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1.
J Antimicrob Chemother ; 79(2): 262-270, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38069908

RESUMO

BACKGROUND: Pathophysiological changes in severely burned patients alter the pharmacokinetics (PK) of anti-infective agents, potentially leading to subtherapeutic concentrations at the target site. Albumin supplementation, to support fluid resuscitation, may affect pharmacokinetic properties by binding drugs. This study aimed to investigate the PK of piperacillin/tazobactam in burn patients admitted to the ICU before and after albumin substitution as total and unbound concentrations in plasma. PATIENTS AND METHODS: Patients admitted to the ICU and scheduled for 4.5 g piperacillin/tazobactam administration and 200 mL of 20% albumin substitution as part of clinical routine were included. Patients underwent IV microdialysis, and simultaneous arterial plasma sampling, at baseline and multiple timepoints after drug administration. PK analysis of total and unbound drug concentrations under steady-state conditions was performed before and after albumin supplementation. RESULTS: A total of seven patients with second- to third-degree burns involving 20%-60% of the total body surface were enrolled. Mean (SD) AUC0-8 (h·mg/L) of total piperacillin/tazobactam before and after albumin substitution were 402.1 (242)/53.2 (27) and 521.8 (363)/59.7 (32), respectively. Unbound mean AUC0-8 before and after albumin supplementation were 398.9 (204)/54.5 (25) and 456.4 (439)/64.5 (82), respectively. CONCLUSIONS: Albumin supplementation had little impact on the PK of piperacillin/tazobactam. After albumin supplementation, there was a numerical increase in mean AUC0-8 of total and unbound piperacillin/tazobactam, whereas similar Cmax values were observed. Future studies may investigate the effect of albumin supplementation on drugs with a higher plasma protein binding.


Assuntos
Antibacterianos , Queimaduras , Humanos , Antibacterianos/uso terapêutico , Piperacilina/farmacocinética , Ácido Penicilânico/farmacocinética , Combinação Piperacilina e Tazobactam/farmacocinética , Queimaduras/complicações , Queimaduras/tratamento farmacológico , Unidades de Terapia Intensiva
2.
Klin Monbl Augenheilkd ; 241(5): 626-632, 2024 May.
Artigo em Inglês, Alemão | MEDLINE | ID: mdl-38574680

RESUMO

Ocular manifestations of rheumatic diseases are common and contribute significantly to the morbidity and reduced quality of life of affected patients. Knowledge of typical clinical manifestations is important for the rheumatologist in order to support the reference of patients with corresponding symptoms for ophthalmological consultation at an early stage of disease, or to initiate regular screening examinations (e.g. in patients with Behçet's syndrome). Conversely, a (possibly urgent) rheumatological assessment is crucial for certain ophthalmological diseases, in order not to overlook a (possibly fatal) systemic associated disease. Patients with rheumatic or inflammatory ocular diseases should always be informed by the treating physician about possible symptoms of other organ manifestations, in order to avoid a delayed diagnosis. "Classic" associations for uveitis are (HLA-B27-associated) spondyloarthritis and acute anterior uveitis, as well as retinal vasculitis with or without panuveitis and Behçet's syndrome. In patients with rheumatoid arthritis or ANCA-associated vasculitis, however, scleritis (with or without peripheral ulcerative keratitis) typically occurs, but a variety of other findings are also possible. Close interdisciplinary collaboration, particularly regarding therapeutic decisions, is crucial to ensuring a good prognosis for the patient.


Assuntos
Oftalmopatias , Doenças Reumáticas , Humanos , Doenças Reumáticas/complicações , Doenças Reumáticas/diagnóstico , Oftalmopatias/etiologia , Oftalmopatias/diagnóstico , Oftalmopatias/terapia , Adulto , Diagnóstico Diferencial , Feminino , Masculino
3.
Chemistry ; 29(57): e202301337, 2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37419861

RESUMO

Organic solar cells have been continuously studied and developed through the last decades. A major step in their development was the introduction of fused-ring non-fullerene electron acceptors. Yet, beside their high efficiency, they suffer from complex synthesis and stability issues. Perylene-based non-fullerene acceptors, in contrast, can be prepared in only a few steps and display good photochemical and thermal stability. Herein, we introduce four monomeric perylene diimide acceptors obtained in a three-step synthesis. In these molecules, the semimetals silicon and germanium were added in the bay position, on one or both sides of the molecules, resulting in asymmetric and symmetric compounds with a red-shifted absorption compared to unsubstituted perylene diimide. Introducing two germanium atoms improved the crystallinity and charge carrier mobility in the blend with the conjugated polymer PM6. In addition, charge carrier separation is significantly influenced by the high crystallinity of this blend, as shown by transient absorption spectroscopy. As a result, the solar cells reached a power conversion efficiency of 5.38 %, which is one of the highest efficiencies of monomeric perylene diimide-based solar cells recorded to date.

4.
Nephrol Dial Transplant ; 39(1): 141-150, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-37391381

RESUMO

BACKGROUND: We previously reported excellent efficacy and improved safety aspects of rapid steroid withdrawal (RSWD) in the randomized controlled 1-year "Harmony" trial with 587 predominantly deceased-donor kidney transplant recipients randomized either to basiliximab or rabbit antithymocyte globulin induction therapy and compared with standard immunosuppressive therapy consisting of basiliximab, low tacrolimus once daily, mycophenolate mofetil and corticosteroids. METHODS: The 5-year post-trial follow-up (FU) data were obtained in an observational manner at a 3- and a 5-year visit only for those Harmony patients who consented to participate and covered clinical events that occurred from the second year onwards. RESULTS: Biopsy-proven acute rejection and death-censored graft loss rates remained low and independent of RSWD. Rapid steroid withdrawal was an independent positive factor for patient survival (adjusted hazard ratio 0.554, 95% confidence interval 0.314-0.976; P = .041).The reduced incidence of post-transplantation diabetes mellitus in RSWD patients during the original 1-year study period was not compensated by later incidences during FU. Incidences of other important outcome parameters such as opportunistic infections, malignancies, cardiovascular morbidity/risk factors, donor-specific antibody formation or kidney function did not differ during FU period. CONCLUSIONS: With all the limitations of a post-trial FU study, the Harmony FU data confirm excellent efficacy and beneficial safety aspects of RSWD under modern immunosuppressive therapy over the course of 5 years after kidney transplantation in an immunologically low-risk, elderly population of Caucasian kidney transplant recipients. Trial registration: Clinical trial registration number: Investigator Initiated Trial (NCT00724022, FU study DRKS00005786).


Assuntos
Transplante de Rim , Idoso , Humanos , Anticorpos Monoclonais , Basiliximab , Seguimentos , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversos , Ácido Micofenólico/uso terapêutico , Esteroides , Tacrolimo/efeitos adversos
5.
Chemistry ; 28(23): e202200276, 2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35218252

RESUMO

A series of non-fullerene acceptors based on perylene monoimides coupled in the peri position through phenylene linkers were synthesized via Suzuki-coupling reactions. Various substitution patterns were investigated using density functional theory (DFT) calculations in combination with experimental data to elucidate the geometry and their optical and electrochemical properties. Further investigations of the bulk properties with grazing incidence wide angle X-ray scattering (GIWAXS) gave insight into the stacking behavior of the acceptor thin films. Electrochemical and morphological properties correlate with the photovoltaic performance of devices with the polymeric donor PBDB-T and a maximum efficiency of 3.17 % was reached. The study gives detailed information about structure-property relationships of perylene-linker-perylene compounds.

6.
Klin Monbl Augenheilkd ; 239(5): 695-701, 2022 May.
Artigo em Inglês, Alemão | MEDLINE | ID: mdl-35426113

RESUMO

A large proportion of patients with visual impairment secondary to non-infectious uveitis may require DMARDs. Although these are highly effective, some patients may require alternatives to the currently available immunomodulators due to an inadequate response or undesirable side effects. Janus Kinase Inhibitors (JAKi) are already approved for several autoimmune diseases in rheumatology, gastroenterology and dermatology. To date, JAKi have been studied in phase 3 trials in various types of uveitis. Mechanism of Action: JAKi work by inhibiting the phosphorylation of Janus kinases, which are transmembrane proteins. This blocks the activation of transcription factors, which in turn downregulates cytokine expression and inflammatory mediators. JAKi represent an extremely effective novel therapeutic approach in rheumatology, gastroenterology and dermatology. They have already been approved for the treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis and atopic eczema. In earlier comparative studies with conventional biologics, a better therapeutic response was reported in some cases. Several published case reports report reduced cortisone levels in patients with uveitis who had responded poorly to conventional and biological DMARDs. Approval studies are under way for JIA-associated and ANA-positive anterior uveitis. In summary, JAKi represent an innovative treatment option for patients with non-infectious uveitis in whom DMARDs are contraindicated or ineffective.


Assuntos
Antirreumáticos , Artrite Psoriásica , Artrite Reumatoide , Inibidores de Janus Quinases , Uveíte , Antirreumáticos/uso terapêutico , Artrite Psoriásica/induzido quimicamente , Artrite Psoriásica/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Humanos , Inibidores de Janus Quinases/farmacologia , Inibidores de Janus Quinases/uso terapêutico , Uveíte/induzido quimicamente , Uveíte/diagnóstico , Uveíte/tratamento farmacológico
7.
Klin Monbl Augenheilkd ; 237(5): 605-613, 2020 May.
Artigo em Alemão | MEDLINE | ID: mdl-32434244

RESUMO

Syphilis is a bacterial infectious disease transmitted by the spirochaete Treponema pallidum. The rate of infection has increased during the last decade. Ocular syphilis is an underestimated presentation of the disease, and it is increased in HIV-positive patients. Even though every part of the eye may be affected, syphilis most commonly occurs with posterior or panuveitis. A distinctive pattern is acute syphilitic placoid chorioretinitis, with typical features in multimodal imaging. If syphilis is suspected, specific and nonspecific Treponema pallidum serological diagnostic tests are mandatory. Clinical outcome, or morphology and vision are commonly improved if antibiotic therapy (penicillin is the drug of choice) is instituted early. Additional corticosteroids are carefully applied according to individual need, and should be initiated after the start of antibiotics.


Assuntos
Coriorretinite/tratamento farmacológico , Endoftalmite/tratamento farmacológico , Infecções Oculares Bacterianas , Pan-Uveíte , Sífilis/tratamento farmacológico , Antibacterianos/uso terapêutico , Humanos
8.
Wien Med Wochenschr ; 169(9-10): 222-225, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29147868

RESUMO

Hydrogen peroxide has been used in medicine for more than 100 years. It is known in surgery as a highly useful irrigation solution by virtue of both its hemostatic and its antimicrobial effects. Due to its possible negative effect on wound healing and its cytotoxic effect in higher concentrations, there are concerns about the safety of its use. The objective of this paper is to review the safety and beneficial effects of hydrogen peroxide.


Assuntos
Peróxido de Hidrogênio/efeitos adversos , Peróxido de Hidrogênio/farmacologia , Cicatrização , Humanos , Procedimentos Cirúrgicos Operatórios , Cicatrização/efeitos dos fármacos
9.
Am J Transplant ; 18(7): 1726-1734, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29337426

RESUMO

Tacrolimus (TAC) increases the risk of posttransplant diabetes (PTDM) compared with cyclosporine A (CYC). The present 12-month, multicenter, investigator-driven, prospective, randomized study was designed to assess whether conversion from tacrolimus to CYC can reverse PTDM after renal transplantation. Predominantly white patients with PTDM according to the 2005 American Diabetes Association criteria were randomized to either replacement of TAC with CYC or continuation of their TAC-based regimen after stratification for type of glucose-lowering therapy, steroid therapy, and hepatitis C status. At 12 months, 14 of 41 patients with complete data in the CYC arm (34%; 95%CI 19%-49%) were free of diabetes, whereas this was the case in only 4 of 39 patients (10%; 95%CI 3%-20%) in the TAC arm (P = .01). At 12 months, 39% of patients in the CYC arm were off glucose-lowering medication vs 13% of patients in the TAC arm (P = .01). The CYC group decreased glycated hemoglobin level during the 12-month follow-up, resulting in significantly lower levels compared with the TAC group (6.0 ± 0.9% vs 7.1 ± 1.7% at 12 months; P = .002). In conclusion, replacement of TAC with CYC significantly improves glucose metabolism and has the potential to reverse diabetes during the first year after conversion. (EU Clinical Trials Register No. 2006-001765-42).


Assuntos
Ciclosporina/uso terapêutico , Diabetes Mellitus/tratamento farmacológico , Glucose/metabolismo , Rejeição de Enxerto/tratamento farmacológico , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Tacrolimo/uso terapêutico , Diabetes Mellitus/etiologia , Diabetes Mellitus/patologia , Feminino , Seguimentos , Taxa de Filtração Glomerular , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto , Humanos , Imunossupressores/uso terapêutico , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Prognóstico , Estudos Prospectivos , Fatores de Risco
10.
Am J Transplant ; 18(12): 2965-2976, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29722128

RESUMO

HERAKLES was a 1-year randomized, multicenter trial. Patients were randomized at 3 months after kidney transplantation to remain on cyclosporine-based therapy, switch to everolimus without a calcineurin inhibitor (CNI), or switch to everolimus with low-exposure cyclosporine. Overall, 417 of 497 (83.9%) patients from the core study entered a 4-year extension study. The randomized regimen was continued to year 5 in 75.9%, 41.9% and 24.6% of patients in the standard-CNI, CNI-free and low-CNI groups, respectively. Adjusted estimated GFR at year 5 was significantly higher in the CNI-free group versus standard CNI (difference 7.2 mL/min/1.73 m2 , P < .001) or low CNI (difference 7.6 mL/min/1.73 m2 , P < .001). For patients who continued randomized therapy for 5 years, differences were 14.4 mL/min/1.73 m2  and 10.1 mL/min/1.73 m2 , respectively. Biopsy-proven acute rejection occurred during the 4-year extension study in 7.6%, 8.6%, and 9.0% of patients in the standard-CNI, CNI-free and low-CNI groups, respectively (P = .927). In conclusion, conversion to a CNI-free everolimus regimen 3 months after kidney transplantation improved long-term graft function, particularly in patients who continued the CNI-free regimen. Low CNI with everolimus did not improve renal function. Efficacy was comparable between groups but frequent immunosuppression changes should be taken into account.


Assuntos
Ciclosporina/uso terapêutico , Everolimo/uso terapêutico , Rejeição de Enxerto/tratamento farmacológico , Sobrevivência de Enxerto/efeitos dos fármacos , Imunossupressores/uso terapêutico , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Taxa de Filtração Glomerular , Rejeição de Enxerto/etiologia , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Prognóstico , Estudos Prospectivos , Fatores de Risco , Suspensão de Tratamento , Adulto Jovem
11.
Clin Transplant ; 32(1)2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29052906

RESUMO

This study assessed adherence to prolonged-release tacrolimus (PR-T)-based immunosuppression during routine maintenance of renal transplant recipients in Germany. Patients had received PR-T for ≥1 month at inclusion. Data were collected during four visits (V): baseline (V1), 6 (V2), 12 (V3), and 18 (V4) months. Composite primary endpoint: nonadherence at V4, defined as self-reported nonadherence on the Basel Assessment of Adherence with Immunosuppressive Medication Scale (BAASIS© ), investigator-rated nonadherence, and/or V4 tacrolimus trough level outside a predefined range. Secondary endpoints: individual BAASIS items, incidence of rejection, kidney function, and safety. Overall, 153 adult kidney recipients (mean [standard deviation] time post-transplant 5.8 [4.6] years) were included. Nonadherence was high at V4 (67.7% [95% confidence interval 58.9%, 75.6%]). Medication-taking adherence was 86.9% and 91.3% at V1 and V4, respectively; adherence to timing of medication intake was 58.2% and 58.3%, with little evidence of missed doses/drug holidays. Investigators rated adherence "good" in 85.6% of patients (V4). Two (1.3%) patients had acute rejection episodes. Kidney function remained stable (mean creatinine clearance, V1: 62.1 mL/min; V4: 65.3 mL/min). Investigators rated effectiveness of PR-T as "very good"/"good" in 91.5% of patients. Most patients (94.7%) found PR-T dosing more convenient than immediate-release tacrolimus. PR-T was well tolerated with high medication persistence.


Assuntos
Preparações de Ação Retardada , Rejeição de Enxerto/prevenção & controle , Falência Renal Crônica/cirurgia , Transplante de Rim/métodos , Adesão à Medicação/estatística & dados numéricos , Complicações Pós-Operatórias , Tacrolimo/administração & dosagem , Esquema de Medicação , Feminino , Seguimentos , Alemanha , Taxa de Filtração Glomerular , Sobrevivência de Enxerto , Humanos , Imunossupressores/administração & dosagem , Testes de Função Renal , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Transplantados
12.
Inorg Chem ; 57(17): 10576-10586, 2018 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-30129362

RESUMO

In this contribution, we present the synthesis and characterization of the mixed-anion halogenobismuthate(III) (CH3NH3)6BiI5.22Cl3.78 (MBIC) as an alternative lead-free perovskite-type semiconductor, and discuss its optical, electronic, and photovoltaic properties in comparison to the methylammonium bismuth iodide (CH3NH3)3Bi2I9 (MBI) compound. The exchange of iodide with chloride during synthesis leads to the formation of an orthorhombic A6BX9-type crystal structure ( Cmma, No. 67) with isolated BiX6 octahedra and methylammonium chloride interlayers. The experimentally found optical indirect band gap of 2.25 eV is in good agreement with the calculated value of 2.50 eV derived from DFT simulations. The valence band maximum and the conduction band minimum were determined to be at -6.2 eV and -4.0 eV vs vacuum. Similar to MBI, thin films of MBIC are composed of microcrystalline platelets. Time-resolved photoluminescence measurements show electron transfer of MBIC to mesoporous TiO2. The photovoltaic behavior of both compounds is compared in solar cells with the following device architecture: glass/ITO/compact TiO2/mesoporous TiO2/MBIC or MBI/spiro-OMeTAD/Au. Despite the zero-dimensional structure of MBIC, a maximum power conversion efficiency of 0.18% and a high fill factor of almost 60% were obtained with this material as absorber layer. When stored under inert conditions, these solar cells show an excellent long-term stability over the investigated period of more than 700 days.

13.
Klin Monbl Augenheilkd ; 235(5): 562-567, 2018 May.
Artigo em Alemão | MEDLINE | ID: mdl-29739025

RESUMO

The first-line therapy of uveitis normally consists of topical and/or systemic corticosteroid use. To achieve long-term ocular quiescence, to prevent uveitic secondary complications, to allow corticosteroid sparing and to avoid corticosteroid-related adverse effects, the application of immunosuppressive drugs (disease modifying antirheumatic drugs; DMARDs) is often necessary during the course of the disease. This article presents a structural overview of the most important conventional synthetic DMARDs, their indication, adverse events and interdisciplinary monitoring.


Assuntos
Antirreumáticos , Uveíte , Corticosteroides , Antirreumáticos/uso terapêutico , Humanos , Uveíte/tratamento farmacológico
14.
Lancet ; 388(10063): 3006-3016, 2016 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-27871759

RESUMO

BACKGROUND: Standard practice for immunosuppressive therapy after renal transplantation is quadruple therapy using antibody induction, low-dose tacrolimus, mycophenolate mofetil, and corticosteroids. Long-term steroid intake significantly increases cardiovascular risk factors with negative effects on the outcome, especially post-transplantation diabetes associated with morbidity and mortality. In this trial, we examined the efficacy and safety parameters of rapid steroid withdrawal after induction therapy with either rabbit antithymocyte globulin (rabbit ATG) or basiliximab in immunologically low-risk patients during the first year after kidney transplantation. METHODS: In this open-label, multicentre, randomised controlled trial, we randomly assigned renal transplant recipients in a 1:1:1 ratio to receive either basiliximab induction with low-dose tacrolimus, mycophenolate mofetil, and steroid maintenance therapy (arm A), rapid corticosteroid withdrawal on day 8 (arm B), or rapid corticosteroid withdrawal on day 8 after rabbit ATG (arm C). The study was done in 21 centres across Germany. Only participants aged between 18 and 75 years with a low immunological risk who were scheduled to receive a single-organ renal transplant from either a living donor or a deceased donor were considered for enrolment. Patients receiving a second renal transplant were eligible, provided that the first allograft was not lost due to acute rejection within the first year after transplantation. Donor and recipient had to be ABO compatible. Grafts with pre-transplant existing donor-specific human leukocyte antigen (HLA) antibodies were not eligible and the recipients had to have a panel-reactive antibody concentration of 30% or less. Pregnant women and nursing mothers were excluded from the study. The primary endpoint was the incidence of biopsy-proven acute rejection (BPAR) at 12 months. All analyses were done by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT00724022. FINDINGS: Between Aug 7, 2008, and Nov 30, 2013, 615 patients were randomly assigned to arm A (206), arm B (189), and arm C (192). BPAR rates were not reduced by rabbit ATG (9·9%) compared with either treatment arm A (11·2%) or B (10·6%; A versus C: p=0·75, B versus C p=0·87). As a secondary endpoint, rapid steroid withdrawal reduced post-transplantation diabetes in arm B to 24% and in arm C to 23% compared with 39% in control arm A (A versus B and C: p=0·0004). Patient survival (94·7% in arm A, 97·4% in arm B, and 96·9% in arm C) and censored graft survival (96·1% in arm A, 96·8% in arm B, and 95·8% in arm C) after 12 months were excellent and equivalent in all arms. Safety parameters such as infections or the incidence of post-transplantation malignancies did not differ between the study arms. INTERPRETATION: Rabbit ATG did not show superiority over basiliximab induction for the prevention of BPAR after rapid steroid withdrawal within 1 year after renal transplantation. Nevertheless, rapid steroid withdrawal after induction therapy for patients with a low immunological risk profile can be achieved without loss of efficacy and is advantageous in regard to post-transplantation diabetes incidence. FUNDING: Investigator Initiated Trial; financial support by Astellas Pharma GmbH, Sanofi, and Roche Pharma AG.


Assuntos
Soro Antilinfocitário/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Imunossupressores/uso terapêutico , Transplante de Rim/métodos , Animais , Anticorpos Monoclonais/uso terapêutico , Basiliximab , Biópsia , Quimioterapia Combinada/métodos , Inibidores Enzimáticos/uso terapêutico , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Coelhos , Proteínas Recombinantes de Fusão/uso terapêutico , Estudos Retrospectivos , Esteroides/uso terapêutico , Tacrolimo/uso terapêutico , Resultado do Tratamento
15.
Nephrol Dial Transplant ; 32(6): 1060-1070, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28605781

RESUMO

BACKGROUND.: Randomized trials have shown that early adoption of everolimus-based immunosuppressive regimens without a calcineurin inhibitor (CNI) improves long-term kidney graft function, but the optimal strategy for CNI minimization remains uncertain. METHODS.: In a prospective, randomized, multicentre, 12-month trial, 499 de novo kidney transplant patients were randomized at Month 3 to (i) remain on standard CNI (cyclosporine) therapy with mycophenolic acid, (ii) convert to everolimus with mycophenolic acid or (iii) start everolimus with reduced CNI and no mycophenolic acid (clinical trials registry: ClinicalTrials.gov-NCT00514514). RESULTS.: The primary endpoint, change in estimated glomerular filtration rate (eGFR) (Nankivell) from randomization to Month 12, was significantly greater in the CNI-free arm versus standard CNI therapy: mean difference 5.6 mL/min/1.73 m 2 [95% confidence interval (CI) 2.8-8.3 mL/min/1.73 m 2 , P < 0.001]. The improvement in eGFR in the CNI-free arm was also higher than in the low-CNI group (mean difference 5.5 mL/min/1.73 m 2 , 95% CI 2.8-8.2 mL/min/1.73 m 2 , P < 0.001), while results were similar in the low-CNI and standard CNI arms. The post-randomization incidence of biopsy-proven acute rejection was 11.7%, 8.1% and 7.9% in the CNI-free, low-CNI and standard CNI groups, respectively (CNI-free versus standard CNI, P = 0.27; low-CNI versus standard CNI, P = 1.00). Adverse events led to study drug discontinuation in 28.7%, 15.5% and 15.2% of CNI-free, low-CNI and standard CNI patients, respectively. CONCLUSIONS.: Everolimus initiation with CNI withdrawal at Month 3 after kidney transplantation achieves a significant improvement in renal function at 12 months, with a similar rate of acute rejection.


Assuntos
Ciclosporina/uso terapêutico , Everolimo/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Imunossupressores/uso terapêutico , Falência Renal Crônica/terapia , Adulto , Inibidores de Calcineurina/uso terapêutico , Quimioterapia Combinada , Feminino , Taxa de Filtração Glomerular , Humanos , Rim/fisiopatologia , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Estudos Prospectivos , Resultado do Tratamento
16.
J Surg Oncol ; 115(1): 54-59, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27338566

RESUMO

BACKGROUND: Harvesting the submental flap for vascularized lymph node transfer (VLNT) presents a challenging procedure because of, the topographic variation of the submental artery (SA) and the marginal mandible nerve (MMN) and the limited pedicle length for a free tissue transfer. The aim of this study was to evaluate surgical anatomical landmarks and variations of the submental lymph node flap (SLNF). METHODS AND MATERIALS: The authors examined the characteristics and landmarks of 18 SLNF in nine fresh cadavers. The diameter, length, and caliber of the SA and its relation to bony anatomic landmarks were measured. In addition, the number of lymph nodes (LNN) was evaluated through dissection and ultrasound. RESULTS: Within the designated SLNF (10 × 5 cm2 ), the number of LNN was on average 3 ± 0.6, with an average size of 4.5 ± 1.8 mm × 2.9 ± 1.2 mm. Projection of the LNN on the mandible, measured from the gnathion (GT, median-sagittal-plane) toward the gonion (GN, mandibular angle), was at 63.4 ± 5.8 mm (e.g., 65%) of the mandible for the first lymph node (LN), and for the following LNN was at 50.4 ± 7.7 mm (e.g., 52%), 44.0 ± 8.6 mm (e.g., 45%), and 40.50 ± 2.1 mm (e.g., 42%). The MMN consistently crossed the mandible body and the facial artery (FA) from dorso-caudal to ventro-cranial at 72 ± 5.2 mm, e.g., 75% of the mandible's length. Here, the nerve always lay superficial to the FA and was on average 0.96 ± 0.14 mm in diameter. Submental artery was located on average at 64 mm (e.g., 66%) of the mandible, with an average diameter of 1.34 ± 0.2 mm. CONCLUSION: The submental lymph node flap has a constant vascular supply by the submental artery. Lymph node count is on average three. Lymph nodes are close to the submental artery and its perforators. Marginal mandibular nerve lies superficial to the facial artery and crosses the artery at 75% of the mandible body length (gnathion to gonion = 100%). J. Surg. Oncol. 2017;115:54-59. © 2016 Wiley Periodicals, Inc.


Assuntos
Linfonodos/anatomia & histologia , Retalho Perfurante/irrigação sanguínea , Retalhos Cirúrgicos/irrigação sanguínea , Idoso de 80 Anos ou mais , Cadáver , Feminino , Humanos , Linfonodos/irrigação sanguínea , Linfonodos/cirurgia , Masculino , Retalho Perfurante/cirurgia , Retalhos Cirúrgicos/cirurgia , Coleta de Tecidos e Órgãos/métodos
17.
J Surg Oncol ; 115(1): 60-62, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27353521

RESUMO

BACKGROUND: Vascularized lymph node transfer is an effective surgical method in reducing lymphedema. This study provides the first detailed description of the surgical anatomy of the supraclavicular lymph node flap in regard to pedicle length, pedicle diameter, and the number of lymph nodes and their exact location inside the flap. METHODS: Bilateral supraclavicular dissections of nine fresh cadavers (five female) were performed. Before the dissection, the exact number of lymph nodes was determined sonographically by an experienced radiologist, and their distance from the jugular notch was measured. After anatomic dissection, the vascular pedicle's diameter and length were measured. RESULTS: The mean number of lymph nodes was 1.5 ± 1.85 on the right side and 3 ± 2.26 on the left. Their mean distance from the jugular notch was 8.29 ± 2.15 cm on the right and 6.10 ± 1.21 cm on the left. The pedicle's length was 4.72 ± 1.03 cm on the right and 4.86 ± 0.99 cm on the left, and its diameter 2.03 ± 0.83 on the right and 1.80 ± 0.77 on the left. CONCLUSION: The pedicle length and diameter of the supraclavicular lymph node flap are suitable for a microvascular tissue transfer. J. Surg. Oncol. 2017;115:60-62. © 2016 Wiley Periodicals, Inc.


Assuntos
Linfonodos/anatomia & histologia , Linfonodos/cirurgia , Retalhos Cirúrgicos/fisiologia , Retalhos Cirúrgicos/cirurgia , Idoso , Idoso de 80 Anos ou mais , Cadáver , Clavícula , Dissecação/métodos , Feminino , Humanos , Linfonodos/irrigação sanguínea , Linfonodos/diagnóstico por imagem , Masculino , Retalhos Cirúrgicos/irrigação sanguínea , Ultrassonografia
18.
J Extra Corpor Technol ; 49(2): 98-106, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28638158

RESUMO

This literature review summarizes recommendations and challenges encountered when establishing cardiac surgery centers in developing countries and common heart diseases encountered abroad. Cardiac surgery is not widely available in most developing countries, and most patients have no choice but to live in morbid conditions. The ideal continuous treatment for these patients would be provided by a local, sustainable cardiac surgery center. A collaborative effort from international volunteers, nongovernmental organizations, local governments, and private benefactors is necessary to facilitate adequate cardiac care in developing countries.


Assuntos
Procedimentos Cirúrgicos Cardíacos/estatística & dados numéricos , Cardiologia/estatística & dados numéricos , Países Desenvolvidos/estatística & dados numéricos , Cardiopatias/epidemiologia , Cardiopatias/cirurgia , Avaliação das Necessidades , Centro Cirúrgico Hospitalar/estatística & dados numéricos , Humanos , Prevalência
19.
Ann Plast Surg ; 77(6): 640-644, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27740958

RESUMO

INTRODUCTION: Facial reanimation surgery is performed in severe cases of facial palsy to restore facial function. In a 1-stage procedure, the spinal accessory nerve can be used as a donor nerve to power a free gracilis muscle transplant for the reanimation of the mouth. The aim of this study was to describe the surgical anatomy of the spinal accessory nerve, provide a guide for reliable donor nerve dissection, and analyze the available donor axon counts. METHODS: Dissections were performed on 10 nonembalmed cadavers (measurements of 20 nerves). Surgical anatomy of the spinal accessory nerve was described and distances to important landmarks were measured. Nerve biopsies were obtained of the main nerve trunk distal to the skull base, caudoposterior to the sternocleidomastoid muscle, proximal to the trapezius muscle and at the level of donor nerve harvest to analyze the myelinated axon count throughout the course of the spinal accessory nerve. The donor nerve length and available donor nerve axon count were the primary outcome parameters in this study. RESULTS: The mean donor nerve length was 11.6 cm. The spinal accessory nerve was transferred to the mandibular angle without tension for ideal coaptation to the free muscle transplant. After retraction of the trapezius muscle, a small distal nerve branch that leaves the main nerve trunk at a 90-degree angle medially was used as a landmark to indicate the level of donor nerve transection. On average, 1400 myelinated donor axons were available for innervation of the gracilis muscle transplant. CONCLUSIONS: This study gives a practical guide for spinal accessory nerve dissection for its application in facial reanimation as a motor source for the innervation of a free muscle transplant.


Assuntos
Nervo Acessório/anatomia & histologia , Nervo Acessório/transplante , Paralisia Facial/cirurgia , Músculo Grácil/inervação , Músculo Grácil/transplante , Procedimentos Neurocirúrgicos/métodos , Idoso , Idoso de 80 Anos ou mais , Pontos de Referência Anatômicos , Dissecação/métodos , Feminino , Humanos , Masculino
20.
Adv Funct Mater ; 25(3): 409-420, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25866496

RESUMO

In this work, molecular tuning of metal xanthate precursors is shown to have a marked effect on the heterojunction morphology of hybrid poly(3-hexylthiophene-2,5-diyl) (P3HT)/CdS blends and, as a result, the photochemical processes and overall performance of in situ fabricated hybrid solar cells. A series of cadmium xanthate complexes is synthesized for use as in situ precursors to cadmium sulfide nanoparticles in hybrid P3HT/CdS solar cells. The formation of CdS domains is studied by simultaneous GIWAXS (grazing incidence wide-angle X-ray scattering) and GISAXS (grazing incidence small-angle X-ray scattering), revealing knowledge about crystal growth and the formation of different morphologies observed using TEM (transmission electron microscopy). These measurements show that there is a strong relationship between precursor structure and heterojunction nanomorphology. A combination of TAS (transient absorption spectroscopy) and photovoltaic device performance measurements is used to show the intricate balance required between charge photogeneration and percolated domains in order to effectively extract charges to maximize device power conversion efficiencies. This study presents a strong case for xanthate complexes as a useful route to designing optimal heterojunction morphologies for use in the emerging field of hybrid organic/inorganic solar cells, due to the fact that the nanomorphology can be tuned via careful design of these precursor materials.

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