Prognostic value of total tumor volume in patients with colorectal liver metastases:A secondary analysis of the randomized CAIRO5 trial with external cohort validation

Background:This study aimed to assess the prognostic value of total tumor volume (TTV) for early recurrence (within 6 months) and overall survival (OS) in patients with colorectal liver metastases (CRLM), treated with induction systemic therapy followed by complete local treatment.Methods: Patients with initially unresectable CRLM from the multicenter randomized phase 3 CAIRO5 trial (NCT02162563) who received induction systemic therapy followed by local treatment were included. Baseline TTV and change in TTV as response to systemic therapy were calculated using the CT scan before and the first after systemic treatment, and were assessed for their added prognostic value. The findings were validated in an external cohort of patients treated at a tertiary center. Results:In total, 215 CAIRO5 patients were included. Baseline TTV and absolute change in TTV were significantly associated with early recurrence (P = 0.005 and P = 0.040, respectively) and OS in multivariable analyses (P = 0.024 and P = 0.006, respectively), whereas RECIST1.1 was not prognostic for early recurrence (P = 0.88) and OS (P = 0.35). In the validation cohort (n = 85), baseline TTV and absolute change in TTV remained prognostic for early recurrence (P = 0.041 and P = 0.021, respectively) and OS in multivariable analyses (P &lt; 0.0001 and P = 0.012, respectively), and showed added prognostic value over conventional clinicopathological variables (increase C-statistic, 0.06; 95 % CI, 0.02 to 0.14; P = 0.008). Conclusion: Total tumor volume is strongly prognostic for early recurrence and OS in patients who underwent complete local treatment of initially unresectable CRLM, both in the CAIRO5 trial and the validation cohort. In contrast, RECIST1.1 did not show prognostic value for neither early recurrence nor OS.</p

Comparison of BNP and NT-proBNP performances for assessing heart failure in a population of patients with high incidence of with renal insufficiency

peer reviewedIntroduction : Le but de notre étude est de comparer les performances du BNP et du NT-proBNP dans le diagnostic d’insuffisance cardiaque dans une population de patients atteints d’insuffisance rénale (créatinine plasmatique > 1,5 mg/dl). Patients et méthodes : Quatre-vingt dix-huit patients furent inclus dans notre étude prospective. Le dosage du BNP et du NT-proBNP a été réalisé respectivement par une technique d’immunofluorecence (Biosite®) et par une technique d’électrochemiluminescence (Roche Diagnostic®). Résultats et discussion : Les taux de BNP et NT-proBNP sont corrélés chez les CRI et NON CRI. Les deux marqueurs sont utiles pour mettre en évidence des patients CRI suspectés d’insuffisance cardiaque. Cependant, chez ceux-ci, une limite de décision plus haute devrait être envisagée pour augmenter la valeur prédictive positive de ces marqueurs.Background: The aim of the study is to compare the performances of BNP and NT-proBNP for diagnosing heart failure (HF) in a population of patients with high incidence of chronic renal insufficiency (CRI, plasma creatinine > 1.5 mg/dl). Patients and methods: Ninety-eight patients were included in this study. BNP and NT-proBNP determinations were performed by an immunofluorescent assay (Biosite®) and by an electrochemiluminescence sandwich immuno assay (Roche Diagnostic®), respectively. Results and discussion: BNP and NTproBNP level are correlated in CRI and non CRI . Both assays are useful to rule out CRI pts suspected of HF. However, in renal failure pts, higher decision limits should be used for improving the positive predictive value of the assays

Mutations in the nebulin gene associated with autosomal recessive nemaline myopathy

The congenital nemaline myopathies are rare hereditary muscle disorders characterized by the presence in the muscle fibers of nemaline bodies consisting of proteins derived from the Z disc and thin filament. In a single large Australian family with an autosomal dominant form of nemaline myopathy, the disease is caused by a mutation in the α-tropomyosin gene TPM3. The typical form of nemaline myopathy is inherited as an autosomal recessive trait, the locus of which we previously assigned to chromosome 2q21.2-q22. We show here that mutations in the nebulin gene located within this region are associated with the disease. The nebulin protein is a giant protein found in the thin filaments of striated muscle. A variety of nebulin isoforms are thought to contribute to the molecular diversity of Z discs. We have studied the 3′ end of the 20.8-kb cDNA encoding the Z disc part of the 800-kDa protein and describe six disease-associated mutations in patients from five families of different ethnic origins. In two families with consanguineous parents, the patients were homozygous for point mutations. In one family with nonconsanguineous parents, the affected siblings were compound heterozygotes for two different mutations, and in two further families with one detected mutation each, haplotypes are compatible with compound heterozygosity. Immunofluorescence studies with antibodies specific to the C-terminal region of nebulin indicate that the mutations may cause protein truncation possibly associated with loss of fiber-type diversity, which may be relevant to disease pathogenesis