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Simple Summary: We investigated a new method for diagnosing and predicting outcomes in canine pulmonary carcinoma. We developed a deep learning-based algorithm that accurately detects tumor nuclei and subsequently measures size and shape parameters. The variation in nuclear size and shape (nuclear pleomorphism) is a crucial malignancy criterion used in the current grading system for canine pulmonary carcinoma. Pathologists currently evaluate it and classify it according to a three-tier system. Manual morphometry is a more objective approach where tumor nuclei are individually encircled and analyzed. This task can be easily performed by an algorithm. Our algorithm's accuracy in correctly detecting and segmenting tumor nuclei was considered good when compared to manual morphometry. By comparing automated morphometry with conventional prognostic tests, such as pathologists' estimates, mitotic count, histological grading, and clinical staging, we found that our approach was equally accurate in terms of prognostic value. The algorithm's advantage lies in its high reproducibility and efficiency. Automated evaluation of nuclear pleomorphism can enhance the efficiency and reliability of canine pulmonary carcinoma diagnosis and grading, effectively addressing issues of inter-observer reproducibility. However, further optimization of the algorithm and validation with a larger study group is necessary to confirm our findings. The integration of deep learning-based tools into diagnostic workflows is increasingly prevalent due to their efficiency and reproducibility in various settings. We investigated the utility of automated nuclear morphometry for assessing nuclear pleomorphism (NP), a criterion of malignancy in the current grading system in canine pulmonary carcinoma (cPC), and its prognostic implications. We developed a deep learning-based algorithm for evaluating NP (variation in size, i.e., anisokaryosis and/or shape) using a segmentation model. Its performance was evaluated on 46 cPC cases with comprehensive follow-up data regarding its accuracy in nuclear segmentation and its prognostic ability. Its assessment of NP was compared to manual morphometry and established prognostic tests (pathologists' NP estimates (n = 11), mitotic count, histological grading, and TNM-stage). The standard deviation (SD) of the nuclear area, indicative of anisokaryosis, exhibited good discriminatory ability for tumor-specific survival, with an area under the curve (AUC) of 0.80 and a hazard ratio (HR) of 3.38. The algorithm achieved values comparable to manual morphometry. In contrast, the pathologists' estimates of anisokaryosis resulted in HR values ranging from 0.86 to 34.8, with slight inter-observer reproducibility (k = 0.204). Other conventional tests had no significant prognostic value in our study cohort. Fully automated morphometry promises a time-efficient and reproducible assessment of NP with a high prognostic value. Further refinement of the algorithm, particularly to address undersegmentation, and application to a larger study population are required. [ABSTRACT FROM AUTHOR]

Simple Summary: Knowledge of telomere maintenance mechanisms (TMMs) in different tumor types is crucial for the development of TMM-specific diagnostics and therapies. Telomerase-independent alternative lengthening of telomeres (ALT) is used more frequently in human sarcoma subtypes than other cancers. However, ALT's prevalence in the aggressive hematopoietic and orphan tumor type termed histiocytic sarcoma (HS) is unknown. The aim of our retrospective study was to assess the ALT activity in canine HS as a surrogate for rare human HS cases. Bernese mountain dogs (BMDs) have a breed predisposition for HS. We show in cohorts of a total of 63 dog patients from two centers, including a homogeneous population of 47 BMDs, that ALT was used only infrequently in the BMDs and not at all in the non-BMD patients here. We conclude that ALT is useful for a few cases only to target HS but can play a role as a resistance mechanism after targeting telomerase. Cancer cells activate telomere maintenance mechanisms (TMMs) to overcome senescence and thus are targets for TMM-specific therapies. Telomerase-independent alternative lengthening of telomeres (ALT) is frequently utilized as a TMM in human sarcoma subtypes. Histiocytic sarcoma (HS) is a rare but aggressive tumor of hematopoietic origin with unknown ALT incidence in humans. ALT has been identified in canine HS, a tumor type comparable to human HS that occurs with high rates in certain canine breeds such as Bernese mountain dogs (BMDs). This retrospective study characterized the frequency of ALT in BMD and non-BMD patients diagnosed with HS as surrogates for humans. Formalin-fixed paraffin-embedded tumor samples from 63 dogs at two centers, including 47 BMDs, were evaluated for their ALT activity and relative telomere content (TC) using a radiolabel C-circle assay (CCA). Known ALT-positive samples served as controls. CCA-positive cases were validated via FISH. Two BMD samples showed ALT activity of 1–14% compared to controls. All other samples were ALT-negative. The TC did not correlate with the CCA results. ALT positivity was validated by the appearance of ultrabright telomere foci. Low ALT activity was present in 4% of BMDs with HS and therefore does not appear to be a common target for therapeutic approaches but can have diagnostic value. [ABSTRACT FROM AUTHOR]

Alternative lengthening of telomeres (ALT) is a telomerase‐independent telomere maintenance mechanism (TMM) with high prevalence in human osteosarcomas but remains unknown in canine osteosarcomas. The aim of this study was to evaluate the prevalence of ALT by detection of extra‐chromosomal circles of telomeric DNA and to assess clinical outcome in canine patients with spontaneous occurring appendicular osteosarcoma. Fifty dogs with histopathological confirmed osteosarcomas were included into this study. Medical records were retrospectively analysed for patient characteristics, oncologic therapy and survival. DNA was isolated from archived FFPE tumour tissue specimens and applied for C‐ and G‐circle assay (CCA and GCA) and for telomeric content (TC) measurement with radiolabeled probes. ALT activity was detected for 10 of 50 (20%) cases by CCA. Four CCA positive cases were detected even with input DNA below 1 ng and demonstrated the high sensitivity of CCA for canine tumours. G‐circles and TC were not suitable to distinguish CCA positive and negative cases. CCA‐status showed an association with male gender and Rottweiler breed. Dogs with CCA positive osteosarcomas had shorter overall survival times than patients with CCA‐tumours and CCA‐status was a significant prognostic factor besides treatment in the Cox proportional hazard model. These findings make canine osteosarcomas an interesting model for comparative TMM research, but future studies are warranted to investigate if CCA‐status can serve as novel prognostic marker. [ABSTRACT FROM AUTHOR]

Simple Summary: This is the first case report of two guinea pigs with insulin-dependent diabetes mellitus (DM) successfully treated with long-acting basal insulin glargine. Both animals presented with typical symptoms and laboratory changes like polyphagia, glucosuria and highly elevated blood glucose levels that suggested the presence of a diabetes mellitus. One of the guinea pigs had asymmetric bilateral cataracts. Mostly, a disorder resembling type II-DM in humans seems to be prevalent in guinea pigs. In this case, the animals did not respond to the standard treatment of a dietary change but responded promptly to insulin treatment. The diabetes has remained controlled for over 1.5 years now. Thus far, there is only sparse scientific information on spontaneous type I diabetes mellitus and treatment modalities in pet guinea pigs. We discuss the current literature including up to date diagnosis, treatment, monitoring with the evaluation of different glucometers and long-time follow-up. Moreover, individual ophthalmic abnormalities and management regarding suspected diabetic cataracts are described in detail. Scientific information on spontaneous type I diabetes mellitus (DM) and treatment modalities in guinea pigs is scarce. As most diabetic guinea pigs are overweight and respond to dietary changes, a disorder resembling type II-DM in humans seems to be most prevalent in this species. In the present report, a nine-month-old female intact guinea pig (GP1) was presented because of a cataract and polyphagia. The physical examinations in GP1 and its littermate, GP2, were unremarkable. Laboratory tests revealed hyperglycemia, hyperlipidemia, elevated fructosamine concentrations, and glucosuria in GP1 and GP2. Not responding to dietary changes, an insulin-dependent diabetes mellitus was suspected in both animals. Treatment with 0.5 IU of glargine insulin (Lantus®) per guinea pig subcutaneously (s.c.) once daily was initiated in both animals. Monitoring included repeated clinical evaluations and the measurement of plasma glucose and fructosamine concentrations. Capillary glucose concentration was measured using a glucometer, and glucosuria was monitored by dipstick. Blood glucose concentrations decreased quickly in both GPs, and glucosuria resolved. Including several dose adjustments, DM remained controlled for over 1.5 years. Bilateral cataracts and lens-induced uveitis in GP1 were medically managed with only slight progression. This is the first report of guinea pigs with insulin-dependent diabetes mellitus that were successfully treated with long-acting basal insulin glargine. [ABSTRACT FROM AUTHOR]

A 3-year-old intact female guinea pig was presented with a history of polydipsia, polyphagia, and hyperactivity combined with non-pruritic hair loss. The physical examination revealed bilateral alopecia mainly including the flanks and the ventral abdomen. Bilateral rounded masses just caudal to the kidneys were detected on abdominal palpation. Abdominal ultrasound examination confirmed bilateral ovarian cysts and an enlarged uterus with cystic lesions. Blood biochemistry revealed highly increased glucose and fructosamine concentrations. The final diagnoses were diabetes mellitus, bilateral ovarian cysts, and pathologic changes of the uterus. The guinea pig underwent ovariohysterectomy. After surgery, diabetes mellitus and all of the existing clinical signs were fully resolved. A causal relationship between hormonally active ovarian cysts and diabetes mellitus that commonly present independently from each other in the guinea pig can be strongly assumed in the present case. In suspicious cases of gestagen-induced diabetes mellitus ovariohysterectomy could be considered a potential treatment option in guinea pigs., Competing Interests: The authors confirm that they do not have any conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)