Low Lymphocyte Levels Research Articles

Clinical characteristics and prognostic factors of pulmonary and extrapulmonary cryptococcosis

BackgroundCryptococcosis is progressively acknowledged among people, irrespective of the human with or without immunodeficiency virus (HIV). This change in epidemiology has been recorded in recent years, prompting closer examination and a broader understanding of the disease manifestations and risk factors.MethodsThe data of cryptococcal infections in China during 11 years were retrospectively analyzed. According to the position of infection, the patients were categorized into the pulmonary infection group and extrapulmonary infection group. The composition of the two groups was compared, and the potential risk factors of disseminated infection were analyzed. Logistic regression was used to analyze the prognostic risk factors of the disease.ResultsA total of 165 patients were enrolled. 113 (68.5%) were male, and the age was 47.49 (18–82) years. 101 cases (61.2%) had a normal immune function and 64 cases (38.8%) had impaired immune function. 45 patients had extrapulmonary infection, involving the central nervous system, bone and joint, skin and bloodstream, and 120 patients had simple pulmonary infection. The mortality of the extrapulmonary infection group (48.9%) was significantly higher than that of the pulmonary infection group (0.8%). According to univariate logistic regression analysis, immune status (hazard ratio [HR], 4.476; 95% confidence interval [CI], 1.725–11.618; P = 0.002), infection position ([HR], 113.826; [CI], 14.607-886.967; P < 0.001), white blood cell count, ([HR],1.209;[CI], 1.054–1.386; P = 0.007), hemoglobin ([HR], 0.970; [CI], 0.955–0.986; P < 0.001), platelet count ([HR], 0.993; [CI], 0.987–0.999; P = 0.026), neutrophil percentage ([HR], 1.115; [CI], 1.065–1.168; P < 0.001), lymphocyte percentage ([HR], 0.875; [CI], 0.827–0.927; P < 0.001), neutrophil-to-lymphocyte Ratio (NLR) ([HR], 1.144; [CI], 1.072–1.221; P < 0.001), monocyte percentage ([HR], 0.752; [CI], 0.618–0.915; P = 0.004) were related to the prognosis. Multivariate logistic regression analysis showed that the infection position was remained related to the prognosis with statistical significance ([HR], 0.018; [CI], 0.001–0.384; P = 0.001).ConclusionExtrapulmonary infection of Cryptococcosis is an important risk factor for prognosis. High levels of neutrophils and NLR, and low levels of lymphocytes and monocytes may lead to disseminated infection of Cryptococcosis. Further studies are needed to reduce the occurrence rate of extrapulmonary infection and mortality.

Clinical Characteristics, Nutritional Status, and Disease Severity in Pediatric Patients with COVID-19

Background: Limited clinical data are available regarding the impact of coronavirus disease 2019 (COVID-19) on children. Objective: This study assessed the clinical characteristics, nutritional status, and disease severity in pediatric patients with COVID-19. Methods: A retrospective study examined medical records of children with COVID-19 admitted to Abuzar Hospital (Ahvaz, Iran) for six months. Data related to their clinical, nutritional status and demographic characteristics were documented. Results: This study included medical records of 500 patients. More than half of them were boys. Different levels of COVID-19 severity were observed in 202, 172, and 126 children as mild, moderate, and severe cases, respectively. Children with severe or moderate COVID-19 had substantially elevated levels of various inflammatory markers, blood urea nitrogen (BUN), gamma-glutamyl transferase (GGT), neutrophils, alanine transaminase (ALT), creatinine, bilirubin, and aspartate aminotransferase (AST) compared to those with mild COVID-19 (p &lt; 0.001). They had lower levels of lymphocytes and vitamin D, as well as longer hospital stays than children with mild COVID-19 (p &lt; 0.001). In addition, 52% and 40.2% of patients had malnutrition and anemia, respectively. The majority of underweight and stunted children had moderate or severe COVID-19. Conclusion: This study revealed a high prevalence of malnutrition, anemia, insufficient levels of vitamin D, elevated levels of inflammatory markers, and abnormal liver and kidney function tests in children with severe or moderate cases of COVID-19 compared to those with mild COVID-19.

Protective effects of Parkin knockout on asthma-induced changes in juvenile mice: inflammation, airway resistance, and oxidative stress

Objective This study aimed to explore the effects of Parkin (Prkn) knockout in a juvenile mouse model of asthma. Methods Prkn knockout (KO) and wild type (WT) mice were utilized to establish a juvenile mouse asthma model. The asthma model involved exposure to hyperoxia/ovalbumin (OVA), encompassing hyperoxia from postnatal day 1 (P1) to P7, sensitization on P21 and P28, and challenge from P36 to P42. Room air/phosphate-buffered saline (PBS) served as the control condition. Following airway resistance measurement, bronchoalveolar lavage fluid (BALF) was collected for cellular analysis, and lung tissues were subjected to histological examination and oxidative stress assessment. Serum levels of ovalbumin-specific immunoglobulin E (IgE), total IgE, interleukin-4 (IL-4), IL-5, and IL-13 were quantified using enzyme-linked immunosorbent assay (ELISA). Results WT mice exposed to hyperoxia/OVA showed decreased body weight and increased airway resistance compared to those exposed to control condition. Conversely, KO mice exhibited increased body weight under asthma conditions. KO mice with asthma had reduced total cell counts, along with lower levels of lymphocytes, eosinophils, and neutrophils, compared to WT asthma mice. Histological assessment showed attenuated inflammation and reduced collagen deposition in KO mice relative to WT mice, with lower serum levels of inflammatory markers and improved lung oxidative stress profiles. No significant differences were observed between KO and WT mice under room air/PBS conditions. Conclusions Parkin knockout in juvenile mice mitigates asthma-related alterations in airway resistance, histopathological changes, inflammation status, and oxidative stress. These findings highlight a protective role of Parkin deficiency against asthma-associated pathologies.

Prognostic Factors That Affect Mortality Patients with Acinetobacter baumannii Bloodstream Infection.

To evaluate the clinical features of patients with Acinetobacter baumannii bloodstream infection (BSI). Totally 200 inpatients with Acinetobacter baumannii BSI were included, clinical features of Acinetobacter baumannii BSI inpatients between 90-day survival and 90-day mortality groups, between 30-day survival and 30-day mortality groups, between patients infected with multidrug-resistant (MDR group) and sensitive Acinetobacter baumannii (sensitive group) were analyzed. The prognostic factors of 90-day mortality were analyzed by univariate logistic regression and multivariate logistic regression. The survival curve in bloodstream infectious patients with multidrug-resistant (MDR group) and sensitive Acinetobacter baumannii (sensitive group) was analyzed by Kaplan-Meier analysis. The 90-day mortality patients had significantly higher carbapenem-resistant bacterial infection and critical care unit (ICU) admission. The 90-day and 30-day mortality groups showed higher C-reactive protein (CRP) and serum creatinine (Scr) levels and lower red blood cells (RBC) and albumin (ALB) levels than their survival counterparts, respectively. Critical surgery, ICU admission and delayed antibiotic treatment were independently prognostic risk predictors for 90-day mortality in Acinetobacter baumannii BSI patients, while critical surgery and diabetes were independently prognostic risk predictors for 90-day mortality in carbapenem-resistant Acinetobacter baumannii BSI patients. Compared with sensitive group, MDR group showed significantly longer ICU and whole hospital stay, lower levels of lymphocytes, RBC, hemoglobin, lactate dehydrogenase and ALB, higher frequency of infection originating from the skin and skin structure. Moreover, patients in the MDR group had a significantly worse overall survival than the sensitive group. We identified the prognostic factors of Acinetobacter baumannii BSI and carbapenem-resistant Acinetobacter baumannii BSI patients. Critical surgery, ICU admission, delayed antibiotic treatment or diabetes were significantly associated with the mortality of those patients. Moreover, aggressive measures to control MDR Acinetobacter baumannii could lead to improved outcomes.

The clinical utility of handgrip strength as a malnutrition screening tool in hospitalized older adults: a cross-sectional study in Saudi Arabia.

Malnutrition is prevalent among hospitalized older patients. Early identification is therefore essential to implementing appropriate therapeutic interventions. This study aimed to explore the correlation between handgrip strength (HGS) and nutritional status in hospitalized older adults. This observational cross-sectional study was conducted at King Abdulaziz University Hospital, where a consecutive cohort of older adult inpatients was enrolled for participation. Shortly after admission, HGS and nutritional status were assessed using a dynamometer and the most recent version of the Mini-Nutritional Assessment Short Form (MNA-SF) test, respectively. Key anthropometric and biochemical indicators were also collected. A total of 135 consecutive patients were evaluated. Among participants with low HGS, 18 (16.22%) were malnourished, 43 (38.74%) were at risk of malnutrition, and 50 (45.05%) had normal nutrition status. The participants with low HGS had low hemoglobin, low lymphocyte levels, high creatinine levels, high BUN levels, high CRP levels, high HbA1c levels, and high vitamin B12 levels. Multiple logistic regression analysis showed that age, hemoglobin, and HbA1C were independently associated with low HGS. Based on the cut-off values for the HGS by the European Working Group on Sarcopenia in Older People-2 (EWGSOP2), low HGS showed high sensitivity to detect "malnourished and at risk of malnutrition" as well as "malnourished alone;" however, the specificity was low to exclude "malnourished and at risk of malnutrition" as well as "malnutrition alone." Age over 75 years, low hemoglobin, and elevated HbA1C levels were independent risk factors for low HGS. While HGS was sensitive in detecting malnutrition or risk, its specificity was low. Therefore, HGS may not be adequate as a standalone tool to assess nutritional status in hospitalized older adults. Replication of this study using locally reliable and validated HGS cut-off values is warranted to confirm these findings.

Assessment of haematological parameters in HIV patients attending Kabutare district Hospital

Background: Human Immunodeficiency virus (HIV) infection is characterized by progressive weakening of the immune system attributed to the decrease in the number of circulating CD4+ T-helper cells. This predisposes HIV patients to a variety of opportunistic infections and neoplastic disorders. also lead to defective hematopoiesis and a decrease in cell lineage. Haematological parameters including red blood cells, white blood cells, platelet and hemoglobin are widely used clinical indicators of health and disease. Aim: The aim of this study was to assess haematological parameters in HIV patients attending Kabutare District hospital. Methodology: This study was a cross-sectional study conducted to assess haematological parameters in HIV patients attending Kabutare District hospital. Venous blood sample were collected for complete blood count which was determined using sysmex 500i machine automation analyser. Results: A total of 80 HIV infected patient participated. 7.5% of the study participants were proven to have white blood cells below the normal range as it was below 4.26.25% of patients were found below the normal range of red blood cells. Hemoglobin and hematocrit levels of 35% patients were found to below their normal ranges. 10% of patient were found to have low platelet and 23.5% were found to have low levels of lymphocytes. Association between CD4 counts and hemoglobin levels was significant with p value of 0.000 as it is less than confidence level of 0.05. Conclusion: This study concluded that haematological parameters are affected by HIV infection and there is association between CD4 counts and hemoglobin concentration levels. I would recommend health practioners to also consider complete blood count as prognostic test of HIV as it is clinical health indicator and diseases. Keywords: Haematological parameters, Human Immunodeficiency virus, CD4 counts, acquired immunodeficiency syndrome.

DIPG-36. DRD2 ANTAGONISM RESCUES IMMUNE-TUMOR SURVEILLANCE, WARMING THE TUMOR IMMUNE MICROENVIRONMENT OF DIFFUSE MIDLINE GLIOMA MODELS

Abstract BACKGROUND Less than 10% of patients with diffuse midline glioma (DMG) survive 2-years post-diagnosis, with no approved treatments other than palliative radiotherapy. Immune-checkpoint inhibition has failed in the clinic, likely due to a lack of tumor infiltrating lymphocytes (TILs) and limited/no expression of immune checkpoint proteins or proinflammatory cytokines in the tumor immune microenvironment (TIME). Similarly, glioblastoma patients suffer from a ‘cold’ TIME, linked to the sequestration of T cells in the bone marrow (BM) through β-arrestin-induced internalization of S1PR1. β-arrestin is activated by Dopamine receptors (DRD2); therefore, we hypothesized that systemic DRD2 antagonism using the antagonist ONC201, might reverse lymphopenia, increasing TIL populations. METHODS Flow cytometry analysis was performed on bloods from DMG patients at diagnosis. Circulating immune cells and BM from the immunocompetent PPK model +/-ONC201 and tumor-naïve mice were analyzed by a hematology analyzer and flow cytometry. Immunocompromised SU-DIPG-VI and HSJD-DIPG-007 and immunocompetent XFM murine models were treated +/-ONC201 and tumors analyzed by immunoblotting, immunohistochemistry, and flow cytometry. scRNAseq and scATACseq analysis was performed on tumors from immunocompetent PPK models +/-ONC201. RESULTS DMG patients displayed low levels of total lymphocytes, including CD4+, CD8+ and NK subsets (n=9). Similarly, DMG-bearing mice displayed lower levels of lymphocytes (CD45+, CD4+, CD8+ subsets, n=3) compared to sham-engrafted mice. ONC201 treated mice showed lymphocyte levels comparative to sham-engrafted mice, reversing tumor-induced lymphopenia. A significant increase of T cells expressing S1PR1+ was seen in the BM following ONC201. Tumor immune cell infiltration following ONC201 was confirmed in both immunocompromised and immunocompetent models. Multiomics analysis identified ONC201 to promote pro-inflammatory polarization of microglia/macrophages (MHC II and CD86) and increase expression of immune checkpoints (VISTA and PD-L1). CONCLUSIONS DMG patients suffer from low peripheral lymphocytes, likely contributing to cold TIME. ONC201 reversed tumor-induced lymphopenia, promoting TIL recruitment within the tumor, warming the TIME.

Towards XAI agnostic explainability to assess differential diagnosis for Meningitis diseases

Meningitis, characterized by meninges and cerebrospinal fluid inflammation, poses diagnostic challenges due to diverse clinical manifestations. This work introduces an explainable AI automatic medical decision methodology that determines critical features and their relevant values for the differential diagnosis of various meningitis cases. We proceed with knowledge acquisition to define the rules for this research. Currently, we have established the etiological diagnosis of Meningococcaemia, Meningococcal Meningitis, Tuberculous Meningitis, Aseptic Meningitis, Haemophilus influenzae Meningitis, and Pneumococcal Meningitis. The data preprocessing was conducted after collecting data from samples with meningitis diseases at Setif Hospital in Algeria. Tree-based ensemble methods were then applied to assess the model’s performance. Finally, we implement an XAI agnostic explainability approach based on the SHapley Additive exPlanations technique to attribute each feature’s contribution to the model’s output. Experiments were conducted on the collected dataset and the SINAN database, obtained from the Brazilian Government’s Health Information System on Notifiable Diseases, which comprises 6729 patients aged over 18 years. The Extreme Gradient Boosting model was chosen for its superior performance metrics (Accuracy: 0.90, AUROC: 0.94, and F1-score: 0.98). Setif’s hospital data revealed notable performance metrics (Accuracy: 0.7143, F1-Score: 0.7857). This study’s findings showcase each feature’s contribution to the model’s predictions and diagnosis. It also reveals critical biomarker ranges associated with distinct types of Meningitis. Significant diagnostic effect was found for Meningococcal Meningitis with elevated neutrophil levels ( > 40%) and balanced lymphocyte levels (40%–60%). Tuberculous Meningitis demonstrated low neutrophil levels ( < 60%) and elevated lymphocyte levels ( > 60%). H. influenzae meningitis exhibited a predominance of neutrophils ( > 80%), while Aseptic meningitis showed lower neutrophil levels ( < 40%) and lymphocyte levels within the range of 50%–60%. The majority of the AI automatic medical decision results are twinned with validation by our team of infectious disease experts, confirming the alignment of algorithmic diagnoses with clinical practices.

Cyclin-dependent kinase inhibitors enhance programmed cell death protein 1 immune checkpoint blockade efficacy in triple-negative breast cancer by affecting the immune microenvironment.

Clinical studies on programmed death-ligand 1 (PD-L1) immune checkpoint inhibitors for treating triple-negative breast cancer (TNBC) have shown unsatisfactory efficacy due to low tumor-infiltrating lymphocyte (TIL) levels. Inhibitors targeting cyclin-dependent kinase (CDK) proteins can affect the immune microenvironment, increase TIL levels, and promote antitumor immunity, thus providing a new direction for TNBC treatment strategies. The authors tested three CDK inhibitors on the TNBC cell lines MDA-MB-231 and 4T1 and validated their antitumor effects and impact on the immune microenvironment using multiple detection methods. They verified the efficacy and immune-related mechanisms of different combination therapy experiments in a 4T1 cell-transplanted BALB/c mouse model. Treatment with CDK inhibitors for 72 hours inhibited cell proliferation, clone formation, migration, and cell-cycle arrest and induced apoptosis in human breast cancer MDA-MB-231 cells and mouse breast cancer 4T1 cells. CDK inhibitors suppressed DNA methylation by downregulating DNMT1, DNMT3a, and DNMT3b expression. These three inhibitors promoted the secretion of various chemokines, enhanced tumor cell antigen presentation, and increased PD-L1 expression. CDK inhibitors improved the efficacy of immunotherapy in animal models and increased TIL levels. Combination therapy with CDK and PD-L1 immune checkpoint inhibitors affects the immune microenvironment, promotes antitumor immunity, and improves the efficacy of immunotherapy for TNBC.

An Evaluation of the Hematological Markers of Systemic Inflammation and Oxidative Stress in Vitiligo: A Case-Control Study.

Introduction Melanocyte dysfunction in vitiligo is considered to be due to genetics, inflammation, and autoimmunity. Research has shown that oxidative stress plays a significant role in triggering these conditions. Currently, there are several markers indicating hematological inflammation and oxidative stress. This study aimed to investigate the status of inflammation and oxidative stress markers in vitiligo. Methods This study included patients with vitiligo and age-gender-matched healthy controls.C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-high-density lipoprotein ratio (MHR) and extent of vitiligo were calculated and compared. Results The study included 138 participants (69 vitiligo and 69 controls). The mean was 41.46 years with a female predominance (55.1%). The patient group demonstrated higher levels of platelets, neutrophils, CRP, NLR, MLR, PLR, and HDL and lower levels of lymphocytes and HDL compared to the control group (p>0,05).The only significantly different value between the groups was MHR (p=0.03). The generalized vitiligo group demonstrated higher levels of platelets, neutrophils, monocytes, CRP, NLR, PLR, and MLR, and lower levels of lymphocytes and HDL compared to the localized group. The only significantly different values between the groups were MHR and MLR (p=0.02, p=0.03). Conclusion This study found that MHR and CRP values were higher in vitiligo patients. Additionally, MHR and MLR values were higher in patients with generalized vitiligo. These results suggest that MHR is a reliable indicator marker for systemic inflammation and oxidative stress in vitiligo.

Role of Ferroptosis in the Progression of COVID-19 and the Development of Long COVID.

To examine the role of ferroptosis on the pathogenesis and progression of COVID-19. A total of 127 patients who were hospitalized for COVID-19 were categorized into two groups according to the intensity of oxygen therapy (high-flow or low-flow). Clinical characteristics, laboratory parameters, plasma markers, and peripheral blood mononuclear cell (PBMC) markers were measured at baseline and one or two weeks after treatment. Telephone follow-up was performed 3 months after discharge to assess long COVID. Patients receiving high-flow oxygen therapy had greater levels of neutrophils; D-dimer; C reactive protein; procalcitonin; plasma protein levels of tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), IL-17, and acyl-CoA synthetase long-chain family member 4 (ACSL4); and PBMC mRNA level of TNF-α; but had lower levels of lymphocytes and plasma glutathione peroxidase 4 (GPX4). There were negative correlations of plasma GPX4 and cystine/glutamate transporter-11 (SLC7A11) with TNF-α, IL-6, and IL-17, and positive correlations of ACSL4 with inflammatory markers in plasma and PBMCs. The plasma levels of TNF-α, IL-6, IL-17, and ACSL4 were significantly lower after treatment than at baseline, but there were higher post-treatment levels of lymphocytes, GPX4, and SLC7A11. Patients with long COVID had a lower baseline level of plasma SLC7A11. Ferroptosis is activated during the progression of COVID-19, and a low baseline level of a ferroptosis marker (SLC7A11) may indicate an increased risk for long COVID-19. Ferroptosis has potential as a clinical indicator of long COVID and as a therapeutic target.

Haematological Profile and ACE2 Levels of COVID-19 Patients in a Metropolis in Ghana

Background: Several studies have linked coronavirus disease 2019 (COVID-19) risk to age and ABO blood groups. Variations in plasma angiotensin-converting enzyme 2 (ACE2) levels and blood counts have been reported, suggesting an association between disease severity and low lymphocyte levels. Aim: this study aimed to understand how these factors relate to COVID-19 in Ghanaian patients, considering geographical and demographic differences. Methods: Participants were recruited from six hospitals in Kumasi, Ghana, between June 2020 and July 2021. Nasopharyngeal swabs were taken to test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and blood samples were collected for complete blood count testing, ABO/Rhesus typing, and assessment of plasma ACE2 levels. Demographic and COVID-19 severity data were gathered, and IBM SPSS version 25.0 was used for analysis. Results: Overall, 515 patients were enrolled, out of which 55.9% (n = 288/515) were males and 50.3% (n = 259/515) tested positive for SARS-CoV-2. The median age was 37 years (IQR = 26–53). Age was significantly associated with SARS-CoV-2 infection (p = 0.002). The severe COVID-19 group was the oldest (70 years, IQR = 35–80) and presented with anaemia (haemoglobin, g/dL: 9.55, IQR = 7.85–11.93), leukocytosis (WBC × 103/μL: 15.87, IQR = 6.68–19.80), neutrophilia (NEUT × 106/μL: 14.69, IQR = 5.70–18.96) and lymphocytopenia (LYMPH × 106/μL: 0.47, IQR = 0.22–0.66). No association was found between SARS-CoV-2 positivity and ABO (p = 0.711) or Rh (p = 0.805) blood groups; no association was also found between plasma ACE2 levels and SARS-CoV-2 status (p = 0.079). However, among COVID-19 participants, plasma ACE2 levels were significantly reduced in the moderate illness group (40.68 ng/mL, IQR = 34.09–48.10) compared with the asymptomatic group (50.61 ng/mL, IQR = 43.90–58.61, p = 0.015). Conclusions: While there may be no real association between the ABO blood group, as well as plasma ACE2 levels, and SARS-CoV-2 infection in Ghanaian patients, older individuals are at a higher risk of severe disease. Anaemia, and leukocytosis with lymphocytopenia may be indicators of poor disease progression.

Evaluation of interferon gamma release assay to measure t-cell response in COVID-19 patients from intensive care units and inpatient departments.

Interferon gamma release assay (IGRA) is an in vitro blood test to measure interferon gamma (IFN-γ) released from antigen-specific Tcells after stimulation with pathogen-specific peptides. In this study, it was aimed to investigate the T-cell response using IGRA and to compare various laboratory values in Coronavirus Disease (COVID-19) patients hospitalized either in hospital inpatient departments or in intensive care units. Atotal of 100 patients (50+50) who were identified as positive for COVID-19 through the molecular method in Selcuk University Faculty of Medicine Infectious Diseases Service and Reanimation Intensive Care Unit were included in the study. IFN-γ levels in blood samples collected from patients were determined using the QuantiFERON Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) (QIAGEN, Germany) kit. The patients' gender, age, c-reactive protein (CRP), aspartate aminotransferase (AST), alanine transaminase (ALT), interleukin (IL)-6, lymphocyte count, procalcitonin, and D-dimer results were obtained from the hospital automation system. Thirty-eight of the IGRA test results were negative, 44 were positive and 18 were inconclusive. The age of patients with negative IGRA test results was significantly higher (p<0.001) compared to patients with positive results. There were no significant differences between patients' IGRA test results and gender, prognosis, IL-6, lymphocyte counts, CRP, AST, and ALT values.Age, death rates, D-dimer, CRP, procalcitonin, AST and ALT values of patients hospitalized in the intensive care unit were significantly higher (p<0.001) compared to the those hospitalized in the inpatient department, while conversely, the lymphocyte values were lower (p<0.001). The relatively higher IGRA negative results in the elderly, negative and intermediate results in intensive-care patients, and low lymphocyte levels in intensive-care patients indicate that the cellular immune response is diminished and/or absent. The death rates, D-dimer, CRP, procalcitonin, AST and ALT values of the patients hospitalized in the intensive care unit were higher compared to those from the in-patient department, indicating the severity of inflammation and signaling the development of organ failure. In the light of these findings, we suggest that IGRA tests may serve as aguide in immunomodulatory therapy (Tab. 2, Fig. 2, Ref.27). Text in PDF www.elis.sk Keywords: COVID-19, interferon gamma release assay test, Tcell response.

Value of Pretreatment Inflammation-nutrition Score to Predict Non-response to Neoadjuvant Chemotherapy in Locally Advanced Rectal Cancer

ObjectiveTo investigate the value of pretreatment inflammatory-nutritional biomarkers in predicting the pathological response of locally advanced rectal cancer (LARC) after neoadjuvant chemotherapy (nCT). MethodsThis retrospective study included eligible participants who underwent nCT followed by radical surgery. Pretreatment inflammatory nutritional biomarkers were calculated within one week prior to nCT. Correlations between biomarkers and pathological responses were analyzed. The cut-off values of the pretreatment biomarkers for predicting non-response were determined using receiver operating characteristic (ROC) curve analysis. The inflammation-nutrition score was calculated using the lymphocyte level, neutrophil-to-lymphocyte ratio (NLR), and prognostic nutritional index (PNI). ResultsA total of 235 patients were retrospectively recruited between January 2017 and September 2022. Lower lymphocyte levels, lymphocyte monocyte ratio (LMR), and PNI, and higher NLR and platelet-to-lymphocyte ratio (PLR) were observed in patients without response. Multivariate logistic regression analysis revealed that NLR could independently predict non-response to nCT in patients with LARC. The sensitivity and specificity of the inflammation-nutrition score for predicting nonresponse were 71.2% and 61.7%, respectively. ConclusionThe pretreatment inflammation-nutrition score is a practical parameter for predicting nonresponse to nCT in patients with LARC. Patients with high scores were more likely to respond poorly to nCT.

Immune-Suppression Modulation in Solid Organ Transplant Recipients Admitted for COVID-19

SARS-CoV-2 infection has significantly impacted solid organ transplant (SOT) recipients, who are at high risk of disease and worse outcomes. Moreover, therapeutic management in this population is not precise yet. Our study aimed to evaluate the overall survival of SOT recipients and predictive factors for mortality. We also aimed to assess the impact of antiviral treatments and immunosuppressant changes on overall mortality and to evaluate the length of hospital stay of SOT compared to the general population. This is a retrospective monocenter study. We included all SOT recipients with laboratory-confirmed SARS-CoV2 infection admitted at Niguarda Hospital in Milan from February 2020 through January 2022. We enrolled 74 solid organ transplant recipients with a median age of 59. The overall mortality rate was 19%. Older age, male sex, diabetes, and high LDH values were associated with an increasing fatality rate. The median length of stay (LoS) was 17 days. Low white blood count and lymphocyte levels were associated with 19 days LoS. Changes in immunosuppression and SARS-CoV-2 antiviral therapies had no impact on mortality and LoS. In this study, we confirm previously described risk factors for worse outcomes. We did not observe beneficial therapies in terms of mortality rate and LoS. Seven patients received antiviral treatment. More studies are needed to assess the best therapeutical options, including immunosuppressant modulation, in SOTs.

Coronavirus Disease 2019 in Rheumatic Patients with Inflammatory Disorders: A Descriptive Study from a High Infection Incidence Region of Northern Spain.

Since the first confirmed case of severe acute respiratory syndrome coronavirus 2 in Spain in January 2020, the susceptibility of patients with rheumatic disease has remained unclear. In this report, we will describe the main features of coronavirus disease 2019 (COVID-19) that occurred in rheumatic patients with inflammatory disorders and try to identify features associated with severe disease. We included all rheumatic patients with immune-mediated diseases followed at 6 centers belonging to the public healthcare system in the Basque Country (Spain) and diagnosed with COVID-19 from March 1, 2020, to May 31, 2020. In total, 131 patients were included in this study. The most frequent rheumatic disease was rheumatoid arthritis (46.6%), and the main comorbidities were arterial hypertension (45%). Fortyseven percent were taking glucocorticoids (GC) (62 patients), 61.8% were under treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARD), and 25 patients (19.1%) were receiving targeted therapies (TT). Thirty-eight percent of patients required hospital admission, 2.3% required transfer to intensive care uni, and the rate of mortality was 9.2%. Associated factors in univariate analysis for a bad outcome were older age, use of GC, obesity, previous cardiovascular disease, and lymphopenia. Use of GC and lymphopenia remained within the multivariate model. The frequency of COVID-19 seems to be similar in rheumatic patients as in the general population. Advanced age, obesity, heart disease, glucocorticoids, and low levels of lymphocytes were more common among the patients with a bad outcome. Neither exposure to csDMARD nor TT was associated with severe cases.

COVID-19 vaccination and its influence on the disease severity among the COVID patients in a tertiary care hospital – A cross sectional study

Introduction: COVID-19 disease was a global health emergency from March 2020 till May 2023 with no effective drug to date. COVID-19 vaccines with other precautious measures like hand washing, disinfection, social distancing etc. were the only ways to decrease the burden of the disease worldwide. The study aimed to determine the association between COVID-19 vaccination and disease severity among COVID-19 patients admitted to a Government Medical College hospital. Methods: This cross sectional study included 983 COVID-19 patients admitted to a tertiary care hospital from March 2021 to December 2021. Secondary data were collected from the case sheets and vaccination details were collected from the patients over the phone and through COWIN App. Chi-square test and binary logistic regression were done and the p value and odds ratio were estimated. Results: 92.9% of study participants were unvaccinated, 2.7% were fully vaccinated, and 4.3% were partially vaccinated. Among fully vaccinated 11.1% had breathlessness, 0% ICU admission, 3.7% died, 20% had COVID pneumonia findings in CT lung, 9% had low lymphocyte levels which were statistically significantly lower than in partially vaccinated (39.5%, 41.9%, 7%, 18.6%, 59.3%, 65.1%, 76.9% respectively) and unvaccinated (31.1%, 27.7%, 2%, 4.6%, 48.2%, 45.2%, 68.4% respectively). Conclusion: Two doses of vaccines provided significant protection from severe forms of the disease. Partially vaccinated were affected more, which may be due to insufficient immunity gained and their careless attitude post-vaccination with decreased shielding behaviour. The present study shows that partial vaccination is not protective against the progression of COVID-19 disease severity. More focus should be made on full vaccination of the community and educating the public about complete vaccination and emphasis on preventive measures even after vaccination must be made to reduce the burden of COVID-19 in the community. Keywords: COVID-19; COWIN App; vaccination; coronavirus disease

Combination of NK and Other Immune Markers at Early Phase Stratify the Risk of Sepsis Patients: A Retrospective Study.

Immune dysfunction plays a pivotal role in sepsis pathogenesis. Previous studies have revealed the crucial role of T cells and human leukocyte antigen-DR (HLA-DR) in sepsis. However, the function of natural killer (NK) cells remains unclear. This study aimed to investigate whether NK cells are associated with sepsis prognosis. In addition, we aimed to explore the interrelation and influence between NK and other immunological features in patients with sepsis. This retrospective, observational study included patients with sepsis from two hospitals in mainland China. The clinical characteristics and immune results during the early phase were collected. Patients were classified according to the level of immune cells to analyze the relationship between immunological features and 28-day mortality. A total of 984 patients were included in this study. Non-survivors were older and had lower levels of lymphocytes, monocytes, NK cells, HLA-DR, and T cells. Patients were classified into eight groups according to their levels of NK cells, HLA-DR, and T cells. Only patients with decreased NK and T cell counts showed a significant increase in 28-day mortality. An increase in CD8+ T cells was correlated with the alleviation of 28-day mortality only among patients with high NK cell levels. This study provides novel insights into the association between NK cells and 28-day mortality as well as the interrelation between NK cells and other immune cells in sepsis. The relationship between CD8+ T cells and 28-day mortality in sepsis is dependent on NK cell count.

High-grade tumor budding is a risk factor for survival in patients with laryngeal squamous cell carcinoma

ObjectiveWith the increasing incidence and mortality of laryngeal squamous cell carcinoma worldwide, researchers continue to search for novel prognostic factors and treatment methods for preventing early laryngeal squamous cell carcinoma from becoming advanced laryngeal squamous cell carcinoma. This study aims to determine if tumor budding is an independent risk factor associated with the survival of patients with laryngeal squamous cell carcinoma. Methods268 cases of laryngeal squamous cell carcinoma were studied, and tumor budding was analyzed for associations with clinicopathological features and clinical outcomes. ResultsTumor budding was divided into low-grade tumor budding (0–6/0.785 mm2) and high-grade tumor budding (≥7/0.785 mm2) based on the results of the receiver operating characteristics curve analysis. Logistic regression analysis showed that smaller tumor cell nests, the low levels of tumor-infiltrating lymphocytes, and higher pathological T staging were the risk factors for high-grade tumor budding (p < 0.05). In the low-grade tumor budding group, there was no statistic difference in survival between patients without tumor budding and those with 1–6/0.785 mm2 tumor budding. Multivariate survival analysis showed high-grade tumor budding (p < 0.001) was independent prognostic factors for disease-free survival and overall survival in laryngeal squamous cell carcinoma. High-grade tumor budding was also an independent prognostic factor for disease-free survival (p = 0.037) and overall survival (p = 0.009) in T1-2N0 laryngeal squamous cell carcinoma. ConclusionsSmaller tumor cell nests, the low levels of tumor-infiltrating lymphocytes, and higher pathological T staging were closely associated with high-grade tumor budding in laryngeal squamous cell carcinoma. High-grade tumor budding may be an adverse risk factor that affects not only the disease-free survival and overall survival of laryngeal squamous cell carcinoma patients but also the survival of T1-2N0 laryngeal squamous cell carcinoma patients. Level of EvidenceLevel 4.

Prognosis Predictive Markers in Patients with Chronic Obstructive Pulmonary Disease and COVID-19.

Some studies have reported that chronic respiratory illnesses in patients with COVID-19 result in an increase in hospitalization and death rates, while other studies reported to the contrary. The present research aims to determine if a predictive model (developed by combing different clinical, imaging, or blood markers) could be established for patients with both chronic obstructive pulmonary disease (COPD) and COVID-19, in order to be able to foresee the outcomes of these patients. A prospective observational cohort of 165 patients with both diseases was analyzed in terms of clinical characteristics, blood tests, and chest computed tomography results. The beta-coefficients from the logistic regression were used to create a score based on the significant identified markers for poor outcomes (transfers to an intensive care unit (ICU) for mechanical ventilation, or death). The severity of COVID-19, renal failure, diabetes, smoking status (current or previous), the requirement for oxygen therapy upon admission, high lactate dehydrogenase (LDH) and C-reactive protein level (CRP readings), and low eosinophil and lymphocyte counts were all identified as being indicators of a poor prognosis. Higher mortality was linked to the occurrence of renal failure, the number of affected lobes, the need for oxygen therapy upon hospital admission, high LDH, and low lymphocyte levels. Patients had an 86.4% chance of dying if their mortality scores were -2.80 or lower, based on the predictive model. The factors that were linked to a poor prognosis in patients who had both COPD and COVID-19 were the same as those that were linked to a poor prognosis in patients who had only COVID-19.