Lower Neutrophil Counts Research Articles

Severity of parechovirus infections in infants under 3 months of age and comparison with enterovirus infections: A French retrospective study

While enteroviruses (EV) are a well-recognized cause of aseptic meningitis in children, human parechoviruses (HPeV), especially genotype 3, have been increasingly reported as a frequent cause of sepsis-like illness and meningitis among young infants. The aim of this study was to describe the epidemiological, clinical, and laboratory characteristics of HPeV infections in infants and to compare them with those of well-known EV infections. This monocentric retrospective study was carried out at the pediatric unit of Nantes University Hospital from January 2015 to August 2018. All patients under 18 years of age with diagnosis codes referring to fever, for whom viral infection was suspected and cerebrospinal fluid (CSF) specimens were collected, were included. All CSF specimens were screened by duplex real-time polymerase chain reaction (PCR) assay that allows for the simultaneous detection of EV and HPeV in clinical samples. During the study period, 1373 CSF specimens from patients under 18 were included. A total of 312 CSF samples were positive for HPeV (n=34) or EV (n=278). Among the 34 HPeV-positive patients, 97% (33/34) were under 3 months of age, whereas the rate was 54% (149/278) for EV-positive patients (P<0.001); thus, patients under 3 months of age were defined as the study population for the rest of this work. A review of the medical records was carried out for the positive cases. In this population, the HPeV detection rate was 5.6% versus 25.3% (P<0.001) for EV. All but one of the HPeV samples available for genotyping were HPeV-3. No seasonality was observed for HPeV infections. Length of hospital stay tended to be longer for children infected with HPeV compared with those infected by EV (3 days vs. 2 days, P=0.05). Clinicians reported more severe illness presentations among HPeV-infected infants, with more frequent administration of fluid bolus (P<0.02). Regarding laboratory characteristics, a significant lack of cellular reaction in the CSF (P=0.004) as well as lower C-reactive protein (CRP) levels (P=0.006) and neutrophil counts (P<0.001) were noted for HPeV infections compared with EV infections. Our results confirm the early onset of HPeV infections (more than 95% of patients aged under 3 months). The clinical presentation and laboratory characteristics of the two infections was similar. However, some higher clinical severity criteria and a lack of CSF pleocytosis were regularly observed in patients with HPeV infections. Considering the significant proportion (5.6%; 95% CI, 3.7–7.5) of all CSF samples in our series, HPeV detection should be systematically included in the microbiological diagnosis of febrile children under 3 months of age.

Clinical and hematologic presentations of adults with COVID-19 patients in Jeddah: A case control study

BackgroundCoronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), is associated with significant morbidity and mortality. The clinical features of COVID-19 were mentioned in previous studies. However, risk factors for COVID-19 are not fully recognized. The aim of this study is to characterize risk factors and clinical features of COVID-19 disease in Jeddah, Saudi Arabia. MethodsA retrospective, chart-review, case-control study was conducted at King Abdulaziz University, Jeddah, Saudi Arabia. Demographic, clinical, radiological, and laboratory data on patients diagnosed between March 18 and May 18, 2020 were collected and analyzed. ResultsWe reviewed medical records on 297 suspected cases of COVID-19. Of these, 175 (59%) tested positive for COVID-19 by polymerase chain reaction (PCR) and considered as cases, while 122 (41%) tested negative and considered as control. COVID-19 positive cases were more likely to be males, and non-health care providers. Hypertension (15%), diabetes (10%) and two or more concurrent comorbidities (54.4%) were more prevalent among COVID-19 patients. Patients presented with fever, cough, and loss of taste/smell were more likely to test positive for COVID-19 (P = 0.001, 0.008, 0.008; respectively). Radiological evidence of pneumonia was associated with confirmed COVID-19 disease (P = 0.001). Shortness of breath and gastrointestinal symptoms were not associated with the risk of COVID-19 at presentation. On admission, white blood cells, neutrophils, lymphocytes, eosinophils, basophils, and platelets were significantly lower among COVID-19 patients compared with controls. Surprisingly, D-Dimer levels were lower among COVID-19 positive patients when compared with controls. ConclusionMale gender, hypertension, and diabetes are the most commonly observed risk factors associated with COVID-19 disease in Jeddah, Saudi Arabia. COVID-19 patient had significantly lower lymphocyte and neutrophil counts.

Haematological findings in 158 cows with acute toxic mastitis with a focus on the leukogram

BackgroundIn cows with acute toxic mastitis (ATM), the leukogram aids in the assessment of the severity of disease. The goal of our study was to compare the leukogram of 158 cows with ATM (cases) and 168 clinically healthy cows (controls). We hypothesised that the leukograms of surviving and non-surviving cows differ and that there are variables of the leukogram with sufficient prognostic potential to be used in the decision to treat or not to treat a cow with ATM. The cows were examined clinically and underwent haematological and biochemical examination of blood and bacteriological culture of milk samples.ResultsAll cows with ATM had a poor appetite or anorexia, and 34 cows (21.5%) were recumbent. A single quarter was affected in 119 cows (75.3%), two quarters in 37 cows (23.4%) and three quarters in two cows (1.3%). Bacteriological culture showed Gram-negative pathogens in 100 cows (63.3%), Gram-positive in 15 (9.5%) and yeast in 4 (2.5%). The median total leukocyte count of cases was 4300 cells/µL (interquartile range = 2300–8200/µL), which was significantly lower than 8000 cells/µL (6525–9300/µL) in controls. Except for band neutrophils and metamyelocytes, the counts of all components of the leukogram were lower in cases compared with controls. Significantly more cows with ATM had leukopenia (60.1 vs. 4.1%) or leukocytosis (10.1 vs. 3.0%) than controls. Diseased cows had significantly lower segmented neutrophil counts than controls (860 vs. 2598 cells/µL), and 69.5 and 17.3%, respectively, had counts below the reference interval. Cases had increased band (77.3%) and metamyelocyte (25.0%) counts compared with controls (0.6 and 0%, respectively). In diseased cows, eosinopenia occurred in 66.4% (controls, 1.8%), monocytopenia in 40.6% (4.2%) and lymphopenia in 60.2% (1.8%). Twenty-one diseased cows (16.4%) had a regenerative and 57 (44.5%) had a degenerative left shift. The median neutrophil-to-lymphocyte ratio was 0.97 in diseased cows and 0.63 in controls. Toxic changes in neutrophils including cytoplasmic basophilia and vacuolisation were seen in 101 (91.8%) of 110 blood smears of diseased cows. The leukogram of the surviving and non-surviving cows did not differ significantly, and the hypothesis was rejected.ConclusionsATM results in severe changes in the leukogram particularly leukopenia, lymphopenia, and degenerative left shift. The hypothesis that the leukograms of surviving and non-surviving cows differ was rejected. The leukogram has not sufficient prognostic potential to be used in the decision to treat or not to treat a cow with ATM.

Haematological responses and erythrocyte osmotic fragility in pregnant Yankasa ewes and their lambs

The aim of the study was to evaluate blood cellular responses and erythrocyte osmotic fragility (EOF), as an index of oxidative stress, in pregnant Yankasa ewes and their lambs. Blood samples were collected from each ewe at pre-gestation, gestation (weeks 3, 10 and 17, corresponding to early-, mid-, and late-gestation, respectively), prepartum (weeks 18 and 19), postpartum (immediately after lambing, weeks 1 and 3); and from their lambs postpartum. The blood samples were used to determine blood cellular parameters and EOF. Results revealed higher (P < 0.05) packed cell volume (PCV) and red blood cell (RBC) counts at mid-gestation than prepartum and postpartum values. Neutrophil-lymphocyte ratio was higher (P < 0.05) on parturition day compared to other stages. There was no significant (P> 0.05) difference in EOF during the different stages in the dams. On the day of lambing, PCV, haemoglobin and lymphocyte counts were higher (P < 0.05) in lambs than dams, but lower neutrophil count was recorded in the lambs compared to dams. The EOF was lower in lambs than their dams (P < 0.05) on the day of lambing. In conclusion, the mid-gestation PCV and RBC values were higher than pre- and post-partum values, whereas parturition influenced neutrophil-lymphocyte ratio compared to other stages. The results showed that most blood cellular changes occurred during the periparturient period, when most life-threatening disorders affect ewes. Erythrocyte membranes of lambs were more resistant to hypotonicity, indicating that the erythrocyte membranes of the lambs were less vulnerable to oxidative stress damage than those of their dams. Hence, Yankasa lambs may be more resistant to immediate postpartum oxidative stress than their dams.

Abstract PS4-17: Association of neutrophil-to-lymphocyte ratio with pathological complete response in locally advanced breast cancer

Abstract Background: Neutrophil-to-lymphocyte ratio (NLR) has emerged as a potential inflammatory blood biomarker for breast cancer (BC) outcomes. Prior analysis suggests that NLR is a reliable prognostic factor for patients with locally advanced breast cancer (LABC) receiving adjuvant chemotherapy. However, the prognostic value in patients receiving neoadjuvant chemotherapy (NAC) remains unclear. We aimed to evaluate the association of baseline NLR with pathological complete response (pCR) among patients with LABC treated with NAC. Methods: We retrospectively analyzed 253 patients with stage II and III BC that received NAC followed by surgery at Montefiore Einstein Cancer Center from 2005 through 2017, and had information regarding baseline NLR and pCR at surgery. Demographic, clinicopathological, laboratory and treatment characteristics were obtained from electronic medical records. Laboratory parameters included absolute neutrophil count and absolute lymphocyte count. pCR was defined as absence of residual invasive carcinoma in both the breast and the lymph nodes (ypT0/ypN0 or ypTis/ypN0) at the time of surgery. The association between NLR and pCR was assessed using the multivariate logistic regression model. The association between NLR and disease free survival (DFS) and overall survival (OS) was assessed using Cox proportional hazards models. Results: Median age at diagnosis was 54 years [interquartile range (IQR)=45-63]. Patients were predominantly non-Hispanic (58%). The most common race was Black (49%) followed by White (32%) and Asian (6%). Pre/perimenopausal and postmenopausal status corresponded to 42% and 59% of patients, respectively. The most common histological subtype was ductal (88%) followed by lobular (7%) adenocarcinoma. High, intermediate and low histological grades were seen in 57%, 36% and 2%, respectively. Triple negative, human epidermal growth factor receptor 2-HER2(+), and hormone receptor-HR(+)/HER2(-) tumors corresponded to 39%, 31% and 30% of patients, respectively. Taxanes and anthracyclines were administered to 96% and 68% of patients, respectively. Mastectomy (63%) was the most common type of surgery followed by breast conserving (37%) surgery. pCR was achieved in 30% of patients. Median NLR was 2.2 [IQR=1.6-3.1] and dichotomized into NLRHIGH (&amp;gt;=2.2) and NLRLOW (&amp;lt;2.2). In the bivariate analysis, there was no statistically significant association between NLRHIGH vs. LOW and pCR (p=0.78). When adjusted for age, race, histological grade, HR status and HER2 status, no statistically significant association was found between NLR and pCR (Odds ratio: 0.82, p=0.51). When adjusted for age, race, histological grade, HR status and HER2 status, no statistically significant association was found between NLR and DFS (Hazard ratio (HR): 0.75, p=0.3) or OS (HR: 0.61, p=0.19). Conclusions: In our study, the baseline NRL was not an independent prognostic factor for pCR, DFS or OS in patients with stage II and III BC treated with NAC. These findings are consistent with prior studies. Patients of Black race have lower baseline neutrophil counts, which could lead to different NLR values than other racial groups. Notably, our population was predominantly Black, in which scarce data exists concerning the association between NLR and BC outcomes. Further studies are needed to elucidate the prognostic value of NLR in the neoadjuvant setting among multiracial groups. Citation Format: Laura S Munoz-Arcos, Ashley Weiner, Jee-Young Moon, Xionan Xue, Jesus Anampa-Mesias. Association of neutrophil-to-lymphocyte ratio with pathological complete response in locally advanced breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS4-17.

Comparing Clinical Features and Outcomes in Mechanically Ventilated Patients with COVID-19 and Acute Respiratory Distress Syndrome.

Rationale: Patients with severe coronavirus disease (COVID-19) meet clinical criteria for the acute respiratory distress syndrome (ARDS), yet early reports suggested they differ physiologically and clinically from patients with non–COVID-19 ARDS, prompting treatment recommendations that deviate from standard evidence-based practices for ARDS.Objectives: To compare respiratory physiology, clinical outcomes, and extrapulmonary clinical features of severe COVID-19 with non–COVID-19 ARDS.Methods: We performed a retrospective cohort study, comparing 130 consecutive mechanically ventilated patients with severe COVID-19 with 382 consecutive mechanically ventilated patients with non–COVID-19 ARDS. Initial respiratory physiology and 28-day outcomes were compared. Extrapulmonary manifestations (inflammation, extrapulmonary organ injury, and coagulation) were compared in an exploratory analysis.Results: Comparison of patients with COVID-19 and non–COVID-19 ARDS suggested small differences in respiratory compliance, ventilatory efficiency, and oxygenation. The 28-day mortality was 30% in patients with COVID-19 and 38% in patients with non–COVID-19 ARDS. In adjusted analysis, point estimates of differences in time to breathing unassisted at 28 days (adjusted subdistributional hazards ratio, 0.98 [95% confidence interval (CI), 0.77–1.26]) and 28-day mortality (risk ratio, 1.01 [95% CI, 0.72–1.42]) were small for COVID-19 versus non–COVID-19 ARDS, although the confidence intervals for these estimates include moderate differences. Patients with COVID-19 had lower neutrophil counts but did not differ in lymphocyte count or other measures of systemic inflammation.Conclusions: In this single-center cohort, we found no evidence for large differences between COVID-19 and non–COVID-19 ARDS. Many key clinical features of severe COVID-19 were similar to those of non–COVID-19 ARDS, including respiratory physiology and clinical outcomes, although our sample size precludes definitive conclusions. Further studies are needed to define COVID-19–specific pathophysiology before a deviation from evidence-based treatment practices can be recommended.

COVID‐19 associated Kikuchi‐Fujimoto disease

We discuss the case of a 17-year-old male who presented with painful lymphadenopathy, fevers, weight loss, anorexia and a history of preceding anosmia. Histological features on lymph node biopsy were in-keeping with Kikuchi-Fujimoto disease (KFD). We later confirmed SARS-CoV-2 (COVID-19) infection on antibody testing. This case describes an atypical presentation of COVID-19 in a young patient and highlights an association between the virus and this rare disease.

The Prognostic Impact of Eosinophils and the Eosinophil-to-Lymphocyte Ratio on Survival Outcomes in Stage II Resectable Pancreatic Cancer.

The relationship between eosinophils and cancer prognosis is unknown. Therefore, we analyzed the relationship between circulating eosinophils and the survival of stage IIA and IIB pancreatic cancer patients who underwent surgical resection. This study included a retrospective cohort of 67 consecutive patients. Patients were categorized into two different groups based on the optimal cutoff for pretreatment levels of each biomarker, according to the receiver operating characteristic curves. The Kaplan-Meier method showed that low eosinophil (P = 0.0403), high neutrophil (P = 0.0066), and high monocyte (P = 0.0003) counts were associated with short overall survival (OS). Low lymphocyte-to-monocyte ratio (P = 0.0194) and eosinophil-to-lymphocyte ratio (ELR) (P = 0.0413) were associated with reduced OS. In multivariate analysis, histological differentiation (P = 0.0014), high neutrophils (P = 0.047), high monocytes (P = 0.029), and low eosinophils (P < 0.0001) were correlated with poorer OS. Histological differentiation (P = 0.033), low lymphocyte-to-monocyte ratio (P = 0.029), and low ELR (P = 0.005) were correlated with poor OS and were significant independent prognostic factors of poor outcomes. Low eosinophils and low ELR were significant independent prognostic factors of poor outcomes.

Current practice of oral care for hematopoietic stem cell transplant patients: A survey of the Eastern Mediterranean Blood and Marrow transplantation group

IntroductionThe oral cavity is one of the most common sites impacted by hematopoietic stem cell transplantation (HSCT) with acute complications including mucositis, bleeding, salivary gland dysfunction, infection, and taste alteration. These complications may result in significant morbidity and can negatively impact outcomes such as length of stay and overall costs. As such, oral care during HSCT for prevention and management of oral toxicities is a standard component of transplant protocols at all centers. The objective of this study was to evaluate the current oral care practices for patients during HSCT at different transplant centers within the Eastern Mediterranean region. Material and methodsAn internet-based survey was directed to 30 transplant centers in the Eastern Mediterranean region. The survey included five sections asking questions related to (1) transplant center demographics; (2) current oral care protocol used at the center and type of collaboration (if any) with a dental service; (3) use of standardized oral assessment tools and grading systems for mucositis; (4) consultations for management of oral complications; and (5) oral health needs at each center. Data are presented as averages and percentages. ResultsA total of 16 responses from 11 countries were collected and analyzed, indicating a response rate of 53%. Eight centers reported that a dentist was part of the HSCT team, with four reporting oral medicine specialists specifically being part of the team. Almost all centers (15/16; 93%) had an affiliated dental service to facilitate pre-HSCT dental clearance with an established dental clearance protocol at 14 centers (87%). Dental extraction was associated with the highest concern for bleeding and the need for platelet transfusion. With respect to infection risk, antibiotic prophylaxis was considered in the setting of low neutrophil counts with restorative dentistry and extraction. All centers provide daily reinforcement of oral hygiene regimen. The most frequently used mouth oral rinses included sodium bicarbonate (68%) and chlorhexidine gluconate (62%), in addition to ice chips for dry mouth (62%). The most frequently used mucositis assessment tools were the World Health Organization scale (7/16; 43%) and visual analogue scale for pain (6/16; 37%). Mucositis pain was managed with lidocaine solution (68.8%), magic mouth wash (68.8%) and/or systemic pain medications (75%). ConclusionsScope and implementation of oral care protocols prior to and during HSCT varied between transplant centers. The lack of a universal protocol may contribute to gaps in oral healthcare needs and management for this group of patients. Further dissemination of and education around available oral care guidelines is warranted.Clinical relevance.Considering oral care during HSCT a standard component of transplant protocols, the current study highlights the common oral care practices for patients at centers within the Eastern Mediterranean region.

The application of 18F-FDG-PET/CT in gastric cancerstaging and factors affecting its sensitivity.

To evaluate the accuracy offluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT), to correctly determine initial tumor stage in treatment-naive gastric cancer patients and to analyze the factors influencing the risk of false negative results. The baseline 18F-FDG PET/CT scans of 111 previously untreated gastric cancer patients were retrospectively assessed. Sensitivity, specificity, positive (PPV) and negative prediction value (NPV) were evaluated. An array of clinical, pathological and metabolic variables was analyzed to identify factors contributing to the risk of a false positive (FP) and false negative (FN) PET/CT result in detecting primary and metastatic tumor sites. The sensitivity, specificity, PPV and NPV of PET/CT to visualize distant metastases were 76.4%; 86.7%; 83% and 81.2%, respectively. In 13 (11.7%) patients the PET/CT exam was able to identify metastatic sites not recognized in radiographic staging, significantly altering the initially planned management. Of 64 PET/CT studies negative for distant metastases, 12 (18.75%) were clinically confirmed to be false negative. The risk of acquiring a FN result for primary tumor was 10.8% (12/111) and the overall risk of any FN readout for either primary and metastatic sites was 18.9% (21/111). The factors that contributed to increased probability of a FN result for primary tumor detection were early primary tumor stage T1-T2 (+16.2%; χ2=5.0, P=0.025), female sex (+10.1%; χ2=5.71, P=0.017) and neutrophil count below 4.2k/μL (9.7%; χ2=6.1, P=0.014). Patients with non-intestinal Lauren histologic type (+18.7%; χ2=8.9, P=0.003) or signet-ring/mucinous carcinoma (+9.6%; χ2=7.7, P=0.005) had increased probability of PET/CT being unable to identify their distant metastases. Women and patients with low neutrophil count featured borderline insignificantly increased percentage of non-intestinal tumor histology (P=0.07 and P=0.057, respectively). Fluorine-18-FDG PET/CT is a valuable diagnostic method in gastric cancer patients which significantly contributes to determining the TNM stage and thus helps choose correct patient management. Histology and primary tumor stage as well as patient cohorts in which these factors may vary should be considered when evaluating results to decrease a chance of a false negative readout.

Meropenem-induced pancytopenia in a preterm neonate: a case report

BackgroundA post-marketing surveillance study has reported an association between meropenem use and the incidence of hematologic abnormalities, including leukopenia, thrombocytopenia, hemolysis, and neutropenia, but the precise incidence in neonates is unknown. Here, we report meropenem-induced pancytopenia in a preterm neonate.Case presentationA preterm newborn Pakistani received intravenous meropenem 40 mg/kg every 8 hours to treat Klebsiella pneumoniae in blood cultures and suspected meningitis. The baby developed severe thrombocytopenia, with a platelet count of 22 × 103 cells/mm3, low hemoglobin level of 9.7 g/dl, and low absolute neutrophil count (ANC) of 816 cells/mm3 on days 3, 14, and 17 of meropenem therapy, respectively. Based on the blood culture and institutional guidelines, meropenem treatment was continued with monitoring and supportive care for a total of 19 days. After discontinuation of meropenem, the baby was monitored continuously for hematological changes, and low counts persisted for 3 days. ANC improved to > 1500 cells/mm3 on the fourth day, and the platelet count reached > 150 × 103 cells/mm3 for the first time on the seventh day of meropenem discontinuation. All subsequent complete blood count (CBC) reports showed improving trends. The baby was discharged on the 48th day of life (DOL), with follow-up monitoring of CBC. The baby was kept on iron supplements, and hemoglobin level of 11.2 g/dl was observed on the 59th DOL.ConclusionNeonatal pancytopenia may lead to serious health complications; therefore, clinicians and pharmacists need to vigilantly monitor CBC in this vulnerable population, even when administering meropenem in septic doses for the recommended duration.

Patterns of Presentation of SARS-CoV-2 Infection in Children. Experience at the Italian Epicentre of the Pandemic.

Background: COVID-19, a disease caused by the new coronavirus SARS-CoV-2, spread worldwide, and Bergamo was one of the most affected areas in Europe. Following the first outbreak, more than half of the population of the Bergamo province had been infected. We aimed to describe the patients admitted to our unit shortly after the first outbreak.Methods: we retrospectively reviewed the notes of all pediatric patients diagnosed with COVID-19. We enrolled patients with positive swabs or serology and classified them based on the pattern and the timing of presentation after the first outbreak. This setting was considered a reliable reflection of the consequences of unmitigated SARS-CoV-2 circulation.Results: We diagnosed 35 patients over a 3-month period and we identified six patterns presenting in two temporal phases: Early phase, Group 1 (median of 20 days from epidemic start, IQR: 15–27): neonatal sepsis (n.7), pneumonia (n.5), flu-like symptoms (n.2). Late phase, Group 2 (59:51–66 days, p < 0.001): MIS-C (n.18), neurological manifestations (n.3). Group 1 differed from Group 2 for younger age (1 vs. 8 years, p = 0.02), lower C-reactive protein (0.9 vs. 16.6 mg/dl, p = 0.008), procalcitonin (0.16 vs. 7.9 ng/ml, p = 0.008) and neutrophil count (3,765 vs. 6,780/μl, p = 0.006), higher rate of positive swabs (14/14 vs. 9/21, p < 0.001), higher lymphocyte count (3,000 vs. 930/μl, p = 0.006) and platelet count (323,000 vs. 210,000/μl, p = 0.009).Conclusions: Following an outbreak of unmitigated SARS-CoV-2 diffusion, infected children may present with clinical patterns suggesting two temporal clusters, the first characterized by markers of direct viral injury, the second suggesting an immune-mediated disease.

Benign ethnic neutropenia in a South African population, and its association with HIV acquisition and adverse event reporting in an HIV vaccine clinical trial.

Benign ethnic neutropenia (BEN) is defined as a neutrophil count of <1.5×109 cells/L in healthy individuals and is more common in populations of certain ethnicities, e.g. African or Middle Eastern ethnicity. Neutrophil values are commonly included in eligibility criteria for research participation, but little is known about the relationship between BEN, HIV acquisition, and the occurrence of adverse events during clinical trials. We investigated these relationships using data from an HIV vaccine efficacy trial of healthy adults from 5 South African sites. We analysed data from the double-blind, placebo-controlled, randomized trial HVTN 503, and its follow-on study HVTN 503-S to assess the prevalence of BEN, its association with HIV infection, and adverse event reporting. These data were then compared with a time- and age-matched, non-pregnant cohort from the National Health and Nutrition Examination Survey (NHANES) conducted between 2007–2008 in the United States (US). The 739 South African participants had a median age of 22.0 years (interquartile range = 20–26) and 56% (n = 412) were male. Amongst the US cohort of 845 participants, the median age was 26 (IQR: 21–30) and the majority (54%, 457/745) were also male. BEN was present at enrolment in 7.0% (n = 52) of South African participants (6% in the placebo group versus 8% in the vaccine group); 81% (n = 42) of those with BEN were male. Pretoria North had the highest prevalence of BEN (11.6%, 5/43), while Cape Town had the lowest (0.7%, 1/152). Participants with BEN had a lower median neutrophil count (1.3 vs. 3.2x109 cells/L; p<0.001) and BMI (20.8 vs. 22.3 kg/m2; p<0.001) when compared to those without BEN. A greater proportion of Black South Africans had neutrophil counts <1.5×109 cells/L compared to US non-Hispanic Whites from the NHANES cohort (7% [52/739] vs. 0.6% [3/540]; p<0.001). BEN did not increase the odds for HIV infection (adjusted odds ratio [aOR]: 1.364, 95% confidence interval [95% CI]: 0.625–2.976; p = 0.4351). However, female gender (aOR: 1.947, 95% CI: 1.265–2.996; p = 0.0025) and cannabis use (aOR: 2.192, 95% CI: 1.126–4.266; p = 0.0209) increased the odds of HIV acquisition. The incidence rates of adverse events were similar between participants in the placebo group with BEN, and those without: 12.1 (95% CI: 7.3–20.1) vs. 16.5 (95% CI: 14.6–18.7; p = 0.06) events per 100 person-years (py) were noted in the infections and infestations system organ class, respectively. The vaccine group had an event incidence rate of 19.7 (95% CI: 13.3–29.2) vs. 14.8 (95% CI: 13.0–16.8; p = 0.07) events per 100py in the group with, and without BEN, respectively. BEN is more prevalent in Black South Africans compared to US Non-Hispanic Whites. Our data do not support excluding populations from HIV vaccine trials because of BEN. BEN was not associated with increased risk for HIV infection or Adverse events on a vaccine trial. Predictors of HIV infection risk were females and cannabis use, underlying the continued importance of prevention programmes in focusing on these populations.

Increase in white blood cell counts by pegbovigrastim in primiparous and multiparous grazing dairy cows and the interaction with prepartum body condition score and non-esterified fatty acids concentration.

The objective of this study was to determine if parity affected the effect of pegbovigrastim (PEG) treatment on white blood cell (WBC) counts in grazing dairy cows. Additionally, the association of prepartum body condition score (BCS) and non-esterified fatty acid (Pre-NEFA) concentration with WBC counts was investigated. The effect of early-lactation disease was included in the statistical analysis. A randomized controlled trial on four commercial grazing dairy farms was performed. Holstein primiparous (Control = 87, PEG = 89) and multiparous (Control = 181, PEG = 184) cows were randomly assigned to one of two treatments: first PEG dose 8 ± 5 (mean ± SD) days before the expected calving date and a second dose within 24 h after calving (PEG) compared to untreated controls (Control). Treatment effects were evaluated with mixed linear regression models. Treatment with PEG increased WBC, neutrophil, lymphocyte and monocyte counts at 6 ± 1 (mean ± SD) days in milk. Parity, BCS and their interactions with treatment were not associated with WBC counts. In control cows, Pre-NEFA concentration was associated with reduced WBC, neutrophil and lymphocyte counts and tended to be associated with reduced monocyte counts. Pegbovigrastim treatment reversed the negative association of Pre-NEFA concentration with neutrophil and monocyte counts and tended to reverse the negative association of Pre-NEFA concentration with WBC counts. In the PEG treated group, cows diagnosed with retained placenta or metritis showed lower neutrophil counts when compared to PEG treated cows without these clinical diseases. These data confirm that PEG treatment increases WBC, neutrophil, lymphocyte and monocyte counts in grazing dairy cows and that this effect is independent of parity. Pegbovigrastim treatment reversed the negative association of Pre-NEFA concentration with neutrophil and monocyte counts, and tended to reverse the negative association of Pre-NEFA concentration with WBC counts.

Evolving Changes in the Full Blood Count in Tuberculosis

Abstract Background: Changes in the full blood count of patients with tuberculosis have been studied previously, but the effect of co-infection with human immunodeficiency virus (HIV) remains to be explored. Objective: To evaluate the changes in full blood count in patients with tuberculosis in an evolving HIV era. Methods: Prospective study of consecutively recruited patients (N = 125) with microbiologically or histologically proven tuberculosis admitted at Chris Hani Baragwanath Academic Hospital between October 2017 and July 2018. Results: Anaemia was found in 60.7% of patients with pulmonary tuberculosis (PTB) and in 61.1% of extra-pulmonary tuberculosis (ETB) patients. ETB patients had lower white cell counts (WCCs) and lower neutrophil counts than PTB patients, (5.59 (3.6–8.1) vs 7.96 (5.27–10.34), p = 0.002) and (4.2 (2.1–7.0) vs 5.5 (3.3–8.4), p = 0.079), respectively. Compared to the HIV-seronegative patients, HIV co-infected PTB patients had lower WCC, lymphocyte counts and neutrophil counts, (6.9 (4.8–9.7) vs 9.4 (8.6–11.4), p = 0.0037), (0.7 (0.46–1.31) vs 1.51 (1.13–2.05), p = 0.0051), and (4.7 (2.8–7.7) vs 8.5 (5.9–10.1), p = 0.0106), respectively. Patients co-infected with HIV on combination antiretroviral therapy and tuberculosis had higher levels of WCC, (7.9 (4.6–10.9) vs 5.8 (4.3–8.3), p = 0.0465). Conclusion: Anaemia is the most common manifestation of tuberculosis. This study highlighted the reactive nature of PTB haematological abnormalities compared to ETB with higher WCCs in both HIV-seropositive and HIV-seronegative patients. Co-infection with HIV was associated with blunting of some of the previously described haematological manifestations among patients with PTB.

Clinical Features and Prognostic Risk Prediction of Non-Hodgkin Lymphoma-Associated Hemophagocytic Syndrome

Background: Malignancies, especially lymphoma, are a common cause of adult secondary HLH and an independent risk factor for the prognosis of HLH patients. Methods: Patients with lymphoma or lymphoma-associated phagocytic syndrome (LAHS) admitted to Beijing Friendship Hospital from January 2016 to December 2020 were enrolled in this study. Findings: In total, there were 348 lymphoma patients, 104 with LAHS and 244 without LAHS. The pathological type of non-LAHS was dominated by B-cell lymphoma, while LAHS was T/NK-cell lymphoma predominantly (p <0.001). Superficial lymph node enlargement was more significant in patients with B-LAHS compared with T/NK-LAHS (p=0.006), while patients with T/NK-LAHS had lower neutrophil counts (p=0.005), lower fibrinogen levels (p <0.001), higher transaminase levels (p <0.001), and were more likely to have co-infection with EBV (p <0.001). B-LAHS had significantly higher IL-10 levels than with T/NK-LAHS (p=0.006), and NK/T-LAHS had significantly higher IP-10 levels than other T-LAHS (p=0.008). Age, platelets count, IPI, history of NK/T lymphoma and no remission of HLH were independent risk factors for poor prognosis in patients with non-Hodgkin lymphoma associated phagocytic syndrome (NHL-LAHS), and a prognostic risk score model for NHL-LAHS was developed. Interpretation: LAHS is a life-threatening disease with poor prognosis. The prognostic risk score model for NHL-LAHS developed with a good fit and good validation for test has value for clinical application. Funding: Beijing Municipal Administration of Hospital Clinical Medicine Development of Special Funding Support (XMLX201823); National Natural Science Foundation of China (81871633); Beijing Natural Science Foundation (7181003); Beijing Municipal Administration of Hospitals’ Ascent Plan (DFL20180101). Declaration of Interest: None to declare. Ethical Approval: It was approved by the Ethics Committee at Beijing Friendship Hospital

Different WBC count in EDTA caused neutrophil aggregation by hematology analyser

Aggregation of neutrophils in peripheral blood smears is a very rare, mostly self-limiting phenomenon and may result in pseudo leukopenia. The exact reason for neutrophil aggregation in vitro has not been clarified, its relation to the use of ethylene diamine tetra acetate acid as an anticoagulant has been described in adults A 3-year-old boy was referred to Valli e Asr hospital Arak, Iran. The EDTA blood sample was first loaded with the Impedance-based KX-11 Sysmex, which showed a decrease in neutrophils and was observed in the peripheral blood of the Neutrophil aggregation. The blood sample was re-read with the XN-L-350 Sysmex, which is based on the optic method, which showed the number of neutrophils in Norman. Although neutrophil aggregation is extremely rare in daily haematological practice, physicians should be aware of this phenomenon as it may be the cause of leukocytopenia. Therefore, manual differentials should be performed in cases flagged for low leukocyte or neutrophil counts.

Game of clones: A case of ELANE gene mutation-related neutropenia

Mutations in the ELANE gene, which encodes the neutrophil elastase (NE) protein in neutrophils, result in ELANE-related neutropenia. ELANE-related neutropenia encompasses both cyclic neutropenia (CN) and severe congenital neutropenia (SCN), with ELANE mutations seen in a majority of SCN and almost all of CN patients. Clinical history in affected individuals typically reveals recurrent episodes of fever, oral ulcerations and bacterial as well as fungal infections, correlating with periodic oscillations or chronically low levels in the absolute neutrophil count (ANC). ELANE-related neutropenia is characterised by severely low neutrophil counts where ANCs may drop as low as zero. A two-year-old child presented at our hospital with a longstanding history of recurrent bacterial infections and previous admissions at another centre during some of these infectious episodes. Her full blood count demonstrated a markedly low ANC, which was chronic on assessment of her previous results. Decreased granulopoiesis with maturation arrest was seen on her bone marrow and genetic testing for the ELANE gene demonstrated a pathogenic variant of the mutation. Treatment with granulocyte colony-stimulating factor (G-CSF) was initiated.

Novel coronavirus disease 2019 and combined autoimmune neutropenia and thrombocytopenia: a case report

Background: Combined autoimmune neutropenia (AIN) and immune thrombocytopenia (ITP) is a rare disease that can present as extremely low neutrophil count and platelet count, respectively [1]. Case Presentation: We describe the first case, to the authors’ knowledge, of the novel SARS CoV-2 infection and combined AIN and ITP in a healthy 27-year-old male. Conclusion: Viruses have been known to trigger autoimmune diseases in people with genetic predisposition. We speculate that the patient’s selective IgM deficiency predisposed him to have autoimmune cytopenia, and SARS-COV-2 triggered him to acquire combined AIN and ITP. Our hypothesis is supported by a lack of evidence of malignancy, a normal morphology on the smear, and an immediate response to IVIG infusion with significant improvement in platelet and neutrophilic count.

Novel Coronavirus Disease 2019 (COVID-19) and Combined Autoimmune Neutropenia (AIN) and Thrombocytopenia (ITP): A Case Report and Literature Review

Combined autoimmune neutropenia (AIN) and Immune thrombocytopenia (ITP) is a rare disease that can present as extremely low neutrophil count and platelet count, respectively [1]. We describe the first case, to our knowledge, of the novel SARS CoV-2 infection and combined autoimmune neutropenia (AIN) and immune thrombocytopenia (ITP) in a healthy 27-year-old male