Liver-to-thoracic volume ratio: use at MR imaging to predict postnatal survival in fetuses with isolated congenital diaphragmatic hernia with or without prenatal tracheal occlusion

Objective

To evaluate the relationship of the liver-to-thoracic volume ratio (LiTR) by MRI with postnatal survival in foetuses with isolated congenital diaphragmatic hernia (CDH).

Methods

In 30 conservatively managed CDH foetuses and in 31 who underwent fetoscopic endoluminal tracheal occlusion (FETO), logistic regression analysis was used to investigate the effect on postnatal survival of the observed-to-expected (O/E) ratio of total foetal lung volume (TFLV), LiTR, gestational age at delivery, CDH side, intrathoracic position of the liver and, for those who underwent FETO, gestational age at FETO and occlusion period. For 19 foetuses undergoing FETO, a post-FETO MRI was available. The proportionate increase in O/E ratio of TFLV at 3–8 weeks after FETO was compared with the pre-FETO value and correlated with pre-FETO LiTR using linear regression analysis.

Results

For conservatively managed foetuses, only LiTR provided a significant prediction of postnatal survival. For foetuses undergoing FETO, LiTR and gestational age at delivery provided a significant independent prediction of postnatal survival. There was a significant inverse association between lung response and pre-FETO LiTR.

Conclusion

In foetuses with CDH with/without FETO treatment, the LiTR is predictive of postnatal survival at discharge. In foetuses treated with FETO, LiTR is predictive of post-FETO lung response.

Key Points

? Congenital diaphragmatic hernia is usually managed conservatively before surgery soon after delivery ? Fetoscopic endoluminal tracheal occlusion (FETO) has been introduced for severely affected foetuses ? In conservatively managed CDH, the liver-to-thoracic volume ratio (LiTR) predicted postnatal survival best. ? In severe CDH with prenatal FETO, LiTR also helped predict postnatal survival. ? LiTR should be integrated into the prenatal decision-making for foetuses with CDH.     

Targetable activating mutations are very frequent in GCB and ABC diffuse large B‐cell lymphoma

Diffuse large B cell lymphoma (DLBCL) is an aggressive and heterogeneous malignancy that can be divided in two major subgroups, germinal center B‐cell‐like (GCB) and activated B‐cell‐like (ABC). Activating mutations of genes involved in the BCR and NF‐κB pathways (CD79A, CD79B, MYD88, and CARD11) or in epigenetic regulation (EZH2) have been recently reported, preferentially in one of the two DLBCL subtypes. We analyzed the mutational status of these five recurrently mutated genes in a cohort of 161 untreated de novo DLBCL. Overall, 93 mutations were detected, in 61 (38%) of the patients. The L265P MYD88 mutation was the most frequent MYD88 variant (n = 18), observed exclusively in the ABC subtype. CD79A/CD79B ITAM domains were targeted in ABC DLBCL (12/77; 16%), whereas CARD11 mutations were equally distributed in the two subtypes. The EZH2 Y641 substitution was found almost exclusively in the GCB subgroup (15/62; 24%). Twenty cases (12%) displayed two activating mutations, including the most frequent CD79/MYD88 variants combination (n = 8) which is observed exclusively in the ABC subtype. When considering only ABC DLBCL patients treated by rituximab plus chemotherapy, the presence of an activating NF‐κB mutation was associated with an unfavorable outcome (3‐years OS 26% for mutated cases versus 67% for the cases without mutations, P = 0.0337). Our study demonstrates that activating and targetable mutations are observed at a very high frequency in DLBCL at the time of diagnosis, indicating that sequencing of a limited number of genes could help tailor an optimal treatment strategy in DLBCL. © 2013 Wiley Periodicals, Inc.     

Care pathways for people with major depressive disorder: A European Brain Council Value of Treatment study

BackgroundDespite well-established guidelines for managing major depressive disorder, its extensive disability burden persists. This Value of Treatment mission from the European Brain Council aimed to elucidate the nature and extent of “gaps” between best-practice and current-practice care, specifically to:

1. Identify current treatment gaps along the care pathway and determine the extent of these gaps in comparison with the stepped-care model and
2. Recommend policies intending to better meet patient needs (i.e., minimize treatment gaps).

MethodsAfter agreement upon a set of relevant treatment gaps, data pertaining to each gap were gathered and synthesized from several sources across six European countries. Subsequently, a modified Delphi approach was undertaken to attain consensus among an expert panel on proposed recommendations for minimizing treatment gaps.ResultsFour recommendations were made to increase the depression diagnosis rate (from ~50% episodes), aiming to both increase the number of patients seeking help, and the likelihood of a practitioner to correctly detect depression. These should reduce time to treatment (from ~1 to ~8 years after illness onset) and increase rates of treatment; nine further recommendations aimed to increase rates of treatment (from ~25 to ~50% of patients currently treated), mainly focused on targeting the best treatment to each patient. To improve follow-up after treatment initiation (from ~30 to ~65% followed up within 3 months), seven recommendations focused on increasing continuity of care. For those not responding, 10 recommendations focused on ensuring access to more specialist care (currently at rates of ~5–25% of patients).ConclusionsThe treatment gaps in depression care are substantial and concerning, from the proportion of people not entering care pathways to those stagnating in primary care with impairing and persistent illness. A wide range of recommendations can be made to enhance care throughout the pathway.     

Oncogenic events rather than antigen selection pressure may be the main driving forces for relapse in diffuse large B‐cell lymphomas

Little is known on the phylogenetic relationship between diagnostic and relapse clones of diffuse large B‐cell lymphoma (DLBCL). We applied high throughput sequencing (HTS) of the VDJ locus of Immunoglobulin heavy chain (IGHV) on 14 DLBCL patients with serial samples, including tumor biopsies and/or peripheral blood mononuclear cells (PBMC). Phylogenetic data were consolidated with targeted sequencing and cytogenetics. Phylogeny clearly showed that DLBCL relapse could occur according either an early or a late divergent mode. These two modes of divergence were independent from the elapsed time between diagnosis and relapse. We found no significant features for antigen selection pressure in complementary determining region both at diagnosis and relapse for 9/12 pairs and a conserved negative selection pressure for the three remaining cases. Targeted HTS and conventional cytogenetics revealed a branched vs. linear evolution for 5/5 IGHV early divergent cases, but unexpected such “oncogenetic” branched evolution could be found in at least 2/7 IGHV late divergent cases. Thus, if BCR signaling is mandatory for DLBCL emergence, oncogenetic events under chemotherapy selection pressure may be the main driving forces at relapse. Finally, circulating subclones with divergent IGHV somatic hypermutations patterns from initial biopsy could be detected in PBMC at diagnosis for 4/6 patients and, for two of them, at least one was similar to the ones found at relapse. This study highlights that oncogenetic intraclonal diversity of DLBCL should be evaluated beyond the scope a single biopsy and represents a rationale for future investigations using peripheral blood for lymphoid malignancies genotyping. Am. J. Hematol. 92:68–76, 2017. © 2016 Wiley Periodicals, Inc.     

Prognostic Significance of Hepatic Venous Pressure Gradient in Medically Treated Alcoholic Cirrhosis: Comparison to Aminopyrine Breath Test

In a long-term survival study, we compared the prognostic significance of the hepatic venous pressure gradient and of the aminopyrine breath test (ABT) in 99 alcoholic cirrhotic patients. Thirty patients survived and had a complete follow-up for at least 4 yr. Mean hepatic venous pressure gradient was 19.1 ± 5.8 mm Hg (range 8–35 mm Hg). Variceal rupture occurred only when the gradient was ±12 mm Hg. Variceal bleeding was observed exclusively in patients with large varices. Survival was not influenced by the level of gradient. We used the ABT to classify patients into three groups (group I, ABT ± 2%; group II, 1%± ABT < 2%; and group III, ABT < 1%). Survival was significantly higher in group I than in group II ( p < 0.05) or III ( p < 0.01), indicating a better prognosis at a residual functional hepatic cellular mass of about 50% of the lower limit of normal value.     

Thallium-201 Per Rectal Scintigraphy Improves Prognostic Evaluation in Alcoholic Liver Cirrhosis of Low and Mid Severity

Objectives: The aim of this work was to assess the contribution of thallium-201 chloride (TI-201) per rectal scintigraphy in long term prognostic evaluation of alcoholic, cirrhotic patients. Methods: The data obtained from 170 biopsy-proven cirrhotic patients have been used in this 4-yr survival study. The severity of the liver disease was assessed by using the classic Child-Turcotte score as modified by Pugh (CTP score). Results: In patients belonging to CTP class A and CTP class B, the TI-201 test allowed the identification of subgroups with different survival rates. In these two classes of patients, the TI-201 per rectal scintigraphy could be used for improving prognostic evaluation. In patients of class C on the other hand, 4-yr survival rales were very low, and the TI-201 test did not bring significant additional prognostic information. Conclusions: Therefore, we suggest performing the TI-201 test in cirrhotic patients of classes A and B as defined by the CTP score.