Improved nationwide survival of sarcoma patients with a network of reference centers.

BACKGROUND: We investigated the impact of the implementation of a network of reference centers for sarcomas (NETSARC) on the care and survival of sarcoma patients in France since 2010. PATIENTS AND METHODS: NETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized multidisciplinary tumor boards (MDTBs), funded by the French National Cancer Institute (INCa) since 2010. Its aims are to improve the quality of diagnosis and care of sarcoma patients. Patients' characteristics, treatments, and outcomes are collected in a nationwide database. The objective of this analysis was to compare the survival of patients in three periods: 2010-2012 (non-exhaustive), 2013-2015, and 2016-2020. RESULTS: A total of 43 975 patients with sarcomas, gastrointestinal stromal tumors (GISTs), or connective tissue tumors of intermediate malignancy were included in the NETSARC+ database since 2010 (n = 9266 before 2013, n = 12 274 between 2013 and 2015, n = 22 435 in 2016-2020). Median age was 56 years, 50.5% were women, and 13.2% had metastasis at diagnosis. Overall survival was significantly superior in the period 2016-2020 versus 2013-2015 versus 2010-2012 for the entire population, for patients >18 years of age, and for both metastatic and non-metastatic patients in univariate and multivariate analyses (P < 0.0001). Over the three periods, we observed a significantly improved compliance to clinical practice guidelines (CPGs) nationwide: the proportion of patients biopsied before surgery increased from 62.9% to 72.6%; the percentage of patients presented to NETSARC MDTBs before first surgery increased from 31.7% to 44.4% (P < 0.0001). The proportion of patients with R0 resection on first surgery increased (from 36.1% to 46.6%), while R2 resection rate decreased (from 10.9% to 7.9%), with a better compliance and improvement in NETSARC centers. CONCLUSIONS: The implementation of the national reference network for sarcoma was associated with an improvement of overall survival and compliance to guidelines nationwide in sarcoma patients. Referral to expert networks for sarcoma patients should be encouraged, though a better compliance to CPGs can still be achieved.

Early infectious risk in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis according to remission-induction therapy.

OBJECTIVE: Few comparative data exist on early infections secondary to remission-induction therapy (RIT) with rituximab (RTX) versus cyclophosphamide (CYC) in newly diagnosed anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients. We compared and analysed the rates and predictors of severe infection in such patients within the first 6 months following RIT. METHOD: From the Caen University Hospital databases, we included all consecutive adults newly diagnosed with ANCA-positive granulomatosis with polyangiitis or microscopic polyangiitis between January 2006 and December 2019. We compared rates of survival without severe infection and survival without infections of any severity within 6 months of RIT and used a multivariate Cox analysis to identify predictors of infection. RESULTS: We included 145 patients, 27 in the RTX and 118 in the CYC group. Patients in the RTX group more frequently had pneumococcal vaccination (p < 0.01) and creatinine < 150 µmol/L; other characteristics were comparable between the two groups. Overall, 37 severe infections and 65 infections of any severity were recorded. Rates of survival without severe infection were similar in both groups (p = 0.69), but survival without infections of any severity was lower in the RTX group (p = 0.005). In multivariate analysis, risk factors at diagnosis for severe infections included chronic urinary tract disease, dialysis, and absence of trimethoprim-sulfamethoxazole prophylaxis (p < 0.01 each). CONCLUSIONS: Within 6 months of RIT, rates of survival without severe infection were similar in newly diagnosed ANCA-positive AAV patients treated with RTX or CYC, but survival rates without infections of any severity appeared to be lower with RTX treatment.

Potential histological discordance revealed by second review in the national rare gynecological cancer network (TMRG).

INTRODUCTION: Since 2010, the network of rare malignant tumors of the ovary (TMRG) was developed to optimize the management of patients, also allowing a histological second opinion of rare ovarian tumors. The aim of this work was to study the contribution of second opinion to improve histological diagnostic accuracy on ovarian rare malignant tumors included in the TMRG database. MATERIAL AND METHODS: Histological data of patients diagnosed with a rare ovarian tumor included in TMRG network over a one-year period (2018) were collected. Initial diagnoses were compared with second opinion from national gynecological pathologist experts. The modalities of histological second opinion requests were studied, as well as the histological characteristics of the tumors. The discordances were classified as minor (if the modification of histological diagnosis did not change patient management) and major (if the patient management can be modified). RESULTS: Of 1185 included patients, 937 matched the inclusion criteria. Full concordance between primary diagnosis and expert second opinion was reached in 611 cases (65,3%), minor discordance was seen in 114 (12,2%) and major discordance in 209 (22,3%) of cases. In systematic review requested by the network, 26% (n = 137) of cases were reported with a change in histological diagnosis, while the change concerned 44% (n = 186) of cases for a second opinion spontaneously requested by the initial pathologist. The discrepancies concerned all categories of ovarian tumors, with a majority of mucinous tumors (43% of major discordances), followed by stromal and sex-cord tumors (13.8% of major discordances) and clear cell tumors (12,4% of major discordances). CONCLUSION: This analysis confirms the diagnostic difficulty of ovarian tumors, due to their rarity and morphological heterogeneity. French pathologists are aware of these difficulties and spontaneously refer ovarian tumors with unusual histology for a second opinion and collaborate with rare tumor networks for systematic review.

[Giant pulmonary artery aneurysms. Case report and proposal of management algorithm]. / Anévrysmes géants de l'artère pulmonaire : cas clinique et proposition d'un algorithme de diagnostic et de prise en charge.

Pulmonary artery aneurysm is a rare and multiform pathology related to multiple etiologies and therefore different pathophysiological mechanisms. Delineating homogenous sub-groups is a pre-requisite to refine medico-surgical management. The case of a giant PAA without pulmonary hypertension but associated to a dysplastic pulmonary valve is reported. This association could be in some instances the result of a congenital anomaly in the development of both the pulmonary valve and the root creating the conditions for further development of a pulmonary artery aneurysm. Whilst minor forms are usually asymptomatic, they can lead to lethal complications in huge sizes and are frequently associated via pulmonary valve insufficiency to right ventricular dysfunction. This specific association is discussed and a diagnostic algorithm for nosologic classification and management is proposed.

L'anévrysme de l'artère pulmonaire est une pathologie rare, qui répond à de multiples étiologies et autant de physiopathologies différentes. L'identification de sous-groupes constituant des entités cliniques homogènes est un prérequis pour préciser la prise en charge médico-chirurgicale optimale. Nous rapportons un cas d'anévrysme géant de l'artère pulmonaire principale, sans hypertension artérielle pulmonaire, mais associé à une dysplasie/dysfonction de la valve pulmonaire. Cette association pourrait être, dans certains cas, congénitale et liée à une anomalie de la morphogénèse de la valve et de la racine pulmonaire, association qui crée les conditions pour le développement d'un anévrysme. Asymptomatiques dans les formes mineures, les anévrysmes pulmonaires peuvent être causes de symptômes ou de complications gravissimes dans les formes très développées et entraînent souvent, par insuffisance pulmonaire, une dysfonction ventriculaire droite. Nous suggérons une classification claire de cette pathologie mal connue et, sur base de la littérature et de notre expérience personnelle, nous proposons un algorithme de prise en charge médico-chirurgicale.

[Evaluation of the management and conformity to clinical practice guidelines of soft tissues lesions. Study performed at the competence center of Lorraine area]. / Évaluation et impact du respect du référentiel ESMO sur la prise en charge des lésions des tissus mous, étude menée au centre de référence de Lorraine.

INTRODUCTION: Despite regular recommendations issued by the European Society for Medical Oncology (ESMO), patients faced still too often inadequate care with a direct influence on prognosis. METHODS: A retrospective study was carried out at the Competence center in Lorraine Area. Patients registered in the NetSarc database between 1st, 2010 and September 1st, 2016 were included. Compliance criteria were established using the latest ESMO 2014 referential. Two groups "conforming" and "non conforming" were analyzed. A first analyze about all of the soft tissue lesion and a second only about sarcomas. RESULTS: In total, 445 patients were eligible, 344 cases were treated according to the ESMO guidelines, giving a 77.3% conformity rate (95% CI: 73.4%, 81.2%). Compliance was better for the competence center than district hospitals (P<0.001), with compliance rates of 88.7%, and 51.6%, respectively. Among the 247 sarcomas, we found a R0 resection rate better according to the ESMO guideline, 55% against 18% (P<0.001). R1 rates were 34% vs. 56% and R2 11 vs. 26% disease free survival was not related significantly to the observance of recommendations in the univariate analysis. After adjustment on potential DFS prognostic factors, in the multivariate analysis, the results were similar. CONCLUSION: Compliance with the ESMO guidelines, through appropriate management, improves the quality of surgical excision for sarcomas and avoids non-corresponding surgical gestures.

Molecular identification of iridoviruses infecting various sturgeon species in Europe.

Iridoviridae are known to cause disease in sturgeons in North America. Here, histological and molecular methods were used to screen for this family of virus in sturgeons from various European farms with low-to-high morbidity. Some histological samples revealed basophilic cells in the gill and labial epithelia, strongly suggesting the accumulation of iridovirus particles. Newly developed generic PCR tests targeting the major capsid protein (MCP) gene of sturgeon iridoviruses identified in North America, namely the white sturgeon iridovirus and the Namao virus (NV), produced positive signals in most samples from four sturgeon species: Russian (Acipenser gueldenstaedtii), Siberian (A. baerii), Adriatic (A. naccarii) and beluga (Huso huso). The sequences of the PCR products were generally highly similar one another, with nucleotide identities greater than 98%. They were also related to (74-88%), although distinct from, American sturgeon iridoviruses. These European viruses were thus considered variants of a single new virus, provisionally named Acipenser iridovirus-European (AcIV-E). Moreover, three samples infected with AcIV-E showed genetic heterogeneity, with the co-existence of two sequences differing by five nucleotides. One of our European samples carried a virus distinct from AcIV-E, but closely related to NV identified in Canada (95%). This study demonstrates the presence of two distinct sturgeon iridoviruses in Europe: a new genotype AcIV-E and an NV-related virus.

Publications presenting negative impacts of pharmacists.

OBJECTIVES: The main objective was to evaluate the rate of publications with at least one indicator of the negative impact of clinical pharmaceutics activity. METHODS: This is a descriptive and retrospective literature review. A literature search was conducted using Pubmed. Articles published between 2009-2014 that described the role and impacts of pharmacists were included. We calculated the rate of publication containing at least one negative indicator. We collected the indicators with negative results. RESULTS: A total of 203 articles were included. Nine articles (4%) that had at least one indicator of negative impact were identified. A total of 66% (6/9) were conducted in the United States. The study designs of the articles included were a meta-analysis (n=1), a systematic review (n=1), randomized studies (n=2), pre-post studies (n=3), a cohort study (n=1) and a survey (n=1). Nine indicators of negative impact were identified. CONCLUSION: There were nine publications with at least one negative indicator of the impact of clinical pharmacy activity. While there are a large number of studies about the positive impact of clinical pharmacy activities; the publication of negative results should be encouraged.

Incidence of occult contralateral carcinomas of the breast following mastoplasty aimed at symmetrization.

INTRODUCTION: Breast carcinomas are the most frequent form of cancer in French women. Following a total mastectomy, only an estimated 25% of patients wish to undergo breast reconstruction. After mammary volume reconstitution, the plastic surgeon often attempts to harmonize the two breasts by carrying out contralateral reduction mammaplasty (CRM). In the literature, the incidence of occult contralateral carcinomas incidentally discovered in surgical specimens ranges from 1.12 to 4.5%. The main objective of this study was to evaluate occurrence of carcinoma in the CRM specimens in the framework of a breast reconstruction operation. The secondary objective was to determine the consequences of the incidentally discovered carcinoma in the contralateral breast. MATERIAL AND METHODS: This was a 6-year, bicentric, retrospective study involving women having undergone breast cancer surgery who later underwent contralateral reduction mammaplasty (CRM), that is to say reconstruction aimed at harmonization of the two breasts. RESULTS: Three hundred and nineteen patients were included in the study. Mean age during the CRM was 55years (29-79). Mean weight of the surgical specimens was 323grams (12-2500). Incidence of occult carcinomas found in the specimens was 0.94% (3 patients). The mean age for these 3 cases was 58years (47-64). All 3 patients had superior pedicle mammaplasty. One of the patients benefited from monobloc resection with orientation of the surgical specimen. In the other 2 cases, there existed 3 surgical resection specimens; in one case, they were oriented; in the other, they were not. In all 3 cases, the histological findings were unifocal ductal carcinomas in situ (DCIS). Mean tumor size was 5.7mm (3-9). Only the patient having had monobloc resection with orientation of the specimen underwent salvage surgery, which consisted in partial mastectomy, otherwise known as secondary lumpectomy. Adjuvant radiotherapy was administered to all of the patients. After 17months of mean follow-up (12-22), no recurrence was found in any of the three cases. CONCLUSION: Incidence of occult contralateral breast carcinomas after symmetrization CRM approximates 1%. Our observations are in agreement with the data in the literature. Incidence is greater than in mammaplasty carried out for esthetic or functional reasons; this is probably due to the higher age and the previous breast cancer history of the breast reconstruction population. Monobloc resection and orientation of the surgical specimens with surgeon's knots facilitate precise pinpointing of the occult carcinoma. A secondary lumpectomy may take place when margins of excision are invaded or inadequate.

Using one-step nucleic acid amplification (OSNA) for intraoperative detection of lymph node metastasis in breast cancer patients avoids second surgery and accelerates initiation of adjuvant therapy.

BACKGROUND: Sentinel lymph node (SLN) analysis is conventionally analyzed using immunohistochemistry and in the case of SLN involvement, justifies a second surgery for axillary lymph node (ALN) resection, thus delaying the initiation of adjuvant therapies. PATIENTS AND METHODS: Three hundred and eighty-one patients with early stage breast cancer (BC) were considered in this retrospective study. SLNs were detected using combined radioisotope and dye detection. SLN involvement was analyzed using routine intraoperative One-Step Nucleic Acid Amplification (OSNA) assay, in 100 patients and compared with the conventional histopathology carried out previously in 281 patients. RESULTS: Considering positive SLNs as '++' (CK19 mRNA copy number>5000), '+' (250 < CK19 mRNA copy number <5000) and positive by inhibition in the OSNA group and macro-, micrometastases and isolated tumor cells in the histopathology group, no difference in SLN involvement rate was found between the two groups with 29.0% and 29.9% of positive SLNs, respectively. Using OSNA intraoperatively, the mean time to process the SLN was 42 min allowing immediate ALN resection, reduced significantly (P < 0.01) the re-intervention rate (9% versus 39%) and significantly (P < 0.01) accelerated the initiation of adjuvant therapy (6.2 versus 8.4 weeks). CONCLUSIONS: Using OSNA for intraoperative SLN analysis avoids second surgery for ALN resection in most patients and accelerates initiation of adjuvant therapy.

Unilateral or bilateral adrenalectomy in PPNAD: six cases from a single family followed up over 40 years.

The most frequent endocrine Carney complex manifestation is a bilateral primary pigmented nodular adrenocortical disease and bilateral adrenalectomy (BA) is therefore its main treatment. In this study, a 40 years follow-up of six members of the same family with heterozygous PRKAR1A germline mutation, is reported over two generations. The first cases, two sisters with severe hyperandrogenism and Cushing syndrome (CS) diagnosed in 1972 at age 14 and 25, were successfully treated with unilateral adrenalectomy (UA). Their two brothers were then diagnosed, one with a CS-related severe osteoporosis treated with BA and the other with CS treated with UA. The second generation was diagnosed with CS signs at 7 and 21 years of age and were treated with BA and UA respectively. Out of the four patients treated with UA, the only event possibly related to CS was spontaneous episode of pulmonary embolism, 30 years after surgery. Hormonal evaluation revealed either eucortisolism in one patient or partial adrenal deficiency in two and mild hypercortisolism in one patient. For the two patients with BA, one of them accidentally died. The second one, surprisingly, recovered progressively normal cortisol secretion and circadian variation. Steroid substitution was stopped 6 years after her surgery and we demonstrated by iodocholesterol scintigraphy the presence of bilateral adrenal remnants. In conclusion, our results of long term evolution of PPNAD patients show that UA in this subset of patients could be considered to treat CS.

Research Note: Effect of a phlorotannin extract of the brown seaweed Ascophyllum nodosum as a potential control strategy against Campylobacter in broilers.

Poultry is generally recognized as the main source of human campylobacteriosis and Campylobacter is highly prevalent at the farm level. To reduce the relative risk of human campylobacteriosis attributable to broiler meat, it is necessary to reduce Campylobacter loads in broiler ceca but to date, no effective, reliable and practical strategy is available. The marine environment is a rich source of original natural compounds exhibiting different biological activities. The objective of this study was to test a phlorotannin extract of the brown seaweed Ascophyllum nodosum as a potential control strategy against Campylobacter in broilers. Bactericidal activity has been demonstrated in vitro, on several Campylobacter spp. strains at a range of 0.06 to 0.47 mg/mL. Therefore, an in vivo trial in experimental facilities was performed to evaluate addition of 0.2% (w/w) of an A. nodosum extract to feed distributed at the end of rearing from day 31 to day 35, and to assess the effect on artificial Campylobacter jejuni colonization. No statistical differences in Campylobacter enumeration were observed between the treated and control groups. Another trial was performed in a commercial broiler flock. Feed containing the extract at 0.2% (w/w) (2 kg/t) was distributed during the last 5 days of rearing (day 33-day 38). No significant effects on Campylobacter colonization and on growth parameters were observed compared to the control group. Additional studies are needed to assess whether active polyphenols are found in the cecum.

High frequency of beta-catenin heterozygous mutations in extra-abdominal fibromatosis: a potential molecular tool for disease management.

BACKGROUND: Fibromatosis comprises distinct clinical entities, including sporadic extra-abdominal fibromatosis, which have a high tendency for recurrence, even after adequate resection. There are no known molecular biomarkers of local recurrence. We searched for beta-catenin mutations in a European multicentre series of fibromatosis tumours to relate beta-catenin mutational status to disease outcome. METHODS: Direct sequencing of exon 3 beta-catenin gene was performed for 155 frozen fibromatosis tissues from all topographies. Correlation of outcome with mutation rate and type was performed on the extra-abdominal fibromatosis group (101 patients). RESULTS: Mutations of beta-catenin were detected in 83% of all cases. Among 101 extra-abdominal fibromatosis, similar mutation rates (87%) were observed, namely T41A (39.5%), S45P (9%), S45F (36.5%), and deletion (2%). None of the clinico-pathological parameters were found to be significantly associated with beta-catenin mutational status. With a median follow-up of 62 months, 51 patients relapsed. Five-year recurrence-free survival was significantly worse in beta-catenin-mutated tumours regardless of a specific genotype, compared with wild-type tumours (49 vs 75%, respectively, P=0.02). CONCLUSION: A high frequency (87%) of beta-catenin mutation hallmarks extra-abdominal fibromatosis from a large multicentric retrospective study. Moreover, wild-type beta-catenin seems to be an interesting prognostic marker that might be useful in the therapeutic management of extra-abdominal fibromatosis.

[Clinical inertia and treatment adherence in the management of chronic valvular heart diseases]. / Inertie clinique et observance thérapeutique dans les valvulopathies chroniques du coeur gauche.

Valvular heart diseases are of increasing importance among the general adult population. When compared with other heart diseases, there are few trials in the field of valvular heart disease and randomized clinical trials are particularly scarce. Two sets of guidelines exist: one in the USA and the other in Europe. However, they are not always consistent due to the lack of randomized data and it appears that, frequently, there is a gap between the existing guidelines and their effective application.

Soft tissue sarcomas of the trunk wall (STS-TW): a study of 343 patients from the French Sarcoma Group (FSG) database.

BACKGROUND: Soft tissue sarcomas of the trunk wall (STS-TW) are usually studied together with soft tissue sarcomas of other locations. We report a study on STS-TW forming part of the French Sarcoma Group database. PATIENTS AND METHODS: Three hundred and forty-three adults were included. We carried out univariate and multivariate analysis for overall survival (OS), metastasis-free survival (MFS) and local recurrence-free survival (LRFS). RESULTS: Tumor locations were as follows: thoracic wall, 82.5%; abdominal wall, 12.3% and pelvic wall, 5.2%. Median tumor size was 6.0 cm. The most frequent tumor types were unclassified sarcoma (27.7%) and myogenic sarcoma (19.2%). A total of 44.6% of cases were grade 3. In all, 21.9% of patients had a previous medical history of radiotherapy (PHR). Median follow-up was 7.6 years. The 5-year OS, MFS and LRFS rates were 60.4%, 68.9% and 58.4%, respectively. Multivariate analysis retained PHR and grade for predicting LRFS and PHR, size and grade as prognostic factors of MFS. Factors influencing OS were age, size, PHR, depth, grade and surgical margins. The predictive factors of incomplete response were PHR, size and T3. CONCLUSIONS: Our results suggest similar classical prognostic factors as compared with sarcomas of other locations. However, a separate analysis of STS-TW revealed a significant poor prognosis subgroup of patients with PHR.

Recessive hereditary methaemoglobinaemia, type II: delineation of the clinical spectrum.

Type II recessive hereditary methaemoglobinaemia (RHM) is a rare disease due to generalized NADH-cytochrome b5 reductase (cytb5r) deficiency. It results in mild cyanosis and severe neurological impairment. The clinical features and long-term outcome are poorly documented, and there are no systematic reviews. We examined six cases of type II RHM, four of which were new, together with 45 previously published cases, in order to establish the range of phenotypic expression. The clinical picture was very similar in most cases, with severe encephalopathy, microcephaly, generalized dystonia, movement disorders and mild cyanosis. The neurological prognosis was poor; in particular, none of the patients walked or spoke. In addition, the possibility of an atypical and milder phenotype was considered. We concluded that children with unexplained severe encephalopathy associated with generalized dystonia should be examined for cyanosis and have a methaemoglobinaemia assay performed. The diagnosis can be confirmed by very low cytb5r activity in both red and white blood cells. Here we report three novel mutations in the NADH-cytochrome b5 reductase gene. Prenatal diagnosis of this extremely severe disease should be proposed to affected families.

Comparison of Three Real-Time PCR Assays for the Detection of PIK3CA Somatic Mutations in Formalin-Fixed Paraffin Embedded Tissues of Patients with Breast Carcinomas.

Breast cancer is the leading cause of cancer-related death in women worldwide. Mutations of the PIK3CA gene are found in approximately 25% of breast carcinomas and are reported as activators of the PI3K/AKT/mTOR pathway. This study aims to compare three assays for the somatic mutation detection of PIK3CA gene in FFPE tissues of patients with breast cancer. We compared Cobas® PIK3CA Mutation Test (Roche Diagnostics, Meylan, France), PCR amplification-refractory mutation system Scorpions® (ARMS) and High-Resolution Melting PCR assay (HRM) for the detection of PIK3CA mutations. Discrepant samples were assessed using Next Generation Sequencing (NGS). 46 FFPE breast carcinomas samples of patients treated for breast cancer have been assessed for PIK3CA mutations using the three PCR assays. Among the 46 samples, 17 (37.8%), 13 (28.36%) and 19 (41.3%) had a PIK3CA mutation, with Cobas®, ARMS and HRM assays respectively. Three different mutations of PIK3CA have been detected for one sample. Calculated kappa were 0.95[0.86;1] between Cobas® and HRM, 0.75[0.55;0.95] between Cobas® and ARMS and 0.72[0.51;0.92] between HRM and ARMS. Five samples were found with discrepant results. Our study shows that the Cobas® assay is suitable for PIK3CA mutation assessment in patients with breast cancer. HRM assay is also suitable for PIK3CA mutation assessment but requires a mutation characterization with a specific assay.

The small hydrophobic (SH) gene of North American turkey AMPV-C does not attenuate nor modify host tropism in recombinant European duck AMPV-C.

Subgroup C Avian Metapneumoviruses (AMPV-C) has two lineages, one mostly in turkeys and one mostly in ducks. To investigate the molecular basis of AMPV-C host tropism, a reverse genetics system for a duck AMPV-C virus was developed. A recombinant copy and a recombinant virus in which the SH protein had been exchanged for that of a turkey AMPV-C were rescued. No change in cytopathogenic effect or replication profile in vitro were observed for either virus compared to the wild type. In SPF Muscovy ducks the wild type and its recombinant copy were equally pathogenic. Exchanging the SH in the recombinant copy produced the same results. In SPF turkeys, neither recombinant virus was pathogenic, although both showed a low level of replication. Thus, from the current model, it appears that AMPV-C SH proteins derived from the different species are compatible and that turkey SH does not affect duck AMPV-C pathogenicity.

Two-dimensional speckle tracking echocardiography in calves: feasibility and repeatability study.

OBJECTIVES: To assess the feasibility and repeatability of two-dimensional speckle tracking echocardiography for the evaluation of left ventricular function in healthy calves. ANIMALS: 12 Holstein calves, 62 ± 11.6 days old; 75.25 ± 5.4 Kg. METHODS: Observational study. Right parasternal short-axis views at papillary muscle level were recorded in standing calves and subsequently analyzed by two-dimensional speckle tracking for global and regional radial and circumferential strains and strain rates and radial displacement. Echocardiographic examinations were performed by 2 observers to evaluate intra- and interobserver repeatability and variability. RESULTS: Two-dimensional speckle tracking was feasible in all calves. Automated tracking was better in systole than in diastole. Repeatability of the technique was good in calves. Systolic radial strain and strain rate peak values showed little variability compared with systolic circumferential strain and strain rate and to all diastolic measurements. Variability of the interobserver measurements was greater than the intraobserver measurements. CONCLUSIONS: Two-dimensional speckle tracking is feasible in calves. As in other species, evaluation of systolic radial left ventricular function is more reliable than circumferential and diastolic left ventricular function.

Tumor lymphocyte immune response to preoperative radiotherapy in locally advanced rectal cancer: The LYMPHOREC study.

Introduction: Some studies have suggested that baseline tumor-infiltrating-lymphocytes (TILs), such as CD8+ and FoxP3+ T-cells, may be associated with a better prognosis in colorectal cancer. We sought to investigate modulation of the immune response by preoperative radiotherapy (preopRT) and its impact on survival in locally advanced rectal cancer (LARC). Materials & Methods: We analyzed data for 237 patients with LARC who received RT. Density of TILS (CD8+ and FoxP3+) in intraepithelial (iTILs) and stromal compartments (sTILs) were evaluated from surgery pathological specimens and biopsies performed at baseline. The primary endpoint was to assess the impact of infiltration of the tumor or tumor site after preopRT on progression-free survival (PFS) and overall survival (OS). Secondary endpoints were the impact of dose fractionation scheme on TILs. Results: In univariate analysis, several factors significantly correlated (p<0.05) with PFS and/or OS (T-stage, M-stage, the delay between RT and surgery). A high level of post-treatment FoxP3+ TIL density correlated significantly with a better PFS (p = 0.007). In multivariate analysis, a decrease in the CD8+/FoxP3+ iTILs ratio after preopRT correlated with better PFS and OS (p = 0.049 and p = 0.024, respectively). More particularly, patients with a delta CD8+/FoxP3+ <-3.8 had better PFS and OS. Interestingly, the dose fractionation scheme significantly influenced the CD8+/FoxP3+ ratio after treatment (p = 0.027) with a lower ratio with hypofractionated RT (≥2 Gy). Conclusion: Patients with LARC who had a significant decrease in the CD8+/FoxP3+ ratio after preopRT were more likely to live longer. This ratio needs to be validated prospectively to guide physicians in adjuvant treatment decision-making.

Membrane-bound cytochrome b5 reductase (methemoglobin reductase) in human erythrocytes. Study in normal and methemoglobinemic subjects.

In this study we present evidence that in human erythrocytes NADH-cytochrome b5 reductase (methemoglobin reductase) is not only soluble but also tightly bound to the membrane. The membrane methemoglobin reductase-like activity is unmasked by Triton X-100 treatment, and represents about half of the total activity in the erythrocytes. Like the amphiphilic microsomal-bound cytochrome b5 reductase, the erythrocyte membrane-bound enzyme is solubilized by cathepsin D. Because this treatment is effective on unsealed ghosts but not on resealed (inside-in) ghosts, it is concluded that the enzyme is strongly bound to the inner face of the membrane. The erythrocyte membrane enzyme is antigenically similar to the soluble enzyme. The two forms of enzyme are specified by the same gene, in that both were found defective in six patients with recessive congenital methemoglobinemia. We suggest that the cytochrome b5 reductase of the erythrocyte membrane is the primary gene product. A posttranslational partial proteolysis probably gives rise to the soluble form of the enzyme, which serves as a methemoglobin reductase.