Search

Background: Pseudohyperkalemia (falsely elevated serum potassium) must be distinguished from true hyperkalemia to avoid unnecessary treatment. Some case reports suggest that pneumatic tube transportation may increase the risk of pseudohyperkalemia, but comprehensive research on the topic is lacking. Here, we aimed to assess the association between WBC levels, pneumatic tube transport, and pseudohyperkalemia prevalence., Methods: We analyzed 1188 samples collected from 240 patients between 2019 and 2022. Samples with elevated WBC counts (≥ 100 × 10 3 /μL) and potassium levels were included in this study. The method of specimen transportation was documented., Results: Pseudohyperkalemia was observed (7/390) in specimens transported using pneumatic tubes. No pseudohyperkalemia was identified with manually transported specimens (0/132). Every increase in WBC count by 100 × 10 3 /μL in the specimens multiplied the odds ratio of pseudohyperkalemia by 3.75 when delivered with pneumatic tube. The prevalence of pseudohyperkalemia increased as WBC count increased, especially at WBC counts greater than 200 × 10 3 /μL., Conclusion: Pneumatic tube transport poses a risk for pseudohyperkalemia in patients with extreme leukocytosis. Physicians should anticipate odd potassium levels when interpreting blood test results. Redrawing of blood samples, manual specimen transportation, or point-of-care testing are suggested to prevent further misdiagnosis., (© 2024. Japanese Society of Hematology.)

Background: Leukocytosis and thrombocytosis often follow splenectomy in blunt trauma patients, complicating the postoperative identification of infection. While the platelet count to white blood cell ratio provides diagnostic assistance to discern between expected laboratory alterations and infection, diagnoses such as leukemia are often overlooked., Case Presentation: A 53-year-old Hispanic male presented with abdominal pain, nausea, tachycardia, and focal peritonitis 4 days after being assaulted and struck multiple times in the abdomen. Initial white blood cell count was 38.4 × 10 9 /L, platelet count was 691 × 10 9 /L, and lipase was 55 U/L. Computed tomography abdomen/pelvis demonstrated a hematoma encasing the distal pancreas and abutting the stomach and colon. Emergent laparotomy revealed a nearly transected pancreas and devascularized colon, necessitating a distal pancreatectomy, splenectomy, and colonic resection with primary anastomosis. Postoperatively, he had a persistently elevated leukocytosis, thrombocytosis, segmented neutrophils, eosinophilia, and basophilia (peak at 70, 2293, 64, 1.1, and 1.2 × 10 9 /L, respectively). Despite sepsis workup, including repeat computed tomography, no source was identified. Hematology/oncology was consulted for concern for hematologic etiology, with genetic testing and bone marrow biopsy performed. The diagnosis of breakpoint cluster-Abelson gene-positive chronic myeloid leukemia was made based on genetic tests, including polymerase chain reaction and fluorescence in situ hybridization analysis, which confirmed the presence of the Philadelphia chromosome. Bone marrow biopsy suggested a chronic phase. The patient was treated with hydroxyurea and transitioned to imatinib., Conclusions: Thrombocytosis following splenectomy is a common complication and a plate count to white blood cell count ratio  < 20 indicates infectious etiology. A significantly elevated white blood cell count (> 50 × 10 9 /L) and thrombocytosis (> 2000 × 10 9 /L) may suggest something more ominous, including chronic myeloid leukemia , particularly when elevated granulocyte counts are present. Chronic myeloid leukemia workup includes peripheral smear, bone marrow aspiration, and determination of Philadelphia chromosome. Post-splenectomy vaccines are still indicated within 14 days; however, the timing of immunization with cancer treatment must be considered. Tyrosine kinase inhibitors are the first-line therapy and benefits of pretreatment with hydroxyurea for cytoreduction remain under investigation. Additionally, tyrosine kinase inhibitors have been associated with gastrointestinal perforation and impaired wound healing, necessitating heightened attention in patients with a new bowel anastomosis., (© 2024. The Author(s).)

Competing Interests: The authors declare no conflict of interest.

Background: Retroperitoneal liposarcoma is a rare and complex tumor originating from the mesenchymal tissues, with no specific manifestations in the early stage, and a large tumor size in the late stage. Patients often consult a physician because of large abdominal mass, increased abdominal circumference, and abdominal pain, and rarely because of leukocytosis., Patient Concerns: A 54-year-old female presented to our hospital with complaints of "abdominal distension for over 3 months, left lumbar pain for over 2 months." Considering the comprehensive symptoms, examinations, computed tomography scans, and pathological results, the possibility of retroperitoneal liposarcoma is high., Diagnoses: Retroperitoneal liposarcoma with leukocytosis., Interventions: Open retroperitoneal mass excision along with transcystoscopic left ureteral Double-J Ureterl Stent Insertion tube placement and left nephrectomy., Outcomes: The postoperative pathological findings of the abdominal mass, combined with morphological and immunohistochemical results, are consistent with retroperitoneal liposarcoma. The patient had no recurrence in 7 months of postoperative follow-up conducted on the telephone and is now in continued follow-up., Conclusion: Retroperitoneal liposarcoma is highly malignant and prone to recurrence. Radical surgery is currently the primary treatment modality for patients with this condition. Analogous to cancer patients, those with elevated white blood cell counts and retroperitoneal liposarcoma may have poor prognoses, with a high likelihood of local recurrence and distant metastasis. Close postoperative follow-up is necessary. Therefore, regular postoperative review of blood routine may be a relatively economical and convenient method for the early detection of recurrence and metastasis of retroperitoneal liposarcoma., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

We describe a case of mandibular gingival carcinoma with hypercalcaemia and leukocytosis caused by tumour-derived parathyroid hormone-related protein (PTHrP) and granulocyte colony-stimulating factor (G-CSF). A 54-year-old man presented to our Department of Oral and Maxillofacial Surgery with a chief complaint of a left-sided mandibular gingival ulcer. A 42 mm × 20 mm sized ulcer was found on the left lower molar gingiva. Squamous cell carcinoma was pathologically diagnosed. The patient underwent a hemimandibulectomy, left-sided radical neck dissection, plate reconstruction, pectoralis major musculocutaneous flap reconstruction, and tracheostomy under general anaesthesia. Pathologically, two metastatic lymph nodes were identified. Residual tumour was suspected at the resection margins. Eight weeks after surgery, the patient started postoperative concurrent chemoradiotherapy (CCRT). Two weeks after CCRT, the patient developed hypercalcaemia. Serum levels of PTHrP and G-CSF increased in parallel with the progression of hypercalcaemia and leukocytosis. Immunohistochemical analysis of the surgical specimen showed positivity for G-CSF. Based on these clinical and pathological findings, the patient was diagnosed with hypercalcaemia and leukocytosis associated with malignancy and was treated with denosumab. Irradiation was terminated at 50 Gy because CT showed rapid disease progression. Chemotherapy was initiated, however, four weeks after the start of chemotherapy, a CT scan showed increased metastases and pleural dissemination. Therefore, chemotherapy was discontinued. One week after the chemotherapy was discontinued, the patient died of respiratory failure., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

B-cell prolymphocytic leukemia (B-PLL) was recognized as a distinct entity in the fourth edition of the World Health Organization (WHO) classification for hematolymphoid neoplasms (WHO-HAEM4); however, its de novo presentation has been removed from the upcoming 5th edition classification (WHO-HAEM5). We present a case of a 65-year-old man with leukocytosis, fatigue, and no organomegaly by imaging. Bone marrow examination showed a prolymphocytoid population comprising 78% of the marrow elements. After thorough exclusion of other entities by clinical parameters and ancillary methods, we concluded that this case represents a de novo case of B-PLL., (© 2024. Japanese Society of Hematology.)

Competing Interests: The authors declare no conflict of interest.

Background: Neutrophilia is an increase in the number of neutrophils over 7.5×103/µL. An increase in leukocytes over 50×103/µL is called a leukemoid reaction; and when it is associated with a solid tumor, it is considered a paraneoplastic syndrome called paraneoplastic leukemoid reaction (PLR). It is a very rare clinical condition and it is very unusual for it to be associated with carcinosarcoma. We present two cases of a leukemoid reaction observed in the Medical Oncology Department of the University Hospital of Salamanca between May and September 2023. The main objectives of our article are to describe the unusual appearance of paraneoplastic leukocytosis at the diagnosis of carcinosarcoma carcinosarcoma, explain in a detailed way its diagnostic procedure and to show the poor prognosis to which it is associated., Case Description: In our presentation, we describe two similar cases: first of all, a 60-year-old woman without relevant medical history. She was referred by her primary physician to the Department of Internal Medicine in August 2023 with asthenia, lumbar pain, and weight loss of 12 kg of 3 months of evolution. The physical examination revealed a palpable hypogastric mass. An abdominal, pelvic, and thoracic computed tomography (CT) scan revealed a heterogenous solid mass with necrotic areas originating in the uterus. The anatomopathological diagnosis was carcinosarcoma. The patient showed a progressive worsening in her renal function associated with hyperviscosity secondary to hyperleukocytosis caused by 170×103/µL neutrophils. In the second case we describe the diagnosis of a PLR secondary to a kidney carcinosarcoma. When the patient started chemotherapy, he presented 55.08×103/µL leukocytes, 53.16×103/µL neutrophils. Eight days after receiving chemotherapy, the patient was admitted as an emergency with oligoanuria and decreased consciousness. He presented creatinine 6.25 mg/dL, phosphate 12.4 mg/dL, leukocytes 1.05×103/µL, and neutrophils 0.71×103/µL. The clinical diagnosis was acute exacerbation of multifactorial mixed (renal and prerenal) chronic kidney disease associated with tumor lysis syndrome and grade 3 neutropenia. The patient presented a poor evolution, dying after 2 months., Conclusions: PLR is a severe paraneoplastic syndrome associated with different types of solid tumors. Its appearance at the time of diagnosis of a tumor implies a poor vital prognosis.

Patients with cancer have a higher risk of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), compared to the general population. Cancer-associated thrombosis (CAT) is a thrombotic event that occurs as a complication of cancer or cancer therapy. Major factors determining VTE risk in cancer patients include not only treatment history and patient characteristics, but also cancer type and site. Cancer types can be broadly divided into three groups based on VTE risk: high risk (pancreatic, ovarian, brain, stomach, gynecologic, and hematologic), intermediate risk (colon and lung), and low risk (breast and prostate). This implies that the mechanism of VTE differs between cancer types and that specific VTE pathways may exist for different cancer types. This review summarizes the specific pathways that contribute to VTE in cancer patients, with a particular focus on leukocytosis, neutrophil extracellular traps (NETs), tissue factor (TF), thrombocytosis, podoplanin (PDPN), plasminogen activator inhibitor-1 (PAI-1), the intrinsic coagulation pathway, and von Willebrand factor (VWF)., (© 2024. Japanese Society of Hematology.)

Systemic effects associated with hormones and cytokines secreted by tumor cells can cause paraneoplastic syndrome. Leukemoid reactions and hypercalcemia are relatively common manifestations of paraneoplastic syndrome. Here, we describe the case of a 90-year-old woman who presented with leukocytosis and hypercalcemia and was diagnosed with granulocyte-colony stimulating factor (G-CSF)-producing cervical cancer with elevated levels of parathyroid hormone-related protein (PTHrP). The patient visited our hospital complaining of general fatigue and anorexia. On admission, she presented with marked leukocytosis, hypercalcemia, and an increase in C-reactive protein level. On the basis of abdominal magnetic resonance imaging and histopathological examination, the patient was diagnosed with cervical cancer. Additional tests confirmed elevated plasma levels of G-CSF, PTHrP, and serum interleukin-6. Immunostaining of pathological specimens of the uterine cervix showed expression of G-CSF in tumor cells. The patient was diagnosed with G-CSF-producing cervical cancer accompanied by elevation of PTHrP levels. As a treatment for hypercalcemia, discontinuation of oral vitamin D derivative and administration of saline and elcatonin were ineffective, and therapeutic intervention with zoledronic acid hydrate was required. Considering the patient's advanced age, surgical resection of cervical cancer was not performed. She died from congestive heart failure approximately 3 months after hospitalization. This case was indicated to be a paraneoplastic syndrome in which G-CSF and PTHrP-induced leukocytosis and hypercalcemia. To the best of our knowledge, there have been no reports of G-CSF-producing cervical cancer with elevated PTHrP levels, and our case is the first report., (© 2023. The Author(s) under exclusive licence to The Japan Society of Nephrology.)

Background/aims: Delayed perforation is a rare but serious adverse event of gastric endoscopic submucosal dissection (ESD). The aim of this study was to clarify the clinical features and appropriate management strategy of patients with delayed perforation., Methods: Among 11,531 patients who underwent gastric ESD, the clinical features and outcomes of patients who experienced delayed perforation were retrospectively reviewed and compared with those of the control group., Results: Delayed perforation occurred in 15 of 11,531 patients (0.13%). The patients with delayed perforation were significantly older than those without delayed perforation (p=0.027). The median time to diagnosis of delayed perforation was 28.8 hours (range, 14 to 71 hours). All 15 patients with delayed perforation complained of severe abdominal pain after gastric ESD and underwent subsequent chest X-rays (CXRs) for evaluation. In subsequent CXR, free air was found in 12 patients (80%). For three (20%) patients without free air in CXR, delayed perforation was finally diagnosed by computed tomography. Leukocytosis was significantly less frequent in the patients without free air in CXR (p=0.022). A perforation hole smaller than 1 cm in size was more frequently observed in the six patients who underwent successful non-surgical treatments than in the nine patients who underwent surgery (p<0.001). There was no mortality related to delayed perforation., Conclusions: One-fifth of the patients with delayed perforation did not show free air in CXR and exhibited less leukocytosis than those with free air. Non-surgical treatments including endoscopic closure might be considered as an initial treatment modality for delayed perforation smaller than 1 cm.

Background: Hyperleukocytosis in patients with acute myeloid leukemia (AML) has been associated with worse outcomes. For cytoreduction, leukapheresis has been used but its clinical utility is unknown, and low-dose cytarabine (LD-cytarabine) is used as an alternative method., Methods: Children with newly diagnosed AML treated between 1997 and 2017 in institutional protocols were studied. Hyperleukocytosis was defined as a leukocyte count of ≥100 × 10 9 /L at diagnosis. Clinical characteristics, early complications, survival data, and effects of cytoreductive methods were reviewed. Among 324 children with newly diagnosed AML, 49 (15.1%) presented with hyperleukocytosis. Initial management of hyperleukocytosis included leukapheresis or exchange transfusion (n = 16, considered as one group), LD-cytarabine (n = 18), hydroxyurea (n = 1), and no leukoreduction (n = 14)., Results: Compared with patients who received leukapheresis, the percentage decrease in leukocyte counts following intervention was greater among those who received LD-cytarabine (48% vs. 75%; p = .02), with longer median time from diagnosis to initiation of protocol therapy (28.1 vs. 95.2 hours; p < .001). The incidence of infection was higher in patients (38%) who had leukapheresis than those who receive LD-cytarabine (0%) or leukoreduction with protocol therapy (14%) (p = .008). No differences were noted in the outcomes among the intervention groups. Although patients with hyperleukocytosis had higher incidences of pulmonary and metabolic complications than did those without, no early deaths occurred, and the complete remission, event-free survival, overall survival rates, and outcomes of both groups were similar., Conclusion: LD-cytarabine treatment appears to be a safe and effective means of cytoreduction for children with AML and hyperleukocytosis., (© 2023 American Cancer Society.)

Background: The objective of this study was to evaluate the clinical utility of a routine predischarge WBC count (RPD-WBC) for predicting postdischarge organ space infection (OSI) in children with complicated appendicitis., Study Design: This was a multicenter study using NSQIP-Pediatric data from 14 hospitals augmented with RPD-WBC data obtained through supplemental chart review. Children with fever or surgical site infection diagnosed during the index admission were excluded. The positive predictive value (PPV) for postdischarge OSI was calculated for RPD-WBC values of persistent leukocytosis (≥9.0 × 10 3 cells/μL), increasing leukocytosis (RPD-WBC > preoperative WBC), quartiles of absolute RPD-WBC, and quartiles of relative proportional change from preoperative WBC. Logistic regression was used to calculate predictive values adjusted for patient age, appendicitis severity, and use of postdischarge antibiotics., Results: A total of 1,264 children were included, of which 348 (27.5%) had a RPD-WBC obtained (hospital range: 0.8 to 100%, p < 0.01). The median RPD-WBC was similar between children who did and did not develop a postdischarge OSI (9.0 vs 8.9; p = 0.57), and leukocytosis was absent in 50% of children who developed a postdischarge OSI. The PPV of RPD-WBC was poor for both persistent and increasing leukocytosis (3.9% and 9.8%, respectively) and for thresholds based on the quartiles of highest RPD-WBC values (>11.1, PPV: 6.4%) and greatest proportional change (<32% decrease from preoperative WBC; PPV: 7.8%)., Conclusions: Routine predischarge WBC data have poor predictive value for identifying children at risk for postdischarge OSI after appendectomy for complicated appendicitis., (Copyright © 2023 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

A 61-year-old Japanese woman presented with epigastric pain and jaundice. Imaging showed the presence of primary distal cholangiocarcinoma (DCC). A subtotal stomach-preserving pancreaticoduodenectomy was performed, followed by chemotherapy using S-1. However, second-line chemotherapy with gemcitabine and cis-diamminedichloroplatinum was required for the treatment of hepatic metastasis of the DCC 3 months following the surgery. Nine months after the surgery, the serum calcium and parathyroid hormone-related peptide concentrations were high, at 16.5 mg/dL and 28.7 pmol/L, respectively, which suggested the presence of humoral hypercalcemia of malignancy (HHM) secondary to the DCC. Moreover, marked leukocytosis, with a white blood cell count of 40,400/μL, was also present. The patient died 11 months after the diagnosis of DCC. Because hypercalcemia of malignancy is associated with a poor prognosis, and HHM and leukocytosis caused by DCC are very rare, we have presented the present case in detail and provide a review of the existing literature.

Background: Laparoscopic cholecystectomies continue to pose trouble for surgeons in the face of severe inflammation. In the advent of inability to perform an adequate dissection, a "bailout cholecystectomy" is advocated. Conversion to open or subtotal cholecystectomy is among the standard bailout procedures in such instances., Methods: We performed a retrospective single institution review from January 2016 to August 2019. All patients who underwent a cholecystectomy were included, while those with a concurrent operation, malignancy, planned as an open cholecystectomy, or performed by a low volume surgeon were excluded. Patient characteristics, operative reports, and outcomes were collected, as were surgeon characteristics such as years of experience, case volume, and bailout rate. Univariable and multivariable analysis were performed., Results: 2458 (92.6%) underwent laparoscopic total cholecystectomy (LTC) and 196 (7.4%) underwent a bailout cholecystectomy (BOC). BOC patients tended to be older (p < 0.001), male (p < 0.001), have a longer duration of symptoms (p < 0.001), and higher ASA class (p < 0.001). They also had more signs of biliary inflammation, as evidenced by increased leukocytosis (p < 0.001), tachycardia (p < 0.001), bilirubinemia (p = 0.003), common bile duct dilation (p < 0.001), and gallbladder wall thickening (p < 0.001). The BOC cohort also had increased rates of complications, including bile leak (16%, p < 0.001), retained stone (5.1%, p = 0.005), operative time (114 min vs 79 min, p < 0.001), and secondary interventions (22.7%, p < 0.001). Male gender (aOR = 2.8, p < 0.001), preoperative diagnosis of acute cholecystitis (aOR = 2.2, p = 0.032), right upper quadrant tenderness (aOR = 3.0, p = 0.008), Asian race (aOR = 2.7, p = 0.014), and intraoperative adhesions (aOR = 13.0, p < 0.001) were found to carry independent risk for BOC. Surgeon bailout rate ≥ 7% was also found to be an independent risk factor for conversion to BOC., Conclusions: Male gender, signs of biliary inflammation (tachycardia, leukocytosis, dilated CBD, and diagnosis of acute cholecystitis), as well as surgeon bailout rate of 7% were independent risk factors for BOC., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The blood cell count is often examined in routine clinical praxis. Physiologic leucocyte count is in range 4-10 × 109 in liter of blood. Abnormal values of leukocytes and subtypes of leukocytes in differential count are often present. Changes in leukocytes counts are caused by variety of benignant or malignant conditions. It is important in clinical praxis to interpret changes in blood cell count correctly and choose adequate approach in investigation process. In general, leukocytosis and leukocytopenia may present in primary hematologic disorder or secondary/reactive states, caused by reaction of hematopoiesis to underlying condition. This article review common causes of leukocytosis or leucopenia and give basic advice how to investigate patients with changes in leukocytes count.

Background: Difficulty in interpreting white blood cell (WBC) counts in cerebrospinal fluid (CSF) complicates the diagnosis of neonatal meningitis in traumatic lumbar punctures (LP). The aim of our study was to determine the correction factor for WBC counts in traumatic LP that offers the greatest diagnostic efficacy in meningitis., Methods: We conducted a retrospective observational study of LP in neonates between January 2014 and December 2020. Traumatic LP was defined as a red blood cell (RBC) count ≥ 1,000 cells/mm 3 CSF and pleocytosis as WBCs ≥ 20 cells/mm 3 CSF. The CSF RBC:WBC ratio was analyzed by linear regression to determine a new correction factor. Cell count adjustments were also studied using the 500:1, the 1,000:1 ratio method, and the peripheral blood RBC:WBC ratio, using ROC curves and studies of accuracy (sensitivity and specificity)., Results: Overall, 41.0% of the 1,053 LPs included in the study were traumatic. The best results for effective WBC correction were the method based on the peripheral blood ratio (sensitivity = 1.0 and specificity = 0.9 for bacterial meningitis and sensitivity = 0.8 and specificity = 0.9 for viral meningitis) and the 400:1 ratio (sensitivity = 1.0 and specificity = 0.8 for bacterial meningitis and sensitivity = 0.8 and specificity = 0.8 for viral meningitis) obtained from linear regression (95% CI 381.7-427.4; R2 = 0.7)., Conclusion: Both the peripheral blood correction and the 400:1 correction reduce the number of neonates classified with pleocytosis who were not eventually diagnosed with meningitis. Both methods might be a useful tool to clarify the neonatal meningitis diagnosis, offering neonatologists the possibility to assess the WBC count in traumatic LP., (© 2022. The Author(s).)

Leukostasis is a life-threatening complication of high concentrations of circulating leukemic cells, most often myeloblasts. Effective care of patients with leukostasis involves early recognition and treatment, and aggressive management of concurrent complications of the underlying leukemia. The relatively poor prognosis in patients with leukostasis underscores the importance of the timely and effective care of this hematologic emergency. While cytoreductive measures such as hydroxyurea, corticosteroids, intravenous chemotherapy, and leukapheresis are available to urgently reduce high cell counts, characterization of the leukemia and initiation of tailored, definitive treatment is a parallel priority. However, data supporting any specific cytoreductive approach are limited, making clinical practice guided primarily by expert opinion. In this review, we discuss the pathophysiology, clinical manifestations, diagnosis, and management of leukemic hyperleukocytosis and leukostasis, with an emphasis on how to acutely manage this oncologic emergency in patients with acute myeloid leukemia, which is the most common cause of symptomatic leukostasis.

► Fever ► Cervical lymphadenopathy ► Leukocytosis.

Purpose: This study evaluated the prognostic value of leukocyte, lymphocyte, and neutrophil counts in anal cancer patients undergoing concurrent chemoradiotherapy (CCRT)., Methods: Multi-institutional retrospective data review included 148 non-metastatic anal cancer patients treated with definitive CCRT with 5-fluorouracil plus mitomycin C between the year 2001 and 2019. The median radiation dose to the primary tumor was 54 Gy with a median pelvic dose of 45 Gy. Median follow-up duration was 56 months, and complete blood cell counts were analyzed from baseline to 1 year after the completion of radiotherapy., Results: Although most patients showed a normal number of blood cells before treatment, 6.1% and 4.1% of patients showed leukocytosis (> 10,000/μl) and neutrophilia (> 7500/μl), respectively. After the initiation of treatment, seven patients (4.7%) displayed grade 4 lymphopenia (< 200/μl) at 1 month. Patients with initial leukocytosis showed inferior progression- and locoregional progression-free survival, and neutrophilia was a prognostic factor in all survival outcomes. Grade 4 lymphopenia at 1 month was also significantly associated with overall, progression-, and distant metastasis-free survival. On multivariate analyses, baseline neutrophilia was associated with 56.8-, 22.6-, 10.7-, and 23.0-fold increased risks of death, disease relapse, locoregional progression, and distant metastasis, respectively. Furthermore, lymphocytes < 200/μl at 1 month was linked to 6.8-, 5.4-, and 6.3-fold increased risks for death, disease relapse, and distant metastasis, respectively., Conclusion: The number of leukocytes, lymphocytes, and neutrophils readily acquired from routine blood tests before and during treatment could be an independent prognostic factor of survival in patients with anal cancer., (© 2021. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Introduction: Despite the benefits of the implantation of cardiac rhythm management devices cardiac implantable electronic device (CIED) infection is an emerging problem New debate emerged about the unclear role of the pre-operative alteration of pro-inflammatory parameters, such as leukocytosis, in the development CIED infection and/or heart failure, and its consequent impact on the timing of ICD implantation/reimplantation., Case Report: A 65 years old patient with a history of Diabetes Mellitus (DM) type II, ventricular and supraventricular arrhythmias, chronic myocardial ischemia, heart failure was admitted to hospital. Healthcare workers opted for ICD implantation despite the presence of a persistent leukocytosis with normothermia. Five days later the implantation, patient showed fever and heart failure; blood culture resulted positive for Staphylococcus Aureus. Patient died for sepsis syndrome due to a cardiac device-related infection after a few days, despite the device extraction., Discussion: Cardiac device implantation remains a necessary surgi-cal procedure in order to reduce sudden cardiac death's rate in patients with heart failure. Leukocytosis is a new potential poor prognosis risk factor. The relationship between pro-inflammatory markers', such as CRP and white blood cell count, and device implantation is still not entirely clear. Pro-inflammatory markers could facilitate an infection development; recent study hypothesized that these markers could promote the development of heart failure., Conclusion: Leukocytosis could represent a poor prognosis risk factor favoring the development of CIED infection and/or heart failure.

Leukocytosis is a common finding in patients with ST elevation myocardial infarction (STEMI) and portends a poor prognosis. Interleukin 1-β regulates leukopoiesis and pre-clinical studies suggest that anakinra (recombinant human interleukin-1 [IL-1] receptor antagonist) suppresses leukocytosis in myocardial infarction. However, the effect of IL-1 blockade with anakinra on leukocyte count in patients with STEMI is unknown. We reviewed the white blood cell (WBC) and differential count of 99 patients enrolled in a clinical trial of anakinra (n = 64) versus placebo (n = 35) for 14 days after STEMI. A complete blood cell count with differential count were obtained at admission, and after 72 h, 14 days and 3 months. After 72 h from treatment, anakinra compared to placebo led to a statistically significant greater percent reduction in total WBC count (- 35% [- 48 to - 24] vs. - 21% [- 34 to - 10], P = 0.008), absolute neutrophil count (- 48% [- 60 to - 22] vs. - 27% [- 46 to - 5], P = 0.004) and to an increase in absolute eosinophil count (+ 50% [0 to + 100] vs. 0% [- 50 to + 62], P = 0.022). These changes persisted while on treatment at 14 days and were no longer apparent at 3 months after treatment discontinuation. We found that in patients with STEMI IL-1 blockade with anakinra accelerates resolution of leukocytosis and neutrophilia. This modulation may represent one of the mechanisms by which IL-1 blockade improves clinical outcomes., (© 2022. The Author(s).)

Objective: To evaluate the accuracy of clinical, laboratory and instrumental methods for diagnosis of intestinal ischemia following small bowel obstruction in emergency hospitals., Material and Methods: Multiple-center observational retrospective study enrolled 158 consecutive patients with benign small bowel obstruction (SBO) treated at four hospitals between May 2017 and December 2019. The role of clinical, laboratory and instrumental diagnostic methods for intestinal ischemia was analyzed. We assessed the impact of CT and contrast-enhanced X-ray examination on survival of patients., Results: Laboratory parameters as criteria of ischemia following SBO were similar (leukocytosis >14·10 9 /l ( p =1.0), serum lactate >2.0 mmol/l ( p =0.28), heart rate >90/min ( p =0.71) and fever ( p =0.74)). The only laboratory indicator with significant differences was serum sodium. Decrease in leukocytosis over time was less common in patients with ischemia (25% vs. 61.3%, p =0.012). Univariate Kaplan-Meier analysis did not establish the effect of CT on survival (7.8% [95% CI 7.6-8.0] vs. 6.5% [95% CI 6.3-6.6], p =0.786). Logistic regression revealed 6.4-fold higher chance of accurate diagnosis (ischemia/non-ischemia) in case of CT-based conclusion of ischemia (95% CI 0.025-0.85). Univariate analysis showed that the use of water-soluble contrast for adhesive SBO was associated with lower mortality (4.1% [95% CI 4.0-4.2] vs. 14.3% [95% CI 13.7-14.9], p =0.032) without assessing the comparability of groups., Conclusion: Routine laboratory tests were not specific for intestinal ischemia. Therefore, they should not be considered as the only criteria for surgical tactics in intestinal obstruction. Only CT showed acceptable diagnostic accuracy, and, apparently, only this method has real prospects for improving the quality of diagnosis due to technical support, training of surgeons and specialists for diagnosis.

Indications of leukapheresis (LPh) and the prophylactic use of rasburicase in tumor lysis syndrome (TLS) of patients with acute leukemia with hyperleukocytosis are not clear. In this retrospective single-center pediatric study, the outcomes of patients with hyperleukocytosis were reviewed. There were 48 patients with acute lymphoblastic leukemia (ALL) and 13 patients with acute myeloblastic leukemia (AML). The treatment strategies included hyperhydration, allopurinol administration, strict monitoring, and early initiation of induction chemotherapy (CT). No patient underwent LPh because it was not available. Rasburicase was used only in 3 ALL patients with hyperuricemia when the drug was available. Laboratory and clinical TLS developed in 54.16% and 14.58% of patients with ALL, respectively. Laboratory and clinical TLS developed in 76.92% and 15.38% of patients with AML, respectively. No patient developed grade III to V TLS requiring dialysis. Thirteen patients (21.3%) had pulmonary leukostasis on admission, but recovered with CT and nasal oxygen. During the first 14 days of presentation, cerebral leukostasis/coagulopathy-related early death (ED) was 4.2% and 7.7% in patients with ALL and AML, respectively, and all of these patients had a white blood cell count ≥400,000/µL. There was also 1 infection-related death. Patients with hyperleukocytosis can be treated without LPh and liberal use of rasburicase. Renal failure is no longer a cause of ED. Intracranial hemorrhage is the main cause of ED, especially in patients already presenting with this complication. LPh may be performed in patients with leukostasis, if it is not possible to start induction CT early. When resources are limited, rasburicase should be administered in patients presenting with or developing hyperuricemia and/or renal dysfunction., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Objectives: The two most common autoimmune encephalitides (AE), N -methyl-D-Aspartate receptor (NMDAR) and Leucine-rich Glioma-Inactivated 1 (LGI1) encephalitis, have been known for more than a decade. Nevertheless, no well-established biomarkers to guide treatment or estimate prognosis exist. Neurofilament light chain (NfL) has become an unspecific screening marker of axonal damage in CNS diseases, and has proven useful as a diagnostic and disease activity marker in neuroinflammatory diseases. Only limited reports on NfL in AE exist. We investigated NfL levels at diagnosis and follow-up in NMDAR and LGI1-AE patients, and evaluated the utility of CSF-NfL as a biomarker in AE., Methods: Patients were included from the National Danish AE cohort (2009-present) and diagnosed based upon autoantibody positivity and diagnostic consensus criteria. CSF-NfL was analyzed by single molecule array technology. Clinical and diagnostic information was retrospectively evaluated and related to NfL levels at baseline and follow-up. NMDAR-AE patients were subdivided into: idiopathic/teratoma associated or secondary NMDAR-AE (post-viral or concomitant with malignancies/demyelinating disease)., Results: A total of 74 CSF samples from 53 AE patients (37 NMDAR and 16 LGI1 positive) were included in the study. Longitudinal CSF-NfL levels was measured in 21 patients. Median follow-up time was 23.8 and 43.9 months for NMDAR and LGI1-AE respectively. Major findings of this study are: i) CSF-NfL levels were higher in LGI1-AE than in idiopathic/teratoma associated NMDAR-AE at diagnosis; ii) CSF-NfL levels in NMDAR-AE patients distinguished idiopathic/teratoma cases from cases with other underlying etiologies (post-viral or malignancies/demyelinating diseases) and iii) Elevated CSF-NfL at diagnosis seems to be associated with worse long-term disease outcomes in both NMDAR and LGI1-AE., Discussion: CSF-NfL measurement may be beneficial as a prognostic biomarker in NMDAR and LGI1-AE, and high CSF-NfL could foster search for underlying etiologies in NMDAR-AE. Further studies on larger cohorts, using standardized methods, are warranted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Nissen, Ryding, Nilsson, Madsen, Olsen, Halekoh, Lydolph, Illes and Blaabjerg.)

Introduction: Developing prognostic markers can be useful for clinical decision-making. Peripheral blood (PB) examination is simple and basic that can be performed in any facility. We aimed to investigate whether PB examination can predict prognosis in coronavirus disease (COVID-19)., Methods: Complete blood count (CBC) and PB cell morphology were examined in 38 healthy controls (HCs) and 40 patients with COVID-19. Patients with COVID-19, including 26 mild and 14 severe cases, were hospitalized in Juntendo University Hospital (Tokyo, Japan) between April 1 and August 6, 2020. PB examinations were performed using Sysmex XN-3000 automated hematology analyzer and Sysmex DI-60 employing the convolutional neural network-based automatic image-recognition system., Results: Compared with mild cases, severe cases showed a significantly higher incidence of anemia, lymphopenia, and leukocytosis (P < .001). Granular lymphocyte counts were normal or higher in mild cases and persistently decreased in fatal cases. Temporary increase in granular lymphocytes was associated with survival of patients with severe infection. Red cell distribution width was significantly higher in severe cases than in mild cases (P < .001). Neutrophil dysplasia was consistently observed in COVID-19 cases, but not in HCs. Levels of giant neutrophils and toxic granulation/Döhle bodies were increased in severe cases., Conclusion: Basic PB examination can be useful to predict the prognosis of COVID-19, by detecting SARS-CoV-2 infection-induced multi-lineage changes in blood cell counts and morphological anomalies. These changes were dynamically correlated with disease severity and may be associated with disruption of hematopoiesis and the immunological system due to bone marrow stress in severe infection., (© 2021 John Wiley & Sons Ltd.)

We report the appearance of clinical symptoms and signs of N-methyl-d-Aspartate (NMDA) receptor encephalitis in a patient presenting just days after contraction of influenza B. The offending mature ovarian teratoma was identified and removed on the 10th day after the appearance of symptoms, with subsequent nearly complete resolution of symptoms over the subsequent 6 months. We provide a focused literature review of the clinical and pathophysiologic literature of anti-NMDA receptor encephalitis pertaining to influenza B virus and the pediatric population. Taken together, this study contributes to the pathophysiological understanding of anti-NMDA receptor encephalitis and aids clinicians in its early recognition and management., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Genitourinary tuberculosis (GUTB) is known to cause high rates of structural organ damage, however, literature on its biochemical manifestations is limited. Additionally, local studies in the Philippine setting, where cases are rampant, are few and dated. This study aimed to determine the serologic and urinary profile of patients with GUTB admitted at a tertiary hospital within January 2009 to March 2020 and their association with short-term outcomes., Methods: This retrospective study included 112 patients with laboratory-confirmed GUTB (i.e., positivity in acid-fast smear, polymerase chain reaction, culture, or histology). Demographic data, clinical characteristics, laboratory and radiologic findings, histopathology reports, treatment, and short-term outcomes were recorded., Results: Bladder (54.5%) and kidney (36.4%) were the most affected organs. The male:female ratio was 1:1.15, and the mean age was 35.79 ± 18.29 years. Weakness (14.29%) was the most common chief complaint. A majority presented with anemia (83.04%), while several had leukocytosis (41.96%) and thrombocytosis (26.79%). Hypoalbuminemia (58.10%), impairment of renal function (36.94%), and electrolyte abnormalities such as hyponatremia (50.93%), hypercalcemia (20.19%), and hypokalemia (21.82%) were common. Proteinuria (67.96%) and pyuria (67.96%) were the most frequent abnormal findings, followed by hematuria (51.46%), acidic urine (45.63%) and low specific gravity (31.07%). Age, leukocytosis, and the need for pressors were all significantly associated with mortality (p values of <0.001, 0.010, and <0.001, respectively)., Conclusions: The young age at presentation with severe clinical and laboratory manifestations may reflect local epidemiology as TB continues to be widespread in the country. Apart from the more commonly cited abnormalities in literature, multiple electrolyte imbalances and urinary concentration defects were also observed in many cases, possibly indicating tubulointerstitial involvement-a complication increasingly mentioned in case reports. As several patient characteristics were found to be associated with the high mortality rates observed in the study, further research is recommended to explore predictive modeling., (© 2021. The Author(s).)

Background: The prognosis of acute kidney injury (AKI) varies in children with nephrotic syndrome (NS), data on factors predicting the recovery and recurrence of AKI in children with NS are limited. This study aimed to explore the possible factors predicting the recovery from and recurrence of AKI in children with primary NS., Methods: Children with primary NS complicated with AKI from 1993 to 2017 in a single centre were reviewed retrospectively. The clinical pictures and possible factors predicting the recovery from and recurrence of AKI in children with primary NS were investigated., Results: Sixty-eight episodes of AKI in 59 children with NS were analysed: 88.2% of AKI recovered within 3 months, and 2.9% of AKI did not recover after 3 months. Survival analysis revealed that leucocyturia is significantly related to the AKI recovery time (P = 0.001), and children with leucocyturia [22 (4, 79) days] recovered significantly slower than did children without leucocyturia [12.0 (2, 39) days]. Renal tubular and interstitial injury were prominent in children with leucocyturia, and 11.9% of children with index AKI experienced the recurrence of AKI., Conclusions: Most episodes of AKI that occurred in children with NS recovered completely. Leucocyturia is a significant factor predicting the recovery time of AKI., (© 2021. Japanese Society of Nephrology.)

A 50-year-old man with mitral regurgitation presented with right frontal subcortical hemorrhage. Although he had no fever and his white blood cell count was in the normal range, CT angiography demonstrated a micro cerebral aneurysm, and all three blood cultures were positive for Staphylococcus warneri (S. warneri). Thus, we diagnosed him with infective endocarditis. His condition improved successfully by immediate antibiotics and cerebral aneurysm clipping. S. warneri is a member of coagulase-negative staphylococci that are low-virulence and resident flora of the skin. S. warneri rarely causes infective endocarditis on native valves. Infective endocarditis caused by S. warneri manifests insidious course without inflammatory reactions such as fever and leukocytosis, and thus, diagnosis can be delayed. Attention should be paid to a patient who develops subcortical hemorrhage without a history of hypertension or inflammatory reactions as in this case.

Children with Down syndrome (DS) are at an increased risk of developing transient abnormal myelopoiesis (TAM) and acute leukemia. Aberrant expression of CD56 has been observed on myeloid leukemic blasts in DS patients. In general, CD56 expression in acute myeloid leukemia (AML) is considered a promoter of leukemogenesis. We did a retrospective flow cytometric study to investigate mature myelomonocytic cell CD56 expression patterns in TAM, non-TAM, and leukemia cases with DS. Flow cytometric analysis showed that granulocyte and monocyte aberrant/dysplastic CD56 expression is an inherent characteristic of most DS patients irrespective of the presence of TAM or leukemia. Increased CD56 expression in monocyte and granulocyte populations in DS could be multifactorial; greater expression of RUNX1 secondary to the gene dose effect of trisomy 21 along with the maturational state of the cells are the potential contributors. Unlike AML seen in non-DS patients, CD56 overexpression in DS AML cases does not appear to play a role in leukemogenesis.

Abstract: Acute myeloid leukemia can rarely cause sudden, unexpected death in children. Presentation may be non-specific and death may occur in children with no prior medical history. Herein we present the case of a previously healthy 2-year and 2 month-old White girl, who on autopsy, was found to have acute myeloid leukemia with KMT2A rearrangement extensively involving all major thoracic and abdominal organs. This case is presented to the forensic community to discuss the presentation and findings in sudden death caused by acute leukemia. The case highlights when acute leukemia should enter the differential as a potential cause of death, as well as potential resources available in the postmortem workup of acute leukemias., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

It is common practice to perform a lumbar puncture in infants presenting with fever and a bulging fontanelle in order to rule out bacterial meningitis. However, most of these infants have benign, self-limiting diseases. The objective was to determine whether there is an association between bulging fontanelle and bacterial meningitis in febrile infants. This retrospective cohort study included febrile children with a bulging fontanelle who underwent lumbar puncture at Meir Medical Center from 2005 through 2015. A total of 764 children ages 2-18 months underwent lumbar puncture during the study period. Among them, 304 had a bulging fontanelle and fever on evaluation and cerebrospinal fluid pleocytosis was found in 115 (37.8%), including 1 case of bacterial meningitis (0.3%). None of the infants described on admission as appearing well on presentation was found to have bacterial meningitis. Of the 764 children who underwent lumbar puncture, 10 infants were diagnosed with bacterial meningitis, and only one (10%) presented with a bulging fontanelle.Conclusion: The finding of a bulging fontanelle has very low sensitivity and specificity for bacterial meningitis. Most causes of a bulging fontanelle in febrile infants are self-limiting diseases. The routine approach of performing a lumbar puncture in febrile infants with a bulging fontanelle should be reconsidered. What is Known: • It is common to perform a lumbar puncture in febrile infants with a bulging fontanelle, to rule out bacterial meningitis. • However, there are only few researches regarding the relationship between bulging fontanelle and bacterial meningitis. What is New: • The finding of a bulging fontanelle has very low sensitivity and specificity for bacterial meningitis • The need for routine lumbar puncture in these cases should be reconsidered.

A concerning development during the coronavirus disease pandemic has been multisystem inflammatory syndrome in children. Reports of this condition in East Asia have been limited. In South Korea, 3 cases were reported to the national surveillance system for multisystem inflammatory syndrome in children. All case-patients were hospitalized and survived with no major disease sequelae.

Particulate matter (PM) induces neutrophilic inflammation and deteriorates the prognosis of diseases such as cardiovascular diseases, cancers, and infections, including COVID-19. Here, we addressed the role of γδ T cells and intestinal microbiome in PM-induced acute neutrophilia. γδ T cells are a heterogeneous population composed of Tγδ1, Tγδ2, Tγδ17, and naïve γδ T cells (TγδN) and commensal bacteria promote local expansion of Tγδ17 cells, particularly in the lung and gut without affecting their Vγ repertoire. Tγδ17 cells are more tissue resident than Tγδ1 cells, while TγδN cells are circulating cells. IL-1R expression in Tγδ17 cells is highest in the lung and they outnumber all the other type 17 cells such as Th17, ILC3, NKT17, and MAIT17 cells. Upon PM exposure, IL-1β-secreting neutrophils and IL-17-producing Tγδ17 cells attract each other around the airways. Accordingly, PM-induced neutrophilia was significantly relieved in γδ T- or IL-17-deficient and germ-free mice. Collectively, these findings show that the commensal microbiome promotes PM-induced neutrophilia in the lung via Tγδ17 cells., Competing Interests: S-HI is the CEO of the ImmunoBiome. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yang, Kwon, Kim, Im and Lee.)