Primary intraocular B-cell lymphoma: case report

Ocular non-Hodgkin's lymphoma is a rare condition that can involve the retina, the vitreous and the optic nerve. It can occur alone or can be associated with lymphoma of the central nervous system and a frequent manifestation is a posterior uveitis of difficult treatment. This kind of ocular tumor is difficult and a challenge to diagnosis. We describe a case of non-Hodgkin's intraocular B-cell lymphoma in a 47-year-old woman who had a posterior uveitis as the first manifestation. We emphasize the importance of a careful investigation and of the general clinical examination since this is the most common type in the eye. We expect to call the attention to this disease that many times appears in an unspecific form with unspecific symptoms.O linfoma não-Hodgkin primariamente intra-ocular é raro, e caracterizado por uma forma extranodal que pode envolver retina, espaço sub-retiniano, vítreo e nervo óptico. Ocorre independente ou associado ao linfoma do sistema nervoso central e freqüentemente na forma de uveíte de difícil tratamento. Esta forma de linfoma é um dos tumores intra-oculares mais desafiantes de se diagnosticar. Relatamos um caso de linfoma não-Hodgkin intra-ocular difuso de células grandes tipo B numa paciente de 47 anos e cuja manifestação inicial foi uma uveíte posterior; enfatizamos a importância de investigação detalhada e da avaliação sistêmica; pois esta é a forma mais freqüente de acometimento ocular. Com esse relato esperamos abordar os principais aspectos desde quadro clínico até diagnóstico chamando a atenção para essa doença que muitas vezes aparece inicialmente com sintomas vagos e inespecíficos.Universidade Federal de São Paulo (UNIFESP) Departamento de OftalmologiaUNIFESP Departamento de OftalmologiaUNIFESP Departamento de Oftalmologia Setor de RetinaUNIFESP Departamento de Oftalmologia Setor de UveítesUNIFESP, Depto. de OftalmologiaUNIFESP, Depto. de OftalmologiaUNIFESP, Depto. de Oftalmologia Setor de RetinaUNIFESP, Depto. de Oftalmologia Setor de UveítesSciEL

An observational study of Donor Ex Vivo Lung Perfusion in UK lung transplantation: DEVELOP-UK

Background: Many patients awaiting lung transplantation die before a donor organ becomes available. Ex vivo lung perfusion (EVLP) allows initially unusable donor lungs to be assessed and reconditioned for clinical use. Objective: The objective of the Donor Ex Vivo Lung Perfusion in UK lung transplantation study was to evaluate the clinical effectiveness and cost-effectiveness of EVLP in increasing UK lung transplant activity. Design: A multicentre, unblinded, non-randomised, non-inferiority observational study to compare transplant outcomes between EVLP-assessed and standard donor lungs. Setting: Multicentre study involving all five UK officially designated NHS adult lung transplant centres. Participants: Patients aged ≥ 18 years with advanced lung disease accepted onto the lung transplant waiting list. Intervention: The study intervention was EVLP assessment of donor lungs before determining suitability for transplantation. Main outcome measures: The primary outcome measure was survival during the first 12 months following lung transplantation. Secondary outcome measures were patient-centred outcomes that are influenced by the effectiveness of lung transplantation and that contribute to the health-care costs. Results: Lungs from 53 donors unsuitable for standard transplant were assessed with EVLP, of which 18 (34%) were subsequently transplanted. A total of 184 participants received standard donor lungs. Owing to the early closure of the study, a non-inferiority analysis was not conducted. The Kaplan–Meier estimate of survival at 12 months was 0.67 [95% confidence interval (CI) 0.40 to 0.83] for the EVLP arm and 0.80 (95% CI 0.74 to 0.85) for the standard arm. The hazard ratio for overall 12-month survival in the EVLP arm relative to the standard arm was 1.96 (95% CI 0.83 to 4.67). Patients in the EVLP arm required ventilation for a longer period and stayed longer in an intensive therapy unit (ITU) than patients in the standard arm, but duration of overall hospital stay was similar in both groups. There was a higher rate of very early grade 3 primary graft dysfunction (PGD) in the EVLP arm, but rates of PGD did not differ between groups after 72 hours. The requirement for extracorporeal membrane oxygenation (ECMO) support was higher in the EVLP arm (7/18, 38.8%) than in the standard arm (6/184, 3.2%). There were no major differences in rates of chest radiograph abnormalities, infection, lung function or rejection by 12 months. The cost of EVLP transplants is approximately £35,000 higher than the cost of standard transplants, as a result of the cost of the EVLP procedure, and the increased ECMO use and ITU stay. Predictors of cost were quality of life on joining the waiting list, type of transplant and number of lungs transplanted. An exploratory model comparing a NHS lung transplant service that includes EVLP and standard lung transplants with one including only standard lung transplants resulted in an incremental cost-effectiveness ratio of £73,000. Interviews showed that patients had a good understanding of the need for, and the processes of, EVLP. If EVLP can increase the number of usable donor lungs and reduce waiting, it is likely to be acceptable to those waiting for lung transplantation. Study limitations include small numbers in the EVLP arm, limiting analysis to descriptive statistics and the EVLP protocol change during the study. Conclusions: Overall, one-third of donor lungs subjected to EVLP were deemed suitable for transplant. Estimated survival over 12 months was lower than in the standard group, but the data were also consistent with no difference in survival between groups. Patients receiving these additional transplants experience a higher rate of early graft injury and need for unplanned ECMO support, at increased cost. The small number of participants in the EVLP arm because of early study termination limits the robustness of these conclusions. The reason for the increased PGD rates, high ECMO requirement and possible differences in lung injury between EVLP protocols needs evaluation

Associations between Use of Antimalarial Medications and Health among U.S. Veterans of the Wars in Iraq and Afghanistan.

Mefloquine (Lariam®; Roche Holding AG, Basel, Switzerland) has been linked to acute neuropsychiatric side effects. This is a concern for U.S. veterans who may have used mefloquine during recent Southwest Asia deployments. Using data from the National Health Study for a New Generation of U.S. Veterans, a population-based study of U.S. veterans who served between 2001 and 2008, we investigated associations between self-reported use of antimalarial medications and overall physical and mental health (MH) using the twelve-item short form, and with other MH outcomes using the post-traumatic stress disorder Checklist-17 and the Patient Health Questionnaire (anxiety, major depression, and self-harm). Multivariable logistic regression was performed to examine associations between health measures and seven antimalarial drug categories: any antimalarial, mefloquine, chloroquine, doxycycline, primaquine, mefloquine plus any other antimalarial, and any other antimalarial or antimalarial combination while adjusting for the effects of deployment and combat exposure. Data from 19,487 veterans showed that although antimalarial use was generally associated with higher odds of negative health outcomes, once deployment and combat exposure were added to the multivariable models, the associations with each of the MH outcomes became attenuated. A positive trend was observed between combat exposure intensity and prevalence of the five MH outcomes. No significant associations were found between mefloquine and MH measures. These data suggest that the poor physical and MH outcomes reported in this study population are largely because of combat deployment exposure

Lipemia retinalis in a 35-day-old infant with hyperlipoproteinemia: case report

A rare case of hyperlipropoteinemia in a 35-day-old infant who presented not only high blood levels of cholesterol and triglycerides but also an ocular manifestation described as lipemia retinalis. the fundoscopic abnormality cleared as the levels of chilomicrons in plasma dropped. Lipemia retinalis is an important and reliable parameter of high levels of chilomicrons and triglycerides and should be considered as a significant clue while diagnosing.Universidade Federal de São Paulo, Dept Ophthalmol, Retina & Vitreous Sect, São Paulo, BrazilSanta Casa Misericordia São Paulo, Dept Ophthalmol, Retina & Vitreous Sect, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Ophthalmol, Retina & Vitreous Sect, São Paulo, BrazilWeb of Scienc

A method for translational rat ex vivo lung perfusion experimentation

The application of ex vivo lung perfusion (EVLP) has significantly increased the successful clinical use of marginal donor lungs. While large animal EVLP models exist to test new strategies to improve organ repair, there is currently no rat EVLP model capable of maintaining long-term lung viability. Here, we describe a new rat EVLP model that addresses this need, while enabling the study of lung injury due to cold ischemic time (CIT). The technique involves perfusing and ventilating male Lewis rat donor lungs for 4 h before transplanting the left lung into a recipient rat and then evaluating lung function 2 h after reperfusion. To test injury within this model, lungs were divided into groups and exposed to different CITs (i.e., 20 min, 6 h, 12 h, 18 h and 24 h). Experiments involving the 24-h-CIT group were prematurely terminated due to the development of severe edema. For the other groups, no differences in the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO₂/FIO₂) were observed during EVLP; however, lung compliance decreased over time in the 18-h group (P = 0.012) and the PaO₂/FIO₂ of the blood from the left pulmonary vein 2 h after transplantation was lower compared with 20-min-CIT group (P = 0.0062). This new model maintained stable lung function during 4-h EVLP and after transplantation when exposed to up to 12 h of CIT

Pyrrolidine dithiocarbamate administered during ex-vivo lung perfusion promotes rehabilitation of injured donor rat lungs obtained after prolonged warm ischemia.

Damaged lung grafts obtained after circulatory death (DCD lungs) and warm ischemia may be at high risk of reperfusion injury after transplantation. Such lungs could be pharmacologically reconditioned using ex-vivo lung perfusion (EVLP). Since acute inflammation related to the activation of nuclear factor kappaB (NF-κB) is instrumental in lung reperfusion injury, we hypothesized that DCD lungs might be treated during EVLP by pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB. Rat lungs exposed to 1h warm ischemia and 2 h cold ischemia were subjected to EVLP during 4h, in absence (CTRL group, N = 6) or in presence of PDTC (2.5g/L, PDTC group, N = 6). Static pulmonary compliance (SPC), peak airway pressure (PAWP), pulmonary vascular resistance (PVR), and oxygenation capacity were determined during EVLP. After EVLP, we measured the weight gain of the heart-lung block (edema), and the concentration of LDH (cell damage), proteins (permeability edema) and of the cytokines IL-6, TNF-α and CINC-1 in bronchoalveolar lavage (BAL), and we evaluated NF-κB activation by the degree of phosphorylation and degradation of its inhibitor IκBα in lung tissue. In CTRL, we found significant NF-κB activation, lung edema, and a massive release of LDH, proteins and cytokines. SPC significantly decreased, PAWP and PVR increased, while oxygenation tended to decrease. Treatment with PDTC during EVLP inhibited NF-κB activation, did not influence LDH release, but markedly reduced lung edema and protein concentration in BAL, suppressed TNFα and IL-6 release, and abrogated the changes in SPC, PAWP and PVR, with unchanged oxygenation. In conclusion, suppression of innate immune activation during EVLP using the NF-κB inhibitor PDTC promotes significant improvement of damaged rat DCD lungs. Future studies will determine if such rehabilitated lungs are suitable for in vivo transplantation

Pediatric lung transplantation and end of life care in cystic fibrosis: Barriers and successful strategies

Pediatric lung transplantation has advanced over the years, providing a potential life-prolonging therapy to patients with cystic fibrosis. Despite this, many challenges in lung transplantation remain and result in worse outcomes than other solid organ transplants. As CF lung disease progresses, children and their caregivers are often simultaneously preparing for lung transplantation and end of life. In this article, we will discuss the current barriers to success in pediatric CF lung transplantation as well as approaches to end of life care in this population

Equilibrium ex vivo calibration of homogenized tissue for in vivo SPME quantitation of doxorubicin in lung tissue

The final publication is available at Elsevier via https://dx.doi.org/10.1016/j.talanta.2018.02.049 © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/The fast and sensitive determination of concentrations of anticancer drugs in specific organs can improve the efficacy of chemotherapy and minimize its adverse effects. In this paper, ex vivo solid-phase microextraction (SPME) coupled to LC-MS/MS as a method for rapidly quantitating doxorubicin (DOX) in lung tissue was optimized. Furthermore, the theoretical and practical challenges related to the real-time monitoring of DOX levels in the lung tissue of a living organism (in vivo SPME) are presented. In addition, several parameters for ex vivo/in vivo SPME studies, such as extraction efficiency of autoclaved fibers, intact/homogenized tissue differences, critical tissue amount, and the absence of an internal standard are thoroughly examined. To both accurately quantify DOX in solid tissue and minimize the error related to the lack of an internal standard, a calibration method at equilibrium conditions was chosen. In optimized ex vivo SPME conditions, the targeted compound was extracted by directly introducing a 15 mm (45 µm thickness) mixed-mode fiber into 15 g of homogenized tissue for 20 min, followed by a desorption step in an optimal solvent mixture. The detection limit for DOX was 2.5 µg g−1 of tissue. The optimized ex vivo SPME method was successfully applied for the analysis of DOX in real pig lung biopsies, providing an averaged accuracy and precision of 103.2% and 12.3%, respectively. Additionally, a comparison between SPME and solid-liquid extraction revealed good agreement. The results presented herein demonstrate that the developed SPME method radically simplifies the sample preparation step and eliminates the need for tissue biopsies. These results suggest that SPME can accurately quantify DOX in different tissue compartments and can be potentially useful for monitoring and adjusting drug dosages during chemotherapy in order to achieve effective and safe concentrations of doxorubicin.Natural Sciences and Engineering Research Council (NSERC) of CanadaCanadian Institutes of Health Research (CIHR) [grant 355935]SK CIHR (grant 190953)GL2 (grant GL2-01-019

Central memory CD8+ T lymphocytes mediate lung allograft acceptance

Memory T lymphocytes are commonly viewed as a major barrier for long-term survival of organ allografts and are thought to accelerate rejection responses due to their rapid infiltration into allografts, low threshold for activation, and ability to produce inflammatory mediators. Because memory T cells are usually associated with rejection, preclinical protocols have been developed to target this population in transplant recipients. Here, using a murine model, we found that costimulatory blockade–mediated lung allograft acceptance depended on the rapid infiltration of the graft by central memory CD8(+) T cells (CD44(hi)CD62L(hi)CCR7(+)). Chemokine receptor signaling and alloantigen recognition were required for trafficking of these memory T cells to lung allografts. Intravital 2-photon imaging revealed that CCR7 expression on CD8(+) T cells was critical for formation of stable synapses with antigen-presenting cells, resulting in IFN-γ production, which induced NO and downregulated alloimmune responses. Thus, we describe a critical role for CD8(+) central memory T cells in lung allograft acceptance and highlight the need for tailored approaches for tolerance induction in the lung