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Introduction: Metabolic flexibility (MetF), defined as the ability to switch between fat and glucose oxidation, is increasingly recognised as a critical marker for assessing responses to dietary interventions. Previously, we showed that the consumption of multifibre bread improved insulin sensitivity and reduced low‐density lipoprotein cholesterol (LDLc) levels in overweight and obese individuals. As a secondary objective, we aimed to explore whether our intervention could also improve MetF. Methods: In this study, 39 subjects at cardiometabolic risk participated in a double‐blind, randomised, crossover trial lasting 8 weeks, repeated twice. During each phase, participants consumed either 150 g of standard bread daily or bread enriched with a mixture of seven dietary fibres. MetF response was assessed using a mixed‐meal tolerance test (MMTT), analysing changes in respiratory quotient (∆RQ) measured using indirect calorimetry. Results: Although there were no significant differences in ∆RQ changes induced by dietary fibre between the two diets, these changes were positively correlated with postprandial triglyceride excursion (∆TG) at baseline. Subgroup analysis of baseline fasting and postprandial plasma metabolites was conducted to characterise MetF responders. These responders exhibited higher baseline fasting LDLc levels and greater post‐MMTT ∆TG. Conclusion: In conclusion, although dietary fibres did not directly impact MetF in this study, our findings highlight potential determinants of MetF response, warranting further investigation in dedicated future interventions. Highlights: The term 'metabolic flexibility' (MetF) was initially used to describe the ability of helminths to generate energy through either aerobic respiration or anaerobic respiration, enabling them to adapt to environmental changes. This concept was later applied to human metabolism, emphasising the body's capacity to switch between different energy sources, such as carbohydrates and fats, based on energy requirements.MetF has been studied in the context of transitions between fasting and fed states, or in response to insulin stimulation. It refers to the body's ability to adapt its energy utilisation in response to changing metabolic demands.Research has shown that insulin resistance, often linked to type 2 diabetes and obesity, may be associated with reduced MetF, characterised by altered patterns of carbohydrate and fat oxidation. [ABSTRACT FROM AUTHOR]

Summary: The potential prognostic influence of genetic aberrations on chronic lymphocytic leukaemia (CLL) can vary based on various factors, such as the immunoglobulin heavy variable (IGHV) status. We conducted an integrative analysis on genetic abnormalities identified through cytogenetics and targeted next‐generation sequencing in 536 CLL patients receiving first‐line chemo(immuno)therapies (CIT) as part of two prospective trials. We evaluated the prognostic implications of the main abnormalities, with specific attention to their relative impact according to IGHV status. In the entire cohort, unmutated (UM)‐IGHV, complex karyotype, del(11q) and ATM mutations correlated significantly with shorter progression‐free survival (PFS). Focusing on the subset of mutated IGHV (M‐IGHV) patients, univariate analysis showed that complex karyotype, del(11q), SF3B1 and SAMHD1 mutations were associated with significant lower PFS. The prognostic influence varied based on the patient's IGHV status, as these abnormalities did not affect outcomes in the UM‐IGHV subgroup. TP53 mutations had no significant impact on outcomes in the M‐IGHV subgroup. Our findings highlight the diverse prognostic influence of genetic aberrations depending on the IGHV status in symptomatic CLL patients receiving first‐line CIT. The prognosis of gene mutations and cytogenetic abnormalities needs to be investigated with a compartmentalized methodology, taking into account the IGVH status of patients receiving first‐line BTK and/or BCL2 inhibitors. [ABSTRACT FROM AUTHOR]

Summary: An efficient immunological reconstitution construes the pillar for the success of allogeneic haematopoietic cell transplantation (HCT) in haematological disorders. Factors influencing post‐transplant immune recovery have been largely investigated across multiple cohorts issuing heterogeneous results. Differences in outcomes in adult and paediatric populations suggest an age‐related contribution to post‐transplant immune reconstitution; however, it is unclear how recipient and donor age may affect the dynamics of single immune cells. Here, we retrospectively collected and analysed immunological data of 174 patients (58 children and 116 adults) consecutively transplanted for haematological disorders in our centre. We show that trajectories of specific immune cells were strictly dependent on recipient age and pretransplant virus exposure, with the strongest effect seen on T CD4+ and B‐cell counterparts, while donor age and transplant platforms had a minimal impact. This mirrored different kinetics of immune reconstitution in adult and paediatric patients, with major divergences in immune cell composition in late post‐transplant phases, featuring better survival, relapse‐free survival and cumulative incidence of pathogen‐specific infections in younger patients. Altogether, these findings underpin the importance of recipient age on post‐transplant immune cell recovery and define the basic dynamics of the immune reconstitution in paediatric and adult populations as a benchmark for future studies. [ABSTRACT FROM AUTHOR]

EARLY CTDNA CLEARANCE AFTER CAR T-CELL INFUSION PREDICTS OUTCOME IN PATIENTS WITH LARGE B-CELL LYMPHOMA: RESULTS FROM ALYCANTE, A PHASE 2 LYSA STUDY B Introduction: b CAR T-cells have significantly improved the outcome of patients with relapsed or refractory ( I R i / I R i ) large B-cell lymphoma (LBCL). The aim of our study was to monitor ctDNA before and after CAR T-cell infusion and correlate the results with clinical outcome in the ALYCANTE trial. [Extracted from the article]

Background: No study has focused on the economic burden in non‐Hodgkin lymphoma (NHL) survivors, even though this knowledge is essential. This study reports on health care resource use and associated health care costs as well as related factors in a series of 1671 French long‐term NHL survivors. Methods: Health care costs were measured from the payer perspective. Only direct medical costs (medical consultations, outpatient treatments, hospitalizations, and medical transport) in the past 12 months were included (reference year 2015). Multiple linear regression was used to search for explanatory factors of health care costs. Results: In total, 1100 survivors (66%) reported having used at least 1 health care resource, and 867 (52%) reported having used at least 1 outpatient treatment. After the authors accounted for missing data, the mean health care cost was estimated at €702 ± €2221. Hospitalizations and outpatient treatments were the main cost drivers. Sensitivity analyses confirmed the robustness of the results. For the 1100 survivors who reported using at least 1 health care resource, the mean health care cost was €1067 ± €2268. Several factors demonstrated statistically significant relationships with health care costs. For instance, cardiovascular disorders increased costs by 66% ± 16%. In contrast, rituximab or autologous stem cell transplantation as initial therapy had no effect on health care costs. Conclusions: The consideration of economic constraints in health care is now a reality. This retrospective study reports on a better understanding of health care resource use and associated health care costs as well as related factors. It may help health care professionals in their ongoing efforts to design person‐centered health care pathways. Improvements in the management of non‐Hodgkin lymphoma (NHL) have led to longer survival with potentially increased health care consumption and costs. This cross‐sectional study in long‐term NHL survivors shows that health care resource use and associated costs are linked to sociodemographic factors and comorbidities with no influence from previous lymphoma treatments (chemotherapy, rituximab, and transplantation). [ABSTRACT FROM AUTHOR]

Objective and design: This study investigated the opposite mechanisms by which IL‐1β and TGF‐β1 modulated the inflammatory and migratory phenotypes in cultured human intimal vascular smooth muscle cells vSMCs. Materials and treatment: Primary human vSMCs, obtained from twelve hypertensive patients who underwent carotid endarterectomy, were incubated for 24 hours with either 40 pM TGF‐β1, or 1 nmol/L IL‐1β, or their combination in presence or absence of anti‐TGF‐β neutralizing antibody. Methods: The expression levels of matrix metalloproteases and their inhibitors, and the elastolytic enzyme cathepsin S (CTSS) and its inhibitor cystatin C were evaluated with RT‐PCR. CTSS activity was measured by fluorometry. Results: TGF‐β1 reversed IL‐1β‐induced expression of iNOS, CXCL6, IL1R1, MMP12, and CTSS, while upregulated TIMP2 expression. Furthermore, anti‐TGF‐β neutralizing antibody abrogated TGF‐β effects. Combination with IL‐1β and TGF‐β1 induced the expression of IL1α, IL1β, IL1R1, and CTSS, but suppressed CST3 expression. CTSS expression in the combination treatment was higher than that of cells treated with anti‐TGF‐β antibodies alone. Moreover, IL‐1β‐induced CTSS enzymatic activity was reduced when human vSMCs were co‐treated with TGF‐β, whereas this reduction was abrogated by anti‐TGF‐β neutralizing antibody. Conclusion: TGF‐β1 abrogated IL‐1β‐induced expression of inflammatory genes and elastolytic activity in cultured human vSMCs. Thus, TGF‐β1 can play a crucial role in impairing IL‐1β‐induced vascular inflammation and damage involved in the etiology of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

There is an apparent reciprocal relationship between magnesium ammonium phosphate (MAP, struvite) and calcium oxalate (CaOx) urolithiasis incidence rate in cats. The number of struvite uroliths submitted for analysis over the past 35 years has been decreasing, with an increase in CaOx urolith submissions. Commercial diets aimed to dissolve struvite uroliths are typically acidified, and it has been suggested that dietary acidification increases urinary calcium excretion and the risk of CaOx crystallization. The objective of this study was to assess the effect of urine acidification on the relative supersaturation (RSS) of CaOx in cats, as a representation of crystallization risk. Four diets were extruded to contain identical nutrient contents, but with gradual acidification (0, 0.6, 1.3 and 1.9% sodium bisulphate substituted sodium chloride in diets A, B, C and D respectively). Thirteen adult cats were fed each diet sequentially for a minimum of 10 days. Average urine pH was 6.4, 6.2, 6.0 and 5.9 on diets A, B, C and D respectively (p < 0.0001). Struvite RSS decreased on diets inducing more acidic urine pH (p < 0.0001). Urinary calcium excretion and concentration increased with diets inducing lower urine pH (p < 0.0001), but oxalate excretion and concentration decreased (p < 0.001). CaOx RSS was not different between diets (p = 0.63). These results suggest that a lower diet base excess and resulting urine pH to support struvite dissolution do not increase the risk for CaOx crystallization in the range of urine pH representative of most commercial feline diets. Long‐term studies are needed to confirm this. [ABSTRACT FROM AUTHOR]

Graft vasculopathy (GV) is the most severe pathologic change of chronic rejection in vascularized composite allotransplantation. Since 2012, the intimal media thickness (IMT) of radial and ulnar arteries was annually monitored by high‐resolution ultrasonography in seven bilateral upper extremity transplant (UET) patients. We also investigated the IMT of seven matched healthy subjects (controls). No significant difference between IMT values of controls and UET patients was found. The median IMT values of recipient radial and ulnar arteries were 0.23 mm and 0.25 mm, respectively, while the median IMT values of grafted radial and ulnar arteries were 0.27 mm and 0.30 mm, respectively. There was a statistically significant difference in the IMT values of the grafted and recipient ulnar arteries (p =.043), but this difference was no longer significant when patient #2 was excluded. He showed a significant difference between recipient and grafted arteries and significantly higher IMT values (p =.001) of his grafted arteries compared with those of all transplanted patients. This patient developed GV leading to graft loss 11 years after the transplantation. In conclusion, this study showed a significant IMT increase in an UET recipient who developed GV. [ABSTRACT FROM AUTHOR]

Lenalidomide is efficient in reducing red blood cell transfusion dependency and markedly lowering platelet counts in MDS/MPN‐RS‐T in the context of major platelet counts. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) frequently causes death in older cats; its early detection is challenging. Objectives: To build a sensitive and specific model for early prediction of CKD in cats using artificial neural network (ANN) techniques applied to routine health screening data. Animals Data from 218 healthy cats ≥7 years of age screened at the Royal Veterinary College (RVC) were used for model building. Performance was tested using data from 3546 cats in the Banfield Pet Hospital records and an additional 60 RCV cats—all initially without a CKD diagnosis. Methods: Artificial neural network (ANN) modeling used a multilayer feed‐forward neural network incorporating a back‐propagation algorithm. Clinical variables from single cat visits were selected using factorial discriminant analysis. Independent submodels were built for different prediction time frames. Two decision threshold strategies were investigated. Results: Input variables retained were plasma creatinine and blood urea concentrations, and urine specific gravity. For prediction of CKD within 12 months, the model had accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 88%, 87%, 70%, 53%, and 92%, respectively. An alternative decision threshold increased specificity and PPV to 98% and 87%, but decreased sensitivity and NPV to 42% and 79%, respectively. Conclusions and Clinical Importance: A model was generated that identified cats in the general population ≥7 years of age that are at risk of developing CKD within 12 months. These individuals can be recommended for further investigation and monitoring more frequently than annually. Predictions were based on single visits using common clinical variables. [ABSTRACT FROM AUTHOR]

Urolithiasis is highly prevalent in dogs and cats, with struvite and calcium oxalate being most commonly diagnosed. Some commercial diets aimed at reducing the risk of urolithiasis are based on inclusion of sodium chloride (NaCl) in an attempt to dilute the urine and the risk of crystallization, but more information on the effect of differing levels of sodium inclusion is needed. The objective of this study was to compare the short‐term effect of four diets differing only in NaCl content (base diet with 0.3% sodium and diets with added NaCl to achieve 0.7, 1.0 and 1.3% sodium as fed) on urinary ion concentrations and relative supersaturation (RSS) of struvite and calcium oxalate in dogs and cats. In both species, there was a significant increase in water intake and urine volume as dietary NaCl increased. Urine sodium concentration increased with increasing dietary NaCl. The highest sodium diet increased urinary calcium excretion in dogs only, while decreasing urinary calcium concentration. Calcium oxalate RSS and struvite RSS both significantly decreased, with the lowest RSS values reported on the highest sodium diet in both dogs and cats (p <.001). These results suggest that an increase in dietary NaCl decreases RSS values in both dogs and cats. Despite an increase in urinary calcium excretion in dogs, urinary calcium concentration and calcium oxalate RSS were lower on high sodium diets due to urine dilution. Long‐term studies are needed to confirm the relationship between RSS and stone occurrence and recurrence. [ABSTRACT FROM AUTHOR]

KILT: A RANDOMIZED NON-COMPARATIVE PHASE II LYSA STUDY OF LACUTAMAB WITH GEMOX VERSUS GEMOX IN RELAPSED/REFRACTORY PERIPHERAL T-CELL LYMPHOMA B Background: b Peripheral T-cell Lymphoma (PTCL) is a heterogeneous group of mature T-cell lymphomas (TCL) with adverse outcomes. KIR3DL2 is a killer immunoglobulin-like receptor that is expressed across different subtypes of TCL, including approximately 40% of PTCL. [Extracted from the article]

B Conclusions: b In the ALYCANTE study, axi-cel as second-line treatment in patients with LBCL who were not deemed candidates for HDCT/HSCT appears feasible and induces high response rates. The final analysis with 22 additional patients ( I n i = 62 vs. 40 patients at current cut-off) and a longer follow-up will be presented at the meeting, including subgroup analysis. B Introduction: b Patients with relapsed or refractory ( I R i / I R i ) large B-cell lymphoma (LBCL) after first-line treatment who are unable to undergo high-dose chemotherapy (HDCT) and hematopoietic stem cell transplantation (HSCT) have poor outcomes and limited treatment options. [Extracted from the article]

B Conclusions: b Our study suggests that radiomics features complementary to TMTV derived from baseline 18F-FDG PET/CT scans can improve outcome prediction for follicular lymphoma patients. A total of 7437 PET and CT features were calculated, including tumor radiomics from segmented lesions and host radiomics from segmented organs and correlated to PFS and OS. [Extracted from the article]

Here, we describe a rare case of acquired von Willebrand syndrome (VWS) associated with intracranial plasmacytoma. The literature includes reports of a few cases of plasmacytoma with central nervous involvement, but none of them with acquired VWS. Diagnosis was made based on a stereotaxic intracerebral biopsy. During this biopsy, a ventriculoperitoneal shunt was established, which was complicated with abnormal bleeding. Subsequent hemostasis assessment related to hemopathy revealed acquired von Willebrand disease. The patient received induction therapy with bortezomib, thalidomide, and dexamethasone (VTD), followed by high-dose melphalan chemotherapy and autologous stem cell transplantation, and then VTD consolidation, and finally maintenance with lenalidomide. Our patient currently remains in very good partial response without neurological symptoms after 4 months of maintenance. The patient is free of progression 14 months after their original presentation. [ABSTRACT FROM AUTHOR]

Background: Long-term survivors of non-Hodgkin lymphoma (NHL) must cope with treatment complications and late toxicities that affect their health-related quality of life. Little is known about the risk-to-benefit ratio of new agents like rituximab. The impact of treatment regimens and health disorders on long-term fatigue levels was investigated in a cross-sectional study.Methods: Two self-administered questionnaires, the 20-item Multidimensional Fatigue Inventory (MFI-20) and a Life Situation Questionnaire, were mailed in 2015 to NHL survivors enrolled onto 12 successive clinical studies (1993-2010) conducted by the Lymphoma Study Association. Private addresses were obtained for 3317 survivors, of whom 1671 (50%) returned the questionnaires. Severe fatigue was defined as MFI-20 scores ≥60 on dimension scales scored from 0 to 100. Linear regression models were used to assess factors that were linked to increased fatigue levels.Results: The study population included 906 men and 765 women, and the median age was 64 years (age range, 24-95 years). Overall, 811 survivors had received cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP)-like chemotherapy, 518 had received high-dose CHOP, and 342 had undergone upfront autologous stem cell transplantation; 829 survivors also had received rituximab. In total, 1100 survivors (66%) reported 1 or more late health disorders. Severe fatigue was reported by 602 survivors (37%). Increased fatigue levels were associated (P < .001) with increased age, obesity, and the presence of health disorders, but not with initial treatment or rituximab.Conclusions: The survey confirms that high proportions long-term NHL survivors have severe fatigue. The results suggest that initial treatment and the receipt of rituximab have no influence on the development of long-term fatigue. [ABSTRACT FROM AUTHOR]

Obesity has been associated with an increased risk of developing acute myeloblastic leukaemia (AML). The outcome of AML patients could thus be dependent on their nutritional status that can be evaluated by the simple measurement of serum albumin (SA) and body mass index (BMI). These two parameters could have a value as prognostic factors to guide patients' management. We evaluated the association between SA levels, BMI, and survival, evaluated as overall survival (OS) and event-free survival. Furthermore, we investigated the association between BMI, SA, and other prognostic factors of interest in AML. This retrospective single-center study included 159 patients diagnosed with AML at Nancy Hospital between 2005 and 2013, treated with aracytine and anthracycline. Forty-four percent of patients presented with normal weight while 56% were obese/overweight. Serum albumin levels were <30 g/L for 49 patients, and ≥30 g/L for 110. Thirty-four patients with low SA levels were also obese. Favourable OS was associated with SA levels ≥30 g/L (HR = 0.467; 95% CI 0.230-0.946; P = .034) but was not impacted by the BMI. Serum albumin levels appear to be an independent prognostic factor in AML and a better parameter than BMI for evaluating the nutritional status of patients at diagnosis. [ABSTRACT FROM AUTHOR]

Contents: Failure of passive immune transfer put puppies at a higher risk of neonatal and weaning mortality due to low immune protection against infectious agents. The aim of this study was to investigate the evolution of the general via serum IgG concentration (IgG) and the specific via serum maternally derived canine parvovirus type 2‐specific antibody titer (CPV2 MDA) passive immune transfer within the first 4 weeks of age. Furthermore, the relationship between general and specific immune transfer and the possibility of non‐invasive evaluation was assessed. Puppies (169) were weighed systematically between birth and Day 28. IgG and CPV2 MDA were assayed in serum samples at 2 and at 28 days of age. At Day 2, there was a positive correlation between IgG and CPV2 MDA (ρ = 0.71; p < 0.001). At Day 2, 17.9% (27/151) of puppies presented a deficit of passive immune transfer according to IgG result (defined as IgG < 2.3 g/L) and 25.8% (39/151) of puppies were under the minimal protective CPV2 MDA titer (defined as <1:160). No correlation between IgG and CPV2 MDA was observed at Day 28 (ρ = 0.14; p = 0.11). Growth rate within the first 48 hours <−2.7% allowed to distinguish puppies at high risk of the general and specific passive immune failure (Youden's index = 0.79 and 0.75, respectively). The threshold value of early growth rate, although applicable only in puppies non‐supplemented with milk replacer, allows identifying via non‐invasive way individuals requiring a special care. Further investigation of the mechanism of passive immune transfer in dogs is necessary to understand the relationship between the general and specific immunoglobulin levels. [ABSTRACT FROM AUTHOR]

Summary: The treatment of low‐tumour burden follicular lymphoma (LTBFL) remains a challenge. Rituximab‐based strategies may be improved by adding chemotherapy. This Lymphoma Study Association multicentre phase II study assessed rituximab and bendamustine in 63 patients with untreated LTBFL who were aged over 60 years old and had a follicular lymphoma International Prognostic Index (FLIPI) score ≥2. Induction comprised 4 weekly cycles of rituximab 375 mg/m2 intravenously combined with 2 cycles of bendamustine 90 mg/m2 days 1–2 with a 28‐day interval, followed by twelve cycles of 375 mg/m2 rituximab maintenance therapy every 8 weeks. The primary endpoint was complete response (CR)/unconfirmed CR (CRu), at 12 weeks. Median age was 67·4 years and median FLIPI was 3. Ultimately, 18 patients (29%) had high tumour burden according to Groupe d'Etude des Lymphomes Folliculaires criteria. The 12‐week CR/CRu rate was 54·0% and the overall response rate was 93·7%. Surprisingly, 3 patients died during maintenance (2 sepsis, 1 neoplasm). Progression‐free survival was 85·4% at 24 months. In LTBFL patients with FLIPI ≥2, two cycles of rituximab and bendamustine result in a CR rate of 54·0%. However, the treatment‐related deaths observed do not allow this regimen to be recommended for LTBFL patients aged over 60 years. EudraCT: 2010‐020757‐14; ClinicalTrials.gov: NCT01313611. [ABSTRACT FROM AUTHOR]

The mean age at diagnosis of chronic lymphocytic leukemia (CLL) is 72 years, with 22.8% of patients being older than 80 years. However, the elderly are underrepresented in clinical studies of CLL. We performed a retrospective study of CLL patients aged 80 years or older at the initiation of first-line therapy in hospitals affiliated with the French intergroup on CLL (French Innovative Leukemia Organization) between 2003 and 2013. Here, we describe the clinical and biological characteristics, treatment, and outcomes for 201 patients. The median age of the cohort was 83.2 years (80-92 years). The median Cumulative Index Rating Scale comorbidity score was 5 and the median creatinine clearance was 48 mL/min (Cockcroft-Gault formula). At treatment initiation, Binet stage was A (26.4%), B (27.9%), or C (40.3%). Therapy consisted mainly of chlorambucil (65.7%), bendamustine (10.5%), and rituximab (44.3%) as follows: chlorambucil alone (45.3%) or immunochemotherapy (48.3%) with rituximab + chlorambucil (22.7%), rituximab + bendamustine (10.4%), or rituximab + cyclophosphamide + dexamethasone (5.5%). The overall response rate was 66.2% with 31.8% clinical complete remission. The median overall and progression-free survival from treatment initiation was 53.7 and 18.3 months, respectively. These results suggest that treatment is feasible in this age group, even with immunochemotherapy. Thus, prospective trials should target this population and oncogeriatric evaluation and new targeted therapies should be part of such future trials. [ABSTRACT FROM AUTHOR]

Contents Colostrum and milk are complex mammary secretions providing the puppy with many nutritional and immunological factors, which play a crucial role for its correct development and survival. In the case of colostrum and/or milk intake deficiency, puppies are at increased risk of infectious diseases. This work reviews the various nutritional hyperimmune supplementations proposed to provide a passive immune protection and to positively impact puppies' health. Some strategies rely on canine immunoglobulins: canine colostrum banking and canine serum/plasma supplementation. Others involve heterologous sources of antibodies and other immune factors: bovine colostrum or hyperimmune egg powder. Among the different solutions evaluated from birth to weaning, canine plasma and hyperimmune egg powder showed promising beneficial effect on puppies' health. Canine plasma seems to positively impact not only growth (increased growth during the neonatal period), but also digestive health (higher species richness of intestinal microbiota) and the general health (tendency of lower morbidity). Puppies supplemented with hyperimmune egg powder presented increased neonatal growth and decreased risk of canine parvovirus infection. Nevertheless, natural canine maternal colostrum and milk ingestion remains the optimal guarantee for puppies' health and survival, as a source of immunity, energy and growth factors. [ABSTRACT FROM AUTHOR]

Contents The objective of this study was to describe efficiency of reproduction of purebred dogs in field breeding conditions, from mating to weaning in France. Data were collected between 2010 and 2014 in 5,667 French breeding kennels via a reproduction management software (Breeding Management System, Royal Canin, Aimargues, France). Effect of breed size (Mini: adult body weight <10 kg; Medium: 10-25 kg; Maxi: 25-40 kg; Giant: >40 kg), age of dam and male on pregnancy rate, abortion rate and litter size were evaluated by multivariable models. Data on 45,913 heats (all with mating), from 27,221 bitches from 248 breeds, were analysed. At mating, mean age (± SD) was 3.1 ± 1.8 years for bitches and 3.3 ± 2.0 for males. Males originated from the same kennel as the females in 88.5% of the matings. Based on breeder's evaluation of the pregnancy status, pregnancy rate (number of pregnant females based on breeders declaration/number of heats) was 87.8% and abortion rate was 6.8%. Finally, 81.9% of the mated females gave birth to a litter. On 37,946 litters (204,537 puppies), mean litter size was 5.4 ± 2.8 puppies (range 1-24), which was influenced by breed size and dam age ( p < .0001). Stillbirth rate was 7.4% and puppy mortality rate (stillbirth + mortality until 2 months of age) was 13.4%. Prolificacy and puppy mortality rates were affected by breed size and within a breed size, by breed. Despite probable approximations (as data originate from breeders declaration), this large-scale analysis provides reference values on reproductive performance in dogs. [ABSTRACT FROM AUTHOR]

Background Fecal calprotectin and immunoglobulin A (IgA) are markers of intestinal inflammation and immunity in adult dogs. Hypothesis Fecal calprotectin and IgA concentrations in puppies are not influenced by fecal moisture in puppies but by enteropathogen shedding. Animals Three hundred and twenty-four puppies. Methods Fecal consistency was assessed by gross examination. Fecal moisture was evaluated before and after lyophilization. Canine parvovirus and coronavirus were detected in feces by qPCR and qRT- PCR respectively. Giardia intestinalis antigen was quantified by ELISA. The standard McMaster flotation technique was used to detect eggs and oocysts in feces. Fecal calprotectin and IgA concentrations were quantified by in-house radioimmunoassays. Results For each marker (IgA and calprotectin), a strong positive correlation was observed between concentration in fresh feces and concentration in fecal dry matter. 75.6% of the puppies were found to be infected by at ≥1 of the enteropathogens evaluated. Fecal calprotectin concentration was significantly influenced by age ( P = .001), with higher concentrations in younger puppies, but not by viral ( P = .863) or parasitic infection ( P = .791). Fecal IgA concentration was significantly influenced by enteropathogen shedding ( P = .01), with a lower fecal IgA concentration in puppies shedding at ≥1 enteropathogen compared to puppies without any enteropathogen shedding, but not by age. Conclusions Fecal calprotectin and IgA are of no diagnostic value to detect presence of enteropathogens in clinically healthy puppies or puppies with abnormal feces, but could help to better understand the maturation of digestive tract. [ABSTRACT FROM AUTHOR]

Introduction Automated haematology analysers may inaccurately determine platelet counts in several circumstances. Spuriously elevated automated platelet counts have been reported in some acute leukaemia ( AL) cases because of fragmentation of circulating blast cells (pseudoplatelets). Haemorrhagic diathesis is a common manifestation of AL, which is often caused by severe thrombocytopenia. Therefore, overestimation of the actual platelet count in patients with AL can affect its clinical management. We aimed to detect the frequency of pseudoplatelets in patients with AL. Methods Complete blood cell counts were performed on 86 AL patients with three automated analysers ( ADVIA 2120, Coulter LH 750 and Sysmex XE-2100D). Platelet counts were also performed by quantitative flow cytometry ( QFC). The platelet counts of the automatic analysers were compared to the platelet counts by QFC. Blood smears were checked for the presence of pseudoplatelets. Results The automated analysers overestimated the platelet count due to the presence of pseudoplatelets in patients with AL. Pseudoplatelets were observed in the blood smears of 11 patients (13%). Three of these patients were near the prophylactic platelet transfusion threshold. Conclusion Spurious increases in automated platelet counts by blast cell fragments are little known but frequent artefacts that should be ruled out by careful examination of peripheral blood smears. [ABSTRACT FROM AUTHOR]

Introduction Chronic lymphocytic leukemia is usually diagnosed through the characteristic morphology/immunophenotype of the lymphocytes, but some CLL cases remain atypical resulting in diagnostic uncertainty. Methods Using flow cytometry analysis, we investigated the expression of CDs160/200 on B cells from 124 patients (82 CLL, 42 other B-cell neoplasms) and nine controls. CDs160/200 measurements were determined as a ratio of the mean fluorescence intensities of leukemic cells/controls and were considered positive when the ratios were ≥2 and 20, respectively. Results Sixty and 83% CLL expressed CDs160/200 as compared to 5% and 10% of other B-cell neoplasms, respectively. None of the controls showed CDs160/200 expressions. Combination of both markers was observed in 55% of CLL but only in 2% of other B-cell neoplasms, and absence of both markers occurred in 12% of CLL but in 86% of other B-cell neoplasms. Conclusion CDs160/200 were associated with markers of the gold standard 'Matutes score' and could be useful markers to differentiate atypical CLL from other B-cell neoplasms in the absence of available biopsies or cytogenetics and molecular studies. [ABSTRACT FROM AUTHOR]

Hairballs are a common problem in cats and may result in intestinal obstruction. Dietary fibre has been recommended to stimulate hair faecal excretion. The objective of this study was to assess the influence of psyllium and different levels of total dietary fibre (6% vs. 11% vs. 15% TdF) on hair faecal excretion in short and long-haired (LH) domestic cats. Twenty-one adult cats were divided into three panels: shedding panel, short-haired (SH) panel and LH panel. Shedding panel was used to assess shedding throughout the study with a normalized brushing. In parallel, SH panel and LH panel were used to evaluate the impact of the diets on faecal hair excretion. They were fed a low-fibre diet during phase 1 (diet 6, 6.0% TdF). In phase 2, panels were fed either diet 11 (11% TdF) or diet 15 (15% TdF). In phase 3, cats returned to diet 6 before a crossover on the other diet in phase 4. Those diets were fed to cats for 14 days. Faecal hair excretion was quantified daily. Data were analysed using a generalized linear model procedure. The assessment of shedding showed that the study did not occur during moulting season. In the LH panel, diet 11 and diet 15 increased ( P < 0.001) faecal hair excretion by 81% and 113% respectively, compared to the control diet. In the SH panel, no influence of the diets was observed. This study supports that fibre affects faecal hair excretion in LH cats, suggesting that a diet with psyllium and 11% or 15% TdF might minimize hairball formation in 14 days and between shedding periods. In SH cats, 11% and 15% fibre levels had no effect on faecal hair excretion. This could be explained by the low quantity of hair ingested outside the shedding season or by the short duration of the study. [ABSTRACT FROM AUTHOR]

The aim of this prospective, double-centre, observational study performed in 116 patients was to describe a new anterior approach of ultrasound-guided intermediate cervical plexus block for carotid endarterectomy. The median (IQR [range]) volume of ropivacaine 0.5% administered was 30 (25-30 [20-45]) ml. Supplemental local anaesthesia (infiltration and topical) was needed in 66 (57%) patients. Overall, 41 (35%) patients needed additional sedation (18 midazolam; 23 remifentanil). There was no intra-operative complication or systemic toxicity of ropivacaine. One regional anaesthesia procedure was converted to general anaesthesia because of patient agitation. Adverse effects were of short duration and did not affect surgery. Satisfaction scores were high for 92 (79%) patients (63 satisfied; 29 very satisfied) and 104 (90%) surgeons (51 satisfied; 53 very satisfied). This study shows that the ultrasound-guided intermediate cervical plexus block using an anterior approach is feasible and provides similar results to other regional techniques during carotid endarterectomy. [ABSTRACT FROM AUTHOR]

Background Cats with hypertrophic cardiomyopathy ( HCM) are larger and have higher insulin-like growth factor-1 ( IGF-1) concentrations than cats without HCM. Hypothesis/Objectives The aim of this study was to assess echocardiographic findings in a colony of adult cats to determine the relationship between early growth and left ventricular hypertrophy ( LVH). Animals Twenty-eight neutered adult cats (20 males, 8 females) from a colony ≥3 years of age for which growth curves were available. Methods Case-control study. Physical examination and echocardiography were performed, and body weight, body condition score ( BCS), and head length and width were measured. Circulating glucose, insulin, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and IGF-1 concentrations were measured and growth data were collected. Stepwise multivariate analyses were performed. Results Mean age was 5.2 ± 1.1 years. Current BCSs ranged from 4 to 9 (median, 6) and mean body weight was 4.88 ± 1.29 kg. Variation in body weight was apparent by 6 (mean = 3.26 ± 0.80 kg) and 12 months of age (mean = 4.02 ± 1.02 kg). Cardiac abnormalities included a cardiac murmur (n = 7; 24%), gallop (n = 3; 10%), and arrhythmia (n = 1; 4%). Fourteen of 28 cats (50%) had echocardiographic evidence of LVH. Head width ( P = .017), body weight ( P < .001), NT-pro BNP ( P = .023), and IGF-1 ( P = .013-.022) were significantly associated with selected measures of LVH. Conclusions and Clinical Importance Potential associations between body size, IGF-1, LVH, and HCM warrant future prospective studies. [ABSTRACT FROM AUTHOR]

A large, multicentre, retrospective survey of patients with hairy cell leukaemia ( HCL) was conducted in France to determine the frequency of second malignancies and to analyse the long-term effects of the established purine nucleoside analogues ( PNAs), cladribine and pentostatin. The survey retrospectively reviewed the medical history of patients and their immediate family, clinical and biological presentation at the time of HCL diagnosis, treatment choice, response to treatment, time to relapse and cause of death. Data were collected for 487 patients with HCL. Of the patients included in the survey, 18% (88/487) had a familial history of cancers, 8% (41/487) presented with malignancies before HCL diagnosis and 10% (48/487) developed second malignancies after HCL was diagnosed. An excess incidence of second malignancies was observed, with a standardized incidence ratio ( SIR) of 1·86 (95% confidence interval ( CI): 1·34-2·51), with no significant difference between PNAs. For second haematological malignancies alone, the SIR was markedly increased at 5·32 (95% CI: 2·90-8·92). This study highlights the high frequency of cancers in HCL patients and their family members. The frequency of second malignancies is notably increased, particularly for haematological malignancies. The respective role of pentostatin and cladribine in the development of second malignancies is debatable. [ABSTRACT FROM AUTHOR]

Follicular Lymphoma ( FL) is the second most common non-Hodgkin lymphoma ( NHL) subtype and its course is heterogeneous. At diagnosis, some patients with FL manifest a detectable leukaemic phase ( FL- LP), but this feature has been seldom described and is poorly characterized. Among 499 patients diagnosed with FL in Lyon-Sud hospital, 37 (7·4%) had characteristic FL- LP (by cytological blood smears and flow cytometric analysis). In addition, 91/1135 FL patients from the PRIMA study presented FL- LP at study entry. In order to evaluate the outcome of this Lyon-Sud cohort, FL- LP patients were matched with 111 newly diagnosed FL without LP according to the Follicular Lymphoma International Prognostic Index ( FLIPI) score, age and treatment. Presence of FL- LP was associated with shorter progression-free survival ( PFS) and overall survival ( OS) ( P = 0·004 and P = 0·031, respectively). Presence of FL- LP and high FLIPI score remained independent prognostic factors in a Cox model for time to progression ( TTP). A number of circulating lymphoma cells ( CLC) >4 × 109/l was the most significant predictor for a shorter TTP in this Cox model. The prognostic impact of FL- LP on TTP was validated in the PRIMA cohort ( P = 0·0004). In conclusion, FL- LP is a rare event associated with shorter PFS and patients with CLC >4 × 109/l have a poorer outcome. These patients should be monitored carefully to consider alternative therapeutic options. [ABSTRACT FROM AUTHOR]

High cortisol and aldosterone levels increase cardiovascular risk, but the respective roles of each hormone within the arterial wall remain controversial. We tested the hypothesis that cortisol production within the arterial wall may contribute to atherosclerotic remodeling and act through illicit activation of the mineralocorticoid receptor ( MR). Gene expression studies of the corticoid system components and marker genes of the atherosclerotic process in human carotid atheroma plaque and nearby macroscopically intact tissue ( MIT) were considered together with clinical data and compared with pharmacological stimulations of human vascular smooth muscle cells ( VSMCs) in contractile or lipid-storing phenotypes. The components of corticoid production and action were present and active within the human carotid wall and VSMCs. Atheroma plaque and lipid-storing VSMCs expressed 11β-hydroxysteroid deshydrogenase-1 (11β- HSD1) at two- to tenfold higher levels than MIT or contractile VSMCs. The 11β- HSD1 expression was stimulated by cortisol and cortisone, especially in lipid-storing VSMCs. MR mRNA level was lower in atheroma and lipid-storing VSMCs and downregulated via MR by fludrocortisone and cortisol. Cortisol upregulated collagen1 and MCP-1 m RNAs via the glucocorticoid receptor ( GRα), in both VSMC phenotypes, whereas fludrocortisone stimulated the collagen1 expression only in lipid-storing VSMCs. The GRα m RNA level in MIT was higher in patients with previous stroke and correlated positively with the collagen1 m RNA but negatively with diastolic blood pressure. Local cortisol production by 11β- HSD1, and its action via high parietal GRα could be relevant from the first step of atherosclerotic remodeling and auto-amplify with transdifferentiation of VSMCs during atheroma progression. [ABSTRACT FROM AUTHOR]