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1.
Eur J Clin Microbiol Infect Dis ; 40(6): 1169-1176, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33415492

RESUMEN

The purpose of this study is to characterize adverse events (AEs) of clinical interest reported with ceftolozane-tazobactam and ceftazidime-avibactam, as an aid in monitoring patients affected by severe multidrug-resistant Gram-negative infections. We queried the worldwide FDA Adverse Event Reporting System (FAERS) and performed disproportionality analysis, selecting only designated medical events (DMEs) where ceftolozane-tazobactam and ceftazidime-avibactam were reported as suspect. Serious neurological AEs were further investigated. The reporting odds ratios were calculated, deemed significant by the lower limit of the 95% confidence interval (LL95% CI) > 1. All other drugs/events recorded in FAERS and cephalosporins showing clinical evidence of neurological AEs were respectively selected as comparator for analysis of DMEs and neurotoxicity. Qualitative analysis including case-by-case assessment and deduplication was also performed. Overall, 654 and 506 reports mentioning respectively ceftolozane-tazobactam and ceftazidime-avibactam were found, with DMEs accounting respectively for 13.1% and 10.9% of cases. Agranulocytosis (N = 12; LL95% CI = 12.40) and pancytopenia (14; 6.18) emerged as unexpected AEs with ceftolozane-tazobactam, while acute pancreatitis (7; 8.63) was an over-reported unexpected DME with ceftazidime-avibactam. After deduplication, four unequivocally different cases of agranulocytosis with ceftolozane-tazobactam were retained, occurring on average after 8.8 days. Causality was probable and possible respectively in three and one case. Among neurological AEs exhibiting significant disproportionality, encephalopathy with both antibiotics and mental status changes with ceftazidime-avibactam were retained in at least three cases after deduplication. Although rare, clinicians should monitor high-risk patients (i.e. individuals affected by haematological malignances, HIV infection, or treated with concomitant myelotoxic agents) for early unexpected occurrence of agranulocytosis with ceftolozane-tazobactam.


Asunto(s)
Agranulocitosis/etiología , Antibacterianos/efectos adversos , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Lactamas/efectos adversos , Inhibidores de beta-Lactamasas/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Compuestos de Azabiciclo/efectos adversos , Compuestos de Azabiciclo/uso terapéutico , Ceftazidima/efectos adversos , Ceftazidima/uso terapéutico , Cefalosporinas/efectos adversos , Cefalosporinas/uso terapéutico , Combinación de Medicamentos , Quimioterapia Combinada/efectos adversos , Femenino , Humanos , Lactamas/uso terapéutico , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Pancitopenia/etiología , Farmacovigilancia , Estudios Retrospectivos , Tazobactam/efectos adversos , Tazobactam/uso terapéutico , Inhibidores de beta-Lactamasas/uso terapéutico
2.
J Med Genet ; 57(1): 18-22, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31413121

RESUMEN

BACKGROUND: Metaphyseal dysplasia without hypotrichosis (MDWH) is a rare form of chondrodysplasia with no extraskeletal manifestations. MDWH is caused by RMRP mutations, but it is differentiated from the allelic condition cartilage-hair hypoplasia (CHH), which in addition to chondrodysplasia is characterised by thin hair, immunodeficiency and increased risk of malignancy. The long-term outcome of MDWH remains unknown. OBJECTIVE: We diagnosed severe agranulocytosis in a subject with RMRP mutations and normal hair. Based on this observation, we hypothesised that MDWH may, similar to CHH, associate with immune deficiency and malignancy. METHODS: We collected clinical and laboratory data for a cohort of 80 patients with RMRP mutations followed for over 30 years and analysed outcome data for those with features consistent with MDWH. RESULTS: In our cohort, we identified 10 patients with skeletal but no extraskeletal features during preschool age. Eight of these patients developed malignancy or clinically significant immunodeficiency during follow-up. Two of them died during chemotherapy for malignancy. At the time of the first extraskeletal manifestation, patients were school aged, 20, 43 and 50 years old. Laboratory signs of immunodeficiency (impaired lymphocyte proliferative responses) were demonstrated in four patients before the onset of symptoms. The patient outside this cohort, who had RMRP mutations, skeletal dysplasia, normal hair and severe agranulocytosis at 18 years of age, underwent haematopoietic stem cell transplantation. CONCLUSIONS: MDWH can present with severe late-onset extraskeletal manifestations and thus should be reclassified and managed as CHH.


Asunto(s)
Agranulocitosis/etiología , Síndromes de Inmunodeficiencia/etiología , Mutación , Neoplasias/etiología , Osteocondrodisplasias/patología , ARN Largo no Codificante/genética , Adulto , Anciano , Femenino , Cabello/anomalías , Enfermedad de Hirschsprung , Humanos , Persona de Mediana Edad , Osteocondrodisplasias/complicaciones , Osteocondrodisplasias/congénito , Osteocondrodisplasias/genética , Osteocondrodisplasias/metabolismo , Enfermedades de Inmunodeficiencia Primaria , Adulto Joven
3.
J Pediatr Hematol Oncol ; 42(8): e750-e755, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-31876777

RESUMEN

INTRODUCTION: Neutropenia and agranulocytosis are rare side effects of deferiprone (DFP) in patients treated for iron overload. Unfortunately, no study directly addressed special risks in countries with a background of ethnic neutropenia, such as Oman. AIM: The aim of this study was to report the incidence of neutropenia in Omani children with ß-thalassemia treated with different iron chelators. METHODS/DESIGN: This was a retrospective study that included 179 Omani pediatric patients. For patients who developed neutropenia, demographic data, iron-chelating agent, clinical presentation, management, and outcome were recorded. Detailed clinical, laboratory±radiologic information was added for patients with agranulocytosis. RESULTS: Neutropenia was encountered in 43.6% of patients: severe neutropenia in 10 patients, moderate in 29, and mild in 69 patients. Severe and moderate neutropenia had similar incidence among DFP-exposed and DFP-naive patients (P=0.515 and 0.421, respectively), while mild neutropenia was common among DFP-naive patients (P=0.0001). A higher incidence of DFP-related agranulocytosis (4.1%) was noted compared with previous reports, but none had a fatal outcome. CONCLUSIONS: In a community with ethnic neutropenia, mild to moderate neutropenia is common. Higher incidence of severe neutropenia and agranulocytosis mandates careful monitoring and rational modification of iron-chelating agents to avoid life-threatening complications.


Asunto(s)
Agranulocitosis/epidemiología , Etnicidad/estadística & datos numéricos , Quelantes del Hierro/efectos adversos , Neutropenia/epidemiología , Talasemia beta/tratamiento farmacológico , Adolescente , Adulto , Agranulocitosis/etiología , Agranulocitosis/patología , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Neutropenia/etiología , Neutropenia/patología , Omán/epidemiología , Pronóstico , Estudios Retrospectivos , Adulto Joven , Talasemia beta/patología
4.
Medicina (Kaunas) ; 56(6)2020 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-32545570

RESUMEN

Agranulocytosis is a rare but very serious complication of thyrostatic therapy. In severe hyperthyroidism, the removal of circulating thyroid hormones by plasmapheresis may be an effective therapeutic option. This report describes the therapeutic difficulties and successful preoperative treatment with plasmapheresis in a 63-year-old patient admitted to the Endocrinology Clinic with severe hyperthyroidism, during the course of giant toxic nodular goiter and agranulocytosis, which occurred after 2 weeks of taking methimazole. During hospitalization, methimazole treatment was discontinued and therapy with steroids, a beta blocker, propylthiouracil, Lugol's solution, lithium carbonate, and antibiotics were initiated. Granulocyte colony growth stimulating factor was also used to resolve agranulocytosis. Due to the failure to achieve euthyreosis using this approach, we decided to conduct thyroid surgery, as a life-saving action, after preparation of the patient by plasmapheresis. Two plasmapheresis procedures were performed, resulting in a decrease in the concentration of free thyroid hormones. Total thyroidectomy was performed and there were no complications during surgery. We conclude that plasmapheresis may be considered as an effective alternative treatment option for the preparation of patients with hyperthyroidism for surgery, when the clinical situations prevent the use of conventional treatments for hyperthyroidism and when immediate life-saving surgery is necessary.


Asunto(s)
Bocio Nodular/terapia , Hipertiroidismo/terapia , Metimazol/efectos adversos , Plasmaféresis/métodos , Cuidados Preoperatorios/normas , Agranulocitosis/etiología , Antitiroideos/efectos adversos , Antitiroideos/uso terapéutico , Electrocardiografía/métodos , Femenino , Humanos , Metimazol/uso terapéutico , Persona de Mediana Edad , Plasmaféresis/estadística & datos numéricos , Cuidados Preoperatorios/métodos , Cuidados Preoperatorios/estadística & datos numéricos , Tiroidectomía/métodos , Resultado del Tratamiento
5.
Acta Haematol ; 140(1): 42-45, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30114687

RESUMEN

Currently, there are only 2 case reports of Waldenström macroglobulinemia (WM) associated with severe neutropenia. This is a case report of a woman with a past medical history of WM who presented with neutropenic fever. The patient's febrile neutropenia resolved after RCD chemotherapy (cyclophosphamide 750 mg/m2, dexamethasone 20 mg, and rituximab 375 mg/m2). Fourteen days after administration, the neutrophil level had started to rise and normalized after 6 days. To the best of our knowledge, this is the 3rd reported case of agranulocytosis due to WM.


Asunto(s)
Agranulocitosis/diagnóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Macroglobulinemia de Waldenström/diagnóstico , Anciano , Agranulocitosis/etiología , Ciclofosfamida/administración & dosificación , Dexametasona/administración & dosificación , Femenino , Humanos , Recuento de Leucocitos , Neutrófilos/citología , Tomografía Computarizada por Tomografía de Emisión de Positrones , Rituximab/administración & dosificación , Macroglobulinemia de Waldenström/complicaciones , Macroglobulinemia de Waldenström/tratamiento farmacológico
6.
Vnitr Lek ; 64(5): 520-525, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30193521

RESUMEN

Granulocytopenia is defined as a decrease of peripheral blood granulocytes below lower limit of normal range. Patients with severe granulocytopenia - agranulocytosis exhibit < 0.5 × 109/l granulocytes in peipheral blood. Granulocytopenia may result from congenital or acquired defective production of granulocyte precursors or it may be a consequence of increased destruction of mature granulocytes, most frequently caused by immune mechanisms. Investigation of origin of granulocytopenia must be connected with exclusion of etiological agents causing secondary neutropenia (infections, autoimmune disorders, drugs, LGL syndrome). Patients with > 0.5 × 109/l of granulocytes usually do not exhibit clinical symptoms unless they do not suffer from a concomitant disease (especially immunodeficiency). Patients with severe granulocytopenia are indicated for supportive treatment and for administration of G-CSF. Children with severe congenital neutropenia (SCN) are at risk of later development of MDS or AML and are candidates for SCT when signs of disease progression appears. Key words: diagnosis - granulocytopenia - growth factors - pathogenesis - transplantation -treatment.


Asunto(s)
Agranulocitosis , Neutropenia , Agranulocitosis/diagnóstico , Agranulocitosis/tratamiento farmacológico , Agranulocitosis/etiología , Enfermedades Autoinmunes/complicaciones , Niño , Factor Estimulante de Colonias de Granulocitos , Granulocitos , Humanos , Infecciones/complicaciones , Recuento de Leucocitos , Neutropenia/etiología
7.
Allergy ; 72(4): 519-533, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27861988

RESUMEN

The monoclonal anti-immunoglobulin E (IgE) antibody, omalizumab, was the first drug approved for use in patients with chronic idiopathic/spontaneous urticaria (CIU/CSU) who remain symptomatic despite H1 -antihistamine treatment. Omalizumab binds to free IgE, which lowers free IgE levels and causes FcεRI receptors on basophils and mast cells to be downregulated. It has been shown to improve symptoms of CIU/CSU, but its mechanism of action is not currently understood. Potential mechanisms in CIU/CSU include reducing mast cell releasability, reversing basopenia and improving basophil IgE receptor function, reducing activity of IgG autoantibodies against FcεRI and IgE, reducing activity of IgE autoantibodies against an antigen or autoantigen that has yet to be definitively identified, reducing the activity of intrinsically 'abnormal' IgE, and decreasing in vitro coagulation abnormalities associated with disease activity. However, none of these theories alone or in combination fully account for the pattern of symptom improvement seen with omalizumab therapy, and therefore, no one mechanism is likely to be the definitive mechanism of action. Additional research is needed to further clarify the involvement of omalizumab in relieving symptoms associated with the complex, multifactorial pathogenesis of CIU/CSU.


Asunto(s)
Antialérgicos/farmacología , Antialérgicos/uso terapéutico , Omalizumab/farmacología , Omalizumab/uso terapéutico , Urticaria/tratamiento farmacológico , Urticaria/etiología , Agranulocitosis/tratamiento farmacológico , Agranulocitosis/etiología , Agranulocitosis/metabolismo , Animales , Anticuerpos Monoclonales Humanizados/farmacología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Autoanticuerpos/inmunología , Basófilos/efectos de los fármacos , Basófilos/inmunología , Basófilos/metabolismo , Basófilos/patología , Enfermedad Crónica , Humanos , Inmunoglobulina E/inmunología , Inmunoglobulina G/inmunología , Mastocitos/inmunología , Mastocitos/metabolismo , Receptores de IgE/metabolismo , Resultado del Tratamiento , Urticaria/metabolismo , Urticaria/patología
8.
Am J Emerg Med ; 35(5): 803.e5-803.e6, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-27912922

RESUMEN

Infectious mononucleosis secondary to Epstein-Barr virus typically follows a relatively benign and self-limited course. A small subset of individuals may develop further progression of disease including hematologic, neurologic, and cardiac abnormalities. A mild transient neutropenia occurring during the first weeks of acute infection is a common finding however in rare cases a more profound neutropenia and agranulocytosis may occur up to 6weeks following the onset of initial symptoms. We describe the case of an 18-year-old woman who presented 26days following an acute infectious mononucleosis diagnosis with agranulocytosis and fever. No source of infection was identified and the patient had rapid improvement in her symptoms and resolution of her neutropenia. The presence of fever recurrence and other non-specific symptoms in individuals 2-6weeks following acute infectious mononucleosis symptom onset may warrant further assessment for this uncommon event.


Asunto(s)
Agranulocitosis/etiología , Antibacterianos/uso terapéutico , Infecciones por Virus de Epstein-Barr/complicaciones , Fiebre/etiología , Mononucleosis Infecciosa/complicaciones , Ácido Penicilánico/análogos & derivados , Adolescente , Agranulocitosis/tratamiento farmacológico , Agranulocitosis/terapia , Progresión de la Enfermedad , Infecciones por Virus de Epstein-Barr/tratamiento farmacológico , Femenino , Humanos , Mononucleosis Infecciosa/tratamiento farmacológico , Ácido Penicilánico/uso terapéutico , Piperacilina/uso terapéutico , Combinación Piperacilina y Tazobactam , Insuficiencia del Tratamiento
9.
J Korean Med Sci ; 32(12): 2021-2028, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29115086

RESUMEN

In epithelial ovarian cancer (EOC), intraperitoneal (IP) administration of chemotherapy is an effective first-line treatment and may improve outcomes, compared with intravenous (IV) chemotherapy. We used Kaplan-Meier survival analysis to compare long-term survival between propensity score-matched patients with advanced EOC receiving IP (n = 34) vs. IV (n = 68) chemotherapy. Additionally, clinical features associated with carboplatin-based (n = 21) and cisplatin-based (n = 16) IP chemotherapy were analyzed and compared with those associated with IV chemotherapy. The IP and IV chemotherapy groups had a median follow-up duration of 67 (range, 3-131) and 62 (range, 0-126) months, respectively, with no significant difference in progression-free survival (PFS) (P = 0.735) and overall survival (OS) (P = 0.776). A significantly higher proportion of patients in the IV (91.2%) than in the IP (67.6%) chemotherapy group (P = 0.004) received ≥ 6 cycles. However, the frequency of toxic events (anemia, granulocytopenia, nausea/vomiting, abdominal pain, hepatotoxicity, neuromuscular effects) was significantly higher in the IP than in the IV group. Within the IP group, no significant differences were observed in PFS (P = 0.533) and OS (P = 0.210) between the cisplatin-based and carboplatin-based chemotherapy subgroups. The 10-year OS was 28.6% and 49.2% in carboplatin-based and cisplatin-based IP chemotherapy groups, respectively. Toxic events (granulocytopenia, leukopenia, nausea/vomiting, abdominal pain, hepatotoxicity, neuromuscular effects) were significantly more common in the cisplatin-based subgroup. In patients with EOC, cisplatin-based IP chemotherapy may be an acceptable alternative to IV chemotherapy regarding long-term survival, but toxicity must be addressed.


Asunto(s)
Carboplatino/uso terapéutico , Cisplatino/uso terapéutico , Infusiones Intravenosas/métodos , Inyecciones Intraperitoneales/métodos , Neoplasias Ováricas/tratamiento farmacológico , Adulto , Anciano , Agranulocitosis/etiología , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Carboplatino/efectos adversos , Cisplatino/efectos adversos , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Náusea/etiología , Estadificación de Neoplasias , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/patología , Vómitos/etiología
11.
Pediatr Neurosurg ; 51(2): 57-60, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26636657

RESUMEN

BACKGROUND: Neutrophilia is associated with brain injury and is frequently accompanied by eosinopenia. Although eosinopenia is a poor prognostic indicator for various diseases, its significance in intracranial events has not been investigated. METHODS: We retrospectively included 22 pediatric patients (≤18 years old) who experienced traumatic intracranial hemorrhage between 2002 and 2015. Patients were divided into two groups based on the presence or absence of eosinopenia on admission, i.e. the proportion of eosinophils to total white blood cells <1.0%. RESULTS: The mean Glasgow Coma Scale score was marginally lower in the eosinopenia group (14.1 vs. 12.0, p = 0.06). The mean Glasgow Outcome Scale-Extended (GOSE) score was significantly lower in the eosinopenia group (7.5 vs. 5.7, p = 0.02), and the mean length of hospital stay tended to be longer in patients with eosinopenia (7.8 vs. 28.4, p = 0.10). In our multivariate logistic regression analysis, eosinopenia was the only significant risk factor for poor outcome (GOSE score 1-7, OR 29.7, p = 0.03) and prolonged hospital stay (>2 weeks, OR 7.1, p = 0.047). CONCLUSION: These results demonstrate the significance of eosinopenia as a novel prognostic factor in traumatic intracranial hemorrhage in children.


Asunto(s)
Agranulocitosis/etiología , Eosinófilos , Hemorragia Intracraneal Traumática/complicaciones , Tiempo de Internación , Niño , Preescolar , Femenino , Escala de Coma de Glasgow , Humanos , Puntaje de Gravedad del Traumatismo , Masculino , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento
12.
Indian J Lepr ; 87(4): 233-239, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29762952

RESUMEN

Dapsone is an extensively Used drug for the treatment of leprosy as well as'some other clinical problems worldwide: Its use has been predicted to increase further, especially in non leprosy conditions. Treatment with Dapsone is sometimes known'to be associated with side-effects, which include gastrointestinal intolerance, haemolysis, methaemoglobinaemia, agranulocytosis, psychosis, peripheral neuritis and varied dermatological conditions, varying from simple rash to severe life threatening epidermolytic reactions and Dapsone hypersensitivity syndrome (DHS). DHS is a rare delayed hypersensitivity reaction involving multiple organs. the condition is associated with high morbidity and is potentially fatal. In this article, the focus is on etiopathogenesis, diagnosis and management of DHS. Awareness of the varied presentation/s of the condition, early recognition, withdrawal of the drug and proper management helps in rapid reduction in morbidity and preventing fatalities associated with it.


Asunto(s)
Dapsona/uso terapéutico , Leprostáticos/uso terapéutico , Lepra/tratamiento farmacológico , Agranulocitosis/etiología , Dapsona/efectos adversos , Síndrome de Hipersensibilidad a Medicamentos/etiología , Humanos , Leprostáticos/efectos adversos , Metahemoglobinemia/etiología , Enfermedades de la Piel/etiología
13.
Am J Hematol ; 89(11): 1055-62, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24912821

RESUMEN

Chronic lymphocytic leukemia (CLL) is frequently complicated by secondary autoimmune cytopenias (AIC) represented by autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), pure red cell aplasia, and autoimmune granulocytopenia. The distinction of immune cytopenias from cytopenias due to bone marrow infiltration, usually associated with a worse outcome and often requiring a different treatment, is mandatory. AIHA and ITP are more frequently found in patients with unfavorable biological risk factors for CLL. AIC secondary to CLL respond less favorably to standard treatments than their primary forms, and treating the underlying CLL with chemotherapy or monoclonal antibodies may ultimately be necessary.


Asunto(s)
Agranulocitosis/etiología , Anemia Hemolítica Autoinmune/etiología , Leucemia Linfocítica Crónica de Células B/complicaciones , Síndromes Paraneoplásicos/etiología , Púrpura Trombocitopénica Idiopática/etiología , Aplasia Pura de Células Rojas/etiología , Corticoesteroides/uso terapéutico , Agranulocitosis/sangre , Agranulocitosis/diagnóstico , Agranulocitosis/terapia , Anemia Hemolítica Autoinmune/sangre , Anemia Hemolítica Autoinmune/diagnóstico , Anemia Hemolítica Autoinmune/terapia , Presentación de Antígeno , Autoanticuerpos/inmunología , Células Sanguíneas/inmunología , Transfusión de Componentes Sanguíneos , Células Clonales/inmunología , Terapia Combinada , Humanos , Inmunoglobulina G/inmunología , Cadenas Pesadas de Inmunoglobulina/genética , Inmunoglobulina M/inmunología , Inmunosupresores/uso terapéutico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/inmunología , Modelos Inmunológicos , Células Madre Neoplásicas/inmunología , Síndromes Paraneoplásicos/sangre , Síndromes Paraneoplásicos/diagnóstico , Síndromes Paraneoplásicos/terapia , Pronóstico , Púrpura Trombocitopénica Idiopática/sangre , Púrpura Trombocitopénica Idiopática/diagnóstico , Púrpura Trombocitopénica Idiopática/terapia , Receptores de Antígenos de Linfocitos B/inmunología , Aplasia Pura de Células Rojas/sangre , Aplasia Pura de Células Rojas/diagnóstico , Aplasia Pura de Células Rojas/terapia , Factores de Riesgo , Esplenectomía , Subgrupos de Linfocitos T/inmunología
14.
Anesteziol Reanimatol ; 59(4): 39-45, 2014.
Artículo en Ruso | MEDLINE | ID: mdl-25549485

RESUMEN

OBJECTIVE: The aim of the study was to assess efficacy of high-doses ofantithrombin 111 (AT) for treatment of septic shock in patients with an agranulocytosis. DESIGN: Prospective, controlled study. PATIENTS: 29 patients from 18 to 74 years old, with blood diseases complicated with septic shock Dates of study: from 2006 to 2012. METHODS: The patients were randomized into two groups. Group-1 included 14 patients, who did not receive AT and group-2 included 15 patients who received AT. RESULTS: Demographic indicators, condition severity according to APACHE II, level of thrombocytopenia, levels ofplasma procalcitonin, interleukin-6 (IL-6) and C-reactive protein (CRP) were the same in both groups. Level of AT was decreased in both groups; however it was higher in the group-1 (50% vs. 60%, p < 0.05). In the group-1, microorganisms were found in the blood of 9 patients. In the group-2, the microorganisms were found in the blood of 11 patients. Inflammation markers were decreased after the treatment of septic shock in both groups (p<0.05). The decreasing of procalcitonin in group-1 was from 43.8 to 1 ng/ml in 14 days and from 12.8 to 1.6 ng/ml in 7 days in group-2. The decreasing of CRP in group-1 was from 224 to 114 mg/l in 7 days and from 146 to 60 mg/l in 14 days in group-2. The decreasing of IL-6 in group-1 was from 1617 to 100 pg/ml in 3 days and from 5895 to 77 pg/ml in 7 days in group-2. A level of AT was increased only in group-2 (under 12% per day). 28-day survival was higher in group-2 (60 +/- 13% vs. 45 +/- 13%, p<0.05). We did not find any complications of the treatment with AT concentrate. CONCLUSION: Treatment of septic shock with high-doses of antithrombin III was effective and safe in patients with an agranulocytosis.


Asunto(s)
Agranulocitosis/tratamiento farmacológico , Antitrombina III/uso terapéutico , Antitrombinas/uso terapéutico , Choque Séptico/tratamiento farmacológico , APACHE , Adolescente , Adulto , Anciano , Agranulocitosis/sangre , Agranulocitosis/etiología , Antitrombina III/administración & dosificación , Antitrombina III/efectos adversos , Antitrombinas/administración & dosificación , Antitrombinas/efectos adversos , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Enfermedades Hematológicas/complicaciones , Enfermedades Hematológicas/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Choque Séptico/sangre , Choque Séptico/etiología , Resultado del Tratamiento , Adulto Joven
15.
Lancet ; 379(9821): 1155-66, 2012 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-22394559

RESUMEN

Thyrotoxicosis is a common disorder, especially in women. The most frequent cause is Graves' disease (autoimmune hyperthyroidism). Other important causes include toxic nodular hyperthyroidism, due to the presence of one or more autonomously functioning thyroid nodules, and thyroiditis caused by inflammation, which results in release of stored hormones. Antithyroid drugs are the usual initial treatment (thionamides such as carbimazole or its active metabolite methimazole are the drugs of choice). A prolonged course leads to remission of Graves' hyperthyroidism in about a third of cases. Because of the low remission rate in Graves' disease and the inability to cure toxic nodular hyperthyroidism with antithyroid drugs alone, radioiodine is increasingly used as first line therapy, and is the preferred choice for relapsed Graves' hyperthyroidism. Total thyroidectomy is an option in selected cases. Future efforts are likely to concentrate on novel and safe ways to modulate the underlying disease process rather than stopping excess thyroid hormone production.


Asunto(s)
Hipertiroidismo/fisiopatología , Hipertiroidismo/terapia , Agranulocitosis/etiología , Amiodarona/efectos adversos , Antitiroideos/administración & dosificación , Antitiroideos/efectos adversos , Antitiroideos/farmacología , Antitiroideos/uso terapéutico , Fibrilación Atrial/etiología , Fibrilación Atrial/fisiopatología , Enfermedades Autoinmunes/fisiopatología , Niño , Tolerancia al Ejercicio/fisiología , Femenino , Bocio Nodular/etiología , Enfermedad de Graves/diagnóstico , Enfermedad de Graves/tratamiento farmacológico , Enfermedad de Graves/fisiopatología , Oftalmopatía de Graves/terapia , Humanos , Hipertiroidismo/complicaciones , Hipertiroidismo/diagnóstico , Hipertiroidismo/cirugía , Radioisótopos de Yodo/uso terapéutico , Embarazo , Recurrencia , Factores de Riesgo , Hormonas Tiroideas/metabolismo , Tiroidectomía , Tiroiditis , Tirotoxicosis/inducido químicamente , Tirotoxicosis/fisiopatología , Tirotropina/sangre
16.
Chemotherapy ; 59(1): 66-73, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23839050

RESUMEN

BACKGROUND: To define the maximum tolerated dose (MTD) tolerability and efficacy of intra-arterial chemotherapy with irinotecan in patients with liver metastases of colorectal carcinoma (CRC). METHODS: Superselective intra-arterial irinotecan was applied on days 1, 14, 28 and 42. The initial dose was 140 mg/m² with escalation in the subsequent patient group to 160 mg/m². The final protocol toxicity evaluation was 260 mg/m². Patients required histologically proven disease and adequate bone marrow, liver and renal function, no extrahepatic metastasis and a life expectancy >12 weeks. results: Thirty-three patients were enrolled (median age 65, range 49-78 years). On dose level VI (240 mg/m²), 1 case of dose-limiting toxicity (DLT) (granulocytopenia) was observed, leading to an enlarged cohort of 6 patients. As no additional DLT was detected on this level, an escalation to level VII was performed. On the dose level of 260 mg/m², irinotecan DLTs were observed, resulting in the termination of escalation and the declaration of dose level VI as MTD. Imaging follow-up with Response Evaluation Criteria in Solid Tumors (RECIST) criteria revealed a complete response in 1 patient, stable disease in 31 patients, and progressed disease in 1 patient. The median time to progression was 4.7 months, the median overall survival 15.6 months. CONCLUSION: The method of intra-arterial chemotherapy with irinotecan is well tolerated and shows promising local response rates in liver metastases of CRC.


Asunto(s)
Antineoplásicos Fitogénicos/uso terapéutico , Camptotecina/análogos & derivados , Neoplasias Colorrectales/patología , Neoplasias Hepáticas/tratamiento farmacológico , Anciano , Agranulocitosis/etiología , Antineoplásicos Fitogénicos/efectos adversos , Camptotecina/efectos adversos , Camptotecina/uso terapéutico , Estudios de Cohortes , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Humanos , Inyecciones Intraarteriales , Irinotecán , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/secundario , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Análisis de Supervivencia , Tomografía Computarizada por Rayos X
17.
Schweiz Monatsschr Zahnmed ; 123(1): 19-31, 2013.
Artículo en Francés, Alemán | MEDLINE | ID: mdl-23426587

RESUMEN

Whenever a dentist is dealing with abscess formation in the oral and maxillofacial region, it is mostly from dental origins. However, sometimes uncommon (co-)factors are present and responsible for major complications. Many general conditions or medications can significantly influence the course of an inflammation. It might spread faster and wider and also be resistant to "correct" therapy. This case report should raise awareness about general conditions supporting inflammation and demonstrate the importance of interdisciplinary treatment in these situations. A 76-year-old patient was referred to the maxillofacial surgery clinic after extraction of two teeth resulted in therapy-resistant painful swelling. Her dentist already had initiated "standard" therapy including Ponstan® (mefenamic acid) and Clamoxyl® (amoxicillin) without success. Initial blood testing came back with severe agranulocytosis. Immediately all potentially myelosuppressing drugs were stopped while myelosupporting drugs were prescribed. Under close interdisciplinary treatment conditions, healing was then uneventful without the necessity of surgical intervention. The challenge in inflammation treatment is to identify patients with uncommonly severe, fast-progressing, or therapy-resistant disease as early as possible. Further examination including blood workup for several medical parameters is indispensable in those patients.


Asunto(s)
Agranulocitosis/etiología , Carcinoma Basocelular/complicaciones , Neoplasias Mandibulares/complicaciones , Extracción Dental/efectos adversos , Anciano , Agranulocitosis/diagnóstico , Amoxicilina/efectos adversos , Carcinoma Basocelular/diagnóstico , Carcinoma Basocelular/cirugía , Diagnóstico Diferencial , Farmacorresistencia Bacteriana , Femenino , Humanos , Enfermedad Iatrogénica , Neoplasias Mandibulares/diagnóstico , Neoplasias Mandibulares/cirugía , Ácido Mefenámico/efectos adversos , Absceso Periodontal/tratamiento farmacológico , Absceso Periodontal/etiología , Trombocitopenia/diagnóstico , Trombocitopenia/etiología
18.
Cancer Med ; 12(19): 19372-19382, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37768027

RESUMEN

BACKGROUND: Infection is the most common adverse event of acute lymphoblastic leukemia (ALL) treatment and is also one of the main causes of death. METHODS: To investigate the clinical characteristics and risk factors of severe infections during the maintenance phase of ALL treatment, we conducted a retrospective study. RESULTS: A total of 181 children were eligible and 46 patients (25.4%) suffered from 51 events of severe infection, most of which occurred in the first half year of the maintenance phase (52.9%). The most common infection was pulmonary infection (86.3%) followed by bloodstream infection (19.6%). The main symptoms of ALL patients with pulmonary infection were fever, cough, and shortness of breath. The main manifestations of computer tomography (CT) were ground glass shadow (56.8%), consolidation shadow (27.3%), and streak shadow (25%). Multivariate binary logistic regression analysis showed that agranulocytosis, agranulocytosis ≥7 days, anemia, and low globulin level were independent risk factors for severe infection during the maintenance phase (all p < 0.05). CONCLUSIONS: Taken together, blood routine examinations and protein levels should be monitored regularly for ALL patients in the maintenance phase, especially in the first 6 months. For ALL patients with risk factors, preventive anti-infective or supportive therapies can be given as appropriate to reduce the occurrence of severe infections.


Asunto(s)
Agranulocitosis , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Niño , Estudios Retrospectivos , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Factores de Riesgo , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Agranulocitosis/tratamiento farmacológico , Agranulocitosis/etiología
19.
Anesteziol Reanimatol ; (2): 41-8, 2012.
Artículo en Ruso | MEDLINE | ID: mdl-22834287

RESUMEN

PURPOSE: Hemostasis disorders are the part of multiple organ failure (mOF) in sepsis. This work objective is to evaluate the system parameters in septic patients. PATIENTS AND METHODS: 55 oncohaematological patients were included in study: 45 with sepsis and 10 patients in control group (no signs of infection). Septic patients were subdivided into septic patients without multiple organ failure, patient with multiple organ failure and patients with septic shock. The C-reactive protein (CRP), procalcitonine (pCT), interleukine-6 (IL-6) serum concentration and fibrinolysis parameters were measured Patients were examined daily during first 5 days, later once a week during 28 days, control group was examined one time. RESULTS: Levels of CRP IL-6 and PCT were raised since 1st day. PCT and IL-6 concentrations were higher in sepsis and MOF group and septic shock group, than in sepsis without MOF group. CRP was raised in all patients. PCT went to normal at 7th day, CRP and IL-6 have started to decrease after 7th day, but both were higher than in control group. T-PA and plasmin inhibitors were comparable to control group and haven't changed significantly. Septic shock patients and patients with MOF have shown a decrease of plasminogen activity. Patients without MOF have shown an initially decreased plasminogen activity, but after 2 days it was similar to control group. PAI-I activity was increased only in septic shock and MOF groups in first days, and was similar to control group in cases of no MOF. Exended XIIa-dependent fibrinolysis time in average was present in all septic patients since 1st day, and extended twice in MOF and septic shock groups. Clot lysis time tended to decrease starting from 8th day, but it was longer than in control group till 28th day. A raised D-dimer concentration compared to control group was present in 75% of patients, but no difference was found among subgroups. A raised D-dimer serum concentration was relevant for prognosis. CONCLUSION: The most sensitive diagnostic test in sepsis is XIIa-dependent fibrinolysis. Plasminogen and PAI-I activity changes are mostly present inpatient with MOF and septic shock. The 28-day survival rate was 60% in MOF and septic shock groups and 95% in no MOF groups. A raised D-dimer concentration was found in 75% of septic patients.


Asunto(s)
Agranulocitosis/sangre , Médula Ósea , Fibrinólisis , Insuficiencia Multiorgánica/sangre , Sepsis/sangre , Adolescente , Adulto , Anciano , Agranulocitosis/etiología , Agranulocitosis/mortalidad , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Transfusión Sanguínea , Femenino , Neoplasias Hematológicas/sangre , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/tratamiento farmacológico , Neoplasias Hematológicas/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia Multiorgánica/etiología , Insuficiencia Multiorgánica/mortalidad , Estudios Prospectivos , Sepsis/etiología , Sepsis/mortalidad , Análisis de Supervivencia , Adulto Joven
20.
Drug Des Devel Ther ; 16: 4269-4277, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36540715

RESUMEN

Aim: To investigate the efficacy and safety of preoperative neoadjuvant therapy (PD-1 inhibitor plus nab-PTX and nedaplatin) for resectable stage III lung squamous cell carcinoma (SCC) patients. Methods: Patients with locally advanced lung SCC (stage IIIA, IIIB) who received PD-1 inhibitor combined with nab-PTX and NED between February 2019 and June 2021 in Weihai Municipal Hospital were included and underwent surgical treatment 4 weeks after 2-4 cycles neoadjuvant therapy. The rate of resection R0, the effective rate, the complete pathological remission rate (pCR) and the rate of major pathological remission (MPR) were observed. Results: A total of 14 initially unresectable male patients with lung SCC were included and received neoadjuvant treatment after evaluation. Nine out of 14 patients (64.3%) experienced treatment-related adverse events (TRAE), among which 8 (57.1%) experienced grade (G) I-II TRAEs including nausea, vomiting, fatigue, constipation, elevated ALT and AST, hyperthyroidism, hypothyroidism, rash, granulocytopenia, and thrombocytopenia, and 1 (7.1%) experienced grade III-V TRAEs (G), including granulocytopenia and atelectasis. Thirteen patients (92.86%) achieved RECIST-assessed partial remission (PR), while 1 patient (7.14%) achieved stable disease (SD) on imaging assessment after neoadjuvant treatment and continued to be progression-free for 26 months. Of the 11 patients who underwent resection, all were alive and recurrence/progression-free. MPR and pCR were observed in 2 (18.18%) and 9 (81.82%), respectively. IHC results exhibited that all NSCLC patients exhibited positive PD-L1 expression (9/14, TPS ≥50% or greater; 5/14, 1% < TPS < 50%). Two were negative for ALK, EGFR, and ros-1, and the rest were not examined for driver oncogene mutation. Conclusion: The neoadjuvant therapy of the PD-1 inhibitor combined with nab-PTX and NED demonstrated remarkable therapeutic efficacy and good safety on stage III lung SCC without increasing the risk of TRAE, mortality and surgery-related complications, or impede surgery feasibility.


Asunto(s)
Agranulocitosis , Carcinoma de Pulmón de Células no Pequeñas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Trombocitopenia , Humanos , Masculino , Paclitaxel Unido a Albúmina/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Terapia Neoadyuvante , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Paclitaxel/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/cirugía , Agranulocitosis/tratamiento farmacológico , Agranulocitosis/etiología , Pulmón/patología
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