RESUMO
The complementation Q group (FANCQ) subtype of Fanconi anemia (FA) caused by the ERCC4/XPF mutation is very rare. Two siblings, aged 13 and 10 with Fanconi phenotypic features, presented with right hemiparesis and focal-onset seizures. In both cases, cranial magnetic resonance imaging (MRI) showed mass-like lesions accompanied by peripheral edema and calcification. In one case, oral steroid treatment and surgical excision were performed, while in the other case, the cranial lesion regressed just with steroid treatment and without surgery. Both siblings remained wheelchair-bound due to neurological dysfunction. One case died due to hepatocellular carcinoma. ERCC4/XPF gene mutation was detected in both siblings.
Assuntos
Proteínas de Ligação a DNA , Anemia de Fanconi , Irmãos , Humanos , Anemia de Fanconi/complicações , Anemia de Fanconi/genética , Anemia de Fanconi/patologia , Masculino , Proteínas de Ligação a DNA/genética , Criança , Adolescente , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/complicações , Feminino , Imageamento por Ressonância Magnética , Mutação , Diagnóstico DiferencialRESUMO
Clear cell sarcoma of the kidney (CCSK) is a rare primary renal tumor in children. It is known for its propensity to metastasize to bones and lungs at initial diagnosis. Distant metastatic relapses occur in about 15-16% of the patients, with the brain being the most frequent site of relapse. Imaging features of brain metastases from CCSK have only been reported in a few cases and most reports lack a detailed description of the imaging findings. We present brain magnetic resonance imaging (MRI) findings in an infant with relapsed CCSK who developed multiple parenchymal metastases with concentric signal alterations and no tumor-associated edema.
Assuntos
Neoplasias Encefálicas , Neoplasias Renais , Sarcoma de Células Claras , Criança , Lactente , Humanos , Sarcoma de Células Claras/diagnóstico por imagem , Sarcoma de Células Claras/patologia , Rim/patologia , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/patologia , Neoplasias Encefálicas/patologia , Imageamento por Ressonância MagnéticaRESUMO
OBJECTIVES: Iron deficiency anemia (IDA) is the most common type of anemia in childhood and it leads to a hypercoagulable state. We investigated endogenous thrombin production in platelet-poor plasma before and after oral iron replacement in children with IDA using the thrombin generation assay (TGA). METHODS: A total of 72 children diagnosed with IDA (IDA group) and 60 healthy children (control group) were included in the study. Blood samples were collected from the patients before and 1 month after oral iron replacement. TGA parameters [lag time, time to peak, peak height, endogenous thrombin potential (ETP)] were studied. RESULTS: In the IDA group, the lag time and time to peak decreased by 8.3% and 10.6%, respectively, and the endogenous thrombin potential (ETP) and peak height both increased by 30% compared to those of the control group. Compared to the values before iron replacement, 1 month after iron replacement, the lag time and time to peak increased by 8.7% and 5%, respectively, and the ETP and peak height decreased by 31% and 31.3%, respectively, and became similar to those of the control group. CONCLUSION: Children with IDA have increased endogenous thrombin production in platelet-poor plasma and a tendency for hypercoagulability. These changes are reversible, and the ETP values become similar to those of healthy children 1 month after iron replacement.
Assuntos
Anemia Ferropriva , Trombofilia , Criança , Humanos , Trombina , Testes de Coagulação Sanguínea , FerroRESUMO
BACKGROUND: Retinoblastoma (RB) is the most common intraocular malignancy in childhood. Advanced RB, associated with exceedingly poor prognosis, requires more intensive multiagent chemotherapy than conventional regimens. Rescue of the bone marrow after intensive chemotherapy is achieved with stem cell transplantation. The sequential courses (tandem transplantation) of high-dose chemotherapy followed by autologous stem cell transplantation allow for even greater dose intensity in consolidation with the potential to use different active chemotherapeutics at each transplant and have proven feasible and successful in treating children with recurrent/refractory solid tumors. CASE DESCRIPTION: We report an infant with trilateral high-risk RB who received tandem high-dose chemotherapy (HDC) followed by autologous stem cell transplantation after the conventional chemotherapy. A 5-month-old female patient presented with strabismus, and the ophthalmoscopic examination showed intraocular tumoral lesions in both eyes. Magnetic resonance imaging (MRI) concluded the trilateral retinoblastoma diagnosis due to a tumoral mass in the optic chiasm. The follow-up ophthalmologic examinations and the MRI detected stable disease after six cycles of multiagent chemotherapy. CONCLUSIONS: Rescue with autologous stem cell transplantation after HDC allows for an increase in chemotherapy intensity. Tandem transplantation provides the chance to perform different chemotherapeutics at each transplant and enables an increase in the chemotherapy intensity, thus providing a positive effect on disease-free survival.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Neoplasias da Retina , Retinoblastoma , Criança , Lactente , Humanos , Feminino , Retinoblastoma/diagnóstico , Retinoblastoma/tratamento farmacológico , Transplante Autólogo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva Local de Neoplasia , Transplante de Células-Tronco , Neoplasias da Retina/diagnóstico , Neoplasias da Retina/tratamento farmacológico , Terapia CombinadaAssuntos
Neoplasias Ósseas , Segunda Neoplasia Primária , Leucemia-Linfoma Linfoblástico de Células Precursoras , Sarcoma de Ewing , Criança , Humanos , Segunda Neoplasia Primária/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológicoRESUMO
In this study, oxidative stress marker (malondialdehyde, MDA) and antioxidant enzymes (glutathione (GSH), catalase (CAT)) levels in the liver and pancreas tissue and the histopathological effects of N-acetylcysteine (NAC) were investigated in l-asparaginase (l-ASP) induced liver and pancreatic damage in rats. Forty male albino rats were divided into four groups. The control group was intraperitoneally injected physiological saline (0.02 mL/g); NAC group was injected NAC (200 mg/kg, five days); l-ASP group was injected single-dose l-ASP (10,000 U/kg), and l-ASP + NAC group was injected NAC for five days following single-dose l-ASP (10,000 U/kg). The surgical operation was performed on all animals on the fifth day. There was no difference between the groups regarding tissue MDA, GSH, and CAT levels (p>.05, for all). In the group receiving NAC after l-ASP, there was a significant improvement in the liver and pancreas damage score than the l-ASP group. NAC was effective in reducing organ damage caused by l-ASP.
Assuntos
Acetilcisteína , Asparaginase , Acetilcisteína/metabolismo , Acetilcisteína/farmacologia , Animais , Asparaginase/farmacologia , Glutationa/metabolismo , Glutationa/farmacologia , Humanos , Fígado , Masculino , Estresse Oxidativo , Pâncreas/metabolismo , Ratos , Ratos WistarRESUMO
We report on a 12-year-old boy with congenital thrombotic thrombocytopenic purpura, on who had an erroneous diagnosis as chronic immune thrombocytopenia. The patient presented with complaints of jaundice and skin rash. Laboratory analysis showed nonimmune hemolytic anemia and severe thrombocytopenia. Peripheral blood smear showed 8% schistocytes, polychromasia, and anisocytosis. The ADAMTS13 antigen and activity were suspected to be lower than 5% with any antibodies against the enzyme. The DNA sequence analyses resulted in compound heterozygosity consisting of c.291_391del in exon 3 and c.4143dupA in exon 29. Schistocyte (fragmented erythrocytes) on the peripheral blood smear is a light that illuminates the diagnosis. Early recognition of the disease can prevent inappropriate treatments and morbidities due to organ damage.
Assuntos
Proteína ADAMTS13 , Sequência de Bases , Eritrócitos Anormais/enzimologia , Éxons , Púrpura Trombocitopênica Trombótica , Deleção de Sequência , Proteína ADAMTS13/sangue , Proteína ADAMTS13/genética , Criança , Humanos , Masculino , Púrpura Trombocitopênica Trombótica/sangue , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/genéticaAssuntos
Fibroma , Dermatopatias , Neoplasias Cutâneas , Fibroma/diagnóstico , Humanos , Lactente , Dedos do PéRESUMO
OBJECTIVE: Neutropenia is defined as an absolute neutrophil count (ANC) below 1500/mm3 in the peripheral blood and is a common condition in childhood. In this study, underlying etiological causes and prognoses in children in follow-up due to neutropenia were analyzed to form a guide for physicians working in primary health care institutions. METHODS: The medical records of pediatric patients who were followed up as an inpatients or outpatients due to neutropenia between October 2014 and October 2017 were reviewed retrospectively. RESULTS: A total of 94 patients were included in the study with a median age of 24 (8-77) months. The median ANC at the time of admission was 600 (300-970)/mm3. The ANC was 0-500/mm3 in 34 patients (36.2%), 500-1000/mm3 in 36 patients (38.3%), and 1000-1500/mm3 in 24 patients (25.5%). Of the total, 43 patients (45.7%) were followed up as inpatients and 51 (54.3%) were followed as outpatients. Fifty-five patients (58.5%) were diagnosed with post-infectious neutropenia. The most common focus of infection was the upper respiratory airway (38.4%). The etiological cause could not be identified in 23 (24.6%) patients, neutropenia developed during drug use in 6 patients (6.3%), 5 patients (5.3%) were diagnosed with Vitamin B12 deficiency (Vitamin B12 level: 168 [129-174] pg/ml, the levels were studied in 48 patients), 2 patients (2%) were diagnosed with chronic benign neutropenia, 1 patient (1.1%) was diagnosed with immune deficiency, 1 patient (1.1%) was diagnosed with autoimmune lymphoproliferative syndrome, and 1 patient (1.1%) was diagnosed with hemophagocytic lymphohistiocytosis secondary to a previous infection. No patient was diagnosed with congenital neutropenia. A total of 91 patients (96.8%) recovered from the neutropenia. Neutropenia did not improve in 3 patients (3.2%). One patient was lost due to infection. CONCLUSION: Etiological cause can be shown in approximately 75% of neutropenic children. The most common etiological cause is infection. Drug use, nutritional deficiencies, and chronic benign neutropenia are less common causes of neutropenia. The clinical course is largely benign and the mortality rate is very low.
RESUMO
OBJECTIVE: This study aims to compare the frequency of respiratory viruses using real-time and multiplex polymerase chain reaction technology and nasopharyngeal swabs taken during exacerbation of patients aged 0-18 years followed for febrile neutropenia (FN) with non-FN children. METHODS: This prospective study included a total of 40 patients with FN and malignancies followed at Eskisehir Osmangazi University, Department of Pediatric Hematology and Oncology. The control group (n=76) consisted of age-matched patients with upper respiratory tract infections (URTIs) or lower respiratory tract infections (LRTIs) who were admitted to the emergency service due to fever. RESULTS: Viral agents were detected in 16 of 53 FN attacks (30.1%). The most commonly isolated viruses were coronavirus (23.7%, n=9), influenza B (18.4%, n=7), and adenovirus (18.4%, n=7). Of 76 children diagnosed with URTI with fever (52.6%) had viral agents, and only 28 of them had a single agent. The most commonly isolated virus was adenovirus (28.6%, n=14). Viral factors were found in 32 of 42 patients (76.1%) patients diagnosed with LRTI, while respiratory syncytial virus was the most common virus in 27 patients (21.7%, n=5). CONCLUSION: Our study results show that viral agents play an important role in the etiology of FN. This is the first study to show that viral agents play an important role in the etiology of this disease and viral factors in non-neutropenic febrile children at the same time period by detecting respiratory viruses in 30% of FN cases. More similar studies provide antiviral therapy in selected patients, as well as these studies lead to reduce the use of antimicrobial agents or allow more selective use of antibiotics and/or the earlier discontinuation of these antibiotics in febrile neutropenic children who have been shown to have viral cause of respiratory tract infection based on clinical and microbiological/molecular diagnostic criteria.
RESUMO
Oxidative stress is a potential mechanism involved in the pathogenesis of iron deficiency anaemia (IDA). Although a tendency for hypercoagulability has been reported in IDA, its underlying mechanism is yet to be elucidated. This study investigated the probable relationship between oxidative stress and hypercoagulability in children with IDA. This study included 57 children diagnosed with IDA (IDA group) between October 2016 and October 2017 in addition to 48 healthy children (control group). The maximum clot firmness (MCF) index, and clot formation time (CFT) index, which are indicators of hypercoagulability in rotational thromboelastometry assays [intrinsic TEM (INTEM) and extrinsic TEM (EXTEM)] derived from our previous study, were recorded. Total oxidant status (TOS), total antioxidant capacity (TAC) and oxidative stress index (OSI) were analysed from serum samples of the individuals. In IDA group, OSI and TOS levels were higher and TAC level was lower compared to the control group (Pâ<â0.001, for all). The EXTEM and INTEM MCF in the IDA group was higher than in the control group, while the INTEM CFT was lower than in the control group (Pâ<â0.001, Pâ<â0.001, Pâ<â0.05, published data).TOS and OSI had a negative correlation with INTEM CFT (r:-0.361, Pâ<â0.001 and r:-0.333, Pâ=â0.001) and a positive correlation with INTEM MCF (r:+0.420, Pâ<â0.001 and r:+0.367, Pâ<â0.001) and EXTEM MCF (r:+0.476, Pâ<â0.001 and r:+0.403, Pâ<â0.001). However, TAC demonstrated no correlation with CFT and MCF index. The oxidant-antioxidant balance is disrupted in favour of oxidative stress in children with IDA. In addition, TOS and OSI, which are parameters of oxidative stress, are correlated with CFT and MCF indices. Oxidative stress appears to be an important factor for the development of tendency to hypercoagulability in IDA.
Assuntos
Anemia Ferropriva/complicações , Trombofilia/complicações , Adolescente , Anemia Ferropriva/sangue , Anemia Ferropriva/metabolismo , Coagulação Sanguínea , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estresse Oxidativo , Trombofilia/sangue , Trombofilia/metabolismoRESUMO
Complications and toxicities of chemotherapy are the significant causes of morbidity and mortality during the treatment of childhood leukemias. Respiratory viral infections are the most common cause of febrile neutropenia episodes and rarely spread to the salivary glands. We submitted 4 patients with acute leukemia who got diagnosed with acute sialadenitis during their chemotherapy period.
Assuntos
Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/tratamento farmacológico , Sialadenite/genética , Doença Aguda/terapia , Criança , Pré-Escolar , Humanos , Masculino , Neutropenia/complicações , Neutropenia/etiologiaRESUMO
BACKGROUND: Changes in oxidative stress and thiol / disulfide balance are thought to play a role in the pathogenesis of idiopathic thrombocytopenic purpura (ITP). Our study investigates total oxidant level (TOS), total antioxidant level (TAS), oxidative stress index (OSI) levels and thiol / disulfide balance in pediatric patients with acute and chronic ITP. METHODS: Thirty four patients with acute ITP, eighteen patients with chronic ITP and thirty three healthy children (control) were included. TOS, TAS, OSI, thiol / disulfide balance were analyzed. RESULTS: In acute ITP, TAS levels were lower than chronic ITP and control, TOS and OSI levels were higher than control, and native thiol level was lower than chronic ITP (p < 0.05). In acute ITP; disulfide level, disulfide / native thiol and disulfide / total thiol ratios were higher than chronic ITP and control, and native thiol / total thiol ratio was lower than chronic ITP and control group (p = 0.038, p = 0.018, respectively). TOS and OSI levels of the chronic ITP were higher than the control group (p < 0.05). CONCLUSIONS: The results of this study have shown that oxidative stress increases in children with acute ITP and chronic ITP, that thiol / disulfide balance is disrupted in favor of disulfide in acute ITP, and that thiol / disulfide balance isn`t disrupted in chronic ITP patients whose platelet count is close to normal and who don`t require treatment.
Assuntos
Dissulfetos , Púrpura Trombocitopênica Idiopática , Antioxidantes/metabolismo , Criança , Humanos , Estresse Oxidativo , Púrpura Trombocitopênica Idiopática/diagnóstico , Compostos de SulfidrilaRESUMO
BACKGROUND: Cerebral sinovenous thrombosis (CSVT) in children is a rare and life-threatening cerebrovascular disease. Hence, we evaluated its clinical presentations, inherited and acquired prothrombotic risk factors along with the accompanying diseases, the thrombosis locations as well as the outcomes of anticoagulant therapy in children with CSVT. METHODS: The medical records of pediatric CSVT patients treated between January 2011 and September 2018 were analyzed retrospectively. RESULTS: The study included 29 children, 15 boys (51.7%) and 14 girls (48.3%), with the median age being 11 years (range:3 days-17 years). The most commonly presented complaint in neonates was seizures and in the non-neonatal age groups was a headache. Also, at least one acquired and/or inherited thrombophilic risk factor was identified in 89.7% of the patients. The most commonly acquired prothrombotic risk factors along with the accompanying diseases included infections, central venous catheter, and dehydration, while the most commonly inherited thrombophilic risk factors included heterozygous factor-V Leiden mutation and elevated lipoprotein (a). The most common thrombosis location was found to be the transverse sinus. Also, none of the patients died due to the thrombotic episode. Complications included epilepsy in five patients, hydrocephalus in one patient, and intracranial hypertension in another patient. CONCLUSIONS: Clinicians need to be well aware of the inherited and acquired prothrombotic risk factors in CSVT. It should also be kept in mind that at-risk patients may also present with nonspecific signs and symptoms with no apparent neurological manifestation. The risk of acute complications and long-term sequelae can be substantially reduced if diagnosed early and initiated with appropriate treatment at the early stages.
Assuntos
Trombose Intracraniana , Trombose dos Seios Intracranianos , Trombose , Criança , Pré-Escolar , Feminino , Humanos , Trombose Intracraniana/diagnóstico , Trombose Intracraniana/epidemiologia , Trombose Intracraniana/etiologia , Masculino , Estudos Retrospectivos , Fatores de Risco , Trombose dos Seios Intracranianos/diagnóstico , Trombose dos Seios Intracranianos/epidemiologia , Trombose dos Seios Intracranianos/etiologiaRESUMO
BACKGROUND: Childhood cancer survivors (CCSs) are at risk for anthracycline-induced cardiotoxicity which tends to be more prominent long after completion of the chemotherapy. The aim of this study was to examine echocardiographic parameters of anthracycline-induced subclinical cardiotoxicity in children who had received chemotherapy. MATERIALS AND METHODS: A cross-sectional single-center study was conducted in a tertiary level university hospital in Eskisehir, Turkey. A total of 50 CCSs and 40 healthy peers were included. The CCSs were divided into 3 subgroups according to cumulative anthracycline dose (100-200 mg/m2, 201-299 mg/m2, and ≥ 300 mg/m2). Biventricular cardiac examination was performed with conventional echocardiography and tissue Doppler echocardiography imaging (TDI). RESULTS: The mean duration from termination of chemotherapy to echocardiographic assessment was 3.9 ± 2.2 years. The mean age of the CCSs was 11.6 ± 3.9 years. TDI-derived mitral annular isovolumetric relaxation time (IVRT) and myocardial performance index (MPI) were higher in the high-dose group of CCSs than in controls (P = .006, P = .007, P < .001, P = .0014, respectively). IVRT was also higher in patients with ≥ 300 mg/m2 cumulative dose than in those with < 200 mg/m2 (P = .007). TDI-derived mitral annular MPI and IVRT were significantly associated with cumulative anthracycline dose (r = 0.288, P = .006, r = 0.340, P = .001). CONCLUSION: A cumulative anthracycline dose > 300 mg/m2 may lead to subclinical cardiotoxicity, and is therefore a potential risk factor for late onset cardiac failure. TDI-derived MPI can be a sensitive tool to reveal subtle signs of myocardial damage, which may facilitate implementation of preventive therapies for patients suspected to be at risk.
RESUMO
Intensive chemotherapy can cause long-lasting immunosuppression in children who survived cancer. The immunosuppression varies according to the type of cancer, intensity of chemotherapy and age of the patient. A sufficient immune reconstruction when has been completed in childhood cancer survivors, the re-vaccination program can achieve sufficient antibody levels for some of the life-threatening vaccine-preventable infectious diseases. This study evaluates the serological status of pediatric acute lymphoblastic leukemia (ALL) cases before and after the intensive chemotherapy treatment. Antibodies against measles, mumps, rubella, varicella, hepatitis A and B were tested with the enzyme-linked immunosorbent assay (ELISA) method. Antibody titers were measured firstly at the leukemia diagnosis time when the chemotherapy was not started. The second evaluation of antibody titers was studied at 6 months after the cessation of chemotherapy for all patients. Forty-six patients with the mean age of 6.1 ± 4.5 years were participated in this study. Changing to seronegative after treatment was significantly different in measles, rubella, hepatitis A and hepatitis B (p < .05). Seventy-eight (28%) antibody levels in the patients were non-protective for all diseases. Only three (7%) patients had protective antibody levels for all diseases in the sixth month of chemotherapy cessation. There was a negative correlation between patient's age and losing protective antibody levels for any vaccine-preventable disease (p < .05). Antibody levels against vaccine-preventable diseases have evident that reduced after ALL treatment at childhood. Pediatric ALL survivors must be re-vaccinated for vaccine-preventable diseases after achieving immune reconstruction.
Assuntos
Sarampo , Caxumba , Leucemia-Linfoma Linfoblástico de Células Precursoras , Rubéola (Sarampo Alemão) , Anticorpos Antivirais , Criança , Pré-Escolar , Humanos , Imunização , Lactente , Vacina contra Sarampo-Caxumba-Rubéola , Sobreviventes , VacinaçãoRESUMO
PURPOSE: Metamizole, which has antipyretic and pain-relieving properties, is generally used to treat fever in children who do not respond to paracetamol treatment. The most remarkable side effect of metamizole is that it causes myelotoxicity independently of dose. In this study, we aimed to present the clinical features of paediatric patients who developed agranulocytosis after the use of metamizole and draw attention to this side effect. METHODS: The patients who were admitted to Eskisehir Osmangazi University Faculty of Medicine Hospital, Pediatric Infectious Diseases and Pediatric Hematology Service, between January 1, 2015, and December 31, 2018, with a diagnosis of secondary agranulocytosis to metamizole use were examined retrospectively. RESULTS: In all, 12 patients were included in the study; oral metamizole was used in these patients for fever reduction. The mean absolute neutrophil count was 225/mm3 ± 226 (0-600/mm3) at admission, and the neutrophil value of 11 patients was < 500/mm3. The mean length of hospitalisation of the patients was 9.92 ± 8 (3-28) days. Eight patients received intravenous antibiotic therapy and four patients received at least one of the following treatments: intravenous immunoglobulin, granulocyte colony-stimulating factor and methylprednisolone. Bone marrow aspiration examination showed neutrophil/band maturation delaying in the myeloid series with normocellular bone marrow in three patients. Hypocellularity in the bone marrow and decrease in myeloid precursors were observed in three patients. There were no fatal cases. CONCLUSION: The development of agranulocytosis after the use of metamizole causes long-term hospitalisation and may require the use of medications in treatment management. Considering the availability of alternative options to treat fever and pain, and given the side-effect profile of metamizole, it should not be the preferred, first-line antipyretic treatment in children.
Assuntos
Agranulocitose/induzido quimicamente , Anti-Inflamatórios não Esteroides/efeitos adversos , Antipiréticos/efeitos adversos , Dipirona/efeitos adversos , Dor/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos RetrospectivosRESUMO
Hepatoblastoma (HBL) is the most frequently detected malignant tumor of the liver in childhood. HBLs detected antenatally or up to 3 months after birth are considered congenital HBLs. We report a five-day-old female infant in whom a hepatic mass was detected at 20 weeks' gestation. At birth (36 weeks), the hepatic mass measured 12x6 cm, and she had respiratory distress. Pulmonary hypertension (PHT) was detected on echocardiographic evaluation. Despite dual medical therapy, her PHT did not improve. Histologically, the biopsy demonstrated a mixed epithelial-mesenchymal HBL with predominance of fetal morphology in the epithelial component. Chemotherapy was initiated on postnatal day 15; however, the baby died of respiratory failure on postnatal day 23. Conclusion: HBL is an embryonal tumor which can develop early in the intrauterine period. Although the mechanism is not known, it may cause PHT which would affect the prognosis negatively.