Semi-automatic detection of myocardial trabeculation using cardiovascular magnetic resonance: correlation with histology and reproducibility in a mouse model of non-compaction

Background

The definition of left ventricular (LV) non-compaction is controversial, and discriminating between normal and excessive LV trabeculation remains challenging. Our goal was to quantify LV trabeculation on cardiovascular magnetic resonance (CMR) images in a genetic mouse model of non-compaction using a dedicated semi-automatic software package and to compare our results to the histology used as a gold standard.

Methods

Adult mice with ventricular non-compaction were generated by conditional trabecular deletion of Nkx2–5. Thirteen mice (5 controls, 8 Nkx2–5 mutants) were included in the study. Cine CMR series were acquired in the mid LV short axis plane (resolution 0.086?×?0.086x1mm³) (11.75 T). In a sub set of 6 mice, 5 to 7 cine CMR were acquired in LV short axis to cover the whole LV with a lower resolution (0.172?×?0.172x1mm3). We used semi-automatic software to quantify the compacted mass (M_c), the trabeculated mass (M_t) and the percentage of trabeculation (M_t/M_c) on all cine acquisitions_. After CMR all hearts were sliced along the short axis and stained with eosin, and histological LV contouring was performed manually, blinded from the CMR results, and M_t, M_c and M_t/M_c were quantified. Intra and interobserver reproducibility was evaluated by computing the intra class correlation coefficient (ICC).

Results

Whole heart acquisition showed no statistical significant difference between trabeculation measured at the basal, midventricular and apical parts of the LV. On the mid-LV cine CMR slice, the median M_t was 0.92 mg (range 0.07–2.56 mg), M_c was 12.24 mg (9.58–17.51 mg), M_t/M_c was 6.74% (0.66–17.33%). There was a strong correlation between CMR and the histology for M_t, M_c and M_t/ M_c with respectively: r²?=?0.94 (p?<?0.001), r²?=?0.91 (p?<?0.001), r²?=?0.83 (p?<?0.001). Intra- and interobserver reproducibility was 0.97 and 0.8 for M_t; 0.98 and 0.97 for M_c; 0.96 and 0.72 for M_t/M_c, respectively and significantly more trabeculation was observed in the M_c Mutant mice than the controls.

Conclusion

The proposed semi-automatic quantification software is accurate in comparison to the histology and reproducible in evaluating M_c, M_t and M_t/ M_c on cine CMR.

     

Unilateral Direct Carotid Cavernous Fistula Causing Bilateral Ocular Manifestation

Unilateral carotid cavernous fistula presents with ipsilateral ocular findings. Bilateral presentation is only seen in bilateral fistulas, usually associated with indirect (dural) carotid cavernous fistulas. Direct carotid cavernous fistulas are an abnormal communication between the internal carotid artery and the cavernous sinus. They typically begin with a traumatic disruption in the artery wall into the cavernous sinus, presenting with a classic triad of unilateral pulsatile exophthalmos, cranial bruit and episcleral venous engorgement. We report the case of a 38-year-old male with traumatic right carotid cavernous sinus fistula and bilateral ocular presentation successfully treated by interventional neuroradiology.Key Words: Exophthalmos, Papilledema, Carotid artery injury, Carotid cavernous sinus fistula, Endovascular procedure, Therapeutic embolization     

Inhibition of rat liver fibrogenesis through noradrenergic antagonism

The effect of adrenergic innervation and/or circulating catecholamines on the function of liver fibrogenic cells is poorly understood. Our aim was to investigate the effects of noradrenergic antagonism on carbon tetrachloride (CCl4)-induced liver fibrosis in rats. Two weeks of CCl4 induced an approximately 5-fold increase in the area of fibrosis as compared with controls. The addition of 6-hydroxydopamine (OHDA), a toxin that destroys noradrenergic fibers, decreased fibrosis by 60%. After 6 weeks of CCl4, the area of fibrosis increased about 30-fold in CCl4-treated animals and was decreased by 36% with OHDA. At 2 weeks, OHDA abrogated the CCl4-induced increase in mRNA level of tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), an inhibitor of extracellular matrix degradation, and it greatly reduced it at 6 weeks. Finally, when rats treated with CCl4 for 2 weeks also received prazosin, an antagonist of alpha1-adrenergic receptors, fibrosis was decreased by 83%. In conclusion, destruction of noradrenergic fibers or antagonism of noradrenergic signaling through alpha1 receptors inhibited the development of liver fibrosis. Because adrenoreceptor antagonists have a very sound safety profile, they appear as attractive drugs to reduce liver fibrogenesis.     

Factors predictive of complete resection of operable esophageal cancer: review of 746 patients

OBJECTIVE: Surgery is the treatment of reference for early-stage esophageal cancer, but 5-year survival is only 20% to 25%. After complete resection (R0), survival is significantly longer than after incomplete resection, with microscopic (R1) or macroscopic (R2) penetration. The purpose of this work was to identify retrospectively the factors predictive of complete resection of operable esophageal cancers.PATIENTS AND METHODS: Between January 1982 and March 2001, 746 patients with esophageal cancer underwent curative surgery. R0 resection was performed in 585 patients (78.4%), R1 in 61 (8.2%) and R2 in 100 (13.4%). Univariate and multivariate analysis included 28 preoperative, clinical, tumor and therapeutic parameters.RESULTS: Multivariate analysis showed that factors predictive of complete resection R0 were: absence of any modification of the esophageal axis on the barium swallow (P=0.054), a partial or complete response to preoperative radio-chemotherapy (P=0.042), tumor height<10 cm (P=0.1) and tumor diameter<30 mm (P=0.01). Three groups of patients were identified from the 2 most significant variables. Group 1: no deviation of the axis on the barium swallow (n=501). Group 2: deviation of the axis on the barium swallow and partial or complete response to radiochemotherapy (n=91). Group 3: deviation of the axis on the barium swallow and no response to radiochemotherapy or no preoperative treatment (n=126). For the three groups, rate of R0 resection was 82.6%, 80.1% and 61.1% and 5-year actuarial survival 36%, 27% and 14%, respectively. These rates were significantly different between groups (P<10(- 4)) and two by two (P<0.04).CONCLUSION: Complete resection of esophageal cancer is predictable. After validation with an independent population the findings presented here could be used to establish stratification criteria for future therapeutic trials.     

Effects of Fecal Microbiota Transplantation on Composition in Mice with CKD

Background: Chronic kidney disease (CKD) is a renal disorder characterized by the accumulation of uremic toxins with limited strategies to reduce their concentrations. A large amount of data supports the pivotal role of intestinal microbiota in CKD complications and as a major source of uremic toxins production. Here, we explored whether fecal microbiota transplantation (FMT) could be attenuated in metabolic complication and uremic toxin accumulation in mice with CKD. Methods: Kidney failure was chemically induced by a diet containing 0.25% (w/w) of adenine for four weeks. Mice were randomized into three groups: control, CKD and CKD + FMT groups. After four weeks, CKD mice underwent fecal microbiota transplantation (FMT) from healthy mice or phosphate buffered saline as control. The gut microbiota structure, uremic toxins plasmatic concentrations, and metabolic profiles were explored three weeks after transplantation. Results: Associated with the increase of alpha diversity, we observed a noticeable improvement of gut microbiota disturbance, after FMT treatment. FMT further decreased p-cresyl sulfate accumulation and improved glucose tolerance. There was no change in kidney function. Conclusions: These data indicate that FMT limited the accumulation of uremic toxins issued from intestinal cresol pathway by a beneficial effect on gut microbiota diversity. Further studies are needed to investigate the FMT efficiency, the timing and feces amount for the transplantation before, to become a therapeutic option in CKD patients.     

Characterization of the human CD4+ T‐cell repertoire specific for major histocompatibility class I‐restricted antigens

While CD4⁺ T lymphocytes usually recognize antigens in the context of major histocompatibility (MHC) class II alleles, occurrence of MHC class‐I restricted CD4⁺ T cells has been reported sporadically. Taking advantage of a highly sensitive MHC tetramer‐based enrichment approach allowing detection and isolation of scarce Ag‐specific T cells, we performed a systematic comparative analysis of HLA‐A*0201‐restricted CD4⁺ and CD8⁺ T‐cell lines directed against several immunodominant viral or tumoral antigens. CD4⁺ T cells directed against every peptide‐MHC class I complexes tested were detected in all donors. These cells yielded strong cytotoxic and T helper 1 cytokine responses when incubated with HLA‐A2⁺ target cells carrying the relevant epitopes. HLA‐A2‐restricted CD4⁺ T cells were seldom expanded in immune HLA‐A2⁺ donors, suggesting that they are not usually engaged in in vivo immune responses against the corresponding peptide‐MHC class I complexes. However, these T cells expressed TCR of very high affinity and were expanded following ex vivo stimulation by relevant tumor cells. Therefore, we describe a versatile and efficient strategy for generation of MHC class‐I restricted T helper cells and high affinity TCR that could be used for adoptive T‐cell transfer‐ or TCR gene transfer‐based immunotherapies.     

Prognostic relevance of clinical and molecular risk factors in children with high-risk medulloblastoma treated in the phase II trial PNET HR+5

BackgroundHigh-risk medulloblastoma is defined by the presence of metastatic disease and/or incomplete resection and/or unfavorable histopathology and/or tumors with MYC amplification. We aimed to assess the 3-year progression-free survival (PFS) and define the molecular characteristics associated with PFS in patients aged 5–19 years with newly diagnosed high-risk medulloblastoma treated according to the phase II trial PNET HR+5.MethodsAll children received postoperative induction chemotherapy (etoposide and carboplatin), followed by 2 high-dose thiotepa courses (600 mg/m²) with hematological stem cell support. At the latest 45 days after the last stem cell rescue, patients received risk-adapted craniospinal radiation therapy. Maintenance treatment with temozolomide was planned to start between 1–3 months after the end of radiotherapy. The primary endpoint was PFS. Outcome and safety analyses were per protocol (all patients who received at least one dose of induction chemotherapy).ResultsFifty-one patients (median age, 8 y; range, 5–19) were enrolled. The median follow-up was 7.1 years (range: 3.4–9.0). The 3 and 5-year PFS with their 95% confidence intervals (95% CI) were 78% (65–88) and 76% (63–86), and the 3 and 5-year OS were 84% (72–92) and 76% (63–86), respectively. Medulloblastoma subtype was a statistically significant prognostic factor (P-value = 0.039) with large-cell/anaplastic being of worse prognosis, as well as a molecular subgroup (P-value = 0.012) with sonic hedgehog (SHH) and group 3 being of worse prognosis than wingless (WNT) and group 4. Therapy was well tolerated.ConclusionsThis treatment based on high-dose chemotherapy and conventional radiotherapy resulted in a high survival rate in children with newly diagnosed high-risk medulloblastoma.     

A Lot of Action,But Not in the Right Direction: Systematic Review and Content Analysis of Smartphone Applications for the Prevention,Detection, and Management of Cancer

Background

Mobile phones have become nearly ubiquitous, offering a promising means to deliver health interventions. However, little is known about smartphone applications (apps) for cancer.

Objective

The purpose of this study was to characterize the purpose and content of cancer-focused smartphone apps available for use by the general public and the evidence on their utility or effectiveness.

Methods

We conducted a systematic review of the official application stores for the four major smartphone platforms: iPhone, Android, Nokia, and BlackBerry. Apps were included in the review if they were focused on cancer and available for use by the general public. This was complemented by a systematic review of literature from MEDLINE, Embase, and the Cochrane Library to identify evaluations of cancer-related smartphone apps.

Results

A total of 295 apps from the smartphone app stores met the inclusion criteria. The majority of apps targeted breast cancer (46.8%, 138/295) or cancer in general (28.5%, 84/295). The reported app purpose was predominantly to raise awareness about cancer (32.2%, 95/295) or to provide educational information about cancer (26.4%, 78/295), followed by apps to support fundraising efforts (12.9%, 38/295), assist in early detection (11.5%, 34/295), promote a charitable organization (10.2%, 30/295), support disease management (3.7%, 11/295), cancer prevention (2.0%, 6/295), or social support (1.0%, 3/295). The majority of the apps did not describe their organizational affiliation (64.1%, 189/295). Apps affiliated with non-profit organizations were more likely to be free of cost (χ² ₁=16.3, P<.001) and have a fundraising or awareness purpose (χ² ₂=13.3, P=.001). The review of the health literature yielded 594 articles, none of which reported an evaluation of a cancer-focused smartphone application.

Conclusions

There are hundreds of cancer-focused apps with the potential to enhance efforts to promote behavior change, to monitor a host of symptoms and physiological indicators of disease, and to provide real-time supportive interventions, conveniently and at low cost. However, there is a lack of evidence on their utility, effectiveness, and safety. Future efforts should focus on improving and consolidating the evidence base into a whitelist for public consumption.