Normal White Blood Cell Count Research Articles

Dialysate cyclophilin A as a predictive marker for historical peritonitis in patients undergoing peritoneal dialysis

IntroductionNo markers have been used to diagnose historical peritoneal dialysis (PD)-related peritonitis. Cyclophilin A (CypA) is associated with glucose toxicity and inflammation. We hypothesize that dialysate CypA can be a marker for historical peritonitis (at least 3 months free from peritonitis). MethodAn enzyme-linked immunosorbent assay kit was used to measure the concentration of dialysate CypA. Clinical and laboratory data were collected to correlate with historical peritonitis. Mann-Whitney U test and Chi-square test were used for analysis. Receiver operating characteristic (ROC) analysis was used to evaluate predictive power. ResultsOut of a total of 31 patients who had undergone PD for at least 2 years, 18 had no history of PD-related peritonitis, while 13 had experienced PD-related peritonitis at least once. Overall, the patients in this population were in good health (normal white blood cell count, no anemia, normal electrolyte and serum albumin levels). There were no significant differences between patients with and without a history of peritonitis, except for blood white blood cell count (5650.6 ± 1848.4 vs. 7154.6 ± 2056.8, p = 0.032) and dialysate CypA value (24.27 ± 22.715 vs. 54.41 ± 45.63, p = 0.020). In the univariate analysis, only the dialysate CypA level showed a statistically significant association with historical peritonitis (HR = 1.030, 95 % CI = 1.010–1.062, p = 0.046). The AUC for dialysate CypA (>34.83 ng/mL) was 0.748, with a sensitivity of 0.615 and specificity of 0.833. ConclusionPD peritonitis poses a significant threat to the long-term use of peritoneal dialysis. Based on our study, even in the absence of concurrent infection, dialysate CypA can serve as a predictive marker for historical peritonitis, demonstrating high predictive power along with fair sensitivity and good specificity.

Effect of Heat-Treated Lactiplantibacillus plantarum nF1 on the Immune System Including Natural Killer Cell Activity: A Randomized, Placebo-Controlled, Double-Blind Study.

Heat-treated Lactiplantibacillus plantarum nF1 (HT-nF1) increases immune cell activation and the production of various immunomodulators (e.g., interleukin (IL)-12) as well as immunoglobulin (Ig) G, which plays an important role in humoral immunity, and IgA, which activates mucosal immunity. To determine the effect of HT-nF1 intake on improving immune function, a randomized, double-blind, placebo-controlled study was conducted on 100 subjects with normal white blood cell counts. The HT-nF1 group was administered capsules containing 5 × 1011 cells of HT-nF1 once a day for 8 weeks. After 8 weeks of HT-nF1 intake, significant changes in IL-12 were observed in the HT-nF1 group (p = 0.045). In particular, the change in natural killer (NK) cell activity significantly increased in subjects with low secretory (s) IgA (≤49.61 μg/mL) and low NK activity (E:T = 10:1) (≤3.59%). These results suggest that HT-nF1 has no safety issues and improves the innate immune function by regulating T helper (Th)1-related immune factors. Therefore, we confirmed that HT-nF1 not only has a positive effect on regulating the body's immunity, but it is also a safe material for the human body, which confirms its potential as a functional health food ingredient.

A retrospective study of ovarian tissue cryopreservation in female patients with hematological diseases for fertility preservation.

To investigate the effect and safety of ovarian tissue cryopreservation (OTC) for fertility preservation in female patients with hematological diseases. We designed a retrospective study. The clinical data of patients with hematological diseases undergoing OTC admitted to Peking University People's Hospital from April 2017 to January 2023 were analyzed and summarized. A total of 24 patients were included in the study, including 19 patients with malignant hematological diseases and 5 patients with non-malignant hematological diseases. The former included 14 patients with acute leukemia, 1 patient with chronic leukemia, and 4 patients with myelodysplastic syndrome, while the latter 5 patients were aplastic anemia (AA). 16 patients had received chemotherapy before OTC. The average age of 24 patients was 22.80 ± 6.81years. The average anti-Mullerian hormone (AMH) was 1.97 ± 2.12ng/mL, and the average follicle-stimulating hormone (FSH) was 7.01 ± 4.24IU/L in examination before OTC. FSH was greater than 10.0IU/L in 4 cases. The pre-OTC laboratory tests showed that the average white blood cell (WBC) count was (3.33 ± 1.35) × 109/L, the average hemoglobin was 91.42 ± 22.84g/L, and the average platelet was (147.38 ± 114.46) × 109/L. After injection of recombinant human granulocyte colony-stimulating factor (rhG-CSF), blood transfusion, and iron supplementation in pre-OTC treatment, the average WBC count was (4.91 ± 3.07) × 109/L, the average hemoglobin was 98.67 ± 15.43g/L, and the average platelet was (156.38 ± 103.22) × 109/L. Of the 24 patients, 22 underwent laparoscopic bilateral partial oophorectomy and oophoroplasty, and 2 underwent laparoscopic unilateral oophorectomy. The average duration of OTC was 59.54 ± 17.58min, and the average blood loss was 32.1 ± 41.6mL. The maximum blood loss was 200mL. There was no significant difference in WBC count and hemoglobin concentration after OTC compared to pre-OTC period. Only the platelet count after OTC surgery was significantly different from that before surgery ([134.54 ± 80.84 vs. 156.38 ± 103.22] × 109/L, p < 0.05). None of the 24 patients had serious complications after OTC. 2 patients had mild infection symptoms, but both recovered well. 23 patients underwent hematopoietic stem cell transplantation (HSCT) after OTC. The median and interquartile range from OTC to the pretreatment of HSCT was 33 (57) days, and the median and interquartile range from OTC to HSCT was 41 (57) days. Seven of them began pretreatment of HSCT within 20days and began HSCT within 30days after OTC. All patients were followed up. Of the 23 patients who underwent HSCT after surgery, 22 presented with amenorrhea and 1 with scanty menstrual episodes. Seven patients underwent hormone replacement therapy (HRT) after HSCT. A patient with AA underwent ovarian tissue transplantation (OTT) 3years after HSCT and resumed regular menstruation 6months after OTT. Ovarian tissue cryopreservation has a promising future in fertility protection in patients with hematological diseases. However, patients with hematological malignancies often have received gonadotoxic therapy before OTC, which may be accompanied by myelosuppression while patients with non-malignant hematological diseases often present with severe hemocytopenia. So perioperative complete blood count of patients should be paid attention to. There was no significant difference in the WBC count and hemoglobin concentration in patients with hematological diseases before and after OTC surgery, and the platelet count decreased slightly within the normal range. Infection is the most common post-OTC complication, and HSCT pretreatment can be accepted as early as the 10th day after OTC. OTC has no adverse effects on patients with hematological diseases and does not delay HSCT treatment. For young patients with hematological diseases, OTC is an effective method of fertility preservation.

The clinical, subclinical characteristics and treatment result of meningitis patients at Thai Nguyen National Hospital

Introduction: Meningitis is a devastating disease with a high case fatality rate, which can lead to serious long-term sequelae if not timely diagnosed, and treated.Objectives: Describing on the clinical, subclinical characteristics and analysing some factors related to the treatment results in meningitis patients at Thai Nguyen National Hospital.Methods: A cross-sectional descriptive study was conducted on 48 meningitis patients were treated at the Department of Neurology and Department of Tropical Diseases at Thai Nguyen National Hospital.Results: The average age of patients in the study was 43.27±15,31 (year); The percentage of male patients was 75,0%. The most common clinical symptom was headache (89.6%), fever (75%); The average white blood cell count in the CSF on admission was 509.92±681.27 (cells/ml) and at discharge was 94.42±102.60 (cells/ml); Protein in CSF on admission was 1.70±1.45 (g/L) and at discharge was 0.72±0.55 (g/L). The everage day of treatment was 12.57.Conclusion: The popularr symptoms of patients with bacterial meningitis are headache, fever, vomiting, nausea, constipation, and stiff neck. There was no relationship between age, gender, white blood cell count and white blood cell count in the CSF at admission to the number of treatment days in meningitis patients.

Questioning the Relevance of Normal White Blood Cell Count under 10,000 Cells per Microlitre in Millard Criteria as an Absolutely Required Parameter for Cleft Lip Repair Surgeries: A Case-Based Literature Review

Leukocytosis, defined as an elevated white blood cell count, has long been regarded as a crucial indicator of inflammation or infection in surgical procedures. In the context of cleft lip surgeries, normal white blood cell count has often been considered an absolute requirement for proceeding with the procedure, as it is believed to signal the presence of a potentially infectious or inflammatory state. Therefore, leukocytosis is thought to be a strong precautionary factor. However, recent evidence challenges this long-held belief, suggesting that elevated white blood cell counts may not necessarily be indicative of adverse outcomes in cleft lip surgeries. To explore this notion, we conducted a comprehensive literature review focusing on two case studies involving unilateral cleft lip patients with presurgical white blood cell counts exceeding 10,000 per microlitre. Both cases underwent successful cleft lip repair and demonstrated excellent post-surgical outcomes without any signs of inflammation or infection. Both cleft lip repair surgeries results showed no complications, and the patient exhibited optimal wound healing and an aesthetically pleasing outcome at the follow-up appointments. These cases challenge the assumption that normal white blood cell count is an absolute requirement for cleft lip surgeries and call for a reconsideration of its significance in predicting post-surgical outcomes. While leukocytosis is an essential parameter to identify potential infectious or inflammatory states, our findings suggest that it should not be solely relied upon in isolation when assessing the suitability for cleft lip surgery and predicting the adverse outcomes in cleft lip surgeries. Further studies are warranted to establish a more nuanced understanding of leukocytosis in the context of cleft lip surgeries, including its association with other clinical parameters and potential alternatives for evaluating surgical candidacy and predicting the adverse outcomes in cleft lip surgeries.

A COMPARATIVE STUDY TO EVALUATE THE POSITIVE PREDICTIVE VALUE OF BIOCHEMICAL MARKERS WITH CLINICAL RIPASA SCORE IN ACUTE APPENDICITIS: AN IN VIVO STUDY

Objective: We evaluated the positive predictive value of biochemical markers with clinical Raja Isteri Pengiran Anak Saleha Appendicitis (RIPASA) score and the sensitivity and diagnostic accuracy. Methods: 75 patients who presented to the Emergency/General Surgery Department of Pacific Medical College and Hospital, Udaipur, with right iliac fossa (RIF) pain and who were suspected of acute appendicitis. A detailed history, clinical examination, and laboratory investigations were done which included a routine RIPASA score calculated. Results: RIF pain was present in all the patients, followed by vomiting (98.67%), and fever in 92%. Twenty-one patients had raised white blood cell (WBC) counts, out of them 15 patients had both raised WBC counts and raised C-reactive protein (CRP) and 6 had normal CRP. 52 patients had raised CRP levels, out of them 15 patients had both raised WBC counts and raised CRP and 37 had normal WBC counts. 17 patients had both CRP and WBC counts in normal range, but were diagnosed to have appendicitis according to RIPASA score. Our results show that raised CRP and WBC counts had a sensitivity of 28.85% and specificity of 73.91% with a diagnostic accuracy of 42.67%. Conclusion: When combined with WBC, CRP has good discriminatory power for appendicitis despite its inability to reliably predict acute appendicitis when used alone. However, a cutoff point for CRP that predicted perforated appendicitis could not be determined.

A nomogram model for predicting the efficacy of cyclosporine in patients with pure red cell aplasia.

Pure red cell aplasia (PRCA) is a rare bone marrow disorder characterized by a severe reduction or absence of erythroid precursor cells, without affecting granulocytes and megakaryocytes. Immunosuppressive therapies, particularly cyclosporine, have demonstrated efficacy as a primary treatment. This study aims to develop a predictive model for assessing the efficacy of cyclosporine in acquired PRCA (aPRCA). This retrospective study encompasses newly treated aPRCA patients at the General Hospital of Tianjin Medical University. Diagnosis criteria include severe anemia, and absolute reticulocyte count below 10 × 109/L, with normal white blood cell and platelet counts, and a severe reduction in bone marrow erythroblasts. Cyclosporine therapy was administered, with dose adjustments based on blood concentration. Response to cyclosporine was evaluated according to established criteria. Statistical analysis involved logistic multi-factor regression, generating a predictive model. The study included 112 aPRCA patients with a median age of 63.5years. Patients presented with severe anemia (median Hb, 56g/L) and reduced reticulocyte levels. Eighty-six patients had no bone marrow nucleated erythroblasts. Primary PRCA accounted for 62 cases (55.4%), and secondary PRCA accounted for 50 cases (44.6%). Univariate analysis revealed that ferritin, platelet to lymphocyte ratio (PLR), and CD4/CD8 ratio influenced treatment response. Multivariate analysis further supported the predictive value of these factors. A prediction model was constructed using ferritin, PLR, and CD4/CD8 ratio, demonstrating high sensitivity and specificity. The ferritin, PLR, and CD4/CD8-based nomogram showed good predictive ability for aPRCA response to cyclosporine. This model has potential clinical value for individualized diagnosis and treatment of aPRCA patients.

February 2024 Imaging Case of the Month: Connecting Some Unusual Dots

No abstract available. Manuscript truncated after 150 words. Clinical History: A 37-year-old woman presents with abdominal pain, tongue and throat swelling, and intermittent shortness of breath and dyspnea on exertion. She also notes some pain on swallowing. The patient’s past medical history was largely unremarkable. Her one prior surgery included cholecystectomy for cholelithiasis, and she was not taking any prescription medications. The patient is a lifelong non-smoker, her only reported allergy due to medications containing sulfa, and she drinks alcohol only socially and denied illicit drug use. Laboratory: A complete blood count showed a normal white blood cell count at 9.7 x 109/L (normal, 3.4 – 9.6 x 109/L), with an elevated absolute neutrophil count of 8.18 x 109/L (normal, 1.4 – 6.6 x 109/L); the percent distribution of lymphocytes, monocytes, and eosinophils was normal. Her hemoglobin and hematocrit values were 15 gm/dL (normal, 13.2 – 16.6 gm/dL) and 46% (normal, 34.9 – 44.5%). The platelet count was normal at 220 x …

Hematological and blood biochemistry parameters as prognostic indicators of survival in canine multicentric lymphoma treated with COP and L-COP protocols.

Hematological and blood chemistry parameters are crucial for evaluating and monitoring canine multicentric lymphoma during chemotherapy. Pre-treatment hematological and blood chemistry parameters can be used as prognostic survival outcomes for this disease. Therefore, this study aimed to investigate the effect of hematological and blood chemistry parameters pre-treatment and 4 weeks post-treatment on the survival outcomes of dogs treated with either a combination of cyclophosphamide, vincristine, and prednisolone (COP) or a combination of COP with L-asparaginase (L-COP) protocols. We conducted a retrospective study. Medical records and hematological and blood chemistry parameters of 41 dogs with multicentric lymphoma treated with L-COP (n = 26) and the COP protocols (n = 15) were obtained from the hospital information system. Most cases were classified as high-grade lymphoma based on the Kiel cytological classification. The effects of hematological and blood chemistry parameters on survival outcomes were investigated using the Cox proportional hazard regression model. The median survival time (MST) for each hematological and blood chemistry parameter affecting survival outcome was established and compared using the Kaplan-Meier product limit method with the log-rank test. Dogs with high-grade multicentric lymphoma that were treated with the COP protocol and had monocytosis at pre-treatment had a significantly shorter MST than dogs with normal monocyte counts (p = 0.033). In addition, dogs with azotemia, both pre-treatment and 4 weeks post-treatment, had a significantly shorter MST than dogs with normal serum creatinine levels (p = 0.012). Dogs with high-grade multicentric lymphoma treated with the L-COP protocol who had hypoalbuminemia (serum albumin concentration <2.5 mg/dL) at both pre-treatment and 4 weeks post-treatment had a significantly shorter MST than dogs with normal serum albumin levels (p < 0.001). Furthermore, dogs with leukocytosis at 4 weeks post-treatment had a significantly shorter MST than those with a normal total white blood cell count (p = 0.024). Serum albumin level can serve as a simple negative prognostic indicator of survival outcomes in dogs with high-grade multicentric lymphoma treated with the L-COP protocol. Dogs with hypoalbuminemia pre-treatment and 4 weeks post-treatment tended to have a shorter MST than those with normal serum albumin concentrations.

Arthrocentesis of suspected septic sternoclavicular arthritis: microbial yield and predictors of culture positivity.

Evaluate the microbial yield and factors predicting culture positivity for image-guided arthrocentesis of suspected septic sternoclavicular (SC) arthritis. An electronic health record search identified image-guided SC joint aspirations for suspected septic arthritis. Data was extracted by retrospective chart review including patient demographics, procedure characteristics, pre-procedure lab testing, joint culture results, final SC joint diagnoses and any effect of positive synovial cultures on subsequent antibiotic therapy. Factors associated with positive joint fluid cultures were assessed using a Chi-squared test for categorical predictors and logistic regression for continuous predictors. A total of 31 SC arthrocenteses met inclusion criteria with most (81%) performed using ultrasound guidance. Synovial fluid was successfully aspirated in 19/31 (61%) of cases, and in all other cases lavage fluid was successfully obtained. Synovial cultures were positive in 9/31 (29%) of cases. A final diagnosis of septic arthritis was assigned to 20/31 cases (65%) in which 9/20 (45%) had positive synovial cultures. There was no statistically significant association between synovial culture positivity and risk factors for septic arthritis, positive blood cultures, pre-aspiration antibiotics and whether synovial fluid or lavage fluid was cultured. Serum white blood cell count (WBC) and erythrocyte sedimentation rate (ESR) demonstrated statistically significant positive correlation with positive synovial cultures. Arthrocentesis is effective for microbial speciation in SC septic arthritis, and diagnostic yield may be increased with lavage when encountering a dry tap. Normal serum WBC and ESR values indicate an extremely low likelihood of positive synovial cultures.

Association of Overweight and Inflammatory Indicators with Breast Cancer: A Cross-Sectional Study in Chinese Women.

This cross-sectional study aimed to explore the association of overweight and inflammatory indicators with breast cancer risk in Chinese patients. Weight, height, and peripheral blood inflammatory indicators, including white blood cell count (WBC), neutrophil count (NE), lymphocyte count (LY), platelet count (PLT) and the concentration of hypersensitivity C-reactive protein (hsCRP), were collected in 383 patients with benign breast lumps (non-cancer) and 358 patients with malignant breast tumors (cancer) at the First Affiliated Hospital of Soochow University, China, from March 2018 to July 2020. Body mass index (BMI), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII) were determined according to the ratio equation. The correlations among overweight, inflammatory indicators, and the proportion of non-cancer or cancer cases were analyzed. BMI is associated with an increased breast cancer risk. Compared with non-cancer patients, the average WBC count, NE count, NLR, and level of hsCRP were significantly higher in cancer patients. The level of hsCRP was closely associated with the size of malignant breast tumors. We conclude that overweight and high levels of hsCRP may serve as putative risk factors for malignant breast tumors in Chinese women.

Admission Total Leukocyte Count as a Predictor of Mortality in Cardiac Intensive Care Unit Patients

BackgroundInflammation is a sequela of cardiovascular critical illness and a risk factor for mortality. ObjectivesThis study aimed to evaluate the association between white blood cell count (WBC) and mortality in a broad population of patients admitted to the cardiac intensive care unit (CICU). MethodsThis retrospective cohort study included patients admitted to the Mayo Clinic CICU between 2007 and 2018. We analyzed WBC as a continuous variable and then categorized WBC as low (<4.0 × 103/mL), normal (≥4.0 to <11.0 × 103/mL), high (≥11.0 to <22.0 × 103/mL), or very high (≥22.0 × 103/mL). The association between WBC and in-hospital mortality was evaluated using multivariable logistic regression and random forest models. ResultsWe included 11,699 patients with a median age of 69.3 years (37.6% females). Median WBC was 9.6 (IQR: 7.4-12.7). Mortality was higher in the low (10.5%), high (12.0%), and very high (33.3%) WBC groups relative to the normal WBC group (5.3%). A rising WBC was incrementally associated with higher in-hospital mortality after adjustment (AICc adjusted OR: 1.03 [95% CI: 1.02-1.04] per 1 × 103 increase in WBC). After adjustment, only the high (AICc adjusted OR: 1.37 [95% CI: 1.15-1.64]) and very high (AICc adjusted OR: 1.99 [1.47-2.71]) WBC groups remained associated with increased risk of in-hospital mortality. ConclusionsLeukocytosis is associated with an increased mortality risk in a diverse cohort of CICU patients. This readily available marker of systemic inflammation may be useful for risk stratification within the increasingly complex CICU patient population.

Initiative to reduce unnecessary routine daily testing of complete blood counts across 11 safety net hospitals.

National societies recommend against performing routine daily laboratory testing without a specific indication. Unnecessary testing can lead to patient harm, such as hospital-acquired anemia. The objective of this study was to reduce repeat complete blood counts (CBCs) after initial testing. This was a quality improvement initiative implemented across 11 safety net hospitals in New York City. A best practice advisory (BPA) was implemented that asked the user to remove a CBC if the last 2 CBCs within 72 hours had normal white blood cell and platelet counts and unchanged hemoglobin levels. The outcome measure was the rate of CBCs per 1000 patient days preintervention (January 8, 2020, to December 22, 2020) to postintervention (December 23, 2020, to December 7, 2021). The process measure was the acceptance rate of the BPA, defined as the number of times the repeat CBC order was removed through the BPA divided by the total number of times the BPA triggered. Across 11 hospitals, repeat CBC testing decreased by 12.3% (73.05 to 64.04 per 1000 patient days, P < .001). Six of the 11 hospitals exhibited statistically significant decreases, ranging from a 10% to 48.9% decrease of repeat CBCs. The overall BPA action rate was 20.0% (24,029 of 119,944 repeat CBCs). This low-effort, electronic health record-based intervention can effectively reduce unnecessary laboratory testing.

A Case Report on Cecal Volvulus: Approach to Management

Cecal volvulus is a rare cause of intestinal obstruction caused by axial twisting of the cecum that occurs in 1–1.5 % of all intestinal obstruction, with an incidence of 2.8–7.1 cases per million annually. Cecal volvulus is potentially life-threatening without prompt surgical intervention. A 57-year-old woman presented with severe abdominal pain and distention. Laboratory examinations revealed normal white blood cell count with neutrophilic predominance. Diagnosis of acute cecal volvulus was made from a “whirl sign” on abdominal computed tomography. An exploratory laparotomy confirmed the diagnosis of cecal volvulus and a segmental ileocolic resection with primary anastomosis was carried out. The patient was discharged improved and returned to her normal activities of daily living. Conclusion: The management of volvulus involves a series of stepwise decisions that must be performed rapidly. Due to the fact that this condition is relatively uncommon makes it more critical for surgeons to maintain a solidified algorithm tailored to the disease process in order to amplify chances of successful outcome. In this case, the diagnosis of acute cecal volvulus was made from a “whirl sign” on abdominal computed tomography. An exploratory laparotomy confirmed the diagnosis of cecal volvulus and a segmental ileocolic resection with primary anastomosis was carried out. The patient was discharged, improved. Key words: Cecal volvulus, ileo-colectomy, whirl sign

Nil Intervention is at Times the Best Intervention

A sudden drop of air-fluid level in the pneumonectomy space in the absence of a bronchopleural fistula and pleural infection is termed benign emptying of the pneumonectomy space (BEPS). We report a 28-year-old female patient who presented to a tertiary care referral centre, in Pondicherry, India in 2020 with multiple episodes of vomiting. Subsequent to a left-sided pneumonectomy due to tuberculosis, she was diagnosed with BEPS. Generally, patients with BEPS are clinically stable, afebrile with no fluid expectoration and have a normal white blood cell count. Bronchoscopy reveals an intact bronchial stump and pleural fluid cultures are often sterile. In terms of management, close monitoring and early detection of a bronchopleural fistula are the key points. BEPS should be a differential diagnosis in case of a drop in the air-fluid level of the post-pneumonectomy space. Awareness of this entity is crucial as it helps prevent unnecessary and morbid surgical interventions. Keywords: Pneumonectomy; Pleura; Hydropneumothorax; Case Report; India.

Mitochondria-Mediated (MAVS) Innate Immune Signaling Drives Inflammation-Induced Bone Marrow Failure

Bone marrow failure syndromes (BMFS) are life threatening diseases, characterized by impaired fitness of hematopoietic stem cells (HSC) and ineffective hematopoiesis causing the absence of one or more hematopoietic lineages in the peripheral blood. Substantial clinical data indicate that hyperactivity of inflammatory cytokines, including TNFα, IL-6, and transforming growth factor-β (TGFβ), directly contribute to BMF. Inflammatory challenges result in irreversible HSC functional decline, including decreased repopulation potential and myeloid-bias differentiation. We recently showed that the combination of inflammatory challenges, including polyinosinc:polycytidilic acid (pIC - a double stranded RNA [dsRNA]) plus high TGFβ causes chronic pancytopenia, anemia, expanded hematopoietic stem and progenitor cell pools, and enhanced bone marrow dysplasia, mimicking a myelodysplastic syndrome (MDS) that developed 3-4 months after pIC challenge (Javier et.al. Haematologica 2022). However, the mechanisms behind this association and/or causality are still ill-defined. Here, we show that mitochondrial antiviral signaling (MAVS) protein can mediate the negative effect of pIC and TGFβ on HSC functions and BMF/ MDS development. Differential gene expression analyses in HSCs suggested that pIC plus TGFβ altered expression of nuclear-encoded mitochondrial genes. Mitochondria serve as platform for the activation of MAVS and downstream innate immune signaling in response to dsRNA. We thus examined the role of mitochondria and MAVS in pIC plus TGFβ-induced BMF/MDS. We show that overexpression TGFβ and pIC together cause alterations in mitochondrial proteins and membrane potential as well as enhanced caspase1 activity, but not the necroptotic signals p-RIP1 and p-RIP3, in HSCs. pIC exposure caused an increase in MAVS expression, and a redistribution into large aggregates that localize onto mitochondria in HSCs, indicative of MAVS activation (two days after pIC exposure in vivo). The MAVS aggregates resolved into smaller and dispersed clusters by 3 months after pIC exposure in control mice. In contrast, in HSCs from TGFβ overexpressing mice, MAVS aggregates persisted 3 months after pIC exposure. To determine the impact of augmented MAVS in dsRNA+TGFβ-driven BMF, we used MAVS deficient mice crossed with TGFβ overexpressing mice. We found that absence of MAVS protein restored normal white blood cell count, including neutrophils and lymphocytes, restored normal red blood cell but not platelet counts in TGFβ overexpressing mice after pIC challenge, compared to controls. Remarkably, MAVS deficiency partially rescued the dysplastic features of bone marrow myeloid cells in TGFβ overexpressing mice after pIC challenge. MAVS-deficiency also reduced the increased caspase1 activity and lowers mitochondria membrane potential in HSCs of these mice. In serial competitive transplant studies, MAVS-deficiency conferred HSC repopulation advantage. These findings suggest that pIC+TGFβ overexpression mediated BMF/MDS phenotype depends on chronic activation of MAVS. Because MAVS aggregation depends on mitochondrial fusion, we used genetic loss of the mitochondrial fission regulator Drp1. Drp1-deficiency caused severe mitochondrial aggregation in HSCs; this was associated with sustained MAVS aggregation. In response to pIC, Drp1-deficient mice exhibited increased caspase-1 activity, increased mitochondrial membrane potential and increase in HSC numbers 6 months after pIC challenges. Drp1 loss resulted in anemia and mild pancytopenia. Interestingly, Drp1-deficient bone marrow myeloid progenitors exhibited severe dysplastic features after pIC challenged. These findings suggest that chronic mitochondrial and MAVS aggregation are sufficient to drive BMF/MDS phenotype. Finally, we investigated the levels of epigenetic markers (acetyl H3K27 and methyl H3 Lys4) in HSCs after pIC stress. H4K4me3 levels were decreased in HSCs long-term after pIC challenges [6 months], this was further decreased in Drp1-deficient HSCs. In conclusion, these findings indicate that non-genetic factors contribute to the onset of BMF/MDS. Mitochondria and MAVS protein together mediate an innate immune mechanism that drives BMF/MDS. This study opens the possibility to target mitochondria-related proteins as a therapeutic strategy to restore ineffective hematopoiesis due to chronic inflammation.

Clinical characteristics, outcomes, and risk factors of SARS-CoV-2 breakthrough infections among 572 fully vaccinated (BBIBP-CorV) hospitalized patients

BackgroundBreakthrough infections have been widely reported in vaccinated individuals. However, the clinical characteristics, outcomes, and risk factors of SARS-CoV-2 breakthrough infections among fully vaccinated (BBIBP-CorV) hospitalized patients have not yet been fully elucidated. MethodsIn the single-center cohort study conducted at Xiangya Hospital of Central South University, we enrolled the hospitalized COVID-19 patients who had received full (2 doses) vaccination with the BBIBP-CorV vaccine between December 5, 2022, and January 31, 2023. We collected and analyzed information related to clinical characteristics, laboratory results, treatments, outcomes and prognostic data. Univariate and multivariable Cox regression were performed to assess the impact of clinical characteristics and laboratory results on the composite outcome (including the initiation of endotracheal intubation, non-invasive respiratory support, intensive care unit admission, and all-cause death). ResultsA total of 572 COVID-19 hospitalized patients with fully vaccinated (BBIBP-CorV) were included. The median age of the patients was 66 years (IQR 53, 74). The most common symptoms included fever (347 [60.7 %]), dry cough (401 [70.1 %]), and expectoration (333 [58.2 %]). Among those with pre-existing chronic comorbidities, 44.2 % had hypertension and 20.5 % had diabetes. Laboratory tests revealed that the majority of patients (425/549 [77.4 %]) had normal white blood cell counts. Composite outcome occurred in 11.9 % of patients, with 96.7 % of patients discharged and 3.3 % of patients died. Multivariate Cox regression analyses suggested that the NLR >4 (adjusted HR, 5.50 [95%CI: 1.56–19.47]; P = 0.008), D-dimer >0.5 mg/ml (adjusted HR, 2.17 [95%CI: 1.03–4.59]; P = 0.042) and procalcitonin >0.1 ng/ml (adjusted HR, 3.22 [95%CI: 1.38–7.52]; P = 0.007) were independently associated with the composite outcome. ConclusionBreakthrough infection after being fully vaccinated (BBIBP-CorV) is more likely to occur in older patients and patients with pre-existing chronic comorbidities. NLR >4, D-dimer >0.5 mg/ml and procalcitonin >0.1 ng/ml were independent risk factors for composite outcome.

Association between the Clinical, Laboratory and Ultrasound Characteristics and the Etiology of Peripheral Lymphadenopathy in Children.

Peripheral lymphadenopathy affects most children at least once in a lifetime and represents a major reason for concern. Therefore, we aimed to identify the most common causes of peripheral lymphadenopathy in hospitalized children and to determine the clinical, laboratory and ultrasound characteristics that enable fast, easy and accurate etiological diagnosis. We performed a cross-sectional study including 139 children who were hospitalized because of peripheral lymphadenopathy. Ultrasound of lymph nodes was performed in 113 (81.3%) patients. Lymphadenopathy was generalized in nine (6.5%) patients. Malignant etiology was established in only three (2.2%) patients. Bacterial lymphadenitis, infectious mononucleosis (IM) and cat scratch disease (CSD) were diagnosed in 66 (47.5%), 31 (22.3%) and 29 (20.9%) patients, respectively. Bacterial lymphadenitis was significantly associated with neutrophilia (p < 0.01), and increased C-reactive protein levels (p < 0.01). IM was associated with pharyngitis (p < 0.01), leukocytosis without neutrophilia (p = 0.03) and increased blood liver enzyme levels (p < 0.01). CSD was associated with recent contact with a cat (p < 0.01), absence of a fever (p < 0.01) and normal white blood cell count (p < 0.01). Thorough history and clinical examination in combination with a few basic laboratory tests enable fast and accurate differentiation between the most common etiologies of lymphadenopathy in children to avoid unnecessary procedures and hospitalizations.

Enterovirus Central Nervous System Infection in Infancy, the Value of Routine Testing.

Human nonpolio enterovirus (EV) is a major cause of infection in neonates and infants; however, the clinical presentation and cerebrospinal fluid findings vary significantly. Infection caused by EV in patients under 1 year of age can present with a broad clinical spectrum, from fever to severe systemic and/or neurological disease. Retrospective cohort analysis of infants with EV central nervous system (CNS) infection presenting to a tertiary center between January 2017 and December 2022. We recorded patient demographics, parent-reported symptoms at presentation, and blood and cerebrospinal fluid (CSF) testing at presentation. Seventy-eight patients were included in the final study. Forty-one percent of infants with an EV CNS infection had a normal CSF white blood cell count. Clinical presentation was similar in infants with and without CSF pleocytosis. Median C-reactive protein was higher in cases of EV CNS infection without pleocytosis. EV CNS infection commonly presents without CSF pleocytosis. Testing for EV should be considered in febrile infants with no source regardless of CSF parameters.

Validation of JRS atypical pneumonia score in patients with community-acquired Chlamydia psittaci pneumonia

IntroductionThe Japanese Respiratory Society (JRS) atypical pneumonia score is a useful tool for the rapid presumptive diagnosis of atypical pneumonia. We investigated the clinical features of community-acquired pneumonia (CAP) due to Chlamydia psittaci and validated the JRS atypical pneumonia score in patients with C. psittaci CAP. MethodsThis study was conducted at 30 institutions and assessed a total of 72 sporadic cases with C. psittaci CAP, 412 cases with Mycoplasma pneumoniae CAP, and 576 cases with Streptococcus pneumoniae CAP. ResultsSixty-two of 72 patients with C. psittaci CAP had a history of avian exposure. Among the six parameters of the JRS score, matching rates of four parameters were significantly lower in the C. psittaci CAP than the M. pneumoniae CAP in the following parameters: age <60 years, no or minor comorbid illness, stubborn or paroxysmal cough, and absence of chest adventitious sounds. The sensitivity of the diagnosis of atypical pneumonia in patients with C. psittaci CAP was significantly lower than the M. pneumoniae CAP (65.3% and 87.4%, p < 0.0001). When the diagnostic sensitivity was analyzed for different ages, the diagnostic sensitivities for the C. psittaci CAP were 90.5% for non-elderly patients and 30.0% for elderly patients. ConclusionsThe JRS atypical pneumonia score is a useful tool for distinguishing between C. psittaci CAP and bacterial CAP in patients aged <60 years, but not in patients aged ≥60 years. A history of avian exposure in middle-aged patients with normal white blood cell count may be suggestive of C. psittaci pneumonia.