RESUMO
Relapsed and/or refractory (R/R) primary central nervous system lymphoma (PCNSL) has a poor prognosis. A 57-year-old man diagnosed with PCNSL achieved a complete response by high-dose methotrexate-based chemotherapy followed by autologous hematopoietic stem cell transplantation (ASCT). The disease was not cured, so he was treated with the anti-CD19 chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel after the third relapse. However, the disease relapsed again 28 days after CAR T-cell therapy. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) was attempted as curative therapy after bridging with second ASCT and tirabrutinib monotherapy. Although a temporary response was achieved, the disease relapsed 98 days after allo-HSCT. While receiving tirabrutinib for relapse after allo-HSCT, the patient developed acute respiratory failure due to transplant-related toxicity and post-transplant thrombotic microangiopathy. He died 175 days after allo-HSCT. Although various treatments for PCNSL have been investigated in recent years, the treatment strategy for R/R PCNSL has not been established. Further studies are warranted to improve the outcomes of patients with R/R PCNSL.
Assuntos
Neoplasias do Sistema Nervoso Central , Transplante de Células-Tronco Hematopoéticas , Recidiva , Transplante Homólogo , Humanos , Neoplasias do Sistema Nervoso Central/terapia , Antígenos CD19/imunologia , Pessoa de Meia-Idade , Masculino , Linfoma/terapia , Receptores de Antígenos QuiméricosRESUMO
Focal segmental glomerulosclerosis (FSGS) is a common glomerular injury leading to end-stage renal disease. Monogenic FSGS is primarily ascribed to decreased podocyte integrity. Variants between residues 184 and 245 of INF2, an actin assembly factor, produce the monogenic FSGS phenotype. Meanwhile, variants between residues 57 and 184 cause a dual-faceted disease involving peripheral neurons and podocytes (Charcot-Marie-Tooth CMT/FSGS). To understand the molecular basis for INF2 disorders, we compared structural and cytoskeletal effects of INF2 variants classified into two subgroups: One (G73D, V108D) causes the CMT/FSGS phenotype, and the other (T161N, N202S) produces monogenic FSGS. Molecular dynamics analysis revealed that all INF2 variants show distinct flexibility compared to the wild-type INF2 and could affect stability of an intramolecular interaction between their N- and C-terminal segments. Immunocytochemistry of cells expressing INF2 variants showed fewer actin stress fibers, and disorganization of cytoplasmic microtubule arrays. Notably, CMT/FSGS variants caused more prominent changes in mitochondrial distribution and fragmentation than FSGS variants and these changes correlated with the severity of cytoskeletal disruption. Our results indicate that CMT/FSGS variants are associated with more severe global cellular defects caused by disrupted cytoskeleton-organelle interactions than are FSGS variants. Further study is needed to clarify tissue-specific pathways and/or cellular functions implicated in FSGS and CMT phenotypes.
Assuntos
Glomerulosclerose Segmentar e Focal , Podócitos , Humanos , Proteínas dos Microfilamentos/metabolismo , Glomerulosclerose Segmentar e Focal/complicações , Forminas/genética , Actinas/genética , Mutação , Citoesqueleto/metabolismo , Podócitos/metabolismoRESUMO
BACKGROUND Choanal atresia with a supernumerary nostril located on the columella is extremely rare. Infants are obligate nasal breathers because the oral airway is invariably blocked during calm respiration. Infants breathe through the mouth only during crying, and they only have nasal breathing until 5 months of life. Congenital nasal anomalies have been reported to be fatal from birth, requiring tracheal intubation or tracheostomy in the early postnatal period. In these cases, it is crucial to maintain an adequate airway. CASE REPORT A 2948-g female infant was born at 40 weeks by normal vaginal delivery. Her Apgar scores were 9 and 9 at 1 and 5 min, respectively. She had retractive breathing, cyanosis, and a supernumerary nostril at birth. She had no other anomalies. Computed tomography showed bilateral membranous choanal atresia. She needed nasal continuous positive pressure or a high-flow nasal canula for oxygen desaturation during crying, apnea, and dyspnea. However, her respiratory symptoms did not improve completely. On day 25 of life, she was given a mouthpiece to support mouth breathing. Her respiratory symptoms improved gradually, and she was discharged on day 73 of life with a mouthpiece. CONCLUSIONS A very rare case of choanal atresia with a supernumerary nostril located on the columella was described. A mouthpiece was effective for breathing, obviating the need for emergency surgical intervention in the early postnatal period. Emergency procedures were avoided, probably because this case involved incomplete bilateral membranous choanal atresia rather than complete bony atresia.
Assuntos
Atresia das Cóanas , Recém-Nascido , Humanos , Lactente , Feminino , Atresia das Cóanas/cirurgia , Atresia das Cóanas/diagnóstico , Septo Nasal , Dispneia , Tomografia Computadorizada por Raios X , TraqueostomiaRESUMO
BACKGROUND: Neuroblastoma is one of the most common childhood solid tumors. Because tumor suppressor genes are often hypermethylated in cancers, DNA methylation has emerged as a target for cancer therapeutics. Nanaomycin A, an inhibitor of DNA methyltransferase 3B, which mediates de novo DNA methylation, reportedly induces death in several types of human cancer cells. OBJECTIVE: To study the antitumor activity of nanaomycin A against neuroblastoma cell lines and its mechanism. METHODS: The anti-tumor effect of nanaomycin A on neuroblastoma cell lines was evaluated based on cell viability, DNA methylation levels, apoptosis-related protein expression, and neuronal-associated mRNA expression. RESULTS: Nanaomycin A decreased genomic DNA methylation levels and induced apoptosis in human neuroblastoma cells. Nanaomycin A also upregulated the expression of mRNAs for several genes related to neuronal maturation. CONCLUSIONS: Nanaomycin A is an effective therapeutic candidate for treating neuroblastoma. Our findings also suggest that the inhibition of DNA methylation is a promising anti-tumor therapy strategy for neuroblastoma.
Assuntos
Naftoquinonas , Neuroblastoma , Humanos , Criança , Neuroblastoma/tratamento farmacológico , Neuroblastoma/genética , Neuroblastoma/metabolismo , DNA (Citosina-5-)-Metiltransferases/metabolismo , Naftoquinonas/farmacologia , Naftoquinonas/uso terapêutico , Metilação de DNA , Linhagem Celular Tumoral , DNA Metiltransferase 3BRESUMO
Atherosclerosis can lead to cardiovascular and cerebrovascular diseases. Atherosclerotic plaque formation is promoted by the accumulation of inflammatory cells. Therefore, modulating monocyte recruitment represents a potential therapeutic strategy. In an inflammatory state, the expression of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) is upregulated in endothelial cells. We previously reported that miR-1914-5p in endothelial cells suppresses interleukin (IL)-1ß-induced ICAM-1 expression and monocyte adhesion to endothelial cells. However, whether monocyte miR-1914-5p affects monocyte recruitment is unclear. In this study, IL-1ß decreased miR-1914-5p expression in a human monocyte cell line. Moreover, miR-1914-5p inhibition enhanced adhesion to endothelial cells with the upregulation of macrophage-1 antigen (Mac-1), a counter-ligand to ICAM-1. Transmigration through the endothelial layer was also promoted with the upregulation of monocyte chemotactic protein-1 (MCP-1). Furthermore, a miR-1914-5p mimic suppressed IL-1ß-induced monocyte adhesion and transmigration in monocytes with Mac-1 and MCP-1 downregulation. Further investigation of miR-1914-5p in monocytes could lead to the development of novel diagnostic markers and therapeutic strategies for atherosclerosis.
Assuntos
Aterosclerose , MicroRNAs , Humanos , Monócitos/metabolismo , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Células Endoteliais/metabolismo , Aterosclerose/genética , Aterosclerose/metabolismo , Adesão Celular/fisiologiaRESUMO
BACKGROUND: Small-for-gestational-age (SGA) infants are at increased risk for transient thrombocytopenia. The aim of this study was to determine whether thrombocytopenia in human SGA infants is due to insufficient thrombopoietin (TPO) production. METHODS: A prospective study of 202 infants with gestational age less than 37 weeks was conducted; 30 of them were SGA infants, and 172 were non-SGA infants. Thrombocytopenia was seen in 17 of 30 SGA infants and 40 of 172 non-SGA infants. RESULTS: Platelet counts were significantly lower in the SGA group than in the non-SGA group at the time of the lowest platelet count within 72 h of birth. The platelet count and immature platelet fraction (IPF) were negatively correlated in non-SGA infants, but not in SGA infants. In addition, the platelet count and TPO were negatively correlated in non-SGA infants. IPF and TPO were significantly lower in SGA than in non-SGA infants with thrombocytopenia. CONCLUSION: IPF increased with thrombocytopenia to promote platelet production in non-SGA infants due to increasing TPO, but not in SGA infants. This study found an association between insufficient TPO production and thrombocytopenia in SGA infants. In addition, this study is important for understanding the etiology of thrombocytopenia in SGA infants. IMPACT: The immature platelet fraction was low, and serum thrombopoietin was not increased in small-for-gestational-age (SGA) infants with thrombocytopenia. Thrombocytopenia in SGA infants is due to insufficient thrombopoietin production. This study is important for understanding the etiology of thrombocytopenia in SGA infants.
Assuntos
Trombocitopenia , Trombopoetina , Feminino , Humanos , Lactente , Estudos Prospectivos , Contagem de Plaquetas , Plaquetas , Retardo do Crescimento FetalRESUMO
The use of linezolid is relatively safe for all age categories, including premature infants. The case of an extremely premature infant with hyperglycemia and lactic acidosis associated with linezolid is reported. A 350-g male infant was born at 24 weeks by cesarean section. His Apgar scores were 1 and 1 at 1 and 5 min, respectively. On the day of life (DOL) 7, linezolid was started at a dose of 10 mg/kg/dose every 8 h for a catheter-related blood stream infection caused by methicillin-resistant coagulase-negative Staphylococci. After linezolid was given, serum lactate and glucose levels increased gradually. After discontinuation of linezolid on DOL 16, hyperglycemia and lactic acidosis improved immediately. In conclusion, a rare case of an extremely premature infant with hyperglycemia and lactic acidosis associated with linezolid was reported. It is crucial to monitor glucose levels along with lactate and pH levels during linezolid therapy.
Assuntos
Acidose Láctica , Feminino , Gravidez , Masculino , Humanos , Recém-Nascido , Acidose Láctica/induzido quimicamente , Linezolida/efeitos adversos , Lactente Extremamente Prematuro , Cesárea , Ácido Láctico , GlucoseRESUMO
BACKGROUND: Antenatal magnesium sulfate (MgSO4 ) has been used with mothers, but the influence of MgSO4 on the fetus is unclear. The purpose of this study is to determine whether longer antenatal MgSO4 exposure correlates with adverse effects in newborns. METHODS: The clinical data of 77 infants born to mothers treated with MgSO4 were collected. The infants were divided into two groups according to (1) the serum Mg concentration, (2) cumulative Mg dose, and (3) duration of antenatal maternal Mg treatment, respectively. RESULTS: The serum Mg level of the infants correlated with that of the mothers but not with the duration of Mg treatment or the cumulative dose of Mg. There were no significant differences in the infants' clinical variables according to either the duration of Mg treatment or the cumulative dose of Mg. By contrast, enteral feeding tolerance began at a significantly later age and the heart rate on admission was significantly lower in infants with a serum Mg level ≥4.0 mmol/L than in those with a serum Mg level <4.0 mmol/L. CONCLUSIONS: Modest effects on the clinical variables of infants with higher serum Mg levels were determined, whereas neither the duration of Mg treatment nor the cumulative Mg dose correlated with the clinical variables of the infants. Thus, in newborns with only moderately elevated serum Mg levels, serious adverse effects are unlikely.
Assuntos
Sulfato de Magnésio , Pré-Eclâmpsia , Feminino , Feto , Humanos , Recém-Nascido , Sulfato de Magnésio/efeitos adversos , GravidezRESUMO
BACKGROUND: Acetaminophen is widely administered to neonates but its effect on unbound bilirubin (UB) levels remains unclear. The aim of this study was to clarify whether administration of acetaminophen is related to an elevation of UB levels. METHOD: Infants with a birthweight of Ë1,500 g admitted to our neonatal intensive care unit between January 2017 and April 2020 were retrospectively reviewed. Seventy-one infants were enrolled, five of whom had received acetaminophen. Clinical data were analyzed when the highest UB value (UB peak) in each infant was recorded. Demographic data and information on treatment within the 24 h before the UB peak were also collected. UB was determined by the glucose oxidase-peroxidase (GOD-POD) method. Infants were categorized according to the presence or absence of acetaminophen administration (acetaminophen and no acetaminophen groups) within 24 h of the UB peak. The relationship between UB values and various clinical variables was then compared. RESULTS: Both the peak UB value and the ratio of gastrointestinal disease were higher in the acetaminophen group than in the no acetaminophen group. Univariate analysis revealed that a total of seven variables were potentially correlated with UB peak values (P < 0.10). Multivariate analysis showed that acetaminophen and direct bilirubin were independently associated with UB peak values. CONCLUSION: Our study suggests that administration of acetaminophen is related to higher UB levels by the GOD-POD method. UB values measured by the GOD-POD method should not be used in infants treated with acetaminophen for evaluation of bilirubin neurotoxicity avoidance.
Assuntos
Icterícia Neonatal , Peroxidase , Acetaminofen/efeitos adversos , Bilirrubina , Glucose Oxidase , Humanos , Lactente , Recém-Nascido , Oxirredutases , Peroxidases , Estudos RetrospectivosAssuntos
Fígado/fisiopatologia , Trombocitopenia/fisiopatologia , Trombopoetina/metabolismo , Animais , Animais Recém-Nascidos , Peso ao Nascer , Feminino , Hipertensão/complicações , Fígado/metabolismo , Gravidez , Complicações Cardiovasculares na Gravidez/etiologia , Ratos , Ratos Wistar , Trombocitopenia/etiologia , Trombocitopenia/metabolismo , Trombopoetina/análiseRESUMO
BACKGROUND: Significant advancements have been achieved in the quality of treatment for relapsed/refractory multiple myeloma (RRMM). Currently, daratumumab (DARA) is a highly effective drug widely used for RRMM; however, the knowledge on its efficacy and safety in Japanese patients remains limited. Accordingly, we aimed to evaluate the efficacy and safety of DARA therapy for RRMM. METHODS: We reviewed the medical records of patients who received DARA combination therapy and evaluated its efficacy and safety in our hospital. RESULTS: DARA was administered to 44 patients between October 2017 and March 2019. The median number of previous therapies was three (range 1-9). The rates of ≥ complete response and overall response were 27.3% and 61.4%, respectively. The median progression-free survival (PFS) duration was 12.3 months [95% confidence interval (CI) 5.1 to not reached (NR)] and estimated 2-year overall survival rate was 63.7% (95% CI 46.9-76.5%). In the multivariate analysis, patients with ≥ three previous lines of therapy and mass lesions showed significantly shorter PFS durations. The observed grade 3/4 adverse events (≥ 10%) included neutropenia (59.0%), thrombocytopenia (29.5%), anemia (36.4%), lymphopenia (38.6%) and febrile neutropenia (18.2%). None of the patients discontinued DARA therapy in spite of these AEs. CONCLUSION: DARA is an effective treatment option for most patients and is tolerable. However, patients with heavy treatment before DARA therapy and mass lesions are likely to show poorer outcomes. Our findings suggest the use of DARA therapy early in the course of the disease.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/induzido quimicamente , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Neutropenia/induzido quimicamente , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy. The pathological mechanism of FPIES is intestinal inflammation, and cell-mediated hypersensitivity is presumed to play an important role in its development. CASE REPORT: The first case in which significant fetal intestinal distension suggested fetal onset of FPIES is reported. A 2,334-g male was born at 34 weeks by vaginal delivery. RESULTS: In utero, he had significant intestinal distension on ultrasonography and MRI. A few hours after the first feeding, he produced bloody stool and showed abdominal distension. In this case, FPIES was not only caused by cow's milk protein diagnosed clinically and by an allergen-specific lymphocyte stimulation test, but also by breast milk diagnosed by oral food challenge. The clinical course and laboratory results strongly suggested not only fetal sensitization but also fetal onset. CONCLUSION: This report might be helpful for prompt diagnosis and treatment and, furthermore, lead to elucidation of the pathogenesis and pathophysiology of FPIES.
Assuntos
Enterocolite/etiologia , Doenças Fetais/diagnóstico por imagem , Hipersensibilidade Alimentar/complicações , Proteínas do Leite/efeitos adversos , Líquido Amniótico/química , Animais , Bovinos , Enterocolite/fisiopatologia , Hipersensibilidade Alimentar/fisiopatologia , Humanos , Lactente , Recém-Nascido Prematuro , Imageamento por Ressonância Magnética , Masculino , Proteínas do Leite/imunologia , Síndrome , Ultrassonografia Pré-NatalRESUMO
BACKGROUND: Late-onset circulatory collapse (LCC) is the transient development of refractory hypotension and oliguria after the early neonatal period, which may cause periventricular leukomalacia (PVL). The aim of this study was to evaluate the endogenous cortisol response to corticotrophin-releasing hormone (CRH) and determine whether it is effective for elucidating the pathology and selecting treatment in LCC. METHODS: This retrospective study examined infants admitted to the neonatal intensive care unit. Included were preterm (gestational age <34 weeks) infants who underwent CRH stimulation test and were treated for LCC with no obvious cause. Hydrocortisone (HC; 3.3-10 mg/kg) was given by bolus injection to the LCC infants. At 2 h after treatment, infants without a 20% rise in blood pressure (systolic or mean) from before treatment were defined as non-responsive to HC, and given catecholamine and/or vasopressin. RESULTS: Sixteen infants (median gestational age, 24 weeks 3 days; birthweight, 638 g) were eligible. Six of the infants had a good response to the CRH stimulation test. HC was effective in only three CRH good-response cases, and catecholamine and/or vasopressin was needed in the three other cases. HC was effective, however, for all CRH non-response cases. CONCLUSIONS: Although HC is the first-choice treatment for LCC, the CRH stimulation test facilitates prompt treatment of LCC, which may prevent PVL. The present findings help elucidate the pathology and aid in the selection of treatment for infants with LCC.
Assuntos
Hormônio Liberador da Corticotropina/efeitos dos fármacos , Hidrocortisona/administração & dosagem , Recém-Nascido Prematuro , Choque/tratamento farmacológico , Pressão Sanguínea/efeitos dos fármacos , Hormônio Liberador da Corticotropina/metabolismo , Feminino , Idade Gestacional , Glucocorticoides/administração & dosagem , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Masculino , Prognóstico , Estudos Retrospectivos , Choque/diagnóstico , Choque/metabolismoRESUMO
Arterial stiffness is an important risk factor for cardiovascular disease (CVD) in patients with end-stage renal failure. However, little is known about the factors that contribute to arterial rigidity in peritoneal dialysis (PD) patients. The aim of this study was to define the pattern and determinants of the longitudinal change in arterial stiffness after PD initiation.Arterial stiffening was estimated for 46 PD patients by using brachial-ankle pulse wave velocity (baPWV) and carotid intima-media thickness (cIMT). The cross-sectional relationship between the arterial markers and their clinical determinants was studied. The longitudinal effects of blood pressure (BP), body fluid status, and glucose were studied over the two years after initiating PD.Multivariate analysis showed that higher baPWV was associated positively with urinary protein excretion (P < 0.001), systolic BP (P = 0.001), and hemoglobin A1c (P = 0.003). In contrast, increased cIMT correlated with smoking (P = 0.004) and hypoalbuminemia (P = 0.04), suggesting that endothelial dysfunction is implicated in the atherogenic process. Neither cIMT nor baPWV correlated significantly with other PD-related covariates of volume overload, peritoneal solute transport, kidney function, and C-reactive protein. Longitudinal observation demonstrated that BP had a greater influence on baPWV changes than hyperglycemia or fluid status.Our study indicates that 1) baPWV represent an arterial marker that integrates multifactorial interaction between modifiable variables including BP and plasma glucose; and 2) intervention aimed at controlling BP as well as nutritional conditions (glucose and albumin) may reduce CVD risk in PD patients.
Assuntos
Falência Renal Crônica/fisiopatologia , Rigidez Vascular , Adulto , Idoso , Espessura Intima-Media Carotídea , Estudos Transversais , Feminino , Humanos , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Diálise Peritoneal , Estudos Prospectivos , Análise de Onda de PulsoRESUMO
BACKGROUND: Pierre Robin sequence (PRS) refers to the association of micrognathia, glossoptosis, and airway obstruction. Cases with severe dyspnea due to upper airway obstruction immediately after birth are very rare. We here report two cases with PRS who developed severe dyspnea due to morphological abnormality immediately after birth and were rescued by fiberoptic nasotracheal intubation. CASE PRESENTATION: The patient in case 1 had micrognathia and cleft palate, and his tongue protruded into the nasal cavity via a cleft palate. His invaginated tongue was considered an extreme type of glossoptosis and he was diagnosed as Pierre Robin sequence. The patient in case 2 also had micrognathia and cleft palate same as case 1 and accompanied some anomalad. Her chromosome analysis confirmed a diagnosis of 1p36 deletion syndrome and she diagnosed as 1p36 deletion syndrome complicated with Pierre Robin sequence. In both cases, tongue protruded into the nasal cavity via a cleft palate occupied pharynx and nasal cavity, resulting in severe dyspnea. Only the backside of the tongue was visible by laryngoscopy and oropharyngeal intubation was impossible. Therefore, fiberoptic nasotracheal intubation was done to secure the airway for resuscitation. CONCLUSION: We conclude that extreme type of glossoptosis in PRS concludes tongue invaginated into nasal cavity which have not reported before and that such cases require resuscitation by fiberoptic intubation immediately after birth. As such, neonatologists should obtain the skill of fiberoptic intubation.
Assuntos
Obstrução das Vias Respiratórias/terapia , Intubação Intratraqueal/métodos , Síndrome de Pierre Robin/complicações , Obstrução das Vias Respiratórias/etiologia , Feminino , Tecnologia de Fibra Óptica , Humanos , Recém-Nascido , MasculinoRESUMO
The bile salt export pump is expressed at the canalicular membrane of hepatocytes and mediates biliary excretion of bile salts. 4-Phenylbutyrate (4 PB), a drug used to treat ornithine transcarbamylase deficiency, has been found to increase the hepatocanalicular expression of bile salt export pump. The beneficial effects of 4-phenylbutyrate therapy have been reported for patients with progressive familial intrahepatic cholestasis, an inherited autosomal recessive liver disease. This is the first study to show the therapeutic effect of 4 PB in a preterm infant with cholestasis and liver fibrosis. The preterm infant had severe cholestasis with jaundice and failure to thrive refractory to ursodeoxycholic acid. Histology indicated giant cell hepatitis, cholestasis, and severe fibrosis. Bile salt export pump immunostaining showed lower expression than in a control. Oral 4 PB was started at a daily dose of 200 mg/kg/day. After the start of 4 PB therapy, cholestasis improved.