Low Lymphocyte Count Research Articles

A rare case of viral-associated trichodysplasia spinulosa in a patient with chronic lymphocytic leukemia.

Dear Editors, Viral-associated trichodysplasia spinulosa (VATS) is a cutaneous eruption of folliculo-centric shiny papules and alopecia that most commonly occurs in transplant recipient patients.1 Here, we present an extremely rare case of VATS in a female patient with chronic lymphocytic leukemia (CLL). An informed consent was obtained from the patient for this report. A 63-year-old female presented with a 2-month history of multiple reddish-pinkish papules on her face in the setting of long-standing CLL. Physical examination also showed leonine facies, superciliary madarosis, and an infiltrative nose. Many spiny red papules and spicules were located on her face, neck, chest, arms, and back (Fig. 1A and B). A punch biopsy of one of the lesions on the back revealed prominent trichohyalin granules with disruption of the normal follicular maturation showing basophilic inclusions within the follicular ostia consistent with VATS (Fig. 2A and B).Fig. 1.: Clinical progression of viral-associated trichodysplasia spinulosa treated with topical cidofovir. Spiny red papules and spicules concentrated on face (A) and upper back (B) found on initial presentation. Face showing dramatically decreased spicules and papules, particularly on cheek and forehead, after 9 months of treatment with topical cidofovir (C).Fig. 2.: Pathological findings of viral-associated trichodysplasia spinulosa showing unusual prominent trichohyalin granules with disruption of the normal follicular maturation showing basophilic inclusions within the follicular ostia, shown at magnification 100× (A) and 400× (B).Importantly, the patient was not on any immunosuppressive therapy when she developed the VATS lesions. The most recent treatment for her CLL had been approximately 1 year ago, when she had finished 6 cycles of bendamustine plus rituximab. Prior to that round of treatment, her small lymphocytic lymphoma had been diagnosed over 20 years ago but had not required therapy for 10 years. A complete work up for immunosuppression including HIV testing, T-cell subsets, immunoglobulins, and re-staging of small lymphocytic lymphoma was performed. She was negative for HIV-1/2 antibody/HIV-1 antigen screening. She had evidence of hypogammaglobulinemia with an IgG of 667 mg/dL and low IgG subclasses 2, 3, and 4 (72, 16, and 1.3 mg/dL, respectively). IgG subclass 1 was normal (482 mg/dL). A peripheral blood flow cytometry showed absolute T-cell lymphopenia with low CD3+ and CD3+CD4+ absolute counts (504 and 267.2/µL, respectively), but no evidence of lymphoproliferative disease. Laboratory values showed a low absolute lymphocyte count of 0.8/µL. Prior treatment of the skin lesions by the primary care physician included topical corticosteroids, topical metronidazole, and oral cephalexin, and were not effective. After the diagnosis was established, the patient was treated with 450 mg valganciclovir twice daily to target the underlying polyomavirus, but showed no improvement over 4 months. 3% topical cidofovir twice daily was then added, and the patient showed significant improvement over the following 9 months on both 450 mg valganciclovir twice daily and 3% topical cidofovir treatment (Fig. 1C). During this period, valganciclovir was discontinued by the patient for a period of 3 months due to apparent lack of efficacy but was restarted based on dermatology recommendation. The plan of care is to continue this treatment indefinitely as maintenance therapy. Although VATS has been reported frequently in transplant recipient patients and patients with acute lymphocytic leukemia and non-Hodgkin’s lymphoma, there are only 3 previously reported account of VATS in a patient with CLL in the literature.2–4 Importantly, the previously reported patient developed VATS just 2 months after ceasing fludarabine,3 whereas our patient had been off immunosuppressive agents for nearly 1 year prior to developing VATS. Thus, our unique case highlights the dermatologically significant impact of CLL-induced immunodeficiency. The etiology of the immunodeficiency caused by CLL is multifactorial, including hypogammaglobulinemia, hypocomplementemia, and altered major histocompatibility complex class II antigens on cancer cells.5 Finally, this case emphasizes the important role that topical cidofovir may have in treating patients with treatment-resistant VATS.6 Conflicts of interest None. Funding None. Study approval N/A. Author contributions RC and SB: Writing and editing manuscript. JM and JP: Interpretation of information and editing. JL: Editing manuscript, supervision.

Humoral response after BNT162b2 vaccine in Japanese hemodialysis patients

BackgroundHemodialysis patients are more likely to be severely affected if infected by COVID-19. Contributing factors include chronic kidney disease, old age, hypertension, type 2 diabetes, heart disease, and cerebrovascular disease. Therefore, action against COVID-19 for hemodialysis patients is an urgent issue. Vaccines are effective in preventing COVID 19 infection. In hemodialysis patients, however, responses to hepatitis B and influenza vaccines are reportedly weak. The BNT162b2 vaccine has shown an efficacy rate of about 95% in the general population, but as far as we know there are only several reports of efficacy data in hemodialysis patients in Japan.MethodsWe assessed serum anti-SARS-CoV-2 IgG antibody (Abbott SARS-CoV-2 IgG II Quan) in 185 hemodialysis patients and 109 health care workers. The exclusion criterion was positivity for SARS-CoV-2 IgG antibody before vaccination. Adverse reactions to BNT162b2 vaccine were evaluated through interviews.ResultsFollowing vaccination, 97.6% of the hemodialysis group and 100% of the control group were positive for the anti-spike antibody. The median level of anti-spike antibody was 2,728.7 AU/mL (IQR, 1,024.2–7,688.2 AU/mL) in the hemodialysis group and 10,500 AU/ml (IQR, 9,346.1–2,4500 AU/mL) in the health care workers group. The factors involved in the low response to the BNT152b2 vaccine included old age, low BMI, low Cr index, low nPCR, low GNRI, low lymphocyte count, steroid administration, and complications related to blood disorders.ConclusionsHumoral responses to BNT162b2 vaccine in hemodialysis patients are weaker than in a healthy control sample. Booster vaccination is necessary for hemodialysis patients, especially those showing a weak or non-response to the two-dose BNT162b2 vaccine.Trial registration UMIN, UMIN000047032. Registered 28 February 2022, https://center6.umin.ac.jp/cgi-bin/ctr/ctr_reg_rec.cgi.

Predictive Values of Hematological Parameters for Determining Imminent Brain Death: A Retrospective Study.

Background and Objectives: The inflammatory cells released after intracranial hemorrhage, such as monocytes, macrophages, and neutrophils, activate the inflammatory system. These parameters can be used to evaluate the clinical course of diseases. This study aims to evaluate these parameters as possible predictors for evaluating the development of brain death. Materials and Methods: Patients with a Glasgow coma scale score below 7 were assigned to Group BD (patients with brain death) and Group ICH (intracranial hemorrhage). The neutrophil, lymphocyte, platelet, monocyte counts, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-neutrophil ratio (PNR) were measured at admission. Results: A high WBC count, neutrophil count, NLR, and PLR and a low lymphocyte count, LMR, and PNR were found to be significant for determining brain death. The area under the curve (AUC) values of NLR, PNR, PLR, and LMR to discriminate brain death were 0.63, 0.61, 0.56, and 0.61, respectively. Conclusion: NLR, PNR, PLR, and LMR are easily accessible and reliable parameters that can be used to predict the development of brain death and can be estimated by a simple complete blood count test.

Leukocyte subtypes and myeloid derived suppressor cells as prognostic markers in metastatic castration resistant prostate cancer treated with cabazitaxel: A satellite study of the CABASTY phase III trial.

126 Background: CABASTY trial investigated the benefit of an adapted schedule of cabazitaxel (16 mg/m2 bi-weekly versus 25 mg/m2 tri-weekly) in mCRPC patients previously treated with docetaxel and alternative androgen-targeted therapy. The study met its endpoints with a significantly decreased incidence of grade ≥ 3 neutropenia without a decrease in overall survival. This preplanned analysis evaluated the prognostic impact of neutrophil-to-lymphocyte ratio (NLR), neutrophil-to-platelets ratio (NPR) myeloid derived suppressor cells (MDSC) and leukocyte subtypes counts in this setting. Methods: 44 patients treated with cabazitaxel were included. Peripheral blood mononuclear cells were isolated and myeloid compartment analysis were performed at baseline, week 6 (S6) and week 12 (S12) of treatment using a multi-parametric flow cytometry panel. We investigated at each timepoints the association of NPR, NLR, MDSC and leukocytes subtypes with PSA response rate (PSArr), Progression Free Survival, and Overall Survival with a preplanned uni- and multivariate analysis. Results: The NLR, NPR, MDSC subtypes and lymphocytes count at baseline were prognostic in the CABASTY trial regardless of the cabazitaxel regimen. Patients with a high lymphocyte count and/or a low NLR, NPR, and MDSC counts at baseline had a significantly improved PSAr, PFS and OS. In the multivariate analysis, a NPR > 1,84 and lymphocytes count < 1,2 G/L at baseline were significantly associated with OS [HR 2.007 (1.3 - 3.1)] and [HR 0.38 (0.20 - 0.73)]. Conclusions: High NLR, NPR, neutrophil and MDSC counts as well as a low lymphocyte count at baseline and during treatment predict poor outcomes in mCRPC patients treated with cabazitaxel. NPR and lymphocyte count are readily available biomarkers that may be useful for risk stratification in future clinical trials and could be incorporated into prognostic nomograms. Clinical trial information: NCT02961257 .

Immunological Findings in a Group of Individuals Who Were Poor or Non-Responders to Standard Two-Dose SARS-CoV-2 Vaccines.

Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been declared a pandemic. However, data on the poor or non-responders to SARS-CoV-2 vaccines in the general population are limited. The objective of this study was to comprehensively compare the immunological characteristics of poor or non-responders to SARS-CoV-2 vaccines in the 18-59-year group with those in the ≥60-year group using internationally recognized cut-off values. The main outcome was effective seroconversion characterized by an anti-SARS-CoV-2 spike IgG level of at least a four-fold increase from baseline. Profiling of naïve immune cells was analyzed prior to vaccination to demonstrate baseline immunity. The outcomes of effective seroconversion in patients aged 18-59 years with those in patients aged ≥60 years were compared. The quantitative level of anti-spike IgG was significantly lower in individuals aged ≥60 and men aged 18-59 years. There were 7.5% of poor or non-responders among the 18-59 years and 11.7% of poor or non-responders in the ≥60 years using a four-fold increase parameter. There were 37.0-58.1% with low lymphocyte count (<1000/mm3), 33.3-45.2% with low CD4 cell counts (<500/mm3), and 74.1-96.8% with low B cell counts (<100/mm3) in the non-seroconversion group. An individual with an anti-SARS-CoV-2 spike IgG titer below 50 BAU/mL might be considered a poor or non-responder between 14 and 90 days after the last vaccine dose. Booster vaccination or additional protective measures should be recommended to poor or non-responders as soon as possible to reduce disease severity and mortality.

Immune cell counts in cerebrospinal fluid predict cognitive function in aging and neurodegenerative disease.

Immune dysfunction is important in aging and neurodegeneration; lacking clinically available tools limits research translation. We tested associations of cerebral spinal fluid (CSF) monocyte-to-lymphocyte ratio (MLR)-innate immune activation surrogate-with cognition in an aging and dementia cohort, hypothesizing that elevated MLR is associated with poorer executive functioning. CSF MLR was calculated in well-characterized, genotyped participants enrolled in studies of aging and dementia at University of California, San Francisco Memory and Aging Center (n=199, mean age 57.5 years, SD 11.9). Linear models tested associations with episodic memory and executive function (verbal fluency, speeded set-shifting). Aging was associated with higher CSF monocyte, lower lymphocyte counts, and higher MLRs (p<0.001). MLR was associated with verbal fluency (p<0.05) only. Using clinical labs, we show an inverse association between CSF MLR and executive function in aging and dementia, supporting the utility of clinical labs in capturing associations between innate immune dysfunction and neurodegeneration.

Sex differences in factors influencing hospital-acquired pneumonia in schizophrenia patients receiving modified electroconvulsive therapy.

Sex differences may be presented in the clinical features or symptoms of schizophrenia patients but also affect the occurrence of hospital-acquired pneumonia (HAP). Modified electroconvulsive therapy (mECT) is a common treatment method for schizophrenia, used in combination with antipsychotics. This retrospective research explores the sex difference in HAP affecting patients with schizophrenia who have received mECT treatment during hospitalization. We included schizophrenia inpatients treated with mECT and antipsychotics between January 2015 and April 2022. Blood-related and demographic data collected on admission were analyzed. Influencing factors of HAP in male and female groups were assessed separately. A total of 951 schizophrenia patients treated with mECT were enrolled in the study, including 375 males and 576 females, of which 62 patients experienced HAP during hospitalization. The risk period of HAP in these patients was found to be the first day after each mECT treatment and the first three sessions of mECT treatment. Statistically significant differences in the incidence of HAP were identified in male vs. female groups, with an incidence in men about 2.3 times higher than that in women (P < 0.001). Lower total cholesterol (Z = -2.147, P = 0.032) and the use of anti-parkinsonian drugs (χ2 = 17.973, P < 0.001) were found to be independent risk factors of HAP in male patients, while lower lymphocyte count (Z = -2.408, P = 0.016), hypertension (χ2 = 9.096, P = 0.003), and use of sedative-hypnotic drugs (χ2 = 13.636, P < 0.001) were identified in female patients. Influencing factors of HAP in schizophrenia patients treated with mECT have gender differences. The first day after each mECT treatment and the first three sessions of mECT treatment were identified to have the greatest risk for HAP development. Therefore, it would be imperative to monitor clinical management and medications during this period according to these gender differences.

Misdiagnosis of multisystem inflammatory syndrome in children: A diagnostic challenge.

Asthe COVID-19 pandemic continues, multisystem inflammatory syndrome in children (MIS-C) maintains its importance in the differential diagnosis of common febrile diseases. MIS-C should be promptly diagnosed because corticosteroid and/or intravenous immunoglobulin treatment can prevent severe clinical outcomes. In this study, we aimed to evaluate clinical presentation, diagnostic parameters and management of MIS-C and compare its clinical features to those of common febrile disease. This study was conducted at a tertiary-level university hospital between December 2020 and October 2022. One hundred and six children who were initially considered to have MIS-C disease were included in the study. During the follow-up period in the hospital, when the clinical and laboratory findings were re-evaluated, 38 out of 106 children were diagnosed differently. The clinical and laboratory findings of 68 children followed up with the diagnosis of MIS-C and 38 children who were initially misdiagnosed as MIS-C but with different final diagnoses were retrospectively compared. We identified 68 patients with MIS-C and 38 patients misdiagnosed as MIS-C during the study period. Infectious causes (71%), predominantly bacterial origin, were the most frequently confused conditions with MIS-C. Patients with MIS-C were older and had a more severe clinical course with high rates of respiratory distress, shock, and paediatric intensive care unit admission. While rash and conjunctivitis were more common among patients with MIS-C, cough, abdominal pain and diarrhoea were observed more frequently in patients misdiagnosed as MIS-C. Lower absolute lymphocyte counts, platelet counts and higher C-reactive protein and fibrinogen levels, pathological findings on echocardiography were the distinctive laboratory parameters for MIS-C. Multivariate analysis showed that older age, presence of conjunctivitis, high level of serum CRP and lower platelets were the most discriminative predictors for the diagnosis of MIS-C. There are still no specific findings to diagnose MIS-C,which therefore can be confused with different clinical conditions. Further data are needed to assist the clinician in the differential diagnosis of MIS-C and the diagnostic criteria should be updated over time.

Pneumocystis pneumonia in COVID-19 patients: A comprehensive review

The admitted patients of intensive care units with coronavirus disease 2019 (COVID-19) meet the challenges of subsequent infections. Opportunistic fungal infections such as Pneumocystis pneumonia (PCP) are among the important factors in the context of COVID-19 patients affecting illness severity and mortality. We reviewed the literature on COVID-19 patients with PCP to identify features of this infection. Although studies confirmed at least the presence of one immunosuppressive condition in half of PCP patients, this disease can also occur in immunocompetent patients who developed the immunosuppressive condition during Covid-19 treatment. The major risk factors associated with COVID-19 patients with PCP can be considered low lymphocyte counts and corticosteroid therapy. Diagnostic and treatment options are complicated by the overlapping clinical and radiologic characteristics of PCP and COVID-19 pneumonia. Therefore, physicians should comprehensively evaluate high-risk patients for PCP prophylaxis.

Peripheral inflammatory immune response differs among sporadic and familial Parkinson’s disease

Peripheral inflammatory immune responses are thought to play a major role in the pathogenesis of Parkinson’s disease (PD). The neutrophil-to-lymphocyte ratio (NLR), a biomarker of systemic inflammation, has been reported to be higher in patients with PD than in healthy controls (HCs). The present study was aimed at determining if the peripheral inflammatory immune response could be influenced by the genetic background of patients with PD. We included a discovery cohort with 222 patients with PD (132 sporadic PD, 44 LRRK2-associated PD (with p.G2019S and p.R1441G variants), and 46 GBA-associated PD), as well as 299 HCs. Demographic and clinical data were recorded. Leukocytes and their subpopulations, and the NLR were measured in peripheral blood. Multivariate lineal regression and post-hoc tests were applied to determine the differences among the groups. Subsequently, a replication study using the Parkinson’s Progression Markers Initiative cohort was performed which included 401 patients with PD (281 sPD patients, 66 LRRK2-PD patients, 54 GBA-PD patients) and a group of 174 HCs. Patients with sporadic PD and GBA-associated PD showed a significantly lower lymphocyte count, a non-significantly higher neutrophil count and a significantly higher NLR than HCs. The peripheral inflammatory immune response of patients with LRRK2-associated PD did not differ from HCs. Our study supports the involvement of a peripheral inflammatory immune response in the pathophysiology of sPD and GBA-associated PD. However, this inflammatory response was not found in LRRK2-associated PD, probably reflecting different pathogenic inflammatory mechanisms.

Investigation of the Value of T 2 Mapping in the Prediction of Eosinophilic Chronic Rhinosinusitis With Nasal Polyps.

Patients with eosinophilic chronic rhinosinusitis with nasal polyps (eosCRSwNP) usually have more extensive sinus disease, severe symptoms, and poorer disease control compared with patients with non-eosCRSwNP. Separating these entities will be crucial for patient management. The purpose of this study is to investigate T 1, T 2 , and apparent diffusion coefficient (ADC) values of the nasal polyps in patients with CRSwNP and evaluate the usefulness of these parameters for differentiating these diseases. Sinonasal magnetic resonance imaging was performed in 36 patients with eosCRSwNP and 20 patients with non-eosCRSwNP (including T 1 mapping, T 2 mapping, and diffusion-weighted imaging) before surgery. The T 1 , T 2 , and ADC values were calculated and correlated with pathologically assessed inflammatory cells of nasal polyps. Significant higher T 2 value, higher eosinophil count, and lower lymphocyte count of the nasal polyps were observed in eosCRSwNP than those in non-eosCRSwNP. There was no significant difference in T 1 or ADC values between the 2 groups. T 2 value was correlated with eosinophil count and lymphocyte count in CRSwNP. The area under the curve of T 2 value for predicting eosCRSwNP was 0.78 with 89.9% sensitivity and 60.0% specificity. T 2 value is a promising imaging biomarker for predicting eosCRSwNP. It can help to distinguish eosCRSwNP from non-eosCRSwNP.

The association between atopic eczema and lymphopenia: Results from a UK cohort study with replication in US survey data.

Lymphocyte skin homing in atopic eczema (AE) may induce lymphopenia. To determine if AE is associated with lymphopenia. We used UK primary care electronic health records (Clinical Practice Research Datalink GOLD) for a matched cohort study in adults (18 years+) (1997-2015) with at least one recorded lymphocyte count. We matched people with AE to up to five people without. We used multivariable logistic regression to estimate the association between AE and lymphopenia (two low lymphocyte counts within 3months) and linear mixed effects regression to estimate the association with absolute lymphocyte counts using all available counts. Cox proportional hazard models were used to investigate the effect of lymphopenia on common infections. We replicated the study using US survey data (National Health and Nutrition Examination Survey [NHANES]). Among 71,731 adults with AE and 126,349 adults without AE, we found an adjusted odds ratio (OR) for lymphopenia of 1.16 (95% CI: 1.09-1.23); the strength of association increased with increasing eczema severity. When comparing all recorded lymphocyte counts from adults with AE (n=1,497,306) to those of people without AE (n=4,035,870) we saw a lower mean lymphocyte (adjusted mean difference -0.047 × 109 /L [95% CI: -0.051 to -0.043]) in those with AE. The difference was larger for men, with increasing age, and with increasing AE severity and was present among people with AE not treated with immunosuppressive drugs. In NHANES (n=22,624), the adjusted OR for lymphopenia in adults with AE was 1.30 (95% CI: 0.80-2.11), and the adjusted mean lymphocyte count difference was -0.03 × 109 /L (95% CI: -0.07 to 0.02). Despite having a lower lymphocyte count, adjusting for time with lymphopenia, did not alter risk estimates of infections. Atopic eczema, including increasing AE severity, is associated with a decreased lymphocyte count, regardless of immunosuppressive drug use. Whether the lower lymphocyte count has wider health implications for people with severe eczema warrants further investigation.

Hemoglobin, Albumin, Lymphocyte, and Platelet Count is a Significant Biomarker Surrogate for Nutritional Status to Predict Overall Survival in Patients Post-radical Cystectomy.

Nutritional status is an independent predictor of overall survival after radical cystectomy. Various biomarkers of nutritional status are proposed to predict postoperative outcome, including albumin, anemia, thrombocytopenia, and sarcopenia. Recently, a score comprising hemoglobin, albumin, lymphocyte, and platelet counts was postulated as an encompassing biomarker to predict overall survival post-radical cystectomy in a single-institution study. However, cutoffs for hemoglobin, albumin, lymphocyte, and platelet count are not well defined. In this study, we analyzed hemoglobin, albumin, lymphocyte, and platelet count thresholds predicting overall survival and examined the platelet-to-lymphocyte as an additional prognostic biomarker. Fifty radical cystectomy patients were retrospectively evaluated from 2010-2021. American Society of Anesthesiologists classification, pathological data, and survival were extracted from our institutional registry. Univariable and multivariable Cox regression analysis was fit to the data to predict overall survival. Median follow-up was 22 (12-54) months. Hemoglobin, albumin, lymphocyte, and platelet count (continuous) was a significant predictor of overall survival on multivariable Cox regression analysis (HR 0.95, 95% CI: 0.90-0.99, P = .03), adjusting for Charlson Comorbidity Index, lymphadenopathy (pN >N0), muscle-invasive disease, and neoadjuvant chemotherapy. Optimal hemoglobin, albumin, lymphocyte, and platelet count cutoff was 25.0. Patients with hemoglobin, albumin, lymphocyte, and platelet count <25.0 had inferior overall survival (median, 33 months) vs with those with hemoglobin, albumin, lymphocyte, and platelet count ≥25.0 (median, not reached) (P = .03). Low hemoglobin, albumin, lymphocyte, and platelet count <25.0 was an independent predictor of inferior overall survival.

Diabetes and hypertension are common comorbidities among Covid-19 patients in Northern Sudan-Atbara

Objectives: The current study aims to identify the clinical and pathological characteristics of Sudanese Covid-19 patients who have either diabetes, hypertension, or both. Method: A retrospective study was carried out in Atbara Isolation Center for Covid-19 patients in River Nile State-Sudan. Data on the clinical and demographic characteristics of 80 Covid-19 patients of various ages and genders who visited the isolation center between December 2021 and February 2022 were gathered from their medical records. Three groups of subjects diabetic, hypertension, and diabetic-hypertensive were created. Result: The mean age of study group was 66 years old. Severe pathological features of Covid-19 were noticed among all study groups. The percenage of patients with low oxygen saturation was 92.3% of diabetics, 89.7% of hypertensive, and 90.9% of diabetic-hypertensive. Lymphocytopenia was observed in 90.9% of diabetic patients, and 82.6% of hypertensive patients, while all diabetic-hypertensive exhibited low lymphocyte count. A percentage of 23.1%, 28.0%, and 30.8% of diabetic, hypertensive, and diabetic-hypertensive patient had low platelet count, respectively. Conclusion: We concluded that diabetic, hypertensive and diabetic-hypertensive patient who were affected with Covid-19 were elderly and suffering from severe pathological features of disease, particularly in those who had both diabetes and hypertension. An intensive care is suggested for Covid-19 patients with diabetes, hypertension, as well as those who were affected with two comorbidities.

Inflammatory phenotype, clinicopathologic variables, and effects of long-term methylene blue in dogs with hereditary methemoglobinemia caused by cytochrome b5 reductase deficiency

To determine whether dogs with cytochrome b5 reductase (CYB5R) deficiency have a constitutive proinflammatory phenotype, characterize hematologic and serum chemistry results, and describe changes in methemoglobin (MetHb) levels and serum C-reactive protein (CRP) concentrations after long-term per os (PO) methylene blue (MB) therapy. 21 client-owned dogs (CYB5R deficient, n = 10; healthy controls, 11). In this prospective, case-control study, methemoglobin levels were measured using a blood gas analyzer with co-oximetry. Plasma tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) concentrations were measured using a canine-specific multiplex bead-based assay. Serum CRP concentrations were measured with a canine-specific commercial ELISA kit. Serum CRP concentration and MetHb levels were measured in 6 dogs with CYB5R deficiency after ≥ 60 days of PO MB therapy. As expected, MetHb levels were higher in dogs with CYB5R deficiency compared to controls (P < .001). Plasma TNF-α, IL-6, IL-10, and serum CRP concentrations were no different between CYB5R-deficient and control dogs. Dogs with CYB5R deficiency had lower absolute lymphocyte (P = .005) and eosinophil counts (P = .04) and higher alanine transaminase (P = .04) and alkaline phosphatase activity (P = .02) than controls, but these changes were not clinically relevant. Methemoglobin levels decreased after PO MB therapy (P = .03). These results suggest that otherwise healthy dogs with CYB5R deficiency do not have a constitutive proinflammatory phenotype and clinically relevant abnormalities in hematologic and serum chemistry panels are not expected. Dogs with decreased quality of life attributed to methemoglobinemia from CYB5R deficiency might benefit from PO MB therapy.

Leukocyte cell population data in patients with cardiac surgery and cardiopulmonary bypass: A potential readily available tool to monitor immunity.

Cardiac surgery with cardiopulmonary bypass triggers sterile inflammation that is responsible for post-operative morbidity. Automated flow cytometry devices used for leucocyte count provide cell population data (CPD) regarding fluorescence intensity, size and granularity of leukocytes that have never been studied in the context of sterile inflammation. Our objective was to explore leukocyte cell population data in patients undergoing cardiac surgery with cardiopulmonary bypass in order to determine whether CPD could be used to monitor immune cell activation. This is an ancillary study of a cohort of patients undergoing cardiac surgery with cardiopulmonary bypass. Cell population data (CPD) extracted from a routine automated flow cytometer were analyzed (Fluorescence targeted to nucleic acids). The time points of interest were: pre-operative, postoperative and 5 days after surgery. The variations in those parameters were studied. Data were then compared between patients according to the occurrence of a composite criteria (supra-ventricular arrythmia, stroke, acute renal failure, and/or death). Data from 1453 patients were analyzed. The neutrophil count, fluorescence granularity (NE-SCC), intensity (NE-SFL) and size (NE-FSC) increased with surgery. Heterogeneity of neutrophils decreased in terms of fluorescence granularity (NE-WX) and size (NE-WZ) but increased in terms of intensity (NE-WY). The lymphocyte count decreased with surgery. While fluorescence granularity (LY-X) and size increased (LY-Z), Lymphocyte intensity decreased (LY-Y). Lymphocytes were less heterogeneous in terms of their granularity, size and intensity after surgery (LY-WX, LY-WY, LY-WZ). Patients who developed the composite complication criteria had a higher pre-operative neutrophil count (5.08 [3.89;6.95] vs 4.76 [3.60;6.13], p = 0.02; AUC = 0.56 [0.51;0.60]), and more heterogeneous neutrophils in terms of fluorescence granularity (NE-WX, AUC = 0.57 [0.52;0.62]) and intensity (NE-WY, AUC 0.61 [0.56;0.65]). Those patients also had lower pre-operative lymphocyte count (1.49 [1.10;1.14] vs 1.81 [1.39;2.39], p<0.01, AUC = 0.61 [0.57;0.66]) and fluorescence granularity (LY-X, AUC = 0.57 [0.53;0.62]). NE-WX, NE-WY and LY-X were associated with post-operative complications after adjustment on the EuroSCORE 2 (adjusted odd ratio of 1.01 [1.00;1.02]; 1.01 [1.00;1.01] and 1.08 [1.02;1.15] respectively). Cardiac surgery with cardiopulmonary bypass was associated with substantial alterations of CPD probably reflecting leukocytes activation in sterile inflammation. Pre-operative NE-WX, NE-WY and LY-X biomarkers levels were associated with post-operative complications, independently of the EuroSCORE 2. Such routine, unexploited and low cost parameters might represent useful tools likely to monitor immune function and predict outcomes for patients undergoing cardiac surgery. Our findings requires validation on a larger external cohort.

C-reactive protein isoforms as prognostic markers of COVID-19 severity.

C-reactive protein (CRP), an active regulator of the innate immune system, has been related to COVID-19 severity. CRP is a dynamic protein undergoing conformational changes upon activation in inflammatory microenvironments between pentameric and monomeric isoforms. Although pentameric CRP is the circulating isoform routinely tested for clinical purposes, monomeric CRP shows more proinflammatory properties. Therefore, we aimed to determine the potential of monomeric CRP in serum as a biomarker of disease severity in COVID-19 patients (admission to intensive care unit [ICU] and/or in-hospital mortality). We retrospectively determined clinical and biological features as well as pentameric and monomeric CRP levels in a cohort of 97 COVID-19 patients within 72h of hospital admission. Patients with severe disease had higher levels of both pentameric and monomeric CRP. However, multivariate analysis showed increased mCRP but not pCRP to be independently associated to disease severity. Notably, mCRP levels higher than 4000 ng/mL (OR: 4.551, 95% CI: 1.329-15.58), together with number of co-morbidities, low lymphocyte count, and procalcitonin levels were independent predictors of disease severity in the multivariate model. Our results show the potential of mCRP levels as a marker of clinical severity in COVID-19 disease.

Anti-SARS-CoV-2 antibodies following vaccination are associated with lymphocyte count and serum immunoglobulins in SLE.

Patients with Systemic Lupus Erythematosus are known to have dysregulated immune responses and may have reduced response to vaccination against COVID-19 while being at risk of severe COVID-19 disease. The aim of this study was to identify whether vaccine responses were attenuated in SLE and to assess disease- and treatment-specific associations. Patients with SLE were matched by age, sex and ethnic background to healthcare worker healthy controls (HC). Anti-SARS-CoV-2 spike glycoprotein antibodies were measured at 4-8weeks following the second COVID-19 vaccine dose (either BNT162b2 or ChAdOx1 nCoV-19) using a CE-marked combined ELISA detecting IgG, IgA and IgM (IgGAM). Antibody levels were considered as a continuous variable and in tertiles and compared between SLE patients and HC and associations with medication, disease activity and serological parameters were determined. Antibody levels were lower in 43 SLE patients compared to 40 HC (p < 0.001). There was no association between antibody levels and medication, lupus disease activity, vaccine type or prior COVID infection. Higher serum IgA, but not IgG or IgM, was associated with being in a higher anti-SARS-CoV-2 antibody level tertile (OR [95% CI] 1.820 [1.050, 3.156] p = 0.033). Similarly, higher lymphocyte count was also associated with being in a higher tertile of anti-SARS-CoV-2 (OR 3.330 [1.505, 7.366] p = 0.003). Patients with SLE have lower antibody levels following 2 doses of COVID-19 vaccines compared to HC. In SLE lower lymphocyte counts and serum IgA levels are associated with lower antibody levels post vaccination, potentially identifying a subgroup of patients who may therefore be at increased risk of infection.

Clinical characteristics and outcomes of critically ill coronavirus disease 2019 patients in Malaysia during the first wave: A multi-center observational study (COVIDICU-MY).

Coronavirus disease 2019 (COVID-19) emerged with a wide range of clinical presentations; Malaysia was not spared from its impact. This study describes the clinical characteristics of COVID-19 patients admitted to intensive care unit, their clinical course, management, and hospital outcomes. COVIDICU-MY is a retrospective analysis of COVID-19 patients from 19 intensive care units (ICU) across Malaysia from 1 March 2020 to 31 May 2020. We collected epidemiological history, demographics, clinical comorbidities, laboratory investigations, respiratory and hemodynamic values, management, length of stay and survival status. We compared these variables between survival and non-survival groups. A total of 170 critically ill patients were included, with 77% above 50 years of age [median age 60, IQR (51-66)] and 75.3% male. Hypertension, diabetes mellitus, hyperlipidemia, chronic cardiac disease, and chronic kidney disease were most common among patients. A high Simplified Acute Physiology Score (SAPS) II score [median 45, IQR (34-49)] and Sequential Organ Failure Assessment (SOFA) score [median 8, IQR (6-11)] were associated with mortality. Patients were profoundly hypoxic with a median lowest PaO2/FiO2 ratio of 150 (IQR 99-220) at admission. 91 patients (53.5%) required intubation on their first day of admission, out of which 38 died (73.1% of the hospital non-survivors). Our sample had more patients with moderate Acute Respiratory Distress Syndrome (ARDS), 58 patients (43.9%), compared to severe ARDS, 33 patients (25%); with both ARDS classification groups contributing to 25 patients (54.4%) and 11 patients (23.9%) of the non-survival group, respectively. Cumulative fluid balance over 24 h was higher in the non-survival group with significant differences on Day 3 (1,953 vs. 622 ml, p < 0.05) and Day 7 of ICU (3,485 vs. 830 ml, p < 0.05). Patients with high serum creatinine, urea, lactate dehydrogenase, aspartate aminotransferase and d-dimer, and low lymphocyte count throughout the stay also had a higher risk of mortality. The hospital mortality rate was 30.6% in our sample. We report high mortality amongst critically ill patients in intensive care units in Malaysia, at 30.6%, during the March to May 2020 period. High admission SAPS II and SOFA, and severe hypoxemia and high cumulative fluid balance were associated with mortality. Higher creatinine, urea, lactate dehydrogenase, aspartate aminotransferase and d-dimer, and lymphopenia were observed in the non-survival group.

INFLUENCE OF PHYTOBIOTIC AND SYNBIOTIC-ACIDIFIER BLEND SUPPLEMENTS ON HEMATO-BIOCHEMICAL INDICES, ANTIOXIDANT ENZYMES AND GUT MICROFLORA OF BROILER CHICKEN

This study examined the effect of phytobiotic (Superliv powder®, SP) and symbiotic-acidifier blend (Bacflora-F®, BF) feed additives on hemato-biochemical indices, antioxidant enzymes, and gut microflora of broiler chicken. A total of 120-day-old Arbor Acres broiler chicks were randomly allotted to four dietary treatments, with three replicates of ten birds per treatment as follows, Diet 1 (basal/control diet), Diet 2 (basal + 0.05 g/kg SP), Diet 3 (basal + 1g/kg BF) and Diet 4 (basal + 0.05g/kg SP and 1g/kg BF). The result revealed significant differences (P &lt;0.05) in values of all haematological parameters except monocyte counts. Broiler chickens fed a diet supplemented with SP and BF had higher packed cell volume, red blood cell, and haemoglobin concentration but lower white blood cells and lymphocyte count compared to the control group. The dietary supplementation of SP and BF did not influence the concentration of alanine aminotransferase, creatinine, total protein, and globulin contents (P &gt; 0.05) but significantly reduced cholesterol levels of the broiler chicken compared to the control group. The result further showed that broiler chickens fed the diet supplemented with of SP and BF had higher (P &lt;0.05) concentration of total glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) compared to the control group. There was no significant difference in aerobic bacteria, lactic acid-producing bacteria and coliform bacteria (p &gt; 0.05) count across the experimental treatments. In conclusion, the dietary supplementation of SP and BF can be used to enhance the antioxidative status, reduce cholesterol levels and maintain the gut health of broiler chickens during production.