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Crohn's disease (CD) is a chronic inflammatory bowel disease that can affect any part of the gastrointestinal tract. The etiology of CD is unknown; however, genetic, epigenetic, environmental, and lifestyle factors could play an essential role in the onset and establishment of the disease. CD results from immune dysregulation due to loss of the healthy symbiotic relationship between host and intestinal flora and or its antigens. It affects both sexes equally with a male to female ratio of 1.0, and its onset can occur at any age, but the diagnosis is most commonly observed in the range of 20 to 40 years of age. CD diminishes quality of life, interferes with social activities, traumatizes due to the stigma of incontinence, fistulae, strictures, and colostomies, and in severe cases, affects survival when compared to the general population. Symptoms fluctuate between periods of remission and activity in which complications such as fistulas, strictures, and the need for bowel resection, surgery, and colostomy implantation make up the most severe aspects of the disease. CD can be progressive and the complications recurrent despite treatment with anti-inflammatory drugs, corticosteroids, immunosuppressants, and biological agents. However, over time many patients become refractory without treatment alternatives, and in this scenario, hematopoietic stem cell transplantation (HSCT) has emerged as a potential treatment option. The rationale for the use of HSCT for CD is anchored in animal studies and human clinical trials where HSCT could reset a patient's immune system by eliminating disease-causing effector cells and upon immune recovery increase regulatory and suppressive immune cells. Autologous HSCT using a non-myeloablative regimen of cyclophosphamide and anti-thymocyte globulin without CD34+ selection has been to date the most common transplant conditioning regimen adopted. In this review we will address the current situation regarding CD treatment with HSCT and emphasize the medical, ethical, and legal aspects that permeate the procedure in Brazil.

Introducción: La hemorragia intracerebral remota es una complicación neuroquirúrgica poco frecuente, ocurre en el 18% de los procedimientos intracraneales y aún menos en la cirugía de columna. Presentación de caso clínico: Un hombre de 89 años con un hematoma subdural derecho, que se sometió a un drenaje por craneotomía, en la tomografía de control presentó un hematoma intraparenquimatoso occipito temporal izquierdo y hemorragia intraventricular. Conclusión: Algunas teorías que han tratado de explicar las causas de la hemorragia intracerebral remota, el síndrome de hiperperfusión, la hipertensión, la angiopatía amiloide, el infarto venoso o el uso de anticoagulantes orales.

Background Decompressive craniectomy (DC) after traumatic brain injury (TBI) is a common surgical procedure. Cranioplasty (CP) is undertaken as a routine secondary operation following DC. In neurosurgical trauma centers, patients who require CPs compete with other patients who require emergency neurosurgical intervention and they are not given enough priority. Methods A retrospective study was conducted of patients who had undergone autologous bone CP after DC for TBI over three years in a 3rd level trauma center in Mexico. All families were administered a questionnaire to assess how the patient judged the cosmetic result of CP. Results A total of 29 patients agreed to participate in this study. 25 patients (86.2%) were satisfied with the aesthetic result and 4 patients (13.8%) were no satisfied with their CP. 4 cases (13.8%) reported medical complications related to CP. Unsatisfied patients complained most likely about the dented aesthetic look, with a moderate negative correlation between this and cosmetic outcome (ρ = −0.483, P = 0.001). Patient age (ρ = 0.194, P = 0.314) and defect size (ρ = 0.156, P = 0.419) was not related to the assessment of the aesthetic result. A strong negative correlation between postoperative infection and the grade of satisfaction (ρ = −0.710, P = 0.001) was also observed. Conclusions Based on our results, overall most of the patients were satisfied with their CP with an acceptable complication rate.

ANTECEDENTES Los abordajes quirurgicos de la region selar han sido un reto para los neurocirujanos. Con la introduccion de la tecnica endoscopica se ha minimizado el trauma quirurgico, pero esta tecnica no se encuentra exenta de complicaciones. OBJETIVO Describir nuestra experiencia institucional en pacientes sometidos a reseccion de macroadenomas hipofisarios por via microquirurgica endonasal transesfenoidal asistida por endoscopia con enfasis en las complicaciones resultantes. METODO Revisamos los expedientes electronicos de 17 pacientes sometidos a dicho procedimiento de manera consecutiva entre 2017 y 2018, y recabamos variables como edad, sexo, clasificacion imagenologica, tiempo de diagnostico al momento de la cirugia, complicaciones posoperatorias y recurrencia. RESULTADOS La edad promedio de los pacientes fue de 45.23 anos y el 70.59% eran mujeres. Radiologicamente predomino el grado 2 Knosp (47.05%). La complicacion principal fue diabetes insipida transitoria (23.52%), seguida por la fistula de liquido cefalorraquideo (11.76%). CONCLUSIONES El manejo microquirurgico asistido por endoscopia ha demostrado ser un recurso valioso para tratar macroadenomas hipofisarios, pero presenta grados variables de complicaciones, por lo cual se requiere la adquisicion de habilidades para el uso del endoscopio, la planeacion preoperatoria adecuada y el manejo conjunto multidisciplinario con el fin de evitarlas. BACKGROUND Surgical approaches to the sellar region have been a challenge for the neurosurgeon. With the introduction of the endoscopic technique, surgical trauma has been minimized, however it is not free of complications. OBJECTIVE To describe our institutional experience in patients undergoing resection of pituitary macroadenomas by endoscopic-assisted microsurgical approach, with emphasis on the resulting complications. METHOD We reviewed the electronic files of 17 patients who underwent this procedure consecutively between 2017 and 2018, collecting variables such as age, sex, imaging classification, time of diagnosis at the time of surgery, postoperative complications and recurrence. RESULTS The average age of the patients was 45.23 years, with 70.59% women. Radiologically, grade 2 Knosp predominated (47.05%). The main complication was transient diabetes insipidus (23.52%) followed by cerebrospinal fluid fistula (11.76%). CONCLUSIONS The endoscopic-assisted microsurgical approach has proven to be a valuable resource for treating pituitary macroadenomas, however it presents variable degrees of complications, which requires the acquisition of skills for the use of the endoscope, adequate preoperative planning, and multidisciplinary joint management in order to avoid them.

Background: In December 2019, in Wuhan, a new virus emerged, causing severe acute respiratory syndrome (SARS) secondary to infection by a type of coronavirus, causing coronavirus disease (COVID-19) The pandemic caused by the new coronavirus has had implications in the central nervous system COVID-19 is known to be characterized by coagulation activation and endothelial dysfunction, causing ischemic and hemorrhagic vascular syndromes Case Description: A 27-year-old male patient case with progressive decrease in visual acuity, associated with respiratory symptoms and intense headache Multilobar infiltrate with a reticulonodular pattern is evident on chest CT scan Brain CT scan with pituitary macroadenoma apoplexy was shown SARS-Cov2 was confirmed, and respiratory support initiated However, the patient died shortly afterward, secondary to pulmonary complications Conclusion: The angiotensin-converting enzyme (ACE) II receptor is expressed in circumventricular organs and in cerebrovascular endothelial cells, which play a role in vascular autoregulation and cerebral blood flow For this reason, is rational the hypothesize that brain ACE II could be involved in COVID-19 infection Underlying mechanisms require further elucidation in the future [ABSTRACT FROM AUTHOR] Copyright of Surgical Neurology International is the property of Scientific Scholar LLC and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission However, users may print, download, or email articles for individual use This abstract may be abridged No warranty is given about the accuracy of the copy Users should refer to the original published version of the material for the full abstract (Copyright applies to all Abstracts )

Crohn's disease (CD) is an inflammatory bowel disease that can affect any site of the digestive system. It occurs due to an immunological imbalance and is responsible for intestinal mucosal lesions and complications such as fistulas and stenoses. Treatment aims to stabilize the disease, reducing the symptoms and healing intestinal lesions. Surgical procedures are common in patients. Cell therapy was initially used to treat this disease in patients who also suffered from lymphoma and leukemia and were considered to be good candidates for autologous and allogeneic transplantation. After transplantation, an improvement was also observed in their CD. In 2003, the procedure began to be used to treat the disease itself, and several case series and randomized studies have been published since then; this approach currently comprises a new option in the treatment of CD. However, considerable doubt along with significant gaps in our knowledge continue to exist in relation to cell therapy for CD. Cell therapy is currently restricted to the autologous modality of hematopoietic stem cell transplantation and, experimentally, to mesenchymal stromal cells to directly treat lesions of the anal mucosa. This article presents the supporting claims for transplantation as well as aspects related to the mobilization regime, conditioning and perspectives of cell therapy.

Background Hematopoietic stem cell transplantation (HSCT) can be used in the treatment of patients with refractory Crohn's disease (CD) when no alternative treatment is available. However, HSCT increases the risk of infections, in particular during the aplasia of mobilization and conditioning. Moreover, intestinal stomas in CD augment the risk of morbidity in immunocompromised patients and under aplastic conditions. The objective of this report was to describe the results of the first year after HSCT in a CD patient with an intestinal stoma. Methods The patient was assessed in respect to disease symptoms and endoscopic findings before the procedure and 30, 90, 180, and 365 days after HSCT. Results No complications were observed during mobilization and conditioning with sufficient CD34+ cells being harvested in just one apheresis session. Toxicity was restricted to the hematological series. Scores of all the CD indexes and the quality of life of the patient improved. However, two of three endoscopic scores remained unchanged even though improvements were found in the appearance of the lesions. Conclusion HSCT may be an alternative treatment for refractory CD in patients with an intestinal stoma, and a priori, carefully selected patients with stomas should not be excluded as candidates for this procedure.

Objective The incidence of adverse events in myeloablative transplant protocols is high in refractory Crohn’s disease; this study used low doses of cyclophosphamide. Fourteen patients were submitted to non-myeloablative autologous hematopoietic stem cell transplantation. Results The average number of days of anemia (hemoglobin 9/L) in the mobilization phase was 1.7 ± 1.5 while it was 7.6 ± 1.4 in the conditioning phase. When comparing the conditioning and mobilization phases, there was an increased number days of leukopenia (white blood cells 9/L), lymphocytopenia (lymphocytes 9/L) and thrombocytopenia (platelets 9/L). Crohn’s Disease Activity Index values before the transplant ranged from 155 to 450.5 (mean 281.2 ± 79.0) and at 30 days after the procedures they ranged from 45.4 to 177 (mean 95.8 ± 35.4). Moreover, the procedure improved in overall quality of life of patients. Non-myeloablative autologous hematopoietic stem cell transplantation with lower doses of cyclophosphamide leads to lower rates of hematological toxicity and adverse events compared to protocols described in the literature. Trial registration NCT 03000296: Date 9 December 2016

Background: Retroclival hematomas are rare and occur mostly in the pediatric population. They are variously attributed to trauma, apoplexy, and vascular lesions. With motor vehicle accidents (MVAs), the mechanism of traumatic injury is forced flexion and extension. There may also be associated cervical spinal and/or clivus fractures warranting fusion. Case Description: A 35-year-old male sustained a traumatic brain injury after a fall of 5 m at work. His Glasgow coma scale (GCS) on admission was 13 (M6V3O4). He had no cranial nerve deficits. The brain computed tomography (CT) showed a retroclival subdural hematoma that extended to the C2 level. Conclusions: Most retroclival hematomas are attributed to MVAs, and cranial CT and magnetic resonance studies typically demonstrate a combination of posterior fossa hemorrhage with retroclival hematomas (intra or extradural). Patients with retroclival hematomas but high GCS scores on admission usually have better prognoses following traumatic brain injuries attributed to MVA. Notable however is the frequent association with additional cervical and/or craniocervical injuries (e.g. such as odontoid fracture) that may warrant surgery/fusión.

PURPOSE To report a case of a patient with ischemic retinopathy associated with Crohn's disease. CASE REPORT This report presents a case of a 28-year-old female patient with Crohn's disease and sudden decrease of visual acuity in the right eye. Fluorescein angiography, optical coherence tomography, and multifocal electroretinography confirmed the clinical features of ischemic retinopathy. After systemic corticosteroid treatment, the patient developed epiretinal membrane without significant improvement in visual acuity. DISCUSSION The patient presented with ischemic retinopathy associated with Crohn's disease with deficiency of central visual acuity. Periodic examination by a retina specialist is recommended for patients being treated for Crohn's disease.

BackgroundTreatment with high doses chemotherapy followed by autologous haematopoietic stem cell transplantation is promising for refractory Crohn’s disease patients with no therapeutic option and at imminent risk of further surgeries.ObjectivesTo evaluate the feasibility and efficacy of haematopoietic progenitor cell mobilization in a group of Crohn’s disease patients preparing for autologous unselected haematopoietic stem cell transplantation in a single institution. This is the first study to evaluate mobilization for Crohn’s disease.MethodsPatients were selected according to criteria of the European Bone Marrow Transplant Society.ResultsAll patients mobilized with the mean number of haematopoietic progenitor cells obtained and infused being 16.17 × 106/CD34+/kg. Most patients required only one leukapheresis session to reach the ideal number of cells. Grafting occurred around ten days after cells infusion. Complications and adverse events during the mobilization period were rare with only one patient presenting sepsis as a relevant event in the period.Most patients 20 (70%) had anaemia from the beginning of the mobilization but only 11 (37.9%) received packed red blood cell transfusions.ConclusionMobilization in patients with Crohn’s disease is effective and it seems they are good mobilizers.

Background Endoscopy has gained a crucial role in high specialty neurosurgery during the last decades. At present, there are well-defined flexible neuroendoscopic procedures to treat ventricular and subarachnoid space pathologies. Neurocysticercosis is recognized as a common cause of neurologic disease in developing countries and the United States. Surgical intervention, especially cerebrospinal fluid diversion, is the key for management of hydrocephalus. In 2002, a consensus suggested that ventricular forms should be treated with endoscopy as the first option. Case description Here, we present the case of a 51-year-old right-handed male, from Estado de Mexico. Two days before admission he experienced holocraneal headache 7/10 on the visual analogue scale which was intermittent, with no response to any medication, sudden worsening of pain to 10/10, nausea, and vomit. On physical examination, he presented with 14 points in the Glasgow coma scale (M6, O4, V4), pupils were 3 mm, there was adequate light-reflex response, and bilateral papilledema. The cranial nerves did not have other pathological responses, extremities had adequate strength of 5/5, and normal reflexes (++/++) were noted. Neuroimaging studies showed dilatation of the four ventricles as well as a cystic lesion in the fourth ventricle. Surgical position was Concorde, and the approach through a suboccipital burr hole was planned preoperatively with craneometric points. A rigid Karl Storz Hopkins II® endoscope was inserted directly through the cerebellum and the cystic lesion was extracted entirely. Conclusion This article presents a useful technique with low morbidity and mortality. Further investigation is needed, especially in our Mexico, where neuroendoscopical techniques are still in the development phase.

Made available in DSpace on 2015-12-07T15:31:04Z (GMT). No. of bitstreams: 0 Previous issue date: 2014. Added 1 bitstream(s) on 2021-07-15T15:00:50Z : No. of bitstreams: 1 S1516-84842014000400264.pdf: 193801 bytes, checksum: 9795657b458ed2fcb50b4e59be9f5a53 (MD5) Autologous hematopoietic stem cell transplantation is a conduct used to treat some hematologic diseases and to consolidate the treatment of others. In the field of nursing, the few published scientific studies on nursing care and early hospital discharge of transplant patients are deficient. Knowledge about the diseases treated using hematopoietic stem cell transplantation, providing guidance to patients and caregivers and patient monitoring are important nursing activities in this process. Guidance may contribute to long-term goals through patients' short-term needs. To analyze the results of early hospital discharge on the treatment of patients submitted to autologous transplantation and the influence of nursing care on this conduct. A retrospective, quantitative, descriptive and transversal study was conducted. The hospital records of 112 consecutive patients submitted to autologous transplantation in the period from January to December 2009 were revisited. Of these, 12 patients, who remained in hospital for more than ten days after transplantation, were excluded from the study. The medical records of 100 patients with a median age of 48.5 years (19-69 years) were analyzed. All patients were mobilized and hematopoietic stem cells were collected by leukapheresis. The most common conditioning regimes were BU12Mel100 and BEAM 400. Toxicity during conditioning was easily managed in the outpatient clinic. Gastrointestinal toxicity, mostly Grades I and II, was seen in 69% of the patients, 62% of patients had diarrhea, 61% of the patients had nausea and vomiting and 58% had Grade I and II mucositis. Ten patients required hospitalization due to the conditioning regimen. Febrile neutropenia was seen in 58% of patients. Two patients died before Day +60 due to infections, one with aplasia. The median times to granulocyte and platelet engraftment were 12 days and 15 days, respectively, with median red blood cell and platelet transfusions until discharge of three and four units, respectively. Twenty-three patients required rehospitalization before being discharged from the outpatient clinic. The median time to granulocyte engraftment was 12 days and during the aplasia phase few patients were hospitalized or suffered infections. The toxicity of the conditioning was the leading cause of rehospitalization. The nursing staff participated by providing guidance to patients and during the mobilization, transplant and outpatient follow-up phases, thus helping to successfully manage toxicity. Universidade de São Paulo (USP), São Paulo, SP, Brazil. Universidade de São Paulo (USP), São Paulo, SP, Brazil; Universidade Nove de Julho (Uninove), São Paulo, SP, Brazil. Hospital Inglês, São Paulo, SP, Brazil. Associação Portuguesa de Beneficência, São José do Rio Preto, SP, Brazil. Universidade do Estado de São Paulo (UNESP), São José do Rio Preto, SP, Brazil. Universidade de São Paulo (USP), São Paulo, SP, Brazil; Hospital Inglês, São Paulo, SP, Brazil. Electronic address: fldulley@usp.br. Universidade do Estado de São Paulo (UNESP), São José do Rio Preto, SP, Brazil.

PURPOSE: To evaluate the variability of subjective corneal topography map classification between different experienced examiners and the impact of changing from an absolute to a normative scale on the classifications. METHODS: Preoperative axial curvature maps using Scheimpflug imaging obtained with the Pentacam HR (Oculus Optikgeräte, Wetzlar, Germany) and clinical parameters were sent to 11 corneal topography specialists for subjective classification according to the Ectasia Risk Scoring System. The study population included two groups: 11 eyes that developed ectasia after LASIK and 14 eyes that had successful and stable LASIK outcomes. Each case was first reviewed using the absolute scale masked to the patient group. After 3 months, the same cases were represented using a normative scale and reviewed again by the same examiners for new classifications masked to the patient group. RESULTS: Using the absolute scale, 17 of 25 (68%) cases had variations on the classifications from 0 to 4 for the same eye across examiners, and the overall agreement with the mode was 60%. Using the normative scale, the classifications from 11 of 25 (44%) cases varied from 0 to 4 for the same eye across examiners, and the overall agreement with the mode was 61%. Eight examiners (73%) reported statistically higher scores ( P < .05) when using the normative scale. Considering all 550 topographic analyses (25 cases, 11 examiners, and two scales), the same classification from the two scales was reported for 121 case pairs (44%). CONCLUSION: There was significant inter-observer variability in the subjective classifications using the same scale, and significant intra-observer variability between scales. Changing from an absolute to a normative scale increased the scores on the classifications by the same examiner, but significant inter-observer variability in the subjective interpretation of the maps still persisted. [ J Refract Surg. 2013;29(11):770–775.]

Made available in DSpace on 2018-12-11T17:36:35Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-02-01. Added 1 bitstream(s) on 2021-07-15T15:22:28Z : No. of bitstreams: 1 S2359-39972018000100021.pdf: 166618 bytes, checksum: c6efd9bc253878c7d54e958992f693f1 (MD5) Objectives: This study aimed to evaluate the frequencies of the angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) and methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphisms in obese patients with and without type 2 diabetes mellitus (T2DM). Subjects and methods: These polymorphisms were analyzed by polymerase chain reaction in 125 patients with obesity, 47 (T2DM) and 78 (Control Group). Results: No significant difference was found on comparing the T2DM and Control Groups in respect to the genotypic frequencies of the polymorphisms - (II: 13.3% vs. 12.0%; ID: 37.8% vs. 37.3; DD: 48.9% vs. 50.7%; CC: 36.2% vs. 39.0%; CT: 46.8% vs. 49.3%; TT: 17.0% vs. 11.7%), and alleles (I: 32.2% vs. 30.7%; D: 67.8% vs. 69.3%; C: 59.6% vs. 63.6%; T: 40.4% vs. 36.4%) and their synergisms in the pathophysiology of T2DM. On analyzing the T2DM Group, there were no significant differences in the presence of complications. In this population of Brazilian obese patients, no correlation was found between the ACE and MTHFR polymorphisms in the development of T2DM. Conclusion: Analyzing only the group with diabetes, there was also no relationship between these polymorphisms and comorbidities. Departamento de Biologia Universidade Estadual Paulista “Júlio de Mesquita Filho” (Unesp) Associação Portuguesa de Beneficência Faculdade de Medicina União das Faculdades dos Grandes Lagos (Unilago) Departamento de Biologia Universidade Estadual Paulista “Júlio de Mesquita Filho” (Unesp)

EnglishThe Autologous Stem Cell Transplantation International Crohn Disease (ASTIC) trial by Dr Hawkey and colleagues1 was interpreted as a failure of autologous hematopoietic stem cell transplantation (HSCT) compared with standard care. However, the ASTIC trial used a complex multifaceted primary end point that included all of the following: Crohn disease activity index less than 150; no active treatment; and endoscopic and radiologic remission. This end point has not been used in any prior study. The data from such a small cohort of patients would have been interpreted as encouraging if the authors had used some of their secondary outcomes as the primary end point, for example, Crohn disease activity index change from baseline (P = .04) or simple endoscopic score of Crohn disease change from baseline (P = .03). EnglishThe ASTIC trial was designed to investigate the possibility, suggested by a number of case reports, that long-term, drug-free cure of Crohn disease could be achieved through autologous HSCT.1 The lack of statistical significance of the primary end point showed that this experience is rare. However, we agree with Dr Burt and colleagues that the extent of improvement in secondary end points suggests possible therapeutic efficacy, albeit falling short of cure.

Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2013-08-22T18:40:42Z No. of bitstreams: 1 S1516-84842012000600010.pdf: 614468 bytes, checksum: d64149a3b77faf179f01947b8ae973b3 (MD5) Made available in DSpace on 2013-08-22T18:40:42Z (GMT). No. of bitstreams: 1 S1516-84842012000600010.pdf: 614468 bytes, checksum: d64149a3b77faf179f01947b8ae973b3 (MD5) Previous issue date: 2012-01-01 Made available in DSpace on 2013-09-30T19:26:40Z (GMT). No. of bitstreams: 2 S1516-84842012000600010.pdf: 614468 bytes, checksum: d64149a3b77faf179f01947b8ae973b3 (MD5) S1516-84842012000600010.pdf.txt: 23597 bytes, checksum: 385ab2b19f8173d4c4c2ebe0bf5d0940 (MD5) Previous issue date: 2012-01-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T14:00:43Z No. of bitstreams: 2 S1516-84842012000600010.pdf: 614468 bytes, checksum: d64149a3b77faf179f01947b8ae973b3 (MD5) S1516-84842012000600010.pdf.txt: 23597 bytes, checksum: 385ab2b19f8173d4c4c2ebe0bf5d0940 (MD5) Made available in DSpace on 2014-05-20T14:00:43Z (GMT). No. of bitstreams: 2 S1516-84842012000600010.pdf: 614468 bytes, checksum: d64149a3b77faf179f01947b8ae973b3 (MD5) S1516-84842012000600010.pdf.txt: 23597 bytes, checksum: 385ab2b19f8173d4c4c2ebe0bf5d0940 (MD5) Previous issue date: 2012-01-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) OBJECTIVE: The oxidative stress in 20 sickle cell anemia patients taking hydroxyurea and 13 sickle cell anemia patients who did not take hydroxyurea was compared with a control group of 96 individuals without any hemoglobinopathy. METHODS: Oxidative stress was assessed by thiobarbituric acid reactive species production, the Trolox-equivalent antioxidant capacity and plasma glutathione levels. RESULTS: Thiobarbituric acid reactive species values were higher in patients without specific medication, followed by patients taking hydroxyurea and the Control Group (p < 0.0001). The antioxidant capacity was higher in patients taking hydroxyurea and lower in the Control Group (p = 0.0002 for Trolox-equivalent antioxidant capacity and p < 0.0292 for plasma glutathione). Thiobarbituric acid reactive species levels were correlated with higher hemoglobin S levels (r = 0.55; p = 0.0040) and lower hemoglobin F concentrations(r = -0.52; p = 0.0067). on the other hand, plasma glutathione levels were negatively correlated with hemoglobin S levels (r = -0.49; p = 0.0111) and positively associated with hemoglobin F values (r = 0.56; p = 0.0031). CONCLUSION: Sickle cell anemia patients have high oxidative stress and, conversely, increased antioxidant activity. The increase in hemoglobin F levels provided by hydroxyurea and its antioxidant action may explain the reduction in lipid peroxidation and increased antioxidant defenses in these individuals. Universidade Estadual Paulista Instituto de Hematologia Arthur de Siqueira Cavalcanti Santa Casa de São Paulo Faculdade de Ciências Médicas Universidade de São Paulo Universidade Estadual Paulista

Currently, there are many unproven or insufficiently proven cell-based treatments commercially available for hopeful individuals seeking cures for a variety of conditions. Typically, these so-called “therapies” are currently being advertised, sold and administered to patients, although they fail to achieve recognized biological/medical standards of proof for safety or efficacy. In addition, they are often expensive and offered outside the cover of routine clinical care for treatments, outside the realm of conventional clinical trials supervised and monitored by regulatory agencies. This paper summarizes a position document to be published by the International Society for Cellular Therapy (ISCT) as an open manuscript intended for professionals and patient associations. Avoiding a systematic overview of the relevant peer-reviewed literature and investigations, its purpose is to examine multiple aspects of unproven cell therapy interventions including definitions, manufacturing issues, regulations, economic factors and communication. With this document, the ISCT intends to promote a cooperative approach to facilitate the development of safe and effective therapies while minimizing and balancing risks for patients to ultimately establish a coalition of stakeholders that fulfill the vision of a broad, pro-patient cell therapy alliance...

Besides the known effects on sleep disorders, studies show that melatonin, a hormone produced mainly by the pineal gland, plays a key role in energy expenditure, food intake, glucose metabolism in adipocytes and regulating the secretion of various cytokines involved in weight control and appetite, such as leptin. In vitro and in vivo, both in animals and in humans, they demonstrate the potential benefits of melatonin supplementation on various diseases, including the metabolic disorders. This work aims to review the physiology of this hormone, its association with diseases such as obesity and diabetes, the benefits of supplementation of this hormone and the importance of research in the area for scientific evidence about the substance of this type. On the other hand, some countries, like Brazil, has regulated the marketing of this product which reduces the clinical research and the benefits that melatonin could bring to several patients.

Introduction Retinitis pigmentosa (RP) is a severe neurodegenerative disease of the retina that can lead to blindness. Even without treatment, a clinical study with the use of stem cells is currently underway and the results are being evaluated. In the present report we assess the vision-related quality of life in patients with RP submitted to intravitreal use of bone marrow-derived stem cells. Method The study included 20 patients with RP submitted to intravitreal use of bone marrow-derived stem cells. We evaluate the vision-related quality of life (VRQOL) of patients using the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25). Patients were scheduled to answer the questionnaire before treatment and 3 and 12 months after treatment. Results All patients completed the survey as scheduled. There was a statistically significant improvement (P

Relatamos o caso de um paciente masculino de 49 anos, portador de oclusão embólica de todas as artérias da perna esquerda. Após múltiplas e fracassadas tentativas de revascularização e, também, simpatectomia lombar em outros serviços, chegou a nós com indicação de amputação no nível de perna. Propusemos o implante de células-tronco autógenas de medula óssea na panturrilha. Obteve-se um excelente resultado, com a supressão da dor em repouso, melhora da hipotermia e palidez, elevação do índice tornozelo/braço, da velocidade sistólica de pico, dos índices cintilográficos e angiográficos e sensível melhora na granulação no local da amputação do quarto e quinto pododáctilo.

A novel association of t(11;19)(q23;p13) and t(5;16)(q13;q22) was detected by G-banding and spectral karyotyping studies in an 18-year-old patient. While balanced t(11;19) has been often described in acute myelocytic leukemia (AML) French-American-British Cooperative Group subtypes M4 and M5, this patient was diagnosed with the variant AML-M4 with eosinophilia (AML-M4Eo), which is associated with abnormalities in 16q22 and has good prognosis. However, the patient relapsed after allogeneic transplant and died within 2 years of diagnosis, which suggests that the association of these two translocations correlates with a poor prognosis. This report expands the molecular basis of the variability in clinical outcomes and adds the novel t(5;16)(q13;q22) to the spectrum of chromosome 16q22 abnormalities in AML.

Body iron disorders have been reported after myeloablative conditioning in patients undergoing hematopoietic stem cell transplantation (HSCT). There is a concern that labile plasma iron (LPI), the redox-active form of iron, can be involved in the occurrence of toxicity and other complications commonly observed in the early post-HSCT period. In order to better understand the LPI kinetics and its determinants and implications, we undertook sequential LPI determinations before and after conditioning until engraftment in 25 auto-HSCT patients. Increased LPI was present in only 5 patients before starting conditioning. Shortly after conditioning, LPI levels were increased in 23 patients, with peak at day 0, returning to normal range upon engraftment in 21 patients. Overall, LPI levels correlated weakly with serum ferritin and more strongly with transferrin saturation; however, both parameters were apparently not applicable as surrogate markers for increased LPI. Although this was a small cohort, logistic regression suggested that baseline LPI levels could predict occurrence of grade III or IV toxicity. In conclusion, LPI kinetics is influenced by aplasia following conditioning and engraftment. Measuring LPI before starting conditioning can offer an opportunity to predict toxicity and, perhaps, the need for chelation therapy.

Cell therapy, known in the media and among laypeople as stem cell treatment, has been under debate on several totally different fronts. The main confusion, which still persists even though it has been about for many years, is related to the use of embryonic stem cells in experimental and pre-clinical studies; today this occurs in most countries(1,2) but great difficulties exist in Brazil until now(3). This issue was debated extensively for four years in the Brazilian society and in 2008 the Supreme Court legalized studies using human embryonic stem cells. Subsequently, this measure allowed the first line of human embryonic stem cells to be obtained in Brazil(4). Notwithstanding the controversial source of the embryo, in its strict sense cell therapy is a medical procedure that is not new as it goes back centuries to the time when human and even animal blood first began to be used for therapeutic purposes. Landsteiner's discovery of the ABO blood group system in 1900, complemented by the Rh blood group system, paved the way for the incorporation of transfusion medicine in the medical practice(5). Cell replacement therapy using red blood cells and blood components enabled the treatment of many diseases and allowed a leap in surgical techniques including solid organ transplants. The fear of nuclear war and its foreseeable immediate and long-term consequences on human beings helped the progression of research which aimed to minimize the effects with the evolution of reparative cell therapy using bone marrow transplants, which are now called hematopoietic stem cell transplantation (HSCT). This procedure is today common practice. Hereditary and acquired hematologic diseases including onco-hematology, autoimmune and immunodeficiency diseases are on the list of indications for HSCT with this list still expanding(6). At the start of this millennium, the studies and results of cell therapy in degenerative and chronic diseases, the emergence of the concepts of cellular plasticity(7-9), transdifferentiation and fusion(10-12), and the description of the paracrine effect of cells(13), opened new perspectives for research in regenerative therapy using different sources of cells including the bone marrow, peripheral blood and umbilical cord blood. So began the era of regenerative cell therapy, a movement that has caught the imagination of the scientific, academic and lay communities with the idea of new approaches to treat incurable diseases and common diseases that lack good therapeutic options(14). Auspicious results have been described using several experimental models including in myocardial infarction after the use of cell therapy in a small sample of patients(15). The number of publications on the use of stem cells has been expanding geometrically and so publications in all areas of medicine are becoming commonplace. The same has occurred in respect to heart disease in Brazil and after the publication of promising results in Chagasic cardiomyopathy(16), a large double-blind, randomized clinical trial was designed involving 1200 patients with diverse heart diseases(17,18). Subsequently, after 2005 government resources are being allocated to research projects; the National Network of Cell Therapy was created resulting in the establishment of several cell therapy Centers (Figure 1)(19). Investment by the Brazilian Government in the area of cell therapy is shown in Table 1. Figure 1 Number of new cell therapy centers by state established after the creation of the National Network of Cell Therapy. Adapted from Mendez-Otero et al.(19) Table 1 Funding Research for Stem Cell Therapy in Brazil Despite these advances, several questions remain unanswered and the pressure of the community continues in light of the positive results that have been observed in different diseases(20-25). These results do not go unnoticed in the electronic communication age; they quickly become common knowledge. This issue was reviewed and discussed in presentations on the theme during the congress of the Sociedade Brasileira de Transplante de Medula Ossea recently held in Sao Paulo. Among the topics presented, the potential of using mesenchymal stem cells (MST) was debated with their possible use in patients with graft-versus-host disease (GVHD) being stressed. This common adverse reaction after allogeneic HSCT is frequently difficult to control and so the use of MST is indicated in these situations. In Brazil the use of MST is restricted to patients enrolled in clinical trials, which makes it difficult for centers around the country, that are both competent and technically prepared, to offer this type of therapy to a larger number of patients(26). The compassionate use of MST in these cases, when necessary, is based on the data available in the medical literature. This topic has been discussed by Medical and Research Ethics Committees with great repercussions; as in countless other situations involving clinical or surgical procedures, cell therapy cannot be postponed at the expense of the patients' health. In Brazil there is a legal inadequacy in respect to compassionate treatment. And do not forget that the patients cannot wait(23,26-28). Cell therapy has flourished in respect to heart diseases in experimental studies on acute myocardial infarction. Soon clinical trials and case reports related to other heart diseases proved the benefits of the procedure. However ten years after the first reports there are still uncertainties about cell therapy(29,30). Doubts related to cell therapy also extrapolate to the clinical parameters employed in previous studies. These include the use of the left ventricle ejection fraction as a clinical outcome as in many studies. Even without improvements in this parameter being observed, increases in survival and quality of life in many patients subjected to this procedure were demonstrated. The review presented at the congress makes us reflect on the interpretation of results obtained using cell therapy in heart disease. The benefits of the use of cell therapy in the treatment of autoimmune, central nervous system and ophthalmological diseases and for orthopedic complications among others were also demonstrated during the scientific event thereby proving the importance of cell therapy as a new modality of therapy. In conclusion, cell therapy has proven to be safe and effective in many situations, in particular in peripheral arterial diseases when there is a risk of amputation(23). This latter example makes us reflect on the current status of the treatment of diverse diseases in which cell therapy may play a leading or supporting role. This procedure remains crucial to relieve the suffering and benefit patients for whom there is no therapeutic option.

Made available in DSpace on 2015-04-27T11:55:53Z (GMT). No. of bitstreams: 0 Previous issue date: 2013Bitstream added on 2015-04-27T12:08:30Z : No. of bitstreams: 1 ISSN2157-7633-2013-S6-08-01-05.pdf: 1119303 bytes, checksum: 83bb37f4d554521491781bf36209bf60 (MD5) The idiopathic dilated cardiomyopathy (IDC) is one of the major public health problems in the western world. Patients with IDC in functional class IV (New York Health Association - NYHA), even after therapeutic optimization, have high mortality. Stem cell therapy has emerged as a potential therapeutic option for cell death-related heart diseases and several positive effects were assigned to cell therapy in cardiomyopathy. The aim of this study was identify short-term result of cell transplantation in idiopathic dilated cardiomyopathy patients (IDC) who were treated by transplantation of autologous bone marrow mononuclear cells (BMMC). Intracoronary injections of autologous BMMC were performed in eight patients with severe ventricle dysfunction (mean of left ventricle ejection fraction – LEVF=20.03%), cardiac mass muscle around 156.2 g and NYHA between III and IV grades, other 8 IDC patients received placebo. The IDCs were followed - up for one and two years, by magnetic resonance imaging (MRI). The results after one year showed significant improvement in LVEF (mean=181.4) and muscle mass increasing (mean=181.4 g), after two years the LVEF continued improving, reaching a mean of 32.69% and the cardiac muscle mass kept stable (mean=179.4 g). Excepted for one patient, all the other had improvement in the NYHA functional class. The placebo group did not show any improvement. We believe that BMMC implant may be a beneficial therapeutic option for IDC patients. Universidade Estadual Paulista Júlio de Mesquita Filho, Departamento de Ciência da Computação e Estatística, Instituto de Biociências Letras e Ciências Exatas de São José do Rio Preto, Sao Jose do Rio Preto, RUA Cristovão Colombo, 2265, Jardim Nazareth, CEP 15054-000, SP, Brasil Universidade Estadual Paulista Júlio de Mesquita Filho, Departamento de Ciência da Computação e Estatística, Instituto de Biociências Letras e Ciências Exatas de São José do Rio Preto

OBJECTIVES: The aim of this retrospective study was to investigate the results of T-cell large granular lymphocytic leukemia treatment with fludarabine by assessing the complete hematologic response, the complete molecular response, progression-free survival, and overall survival. METHODS: We evaluated the records of six patients with T-cell large granular lymphocytic leukemia who were treated with fludarabine as a first-, second-, or third-line therapy, at a dose of 40 mg/m², for three to five days per month and 6 to 8 cycles. RESULTS: Of the six patients investigated with T-cell large granular lymphocytic leukemia who were treated with fludarabine, five (83.3%) were female, and their median age was 36.5 years (range 18 to 73). The median lymphocyte level was 3.4x10(9)/L (0.5 to 8.9). All patients exhibited a monoclonal T-cell receptor gamma gene rearrangement at diagnosis. Two (33.3%) patients received fludarabine as first-line treatment, two (33.3%) for refractory disease, one (16.6%) for relapsed disease after the suspension of methotrexate treatment dueto liver toxicity, and one (16.6%) due to dyspesia. A complete hematologic response was achieved in all cases, and a complete molecular response was achieved in five out six cases (83.3%). During a mean follow-up period of 12 months, both the progression-free survival and overall survival rates were 100%. CONCLUSION: T-cell large granular lymphocytic leukemia demonstrated a high rate of complete hematologic and molecular response to fludarabine, with excellent compliance and tolerability rates. To confirm our results in this rare disease, we believe that fludarabine should be tested in clinical trials as a first-line treatment for T-cell large granular lymphocytic leukemia.

BACKGROUND: Hodgkin's lymphoma has high rates of cure, but in 15% to 20% of general patients and between 35% and 40% of those in advanced stages, the disease will progress or will relapse after initial treatment. For this group, hematopoietic stem cell transplantation is considered one option of salvage therapy. OBJECTIVES: To evaluate a group of 106 patients with Hodgkin's lymphoma, who suffered relapse or who were refractory to treatment, submitted to autologous hematopoietic stem cell transplantation in a single transplant center. METHODS: A retrospective study was performed with data collected from patient charts. The analysis involved 106 classical Hodgkin's lymphoma patients who were consecutively submitted to high-dose chemotherapy followed by autologous transplants in a single institution from April 1993 to December 2006. RESULTS: The overall survival rates of this population at five and ten years were 86% and 70%, respectively. The disease-free survival was approximately 60% at five years. Four patients died of procedure-related causes but relapse of classical Hodgkin's lymphoma after transplant was the most frequent cause of death. Univariate analysis shows that sensitivity to pre-transplant treatment and hemoglobin < 10 g/dL at diagnosis had an impact on patient survival. Unlike other studies, B-type symptoms did not seem to affect overall survival. Lactic dehydrogenase and serum albumin concentrations analyzed at diagnosis did not influence patient survival either. CONCLUSION: Autologous hematopoietic stem cell transplantation is an effective treatment strategy for early and late relapse in classical Hodgkin's lymphoma for cases that were responsive to pre-transplant chemotherapy. Refractory to treatment is a sign of worse prognosis. Additionally, a hemoglobin concentration below 10 g/dL at diagnosis of Hodgkin's lymphoma has a negative impact on the survival of patients after transplant. As far as we know this relationship has not been previously reported.

Made available in DSpace on 2013-09-27T14:53:53Z (GMT). No. of bitstreams: 1 WOS000208709800007.pdf: 531167 bytes, checksum: 8b937e39a1c7e78e8c4d0ed2acbb1a4e (MD5) Previous issue date: 2011-01-01 Made available in DSpace on 2013-09-30T19:24:06Z (GMT). No. of bitstreams: 1 WOS000208709800007.pdf: 531167 bytes, checksum: 8b937e39a1c7e78e8c4d0ed2acbb1a4e (MD5) Previous issue date: 2011-01-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T15:34:27Z No. of bitstreams: 1 WOS000208709800007.pdf: 531167 bytes, checksum: 8b937e39a1c7e78e8c4d0ed2acbb1a4e (MD5) Made available in DSpace on 2014-05-20T15:34:27Z (GMT). No. of bitstreams: 1 WOS000208709800007.pdf: 531167 bytes, checksum: 8b937e39a1c7e78e8c4d0ed2acbb1a4e (MD5) Previous issue date: 2011-01-01 Cardiovascular Disease Institute (IMC, Sao Jose do Rio Preto, SP, Brazil) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Within the chronic obstructive pulmonary disease (COPD) spectrum, lung emphysema presents, as a primarily histopathologic feature, the destruction of pulmonary parenchyma and, accordingly, an increase in the airflow obstruction distal to the terminal bronchiole. Notwithstanding the significant advances in prevention and treatment of symptoms, no effective or curative therapy has been accomplished. In this context, cellular therapy with stem cells (SCs) arises as a new therapeutic approach, with a wide application potential. The -purpose of this study is to evaluate the safety of SCs infusion procedure in patients with advanced COPD (stage IV dyspnea). After selection, patients underwent clinical examination and received granulocyte colony-stimulating factor, immediately prior to the bone marrow harvest. The bone marrow mononuclear cells (BMMC) were isolated and infused into a peripheral vein. The 12-month follow-up showed a significant improvement in the quality of life, as well as a clinical stable condition, which suggest a change in the natural process of the disease. Therefore, the proposed methodology in this study for BMMC cell therapy in sufferers of advanced COPD was demonstrated to be free of significant adverse effects. Although a larger sample and a greater follow-up period are needed, it is possible to infer that BMMC cell therapy introduces an unprecedented change in the course or in the natural history of emphysema, inhibiting or slowing the progression of disease. This clinical trial was registered with ClinicalTrials.gov (NCT01110252) and was approved by the Brazilian National Committee of Ethics in Research (registration no. 14764, CONEP report 233/2009). Univ Estadual Paulista UNESP, Assis, SP, Brazil Cardiovasc Dis Inst IMC, Sao Jose do Rio Preto, SP, Brazil USP IPT I, Interunits Biotechnol Post Grad Program, São Paulo, Brazil Univ Estadual Paulista UNESP, Assis, SP, Brazil

Foram apresentadas as alterações hematológicas do sangue periférico e da medula óssea em pacientes expostos cronicamente ao benzeno. Foram descritos a biotransformação metabólica e os possíveis mecanismos envolvidos neste tipo de toxicidade. Os dados hematológicos do sangue periférico são mostrados e avaliados em sua importância, sendo a macrocitose e a linfocitopenia sinais precoces de toxicidade ao benzeno. As alterações da medula óssea observadas são demonstradas pelos métodos complementares citológico e histológico. A anormalidade histológica de maior importância foi a hipocelularidade global devida principalmente ao setor granulocítico. Foi observado também aumento do percentual de eosinófilos, de mastócitos e de atipias no setor megacariocítico. Foram observadas alterações de caráter inflamatório e ressaltada a presença de sinais de dismielopoiese. Foram enfatizadas a necessidade da valorização das alterações hematológicas do sangue periférico e a visão critica e global desse importante problema de saúde pública.

The Guidelines Project of the Associacao Medica Brasileira (AMB) and of the Conselho Federal de Medicina (CFM) began in 2000 with specialist societies participating in the preparation of the texts. The guidelines are based on research and contain solid advice on the diagnosis, therapy, and prevention of diseases. Grounded in evidence-based medicine, they seek to answer specific or crucial questions regarding the disease. A review of the literature is performed and, using pre-established criteria, studies on the disease are selected and graded according to their characteristics and type. Randomized clinical trials and meta-analyses have the highest value (A). Second in importance are observational and clinical studies (B), then case reports and case series (C), and finally, publications of consensuses and opinions (D). Due to the methodology employed, current systematic reviews are clearly more relevant when compared to those written in the past. Historically, reviews were much more based on personal opinions and subject to the author's interest, that is, more concerned with the individual point of view and based on personal experience.1 The Associacao Brasileira de Hematologia, Hemoterapia e Terapia Celular (ABHH) began to participate effectively in the development of the guidelines of the AMB in 2009, with contributions by several experts as shown in Table 1; previously, the collection was limited, with fewer themes. After 2012, guidelines on several diseases were completed and published in the Revista Brasileira de Hematologia e Hemoterapia (RBHH); chronic myelogenous leukemia,2 multiple myeloma,3 and diagnosis4 and treatment of immune thrombocytopenic purpura.5 It is also important to quote other systematic reviews published in the RBHH, such as preventive practices in longterm hematopoietic stem cell transplantation survivors, with the participation of experts from several different countries.6 The consensus of the Sociedade Brasileira de Transplante de Medula Ossea (SBTMO) produced the famous 'Pink Book'; this was rounded out with two publications on transplantation in acute myeloid leukemia7 and autoimmune diseases.8 Table 1 Guidelines published on hematological diseases. Acute promyelocytic leukemia (APL) has well-defined clinical, cytogenetic, and morphological characteristics; it encompasses 10% to 15% of all myeloid-type leukemias. Its molecular bases are well defined, with different variations influencing the treatment of patients.9 The results, as reported by the International Consortium on APL, established the treatment strategies and the conduct for the disease in developing countries.10,11 The guidelines for the diagnosis and treatment of APL12 are published in this issue of the RBHH, the first in 2014, thereby adding to those already published. Hopefully, this will stimulate other experts to continue this hard work, aiming to contribute to medical practice and to solidify the knowledge on the diagnoses and treatment of hematologic diseases.

CONTEXT AND OBJECTIVE: Gene expression and immunohistochemical profiling of diffuse large B-cell lymphoma (DLBCL) have revealed important prognostic subgroups: germinal center B-cell-like (GCB-like) DLBCL and activated B cell-like (ABC-like) DLBCL. Although few reports on high-risk DLBCL are available, the prognosis for the GCB-like subgroup has been shown to be better than that of the ABC-like subgroup. The role of Bcl-2 as a predictor of survival in DLBCL cases is unclear and its expression varies between the two subgroups of DLBCL. In this study, we analyzed the frequency and prognostic impact of Bcl-2 protein expression in high-risk DLBCL cases. DESIGN AND SETTING: Retrospective cohort study among DLBCL patients treated at Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP). METHODS: The prognostic impact of the expression of the proteins CD10, Bcl-6, MUM1 (multiple myeloma oncogene-1) and Bcl-2 on high-risk DLBCL cases was evaluated by means of immunohistochemistry. Seventy-three patients aged 18-60 years were evaluated for all these markers. RESULTS: Twenty-four cases (32.9%) were GCB-like and 49 (67.1%) were ABC-like, with no difference regarding complete remission, disease-free survival or overall survival rates. Twenty-seven patients (37%) showed Bcl-2 expression, which was the only independent factor predicting a worse prognosis for overall survival according to multivariate analysis. CONCLUSION: Bcl-2 protein was expressed in 37% of the high-risk DLBCL patients, without any difference between the ABC-like DLBCL and GCB-like DLBCL cases.

Neste fasciculo organizado e conduzido pelo co-editorRodolfo Delfini Cancado, produto de um evento de granderepercussao nacional sobre anemia falciforme, discutem-seas varias nuances clinicas e hematologicas sobre o tema.A anemia falciforme, do ponto de vista historico, e doconhecimento da humanidade desde os tempos imemoriais econstatadas como secular na Africa pelo habito existente emdiversas tribos do continente de tatuar os portadores e ospacientes para identificar a doenca. O primeiro relato em rela-cao a doenca ocorreu nos Estados Unidos da America emnecropsias de pacientes nos quais se identificou agenesiaesplenica em afro-americano com antecedentes clinicos cro-nicos similares ao da anemia falciforme.

O transplante de células-tronco é uma nova terapia com objetivo de produzir regeneração cardíaca pela diferenciação ou aumento dos miócitos cardíacos ou proliferação neovascular em pacientes no estágio final de insuficiência cardíaca congestiva secundária a cardiomiopatia dilatada¹, mas os resultados são desconhecidos2,3. Stem cell transplantation is a new therapy applied to produce cardiac regeneration through differentiation or increase of heart myocytes or neovascular proliferation in patients in the end stage of congestive heart failure secondary to dilated cardiomyopathy¹, but the results are still unknown2,3.

The incidence of Gram-negative bacteremia has increased in hematopoietic stem cell transplant (HSCT) recipients. We prospectively collected data from 13 Brazilian HSCT centers to characterize the epidemiology of bacteremia occurring early post transplant, and to identify factors associated with infection due to multi-drug-resistant (MDR) Gram-negative isolates. MDR was defined as an isolate with resistance to at least two of the following: third- or fourth-generation cephalosporins, carbapenems or piperacillin-tazobactam. Among 411 HSCT, fever occurred in 333, and 91 developed bacteremia (118 isolates): 47% owing to Gram-positive, 37% owing to Gram-negative, and 16% caused by Gram-positive and Gram-negative bacteria. Pseudomonas aeruginosa (22%), Klebsiella pneumoniae (19%) and Escherichia coli (17%) accounted for the majority of Gram-negative isolates, and 37% were MDR. These isolates were recovered from 20 patients, representing 5% of all 411 HSCT and 22% of the episodes with bacteremia. By multivariate analysis, treatment with third-generation cephalosporins (odds ratio (OR) 10.65, 95% confidence interval (CI) 3.75-30.27) and being at one of the hospitals (OR 9.47, 95% CI 2.60-34.40) were associated with infection due to MDR Gram-negative isolates. These findings may have important clinical implications in the decision of giving prophylaxis and selecting the empiric antibiotic regimen.

Nontransferrin-bound iron (NTBI) has been reported shortly after myeloablative conditioning in patients undergoing hematopoietic stem cell transplantation (HSCT), and it is assumed that the appearance of unbound iron in this nontransfusion setting possibly reflects a major disturbance in body iron distribution, which is related mainly to its underutilization due to erythropoiesis suppression. There is a concern that labile plasma iron (LPI), the most toxic fraction of NTBI that includes the redox-active forms of iron, can be involved in the occurrence of toxicity and other complications commonly observed in the early post-HSCT period. Recently, we demonstrated that LPI levels, albeit normal at baseline measurements, increased substantially 48 hours after the start of conditioning in HSCT patients and remained increased until engraftment, when it returned to normal levels (Acta Haematol 2014;131:222-226). Here we provide a more detailed analysis of iron status in HSCT patients by adding determinations of hepcidin and standard iron parameters along with LPI in 25 adult patients undergoing first autologous HSCT following myeloablative conditioning. All iron parameters were determined before the start of conditioning (baseline), on day 0 (before stem cells infusion) and upon documented engraftment (Table). The fast and substantial increase in LPI levels on day 0, indeed reflected a disruption of iron homeostasis by conditioning, that was accompanied by a response in hepcidin and TfS levels. However, reutilization of iron by a restored erythropoiesis upon engraftment lead to a substantial drop in LPI, but not in hepcidin levels, possibly due to the fact that production of hepcidin by the liver is not only modulated by iron loading and erythropoietic activity, but also inflammation. Ferritin baseline levels were already increased and did not change throughout the study. Considering all determinations (baseline, day 0 and engraftment), hepcidin levels correlated positively with ferritin (r=0,43; p=0,01; Figure Panel A) and TfS (r=0,37; p=0,02; Figure Panel B); and LPI correlated positively with TfS (r=4,3; p=0,002; Figure Panel C), although increased LPI levels were observed with normal TfS levels in some patients. A tendency of correlation between hepcidin and LPI was found considering only baseline and day 0 levels (r=0,30; p=0,05; Figure Panel D). These results indicate that LPI reflected better the changes in iron status caused by cytotoxic chemotherapy in HSCT patients, and could serve as a target in the eventuality of chelation therapy in the early period of HSCT. The other iron parameters were probably influenced by inflammation, even upon engraftment, and would not behave as appropriate surrogate markers for increased LPI levels. *LPI levels Figure. Correlations between LPI, hepcidin and transferrin saturation levels throughout the study. Figure. Correlations between LPI, hepcidin and transferrin saturation levels throughout the study. Disclosures No relevant conflicts of interest to declare.

T-cell non-Hodgkin Lymphoma (T-NHL) are uncommon malignancies that represent approximately 10% of all NHL. With few exceptions T-NHL have generally been reported to have a worse prognosis compared with B-cell lymphomas. Standard therapy for most T-NHL still need to be defined. To elucidate the feasibility and efficacy, we retrospectively analysed the data of 11 patients who underwent allogeneic hematopoietic stem cell transplantation from July 1991 to july 2006. Five female and five male patients with a matched sibling donor and a female mismatched underwent a transplant. The median age was 22 years (16 – 34). Six patients were diagnosed as lymphoblastic T, two were anaplastic large cell, two were peripheral T-cell unspecified and one was NK/T extranodal nasal-type. One was in first hard remission, three in second remission, one in third complete remission, one in early first relapse, one in second partial remission and four had refractory disease. Six patients were conditioned with TBI + cyclophosphamide (CY-TBI) and five with busulfan 16 mg/kg and melphalan 140 mg/sqm (Bu-Mel). Graft versus host disease (GVHD) prophylaxis was done with cyclosporin and short course methotrexate for most of the cases. 63 % had acute GVHD grade I to III and 45% had chronic GVHD. Overall survival is 36%. Four of the 11 patients are alive, still in complete remission, after one year, 12 years, 14 years, and 15 years from transplantation. Two of these patients were conditioned with CY-TBI and two with Bu-Mel. Allogeneic transplant can be useful to treat advanced T-NHL patients.

Hematopoietic stem cell transplantation is a valid alternative as post-remission therapy in ALL. Our aim was analyzed retrospectively the clinical outcomes of 97 ALL patients with HLA identical sibling donors who underwent an allo PBSCT. Median age was 24 ys (2–45), advanced disease was present in 74%, conditioning without irradiation was 56%; GVHD prophylaxis with MTX/CsA was 91%; CD34+ median was 4.6X106/kg (1.2–24); the median follow-up for surviving patients was 22 months (1.6–93). Median day for neutrophils and platelets engraftment was 15 and 13, respectively; no TBI conditioning, no MTX/CsA, were associated significantly with faster neutrophils engraftment; no MTX/CsA with platelets. Cumulative incidence (CI) for ≥ 2 aGVHD was 45%, extensive cGVHD 50%; aGVHD in patients who received TBI conditioning was 34% (P=0.04). The estimates of OS and DFS at 92 months was 21% and 31%, respectively; OS for patients >36ys was 16% (P=0.04), for patients with aGVHD 11% (P=0.03); there was a trend towards better OS and DFS in patients with cGVHD (54%, 63%; P=0.07, P=0.06). CI for relapses was 60%; relapses for cGVHD patients were 36% (P= 0.05), and there was a trend towards higher relapses in advanced disease (66%, P=0.06). TRM was 64%; in those patients with aGVHD, 73% (P=0.008). In multivariate analyses no MTX/CsA was related with the speed of platelets engraftment (P=0.007); TBI conditioning was associated with less aGVHD and TRM (P=0.05, P=0.01); aGVHD had a negative impact on OS with higher TRM (P=0.02, P=0.02). Although not confirmed in the multivariate analyses, fewer relapses, and a trend towards better OS, and DFS were found in patients with extensive cGVHD. However, further follow up will be necessary to confirm these results.

This is a retrospective analysis of 1084 patients who received an allogeneic HSCT in 10 Brazilian Centers, from February 1983 to March 2003, aiming to validate the EBMT risk score. Data from transplanted patients and donors regarding patients age, disease stage at transplantation, HLA full-match sibling donor or full-match unrelated donors, donor-recipient gender match and the interval from diagnosis to transplantation, were used as variables to calculate the EBMT risk score. This score was analyzed using Cox Proportional Hazards Model. The OS, DFS, TRM and relapse were analyzed using Kaplan-Meier and cumulative incidence, whenever appropriate. In all there were 647 (60%) males and 437 (40%) females, the median age was 32 years old (range 1 – 59); 898 (83%) were in chronic phase, 146 (13%) were in accelerated phase and 40 (4%) were in blast crisis; 151 (14%) were younger than 20 years old, 620 (57%) were between 20 and 40 and 313 (29%) were older than 40; 1025 (95%) received HLA full-match sibling transplant and only 59 (5%) received an unrelated transplant. Female donor to male recipient occurred in 283 (26%) transplants. The interval from diagnosis to transplantation was less than 12 months in 223 (21%) cases and greater in 861 (79%). The OS, DFS, TRM and, relapse were 49%, 50%, 45%, 25%, respectively. The risk score 0–1 occurred in 179 (17%), score 2 in 397 (37%), score 3 in 345 (32%), score 4 in 135 (12%), and score 5–6 in 28 (2%). The risk scores 0–1 and 2 did not show any difference in terms of OS (58% and 55%, respectively) but they were significantly better than scores 3 or more (score 3 – 44%, 4 – 36 % and, 5-6 - 27%, respectively) (P

Uncertainty still exists with the effects of allogeneic PBSCT on the clinical outcomes of patients with hematological malignancies. Our aim was analyzed retrospectively the clinical outcomes of 483 patients who underwent an allo PBSCT in 9 Brazilians centers from May 1994 to February 2004. The analyzes included patients with hematological malignancies who underwent PBSCT from HLA identical siblings donors treated with G-CSF at a dose of 10mgr/kg/day, 5 days. Median age was 34ys old (2–57), advanced disease was present in 58%, conditioning without irradiation was 85%; GVHD prophylaxis with MTX/CsA was 91%; CD34+ median was 4.7X106/kg (0.51–71.6); the median follow-up for surviving patients was 797 days (8–3420); median day for neutrophils and platelets engraftment was 15 and 14, respectively; cumulative incidence (CI) for ³ 2 aGVHD was 38%; extensive cGVHD 63%; CI for transplant relate mortality (TRM) 59%; CI for relapse 37%; the estimates of OS and DFS at 9 ys are 33% and 42, respectively. The following factors were significantly associated with better outcomes for engraftment, aGVHD, cGVHD, OS, DFS, relapse, and TRM in univariate analyzes, respectively: neutrophils and platelets engraftment: CD34+ cell dose > 2.8X106/kg, GVHD prophylaxis other than MTX/CsA, and sex match other than female donor for male recipient; aGVHD: age 4.7X106/kg; cGVHD: age < 25ys, sex match other than female donor for male recipient, advanced disease and CD3+ dose < 170X106/kg; OS: early disease; DFS: early disease, CD34+ dose > 4.7X106/kg; relapse: age> 25ys, CD34+ cell dose > 2.8X106/kg, and early disease; TRM: early disease. All the results remained significant in multivariate analyzes, but CD34+ dose and platelet engraftment; age and CD34+ dose in aGVHD; age and CD3+ in cGVHD, and age in relapse. In our experience, sex match, CD34+ dose, GVHD prophylaxis may influence the engrafment, and sex match and disease phase the cGVHD. Furthermore, advanced disease had a negative impact on OS and TRM;. CD34+ higher dose and early disease were associated with better DFS and lower relapse.

The craniofacial reconstruction after a craniotomy can sometimes be challenging due to the complexity of the fronto-orbital region, an adequate reconstruction can be achieved with combination of autologous bone and alloplastic materials, with low morbidity and mortality rates, even though it is still needed to perform more studies about this technique to assess its functional and aesthetic outcomes. At this paper we present one single case of a 19 year old male patient in who we performed a cranioplasty of fronto-orbital region, with a multifragmented autologous bone after 7 months of cryopreservation. The cranioplasty was performed with bone fragments and titanium mini plates to achieve a good functional and aesthetic outcome, without resorption, infection or complications. We described our method of cryopreservation and sterilization.

Objective: To describe episodes of venous thrombosis in two young patients with combined congenital and acquired thrombophilias. Patients: Two patients attending a university hospital with episodes of deep vein thrombosis presenting at an unusually young age were studied. Tests for thrombo-philias showed these patients had protein S deficiency combined with high titres of cardiolipin antibodies. Interventions: The patients were anticoagulated with oral anticoagulants. Results: No further episode of thrombosis was seen in either patient over the following 2 years. Cnclusions: A detailed search for inherited and acquired thrombophilias should be undertaken in patients presenting with extensive venous thrombosis at an unusually young age. Oral anticoagulants are effective in managing this clinical problem. Indefinite anticoagulation may be required in patients presenting with combined thrombophilias.