Search

Background: Plasma cell-free DNA Next-Generation Sequencing has been used as a non-invasive and comprehensive method for the etiological diagnosis of infectious diseases. However, only a handful of studies have described the real-world utility of this technique in patients with hematological disorders, a cohort of patients that are distinctive due to neutropenia and weakened immune functions., Methods: We retrospectively analyzed the results of plasma cell-free DNA sequencing performed on 184 and 163 specimens collected from hematological patients suspected of infections with (Group I) or without (Group II) neutropenia, respectively. The diagnostic performance and the clinical impact of plasma sequencing were comparatively evaluated to conventional microbiological tests and a composite reference standard (conventional tests combined with the clinical assessment)., Results: The overall positive detection rate of plasma cell-free DNA sequencing was significantly higher than that of conventional microbiological tests (72.6% vs.31.4%, P < 0.001). The positive rate of conventional microbiological tests in Group I was lower than that in Group II (25.5% vs. 38.0%, P = 0.012). Combining plasma sequencing with conventional tests yielded a positive detection rate of 75.0% and 74.8% for these two groups, respectively. Using the composite reference standard, the sensitivity and specificity of plasma sequencing were 89.1% and 65.1%, respectively. The proportions of the positive impact of cell-free DNA sequencing results in the Group I were higher than in the Group II in terms of both diagnosis and treatment (diagnosis: 54.3% vs. 40.5%, P = 0.013; treatment: 45.7% vs.30.7%, P = 0.004). A total of 73 patients (21.0%) benefited from plasma sequencing through adjustment of the antibiotic regimen., Conclusions: The diagnostic yield of conventional microbiological tests was low in patients with neutropenia. Combining conventional tests with plasma cell-free DNA sequencing significantly improved the detection rate for pathogens and optimized antibiotic treatment. Our findings on the clinical impact warrant confirmation through larger, multicenter, randomized controlled trials. Moreover, the cost-effectiveness of this testing strategy remains unknown and requires further exploration., Competing Interests: Declaration of Competing Interest The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Pulmonary complications are common in children with hematologic or oncologic diseases, and many experience long-term effects even after the primary disease has been cured. This article reviews pulmonary complications in children with cancer, after hematopoietic stem cell transplant, and caused by sickle cell disease and discusses their management., Competing Interests: Disclosure This research was funded by the American Lebanese Syrian Associated Charities (ALSAC)., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: There has been a dramatic increase in penetrating gunshot-inflicted civilian penetrating brain injuries (cvPBI). We undertook a systematic review with exclusive focus on the management of cvPBI., Methods: We explored: (1) cervical spine immobilization, (2) seizure incidence and prophylaxis, (3) infection incidence and antibiotic prophylaxis, (4) coagulopathy (5) vascular complications, and (6) surgical management. We searched PubMed, EMBASE, and Cochrane (1985-2019). The PRISMA guidelines were followed. The Newcastle-Ottawa Scale was employed for qualitative assessment; risk of bias was evaluated based upon the RTI item bank. The full protocol was registered to PROSPERO (CRD42019118877)., Results: The literature is scant, and of overall low quality and high risk of bias. Incidence of c-spine injury with no direct trauma is low; incidence of seizures does not appear to be different from non-penetrating mechanisms; there is no robust data for prophylactic antibiotics; coagulopathy is prevalent and has been independently associated with outcome; there is a high incidence of vascular injuries with traumatic intracranial aneurysms the most common sequelae; neurosurgical decision-making appears largely influenced by operator's assessment of salvageability. Surgery has been associated with decreased mortality., Conclusions: Limited amount of published work is clinically meaningful; this systematic review identified key knowledge gaps., (Copyright © 2019. Published by Elsevier Inc.)

Abnormal uterine bleeding is common in adolescents and is thought to affect 9% to 14% of women in their reproductive years. Certain unique aspects of underlying inherited or acquired blood disorders exacerbate the "expected" hormonal imbalance at this age, thereby increasing the morbidity of the underlying problem. A multifactorial etiology demands a collaborative approach between hematologists and gynecologists or adolescent medicine physicians to effectively manage abnormal uterine bleeding in young women with blood disorders., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Invasive fungal disease (IFD) is a disease of immunocompromised hosts. Cytokines are important mediators of innate and adaptive immune system. The aim of this study was to identify cytokine profiles that correlate with increased risk of IFD., Methods: We prospectively enrolled 172 adult haematology patients undergoing intensive chemotherapy, immunosuppressive therapy, and haematopoietic stem cell transplantation. Pro-inflammatory cytokine profiling using 30-plex Luminex assay was performed at baseline and during treatment. Nine single nucleotide polymorphisms (TLR1, TLR2, TLR3, TLR4.1, TLR4.2, TLR6, CLEC7A, CARD9, and INFG) were investigated among transplant recipients and donors., Findings: The incidence of IFD in this cohort was 16.9% (29/172). Median baseline serum concentrations of IL-15, IL-2R, CCL2, and MIP-1α were significantly higher whilst IL-4 was lower in patients with proven/probable IFD compared to those with no evidence of IFD. Baseline high IL-2R and CCL2 were associated with increased risk of IFD in the multivariate analysis (adjusted hazard ratio 2.3 [95% CI 1.1-5.1; P = 0.037], and hazard ratio 2.7 [95% CI 1.2-6.1; P = 0.016], respectively). However, these differences were not significant in follow up measurements. Similarly, no significant independent prognostic value was associated with baseline cytokine profile., Interpretation: High baseline IL-2R and CCL2 concentrations were independent indicators of the risk of developing IFD and could be used to identify patients for enhanced prophylaxis and early antifungal therapy., (Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.)

Clinical trials have provided guidance in developing triggers for transfusing in the hemodynamically stable patient. These studies have identified that improved outcomes can be obtained in the massively transfused patient when platelets and fresh frozen plasma are transfused with packed red blood cells. Studies that characterize the complications of transfusions, such as transfusion-related acute lung injury and poor cancer-related outcomes, are discussed. Emerging data that characterize the risk factors associated with transfusion-related acute lung injury and suggest metastasis and local recurrence occur at a higher rate in the transfused patient are discussed. Hematologic disorders commonly encountered by surgeons are discussed., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Aims: This paper describes a national audit of the indications for, and techniques and toxicity of, palliative splenic radiotherapy in haematological disorders., Materials and Methods: A postal questionnaire was sent to consultant clinical oncologists treating haematological malignancies in the UK., Results: The response rate was 76%. The audit shows chronic lymphocytic leukaemia, myelofibrosis and chronic myeloid leukaemia to be the most common underlying conditions in which splenic irradiation is used. Painful splenomegaly and hypersplenism were the most common indications. Dose fractionation schedules vary widely across the UK, and also the level of full blood counts used to interrupt radiotherapy., Conclusions: Palliative splenic radiotherapy continues to be widely used in the UK in small numbers of patients and seems to be well tolerated. Re-irradiation for further symptomatic progression is also commonly carried out.

The prototype member of the Betaherpesvirinae subfamily, cytomegalovirus (CMV), is the most important infectious pathogen in transplant recipients, including those receiving bone marrow or stem cell grafts. Overt CMV disease such as pneumonitis is notoriously difficult to treat. Antiviral prophylaxis, rapid diagnostic tests to identify CMV infection, and preemptive antiviral chemotherapy are significant improvements in the management of CMV. As the kinetics of the immune response to CMV become better defined, immunotherapeutic approaches should be introduced to complement current management strategies. Two newly identified betaherpesviruses, human herpesvirus-6 (HHV-6) and human herpesvirus-7 (HHV-7), are genetically more closely related to each other than to CMV. Both are highly prevalent in the general population and infections post-bone marrow transplantation are common. These viruses are not as pathogenic as CMV but HHV-6 at least can cause disease such as encephalitis, hepatitis, and bone marrow suppression. Both of these newer herpesviruses are potentially susceptible to existing and licensed antiherpesvirus drugs., (Copyright 2003 Elsevier Inc. All rights reserved.)

Although the risk factors for stroke in children are numerous and differ greatly from the causes of stroke in adults, a thorough diagnostic evaluation can identify one or more risk factors in most patients. Cardiac disorders and hemoglobinopathy are the most common causes of ischemic infarction, whereas various congenital anomalies of the blood vessels or defects in coagulation or platelet function are often found in children with intraparenchymal hemorrhage. More than one risk factor is commonly identified, especially in children with dural venous thrombosis. Identification of the underlying risk factors for cerebrovascular disorders in children is important because many of the risk factors can be treated, reducing the risk of subsequent strokes.

This article has reviewed the causes and potential therapies for PPH. These include both predictable and unpreventable causes and methods of differential diagnosis. Triage of therapeutic interventions and prompt diagnosis are critical in reducing morbidity and mortality caused by PPH.

Hematologic disorders are implicated in approximately 10% to 27% of cases of nonimmune hydrops fetalis. In almost all of these disorders, anemia leading to heart failure, edema, ascites, and anasarca is the final common denominator. The etiology of the anemia in these cases can be conveniently divided into two categories: (1) excessive erythrocyte loss by hemolysis or hemorrhage, and (2) erythrocyte underproduction. The former include intrinsic erythrocyte abnormalities such as alpha-thalassemia and glucose-6-phosphate dehydrogenase deficiency, and conditions with excessive fetal blood loss such as fetomaternal hemorrhage and twin-twin transfusion. The latter include bone marrow replacement syndromes and conditions associated with failure of erythrocyte production. The presentation, diagnosis, and management of hematologic disorders associated with nonimmune hydrops fetalis are reviewed.

Brain infarcts and brain hemorrhages in patients younger than 20 years are significantly less common than among those older than 65 years; also, their clinical expressions are different from those common to older patients. Congenital defects involving the heart and the arteries supplying the brain are among the most common causes of stroke in the young. In addition to the structural changes affecting the heart and blood vessels, various genetic disorders (hematologic, mitochondrial, and others) are being identified as significant risk factors in an increasing number of young stroke victims.

In recent years, biologic response modifiers, including recombinant cytokines and hematopoietic growth factors, have been used to treat patients with refractory hematologic malignancies and solid tumors, as well as chemotherapy-associated myelosuppression and thrombocytopenia and treatment- and/or malignancy-related anemia. Various cytokines appear to be effective in patients with hematologic malignancies, but long-term and durable responses in the salvage setting are rare. In patients with solid tumors, such as renal cell carcinoma, malignant melanoma, and colorectal cancer, cytokines may have a limited role in primary therapy but are of little value in salvage therapy. Complications of malignancy and antineoplastic therapy are widely treated with hematopoietic growth factors, like granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor, and more recently the interferons and interleukins have demonstrated a potential role in this setting.

In summary, NIHF is a heterogenous disorder resulting from a vast number of underlying pathologies. A thorough evaluation should be performed in all cases to attempt to establish the etiology. This requires a systematic approach that should logically proceed from least to most invasive testing. Despite increasing availability of treatment for some causes of NIHF, the prognosis for this condition in general remains poor. In cases of fetal or neonatal demise, autopsy should be encouraged to aid in confirming or making a diagnosis. It is especially important to rule out potentially treatable conditions, as well as genetic disorders with a risk of recurrence in future pregnancies.

Pyomyositis (PMS) is a primary infection of striated muscle. Recent scanty reports suggest that non-tropical PMS may differ from classical tropical PMS. To address this question, 12 cases of nontropical PMS seen at two hospitals between 1976 and 1992 were reviewed and an English-literature search of similar cases was conducted. Both the series and reported cases are pooled together and herein reported. The age distribution of the 97 patients showed 30-50 and 60-70-year peaks, with a 3:1 (male-female) ratio. Fever, high erythrocyte sedimentation rate, and muscle stiffness or inflammation were present in more than 75% of patients. Muscles of the thigh (54%), back (13%), buttock (11%), arm (9%), or chest wall (4%) were involved. Staphylococci (61%), gram-negative bacilli (16%), streptococci (12%), and fungi (2%) were isolated from muscle specimens. Human immunodeficiency virus infection, diabetes mellitus, hemopoietic disorders, and other conditions with defective neutrophil function were present in 64 patients (66%). Drainage of pus and antibiotic therapy were the standard treatments. The mortality rate reached 10%. Analysis of patients classified by the comorbid condition showed differences in age, causative microorganisms, clinical features, and death rate. It is concluded that several clinical presentations of nontropical PMS are at variance with that of tropical PMS.

Spontaneous ICH is an unusual and potentially disastrous event that may complicate primary and secondary hemostatic abnormalities. Among the primary abnormalities, deficiencies of coagulation factors I, VII, VIII, IX and XIII as well as von Willebrand factor have been clearly associated with ICH. Specific factor replacement or supportive management to normalize the hemostatic defect is indicated in each case. Among secondary alterations in hemostasis, thrombocytopenia, platelet function abnormalities, or factor consumption contribute to the risk of ICH in patients with ITP, TTP, disseminated intravascular coagulation, myeloproliferative or myelodysplastic disorders, and exposure to certain medications. The precise incidence of spontaneous hemorrhage among these disorders is unknown but low. Platelet transfusion and fibrinogen replacement are appropriate in specific cases; however, treatment of the underlying cause is usually required. The association of hemorrhage with antithrombotic agents in several settings is better defined. Cessation of the medication is required in each instance. Fibrinogen replacement may be required after the use of fibrinolytic agents. In all cases, an assessment of the precise hemostatic defect is recommended.

Invasive pulmonary aspergillosis is a necrotizing pneumonia that is most frequently seen in association with profound granulocytopenia as a consequence of cytotoxic chemotherapy that is used to treat hematologic neoplasms. There is considerable evidence that the incidence of this infection is increasing over the past decade as a result of improved medical support used in the management of "at risk" patients. Heightened clinical awareness coupled with advances in diagnostic techniques have led to earlier treatment and improved outcomes of this once uniformly fatal infection. Amphotericin B remains the treatment of choice; however, newer therapeutics (azoles) and strategies (combination chemotherapy, biological response modifiers) show promise as alternative regimens. Novel approaches in preventing the acquisition of pulmonary aspergillosis in the "at risk" patient are being explored.

The mesenteric circulation is acutely sensitive to processes that affect the entire body. Such systemic diseases and syndromes are reviewed with particular emphasis on the mechanisms by which they influence the mesenteric vasculature and blood flow.

Significant oral health problems are associated with medical, physical, or mental disorders that occur in children. The pediatrician has the opportunity through early intervention to set the tone for a health care practice that will improve the quality of life for many disadvantaged children. When the pediatrician and pediatric dentist work hand in hand, the children can often expect a happy, healthy future.

Several lines of indirect evidence implicate vitamin A intoxication, associated mainly with impaired renal function, in the etiopathogenesis of gouty arthritis. The enzyme xanthine oxidase is involved not only in the conversion of xanthine to uric acid but also in that of retinol to its more toxic metabolite, retinoic acid. Retinoic acid should therefore be present in high concentration in hyperuricemic states.

Antiphospholipid antibody is associated with a clinical syndrome of vascular thrombosis, thrombocytopenia, recurrent fetal loss, and livedo reticularis, whether or not a clinical diagnosis of systemic lupus erythematosus (SLE) coexists. A positive antiphospholipid antibody test is defined by enzyme-linked immunosorbent assay (ELISA) (antiphospholipid antibody itself) or by coagulation assay (lupus anticoagulant). These are similar but not identical antibodies. The test for syphilis is less closely related to the preceding two and is less regularly associated with clinical complications. The mechanism of action of either antiphospholipid antibody or lupus anticoagulant is as yet unknown. SLE-induced but not infection-induced antiphospholipid antibody has immunoglobulin G2 (IgG2) and IgG4 predominance. It recognizes all negatively charged phospholipids, but various physical characteristics of the phospholipids alter the recognition patterns. Treatment for the antiphospholipid antibody syndrome has not been clearly defined. Anticoagulation with aspirin, heparin, or warfarin is currently favored. A role for corticosteroid remains to be demonstrated.

Serial determinations of C-reactive protein (CRP) were performed by single radial immunodiffusion in four groups of patients with fungal disease in order to determine its use as an aid to diagnosis. Elevated values (17-284 mg/l) of CRP were seen in 13 patients with fungal septicaemia before and/or within a few days after the first positive blood culture. C-reactive protein was not elevated in two patients with transient fungaemia. In 76 per cent (25/33) of deep-seated fungal infections in patients with malignant disorders of the blood CRP increased to 104-380 mg/l. In the remainder values of 36-92 mg/l were seen. In 37 per cent (19/51) of episodes of acute uncomplicated fungal stomatitis in patients with malignant disorders of the blood CRP rose to 110-320 mg/l. C-reactive protein was not found to be raised from the normal value (less than or equal to 6 mg/l) in 6 per cent of the episodes; in the rest, values below 100 mg/l were seen. CRP in 23 patients with acute fungal stomatitis but who were not immunocompromised remained normal. Thus, with regard to its ability to induce high (greater than 100 mg/l) CRP values, deep-seated fungal disease would seem to resemble bacterial rather than viral infection.

As the presenting complaint in 7 per cent of pediatrician visits, pain in the limbs is a common problem in childhood. It is important that the diagnosis be made expeditiously. The authors review the possible organic cause of limb pain, as well as limb pain from conversion reactions and from growing pains, giving special attention to the differential diagnosis so that appropriate treatment for the pain can be initiated.

The recurring of abdominal pain can be a taxing clinical ordeal for the primary care physician or consultant. It often is a test of stamina, of diagnostic self-confidence, of fiscal constraint, and of vigilance for rare conditions. The clinician is apt to be haunted by the lingering question: "Am I missing something?" That which might or might not be "missed" comprises the content as well as the rationale for this review.

Ulcers of the foot and ankle secondary to blood dyscrasias may become more common as a result of modern medicine's ability to keep patients alive long enough to become victims of chronic disease. Also, many pharmaceutic agents have, among their side effects, the ability to produce hematologic complications. The physician should consider that hematologic disorders may be among the etiologic agents responsible for foot and ankle ulcers.

The problems and complications of the fluid resuscitation phase of the treatment of major thermal burns are many and varied. Emphasis has been placed on the most important organ system responses commonly observed in the first week after injury. The efficacy of treatment and the lack of available treatment are outlined. The mechanical complications occurring from poorly selected and monitored fluid administration sites, complications of monitoring, problems of constrictive edema (usually in the extremities), airway problems, respiratory care, and innumerable other technical aspects were purposely omitted. While these problems and complications are extremely important and occur commonly in our experience, they are in the realm of technical performance of good emergency and intensive care medicine and their optimal management does not affect the problems and complications of the residual organ systems.