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Patients with relapsed refractory multiple myeloma (RRMM) that are triple-exposed to immunomodulatory drugs, proteasome inhibitors, and anti-CD38 monoclonal antibodies have a poor prognosis. Standard treatment for these patients has not been established. Patients with extramedullary disease or secondary plasma cell leukemia often display high tumor cell proliferation and might therefore be susceptible to chemotherapy. While current regimens are often platinum-based, we present single-center data on 70 patients with RRMM who were treated with cyclophosphamide, etoposide, and dexamethasone (CED) after a median of four lines of therapy. An overall response rate of 52% was achieved after 1-6 cycles, with 23% of patients having a very good partial response. Comparable response rates and survival were observed in patients with extramedullary disease and high-risk cytogenetics. Treatment resulted in non-hematological °III-IV adverse events in 31% of patients. No treatment-related deaths occurred. The median progression-free and overall survival were 6.2 and 10.9 months, respectively. 23% of patients were bridged to autologous stem cell transplantation (ASCT) or chimeric antigen receptor (CAR) T cell therapy. In summary, CED is an effective treatment regimen for RRMM cases with a tolerable safety profile and suitable as bridging therapy to CAR T cell treatment and ASCT.
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Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/tratamento farmacológico , Ciclofosfamida , Etoposídeo , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Transplante Autólogo , Dexametasona , Terapia de SalvaçãoRESUMO
PURPOSE: To describe the clinical and multimodal imaging features of stellate multiform amelanotic choroidopathy (SMACH; also known as serous maculopathy due to aspecific choroidopathy). METHODS: Retrospective observational case series of eyes presenting with SMACH. Multimodal imaging including fundus photography, optical coherence tomography (OCT), OCT angiography (OCTA), and indocyanine green angiography (ICGA) was analyzed. RESULTS: Eighteen eyes from 18 patients (mean age: 28 ± 19 years) were included. The mean follow-up duration was 9 years. Ophthalmoscopy showed a yellowish orange, dendriform choroidal lesion. At presentation, subretinal fluid (SRF) was seen in 10 of 18 cases (56%). Eight patients (44%) showed no evidence of SRF during a mean follow-up of 6 years. Cross-sectional OCT showed hyperreflective fibrous-like changes within the inner choroid with choriocapillaris flow preservation on OCTA. En face OCT showed a hyperreflective choroidal lesion with finger-like projections oriented in a stellate configuration. On ICGA, SMACH showed early and late hypofluorescence. None of the cases showed lesion growth. CONCLUSION: SMACH seems to be a unilateral choroidopathy characterized by distinctive multimodal imaging features. As SRF was absent in some cases, while a dendriform pattern was a consistent finding in all eyes, the authors propose renaming this entity "stellate multiform amelanotic choroidopathy," a name that retains its previous abbreviation "SMACH."
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Doenças Retinianas , Adolescente , Adulto , Criança , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Corioide/patologia , Estudos Transversais , Angiofluoresceinografia/métodos , Verde de Indocianina , Imagem Multimodal/métodos , Doenças Retinianas/patologia , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodosRESUMO
Through the combination of reaction kinetics (both stoichiometric and catalytic), solution- and solid-state characterization of arylpalladium(II) arylsilanolates, and computational analysis, the intermediacy of covalent adducts containing Si-O-Pd linkages in the cross-coupling reactions of arylsilanolates has been unambiguously established. Two mechanistically distinct pathways have been demonstrated: (1) transmetalation via a neutral 8-Si-4 intermediate that dominates in the absence of free silanolate (i.e., stoichiometric reactions of arylpalladium(II) arylsilanolate complexes), and (2) transmetalation via an anionic 10-Si-5 intermediate that dominates in the cross-coupling under catalytic conditions (i.e., in the presence of free silanolate). Arylpalladium(II) arylsilanolate complexes bearing various phosphine ligands have been isolated, fully characterized, and evaluated for their kinetic competence under thermal (stoichiometric) and anionic (catalytic) conditions. Comparison of the rates for thermal and anionic activation suggested, but did not prove, that intermediates containing the Si-O-Pd linkage were involved in the cross-coupling process. The isolation of a coordinatively unsaturated, T-shaped arylpalladium(II) arylsilanolate complex ligated with t-Bu3P allowed the unambiguous demonstration of the operation of both pathways involving 8-Si-4 and 10-Si-5 intermediates. Three kinetic regimes were identified: (1) with 0.5-1.0 equiv of added silanolate (with respect to arylpalladium bromide), thermal transmetalation via a neutral 8-Si-4 intermediate; (2) with 1.0-5.0 equiv of added silanolate, activated transmetalation via an anionic 10-Si-5 intermediate; and (3) with >5.0 equiv of added silanolate, concentration-independent (saturation) activated transmetalation via an anionic 10-Si-5 intermediate. Transition states for the intramolecular transmetalation of neutral (8-Si-4) and anionic (10-Si-5) intermediates have been located computationally, and the anionic pathway is favored by 1.8 kcal/mol. The energies of all intermediates and transition states are highly dependent on the configuration around the palladium atom.
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Hidrocarbonetos Aromáticos/química , Paládio/química , Silanos/química , Ânions/síntese química , Ânions/química , Brometos/síntese química , Brometos/química , Catálise , Hidrocarbonetos Aromáticos/síntese química , Cinética , Ligantes , Modelos Moleculares , Silanos/síntese química , TermodinâmicaAssuntos
Anti-Inflamatórios/toxicidade , Cegueira/induzido quimicamente , Extração de Catarata , Acetato de Metilprednisolona/toxicidade , Retina/efeitos dos fármacos , Síndrome de Necrose Retiniana Aguda/induzido quimicamente , Idoso , Cegueira/diagnóstico , Humanos , Injeções Intraoculares , Masculino , Síndrome de Necrose Retiniana Aguda/diagnóstico , Acuidade VisualRESUMO
PURPOSE: To describe a new classification of stellate nonhereditary idiopathic foveomacular retinoschisis (SNIFR). DESIGN: Retrospective case series and literature review. PARTICIPANTS: A total of 17 patients from 5 institutions. METHODS: Detailed case history, multimodal imaging, and genetic testing were reviewed for patients with macular schisis without a known predisposing condition. Patients with a stellate appearance centered on the fovea with correlating confirmed expansion of the outer plexiform layer (OPL) by optical coherence tomography (OCT) were included. Exclusion criteria included a family history of macular retinoschisis, a known genetic abnormality associated with retinoschisis, myopic traction maculopathy, epiretinal membrane, vitreoretinal traction, optic or scleral pit, or advanced glaucomatous optic nerve changes. MAIN OUTCOME MEASURES: Clinical features, anatomic characteristics, and visual acuity. RESULTS: A total of 22 eyes from 16 female patients and 1 male patient with foveomacular schisis were reviewed from 5 institutions. Initial visual acuity was ≥ 20/50 in all eyes (mean, 20/27), but visual acuity in a single eye decreased from 20/20 to 20/200 after the development of subfoveal fluid. The refractive status was myopic in 16 eyes, plano in 3 eyes, and hyperopic in 2 eyes. Three eyes had a preexisting vitreous separation, and 19 eyes had an attached posterior hyaloid. Follow-up ranged from 6 months to >5 years. CONCLUSIONS: In this largest known series of patients with SNIFR, all patients demonstrated splitting of the OPL in the macula with relatively preserved visual acuity (≥ 20/40) except in a single patient in whom subretinal fluid developed under the fovea.
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Imagem Multimodal , Retina/patologia , Retinosquise/classificação , Retinosquise/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas do Olho/genética , Feminino , Angiofluoresceinografia , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Retinosquise/fisiopatologia , Estudos Retrospectivos , Tomografia de Coerência Óptica , Acuidade Visual/fisiologiaRESUMO
BACKGROUND: Navilas laser is a novel technology combining photocoagulation with imaging, including fluorescein angiographic (FA) images which are annotated and aligned to a live fundus view. We determine the time necessary for planning and treatment of macular edema utilizing the Navilas. METHODS: The screen recordings during treatments were retrospectively analyzed for treatment type, number of laser shots, the duration of planning (measured from the time the planning image was selected to time of marking the last planned treatment spot), and total time of laser application. RESULTS: A total of 93 treatments (30 grid, 30 focal and 33 combined treatments) by four physicians from three sites were included. An average of 125 spots were applied to each eye. The total time spent for each focal treatment - including the planning was 7 min 47 s (±3 min and 32 s). CONCLUSIONS: Navilas is a novel device providing a time efficient platform for evaluating FA images and performing threshold macular laser photocoagulation.
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Angiofluoresceinografia , Fotocoagulação a Laser/métodos , Edema Macular/cirurgia , Oclusão da Veia Retiniana/cirurgia , Humanos , Fotocoagulação a Laser/instrumentação , Edema Macular/diagnóstico , Edema Macular/etiologia , Oclusão da Veia Retiniana/complicações , Oclusão da Veia Retiniana/diagnóstico , Estudos Retrospectivos , Fatores de TempoRESUMO
PURPOSE: To estimate the duration of activity for intravitreal triamcinolone injected with a new technique using centrifuge concentration (Centrifuge concentrated IntraVitreal Triamcinolone, C-IVT). METHODS: All injections were performed by a single surgeon (M.D.O.) using a 30-gauge needle. A vial of Triesence (triamcinolone; Alcon Laboratories, Fort Worth, TX) was drawn into a 1-mL syringe and the plunger cut off. The contents were spun in a centrifuge, and a second plunger was placed. Records of all patients receiving C-IVT with 0.05 mL or 0.1 mL from January 1, 2009, through December 31, 2009, were retrospectively reviewed. RESULTS: Eighty-four injections from 69 eyes of 57 patients were included. Sixty-nine injections from 54 eyes of 44 patients received 0.05 mL of C-IVT, whereas 15 injections from 15 eyes of 13 patients received 0.1 mL of C-IVT. Triamcinolone acetonide was still visualized in the vitreous on an average of 5.0 ± 2.4 months (median 5 months) after 0.05 mL of C-IVT and 8.3 ± 4.0 months (median 8 months) after 0.1 mL of C-IVT during follow-up visits. The longest duration recorded was 14 months for the 0.05-mL group and 18 months for the 0.l-mL group. CONCLUSION: The C-IVT results in a long duration of effect that seems to be greater than previously published techniques. It may be considered for patients requiring chronic steroid therapy, in which the benefits of long-term intravitreal steroids are believed to outweigh their risk.
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Centrifugação , Glucocorticoides/administração & dosagem , Triancinolona Acetonida/administração & dosagem , Corpo Vítreo/efeitos dos fármacos , Disponibilidade Biológica , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/metabolismo , Glucocorticoides/química , Glucocorticoides/farmacocinética , Humanos , Injeções Intravítreas , Edema Macular/tratamento farmacológico , Edema Macular/metabolismo , Vasculite Retiniana/tratamento farmacológico , Vasculite Retiniana/metabolismo , Oclusão da Veia Retiniana/tratamento farmacológico , Oclusão da Veia Retiniana/metabolismo , Estudos Retrospectivos , Fatores de Tempo , Triancinolona Acetonida/química , Triancinolona Acetonida/farmacocinética , Uveíte/tratamento farmacológico , Uveíte/metabolismo , Corpo Vítreo/metabolismoRESUMO
This article was migrated. The article was marked as recommended. The challenges, importance, and state of physician wellness and burnout have been well documented throughout the literature.Research continues to prove the value of tools and interventions while institutions appear to be listening and adapting important practices. However, although the wellness literature encourages a review of organizational challenges, local needs, and individual solutions, organizations may fail to align these efforts along with equity, diversity, inclusion, and belonging (EDIB). A pandemic and recent events in our society heightened awareness about health inequities, structural violence and racism, and demand that we look within our institutions and health systems. It also demands that we speak of wellness and equity together. We cannot engage in conversations about wellness without asking about equity...because equity and inclusion lead to wellness. We simply cannot expect our healthcare workforce, faculty, and physicians of color to be "well" if they are experiencing exclusion and inequality. In this article, we present the concepts of inclusive excellence and leading with wellness in mind while calling for more inclusive physician wellness efforts.
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PURPOSE: Linezolid is an option for the treatment of infections caused by multiresistant Gram-positive bacteria. The survival of critically ill patients with acute renal failure (ARF) can be improved by increasing the dose of renal replacement therapy. Extended (daily) dialysis (ED) is a new and important approach to renal replacement therapy in intensive care units. The aim of the study was to evaluate the pharmacokinetics of linezolid in septic patients without ED and on ED, respectively. METHODS: We studied the pharmacokinetics of linezolid in adult intensive care patients with sepsis (n = 5) and anuric septic patients with ARF being treated with ED (n = 10). Linezolid 600 mg was administered intravenously twice daily. The pharmacokinetic parameters, their variability, and possible covariates were analyzed using NONMEM. RESULTS: The pharmacokinetics of linezolid followed a two-compartment model with clearance (Cl) = 0.159 L h(-1) kg(-1) +/- 51% (population mean +/- interindividual variability), central volume of distribution (V(1)) = 0.273 L/kg +/- 21%, intercompartmental clearance (Q) = 0.369 L h(-1) kg(-1), and peripheral volume of distribution (V(2)) = 0.271 L/kg. The clearance in ED patients while on dialysis was increased by 3.5 L/h, and patients with liver transplantation/resection had their clearance reduced by 60%. Intra-individual variability was much smaller than inter-individual variability. CONCLUSIONS: Our results suggest that linezolid pharmacokinetics in critically ill patients with ARF undergoing ED is not comparable to that in healthy subjects and patients without ARF. The best method of managing linezolid dosage in such a complex group of patients, whose physiology can vary daily, would be to use therapeutic drug monitoring.
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Acetamidas/farmacocinética , Injúria Renal Aguda/terapia , Anti-Infecciosos/farmacocinética , Oxazolidinonas/farmacocinética , Diálise Renal/métodos , Sepse/tratamento farmacológico , Acetamidas/administração & dosagem , Injúria Renal Aguda/sangue , Injúria Renal Aguda/complicações , Idoso , Anti-Infecciosos/administração & dosagem , Cuidados Críticos , Monitoramento de Medicamentos , Feminino , Hepatectomia , Humanos , Infusões Intravenosas , Linezolida , Transplante de Fígado , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Modelos Biológicos , Oxazolidinonas/administração & dosagem , Sepse/sangue , Sepse/complicações , Resultado do TratamentoRESUMO
PURPOSE: To describe clinical findings, laboratory values, and treatment response of patients with monoclonal gammopathy of undetermined significance (MGUS) demonstrating neurosensory macular detachment. DESIGN: Retrospective case series. PARTICIPANTS: Seven eyes of 4 patients (3 men and 1 woman; age range, 60-81 years) with neurosensory macular detachment, treatment-resistant submacular fluid, and vitelliform material. METHODS: We retrospectively reviewed the medical and ocular histories, ocular examination findings, retinal imaging, ocular disease course, and laboratory findings in 4 patients with submacular fluid associated with MGUS. MAIN OUTCOME MEASURES: Description of the macular findings and treatment courses of 4 patients diagnosed with MGUS maculopathy. RESULTS: Seven eyes of 4 patients demonstrated neurosensory macular detachment with treatment-resistant submacular fluid and vitelliform material. No eyes demonstrated signs of significant hyperviscosity retinopathy. Fluorescein angiography showed no definite leakage in any involved eye. Laboratory evaluation revealed immunoglobulin G MGUS in all 4 patients. All 4 patients were resistant to treatments aimed at resolving the subretinal fluid, including some combination of anti-vascular endothelial growth factor injections, photodynamic therapy, topical dorzolamide, oral dosing of eplerenone or acetazolamide, or some combination thereof. In 3 patients, MGUS underwent malignant transformation 24 to 144 months after diagnosis, in 1 patient to lymphoplasmacytic lymphoma and in 2 patients to multiple myeloma. The fourth patient showed no evidence of malignancy 8 years after diagnosis. CONCLUSIONS: Submacular fluid without fluorescein leakage and unresponsive to conventional treatment may suggest an underlying immunoproliferative disorder that we have termed monoclonal gammopathy of macular significance. Given the propensity for monoclonal gammopathy of macular significance to transform into malignant disease in our series, serum protein analysis should be considered in patients with neurosensory macular detachment not attributable to known causes.
Assuntos
Macula Lutea/patologia , Gamopatia Monoclonal de Significância Indeterminada/complicações , Doenças Retinianas/etiologia , Idoso , Feminino , Angiofluoresceinografia/métodos , Fundo de Olho , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Retinianas/diagnóstico , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodosRESUMO
OBJECTIVES: Moxifloxacin, the newest fourth-generation fluoroquinolone, has a broad spectrum of antibacterial activity covering both Gram-positive and Gram-negative aerobic and anaerobic bacteria and is therefore very well suited for the treatment of biliary tract infections. The present study aimed to determine the penetration of moxifloxacin into gallbladder tissue to evaluate its antibiotic potential in this indication. PATIENTS AND METHODS: Hospitalized patients with acute cholecystitis received a single, 1 h infusion of 400 mg of moxifloxacin before cholecystectomy. Serum and gallbladder wall tissue samples were collected during surgery, and the moxifloxacin concentrations were measured by HPLC. RESULTS: Sixteen patients (eight men and eight women) were included between January 2007 and April 2008. The time between start of infusion and gallbladder removal ranged from 50 min to 21 h 10 min. The serum concentration at the time of cholecystectomy was between 0.39 and 4.37 mg/L, and the tissue concentration between 1.73 and 17.08 mg/kg. The tissue-to-serum concentration ratio ranged from 1.72 to 6.33. CONCLUSIONS: The results show that moxifloxacin penetrates well into gallbladder tissue and is therefore a therapeutic option for biliary tract infection. The highest concentrations in serum and gallbladder tissue were measured shortly after the end of a 1 h infusion. As perioperative prophylaxis, moxifloxacin should therefore be administered 30-60 min before the first surgical incision.
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Antibacterianos/farmacocinética , Compostos Aza/farmacocinética , Infecções Bacterianas/tratamento farmacológico , Doenças Biliares/tratamento farmacológico , Colecistite/tratamento farmacológico , Vesícula Biliar/química , Quinolinas/farmacocinética , Adulto , Idoso , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Compostos Aza/administração & dosagem , Compostos Aza/uso terapêutico , Cromatografia Líquida de Alta Pressão/métodos , Feminino , Fluoroquinolonas , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Moxifloxacina , Quinolinas/administração & dosagem , Quinolinas/uso terapêutico , Soro/química , Fatores de Tempo , Adulto JovemRESUMO
OBJECTIVES: There is limited data regarding the prevalence of hepatobiliary disease in North American patients with cystic fibrosis (CF) through adulthood. Our aim was to determine the prevalence of, and risk factors for, CF-related hepatobiliary abnormalities and determine factors that predict the development of CF-related hepatobiliary disease. METHODS: We performed a retrospective cohort study of all CF patients who presented to a UnitedStates tertiary care referral academic center over a 32-year period. "CF-related hepatobiliary abnormality" was defined as the presence of abnormal liver chemistries on one or more occasion and "CF-related hepatobiliary disease" was defined as biochemical, physical examination, or ultrasonographic abnormalities on at least 2 consecutive examinations spanning a 1-year period. RESULTS: Two-hundred eighty-three CF patients who presented between the years 1970 and 2002 were identified, with an age range of 2 months to 63 years. Sixty-five percent had CF-related hepatobiliary abnormalities with a higher prevalence seen in CF patients <18 years of age (84% vs. 16%, P<0.01). Fifteen percent of our cohort had CF-related hepatobiliary disease with 93% of cases occurring in individuals before age 18. One quarter of individuals with CF-related hepatobiliary abnormalities developed hepatobiliary disease. CONCLUSIONS: Abnormal liver chemistries in CF are common though most of CF patients lack clinical evidence of liver disease and the severe complications of fibrosis/cirrhosis are rare. The risk of liver involvement decreases significantly with age, falling by 10% per annum for those described as having CF-related hepatobiliary disease. CF-related hepatobiliary disease is a rare occurrence after age 18.
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Doenças Biliares/epidemiologia , Fibrose Cística/epidemiologia , Hepatopatias/epidemiologia , Centros Médicos Acadêmicos , Adolescente , Adulto , Fatores Etários , Idoso , Doenças Biliares/diagnóstico , Doenças Biliares/etiologia , Doenças Biliares/mortalidade , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Fibrose Cística/complicações , Fibrose Cística/mortalidade , Feminino , Humanos , Indiana/epidemiologia , Lactente , Modelos Lineares , Hepatopatias/diagnóstico , Hepatopatias/etiologia , Hepatopatias/mortalidade , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: Considering the complexity of diagnosis, high costs of therapy and high morbidity and mortality of systemic fungal infections, antifungal therapy of intensive care patients should follow clearly defined guidelines. We outline the impact of a standardised practice of antifungal treatment in an interdisciplinary surgical intensive care unit of a university hospital. METHODS: Therapy was intended to be optimised by implementation of standardised practice guidelines supported by the clinical pharmacist. Costs for antifungal agents during a period of 18 months before and after implementation of the practice guidelines were compared, respectively. RESULTS: The intervention was associated with a significant decrease in use of antifungal agents. Analysis of data revealed a reduction in costs by 50%. This could substantially be attributed to the implementation of the practice guidelines. CONCLUSION: The implementation of standardised practice guidelines for antifungal therapy in intensive care units decreased the use of selected antifungal agents and resulted in substantial reduction in expenditure on antifungal agents.
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Antifúngicos/administração & dosagem , Cuidados Críticos/organização & administração , Micoses/tratamento farmacológico , Guias de Prática Clínica como Assunto , Antifúngicos/economia , Antifúngicos/uso terapêutico , Cuidados Críticos/economia , Custos de Medicamentos , Farmacoeconomia , Feminino , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Farmacêuticos/organização & administração , Papel ProfissionalRESUMO
OBJECTIVES: Adequate antimicrobial therapy is crucial for the survival of critically ill patients with severe nosocomial infections. Tigecycline, the first available agent in the new class of glycylcyclines, is active against multiresistant gram-positive and gram-negative bacteria. The aim of this observational, retrospective evaluation was to assess tigecycline use patterns in a surgical intensive care unit (SICU) of a tertiary care centre. METHODS: Data from 70 patients receiving tigecycline in the SICU were analysed. We reviewed tigecycline use in terms of demographic data and co-morbidities, disease severity, clinical indication, microbiology, therapy regimens and mortality. A logistic regression analysis was performed to identify prognostic factors for mortality. RESULTS: The majority of patients had co-morbidities such as cancer (51%) or renal replacement therapy (57%). The mean Acute Physiology and Chronic Health Evaluation (APACHE) II score of patients at admission was 27. Intra-abdominal infection was most frequently diagnosed (50% of patients); intra-abdominal infection and pneumonia were diagnosed in 14%. Methicillin-resistant Staphylococcus aureus was found in 16% of patients (colonization; infection: 6%) and vancomycin-resistant enterococci in 27% (colonization; infection: 21%). The mean duration of tigecycline therapy was 9 +/- 4 days; 76% of patients received tigecycline in combination, with 64% being treated second line. APACHE score and renal replacement were identified as predictive factors for mortality. SICU mortality was 30%. CONCLUSIONS: Tigecycline treatment of critically ill SICU patients with severe sepsis or septic shock appeared to result in remarkably low mortality. Tigecycline may be an important treatment option for septic patients with infections resistant to other available agents.
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Cuidados Críticos/métodos , Unidades de Terapia Intensiva , Minociclina/análogos & derivados , Choque Séptico/tratamento farmacológico , Idoso , Avaliação de Medicamentos/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Minociclina/uso terapêutico , Estudos Retrospectivos , Sepse/tratamento farmacológico , Sepse/mortalidade , Choque Séptico/mortalidade , Tigeciclina , Resultado do TratamentoRESUMO
ARDS secondary to blastomycosis is associated with a high mortality rate despite appropriate antifungal therapy. Corticosteroids are of proven benefit in the treatment of severe Pneumocystis jiroveci pneumonia and are recommended for the treatment of severe pulmonary infections with Histoplasma capsulatum. However, their role in the treatment of severe pulmonary infections with Blastomyces dermatitidis has not been established. We report the cases of two previously healthy men who presented with severe ARDS secondary to blastomycosis. Refractory hypoxemia developed in both patients despite adequate antifungal coverage with amphotericin B. Dramatic improvement was seen in each patient after initiation of corticosteroids in addition to amphotericin B. Both patients survived and did well on follow-up. We suggest that treatment with corticosteroids may be of benefit in patients with blastomycosis-induced ARDS. This may be due to a decrease in the severity of the inflammatory response.
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Corticosteroides/uso terapêutico , Blastomicose/complicações , Blastomicose/tratamento farmacológico , Síndrome do Desconforto Respiratório/etiologia , Adulto , Antifúngicos/uso terapêutico , Blastomicose/fisiopatologia , Humanos , Masculino , Respiração com Pressão Positiva , Síndrome do Desconforto Respiratório/terapiaRESUMO
PURPOSE: To present the initial multicenter experience of using subretinal air injection in combination with tissue plasminogen activator (tPA) at the time of pars plana vitrectomy (PPV) to displace submacular hemorrhage (SMH). DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: Patients with SMH resulting from age-related macular degeneration or polypoidal choroidal vasculopathy. METHODS: Chart review of patients who underwent displacement of SMH with PPV, subretinal injection of air and tPA (125 mg/mL), partial fluid-air exchange with gas tamponade, and preoperative, intraoperative, or postoperative intravitreal injection of anti-vascular endothelial growth factor agent at 5 sites in the United States. None of the surgeons had prior experience with using subretinal air. MAIN OUTCOME MEASURES: Frequency and extent of SMH displacement, preoperative and postoperative visual acuities and retinal thickness, and postoperative complications. RESULTS: Twenty-four eyes of 24 patients were included (11 men; mean age, 79.1 years) with a mean follow-up of 12.5 months (range, 3-28 months). At 3 months after surgery, complete displacement of SMH from the foveal center was achieved in 24 eyes (100%), displaced beyond the arcades in 75% and beyond the equator in 20%. Residual subretinal pigment epithelial hemorrhage was seen in 5 eyes (20.8%). Mean preoperative and postoperative visual acuity was 1.95 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, 20/1783) and 0.85 logMAR (Snellen equivalent, 20/141; P < 0.0001), respectively. Visual acuity improved in 23 eyes (95.8%) and was unchanged in 1 eye. Mean central retinal thickness improved from 463.7 µm before surgery to 311.3 µm at the final visit (P = 0.026). CONCLUSIONS: This initial experience of injecting subretinal air at the time of tPA injection during PPV showed the technique to be effective, with high consistency to displace SMH away from the fovea and even out to the periphery, and resulted in improved VA and retinal thickness. Some cases of subretinal pigment epithelial hemorrhage also benefit from this technique.
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Tamponamento Interno/métodos , Retina/diagnóstico por imagem , Hemorragia Retiniana/terapia , Ativador de Plasminogênio Tecidual/administração & dosagem , Vitrectomia/métodos , Idoso , Idoso de 80 Anos ou mais , Ar , Feminino , Fibrinolíticos/administração & dosagem , Angiofluoresceinografia , Seguimentos , Fundo de Olho , Humanos , Injeções Intraoculares , Masculino , Pessoa de Meia-Idade , Hemorragia Retiniana/diagnóstico , Estudos Retrospectivos , Fatores de Tempo , Tomografia de Coerência Óptica , Resultado do Tratamento , Estados Unidos , Acuidade VisualRESUMO
Luteinizing hormone (LH), produced in the anterior pituitary, has been detected in cadaver eyes and LH receptors (LHRs) have been identified in the retina, with the highest density in cone photoreceptors. Our aim was to confirm the presence of LH in the living, human eye as well as to examine the potential impact of a reduction in LHR signaling on visual processing. Vitreous samples were collected from 40 patients (23 diabetics, 17 non-diabetics) who were undergoing vitrectomies for various indications. LH concentration was quantified in each sample via an electro-chemiluminescence immunoassay and Meso Scale Discovery platform and normalized to total protein. In addition, full-field electroretinography (ERG) was performed on 11 adult LHR knockout heterozygous mice (B6;129X1-Lhcgrtm1Zmlei/J) and 11 wild types using the Celeris-Diagnosys system. The median LH values (pg/mg total protein) for non-diabetics, diabetics without proliferative diabetic retinopathy (PDR) and diabetics with PDR were 40.7, 41.9 and 167.8 respectively. LH levels were significantly higher in diabetics with PDR. In our ERG investigation, heterozygous LHRKOs were found to have significantly reduced amplitudes of a-wave and b-waves at high stimulus intensities with no significant change in a-wave or b-wave amplitudes at lower intensities; this is consistent with a selective impairment of cone-mediated responses. Our findings confirm LH is present in the adult human eye. Our findings also suggest that a reduction in LH receptor signaling negatively impacts visual processing of the cone photoreceptors. Overall, our study results support the theory that LH likely plays a physiologic role in the eye.
Assuntos
Hormônio Luteinizante/metabolismo , Receptores do LH/metabolismo , Retina/metabolismo , Corpo Vítreo/metabolismo , Animais , Retinopatia Diabética/metabolismo , Eletrorretinografia , Humanos , Camundongos , Camundongos Knockout , Receptores do LH/genéticaRESUMO
PURPOSE: To describe a previously unreported clinical entity superficially resembling macular serpiginous choroiditis but with a distinct presentation and clinical course. DESIGN: Retrospective observational case series. PARTICIPANTS: Six patients, 50 to 68 years old, exhibiting this entity who were seen at 5 different centers from 1984 to 2006. METHODS: Review of medical records. MAIN OUTCOME MEASURES: Best-corrected visual acuity (VA) and clinical and angiographic findings. RESULTS: The lesions in our patients are similar to those of acute macular serpiginous choroiditis. Our patients had well-delineated whitish plaquelike lesions involving the macula and sparing the peripapillary areas of both eyes. In contrast to serpiginous choroiditis, VA remained good despite early involvement of the fovea until complications related to choroidal neovascularization or pigmentary mottling developed. Angiographic characteristics and the clinical course were also atypical. Fluorescein angiography revealed well-defined early hypofluorescent areas that partially filled in in the late phase. Indocyanine green angiography showed the hypofluorescence to be persistent. Unlike serpiginous choroiditis, the white macular lesions faded over a period of months to years, whereas the characteristic angiographic findings often persisted longer. Choroidal neovascularization developed in 11 of 12 eyes, with subsequent conversion to disciform macular scars in 9 of 12 eyes. Unlike serpiginous choroiditis, none of the eyes showed chorioretinal scar formation unless related to choroidal neovascularization. CONCLUSION: Persistent placoid maculopathy has features resembling macular serpiginous choroiditis but differs in its clinical course and effect on VA. It appears to be a new entity. The majority of eyes develop choroidal neovascularization that results in loss of central vision.
Assuntos
Macula Lutea/patologia , Doenças Retinianas/complicações , Idoso , Neovascularização de Coroide/etiologia , Feminino , Angiofluoresceinografia , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Retinianas/diagnóstico , Doenças Retinianas/tratamento farmacológico , Estudos Retrospectivos , Transtornos da Visão/etiologia , Acuidade VisualRESUMO
OBJECTIVE: To determine the safety and efficacy of VIT100 (Immusol, Inc, San Diego, California), a ribozyme to proliferating cell nuclear antigen, in preventing recurrent proliferative vitreoretinopathy (PVR) in patients with established PVR who undergo vitrectomy for retinal reattachment repair. METHODS: A multicenter, double-masked, placebo-controlled, randomized clinical trial. One hundred seventy-five eyes from 175 patients with grade C or worse PVR were randomly assigned to receive high-dose VIT100, low-dose VIT100, or placebo by intravitreal injection at the conclusion of retinal reattachment surgery. MAIN OUTCOME MEASURES: The primary efficacy end point was recurrent retinal detachment secondary to PVR. The secondary end point was recurrent retinal detachment due to any cause. RESULTS: One hundred fifty-four patients completed the study. Forty-one patients (27%) developed recurrent retinal detachment due to PVR by 24 weeks, including 18 patients (33%) in the group receiving 0.75 mg, 13 patients (24%) in the group receiving 0.15 mg, and 10 patients (22%) in the placebo group. There was no statistically significant difference in patients reaching this end point by 24 weeks (P = .37). Ancillary statistical analyses are reported. CONCLUSIONS: VIT100 was not effective in preventing PVR recurrence in patients with established grade C or worse PVR. APPLICATION TO CLINICAL PRACTICE: To our knowledge, this is the most recent, meticulously designed clinical trial in PVR.