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Abstract Background Hypercortisolism affects calcium and phosphate metabolism in dogs; however, the exact mechanisms are not completely understood. Objectives To evaluate circulating concentrations of whole parathormone (wPTH), 25-hydroxyvitamin D (25-(OH)D), calcitriol, and fibroblast growth factor-23 (FGF-23) in dogs with naturally occurring hypercortisolism (NOHC) and healthy dogs, and their association with calcium and phosphate homeostasis. Animals Twenty-three client-owned dogs with NOHC, and 12 client or staff-owned healthy dogs. Methods Prospective cross-sectional study. The circulating concentrations of total calcium, ionized calcium (iCa), phosphate, wPTH, 25-(OH)D, calcitriol and FGF-23, and the urinary fractional excretion of phosphate (FEP) and calcium (FECa) were compared between dogs with NOHC before treatment and healthy dogs. Results Dogs with NOHC had higher mean serum phosphate concentrations (4.81 mg/dL, SD ± 0.71 vs 3.86 mg/dL, SD ± 0.60; P < .001), median FECa (0.43%, range, 0.03-2.44 vs 0.15%, range, 0.06-0.35; P = .005), and median serum wPTH concentrations (54.6 pg/mL, range, 23.7-490 vs 24.6 pg/mL, range, 5.5-56.4; P = .003) as compared to the controls. Circulating concentrations of total calcium, iCa, and calcitriol and the FEP did not differ between groups, whereas the serum 25-(OH)D concentrations were lower in dogs with NOHC as compared to the controls (70.2 pg/mL, SD ± 42.3 vs 106.3 pg/mL, SD ± 35.3; P = .02). The dogs with NOHC had lower plasma FGF-23 concentrations than controls (316.6 pg/mL, range, 120.8-575.6 vs 448.7 pg/mL, range, 244.8-753; P = .03). Conclusions and Clinical Importance Urine loss of calcium and hyperphosphatemia could contribute to the adrenal secondary hyperparathyroidism.

Leptospirosis is an infectious disease that causes serious illness in dogs. For this reason, epidemiological and clinical studies focusing on disease characterization are widely advocated. The aim of this study was to characterize the leptospires identified in dogs with confirmed symptomatic acute leptospirosis. Leptospira spp. DNA detected in urine, blood, or both samples from nine infected dogs was analyzed using the multi-locus sequence typing (MLST) technique. Leptospires from two dogs were successfully typed: one was identified as belonging to Sequence Type (ST) 17 and one to ST198, both within the L. interrogans species, serogroups Icterohaemorrhagiae and Australis, respectively. Based on the results of routine serologic tests, antibodies reactive toward these serogroups are commonly revealed in dogs in Italy. This study provides the first molecular analysis that identifies infecting Leptospira directly on DNA from biological samples of dogs, showing that serogroup Australis can lead to a severe clinical presentation of leptospirosis in infected dogs.

The microscopic agglutination test (MAT) assay is adopted as a world-wide reference test for the serodiagnosis of leptospirosis in humans and animals. One of the main limitations of MAT is the lack of sensitivity and serodiagnostic antigens should be periodically updated with locally circulating serovars in order to optimise its performance. The aim of this study was to determine the need to implement the antigen panel currently adopted in Northern Italy for the diagnosis of Leptospira infection in dogs. For this purpose, a group of 288 dogs with and without clinical signs potentially consistent with Leptospira infection or found to have an increased C-reactive protein (CRP) serum concentration, sampled in 2013–2016 in Northern Italy, were tested by MAT comparing the results obtained with a nine antigens panel (Australis-Bratislava, Ballum-Ballum, Canicola-Canicola, Grippotyphosa-Grippotyphosa, Icterohaemorrhagiae-Copenhageni, Icterohaemorrhagiae-Icterohaemorrhagiae, Sejroe-Hardjo, Pomona-Pomona and Tarassovi-Tarassovi serovars) routinely adopted and a panel expanded to 27 antigens. In general, the antigen panel currently adopted in Northern Italy for the routine MAT assay resulted adequate for the diagnosis of Leptospira infection in dogs. The main exception concerns the Sejroe serogroup, with the Saxkoebing and Sejroe serovars that were more effective than Hardjo for diagnosis in dogs and whose inclusion in the antigen panel is recommended. Among other antigens evaluated in this study, Cynopteri serovar was detected with high frequency but its pathogenic role in dogs and as public health threat deserve further investigation.

The limping syndrome is occasionally reported during acute feline calicivirus (FCV) infections or as consequence of vaccination. In this retrospective study, three clinical cases of lameness in household cats naturally infected by FCV were described and phylogeny of the virus were investigated by analysing the hypervariable E region of the ORF2 viral gene. Cats were diagnosed with polyarthritis and FCV RNA or antigens were detected in symptomatic joints. One cat, euthanized for ethical reasons, underwent a complete post-mortem examination and was subjected to histopathological and immunohistochemical investigations. No phylogenetic subgrouping were evident for the sequenced FCV. Histopathology of the euthanized cat revealed diffuse fibrinous synovitis and osteoarthritis eight months after the onset of lameness and the first detection of FCV RNA, supporting the hypothesis of a persistent infection. FCV was demonstrated by immunohistochemistry in synoviocytes and fibroblasts of the synovial membranes. This study provides new data on the occurrence of polyarthritis in FCV-infected cats, demonstrates by immunohistochemistry the presence of FCV in the synovial membranes of a cat with persistent polyarthritis and supports the absence of correlation between limping syndrome and phylogenetic subgrouping of viruses.

Patients with multiple myeloma are generally older and vary in fitness levels, which may influence the clinical benefit of treatment. Patients from the large, phase 3 FIRST trial in newly diagnosed multiple myeloma (NDMM) were retrospectively investigated to determine outcomes based on frailty using scores for age, Charlson Comorbidity Index (CCI), and Eastern Cooperative Oncology Group performance status (ECOG PS), instead of the EQ-5D quality-of-life questionnaire, as previously reported. ECOG PS (n = 1618) was investigated in frailty groups: frail (49%) and nonfrail (51%). Frail patients experienced worse progression-free and overall survival vs nonfrail patients. Prognostic assessment was improved when combining frailty and International Staging System stage (I/II vs III). Frail patients had a higher risk of developing grade 3/4 treatment-emergent adverse events. Treatment effects observed in the FIRST trial were confirmed per frailty group and per frailty and ISS group. The use of this ECOG PS–containing frailty scale as a predictive measure of clinical outcomes in patients with transplant-ineligible NDMM is supported by data from the FIRST trial. This score, based on age, CCI, and ECOG PS, can be easily replicated and may help design future myeloma studies in frail or nonfrail elderly patients.

Background Per- and polyfluoroalkyl substances (PFAS) are associated with many adverse health conditions. Among the main effects is carcinogenicity in humans, which deserves to be further clarified. An evident association has been reported for kidney cancer and testicular cancer. In 2013, a large episode of surface, ground and drinking water contamination with PFAS was uncovered in three provinces of the Veneto Region (northern Italy) involving 30 municipalities and a population of about 150,000. We report on the temporal evolution of all-cause mortality and selected cause-specific mortality by calendar period and birth cohort in the local population between 1980 and 2018. Methods The Italian National Institute of Health pre-processed and made available anonymous data from the Italian National Institute of Statistics death certificate archives for residents of the provinces of Vicenza, Padua and Verona (males, n  = 29,629; females, n  = 29,518) who died between 1980 and 2018. Calendar period analysis was done by calculating standardised mortality ratios using the total population of the three provinces in the same calendar period as reference. The birth cohort analysis was performed using 20–84 years cumulative standardised mortality ratios. Exposure was defined as being resident in one of the 30 municipalities of the Red area , where the aqueduct supplying drinking water was fed by the contaminated groundwater. Results During the 34 years between 1985 (assumed as beginning date of water contamination) and 2018 (last year of availability of cause-specific mortality data), in the resident population of the Red area we observed 51,621 deaths vs. 47,731 expected (age- and sex-SMR: 108; 90% CI: 107–109). We found evidence of raised mortality from cardiovascular disease (in particular, heart diseases and ischemic heart disease) and malignant neoplastic diseases, including kidney cancer and testicular cancer. Conclusions For the first time, an association of PFAS exposure with mortality from cardiovascular disease was formally demonstrated. The evidence regarding kidney cancer and testicular cancer is consistent with previously reported data.

Purpose This study aims to evaluate whether using a combined oral contraceptive pill (COCP) pre-treatment before controlled ovarian hyperstimulation (COH) may negatively influence ovarian response in donors and treatments outcomes in recipients when a progestin-primed ovarian stimulation (PPOS) protocol is used in oocyte donation treatments. Methods Multicenter retrospective cohort study evaluating outcomes of 397 COH cycles in oocyte donors, with and without COCP pre-treatment. The retrieved oocytes were used for 216 oocyte donation cycles in recipients. Results In donors, the No-COCP group obtained a higher number of total, MII, and useful oocytes, similar stimulation days, total FSH dose used, and cancellation rate due to low response, while the COCP group showed significantly higher cancellations for low LH levels, indicative of long-lasting pituitary suppression COCP related. In recipients, both groups showed similar fertilization rate and blastocyst formation rate. Miscarriage rate (MR) was significantly higher in the COCP group, while higher implantation rate, ongoing pregnancy rate (OPR), and live birth rate (LBR) were obtained in the No-COCP group. Conclusions Donor response to COH with PPOS protocol appears to be negatively influenced by COCP pre-treatment, with implications for oocyte donation treatment outcomes in recipients, including higher MR and lower OPR/LBR. Further studies are needed to confirm these findings.

Previous trials showed the tolerability and efficacy of a palliative radiotherapy (RT) regimen (SHARON) based on the 4 fractions delivered in 2 days in different oncological settings. In order to identify possible predictors of symptomatic response, the purpose of this study is to perform a pooled analysis of previous trials. We analyzed the impact on symptomatic response of the following parameters: tumor site, histological type, performance status (ECOG), dominant symptom, and RT dose using the Chi-square test and Fisher’s exact test. One-hundred-eighty patients were analyzed. Median RT dose was 20 Gy (range: 14–20 Gy). The overall response rate was 88.8% (95% CI 83.3–92.7%) while pre- and post-treatment mean VAS was 5.3 (± 7.7) and 2.2 (± 2.2), respectively ( p  < 0.001). The overall response rate of pain, dyspnea, bleeding, dysphagia, and other symptoms was 86.2%, 90.9%, 100%, 87.5%, and 100%, respectively. Comparing the symptomatic effect based on the analyzed parameters no significant differences were recorded. However, patients with locally advanced disease showed a higher rate of symptomatic responses than metastatic ones (97.3% vs 83.0%; p  = 0.021). Finally, the complete pain response rate was more than double in patients with mild to moderate (VAS: 4–7) compared to those with severe (VAS > 7) pain (36.0% vs 14.3%; p  = 0.028). This pooled analysis showed high efficacy of the SHARON regimen in the relief of several cancer-related symptoms. The markedly and significantly higher complete pain response rate, in patients with mild-moderate pain, suggests early referral to palliative RT for patients with cancer-related pain.

Multiple myeloma (MM) is a plasma cell (PC) disorder characterized by skeletal involvement at the time of diagnosis. Recently, cell-free DNA (cfDNA) has been proven to recapitulate the heterogeneity of bone marrow (BM) disease. Our aim was to evaluate the prognostic role of cfDNA at diagnosis according to disease distribution, and to investigate the role of the MM microenvironment inflammatory state in supplying the release of cfDNA. A total of 162 newly diagnosed MM patients were screened using 18F-FDG PET/CT and assessed by ultra low-pass whole genome sequencing (ULP-WGS). High cfDNA tumor fraction (ctDNA) levels were correlated with different tumor mass markers, and patients with high ctDNA levels at diagnosis were more likely to present with metabolically active paraskeletal (PS) and extramedullary (EM) lesions. Moreover, we demonstrated that microenvironment cancer-associated fibroblast (CAFs)-mediated inflammation might correlate with high ctDNA levels. Indeed, a high cfDNA TF level at diagnosis predicted a poorer prognosis, independent of R-ISS III and 1q amplification; the inclusion of >12% ctDNA in the current R-ISS risk score enables a better identification of high-risk patients. ctDNA can be a reliable and less invasive marker for disease characterization, and can refine patient risk.

The complexity of Multiple Myeloma (MM) is driven by several genomic aberrations, interacting with disease-related and/or -unrelated factors and conditioning patients’ clinical outcome. Patient’s prognosis is hardly predictable, as commonly employed MM risk models do not precisely partition high- from low-risk patients, preventing the reliable recognition of early relapsing/refractory patients. By a dimensionality reduction approach, here we dissect the genomic landscape of a large cohort of newly diagnosed MM patients, modelling all the possible interactions between any MM chromosomal alterations. We highlight the presence of a distinguished cluster of patients in the low-dimensionality space, with unfavorable clinical behavior, whose biology was driven by the co-occurrence of chromosomes 1q CN gain and 13 CN loss. Presence or absence of these alterations define MM patients overexpressing either CCND2 or CCND1 , fostering the implementation of biology-based patients’ classification models to describe the different MM clinical behaviors. The characterisation of the molecular features of multiple myeloma (MM) remains challenging. Here, the authors identify a subset of MM patients with a dismal clinical outcome, harbouring both chromosomes 1q CN gain and 13 CN loss and overexpressing CCND2.