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1.
Eur J Haematol ; 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33544940

RESUMO

OBJECTIVES: To estimate the risk of thrombocytopenia in various cancers and chemotherapy regimens. METHODS: Structured patient-level data from the Flatiron Health Electronic Health Record database were used to identify adult patients who received chemotherapy for a solid tumor or hematologic malignancy from 2012 to 2017. Three-month cumulative incidence of thrombocytopenia was assessed based on platelet counts, overall and by grade of thrombocytopenia. Co-occurrence of anemia, neutropenia, and leukopenia was evaluated. RESULTS: Of 15,521 patients with solid tumors, 13% had thrombocytopenia within 3 months (platelet count < 100 × 109 /L); 4% had grade 3 (25 to < 50 × 109 /L), and 2% grade 4 (<25 × 109 /L) thrombocytopenia. Of 2537 patients with hematologic malignancies, 28% had any thrombocytopenia, 16% with grade 3, and 12% with grade 4. Among patients with thrombocytopenia, it occurred without another cytopenia in 18% of solid tumors and 7% of hematologic malignancies. CONCLUSIONS: In a large, US-representative sample of patients undergoing chemotherapy in clinical practice, thrombocytopenia incidence varied across tumor and regimen types. Despite recommendations to alter chemotherapy to avoid severe thrombocytopenia, 4% of patients with solid tumors and 16% with hematologic malignancies experienced grade 3 thrombocytopenia. Prediction and prevention of thrombocytopenia may help oncologists avoid dose modifications and their adverse effects on survival.

2.
BJU Int ; 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33556233

RESUMO

OBJECTIVES: To compare clinical outcomes between patients with locally advanced (unresectable) or metastatic urothelial carcinoma (aUC) in the upper and lower urinary tract receiving immune checkpoint inhibitors (ICIs). PATIENTS AND METHODS: We performed a retrospective cohort study collecting clinicopathological, treatment, and outcome data for patients with aUC receiving ICIs from 2013 to 2020 across 24 institutions. We compared the objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) between patients with upper and lower tract UC (UTUC, LTUC). Uni- and multivariable logistic and Cox regression were used to assess the effect of UTUC on ORR, OS, and PFS. Subgroup analyses were performed stratified based on histology (pure, mixed) and line of treatment (first line, subsequent line). RESULTS: Out of a total of 746 eligible patients, 707, 717, and 738 were included in the ORR, OS, and PFS analyses, respectively. Our results did not contradict the hypothesis that patients with UTUC and LTUC had similar ORRs (24% vs 28%; adjusted odds ratio [aOR] 0.73, 95% confidence interval [CI] 0.43-1.24), OS (median 9.8 vs 9.6 months; adjusted hazard ratio [aHR] 0.93, 95% CI 0.73-1.19), and PFS (median 4.3 vs 4.1 months; aHR 1.01, 95% CI 0.81-1.27). Patients with mixed-histology UTUC had a significantly lower ORR and shorter PFS vs mixed-histology LTUC (aOR 0.20, 95% CI 0.05-0.91 and aHR 1.66, 95% CI 1.06-2.59), respectively). CONCLUSION: Overall, patients with UTUC and LTUC receiving ICIs have comparable treatment response and outcomes. Subgroup analyses based on histology showed that those with mixed-histology UTUC had a lower ORR and shorter PFS compared to mixed-histology LTUC. Further studies and evaluation of molecular biomarkers can help refine patient selection for immunotherapy.

3.
Eur Urol Oncol ; 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33423945

RESUMO

BACKGROUND: While immune checkpoint inhibitors (ICIs) are approved in the first-line (1L) setting for cisplatin-unfit patients with programmed death-ligand 1 (PD-L1)-high tumors or for platinum (cisplatin/carboplatin)-unfit patients, response rates remain modest and outcomes vary with no clinically useful biomarkers (except for PD-L1). OBJECTIVE: We aimed to develop a prognostic model for overall survival (OS) in patients receiving 1L ICIs for advanced urothelial cancer (aUC) in a multicenter cohort study. DESIGN, SETTING, AND PARTICIPANTS: Patients treated with 1L ICIs for aUC across 24 institutions and five countries (in the USA and Europe) outside clinical trials were included in this study. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We used a stepwise, hypothesis-driven approach using clinician-selected covariates to develop a new risk score for patients receiving ICIs in the 1L setting. Demographics, clinicopathologic data, treatment patterns, and OS were collected uniformly. Univariate Cox regression was performed on 18 covariates hypothesized to be associated with OS based on published data. Variables were retained for multivariate analysis (MVA) if they correlated with OS (p < 0.2) and were included in the final model if p < 0.05 on MVA. Retained covariates were assigned points based on the beta coefficient to create a risk score. Stratified median OS and C-statistic were calculated. RESULTS AND LIMITATIONS: Among 984 patients, 357 with a mean age of 71 yr were included in the analysis, 27% were female, 68% had pure UC, and 13% had upper tract UC. Eastern Cooperative Oncology Group performance status ≥2, albumin <3.5 g/dl, neutrophil:lymphocyte ratio >5, and liver metastases were significant prognostic factors on MVA and were included in the risk score. C index for new 1L risk score was 0.68 (95% confidence interval 0.65-0.71). Limitations include retrospective nature and lack of external validation. CONCLUSIONS: We developed a new 1L ICI risk score for OS based on data from patients with aUC treated with ICIs in the USA and Europe outside of clinical trials. The score components highlight readily available factors related to tumor biology and treatment response. External validation is being pursued. PATIENT SUMMARY: With multiple new treatments under development and approved for advanced urothelial carcinoma, it can be difficult to identify the best treatment sequence for each patient. The risk score may help inform treatment discussions and estimate outcomes in patients treated with first-line immune checkpoint inhibitors, while it can also impact clinical trial design and endpoints. TAKE HOME MESSAGE: A new risk score was developed for advanced urothelial carcinoma treated with first-line immune checkpoint inhibitors. The score assigned Eastern Cooperative Oncology Group performance status ≥2, albumin <3.5 g/dl, neutrophil:lymphocyte ratio >5, and liver metastases each one point, with a higher score being associated with worse overall survival.

4.
Invest Ophthalmol Vis Sci ; 62(1): 1, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33393967

RESUMO

Purpose: In order to clarify the role of the optic nerve (ON) as a load on ocular rotation, we developed a finite element model (FEM) of incremental adduction induced by active contractility of extraocular muscles (EOMs), with and without tethering by the ON. Methods: Three-dimensional (3-D) horizontal rectus EOM geometries were obtained from magnetic resonance imaging of five healthy adults, and measured constitutive tissue properties were used. Active and passive strain energies of EOMs were defined using ABAQUS (Dassault Systemes) software. All deformations were assumed to be caused by EOM twitch activation that rotated the eye about a fixed center. The medial rectus (MR) muscle was commanded to additionally contract starting from 26 degrees adducted position, and the lateral rectus (LR) to relax, further adducting the eye either with or without loading by the ON. Tridimensional heat maps were generated to represent the stress and strain distributions. Results: Tensions in the EOMs were physiologically plausible during incremental adduction. Force in the MR increased from 10 gm at 26 degrees adduction to approximately 28 gm at 32 degrees adduction. Under identical MR contraction, adduction with ON loading reached 32 degrees but 36 degrees without it. Maximum and minimum principal strains within the MR were 16% and 22%, respectively, but when ON loading was included, resulting stress and strain were concentrated at the optic disc. Conclusions: This physiologically plausible method of simulating EOM activation can provide realistic input to model biomechanical behavior of active and passive tissues in the orbit to clarify biomechanical consequences of ON traction during adduction.

5.
South Med J ; 114(1): 8-12, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33398353

RESUMO

OBJECTIVES: There are many factors that influence medical students' (MS) decisions when choosing a career. Some prominent factors include life-work balance, indebtedness, and flexibility of work hours. Whereas the expression of empathy has many positive correlates with a trusting and meaningful physician-patient interaction, only a few studies have analyzed the association of MS empathy expression and primary care residency selection. The results of these studies about the relationship of MS expression of empathy and their selection of primary care specialties have been conflicting, depending on the empathy instrument used. In addition, there have been other variables that have affected career decision making in more recent years not previously encountered. The objectives of our study were to analyze the association of The George Washington University School of Medicine and Health Sciences (GWU) MS Interpersonal Reactivity Index (IRI) scores and their residency selection, to compare our results with previous studies to determine whether the IRI provided more definitive relationships between empathy and career choice, and to assess whether our results confirmed the theoretical construct linking empathy with primary care physicians. METHODS: GWU third-year MS (MS3s), representing the classes of 2008-2011, completed the perspective taking and empathy subscales of the IRI, which measure cognitive and affective empathy, respectively. MS empathy scores for individual specialty were compared to those scores in internal medicine (IM) using a linear regression model. Empathy scores for patient-oriented versus technology-oriented specialties and primary versus surgical specialties were compared using the independent t test. RESULTS: A total of 593 (77.5%) MS3s had mean IRI scores of 45.1 (standard error 4.8), higher than a recent study involving MS. There were no significant differences between patient- and technology-oriented specialties (-0.65 to 0.88), primary care versus surgical residencies (-0.87 to 1.4), and women versus men (-0.20 to 1.4). Our study did not clarify previous conflicting studies in the literature. CONCLUSIONS: There are no significant differences in expression of empathy in GWU students who chose patient- versus technology-oriented and primary care versus surgical residencies. The authors can only speculate why students' high expression of empathy was not associated with selecting primary care residencies, namely, women are outnumbering men entering medicine and are selecting technology-related specialties previously identified predominantly with men, and millennials have specific traits inherent in their generation that can affect their specialty choice. The results of our study shed doubt that the theoretical construct linking MS high empathy expression and choice of primary care careers is valid today.

6.
Nat Med ; 27(1): 66-72, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33432171

RESUMO

The clinical impact of rare loss-of-function variants has yet to be determined for most genes. Integration of DNA sequencing data with electronic health records (EHRs) could enhance our understanding of the contribution of rare genetic variation to human disease1. By leveraging 10,900 whole-exome sequences linked to EHR data in the Penn Medicine Biobank, we addressed the association of the cumulative effects of rare predicted loss-of-function variants for each individual gene on human disease on an exome-wide scale, as assessed using a set of diverse EHR phenotypes. After discovering 97 genes with exome-by-phenome-wide significant phenotype associations (P < 10-6), we replicated 26 of these in the Penn Medicine Biobank, as well as in three other medical biobanks and the population-based UK Biobank. Of these 26 genes, five had associations that have been previously reported and represented positive controls, whereas 21 had phenotype associations not previously reported, among which were genes implicated in glaucoma, aortic ectasia, diabetes mellitus, muscular dystrophy and hearing loss. These findings show the value of aggregating rare predicted loss-of-function variants into 'gene burdens' for identifying new gene-disease associations using EHR phenotypes in a medical biobank. We suggest that application of this approach to even larger numbers of individuals will provide the statistical power required to uncover unexplored relationships between rare genetic variation and disease phenotypes.


Assuntos
Registros Eletrônicos de Saúde , Exoma , Genótipo , Fenótipo , Idoso , Biologia Computacional , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Sequenciamento Completo do Exoma
7.
Sci Transl Med ; 13(576)2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33441424

RESUMO

More than 800 million people in the world suffer from chronic kidney disease (CKD). Genome-wide association studies (GWAS) have identified hundreds of loci where genetic variants are associated with kidney function; however, causal genes and pathways for CKD remain unknown. Here, we performed integration of kidney function GWAS and human kidney-specific expression quantitative trait analysis and identified that the expression of beta-mannosidase (MANBA) was lower in kidneys of subjects with CKD risk genotype. We also show an increased incidence of renal failure in subjects with rare heterozygous loss-of-function coding variants in MANBA using phenome-wide association analysis of 40,963 subjects with exome sequencing data. MANBA is a lysosomal gene highly expressed in kidney tubule cells. Deep phenotyping revealed structural and functional lysosomal alterations in human kidneys from subjects with CKD risk alleles and mice with genetic deletion of Manba Manba heterozygous and knockout mice developed more severe kidney fibrosis when subjected to toxic injury induced by cisplatin or folic acid. Manba loss altered multiple pathways, including endocytosis and autophagy. In the absence of Manba, toxic acute tubule injury induced inflammasome activation and fibrosis. Together, these results illustrate the convergence of common noncoding and rare coding variants in MANBA in kidney disease development and demonstrate the role of the endolysosomal system in kidney disease development.

8.
Cancer Treat Res Commun ; 25: 100251, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33310369

RESUMO

INTRODUCTION: Immune checkpoint inhibitors (CPIs) were recently approved in advanced clear cell renal cell carcinoma (RCC) and could be a promising option for metastatic RCC with sarcomatoid differentiation (sRCC) which otherwise carry a poor prognosis. We sought to compare outcomes between patients who received immunotherapy (IO) including CPIs or high dose interleukin-2 (HD IL2) for metastatic sRCC versus those who did not. PATIENTS AND METHODS: We performed a single-center retrospective data analysis of 44 consecutive sRCC patients with any percentage of sarcomatoid differentiation from our institutional RCC database of whom 34 received IO and 10 patients did not. RESULTS: Baseline variables between the two groups were not significantly different except for a greater percentage of patients with ≥40% sarcomatoid differentiation in the non-IO cohort. At a median follow-up of 27.6 months, patients treated with IO had a median overall survival of 57.6 months compared to 6.6 months in patients not treated with IO (p = 0.0002). Overall response rates (ORR) between the IO and non-IO group were 35.3% and 0% respectively (p = 0.06). When IO was given in the 1st line setting, the ORR was 25.0%, as compared to 44.4% in the 2nd line setting and beyond though limitations of small sample sizes apply. Immune-related adverse events (IRAE) occurred in 38.2% of patients in the IO group, with grade 3 events (mostly gastrointestinal) in 20.6% with no grade 4 or 5 events. IRAEs led to interruption or discontinuation of immunotherapy in 26.5%. CONCLUSION: Our results support IO as an effective therapeutic option for patients with metastatic sarcomatoid RCC. Further study of various IO regimens, including those affecting the interleukin-2 signaling pathway, and their efficacy in neoadjuvant and adjuvant settings are warranted in sRCC.

9.
Otolaryngol Head Neck Surg ; : 194599820965910, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33170765

RESUMO

OBJECTIVE: This state-of-the-art article reviews the epidemiology, diagnosis, and management of vocal fold leukoplakia, with focus on recent advances. It focuses on the clinical challenges that otolaryngologists face balancing both oncological efficacy and functional outcomes in leukoplakia and presents the current philosophies and techniques to consider when managing such patients. DATA SOURCES: PubMed/MEDLINE. REVIEW METHODS: We conducted a detailed review of publications related to vocal cord and laryngeal leukoplakia, dysplasia, hyperkeratosis, leukoplakia endoscopy, and leukoplakia management focusing specifically on oncologic outcomes, voice preservation, current and emerging diagnosis, and management techniques. CONCLUSIONS: There has been a paradigm shift away from performing "vocal cord stripping" procedures that can cause irreversible hoarseness toward voice preservation surgery while achieving comparable oncologic control. Surgical technical and instrumental developments have been designed to maximally treat superficial disease while preserving underling vibratory mucosa. Recent improvements in histopathological grading systems and advances in biomarker classification may allow for improved oncologic risk stratification. Furthermore, improvements in endoscopic imaging capabilities and contact endoscopy are currently being studied for their potential diagnostic significance. IMPLICATIONS FOR PRACTICE: To optimally manage vocal fold leukoplakia, the otolaryngologist should become familiar with the oncologic implications of the disease and the importance of obtaining pathologic diagnosis to rule out malignancy. In addition, the surgeon should maintain surgical techniques and knowledge of available instruments and lasers that can assist in surgical management while prioritizing the preservation of vibratory tissue and voice quality. Finally, the surgeon and the patient should understand the clinical importance of routine endoscopic surveillance.

10.
Arch Craniofac Surg ; 21(5): 301-304, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33143398

RESUMO

Orthognathic surgeries often utilize rigid fixation for stabilization of the osteotomy site. The longterm fate of rigid fixations is still under investigation, and whether they should be routinely removed is under debate despite their low complication rates. Here, we report a case where a 26-year-old man suffered high-velocity trauma to his face 7 years after a two-jaw surgery. Computed tomography examination revealed a zygomaticomaxillary complex fracture, and open reduction and internal fixation was performed along with anterior maxillary wall reconstruction using absorbable mesh. Intraoperative examination revealed a broken L-shaped titanium plate near the fracture site with multiple bony fragments near each titanium screw. The rigid titanium system may have caused comminution of the fracture pattern, worsening the severity of the fracture.

11.
Foot Ankle Spec ; : 1938640020952301, 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32865044

RESUMO

BACKGROUND: ViviGen is an allogeneic cellular bone matrix product containing lineage-committed bone cells, and can be used as an alternative to autograft bone or other augments to aid in arthrodesis or to enhance bony healing in open reduction and internal fixation (ORIF) procedures. METHODS: This study included 153 consecutive patients undergoing ankle, midfoot, or hindfoot arthrodesis or ORIF procedures from January 2017 to October 2018, in which an allogeneic cellular bone matrix product was used to aid in bony healing. Retrospective chart review identified patient demographic factors and medical comorbidities and evaluated clinical and radiographic data to determine fusion/union rate and complications. RESULTS: The overall fusion rate for the arthrodesis cohort was 97/113 (85.8%). The overall complication rate in this cohort was 22/113 (19.5%). Smokers had significantly lower rates of fusion compared with nonsmokers (P = .01). The observed bony healing rate for the ORIF cohort was 19/22 (86.4%), with a complication rate of 3/22 (13.6%). CONCLUSION: With satisfactory fusion rates and relatively few complications, our findings suggest that ViviGen is a safe and efficacious alternative to other forms of bone graft augmentation for fusion and ORIF procedures about the foot and ankle. Further study is needed to compare the efficacy of ViviGen with autograft bone and other augments. LEVELS OF EVIDENCE: Level IV: Case series.

12.
Clin Sports Med ; 39(4): 819-828, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32892969

RESUMO

Common peroneal nerve dysfunction after a multiligament knee injury can be devastating. In patients with persistent foot drop, posterior tibial tendon transfer to the dorsum of the foot is a reliable and safe procedure to restore dorsiflexion. These authors favor passing the posterior tibial tendon through the interosseous membrane and docking it into the lateral/middle cuneiforms. A Strayer procedure or tendo-Achilles lengthening must be performed in patients unable to achieve at least 10° of passive dorsiflexion. Despite the operative limb having 30% to 40% of ankle dorsiflexion strength of the uninjured limb, short- and long-term functional outcomes are excellent.

13.
Clin Sports Med ; 39(4): xv-xvi, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32892977
14.
Foot Ankle Spec ; : 1938640020950153, 2020 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-32830574

RESUMO

BACKGROUND: Tibiotalocalcaneal (TTC) arthrodesis is a salvage reconstructive procedure for ankle and subtalar arthritis and deformity. This study aims to identify fusion rates and complications of TTC arthrodesis procedures performed at our institution using a specific retrograde intramedullary nail. Additionally, we analyzed the subpopulation that sustained an intramedullary nail break. METHODS: A retrospective review was conducted of 45 patients who underwent 47 TTC arthrodesis procedures with intramedullary fixation using the Phoenix nail at our institution from October 2010 to September 2017. Patient age, body mass index, sex, smoking status, diabetes diagnosis, peripheral vascular disease, thyroid disease, inflammatory arthritis, steroid use, prior ankle fractures and procedures, fusion rates, nail diameter, time to hardware failure, preoperative coronal plane deformity, and return to work were obtained. RESULTS: Successful fusion was confirmed in 79% of tibiotalar, 70% of subtalar, and 66% of combined tibiotalar and subtalar joints. Eight of 47 (17%) TTC nails suffered nail breakage postoperatively. Although statistical analysis was not performed due to the small population size, patients with nail failure had lower rates of tibiotalar (38% vs 87% of patients without nail failure) and combined tibiotalar/subtalar fusion (25% vs 74%). Ten percent of patients without nail breakage required revision surgery, compared to 75% of patient with nail breakage. CONCLUSION: This study describes TTC arthrodesis outcomes at our institution. It demonstrates a high complication rate using a specific retrograde intramedullary nail, including nail breakage and non-union. Further analysis and improvement in technique and implant design may decrease revision rates and improve outcomes. LEVELS OF EVIDENCE: Therapeutic, Level IV.

16.
Cureus ; 12(7): e9152, 2020 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-32789089

RESUMO

Acquired hemophilia A (AHA) is an uncommon complication caused by autoantibodies against Factor VIII. The main concern with these patients is hemorrhage, which is often treated with Factor VIII inhibitor bypassing activity (FEIBA). On rare occasions, treatment with FEIBA can result in thromboembolism, a potentially fatal complication. This unfortunate situation occurred in our patient, a 64-year-old female who was treated with FEIBA after being diagnosed with AHA. After initiating FEIBA, she developed clinical signs and symptoms of pulmonary embolism, which was ultimately responsible for her acute death. While pulmonary embolism may be a rare complication of FEIBA treatment, clinicians should be aware of its possibility, especially as the complete safety profile for this treatment is not well known.

17.
Transplant Proc ; 52(6): 1864-1868, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32446692

RESUMO

BACKGROUND: Expression of genes with immunoregulatory capacity can potentially decrease rejection of allograft. According to recent studies, viral interleukin (IL)-10 can reduce immune response during allotransplantation and is one of the most promising methods for the prevention of rejection. Our study aimed to analyze the immunosuppressive potential of recombinant adenovirus-mediated rat IL-10 in rat skin allograft. METHODS: We performed skin graft surgery 1 hour after infecting the donated skin with adenovirus-mediated rat IL-10. On day 7 postoperatively, the skin allografts were harvested, and acute rejection was graded histologically. RESULTS: Viral IL-10 gene transfer into rat skin allografts improved graft survival and reduced acute rejections. CONCLUSION: The results of our study suggest that the therapeutic potential of graft viral IL-10 gene transfer is an effective immunosuppressive method for preventing skin allograft rejection.


Assuntos
Terapia Genética/métodos , Rejeição de Enxerto/imunologia , Interleucina-10/imunologia , Transplante de Pele , Adenoviridae/genética , Animais , Vetores Genéticos , Rejeição de Enxerto/prevenção & controle , Interleucina-10/genética , Masculino , Ratos , Ratos Endogâmicos F344 , Ratos Endogâmicos Lew , Transfecção/métodos , Transplante Homólogo
19.
Br J Haematol ; 190(6): 923-932, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32311075

RESUMO

Antibodies to first-generation recombinant thrombopoietin (TPO) neutralized endogenous TPO and caused thrombocytopenia in some healthy subjects and chemotherapy patients. The second-generation TPO receptor agonist romiplostim, having no sequence homology to TPO, was developed to avoid immunogenicity. This analysis examined development of binding and neutralising antibodies to romiplostim or TPO among adults with immune thrombocytopenia (ITP) in 13 clinical trials and a global postmarketing registry. 60/961 (6·2%) patients from clinical trials developed anti-romiplostim-binding antibodies post-baseline. The first positive binding antibody was detected 14 weeks (median) after starting romiplostim, at median romiplostim dose of 2 µg/kg and median platelet count of 29.5 × 109 /l; most subjects had ≥98·5% of platelet assessments showing response. Neutralising antibodies to romiplostim developed in 0·4% of patients, but were unrelated to romiplostim dose and did not affect platelet count. Thirty-three patients (3·4%) developed anti-TPO-binding antibodies; none developed anti-TPO-neutralising antibodies. In the global postmarketing registry, 9/184 (4·9%) patients with spontaneously submitted samples had binding antibodies. One patient with loss of response had anti-romiplostim-neutralising antibodies (negative at follow-up). Collectively, anti-romiplostim-binding antibodies developed infrequently. In the few patients who developed neutralising antibodies to romiplostim, there was no cross-reactivity with TPO and no associated loss of platelet response.

20.
Ophthalmic Plast Reconstr Surg ; 36(6): 562-565, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32221102

RESUMO

INTRODUCTION: The floppy eyelid syndrome describes an eyelid disorder characterized by floppy tarsal plates that may be caused by a loss of elastin. The authors attempted to create floppy eyelids by digesting elastin from cadaveric tarsus and then treated them with cross-linking using ultraviolet A and riboflavin. METHODS: Nine right and 9 left upper eyelids were excised from cadavers. Four vertical strips of central tarsus were removed from each eyelid. One strip of tarsus from each eyelid was treated with 10 units/ml of elastase for 2 hours. Another tarsal strip from each eyelid was immersed in normal saline for 2 hours (control). A third strip from the same eyelid was cross-linked using ultraviolet A at 6 mW/cm for 18 minutes. Finally, a fourth strip of tarsus was cross-linked in the same manner following treatment with elastase for 2 hours. A microtensile load cell was used to measure the Young modulus (stiffness) of each tissue. RESULTS: Mean (standard deviation) Young modulus for controls (18.9 ± 3.6 MPa) was significantly higher than samples treated with elastase alone (6.6 ± 3.8 MPa, p <0.01). Samples that were treated with cross-linking after elastase had a mean (standard deviation) Young modulus of 26 ± 2.3 MPa, while those treated with cross-linking alone had a mean (standard deviation) Young modulus of 34 ± 0.15 MPa. The differences in stiffness between all groups were significant (p <0.01). DISCUSSION: Treatment with elastase significantly reduces the stiffness of tarsal plates. This effect is reversed by cross-linking, raising the possibility of using this modality for the treatment of FES.

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