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Gaetano Pezzicoli,1,2 Elisabetta Filoni,1,2 Angela Gernone,2 Laura Cosmai,3 Mimma Rizzo,4 Camillo Porta2,5 1Department of Biomedical Sciences and Human Oncology, Post-Graduate School of Specialization in Medical Oncology, University of Bari ‘A. Moro’, Bari, Italy; 2Division of Medical Oncology, A.O.U. Consorziale Policlinico di Bari, Bari, Italy; 3Onconephrology Outpatient Clinic, Division of Nephrology and Dialysis, A.S.S.T. Fatebenefratelli-Sacco, Fatebenefratelli Hospital, Milan, Italy; 4Division of Translational Oncology, I.R.C.C.S. Istituti Clinici Scientifici Maugeri, Pavia, Italy; 5Chair of Oncology, Department of Biomedical Sciences and Human Oncology, University of Bari ‘A. Moro’, Bari, ItalyCorrespondence: Camillo PortaDivision of Medical Oncology, A.O.U. Consorziale Policlinico di Bari, Piazza Giulio Cesare, 11, Bari, 70124, ItalyTel +39-080-5594167Fax +39-080-5593477Email camillo.porta@gmail.com; camillo.porta@uniba.itAbstract: In the last decade, the inhibition of the mechanistic target of Rapamycin (mTOR) in renal clear cell carcinoma (RCC) has disappointed the clinician’s expectations. Many clinical trials highlighted the low efficacy and unmanageable safety profile of first-generation mTOR inhibitors (Rapalogs), thus limiting their use in the clinical practice only to those patients who already failed several therapy lines. In this review, we analyze the major resistance mechanisms that undermine the efficacy of this class of drugs. Moreover, we describe some of the possible strategies to overcome the mechanisms of resistance and their clinical experimentation, with particular focus on novel mTOR inhibitors and the combinations of mTOR inhibitors and other anti-cancer drugs.Keywords: everolimus, temsirolimus, Rapa-Link, anti-angiogenics, autophagy

Canine heartworm disease by Dirofilaria immitis and canine leishmaniosis by Leishmania infantum (CanL) are both vector-borne diseases with frequently overlapping endemicity and able to trigger the acute phase response, being characterized by variations in acute phase proteins (APP). Recently, erythrocyte sedimentation rate (ESR), an indicator of inflammation, has gained attention in veterinary medicine, proving useful in several conditions that include CanL active forms in dogs. This study aims to evaluate ESR in heartworm-infected dogs, compare levels with heartworm-infected and L. infantum seropositive dogs as well as clinically healthy dogs, and assess correlations with other laboratory parameters. From October 2022 to January 2023, a prospective observational study was conducted enrolling heartworm-infected (Dirofilaria group) and heartworm-infected L. infantum seropositive (Dirofilaria/Leishmania group) animals subgrouped according to the CanL clinical form (Dirofilaria/Leishmania active and non-active groups). A group of clinically healthy dogs (control group) was also included. For each dog enrolled physical examination and laboratory tests (complete blood count, biochemical panel including APP, serum protein electrophoresis) were performed. Dirofilaria and Dirofilaria/Leishmania groups presented a significantly higher ESR level compared to healthy dogs. Dirofilaria/Leishmania active group had the highest ESR level among the groups considered. Dirofilaria/Leishmania non-active group had an ESR similar to the Dirofilaria group, but significantly higher and lower compared to the control and the Dirofilaria/Leishmania active group, respectively. A significant positive correlation between ESR and C-Reactive Protein has been found in all groups except for the Dirofilaria/Leishmania non-active group. In Dirofilaria/Leishmania active group a strong positive correlation between ESR and gamma globulins percentage as well as a strong negative correlation between ESR and albumin, albumin/globulins ratio were found. Overall, the ESR was confirmed to be an inflammation marker as well as a helpful disease index, being notably increased in heartworm-infected dogs affected by an active form of CanL.

Abstract We demonstrated the non-inferiority of a dexamethasone (DEX)-sparing (single-dose) regimen with NEPA, a netupitant/palonosetron fixed combination, for preventing chemotherapy-induced nausea and vomiting (CINV) caused by cisplatin. This pre-planned exploratory analysis assessed the effect of the DEX-sparing regimen on a patient’s food intake. Chemotherapy-naïve patients undergoing cisplatin (≥ 70 mg/m2) were given NEPA and DEX (12 mg) on day 1 and randomized to receive either no further DEX (DEX1), or oral DEX (4 mg BID) on days 2–4 (DEX4). Patient-reported endpoint maintenance of usual daily food intake was assessed during the 5-days post-chemotherapy. The relationship between usual daily food intake and CINV control, pre-chemotherapy self-rated food intake and BMI-adjusted weight loss (WL) were evaluated. One-hundred fifty-two patients (76/group) were assessable. The proportion of patients reporting maintenance of usual daily food intake was similar in both groups: 69.7% (95% CI, 58.6–78.9) for DEX1 vs. 72.4% (95% CI, 61.4–81.2) for DEX4. Only CINV control was significantly associated with maintenance of usual daily food intake (P ≤ 0.001) during the overall phase. The DEX-sparing regimen does not adversely affect patient-reported daily food intake post-chemotherapy. The current analysis adds further insights into antiemetic efficacy of DEX sparing beyond day 1 in the challenging setting of cisplatin. Trial registration: The parent study was registered on ClinicalTrials.gov (NCT04201769).

IntroductionAdvanced urothelial carcinoma remains aggressive and very hard to cure, while new treatments will pose a challenge for clinicians and healthcare funding policymakers alike. The U-CHANGE Project aimed to redesign the current model of care for advanced urothelial carcinoma patients to identify limitations (“as is” scenario) and recommend future actions (“to be” scenario).MethodsTwenty-three subject-matter experts, divided into three groups, analyzed the two scenarios as part of a multidimensional consensus process, developing statements for specific domains of the disease, and a simplified Delphi methodology was used to establish consensus among the experts.ResultsRecommended actions included increasing awareness of the disease, increased training of healthcare professionals, improvement of screening strategies and care pathways, increased support for patients and caregivers and relevant recommendations from molecular tumor boards when comprehensive genomic profiling has to be provided for appropriate patient selection to ad hoc targeted therapies.DiscussionWhile the innovative new targeted agents have the potential to significantly alter the clinical approach to this highly aggressive disease, the U-CHANGE Project experience shows that the use of these new agents will require a radical shift in the entire model of care, implementing sustainable changes which anticipate the benefits of future treatments, capable of targeting the right patient with the right agent at different stages of the disease.

Abstract Background The non-inferiority of dexamethasone (DEX) on day 1, with or without low-dose DEX on days 2 and 3, combined with oral NEPA (netupitant/palonosetron), compared with the guideline-consistent use of DEX was demonstrated in cisplatin. Here, we complete the analysis by assessing the impact of emesis on daily lives of patients receiving DEX-sparing regimens using the Functional Living Index-Emesis (FLIE). Methods Chemotherapy-naïve patients undergoing cisplatin (≥70 mg/m2), were given NEPA and DEX (12 mg) on day 1 and randomized to receive either 1) no further DEX (DEX1), 2) oral DEX (4 mg daily) on days 2–3 (DEX3), or 3) DEX (4 mg twice daily) on days 2–4 (DEX4; control). Patients completed the FLIE questionnaire on day 6 of cycle 1. Endpoints included the FLIE nausea domain, vomiting domain, and overall combined domain scores, as well as the proportion of patients with no impact on daily life (NIDL; overall score > 108). This was a protocol-planned analysis. Results In the DEX1 group, no significant differences were observed in the FLIE nausea score (48.9 [±1.8; SE] vs. 53.7 [±1.5]), vomiting score (56.6 [±1.4] vs. 58.7 [±0.8]) and overall score (105.6 [±2.8] vs.112.4 [±1.9]) versus DEX4 control; similar results were observed in the DEX3 group for nausea score (49.6 [±1.7]), vomiting score (58.2 [±1]) and overall score (107.8 [±2.4]) versus control. There were no significant between-group differences in the proportion of patients reporting NIDL. Conclusion Reducing DEX, when administered with NEPA, does not seem to adversely impact the daily functioning in patients undergoing cisplatin. Trial registration ClinicalTrials.gov NCT04201769 . Registration date: 17/12/2019 - Retrospectively registered.

This prospective study aimed to evaluate inflammatory status in cats affected by chronic kidney disease (CKD) at IRIS stages 2–4, using serum amyloid A (SAA) and the erythrocyte sedimentation rate (ESR) as inflammatory markers. Thirty-two cats with CKD and ten clinically healthy cats (i.e., control group) were enrolled. The recording of signalment data, complete physical examinations, and abdominal ultrasonography were performed for each animal. Additionally, ESR levels, complete blood count, clinical chemistry (including SAA determination), serum protein electrophoresis, and complete urinalysis were executed. This study’s results showed that mean ESR and SAA concentrations in cats with CKD were statistically higher compared to those of the control group (p = 0.0005 and p = 0.007, respectively). The SAA concentration was significantly increased at IRIS stages 2, 3, and 4 compared to the control group. Meanwhile, the ESR was significantly higher in cats at IRIS stages 3 and 4 (p = 0.0003 and p = 0.0007, respectively), but not at IRIS stage 2, compared to the control group. These results provide evidence that feline CKD is associated with a systemic inflammatory status. Moreover, the rise in ESR appears to be more linked to advanced stages of the disease and could, therefore, correlate with the uremic condition.

The trypanosomatid protist Leishmania tarentolae is a saurian-associated parasite vectored by the Sergentomyia minuta sand fly. This study aimed to confirm the circulation of L. infantum and L. tarentolae in sand flies, reptiles and dogs and to isolate new strains of these protists. Reptilian and sheltered dog blood samples were collected, and sand flies were captured. Samples were tested for Leishmania spp. using duplex real-time PCR (dqPCR) and real-time PCR (qPCR); the origin of blood meal was identified in engorged sand flies by conventional PCR. The reptilian blood and intestinal content of sand fly females were cultured. Dog sera were tested by IFAT using both Leishmania species. Four Tarentola mauritanica geckoes were molecularly positive for L. infantum or L. tarentolae, with no co-infections; moreover, amastigote-like forms of L. infantum were observed in the bone marrow. 24/294 sand flies scored positive for Leishmania spp. by dqPCR, 21 S. minuta and two Phlebotomus perniciosus were positive for L. tarentolae, while only a single Ph. perniciosus was positive for L. infantum. Blood meal analysis confirmed reptile and dog in S. minuta, dog and human in Ph. perniciosus and dog in Phlebotomus neglectus. Two axenic strains of L. tarentolae were obtained. Twelve of 19 dogs scored positive for L. infantum and L. tarentolae by IFAT and three of them also for L. infantum by dqPCR, and six by qPCR. These data confirm the sympatric circulation of L. infantum and L. tarentolae in geckoes, sand flies, and dogs, and suggest that geckoes may be infected with L. infantum.

Lower urinary tract disease (LUTD) includes abnormalities in the structure and function of the bladder and the urethra. LUTD caused by neurological disease is defined neurogenic bladder (NB). The integrity of the central nervous system (CNS) and peripheral nervous system (PNS) is required to explicate normal micturition, maintaining the proper function of bladder and urethra. The location and type of neurological lesions influence the pattern of clinical manifestations, potential treatment, and prognosis. Though, in dogs and cats, spinal cord injury is considered mainly responsible for bladder and/or urethra incompetence, other disorders, congenital or acquired, involving CNS or PNS, could play a role in NB. In veterinary medicine, the information about the epidemiology, prevalence, etiopathogenesis, diagnosis and treatment of NB are scattered. The aim of this study is to provide an overview of the epidemiology, prevalence, clinical findings, diagnosis and prognosis for NB in dogs and cats compared with humans.

Background: This prospective, multicentre, observational INVIDIa-2 study is investigating the clinical efficacy of influenza vaccination in advanced-cancer patients receiving immune-checkpoint inhibitors (ICIs), enrolled in 82 Italian centres, from October 2019 to January 2020. The primary endpoint was the incidence of influenza-like illness (ILI) until 30 April 2020. All the ILI episodes, laboratory tests, complications, hospitalizations and pneumonitis were recorded. Therefore, the study prospectively recorded all the COVID-19 ILI events. Patients and methods: Patients were included in this non-prespecified COVID-19 analysis, if alive on 31 January 2020, when the Italian government declared the national emergency. The prevalence of confirmed COVID-19 cases was detected as ILI episode with laboratory confirmation of SARS-CoV-2. Cases with clinical-radiological diagnosis of COVID-19 (COVID-like ILIs), were also reported. Results: Out of 1257 enrolled patients, 955 matched the inclusion criteria for this unplanned analysis. From 31 January to 30 April 2020, 66 patients had ILI: 9 of 955 cases were confirmed COVID-19 ILIs, with prevalence of 0.9% [95% confidence interval (CI): 0.3–2.4], a hospitalization rate of 100% and a mortality rate of 77.8%. Including 5 COVID-like ILIs, the overall COVID-19 prevalence was 1.5% (95% CI: 0.5–3.1), with 100% hospitalization and 64% mortality. The presence of elderly, males and comorbidities was significantly higher among patients vaccinated against influenza versus unvaccinated ( p = 0.009, p

Abstract Background Chronic kidney disease (CKD) represents the main cause of mortality in dogs with leishmaniosis. Domperidone has recently been reported to improve kidney function in leishmaniotic dogs affected by CKD. Serum symmetric dimethylarginine (sSDMA) has also been shown to be a useful biomarker for earlier detection of decreased kidney function when compared to serum creatinine (sCr). This study aimed to assess the efficacy of domperidone plus renal diet in slowing the progression of nephropathy in leishmaniotic dogs with CKD, evaluating sSDMA and sCr as markers of kidney function. Methods This study was a therapeutic, prospective, randomized, controlled, 11-month-long field trial. Dogs were recruited if classified as “exposed” to or “infected” with Leishmania infantum and affected by CKD at early stages. After enrolment (T0), dogs were randomized into groups T (treatment) and C (control). All dogs were fed a renal diet and then followed up at 90 (T1), 210 (T2), and 330 (T3) days after inclusion in the study. At T1 and T2, dogs in group T received an oral suspension of domperidone (1 ml/10 kg once a day for up to 28 days). Results Twenty-two dogs (i.e., n = 12 in group T and n = 10 in group C) completed the study. At T0, the entire population of enrolled dogs presented a mean sSDMA value of 16.5 ± 3.4 μg/dl. At T1 (i.e., after 3 months of renal diet), sSDMA was significantly decreased in both groups, with an sSDMA of 13.1 ± 4.4 μg/dl for the entire population involved. From T1 to T3, sSDMA gradually increased in group C, while remaining stable in group T, which continued to show a significantly lower value of sSDMA at T3 than at T0. Regarding sCr, at T0 and T1, the mean values of the entire population of dogs were 1.1 ± 0.3 and 1.0 ± 0.4 mg/dl, respectively, with no statistical differences between groups T and C. In group T, sCr decreased significantly from T0 to T1, while returning at T3 to values similar to T0. Conclusions In this study, domperidone plus renal diet reduced the progression of kidney disease in leishmaniotic dogs affected by CKD. Graphical Abstract

Abstract Background Immunotherapeutic drugs, such as domperidone, have been shown to be promising treatments against canine leishmaniosis (CanL), but limited data are available. The aim of this pilot study (therapeutic, prospective and non-controlled) was to evaluate the effect of domperidone on serum antibody titers of Leishmania infantum, globulins, gamma globulins, acute-phase proteins (e.g. C-reactive protein [CRP]), big endothelin-1 (big ET-1), serum creatinine (SC) and proteinuria in dogs with leishmaniosis affected by chronic kidney disease (CKD). Methods Dogs were recruited if “exposed” to or “infected” with L. infantum and affected by CKD (IRIS stage 1 [proteinuric] or IRIS stage 2–3a [SC

Collecting duct carcinomas (CDCs) are a particularly rare subtype of kidney cancer, endowed by a particularly poor prognosis. Since no active treatments have been established for CDCs, due to similarities with upper tract urothelial carcinomas, the use of the cisplatin-gemcitabine doublet is usually recommended. Here we report a retrospective analysis of 36 metastatic CDCs treated, as everyday clinical practice, with either cisplatin-gemcitabine or cisplatin-gemcitabine-paclitaxel from 2005 to 2021. Thirty-three patients received gemcitabine (1000 mg/m2, days 1 and 8) and cisplatin (70 mg/m2, day 1), while 3 were treated with paclitaxel (80 mg/m2, days 1 and 8), gemcitabine (1000 mg/m2, days 1 and 8) and cisplatin (70 mg/m2, day 1), every 21 days for a maximum of 6 cycles. Eight out of 36 patients (22.2%) experienced a partial response, while 9 others (25%) had a disease stabilization. No benefit was observed in the only 3 patients treated with the triplet. Median PFS was just 6 months, while median OS was 8 months. The commonest grade ≥3 treatment-related adverse events were: neutropenia (75%, 11.1% of febrile neutropenia), anemia (50%), thrombocytopenia (38.8%), and vomiting (8.3%). Dose omissions and dose reductions were common, and few frail patients started the treatment with a 25% dose reduction. In conclusion, our real-world experience confirmed the modest activity and relevant toxicity of cisplatin-based chemotherapy for the treatment of CDCs. More translational studies and novel study designs are thus badly needed in these still orphan tumors.

This study aims to evaluate the erythrocyte sedimentation rate (ESR) in Leishmania infantum-seropositive dogs compared with healthy dogs and to assess the existence of a correlation between ESR and clinical form of Canine leishmaniosis (CanL) as well as acute phase proteins (APPs). From October 2021 to January 2022, dogs were recruited in this study if L. infantum-seropositive by enzyme-linked immunoassay and classified as exposed or affected by a CanL active form based on physical examination, clinical score, and laboratory results [i.e., complete blood count, biochemical panel such as C-reactive protein (CRP) and serum ferritin, serum protein electrophoresis, and fibrinogen concentration measurement]. To evaluate the ESR of the dogs, a point-of-care device was used with a reference interval of 0–10 mm/h. Moreover, the ESR evaluation has been also performed in clinically healthy dogs, as control group. Thirty-six L. infantum-seropositive dogs [i.e., exposed (n = 10) and affected by CanL active form (n = 26)] were included in the study. Twenty-two healthy dogs were also enrolled. The mean value of ESR in dogs affected by a CanL active form was significantly higher than in exposed and healthy dogs (p < 0.0001). The ESR level was increased in 92% of dogs with CanL active form while positive APPs such as CRP, fibrinogen, and serum ferritin were increased only in 46, 48, and 58% of the animals, respectively. In exposed dogs, the ESR level was increased in 40% of cases. In dogs with active form, a significant positive correlation between ESR and total proteins, globulins, CRP, and fibrinogen, as well as a significant negative correlation between ESR and hematocrit, hemoglobin, and albumin/globulin ratio were detected. This study provides for the first-time data on ESR in L. infantum-seropositive dogs demonstrating dogs affected by a CanL active form have the highest ESR level and the majority of these dogs presented an increased ESR compared with exposed and healthy dogs. The evaluation of ESR by a point-of-care device proved to be a simple, inexpensive, and ready-to-use benchtop tool and ESR can be considered a helpful and timely inflammatory biomarker for the diagnosis of a CanL active form.

Background: Considering the growing genitourinary (GU) cancer population undergoing systemic treatment with immune checkpoint inhibitors (ICIs) in the context of the COVID-19 pandemic, we planned a clinical audit in 24 Italian institutions treating GU malignancies. Objective: The primary objective was investigating the clinical impact of COVID-19 in GU cancer patients undergoing ICI-based therapy during the first outbreak of SARS-CoV-2 contagion in Italy. Design, setting, and participants: The included centers were 24 Oncology Departments. Two online forms were completed by the responsible Oncology Consultants, respectively, for metastatic renal cell carcinoma (mRCC) and metastatic urothelial carcinoma (mUC) patients receiving at least one administration of ICIs between 31 January 2020 and 30 June 2020. Results and limitation: In total, 287 mRCC patients and 130 mUC patients were included. The COVID-19 incidence was, respectively, 3.5%, with mortality 1%, in mRCC patients and 7.7%, with mortality 3.1%, in mUC patients. In both groups, 40% of patients developing COVID-19 permanently discontinued anticancer treatment. The pre-test SARS-CoV-2 probability in the subgroup of patients who underwent nasal/pharyngeal swab ranged from 14% in mRCC to 26% in mUC. The main limitation of the work was its nature of audit: data were not recorded at the single-patient level. Conclusion: GU cancer patients undergoing active treatment with ICIs have meaningful risk factors for developing severe events from COVID-19 and permanent discontinuation of therapy after the infection. Treatment delays due to organizational issues during the pandemic were unlikely to affect the treatment outcome in this population.

Canine idiopathic epilepsy is a common neurological disease characterized by the enduring predisposition of the cerebral cortex to generate seizures. An etiological explanation has not been fully identified in humans and dogs, and, among the presumed causes, several studies support the possible involvement of gut microbiota. In this review, the authors summarize the evidence of the reasonable role of gut microbiota in epilepsy through the so-called gut–brain axis. The authors provide an overview of recent clinical and preclinical studies in humans and dogs in which the modulation of intestinal permeability, the alteration of local immune response, and the alteration in production of essential metabolites and neurotransmitters associated with dysbiosis could be responsible for the pathogenesis of canine epilepsy. A systematic review of the literature, following the PRISMA guidelines, was performed in two databases (PubMed and Web of Science). Eleven studies were included and reviewed supporting the connection between gut microbiota and epilepsy via the gut–brain axis.

Conjunctival swabs (CS) are the most promising non-invasive samples for the diagnosis and the regular screening of Leishmania infantum infection in dogs although knowledge on their diagnostic performance is still inconclusive. This study evaluates CS real time-PCR (qPCR) analysis for the diagnosis of canine leishmaniosis (CanL) and its prognostic value in seropositive dogs from an endemic area. In October 2020 (T0), 26 dogs were enrolled, divided in two groups according to anti-L. infantum antibody titres (n = 13, group low titre (LT) and n = 13, group high titre (HT)), and followed-up in August 2021. At both timepoints, animals underwent clinical examination, complete blood count and biochemical analyses, and serological (indirect fluorescent antibody test) and molecular (CS and peripheral blood qPCR) testing. At T0, 10 out of 26 enrolled dogs were positive at CS qPCR, with the number of positive animals significantly higher in group HT than in LT. After 10 months, only 5 out of 21 dogs that completed the trial still tested CS qPCR positive, and none of them developed an active CanL based on clinical score and antibody titre. None of the dogs required any leishmanicidal and/or leishmaniostatic treatments. This prospective study showed unsatisfying diagnostic and prognostic performances of CS qPCR analysis in L. infantum seropositive asymptomatic dogs from an endemic area.

Thiamine is a water-soluble vitamin, which participates in several vital metabolic pathways involved in energy metabolism and neurotransmitter synthesis of mammals. In companion animals thiamine deficiency is classically associated with signs of diffuse encephalopathy and lesions on brainstem nuclei and mesencephalic colliculi evident on magnetic resonance imaging. This paper describes a novel clinical presentation in a thiamine-deficient dog showing multifocal, central and peripheral nervous and cardiovascular system alterations. Brain MRI showed bilateral caudate nuclei damage, with necrotic-malacic evolution, similar to the atypical MRI pattern found in Wernicke’s encephalopathy in humans. Detection of bilateral symmetrical lesions of the caudate nuclei in dogs should prompt consideration of a thiamine deficiency among the differential diagnoses.

A wild young male red fox (Vulpes vulpes) was found in the mountainous hinterland of Rome (Italy) with a heavily depressed mental status and unresponsive to the surrounding environment. Neurological examination revealed depression, left circling, right head tilt, ventromedial positional strabismus and decreased postural reactions on the left side. Neurological abnormalities were suggestive of central vestibular syndrome. Two consecutive MRIs performed with 30 days interval were compatible with lacunar ischemic infarct in the territory of right caudal cerebral artery and its collateral branches. The lesion epicentre was in the right periaqueductal portion of the rostral mesencephalic tegmentum. Neuroanatomical and neurophysiological correlation between lesion localization and clinical presentation are discussed.

Renal maldevelopment (RM) has been proposed to replace the old and sometimes misused term “renal dysplasia” in dogs. Although renal dysplasia has been described in Boxers, hereditary transmission has only been hypothesized. This study reports clinical and renal histological findings in Boxer dogs with RM, proposing a possible mode of inheritance. Medical records of 9 female Boxer dogs, older than 5 months and with a clinical diagnosis of chronic kidney disease prior to one year of age, were retrospectively reviewed. Polyuria and polydipsia (PU/PD), decreased appetite, weight loss, lethargy and weakness were described in all affected dogs. Common laboratory findings were proteinuria, diluted urine, non-regenerative anemia, azotemia, hyperphosphatemia, hypoalbuminemia and hypercholesterolemia. Histopathology of the kidneys revealed the presence of immature glomeruli in all dogs, which is consistent with RM. In 7 related dogs, the pedigree analysis showed that a simple autosomal recessive trait may be a possible mode of inheritance. Renal maldevelopment should be suspected in young Boxer dogs with a history of PU/PD, decreased appetite, weight loss, lethargy, weakness and proteinuria. Due to its possible inheritance, an early diagnosis of RM may allow clinicians to promptly identify other potentially affected dogs among the relatives of the diagnosed case.

Clear cell renal cell carcinoma (ccRCC) is fundamentally a metabolic disease. Given the importance of lipids in many cellular processes, in this study we delineated a lipidomic profile of human ccRCC and integrated it with transcriptomic data to connect the variations in cancer lipid metabolism with gene expression changes. Untargeted lipidomic analysis was performed on 20 ccRCC and 20 paired normal tissues, using LC-MS and GC-MS. Different lipid classes were altered in cancer compared to normal tissue. Among the long chain fatty acids (LCFAs), significant accumulations of polyunsaturated fatty acids (PUFAs) were found. Integrated lipidomic and transcriptomic analysis showed that fatty acid desaturation and elongation pathways were enriched in neoplastic tissue. Consistent with these findings, we observed increased expression of stearoyl-CoA desaturase (SCD1) and FA elongase 2 and 5 in ccRCC. Primary renal cancer cells treated with a small molecule SCD1 inhibitor (A939572) proliferated at a slower rate than untreated cancer cells. In addition, after cisplatin treatment, the death rate of tumor cells treated with A939572 was significantly greater than that of untreated cancer cells. In conclusion, our findings delineate a ccRCC lipidomic signature and showed that SCD1 inhibition significantly reduced cancer cell proliferation and increased cisplatin sensitivity, suggesting that this pathway can be involved in ccRCC chemotherapy resistance.

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Un numero sempre maggiore di pazienti anziani inizia la dialisi. Tuttavia, malgrado i potenziali vantaggi della DP rispetto all'HD, tale tecnica è sottoutilizzata, specialmente nell'anziano. È, di recente, comparso un dibattito sulla rivista Seminars in Dialysis, relativamente al fatto di considerare o meno la DP come terapia sostitutiva di prima scelta per il paziente anziano.

An 8-year-old intact male Lagotto Romagnolo was presented with forebrain signs. Neuroanatomic localization was diffuse prosencephalon. MRI revealed diffuse, bilateral, and symmetric T2 and FLAIR hyperintensities in the parieto-occipital white matter and corpus callosum. No mass effect or contrast enhancement was noted. Analysis of cerebrospinal fluid revealed normal protein content and mild mononuclear pleocytosis. Atypical cells were not identified. 15 days later because of the worsening of clinical condition the patient was euthanized upon owner’s request. Neuropathological investigations were consistent with gliomatosis cerebri (GC). Such an unusual imaging pattern appeared similar to some cases of human GC and to a previous reported case in a dog, suggesting a possible repeatable imaging findings for this rare brain neoplasm. GC should be included in the MRI differentials for diffuse bilateral white matter signal changes and specific MRI findings described in this report may help in reaching a presumptive diagnosis of this tumor.

La diagnosi differenziale nei casi d'insufficienza renale acuta del postpartum associata ad anemia emolitica microangiopatica e trombocitopenia, include, tra le altre: pre-clampsia grave/eclampsia, grave eclampsia, la sindrome HELLP (Hemolysis, Elevated Liver enzyme, Low Platelet), la acute fatty liver of pregnancy (AFLP), la porpora trombotica trombocitopenica/sindrome emolitico-uremica associata alla gravidanza (TTP/aHUS), esordio acuto o flare di LES in gravidanza e la sindrome catastrofica da anticorpi antifosfolipidi (CAPS). Si tratta di condizioni potenzialmente pericolose per la vita data la presenza di disfunzione multiorgano. Il verificarsi di uno stato di ipercoagulabilità e la concentrazione decrescente di ADAMTS 13 in gravidanza e nel post-parto aumentano il rischio di sviluppare porpora trombotica trombocitopenica (TTP). Vi è però una notevole sovrapposizione riguardo la clinica ed i test di laboratorio tra queste condizioni, e quindi la diagnosi può essere un problema anche per clinici esperti. Tuttavia è importante stabilire un'accurata diagnosi poiché la gestione e le complicanze di tali sindromi possono essere differenti. Il caso presentato sottolinea la complessità connessa alla diagnosi differenziale dei quadri clinici che includono anemia emolitica microangiopatica e trombocitopenia connessi alla gravidanza ed il ruolo del plasma exchange nella loro gestione.