Is severe hypocalcemia immediately life-threatening?

Objective: Severe hypocalcemia (Ca <1.9 mmol/L) is often considered an emergency because of a potential risk of cardiac arrest or seizures. However, there is little evidence to support this. The aim of our study was to assess whether severe hypocalcemia was associated with immediately life-threatening cardiac arrhythmias or neurological complications. Methods: A retrospective observational study was carried out over a 2 years period in the Adult Emergency Department (ED) of Nantes University Hospital. All patients who had a protein-corrected calcium concentration measure were eligible for inclusion. Patients with multiple myeloma were excluded. The primary outcome was the number of life-threatening cardiac arrhythmias and/or neurological complications during the stay in the ED. Results: A total of 41,823 patients had protein-corrected calcium (pcCa) concentrations measured, 155 had severe hypocalcaemia, 22 were excluded because of myeloma leaving 133 for analysis. Median pcCa concentration was 1.73 mmol/L [1.57-1.84]. Seventeen (12.8%) patients presented a life threatening condition, 14 (10.5%) neurological and 3 (2.2%) cardiac during ED stay. However these complications could be explained by the presence of underlying co-morbidities and or electrolyte disturbances other than hypocalcaemia. Overall 24 (18%) patients died in hospital. Vitamin D deficiency, chronic kidney disease and hypoparathyroidism were the most frequently found causes of hypocalcemia. Conclusion: 13% of patients with severe hypocalcaemia presented a life-threatening cardiac or neurological complication on the ED. However a perfectly valid alternative cause could account for these complications. Further research is warranted to define the precise role of hypocalcaemia.

Detection of EGFR gene mutations in non-small cell lung cancer: lessons from a single-institution routine analysis of 1,403 tumor samples.

Activating mutations of the epidermal growth factor receptor (EGFR) in lung tumors are associated with a dramatic response to tyrosine kinase inhibitors. Therefore, routine analysis of pathological specimens is mandatory in clinical practice. We have prospectively tested tumors from Caucasian lung tumor patients between January 2010 and June 2012. DNA was extracted from formalin-fixed paraffin-embedded tissues following macrodissection. The p.L858R substitution was assessed by allele-specific PCR and exon 19 deletions by PCR and DNA fragment analysis. Using a robust process from patient sampling to screening methods, we analyzed samples from 1,403 patients. The EGFR status could be successfully determined for 1,322 patients. EGFR mutations were detected in 179 (13.5%) patients, with female and adenocarcinoma histology predominance. Mutated patients were significantly older than non-mutated patients. Similar mutation rates were obtained with primary tumors and metastases, and with surgical resection, bronchial biopsies, CT-guided needle biopsies and transbronchial needle aspiration. The sensitivity of our assays allowed us to detect EGFR mutations in samples poor (<10%) in tumor cells. Finally, the mutation rate was much higher in tumors expressing the TTF-1 antigen (145/820; 17.7%) than in TTF-1 negative tumors (3/218; 1.4%). The results obtained through routine analysis of more than 1,300 samples indicated that all types of specimen can be analyzed without any significant bias. TTF-1 immunostaining may be used to predict negative EGFR mutation status.

Plasma PCSK9 is a late biomarker of severity in patients with severe trauma injury.

CONTEXT: PCSK9 (proprotein convertase subtilisin kexin type 9) is a secreted protease that modulates cholesterol homeostasis by decreasing low-density lipoprotein receptor expression. Low levels of plasma lipoproteins are related to severity of illness and survival in patients of intensive care units (ICU). OBJECTIVE: The aim of the study was to investigate the regulation of plasma PCSK9 and its association with plasma lipid parameters and clinical markers of severity during critical illness. DESIGN AND PATIENTS: The plasma biobank from the previously published HYPOLYTE prospective study was used to measure PCSK9 concentrations by ELISA at days 0 and 8 in 111 patients admitted to surgical ICU for severe multiple trauma. Patients were randomly assigned to hydrocortisone therapy or placebo. RESULTS: Plasma PCSK9 levels were increased by 2-fold between days 0 and 8 (231 ± 116 vs 481 ± 227 ng/ml; P = .0001). Hydrocortisone therapy did not alter PCSK9 concentrations (451 ± 216 vs 511 ± 239 ng/ml in placebo group; P = .33). PCSK9 was positively associated with low-density lipoprotein-cholesterol (Pearson coefficient, 0.26; P = .007) at day 0, but not at day 8. At day 8, an inverse correlation was found between PCSK9 and high-density lipoprotein-cholesterol (ß = -653; P = .004). Although baseline PCSK9 concentrations were not associated to severity scores, PCSK9 values at day 8 were related to injury severity score (ß = 6.17; P = .0007), length of stay in ICU (ß = 6.14; P = .0001), and duration of both mechanical ventilation (ß = 8.26; P = .0001) and norepinephrine infusion (ß = 18.57; P = .015). CONCLUSIONS: Plasma PCSK9 appears as a late biomarker of illness severity in patients with severe multiple trauma.

Disturbance of apolipoprotein B100 containing lipoprotein metabolism in severe hyperlipidemic and lipodystrophic HIV patients on combined antiretroviral therapy: evidences of insulin resistance effect.

The aim was to study the mechanisms involved in the dyslipidemia associated with lipodystrophy in HIV infected patients on antiretroviral therapy (ART). We investigated the in vivo kinetics of apolipoprotein B100 (apoB) containing lipoproteins using a 14 h primed constant infusion of [5,5,5, (2)H(3)] leucine and compartmental modelling in normolipidemic without lipodystrophy (7 patients, NLD) or dyslipidemic with lipodystrophy (7 patients, LD) treated with ART. Subjects in group LD showed higher plasma triglycerides (5.73+/-3.58 vs 1.29+/-0.54 g/L, p<0.005), total cholesterol (2.98+/-0.95 vs 1.74+/-0.26 g/L, p<0.05), apoB (1.49+/-1.11 vs 0.51+/-0.11 g/L, p<0.005) and apolipoprotein CIII in apoB containing lipoproteins (117.7+/-42.2 vs 22.6+/-23.9 g/L, p<0.005). LD subjects exhibited an insulin resistant as observed by higher HOMA (3.44+/-1.62 vs 1.60+/-0.61, p<0.05). They exhibited an increase in VLDL (1.24+/-0.33 vs 0.80+/-0.21 mg/kg/h, p<0.05), decrease in IDL (0.20+/-0.10 vs 0.48+/-0.24 mg/kg/h, p<0.05) and no difference in LDL (0.38+/-0.19 vs 0.45+/-0.25 mg/kg/h) production rate. LD subject also showed a dramatic decrease in transformation of VLDL to IDL (0.013+/-0.010 vs 0.258+/-0.206 h(-1), p<0.005) and IDL to LDL (0.088+/-0.093 vs 0.366+/-0.189 h(-1), p<0.05) and a decrease in fractional catabolic rate (FCR) of VLDL (0.199+/-0.132 vs 0.555+/-0.398 h(-1), p<0.05), IDL (0.110+/-0.08 vs 0.523+/-0.275 h(-1), p<0.05) and LDL (0.010+/-0.005 vs 0.025+/-0.014 h(-1), p<0.05). These disturbances, overproduction and an overall delayed catabolism of apoB, are similar to those observed using the same protocol in insulin resistant subjects. Our study suggests that metabolic disturbance of apoB100 observed in lipodystrophic HIV in combined antiretroviral therapy are consecutive to insulin resistance induced by the treatment.

Active smoking compromises IVF outcome and affects ovarian reserve.

Although the association between smoking and female infertility is now largely demonstrated, the proportion of smokers in women of reproductive age remains important. Tobacco contains numerous toxicants that could affect ovarian reserve and lead to poor prognosis in assisted reproductive techniques. To investigate the effect of female active smoking on ovarian reserve and IVF outcome, smoking status, hormonal status, i.e. serum FSH, oestradiol and anti-Müllerian hormone (AMH), ovarian response to hyperstimulation, i.e. mature oocytes retrieved, and IVF outcome, i.e. clinical pregnancy, were retrospectively analysed in 111 women undergoing IVF-embryo transfer cycles. Compared with non-smokers (n = 71), active smoking women (n = 40) had decreased ovarian response (12.12 +/- 5 versus 8.62 +/- 4 mature oocytes retrieved) to hyperstimulation and lower clinical pregnancy rate (29.6 versus 10.0%). Serum AMH concentrations were lower in the smoker group (3.86 +/- 1.92 versus 3.06 +/- 1.68 mug/l) and had no predictive value for ovarian response, inversely to non-smokers. In conclusion, active smoking is associated with poor prognosis in assisted reproduction cycles, i.e. ovarian response and pregnancy, and leads to altered ovarian reserve, as reflected by decreased serum AMH concentrations.