Karmacharya, Paras

Abstract Objectives To examine multimorbidity in psoriasis and its association with the development of psoriatic arthritis (PsA). Methods A retrospective cohort study was performed using the Rochester Epidemiology Project. Population-based incidence (2000–09) and prevalence (1 January 2010) cohorts of psoriasis were identified by manual chart review. A cohort of individuals without psoriasis (comparators) were identified (1:1 matched on age, sex and county). Morbidities were defined using two or more Clinical Classification Software codes ≥30 days apart within prior 5 years. PsA was defined using ClASsification of Psoriatic ARthritis (CASPAR) criteria. χ2 and rank-sum tests were used to compare morbidities, and age-, sex- and race-adjusted Cox models to examine the association of baseline morbidities in psoriasis with development of PsA. Results Among 817 incident psoriasis patients, the mean age was 45.2 years with 52.0% females, and 82.0% moderate/severe psoriasis. No multimorbidity differences were found between incident psoriasis patients and comparators. However, in the 1088 prevalent psoriasis patients, multimorbidity was significantly more common compared with 1086 comparators (odds ratio 1.35 and 1.48 for two or more and five or more morbidities, respectively). Over a median 13.3-year follow-up, 23 patients (cumulative incidence: 2.9% by 15 years) developed PsA. Multimorbidity (two or more morbidities) was associated with a 3-fold higher risk of developing PsA. Conclusion Multimorbidity was more common in the prevalent but not incident cohort of psoriasis compared with the general population, suggesting that patients with psoriasis may experience accelerated development of multimorbidity. Moreover, multimorbidity at psoriasis onset significantly increased the risk of developing PsA, highlighting the importance of monitoring multimorbid psoriasis patients for the development of PsA.

ObjectiveTo determine if the efficacy of biologics differ based on magnetic resonance imaging (MRI) and C‐reactive protein (CRP) findings.MethodsWe compared four subgroups (MRI+/CRP+, MRI+/CRP−, MRI−/CRP+, MRI−/CRP−) from randomized controlled trials (RCTs). A comprehensive database search was performed to include axial spondylarthritis (axSpA; both radiographic axSpA [r‐axSpA] and nonradiographic axSpA [nr‐axSpA]) RCTs with treatment efficacy reported by different MRI and CRP subgroups. Study‐specific disease activity scores (at 12‐16 weeks) were pooled using a random‐effects model and compared between the four subgroups.ResultsFive trials (all nr‐axSpA) were included: three with tumor necrosis factor inhibitors (TNFi, N = 729) and two with interleukin‐17 inhibitors (IL‐17i, N = 794). TNFi and IL‐17i showed efficacy based on the Assessment of Spondyloarthritis International Society 40 (ASAS40) and Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI50) in all MRI and CRP subgroups, except the CRP−/MRI− subgroup, which had a single study with only 39 patients. There was no statistically significant difference between the four subgroups in terms of patients achieving ASAS40 (P = 0.60, I2 = 0%) or BASDAI50 (P = 0.27, I2 = 23.9%). The number needed to treat was three for the CRP+/MRI+ and CRP+/MRI− subgroups and six for the CRP−/MRI+ and CRP−/MRI− subgroups. All trials had a low risk of bias. Between‐study heterogeneity was low to moderate. Sensitivity analyses comparing TNFi or IL‐17i versus placebo similarly showed no difference between subgroups in terms of ASAS40 (TNFi, P = 0.57; IL‐17i, P = 0.28) and BASDAI50 (TNFi, P = 0.37; IL‐17i, P = 0.18).ConclusionIn this systematic review, there was no statistically significant difference between the four subgroups in terms of efficacy based on ASAS40 or BASDAI50.

ObjectivePsoriatic arthritis (PsA) and ankylosing spondylitis (AS) are chronic inflammatory diseases associated with a higher risk of cardiometabolic comorbidities compared to the general population. Individual studies examining mortality in these patients have produced conflicting results. The present study was undertaken to perform a systematic review and meta‐analysis to analyze the all‐cause and cause‐specific mortality in PsA and AS from the available literature.MethodsA comprehensive database search was performed for studies reporting all‐cause or cause‐specific mortality in patients with PsA and AS compared with the general population. Pooled relative risks (RRs) were calculated using a random‐effects model.ResultsWe included 19 studies (11 of PsA, 7 of AS, 1 of both). In PsA studies, there was no increased mortality compared to the general population (RR 1.12 [95% confidence interval (95% CI) 0.96–1.30]; n = 10 studies). We found a higher all‐cause mortality in female (RR 1.19 [95% CI 1.04–1.36]) but not in male (RR 1.02 [95% CI 0.66–1.59]) PsA patients. Cardiovascular‐, respiratory‐, and infection‐specific mortality risks were significantly higher for PsA patients (RR 1.21 [95% CI 1.06–1.38], RR 3.37 [95% CI 1.30–8.72], and RR 2.43 [95% CI 1.01–5.84], respectively), but not cancer‐related mortality (RR 1.01 [95% CI 0.91–1.11]). In AS, we found a higher risk of death from all causes (RR 1.64 [95% CI 1.49–1.80]; n = 6 studies) and cardiovascular causes (RR 1.35 [95% CI 1.01–1.81]; n = 3 studies) compared to the general population. All‐cause mortality was high in both male (RR 1.56 [95% CI 1.43–1.71]) and female (RR 1.85 [95% CI 1.56–2.18]) AS patients. The included AS studies did not report mortality data for non‐cardiovascular causes.ConclusionThis systematic review and meta‐analysis showed a significantly increased risk of overall mortality in AS but not PsA. Cardiovascular‐specific mortality was higher for both PsA and AS, which emphasizes the importance of early screening and management of cardiovascular risk factors.

ObjectiveTo determine the incidence of psoriatic arthritis (PsA) in a US population and describe trends in incidence and mortality over 5 decades.MethodsThe previously identified population‐based cohort that included Olmsted County, Minnesota residents ≥18 years of age who fulfilled PsA criteria during 1970–1999 was extended to include patients with incident PsA during 2000–2017. Age‐ and sex‐specific incidence rates and point prevalence, adjusted to the 2010 US White population, were reported.ResultsThere were 164 incident cases of PsA in 2000–2017 (mean ± SD age 46.4 ± 12.0 years; 47% female). The overall age‐ and sex‐adjusted annual incidence of PsA per 100,000 population was 8.5 (95% confidence interval [95% CI] 7.2–9.8) and was higher in men (9.3 [95% CI 7.4–11.3]) than women (7.7 [95% CI 5.9–9.4]) in 2000–2017. Overall incidence was highest in the 40–59 years age group. The incidence rate was relatively stable during 2000–2017, with no evidence of an overall increase or an increase in men only (but a modest increase of 3% per year in women), compared to 1970–1999 when a 4%‐per‐year increase in incidence was observed. Point prevalence was 181.8 per 100,000 population (95% CI 156.5–207.1) in 2015. The percentage of women among those with PsA increased from 39% in 1970–1999 and 41% in 2000–2009 to 54% in 2010–2017 (P = 0.08). Overall survival in PsA did not differ from the general population (standardized mortality ratio 0.85 [95% CI 0.61–1.15]).ConclusionThe incidence of PsA in this predominantly White US population was stable in 2000–2017, in contrast to previous years. However, an increasing proportion of women with PsA was found in this study.

Psoriatic arthritis (PsA) is associated with a higher burden of cardiometabolic disorders, such as hypertension, dyslipidemia, diabetes, obesity, and cardiovascular disease (CVD), compared with the general population. These comorbidities are associated with the severity of disease, and adversely affect treatment outcomes in PsA. Comorbidities lead to increased physician visits and medications for patients and make the selection and maintenance of therapies challenging for physicians. Moreover, CVD is a leading cause of mortality in PsA. Therefore, optimal management of PsA should include not only treating the skin and joint disease, but also identifying comorbidities early, and managing them to improve long-term outcomes. Further studies are needed to understand the complex mechanisms, interactions, and trajectories of cardiometabolic comorbidities in psoriatic disease. Plain Language Summary Psoriatic arthritis and the association with cardiometabolic disease Psoriatic arthritis (PsA) is associated with a higher incidence and prevalence of cardiometabolic comorbidities compared with the general population, and higher than psoriasis and other inflammatory arthritides, such as rheumatoid arthritis and other spondyloarthritides. Obesity and hyperlipidemia are associated with an increased risk of developing PsA. Cardiometabolic comorbidities in PsA are associated with more severe disease and a lower likelihood of response to therapy. Suggested approaches to improve screening and management of CVD in PsA include education of family physicians and relevant specialists, development of mechanisms to improve communication between the rheumatologists and primary care providers, and novel models of care, including interdisciplinary cardio-rheumatology clinics.

Objective To investigate the effect of therapies on radiographic progression in patients with axial spondyloarthritis (SpA). Methods A comprehensive database search for studies assessing radiographic progression in axial SpA (particular treatment versus no treatment of interest) was performed. Study‐specific standardized mean differences in treatment outcomes at 2 and ≥4 years were estimated and combined using random‐effects models. Results Twenty‐four studies in patients with axial SpA were identified, of which 18 involved tumor necrosis factor inhibitors ( TNF i), 8 involved nonsteroidal antiinflammatory drugs ( NSAID s), and 1 involved secukinumab. Spinal radiographic progression, as measured by the modified Stoke Ankylosing Spondylitis Spine Score ( mSASSS ), was not significantly different between TNF i‐treated and biologics‐naive patients at 2 years ( mSASSS difference −0.73 [95% confidence interval (95% CI ) −1.52, 0.12], I 2 = 28%) and ≥4 years ( mSASSS difference −2.03 [95% CI −4.63, 0.72], I 2 = 63%). Sensitivity analyses restricted to studies with a low risk of bias showed a significant difference in spinal radiographic progression between TNF i‐treated and biologics‐naive patients at ≥4 years ( mSASSS difference −2.17 [95% CI −4.19, −0.15]). No significant difference in spinal radiographic progression was observed between NSAID ‐treated and control patients ( mSASSS difference −0.30 [95% CI −2.62, 1.31], I 2 = 71%) or between secukinumab‐treated and biologics‐naive patients ( mSASSS difference −0.34 [95% CI −0.85, 0.17]). With regard to treatment differences in patients with nonradiographic axial SpA or in patients with radiographic progression measured using the sacroiliac joint score, an insufficient number of studies were available for analysis. Conclusion Although no significant protective effect of TNF i treatment on spinal radiographic progression was seen over the course of 2 years or ≥4 years in patients with axial SpA, our analysis restricted to studies with a low risk of bias showed a protective effect of TNF i after ≥4 years. Therefore, long‐term TNF i exposure might confer beneficial effects on spinal radiographic progression in axial SpA. No difference in radiographic progression at 2 years was seen in either the NSAID or secukinumab treatment groups compared to their controls. Future studies should explore the effects of biologic treatment on radiographic progression, as well as the effects of long‐term biologics exposure, in patients with early axial SpA or those with nonradiographic axial SpA.

Abstract Background Morbidity and mortality in tumor lysis syndrome (TLS) remains high despite increasing efforts for prevention, early detection and treatment in recent years. The current risk stratification system and treatment guidelines are largely consensus based without strong evidence. There is paucity of data on the in-hospital mortality and predictors of poor clinical outcome in this population. Methods We used the 2009-2011 Nationwide Inpatient Sample database to identify hospitalizations in patients ≥18 years with a diagnosis of TLS (International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM] code 277.88). Nationwide Inpatient Sample is the largest all-payer publicly available inpatient care database in the US. It contains data from five to eight million hospital stays from about 1,000 hospitals across the country and approximates a 20% sample of all US hospitals. The interval 2009-2011 was selected as ICD-9-CM code 277.88 for TLS was only introduced from the year 2009 onwards. Univariate and multivariate logistic regression were used to determine the independent predictors of in-hospital mortality. Data analysis was done using STATA version 13.0 (College Station, TX). Results Among the 997 admissions (mean age ± SD 67.58±3.33, 62.6 % males, and 80.4 % white) with TLS, in-hospital mortality was 14.44 %. Based on the results of univariate analyses (table 1), we used obesity, coronary artery disease, cardiac dysrhythmias, acute kidney injury and sepsis in the final regression model. We found that cardiac dysrhythmias (OR 4.79; 95% CI, 1.67-13.77; p=0.004) and sepsis (OR 19.70; 95% CI, 5.33-72.78; p<0.001) were independent predictors of increased in-hospital mortality in patients with TLS. Although certain myeloid and lymphoid malignancies are associated with higher risk of tumor lysis syndrome, we did not observe any statistically significant increased risk of mortality with one specific type of malignancy over the other. Similarly, none of the demographic characteristics (age <40 vs ≥40, sex or race), or hospital characteristics (rural vs urban, teaching vs non-teaching, small vs large bed-size or geographic region) predicted increased in-hospital mortality in these patients. Conclusion In this study of large national database, patients with TLS had an in-hospital mortality of 14.44 %. Independent predictors of in-hospital mortality were cardiac dysrhythmias and sepsis. Our findings might help physicians to identify sub-group of patients with TLS that are at increased risk of in-hospital mortality. Table 1 Baseline characteristics of patients with tumor lysis syndrome according to in-hospital survival Characteristics Survivors (n=853) Non-survivors (n=144) p Age( in years) Mean 68.40±3.06 67.58±3.33 0.73 Male sex 62.1 65.8 0.69 Race 0.16 White 81.52 73.54 Black 14.98 22.8 Hispanic 2.27 0 Others/unknown 1.22 3.66 Insurance status 0.41 Medicare 65.55 48.15 Medicaid 5.56 13.34 Private insurance 24.89 32.58 Self-Pay 0.65 2.99 No charge 0.63 0 Other 2.72 2.93 Region 0.13 Northeast 27.59 37.74 Midwest 28.23 12.92 South 31.34 39.9 West 12.84 9.44 Location/teaching status 0.59 Rural 7.87 10.16 Urban nonteaching 26.01 33.52 Urban teaching 66.12 56.32 Bed-size 0.84 Small 11.11 8.91 Medium 21.04 24.55 Large 67.85 66.54 Malignancies ALL 1.19 6.79 0.25 AML 2.34 6.99 0.29 CLL 27.86 16.83 0.18 CML 1.85 3.19 0.68 NHL 36.33 22.37 0.1 HD 0.53 0 0.32 Multiple Myeloma 7.39 6.56 0.82 Other hematologic malignancies 38.67 25.99 0.16 Solid tumors 35.87 26.8 0.32 Co-morbidities Smoking 15.89 21.87 0.46 Obesity 5.16 0 0.005 Dyslipidemia 27.8 16.86 0.18 Hypertension 54.17 49.19 0.63 Diabetes mellitus 27.81 16.65 0.15 PVD 1.71 3.19 0.65 CAD 13.78 3.19 0.02 AKI 60.06 79.54 0.03 CKD 28.81 25.23 0.65 Stroke 0.63 0 0.32 Sepsis 3.58 31.81 0.003 Cardiac dysrhythmias 17.96 43.42 0.04 Acute CHF 11.44 7.08 0.43 AKI=Acute Kidney Injury; ALL=Acute Lymphoblastic Leukemia; AML=Acute Myelogenous Leukemia; CAD=Coronary Artery Disease; CHF=Congestive Heart Failure; CKD=Chronic Kidney Disease; CLL=Chronic Lymphocytic Leukemia; CML=Chronic Myelogenous Leukemia; HD=Hodgkin Disease; NHL=Non Hodgkin Lymphoma; PVD=Peripheral Vascular Disease Disclosures No relevant conflicts of interest to declare.

IgG4-related sclerosing cholangitis (IgG4-SC) is one of the most common extra-pancreatic manifestation of IgG4-related disease (IgG4-RD) and is clinically distinct from primary sclerosing cholangitis (PSC). IgG4-RD is an increasingly recognized immune-mediated fibroinflammatory systemic disease, mostly affecting middle-aged and older male populations that can affect multiple organs. The presence of extra-biliary clinical manifestations of IgG4-RD, such as parotid and lacrimal swelling, lymphadenopathy, autoimmune pancreatitis, and retroperitoneal fibrosis, if present could provide important clues to diagnosis. High serum IgG4 levels, characteristic radiological (e.g., sausage-shaped pancreas or periaortitis) or biopsy findings (high percentage of IgG4+ plasma cells, lymphoplasmacytic infiltrate, storiform fibrosis, or obliterative phlebitis) in the setting of these features is diagnostic of this disease process. However, isolated IgG4-SC might be a diagnostic challenge, and the distinction is important as management of this disorder is vastly different from other causes of cholangitis such as PSC. Systemic corticosteroid therapy is the mainstay of therapy.