Renal Cell Carcinoma Presenting With Combined Cervical Lymphadenopathy and Cardiac Metastasis Without Inferior Vena Cava Involvement.

Renal cell cancer is the third most common urological malignancy following prostate and bladder malignancies. Cardiac metastases to the right side of the heart without inferior vena cava (IVC) involvement are exceedingly rare, with only a handful of cases described in the literature. Metastasis to the head and neck region is also rare, occurring in an estimated 1% of cases. Here we present a case of a patient with recurrent syncopal events secondary to renal cell carcinoma without IVC involvement, with metastases both to the right ventricle and cervical lymph nodes. To our knowledge, this is the first case that presents with both of these rare findings together and that highlights cancer screening in patients with high risk factors and new exam findings in patients with syncopal events having negative initial workup.

Bloodstream Infections With a Novel Nontuberculous Mycobacterium Involving 52 Outpatient Oncology Clinic Patients-Arkansas, 2018.

BACKGROUND: In July 2018, the Arkansas Department of Health (ADH) was notified by hospital A of 3 patients with bloodstream infections (BSIs) with a rapidly growing nontuberculous Mycobacterium (NTM) species; on 5 September 2018, 6 additional BSIs were reported. All were among oncology patients at clinic A. We investigated to identify sources and to prevent further infections. METHODS: ADH performed an onsite investigation at clinic A on 7 September 2018 and reviewed patient charts, obtained environmental samples, and cultured isolates. The isolates were sequenced (whole genome, 16S, rpoB) by the Centers for Disease Control and Prevention to determine species identity and relatedness. RESULTS: By 31 December 2018, 52 of 151 (34%) oncology patients with chemotherapy ports accessed at clinic A during 22 March-12 September 2018 had NTM BSIs. Infected patients received significantly more saline flushes than uninfected patients (P < .001) during the risk period. NTM grew from 6 unused saline flushes compounded by clinic A. The identified species was novel and designated Mycobacterium FVL 201832. Isolates from patients and saline flushes were highly related by whole-genome sequencing, indicating a common source. Clinic A changed to prefilled saline flushes on 12 September as recommended. CONCLUSIONS: Mycobacterium FVL 201832 caused BSIs in oncology clinic patients. Laboratory data allowed investigators to rapidly link infections to contaminated saline flushes; cooperation between multiple institutions resulted in timely outbreak resolution. New state policies being considered because of this outbreak include adding extrapulmonary NTM to ADH's reportable disease list and providing more oversight to outpatient oncology clinics.

Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium.

BACKGROUND: Invasive fungal diseases (IFDs) remain important causes of morbidity and mortality. The consensus definitions of the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group have been of immense value to researchers who conduct clinical trials of antifungals, assess diagnostic tests, and undertake epidemiologic studies. However, their utility has not extended beyond patients with cancer or recipients of stem cell or solid organ transplants. With newer diagnostic techniques available, it was clear that an update of these definitions was essential. METHODS: To achieve this, 10 working groups looked closely at imaging, laboratory diagnosis, and special populations at risk of IFD. A final version of the manuscript was agreed upon after the groups' findings were presented at a scientific symposium and after a 3-month period for public comment. There were several rounds of discussion before a final version of the manuscript was approved. RESULTS: There is no change in the classifications of "proven," "probable," and "possible" IFD, although the definition of "probable" has been expanded and the scope of the category "possible" has been diminished. The category of proven IFD can apply to any patient, regardless of whether the patient is immunocompromised. The probable and possible categories are proposed for immunocompromised patients only, except for endemic mycoses. CONCLUSIONS: These updated definitions of IFDs should prove applicable in clinical, diagnostic, and epidemiologic research of a broader range of patients at high-risk.

Serendipitous Treatment of Tularemia in Pregnancy.

We present a young pregnant woman who developed ulceroglandular tularaemia following a bite wound from a kitten. She grew Francisella tularensis from the ulcer. While awaiting bacterial culture results and serology for Bartonella, she was treated with azithromycin, with resolution of fever and axillary tenderness. Treatment recommendations for tularemia are either gentamicin or doxycycline, both of which can be perilous to the fetus. A Centers for Disease Control and Prevention report on the macrolide susceptibility of North American isolates of this organism has been underappreciated. The unanticipated result from this patient may give another potential option for treatment of tularemia in pregnancy.

Choice of Intravenous Crystalloid Fluid and Mortality in Critically Ill Adult Patients.

OBJECTIVES: Intravenous balanced crystalloid fluid therapy may improve mortality and other outcomes in critically ill adult patients, but data are conflicting. We conducted a meta-analysis and literature review to evaluate the impact of intravenous balanced crystalloid, as compared with normal saline, fluid therapy on outcomes in critically ill adult patients. METHODS: We searched PubMed, Scopus, MEDLINE, and the Cochrane Register of Clinical Trials for relevant studies. Randomized controlled trials comparing the effects of balanced intravenous crystalloids with normal saline on intensive care unit (ICU) or hospital mortality were included. Pooled risk ratios (RRs) were calculated using a fixed effects model. Heterogeneity was calculated using the I2 statistic. The risk of bias was assessed using the Cochrane tool. RESULTS: Seven randomized controlled trials with 20,171 patients (10,179 participants received balanced crystalloids and 9992 participants received normal saline) were included. For hospital mortality, the pooled RR (95% confidence interval [CI]) was 0.92 (0.85-1.00). For ICU mortality, the pooled RR (95% CI) was 0.91 (0.82-1.00). For major adverse kidney events at 30 days, pooled RR (95% CI) was 0.95 (0.88-1.01). For stage ≥2 acute kidney injury, the pooled RR (95% CI) was 0.94 (0.86-1.02). For receipt of new renal replacement therapy, the pooled RR (95% CI) was 0.91 (0.77-1.07). None of these findings reached statistical significance. CONCLUSIONS: Intravenous balanced crystalloid use, compared with normal saline, does not result in a statistically significant reduction in hospital or ICU mortality, major adverse kidney events at 30 days, stage ≥2 acute kidney injury, or receipt of new renal replacement therapy in critically ill adult patients.

Intermediate care to intensive care triage: A quality improvement project to reduce mortality.

PURPOSE: Medical patients whose care needs exceed what is feasible on a general ward, but who do not clearly require critical care, may be admitted to an intermediate care unit (IMCU). Some IMCU patients deteriorate and require medical intensive care unit (MICU) admission. In 2012, staff in the Johns Hopkins IMCU expressed concern that patient acuity and the threshold for MICU admission were too high. Further, shared triage decision-making between residents and supervising physicians did not consistently occur. METHODS: To improve our triage process, we used a 4Es quality improvement framework (engage, educate, execute, evaluate) to (1) educate residents and fellows regarding principles of triage and (2) facilitate real-time communication between MICU residents conducting triage and supervising physicians. RESULTS: Among patients transferred from the IMCU to the MICU during baseline (n=83;July-December 2012) and intervention phases (n=94;July-December 2013), unadjusted mortality decreased from 34% to 21% (p=0.06). After adjusting for severity of illness, admitting diagnosis, and bed availability, the odds of death were lower during the intervention vs. baseline phase (OR 0.33; 95%CI 0.11-0.98). CONCLUSIONS: Using a structured quality improvement process targeting triage education and increased resident/supervisor communication, we demonstrated reduced mortality among patients transferred from the IMCU to the MICU.

Possible Transfusion-Transmitted Babesia divergens-like/MO-1 Infection in an Arkansas Patient.

A patient with asplenia and multiple red blood cell transfusions acquired babesiosis infection with Babesia divergens-like/MO-1 organisms and not Babesia microti, the common United States species. He had no known tick exposure. This is believed to be the first transfusion-transmitted case and the fifth documented case of B. divergens-like/MO-1 infection.

Outcomes of Emergency Medical Patients Admitted to an Intermediate Care Unit With Detailed Admission Guidelines.

BACKGROUND: An important, but not well characterized, population receiving intermediate care is that of medical patients admitted directly from the emergency department. OBJECTIVE: To characterize emergency medical patients and their outcomes when admitted to an intermediate care unit with clearly defined admission guidelines. METHODS: Demographic data, admitting diagnoses, illness severity, comorbid conditions, lengths of stay, and hospital mortality were characterized for all emergency medical patients admitted directly to an intermediate care unit from July through December 2012. RESULTS: A total of 317 unique patients were admitted (mean age, 54 [SD, 16] years). Most patients were admitted with respiratory (26.5%) or cardiac (17.0%) syndromes. The mean (SD) Acute Physiology and Chronic Health Evaluation score version II, Simplified Acute Physiology Score version II, and Charlson Comorbidity Index were 15.6 (6.5), 20.7 (11.8), and 2.7 (2.3), respectively. Severity of illness and length of stay were significantly different for patients who required intensive care within 24 hours of admission (n = 16) or later (n = 25), patients who continued with inter mediate care for more than 24 hours (n = 247), and patients who were downgraded or discharged in less than 24 hours (n = 29). Overall hospital mortality was 4.4% (14 deaths). CONCLUSIONS: Emergency medical patients with moderate severity of illness and comorbidity can be admitted to an intermediate level of care with relatively infrequent transfer to intensive care and relatively low mortality.

The endemic mimic: blastomycosis an illness often misdiagnosed.

One of the endemic fungi, Blastomyces dermatitidis, can cause epidemics of infection with multiple persons involved in a point source outbreak but more commonly causes sporadic cases of infection within the areas of endemicity. Blastomycosis can present as an acute pneumonia which is often misdiagnosed as acute pneumococcal pneumonia or the infection may present as a chronic pneumonia along with weight loss, night sweats, hemoptysis, and a lung mass suggesting tuberculosis or carcinoma of the lung. Extrapulmonary infection with B. dermatitidis is protean with many different manifestations. Most commonly, skin or subcutaneous lesions are found with either a verrucous or warty appearance or in an ulcerative form. Cases have been misidentified as keratoacanthoma, pyoderma gangrenosum, carcinoma, or as Weber-Christian panniculitis if there are nodular subcutaneous lesions. Essentially any site or organ can have lesions of disseminated blastomycosis. In our series, cases of laryngeal carcinoma, adrenal insufficiency, thyroid nodules, granulomatous hypercalcemia, abnormal mammograms thought to represent breast carcinoma, otitis media with cranial extension, immune thrombocytopenic purpura, and hemolytic anemia of unknown cause have been misdiagnosed and blastomycosis subsequently identified as the cause. This infection causes manifestations which mimic many other more commonly diagnosed conditions and must always be considered by clinicians practicing in the endemic region.

Influenza a outbreak in an ambulatory stem cell transplant center.

BACKGROUND: In the era of cost-consciousness regarding healthcare , provision of medical services in an outpatient setting has become increasingly attractive. We report an influenza outbreak in an ambulatory stem cell transplant center in 2013 that highlights unique identification and infection control challenges in this setting. METHODS: Nasopharyngeal swabs were performed on patients with suspected influenza-like illnesses (ILI), defined by subjective fever or measured temperature of ≥37.7°C (≥100°F) with cough or sore throat during July 25, 2013 through August 7, 2013. In addition, testing was triggered by an elevated C-reactive protein (CRP). Specimens were analyzed by using eSensor Respiratory Viral Panel. Clinical and epidemiologic information was collected in real time, and frequencies were calculated on demographics, baseline clinical parameters, treatment methods, comorbidities, and symptoms of affected persons. RESULTS: Thirty-one patients had influenza A (H3N2) infection during July 25, 2013 through August 7, 2013. Only 7 patients (23%) met the Centers for Disease Control and Prevention and Council of State and Territorial Epidemiologists ILI case definition. Twenty-five patients (81%) had received ≥1 transplant, with 13 (42%) having occurred within 1 year before the outbreak. Twenty-five patients (81%) had received B-cell active chemotherapy <60 days before influenza diagnosis, 6 (19%) were neutropenic, and 25 (81%) lymphopenic. Among clinical and laboratory markers analyzed, abnormal CRP was the most sensitive screening tool for influenza. Twelve (39%) patients were hospitalized (median stay, 10 days; range, 2-20). No deaths occurred. CONCLUSIONS: Immunocompromised hosts with influenza have atypical presentations. Existing surveillance case definitions might be insufficient to reliably identify influenza outbreaks in such patients.

Blastomyces dermatitidis antigen detection by quantitative enzyme immunoassay.

The second-generation MVista Blastomyces antigen enzyme immunoassay was not quantitative; therefore, specimens obtained previously were tested in the same assay as new specimens to assess the change in antigen levels. Furthermore, the sensitivity in serum had not been fully evaluated. The purpose of this study was to evaluate a quantitative Blastomyces antigen assay and detection of antigen in serum. Calibrators containing known concentrations of Blastomyces galactomannan were used to quantify antigen in urine and serum from patients with proven blastomycosis and from controls. Paired current and previously obtained urine specimens were tested to determine if quantification eliminated the need for concurrent testing to assess change in antigen. Pretreatment of serum with EDTA at 104°C was evaluated to determine if dissociation of immune complexes improved detection of antigenemia. Antigenuria was detected in 89.9% of patients with culture- or histopathology-proven blastomycosis. Specificity was 99.0% in patients with nonfungal infections and healthy subjects, but cross-reactions occurred in 95.6% of patients with histoplasmosis. Change in antigen level categorized as increase, no change, or decrease based on antigen units determined in the same assay agreed closely with the category of change in ng/ml determined from different assays. Pretreatment increased the sensitivity of detection of antigenemia from 35.7% to 57.1%. Quantification eliminated the need for concurrent testing of current and previously obtained specimens for assessment of changes in antigen concentration. Pretreatment increased the sensitivity for detection of antigenemia. Differentiation of histoplasmosis and blastomycosis is not possible by antigen detection.

Detection of Blastomyces dermatitidis antigen in patients with newly diagnosed blastomycosis.

Blastomycosis is a serious and potentially fatal infection, and diagnosis can be difficult at times. We evaluated the diagnostic utility of a commercially available assay for detection of Blastomyces dermatitidis antigen, recently modified to permit quantitation, in subjects with newly diagnosed blastomycosis. Twenty-three of 27 (85.1%) subjects had detectable B. dermatitidis antigenuria. In 2 of these 23, positive results were obtained after concentration of the urine specimen. Nine of 11 (81.8%) subjects had detectable B. dermatitidis antigen in serum, including 3 subjects with negative results before treatment of serum with ethylenediaminetetraacetic acid (EDTA) and positive results after EDTA treatment. B. dermatitidis antigen was not detected in specimens from 50 control subjects but was detected in 15 patients with histoplasmosis. B. dermatitidis antigen was detected in most of the patients with blastomycosis and can be a useful tool for timely diagnosis.

Treatment of endemic mycoses.

The endemic mycoses are a diverse group of diseases caused by thermally dimorphic fungi. While they share many characteristics, each has unique aspects with regards to their clinical course, diagnosis and management. Diagnosis may be difficult and delayed owing to the varied manifestations and wide differential diagnosis. Historically, treatment has been with amphotericin B, which has been limited by its significant toxicity. The advent of the azole class of medications has allowed for safer alternatives to amphotericin B. The azoles have become the mainstay of treatment for many, if not most, forms of these diseases. Guidelines have been released for the management of each of the North American endemic mycoses; however, many questions remain as to the best strategies for the diagnosis and management of various manifestations of these diseases.

A clinical review of Lyme disease in Arkansas.

Lyme disease is the most common tick-borne disease in the northern hemisphere. Since it was first described more than 30 years ago, Lyme disease has generated a great deal of controversy. Lyme disease is not endemic in Arkansas, and testing for Borrelia burgdorferi can lead to clinical confusion, unnecessary treatment and excess cost. This article will present a brief review of Lyme disease, with an emphasis on what is known regarding Lyme disease in Arkansas.

Blastomycosis of the central nervous system: a multicenter review of diagnosis and treatment in the modern era.

BACKGROUND: Central nervous system (CNS) involvement with Blastomyces dermatitidis is an uncommon and potentially fatal complication of blastomycosis. METHODS: We retrospectively reviewed 22 patients with CNS blastomycosis at our institutions from 1990 through 2008 (13 proven, 5 probable, and 4 possible cases). RESULTS: Magnetic resonance imaging was used in most patients, alone or in addition to computed tomography. CNS blastomycosis manifested as epidural abscess (1 of 22), meningitis (7 of 22), intracranial mass lesions (10 of 22), and concomitant intracranial mass lesions and meningitis (4 of 22). All patients received amphotericin B deoxycholate or a lipid formulation of amphotericin B as part of their treatment regimens. Most patients received amphotericin B followed by a prolonged course of oral azole therapy (voriconazole, fluconazole, or itraconazole). Four (18%) of 22 patients died during follow-up. CONCLUSIONS: On the basis of these data, we recommend initial treatment with a lipid formulation of amphotericin B followed by a prolonged course of oral azole therapy, preferably voriconazole.

Estrogens attenuate oxidative stress and the differentiation and apoptosis of osteoblasts by DNA-binding-independent actions of the ERalpha.

Estrogens diminish oxidative stress in bone and bone marrow, attenuate the generation of osteoblasts, and decrease the prevalence of mature osteoblast apoptosis. We have searched for the molecular mechanism of these effects using as tools a mouse model bearing an estrogen receptor alpha (ERalpha) knock-in mutation that prevents binding to DNA (ERalpha(NERKI/-)) and several osteoblast progenitor cell models expressing the wild-type ERalpha or the ERalpha(NERKI/-). We report that the ability of estrogens to diminish the generation of reactive oxygen species, stimulate the activity of glutathione reductase, and decrease the phosphorylation of p66(shc), as well as osteoblastogenesis and osteoblast number and apoptosis, were fully preserved in ERalpha(NERKI/-) mice, indicating that the DNA-binding function of the ERalpha is dispensable for all these effects. Consistent with the attenuation of osteoblastogenesis in this animal model, 17beta-estradiol attenuated bone morphogenetic protein 2 (BMP-2)-induced gene transcription and osteoblast commitment and differentiation in murine and human osteoblastic cell lines. Moreover, 17beta-estradiol attenuated BMP-2-induced differentiation of primary cultures of calvaria- or bone marrow-derived osteoblastic cells from ERalpha(NERKI/-) mice as effectively as in cells from wild-type littermates. The inhibitory effect of the hormone on BMP-2 signaling resulted from an ERalpha-mediated activation of ERKs and the phosphorylation of Smad1 at the linker region of the protein, which leads to proteasomal degradation. These results illustrate that the effects of estrogens on oxidative stress and the birth and death of osteoblasts do not require the binding of ERalpha to DNA response elements, but instead they result from the activation of cytoplasmic kinases.