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Background. Hereditary bone marrow failure syndromes are a category of biologically different syndromes that can cause cytopenia in at least one hematopoietic cell lineage. Case. We present a 29-week-old male infant who had a low Apgar Score, advanced delivery room resuscitation, widespread petechial rash, and ecchymoses at birth, without any dysmorphic features. Initial laboratory tests revealed bicytopenia (platelet count 7x10 3 /uL, hemoglobin of 3.9 g/dL, neutrophil 2.0x103 /uL) with findings of disseminated intravasculer coagulation (DIC). Imaging studies demonstrated accompanying left-sided congenital pulmonary airway malformation. On the second postnatal week pancytopenia occurred and the bone marrow findings were consistent with congenital amegakaryocytic thrombocytopenia. Further evaluations for differential diagnosis of pancitopenia were performed and the results of congenital viral infections, metabolic and immunologic tests were negative. While supportive treatments were in progress, haploidentical bone marrow transplantation (BMT) was performed from the father at 84th day due to unavailability of HLA-matched relative or nonrelative donor. Whole exome sequencing revealed a novel heterozygous frameshift variation (c.1242dupT [p. Thr538fs]) in exon 8 of the MECOM gene and validated by Sanger sequencing. No variation was detected in the parents genetic analysis. Conclusions. In this report, we present a patient with congenital bone marrow failure successfully treated with haploidentic BMT and describe a novel, de novo pathogenic variant in MECOM gene. © 2022, Turkish National Pediatric Society. All rights reserved.

The literature on neonates with SARS-CoV-2 is mainly concerned with perinatal cases, and scanty data are available about environmentally infected neonates. To fill knowledge gaps on the course and prognosis of neonatal cases, we analyzed 1-year data from the Turkish Neonatal Society in this prospective cohort study of neonates with postnatal transmission. Data from 44 neonatal intensive care units (NICUs), of neonates with positive RT-PCR results at days 5–28 of life, were extracted from the online registry system and analyzed. Of 176 cases, most were term infants with normal birth weight. Fever was the most common symptom (64.2%), followed by feeding intolerance (25.6%), and cough (21.6%). The median length of hospitalization was 9 days, with approximately one quarter of infants receiving some type of ventilatory support. Myocarditis (5.7%) was the most common complication during follow-up. Among the clinical findings, cough (odds ratio [OR]: 9.52, 95% confidence interval [CI]: 4.17–21.71), tachypnea (OR: 26.5, 95% CI: 9.59–73.19), and chest retractions (OR: 27.5, 95% CI: 5.96–126.96) were associated with more severe clinical disease. Also, there were significant differences in the C-reactive protein level, prothrombin time (PT), partial thromboplastin time, international normalized ratio, and days in the NICU (p = 0.002, p = 0.012, p = 0.034, p = 0.008, and p < 0.001, respectively) between patients with mild-moderate and severe-critical presentations. A PT above 14 s was a significant predictor of severe/critical cases, with a sensitivity of 64% and specificity of 73%. Conclusions: Our data showed that late-onset COVID-19 infection in neonates who need hospitalization can be severe, showing associations with high rates of ventilatory support and myocarditis. Cough, tachypnea, and retractions on admission suggest a severe disease course. Trial registration: ClinicalTrials.gov identifier: NCT04401540.What is Known:• Neonatal cases of COVID-19 infection are mainly reported as perinatal COVID-19 cases.• Neonates with perinatal transmission have a mild course and favorable prognosis.What is New:• Among symptomatic neonates with late-onset COVID-19 infection, fever was the most common symptom, and almost one quarter of hospitalized cases needed some type of respiratory support. Myocarditis was the most common complication.• The presence of cough, tachypnea, retractions, and a PT above 14 s were associated with an increased risk of severe COVID-19. © 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

The association of cancer and pregnancy is increasingly encountered nowadays in clinical practice. Due to the relative rarity of the situation, it lacks a systematized approach. Different systemic therapies are used in managing cancer with uncertainty regarding the potential hazards they could pose on the pregnancy and/or the fetus. We have performed a systematic review of literature to identify all reports addressing cancer patients who were exposed to any of the known systemic therapies during the course of the pregnancy. The results were discussed in two parts; part I addresses pregnant patients with solid tumors while part I for those with hematological malignancies. In part I, we identified different solid tumors diagnosed and treated during the course of pregnancy. Breast cancer was the most commonly treated followed by ovarian cancer. Other tumors were treated as well including lung cancer, cervical cancer, sarcoma and melanomas. It is important to acknowledge the intent of therapy (palliative vs. curative) and the patients has to be properly counseled to reach an informed decision. We aim to provide a more robust consensus on how to approach these cases and provide a higher degree of evidence to support the safety of applying certain management strategies over the other.

The most important adverse effect of antithrombotic treatment is the occurrence of bleeding. in case of serious or even life-threatening bleeding in a patient who uses anticoagulant agents or when patient on anticoagulants needs to undergo an urgent invasive procedure, anticoagulant treatment can be reversed by various specific strategies. heparin and heparin derivatives can be counteracted by protamine sulphate, whereas the anticoagulant effect of vitamin K antagonists may be neutralised by administration of vitamin K or prothrombin complex concentrates. the antihaemostatic effect of aspirin and other antiplatelet strategies can be corrected by the administration of platelet concentrate and/or desmopressin, if needed. recently, a new generation of anticoagulants with a greater specificity towards activated coagulation factors has been introduced and most of these agents are currently being evaluated in clinical studies, showing promising results. the new-generation anticoagulants include specific inhibitors of factor iia or factor Xa (including pentasaccharides) and antiplatelet agents belonging to the class of thienopyridine derivatives. a limitation of the new class of anti-iia and anti-Xa agents may be the lack of an appropriate strategy to reverse the effect if a bleeding event occurs, although in some cases the administration of recombinant factor VIIa may be an option. © Van Zuiden Communications B.V. All rights reserved.

In this meeting report, particularly addressing the topic of protection of the cardiovascular system from ischemia/reperfusion injury, highlights are presented that relate to conditioning strategies of the heart with respect to molecular mechanisms and outcome in patients’ cohorts, the influence of co-morbidities and medications, as well as the contribution of innate immune reactions in cardioprotection. Moreover, developmental or systems biology approaches bear great potential in systematically uncovering unexpected components involved in ischemia–reperfusion injury or heart regeneration. Based on the characterization of particular platelet integrins, mitochondrial redox-linked proteins, or lipid-diol compounds in cardiovascular diseases, their targeting by newly developed theranostics and technologies opens new avenues for diagnosis and therapy of myocardial infarction to improve the patients’ outcome. © 2016, The Author(s).

Background: Disseminated intravascular coagulation (DIC) is an acquired syndrome characterized by systemic intravascular activation of coagulation, leading to deposition of fibrin in the bloodstream. It may occur in patients with acute and chronic leukemia and is particularly associated with acute promyelocytic leukemia (a subtype of acute myeloid leukemia). Objectives: To assess the clinical benefits and harms of any pharmacological intervention for treating DIC in patients with acute or chronic leukemia. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2015, Issue 05), MEDLINE (1946 to 7 May 2015), LILACS (1982 to 7 May 2015) and African Index Medicus (7 May 2015). There was no language restrictions. We sought additional randomized controlled trials (RCTs) from the World Health Organization International Clinical Trials Registry Platform and the reference lists of primary studies identified. Selection criteria: RCTs assessing the clinical benefits and harms of interventions for treating DIC in patients with acute and chronic leukemia. Data collection and analysis: Two review authors independently performed trial selection, 'Risk of bias' assessment and data extraction. Primary outcomes were overall mortality, in-hospital mortality from any cause (15-day and 30-day) and adverse events. Main results: In this Cochrane Review update we did not include any new RCT compared with the first review version. Accordingly, four RCTs (388 participants) met the inclusion criteria. These trials evaluated the human activated protein C, recombinant human soluble thrombomodulin, tranexamic acid and dermatan sulphate. Included trials reported data on mortality and bleeding. The studies were conducted in Japan, Italy and the Netherlands. We classified the included trials as: 1) including patients with or without leukemia which did not report data for the leukemia subgroup (366 participants); and 2) only including patients with leukemia (22 participants). Overall, the risk of bias of the included trials was high, since the trial authors did not provide a detailed description about trial design and execution. According to the GRADE recommendations, we judged the overall quality of the body of evidence for all prefixed outcomes as 'very low', due to methodological limitations and very small sample size. One trial, including 10 participants with leukemia and comparing dermatan sulphate with heparin, reported no deaths during trial treatment. In terms of bleeding data, we were unable to pool results from two studies that were only conducted with leukemia patients due to the inconsistency in the measurement and reporting of this outcome. One trial, including 12 participants with leukemia, found very low quality evidence that tranexamic acid can reduce the cumulative hemorrhagic score in participants compared with those assigned to placebo (P = 0.0015, very low quality evidence). On the contrary, there is no evidence that dermatan sulphate compared with placebo reduces new events of hemorrhagic diathesis (1/5 (20%) versus 2/5 (40%); RR 0.50; 95% CI 0.06 to 3.91; P = 0.51, very low quality evidence). No thromboembolic complications were reported in either trial that included patients with leukemia only (very low quality evidence). The safety profile was inconclusive. The included trials did not assess overall mortality, resolution of respiratory failure, renal failure or shock. Authors' conclusions: Due to a lack of new RCTs, our conclusions in this Cochrane Review update are the same as the previous review version. We included four RCTs which reported mortality and bleeding data. It is not possible to determine whether human activated protein C, recombinant human soluble thrombomodulin, tranexamic acid and dermatan sulphate are effective or harmful for patients presenting with DIC related to acute or chronic leukemia. The quality of the evidence was low to very low. Therefore, prescription of these interventions for treating DIC in patients with acute and chronic leukemia can neither be supported nor rejected, unless new evidence from a large high-quality trial alters this conclusion. © 2015 The Cochrane Collaboration.

Objective: Lung cancer is an uncommon diagnosis during pregnancy. The combination of smoking in young women, increased maternal age during pregnancy, and increasing incidence of lung cancer worldwide may cause an increase of pregnancy associated lung cancer. The aim of this study was to describe all cases of lung cancer during pregnancy, registered in the international Cancer in Pregnancy registration study (CIP study; www.cancerinpregnancy.org). Materials and methods: We present nine cases, all advanced lung cancer during the course of pregnancy. Collected data included demographic features of the study patients, cancer treatment, pregnancy outcome as well as maternal and fetal outcomes. Results and conclusion: Nine pregnant patients from 4 European centres with a median age of 33 years old (range, 26-42) were included. The median gestational age at diagnosis was 17 weeks (range, 6-28). All patients presented with metastatic disease including bone, lung, brain, spinal cord, pleura, lymph nodes, adrenal and liver. Histopathology was compatible with adenocarcinoma in 4 patients, non-small cell lung cancer with unidentified subtype in 2 patients and squamous-cell, large-cell and a poorly differentiated carcinoma in 3 patients, respectively. Eight patients were treated with systemic therapy, five of them during gestation. No responses were seen. The maternal postpartum outcome was poor with less than one year survival following delivery. One patient experienced a spontaneous abortion and three pregnancies were terminated. Five infants were all born premature due to poor maternal status by cesarean section, with a median gestational age of 30 weeks (range 26-33). To summarize, lung cancer in pregnancy has a dismal maternal outcome in our series. We add nine new cases and discuss both therapeutic and prognostic results. (C) 2013 Elsevier Ireland Ltd. All rights reserved

Currently the treatment mainstay of sepsis is early and appropriate antibiotic therapy, accompanied by aggressive fluid administration, the use of vasopressors when needed and the prompt initiation of measures to support each failing organ. Activated protein C and hydrocortisone, when used accordingly can affect mortality. As the pathophysiologic events that take place during sepsis are being elucidated, new molecules that target each step of those pathways are being tested. However, a lot of those molecules affect various mediators of the sepsis cascade including inflammatory cytokines, cellular receptors, nuclear transcription factors, coagulation activators and apoptosis regulators. Over the last decade, a multitude of clinical trials and animal studies have investigated strategies that aimed to restore immune homeostasis either by reducing inflammation or by stimulating the innate and adaptive immune responses. Antibiotics, statins and other molecules with multipotent immunomodulatory actions have also been studied in the treatment of sepsis. © 2011 Expert Reviews Ltd. 9 11 1013 1033

Sepsis/endotoxemia causes platelet dysfunctions, abnormalities in coagulation and hemostatic mechanisms leading to organ dysfunctions and mortality. Choline prevents organ injury and improves survival during endotoxemia. The main objective of the present study was to determine the effects of choline or cytidine-5'-diphosphocholine (CDP-choline) on endotoxin-induced activation of coagulation and development of disseminated intravascular coagulation (DIC). Dogs were treated intravenously (i.v.) with saline, choline (20 mg/kg), or CDP-choline (70 mg/kg) three times with 4-h intervals starting 5 min before i.v. injection of endotoxin (1 mg/kg). Platelet counts and functions, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, coagulation factors, D-dimer and antithrombin (AT) were measured before and at 0.5-96 h after endotoxin. Circulating platelet, fibrinogen, coagulation factors and AT were decreased, whereas PT and aPTT were prolonged and serum D-dimer levels were elevated after endotoxin. Endotoxin-induced reductions in platelet counts and functions, fibrinogen, coagulation factors and AT were attenuated or blocked by choline or CDP-choline. Choline or CDP-choline blocked endotoxin-induced prolongation in PT and aPTT and enhancement in D-dimer. Elevated DIC scores were attenuated by choline and blocked by CDP-choline. Choline administration increased serum choline concentrations and caused bradycardia. Choline also increased choline and acetylcholine contents of circulating mononuclear cells and inhibited radioligand binding to their cholinergic receptors. These data show that choline administration, as choline chloride or CDP-choline, restores the abnormalities in the primary, secondary, and tertiary hemostasis and prevents the development of DIC during experimental endotoxemia in dogs probably by increasing both neuronal and nonneuronal cholinergic activity. Blood Coagul Fibrinolysis 21:339-348 Türkiye Bilimler Akademisi (TÜBA)

The most important adverse effect of antithrombotic treatment is the occurrence of bleeding. in case of serious or even life-threatening bleeding in a patient who uses anticoagulant agents or when patient on anticoagulants needs to undergo an urgent invasive procedure, anticoagulant treatment can be reversed by various specific strategies. heparin and heparin derivatives can be counteracted by protamine sulphate, whereas the anticoagulant effect of vitamin K antagonists may be neutralised by administration of vitamin K or prothrombin complex concentrates. the antihaemostatic effect of aspirin and other antiplatelet strategies can be corrected by the administration of platelet concentrate and/or desmopressin, if needed. recently, a new generation of anticoagulants with a greater specificity towards activated coagulation factors has been introduced and most of these agents are currently being evaluated in clinical studies, showing promising results. the new-generation anticoagulants include specific inhibitors of factor iia or factor Xa (including pentasaccharides) and antiplatelet agents belonging to the class of thienopyridine derivatives. a limitation of the new class of anti-iia and anti-Xa agents may be the lack of an appropriate strategy to reverse the effect if a bleeding event occurs, although in some cases the administration of recombinant factor VIIa may be an option. © Van Zuiden Communications B.V. All rights reserved.

Imatinib has shown significant clinical and cytogenetic success in the treatment of chronic myeloid leukemia. Although resistance has been observed in a proportion of patients, sudden blastic crisis is a rare event during imatinib therapy. We describe a 24-year-old male patient with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase who developed sudden blastic crisis in the 24th month of imatinib therapy, with loss of complete cytogenetic response. At this time, the patient had splenomegaly, severe anemia, thrombocytopenia, and leukocytosis. Bone marrow aspirate revealed the presence of massive blastic infiltration with myeloid morphology. Flow cytometric analysis of the bone marrow cells showed positivity for CD45, CD34, CD13, CD33, CD19, CD41, C1361, and glycophorin-A. Trephine biopsy specimens showed 100% cellular marrow with diffuse infiltrate by blasts. A reticulin stain of the bone marrow biopsy section demonstrated severe diffuse fibrosis. Cytogenetic analysis by fluorescence in situ hybridization (FISH) revealed that 92% of the cells were positive for the BCR/ABL fusion signal and had increased copy numbers for chromosomes 8,13,19, and 21. The patient's prognosis was unfavorable. In conclusion, chronic myeloid leukemia remains complex and includes unanswered questions. The presented case with a rare event during imatinib therapy highlights the need for the continued monitoring of residual disease and the development of strategies to eliminate residual leukemia cells in patients showing a complete cytogenetic response. Novartis İlaç

The clinical manifestation of disseminated intravascular coagulation (DIC) as paraneoplastic phenomenon is common in patients with lung cancer (especially in those with non small cell lung cancer).Surprisingly, only few data have been published on the prevalence of this phenomenon. Herein we present the case of a patient with metastatic giant-cell carcinoma of the lung complicated by DIC leading the patient to death. We also review the literature regarding the incidence, the pathogenesis and the therapy of DIC in NSCLC. As more effective therapy for lung cancer becomes available and patients live longer, DIC can be expected to be encountered more frequently. Because of this fact clinicians should be alert to the occurrence of such clotting disorders and should be familiar with their diagnosis and management. © 2008 Elsevier Ireland Ltd. All rights reserved. 64 2 247 249

Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:23:46Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:40:54Z : No. of bitstreams: 1 2-s2.0-67049119580.pdf: 506718 bytes, checksum: 05d454fc8d4584ea8b51bbf14cbcbe63 (MD5) Made available in DSpace on 2014-05-27T11:23:46Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-12-01 O choque vasodilatador mais freqüente resulta de sepse, uma inflamação sistêmica em resposta a uma infecção que se caracteriza por hipotensão, hiporreatividade às catecolaminas e coagulação intravascular disseminada. A causa mais comum de sepse é a infecção por bactérias Gram-negativas, principalmente de Escherichia coli, resultando na liberação de lipopolissacarídeos (endotoxinas) da parede celular, quando da morte ou lise do microrganismo, com o envolvimento de muitos mediadores, incluindo o óxido nítrico. Mais tarde descobriu-se que os níveis sanguíneos de vasopressina, em pacientes com sepse, eram anormalmente baixos, e observou-se que alguns destes pacientes, com choque séptico avançado, eram extremamente sensíveis às ações pressóricas da vasopressina exógena. Palavras-chave: endotoxina; vasopressina; choque séptico; sepse; hiporreatividade; choque vasodilatador. The most frequent cause of vasodilatory shockis outcome from sepsis, a systemic inflammatory response to infection, characterized by hypotension, hyporeactivity to the catecholamines and disseminated intravascular coagulation. The commonest cause of sepsis has reported to be infection with Gram-negative bacteria, typically E. coli, resulting in the release of lipopolysaccharide (endotoxin) from the bacterial outer membrane during autolysis or death of these microorganisms, with the involvement of many mediators, including nitric oxide. Later it was found that plasma levels of vasopressin in sepsis patients were abnormally low and observed that some patients with advanced septic shock were extremely sensitive to the activity actions of exogenous vasopressin. Departamento de Princlpios Ativos Naturais e Toxicologia Faculdade de Ctěncias Farmacéuticas Universidade Estadual Paulista, UNESP, Araraquara, SP Departamento de Principios Ativos Naturais e Toxicologia Faculdade de Ciencias Farmaceuticas Universidade Estadual Paulista, UNSEP, Rodovia Araraquara-Jau km 01, 14801-902-Araraquara-SP Departamento de Princlpios Ativos Naturais e Toxicologia Faculdade de Ctěncias Farmacéuticas Universidade Estadual Paulista, UNESP, Araraquara, SP Departamento de Principios Ativos Naturais e Toxicologia Faculdade de Ciencias Farmaceuticas Universidade Estadual Paulista, UNSEP, Rodovia Araraquara-Jau km 01, 14801-902-Araraquara-SP

Topical use of corticosteroids may cause immunosuppression and iatrogenic Cushing's syndrome via hypothalamic-pituitary-adrenal axis. We report two cases with iatrogenic Cushing's syndrome with different clinical outcomes due to abuse of same potent topical steroid clobetasol propionate. One of them died because of fatal disseminated cytomegalovirus infection. The other patient recovered completely. Physicians and parents should be informed about the adverse effects of such potent topical corticosteroids and physicians should prescribe less potent agents, especially during infancy. © 2008 The Authors.

Background: During catastrophic earthquakes, crush syndrome is the second most frequent cause of death after the direct impact of trauma. The Marmara earthquake, which struck Northwestern Turkey in August 1999, was characterized by 639 crush syndrome victims with acute renal problems. The factors influencing their final outcome have been the subject of this study. Patients/ methods: Within the first week of the disaster questionnaires asking about 63 clinical and laboratory variables were sent to 35 reference hospitals that treated the victims. Information obtained by means of these questionnaires, including the factors with a potential influence on outcome, was submitted to analysis. Results: Overall mortality rate was 15.2%. In univariate analysis, nonsurvivors were older (p = 0.048); the highest mortality rates were observed among the victims coming from the closest cities to the reference hospitals. Admission within the first 3 days of the disaster (p = 0.016), with oliguria (p = 0.042), lower figures for blood pressure (p < 0.001), platelets (p = 0.004) and serum albumin (p = 0.005) were associated with mortality. Also, higher body temperature (p = 0.013) and serum potassium (p < 0.001) as well as suffering from thoracic or abdominal traumas, extremity amputations and medical complications other than renal failure (for all 4: p < 0.0001) in addition to need of dialysis support (p = 0.015) and mechanical ventilation (p < 0.0001) indicated higher risk of death. In the multivariate analysis, age (p = 0.030, OR = 1.02), presence of disseminated intravascular coagulation (p = 0.001, OR = 4.49), abdominal trauma (p = 0.012, OR = 4.05) and amputations (p = 0.010, OR = 2.81) were predictors of mortality. Dialyzed patients were characterized by higher mortality rates than nondialyzed victims (17.2% versus 9.3%, p = 0.015). Conclusion: Outcome of the renal victims of catastrophic earthquakes is influenced by the type of trauma, comorbid events and complications observed during the clinical course as well as epidemiological features such as age, distance to reference hospitals and time lapse between disaster and admission to reference hospitals.