Serum calcium levels independently predict in-hospital mortality in patients with acute myocardial infarction

Background and aim

Serum calcium levels (sCa) were reported to be associated with cardiovascular risk factors, incidence of coronary artery disease and acute myocardial infarction (AMI). The current study evaluated the association between sCa and in-hospital mortality among AMI patients.

Effect of nutritional counseling on low-density lipoprotein cholesterol among Thai HIV-infected adults receiving antiretroviral therapy

HIV-infected patients receiving antiretroviral therapy have increased risk of metabolic syndrome, including dyslipidemia. In this study, we determined whether individual nutritional counseling reduced dyslipidemia, particularly low-density lipoprotein (LDL) cholesterol, among HIV-infected patients with dyslipidemia not currently taking lipid-lowering medication. We conducted a randomized 24-week trial among HIV-infected patients with dyslipidemia who were on antiretroviral therapy and were eligible to initiate therapeutic lifestyle changes according to the Thai National Cholesterol Education Program. Participants were randomly assigned to an intervention group that received individual counseling with a nutritionist for seven sessions (baseline, weeks 2, 4, 8, 12, 18, and 24) and a control group that received standard verbal diet information at baseline and nutritional counseling only at week 24. A 24-h recall technique was used to assess dietary intake for both groups at baseline and week 24. Lipid profile (total cholesterol, LDL, high-density lipoprotein (HDL), and triglyceride) was measured at baseline and after 12 and 24 weeks of therapy. An intention-to-treat and linear mixed model were used. Seventy-two patients were randomly assigned, and 62 (86%) participants completed their lipid profile test. After 12 weeks of follow-up, there were significant reductions in the intervention group for total cholesterol (?14.4?±?4.6?mg/dL, P?=?.002), LDL cholesterol (?13.7?±?4.1?mg/dL, P?=?.001), and triglyceride (?30.4?±?13.8?mg/dL, P?=?.03). A significant reduction in LDL cholesterol was also observed in the control group (?7.7?±?3.8?mg/dL, P?=?.04), but there were no significant differences in change of mean lipid levels between the groups at 12 weeks of follow-up. After 24 weeks, participants assigned to the intervention group demonstrated significantly greater decreases in serum total cholesterol (?19.0?±?4.6?vs. 0.2?±?4.3?mg/dL, P?=?.003) and LDL cholesterol (?21.5?±?4.1?vs. ?6.8?±?3.8?mg/dL, P?=?.009). There were no significant changes in HDL cholesterol or triglyceride levels in either group.     

The velocity of home blood pressure reduction in response to low-dose eplerenone combined with other antihypertensive drugs determined by exponential decay function analysis

Background/objective: Eplerenone is a highly selective aldosterone blocker, which has the potential to lower blood pressure (BP) in patients with hypertension. The objective of this study was to assess the hypotensive effects of low-dose eplerenone (25?mg) using home BP measurements. We also assessed the time required to reach 95% of the maximum antihypertensive effect (stabilization time) by analyzing exponential decay functions using home BP measurements.

Methods: We reviewed the medical records of 83 hypertensive patients who were taking eplerenone 25?mg (age, 68.6?±?11.8?years; men, 36.1%) in addition to other antihypertensive agents. Home BPs were averaged in each patient for the last 5?days of each observation period. The morning versus evening effect (M/E ratio) and the evening versus morning effect (E/M ratio) were calculated to assess the duration of action of eplerenone.

Results: The mean home systolic/diastolic BPs at baseline were 136.8?±?8.8/77.2?±?9.3?mmHg, respectively. After 8?weeks of treatment with eplerenone, home systolic/diastolic BP significantly decreased by ?7.1?±?10.1/?2.6?±?5.0?mmHg (p?p?=?0.006) and 16.5 days (p?=?0.001), respectively. When eplerenone was administered in the morning, the M/E ratio was 1.1?±?0.3. The corresponding E/M ratio for evening administration was 0.9?±?0.6. Although no nocturia was observed, there was a slight but significant increase in serum potassium levels (p?=?0.03).

Conclusions: Our data suggest that the combination of eplerenone with other antihypertensive drugs may be a promising therapeutic strategy for the treatment of essential hypertension.     

Lanreotide in the management of small bowel angioectasias: seven-year data from a tertiary centre

Background and aims: Haemorrhage from small bowel angioectasias (SBAs) can be debilitating to patients who are very often elderly and have multiple comorbidities. Our aim was to assess the use of lanreotide in addition to endotherapy in patients with SBAs.

Method: Patients with SBAs on capsule endoscopy (CE) who received lanreotide injections from January 2010 to till the present day at the Royal Hallamshire Hospital in Sheffield were included. Baseline demographics were recorded. Efficacy was evaluated in terms of improvement in mean haemoglobin, transfusion requirements and bleeding episodes.

Results: Twelve patients (67% males, mean age 74 SD?±?15.5 years) were included. All patients had multiple comorbidities. Lanreotide was given at a dosage of 60?mg (42%), 90?mg (33%) or 120?mg (25%). It was given at a four-week interval in 75% of patients and at a six-week interval in 17% of patients. One patient (8%) received a single dose. The mean duration of treatment was 19 months SD?±?14.5. Only 17% of patients had their lanreotide stopped due to cholelithiasis.

There was a significant improvement in mean haemoglobin: 86.8 versus 98.0 (131–166?g/L, p?=?.012). The mean number of bleeding episodes (4.18 versus 1.09, p?=?.010) and packed red cells (323 versus 152, p?=?.006) received improved. Patients required less DBEs?±?APCs after starting lanreotide (19 versus 11 p?=?.048).

Conclusion: Lanreotide is a useful adjuvant treatment to therapeutic enteroscopy in patients with refractory obscure gastrointestinal bleeding due to SBAs. It improves haemoglobin levels, reduces transfusion requirements, bleeding episodes and number of DBEs. Overall, it has a good safety profile.     

High anti-TNF alfa drugs trough levels are not associated with the occurrence of adverse events in patients with inflammatory bowel disease

Abstract

Objectives: Up to 40% of inflammatory bowel disease (IBD) patients treated with anti-TNF drugs lose response within 1 year of treatment, therefore requiring drug optimization. Although higher drug trough levels (TLs) are associated with sustained clinical outcomes, there are concerns that they may be associated with a higher risk of adverse events (AEs). The aim was to evaluate the presence of a possible association between drug TLs and the occurrence of AEs in IBD patients treated with anti-TNF drugs.

Methods: We retrospectively studied a cohort of 113 IBD patients treated with adalimumab or infliximab, of whom 27 were in combination therapy with immunosuppressants. TLs were measured using a homogeneous mobility shift assay.

Results: During a median follow-up of 16?months (range 1–144), we observed 103 AEs occurring in 58 patients. We found no statistically significant difference (p?=?.21) in median TLs between patients who did 6.7?mcg/mL; range 0.0–36.2) or did not (7.7?mcg/mL; range 0.0–20.7) experience an AE. No difference was observed in the rate of AEs between patients in mono- or combination therapy (p?=?.38), as well as between elderly (i.e., >65?years) and younger patients (p?=?.32). Considering a TL cutoff of 7?mcg/mL for infliximab and 12?mcg/mL for adalimumab, or even double these TL values, we observed no statistically significant difference in the rate of AEs occurrence.

Conclusion: Our study suggests that, when clinically required, anti-TNF drug dosage may be increased without particular concerns regarding the risk of AEs occurrence in IBD patients, even in patients on combination therapy and elderly ones.     

Non-selective beta-blocker treatment does not impact on kidney function in cirrhotic patients with varices

Goals and background: Non-selective beta-blockers (NSBBs) are used for bleeding prophylaxis in cirrhotic patients with gastroesophageal varices (GEVs). Recent data suggested that NSBB treatment might increase the risk of renal dysfunction in patients with refractory ascites due to an impaired response to acute haemodynamic stress.

Study: Retrospective longitudinal assessment of kidney function in a cohort of cirrhotic patients with GEVs with vs. without NSBB therapy. Serum creatinine (SCre), estimated glomerular filtration rate (eGFR), incidence of acute kidney injury (AKI), new onset of large volume ascites and TIPS-/transplant-free survival were compared.

Results: Among 176 patients, 93 patients received NSBBs, while 83 did not. Most patients were male (77.8%), had alcoholic aetiology (52.3%) and compensated cirrhosis (51.1% Child-A, MELD: 12.1?±?3.8). Over a 3-year follow-up, renal function was comparable between patients with and without NSBB treatment. Incidence of AKI was similar in NSBB vs. no-NSBB patients (p?=?.323). Even in potential risk groups (ascites, MAP <90?mmHg, baseline creatinine?>?ULN, hyponatraemia, MELD score ≥15 points, Child–Pugh B/C), there was no difference in SCre or eGFR with vs. without NSBBs (p?=?n.s. at 74/78 and 76/78 of analysed time points). However, multivariate analysis revealed that the presence of ascites (HR: 3.901, 95%CI: 1.352–11.251; p?=?.012) and pre-existing renal impairment (HR: 4.315, 95%CI: 1.054–17.672; p?=?.042) were independent risk factors for AKI. Importantly, NSBB use (HR: 0.319, 95%CI: 0.120–0.848; p?=?.022) was independently associated with improved TIPS-/transplant-free survival.

Conclusions: In our cohort of unselected, mostly compensated cirrhotic patients with GEVs, NSBB treatment was neither associated with worsening of kidney function nor with increased incidence of AKI. On the contrary, NSBB treatment improved TIPS-/transplant-free survival.     

Noninvasive assessment and risk factors of liver fibrosis in patients with thalassemia major using shear wave elastography

Objectives: This study aimed to estimate the prevalence of liver fibrosis and assess the risk factors for developing significant liver fibrosis in patients with Thalassemia Major (TM).

Methods: All patients with TM over the age of 10 years were included in the study.

Results: A total of 94 eligible patients underwent 2-D SWE. The median age was 26.7 years. The median of the average 5-year serum ferritin (5yrSF) and liver iron concentration (LIC) assessed by MRI T2* were 1326?µg/L and 6.7?mg/g?dw, respectively. Hepatitis C and hepatitis B core antibodies were positive in 38% and 1% of the patients respectively. The proportion of patients with significant fibrosis was 60%. Male gender increased the risk of significant fibrosis (Odds ratio of 0.4; p?=?.0373). Additionally, the 5yrSF (p?=?.00661), the LIC (p?=?.0225) and the lowest LIC of the previous 5 years (p?=?.0211) were significant. In the multivariable logistic regression model, only 5yrSF (p?=?.0035) and gender (p?=?.00984) remained significant.

Conclusions: The risk of liver fibrosis is associated with iron overload and gender in patients with TM.     

Prophylaxis of acute flares when initiating febuxostat for chronic gouty arthritis in a real-world clinical setting

Objective: Flare prophylaxis is recommended during urate-lowering therapy (ULT) despite lack of proven benefit especially when initiating febuxostat. We investigated if colchicine or steroids administration during initiation of febuxostat for chronic gouty arthritis reduces the frequency and/or severity of acute gout flares.

Methods: Patients with confirmed diagnosis of gout starting febuxostat were retrospectively studied. Frequency, severity, and length of flares were analyzed. Assessment of severity based on a visual analog scale (VAS).

Results: Two hundred and seventy-three patients were studied. The mean dose of colchicine and steroids was 0.53?±?0.15?mg PO QD and 7.55?±?1.30?mg prednisone equivalent PO QD; while the duration was 6.13?±?1.14 and 6.20?±?1.36 months, respectively. Subjects treated with colchicine and steroids suffered fewer total flares (0.30, 0.96 vs 2.47, p?=?.000), fewer flares from 0 to 3 months (0.26, 0.71 vs 1.72, p?=?.000), less severe flares assessed by VAS than those without prophylactic therapy (3.65, 3.49 vs 5.54, p?=?.000). Both total flares (p?=?.003) and flares from 0 to 3 months (p?=?.008) of the colchicine group were fewer than the steroids group. There were no significant differences in length of flares among groups (p?=?.815). Both colchicine and steroids were well tolerated.

Conclusion: The use of colchicine or steroids prophylaxis reduces the frequency and severity of acute gout flares during initiation of febuxostat for chronic gouty arthritis. Colchicine is superior to steroids in flares prophylaxis. Prophylactic therapy with colchicine 0.5?mg PO QD or steroids 7.5?mg prednisone equivalent PO QD for 6 months is suggested.     

Diffusion-weighted magnetic resonance imaging of parotid glands before and after abatacept therapy in patients with Sjögren’s syndrome associated with rheumatoid arthritis: Utility to evaluate and predict response to treatment

Objective: To compare parotid diffusion-weighted images (DWIs) taken before and after abatacept therapy in patients with Sjögren’s syndrome (SS) associated with rheumatoid arthritis (RA) and to examine the utility in evaluation and prediction of response to therapy.

Methods: DWIs of the parotid glands taken at baseline and 52 weeks after initiation of abatacept were analyzed in nine SS patients with RA using relative standard deviation (RSD) of the entire glands and signal intensity ratio (SIR) within the residual parenchyma. The correlation between changes in RSD and SIR and changes in salivary secretion based on Saxon’s test was examined. Furthermore, baseline characteristics were compared in patients with increased and decreased salivary secretion after treatment. The predictive power of the parameter at baseline was examined using receiver operating characteristic (ROC) analysis.

Results: Abatacept improved salivary secretion from 2076?±?1535 at baseline to 2857?±?1431?mg/2?min at 52 weeks (n?=?9, p?=?.05). Increase of salivary secretion was significantly higher in patients with decreased RSD (n?=?6) than increased RSD (n?=?3) (1241?±?713, –137?±?142?mg/2?min, p?=?.02). The increase and decrease in RSD completely accorded with those of salivary secretion. Furthermore, SIR was the only parameter that was significantly different between patients with posttreatment increase and decrease in salivary secretion (p?=?.04). ROC analysis showed the sensitivity and specificity of SIR at baseline of ≥13.0?×?10^?2 for the prediction of the response to abatacept were 75.0% and 83.3%, respectively.

Conclusions: Parotid DWI seems to be useful for evaluating and predicting the response in salivary secretion to abatacept in SS patients with RA.     

Clinical applicability of Tokyo guidelines 2018/2013 in diagnosis and severity evaluation of acute cholangitis and determination of a new severity model

Objective: To determine the diagnostic accuracy of Tokyo guidelines (TG) 2018/2013 (TG18/TG13) and predictors of poor prognosis in acute cholangitis.

Methods: Retrospective 1-year study of consecutive hospital admissions for acute cholangitis. Prognosis was defined in terms of 30 d in-hospital mortality.

Results: Of the 183 patients with acute cholangitis, diagnostic accuracy based on Charcot’s triad, TG07 and TG18/TG13 was 67.8, 86.9 and 92.3% (p?p?p?=?.006), active oncology disease (OR 3.818; p?=?.006) and malignant aetiology of obstructive jaundice (OR 2.224; p?=?.021) were independent predictors of poor prognosis. The discriminative ability of the model with these four variables was high (AUROC 0.842; p?p?=?.005).

Conclusions: TG18/TG13 showed high diagnostic accuracy in acute cholangitis. Compared with TG18/TG13, the simplified severity model ≥2 allows easy selection of patients who will benefit from admission to the intensive care unit and early biliary decompression.     

The severity of anemia does not correlate with the risk of gastrointestinal cancer in subsequent evaluation

Abstract

Introduction: Iron deficiency anemia (IDA) is a risk factor for gastrointestinal (GI) malignancies. Little is known regarding the correlation between the depth of anemia and the risk for GI malignancy. The aim of this study was to test the hypothesis that very low hemoglobin levels pose an additional risk compared to low hemoglobin levels.

Methods: Patients 40–70?years old, presenting to the ER with IDA during years 2016–2017 were retrospectively analyzed. Comparison was performed between two groups, one with a very low hemoglobin level (below 8?g/dL) and the other a low hemoglobin level (between 8–10?g/dL).

Results: 1020 patients were analyzed, and 107 fulfilled the inclusion criteria. Seventy-five patients (70%) were in the very low hemoglobin group and 21 patients (19.6%) were diagnosed with a new GI malignancy. Mean age was 56, 49 (45%) were females, and 68 (63%) underwent esophagogastroduodenoscopy (EGD) or/and colonoscopy during the index hospitalization. The median hemoglobin and MCV were 7.3?G/dL, and 73?fL, respectively. New malignancies were found in 15/75 (20%) and 6/32 (19%) of patients with very low and low hemoglobin levels, respectively (p?=?.88). GI malignancies were more commonly found in females compared to males, 14 (29%) vs. 7 (12%), p?=?.032, respectively. The right colon was the most common site for malignancy. Active GI bleeding was not a risk factor for GI malignancy.

Conclusions: Very low hemoglobin levels and overt GI bleeding do not pose an additional risk factor for GI malignancy, compared to low hemoglobin levels and no overt GI bleeding.     

Teprenone for the prevention of low-dose aspirin-induced gastric mucosal injury in Helicobacter pylori-negative patients

Abstract

Objectives: Low-dose aspirin is the standard treatment for the prevention of cardiovascular events in at-risk patients. We performed a randomized, placebo-controlled study to determine the efficacy of teprenone for primary prevention of gastrointestinal injury in patients taking LDA for vascular protection.

Methods: Patients were eligible for enrollment if they required aspirin 100?mg/day. Aspirin- naïve patients without gastroduodenal ulcer and Helicobacter pylori infection were randomized to receive teprenone 150?mg/day or placebo for 12?weeks. Primary outcome was assessed by the incidence rate of gastroduodenal ulcer. Secondary outcomes were assessed by the incidence rate of gastric mucosal injury, the improvement in modified Lanza score (MLS), gastrointestinal symptom rating scale (GSRS) and the change of gastric immunohistochemical expression for COX-1.

Results: Total of 130 patients were randomized, 64 in teprenone group and 66 in placebo group. There was no incidence of ulcer after 12?weeks in both groups. Incidence of gastric mucosal injury was higher in placebo group than in teprenone group (40.0 vs. 13.38%, p?=?.039). Mean change of MLS was higher in placebo group than in teprenone group (0.767?±?0.467 vs. 0.271?±?0.158, p?=?.003). Scores of mucosal edema, hyperemia and hemorrhage and the change of GSRS were not different between the two groups. Change of COX-1 immunoreactive score was higher in placebo group than in teprenone group (2.433?±?1.476 vs. 1.233?±?0.955, p?=?.001). There were no treatment-related adverse events.

Conclusions: Teprenone is effective in preventing gastric mucosal injury in patients taking LDA. Preventive effects of teprenone on LDA-related gastroduodenal ulcers require further investigation.     

Fibrinogen levels are associated with bleeding in patients with primary immune thrombocytopenia

Abstract

Bleeding is the most common clinical symptom and the leading cause of death in patients with primary immune thrombocytopenia (ITP). Our research intends to verify the role of fibrinogen levels as independent determinants of bleeding. We retrospectively analyzed the relationship between fibrinogen levels and bleeding events in 463 patients. Additionally, we confirmed the impact of fibrinogen level on clot firmness in 25 patients via thrombelastography (TEG). Fibrinogen levels (median and inter-quartile range, IQR) were significantly different (p < .001) between bleeding and non-bleeding patients [258(207–314) mg/dL vs. 315(262–407) mg/dL, respectively]. Further analyzes in three subgroups based on platelet (PLT) count showed that non-bleeding patients still had higher fibrinogen levels than bleeding patients. The optimal discriminant threshold of fibrinogen in bleeding was 288.5 mg/dL according to receiver operating characteristic (ROC) curves. Patients were divided into low (LF, 230[193–258] mg/dL) and high (HF, 349[313–424] mg/dL) fibrinogen groups based on this threshold. Bleeding event rates were significantly different (LF: 84.6% vs. HF: 60.4%, P < .001) between the two groups. Multivariable analyses further confirmed these differences. Moreover, TEG parameters showed elevated clot firmness in the HF group. Our data suggest that high fibrinogen levels are associated with reduced bleeding events.     

An altered composition of the microbiome in microscopic colitis is driven towards the composition in healthy controls by treatment with budesonide

Background and aim: Microscopic colitis (MC) is an inflammatory disease of the bowel, hypothetically induced by an immunologic response to a luminal microbial agent. We aimed to characterize the microbiome composition in MC and subtypes collagenous colitis (CC) and lymphocytic colitis (LC) and to identify a possible microbial effect of treatment.

Method: Stool samples were collected from MC patients prior to treatment, at 8 weeks (during treatment) and at 16 weeks (after treatment), and from healthy controls, not receiving treatment, at matched time-points. Microbiome composition was analyzed by sequencing of the 16S and 18S genes. Differences between patients and controls were analyzed by Shannon’s diversity index (mean, standard deviation (SD)) and principal coordinate analysis (PCoA) complemented with a permanova test of UniFrac distances.

Results: Ten LC patients, 10?CC patients and 10 controls were included. By PCoA, the bacterial composition in MC patients differed from controls at baseline (p?=?.02), but not during and after treatment (p?=?.09 and p?=?.33, respectively). At baseline, bacterial diversity was lower in MC patients compared to controls (2.5, SD: 0.5 vs 3.5, SD: 0.3, p?<?.05). Diversity in MC patients increased during (3.0, SD: 0.6) and after treatment and (2.9, SD: 0.5) compared with baseline (p?<?.01). Eukaryotes were detected in fewer samples from MC patients compared with controls (11/20 (55%) vs. 9/10 (90%), p?=?.06) with no effect of treatment.

Conclusion: Microbiome composition is altered in MC patients. During and after treatment with budesonide the microbiome composition in MC patients was driven towards the composition in healthy controls.     

Soluble programmed death-1 levels are associated with disease activity and treatment response in patients with autoimmune hepatitis

Purpose: Autoimmune hepatitis (AIH) is a chronic liver disease caused by impaired immune regulation. Programmed death-1 (PD-1) is an inhibitory receptor mainly expressed by T cells and with its ligands, PD-L1 and PD-L2 present on antigen-presenting cells. We hypothesised the PD-1 axis to be impaired in AIH and investigated systemic levels of soluble(s) PD-1 and T cells ability to up-regulate PD-1 following in vitro activation in AIH patients.

Materials and methods: We included 67 AIH patients; 9 with active disease, 31 responders and 27 incomplete-responders to standard therapy. Forty-seven healthy controls (HC) were included for comparison. Soluble PD-1 was measured by enzyme-linked immunosorbent assay. The PD-1 expression on T cells was measured using flow cytometry before and after 48-h stimulation in vitro with CD3/CD28 in 13 AIH patients and 10 HC.

Results: Soluble PD-1 was significantly elevated in AIH patients with active disease [0.24?ng/mL (range 0.16–0.28)] and in incomplete responders to standard therapy [0.17 (0.11–0.22)] compared with responders [0.11 (0.08–0.16), p?=?.008 and p?=?.01, respectively] and HC [0.12 (0.05–0.16), p?=?.02, both]. Following in vitro activation, PD-1 was significantly up-regulated (3.3-fold) on CD4⁺?T cells from AIH patients compared with HC (1.5-fold) (p?=?.0006).

Conclusions: AIH patients with active disease and incomplete response to standard treatment have similarly increased sPD-1 levels. Further, AIH patients have increased ability to up-regulate PD-1 following in vitro activation. Together these data suggests an impaired PD-1 axis in AIH.     

Choledocholithiasis in elderly patients with gallbladder in situ - is ERCP sufficient?

Abstract

Introduction: Along with increased life expectancy, the proportion of elderly patients with choledocholithiasis will increase and with this, the need for endoscopic cholangiopancreatography (ERCP). Current recommendations suggest laparoscopic cholecystectomy in all patients with choledocholithiasis to prevent biliary events. However, adherence to these recommendations is low, especially in older patients.

Methods: Retrospective study that included non-cholecystectomized patients aged >?=75 years who underwent ERCP for choledocholithiasis from 2013–2016 (n?=?131). A new biliary event was defined as the need for a new ERCP, cholecystitis, cholangitis or gallstone pancreatitis.

Aim: The aim of this study was to compare the outcomes of new biliary events and mortality in cholecystectomized vs non-cholecystectomized patients after ERCP.

Results: Cholecystectomy was performed in 22% of the patients (92% laparoscopic). The post-cholecystectomy complication rate was 13% and the mortality rate was 7%. During the follow-up period (669?±?487 days) a new biliary event occurred in 20% of patients - 10% new ERCP, 9% cholecystitis, 9% cholangitis and 2% pancreatitis. Cholecystectomized patients had fewer events (7% vs 24%, p?=?.048) and longer time to event (p?=?.016). There was no statistically significant difference in all-cause mortality (14% vs 27%, p?=?.13), mortality related to lithiasis (0% vs 9%, p?=?.11) or time to mortality from all causes (p?=?.07) and related to biliary events (p?=?.07).

Conclusions: In this group of elderly patients, cholecystectomy after ERCP prevented the occurrence of new biliary events but resulted in a non-statistically significant difference in mortality.     

Hypoparathyroidism concomitant with macrothrombocytopenia in an elderly woman with 22q11.2 deletion syndrome

We describe the case of a 62-year-old woman with schizophrenia and intellectual disability, who presented with intermittent muscle cramping for 2 weeks. A dysmorphic face and a positive Trousseau’s sign, but without ecchymosis or petechial lesion were noted. Laboratory data revealed impaired renal function (creatinine level = 1.6 mg/dL), severe hypocalcaemia (total calcium level = 5.7 mg/dL) with low urinary calcium excretion (13.2 mg/day), hyperphosphatemia (phosphate level = 7.3 mg/dL), and low intact parathyroid hormone level (52.5 pg/mL)—indicating primary hypoparathyroidism. A blood smear revealed thrombocytopenia (30,000 thrombocytes/µL) and giant platelets—indicating macrothrombocytopenia. Chromosome 22q11.2 deletion syndrome (22q11.2DS) in the deficient chromosome 22 was confirmed using multiplex ligation-dependent probe amplification showing haploinsufficiency in GP1BB and TBX-1. Cooccurrence of hypoparathyroidism and macrothrombocytopenia in 22q11.2DS is rare and can easily be misdiagnosed as idiopathic thrombocytopenia purpura and inappropriate splenectomy or chemotherapy can aggravate hypoparathyroidism. Early diagnosis of 22q11.2DS, characterized by hypoparathyroidism and macrothrombocytopenia, in elderly patients with schizophrenia can facilitate in avoiding circuitous diagnosis and inappropriate management.     

Smoking is associated with severity of liver fibrosis but not with histological severity in nonalcoholic fatty liver disease. Results from a cross-sectional study

Objectives: To assess the influence of smoking on histological disease severity and fibrosis in real-world NAFLD patients.

Material and methods: Consecutive NAFLD patients were identified with liver biopsies performed between 2008 and 2015. Characteristics such as smoking status and total number of pack years were collected. Biopsies were revised and BRUNT fibrosis and NAFLD activity score (NAS) determined. Patients with a high NAS (≥5) were compared to patients with a low NAS (<5) and with advanced fibrosis (stage 3–4) to patients with no-early fibrosis (stage 0–2). Patients with a history of smoking (current or past smoker) were defined ever smokers.

Results: Fifty-six patients were included (mean age 49?±?14.3, 68.9% males and 39.3% history of smoking). Ever smokers had a higher fibrosis score than never smokers; two (IQR 0–3) versus one (IQR 1–1.5) (p?=?.040). Patients with advanced fibrosis smoked significantly more pack years than patients with no-early fibrosis; 10.6 (IQR 0–25.8) versus 0 (IQR 0–7) (p?=?.011). There is a weak to moderate correlation between fibrosis stage and number of pack years (Spearman’s Rho?=?0.341, p?=?.012). There was no difference in NAS between never and ever smokers; 2.8?±?1.5 versus 3.3?±?1.4 (p?=?.205). Patients with NAS <5 had a median number of pack years of 0 (IQR 0–9) versus a median of 10.3 pack years (IQR 0–24) in patients with NAS ≥5 (p?=?.127).

Conclusion: Smoking is associated with severity of NAFLD-related liver fibrosis but not with histological disease severity. This supports the recommendation to cease smoking for NAFLD patients.     

Efficacy and safety of sirukumab in Japanese patients with active rheumatoid arthritis who were refractory or intolerant to anti-tumor necrosis factor therapy: Subgroup analysis of a randomized,double-blind,multicenter, phase 3 study (SIRROUND-T)

Abstract

Objective: To evaluate the efficacy and safety of sirukumab, a human anti-interleukin six monoclonal antibody, in Japanese patients with rheumatoid arthritis who were refractory to anti-tumor necrosis factor therapy.

Methods: This subgroup analysis, based on a double-blind, placebo-controlled, 52-week phase 3, global study (SIRROUND-T) assessed the American College of Rheumatology (ACR) 20 response at week 16 (primary endpoint). Secondary endpoints: ACR 50, Disease Activity Score in 28 joints-C reactive protein, Health Assessment Questionnaire-Disability Index and safety were assessed.

Results 116/878 patients received sirukumab 50?mg/4 weeks (q4w, n?=?35), 100?mg/2 weeks (q2w, n?=?44) or placebo (n?=?37) subcutaneously. Significantly more patients achieved ACR 20 response at week 16 with sirukumab (50?mg q4w:20 [57.1%]; p?<?.001, 100?mg q2w:24 [54.5%]; p?=?.001) versus placebo (7 [18.9%]); consistent significant improvement in secondary endpoints at week 24 and 52 was observed. At week 24, incidence of treatment-emergent adverse events (TEAEs) was numerically higher with sirukumab groups (50?mg q4w:29 [82.9%]; 100?mg q2w:38 [86.4%] versus placebo (28 [75.7%]); however, at week 52, sirukumab combined groups had comparable incidence of TEAEs.

Conclusion: Efficacy findings through 52 weeks were comparable between sirukumab doses in Japanese patients and consistent with primary SIRROUND-T study results. No new safety signals were observed.