Porcine circovirus 2 and 3 in wild boars in Southern Brazil

ABSTRACT: Porcine circovirus 2 (PCV2) has a considerable economic impact on the pork industry worldwide for more than two decades. In 2016, a new circovirus, porcine circovirus 3 (PCV3), was described; since then, it has been reported to be associated with diseased or even in clinically healthy swine in several countries. Considering the importance of wild boars as reservoirs of swine pathogens and the extensive distribution of these animals in Rio Grande do Sul and throughout the national territory, we searched for PCV2 and PCV3 in twenty-six wild boars coupled with necropsy and histologic examination of the sampled animals. Using PCR, 182 tissue samples were analyzed, including the heart, kidneys, liver, lung, lymph nodes, spleen, and tonsils. PCV2 and PCV3 were detected in 57.7% (15/26) and 15.4% (4/26) of wild boars, respectively. Furthermore, co-infection with PCV2 and PCV3 was detected in one of these animals, with PCV2 or PCV3 DNA detection in multiple organs. Histological examination showed mild to moderate and multifocal lymphoplasmacytic interstitial nephritis distributed randomly throughout the renal cortex, apparently unrelated to PCV2 or PCV3 detection. The wild boar population in Brazil is extensive, indicating the presence of a larger number of swine pathogen hosts. In the present study, more than half of the wild boars harbored PCV2; and although less frequently, PCV3 was also detected. Therefore, free-living wild boars can serve as reservoirs of swine circoviruses in southern Brazil.

Rare incidence of non-secretory myeloma with talaromycosis: a case report

Background Talaromyces marneffei (TM) primarily infects patients with co-morbidities that cause immunodeficiency, but non-secretory myeloma (NSMM) is rare. TSM and NSMM are associated with fever, osteolysis, and swollen lymph nodes, thereby making it difficult for clinicians to make differential diagnosis. In this case, we describe TM infection coexisting with NSMM. Case presentation We retrospectively reviewed the case of a male (without human immunodeficiency virus infection) with fever, thoracalgia, swollen lymph nodes, and subcutaneous nodules who presented to the First Affiliated Hospital of Guangxi Medical University in February 2014. Chest computed tomography revealed patchy infiltration and positron emission tomography/computed tomography showed increased metabolic activity in the lower-right lung, lymph nodes, left ninth rib, and right ilium. Pathological examination of the lung, lymph nodes, subcutaneous nodules, and bone marrow showed no malignancy, he was diagnosed with community-acquired pneumonia. His clinical symptoms did not improve after anti-bacterial, anti-Mycobacterium tuberculosis, and anti-non-M. tuberculosis treatment. Later, etiological culture and pathological examination of the subcutaneous nodule proved TM infection, and the patient was re-diagnosed with disseminated TSM, which involved the lungs, lymph nodes, skin, bone, and subcutaneous tissue. After antifungal treatment, the patient showed significant improvement, except for the pain in his bones. Imaging showed aggravated osteolysis, and bone marrow biopsy and immunohistochemistry indicated NSMM. Thus, we conclusively diagnosed the case as NSMM with TSM (involving the lungs, lymph nodes, skin, and subcutaneous tissue). His condition improved after chemotherapy, and he was symptom-free for 7 years. Conclusion TM infection is rare in individual with NSMM. Since they have clinical manifestation in common, easily causing misdiagnosis and missed diagnosis, multiple pathological examinations and tissue cultures are essential to provide a differential diagnosis.

Cutaneous Metastasis of Thymic Carcinoma to the Frontal Scalp

Thymic carcinomas are a rare variant of thymic epithelial tumors. Compared to thymomas, they are much more aggressive, difficult to treat, and have a higher mortality rate. Metastasis outside of the mediastinum is rare and usually to sites such as the lung, lymph nodes, liver, pleura, or bones. We report a case of immunohistochemistry proven thymic carcinoma metastasis to the cutaneous surface of the frontal scalp in a 53-year-old Asian female.

Fostering Trust With a Young Man Experiencing Homelessness and Advanced Cancer

Persons experiencing homelessness (PEH) face countless barriers to equitable health, social, and palliative care across all settings. Brandon was a 23-year-old male, well-spoken, groomed, and polite despite difficult circumstances. He was severely abused then abandoned as a child, living in multiple foster homes until 18. With no consistent caring adult figure, he predictably fell into a chaotic lifestyle, had 3 children by different mothers, and became homeless in New York City. He presented with newly diagnosed renal cell carcinoma metastatic to lung, lymph nodes, and bone. Spine and pelvic metastases caused paralyzing somatic pain that interfered with walking and sitting and prevented Brandon from performing the activities of daily living essential for his survival on the streets and safekeeping of opioids. Lack of basic social support and a history of multiple abandonments made a care plan for this young, homeless, and truly isolated man very challenging. The inpatient and outpatient interdisciplinary team members partnering with Brandon each earned his trust with time. A “safe place” opened hearts on all sides of the therapeutic relationship and led to a plan that was acceptable for both the patient and the palliative care team. Clinicians are often challenged to provide sustained and pragmatic palliative care services for PEH due to complex barriers. Continued advocacy for equitable and tailored services that ensure high-quality palliative care for PEH is critical at individual, institutional, and system levels to promote health equity and dignified care.

An Unusual Case of Gastrointestinal Bleeding in Metastatic Renal Cell Carcinoma

Approximately 340 patients are diagnosed with renal cell cancer (RCC) in Ireland each year. Metastatic spread to the lung, lymph nodes and bones is common. Metastatic spread to the gastrointestinal tract, including the small bowel, is a rare phenomenon. Therapeutic advances have led to an improved overall survival in RCC and, as a result, unusual sites of metastatic spread are becoming more common. We present the case of a 68-year-old gentleman presenting with upper gastrointestinal bleeding as a result of metastases to the duodenum from renal cell carcinoma.

Targeted therapies: How can CT imaging improve evaluations and help understand mechanism of drug action?

e13012 Background: We compared the therapeutic response between Varlitinib plus Capecitabine (VC) and Lapatinib plus Capecitabine (LC) by stratifying changes in tumor’s longest diameter (LD) and volume (VOL) per tumor location in patients with HER2+ metastatic breast cancer after trastuzumab therapy. Methods: We retrospectively analyzed the ASLAN001-003 double-arm trial (NCT02338245). We first tested the intra and inter-arm equivalence in number and size of tumors at each location of the disease.Second, we compared the inter-arm average changes in 1) tumor burden according to RECIST; 2) stratified tumor burden in summing, for each patient, the target lesions from the same organ locations; 3) tumors considered independent but grouped per organ location of the disease.Third, we tested the intra-arm differential responses of pairwise groups of tumor locations: breast-lung, breast-liver, breast-lymph nodes, lung-liver, lung-lymph nodes and liver-lymph nodes. A sensitivity analysis tested the robustness of our results. Results: We followed 74 tumors in 35 patients (14 VC; 21 LC) after 12 weeks of treatment. Primary breast tumors had a larger size than metastasis (p < 0.002). Tumor proportions at each organ location of the disease were not significantly different. The inter-arm difference in changes of tumor burden yielded: p = 0.086 (LD) and p = 0.13 (VOL); in stratifying patients per breast tumors: p = 0.002 (LD) and p < 0.001 (VOL); and for independent breast tumors: p = 0.001 (LD) and p < 0.001 (VOL). We found differential responses in the LC arm for breast-liver (p = 0.007 (VOL)) and Liver-Lymph node (p = 0.06 (VOL)). After outlier’s removal, the inter-arm difference was confirmed for breast tumors (p = 0.004 (LD); p < 0.001 (VOL)) and when considering all tumors as independent (p < 0.01(LD); p = 0.04 (VOL)). The differential Breast-Liver response in the VC arm was confirmed p < 0.05 (LD or VOL). Conclusions: Differential imaging responses were found across treatment arms and tumor locations. The stratification of changes provides new insights into responses of targeted therapies and more accurate drug comparisons. The stratification is a promising approach to better understand therapy mechanisms of action behind tumor heterogeneity.

Prevention of tuberculosis in macaques after intravenous BCG immunization

Mycobacterium tuberculosis (Mtb) is the leading cause of death from infection worldwide1. The only available vaccine, BCG (Bacillus Calmette–Guérin), is given intradermally and has variable efficacy against pulmonary tuberculosis, the major cause of mortality and disease transmission1,2. Here we show that intravenous administration of BCG profoundly alters the protective outcome of Mtb challenge in non-human primates (Macaca mulatta). Compared with intradermal or aerosol delivery, intravenous immunization induced substantially more antigen-responsive CD4 and CD8 T cell responses in blood, spleen, bronchoalveolar lavage and lung lymph nodes. Moreover, intravenous immunization induced a high frequency of antigen-responsive T cells across all lung parenchymal tissues. Six months after BCG vaccination, macaques were challenged with virulent Mtb. Notably, nine out of ten macaques that received intravenous BCG vaccination were highly protected, with six macaques showing no detectable levels of infection, as determined by positron emission tomography–computed tomography imaging, mycobacterial growth, pathology and granuloma formation. The finding that intravenous BCG prevents or substantially limits Mtb infection in highly susceptible rhesus macaques has important implications for vaccine delivery and clinical development, and provides a model for defining immune correlates and mechanisms of vaccine-elicited protection against tuberculosis.

Staccato pulse interleukin-2 (IL-2) in metastatic melanoma (MM) previously treated with checkpoint inhibitors (CPI).

e21022 Background: The CPI ipilimumab, nivolumab, and pembrolizumab have been adopted into common use for patients (pts) with MM. While their clinical activity is undeniable, a substantial fraction of pts treated with these agents experience disease progression. Additional approaches are therefore needed. Intravenous IL-2 given via daily single intravenous infusions (pulses) has been developed to mitigate toxicity while maintaining anticancer activity against MM. Staccato pulse IL-2 is based on three prior observations. Daily IL-2 schedules have previously been demonstrated to induce Lymphokine Activated Killer cell (LAK) activity [Mitchell, 1989]. LAK generated by IL-2 then subsequently exposed to more IL-2 display enhanced cytotoxicity in vitro [Hank, 1990]. Increased numbers of LAK are seen in pts with melanoma treated with daily IL-2 [Quan, 2011]. Methods: In this retrospective study, ten pts with MM were treated with IL-2 18 Million IU/M2 intravenously over 15-30 minutes on days 1-3 and 21.6 Million IU/M2 intravenously over 15-30 minutes on day 5 on an outpatient basis. Cycles were repeated every 3 weeks. Results: Characteristics: 8 females/ 2 males, median age-56 (range: 21-74), median ECOG-1 (0-1); common disease sites: lymph nodes (12), subcutaneous (6), lungs (5), soft tissue (4). Prior CPI: Ipilimumab (8); Pembrolizumab (5); Nivolumab (2). Common toxicities: nausea/emesis (8), myalgia/arthralgia (5), sinus/catarrhal symptoms (5), fatigue (5), and hypotension requiring intravenous fluids (5). No pts required hospitalization for toxicity related to therapy. Median number of cycles: 3 (2-8). Four pts have had partial responses (total response rate = 40%; 95% CI: 10-70%). The median duration of response exceeds 7.4+ months. One pt having had resolution of prior lung, lymph node, and peritoneal metastases (partial response of 24.5+ months) underwent surgical resection of the residual intraabdominal disease focus and is free of disease at 36.5+ months. Overall, responses have occurred in lung, lymph nodes, subcutaneous, bones, peritoneum, small bowel, and soft tissue sites. Conclusions: Staccato pulse intravenous IL-2 has activity in melanoma pts previously treated with CPI.

Sidedness in metastatic colorectal carcinoma: Which are the factors which influence the prognosis?

497 Background: Recent reports demonstrate prognostic and predictive impacts of the location of the primary tumor in metastatic colorectal cancer (mCRC). Our retrospective analysis aimed to determine the influence of primary site on metastatic distribution and disease evolution. Methods: From our database all patients (pts) with mCRC (except transverse carcinoma) treated from 1/12/2007 to 1/12/2016 in our institution were collected. Univariate and multivariate analyses were performed to identify predictors of overall survival (OS). Results: A total of 284 pts with available data were analyzed: 83 with Right-sided Colon Cancer (RCC) (29%), 123 with Left-sided Colon Cancer (LCC) (43%) and 78pts with Rectal Cancer (RC) (28%). Hepatic, lung, lymph nodes and peritoneal metastases were respectively found in 63%, 36%, 23% and 20% of the population. The incidence or number of liver metastases were not influenced by sidedness (p = 0.06), LCC presented more bilobar involvement compared to RCC and RC (p = 0.017). Peritoneal carcinomatosis was significantly correlated to colon cancer (p = 0.002), whereas lung metastases were more common in RC (p < 0.001). Patients with RCC more often presented distal lymph node involvement (p = 0.008). RAS mutation status was known for 241pts (80%), of those 110 (37%) were RAS mutated with no significant differences between RCC, LCC and RC (p = 0.4), BRAF mutation (p = 0.007) was more common in RCC. On a multivariable analysis, primary tumor resection (PTR) and complete response after first line therapy were associated with a better OS but only a trend was observed for LCC and RC. Lung, lymph and peritoneal metastasis were associated with worse OS (Table). Conclusions: These results suggests that mCRC had different clinical presentation at diagnosis, the association with molecular features may explain the independent prognostic factor for OS of the sidedness. [Table: see text]

Morbillivirus-associated lipid pneumonia in Arctic foxes

We describe lipid pneumonia in 5 of 24 Arctic foxes ( Vulpes lagopus) in association with morbillivirus infection, and lymphoid depletion in 3 of these 5 foxes. Canine distemper virus (CDV) immunohistochemistry yielded positive staining in lung, lymph nodes, spleen, adipose tissue, and renal pelvic urothelial cells in 5 cases. Liver and bone marrow samples collected from these cases tested positive for morbillivirus by reverse-transcription PCR assay. Strains belonged to the CDV Arctic lineage based on sequencing of the hemagglutinin gene followed by phylogenetic analysis. Phylogenetic analysis of the phosphoprotein gene showed that the identified CDV strains were not closely related to any previously documented strains responsible for outbreaks in different animals in other parts of the world.