, we found 331 patients ever starting FTY and 283 of them had used FTY for at least 6 months. Among these 283 patients we discovered a total of 114 discontinuation events in 110 patients. Of the discontinuations, 32 (28 %) were followed by a relapse: 20 (17.5 %) were ordinary relapses not fulfilling rebound criteria, and 12 (10.5 %) were rebounds. The median time to an ordinary relapse and rebound were similar: 8.5 weeks (range 1.3–23) and 9.9 weeks (range 5.9–15.9), respectively. The rebound group was younger at diagnosis (p = 0.034) and had used FTY for a longer time (p = 0.048) before discontinuation compared to the group without a relapse. After discontinuation, rebound group had lower lymphocyte values as compared to both ordinary relapse group (p = 0.027) and no-relapse group (p = 0.006) and neutrophil to lymphocyte ratio (NLR) was increased compared to the no-relapse group (p = 0.019). ConclusionIn this study, 10.5 % of patients experienced a rebound, which is similar to the frequencies (10.3–12.5 %) obtained in other larger studies with >100 discontinuations. Relapses of any severity occurred in 28 % of patients discontinuing FTY, and therefore initiation of subsequent disease modifying therapies should occur promptly after discontinuation. Younger age at diagnosis, longer exposure to FTY and lower lymphocyte count as well as higher NLR after discontinuation were identified as risk factors for a rebound. The differences in blood leukocytes indicate that rebound might be a distinct pathophysiological phenomenon compared to an ordinary relapse.

New insights on the mechanisms of myocardial injury in hypertensive patients with COVID-19

Abstract Introduction Cardiac comorbidities, particularly hypertension, are highly prevalent in patients hospitalized with COVID-19 and are related directly to the risk of clinical disease progression. Cardiac injury is the most frequently reported cardiac abnormality in these patients. Diverse forms and mechanisms of myocardial injury, including acute myocardial ischemia due to plaque rupture, oxygen supply/demand imbalance, non-ischemic injuries such as myocarditis, direct virus-mediated injury, and immune system dysregulation, have been described in patients with COVID-19. Purpose The mechanism of the association among hypertension, COVID-19 and cardiac injury and the reasons for worse clinical progression in these patients have not been elucidated clearly. Considering that myocardial injury due to direct SARS-CoV-2 infection is rare and that the immune system is often dysregulated in patients with COVID-19, and also that cytokine storm and lymphopenia are important immune markers of progression to severe disease, the present study aimed to investigate the immune profile of hypertensive patients with COVID-19 and myocardial injury to obtain a better understanding of the immune dysregulation and to provide new insights on the mechanism of myocardial injury in hypertensive patients with this disease. Methods All patients were selected prospectively from a multicenter registry of adults hospitalized with confirmed COVID-19. Cases had hypertension and myocardial injury, defined by troponin levels above the 99th percentile upper reference limit, and controls were hypertensive patients with no myocardial injury. Biomarkers and immune cell subsets were quantified and compared between the two groups. A multiple logistic regression model was used to analyze the associations of clinical and immune variables with myocardial injury. Results The sample comprised 193 patients divided into two groups: 47 cases and 146 controls. Relative to controls, cases had lower total lymphocyte count, percentage of T lymphocytes, CD8+CD38+ mean fluorescence intensity (MFI), and percentage of CD8+ human leukocyte antigen DR isotope (HLA-DR)+ CD38–cells and higher percentage of natural killer lymphocytes, natural killer group 2A (NKG2A)+ MFI, percentage of CD8+CD38+cells, CD8+HLA-DR+MFI, CD8+NKG2A+MFI, and percentage of CD8+HLA-DR–CD38+cells. On multivariate regression, the CD8+HLA-DR+MFI, CD8+CD38+MFI, and total lymphocyte count were associated significantly with myocardial injury. Conclusion Our findings suggest that lymphopenia, CD8+CD38+MFI, and CD8+HLA-DR+MFI are immune biomarkers of myocardial injury in hypertensive patients with COVID-19. The immune signature described here may aid in understanding the mechanisms underlying myocardial injury in these patients. The study data might open a new window for improvement in the treatment of hypertensive patients with COVID-19 and myocardial injury.

Comparative Analysis of Hematological and Inflammatory Biomarkers in Moderate and Severe COVID-19 Patients

In COVID-19 patients, abnormal blood clotting is common, characterized by elevated D-dimer and fibrinogen levels, reduced platelets, and prolonged clotting times. The second week of infection can trigger a cytokine storm, marked by heightened proinflammatory Interleukin-6 (IL-6) levels, associated with Acute Respiratory Distress Syndrome (ARDS) and organ failure. This study compared hematological biomarkers, D-dimer, and IL-6 in moderate and severe COVID-19 cases. In a cross-sectional study, 81 patients meeting inclusion criteria were examined at a leading private COVID-19 referral hospital in Malang Regency. Data from clinical records and lab results encompassing blood counts, D-dimer, and IL-6 levels were collected. D-dimer was assessed through immunoturbidimetry (STA-Procoag-PPL, Diagnostica Stago S.A.S.), while IL-6 was measured using a chemiluminescent immunoassay (Cobas e411 Elecsys, Roche). Data distribution normality was assessed using Kolmogorov-Smirnov and Shapiro-Wilk tests. Non-normally distributed data were analyzed using the Mann-Whitney U test for numerical data and the Fisher exact test for comorbidity-severity correlation. Moderate COVID-19 cases disproportionately affected females, while severe cases had an even gender distribution. The median age was comparable, but mild cases were typically younger. Hemoglobin, hematocrit, leukocyte, neutrophil, platelet, and procalcitonin levels were normal in both groups, with lowered lymphocyte counts. Severe cases displayed a higher Neutrophil-to-Lymphocyte Ratio (NLR). D-dimer and IL-6 were significantly elevated in extreme cases. This study underscores potential gender and age-related discrepancies in COVID-19 severity, emphasizing the significance of monitoring specific blood parameters for disease progression indicators. Further investigation is vital to unveil underlying mechanisms and clinical implications, aiding the management of COVID-19 patients.

The Efficacy of Hetrombopag Combined with Cyclosporine a in Patients with Transfusion-Dependent Non-Severe Aplastic Anemia

Objective: Thetherapeutic approach for transfusion-dependent non-severe aplastic anemia (TD-NSAA) is undetermined. Though the British guideline recommended intensive immunosuppressive therapy (IST) as front-line therapy for TD-NSAA ( Killick SB, et al. British Journal of Haematology. 2016; 172(2): 187-207), the cost and risk were relatively high. Hetrombopag is a thrombopoietin receptor agonist approved for IST-refractory severe aplastic anemia (SAA) by the China Food and Drug Administration in 2021 ( Peng G, et al. Ther Adv Hematol. 2022; 13: 20406207221085197). This study aimed to evaluate the efficacy of hetrombopag plus cyclosporine A (CsA) for TD-NSAA. Methods: 24 eligible patients receiving hetrombopag plus CsA from September 2021 to July 2023 were collected by prospective registration (ChiCTR2100045895) in the Chinese Eastern Collaboration Group of Anemia (CECGA). A historical cohort (n=79) receiving CsA alone from December 2013 to January 2017 in the CECGA was used as a comparator (Table 1). Primary endpoint was overall response at 24 weeks, defined as hematologic response in ≥ 1 lineage. Secondary endpoints were overall response at 12 and 48 weeks, complete response at 48 weeks, overall survival, transformation to SAA and treatment-related adverse events. Results: At 24 weeks, the overall response rate was 74% in hetrombopag plus CsA cohort and 16% in CsA cohort (odds ratio [OR]: 14.7; 95% confidence interval [CI]: 4.1 ~ 52.4; p＜0.001). The overall response rates at 12 and 48 weeks were also significantly higher in hetrombopag plus CsA cohort than those in CsA cohort (43% vs 8%, OR: 9.1, 95% CI: 2.7 ~ 31.1, p＜0.001; 85% vs 30%, OR: 13.0, 95% CI: 2.5 ~ 66.2, p = 0.001, respectively). At 48 weeks, the complete response rate was 23% in hetrombopag plus CsA cohort and 2% in CsA cohort (OR: 13.8; 95% CI: 1.3 ~ 146.8; p = 0.029). The median time to initial response was 11.6 [95% CI: 2.9~20.3] weeks in hetrombopag plus CsA cohort, significantly shorter than that in CsA cohort (hazard ratio: 5.0; 95% CI: 2.1 ~ 12.1; p＜0.0001) (Figure 1). The median time to erythroid, platelet and neutrophil responses in hetrombopag plus CsA cohort were 20.6 [95% CI: 9.1 ~ 32.0], 16.4 [95% CI: 3.0 ~ 29.9] and 23.0 [95% CI: 10.6 ~ 35.4] weeks, respectively. The 1-year survival rates in hetrombopag plus CsA cohort and in CsA cohort were similar (90% vs 94%; hazard ratio: 1.9; 95% CI: 0.2 ~ 15; p = 0.5). The percentage of patients transforming to SAA was 8% in hetrombopag plus CsA cohort and 34% in CsA cohort (OR: 0.2; 95% CI: 0.0 ~ 0.8; p = 0.018). Treatment-related hepatic or renal injury occurred in 7 patients (29%) in hetrombopag plus CsA cohort with only one ≥ Grade 3; all gained remission after dose reduction or discontinuation. Multivariate analysis of clinical parameters of all patients from both cohorts revealed that adding hetrombopag to therapy was strongly correlated with response (OR: 43; 95% CI: 4 ~ 528; p = 0.003), as was lower lymphocyte count (OR: 0.5; 95% CI: 0.3 ~ 0.8; p = 0.011). Conclusion: The combination of hetrombopag with CsA improved the rate, rapidity, and strength of hematologic response among patients with TD-NSAA, and lowered their risks of transforming to SAA. Disclosure: This study is supported by National Natural Science Foundation of China (81900109). The authors declare that there is no conflict of interest.

In-Depth Immune Profiling in Children with BCP-ALL within the AIEOP-BFM ALL 2017 Study

The international multicenter frontline therapy trial AIEOP-BFM ALL 2017 prospectively randomizes CD19-targeting T-cell engager blinatumomab (BLN) against standard of care (SOC) to improve outcomes in pediatric patients (pts) with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) stratified for high (HR) and medium (MR) risks of relapse. In HR arm BLN is given earlier, directly after intensified HR therapy block, while in the MR arm, it is given towards the end of chemotherapy, before maintenance. The immune composition prior to BLN might thus differ between both treatment groups (HR vs MR) which may impact BLN-mediated anti-leukemic activity. Within the Germany-wide immune monitoring program accompanying the AIEOP-BFM ALL 2017 trial we addressed this question and studied a total of 1056 longitudinal peripheral blood samples collected between 11/2018 and 05/2022 from 381 BCP-ALL pts. Samples were prospectively analyzed with multicolor flow cytometry to study immune cell composition (Panel 1) at the time of BLN application (d0) and under ongoing immunotherapy within first 24h (d1), at day 14 (d14), at the end of the cycle I (d28) and end of cycle 2 (day28_II), if applicable (Figure 1A). In-depth T-cell profiling was performed in the BLN arm, utilizing 4 additional 12-color panels concentrated on markers associated with T-cell functionality (measured with standardized cytometer settings). Data were analyzed using classical 2D-manual gating strategies (&amp;gt; 2000 variables) and completed with R-based machine learning algorithms; namely partial Least-Squares Discriminant Analysis (PLS-DA), a multivariate dimensionality-reduction tool for identifying HR- and MR-defining immune signatures and PhenoGraph algorithm for unsupervised T-cell cluster detection. T-cell receptor excision circles (TRECs) and TR-repertoire analysis were also performed among paired samples of 117 BLN-treated pts. Baseline immune composition differed notably between HR and MR pts directly prior to BLN therapy, as shown by PLS-DA analysis on manually gated immune subsets. HR pts showed higher neutrophil counts and lower lymphocyte and monocyte counts compared to MR pts. Interestingly, MR pts had higher levels of B- and T-cells, which are crucial for BLN-mediated T-cell activation. HR pts displayed an elevated CD4+/CD8+ ratio, shifted naïve/memory T-cell phenotypes and increased proportions of immunosuppressive T-regulatory cells. These results suggest that more intensive therapy protocols directly prior to BLN influence the immune composition towards compromised states in the HR arm, potentially affecting BLN-mediated T-cell leukemia control. BLN effectively depleted CD19+ cells in 221 out of 224 pts. We observed significantly stronger T-cell activation/expansion in MR pts compared to HR pts under BLN therapy. This expansion that was primarily attributed to naïve CD8+ T-cell populations, resulting from clonal T-cell proliferation independent of thymic contribution, as supported by TREC and TR-repertoire analysis. The PhenoGraph clustering also identified this expanding naïve CD8+ T-cell populations, surprisingly marked by loss of adhesion molecule DNAM1 (panel 1), normally involved in NK and T-cell mediated cytotoxicity and by gaining the expression of TIM-3 (panel 3), an inhibitory molecule usually co-expressed with PD1 on exhausted T-cells with memory phenotypes. In this setting however, TIM3 was not co-expressed with PD1 (Figure 1B) and its expression was correlated with the B-cell levels at baseline and was strongest in MR pts under BLN therapy. Our data suggest an until now undescribed association between DNAM1 and TIM3 with BLN-mediated T-cell activation, hinting that they may serve as a measure of T-cell activation strength or an early T-cell exhaustion marker. In conclusion our study provides clinically relevant insights in how chemotherapy prior BLN might affect the patients´ immune system, possibly influencing the BLN anti-leukemic activity, and helps to determine the optimal place of immunotherapy with BLN in multimodal treatment schedules. Here, we report until know undescribed effect of BLN on T-cell compartment. Upcoming clinical data, which will be correlated with obtained immune profiles will answer the open question regarding the clinical relevance of these findings, and shed light into the mechanisms determining response to BLN, for its maximum benefit in childhood ALL.

Decreased Peripheral Blood Lymphocyte Count Predicts Poor Treatment Response in Peritoneal Dialysis-Associated Peritonitis.

Peripheral blood lymphocyte counts is a pivotal parameter in assessing the host's immune response during maladies and the equilibrium of the immune system which has been found to correlate with various diseases progression and prognosis. However, there was no study on patients with peritoneal dialysis-associated peritonitis (PDAP). We sought to investigate the prognostic value of baseline peripheral blood lymphocyte count in PDAP patients. This retrospective study analyzed data from 286 PDAP patients over nine years. Episodes were categorized according to the tertiles of peripheral blood lymphocyte counts (Very Low Lymphocyte Count (VLLC) Group, <0.72×106/L; Low Lymphocyte Count (LLC) Group, 0.72-1.11×106/L; Normal Lymphocyte Count (NLC) Group, ≥ 1.11×106/L). Demographic, laboratory, and infection-related variables were analyzed. Cox regression and generalized estimating equation (GEE) models were used to estimate the association between lymphocyte counts and PDAP treatment failure, which included PD catheter removal and death. After adjusting for other potential predictors, decreased lymphocyte counts exhibited an incremental relationship with the risk of treatment failure. The VLLC group indicated a 270% (95% CI, 1.168-6.247, P=0.020) and 273% (95% CI, 1.028-7.269, P=0.044) increased venture of treatment failure in Cox regression and GEE analyses, respectively, compared with the NLC group. As a continuous variable, the restricted cubic spline showed a linear negative correlation between lymphocyte counts and the treatment failure risk (P for overall = 0.026). The multivariate model C (combined lymphocyte count with baseline age, sex, dialysis age, Charlson Comorbidity index (CCI), etiology of kidney failure, hemoglobin, albumin, total bilirubin and infection type) showed an area under the curve of 0.824 (95% CI, 0.767-0.881, P=0.001) for the prediction of treatment failure. Lower lymphocyte counts are linked to increased PDAP treatment failure risk. This highlights lymphocyte count's potential as a prognostic indicator for PDAP.

Clinical manifestations and risk factors of shock in children with multisystem inflammatory syndrome

Multisystem inflammatory syndrome in children (MIS-C) is a novel disease associated with COVID-19. The COVID-19 epidemic peaked in May 2022 in Taiwan, and we encountered our first case of MIS-C in late May 2022. We aimed to present patients' clinical manifestations and identify risk factors for shock. We included patients diagnosed with MIS-C at two medical centers from May 2022 to August 2022. We separated those patients into two groups according to whether they experienced shock. We collected demographic, clinical manifestation, and laboratory data of the patients and performed statistical analysis between the two groups. We enrolled 28 patients, including 13 (46%) with shock and 15 (54%) without shock. The median age was 6.4 years (IQR: 1.9-7.5). In single variable analysis, patients with shock tended to be older, had more neurological symptoms, more conjunctivitis and strawberry tongue, lower lymphocyte count, lower platelet counts, and higher C-reactive protein, higher procalcitonin, higher ferritin, and higher D-dimer levels than those without shock. The area under the ROC curve that used procalcitonin to be the risk factor of shock with MIS-C was 0.815 (95% CI 0.644 to 0.987). The cutoff value obtained by ROC analysis of procalcitonin was 1.68ng/mL. With this cutoff, the test characteristics of procalcitonin were as follows: sensitivity 77%, specificity 93%, positive predictive value 91%, negative predictive value 82%. Multivariable analysis revealed that procalcitonin was the only independent risk factor of shock with MIS-C on admission (OR, 26.00, 95% CI, 1.01-668.89). MIS-C patients with high initial procalcitonin levels have higher risks of experiencing shock and may need ICU admission.

Safety and persistence of dimethyl fumarate as a treatment for relapsing-remitting multiple-sclerosis

ObjectiveDimethyl fumarate is a medication approved for the treatment of relapsing-remitting multiple sclerosis. The purpose of the study was to evaluate the safety and persistence of dimethyl fumarate in clinical practice and analyze the occurrence of lymphopenia is patients treated with dimethyl fumarate over a period of at least 6 months. MethodThis is a retrospective longitudinal observational study carried out between August 2015 and March 2019. The study cohort was made up of patients who had been treated with dimethyl fumarate for at least 6 months. Lymphocyte counts were recorded at different points of time (pre-treatment, at 3, 6, 12 months, and at the end of the study period). The evolution of lymphopenia was evaluated by means of a logistic regression statistical model. An analysis was performed of the relationship between a decreased lymphocyte count over the first 6 months of treatment and the development, by the end of the study, of grade II-III lymphopenia necessitating discontinuation of dimethyl fumarate. Other safety indicators were also evaluated including adverse events and interruptions or discontinuations of treatment. Persistence was determined by measuring the time to discontinuation of treatment. ResultsThe study included a total of 55 patients, of whom 80% were female. The most common adverse events were lymphopenia (27), rubefaction (16), digestive symptoms (11), fatigue (9), headache (3) and sleep disturbances (2). Eleven subjects interrupted/discontinued their treatment during the study period; reasons were as follows: pregnancy (2), personal decision (2), John Cunningham virus infection (1), allergy to the drug (2), and lymphopenia (4). Median duration of treatment was 23 months (4-43 months). A statistically significant association was found between a lower lymphocyte count over the first 6 months of treatment and the development of severe lymphopenia by the end of the study [OR = 1.34 (1.27-11.41); 95% CI (p = 0.001)]. ConclusionsThe adverse events observed in the present study are in line with those reported in previous analyses. Lymphopenia was the most common adverse event. The persistence of the medication was similar to that found in pivotal trials. The significant association found between a decreased lymphocyte count over the first 6 months of treatment and the development of severe lymphopenia by the end of the study suggests a connection between both variables, which could be instrumental in being able to predict and even prevent the occurrence of such lymphopenias.

SUPER Score Contributes to Warning and Management in Early-Stage COVID-19

BackgroundSome COVID-19 patients deteriorate to severe cases with relatively higher case-fatality rates, which increases the medical burden. This necessitates identification of patients at risk of severe disease. Early assessment plays a crucial role in identifying patients at risk of severe disease. This study is to assess the effectiveness of SUPER score as a predictor of severe COVID-19 cases. MethodsWe consecutively enrolled COVID-19 patients admitted to a comprehensive medical center in Wuhan, China, and recorded clinical characteristics and laboratory indexes. The SUPER score was calculated using parameters including oxygen saturation, urine volume, pulse, emotional state, and respiratory rate. In addition, the area under the receiver operating characteristic curve (AUC), specificity, and sensitivity of the SUPER score for the diagnosis of severe COVID-19 were calculated and compared with the National Early Warning Score 2 (NEWS2). ResultsThe SUPER score at admission, with a threshold of 4, exhibited good predictive performance for early identification of severe COVID-19 cases, yielding an AUC of 0.985 (95% confidence interval [CI] 0.897–1.000), sensitivity of 1.00 (95% CI 0.715–1.000), and specificity of 0.92 (95% CI 0.775–0.982), similar to NEWS2 (AUC 0.984; 95% CI 0.895–1.000, sensitivity 0.91; 95% CI 0.587–0.998, specificity 0.97; 95% CI 0.858–0.999). Compared with patients with a SUPER score<4, patients in the high-risk group exhibited lower lymphocyte counts, interleukin-2, interleukin-4 and higher fibrinogen, C-reactive protein, aspartate aminotransferase, and lactate dehydrogenase levels. ConclusionsIn conclusion, the SUPER score demonstrated equivalent accuracy to the NEWS2 score in predicting severe COVID-19. Its application in prognostic assessment therefore offers an effective early warning system for critical management and facilitating efficient allocation of health resources.

Peripheral blood cell count ratios as a predictor of poor functional outcome in patients with acute ischemic stroke

ABSTRACT Background and aims Acute ischemic stroke (AIS) is a leading cause of death and long-term disability worldwide. Thromboinflammation plays an important role in the pathophysiology of stroke. The peripheral blood cell count ratios (PBCCR): neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), and lymphocyte‐to‐monocyte ratio (LMR), are global inflammatory indicators with prognostic value for the clinical outcome after stroke. We aimed to determine the relationship between NLR, PLR, or LMR and the functional outcome three months post-stroke. Methods A prospective, hospital-based study, including 141 participants with AIS, was conducted at a referral stroke center in North-Eastern Bulgaria. The PBCCRs were obtained during the first 24 hours after stroke onset. Stroke severity was measured using the NIHSS scale, and functional outcome was assessed with the modified Rankin Scale (mRS) at discharge and 3 months post-stroke. Results We found significantly lower total lymphocyte counts, and higher NLR, PLR, and C-reactive protein in the poor-outcome group (mRS>3) three months post-stroke. A positive correlation was found between the NIHSS score and mRS score on discharge, NLR, and PLR with the worse outcome on the third month. The receiver operating characteristic (ROC) curves showed the predictability of NLR (AUC, 0.626, 95%CI: 0.524–0.724, p = 0.018), and for PLR– (AUC, 0.613, 95%CI: 0.510–0.716, p = 0.031). The optimal cutoff value for NLR was 2.68 (sensitivity 77.8% and specificity 60.4%), and for PLR - 122.6 (sensitivity 77.8% and specificity 61.5%). Conclusion Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio are simple, widely available, and cost-effective biomarkers with high prognostic value for the clinical outcome three months post-stroke.

The Role of Neutrophil to Lymphocyte Ratio (NLR) and Platelet to Lymphocyte Ratio (PLR) in Appendicitis

Aim: Predictive values of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are associated with poor outcomes in several diseases. Furthermore, there has been limited publication of those parameters in appendicitis patients in Indonesia. This study aims to evaluate the role of NLR and PLR in differentiating complicated appendicitis and uncomplicated appendicitis. Methods: The design of this study is a retrospective using medical records of appendicitis patients from January 1, 2016, to December 31, 2020, conducted at PKU Muhammadiyah Bantul Hospital. There are 408 data on appendicitis patients that can be analyzed. Results: The WBC, neutrophils, NLR, and PLR was significantly higher in the complicated appendicitis group than in the uncomplicated group [11,5 (3.79-35.2) vs. 8.42 (3.32-39.30), p&lt;0.0001; 8.63 (2.359-2.647) vs. 5.446 (1.691-35.960), p&lt;0.0001; 5.65 (0.95-23.86) vs.3.82 (0.81-23.86), p&lt;0.0001; 168.57 (37.27-974.03) vs.139.40 (56.84-1274.31), p&lt;0.0001, respectively] followed by a significantly lower lymphocyte count [1.709 (0.154-5.71) vs. 2.094 (0.401-5.812), p&lt;0.0001, respectively]. The area under the receiver operating characteristic (ROC) curve, cutoff point, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and likelihood ratio of NLR for diagnosis of complicated appendicitis were 0.76, &gt;2.84, 75.21%, 62.65%, 74.6%, 63.4%, 2.01, 0.40, respectively. In contrast, an area under ROC curve, cutoff point, sensitivity, specificity, PPV, NPV, and likelihood ratio of PLR for differentiating complicated and uncomplicated appendicitis were 0.605, &gt;140.6, 65.70%, 51.81%, 66.5%, 50.9%, 1.36, and 0.66 respectively. Conclusion: The cutoff values of NLR (&gt;2.84) and PLR (&gt;140.6) were significant diagnostic parameters for complicated appendicitis (p = 0.0001). Hence, NLR and PLR can assist in diagnosing complicated appendicitis.

Disease Outcomes of COVID-19 in Diabetic and Hypertensive Patients During the Hospital Stay.

Background A single-stranded RNA genome-encapsulated virus known as severe acute respiratory syndrome coronavirus 2 is known to cause severe acute respiratory syndrome in humans. People with diabetes and hypertension are often more susceptible to developing coronavirus disease 2019 (COVID-19) and experience a disproportionately higher rate of morbidity and death compared to the general population. The COVID-19 pandemic has become an urgent worldwide issue. Therefore, the main goal of this study is to assess how diabetes and hypertension,both separately and together, affect clinical outcomes in terms of morbidity and mortality in patients hospitalized with COVID-19. This study aimed to evaluate the disease outcomes in hypertensive and diabetic patients hospitalized with COVID-19. Methodology This descriptive, cross-sectional study was conducted from June 2022 to November 2022. Using purposive selective sampling, a total of 90 known hypertensive and diabetic patients with COVID-19 aged 18-90 years admitted in COVID-19 isolation wards and intensive care units (ICUs) of Mayo Hospital Lahore were recruited in this study after obtaining informed consent and IRB approval from the Institutional Review Board of King Edward Medical University, Lahore. Patients who did not provide consent, patients whose positive polymerase chain reaction reports for COVID-19 were not available, pregnant females, and patients with other comorbidities were excluded from the study. Data were collected from the COVID-19 isolation medical wards and ICUs from patient charts containing age, the status of hypertension and diabetes, disease status, severity, and levels of inflammatory markers, i.e., D-dimers, serum lactate dehydrogenase (LDH), serum ferritin, C-reactive protein (CRP). Data were analyzed using SPSS version 23 (IBM Corp., Armonk, NY, USA). Quantitative variables such as age were presented as mean ± SD. Qualitative variables such as hypertension, diabetes, and levels of inflammatory markers were presented as frequency and percentages. Results In this study, 90 patients were included, with 51 (57%) females and 39 (43%) males, all of whom were either hypertensive, diabetic, or both. In total, 70 (78%) patients were admitted to ICUs and 20 (22%) to COVID-19 medical isolation wards. Among 70 ICU patients, 39 (43.3%) were on continuous positive airway pressure/bilevel positive airway pressure, seven (7.8%) were on ventilators, and 44 (48.8%) were on normal oxygen masks/non-rebreather masks with high-flow oxygen. Overall, 100% of the patients included in the study had raised levels of inflammatory markers, low lymphocyte count, and increased neutrophil count. In total, 84 (93%) patients had severely high and six (7%) patients had moderately high CRP levels. Moreover, 33 (36.7%) patients had severely high and 57 (63.3%) patients had moderately high D-dimer levels. Further, 25 (28%) patients had severely high, 26 (29%) patients had moderately high, and 39 (43.3%) patients had significantly raised levels of serum ferritin. In total, 21 (23%) patients had severely high, 37 (41%) had moderately high, and 32 (36%) had significantly raised levels of serum LDH. Among the 90 patients, 65 (73%) expired and 25 (27%) survived. Of the expired patients, 62 (95%) were admitted to ICUs, and three (5%) were admitted to wards. Conclusions Diabetes and hypertension are strong predictors of COVID-19 severity in terms of morbidity and mortality due to respiratory deterioration.

Risk of cytomegalovirus infection and subsequent allograft failure after pancreas transplantation

Cytomegalovirus (CMV) is a common cause of infection after transplantation, but few studies have evaluated its epidemiology, risk factors, and outcomes among pancreas transplant recipients. We performed a retrospective cohort study of adults who underwent pancreas transplantation from January 1, 2010, through December 31, 2020, at 3 sites in Arizona, Florida, and Minnesota. The primary outcome was clinically significant CMV infection (csCMVi), defined as CMV disease or infection requiring antiviral therapy. The secondary outcome was pancreas allograft failure. Among 471 pancreas transplant recipients, 117 (24.8%) developed csCMVi after a median of 226 (interquartile range 154-289) days. CMV donor (D)+/R- patients had a significantly higher incidence of csCMVi (hazard ratio [HR] 4.01, 95% confidence interval [CI] 2.10-7.64; P < .001). In adjusted analysis, a lower absolute lymphocyte count (ALC) was associated with a greater risk of csCMVi among seropositive recipients (HR 1.39 per 50% decrease, 95% CI 1.13-1.73; P = .002) but not among D+/R- patients (HR 1.04 per 50% decrease, 95% CI 0.89-1.23; P = .595). csCMVi, lower ALC, and acute rejection (P < .001) were independently associated with pancreas allograft failure. In conclusion, CMV D+/R- was associated with csCMVi in pancreas recipients, although ALC was associated with csCMVi only among seropositive patients. The development of csCMVi in pancreas recipients was associated with poor pancreas allograft outcomes.

Isolation of Epstein-Barr virus-deoxyribonucleic acid in the lower respiratory tract for distinguishing critically ill patients from those with influenza-associated pneumonia: A pilot study.

When influenza A-related pneumonia is complicated by bacteria, aspergillus, and other infections, the disease is aggravated, while there is no research on the role of Epstein-Barr virus (EBV) on patients with influenza A-related pneumonia. This study aimed to evaluate the relationship between the isolation of EBV and influenza A-related pneumonia. This is a clinical study based on the baseline data of a retrospective cohort. A total of 113 cases of influenza A-related pneumonia who underwent polymerase chain reaction test for isolation of EBV-DNA in lower respiratory tract specimens during six influenza seasons from 2013-2014 to 2018-2019 were enrolled. According to the results of EBV-DNA, patients were divided into EBV-positive group and EBV-negative group, and the role of EBV-DNA on patients with influenza A-related pneumonia was analyzed. Regression analysis was used to explore the potential risk factors for the development of moderate-to-severe acute respiratory distress syndrome (ARDS) in patients with influenza A-related pneumonia during hospitalization. Among 113 patients with influenza A-related pneumonia, there were 53 patients with EBV-positive and 60 patients with EBV-negative. The EBV-positive group had higher intensive care unit admission rate, hospital stay, invasive mechanical ventilation rate, extracorporeal membrane oxygenation rate, Sequential Organ Failure Assessment (SOFA) score, and moderate-to-severe ARDS rate. Patients were divided into severe group and mild group. Patients in severe group had lower lymphocyte count, platelet count, and albumin level, while the levels of aspartate aminotransferase, alanine transaminase, creatine kinase, lactic dehydrogenase, and total bilirubin were higher in severe group. The levels of D-dimer, serum ferritin, C-reactive protein, and procalcitonin were higher in severe group than those in the mild group. Multivariate logistic regression analysis revealed that the isolation of EBV (odds ratio = 2.713, 95% confidence interval: 1.094-6.729, P = 0.031) and lymphocyte count (odds ratio = 3.585, 95% confidence interval: 1.157-11.101, P = 0.027) were independent risk factors for moderate-to-severe ARDS in patients with influenza A-related pneumonia. The isolation rate of EBV in the lower respiratory tract was 46.9%. The length of hospital stays, intensive care unit admission rate, invasive mechanical ventilation rate, extracorporeal membrane oxygenation rate, SOFA score, and the proportion of moderate-to-severe ARDS in the EBV-positive group were higher than those in the EBV-negative group, while there was no effect on the death during hospitalization. The isolation of EBV in the lower respiratory tract and low lymphocyte count are independent risk factors for the development of moderate-to-severe ARDS in patients with influenza A-related pneumonia.

Serum hyaluronic acid and procollagen III, N-terminal propeptide levels are highly associated with disease severity and predict the progression of COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic is a rapidly evolving global emergency and continuously poses a serious threat to public health, highlighting the urgent need of identifying biomarkers for disease severity and progression. In order to early identify severe and critical patients, we retrospectively analyze the clinical characteristics and risk indicators of severe disease in patients with corona virus disease 2019 (COVID-19). A total of 420 confirmed COVID-19 patients were included in the study. According to the "Diagnosis and Treatment of novel coronavirus Pneumonia (10th Edition)", the cases were divided into mild group (n = 243) and severe group (n =177). Laboratory parameters were analyzed in combination with clinical data. Male patients over 46 years who have smoking habits were more likely to suffer from severe COVID-19. Critically ill patients had lower lymphocyte counts and red blood cell counts, and higher white blood cell counts (P<0.05). Expectedly, serum inflammatory factors (NLR, PLR, LMR, CLR, PCT, CRP), coagulation markers (APTT, PT, TT, FIB, D-Dimer), Myocardial damage markers (hs-TNT, LDH) were significantly increased (P<0.05) in severe COVID-19 patients. Surprisedly, those patients showed obviously elevated levels of common tumor markers (ProGRP, CYFRA21-1, SCC, NSE) (P<0.05). In this case, the levels of tumor marker reflected more the condition of inflammation than the growth of tumor. More importantly, HA and PIIIN-P were highly associated with COVID-19 severity. The AUC of the ROC curve for the diagnosis of severe COVID-19 by HA and PIIIN-P was 0.826. Meanwhile, HA was positively correlated with myocardial damage markers (hs-TNT, LDH). PIIIN-P was positively correlated with myocardial damage markers (hs-TNT, LDH) and inflammatory factors (NLR, PLR, LMR, CLR, ProGRP, SCC, PCT, CRP). On the contrary, PIIIN-P was negatively correlated with pulmonary function indexes (oxygenation index and oxygen saturation of hemoglobin). HA and PIIIN-P are highly associated with disease severity and progression of COVID-19 and can be used as new markers for the prediction of severe COVID-19.