Impact of body mass index on pathological response after neoadjuvant chemotherapy: results from the I-SPY 2 trial.

PURPOSE: Increased body mass index (BMI) has been associated with poor outcomes in women with breast cancer. We evaluated the association between BMI and pathological complete response (pCR) in the I-SPY 2 trial. METHODS: 978 patients enrolled in the I-SPY 2 trial 3/2010-11/2016 and had a recorded baseline BMI prior to treatment were included in the analysis. Tumor subtypes were defined by hormone receptor and HER2 status. Pretreatment BMI was categorized as obese (BMI ≥ 30 kg/m2), overweight (25 ≤ BMI < 30 kg/m2), and normal/underweight (< 25 kg/m2). pCR was defined as elimination of detectable invasive cancer in the breast and lymph nodes (ypT0/Tis and ypN0) at the time of surgery. Logistic regression analysis was used to determine associations between BMI and pCR. Event-free survival (EFS) and overall survival (OS) between different BMI categories were examined using Cox proportional hazards regression. RESULTS: The median age in the study population was 49 years. pCR rates were 32.8% in normal/underweight, 31.4% in overweight, and 32.5% in obese patients. In univariable analysis, there was no significant difference in pCR with BMI. In multivariable analysis adjusted for race/ethnicity, age, menopausal status, breast cancer subtype, and clinical stage, there was no significant difference in pCR after neoadjuvant chemotherapy for obese compared with normal/underweight patients (OR = 1.1, 95% CI 0.68-1.63, P = 0.83), and for overweight compared with normal/underweight (OR = 1, 95% CI 0.64-1.47, P = 0.88). We tested for potential interaction between BMI and breast cancer subtype; however, the interaction was not significant in the multivariable model (P = 0.09). Multivariate Cox regression showed there was no difference in EFS (P = 0.81) or OS (P = 0.52) between obese, overweight, and normal/underweight breast cancer patients with a median follow-up time of 3.8 years. CONCLUSION: We found no difference in pCR rates by BMI with actual body weight-based neoadjuvant chemotherapy in this biologically high-risk breast cancer population in the I-SPY2 trial.

Impact of Body Mass Index on Pathological Response after Neoadjuvant Chemotherapy: Results from the I-SPY 2 trial.

Purpose: Increased body mass index (BMI) has been associated with poor outcomes in women with breast cancer. We evaluated the association between BMI and pathological complete response (pCR) in the I-SPY 2 trial. Methods: 978 patientsenrolled in the I-SPY 2 trial 3/2010-11/2016 and had a recorded baseline BMI prior to treatment were included in the analysis. Tumor subtypes were defined by hormone receptor and HER2 status. Pretreatment BMI was categorized as obese (BMI≥30 kg/m2), overweight (25≤BMI < 30 kg/m2), and normal/underweight (< 25 kg/m2). pCR was defined as elimination of detectable invasive cancer in the breast and lymph nodes (ypT0/Tis and ypN0) at the time of surgery. Logistic regression analysis was used to determine associations between BMI and pCR. Event-free survival (EFS) and overall survival (OS) between different BMI categories were examined using Cox proportional hazards regression. Results: The median age in the study population was 49 years. pCR rates were 32.8% in normal/underweight, 31.4% in overweight, and 32.5% in obese patients. In univariable analysis, there was no significant difference in pCR with BMI. In multivariable analysis adjusted for race/ethnicity, age, menopausal status, breast cancer subtype, and clinical stage, there was no significant difference in pCR after neoadjuvant chemotherapy for obese compared with normal/underweight patients (OR = 1.1, 95% CI: 0.68-1.63, p = 0.83), and for overweight compared with normal/underweight (OR = 1, 95% CI: 0.64-1.47, p = 0.88). We tested for potential interaction between BMI and breast cancer subtype; however, the interaction was not significant in the multivariable model (p = 0.09). Multivariate Cox regression showed there was no difference in EFS (p = 0.81) or OS (p = 0.52) between obese, overweight, and normal/underweight breast cancer patients with a median follow-up time of 3.8 years. Conclusions: We found no difference in pCR rates by BMI with actual body weight based neoadjuvant chemotherapy in this biologically high-risk breast cancer population in the I-SPY2 trial.

Dysautonomia in two littermate kittens.

Case summary: Two 6-month-old littermate Russian Blue cross kittens presented for megaesophagus, intermittent vomiting and regurgitation. The male kitten was diagnosed with aspiration pneumonia and was suspected to have a hiatal hernia on thoracic radiographs. It presented 1 month later in acute respiratory distress and was euthanized. Post-mortem examination revealed a severe gastroesophageal intussusception with approximately 90% of the stomach inverted into the distal esophagus. Histologic examination confirmed dysautonomia with marked neuronal dropout and degeneration with necrosis, satellitosis of the celiac ganglion and the myenteric and submucosal plexuses throughout the gastrointestinal tract. The less-affected littermate showed improvement on cisapride and was doing well at home at the time of writing. Relevance and novel information: Dysautonomia is rare in cats, with only a few reports of affected littermates. Both kittens are significantly younger than the median age previously reported. Detailed descriptions of diagnostic and histopathology findings are included. Gastroesophageal intussusception is a novel complication to consider when managing feline dysautonomia.

Transcutaneous Detection of Intramural Microchips for Tracking the Migration of the Equine Large Colon: A Pilot Study.

Colic remains the number one cause of mortality in horses, and large colon displacement including colonic volvulus is one of the leading causes for equine hospitalization and surgery. Currently, there is not an adequate model to study the pathophysiology of this condition. The objective of this proof-of-concept study was to determine if subserosal implantation of bioinert microchips in the large intestine would be detectable by a RFID (radio-frequency identification) receiver when the implanted microchips were adjacent to the body wall, thus identifying the location of the colon within the abdomen. A horse with no history of gastrointestinal disease underwent a ventral midline celiotomy to implant twelve bioinert microchips into the subserosa at predetermined locations within the large colon and cecum. A RFID scanner was used to monitor the location of the colon via transcutaneous identification 1-3 times daily for a one-month period. Following humane euthanasia, a postmortem examination of the horse was performed to assess microchip implantation sites for migration and histologic assessment. Eleven out of the 12 implanted microchips were successfully identified transcutaneously at occurrences as high as 100%. Odds ratios were calculated for the likelihood of identifying each chip in a location different from its most common location. Microchips implanted into the subserosa of the equine large colon can be used as a means of identifying the approximate location of the equine large colon via transcutaneous identification with an RFID scanner.

Disease progression, pathologic, and virologic findings of an equine influenza outbreak in rescue donkeys.

BACKGROUND: Equine influenza virus is a common cause of respiratory disease in equids. Few reports describe clinical presentation and disease progression in donkeys. HYPOTHESIS/OBJECTIVES: Describe the clinical and diagnostic findings, outcome, and pathologic lesions associated with influenza pneumonia in donkeys. ANIMALS: Thirteen unvaccinated donkeys ranging from 1 week to 12 years of age and sharing clinical signs and exposure history. METHODS: Retrospective case series. Medical records from June to July 2020 at the Colorado State Veterinary Teaching Hospital and collaborating referring veterinary practices were reviewed. The diagnosis was confirmed by molecular testing, virus isolation, and partial genetic and phylogenetic analysis of the virus. RESULTS: Survival in donkeys <1 year old was 16.6% (1/6) whereas survival in animals >1 year of age was 85.7% (6/7). Hemagglutinin gene sequencing and phylogenetic analysis confirmed a contemporary clade 1 Florida sublineage H3 virus as the causative agent. CONCLUSIONS AND CLINICAL IMPORTANCE: Clinical signs of equine influenza virus infection in donkeys are similar to those observed in horses. Prognosis for survival generally is good, but deaths have been observed especially in foals born to seronegative dams. This finding emphasizes the importance of prenatal vaccination protocols in all equids, including donkeys.

Intranasal mast cell tumors: Clinical, immunohistochemical, and molecular features in 20 dogs.

Mast cell tumors (MCTs) are an uncommon primary neoplasm of the nasal cavity in dogs for which there is a paucity of existing literature regarding their clinical behavior and molecular features. The objectives of this retrospective study were to examine the clinical findings, histopathologic and immunohistochemical features, and c-KIT mutation status of primary intranasal MCTs in dogs and identify potential prognostic factors. Canine biopsies submitted to a diagnostic laboratory in Colorado between 2010 and 2019 with intranasal neoplasms diagnosed as MCTs and no history of cutaneous or oral MCT were considered. Immunohistochemistry for CD117 and Ki67 and polymerase chain reaction (PCR) for internal tandem duplications at exons 8 and 11 of the c-KIT gene were performed. Twenty out of 1849 (1%) primary intranasal neoplasms were MCTs. Metastases were reported in 11/20 cases (55%), with the mandibular lymph node representing the most common site. One case had distant metastases to abdominal viscera. Of the cases with available outcome data, 6/14 (43%) died or were euthanized from MCT-related disease within 1 year of the onset of clinical signs. Only one case had a c-KIT mutation at exon 11. In our study, intranasal MCTs were prone to metastasize and had a generally poor prognosis, resembling the behavior of MCTs arising in other mucosal locations. While dogs with metastatic disease and survival times of <1 year tended to have atypical KIT localization, moderate to high Ki67 indices, and mitotic counts ≥8, definitive prognosticators could not be identified due to the limited number of cases with favorable clinical outcomes.

Early Clostridioides difficile infection characterizations, risks, and outcomes in allogeneic hematopoietic stem cell and solid organ transplant recipients.

BACKGROUND: Clostridioides difficile infection (CDI) frequently complicates allogeneic hematopoietic stem cell (allo-HCT) and solid organ transplantation (SOT). METHODS: We retrospectively analyzed risk factors and outcomes of CDI occurring within 30 days of transplant. RESULTS: Between March 2010 and June 2015, 466 allo-HCT and 1454 SOT were performed. The CDI cumulative incidence (95% CI) was 10% (8-13) and 4% (3-5), following allo-HCT and SOT, respectively (p < .01), occurring at a median (range) 7.5 days (1-30) and 11 (1-30), respectively (p = .18). In multivariate analysis, fluoroquinolones use within 14 days pre-transplantation was a risk factor for CDI following allo-HCT (HR 4.06 [95% CI 1.31-12.63], p = .02), and thoracic organ(s) transplantation was a risk factor for CDI following SOT (HR 3.03 [95% CI 1.31-6.98]) for lung and 3.90 (1.58-9.63) for heart and heart/kidney transplant, p = .02. Compared with no-CDI patients, the length of stay (LOS) was prolonged in both allo-HCT (35 days [19-141] vs. 29 [13-164], p < .01) and SOT with CDI (16.5 [4-101] vs. 7 [0-159], p < .01), though not directly attributed to CDI. In allo-HCT, severe acute graft-versus-host disease (aGVHD) occurred more frequently in patients with CDI (33.3% vs. 15.8% without CDI, p = .01) and most aGVHD (87.5%) followed CDI. Non-relapse mortality or overall survival, not attributed to CDI, were also similar in both allo-HCT and SOT. CONCLUSIONS: Early post-transplant CDI is frequent, associated with fluoroquinolones use in allo-HCT and the transplanted organ in SOT, and is associated with longer LOS in both the groups without difference in survival but with increased aGVHD in allo-HCT.

Triple Aberrant Prostate Cancer (TAPC) - Aggregate role of aberrations in TP53, PTEN and RB1 on ETS gene fusions and prognosis in metastatic castrate resistant prostate cancer.

BACKGROUND: Aberrations in TP53, PTEN and RB1 are key drivers of therapy resistance in prostate cancer. Up to 50% of prostate cancers harbor ETS gene rearrangements, a potentially compounding aggressive biological event. Little is known about the impact of aggregate aberrations and gene fusion events in prostate cancer. METHODS: Using cBioportal for Cancer Genomics, an open-access resource for exploration of multidimensional cancer genomics data, we integrate whole-exome sequencing, gene expression, and histopathology with longitudinal clinical outcomes. Subsets of prostate tumors with aberrations in all three genes TP53, PTEN and RB1 were identified and correlated with prevalence of gene fusions. Prostate tumors with aberrations in TP53, PTEN, and RB1 were termed "triple aberrant prostate cancer" (TAPC). RESULTS: Of 479 metastatic prostate tumors, 195 (40.7%) were TAPC, versus 21 of 594 (3.5%) of primary prostate tumors. Patients with metastatic TAPC showed a trend toward poorer overall survival than patients harboring 0, 1 or 2 of these aberrations. Twenty-five distinct fusions were identified, all involving ETS transcription factors. Both primary and metastatic prostate cancers with ETS fusions were significantly more likely to be TAPC than those without ETS fusions. CONCLUSIONS: This study identified a unique molecular signature consisting of combined aberrations in TP53, PTEN and RB1 that is associated with poorer overall survival, as well as increasing prevalence of ETS gene fusions and differential gene expression patterns favoring aggressive disease and tumor progression. Identification of this subset of patients could inform prognostic decisions and provide a rationale for more aggressive or unique therapeutic approaches.

Hand-foot skin reaction with primarily dorsal involvement in a patient with metastatic renal cell carcinoma on cabozantinib.

A 61-year-old man with metastatic renal cell carcinoma on cabozantinib developed hand-foot skin reaction with predominantly dorsal involvement including painful violaceous plaques over the joints and keratotic yellow plaques on the palmar fingers. The medication was discontinued with resolution of the plaques and later reinitiated at a lower dose uneventfully.

Imaging and clinical features of a true gastrogastric intussusception in a dog.

An 18-month-old male mixed breed dog was evaluated for acute vomiting and hematemesis. Clinical signs and initial radiographic findings shared commonalities with reported cases of pylorogastric intussusception in dogs. However, unlike previously reported cases, additional imaging [including ultrasound and computed tomography (CT)] revealed invagination of the gastric fundus into the gastric body, consistent with true gastrogastric intussusception. These findings were confirmed with histopathology and on necropsy. Key clinical message: Although extremely rare, gastrogastric intussusception should be included as a differential diagnosis for any patient presenting with acute vomiting, abdominal pain, dehydration, or tachycardia in combination with the diagnostic imaging findings described in this report.

Caractéristiques cliniques et d'imagerie d'une intussusception gastro-gastrique vraie chez un chien. Un chien mâle de race croisée âgé de 18 mois fut évalué pour des vomissements aigus et de l'hématémèse. Les signes cliniques et les trouvailles radiographiques initiales partageaient des similarités avec des cas rapportés d'intussusception pyloro-gastrique chez des chiens. Toutefois, contrairement aux cas rapportés précédemment, des examens d'imagerie supplémentaires [incluant l'échographie et la tomodensitométrie (CT)] ont révélé une invagination du fundus gastrique dans le corps de l'estomac, compatible avec une intussusception gastro-gastrique vraie. Ces données furent confirmées lors de l'examen histopathologique et de la nécropsie.Message clinique clé :Bien qu'extrêmement rare, l'intussusception gastro-gastrique devrait être incluse dans le diagnostic différentiel pour tout patient présenté avec des vomissements aigus, de la douleur abdominale, de la déshydratation ou de la tachycardie en combinaison avec les trouvailles en imagerie diagnostique décrites dans le présent rapport.(Traduit par Dr Serge Messier).

Assessing the role of ketogenic dietary therapy in ring chromosome 20 syndrome: A patient-led approach.

Ring chromosome 20 syndrome (r(20)) is an ultra-rare disease characterized by drug-refractory epilepsy, cognitive impairment, and behavioral problems. Nonpharmacological treatments alongside antiepileptic drugs early after diagnosis may help reduce seizure frequency and preserve cognition. Ketogenic dietary therapy (KDT) has benefitted children with complex, refractory epilepsies, but its efficacy in r(20) is unknown. We assessed clinical prescription, implementation, and patient experience of KDT in r(20) through online surveys and a workshop. Forty-two patients, families, carers, and 23 healthcare professionals completed the surveys. While nearly all patients were familiar with KDT, only half had tried it. Significant improvement in seizure activity, cognition, and alertness was reported; side effects were typically mild but with one report of increased seizure frequency. A high rate of co-morbidity, older age at presentation, behavioral problems, and cognitive impairment can make implementing KDT in r(20) challenging. In the UK, NHS KDT services are predominantly available to pediatric patients, with very limited adult access. A health economic analysis illustrating reduced acute care costs or improved quality of life may support more widespread KDT implementation. Growing evidence supports KDT as an effective and safe intervention, but further research is needed to understand the mechanisms of r(20) and its interaction with ketosis.

CLINICOPATHOLOGICAL FEATURES OF TOXOPLASMOSIS IN FOUR RED PANDAS (AILURUS FULGENS).

Two geriatric red pandas (Ailurus fulgens) over a 4-yr period presented with vague clinical signs including anorexia, lethargy, and difficulty ambulating. Treatment protocols using enrofloxacin, steroids, and clindamycin were unsuccessful. Necropsy examination confirmed disseminated toxoplasmosis infection in these cases, and a modified agglutination test had been positive for a prolonged period of time before one panda showed signs of disease. A review of the Red Panda Species Survival Plan pathology database revealed two additional cases of disseminated toxoplasmosis in geriatric red pandas. Many organ systems were affected, but dissemination to the brain, lungs, and liver predominated. Immunohistochemistry or polymerase chain reaction was required to confirm a diagnosis in serologically positive animals, as well as in animals in which a histological diagnosis was suspected. This case series describes the clinical and pathological features of toxoplasmosis in geriatric red pandas.

Natural Canine Distemper Virus Infection in Linnaeus's 2-Toed Sloths (Choloepus didactylus).

An outbreak of canine distemper virus in a private zoo in eastern Tennessee in July 2016 led to fatal clinical disease in 5 adult, wild-caught Linnaeus's 2-toed sloths (Choloepus didactylus). Clinical signs included hyporexia, lethargy, mucopurulent nasal discharge, and oral and facial ulcers. At necropsy, affected animals had crusts and ulcers on the lips, nose, tongue, and oral cavity. Microscopically, all sloths had widespread, random, hepatic necrosis; lymphoid depletion; and bronchointerstitial pneumonia. The central nervous system did not contain gross or histopathologic lesions in any of the 5 sloths, although immunoreactivity for viral antigen was present within vessel walls. Epithelial cells and histiocytes within numerous organs contained intranuclear and intracytoplasmic inclusions and occasional syncytial cells. Canine distemper virus was confirmed with immunohistochemistry and virus isolation. Viral sequencing identified the novel American-4 strain prevalent in eastern Tennessee wildlife. This is the first pathologic characterization of canine distemper virus infection in sloths (family Choloepodidae, order Pilosa) and emphasizes the significant morbidity and mortality in this species.

Uterine Torsion Dystocia Complicated by Perosomus Elumbis in an Angus Calf Associated with a Consanguineous Mating.

A six-year-old multiparous Angus cow was presented for dystocia. Vaginal and rectal examinations revealed an approximately 360° counterclockwise uterine torsion. The torsion was corrected by rolling the cow counterclockwise (three episodes) with the aid of a plank coupled with manual detorsion via the vagina. The placement of obstetric chains followed by manual traction ultimately delivered a stillborn male calf with evidence of vertebral aplasia, arthrogryposis, and abdominal organ herniation. Patient history and subsequent parentage verification revealed that the calf was the result of a consanguineous (mother to son) mating. Tissue samples from the affected calf and blood samples from the dam, sire, and ten half siblings were collected for genetic testing and parentage verification. Necropsy, radiographic, and computed tomography examinations all supported a diagnosis of perosomus elumbis. Perosomus elumbis is a congenital abnormality of unknown origin(s), and this is the first report of a case associated with a consanguineous mating.

Eimeria gilruthi-associated abomasitis in a group of ewes.

Nine of 23 (39%) research ewes with severe diarrhea and weight loss had histologic lesions consistent with Eimeria gilruthi infection in their abomasa. Gross anatomic lesions included hundreds of opaque 1-mm nodules in abomasal mucosa that corresponded microscopically to 200-300 µm diameter organisms surrounded by areas of necrosis. Analysis of fecal samples from 4 ewes demonstrated oocysts from typical ovine Eimeria species, none of which were E. gilruthi. Two separate PCR reactions were performed on abomasal tissue from 4 sheep to amplify the 18S ribosomal DNA (rDNA) and internal transcribed spacer (ITS) region of the rDNA, respectively. The resultant 18S rDNA nucleotide sequences shared 99% homology with multiple Eimeria species in GenBank. The ITS region shared 77% homology with E. ellipsoidalis in GenBank. Further studies are needed to understand the life cycle and pathogenicity of E. gilruthi. Our results underscore the inclusion of E. gilruthi in the differential diagnosis of diarrhea and weight loss in sheep.

Life-Threatening Hypertriglyceridemia in a Patient on Ruxolitinib and Sirolimus for Chronic Graft-versus-Host Disease.

Ruxolitinib is an oral selective Janus-associated kinase 1 (JAK1) and JAK2 inhibitor that was initially approved by the FDA in 2014 for treatment of myelofibrosis. In preclinical and retrospective clinical studies, use of ruxolitinib was shown to reduce graft-versus-host-disease (GVHD) in allograft recipients with moderate/severe corticosteroid-dependent or refractory chronic GVHD. While the exact mechanism for action in GVHD is not yet fully understood, prospective studies are ongoing and some patients are receiving ruxolitinib in the setting of steroid refractory GVHD. Although ruxolitinib is generally well tolerated, here we describe a case involving a 50-year-old man with acute myeloid leukemia and chronic GVHD who experienced life-threatening hypertriglyceridemia associated with concomitant use of sirolimus and ruxolitinib for GVHD. This case report highlights the importance of vigilance for severe side effects in novel immunosuppressive drug combinations.

A pilot study evaluating chemotherapy tolerability for breast cancer patients who have received prior treatment and chest radiation for Hodgkin Lymphoma.

MICROABSTRACT: Women treated with chest radiation for Hodgkin lymphoma (HL) have significantly higher risk of developing breast cancer, and little is known about how these patients tolerate chemotherapy for breast cancer. This small retrospective study identified 15 patients, noting that these patients tolerate proposed chemotherapy regimens for breast cancer in rates similar to those without prior HL and therapeutic radiation. PURPOSE: Women treated for Hodgkin lymphoma (HL) with chest radiation have significantly higher risk of developing breast cancer, and little is known about how these patients tolerate chemotherapy for breast cancer. METHODS: Women with breast cancer diagnosed from 1986-2015 after radiation for HL were identified from hospitals and clinics in St. Paul and Minneapolis, Minnesota. Patient, tumor and treatment characteristics, and clinical outcomes were abstracted from medical records and summarized using descriptive statistics. Chemotherapy was defined as tolerated if all scheduled doses and cycles were completed without deviation from the initial plan, with lack of grade 3 or higher toxicity attributable to chemotherapy in categories including blood, cardiac, gastrointestinal, fatigue and pain. RESULTS: Forty-two patients with breast cancer and prior radiation for HL were identified, 15 of which received chemotherapy for breast cancer. We noted 75% tolerability of taxane-based and 100% tolerability of anthracycline-based chemotherapy, suggesting that most patients with prior radiation for HL tolerate chemotherapy for breast cancer. A subset of patients (N = 7) in this study were also treated with chemotherapy for HL prior to breast cancer diagnosis, and 86% (6 of 7) also tolerated chemotherapy for breast cancer. CONCLUSIONS: Treatment of breast cancer is strongly influenced by prior treatment of HL. Although this study was small and did not meet statistical significance, the data suggest that these patients tolerate proposed chemotherapy regimens for breast cancer in rates similar to those without prior HL and therapeutic radiation. Larger studies comparing specific chemotherapy dosing schedules are needed to address this complicated population.