Hematogenous Route Research Articles

Routes of Zika virus dissemination in the testis and epididymis of immunodeficient mice

Sexual transmission and persistence of Zika virus (ZIKV) in the male reproductive tract (MRT) poses new challenges for controlling virus outbreaks and developing live-attenuated vaccines. To elucidate routes of ZIKV dissemination in the MRT, we here generate microRNA-targeted ZIKV clones that lose the infectivity for (1) the cells inside seminiferous tubules of the testis, or (2) epithelial cells of the epididymis. We trace ZIKV dissemination in the MRT using an established mouse model of ZIKV pathogenesis. Our results support a model in which ZIKV infects the testis via a hematogenous route, while infection of the epididymis can occur via two routes: (1) hematogenous/lymphogenous and (2) excurrent testicular. Co-targeting of the ZIKV genome with brain-, testis-, and epididymis-specific microRNAs restricts virus infection of these organs, but does not affect virus-induced protective immunity in mice and monkeys. These defined alterations of ZIKV tropism represent a rational design of a safe live-attenuated ZIKV vaccine.

Tuberculosis of the central nervous system in cattle in Paraíba, Brazil

ABSTRACT: This paper describes six cases of tuberculosis in the central nervous system (CNS) of cattle in the state of Paraíba in northeastern Brazil. We reviewed the autopsy reports of 851 bovine necropsies performed from 2003 to 2016. Seventy-three (8.6%) cattle were diagnosed with tuberculosis and six showed lesions in the CNS. Three cases affected cattle up to two-year-old and other three affected adults. Three cattle presented exclusively nervous signs, two had respiratory signs and weight loss and one did not present any clinical signs. At necropsy, five cattle had thickening of the leptomeninges of the cerebellum, pons, obex, spinal cord and cortex, mainly, in the region near the brain basilar Willis´ circle. Another animal, presented a single focal lesion in the cerebellum. Microscopically we observed moderate to severe granulomatous meningitis and encephalitis. Five cattle presented lesions in the lungs and mediastinal lymph nodes and three of them had disseminated lesions in other organs. In all cattle acid-fast bacilli were observed in the lesions and marked positive for immunohistochemistry with polyclonal antibody anti-Mycobacterium tuberculosis. It is concluded that bovine tuberculosis of central nervous system occurs sporadically in Paraíba, in cattle of different ages, most of them with disseminate lesions in other organs. The location of the lesions suggests that the agent invaded the brain by hematogenous route through the circle of Willis.

Origin and characteristics of haematogenous periprosthetic joint infection

ObjectivesRecognition of infectious origin of haematogenous periprosthetic joint infections (PJI) is crucial. We investigated the primary focus and characteristics of haematogenous PJI. MethodsConsecutive patients who presented with haematogenous PJI between 01/2010 and 01/2018 were retrospectively analysed. Haematogenous PJI was defined by diagnosis of infection ≥1 month after surgery, acute manifestation after a pain-free period and positive blood or prosthetic-site culture and/or evidence of distant infectious focus consistent with the pathogen. Fisher's exact, Student's t and Mann–Whitney U tests were used, as appropriate. ResultsA total of 106 episodes of PJI were included, involving 59 knee, 45 hip, one shoulder and one elbow prostheses. The median time from last surgery until haematogenous PJI was 47 months (range, 1–417 months). The pathogen was identified in 105 episodes (99%), including Staphylococcus aureus (n = 43), streptococci (n = 32), enterococci (n = 13), Gram-negative bacteria (n = 9) and coagulase-negative staphylococci (n = 8). Gram-negative bacteria were significantly more often found in hip joints than in knee joints. Blood cultures grew the pathogen in 43 of 70 episodes (61%). The primary infectious focus was identified in 72 episodes (68%) and included infections of intravascular devices or heart valves (22 episodes), skin and soft tissue (16 episodes), the oral cavity (12 episodes), urogenital (12 episodes) or gastrointestinal tract (seven episodes) and other sites (three episodes). ConclusionsIn acute PJI manifesting after a pain-free period, the haematogenous infection route should be considered and the primary infectious focus should be actively searched for. The cardiovascular system, skin and soft tissue, oral cavity, urogenital and gastrointestinal tracts were common origins of haematogenous PJI.

A Rare Case of Primary Ovarian Squamous Cell Cancer Metastatic to Colon

Metastatic lesions of the colon are rare and can be challenging in management. The incidence of these metastases appears to be increasing, as a result of increasing awareness and screening for colonic cancer. Colonic metastases of ovarian origin account for 4-6% of cases. We present a unique case of pure primary ovarian in situ squamous cell carcinoma (SCC) that presented with metastasis to the colon. A 66-year-old female from the Caribbean with a history of in situ ovarian SCC with bilateral oophorectomy about a year ago, presented with complaints of diffuse abdominal pain for 1 week with associated nausea, vomiting, and constipation. Physical exam was remarkable for abdominal distension. Initial labs were unremarkable. A Computed Tomography scan of the abdomen and pelvis revealed moderate distention of the transverse and right colon. Right colon was dilated to 9.4 cm with gradually tapering to the level of the mid sigmoid colon (Fig 1). With concern for intestinal obstruction, the patient had an exploratory laparotomy. Findings on surgery included multiple adhesions which were extensively lysed. A dilated cecum requiring cecostomy and a rectosigmoid mass which was removed en-bloc.Pathology of the rectosigmoid mass revealed metastatic squamous cell carcinoma, with moderate differentiation extending through the colonic wall (Fig 2,3).Patient was started on palliative chemotherapy with 4 cycles of paclitaxel combined with carboplatin and is responding to chemotherapy.1567_A Figure 1. Colonic dilation secondary to obstruction1567_B Figure 2. Arrow showing carcinoma cells on H&E stain1567_C Figure 3. Arrow showing squamous cancer cells on immunohistochemical stain with P63SCC of the ovary may be metastatic in 2% of all the ovarian cancers. Metastatic ovarian cancer, to colon or rectum, are extremely rare. Spread of ovarian neoplasm to the colon and rectum may involve a lymphogenous, hematogenous route, direct infiltration of the bowel wall, or through the peritoneum. The interval between the initial diagnosis and the development of metastases to the colon is variable with a mean interval of 9 years. However synchronous manifestation of colonic metastasis with ovarian carcinoma has been described. Immunohistochemical staining positive for CK7, CA-125, estrogen and progesterone receptors is considered indicative of an ovarian origin of the mass. This case is a unique case of pure primary ovarian in-situ carcinoma that presents within a short duration as metastatic SCC of the colon. This case highlights the significance of recognizing that not all colonic mass are primary colorectal carcinoma.

AN UNUSUAL CASE OF DISSEMINATED CRYPTOCOCCOSIS

SESSION TITLE: Chest Infections 3 SESSION TYPE: Fellow Case Reports PRESENTED ON: 10/08/2018 11:00 AM - 12:00 PM INTRODUCTION: Cryptococcus neoformans is frequently present as an opportunistic pathogen mainly affecting immunocompromised populations.Disseminated infection in immunocompetent population is rare.We describe one such unique case in a young male,whose sole risk factor turned out to be where he lived. CASE PRESENTATION: 23 year old male,non-smoker, was referred to thoracic surgery clinic from an urgent care center for abnormal CT chest. He initially presented to the urgent care center with intermittent chest pain for 2 weeks. Chest x-ray there showed left lower lobe infiltrates and he was treated with oral antibiotics.On persistence of symptoms,he had a CT chest which showed bilateral lower lobe consolidations,hilar and mediastinal lymphadenopathy. He attested to low grade fevers but denied other complaints. Due to concern for possible malignancy he underwent a PET CT,which showed the lower lobe masses to be have FDG uptake of SUV 3.3.It also revealed an expansile bone lesion in the mandible with similar FDG uptake.He then underwent a wedge biopsy of his left lower lobe lesion. Histopathological examination of the specimen revealed organizing pneumonia with fungal organisms consistent with crytococcus neoformans. Cultures were negative.On detailed interview,it was found he lived near a train station which has been a nesting place for pigeons and other birds. Complete work up for risk factors including HIV infection was negative.Patient was started on itraconazole with good clinical and radiological improvement. His 3 month follow up CT shows complete resolution of all the lung and bone lesions. DISCUSSION: Cryptococcus neoformans is ubiquitous encapsulated yeast and is generally considered as an opportunistic pathogen. The lungs are predominantly the primary locus of infection, with extra-pulmonary dissemination through hematogenous route affecting the meninges and, less commonly, the skin, bones, prostate, and other organs. Lung involvement typically consists of granulomatous reactions, and infiltrates. Most cutaneous infection occurs as a sign of disseminated Cryptococcal infection, which can be seen in 10–15% of the cases. Diagnosis is based on cultural examination of blood, cerebrospinal fluid, direct microscopic observation of the pathogen and PAS stain positivity on histochemical analysis. Our patient was negative for repeated cultures, which might indicate the insensitivity of culture at the early stage of infection. Treatment usually involves azoles and in severe cases amphotericin and surgical debridement of the lesions. CONCLUSIONS: Though historically viewed as an opportunistic pathogen, fungal diseases are rapidly increasing in incidence, in its presentation in immunocompetent patients. Our case is unique as < 10 cases has been reported in literature,of disseminated crytococcal infection in an immunocompetent adult, that did not involve the nervous system. Reference #1: 1. Ruan Q, Zhu Y, Chen S, Zhu L, Zhang S, Zhang W. Disseminated cryptococcosis with recurrent multiple abscesses in an immunocompetent patient: a case report and literature review. BMC Infectious Diseases. 2017;17:369. https://doi.org/10.1186/s12879-017-2459-9. Reference #2: S. Suchitha, C. S. Sheeladevi, R. Sunila, and G. V. Manjunath, “Disseminated Cryptococcosis in an Immunocompetent Patient: A Case Report,” Case Reports in Pathology, vol. 2012, Article ID 652351, 3 pages, 2012. https://doi.org/10.1155/2012/652351 DISCLOSURES: No relevant relationships by Anna Abbasi, source=Web Response No relevant relationships by Michael Bergman, source=Admin input No relevant relationships by Prarthna Chandar, source=Web Response No relevant relationships by Kabu Chawla, source=Admin input No relevant relationships by Sakthidev Kulandaisamy, source=Web Response No relevant relationships by William Pascal, source=Web Response No relevant relationships by Arjun Saradna, source=Web Response No relevant relationships by Shyam Shankar, source=Web Response

Breast Cancer with Isolated Metastatic Temporomandibular Joint: A Surgeon’s Challenge

Breast cancer is the number one malignancy in women worldwide. It tends to metastasize distantly via lymphatic and haematogenous route. Skeletal metastases are frequent with more than three quarter of cases in all malignant bone tumours. Breast cancer can infiltrate the axial bone especially spine, but rarely affect the temporomandibular joint. In view of its rarity and the significance of early detection, the diagnosis is always challenging and shall be considered in the differential diagnosis. We endeavour to highlight this unfortunate 37-year-old premenopausal lady who had just undergone left mastectomy and axillary dissection but was complicated with left temporomandibular joint metastasis.

Chrysin disrupts intracellular homeostasis through mitochondria-mediated cell death in human choriocarcinoma cells

The trophoblast cells which form the placenta, have a high potential for invading other tissues. Owing to certain mechanisms, trophoblast cells may lose their ability to control cell proliferation, and develop into pregnancy-related tumors, known as choriocarcinomas. Choriocarcinomas mostly develop from the hydatidiform mole, which is frequently found in pregnant women. Owing to their ability to rapidly metastasize through the hematogenous route, choriocarcinomas are very hard to cure if not detected at the proper time. Although numerous studies are attempting to identify the major pathways in choriocarcinoma cells, the critical pathway responsible for the origin of choriocarcinomas is still unclear. In this study, we identified that chrysin has inhibitory effects on human choriocarcinoma cells. The study demonstrated that chrysin disrupts intracellular homeostasis by altering the mitochondrial membrane potential (MMP), cytosolic Ca2+ levels, production of reactive oxygen species (ROS), and lipid peroxidation, leading to the death of choriocarcinoma cells (JAR and JEG3). Additionally, the effects of chrysin on choriocarcinoma cells were found to be mediated via the regulation of the AKT, ERK1/2, and JNK signaling pathways. Altogether, the anti-cancer effects of chrysin can aid the development of a novel therapeutic strategy against the progression of human choriocarcinomas.

Recién Nacidos con Sífilis Congénita y sus madres atendidas en el atendidas en el Servicio de Neonatología del Hospital ELOÍSA TORRENT DE VIDAL Corrientes. Años 2015-2016

SUMMARY: Congenital syphilis occurs when the mother with syphilis transmits the infection to the fetus during gestation by hematogenous route or during delivery by direct contact of the neonate with maternal genital lesions. It is an increasing social problem, which is why it was necessary to contextualize it in our environment. Objective: To determine the characteristics of newborns with congenital syphilis, assisted in the neonatology service of the Eloísa Torrent de Vidal Hospital in the city of Corrientes from January 1, 2015 to December 31, 2016. Material and method: Descriptive study , retrospective, cross-sectional, data source clinical histories, variables analyzed were gestational age, birth weight, need for hospitalization, time of hospitalization, epidemiological criteria for the diagnosis of syphilis, the mother's age, treatment of syphilis in the mothers and origin of the mother. Results: 65 neonates with congenital syphilis attended between 2015 and 2016 were detected. Of these, 24 were male and 41 female, in relation to gestational age, the minimum was 20 weeks, the maximum 40 weeks, the most frequent 37 weeks (22 %); 43 newborns presented adequate weight for gestational age. The most frequent period of hospitalization was 10 days. Regarding the epidemiological criteria for the diagnosis of syphilis, 28 cases were confirmed. With regard to maternal age, a range of ages between 16 and 40 years was presented, categorized in adolescents from 16 to 19 years old, 41%, young people from 20 to 34 years old, 54% and old people from 35 to 40 years old, 5%. When considering the origin of mothers with syphilis 77% resided in capital and 23% came from the provincial interior. In reference to the maternal treatment of syphilis, 2 cases were observed that completed the treatment, 36 with incomplete treatment and no treatment 27. The cases with confirmed diagnosis were 28, with weights between 900 and 4200 grams, with gestational age between 26 and 40 weeks, 20 mothers without treatment and 8 with incomplete treatment, 22 with domicile in the capital and 6 of the provincial interior. Conclusions: 65 cases were detected that received treatment for congenital syphilis, 28 of them had confirmation of the diagnosis, with gestational age between 26 and 40 weeks. In the origin of the mothers 77% resided in capital and 23% in the interior; 63 mothers had not received treatment or did not complete it during the prenatal period, observing a lack of attendance at the follow-up controls of the pregnancy, being the most remarkable and worrisome in our conclusions.

Successful Treatment of Ascites with Cholecystitis in A Dog

Ascites referred as accumulation of serous fluid in peritoneal cavity, has been attributed to chronic hepatic failure, congestive heart failure, nephritic syndrome, malnutrition, ancylostomiasis and protein losing enteropathy in canine (Pradhan et al., 2008). Multiple organ disorders, hypoproteinaemia (Dabas et al., 2011), and right side heart failure (Ettinger and Feldman, 2005) are the common causes associated with ascites in dogs. Cholecystitis is a disease of the gall bladder characterized by infections, idiopathic inflammation or urolith obstruction, which is commonly caused by bacteria ascending from the intestine via the common bile duct or by haematogenous routes (Karlapudi and Devarakonda 2014a).

Pathology and pathogenesis of human leptospirosis: a commented review.

ABSTRACTLeptospirosis is an acute bacterial septicemic febrile disease caused by pathogenic leptospires, which affect humans and animals in all parts of the world. Transmission can occur by direct contact with infected animals or, more commonly, through indirect contact with water or soil contaminated with urine from infected animals. Leptospires enter the body by penetrating mucous membranes or skin abrasions and disseminate through the hematogenic route. In humans, leptospirosis may cause a wide spectrum of symptoms. Most cases have a biphasic clinical presentation, which begins with the septicemic phase followed by immune manifestations. The severe forms of the disease may be life threatening with multisystem damage including renal failure, hepatic dysfunction, vascular damage, pulmonary hemorrhage and muscle lesions. In this review, we present and discuss the pathogenesis of the human disease and the mechanisms of cell membrane injuries, which occur mainly due to the presence of leptospires and/or their antigen/s in the host tissues.

Tuberculosis verrucosa cutis: case report of a diagnostic challenge

&lt;p class="abstract"&gt;Cutaneous tuberculosis occurs by either exogenous inoculation in a previously sensitized or non-immune host or endogenous spread from an internal focus by contiguous, hematogenous or lymphatic route. Inoculation occurs at sites of minor wounds or abrasions, sometimes from the patient’s own sputum. Cutaneous tuberculosis includes lupus vulgaris and tuberculosis verrucosa cutis (TVC) at one end and scrofuloderma and tuberculosis cutis orificialis at the other end with decrease in cell-mediated immunity across the spectrum. Of various cutaneous forms, we report a case of tuberculosis verrucosa cutis in a 14 year old girl who presented with a hyperpigmented verrucous plaque over foot since three years. Histopathological characteristics, GeneXpert and response to antitubercular therapy confirmed the diagnosis.&lt;/p&gt;&lt;p class="abstract"&gt; &lt;/p&gt;

Aggressive Phenotype of Cells Disseminated via Hematogenous and Lymphatic Route in Breast Cancer Patients

Intratumoral heterogeneity of breast cancer remains a major challenge in successful treatment. Failure of cancer therapies can also be accredited to inability to systemically eradicate cancer stem cells (CSCs). Recent evidence points to the role of epithelial-mesenchymal transition (EMT) in expanding the pool of tumor cells with CSCs features. Thus, we assessed expression level as well as heterogeneity of CSCs markers in primary tumors (PT), lymph node metastasis (LNM), and circulating tumor cells (CTCs)–enriched blood fractions in order to correlate them with signs of EMT activation as well as clinicopathological data of breast cancer patients. Level of CSCs markers (ALDH1, CD44, CD133, OCT-4, NANOG) and EMT markers was quantified in PT (N=107), LNM (N=56), and CTCs-enriched blood fractions (N=85). Heterogeneity of CSCs markers expression within each PT and LNM was assessed by calculating Gini Index. Percentage of ALDH1-positive cells was elevated in PT in comparison to LNM (P = .005). However, heterogeneity of the four CSCs markers: ALDH1 (P = .019), CD133 (P = .009), OCT-4 (P = .027), and CD44 (P < .001) was decreased in LNM. Samples classified as mesenchymal (post-EMT) showed elevated expression of CSCs markers (OCT-4 and CD44 in PT; OCT-4 in LNM; ALDH1, OCT-4, NANOG, CD44 in CTCs). Patients with mesenchymal-like CTCs had worse prognosis than patients with epithelial-like or no CTCs (P = .0025). CSCs markers are enriched in PT, LNM, and CTCs with mesenchymal features, but their heterogeneity is decreased in metastatic lymph nodes. Mesenchymal CTCs phenotype correlates with poor prognosis of the patients.

Highlights from Recent Cancer Literature

Highlights from Recent Cancer Literature

Brain-resident memory CD8+ Tcells induced by congenital CMV infection prevent brain pathology and virus reactivation.

Congenital HCMV infection is a leading infectious cause of long-term neurodevelopmental sequelae. Infection of newborn mice with mouse cytomegalovirus (MCMV) intraperitoneally is a well-established model of congenital human cytomegalovirus infection, which best recapitulates the hematogenous route of virus spread to brain and subsequent pathology. Here, we used this model to investigate the role, dynamics, and phenotype of CD8+ Tcells in the brain following infection of newborn mice. We show that CD8+ Tcells infiltrate the brain and form a pool of tissue-resident memory Tcells (TRM cells) that persist for lifetime. Adoptively transferred virus-specific CD8+ Tcells provide protection against primary MCMV infection in newborn mice, reduce brain pathology, and remain in the brain as TRM cells. Brain CD8+ TRM cells were long-lived, slowly proliferating cells able to respond to local challenge infection. Importantly, brain CD8+ TRM cells controlled latent MCMV and their depletion resulted in virus reactivation and enhanced inflammation in brain.

Donor mesenchymal stem cell linetics after transamniotic stem cell therapy (TRASCET) for experimental spina bifida

PurposeWe sought to examine donor mesenchymal stem cell (MSC) kinetics after transamniotic stem cell therapy (TRASCET) in experimental spina bifida. MethodsPregnant Sprague–Dawley dams exposed to retinoic acid for the induction of fetal neural tube defects received volume-matched intra-amniotic injections on gestational day 17 (E17; term=E22): either amniotic fluid MSCs (afMSCs) labeled with a luciferase reporter gene (n=78), or luciferase protein alone (n=66). Samples from twelve organ systems from each surviving fetus with spina bifida (total n=60) were screened via microplate luminometry at term. ResultsDonor afMSCs were identified exclusively in the placenta, umbilical cord, spleen, bone marrow, hip bones, defect, and brain. Luminometry was negative in control fetuses receiving luciferase alone (p<0.001). Signal intensity in relative light units (RLUs) was moderately correlated between the defect and the hip bones (rho=0.38, p=0.048), and between the placenta and the brain (rho=0.40, p=0.038). ConclusionsAmniotic mesenchymal stem cells engraft to specific sites after concentrated intra-amniotic injection in the setting of spina bifida. A hematogenous route encompassing the bone marrow as well as distant central nervous system homing are fundamental constituents of cell trafficking. These findings must be considered during eventual patient selection for transamniotic stem cell therapy in the prenatal management of spina bifida.

Renal capsule metastasis from renal pelvic cancer: a case report

BackgroundMetastatic renal cancers are relatively common. Most are metastases to the renal parenchyma via a hematogenous route and are derived from lung, breast, and gastrointestinal cancer, malignant melanoma, and hematologic malignant cancer. However, little is known about renal capsule metastasis from other cancers.Case presentationWe report a 71-year-old woman with breast cancer who was treated with endocrine therapy. She presented with gross hematuria and was diagnosed as having right renal pelvic cancer and renal cell cancer. She underwent right laparoscopic radical nephroureterectomy. Pathological findings revealed right pelvic cancer and renal capsule metastasis.ConclusionRenal capsule metastasis derived from renal pelvic cancer is very rare. When diagnosing renal capsule cancer, we believe that renal capsule metastasis should also be taken into consideration. Clinical and radiological differential diagnosis of renal capsule metastasis from renal cell cancer and primary renal capsule cancer is difficult. Assessment of the histopathological findings of the surgical specimens seems to be the only realistic approach to achieving the correct diagnosis.

Pneumococcal Cellulitis in a Multiple Myeloma Patient

Pneumococcal Cellulitis in a Multiple Myeloma Patient

Evolutionary history of metastatic breast cancer reveals minimal seeding from axillary lymph nodes.

Metastatic breast cancers are still incurable. Characterizing the evolutionary landscape of these cancers, including the role of metastatic axillary lymph nodes (ALNs) in seeding distant organ metastasis, can provide a rational basis for effective treatments. Here, we have described the genomic analyses of the primary tumors and metastatic lesions from 99 samples obtained from 20 patients with breast cancer. Our evolutionary analyses revealed diverse spreading and seeding patterns that govern tumor progression. Although linear evolution to successive metastatic sites was common, parallel evolution from the primary tumor to multiple distant sites was also evident. Metastatic spreading was frequently coupled with polyclonal seeding, in which multiple metastatic subclones originated from the primary tumor and/or other distant metastases. Synchronous ALN metastasis, a well-established prognosticator of breast cancer, was not involved in seeding the distant metastasis, suggesting a hematogenous route for cancer dissemination. Clonal evolution coincided frequently with emerging driver alterations and evolving mutational processes, notably an increase in apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like-associated (APOBEC-associated) mutagenesis. Our data provide genomic evidence for a role of ALN metastasis in seeding distant organ metastasis and elucidate the evolving mutational landscape during cancer progression.

Abstract P1-01-03: Preclinical evidence that distant metastases occur via the lymphatic route

Abstract Cancer that metastasizes beyond the lymph nodes is almost invariably terminal. Therefore, understanding how cancer metastasizes is a critical aspect to understanding and eventually preventing cancer spreading from tissue to tissue. A major question that remains controversial is whether cancer cells that metastasize to the LNs are able to physically leave the LNs to colonize distant tissues. Moreover, whether cancer cell metastasis between different tissues involves unique genes is a question that requires further research. Using the metastatic mouse breast carcinoma line 4T1 in an LN microinjection model, we provide evidence suggesting that cancer cells can indeed metastasize and colonize distant tissues after direct implantation into the LNs. Interestingly, direct comparison of distant tissue metastatic capability comparing LN-microinjected cells and tail vein-injected cells suggests that the lymphatic route of cancer cell spreading may be a more efficient mechanism of metastasis than the hematogenous route. Moreover, our comparative transcriptome analysis results suggest that LN metastases show unique gene expression profiles relative to the primary breast tumors and distant metastases. We identified several genes that are up- or down-regulated in an LN-specific manner and thus may play a role in metastasis to the LNs and beyond. Collectively, our results suggest that LN metastases constitute an active “staging site” from which breast cancer cells can further metastasize to distant sites. Furthermore, we identify a unique set of genes that may be involved in the breast cancer metastatic process, several of which are potentially targetable using currently available inhibitors. Citation Format: Leslie PL, Ghosh SK, Porrello A, Cooley BC, Pecot CV. Preclinical evidence that distant metastases occur via the lymphatic route [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-01-03.

Current evidence does not support systematic antibiotherapy prior to joint arthroplasty in patients with asymptomatic bacteriuria-a meta analysis.

Many orthopaedic surgeons worry about asymptomatic bacteriuria (ASB) as a possible risk factor for prosthetic joint infection (PJI). However, available evidence establishing a direct link between ASB and PJI is limited. This meta-analysis aimed to investigate whether ASB is a factor for PJI and whether pre-operative antibiotic treatment shows benefit. We systematically searched major databases such as PubMed, Web of Science, the Cochrane Library and EMBASE for studies. Risk ratio (RR) was calculated for included studies that reported raw counts with 95% confidence interval (CI). Five studies involved 3588 joint arthroplasties and 441 cases of ASB (overall incidence 12.3%). Compared with the control group, PJI was more common in both patients in the ASB group (RR = 2.87; 95% CI, 1.65-5.00). But in all five studies, the micro-organisms isolated from PJI and urine cultures were not the same. Three of the five studies reported that the antibiotic treated the ASB prior to joint arthroplasty and compared the untreated ASB group.There was no significant difference between groups (RR = 0.89; 95% CI, 0.36-2.20). PJI occurring via the haematogenous route from the genitourinary tract harbouring bacteria in ASB is impossible. Pre-operative antibiotic treatment has no benefit. A plausible explanation could be an indicator of frailty and increased susceptibility to infection. ASB increased the risk of PJI in the meta-analysis. However, current evidence does not support systematic antibiotherapy prior to joint arthroplasty and screening for ASB.