High serum magnesium is associated with lower risk of hepatocellular carcinoma among patients with nonalcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a major contributor to the rising incidence of hepatocellular carcinoma (HCC). Magnesium is a major cation in cellular activities. Epidemiological data on magnesium level and its relation to HCC are sparse. This study aimed to examine the associations between serum levels of magnesium and the risk of HCC among patients with NAFLD. METHODS: A total of 26,053 patients with NAFLD were identified in the University of Pittsburgh Medical Center Electronic Health Records from 2004 through 2018. After an average of 5.15 years of follow-up, 395 patients developed HCC after the first measurement of serum magnesium. Cox proportional hazards regression model was used to calculate hazard ratios (HRs) and 95% CIs of HCC incidence associated with quartile levels of serum magnesium after adjustment for age, sex, race, body mass index, diuretics use, history of type 2 diabetes, history of hypertension, history of hyperlipidemia, and tobacco smoking. RESULTS: Patients with NAFLD who developed HCC had a significantly lower mean (± standard deviation) serum magnesium (0.769 ± 0.131 mmol/L) than those who remained free of HCC (0.789 ± 0.125 mmol/L; p = .003). Compared with the lowest quartile, the HRs (95% CIs) of HCC second, third, and fourth quartiles of serum magnesium were 0.87 (0.67-1.12), 0.77 (0.57-1.04), and 0.73 (0.56-0.96), respectively, after adjustment for multiple potential confounders (P trend  = .02). CONCLUSION: This finding suggests higher levels of serum magnesium were significantly associated with decreased risk of HCC among patients with NAFLD.

Relationship of circulating levels of long-chain fatty acids to persistent organ failure in acute pancreatitis.

During acute pancreatitis (AP), free fatty acids (FFAs) are liberated from circulating triglycerides (TG) and injured adipocytes by pancreatic lipase. Circulating FFAs have been suspected as a source of systemic lipotoxicity in AP. However, assessment of FFAs is difficult and time-consuming, and little is known about relative levels of FFAs between patients with different severities of AP and controls. This study's aims were to assess early circulating levels of FFAs, (both saturated and unsaturated) in patients with AP vs. controls, and associations between FFA levels and AP severity. Serum samples from patients with AP were collected at enrollment (day 1 of hospital stay); serum samples were also collected from controls. FFAs including palmitic, palmitoleic, stearic, oleic, and linoleic acid were extracted and quantitated using gas chromatography separation. Severity of AP was determined by Revised Atlanta Classification. Differences in FFA levels and percentages of total FFAs were assessed between patients with AP and controls and patients with AP of different severity grades. A total of 93 patients with AP (48 female, 52%) and 29 controls (20 female, 69%) were enrolled. Of the patients with AP, 74 had mild/moderate and 19 had severe AP. Serum levels of all FFAs except stearic acid were significantly higher in patients with AP compared with controls. A strong and independent association between elevated palmitoleic acid levels and severe AP was found. Serum unsaturated FFA levels, specifically palmitoleic acid, appear to correlate with severe AP. These findings have potential clinical implications for targeted AP therapies.NEW & NOTEWORTHY Drivers of the inflammatory response in acute pancreatitis remain incompletely understood. Unsaturated fatty acids, specifically palmitoleic, appear to have an association with more severe acute pancreatitis. This finding presents a new clinical understanding of fatty acid toxicity and highlights a potential future target for treatment in severe acute pancreatitis.

Lactated Ringers Use in the First 24 Hours of Hospitalization Is Associated With Improved Outcomes in 999 Patients With Acute Pancreatitis.

INTRODUCTION: Recent pilot trials in acute pancreatitis (AP) found that lactated ringers (LR) usage may result in decreased risk of moderately severe/severe AP compared with normal saline, but their small sample sizes limit statistical power. We investigated whether LR usage is associated with improved outcomes in AP in an international multicenter prospective study. METHODS: Patients directly admitted with the diagnosis of AP were prospectively enrolled at 22 international sites between 2015 and 2018. Demographics, fluid administration, and AP severity data were collected in a standardized prospective manner to examine the association between LR and AP severity outcomes. Mixed-effects logistic regression analysis was performed to determine the direction and magnitude of the relationship between the type of fluid administered during the first 24 hours and the development of moderately severe/severe AP. RESULTS: Data from 999 patients were analyzed (mean age 51 years, female 52%, moderately severe/severe AP 24%). Usage of LR during the first 24 hours was associated with reduced odds of moderately severe/severe AP (adjusted odds ratio 0.52; P = 0.014) compared with normal saline after adjusting for region of enrollment, etiology, body mass index, and fluid volume and accounting for the variation across centers. Similar results were observed in sensitivity analyses eliminating the effects of admission organ failure, etiology, and excessive total fluid volume. DISCUSSION: LR administration in the first 24 hours of hospitalization was associated with improved AP severity. A large-scale randomized clinical trial is needed to confirm these findings.

Incident diabetes following acute pancreatitis in a multicenter prospective observational cohort.

Diabetes mellitus following an episode of acute pancreatitis (AP) is an increasingly discussed complication, but there are sparse prospective data on the incidence and risk factors. We evaluated data from a prospective, multicenter observational cohort study that enrolled adults hospitalized with AP between 2017 and 2021 and followed them for one year. Ninety-eight participants who completed 12-month follow-up were included in this analysis. Diabetes status was assessed using a combination of measured glycated hemoglobin (HbA1c) at predetermined time intervals or physician diagnosis. In 68 participants without diabetes at enrollment, the cumulative incidence of new-onset diabetes was 4.4 % (n = 3) at 3 months and 10.3 % (n = 7) at 12 months. No differences were observed in demographic or pancreatitis-related characteristics between those who did versus did not develop diabetes, in part due to small sample size. In summary, new-onset diabetes was identified in approximately 10 % within one year after an episode of AP. Larger prospective studies are needed to further define the incidence, risk factors, and mechanisms of diabetes and pre-diabetes following AP. NCT03063398.

Composite dietary antioxidant index and the risk of colorectal cancer: Findings from the Singapore Chinese Health Study.

Colorectal cancer (CRC) is a major contributor to cancer death globally. Several studies showed some protections by certain individual dietary antioxidants against CRC development. Epidemiologic data on the composite dietary antioxidant index (CDAI) in relation to CRC risk are sparse. Using the Singapore Chinese Health Study, an ongoing prospective cohort consisting of 61 321 cancer-free participants aged 45 to 74 years at baseline, a food-based CDAI was calculated according to a previously established and validated method that included six food-sourced antioxidants including vitamins A, C and E, manganese, selenium and zinc. Cox proportional hazard regression method was used to estimate the hazard ratios (HRs) and their 95% confidence intervals (CIs) for CRC associated with various levels of CDAI with adjustment for multiple potential confounders. After an average of 17.5 years of follow-up, 2140 participants developed CRC. HRs (95% CIs) of CRC for quartiles 2, 3 and 4 of CDAI were 0.94 (0.83-1.07), 0.86 (0.75-1.00) and 0.80 (0.66-0.98), respectively, compared to the lowest quartile (Ptrend  = .02). This inverse association between CDAI and CRC risk was more apparent in women or those without a history of diabetes, without family history of CRC, never smokers or overweight/obese individuals. However, none of the heterogeneity tests for the CDAI-CRC risk association reached statistical significance. Our findings suggest that food-based antioxidants may be beneficial for reducing the risk of CRC in the general population.

Severe acute pancreatitis exhibits distinct cytokine signatures and trajectories in humans: a prospective observational study.

Severe acute pancreatitis (SAP) is associated with substantial morbidity and mortality. Several cytokines have been identified to have pathophysiological significance in SAP, but studies characterizing their early trajectories are lacking. Here we characterize the early trajectories of seven key cytokines associated with SAP and compare them with non-SAP subjects. Five proinflammatory cytokines (angiopoietin-2, interleukin-6, interleukin-8, monocyte chemoattractant protein-1, resistin) and two anti-inflammatory cytokines (hepatocyte growth factor, and soluble tumor necrosis factor-α receptor-1A) were measured in a prospective cohort of acute pancreatitis subjects (2012-2016) at the time of enrollment and then every 24 h for 5 days or until discharge. The cytokines' levels and trajectories were calibrated based on date of pain onset and were compared between healthy controls and three severity categories (mild, moderate, and severe). The cohort (n = 170) consisted of 27 healthy controls, 65 mild, 38 moderate, and 40 SAP. From day 1 of symptom onset, SAP subjects exhibited significantly higher levels of both pro- and anti-inflammatory cytokines compared with non-SAP and healthy subjects. But in SAP subjects, all proinflammatory cytokines' levels trended downward after day 2 (except for a flat slope for angiopoeitin-2) whereas for non-SAP subjects, the trajectory was upward: this trajectory difference between SAP versus non-SAP subjects resulted in narrowing of the differences initially seen on day 1 for proinflammatory cytokines. For anti-inflammatory cytokines, the trajectories were uniformly upward for both SAP and non-SAP subjects. Proinflammatory cytokine response is an early and time-sensitive event in SAP that should be accounted for when designing future biomarker studies and/or therapeutic trials.NEW & NOTEWORTHY In this study, we showed that the proinflammatory cytokine response in SAP is an early event, with subsequent downregulation of proinflammatory cytokines beginning at day 1 of symptom onset. Our findings underscore the importance of enrolling subjects very early in the disease course when conducting studies to investigate early immune events of SAP; this current study also serves as an important reference for the design of future biomarker studies and therapeutic trials in SAP.

The Modified Pancreatitis Activity Scoring System Shows Distinct Trajectories in Acute Pancreatitis: An International Study.

BACKGROUND & AIMS: The aims of this study were to: (1) assess the performance of the Pancreatitis Activity Scoring System (PASS) in a large intercontinental cohort of patients with acute pancreatitis (AP); and (2) investigate whether a modified PASS (mPASS) yields a similar predictive accuracy and produces distinct early trajectories between severity subgroups. METHODS: Data was prospectively collected through the Acute Pancreatitis Patient Registry to Examine Novel Therapies In Clinical Experience (APPRENTICE) consortium (2015-2018) involving 22 centers from 4 continents. AP severity was categorized per the revised Atlanta classification. PASS trajectories were compared between the three severity groups using the generalized estimating equations model. Four mPASS models were generated by modifying the morphine equivalent dose (MED), and their trajectories were compared. RESULTS: A total of 1393 subjects were enrolled (median age, 49 years; 51% males). The study cohort included 950 mild (68.2%), 315 (22.6%) moderately severe, and 128 (9.2%) severe AP. Mild cases had the lowest PASS at each study time point (all P < .001). A subset of patients with outlier admission PASS values was identified. In the outlier group, 70% of the PASS variation was attributed to the MED, and 66% of these patients were from the United States centers. Among the 4 modified models, the mPASS-1 (excluding MED from PASS) demonstrated high performance in predicting severe AP with an area under the receiver operating characteristic curve of 0.88 (vs area under the receiver operating characteristic of 0.83 in conventional PASS) and produced distinct trajectories with distinct slopes between severity subgroups (all P < .001). CONCLUSION: We propose a modified model by removing the MED component, which is easier to calculate, predicts accurately severe AP, and maintains significantly distinct early trajectories.

The relationship between pre-existing diabetes mellitus and the severity of acute pancreatitis: Report from a large international registry.

BACKGROUND/OBJECTIVES: The relationship between pre-existing diabetes mellitus (DM) and acute pancreatitis (AP) severity has not been established. We assessed the impact of pre-existing DM on AP severity in an international, prospectively ascertained registry. METHODS: APPRENTICE registry prospectively enrolled 1543 AP patients from 22 centers across 4 continents (8 US, 6 Europe, 5 Latin America, 3 India) between 2015 and 2018, and collected detailed clinical information. Pre-existing DM was defined a diagnosis of DM prior to AP admission. The primary outcome was AP severity defined by the Revised Atlanta Classification (RAC). Secondary outcomes were development of systemic inflammatory response syndrome (SIRS) or intensive care unit (ICU) admission. RESULTS: Pre-existing DM was present in 270 (17.5%) AP patients, of whom 252 (93.3%) had type 2 DM. Patients with pre-existing DM were significantly (p < 0.05) older (55.8 ± 16 vs. 48.3 ± 18.7 years), more likely to be overweight (BMI 29.5 ± 7 vs. 27.2 ± 6.2), have hypertriglyceridemia as the etiology (15% vs. 2%) and prior AP (33 vs. 24%). Mild, moderate, and severe AP were noted in 66%, 23%, and 11% of patients, respectively. On multivariable analysis, pre-existing DM did not significantly impact AP severity assessed by the RAC (moderate-severe vs. mild AP, OR = 0.86, 95% CI 0.63-1.18; severe vs. mild-moderate AP, OR = 1.05, 95% CI, 0.67-1.63), development of SIRS, or the need for ICU admission. No interaction was noted between DM status and continent. CONCLUSION: About one in 5 patients with AP have pre-existing DM. Once confounding risk factors are considered, pre-existing DM per se is not a risk factor for severe AP.

Groove pancreatitis has a spectrum of severity and can be managed conservatively.

BACKGROUND & AIMS: The natural history of groove pancreatitis is incompletely characterized. Published literature suggests a high rate of surgery. We describe the short- and long-term outcomes in a cohort of patients with groove pancreatitis treated at our institution. METHODS: Medical records of patients hospitalized in the University of Pittsburgh Medical Center system from 2000 to 2014 and diagnosed with groove pancreatitis based on imaging were retrospectively reviewed. Clinical presentation and outcomes during index admission and follow-up were recorded. RESULTS: Forty-eight patients with groove pancreatitis were identified (mean age 53.2 years, 79% male). Seventy-one percent were alcohol abusers and an equal number were cigarette smokers. Prior histories of acute and chronic pancreatitis were noted in 30 (62.5%) and 21 (43.8%), respectively. Forty-four (91.7%) met criteria for acute pancreatitis during their index admission. Alcohol was the most common etiology (68.8%). No patient experienced organ failure. The most frequent imaging findings were fat stranding in the groove (83.3%), duodenal wall thickening (52.1%), and soft tissue mass/thickening in the groove (50%). Over a mean follow-up of 5.0 years, seven (14.6%) required a pancreas-related surgery. Patients had a high burden of pancreatitis-related readmissions (68.8%, 69.4/100 patient-years). Incident diabetes and chronic pancreatitis were diagnosed in 5 (13.9% of patients at risk) and 8 (29.6% of patients at risk) respectively. CONCLUSIONS: Groove pancreatitis has a wide spectrum of severity; most patients have mild disease. These patients have a high burden of readmissions and progression to chronic pancreatitis. A small minority requires surgical intervention.

Dynamic changes in the pancreatitis activity scoring system during hospital course in a multicenter, prospective cohort.

BACKGROUND AND AIM: The primary aim was to validate the Pancreatitis Activity Scoring System (PASS) in a multicenter prospectively ascertained acute pancreatitis (AP) cohort. Second, we investigated the association of early PASS trajectories with disease severity and length of hospital stay (LOS). METHODS: Data were prospectively collected through the APPRENTICE consortium (2015-2018). AP severity was categorized based on revised Atlanta classification. Delta PASS (ΔPASS) was calculated by subtracting activity score from baseline value. PASS trajectories were compared between severity subsets. Subsequently, the cohort was subdivided into three LOS subgroups as short (S-LOS): 2-3 days; intermediate (I-LOS): 3-7 days; and long (L-LOS): ≥7 days. The generalized estimating equations model was implemented to compare PASS trajectories. RESULTS: There were 434 subjects analyzed including 322 (74%) mild, 86 (20%) moderately severe, and 26 (6%) severe AP. Severe AP subjects had the highest activity levels and the slowest rate of decline in activity (P = 0.039). Focusing on mild AP, L-LOS subjects (34%) had 28 points per day slower decline; whereas, S-LOS group (13%) showed 34 points per day sharper decrease compared with I-LOS (53%; P < 0.001). We noticed an outlier subset with a median admission-PASS of 466 compared with 140 in the rest. Morphine equivalent dose constituted 80% of the total PASS in the outliers (median morphine equivalent dose score = 392), compared with only 25% in normal-range subjects (score = 33, P value < 0.001). CONCLUSIONS: This study highlighted that PASS can quantify AP activity. Significant differences in PASS trajectories were found both in revised Atlanta classification severity and LOS groups, which can be harnessed in AP monitoring/management (ClincialTrials.gov number, NCT03075618).

Association of Serum Triglyceride Levels with Severity in Acute Pancreatitis: Results from an International, Multicenter Cohort Study.

BACKGROUND: Hypertriglyceridemia (HTG) is considered within the top 5 etiologies in acute pancreatitis (AP), but the association of serum triglyceride (TG) levels with the clinical course of AP remains controversial. OBJECTIVES: This study aims to examine the effect of TG levels on severity of AP. METHODS: Patients were enrolled prospectively through APPRENTICE. High TG levels were defined based on the Endocrine Society Clinical Practice Guidelines. HTG was categorized as mild (serum TG levels 150-199 mg/dL), moderate (200-999 mg/dL), severe (1,000-1,999 mg/dL), and very severe (≥2,000 mg/dL). Severity of AP was based on the revised Atlanta classification criteria. RESULTS: Early TG levels were measured in 764 subjects and found elevated in 342 (120 with mild; 176, moderate; and 46, severe/very severe HTG). Patients with increased TG levels were younger (age ≥60, 16.7 vs. 30.3%), more likely to be male (66.1 vs. 51.2%), with more frequent alcohol use (62.8 vs. 50.7%), and diabetes mellitus (30.2 vs. 12.3%; all p ≤ 0.005). Severe AP (24.9 vs. 10.0%), ICU admission (32.5 vs. 19.7%), and mortality (5.3 vs. 1.7%; all p ≤ 0.005) were more frequently seen in patients with elevated TG levels. Based on multivariable analysis, elevated TG levels were independently associated with severe AP (p < 0.05). CONCLUSION: This large multicenter study confirms that elevated TG levels are associated with severe disease regardless of AP etiology.

Severe acute pancreatitis: capillary permeability model linking systemic inflammation to multiorgan failure.

Severe acute pancreatitis (SAP) includes persistent systemic inflammation (SIRS) and multiorgan failure (MOF). The mechanism of transition from SIRS to MOF is unclear. We developed a fluid compartment model and used clinical data to test predictions. The model includes vascular, interstitial and "third-space" compartments with variable permeability of plasma proteins at the capillaries. Consented patients from University of Pittsburgh Medical Center Presbyterian Hospital were studied. Preadmission and daily hematocrit (HCT), blood urea nitrogen (BUN), creatine (Cr), albumin (Alb), and total protein (TP) were collected, and nonalbumin plasma protein (NAPP = TP minus the Alb) was calculated. Subjects served as their own controls for trajectory analysis. Of 57 SAP subjects, 18 developed MOF (5 died), and 39 were non-MOF (0 died). Compared with preadmission levels, admission HCT increased in MOF +5.00 [25%-75% interquartile range, IQR] versus non-MOF -0.10 [-1.55, 1.40] (P < 0.002) with HCT > +3 distinguishing MOF from non-MOF (odds ratio 17.7, P = 0.014). Preadmission Alb fell faster in MOF than non-MOF (P < 0.01). By day 2, TP and NAPP dropped in MOF but not non-MOF (P < 0.001). BUN and Cr levels increased in MOF (P = 0.001), but BUN-to-Cr ratios remained constant. Pancreatic necrosis was more common in MOF (56%) than non-MOF (23%). Changing capillary permeability to allow loss of NAPP in this model predicts loss of plasma oncotic pressure and reduced vascular volume, hypotension with prerenal azotemia and acute kidney dysfunction, pancreas necrosis, and pulmonary edema from capillary leak in the lung with acute respiratory distress syndrome. Sequential biomarker analysis in humans with or without MOF is consistent with this model. This study is registered on https://clinicaltrials.gov at NCT03075605.NEW & NOTEWORTHY Acute pancreatitis is a sudden inflammatory response to pancreatic injury that may spread to systemic inflammation, multiorgan failure, and death in some patients. With the use of the predictions of a new mechanistic model, we compared patients with severe acute pancreatitis with or without multiorgan failure. All biomarkers of capillary leak and clinical features of multiorgan failure were accurately predicted. This provides a new paradigm for understanding and developing new treatments for patients with severe acute pancreatitis.

Worldwide Variations in Demographics, Management, and Outcomes of Acute Pancreatitis.

BACKGROUND & AIMS: Few studies have compared regional differences in acute pancreatitis. We analyzed data from an international registry of patients with acute pancreatitis to evaluate geographic variations in patient characteristics, management, and outcomes. METHODS: We collected data from the APPRENTICE registry of patients with acute pancreatitis, which obtains information from patients in Europe (6 centers), India (3 centers), Latin America (5 centers), and North America (8 centers) using standardized questionnaires. Our final analysis included 1612 patients with acute pancreatitis (median age, 49 years; 53% male, 62% white) enrolled from August 2015 through January 2018. RESULTS: Biliary (45%) and alcoholic acute pancreatitis (21%) were the most common etiologies. Based on the revised Atlanta classification, 65% of patients developed mild disease, 23% moderate, and 12% severe. The mean age of patients in Europe (58 years) was older than mean age for all 4 regions (46 years) and a higher proportion of patients in Europe had comorbid conditions (73% vs 50% overall). The predominant etiology of acute pancreatitis in Latin America was biliary (78%), whereas alcohol-associated pancreatitis accounted for the highest proportion of acute pancreatitis cases in India (45%). Pain was managed with opioid analgesics in 93% of patients in North America versus 27% of patients in the other 3 regions. Cholecystectomies were performed at the time of hospital admission for most patients in Latin America (60% vs 15% overall). A higher proportion of European patients with severe acute pancreatitis died during the original hospital stay (44%) compared with the other 3 regions (15%). CONCLUSIONS: We found significant variation in demographics, etiologies, management practices, and outcomes of acute pancreatitis worldwide. ClinicalTrials.gov number: NCT03075618.

Clinical features of hypertriglyceridemia-induced acute pancreatitis in an international, multicenter, prospective cohort (APPRENTICE consortium).

BACKGROUND: The clinical features and outcomes of hypertriglyceridemia-induced acute pancreatitis (HTG-AP) are not well-established. OBJECTIVE: To evaluate the clinical characteristics of HTG-AP in an international, multicenter prospective cohort. METHODS: Data collection was conducted prospectively through APPRENTICE between 2015 and 2018. HTG-AP was defined as serum TG levels >500 mg/dl in the absence of other common etiologies of AP. Three multivariate logistic regression models were performed to assess whether HTG-AP is associated with SIRS positive status, ICU admission and/or moderately-severe/severe AP. RESULTS: 1,478 patients were included in the study; 69 subjects (4.7%) were diagnosed with HTG-AP. HTG-AP patients were more likely to be younger (mean 40 vs 50 years; p < 0.001), male (67% vs 52%; p = 0.018), and with a higher BMI (mean 30.4 vs 27.5 kg/m2; p = 0.0002). HTG-AP subjects reported more frequent active alcohol use (71% vs 49%; p < 0.001), and diabetes mellitus (59% vs 15%; p < 0.001). None of the above risk factors/variables was found to be independently associated with SIRS positive status, ICU admission, or severity in the multivariate logistic regression models. These results were similar when including only the 785 subjects with TG levels measured within 48 h from admission. CONCLUSION: HTG-AP was found to be the 4th most common etiology of AP. HTG-AP patients had distinct baseline characteristics, but their clinical outcomes were similar compared to other etiologies of AP.

Prevalence and Severity of Depression and Anxiety in Patients With Systemic Sclerosis: An Epidemiologic Survey and Investigation of Clinical Correlates.

BACKGROUND: Systemic sclerosis (SSc) is a chronic multisystem connective tissue disorder with detrimental impact on quality of life. Patients with SSc face emotional distress and frequently meet criteria for a psychiatric disorder. However, the pattern of psychiatric manifestations may vary according to socioethnic background. OBJECTIVES: We investigated the prevalence of depressive and anxiety symptoms and examined their association with sociodemographic and clinical factors in Iranian SSc patients. METHODS: Depressive and anxiety symptoms were evaluated by Beck Depression Inventory and Cattell questionnaire in 114 SSc patients. The associations between sociodemographic and clinical factors and depressive/anxiety symptoms were examined via multivariate analysis. RESULTS: The prevalence of depressive symptoms was 68.4%. There was a significant association between depressive symptoms and pulmonary and gastrointestinal manifestations. Also, diffuse SSc patients were more prone to depressive symptoms. Mean Rodnan scores were significantly higher in patients with depressive symptoms in comparison with subjects with no depressive symptoms. The prevalence of anxiety symptoms was 23.6%. Anxiety symptoms were not associated with demographic characteristics, SSc subtype, disease duration, Rodnan score, other clinical features, and previous history of depression in the patients or their family. The coincidence of anxiety and depression was 82.8%. CONCLUSIONS: Depressive and anxiety symptoms are prevalent among Iranian SSc population. The depressive symptoms showed correlation with pulmonary and gastrointestinal involvement, as well as diffuse SSc subtype.

Anxiety and depression in rheumatoid arthritis: an epidemiologic survey and investigation of clinical correlates in Iranian population.

Psychiatric disorders occur in a considerable proportion of patients with rheumatoid arthritis (RA). This study was conducted in order to evaluate the prevalence of anxiety and depression in Iranian RA patients. In the cross sectional study, 414 RA patients were enrolled prospectively during a period of 6 months from RA clinic of Rheumatology Research Center. Beck's and Cattell's inventories were applied to investigate depression and anxiety in RA patients. RA activity was measured by Disease Activity Score and patients' disability was assessed by Health Assessment Questionnaire. Levels of pain perception were stratified based on Visual Analog Scale. The prevalence of depression was 63.6 % and anxiety was in 84.1 % among RA patients. Mixed anxiety and depression was detected in 60.2 % of the study population. Functional disability was significantly associated with severity of depressive and anxiety symptoms (p < 0.001); however there was no association between disease activity and depression or anxiety (p = 0.420). There was weak correlation between disease activity score and functional disability (Spearman's rho = 0.33; p < 0.01). Severe levels of depression and anxiety were associated with higher levels of pain perception (p < 0.001). Our study stressed the impact of depressive and anxiety symptoms in functional disability and pain perception of RA patients. Our results point out the multidisciplinary management of RA.

Validity and reliability of the Persian version of Behçet's disease quality-of-life (BD-QoL) questionnaire: a cross-cultural adaptation.

The Leeds Behçet's disease quality-of-life (BD-QoL) questionnaire is a specific and valid measure which is applied in English-speaking patients. We conducted Persian adaptation of BD-QoL questionnaire. Between June and December 2012, 220 Iranian patients fulfilling International Study Group criteria for the diagnosis of BD attending the rheumatology clinics at Tehran University of Medical Sciences were enrolled. Bilingual translators undertook the forward translation and cross-cultural adaptation of the BD-QoL questionnaire. Back-translation was conducted, and this version was sent to the designer of the questionnaire and revised accordingly. SF-36 health survey, Iranian Behçet's disease dynamic activity measure (IBDDAM), and Behçet's Disease Current Activity Form (BDCAF) were other administered measures. The Varimax rotation method with Kaiser normalization defined 5 factors with eigenvalues greater than 1.0. Studied cases were comprised of 118 males (53.6 %) and 102 females (46.4 %). Mean age of the patients was 38.3 ± 11.3 years (range 16-73). The mean BD-QoL score was 10.3 ± 8.8. Test-retest reliability was high, and two time points were significantly correlated (Spearman's correlation coefficient of 0.75-0.84). Cronbach's α coefficient of 0.949 demonstrated the excellent internal consistency. These factors cumulatively explained 58.74 % of total variance. The ratio of first to second eigenvalue was 7.08, which underlined the undimensionality. The results revealed adapted BD-QoL scores had significant correlation with IBDDAM (correlation coefficient = 0.19, P value = 0.005) and BDCAF (correlation coefficient = 0.21, P value = 0.002). Conversely, no significant correlation between BD-QoL and SF-36 results was detected (P value = 0.078). The Persian version of BD-QoL was shown to be unidimensional, highly reliable, and adequate construct validity.

The effect of Ramadan fasting on quiescent systemic lupus erythematosus (SLE) patients' disease activity, health quality of life and lipid profile: a pilot study.

SLE is a common autoimmune disease with considerable morbidity. Ramadan fasting is a religious custom Muslims regularly practice. We aimed to evaluate the effect of Ramadan fasting on SLE patients' disease activity, health quality of life and lipid profile. We conducted this case control study as a pilot study in 40 quiescent SLE patients, 21 cases who decided to fast and 19 controls who decided not to have Ramadan fasting between August and November 2009 in lupus unit of Rheumatology Research Center in Tehran University of Medical Sciences, Iran. They were assessed for SLE Disease Activity Index, lipid profile and quality of life with Short-Form 36 (SF-36) Health Survey, 1 day before Ramadan, the day after and 3 months after Ramadan fasting. After 24.1 ± 5.4 (mean ± SD) days of fasting, anti-ds DNA increased for 0.34 ± 0.41 mmol/dL in cases versus 0.07 ± 0.31 in controls (P = 0.026). Likewise C3 increased more dramatically in cases (16.8 ± 17.5 vs. 2.3 ± 13.2 mg/dL, P = 0.006). Three months after fasting, anti-ds DNA was still increased 0.28 ± 0.46 mmol/dL in cases while a 0.02 ± 0.43 mmol/dL drop in controls was detected (P = 0.04). On the contrary, C3 returned to baseline. These changes were not accompanied with significant changes in disease activity and health quality of life. Ramadan fasting had no effect on lipid profile except for delayed total cholesterol decrease in cases in comparison with controls (16.4 ± 29.4 decrease vs. 4.6 ± 23.9 mg/dL decrease, P = 0.018). Ramadan fasting probably has no detrimental effect on SLE patients' disease activity and their quality of life in the quiescent phase of disease.

Prevalence and severity of depression and anxiety in patients with systemic lupus erythematosus: An epidemiologic study in Iranian patients.

OBJECTIVES: We aimed to evaluate the prevalence of depression and anxiety in patients with systemic lupus erythematosus (SLE) and explore their association with demographic and clinical features. METHODS: In this cross-sectional study, 166 SLE patients in rheumatology center of Shariati hospital, Tehran University of Medical Sciences were enrolled. SLE disease activity index (SLEDAI) and Beck and Cattell inventories for evaluation of depression and anxiety were completed for each patient. RESULTS: The mean age of patients was 33.1 ± 11.1 years and 92.2% of them were female. Two patients (1.2%) had only depression (without anxiety), while 36 patients (21.6%) had only anxiety (without depression). Meanwhile, 105 patients (63.3%) had mixed depression-anxiety and 23 patients (13.8%) did not have either depression or anxiety. Mean daily dose of prednisolone and number of administered drugs did not show significant difference between different subgroups of patients. In assessment of clinical and therapeutic items, no significant correlation between severity of depression (P = 0.65) and anxiety (P = 0.36) with daily dose of prednisolone in SLE patients was observed. There was no significant association between SLEDAI and severity of depression or anxiety. Occupational status had significant correlation with severity of depression and anxiety (P = 0.005).On the contrary, no significant correlation between number of administered drugs and severity of depression and anxiety was present. CONCLUSION: This study indicated the high prevalence of depression and anxiety among SLE patients and reinforced the need of a comprehensive psychiatric work-up in SLE.

Non-corticosteroid risk factors of symptomatic avascular necrosis of bone in systemic lupus erythematosus: A retrospective case-control study.

OBJECTIVE: Avascular necrosis of bone (AVN) is an important complication of systemic lupus erythematosus (SLE). Corticosteroid therapy has been underlined as a main risk factor for osteonecrosis. However, AVN development in patients who have never received corticosteroid and the absence of AVN in the majority of the patients, who received corticosteroid, propose a role for non-corticosteroid risk factors in AVN development. METHODS: This case-control study included two subsets: oral corticosteroid (66 AVN and 248 non-AVN patients) and pulse-therapy subset (39 AVN and 312 non-AVN patients) who have attended our Lupus clinic from 1979 to 2009. Patients received similar cumulative dose corticosteroid, equal maximum dose and 1-year maximum dose of corticosteroid. The demographic data (including sex, age of disease onset, age at the diagnosis of AVN), organs involvement, SLE Disease Activity Index (SLEDAI), Systemic Lupus International Collaborating Clinics/American College of Rheumatology-Damage index (SLICC/ACR-DI), number of disease flare ups were compared between two subsets. RESULTS: The mean age of SLE onset was younger (P value = 0.04) in the AVN patients. In oral corticosteroid subset, malar rash (P value < 0.001) and oral ulcer (P value = 0.003) were seen more frequently in non-AVN patients, whereas psychosis (P value = 0.03) was significantly more prevalent AVN subset in oral corticosteroid subset. In corticosteroid pulse subset, no significant difference in clinical features was noted. CONCLUSION: In oral corticosteroid subset, younger age of disease onset and psychosis were significantly associated with AVN, whereas malar rash and oral ulcer showed negative association AVN.