Muckle–Wells syndrome in an Indian family associated with NLRP3 mutation

Muckle — Wells syndrome (MWS) is a rare autosomal dominant disease that belongs to a group of hereditary periodic fever syndromes. It is part of the wider spectrum of the cryopyrin-associated periodic syndrome (CAPS) which has only rarely been described in non-Caucasian individuals. It is characterized by recurrent self-limiting episodes of fever, urticaria, arthralgia, myalgia and conjunctivitis from childhood. Progressive sensorineural hearing loss and amyloidosis are two late complications. MWS is caused by gain of function mutations in the NLRP3 gene, which encodes cryopyrin, a protein involved in regulating the production of proinflammatory cytokines. We report two patients with MWS in an Indian family associated with the p.D303N mutation in the NLRP3 gene. These findings promote awareness of these hereditary periodic fever syndromes as a cause for recurrent fevers from childhood in the Indian population.KEY WORDS: Hereditary periodic fever, D303N mutation, Indian family, Muckle—Wells syndrome, p.D303N mutation     

Accuracy of multi-slice computed tomography for measurement of left ventricular ejection fraction compared with cardiac magnetic resonance imaging and two-dimensional transthoracic echocardiography: a systematic review and meta-analysis

Background

Multi-slice computed tomography (MSCT) allows non-invasive assessment of the coronary arteries and simultaneously can provide measurement of left ventricular ejection fraction (LVEF). The accuracy of newer MSCT generations (64-slice or more) for assessment of LVEF compared with magnetic resonance imaging (MRI) and two-dimensional transthoracic echocardiography (TTE) has not been evaluated in a meta-analysis.

Purpose

To evaluate, via a systematic literature review and meta-analysis, whether MSCT can assess LVEF with high accuracy compared with MRI and TTE.

Methods

Electronic databases and reference lists for relevant published studies were searched. Twenty-seven eligible studies provided mean LVEF% with its standard deviation (SD) measured by MSCT versus MRI and TTE. Meta-analysis of weighted mean difference (WMD) and Bland–Altman method were used to quantify the mean difference and agreement between MSCT compared with MRI and TTE.

Results

The results of combining 12 studies showed no significant difference in LVEF% between MSCT and MRI with a WMD of −0.11 (−1.48, 1.26, 95% CI), p = 0.88. Bland–Altman analysis showed excellent agreement between MSCT and MRI with a bias of 0.0 (−3.7, 3.7 ± 1.96SD) with 95% CI. The results of combining 15 studies showed no significant difference in LVEF between MSCT versus TTE measurements with a WMD of 0.19 (−1.13 to 1.50; 95% CI), p = 0.87. Bland–Altman analysis showed excellent agreement between MSCT and TTE with a bias of 0.3 (−4.7, 5.7 ± 1.96SD) with 95% CI.

Conclusion

The newer MSCT generations can provide accurate LVEF measurement compared to MRI and TTE. MSCT represents a valid technique for the combined evaluation of LVEF and coronary artery disease.     

Evaluation of Naturally Occurring Radioactive Materials (NORMs) in Inorganic and Organic Oilfield Scales from the Middle East

The distribution of natural nuclide gamma-ray activities and their respective annual effective dose rates, produced by potassium-40 (⁴⁰K), uranium-238 (²³⁸U), thorium-232 (²³²Th), and radium-226 (²²⁶Ra), were determined for 14 oilfield scale samples from the Middle East. Accumulated radioactive materials concentrate in tubing and surface equipment, and workers at equipment-cleaning facilities and naturally occurring radioactive materials (NORMs) disposal facilities are the population most at risk for exposure to NORM radiation. Gamma-spectra analysis indicated that photo-gamma lines represent the parents of 10 radioactive nuclides: ²³⁴Th, plutonium-239, actinium-228, ²²⁶Ra, lead-212 (²¹²Pb), ²¹⁴Pb, thallium-238 (²⁰⁸Tl), bismuth-212 (²¹²Bi), ²¹⁴Bi, and ⁴⁰K. These nuclides represent the daughters of the natural radioactive series ²³⁸U and ²³²Th with ⁴⁰K as well. The mean activity concentration of ²³⁸U, ²³²Th, and ⁴⁰K were found to be 25.8 ± 11.6, 18.3 ± 8.1, and 4487.2 ± 2.5% Bq kg⁻¹ (average values for 14 samples), respectively. The annual effective dose rates and the absorbed doses in air, both indoor and outdoor, for the samples were obtained as well. The results can be used to assess the respective hazard on workers in the field and represent a basis for revisiting current engineering practices.     

Isolated ultrafiltration in the therapy of volume overload accompanying oliguric vascular shock states.

Isolated ultrafiltration (removal of plasma water and solute without dialysis) was used as a "last resort" therapy in three patients with diuretic and pressor resistant oliguria complicating severe volume overload and vascular shock. The improvement in clinical and hemodynamic parameters is reported and the possible mechanisms of action (decreased pulmonary capillary wedge pressure and increased colloid osmotic pressure) are discussed.     

Impact of obesity as a mortality predictor in high-risk patients with myocardial infarction or chronic heart failure: a pooled analysis of five registries

AIMS: To explore the influence of obesity on prognosis in high-risk patients with myocardial infarction (MI) or heart failure (HF). METHODS AND RESULTS: Individual data of 21 570 consecutively hospitalized patients from five Danish registries were pooled together. After a follow-up of 10.4 years, all-cause mortality using multivariate model and adjusted hazard ratios (HR) with 95% confidence intervals were calculated. Compared with normal weight [body mass index (BMI) 18.5-24.9 kg/m2], obesity class II (BMI >or= 35 kg/m2) was associated with increased risk of death in patients with MI but not HF [HR = 1.23 (1.06-1.44), P = 0.006 and HR = 1.13 (0.95-1.36), P = 0.95] (P-value for interaction = 0.004). Obesity class I (BMI 30-34.9 kg/m2) was not associated with increased risk of death in MI or HF [HR = 0.99 (0.92-1.08) and 1.00 (0.90-1.11), P > 0.1]. Pre-obesity (BMI 25-29.9 kg/m2) was associated with decreased death risk in MI but not HF [HR = 0.91 (0.87-0.96), P = 0.0006 and 1.04 (0.97-1.12), P = 0.34] (P-value for interaction = 0.007). Underweight (BMI < 18.5 kg/m2) patients were in increased death risk regardless of MI or HF [HR = 1.54 (1.35-1.75) and 1.37 (1.18-1.59), P < 0.001]. CONCLUSION: In patients with MI but not HF, the relationship between BMI and mortality is U-shaped with highest mortality in underweight and obese class II, but lowest in the other BMI classes.     

Metformin in Peritoneal Dialysis: A Pilot Experience

♦ Objective: In a number of patients, the antidiabetic drug metformin has been associated with lactic acidosis. Despite the fact that diabetes mellitus is the most common cause of end-stage renal disease (ESRD) and that peritoneal dialysis (PD) is an expanding modality of treatment, little is known about optimal treatment strategies in the large group of PD patients with diabetes. In patients with ESRD, the use of metformin has been limited because of the perceived risk of lactic acidosis or severe hypoglycemia. However, metformin use is likely to be beneficial, and PD might itself be a safeguard against the alleged complications.♦ Methods: Our study involved 35 patients with insulin-dependent type 2 diabetes [median age: 54 years; interquartile range (IQR): 47-59 years] on automated PD (APD) therapy. Patients with additional risk factors for lactic acidosis were excluded. Metformin was introduced at a daily dose in the range 0.5 - 1.0 g. All patients were monitored for glycemic control by blood sugar levels and HbA1c. Plasma lactic acid levels were measured weekly for 4 weeks and then monthly to the end of the study. Plasma and effluent metformin and plasma lactate levels were measured simultaneously.♦ Results: In this cohort, the median duration of diabetes was 18 years (IQR: 14 - 21 years), median time on PD was 31 months (IQR: 27 - 36 months), and median HbA1c was 6.8% (IQR: 5.9% - 6.9%). At metformin introduction and at the end of the study, the median anion gap was 11 mmol/L (IQR: 9 - 16 mmol/L) and 12 mmol/L (IQR: 9 - 16 mmol/L; p > 0.05) respectively, median pH was 7.33 (IQR: 7.32 - 7.36) and 7.34 (IQR: 7.32 - 7.36, p > 0.05) respectively, and mean metformin concentration in plasma and peritoneal fluid was 2.57 ± 1.49 mg/L and 2.83 ± 1.7 mg/L respectively. In the group overall, mean lactate was 1.39 ± 0.61 mmol/L, and hyperlactemia (>2 mmol/L to 5 mmol/L) was found in 4 of 525 plasma samples (0.76%), but the patients presented no symptoms. None of the patients registered a plasma lactate level above 5 mmol/L. We observed no correlation between plasma metformin and plasma lactate (r = 0.27).♦ Conclusions: Metformin may be used with caution in APD patients with insulin-dependent type 2 diabetes. Although our study demonstrated the feasibility of metformin use in APD, it was not large enough to demonstrate safety; a large-scale study is needed.