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1.
Curr Opin Crit Care ; 29(6): 587-594, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37861189

RESUMO

PURPOSE OF REVIEW: Kidney transplantation is the ideal treatment for patients with chronic kidney disease and end stage renal disease. While centers are performing more transplants every year, the need for organ transplantation outpaces the supply of organ donors. Due to a growing population of patients with advanced kidney disease and a scarcity of kidneys from deceased donors, patients face extended wait times. By the time patients approach transplantation they have multiple comorbidities, in particular cardiovascular complications. Their risk of complications is further compounded by exposure to immunosuppression post kidney transplantation. Kidney transplant recipients (KTRs) are medically complex and may require acute management in the intensive care unit (ICU), as a result of cardiovascular complications, infections, and/or respiratory compromise from lung infections and/or acute pulmonary edema. Acute complication of immunosuppression, such as thrombotic microangiopathy and posterior reversible encephalopathy syndrome may also warrant ICU admission. This review will cover assessment of high-risk complications and management strategies following kidney transplantation. RECENT FINDINGS: For intensivists caring for KTRs, it is imperative to understand anatomical considerations of the transplanted kidney, unique infectious risks faced by this population, and appropriate modulation of immunosuppression. SUMMARY: Recognizing potential complications and implementing appropriate management strategies for KTRs admitted to the ICU will improve kidney allograft and patient survival outcomes.


Assuntos
Transplante de Rim , Síndrome da Leucoencefalopatia Posterior , Humanos , Transplante de Rim/efeitos adversos , Rim , Doadores de Tecidos , Unidades de Terapia Intensiva
2.
Yale J Biol Med ; 96(1): 13-21, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-37009195

RESUMO

Sickle cell disease (SCD) is an inherited monogenic disease which is characterized by distorted red blood cells (RBCs) that cause vaso-occlusion and vasculopathy. In the pathogenesis of SCD, polymerized hemoglobin turn RBCs into fragile, less deformable cells, and are subsequently more susceptible to endothelial adhesion after deoxygenation. Presently, electrophoresis and genotyping are used as routine tests for diagnosis of SCD. These techniques are expensive and require specialized laboratories. Lab-on-a-chip technology is a low-cost microfluidics-based diagnostic tool which holds significant promise for rapid screening of RBC deformability. To explore the sickle RBC mechanics for screening purposes, we present a mathematical model for the flow of single RBC with altered rheological properties and slip effect on capillary wall in microcirculation. We consider single-file flow of cells through the axis symmetrical cylindrical duct, applying lubrication theory as plasma trapped between successive red blood cells. The rheological parameters used from published literature for normal RBC and corresponding variation has been taken for the purpose of this simulation to present the condition of the disease. An analytical solution has been found for realistic boundary conditions and results are simulated using MATLAB. We found that the height of plasma film in the capillary increases with increase in cell deformability and compliance which affects the forward flow velocity in the capillary. Rigid RBCs with increased adhesion between cell and capillary wall shows reduction in velocity and occurrence of vaso-occlusion events in extreme conditions. These rheological properties of the cells coupled with microfluidics mechanics can mimic the physiological condition and provides unique insights with novel possibilities for the design of microfluidics base diagnostic kit towards effective therapeutic intervention of SCD.


Assuntos
Anemia Falciforme , Eritrócitos , Humanos , Eritrócitos/patologia , Anemia Falciforme/patologia , Microfluídica/métodos , Simulação por Computador , Microvasos
3.
Kidney Int ; 97(6): 1076-1082, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32354637

RESUMO

By 21 March 2020 infections related to the novel coronavirus SARS-CoV-2 had affected people from 177 countries and caused 11,252 reported deaths worldwide. Little is known about risk, presentation and outcomes of SARS-CoV-2 (COVID-19) infection in kidney transplantation recipients, who may be at high-risk due to long-term immunosuppression, comorbidity and residual chronic kidney disease. Whilst COVID-19 is predominantly a respiratory disease, in severe cases it can cause kidney and multi-organ failure. It is unknown if immunocompromised hosts are at higher risk of more severe systemic disease. Therefore, we report on seven cases of COVID-19 in kidney transplant recipients (median age 54 (range 45-69), three females, from a cohort of 2082 managed transplant follow-up patients) over a six-week period in three south London hospitals. Two of seven patients presented within three months of transplantation. Overall, two were managed on an out-patient basis, but the remaining five required hospital admission, four in intensive care units. All patients displayed respiratory symptoms and fever. Other common clinical features included hypoxia, chest crepitation, lymphopenia and high C-reactive protein. Very high D dimer, ferritin and troponin levels occurred in severe cases and likely prognostic. Immunosuppression was modified in six of seven patients. Three patients with severe disease were diabetic. During a three week follow up one patient recovered, and one patient died. Thus, our findings suggest COVID-19 infection in kidney transplant patients may be severe, requiring intensive care admission. The symptoms are predominantly respiratory and associated with fever. Most patients had their immunosuppression reduced and were treated with supportive therapy.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/epidemiologia , Febre/epidemiologia , Terapia de Imunossupressão/efeitos adversos , Transplante de Rim/efeitos adversos , Pneumonia Viral/epidemiologia , Idoso , Betacoronavirus/imunologia , Betacoronavirus/isolamento & purificação , COVID-19 , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Feminino , Febre/diagnóstico , Febre/imunologia , Febre/virologia , Seguimentos , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Humanos , Hospedeiro Imunocomprometido/imunologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , SARS-CoV-2 , Índice de Gravidade de Doença , Transplantados/estatística & dados numéricos
4.
Am J Transplant ; 20(8): 2260-2263, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-31970896

RESUMO

Hereditary complement C3 deficiency is associated with recurrent bacterial infections and proliferative glomerulonephritis. We describe a case of an adult with complete deficiency of complement C3 due to homozygous mutations in C3 gene: c.1811delT (Val604Glyfs*2), recurrent bacterial infections, crescentic glomerulonephritis, and end-stage renal failure. Following isolated kidney transplantation he would remain C3 deficient with a similar, or increased, risk of infections and glomerulonephritis. As C3 is predominantly synthesized in the liver, with a small proportion of C3 monocyte derived and kidney derived, he proceeded to simultaneous liver-kidney transplantation. The procedure has been successful with restoration of his circulating C3 levels, normal liver and kidney function at 26 months of follow-up. Simultaneous liver-kidney transplant is a viable option to be considered in this rare setting.


Assuntos
Glomerulonefrite , Falência Renal Crônica , Transplante de Rim , Adulto , Complemento C3/genética , Humanos , Rim , Falência Renal Crônica/cirurgia , Fígado , Masculino
5.
Clin Transplant ; 33(6): e13582, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31050035

RESUMO

The discovery of apolipoprotein L1 (APOL1) gene variants and its association with kidney disease in African-Americans represent a significant breakthrough in understanding the genetic basis of ancestry-based differences in a public health problem. The role these variants play in renal transplantation is still incompletely understood. This article reviews the epidemiologic data and current reports of APOL1 variant pathogenesis in transplantation. We examine existing data on outcomes in APOL1 high-risk kidneys, high-risk APOL1 recipients, live donors with high-risk mutations and non-renal transplantation of high-risk APOL1 organs. We discuss the rapidly evolving role and potential pros and cons of APOL1 genotyping of donors and recipients in transplantation. Finally, we highlight the ongoing nationwide National Institutes of Health-sponsored "APOL1 Long-term Kidney Transplantation Outcomes (APOLLO)" study, which will quantify outcomes and "second hits" in pertinent to APOL1 high-risk variants in renal transplantation.


Assuntos
Apolipoproteína L1/genética , Seleção do Doador , Predisposição Genética para Doença , Sobrevivência de Enxerto/genética , Transplante de Rim/estatística & dados numéricos , Mutação , Genótipo , Humanos , Fatores de Risco
6.
Transpl Int ; 32(4): 431-442, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30549305

RESUMO

Blood group O or B recipients wait longer for a kidney transplant. We studied the distribution of anti-ABO blood group antibody titres in patients awaiting a kidney transplant, and modelled the effect of altering the UK National Kidney Allocation Scheme to allow for patients with 'LOW' titres (≤1:8, ≤3 dilutions) to receive a deceased donor ABOi (ddABOi) transplant. In a prospective study of 239 adult patients on the waiting list for a transplant in 2 UK centres, ABO-antibody titres (anti-A and anti-B) were measured. Based on the proportions of 'LOW' anti-A or anti-B antibodies, four simulations were performed to model the current allocation rules compared with variations allowing ddABOi allocation under various conditions of blood group, HLA matching, and waiting time. The simulations permitting ddABOi resulted in more blood group B recipients being transplanted, with median waiting time reduced for this group of recipients, and more equitable waiting times across blood groups. Additionally, permitting ddABOi resulted in greater numbers of 000MM allocations overall in compatible transplants under modelled conditions. Changing allocation in the UK to permit ddABOi in patients with 'LOW' titres would not change the total number of transplants, but redistributes allocation more equitably amongst blood groups, altering waiting times accordingly.


Assuntos
Sistema ABO de Grupos Sanguíneos , Transplante de Rim , Doadores de Tecidos , Listas de Espera , Sistema ABO de Grupos Sanguíneos/imunologia , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Obtenção de Tecidos e Órgãos
8.
Allergy Asthma Proc ; 35(5): 409-14, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25295809

RESUMO

Eosinophilic esophagitis (EoE) is a clinicopathological diagnosis seen in children as well as adults. Growing evidence suggests that EoE is strongly associated with atopic disorders. Presenting symptoms differ in children and adults and it is not known whether atopic features vary by age. This study was designed to compare atopic features and allergic sensitization between children and adults with EoE. We conducted a retrospective analysis of demographic and clinical data from 50 children (aged 2-18 years) and 50 adults (aged 21-75 years) with a biopsy-proven diagnosis of EoE referred to our allergy clinic. Data regarding patient characteristics, history of atopic diseases, and allergy test results were collected for analysis. The majority of children and adults were white and male patients. When compared with adults, a higher percentage of children had a history of asthma (52% versus 24%; p < 0.05). There was no statistically significant difference between adults and children regarding history of allergic rhinitis, atopic dermatitis, immunoglobulin E-mediated food allergy, and family history of atopy. There was no statistically significant difference between children and adults regarding immediate-type sensitization to foods and aeroallergens. Compared with adults, a higher percentage of children showed a positive reaction to one or more foods on patch testing (62% versus 31%; p = 0.01). A high prevalence of comorbid atopic diseases and sensitizations to food and environmental allergens was seen in both children and adults. Children had a significantly higher rate of asthma and positive patch test to foods compared with adults.


Assuntos
Esofagite Eosinofílica/diagnóstico , Esofagite Eosinofílica/imunologia , Hipersensibilidade Imediata/imunologia , Adolescente , Adulto , Fatores Etários , Idoso , Poluentes Atmosféricos/imunologia , Alérgenos/imunologia , Criança , Pré-Escolar , Esofagite Eosinofílica/complicações , Feminino , Alimentos/efeitos adversos , Hipersensibilidade Alimentar/complicações , Humanos , Hipersensibilidade Tardia/complicações , Hipersensibilidade Imediata/complicações , Masculino , Pessoa de Meia-Idade , Testes Cutâneos , Adulto Jovem
9.
AACE Clin Case Rep ; 10(1): 20-23, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38303768

RESUMO

Background/Objective: To report a case of adenomyosis in a woman with hyperprolactinemia which resolved after initiation of dopamine agonist therapy. Case Report: A 35-year-old woman with a history of Graves' disease was referred for evaluation of hyperthyroidism in March 2020. She was started on methimazole and thyroid function normalized. The patient also had a history of a pituitary microadenoma and was previously treated with cabergoline which was stopped after 12 months as she became pregnant.In July 2020, the patient began to have polymenorrhea. Hyperprolactinemia was thought to be an unlikely cause as it most often causes hypogonadotropic hypogonadism with amenorrhea. A pelvic ultrasound demonstrated a bulky uterus with adenomyosis. Gynecology recommended treating adenomyosis by lowering her prolactin levels. She was started on cabergoline 0.25 mg weekly in October 2021. Within 2 months of initiation of cabergoline, she had resolution of symptoms and radiological resolution of adenomyosis. Discussion: Prolactin has been implicated in the pathogenesis of adenomyosis, endometriosis and leiomyomas suggesting that a decrease in prolactin levels may suppress these lesions. The pathogenesis of adenomyosis has been related to direct prolactin effects in the promotion of gland/cell proliferation and function. Conclusion: We conclude that prolonged elevation in prolactin may result in the development of adenomyosis and subsequent prolonged abnormal uterine bleeding. Dopamine agonists, like cabergoline, inhibit the synthesis and secretion of prolactin from the pituitary gland and may have a role in the management of adenomyosis in patients with hyperprolactinemia.

10.
J Genet Eng Biotechnol ; 22(1): 100337, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38494261

RESUMO

BACKGROUND: The hepatocellular carcinoma (HCC) incident rate is gradually increasing yearly despite all the research and efforts taken by scientific communities and governing bodies. Approximately 90% of all liver cancer cases belong to HCC. Usually, HCC patients approach the treatment in the late stages of this malignancy which becomes the primary cause of high mortality rate. The knowledge about molecular pathogenesis of HCC is limited and needs more attention from researchers to identify the driver genes and miRNAs, which causes to translate this information into clinical practice. Therefore, the key regulators identification of miRNA-mRNA regulatory network is essential to identify HCC-associated genes. METHODOLOGY: We extracted microRNA (miRNA) and messenger RNA (mRNA) expression datasets of normal and tumor HCC patient samples from UCSC Xena followed by identifying differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs). Univariate and multivariate cox-proportional hazard models were utilized to identify DEMs having significant association with overall survival (OS). Kaplan-Meier (KM) plotter was used to validate the presence of prognostic DEMs. A risk-score model was used to evaluate the effectiveness of KM-plotter validated DEMs combination on risk of samples. Target DEGs of prognostic miRNAs were identified via sources such as miRTargetLink and miRWalk followed by their validation in an external microarray cohort and enrichment analysis. RESULTS: 562 DEGs and 388 DEMs were identified followed by seven prognostic miRNAs (i.e., miR-19a, miR-19b, miR-30d-5p, miR-424-5p, miR-3677-5p, miR-3913-5p, miR-7705) post univariate, multivariate, risk-score model evaluation and KM-plotter analyses. ANLN, MRO, CPEB3 were their targets and were also validated in GSE84005 dataset. CONCLUSIONS: The findings of this study decipher that most significant miRNAs and their identified target genes have association with apoptosis, inflammation, cell cycle regulation and cancer-related pathways, which appear to contribute to HCC pathogenesis and therefore, the discovery of new targets.

11.
Healthcare (Basel) ; 11(23)2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38063628

RESUMO

BACKGROUND: The application of enhanced recovery after surgery principles decreases postoperative complications (POCs), length of stay (LOS), and readmissions. Pharmacoprophylaxis decreases morbidity, but the effect of specific regimens on clinical outcomes is unclear. METHODS AND MATERIALS: Records of 476 randomly selected adult patients who underwent elective colorectal surgeries (ECRS) at 10 US hospitals were abstracted. Primary outcomes were surgical site infection (SSI), venous thromboembolism (VTE), postoperative nausea and vomiting (PONV), pain, and ileus rates. Secondary outcomes included LOS and 7- and 30-day readmission rates. RESULTS: POC rates were SSI (3.4%), VTE (1.5%), PONV (47.9%), pain (58.1%), and ileus (16.1%). Cefazolin 2 g/metronidazole 500 mg and ertapenem 1 g were associated with the shortest LOS; cefotetan 2 g and cefoxitin 2 g with the longest LOS. No SSI occurred with ertapenem and cefotetan. More Caucasians than Blacks received oral antibiotics before intravenous antibiotics without impact. Enoxaparin 40 mg subcutaneously daily was the most common inpatient and discharge VTE prophylaxis. All in-hospital VTEs occurred with unfractionated heparin. Most received rescue rather than around-the-clock antiemetics. Scopolamine patches, spinal opioids, and IV lidocaine continuous infusion were associated with lower PONV. Transversus abdominis plane block with long-acting local anesthetics, celecoxib, non-anesthetic ketamine bolus, ketorolac IV, lidocaine IV, and pregabalin were associated with lower in-hospital pain severity rates. Gabapentinoids and alvimopan were associated with lower ileus rates. Acetaminophen, alvimopan, famotidine, and lidocaine patches were associated with shorter LOS. CONCLUSIONS: Significant differences in pharmacotherapy regimens that may improve primary and secondary outcomes in ECRS were identified. In adult ECRS, cefotetan or ertapenem may be better regimens for preventing in-hospital SSI, while ertapenem or C/M may lead to shorter LOS. The value of OA to prevent SSI was not demonstrated. Inpatient enoxaparin, compared to UFH, may reduce VTE rates with a similar LOS. A minority of patients had a documented PONV risk assessment, and a majority used as-needed rather than around-the-clock strategies. Preoperative scopolamine patches continued postoperatively may lower PONV and PDNV severity and shorter LOS. Alvimopan may reduce ileus and shorten LOS. Anesthesia that includes TAP block, ketorolac IV, and pregabalin use may lead to reduced pain rates. Acetaminophen, alvimopan, famotidine, and lidocaine patches may shorten LOS. Given the challenges of pain management and the incidence of PONV/PDNV found in this study, additional studies should be conducted to determine optimal opioid-free anesthesia and the benefit of newer antiemetics on patient outcomes. Moreover, future research should identify latent pharmacotherapy variables that impact patient outcomes, correlate pertinent laboratory results, and examine the impact of order or care sets used for ECRS at study hospitals.

12.
EClinicalMedicine ; 56: 101819, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36684392

RESUMO

Background: 3% of kidney transplant recipients return to dialysis annually upon allograft failure. Development of antibodies (Ab) against human leukocyte antigens (HLA) is a validated prognostic biomarker of allograft failure. We tested whether screening for HLA Ab, combined with an intervention to improve adherence and optimization of immunosuppression could prevent allograft failure. Methods: Prospective, open-labelled randomised biomarker-based strategy (hybrid) trial in 13 UK transplant centres [EudraCT (2012-004308-36) and ISRCTN (46157828)]. Patients were randomly allocated (1:1) to unblinded or double-blinded arms and screened every 8 months. Unblinded HLA Ab+ patients were interviewed to encourage medication adherence and had tailored optimisation of Tacrolimus, Mycophenolate mofetil and Prednisolone. The primary outcome was time to graft failure in an intention to treat analysis. The trial had 80% power to detect a hazard ratio of 0.49 in donor specific antibody (DSA)+ patients. Findings: From 11/9/13 to 27/10/16, 5519 were screened for eligibility and 2037 randomised (1028 to unblinded care and 1009 to double blinded care). We identified 198 with DSA and 818 with non-DSA. Development of DSA, but not non-DSA was predictive of graft failure. HRs for graft failure in unblinded DSA+ and non-DSA+ groups were 1.54 (95% CI: 0.72 to 3.30) and 0.97 (0.54-1.74) respectively, providing no evidence of an intervention effect. Non-inferiority for the overall unblinded versus blinded comparison was not demonstrated as the upper confidence limit of the HR for graft failure exceeded 1.4 (1.02, 95% CI: 0.72 to 1.44). The only secondary endpoint reduced in the unblinded arm was biopsy-proven rejection. Interpretation: Intervention to improve adherence and optimize immunosuppression does not delay failure of renal transplants after development of DSA. Whilst DSA predicts increased risk of allograft failure, novel interventions are needed before screening can be used to direct therapy. Funding: The National Institute for Health Research Efficacy and Mechanism Evaluation programme grant (ref 11/100/34).

13.
Artigo em Inglês | MEDLINE | ID: mdl-22288841

RESUMO

A novel bioreactor containing viable APA microencapsulated yeast cells was designed. Rat plasma was used for perfusion. Yeast cell loading and perfusion flow rate were studied to maximize urea removal. An increase in column loading from 25% to 100%, increased urea removal from 5.67 ± 1.34% to 30.45 ± 0.48%. An increase in flow rate from low to high, increased urea removal from 30.46% to 40.4%. At 100% column loading and high flow rate, the creatinine and phosphate concentrations decreased by 22% and 10%, respectively, while ammonia concentrations increased by 58.9% (p < 0.05). Our in-vitro perfusion study demonstrates that microencapsulated yeast cells can remove urea efficiently.


Assuntos
Reatores Biológicos/microbiologia , Insuficiência Renal/complicações , Terapia de Substituição Renal/instrumentação , Saccharomyces cerevisiae/citologia , Uremia/complicações , Uremia/terapia , Amônia/sangue , Animais , Cápsulas , Sobrevivência Celular , Creatinina/sangue , Perfusão , Fosfatos/sangue , Plasma , Ratos , Ureia/sangue
14.
Front Nutr ; 9: 887580, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35677553

RESUMO

Half of kidney transplant recipients (KTRs) gain more than 5% of their body weight in the first year following transplantation. KTRs have requested support with physical activity (PA) and weight gain prevention, but there is no routine care offered. There are few high-quality studies investigating the clinical value of diet, PA or combined interventions to prevent weight gain. The development and evaluation of theoretically informed complex-interventions to mitigate weight gain are warranted. The aims of this mixed-methods randomized controlled trial (RCT) were to explore the feasibility, acceptability and user-experience of a digital healthcare intervention (DHI) designed to prevent post-transplant weight gain, in preparation for a large multi-center trial. New KTRs (<3 months) with access to an internet compatible device were recruited from a London transplant center. The usual care (UC) group received standard dietary and PA advice. The intervention group (IG) received access to a 12-week DHI designed to prevent post-transplant weight gain. Primary feasibility outcomes included screening, recruitment, retention, adherence, safety and hospitalizations and engagement and experience with the DHI. Secondary outcomes (anthropometrics, bioimpedance, arterial stiffness, 6-minute walk distance and questionnaires) were measured at baseline, 3- and 12-months. 38 KTRs were screened, of which 32 (84.2%) were eligible, and of those 20 (62.5%) consented, with 17 participants (85%) completing baseline assessment (Median 49 years, 58.8% male, Median 62 days post-transplant). Participants were randomized using a computer-generated list (n = 9 IG, n = 8 UC). Retention at 12-months was 13 (76.4%) (n = 6 IG, n = 7 UC). All a priori progression criteria were achieved. There were no associated adverse events. Reflexive thematic analysis revealed four themes regarding trial participation and experience whilst using the DHI. Halting recruitment due to COVID-19 resulted in the recruitment of 40% of the target sample size. Mixed-methods data provided important insights for future trial design. A definitive RCT is warranted and welcomed by KTRs. Clinical Trial Registration: www.clinicalTrials.gov, identifier: NCT03996551.

15.
Clin J Am Soc Nephrol ; 17(9): 1325-1336, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35918106

RESUMO

BACKGROUND AND OBJECTIVES: Daprodustat is a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) being investigated for the treatment of anemia of CKD. In this noninferiority trial, we compared daprodustat administered three times weekly with epoetin alfa (epoetin) in patients on prevalent hemodialysis switching from a prior erythropoiesis-stimulating agent (ESA). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients on hemodialysis with a baseline hemoglobin of 8-11.5 g/dl receiving an ESA were randomized 2:1 to daprodustat three times weekly (n=270) or conventional epoetin (n=137) for 52 weeks. Dosing algorithms aimed to maintain hemoglobin between 10 and 11 g/dl. The primary end point was mean change in hemoglobin from baseline to the average during the evaluation period (weeks 28-52). The principal secondary end point was average monthly intravenous iron dose. Other secondary end points included BP and hemoglobin variability. RESULTS: Daprodustat three times weekly was noninferior to epoetin for mean change in hemoglobin (model-adjusted mean treatment difference [daprodustat-epoetin], -0.05; 95% confidence interval, -0.21 to 0.10). During the evaluation period, mean (SD) hemoglobin values were 10.45 (0.55) and 10.51 (0.85) g/dl for daprodustat and epoetin groups, respectively. Responders (defined as mean hemoglobin during the evaluation period in the analysis range of 10 to 11.5 g/dl) were 80% in the daprodustat group versus 64% in the epoetin group. Proportionately fewer participants in the daprodustat group versus the epoetin group had hemoglobin values either below 10 g/dl or above 11.5 g/dl during the evaluation period. Mean monthly intravenous iron use was not significantly lower with daprodustat versus epoetin. The effect on BP was similar between groups. The percentage of treatment-emergent adverse events was similar between daprodustat (75%) and epoetin (79%). CONCLUSIONS: Daprodustat was noninferior to epoetin in hemoglobin response and was generally well tolerated. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Anemia Studies in Chronic Kidney Disease: Erythropoiesis via a Novel Prolyl Hydroxylase Inhibitor Daprodustat-Three Times Weekly Dosing in Dialysis (ASCEND-TD), NCT03400033.


Assuntos
Anemia , Eritropoetina , Hematínicos , Inibidores de Prolil-Hidrolase , Insuficiência Renal Crônica , Humanos , Anemia/tratamento farmacológico , Anemia/etiologia , Epoetina alfa , Eritropoetina/uso terapêutico , Hemoglobinas , Ferro , Inibidores de Prolil-Hidrolase/efeitos adversos , Proteínas Recombinantes/efeitos adversos , Diálise Renal/efeitos adversos , Insuficiência Renal Crônica/terapia , Insuficiência Renal Crônica/tratamento farmacológico , Resultado do Tratamento , Método Duplo-Cego
16.
Ann Card Anaesth ; 24(2): 203-208, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33884977

RESUMO

Background: Extra Corporeal Membrane Oxygenation (ECMO) is a well-known tool for providing life-saving support in patients developing post cardiotomy cardiogenic shock in post cardiac surgeries. The current study was designed to evaluate blood transfusion requirements and its relation to mortality in neonate and pediatric cardiac patients requiring venoarterial cardiac ECMO during post-operative period following cardiac surgery. Materials and Methods: Overall 24 pediatric patients (including neonates) who underwent VA ECMO in post cardiac surgery at our institute from January 2016 to October 2017 were included in the study. The details of demographics, blood transfusion, ECMO, and morbidity and mortality were collected for all the patients. Objective of the Study: The primary objective of our study was to assess the outcome of patients on ECMO in post pediatric cardiac surgery. The secondary objective of the study was to assess the effect of blood transfusion on the outcome of the patients. Results: Overall mortality rate was 50% (n = 12). The overall transfusion rate of packed red blood cells was higher in patients who did not survive even after institution of VA ECMO. The transfusion of other blood products like platelets, cryoprecipitate, and fresh frozen plasma were also higher in this group of patients though it was statistically non-significant except for packed red cell transfusion. Though statistically non-significant, the patients who didn't survive even after institution of VA ECMO post-surgery had relatively higher mean age (703.88 ± 998.94 days) as compared to their counterparts (510.63 ± 384.36 days). Conclusion: The use of ECMO is associated with considerable morbidity and mortality. Packed red cell transfusion is definitely higher in expired patients, indicative of deteriorated status of the patient. However, considering non-significant association of other blood components, except packed red cell it is recommended that patients' overall clinical condition should be taken into consideration for transfusion of blood products and not only targeting the transfusion triggers.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Oxigenação por Membrana Extracorpórea , Criança , Transfusão de Eritrócitos , Humanos , Estudos Retrospectivos , Choque Cardiogênico
17.
Am J Med ; 134(8): 952-962.e4, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33775644

RESUMO

Optimal strategies for integration of clinical practice guidelines into electronic medical records and its impact on processes of care and clinical outcomes in diabetic patients are not well understood. A systematic review of CINAHL, MEDLINE, PubMed, and Cochrane Library databases in August 2016, November 2017, and June 2020 was conducted. Studies investigating integration of diabetes guidelines into ambulatory care electronic medical records reporting quantitative results were included. After screening 15,783 records, 21 articles were included. Lipid and blood pressure control consistently improved with guideline integration, but A1c control remained equivocal. Electronic guideline integration improved microvascular complication screening, vaccination, and documentation of cardiovascular risk factors, while medication prescription and blood pressure, lipid, and A1c documentation did not improve. Studies employing a combination of electronic record intervention strategies were associated with improvement in monitoring and attainment of guideline and screening targets. Thus, strategies employing combinations of interventions to incorporate guidelines into electronic records may improve processes of care and some clinical outcomes.


Assuntos
Diabetes Mellitus/terapia , Registros Eletrônicos de Saúde , Guias de Prática Clínica como Assunto , Humanos , Resultado do Tratamento
18.
Chest ; 160(2): e173-e176, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34366039

RESUMO

Sweet's Syndrome (SS), also known as acute febrile neutrophilic dermatosis, is one of several cutaneous inflammatory disorders classified as neutrophilic dermatoses. Respiratory complications are described in <50 cases in the literature,1 without prior report of lung transplantation (LT). This article explains the clinical course of the first patient to receive LT for pulmonary SS and presents evidence suggesting recurrence of the primary lung disease in the allograft.


Assuntos
Transplante de Pulmão , Síndrome de Sweet/diagnóstico , Corticosteroides/uso terapêutico , Adulto , Diagnóstico Diferencial , Diagnóstico por Imagem , Feminino , Humanos , Imunossupressores/uso terapêutico , Testes de Função Respiratória , Síndrome de Sweet/tratamento farmacológico
19.
Can J Diabetes ; 44(1): 30-36.e2, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31399366

RESUMO

OBJECTIVES: In recent years there has been an increased emphasis on competency-based medical education (CBME) in Canada and internationally, as can be seen with the implementation of competency-based curriculums for postgraduate medical education (PGME) through the Royal College of Physicians and Surgeons of Canada. Currently, no Canada-wide consensus exists on educational competencies relating to diabetes in undergraduate medical education (UGME). Our aim in this study was to develop a list of competencies and objectives for UGME in diabetes using a modified Delphi method. METHODS: Representatives involved in the development of the diabetes curriculum at all 17 medical schools across Canada were contacted. A draft list of competencies and objectives was developed by the research team using the existing curriculums at 9 Canadian medical schools and was organized using the CanMEDS framework. A Delphi method was used, with 2 iterations in order to reach consensus. RESULTS: Twelve of 17 medical schools agreed to participate. Of the 12 surveys sent in the first round, 8 responses were received (response rate 66.7%). The revised version was then resent to the 8 respondents and 7 responses were received (response rate 87.5%). A list of 9 competencies and 62 objectives was finalized. CONCLUSIONS: A competency-based consensus curriculum for diabetes education for undergraduate medical students was developed using a modified Delphi method. The final consensus syllabus will be disseminated across the country. This curriculum serves as a step in the transition to competency-based UGME and in ensuring that future medical school graduates are proficient in diabetes care.


Assuntos
Competência Clínica/normas , Currículo/normas , Técnica Delphi , Diabetes Mellitus/prevenção & controle , Educação de Graduação em Medicina/normas , Educação em Saúde , Canadá/epidemiologia , Diabetes Mellitus/epidemiologia , Educação de Graduação em Medicina/métodos , Humanos , Inquéritos e Questionários
20.
Respir Med Case Rep ; 31: 101193, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32874911

RESUMO

A 47-year-old male with morbid obesity and progressive pulmonary fibrosis was admitted to the intensive care unit (ICU) with worsening hypoxia and nocturnal ventilator dependence. Due to a significant oxygen requirement, the patient could only safely remain in an acute care setting. Unfortunately, he was not eligible for lung transplantation due to having obesity, a relative contraindication to lung transplantation due to potential for post transplantation complications and increased mortality. Therefore, we treated the patient with a modified very low calorie diet (MVLCD) to achieve weight loss. He had successful, sustained weight loss over a period of seven weeks and reached a target weight that made him eligible for transplantation. He subsequently underwent successful bilateral lung transplantation. The patient had improved metabolic parameters and no side effects attributable to the reduced calorie diet. This report shows that in patients with end stage lung disease and a poor prognosis without transplantation, inpatient weight loss is safe and may allow for potentially lifesaving lung transplantation.

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