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1.
Ophthalmology ; 131(4): 458-467, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37852417

RESUMO

PURPOSE: To assess the duration, incidence, reversibility, and severity of adverse events (AEs) in patients with thyroid eye disease (TED) treated with teprotumumab. DESIGN: Multicenter, retrospective, observational cohort study. PARTICIPANTS: Patients with TED of all stages and activity levels treated with at least 4 infusions of teprotumumab. METHODS: Patients were treated with teprotumumab between February 2020 and October 2022 at 6 tertiary centers. Adverse event metrics were recorded at each visit. MAIN OUTCOME MEASURES: The primary outcomes measure was AE incidence and onset. Secondary outcome measures included AE severity, AE reversibility, AE duration, proptosis response, clinical activity score (CAS) reduction, and Gorman diplopia score improvement. RESULTS: The study evaluated 131 patients. Proptosis improved by 2 mm or more in 77% of patients (101/131), with average proptosis improvement of 3.0 ± 2.1 mm and average CAS reduction of 3.2 points. Gorman diplopia score improved by at least 1 point for 50% of patients (36/72) with baseline diplopia. Adverse events occurred in 81.7% of patients (107/131). Patients experienced a median of 4 AEs. Most AEs were mild (74.0% [97/131]), 28.2% (37/131) were moderate, and 8.4% (11/131) were severe. Mean interval AE onset was 7.9 weeks after the first infusion. Mean resolved AE duration was 17.6 weeks. Forty-six percent of patients (60/131) demonstrated at least 1 persistent AE at last follow-up. Mean follow-up was 70.2 ± 38.5 weeks after the first infusion. The most common type of AEs was musculoskeletal (58.0% [76/131]), followed by gastrointestinal (38.2% [50/131]), skin (38.2% [50/131]), ear and labyrinth (30.5% [40/131]), nervous system (20.6% [27/131]), metabolic (15.3% [20/131]), and reproductive system (12.2% [16/131]). Sixteen patients (12.2%) discontinued therapy because of AEs, including hearing loss (n = 4), inflammatory bowel disease flare (n = 2), hyperglycemia (n = 1), muscle spasms (n = 1), and multiple AEs (n = 8). CONCLUSIONS: Adverse events are commonly reported while receiving teprotumumab treatment. Most are mild and reversible; however, serious AEs can occur and may warrant treatment cessation. Treating physicians should inform patients about AE risk, properly screen patients before treatment, monitor patients closely throughout therapy, and understand how to manage AEs should they develop. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.


Assuntos
Anticorpos Monoclonais Humanizados , Exoftalmia , Oftalmopatia de Graves , Humanos , Oftalmopatia de Graves/tratamento farmacológico , Estudos Retrospectivos , Diplopia/induzido quimicamente
2.
J Med Internet Res ; 26: e47667, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38393776

RESUMO

On January 30, 2023, the Biden Administration announced its intention to end the existing COVID-19 public health emergency declaration. The transition to a "postpandemic" landscape presents a unique opportunity to sustain and strengthen pandemic-era changes in care delivery. With this in mind, we present 3 critical lessons learned from a primary care perspective during the COVID-19 pandemic. First, clinical workflows must support both in-person and internet-based care delivery. Second, the integration of asynchronous care delivery is critical. Third, planning for the future means planning for everyone, including those with potentially limited access to health care due to barriers in technology and communication. While these lessons are neither unique to primary care settings nor all-encompassing, they establish a grounded foundation on which to construct higher-quality, more resilient, and more equitable health systems.


Assuntos
COVID-19 , Telemedicina , Humanos , Pandemias/prevenção & controle , Comunicação , Intenção , Atenção Primária à Saúde
3.
Transpl Infect Dis ; 25 Suppl 1: e14162, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37794708

RESUMO

BACKGROUND: Isavuconazole (ISA) is a newer antifungal used in patients with history of hematologic malignancies and hematopoietic transplant and cellular therapies (HM/TCT). Although it has a more favorable side-effect profile, breakthrough invasive fungal infections (bIFIs) while on ISA have been reported. METHODS: In this single-center retrospective study evaluating HM/TCT patients who received prophylactic ISA for ≥7 days, we evaluated the incidence and potential risk factors for bIFIs. RESULTS: We evaluated 106 patients who received prophylactic ISA. The patients were predominantly male (60.4%) with median age of 65 (range: 21-91) years. Acute myeloid leukemia (48/106, 45.3%) was the most common HM, with majority having relapsed and/or refractory disease (43/106, 40.6%) or receiving ongoing therapy (38/106, 35.8%). Nineteen patients (17.9%) developed bIFIs-nine proven [Fusarium (3), Candida (2), Mucorales plus Aspergillus (2), Mucorales (1), Colletotrichum (1)], four probable invasive pulmonary Aspergillus, and six possible infections. Twelve patients were neutropenic for a median of 28 (8-253) days prior to bIFI diagnosis. ISA levels checked within 7 days of bIFI diagnosis (median: 3.65 µg/mL) were comparable to industry-sponsored clinical trials. All-cause mortality among the bIFI cases was 47.4% (9/19).We also noted clinically significant cytomegalovirus co-infection in 5.3% (1/19). On univariate analysis, there were no significant differences in baseline comorbidities and potential risk factors between the two groups. CONCLUSION: ISA prophylaxis was associated with a significant cumulative incidence of bIFIs. Despite the appealing side-effect and drug-interaction profile of ISA, clinicians must be vigilant about the potential risk for bIFIs.


Assuntos
Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Infecções Fúngicas Invasivas , Humanos , Masculino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Estudos Retrospectivos , Antifúngicos/uso terapêutico , Infecções Fúngicas Invasivas/epidemiologia , Infecções Fúngicas Invasivas/prevenção & controle , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos
4.
J Oncol Pharm Pract ; 29(6): 1398-1403, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36245321

RESUMO

High-dose melphalan-based autologous stem cell transplant (ASCT) remains a standard of care for plasma cell disorders (PCDs). Currently, there is variability in the literature surrounding the timing of melphalan administration to avoid potential cytotoxic effects, although the administration has been safely proposed when given at least 8 hours prior to stem cell infusion. The objectives of this study were to assess differences in safety and efficacy outcomes between day -1 and day -2 single-dose melphalan administration in patients undergoing ASCT for PCDs. A retrospective chart review was performed at our institution comparing patients receiving melphalan on day -1 to an equal number of patients receiving melphalan on day -2. The primary endpoint was time to neutrophil engraftment from stem cell infusion. Univariate analyses were performed. Mean time to neutrophil engraftment from stem cell infusion was identical at 10.7 days for both cohorts (p = 0.88). Mean time to platelet engraftment from stem cell infusion was shorter with day -1 administration (17.4 vs. 18.6 days, p = 0.06). Mean time to neutrophil and platelet engraftment from melphalan infusion were significantly shorter with day -1 administration. Similar outcomes were observed for length of hospitalization, infection- and mucositis-related toxicities, hematologic response, transplant-related mortality, and overall survival. Our findings show no difference in time to neutrophil engraftment from stem cell infusion and a trend toward shorter time to platelet engraftment with day -1 administration. Based on our study, day -1 melphalan administration is an acceptable and safe practice.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Humanos , Melfalan , Estudos Retrospectivos , Plasmócitos , Transplante Autólogo , Transplante de Células-Tronco , Condicionamento Pré-Transplante/efeitos adversos
5.
J Indian Assoc Pediatr Surg ; 28(6): 479-485, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38173638

RESUMO

Background: Preoperative anxiety (PA) in children is a common phenomenon associated with various negative patient outcomes. Allaying PA is accepted as a standard of care, but its use is not universal and often overlooked. This survey is designed to evaluate the nationwide current practice patterns and attitudes of anesthesiologists toward the practice of allaying PA in children. Materials and Methods: A questionnaire of 25 questions, including information on methods of relieving PA in children, reasons for noncompliance, and associated complications, was framed. It was circulated among members of the Indian Society of Anaesthesiologists through an online survey of Google Forms and manually. Results: Four hundred and fifty anesthesiologists were surveyed. Responses were predominantly from anesthesiologists practicing in medical colleges across the country. Although 97% of the surveyed respondents practiced anxiety-relieving strategies, only 37% used it consistently. Seventy-three percent of anesthesiologists practiced both pharmacological and nonpharmacological techniques. The most common reason for avoiding premedication was an anticipated difficult airway (88%). Inadequate sedation was a commonly reported problem. Ninety-five percent of participants felt that PA-relieving strategies should be integral to pediatric anesthesia practice. The most common reason for not following these practices was an inadequate hospital infrastructure (67%). Ninety-seven percent of the participants believed that more awareness is required on this crucial perioperative issue. Conclusion: Only 37% of the surveyed anesthesiologists consistently used some form of PA-relieving strategy and the practice varied widely. Further improvement and team approach involving anesthesiologists, surgeons, and nurses is required to ensure the quality of pediatric PA-relieving services and establish it as a standard of care.

6.
Aesthet Surg J ; 42(12): NP788-NP797, 2022 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-35675468

RESUMO

BACKGROUND: The utilization of social media in plastic surgery is expanding. The Twitter Academic Research Product Tract (TARPT) database provides plastic surgeons the opportunity to monitor public interest in plastic surgery procedures. Previously, TARPT was shown to be effective in tracking public interest in surgical cosmetic facial and body procedures. OBJECTIVES: The authors sought to determine the ability of the TARPT tool to track and predict public interest in nonsurgical cosmetic procedures and to examine temporal public interest trends in nonsurgical cosmetic procedures. METHODS: The authors employed the TARPT tool to calculate the total number of tweets containing keywords related to 15 nonsurgical cosmetic procedures from 2010 to 2020. Annual case volumes were obtained for each of the 15 procedures from annual reports provided by the American Society of Plastic Surgeons. Univariate linear regression was employed to compare tweet volumes and procedure volumes, with P < 0.05 as a threshold for significance. RESULTS: Univariate linear regression revealed significant positive correlations between tweet volumes and American Society of Plastic Surgeons procedure volumes for 10 search terms representing 6 nonsurgical cosmetic procedures: "xeomin," "microdermabrasion," "facial filler," "fat filler," "fat injections," "fat transfer," "hyaluronic acid filler," "hyaluronic acid injection," "HA filler," and "PRP filler." Thirty-two search terms did not demonstrate a significant relationship. CONCLUSIONS: The TARPT tool is an informative data source for plastic surgeons with the potential to guide marketing and advertising strategies, and monitor public interest in nonsurgical cosmetic procedures, helping surgeons respond to patients' evolving needs.


Assuntos
Procedimentos de Cirurgia Plástica , Mídias Sociais , Cirurgia Plástica , Humanos , Estados Unidos , Ácido Hialurônico , Face/cirurgia
8.
Biol Blood Marrow Transplant ; 24(2): 288-293, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29061534

RESUMO

Administration of granulocyte colony-stimulating factor (G-CSF) after autologous peripheral blood stem cell transplantation (PBSCT) is generally recommended to reduce the duration of severe neutropenia; however, data regarding the optimal timing of G-CSFs post-transplantation are limited and conflicting. This retrospective study was performed at NewYork-Presbyterian/Weill Cornell Medical Center between November 5, 2013, and August 9, 2016, of adult inpatient autologous PBSCT recipients who received G-CSF empirically starting on day +5 (early) versus on those who received G-CSF on day +12 only if absolute neutrophil count (ANC) was <0.5 × 109/L (ANC-driven). G-CSF was dosed at 300 µg in patients weighing <75 kg and 480 µg in those weighing ≥75 kg. One hundred consecutive patients underwent autologous PBSCT using either the early (n = 50) or ANC-driven (n = 50) G-CSF regimen. Patient and transplantation characteristics were comparable in the 2 groups. In the ANC-driven group, 24% (n = 12) received G-CSF on day +12 and 60% (n = 30) started G-CSF earlier due to febrile neutropenia or at the physician's discretion, 6% (n = 3) started after day +12 at the physician's discretion, and 10% (n = 5) did not receive any G-CSF. The median start day of G-CSF therapy was day +10 in the ANC-driven group versus day +5 in the early group (P < .0001). For the primary outcome, the median time to neutrophil engraftment was 12 days (interquartile range [IQR] 11-13 days) in the early group versus 13 days (IQR, 12-14 days) in the ANC-driven group (P = .07). There were no significant between-group differences in time to platelet engraftment, 1-year relapse rate, or 1-year overall survival. The incidence of febrile neutropenia was 74% in the early group versus 90% in the ANC-driven group (P = .04); however, there was no significant between-group difference in the incidence of positive bacterial cultures or transfer to the intensive care unit. The duration of G-CSF administration until neutrophil engraftment was 6 days in the early group versus 3 days in the ANC-driven group (P < .0001). The median duration of post-transplantation hospitalization was 15 days (IQR, 14-19 days) in the early group versus 16 days (IQR, 15-22 days) in the ANC-driven group (P = .28). Our data show that early initiation of G-CSF (on day +5) and ANC-driven initiation of G-CSF following autologous PBSCT were associated with a similar time to neutrophil engraftment, length of stay post-transplantation, and 1-year overall survival.


Assuntos
Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Transplante de Células-Tronco de Sangue Periférico/métodos , Idoso , Feminino , Sobrevivência de Enxerto , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Neutrófilos/citologia , Transplante de Células-Tronco de Sangue Periférico/mortalidade , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Transplante Autólogo/métodos , Transplante Autólogo/mortalidade
9.
BMC Microbiol ; 18(1): 173, 2018 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-30390625

RESUMO

BACKGROUND: Biofilms are formed by a complex bacterial community encapsulated by a polymeric matrix, with strong adherent properties and persistent phenotype. Biofilms are considered one of the most challenging areas of modern medicine. Existing antibiotics have been developed against free-floating bacterial cells, and thus, many treatments of biofilm-related infection fail. In this study, we compared the effects of different media on biofilm growth of clinical reference strains of Staphylococci and Enterococci, including multi-drug resistant representatives. Further, we optimized the resazurin-based assay for determining the minimal biofilm inhibitory concentration (MBIC) of standard antibiotics, and evaluated its use for the determination of minimal biofilm eradication concentration (MBEC). RESULTS: We showed that tryptic soy broth supplemented with 1% glucose was an optimal media for maximum biofilm growth of all strains tested, with an extended incubation time for Enterococci. A range of parameters were tested for the resazurin assay, including concentration, temperature and time of incubation. Using quality parameters to analyze the assay's performance, the conditions for the resazurin assay were set as follows: 4 µg/mL and 8 µg/mL, with incubation at 25 °C for 20 min and 40 min for Staphylococci and Enterococci, respectively. CONCLUSIONS: In summary, we defined conditions for optimal biofilm growth and for standardized resazurin assay for MBIC determination against six Gram-positive clinical reference strains. We also observed that MBEC determination by the resazurin-based assay is limited due to the poor detection limit of the assay. Complementary cell counting data is needed for precise determination of MBEC.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Meios de Cultura/química , Bactérias Gram-Positivas/efeitos dos fármacos , Testes de Sensibilidade Microbiana/métodos , Biofilmes/crescimento & desenvolvimento , Caseínas/química , Enterococcus/efeitos dos fármacos , Enterococcus/crescimento & desenvolvimento , Glucose/química , Bactérias Gram-Positivas/crescimento & desenvolvimento , Infecções por Bactérias Gram-Positivas/microbiologia , Limite de Detecção , Testes de Sensibilidade Microbiana/normas , Oxazinas/química , Hidrolisados de Proteína/química , Padrões de Referência , Staphylococcus/efeitos dos fármacos , Staphylococcus/crescimento & desenvolvimento , Xantenos/química
10.
Am J Dent ; 31(2): 97-102, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29630794

RESUMO

PURPOSE: To evaluate the effect of different surface treatments and primers with a CAD/CAM resin composite block on its crown retention. METHODS: 120 human molars were prepared with a 24° total convergence angle, 1.5 mm height, and axial walls in dentin. Surface area was measured by digital microscopy. Crowns were machined from CAD/CAM resin composite blocks. Teeth were randomly allocated to 12 groups (n= 10) based on possible combinations of three surface treatments: [Control, Alumina air abrasion (50-µm Al2O3 at 0.28 MPa) ]; 5% hydrofluoric acid etch (20-second scrub); silane application (with or without Kerr Silane primer); and adhesive application (with or without Optibond XTR Adhesive). Optibond XTR Adhesive was applied to the tooth preparations and crowns were bonded with MaxCem Elite cement. Crowns were fatigued for 100,000 cycles at 100 N in water and debonded in tension (1 mm/minute). Crown retention strength (maximum load/surface area) values were analyzed using a three-way ANOVA with Tukey's post-hoc tests (α= 0.05). RESULTS: Surface treatment, silane and adhesive applications independently affect retention force (P< 0.05). All interactions were not significant (P> 0.05). Alumina airborne abrasion surface treatment, silane and adhesive applications all improve retention strength. Therefore, CAD/CAM resin composite crowns can withstand debonding while undergoing mechanical fatigue. Although all forms of surface treatment and primer application improve bond strength, the highest mean retention strength values were recorded when the crowns were alumina particle abraded and coated with adhesive (with or without silane). CLINICAL SIGNIFICANCE: In order to improve the bonding of resin composite crowns, application of alumina airborne particle abrasion and a coat of adhesive (proceeded by an optional coat of silane) is recommended. If hydrofluoric acid is utilized, the crowns should be treated with a coat of silane followed by adhesive application.


Assuntos
Resinas Compostas , Desenho Assistido por Computador , Coroas , Colagem Dentária , Cimentos Dentários , Análise do Estresse Dentário , Humanos , Teste de Materiais , Distribuição Aleatória , Cimentos de Resina , Estresse Mecânico , Propriedades de Superfície
11.
J Biol Chem ; 291(49): 25716-25728, 2016 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-27784788

RESUMO

Hyperactive Wnt/ß-catenin signaling is linked to cancer progression and developmental abnormalities, making identification of mechanisms controlling Wnt/ß-catenin signaling vital. Transforming growth factor ß type III receptor (TßRIII/betaglycan) is a transmembrane proteoglycan co-receptor that exists with or without heparan and/or chondroitin sulfate glycosaminoglycan (GAG) modifications in cells and has established roles in development and cancer. Our studies here demonstrate that TßRIII, independent of its TGFß co-receptor function, regulates canonical Wnt3a signaling by controlling Wnt3a availability through its sulfated GAG chains. Our findings revealed, for the first time, opposing functions for the different GAG modifications on TßRIII suggesting that Wnt interactions with the TßRIII heparan sulfate chains result in inhibition of Wnt signaling, likely via Wnt sequestration, whereas the chondroitin sulfate GAG chains on TßRIII promote Wnt3a signaling. These studies identify a novel, dual role for TßRIII/betaglycan and define a key requirement for the balance between chondroitin sulfate and heparan sulfate chains in dictating ligand responses with implications for both development and cancer.


Assuntos
Sulfatos de Condroitina/metabolismo , Heparitina Sulfato/metabolismo , Proteoglicanas/metabolismo , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Via de Sinalização Wnt/fisiologia , Proteína Wnt3A/metabolismo , Animais , Células COS , Linhagem Celular Tumoral , Chlorocebus aethiops , Sulfatos de Condroitina/genética , Heparitina Sulfato/genética , Humanos , Proteoglicanas/genética , Receptores de Fatores de Crescimento Transformadores beta/genética , Proteína Wnt3A/genética
12.
Graefes Arch Clin Exp Ophthalmol ; 255(5): 1027-1036, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28224290

RESUMO

OBJECTIVE: To introduce and validate the pediatric ocular trauma score (POTS) - a mathematical model to predict visual outcome trauma in children with traumatic cataract METHODS: In this retrospective cohort study, medical records of consecutive children with traumatic cataracts aged 18 and below were retrieved and analysed. Data collected included age, gender, visual acuity, anterior segment and posterior segment findings, nature of surgery, treatment for amblyopia, follow-up, and final outcome was recorded on a precoded data information sheet. POTS was derived based on the ocular trauma score (OTS), adjusting for age of patient and location of the injury. Visual outcome was predicted using the OTS and the POTS and using receiver operating characteristic (ROC) curves. RESULTS: POTS predicted outcomes were more accurate compared to that of OTS (p = 0.014). CONCLUSION: POTS is a more sensitive and specific score with more accurate predicted outcomes compared to OTS, and is a viable tool to predict visual outcomes of pediatric ocular trauma with traumatic cataract.


Assuntos
Extração de Catarata , Catarata/etiologia , Gerenciamento Clínico , Traumatismos Oculares/diagnóstico , Modelos Teóricos , Adolescente , Catarata/diagnóstico , Catarata/epidemiologia , Criança , Pré-Escolar , Traumatismos Oculares/complicações , Traumatismos Oculares/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Índia/epidemiologia , Lactente , Recém-Nascido , Masculino , Prognóstico , Estudos Retrospectivos , Fatores de Tempo , Índices de Gravidade do Trauma , Acuidade Visual
13.
Biol Blood Marrow Transplant ; 22(3): 456-61, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26524732

RESUMO

The objective of this study was to compare infusion-related reactions and outcomes of using subcutaneous (subQ) alemtuzumab versus intravenous (i.v.) alemtuzumab as graft-versus-host disease (GVHD) prophylaxis for matched unrelated donor stem cell transplantations. Outcomes include incidence of cytomegalovirus (CMV)/Epstein-Barr (EBV) viremia, development of CMV disease or post-transplantation lymphoproliferative disorder, fatal infections, acute and chronic GVHD, time to engraftment, relapse rate, and survival. We conducted a retrospective study of all adult matched unrelated donor stem cell transplantations patients who received fludarabine/melphalan with subQ or i.v. alemtuzumab in combination with tacrolimus as part of their conditioning for unrelated donor transplantation at New York-Presbyterian/Weill Cornell Medical Center from January 1, 2012 to March 21, 2014. Alemtuzumab was administered at a total cumulative dose of 100 mg (divided over days -7 to -3). Forty-six patients received an unrelated donor stem cell transplantation with fludarabine/melphalan and either subQ (n = 26) or i.v. (n = 20) alemtuzumab in combination with tacrolimus. Within the evaluable population, 130 subQ and 100 i.v. alemtuzumab doses were administered. For the primary outcome, ≥grade 2 infusion-related reactions occurred in 11 (8%) versus 25 (25%) infusions in the subQ and i.v. cohorts, respectively (P = .001). Overall, 12 injections (9%) in the subQ arm versus 26 infusions (26%) in the i.v. arm experienced an infusion-related reaction of any grade (P = .001). There were no significant differences between the subQ and i.v. arms in rates of reactivation of CMV/EBV, development of CMV disease or post-transplantation lymphoproliferative disorder, fatal infections, acute and chronic GVHD, relapse, or survival. Subcutaneous administration of alemtuzumab for GVHD prophylaxis was associated with fewer infusion-related reactions compared with i.v. administration in the SCT setting. Incidences of acute and chronic GVHD were similar between both arms. There was also no difference in reactivation of CMV/EBV viremia, development of CMV disease or post-transplantation lymphoproliferative disorder, fatal infections, relapse, or survival.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas , Melfalan/administração & dosagem , Condicionamento Pré-Transplante , Doadores não Relacionados , Vidarabina/análogos & derivados , Administração Intravenosa , Adulto , Idoso , Alemtuzumab , Aloenxertos , Feminino , Doença Enxerto-Hospedeiro/mortalidade , Teste de Histocompatibilidade , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Vidarabina/administração & dosagem
14.
PLoS Genet ; 9(8): e1003708, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23990801

RESUMO

Most yeast ribosomal protein genes are duplicated and their characterization has led to hypotheses regarding the existence of specialized ribosomes with different subunit composition or specifically-tailored functions. In yeast, ribosomal protein genes are generally duplicated and evidence has emerged that paralogs might have specific roles. Unlike yeast, most mammalian ribosomal proteins are thought to be encoded by a single gene copy, raising the possibility that heterogenous populations of ribosomes are unique to yeast. Here, we examine the roles of the mammalian Rpl22, finding that Rpl22(-/-) mice have only subtle phenotypes with no significant translation defects. We find that in the Rpl22(-/-) mouse there is a compensatory increase in Rpl22-like1 (Rpl22l1) expression and incorporation into ribosomes. Consistent with the hypothesis that either ribosomal protein can support translation, knockdown of Rpl22l1 impairs growth of cells lacking Rpl22. Mechanistically, Rpl22 regulates Rpl22l1 directly by binding to an internal hairpin structure and repressing its expression. We propose that ribosome specificity may exist in mammals, providing evidence that one ribosomal protein can influence composition of the ribosome by regulating its own paralog.


Assuntos
Proteínas de Ligação a RNA/genética , RNA/genética , Proteínas Ribossômicas/genética , Ribossomos/genética , Homologia de Sequência de Aminoácidos , Sequência de Aminoácidos , Animais , Regulação da Expressão Gênica , Camundongos , Dados de Sequência Molecular , Biossíntese de Proteínas , RNA/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteínas Ribossômicas/metabolismo , Ribossomos/metabolismo
15.
J Oncol Pharm Pract ; 21(4): 305-9, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24714130

RESUMO

BACKGROUND: Herpes simplex virus and varicella zoster virus reactivation can occur in up to 32% and 40% of patients, respectively in the first year post-transplant without prophylaxis. Antiviral therapy consisting of acyclovir or valacyclovir is recommended for at least 1 year post stem cell transplant per evidence-based guidelines. OBJECTIVE: In the event of a contraindication or hypersensitivity reaction to either drug, an alternative is essential based on the proven efficacy in reducing clinically significant herpes simplex virus and varicella zoster virus reactivations. We report two cases of successful initiation of famciclovir in stem cell transplant recipients experiencing hypersensitivity to valacyclovir or acyclovir. DISCUSSION: In both cases, there were no hypersensitivity reactions or breakthrough viral infections after famciclovir initiation but this observation is limited by a small patient population. CONCLUSION: Due to the limited data available, famciclovir appears to be a reasonable option in immunocompromised patients with a mild valacyclovir or acyclovir hypersensitivity reaction.


Assuntos
2-Aminopurina/análogos & derivados , Aciclovir/análogos & derivados , Hipersensibilidade a Drogas/prevenção & controle , Transplante de Células-Tronco/efeitos adversos , Valina/análogos & derivados , 2-Aminopurina/uso terapêutico , Aciclovir/efeitos adversos , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Hipersensibilidade a Drogas/diagnóstico , Famciclovir , Feminino , Humanos , Hospedeiro Imunocomprometido/efeitos dos fármacos , Pessoa de Meia-Idade , Valaciclovir , Valina/efeitos adversos
17.
Am J Perinatol ; 31(11): 933-8, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24515618

RESUMO

OBJECTIVE: The aim of this study is to assess the influence of parenteral nutrition (PN) on the time to regain birth weight in premature neonates born between 1,500 and 2,499 g. STUDY DESIGN: A retrospective analysis stratified premature neonates born between 1,500 and 2,499 g by receipt of PN or intravenous dextrose at ≤ 72 hours of age. The primary outcome was the time to regain birth weight. Secondary measures included preterm-associated morbidities, time to achieve predefined enteral nutrition milestones, and length of stay. Multivariable regression estimated associations between PN and time to achieve nutrition milestones. RESULTS: Among 260 eligible neonates, those receiving PN (53%) were less mature, weighed less at birth, had a higher index of illness severity, and higher prevalence of preterm-associated morbidities (p < 0.01). The time to regain birth weight (PN, 9.4 ± 3.5 d; no PN, 9.5 ± 3.4 d) was similar between groups. Regression analysis adjusting for gestational age, illness severity, and sepsis demonstrated that PN exposure was associated with a greater time to achieve nutrition milestones and length of stay (p < 0.05). CONCLUSION: Although its impact on growth remains uncertain among premature neonates born between 1,500 and 2,499 g, PN was independently associated with a greater time to achieve nutrition milestones.


Assuntos
Recém-Nascido de Baixo Peso , Nutrição Parenteral , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Tempo de Internação , Estudos Retrospectivos
18.
JAMA ; 322(4): 301-302, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31251325
19.
Int Ophthalmol ; 34(4): 845-9, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24356776

RESUMO

To compare our innovative, cost-effective method of lacrimal surgery with other methods. A prospective cohort study. The study included 80 eyes of 80 consecutive patients who presented to our clinic between January 2009 and December 2011. The patients underwent surgery using a new technique with a specially designed cannula and were followed according to our protocol. Patency on irrigation. Of the 80 cases enrolled, the procedure was successful in 52.5 % with a mean follow-up of 247.2 days. The success rate was significantly affected by the preoperative conditions (p = 0.001) and follow-up duration (p = 0.006). This simple innovative technique was cost-effective and the results were comparable with those of other techniques.


Assuntos
Dacriocistorinostomia , Dacriocistorinostomia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Cateterismo/instrumentação , Cateterismo/métodos , Análise Custo-Benefício , Dacriocistorinostomia/economia , Dacriocistorinostomia/instrumentação , Endoscopia/instrumentação , Feminino , Seguimentos , Humanos , Aparelho Lacrimal/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
20.
Artigo em Inglês | MEDLINE | ID: mdl-38485549

RESUMO

High-dose chemotherapy with autologous hematopoietic stem cell transplantation (auto-HSCT) improved 5-year overall survival rates in relapsed/refractory germ cell tumors (GCTs) from 10% to 52%. Nearly 30% of GCT patients are deemed poor mobilizers after receiving several lines of prior therapy. There is limited data available regarding upfront plerixafor use in GCT patients. We predicted upfront plerixafor use would increase the amount of stem cells collected preventing subsequent mobilizations and improve time to curative therapy. A retrospective, single center, chart review of adult GCT patients who received plerixafor upfront for mobilization at a single center between January 1, 2013 and August 31, 2021 was performed. The primary objective was to evaluate the rate of successful peripheral blood CD34+ cell collections. Secondary objectives consisted of describing the impact of plerixafor use on mobilization and assessing auto-HSCT related outcomes. Sixteen patients received plerixafor upfront after an average of three prior lines of therapy (range: 2-5 lines). Successful collection (≥4 × 106 CD34+ cells/Kg collected within four days) was achieved in 15 (94%) patients in a median of one apheresis day (interquartile range: 1-2 days). All patients proceeded to an initial auto-HSCT and 12 patients (75%) completed both transplants as planned. Survival at 12 months was 50%. The significantly higher amount of CD34+ cells collected over less apheresis days demonstrated the clinical utility of upfront plerixafor and its potential to facilitate more efficient stem cell mobilization. There is a need for larger randomized studies with upfront plerixafor use in this unique patient population.

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