Presence Of Connective Tissue Disease Research Articles

Idiopathic pulmonary arterial hypertension, associated with connective tissue disease and comorbidities: prognostic differences? Results the Spanish Registry of pulmonary hypertension (REHAP Registry)

Abstract Introduction Idiopathic pulmonary arterial hypertension (iPAH) and associated with connective tissue disease (PAH-SSc) are the most frequent groups of pulmonary arterial hypertension (PAH) but their long-term survival is usually unequal. Comorbidities, increasing in frequency in these patients, show prognostic influences but it is not known whether these differ in both groups of patients. Methods We collected patients diagnosed with iPAH, heritable, associated with drug or toxine exposure and PAH-SSc between 2014 and 2023 from the Spanish Registry of Pulmonary Hypertension. Patients are classifies into iPAH and PAH-SSc. We analyzed baseline characteristics and the distribution of the different comorbidities in the two groups. Survival analyses estimated by Kaplan-Meier analysis using the log-rank test were done according to PAH etiology and comorbidities and Cox proportional hazard analyses were performed to determine the effects of baseline characteristics on survival. Results Seven hundred and fifty-seven patients were selected for this study. The characteristics of the patients are shown in Table 1. Patients with PAH-SSc compared to iPAH were older (62 vs 56 years), more female (81.8% vs 62.4%), had a more favorable hemodynamic profile, TAPSE/sPAP ratio and lower NT-proBNP levels. No differences were found in functional class or 6MWT. We found a higher proportion of patients in a low and intermediate risk profile, according to ESC, in patients with PAH-SSC as opposed to PAHi (46.8/50.9% vs. 29.3/64.5%; p<0.001). Regarding comorbidities, history of smoking (27.1 vs 54%; p<0-001), obesity (17.1 vs 20.7%; p<0.001) and diabetes (9.4 vs 22.1%; p<0.001) are less frequent in PAH-SSc than in iPAH. There are no differences in the rest of the comorbidities studied in the two groups of patients. In a survival analysis, we found no differences between patients with iPAH and PAH-SSc at 7-year follow-up. Patients with ≥ 3 comorbidities had statistically significantly higher mortality (p<0.001) compared to those with 0 or 1-2 comorbidities in both etiologies. There were no differences between 0 and 1-2 comorbidities. (Figure 1). Variables associated with mortality were male sex (HR 1.9, 95% CI 1,28 – 2.8), age (HR 1.04, 95% CI 1.02 – 1.06), the intermediate risk profile (HR 2.64, 95% CI 1.62 – 4.32) and high risk profile (HR 9.97, 95% CI 4.36 – 18.47), but not etiology. The presence of connective tissue diseases, were not associated with increased mortality. Conclusions Patients with PAH-SSc show lower comorbidities, better hemodynamic profile, RV-PA coupling and risk profile than those with iPAH. Comorbidity has a great relevance in survival but without differences according to etiology. The presence of male sex, age, the intermediate and high risk profile is associated with worse survival, but not the connective tissue diseases.

The importance of comorbidities in idiopathic and associated with connective tissue disease pulmonary arterial hypertension: from the Spanish Registry of Pulmonary Hypertension (REHAP Registry)

Abstract Introduction Comorbidities play a major role in the prognosis of patients with pulmonary arterial hypertension (PAH). These comorbidities are present in more than 80% of patients diagnosed in the last years with idiopathic PAH (iPAH) and their presence is associated with increased morbidity and mortality although its influence on PAH associated with connective tissue disease (PAH-SSc) is unknown. We studied the impact of comorbidities on iPAH and PAH-SSc in the Spanish population. Methods We collected patients diagnosed with iPAH, heritable, associated with drug or toxine exposure and PAH-SSc between 2014 and 2023 from the Spanish Registry of Pulmonary Hypertension. Patients are classified into: no comorbidities, 1-2 comorbidities and ≥3 comorbidities. We analyzed the impact of comorbidities in baseline characteristics, exercise capacity and hemodynamic profile, as well as in the risk profile and initial treatment. Survival analyses estimated by Kaplan-Meier analysis using the log-rank test and Cox proportional hazard analyses were performed to determine the effects of baseline characteristics on survival. Results 757 patients were selected for this study. The characteristics of the patients are shown in Table 1. As the number of comorbidities increases (0/1-2/≥3) we found higher age (49/59/67 years; p<0.001), higher percentage of male sex (12.9/29.9/43.4%; p<0.001) and higher FC III at diagnosis (42.7/46.9/59.6%; p=0.013). We observed a shorter distance in 6MWD, higher NT-proBNP levels, lower DLCO and a less unfavorable hemodynamic profile (PAPm, PAWP, CI and PVR). The most frequent comorbidities were a history of smoking (46.4%), followed by arterial hypertension (41.5%), obesity (24.6%) and chronic kidney disease (19.2%). Diabetes mellitus, although less frequent, reached more than 55% in patients with ≥3 comorbidities (p<0.001). The presence of ≥ 3 comorbidities was more frequent in iPAH than PAH-SSc (p<0,001). Intermediate risk profile was the most common (58.4%) and this reached 68.7% in those with ≥3 comorbidities due to a lower number of patients in a low-risk profile (p<0.001). A statistically significant lower survival (p<0.001) was observed in patients with ≥ 3 comorbidities; however, we found no differences between 0 and 1-2 comorbidities at 7-year follow-up (Figure 1). Variables associated with mortality were male sex (HR 1.88, 95% CI 1,26 – 2.8), age (HR 1.04, 95% CI 1.02 – 1.06) and the presence of ≥3 comorbidities (HR 1.49, 95% CI 0.98 – 2.27), not the presence of connective tissue diseases, which were not associated with increased mortality in our study. Conclusions The presence of comorbidities in iPAH and PAH-SSc is very frequent in the Spanish population. They are associated with a worse clinical profile, risk profile, lower use of oral double theraphy and prostacyclins. The presence of ≥3 comorbidities is associated with worse survival, not the presence of 1-2 comorbidities or connective tissue disease.

Thyroid cancer and autoimmune connective tissue disorders.

There are substantial data confirming the association between autoimmune disorders, including connective tissue diseases (CTDs), and an increased risk of thyroid malignancy. CTDs and thyroid cancer may co-exist as 2 separate diseases because of their relatively high incidence rates in the population. They can arise from each other due to the increased risk of thyroid cancer in patients with idiopathic inflammatory myositis, rheumatoid arthritis, systemic sclerosis, primary Sjögren's syndrome, and systemic lupus erythematosus. Moreover, in some scarce cases, CTDs may act as the paraneoplastic syndromes of thyroid cancer. The presence of CTDs may impact the diagnostic process, especially distorting the results of imaging tests or falsely indicating the increase of thyroglobulin or calcitonin. Finally, TSH suppression is a crucial element of the treatment of differentiated thyroid cancer, which may decrease bone mineral density and increase the risk of osteoporosis by accelerating bone turnover and shortening the bone remodeling cycle. The aim of this review is to emphasise the vital aspects of this interrelationship. The authors discuss this phenomenon aiming at the explanation of possible linking mechanisms. The impact of selected CTDs on thyroid cancer management is presented, as well as the possible effects of cancer therapy on skeletal health.

Clinical features and prognosis of lung cancer in patients with connective tissue diseases: a retrospective cohort study.

Studies have demonstrated a close association between connective tissue diseases (CTDs) and lung cancer (LC). Evidence supports that poor survival may be associated with the presence of CTDs in patients with LC. This retrospective cohort study investigated 29 patients with LC with CTDs, and 116 patients with LC without CTDs were enrolled as case-matched control cohorts. Medical records, therapeutic efficacy of cancer, and outcomes were analyzed. The median duration from the diagnosis of CTDs to LC was 17 years. The Eastern Cooperative Oncology Group (ECOG) performance score for LC-CTD patients was worse than that for matched non-CTD LC patients. The median progression-free survival (mPFS) and overall survival (mOS) of first-line chemotherapy did not differ between patients with lung adenocarcinoma (AC) with and without CTDs. A significant difference was observed in mPFS [4 months vs. 17 months; hazard ratio (HR), 9.987; p = 0.004] and mOS (6 months vs. 35 months; HR, 26.009; p < 0.001) of first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment between patients with AC with and without CTDs. The presence of CTD, sex, ECOG performance status, and tumor-node-metastasis clinical stage were the independent prognostic factors in all patients with non-small cell LC (NSCLC). ECOG performance status was determined to be an independent prognostic factor in patients with LC-CTD. In patients with NSCLC with CTD (n = 26), sex (male) and worse ECOG score were the independent poor prognostic factors. CTDs were associated with poor survival in patients with LC. The therapeutic efficacy of first-line EGFR-TKI therapy was significantly worse in patients with lung AC with CTDs than in those without CTDs. ECOG performance status was determined as an independent prognostic factor for patients with LC and CTDs.

A RARE CASE REPORT OF MULTIPLE CONNECTIVE TISSUE DISEASE WITH SEVERE PULMONARY HYPERTENSION

A 38 year old female presented with complaints of tightness, dryness, hyperpigmentation of skin , tightness of mouth, tingling numbness and pain in ngers while handling cold water since 6 months. Exertional breathelessness since 1 month .She had history of swelling of hands six months back. Finger examination showed sclerodactyly and ulceration over skin on interphalangeal joints of both hands without any deformity .Since clinical ndings were suggestive of Raynaud's phenomenon, sclerodactyly, swelling of hands , scleroderma, she was further investigated for presence of connective tissue disease . On immunological investigations , ANA prole was positive with presence of strong positive U1RNP antibodies (titre&gt;1:1600). Chest x ray and 2d echocardiography revealed presence of Pulmonary Hypertension. She was diagnosed with Multiple Connective Tissue Disease (MCTD) with severe pulmonary hypertension based on clinical , radiological and laboratory ndings satisfying Alarcon Segovia criteria.

Infrared thermography and capillaroscopy in the diagnosis of Raynaud's phenomenon.

Raynaud's phenomenon (RP) is a relatively common disease. There are two distinct forms of RP - primary (PRP), where no other associated diseases are present, and secondary (SRP), where RP is associated with other diseases. It can be challenging to differentiate between RP and other diseases through medical history alone, due to the episodic nature of RP. Objective analysis of anamnestic data was performed in our study using infrared thermography (IRT) and a cold pressor test (CPT). Capillaroscopy was performed to assess morphological changes in the acral circulation. Patients with a history of cold hands were included in the study. IRT was performed before and after the CPT, and then capillaroscopy was performed. The results (including epidemiologic data) were statistically evaluated. A total of 150 patients were included in the study. Summarisation of the results from the IRT and capillaroscopy determined the final diagnosis - 4.7% acrocyanosis, 10.7% physiologic findings, 31.3% PRP, 29.3% borderline SRP and 24% SRP. The coldest fingers following the CPT were, in most patients, the 2nd and 3rd fingers. The correlation between the presence of connective tissue disease and the diagnosis of borderline SRP and SRP was significant (P=0.0001). Using the combination of the IRT and capillaroscopy in the diagnostic algorithm for RP has its justification. IRT distinguishes healthy patients from patients with RP, and capillaroscopy can then be used to differentiate PRP from SRP. IRT can also detect which fingers are more affected, and then these can direct the focus of capillaroscopy.

Genetic Background of Hypertension in Connective Tissue Diseases.

Peroxisome proliferator-activated receptors (PPAR gamma-2) and beta-3-adrenergic receptors (ADRB3) are involved in the risk of hypertension. But their exact role in blood pressure modulation in patients with connective tissue diseases (CTD) is still not well defined. In this study, 104 patients with CTD and 103 gender- and age-matched controls were genotyped for Pro12Ala and C1431T polymorphisms of the PPAR gamma-2 gene and Trp64Arg polymorphism of the ADRB gene. Anthropometric and biochemical measurements were evaluated, followed by genotyping using TaqMan® SNP genotyping assays and polymerase chain reaction-restriction fragment length polymorphism. The prevalence of analyzed genotypes and alleles was comparable between patients with CTD and the control group, as well as hypertensive and normotensive subjects. Patients with CTD have lower body fat and higher body water amount, serum glucose, and triglyceride (TG) levels. Hypertensive subjects are older and have higher body mass, BMI, waist circumference (WC), body water content, glucose, and TG concentration. The multivariate analysis revealed that hypertensive subjects with Ala12/X or Trp64Trp have higher body mass and WC when compared to normotensive subjects. Trp64Trp polymorphism was also characterized by a higher TG level, while T1431/X subjects had higher WC. The presence of CTD, visceral fat distribution, and increased age are the predictors of hypertension development. Hypertensive patients with CTD and Trp64Trp polymorphism have an increased risk of visceral obesity development and metabolic complications, which in turn affects the value of blood pressure. In addition, either Ala12/X or T1431/X predicts the visceral body fat distribution in hypertensive subjects.

Bilateral Extracranial Carotid Artery Aneurysms: A Rare Complication of Marfan Syndrome

Marfan Syndrome (MFS) is an autosomal dominant connective tissue disorder caused by a mutation in the FBN1 gene that encodes for the extracellular matrix protein fibrillin-1. The clinical manifestations of MFS which lead to morbidity and mortality are primarily those involving aortic disease, such as aneurysmal dilation, aortic regurgitation, and aortic dissection. Despite 60-80% of adults with MFS having some degree of aortic disease, carotid artery aneurysms are rare and usually represent extensions of aortic dissections.1 We report a 70-year-old female with a history of ectopia lentis and family history of MFS who presented to the ED with epistaxis and anemia. An arteriogram revealed an incidental finding of bilateral carotid artery aneurysms a rare phenomenon even in the presence of connective tissue disease. Review of the literature reveals very little data on the clinical presentation, treatment, and outcome of MFS patients with extracranial carotid artery aneurysms (ECAAs). We discuss presentation, etiology, and management options reported for these rare occurrences.

Nailfold Capillaroscopy of Resting Peripheral Blood Flow in Exfoliation Glaucoma and Primary Open-Angle Glaucoma

Systemic blood flow alterations have been described using video nailfold capillaroscopy (NFC) in high-tension glaucoma (HTG) and normal-tension glaucoma (NTG) variants of primary open-angle glaucoma (POAG). To date, no previous studies have explored alterations in nailfold capillary blood flow in exfoliation glaucoma (XFG). To investigate the measure of peripheral blood flow as a surrogate marker of systemic vascular involvement in patients with XFG, HTG, and NTG, as well as in individuals serving as controls, using NFC. A cross-sectional clinic-based study at the New York Eye and Ear Infirmary of Mount Sinai was conducted from July 6, 2017, to May 18, 2018. A total of 111 participants (30 XFG, 30 NTG, 30 HTG, and 21 controls) received a comprehensive ophthalmic examination to confirm eligibility. Exclusion criteria were the presence of connective tissue disease, uncontrolled diabetes, history of bleeding disorders, and/or history of trauma or surgery to the nondominant hand. Resting capillary blood flow at the nailfold of the fourth digit of the nondominant hand in patients with NTG, HTG, XFG, and controls, using NFC. Two participants were excluded owing to poor nailfold image quality, resulting in 109 participants. Sixty-two participants (57%) were women and 79 (72%) were white. Mean (SD) age of the participants was 67.9 (11.7) years. Mean (SD) resting peripheral capillary blood flow at the nailfold for controls was 70.9 (52.4) picoliters/s (pL/s); HTG, 47.5 (41.9) pL/s; NTG, 40.1 (16.6) pL/s; and XFG, 30.6 (20.0) pL/s. Multivariable analysis of the differences of flow in HTG vs control participants showed values of -18.97 (95% CI, -39.22 to 1.27; P = .07) pL/s, NTG vs controls of -25.17 (95% CI, -45.92 to -4.41; P = .02) pL/s, and XFG vs controls of -28.99 (95% CI, -51.35 to -6.63; P = .01) pL/s. Decreased resting peripheral capillary blood flow may occur in patients with XFG and NTG compared with individuals without glaucoma. These findings may contribute to understanding the possible systemic nature of glaucoma.

Computer Aided Diagnosis for Anti-Nuclear Antibodies HEp-2 images: Progress and challenges

The Anti-Nuclear Antibodies (ANA) test using Human Epithelial (HEp-2) cells has been the gold standard to identify the presence of Connective Tissue Diseases (CTD) such us Systemic Lupus Erythomatus (SLE). As the ANA test is time consuming, labor intensive and subjective, there has been an on-going effort to develop image-based Computer Aided Diagnosis (CAD) systems. This paper discusses the current progress and challenges in this field and will highlight areas which require more attention.

Thrombotic thrombocytopenic purpura in the presence of connective tissue disease and HIV infection: A diagnostic and therapeutic challenge in a resource- constrained setting.

Thrombotic thrombocytopenic purpura is a catastrophic disease and may occur in the presence of other confounding diseases. We present a case of TTP in a patient with connective tissue disease and HIV infection, in whom the diagnosis and management of TTP was challenging. It is important to understand the various underlying mechanisms that drive TTP in the presence of these comorbid diseases, so that an appropriate treatment strategy can be initiated. Our patient failed an initial trial of plasma infusion alone, but responded well to plasma exchange.

Increased Prevalence of Autoimmunity and Connective Tissue Diseases in Sickle Cell Disease

Connective tissue disease (CTD) and sickle cell disease (SCD) are diverse group of disorders; however, both of these diseases are characterized by underlying chronic inflammation. CTD is perceived to have a higher incidence and to affect the disease severity in SCD. Objectives: We seek to describe prevalence of autoimmunity and CTD and itsimpact on SCD disease severity as this is not well described in the literature. Methods: We retrospectively reviewed the medical records of 722 patients with SCD, seen over an 11 year period followed at a tertiary care hospital in London, UK. During the last 2 years of the study, number of hospitalizations and length of hospital stay were compared in patients with SCD with and without CTD. Results: In the study cohort, hemoglobin SS was the most common genotype (n = 451; 62%) and 411 (57%) were female. Twenty-three patients (3.1% had documented evidence of CTD, with rheumatoid arthritis (n = 14; 2%) and systemic lupus erythematosus (n = 2; 0.3%) being the most common. Antinuclear antibody was present in 108 (15%) of the patients and anti-smooth muscle antibody was present in 60 (8%). The mean number of hospitalizations (1.9 ± 2.7 vs. 1.5 ± 2.7) and mean length of hospital stay (6 days ± 4.1 vs. 7 days ± 11.4) were not different between those with or without autoimmunity and/or CTD. Avascular necrosis was the most common non-CTD musculoskeletal complication, affecting 72 (10%) patients. Conclusion: Our study suggests that positive autoimmune serology and CTD were more common in SCD compared to non-SCD population of similar ethnic background; however, presence of CTD does not appear to affect the SCD severity. The high frequency of CTD and overlapping of clinical symptoms suggest a need for diagnostic vigilance in diagnosing CTD in patients with SCD.

Influence of autoimmune biomarkers on interstitial lung diseases: A tertiary referral center based case-control study

BackgroundThe benefit of routinely measuring autoimmune biomarkers to evaluate patients with interstitial lung disease (ILD) remains debated outside specific contexts such as connective tissue disease (CTD). This study aimed at evaluating the influence of biomarkers on outcome on patients with ILD in a case-control study at a tertiary referral center. We hypothesized that patients with positive autoimmune biomarkers have increased odds of developing ILD even in the absence of CTD.MethodsWe reviewed the medical records of 3573 patients seen at the ILD clinic in Mayo Clinic Rochester between September 2001 and September 2006. We assessed their clinical course through June 25, 2013. We included patients with patterns of ILD most often associated with CTD (n=1256) while excluding patients with other known causes of ILD. Controls (n=2317) included cases seen at the ILD clinic without evidence of ILD.ResultsWe identified 930 (26%) cases of ILD alone, 124 (3%) CTD alone, 326 (9%) ILD combined with CTD, and 2193 (61%) with no ILD or CTD. Positive antinuclear antibodies (ANA), rheumatoid factor and aldolase were associated with ILD. After adjustment for age, gender, race, smoking history and CTD, ANA remained an independent risk factor for ILD (OR 1.70, 95% CI 1.33–2.17). Among patients with ILD, the presence of CTD but not biomarker alone was associated with a better survival.ConclusionIn this study, the presence of positive biomarkers was associated with increased odds of ILD, even in the absence of overt CTD, but was not associated with a better outcome.

Causes of Pulmonary Hypertension in the Elderly

Pulmonary hypertension (PH) is common in elderly patients, but a detailed analysis of the causes of PH in the elderly has not been performed. We hypothesized that pulmonary arterial hypertension (PAH) is rare in elderly patients and sought to describe the characteristics of these patients at a large referral center. Clinical and hemodynamic data were collected on consecutive patients ≥ 65 years of age referred for evaluation of PH. The subtype of PH was determined after standard evaluation using the World Health Organization (WHO) classification. Patients with PH not meeting criteria for PAH with "out-of-proportion" PH related to group 2 or group 3 disease were classified as "other/mixed PH." A model using age, presence of connective tissue disease, and left atrial size was developed to predict the probability of PAH diagnosis. Two hundred forty-six elderly patients were evaluated (mean age, 72.9 ± 5.5 years, 78% women); 36 had PAH (15%). Idiopathic PAH was rare (four patients, 1.6%). WHO group 2 PH was the most frequent diagnosis (n = 70, 28% of cohort); mixed/other PH (n = 43, 17%) and WHO group 3 PH (n = 34, 14%) were also common diagnoses. Connective tissue disease strongly predicted PAH diagnosis (OR, 27.2; 95% CI, 9.5-77.6). PAH is an uncommon cause of PH in elderly patients, most frequently associated with connective tissue disease. WHO group 2 PH and mixed disease are common, highlighting a need for careful phenotyping of elderly patients with PH prior to initiating PAH therapy.

Factors Associated With Positive Findings From Capsule Endoscopy in Patients With Obscure Gastrointestinal Bleeding

Capsule endoscopy (CE) is used most frequently to identify causes of obscure gastrointestinal bleeding (OGIB). Identifying factors associated with the detection of lesions by CE could improve resource utilization and thereby improve patient selection for CE examination. We sought to identify clinical factors associated with positive findings from CE in patients with OGIB. We analyzed data from 698 CE procedures performed between December 2001 and April 2011 at St Paul's Hospital, Vancouver, Canada (50.3% of patients were female; mean age, 63.4 years). A positive finding was defined as a lesion that was believed to be the source of the bleeding (ulceration, mass lesion, vascular lesion, or visible blood). Univariate and multivariate logistic regression analyses were used to correlate demographic and clinical parameters with positive findings. A lesion believed to be the cause of bleeding was identified in 42% of cases. In univariate analysis, the number of esophagogastroduodenoscopies (EGDs), the presence of connective tissue disease or diabetes with end-organ damage, Charlson comorbidity index scores, and increasing transfusion requirements were significantly associated with identification of causative pathology from CE (all P < .027). In multivariate analysis, increasing number of EGDs (odds ratio [OR], 1.17; 95% confidence interval [CI], 1.00-1.37), increasing transfusion requirements (3-9 units: OR, 1.70; 95% CI, 1.08-2.66, and ≥10 units: OR, 2.72; 95% CI, 1.69-4.37), and connective tissue disease (OR, 2.24; 95% CI, 1.14-4.41) were all significantly associated with identification of positive findings by using CE (all P < .045). Patients with a higher number of precapsule EGDs or transfusions, or connective tissue disease, are superior candidates for analysis of OGIB by CE.

Sa1706 Cessation of Potentially Causative Medications Decreases Rebleeding Rate in Patients of Obscure GI Bleeding Without Definite Lesions on Capsule Endoscopy

organ damage (OR 1.89, 95%CI 1.07 3.35), connective tissue disease (OR 2.09, 95%CI 1.1 4.0), Charlson comorbidity index (OR 1.11, 95%CI 1.02 1.20), and increasing transfusion requirements (3-9 units OR 1.72, 95%CI 1.13 2.63; 10 units OR 2.85, 95%CI 1.89 4.30) were significantly associated with positive findings on CE (all p 0.027). Following multivariable analysis, only increasing transfusion requirements (3-9 units OR 1.63, 95%CI 1.04 2.56; 10 units OR 2.63, 95%CI 1.62 4.26) and connective tissue disease (OR 2.18, 95%CI 1.09 4.31) remained significant (all p 0.033). Conclusions: While a number of trends were seen in the univariable analysis, only transfusion requirements and the presence of connective tissue disease were identified as significant factors associated with positive outcomes in the multivariable analysis. The low number of positive predictors limits our ability to utilize demographic and clinical factors as a tool to improve efficiency in selecting patients for CE.

Does the presence of connective tissue disease modify survival in patients with pulmonary fibrosis?

Previous studies into the survival differences between individuals with idiopathic pulmonary fibrosis and those with connective tissue disease associated pulmonary fibrosis (CTD-PF) have yielded mixed results. The aim of this study is to compare the survival of individuals with CTD-PF to those with idiopathic pulmonary fibrosis clinical syndrome (IPF-CS) using data derived from The Health Improvement network, a large primary care database in the UK. Incident cases of CTD-PF and IPF-CS between the years 2000-2009 were identified. Survival analysis was performed using Kaplan-Meier methods, stratified by type of connective tissue disease. Cox regression was then used to compare mortality rates between the groups, adjusting for age, gender and year of diagnosis. A total of 324 cases of CTD-PF and 2209 cases of IPF-CS were followed up over a mean period of 2.3 years. During this period, 113 (34.9%) cases of CTD-PF and 1073 (48.6%) cases of IPF-CS died. The mortality rates for cases with CTD-PF and IPF-CS were 123.6 per 1000 person years (95%CI: 102.8-148.9) and 229.8 per 1000 person years (95% CI: 216.4-244.0) respectively. After adjusting for age, sex and year of diagnosis, cases with CTD-PF had a better prognosis compared to those with IPF-CS (HR 0.76,95%CI: 0.62-0.92). The prognosis of individuals with CTD-PF appears to be significantly better than those with IPF-CS, but remains an important cause of death in patients with connective tissue disease, and requires more effective treatment options.

Prevalence and risk factors for methicillin-resistant Staphylococcus aureus colonization in a diabetic outpatient population: A prospective cohort study

Diabetes mellitus is a risk factor for methicillin-resistant Staphylococcus aureus (MRSA) colonization and infection. We attempted to determine the prevalence and risk factors for MRSA colonization in a population of outpatients with diabetes. This prospective cohort study enrolled patients with diabetes. Anterior nares cultures were obtained from patients with diabetes admitted to outpatient endocrinology and metabolism clinics, and risk factors for MRSA colonization were analyzed. Out of the 304 patients evaluated, 127 (41.9%) were colonized with S aureus and 30 (9.9%) were colonized with MRSA. Overall, 23.6% of all S aureus isolates were MRSA. In multivariate analysis, factors independently associated with an increased risk of MRSA colonization included the presence of connective tissue disease (odds ratio, 7.075; 95% confidence interval, 2.157-23.209; P = .001) and insulin therapy (odds ratio, 3.910; 95% confidence interval, 1.652-9.251; P = .002). The prevalence of MRSA colonization in our sample of diabetic outpatients was 9.9%. Independent risk factors for MRSA colonization were the presence of connective tissue disease and insulin use. A better understanding of the epidemiology and risk factors for nasal MRSA colonization in the persons with diabetes may have significant implications for the treatment and prevention of MRSA infections.

Outcomes of hospitalisation for right heart failure in pulmonary arterial hypertension

The aim of this study was to examine the causes and outcomes of hospitalisation in patients with pulmonary arterial hypertension (PAH). 205 consecutive hospitalisations occurring between 2000 and 2009 in 90 PAH patients were studied. The leading causes for hospitalisation were right heart failure (RHF; 56%), infection (16%) and bleeding disorders (8%). For patients with RHF, in-hospital mortality was 14% overall, 46% for patients receiving inotropes and 48% for those admitted to the intensive care unit. The predictors for in-hospital mortality were the presence of connective tissue disease (CTD) (OR 4.92), systolic blood pressure <100 mmHg (OR 4.32) and Na ≤ 136 mEq · L(-1) (OR 4.29). Mortality after discharge was 13, 26 and 35% at 3, 6 and 12 months, respectively. World Health Organization functional class prior to admission, renal dysfunction, Charlson comorbidity index, and the presence of CTD were all predictors of mortality after discharge. Hyponatraemia and low systolic blood pressure upon admission and underlying CTD are the main prognostic factors for in-hospital mortality in patients with PAH admitted for RHF. The short-term outcomes after discharge are poor and remarkably worse in patients with underlying CTD or renal impairment. Early recognition of these factors may guide decisions regarding more aggressive therapy, including consideration for lung transplantation.

Does rapid dose titration affect the hepatic safety profile of Bosentan?

Rationale Bosentan, a dual endothelin receptor antagonist, has proven efficacy in pulmonary hypertension. Due to an association with hepatic dysfunction, it is typically initiated at a sub-therapeutic dose for 4 weeks before titration to a therapeutic dose. At our institution some patients have undergone rapid titration, to potentially benefit from therapy earlier. This study assesses the impact of this practice on hepatic safety. Method All patients initiated on bosentan therapy before April 2005 were included. Rapidly titrated patients achieved a therapeutic dose by 3 days, whereas standard titration patients were titrated at 4 weeks. All patients were monitored with monthly liver function tests. Results 149 patients commenced bosentan, of which 55 were rapidly titrated. At baseline, the two groups were similar in age, BMI, diagnosis, 6-min walking distance, alanine aminotransferase (ALT), cardiac index and pulmonary artery pressures. The rapid group had elevated right atrial pressures (9.7 mm Hg versus 7.4 mm Hg, p = 0.016) and worse WHO functional class ( p = 0.008) and included less females (31% versus 69%, p = 0.024). The incidence of hepatic dysfunction in all patients was 12.8% at 12 months. There was no statistical difference in incidence between the rapid and standard groups (4% versus 11% at 3 months, p = 0.211 and 6% versus 15% at 12 months, p = 0.219). Of all patients on bosentan, hepatic dysfunction was most significantly associated with a higher baseline ALT ( p = 0.021), female sex ( p = 0.003) and underlying connective tissue disease ( p = 0.025). Subgroup analysis suggested these factors were not confounders when comparing rapid and standard titration. Conclusions Rapid and standard titration of bosentan resulted in similar hepatic safety profiles. Baseline ALT, female sex and the presence of connective tissue disease increased the risk of hepatic dysfunction independent of the titration method used.