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BACKGROUND: Cell-free DNA (cfDNA) is a noninvasive marker of cellular injury. Its significance in pulmonary arterial hypertension (PAH) is unknown. METHODS: Plasma cfDNA was measured in 2 PAH cohorts (A, n=48; B, n=161) and controls (n=48). Data were collected for REVEAL 2.0 (Registry to Evaluate Early and Long-Term PAH Disease Management) scores and outcome determinations. Patients were divided into the following REVEAL risk groups: low (≤6), medium (7-8), and high (≥9). Total cfDNA concentrations were compared among controls and PAH risk groups by 1-way analysis of variance. Log-rank tests compared survival between cfDNA tertiles and REVEAL risk groups. Areas under the receiver operating characteristic curve were estimated from logistic regression models. A sample subset from cohort B (n=96) and controls (n=16) underwent bisulfite sequencing followed by a deconvolution algorithm to map cell-specific cfDNA methylation patterns, with concentrations compared using t tests. RESULTS: In cohort A, median (interquartile range) age was 62 years (47-71), with 75% female, and median (interquartile range) REVEAL 2.0 was 6 (4-9). In cohort B, median (interquartile range) age was 59 years (49-71), with 69% female, and median (interquartile range) REVEAL 2.0 was 7 (6-9). In both cohorts, cfDNA concentrations differed among patients with PAH of varying REVEAL risk and controls (analysis of variance P≤0.002) and were greater in the high-risk compared with the low-risk category (P≤0.002). In cohort B, death or lung transplant occurred in 14 of 54, 23 of 53, and 35 of 54 patients in the lowest, middle, and highest cfDNA tertiles, respectively. cfDNA levels stratified as tertiles (log-rank: P=0.0001) and REVEAL risk groups (log-rank: P<0.0001) each predicted transplant-free survival. The addition of cfDNA to REVEAL improved discrimination (area under the receiver operating characteristic curve, 0.72-0.78; P=0.02). Compared with controls, methylation analysis in patients with PAH revealed increased cfDNA originating from erythrocyte progenitors, neutrophils, monocytes, adipocytes, natural killer cells, vascular endothelium, and cardiac myocytes (Bonferroni adjusted P<0.05). cfDNA concentrations derived from erythrocyte progenitor cells, cardiac myocytes, and vascular endothelium were greater in patients with PAH with high-risk versus low-risk REVEAL scores (P≤0.02). CONCLUSIONS: Circulating cfDNA is elevated in patients with PAH, correlates with disease severity, and predicts worse survival. Results from cfDNA methylation analyses in patients with PAH are consistent with prevailing paradigms of disease pathogenesis.
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Ácidos Nucleicos Livres , Hipertensão Arterial Pulmonar , Idoso , Biomarcadores , Ácidos Nucleicos Livres/genética , Hipertensão Pulmonar Primária Familiar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Hipertensão Arterial Pulmonar/diagnóstico , Hipertensão Arterial Pulmonar/genética , Curva ROCRESUMO
PURPOSE OF REVIEW: Cardiogenic shock (CS) is a highly morbid condition with mortality remaining greater than 30% despite improved pathophysiologic understanding and access to mechanical circulatory support (MCS). In response, shock teams modeled on successful multidisciplinary care structures for other diseases are being implemented nationwide. RECENT FINDINGS: Primary data supporting a benefit of shock team implementation on patient outcomes are relatively limited and entirely observational. Four single-center before-and-after studies and one multicenter registry study have demonstrated improved outcomes in patients with CS, potentially driven by increased pulmonary artery catheter (PAC) utilization and earlier (and more appropriate) initiation of MCS. Shock teams are also supported by a growing body of literature recognizing the independent benefit of the interventions they seek to implement, including patient phenotyping with PAC use and an algorithmic approach to CS care. Though debated, MCS is also highly likely to improve CS outcomes when applied appropriately, which further supports a multidisciplinary shock team approach to patient and device selection. SUMMARY: Shock teams likely improve patient outcomes by facilitating early patient phenotyping and appropriate intervention. Institutions should strongly consider adopting a multidisciplinary shock team approach to CS care, though additional data supporting these interventions are needed.
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Coração Auxiliar , Choque Cardiogênico , Humanos , Estudos Multicêntricos como Assunto , Sistema de Registros , Choque Cardiogênico/terapiaRESUMO
PURPOSE OF REVIEW: The 6th World Symposium on Pulmonary Hypertension (WSPH) proposed lowering the mean pulmonary artery pressure (mPAP) threshold that defines pulmonary hypertension from ≥ 25 to > 20âmmHg. The historical context and evolution of the pulmonary hypertension definition and the data used to rationalize recent changes are reviewed here. RECENT FINDINGS: There are accumulating data on the clinical significance of mildly elevated mPAPs (21-24âmmHg). Studies have demonstrated lower exercise capacity and an increased risk of progression to overt pulmonary hypertension (mPAPâ≥â25âmmHg) in specific at-risk patient populations. Further, large registries across diverse pulmonary hypertension populations have identified increased mortality in patients with mPAPs 21-24âmmHg. Although the clinical sequelae of lowering the mPAP threshold remain unclear, this uncertainty has fueled recent debates within the pulmonary hypertension community. SUMMARY: The changes to the pulmonary hypertension definition proposed by the 6th WSPH are supported by normative hemodynamic data in healthy individuals as well as studies demonstrating an association between mPAPs above this normal range and increased mortality. Whether the higher mortality observed in patients with mildly elevated mPAPs is directly attributable to pulmonary vascular disease that is amenable to therapeutic intervention remains to be determined.
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Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/fisiopatologia , Artéria Pulmonar/fisiopatologia , Pressão Arterial , Congressos como Assunto , Progressão da Doença , Humanos , Fatores de Risco , Resistência VascularRESUMO
PURPOSE OF REVIEW: Despite the progress toward understanding the molecular pathogenesis of rheumatoid arthritis (RA), its cause remains elusive. Genes are important but rather insufficient to explain the majority of RA cases. This review describes the novel data supporting the microbiome and its interactions with the human host as potential en('in')vironmental factors in RA pathogenesis. RECENT FINDINGS: Animal models of inflammatory arthritis have shown that the presence of bacteria in mucosal surfaces is sufficient to alter local and systemic host immune responses and elicit joint inflammation. Human RA studies have focused on three mucosal sites: the gut, the gingiva, and the respiratory tree. The oral microbiome, and specifically Porphyromonas gingivalis, has long been implicated. Novel sequencing technologies have allowed investigations into the role of the gut microbiome in the development of autoimmune arthritis. Most recently, the pulmonary parenchyma has also been described as yet another possible mucosal site of initiation of autoimmunity in RA. SUMMARY: Emerging data implicate the microbiome in RA pathogenesis. Mucosal sites exposed to a high load of bacterial antigens--such as the periodontium, lung, and gut--may represent the initial site of autoimmune generation. If validated, these findings could lead to the discovery of potential biomarkers and therapeutic approaches in the preclinical and clinical phases of RA.
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Artrite Reumatoide/etiologia , Inflamação/complicações , Microbiota , Animais , Antígenos de Bactérias/imunologia , Artrite Experimental/imunologia , Artrite Experimental/microbiologia , Artrite Reumatoide/imunologia , Artrite Reumatoide/microbiologia , Autoimunidade/imunologia , Modelos Animais de Doenças , Disbiose/complicações , Disbiose/imunologia , Humanos , Inflamação/imunologia , Camundongos , Mucosa/imunologia , Mucosa/microbiologia , Doenças Periodontais/complicações , Doenças Periodontais/imunologiaRESUMO
Cardiogenic shock (CS) is a heterogenous syndrome broadly characterized by inadequate cardiac output leading to tissue hypoperfusion and multisystem organ dysfunction that carries an ongoing high mortality burden. The management of CS has advanced rapidly, especially with the incorporation of temporary mechanical circulatory support (tMCS) devices. A thorough understanding of how to approach a patient with CS and to select appropriate monitoring and treatment paradigms is essential in modern ICUs. Timely characterization of CS severity and hemodynamics is necessary to optimize outcomes, and this may be performed best by multidisciplinary shock-focused teams. In this article, we provide a review of CS aimed to inform both the cardiology-trained and non-cardiology-trained intensivist provider. We briefly describe the causes, pathophysiologic features, diagnosis, and severity staging of CS, focusing on gathering key information that is necessary for making management decisions. We go on to provide a more detailed review of CS management principles and practical applications, with a focus on tMCS. Medical management focuses on appropriate medication therapy to optimize perfusion-by enhancing contractility and minimizing afterload-and to facilitate decongestion. For more severe CS, or for patients with decompensating hemodynamic status despite medical therapy, initiation of the appropriate tMCS increasingly is common. We discuss the most common devices currently used for patients with CS-phenotyping patients as having left ventricular failure, right ventricular failure, or biventricular failure-and highlight key available data and particular points of consideration that inform tMCS device selection. Finally, we highlight core components of sedation and respiratory failure management for patients with CS.
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Cardiogenic shock is an extreme manifestation of acute decompensated heart failure. Cardiogenic shock is often caused by-and has traditionally been studied in the setting of-acute myocardial infarction (AMI CS); however, there is increasing incidence and recognition of cardiogenic shock not associated with acute myocardial infarction (non-AMI CS) as a distinct entity. Despite decades of study and technologic advancements, cardiogenic shock mortality remains as high as 50%, regardless of etiology. New approaches to shock phenotyping and classification have emerged, with a focus on appropriately matching patient physiology to a growing list of available interventions. Further study is needed to determine whether these efforts will lead to more nuanced use of mechanical circulatory support and improved patient outcomes, especially in non-AMI CS. In the meantime, models of care incorporating multidisciplinary decision making, such as shock teams, may improve patient selection and outcomes.
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Insuficiência Cardíaca , Infarto do Miocárdio , Humanos , Choque Cardiogênico/terapia , Choque Cardiogênico/complicações , Infarto do Miocárdio/complicações , Infarto do Miocárdio/terapia , Insuficiência Cardíaca/complicações , Resultado do TratamentoRESUMO
BACKGROUND: Demographics in cardiac intensive care units (CICUs) have evolved, with increased prevalence of noncardiac critical illnesses. OBJECTIVES: This study compares outcomes of patients with primary cardiac diagnoses admitted to CICUs vs those of patients with primary cardiac diagnoses admitted to noncardiac ICUs. METHODS: The Cerner Health Facts Database was queried to identify adults with primary cardiac diagnoses admitted to ICUs within 48 hours of presentation between 2009 and 2014. Only hospitals with multiple ICUs including a CICU were studied. Information on ICU staffing was not available. A univariate analysis of ICU type (model 1) and multivariate analyses incorporating patient- and hospital-level variables (model 2) and concurrent, noncardiac, ICU-level diagnoses (model 3) were utilized to assess the impact of ICU type on inpatient mortality. RESULTS: Of 16,163 encounters across 14 hospitals, 8,499 (52.6%) were admitted to CICUs and 7,664 (47.4%) to noncardiac ICUs. Univariate analysis (model 1) demonstrated increased mortality in noncardiac ICUs compared to CICUs (odds ratio [OR]: 1.47, 95% CI: 1.32-1.64; P < 0.0001). This risk dissipated (OR: 1.04, 95% CI: 0.91-1.18; P = 0.56) after controlling for patient- and hospital-level variables (model 2). Inclusion of concurrent, noncardiac, ICU-level diagnoses (model 3) lead to a reversal with decreased mortality in noncardiac ICUs (OR: 0.86, 95% CI: 0.76-0.98; P = 0.03). CONCLUSIONS: In this historical cohort study evaluating CICU outcomes prior to the evolution of proposed staffing and care model modernization, survival of cardiac patients with concurrent, noncardiac critical illnesses may have been better with the expertise available in general system ICUs. These results may support contemporary efforts to increase the capacity to manage noncardiac critical illnesses in CICUs.
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Oxygen supplementation has been a mainstay in the management of patients with acute cardiac disease. While hypoxia is known to be detrimental, the adverse effects of artificially high oxygen levels (hyperoxia) have only recently been recognized. Hyperoxia may induce harmful hemodynamic effects, including peripheral and coronary vasoconstriction, and direct cellular toxicity through the production of reactive oxygen species. In addition, emerging evidence has shown that hyperoxia is associated with adverse clinical outcomes. Thus, it is essential for the cardiac intensive care unit (CICU) clinician to understand the available evidence and titrate oxygen therapies to specific goals. This review summarizes the pathophysiology of oxygen within the cardiovascular system and the association between supplemental oxygen and hyperoxia in patients with common CICU diagnoses, including acute myocardial infarction, heart failure, shock, cardiac arrest, pulmonary hypertension, and respiratory failure. Finally, we highlight lessons learned from available trials, gaps in knowledge, and future directions.
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PURPOSE: COVID-19 challenged medical practice and graduate medical education. Building on previous initiatives, we describe and reflect on the formative process and goals of the Hematology-Oncology Collaborative Videoconferencing Learning Initiative, a trainee-led multi-institutional virtual COVID-19 learning model. METHODS: Clinical fellows and faculty from 13 US training institutions developed consensus needs, goals, and objectives, recruited presenters, and generated a multidisciplinary COVID-19 curriculum. Weekly Zoom conferences consisted of two trainee-led instructional segments and a trainee-moderated faculty Q&A panel. Hematology-oncology training program faculty and trainees were the targeted audience. Leadership evaluations consisted of anonymized baseline and concluding mixed methods surveys. Presenter evaluations consisted of session debriefs and two structured focus groups. Conference evaluations consisted of attendance, demographics, and pre- or postmultiple-choice questions on topic learning objectives. RESULTS: In 6 weeks, the initiative produced five conferences: antivirals, anticoagulation, pulmonology, provider resilience, and resource scarcity ethics. The average attendance was 100 (range 57-185). Among attendees providing both pre- and postconference data, group-level knowledge appeared to increase: antiviral (n = 46) pre-/postcorrect 82.6%/97.8% and incorrect 10.9%/2.2%, anticoagulation (n = 60) pre-/postcorrect 75%/93.3% and incorrect 15%/6.7%, and pulmonary (n = 21) pre-/postcorrect 66.7%/95.2% and incorrect 33.3%/4.8%. Although pulmonary management comfort appeared to increase, comfort managing of antivirals and anticoagulation was unchanged. At the conclusion of the pilot, leadership trainees reported improved self-confidence organizing multi-institutional collaborations, median (interquartile range) 58.5 (50-64) compared with baseline 34 (26-39), but did not report improved confidence in other educational or leadership skills. CONCLUSION: During crisis, trainees built a multi-institutional virtual education platform for the purposes of sharing pandemic experiences and knowledge. Accomplishment of initiative goals was mixed. Lessons learned from the process and goals may improve future disaster educational initiatives.
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COVID-19 , Educação a Distância , Hematologia , Hematologia/educação , Humanos , SARS-CoV-2 , Comunicação por VideoconferênciaRESUMO
Pulmonary arterial hypertension is characterized by endothelial dysfunction and microthrombi formation. The role of anticoagulation remains controversial, with studies demonstrating inconsistent effects on pulmonary arterial hypertension mortality. Clinical anticoagulation practices are currently heterogeneous, reflecting physician preference. This study uses thrombelastography and hematology markers to evaluate whether clot formation and fibrinolysis are abnormal in pulmonary arterial hypertension patients. Venous blood was collected from healthy volunteers (n = 20) and patients with pulmonary arterial hypertension (n = 20) on stable medical therapy for thrombelastography analysis. Individual thrombelastography parameters and a calculated coagulation index were used for comparison. In addition, hematologic markers, including fibrinogen, factor VIII activity, von Willebrand factor activity, von Willebrand factor antigen, and alpha2-antiplasmin, were measured in pulmonary arterial hypertension patients and compared to healthy volunteers. Between group differences were analyzed using t tests and linear mixed models, accounting for repeated measures when applicable. Although the degree of fibrinolysis (LY30) was significantly lower in pulmonary arterial hypertension patients compared to healthy volunteers (0.3% ± 0.6 versus 1.3% ± 1.1, p = 0.04), all values were within the normal reference range (0-8%). All other thrombelastography parameters were not significantly different between pulmonary arterial hypertension patients and healthy volunteers (p ≥ 0.15 for all). Similarly, alpha2-antiplasmin activity levels were higher in pulmonary arterial hypertension patients compared to healthy volunteers (103.7% ± 13.6 versus 82.6% ± 9.5, p < 0.0001), but all individual values were within the normal range (75-132%). There were no other significant differences in hematologic markers between pulmonary arterial hypertension patients and healthy volunteers (p ≥ 0.07 for all). Sub-group analysis comparing thrombelastography results in patients treated with or without prostacyclin pathway targeted therapies were also non-significant. In conclusion, treated pulmonary arterial hypertension patients do not demonstrate abnormal clotting kinetics or fibrinolysis by thrombelastography.
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Acute kidney injury (AKI) and cardiorenal syndrome (CRS) are increasingly prevalent in hospitalized patients with cardiovascular disease and remain associated with poor short- and long-term outcomes. There are no specific therapies to reduce mortality related to either AKI or CRS, apart from supportive care and volume status management. Acute renal replacement therapies (RRTs), including ultrafiltration, intermittent hemodialysis, and continuous RRT are used to manage complications of medically refractory AKI and CRS and may restore normal electrolyte, acid-base, and fluid balance before renal recovery. Patients who require acute RRT have a significant risk of mortality and long-term dialysis dependence, emphasizing the importance of appropriate patient selection. Despite the growing use of RRT in the cardiac intensive care unit, there are few resources for the cardiovascular specialist that integrate the epidemiology, diagnostic workup, and medical management of AKI and CRS with an overview of indications, multidisciplinary team management, and transition off of RRT.
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Injúria Renal Aguda/terapia , Síndrome Cardiorrenal/terapia , Gerenciamento Clínico , Terapia de Substituição Renal/normas , Índice de Gravidade de Doença , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/fisiopatologia , Síndrome Cardiorrenal/epidemiologia , Síndrome Cardiorrenal/fisiopatologia , Cardiologia/métodos , Cardiologia/normas , Hemofiltração/métodos , Hemofiltração/normas , Humanos , Diálise Renal/métodos , Diálise Renal/normas , Terapia de Substituição Renal/métodos , Estados Unidos/epidemiologia , Equilíbrio Hidroeletrolítico/fisiologiaRESUMO
The COVID-19 pandemic has presented a major unanticipated stress on the workforce, organizational structure, systems of care, and critical resource supplies. To ensure provider safety, to maximize efficiency, and to optimize patient outcomes, health systems need to be agile. Critical care cardiologists may be uniquely positioned to treat the numerous respiratory and cardiovascular complications of the SARS-CoV-2 and support clinicians without critical care training who may be suddenly asked to care for critically ill patients. This review draws upon the experiences of colleagues from heavily impacted regions of the United States and Europe, as well as lessons learned from military mass casualty medicine. This review offers pragmatic suggestions on how to implement scalable models for critical care delivery, cultivate educational tools for team training, and embrace technologies (e.g., telemedicine) to enable effective collaboration despite social distancing imperatives.
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Serviço Hospitalar de Cardiologia , Infecções por Coronavirus , Cuidados Críticos , Atenção à Saúde , Inovação Organizacional , Pandemias/prevenção & controle , Pneumonia Viral , Betacoronavirus/isolamento & purificação , COVID-19 , Serviço Hospitalar de Cardiologia/organização & administração , Serviço Hospitalar de Cardiologia/tendências , Defesa Civil/métodos , Defesa Civil/organização & administração , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Cuidados Críticos/métodos , Cuidados Críticos/organização & administração , Cuidados Críticos/tendências , Atenção à Saúde/métodos , Atenção à Saúde/organização & administração , Atenção à Saúde/tendências , Humanos , Objetivos Organizacionais , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , SARS-CoV-2RESUMO
Background Cardiovascular intensive care units ( CICUs ) have evolved from coronary care wards into distinct units for critically ill patients with primary cardiac diseases, often suffering from illnesses that cross multiple disciplines. Mounting evidence has demonstrated improved survival with the incorporation of dedicated CICU providers with expertise in critical care medicine ( CCM ). This is the first study to systematically survey dual certified physicians in order to assess the relevance of CCM training to contemporary CICU care. Methods and Results Utilizing American Board of Internal Medicine data through 2014, 397 eligible physicians had obtained initial certification in both cardiovascular disease and CCM . A survey to delineate the role of critical care training in the CICU was provided to these physicians. Among those surveyed, 120 physicians (30%) responded. Dual certified physicians reported frequent use of their CCM skills in the CICU , highlighting ventilator management, multiorgan dysfunction management, end-of-life care, and airway management. The majority (85%) cited these skills as the reason CCM training should be prioritized by future CICU providers. Few (17%) agreed that general cardiology fellowship alone is currently sufficient to care for patients in the modern CICU . Furthermore, there was a consensus that there is an unmet need for cardiologists trained in CCM (70%) and that CICU s should adopt a level system similar to trauma centers (61%). Conclusions Citing specific skills acquired during CCM training, dual certified critical care cardiologists reported that their additional critical care experience was necessary in their practice to effectively deliver care in the modern CICU .
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Cardiologistas/educação , Doenças Cardiovasculares/terapia , Certificação/métodos , Competência Clínica , Cuidados Críticos , Educação de Pós-Graduação em Medicina/métodos , Unidades de Terapia Intensiva/estatística & dados numéricos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estados UnidosRESUMO
Two new definitions of exercise-induced pulmonary hypertension (EIPH) have emerged. Both rely on measuring cardiac output (CO), yet this remains unstandardized. In our cohort of patients undergoing invasive cardiopulmonary exercise testing, we found that using thermodilution CO rather than direct Fick CO led to a significant excess of EIPH diagnoses.
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OBJECTIVE: To characterize the diversity and taxonomic relative abundance of the gut microbiota in patients with never-treated, recent-onset psoriatic arthritis (PsA). METHODS: High-throughput 16S ribosomal RNA pyrosequencing was utilized to compare the community composition of gut microbiota in patients with PsA (n = 16), patients with psoriasis of the skin (n = 15), and healthy, matched control subjects (n = 17). Samples were further assessed for the presence and levels of fecal and serum secretory IgA (sIgA), proinflammatory proteins, and fatty acids. RESULTS: The gut microbiota observed in patients with PsA and patients with skin psoriasis was less diverse when compared to that in healthy controls. This could be attributed to the reduced presence of several taxa. Samples from both patient groups showed a relative decrease in abundance of Coprococcus species, while samples from PsA patients were also characterized by a significant reduction in Akkermansia, Ruminococcus, and Pseudobutyrivibrio. Supernatants of fecal samples from PsA patients revealed an increase in sIgA levels and decrease in RANKL levels. Analysis of fatty acids revealed low fecal quantities of hexanoate and heptanoate in both patients with PsA and patients with psoriasis. CONCLUSION: Patients with PsA and patients with skin psoriasis had a lower relative abundance of multiple intestinal bacteria. Although some genera were concomitantly decreased in both conditions, PsA samples had a lower abundance of reportedly beneficial taxa. This gut microbiota profile in PsA was similar to that previously described in patients with inflammatory bowel disease and was associated with changes in specific inflammatory proteins unique to this group, and distinct from that in patients with skin psoriasis and healthy controls. Thus, the role of the gut microbiome in the continuum of psoriasis-PsA pathogenesis and the associated immune response merits further study.