RESUMO
AIMS: Lifestyle and dietary modification are effective in the prevention and management of Type 2 diabetes Mellitus (T2DM). However, South Asian (SA) populations living in Western countries have low adherence rates to healthcare advice and experience poor diabetes control and clinical outcomes compared with the general population. This systematic review aimed to summarise the barriers and facilitators of dietary modification within people from South Asian (SA) ethnicity with T2DM or pre-diabetes. METHODS: A systematic search of PubMed, Web of Science and Scopus generated 3739 articles, of which seven were included. Qualitative and quantitative data were inputted utilising COVIDENCE. Qualitative data were analysed by thematic analysis. RESULTS: Thematic analysis identified three facilitators: (1) cultural sensitivity, (2) health education and (3) support networks. Barriers include (1) healthcare inequity, (2) cultural insensitivity, (3) social pressures, (4) misconceptions and (5) time constraints. Good access to health care and motivation were the most common facilitators discussed. Misconceptions on T2DM management and cultural insensitivity contributed to the majority of barriers discussed. CONCLUSIONS: Culturally tailored interventions could improve adherence to diet modification in people with T2DM from SA ethnicity. Interventions involving the application of social media to challenge intergenerational stigmas and misinformation, distributing culturally appropriate resources and providing diets tailored to the SA palate could help.
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Diabetes Mellitus Tipo 2 , Dieta , Estado Pré-Diabético , Humanos , Povo Asiático , Diabetes Mellitus Tipo 2/prevenção & controle , Dieta/etnologia , Etnicidade , Estado Pré-Diabético/terapia , População do Sul da Ásia , Assistência à Saúde Culturalmente Competente , Acessibilidade aos Serviços de SaúdeRESUMO
AIMS: To investigate characteristics of people hospitalized with coronavirus-disease-2019 (COVID-19) and diabetic ketoacidosis (DKA) or hyperosmolar hyperglycaemic state (HHS), and to identify risk factors for mortality and intensive care admission. MATERIALS AND METHODS: Retrospective cohort study with anonymized data from the Association of British Clinical Diabetologists nationwide audit of hospital admissions with COVID-19 and diabetes, from start of pandemic to November 2021. The primary outcome was inpatient mortality. DKA and HHS were adjudicated against national criteria. Age-adjusted odds ratios were calculated using logistic regression. RESULTS: In total, 85 confirmed DKA cases, and 20 HHS, occurred among 4073 people (211 type 1 diabetes, 3748 type 2 diabetes, 114 unknown type) hospitalized with COVID-19. Mean (SD) age was 60 (18.2) years in DKA and 74 (11.8) years in HHS (p < .001). A higher proportion of patients with HHS than with DKA were of non-White ethnicity (71.4% vs 39.0% p = .038). Mortality in DKA was 36.8% (n = 57) and 3.8% (n = 26) in type 2 and type 1 diabetes respectively. Among people with type 2 diabetes and DKA, mortality was lower in insulin users compared with non-users [21.4% vs. 52.2%; age-adjusted odds ratio 0.13 (95% CI 0.03-0.60)]. Crude mortality was lower in DKA than HHS (25.9% vs. 65.0%, p = .001) and in statin users versus non-users (36.4% vs. 100%; p = .035) but these were not statistically significant after age adjustment. CONCLUSIONS: Hospitalization with COVID-19 and adjudicated DKA is four times more common than HHS but both associate with substantial mortality. There is a strong association of previous insulin therapy with survival in type 2 diabetes-associated DKA.
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COVID-19 , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Cetoacidose Diabética , Hiperglicemia , Coma Hiperglicêmico Hiperosmolar não Cetótico , Humanos , Adulto , Pessoa de Meia-Idade , Cetoacidose Diabética/epidemiologia , Cetoacidose Diabética/etiologia , Coma Hiperglicêmico Hiperosmolar não Cetótico/complicações , Coma Hiperglicêmico Hiperosmolar não Cetótico/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Estudos Retrospectivos , Hiperglicemia/tratamento farmacológico , COVID-19/complicações , COVID-19/epidemiologia , Hospitais , Hospitalização , Insulina Regular Humana , Insulina/uso terapêutico , Reino Unido/epidemiologiaRESUMO
Lobular neoplasia (LN) involves proliferative changes within the breast lobules. LN is divided into lobular carcinoma in situ (LCIS) and atypical lobular hyperplasia (ALH). LCIS can be further subdivided into three subtypes: classic LCIS, pleomorphic LCIS, and LCIS with necrosis (florid type). Because classic LCIS is now considered as a benign etiology, current guidelines recommend close follow-up with imaging versus surgical excision. The goal of our study was to determine if the diagnosis of classic LN on core needle biopsy (CNB) merits surgical excision. This is a retrospective, observational study conducted at Mount Auburn Hospital, Cambridge, MA, from May 17, 2017, through June 30, 2020. We reviewed the data of breast biopsies conducted at our hospital over this period and included patients who were diagnosed with classic LN (LCIS and/or ALH) and excluded patients having any other atypical lesions on CNB. All known cancer patients were excluded. Of the 2707 CNBs performed during the study period, we identified 68 women who were diagnosed with ALH or LCIS on CNB. CNB was performed for an abnormal mammogram in the majority of patients (60; 88%) while 7(10.3%) had an abnormal breast magnetic resonance imaging study (MRI), and 1 had an abnormal ultrasound (US). A total of 58 patients (85%) underwent excisional biopsy, of which 3 (5.2%) showed malignancy, including 2 cases of DCIS and 1 invasive carcinoma. In addition, there was 1 case (1.7%) with pleomorphic LCIS and 11 cases with ADH (15.5%). The management of LN found on core biopsy is evolving, with some advocating surgical excision and others recommending observation. Our data show a change in diagnosis with excisional biopsy in 13 (22.4%) of patients with 2 cases of DCIS, 1 invasive carcinoma, 1 pleomorphic LCIS, and 9 cases of ADH, diagnosed on excisional biopsy. While ALH and classic LCIS are considered benign, the choice of ongoing surveillance versus excisional biopsy should be made with shared decision making with the patient, with consideration of personal and family history, as well as patient preferences.
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Carcinoma de Mama in situ , Neoplasias da Mama , Carcinoma in Situ , Carcinoma Intraductal não Infiltrante , Carcinoma Lobular , Lesões Pré-Cancerosas , Feminino , Humanos , Biópsia , Biópsia com Agulha de Grande Calibre , Carcinoma de Mama in situ/diagnóstico por imagem , Carcinoma de Mama in situ/cirurgia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/patologia , Carcinoma in Situ/cirurgia , Carcinoma Intraductal não Infiltrante/diagnóstico por imagem , Carcinoma Intraductal não Infiltrante/cirurgia , Carcinoma Lobular/diagnóstico por imagem , Carcinoma Lobular/cirurgia , Hiperplasia , Estudos Observacionais como Assunto , Lesões Pré-Cancerosas/patologiaRESUMO
A significant percentage of people with diabetes develop chronic kidney disease and diabetes is also a leading cause of end-stage kidney disease (ESKD). The term diabetic kidney disease (DKD) includes both diabetic nephropathy (DN) and diabetes mellitus and chronic kidney disease (DM CKD). DKD is associated with high morbidity and mortality, which are predominantly related to cardiovascular disease. Hyperglycaemia is a modifiable risk factor for cardiovascular complications and progression of DKD. Recent clinical trials of people with DKD have demonstrated improvement in clinical outcomes with sodium glucose co-transporter-2 (SGLT-2) inhibitors. SGLT-2 inhibitors have significantly reduced progression of DKD and onset of ESKD and these reno-protective effects are independent of glucose lowering. At the time of this update Canagliflozin and Dapagliflozin have been approved for delaying the progression of DKD. The Association of British Clinical Diabetologists (ABCD) and UK Kidney Association (UKKA) Diabetic Kidney Disease Clinical Speciality Group have undertaken a literature review and critical appraisal of the available evidence to inform clinical practice guidelines for management of hyperglycaemia in adults with DKD. This 2021 guidance is for the variety of clinicians who treat people with DKD, including GPs and specialists in diabetes, cardiology and nephrology.
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Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Hiperglicemia , Insuficiência Renal Crônica , Inibidores do Transportador 2 de Sódio-Glicose , Adulto , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/terapia , Nefropatias Diabéticas/complicações , Feminino , Glucose , Humanos , Hiperglicemia/complicações , Hiperglicemia/tratamento farmacológico , Hiperglicemia/prevenção & controle , Masculino , Insuficiência Renal Crônica/complicações , Sociedades Médicas , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêuticoRESUMO
Dapagliflozin (SGLT-2 inhibitor) and sotagliflozin (SGLT1/2 inhibitor) are two of the drugs of SGLT inhibitor class which have been recommended by the National Institute for Health and Care Excellence (NICE) in people with type 1 diabetes with BMI ≥27 kg/m2 . Dapagliflozin is licensed in the UK for use in the NHS while sotagliflozin may be available in future. These and possibly other SGLT inhibitors may be increasingly used in people with type 1 diabetes as new licences are obtained. These drugs have the potential to improve glycaemic control in people with type 1 diabetes with the added benefit of weight loss, better control of blood pressure and more time in optimal glucose range. However, SGLT inhibitors are associated with a higher incidence of diabetic ketoacidosis without significant hyperglycaemia. The present ABCD/Diabetes UK joint updated position statement is to guide people with type 1 diabetes and clinicians using these drugs help mitigate this risk and other potential complications. Particularly, caution needs to be exercised in people who are at risk of diabetic ketoacidosis due to low calorie diets, illnesses, injuries, starvation, excessive exercise, excessive alcohol consumption and reduced insulin administration among other precipitating factors for diabetic ketoacidosis.
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Diabetes Mellitus Tipo 1/tratamento farmacológico , Cetoacidose Diabética/epidemiologia , Sobrepeso/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Compostos Benzidrílicos/uso terapêutico , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/metabolismo , Quimioterapia Combinada , Glucosídeos/uso terapêutico , Glicosídeos/uso terapêutico , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Sobrepeso/complicações , Guias de Prática Clínica como Assunto , Reino UnidoRESUMO
Post-transplant diabetes mellitus (PTDM) is common after solid organ transplantation (SOT) and associated with increased morbidity and mortality for allograft recipients. Despite the significant burden of disease, there is a paucity of literature with regards to detection, prevention and management. Evidence from the general population with diabetes may not be translatable to the unique context of SOT. In light of emerging clinical evidence and novel anti-diabetic agents, there is an urgent need for updated guidance and recommendations in this high-risk cohort. The Association of British Clinical Diabetologists (ABCD) and Renal Association (RA) Diabetic Kidney Disease Clinical Speciality Group has undertaken a systematic review and critical appraisal of the available evidence. Areas of focus are; (1) epidemiology, (2) pathogenesis, (3) detection, (4) management, (5) modification of immunosuppression, (6) prevention, and (7) PTDM in the non-renal setting. Evidence-graded recommendations are provided for the detection, management and prevention of PTDM, with suggested areas for future research and potential audit standards. The guidelines are endorsed by Diabetes UK, the British Transplantation Society and the Royal College of Physicians of London. The full guidelines are available freely online for the diabetes, renal and transplantation community using the link below. The aim of this review article is to introduce an abridged version of this new clinical guideline ( https://abcd.care/sites/abcd.care/files/site_uploads/Resources/Position-Papers/ABCD-RA%20PTDM%20v14.pdf).
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Diabetes Mellitus/etiologia , Medicina Interna , Nefrologia , Transplante de Órgãos/efeitos adversos , Complicações Pós-Operatórias/terapia , Guias de Prática Clínica como Assunto , Sociedades Médicas , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/terapia , Humanos , Terapia de Imunossupressão/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologiaRESUMO
The modern era has brought the concept of preparedness for mass casualties and disasters to the forefront of every health systems' concerns as one of their most urgent needs. Anesthesiologists, and the components of their departments, are vital to include in organizing and coordinating clinical and administrative services for an effective and comprehensive plan of action.
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Anestesia/métodos , Cuidados Críticos/métodos , Planejamento em Desastres/métodos , Incidentes com Feridos em Massa , Serviços Médicos de Emergência/organização & administração , Humanos , Unidades de Terapia Intensiva/organização & administração , Papel do Médico , Triagem/organização & administraçãoRESUMO
EXECUTIVE SUMMARY: This article illustrates the successful application of principles established by the American Hospital Association (AHA) to foster hospital transformations (). We examined a small community hospital's successful transition from one emergency care center (ECC) physician group to another and the methods by which significant improvements in outcomes were achieved. The foundation of this transformation included a generative governance style at the board level, a shared governance model at the employee level, a renewed sense of employee and physician engagement, and a sense of individual accountability. Outcomes included improved communication, a more unified vision throughout the ECC (which led to improved efficiency and accountability among staff), improved metrics, and a positive impact on the community's perception of care. Press Ganey scores and ECC operational metrics demonstrated significant increases in patient satisfaction and decreases in wait times for seven operational metrics. These data serve as a proxy for the transformation's success. Structured interviews revealed an increase in employee satisfaction associated with the transition. The positive outcomes demonstrate the importance of the AHA-articulated governance principles. The AHA recommendations for a superior value-based care model closely align with the methods illustrated through Bristol Hospital's successful transformation. Other institutions can apply the lessons from this case study to drive positive change and improve patient care.
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Hospitais Comunitários , Satisfação do Paciente , HumanosRESUMO
Kinetic perimetry is used to quantify visual field size/sensitivity. Clinically, perimetry can be used to diagnose and monitor ophthalmic and neuro-ophthalmic disease. Normative data are integral to the interpretation of these findings. However, there are few computational developments that allow clinicians to collect and analyze normative data from kinetic perimeters. In this article we describe an approach to fitting kinetic responses using linear quantile mixed models. Analogously to traditional linear mixed-effects models for the mean, linear quantile mixed models account for repeated measurements taken from the same individual, but differently from linear mixed-effects models, they are more flexible as they require weaker distributional assumptions and allow for quantile-specific inference. Our approach improves on parametric alternatives based on normal assumptions. We introduce the R package kineticF, a freely available and open-access resource for the analysis of perimetry data. Our proposed approach can be used to analyze normative data from further studies.
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Testes de Campo Visual , Campos Visuais/fisiologia , Adolescente , Criança , Pré-Escolar , Humanos , Cinética , Modelos LinearesRESUMO
The spread of antibiotic resistance among Gram-negative bacteria is a serious clinical threat, and infections with these organisms are a leading cause of mortality worldwide. Traditional novel drug development inevitably leads to the emergence of new resistant strains, rendering the new drugs ineffective. Therefore, reviving the therapeutic potentials of existing antibiotics represents an attractive novel strategy. Novicidin, a novel cationic antimicrobial peptide, is effective against Gram-negative bacteria. Here, we investigated novicidin as a possible antibiotic enhancer. The actions of novicidin in combination with rifampin, ceftriaxone, or ceftazidime were investigated against 94 antibiotic-resistant clinical Gram-negative isolates and 7 strains expressing New Delhi metallo-ß-lactamase-1. Using the checkerboard method, novicidin combined with rifampin showed synergy with >70% of the strains, reducing the MICs significantly. The combination of novicidin with ceftriaxone or ceftazidime was synergistic against 89.7% of the ceftriaxone-resistant strains and 94.1% of the ceftazidime-resistant strains. Synergistic interactions were confirmed using time-kill studies with multiple strains. Furthermore, novicidin increased the postantibiotic effect when combined with rifampin or ceftriaxone. Membrane depolarization assays revealed that novicidin alters the cytoplasmic membrane potential of Gram-negative bacteria. In vitro toxicology tests showed novicidin to have low hemolytic activity and no detrimental effect on cell cultures. We demonstrated that novicidin strongly rejuvenates the therapeutic potencies of ceftriaxone or ceftazidime against resistant Gram-negative bacteria in vitro. In addition, novicidin boosted the activity of rifampin. This strategy can have major clinical implications in our fight against antibiotic-resistant bacterial infections.
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Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Ceftazidima/farmacologia , Ceftriaxona/farmacologia , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Rifampina/farmacologia , Animais , Linhagem Celular , Sinergismo Farmacológico , Quimioterapia Combinada , Enterobacter/efeitos dos fármacos , Enterobacter/crescimento & desenvolvimento , Eritrócitos/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Fibroblastos/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/crescimento & desenvolvimento , Potenciais da Membrana/efeitos dos fármacos , Camundongos , Testes de Sensibilidade Microbiana , Serratia/efeitos dos fármacos , Serratia/crescimento & desenvolvimentoRESUMO
PURPOSE: We sought to define normative visual field (VF) values for children using common clinical test protocols for kinetic and static perimetry. DESIGN: Prospective, observational study. SUBJECTS: We recruited 154 children aged 5 to 15 years without any ophthalmic condition that would affect the VF (controls) from pediatric clinics at Moorfields Eye Hospital. METHODS: Children performed perimetric assessments in a randomized order using Goldmann and Octopus kinetic perimetry, and Humphrey static perimetry (Swedish Interactive Thresholding Algorithm [SITA] 24-2 FAST), in a single sitting, using standardized clinical protocols, with assessment by a single examiner. Unreliable results (assessed qualitatively) were excluded from the normative data analysis. Linear, piecewise, and quantile mixed-effects regression models were used. We developed a method to display age-specific normative isopters graphically on a VF plot to aid interpretation. MAIN OUTCOME MEASURES: Summary measures and graphical plots describing normative VF data for 3 common perimetric tests. RESULTS: Visual field area increased with age on testing with Goldmann isopters III4e, I4e, and I2e (linear regression; P < 0.001) and for Octopus isopters III4e and I4e (linear regression; P < 0.005). Visual field development occurs predominately in the inferotemporal field. Humphrey mean deviation (MD) showed an increase of 0.3 decibels (dB; 95% CI, 0.21-0.40) MD per year up to 12 years of age, when adult MD values were reached and thereafter maintained. CONCLUSIONS: Visual field size and sensitivity increase with age in patterns that are specific to the perimetric approach used. These developmental changes should be accounted for when interpreting perimetric test results in children, particularly when monitoring change over time.
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Envelhecimento/fisiologia , Testes de Campo Visual/instrumentação , Campos Visuais/fisiologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estudos Prospectivos , Valores de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Testes de Campo Visual/métodosRESUMO
BACKGROUND: Evidence on the socioeconomic burden associated with childhood visual impairment, severe visual impairment and blindness (VI/SVI/BL) is needed to inform economic evaluations of existing and emerging interventions aimed at protecting or improving vision. This study aimed to evaluate the quantity and quality of literature on resource use and/or costs associated with childhood VI/SVI/BL disorders. METHODS: PubMed, Web of Science (Ovid), the National Health Service (NHS) Economic Evaluation Database and grey literature were searched in November 2020. The PubMed search was rerun in February 2022. Original articles reporting unique estimates of resource use or cost data on conditions resulting in bilateral VI/SVI/BL were eligible for data extraction. Quality assessment (QA) was undertaken using the Drummond checklist adapted for cost-of-illness (COI) studies. RESULTS: We identified 31 eligible articles, 27 from the peer-reviewed literature and four from the grey literature. Two reported on resource use, and 29 reported on costs. Cerebral visual impairment and optic nerve disorders were not examined in any included studies, whereas retinopathy of prematurity was the most frequently examined condition. The quality of studies varied, with economic evaluations having higher mean QA scores (82%) compared to COI studies (77%). Deficiencies in reporting were seen, particularly in the clinical definitions of conditions in economic evaluations and a lack of discounting and sensitivity analyses in COI studies. CONCLUSIONS: There is sparse literature on resource use or costs associated with childhood visual impairment disorders. The first step in addressing this important evidence gap is to ensure core visual impairment outcomes are measured in future randomised control trials of interventions as well as cohort studies and are reported as a discrete health outcome.
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Efeitos Psicossociais da Doença , Medicina Estatal , Recém-Nascido , Humanos , Criança , Recém-Nascido Prematuro , Análise Custo-Benefício , Transtornos da Visão/terapiaRESUMO
Inferior vena cava (IVC) filters are used to prevent fatal and nonfatal pulmonary embolism in patients who otherwise cannot receive anticoagulation for venous thrombosis. While generally safe and effective, complications can arise, especially after prolonged implantation. Timely retrieval is essential once the indication for insertion has resolved. However, encountering patients with long-standing embedded filters is not uncommon. This case report discusses the successful retrieval of a permanent Greenfield IVC filter after 29 years.
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Remoção de Dispositivo , Desenho de Prótese , Embolia Pulmonar , Filtros de Veia Cava , Humanos , Resultado do Tratamento , Fatores de Tempo , Embolia Pulmonar/prevenção & controle , Embolia Pulmonar/etiologia , Embolia Pulmonar/diagnóstico por imagem , Flebografia , Implantação de Prótese/instrumentação , Implantação de Prótese/efeitos adversos , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/terapia , Trombose Venosa/etiologia , Feminino , Masculino , Pessoa de Meia-Idade , Veia Cava Inferior/diagnóstico por imagemRESUMO
Introduction: The health of the United Kingdom workforce is key; approximately 186 million days are lost to sickness each year. Obesity and type 2 diabetes (T2D) remain major global health challenges. The aim of this retrospective service evaluation was to assess the impact of a digitally enabled, time-restricted eating (TRE) intervention (Roczen Program, Reset Health Ltd) on weight and other health-related outcomes. Methods: This service evaluation was conducted in people living with overweight/obesity, with 89% referred from public sector employers. Participants were placed on a TRE, low-carbohydrate, moderate protein plan delivered by clinicians and mentors with regular follow up, dietary guidance, goal setting, feedback, and social support. Results: A total of 660 members enrolled and retention was 41% at 12 months. The majority were female (73.2%), 58.9% were of White ethnicity, with a mean (SD) age of 47.5 years (10.1), and a body mass index of 35.0 kg/m2 (5.7). Data were available for 82 members at 12-month. At 12-month, members mean actual and percentage weight loss was -9.0 kg (7.0; p < 0.001) and -9.2% (6.7, p < 0.001) respectively and waist circumference reduced by -10.3 cm (10.7 p < 0.001), with 45.1% of members achieving ≥10% weight loss. Glycated hemoglobin was significantly improved at 6 months in people living with T2D (-11 mmol/mol [5.7] p = 0.012). Binge eating score significantly reduced (-4.4 [7.0] p = 0.006), despite cognitive restraint increasing (0.37 [0.6] p = 0.006). Conclusion: Our service evaluation showed that the Roczen program led to clinically meaningful improvements in body weight, health-related outcomes and eating behaviors that were sustained at 12-month.
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Multiple autoimmune diseases are characterized by the involvement of autoreactive Abs in pathogenesis. Problems associated with existing therapeutics such as the delivery of intravenous immunoglobulin have led to interest in developing alternative approaches using recombinant or synthetic methods. Toward this aim, in the current study, we demonstrate that the use of Fc-engineered Abs (Abs that enhance IgG degradation [Abdegs]) to block neonatal FcR (FcRn) through high-affinity, Fc region binding is an effective strategy for the treatment of Ab-mediated disease. Specifically, Abdegs can be used at low, single doses to treat disease in the K/B×N serum transfer model of arthritis using BALB/c mice as recipients. Similar therapeutic effects are induced by 25- to 50-fold higher doses of i.v. Ig. Importantly, we show that FcRn blockade is a primary contributing factor toward the observed reduction in disease severity. The levels of albumin, which is also recycled by FcRn, are not affected by Abdeg delivery. Consequently, Abdegs do not alter FcRn expression levels or subcellular trafficking behavior. The engineering of Ab Fc regions to generate potent FcRn blockers therefore holds promise for the therapy of Ab-mediated autoimmunity.
Assuntos
Afinidade de Anticorpos , Artrite Experimental/imunologia , Artrite Experimental/terapia , Fragmentos Fc das Imunoglobulinas/uso terapêutico , Engenharia de Proteínas/métodos , Receptores Fc/antagonistas & inibidores , Animais , Anti-Inflamatórios não Esteroides/metabolismo , Anti-Inflamatórios não Esteroides/uso terapêutico , Anticorpos Bloqueadores/genética , Anticorpos Bloqueadores/metabolismo , Anticorpos Bloqueadores/uso terapêutico , Afinidade de Anticorpos/genética , Artrite Experimental/patologia , Glucose-6-Fosfato Isomerase/imunologia , Antígenos de Histocompatibilidade Classe I/metabolismo , Humanos , Fragmentos Fc das Imunoglobulinas/genética , Fragmentos Fc das Imunoglobulinas/metabolismo , Imunoglobulina G/genética , Imunoglobulina G/metabolismo , Imunoglobulina G/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos NOD , Camundongos Transgênicos , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Receptores Fc/deficiência , Receptores Fc/metabolismo , Proteínas Recombinantes/síntese química , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/uso terapêutico , Índice de Gravidade de DoençaRESUMO
Eccrine carcinomas are rare cutaneous cancers that tend to be locally aggressive. Here we report a rare case of a mucinous eccrine carcinoma presenting in axillary lymph nodes without an identifiable primary lesion. This is a 69-year-old male with a past medical history of benign prostatic hyperplasia, melanoma, basal cell carcinoma, hypercholesterolemia, hypertension, and arthritis who was found to have an elevated prostate-specific antigen. Transrectal prostate biopsies confirmed adenocarcinoma of the prostate. A chest CT scan performed for further staging of prostate cancer identified new left axillary lymphadenopathy and positron emission tomography (PET)-CT imaging showed moderate fluorodeoxyglucose (FDG) uptake in the lymph nodes of the left axilla and left subpectoral regions. Lymph node tissue obtained by core needle biopsy demonstrated high-grade carcinoma with a nonspecific immunohistochemical profile. Complete left axillary lymphadenectomy was performed, revealing mucinous eccrine carcinoma. He was started on hormonal therapy for prostate cancer and radiation therapy for axillary eccrine carcinoma at the same time. Based on our literature review, this appears to be the first case of eccrine carcinoma in axillary lymph nodes with an unknown primary. This case is further complicated by synchronous primary prostate cancer. After a multidisciplinary tumor board review, it was decided that his axillary disease should be treated as a primary mucinous carcinoma with complete lymphadenectomy followed by localized radiation. The patient had stable disease at the six-month follow-up. Cancers with unknown primary lesions pose unique challenges in disease management. Without established recommendations or guidelines, multidisciplinary discussions and a collaborative approach are needed.
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CASE PRESENTATION: A 54-year-old South African man with a medical history of type 2 diabetes mellitus, seizure disorder, OSA, and latent TB presented to the ER with gradually progressive dyspnea over months. He also reported occasional dry cough and fatigue at presentation but denied fever, chills, chest pain, leg swelling, palpitations, or lightheadedness. He was treated with a course of levofloxacin for presumed community-acquired pneumonia as an outpatient without improvement and had tested negative for COVID-19. He denied occupational or environmental exposures or sick contacts, though he had traveled back to South Africa 1 year before presentation. He had complex partial seizures for the past 22 years, which had been well controlled on phenytoin (300 mg daily). His other home medications included dulaglutide, sertraline, and atorvastatin and had no recent changes. He quit smoking 30 years ago after smoking one pack per day for 10 years.