How I manage inpatient consultations for quantitative neutrophil abnormalities in adults.

Neutrophilia and neutropenia commonly lead to inpatient hematology consultation. Quantitative neutrophil abnormalities have a broad differential and include diagnoses that are important to recognize because they may be associated with increased mortality. Neutrophilia can reflect etiologies such as infection, medications, inflammation, splenectomy, and congenital disorders. Neutropenia can arise from infection, medications, autoimmune destruction, sequestration, nutritional deficiency, malignancy, and congenital neutropenia syndromes. In the evaluation of all abnormalities of neutrophil number, the timing of the change, and the patient's historical neutrophil count are crucial.

Inhalations with thermal waters in respiratory diseases.

ETHNOPHARMACOLOGICAL RELEVANCE: Inhalations with thermal waters are an old therapeutic method used in the therapy of respiratory diseases as a treatment of choice showing a long-lasting outcome with no side effects. Paradoxically, there is little well-established research on their mechanisms of action. AIM OF THE STUDY: The aim of this paper is therefore to summarize the influence of inhalatory treatment with thermal waters on the main symptoms and features of respiratory disorders including allergy-like symptoms, inflammation, oxidant-anti-oxidant balance, cellular influx, disturbed mucus secretions, recurrent infections, pulmonary and nasal function and quality of life. A short history of inhalations is also presented. MATERIALS AND METHODS: The present paper is a sum-up of research articles on the use of inhalations with thermal waters in respiratory disorders. RESULTS: According to the herein presented literature, the use of thermal water inhalations is beneficial for almost all manifestations of respiratory diseases. The mode of their action remains still unclear; however, it seems that the most important one relies on the restoration of proper defense mechanisms of the organism. CONCLUSIONS: Inhalations with thermal waters alleviate symptoms of respiratory diseases. They also improve the quality of life of the patients and seem to be a good add-on therapy in the treatment of disorders of the respiratory system.

Leukocyte-Related Disorders: A Review for the Pediatrician.

Leukocytes, or white blood cells, are part of the innate immune system that defends against infectious and foreign agents. In pediatrics, it is important to use age-specific laboratory values when interpreting results. Infections are the most common cause of leukocytosis or leukopenia in children. Symptoms suggestive of more serious etiologies include persistent fevers, weight loss, bruising, fatigue, and adenopathy. Neutropenia is of special importance in pediatrics due to associations of severe neutropenia with genetic syndromes and overlapping presentations with primary immunodeficiencies. Although the discovery of novel genetic mutations has aided the hematologist/oncologist and the immunologist in managing these conditions, the relationship between clinical phenotype and mutation is still not well known. [Pediatr Ann. 2020;49(1):e17-e26.].

Flushing Disorders Associated with Gastrointestinal Symptoms: Part 1, Neuroendocrine Tumors, Mast Cell Disorders and Hyperbasophila.

Flushing is the subjective sensation of warmth accompanied by visible cutaneous erythema occurring throughout the body with a predilection for the face, neck, pinnae, and upper trunk where the skin is thinnest and cutaneous vessels are superficially located and in greatest numbers. Flushing can be present in either a wet or dry form depending upon whether neural-mediated mechanisms are involved. Activation of the sympathetic nervous system results in wet flushing, accompanied by diaphoresis, due to concomitant stimulation of eccrine sweat glands. Wet flushing is caused by certain medications, panic disorder and paroxysmal extreme pain disorder (PEPD). Vasodilator mediated flushing due to the formation and release of a variety of biogenic amines, neuropeptides and phospholipid mediators such as histamine, serotonin and prostaglandins, respectively, typically presents as dry flushing where sweating is characteristically absent. Flushing occurring with neuroendocrine tumors accompanied by gastrointestinal symptoms is generally of the dry flushing variant, which may be an important clinical clue to the differential diagnosis. A number of primary diseases of the gastrointestinal tract cause flushing, and conversely extra-intestinal conditions are associated with flushing and gastrointestinal symptoms. Gastrointestinal findings vary and include one or more of the following non-specific symptoms such as abdominal pain, nausea, vomiting, diarrhea or constipation. The purpose of this review is to provide a focused comprehensive discussion on the presentation, pathophysiology, diagnostic evaluation and management of those diseases that arise from the gastrointestinal tract or other site that may cause gastrointestinal symptoms secondarily accompanied by flushing. This review is divided into two parts given the scope of conditions that cause flushing and affect the gastrointestinal tract: Part 1 covers neuroendocrine tumors (carcinoid, pheochromocytomas, vasoactive intestinal polypeptide, medullary carcinoma of the thyroid), polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes (POEMS), and conditions involving mast cells and basophils; while Part 2 covers dumping syndrome, mesenteric traction syndrome, rosacea, hyperthyroidism and thyroid storm, anaphylaxis, panic disorders, paroxysmal extreme pain disorder, and food, alcohol and medications.

Proposed diagnostic criteria and classification of basophilic leukemias and related disorders.

Basophils form a distinct cell lineage within the hematopoietic cell family. In various myeloid neoplasms, including chronic myeloid leukemia, basophilia is frequently seen. Acute and chronic basophilic leukemias, albeit rare, have also been described. However, no generally accepted criteria and classification of basophilic leukemias have been presented to date. To address this unmet need, a series of Working Conferences and other meetings were organized between March 2015 and March 2016. The current article provides a summary of consensus statements from these meetings, together with proposed criteria to delineate acute basophilic leukemia (ABL) from chronic basophilic leukemia (CBL) and primary forms of the disease where no preceding myeloid malignancy is detected, from the more common 'secondary' variants. Moreover, the term hyperbasophilia (HB) is proposed for cases with a persistent peripheral basophil count ⩾1000 per µl of blood. This condition, HB, is highly indicative of the presence of an underlying myeloid neoplasm. Therefore, HB is an important checkpoint in the diagnostic algorithm and requires a detailed hematologic investigation. In these patients, an underlying myeloid malignancy is often found and is then labeled with the appendix -baso, whereas primary cases of ABL or CBL are very rare. The criteria and classification proposed in this article should facilitate the diagnosis and management of patients with unexplained basophilia and basophil neoplasms in routine practice, and in clinical studies.

Neutrophilic dermatosis of the dorsal hands: a restrictive designation for an acral entity.

In 2000, Galaria et al. proposed the designation neutrophilic dermatosis of the dorsal hands (NDDH). The authors describe a case of NDDH with predominant involvement of the palmar aspect of the hands in a patient suffering from lung cancer, a possible paraneoplastic manifestation. Therefore, the term NDDH is not accurate because palmar manifestations of this dermatosis are also possible.

[Neutrophil disorders: diagnosis and hematopoietic stem cell transplantation].

Neutrophil disorders are classified into abnormal neutrophil function and granulopoiesis. The identification of genetic defects causing neutropenia and neutrophil dysfunction has revealed the mechanisms controlling myeloid differentiation and their functions. The International Union of Immunological Societies of Primary Immunodeficiencies represents the most current catalog of approximately 30 neutrophil disorders. In this report, we show the progress made in studies of the pathophysiology and treatment of these disorders, focusing on chronic granulomatous disease (CGD) and severe congenital neutropenia (SCN). Hematopoietic stem cell transplantation (HSCT) is the only available curative therapy for CGD and SCN. However, the use of HSCT as treatment for both diseases is limited by transplant-related mortality (TRM) because of active infections and intractable inflammatory complications. Recently, reduced-intensity conditioning regimens have been introduced to minimize the TRM and the late adverse effects of HSCT for both diseases. The results of HSCT using the RIC regimen for 40 patients with CGD and SCN in Hiroshima University Hospital are summarized herein. Determining the optimal line of treatment will require further accumulation to cases to refine HSCT for both diseases.

Granulocyte transfusions for preventing infections in people with neutropenia or neutrophil dysfunction.

BACKGROUND: Despite modern antimicrobials and supportive therapy, bacterial and fungal infections are still major complications in people with prolonged disease-related or therapy-related neutropenia. Since the late 1990s there has been increasing demand for donated granulocyte transfusions to treat or prevent severe infections in people who lack their own functional granulocytes. This is an update of a Cochrane review first published in 2009. OBJECTIVES: To determine the effectiveness and safety of prophylactic granulocyte transfusions compared with a control population not receiving this intervention for preventing all-cause mortality, mortality due to infection, and evidence of infection due to infection or due to any other cause in people with neutropenia or disorders of neutrophil function. SEARCH METHODS: We searched for randomised controlled trials (RCTs) and quasi-RCTs in the Cochrane Central Register of Controlled Trials (Cochrane Library 2015, Issue 3), MEDLINE (from 1946), EMBASE (from 1974), CINAHL (from 1937), theTransfusion Evidence Library (from 1980) and ongoing trial databases to April 20 2015. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs comparing people receiving granulocyte transfusions to prevent the development of infection with a control group receiving no granulocyte transfusions. Neonates are the subject of another Cochrane review and were excluded from this review. There was no restriction by outcomes examined, but this review focuses on mortality, mortality due to infection and adverse events. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by The Cochrane Collaboration. MAIN RESULTS: Twelve trials met the inclusion criteria. One trial is still ongoing, leaving a total of 11 trials eligible involving 653 participants. These trials were conducted between 1978 and 2006 and enrolled participants from fairly comparable patient populations. None of the studies included people with neutrophil dysfunction. Ten studies included only adults, and two studies included children and adults. Ten of these studies contained separate data for each arm and were able to be critically appraised. One study re-randomised people and therefore quantitative analysis was unable to be performed.Overall, the quality of the evidence was very low to low across different outcomes according to GRADE methodology. This was due to many of the studies being at high risk of bias, and many of the outcome estimates being imprecise.All-cause mortality was reported for nine studies (609 participants). There was no difference in all-cause mortality over 30 days between people receiving prophylactic granulocyte transfusions and those that did not (seven studies; 437 participants; RR 0.92, 95% CI 0.63 to 1.36, very low-quality evidence).Mortality due to infection was reported for seven studies (398 participants). There was no difference in mortality due to infection over 30 days between people receiving prophylactic granulocyte transfusions and those that did not (six studies; 286 participants; RR 0.69, 95% CI 0.33 to 1.44, very low-quality evidence).The number of people with localised or systemic bacterial or fungal infections was reported for nine studies (609 participants). There were differences between the granulocyte dose subgroups (test for subgroup differences P = 0.01). There was no difference in the number of people with infections over 30 days between people receiving prophylactic granulocyte transfusions and those that did not in the low-dose granulocyte group (< 1.0 x 10(10) granulocytes per day) (four studies, 204 participants; RR 0.84, 95% CI 0.58 to 1.20; very low-quality evidence). There was a decreased number of people with infections over 30 days in the people receiving prophylactic granulocyte transfusions in the intermediate-dose granulocyte group (1.0 x 10(10) to 4.0 x 10(10) granulocytes per day) (4 studies; 293 participants; RR 0.40, 95% CI 0.26 to 0.63, low-quality evidence).There was a decreased number of participants with bacteraemia and fungaemia in the participants receiving prophylactic granulocyte transfusions (nine studies; 609 participants; RR 0.45, 95% CI 0.30 to 0.65, low-quality evidence).There was no difference in the number of participants with localised bacterial or fungal infection in the participants receiving prophylactic granulocyte transfusions (six studies; 296 participants; RR 0.75, 95% CI 0.50 to 1.14; very low-quality evidence).Serious adverse events were only reported for participants receiving granulocyte transfusions and donors of granulocyte transfusions. AUTHORS' CONCLUSIONS: In people who are neutropenic due to myelosuppressive chemotherapy or a haematopoietic stem cell transplant, there is low-grade evidence that prophylactic granulocyte transfusions decrease the risk of bacteraemia or fungaemia. There is low-grade evidence that the effect of prophylactic granulocyte transfusions may be dose-dependent, a dose of at least 10 x 10(10) per day being more effective at decreasing the risk of infection. There is insufficient evidence to determine any difference in mortality rates due to infection, all-cause mortality, or serious adverse events.

Evaluation of neutropenia and neutrophilia in preterm infants.

OBJECTIVE: Neutrophil counts are used routinely as part of the sepsis evaluation in newborn infants. In this article, we review the normal blood neutrophil concentrations and the clinical approach to neutropenia and neutrophilia in the neonatal period. METHODS: A literature search was performed using the databases PubMed, EMBASE, and Scopus, and the electronic archive of abstracts presented at the annual meetings of the Pediatric Academic Societies. RESULTS: Neutropenia and neutrophilia are documented frequently in premature infants. Neutropenia can be seen in up to 8% of all infants admitted to neonatal intensive care. Neutrophilia is even more common, reported in up to 40% of all preterm infants. CONCLUSIONS: Neutrophil counts should be carefully evaluated in premature neonates. Maternal and perinatal history, physical examination, and a limited laboratory assessment is usually adequate for making a diagnosis in most infants.

Preoperative preparation of the patient with the abnormalities of red and white blood cells.

The complete peripheral blood count analysis including laboratory screening tests of haemostasis and coagulation should be done in every patient before surgery, in order to detect specific abnormalities for primary or secundary haematologic disorder. These abnormalities might be very important course of perioperative and postoperative complications. Anaemia is the most frequent haematologic abnormality seen during preoperative period. Therapy approach depends on the type and anaemia degree, and also on the type and time of surgery. If surgery is not urgent specific therapy according to the anaemia type (iron therapy, vitamin B12, folic acid, corticosteroids, recombinant erythropoietin) should be given in all anaemias with deficiency of iron, megaloblastic anaemias, acquired haemolytic anaemias and anaemias in end stage renal disease. Transfusion of red cells are most frequently given in patients with normovolemic anaemias with haemoglobin level of 10.0 g/dl and hematocrit of 0.30, but lower levels in haemodynamic stable patients. Venesections should be done in patients with erythrocytosis in order to reduce total red cell volume, but taking into account the perioperative bleeding. Patients with leukocyte abnormalities suspected on primary haematologic disorder need urgent haematologic diagnostic procedures. In patients with leucocytosis the actual level of neutropenia is the bigger problem than the level of leucocytosis. In those patients treatment generally involves preventing infections, managing of febrile neutropenia with broad spectrum antibiotics and antifungal drugs, treatment with recombinant granulocyte hematopoetic factor, rarely transfusions of granulocyte concentrates and intravenous immunoglobulins.

Granulocyte transfusions for preventing infections in patients with neutropenia or neutrophil dysfunction.

BACKGROUND: Since the late 1990s there has been increasing demand for donated granulocyte transfusions to treat or prevent severe infections in patients who lack their own functional granulocytes. Other than in neonates, no systematic reviews have been performed for over 10 years relating to the efficacy of prophylactic granulocyte transfusions. OBJECTIVES: To determine the effectiveness and safety of granulocyte transfusions compared with a control population not receiving this intervention for preventing mortality due to infection or due to any other cause in patients with neutropenia or disorders of neutrophil function. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) Issue 3, 2008, MEDLINE, EMBASE and other specialised databases up to October 2008. We also searched reference lists of articles and contacted experts in the field. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing patients receiving granulocyte transfusions to prevent the development of infection with a control group receiving no granulocyte transfusions. Neonates have been the subject of a recent review and were excluded. There was no restriction by outcomes examined, but this review focuses on mortality, mortality due to infection and adverse events. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed potentially relevant studies for inclusion. Data were extracted by two review authors and the methodological quality was examined. Data were analysed using random and fixed effects models. MAIN RESULTS: Ten trials met the inclusion criteria. Allocation in all trials was random, with the control arm receiving no prophylactic therapy, except one trial in which the control group received specific prophylactic antibiotics. One study reported biological randomisation based upon the availability of suitably matched, related donors rather than strict randomisation. All trials were conducted over twenty years ago with one exception, a study from 2006 in which donors were pre-medicated with granulocyte colony stimulating factor (G-CSF) resulting in significantly higher mean doses of granulocytes collected for transfusion. Different policies otherwise applied for the schedule for transfusion, method of granulocyte procurement and criteria for defining infection. Combining the results showed a relative risk (RR) for mortality of 0.94 (95% confidence intervals (CI) 0.71 to 1.25). Exclusion of the two trials which reported transfusion of an average number of granulocytes below 1 x 10(10) indicated a summary RR for mortality and mortality due to infection of 0.89 (CI 0.64 to 1.24) and 0.36 (0.14 to 0.96) respectively. IMPLICATIONS FOR CLINICAL PRACTICE: The controlled trials that have been identified raise the possibility that prophylactic granulocyte transfusions at a dose of at least 1 x 10(10) may reduce the risk of mortality from infection. Overall mortality was not affected. However, the majority of studies were performed decades ago, and standards of supportive care have advanced considerably. These earlier trials were also based on transfusing lower yields of collected granulocytes than currently recommended. It is difficult to recommend prophylactic granulocyte transfusions outside the setting of ongoing controlled trials, given the resource and cost implications. IMPLICATIONS FOR RESEARCH: Larger trials are needed to establish the validity of the potential benefits raised by this review, in view of the methodological limitations, the small sample sizes and the heterogeneous definitions of infection that were encountered in the included studies.

[Relationship between electroacupuncture-induced regulatory effect on leukocytes and the caliber of splenic sinusoid basal lamina eyehole on rabbits].

OBJECTIVE: To study the underlining mechanism of electroacupuncture (EA) in regulating leukocyte counts in the rabbit. METHODS: A total of 75 rabbits were randomly divided into normal control, leukocytosis model, leukocytosis + EA, leukopenia model, leukopenia+EA groups, with 15 cases in each. EA (2-20 Hz, 1-2 mA) was applied to "Dazhui" (DU 14), bilateral "Zusanli" (ST 36) and bilateral "Geshu" (BL 17) for 20 min, once daily for 5 days. Leukocytosis and leukopenia models were duplicated by intravenous injection of coliform (0.1 ml/kg) and cyclophosphamide (30 mg/kg) separately. Peripheral blood leukocyte counts were detected every day. At the end of the experiment, the rabbit's spleen tissue was collected under anesthesia, and the diameter of splenic sinusoid basal lamina eyehole was measured under scanning electronic microscope. RESULTS: Compared with normal control group, after i.v. coliform and cyclophosphamide, leukocytes increased and decreased significantly and respectively, while the area of the splenic sinusoid basal lamina eyehole in leukocytosis model group increased lightly and that of leukopenia model group reduced obviously (P < 0.01). In comparison with their individual model group, the leukocyte count in leukocytosis + EA group decreased considerably (P < 0.05), while that of leukopenia + EA group increased markedly (P < 0.01). The area of splenic sinusoid basal lamina eyehole in leukocytosis+ EA group decreased apparently (P < 0.05), and that in leukopenia+ EA group increased remarkably (P < 0.05). CONCLUSION EA is able to regulate the leukocyte counts in coliform-induced leukocytosis and cyclophosphamide-induced leukopenia rabbits, which may be related with its effects in improving the splenic sinusoid basal lamina eyehole activity.

Reversal in fatigued athletes of a defect in interferon gamma secretion after administration of Lactobacillus acidophilus.

BACKGROUND: Fatigue and impaired performance in athletes is well recognised and has been loosely linked to "overtraining". Reduced concentration of IgA in the saliva and increased shedding of Epstein Barr virus (EBV) have been associated with intense training in elite athletes. OBJECTIVE: To determine whether athletes presenting with fatigue and impaired performance had an immune defect relevant to defective containment of EBV infection, and whether a probiotic preparation (Lactobacillus acidophilus) shown to enhance mucosal immunity in animal models could reverse any detected abnormality. RESULTS: The fatigued athletes had clinical characteristics consistent with re-activation of EBV infection and significantly (p = 0.02) less secretion of interferon (IFN) gamma from blood CD4 positive T cells. After one month of daily capsules containing 2 x 10(10) colony forming units of L acidophilus, secretion of IFNgamma from T cells had increased significantly (p = 0.01) to levels found in healthy control athletes. A significant (p = 0.03) increase in salivary IFNgamma concentrations in healthy control athletes after the one month course of L acidophilus demonstrated in man the capacity for this probiotic to enhance the mucosal IFNgamma concentration. CONCLUSION: This is the first evidence of a T cell defect in fatigued athletes, and of its reversal following probiotic therapy.

Recurrent lymphocytic hypophysitis in a woman 27 years after subtotal adrenalectomy for hypercortisolism possibly of autoimmune origin.

Lymphocytic hypophysitis commonly occurs in females in peripartum period but several unusual presentations have been reported. Here we report a rare case of recurrent lymphocytic hypophysitis in a woman who had subtotal adrenalectomy for hypercortisolism 27 years back. Polyglandular autoimmune endocrinopathy with an uncommon combination of Cushing's syndrome and recurrent hypophysitis is a strong possibility in this case. Treatment with steroids has been found to have beneficial effect.

Toward gene therapy for human CD3 deficiencies.

The CD3 subunits of the T cell receptor-CD3 complex (TCR-CD3) help to regulate surface TCR-CD3 expression, and participate in signal transduction leading to intrathymic selection and peripheral antigen recognition by T lymphocytes. Humans who lack individual CD3 chains show impairments in the expression and activation-induced downregulation of TCR-CD3, and the defective immune responses that result may be lethal. We have investigated delivery of a normal CD3 chain to treat disorders of this type. Retroviral transduction of CD3gamma into CD3gamma-deficient peripheral blood T lymphocytes from two unrelated patients selectively corrected the observed TCR-CD3 expression and downregulation defects, but unexpectedly seemed to cause adverse effects that can be explained by an autoreactive recognition mechanism. These data support the feasibility of gene therapy for human CD3 deficiencies, but also suggest that gene transfer into postthymic lymphocytes carrying mutations on T cell recognition or activation pathways may disrupt their intrathymic calibration and become harmful to the host.

A practical approach to neutrophil disorders.

This review discusses disorders of altered neutrophil number and function and provide a basic framework for patient evaluation and management. The sections begin with neutropenia, neutrophilia and neutrophil dysfunction with a general screening approach to differentiate common, more benign syndromes from rare, often more serious disorders. Also included is a detailed discussion of some specific primary neutrophil syndromes at the end of each section. Focus is placed on specific disorders that are clinically common or particularly instructive.