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Objectives: MRI has allowed the study of mineral deposition in the brain throughout life and in disease. However, studies differ in their reporting of minerals on MRI for reasons that are unclear.Methods: We conducted a systematic review from 1985 to July 2011 to determine the appearance of iron, calcium, copper and manganese on MRI and CT and their reliability. We assessed which imaging investigations provided the most consistent results compared with histology.Results: Of 325 papers on minerals imaging, we included 46 studies that confirmed findings either directly or indirectly using a non-imaging method such as histology. Within this group, there was inconsistency in the identification of iron probably because of changes in its paramagnetic properties during its degradation. Iron appeared consistently hypointense only on T2*-weighted MRI, and along with calcified areas, hyperattenuated on CT. Appearance of copper, calcium and manganese, although consistently reported as hyperintense on T1-weighted MRI, was confirmed histologically in few studies. On T2-weighted imaging, calcified areas were always reported as hypointense, while the appearance of iron depended on the concentration, location and degradation stage.Conclusions: More work is required to improve the reliability of imaging methods to detect and differentiate brain mineral deposition accurately.Key Points: There is inconsistency in reporting the appearance of minerals on radiological images. • Only 46 studies confirmed mineral appearance using a non-imaging method. • Iron is the mineral more widely studied, consistently hypointense on T2*-weighted MRI. • T1-weighted MRI consistently reported copper, calcium and manganese hyperintense. • Calcium is consistently reported hypointense on T2-weighted MRI and hyperattenuating on CT. [ABSTRACT FROM AUTHOR]

Al-Anon World Service Office recruited nine experienced Al-Anon members to hold an online Al-Anon meeting in a chat room on the Web site of the primary author. A transcript of this meeting with commentary by the authors is published in its entirety in this article. This transcript offers first-hand data about the process of a Twelve Step meeting and the use of the Internet for the purpose of supporting recovery from addiction. The theme of the meeting, the Second Step of the Twelve Steps of recovery from addiction, illustrates the role of spirituality in recovery from addiction. This theme is also reflected in the group's process. [ABSTRACT FROM AUTHOR]

Al-Anon World Service Office recruited 11 experienced Al-Anon members to hold an online Al-Anon meeting in a chat room on the Web site of the primary author. A transcript of this meeting with commentary by the authors is published in its entirety in this paper. This transcript represents the first opportunity for a professional audience to have first-hand data about the process of a Twelve Step meeting without actually attending a face-to-face meeting. The paper also examines the implications of using the Internet for the purpose of supporting recovery from addiction. [ABSTRACT FROM AUTHOR]

The castor plant (Ricinus communis L.) is a versatile industrial oilseed crop with a diversity of sex patterns, its hybrid breeding for improving yield and high purity is still hampered by genetic instability of female and poor knowledge of sex expression mechanisms. To obtain some hints involved in sex expression and provide the basis for further insight into the molecular mechanisms of castor plant sex determination, we performed DGE analysis to investigate differences between the transcriptomes of apices and racemes derived from female (JXBM0705P) and monoecious (JXBM0705M) lines. A total of 18 DGE libraries were constructed from the apices and racemes of a wild monoecious line and its isogenic female derivative at three stages of apex development, in triplicate. Approximately 5.7 million clean tags per library were generated and mapped to the reference castor genome. Transcriptomic analysis showed that identical dynamic changes of gene expression were indicated in monoecious and female apical bud during its development from vegetation to reproduction, with more genes expressed at the raceme formation and infant raceme stages compare to the early leaf bud stage. More than 3 thousands of differentially expressed genes (DEGs) were detected in Ricinus apices at three developmental stages between two different sex types. A number of DEGs involved in hormone response and biosynthesis, especially auxin response and transport, transcription factors, signal transduction, histone demethylation/methylation, programmed cell death, and pollination, putatively associated with sex expression and reproduction were discovered, and the selected DEGs showed consistent expression between qRT-PCR validation and the DGE patterns. Most of those DEGs were suppressed at the early leaf stage in buds of the mutant, but then activated at the following transition stage (5-7-leaf stage) of buds in the mutant, and ultimately, the number of up-regulated DEGs was equal to that of down-regulation in the small raceme of the mutant. In this study, a large number of DEGs and some suggestions involved in sex expression and reproduction were discovered using DGE analysis, which provides large information and valuable hints for next insights into the molecular mechanism of sex determination. It is useful for other further studies in Ricinus.

The appearance of autoantibody to DNA followed sequentially by the disappearance of anti-DNA and appearance of DNA antigen in a patient with systemic lupus erythematosus demonstrated that autoantibodies participate in immune complex-mediated pathogenesis. Continuing studies showed that autoantibodies are also useful biomarkers in clinical diagnosis and important reagents for elucidating the structure and function of intracellular proteins in cell biology. Recently, autoantibodies to tumor-associated antigens have been identified in cancer, and these findings have expanded the field of cancer immunodiagnostics. [ABSTRACT FROM AUTHOR]

Objectives: Examine the understanding of terminologies and management patterns of bacillus Calmette-Guérin (BCG)-unresponsive nonmuscle invasive bladder cancer (NMIBC) in six territories in Asia-Pacific., Methods: This study involved two phases: (1) a survey with 32 urologists and 7 medical oncologists (MOs) and (2) a factorial experiment and in-depth interviews with 23 urologists and 2 MOs. All clinicians had ≥8 years' experience managing NMIBC patients in Australia, Hong Kong, Japan, South Korea, Singapore, and Taiwan. Data from Phase 1 were summarized using descriptive statistics; content and thematic analyses applied in Phase 2., Results: In phase 1, 35% of clinicians defined BCG-unresponsive as BCG-refractory, -relapse and -resistant, 6% defined it as BCG-refractory and -relapse; 22% classified BCG-failure as BCG-refractory, -relapse, -resistant, and when muscle-invasive bladder cancer is detected. If eligible and willing, 50% (interquartile range [IQR], 50%-80%) of BCG-unresponsive patients would undergo radical cystectomy (RC), and 50% (IQR 20%-50%) of RC-eligible patients would receive bladder-sparing treatment or surveillance. In phase 2, we found that 32%, 88%, and 48% of clinicians, respectively, used "BCG-unresponsive," "BCG-refractory," and "BCG-relapse" in clinical practice but with no consistent interpretation of the terms. Compared with EAU definitions, 8%-60% of clinicians appropriately classified 9 tumor types that are persistent or recurrent after adequate BCG. Fifty percent of clinicians mentioned a lack of bladder-preserving treatment that outperforms RC in quality of life as a reason to retreat BCG-unresponsive patients with BCG., Conclusions: Our study revealed varied understanding and application of BCG-unresponsive terminologies in practice. There is a need for a uniform and simple definition of BCG-unresponsive disease in Asia-Pacific., (© 2023 Merck Sharp & Dohme, LLC and The Authors. International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Urological Association.)

Objectives: To develop consensus on patient characteristics and disease-related factors considered in deciding treatment approaches for locally advanced head and neck squamous cell carcinoma (LA-HNSCC) based on real-world treatment patterns in 4 territories in Asia-Pacific., Methods: A three-round modified Delphi involving a multidisciplinary panel of HN surgeons, medical oncologists, and radiation oncologists was used. Of 41 panelists recruited, responses of 26 from Australia, Japan, Singapore, and Taiwan were analyzed. All panelists had ≥five years' experience managing LA-HNSCC patients and treated ≥15 patients with LA-HNSCC annually., Results: All statements on definitions of LA-HNSCC, treatment intolerance and cisplatin dosing reached consensus. 4 of 7 statements on unresectability, 2 of 4 on adjuvant chemoradiotherapy, 7 of 13 on induction chemotherapy, 1 of 8 on absolute contraindications and 7 of 11 on relative contraindications to high-dose cisplatin did not reach consensus. In all territories except Taiwan, high-dose cisplatin was preferred in definitive and adjuvant settings for patients with no contraindications to cisplatin; weekly cisplatin (40 mg/m 2 ) preferred for patients with relative contraindications to high-dose cisplatin. For Taiwan, the main treatment option was weekly cisplatin. For patients with absolute contraindications to cisplatin, carboplatin ± 5-fluorouracil or radiotherapy alone were preferred alternatives in both definitive and adjuvant settings., Conclusion: This multidisciplinary consensus provides insights into management of LA-HNSCC in Asia-Pacific based on patient- and disease-related factors that guide selection of treatment modality and systemic treatment. Despite strong consensus on use of cisplatin-based regimens, areas of non-consensus showed that variability in practice exists where there is limited evidence., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA., The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: Multiple clinical practice guidelines, conflicting evidence, and physician perceptions result in variations in risk stratification among patients with non-muscle-invasive bladder cancer (NMIBC). This study aims to describe the extent of this variation and its impact on management approaches in the Asia-Pacific region., Methods: We conducted a cross-sectional survey involving 32 urologists and seven medical oncologists with ≥8 years of experience managing early-stage bladder cancer patients across Australia, Hong Kong, Japan, South Korea, Singapore, and Taiwan. The physicians completed an anonymous questionnaire that assessed their risk stratification and respective management approaches, based on 19 NMIBC characteristics. For each NMIBC characteristic, they were required to select one risk group, and their most preferred management approach., Results: Our results demonstrated a higher consensus on risk classification versus management approaches. More than 50% of the respondents agreed on the risk classification of all NMIBC characteristics, but 42% or fewer chose the same treatment option as their preferred choice for all but two characteristics-existence of variant histology (55%) and persistent high-grade T1 disease on repeat resection (52%). Across territories, there was the greatest variation in preferred treatment options (i.e., no treatment, intravesical chemotherapy, or Bacillus Calmette-Guérin [BCG] treatment) for intermediate-risk patients and the highest consensus on the treatment of very high-risk patients, namely radical cystectomy., Conclusions: Our study revealed considerable variation in risk stratification and management of NMIBC in the region. It is critical to develop practical algorithms to facilitate the recognition of NMIBC and standardize the treatment of NMIBC patients., (© 2023 Merck Sharp & Dohme LLC, and The Authors. International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Urological Association.)

Objective: To compare the predictive performance of Epic Systems Corporation's proprietary intensive care unit (ICU) mortality risk model (IMRM) with that of the Acute Physiology and Chronic Health Evaluation (APACHE) IV score., Methods: This is a retrospective cohort study of patients treated from January 1, 2008, through January 1, 2018. This single-center study was performed at Mayo Clinic (Rochester, MN), a tertiary care teaching and referral center. The primary outcome was death in the ICU. Discrimination of each risk model for hospital mortality was assessed by comparing area under the receiver operating characteristic curve (AUROC)., Results: The cohort mostly comprised older patients (median age, 64 years) and men (56.7%). The mortality rate of the cohort was 3.5% (2251 of 63,775 patients). The AUROC for mortality prediction was 89.7% (95% CI, 89.5% to 89.9%) for the IMRM, which was significantly greater than the AUROC of 88.2% (95% CI, 87.9% to 88.4%) for APACHE IV ( P <.001)., Conclusion: The IMRM was superior to the commonly used APACHE IV score and may be easily integrated into electronic health records at any hospital using Epic software., (© 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc.)

Competing Interests: Competing interests: None declared.

Objective: To describe and compare the clinical presentation, management, and outcomes of cardiovascular implantable electronic device (CIED) infections due to gram-negative bacteria (GNB) and CIED infections due to gram-positive bacteria (GPB)., Patients and Methods: We retrospectively reviewed all CIED infection cases at Mayo Clinic from January 1, 1992, through December 31, 2015. Cases were classified based on positive microbiology data from extracted devices or blood cultures., Results: Of the 623 CIED infections during the study period, 31 (5.0%) were caused by GNB and 323 (51.8%) by GPB. Patients in the GNB group were more likely to present with local inflammatory findings at the pocket site (90.3% vs 72.4%; P=.03). All patients with bacteremia due to GNB had concomitant pocket infection compared with those with GPB (100% vs 33.9%; P=.002). After extraction, 41.9% of patients in the GNB group were managed with oral antibiotics vs 2.4% in the GPB group (P<.001). There were no statistically significant differences in infection relapse/recurrence or 1-year survival rates between the 2 groups., Conclusion: Compared with CIED infections caused by GPB, those due to GNB are more likely to present with pocket infection. Device-related GNB bacteremia almost always originates from the generator pocket. After extraction, oral antibiotic drug therapy may be a reasonable option in select cases of pocket infections due to GNB. No difference in outcomes was observed between the 2 groups., (Copyright © 2018 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

A 51-year-old man with a medical history of coronary artery disease and dyslipidaemia presented with acute myocardial infarction resulting in cardiogenic shock, necessitating intra-aortic balloon pump placement and extracorporeal membrane oxygenation (ECMO). His hospital course was complicated by several infectious complications including ECMO circuit Pseudomonas aeruginosa bloodstream infection and presumed infected right atrial thrombus. He subsequently underwent urgent left ventricular assist device placement and had a prolonged hospital stay. On day 100 of admission, he developed acute hypoxic respiratory distress with new pulmonary infiltrates. Sputum cultures grew Cryptococcus neoformans Blood culture also grew C. neoformans after 96 hours of incubation and cryptococcal serum antigen was elevated at 1:20. Cerebrospinal fluid studies from a lumbar puncture were normal. He was treated with 2 weeks of combination antifungal therapy followed by life-long fluconazole suppression., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Immunocompromised travelers (ICTs) are medically complex and challenging for travel medicine providers. Our study hypothesizes that ICTs have high-risk travel itineraries and do not have adequate immunity against vaccine-preventable infections., Methods: This retrospective review of 321 ICTs from 2004 to 2015 included patients with solid organ transplant (SOT, n = 134), connective tissue disease (CTD, n = 121), inflammatory bowel disease (IBD, n = 46), and human immunodeficiency virus (HIV, n = 20). Variables included immunosuppressive medications, hepatitis A and B vaccination and serology, gamma-globulin use, and antimalarial and antidiarrheal prophylaxis. Chi-square analysis was used for categorical variables and Kruskal-Wallis for continuous variables., Results: Malaria-endemic regions accounted for 38.9% (125/321) of travel destinations. High-risk activities were planned by 37.4% (120/321) of travelers. A significant proportion of HIV patients [70.0% (14/20)] visited friends and relatives, whereas other ICTs traveled for tourism. Hepatitis A and B vaccination rates were 77.3% (248/321) and 72.3% (232/321). Post-vaccination hepatitis A and B serologic testing were completed by 66.1% (41/62) and 61.1% (11/18) of travelers, respectively., Conclusion: ICTs demonstrate differences in travel patterns and risk. Serologic testing was uncommon, and vaccination rates were low. Providers should screen ICTs early for upcoming travel plans and advise vaccine completion prior to departure., (Copyright © 2018 Australasian College for Infection Prevention and Control. Published by Elsevier B.V. All rights reserved.)

Background: International travelers are at high risk of acquiring travelers' diarrhea. Pre-travel consultation has been associated with lower rates of malaria, hepatitis, and human immunodeficiency virus (HIV) infections. The objective was to study the impact of pre-travel consultation on clinical management and outcomes of travelers' diarrhea., Methods: This retrospective cohort study analyzed 1160 patients diagnosed with travelers' diarrhea at Mayo Clinic Rochester, MN from 1994 to 2017. Variables included high-risk activities, post-travel care utilization, antimicrobial prescriptions, hospitalizations, and complications. Travelers were divided into those who sought ( n  = 256) and did not seek ( n  = 904) pre-travel consultation. The two groups were compared using the Wilcoxon test for continuous variables and chi-square test for categorical variables. Multivariate logistic regression was used to adjust for differences in traveler characteristics., Results: More pre-travel consultation recipients were young Caucasians who had more post-travel infectious disease (ID) consultation [OR 3.1 (95% CI 1.9-5.3)], more stool sampling [OR 1.6 (95% CI 1.1-2.4)], and more antimicrobial prescriptions [OR 1.6 (95% CI 1.1-2.5)] for travelers' diarrhea compared to the non-pre-travel consultation group. The pre-travel consultation group had shorter hospital stays (mean 1.8 days for pre-travel versus 3.3 days for non-pre-travel consultation group, p  = 0.006) and reduced gastroenterology consultation rates [OR 0.4 (95% CI 0.2-0.9)]. 23 patients with positive stool cultures had Campylobacter susceptibilities performed; 65% (15/23) demonstrated intermediate susceptibility or resistance to ciprofloxacin., Conclusion: Pre-travel consultation was associated with higher rates of stool testing and antimicrobial prescriptions. The high rate of quinolone-resistant Campylobacter in our small sample suggests the need for judicious antimicrobial utilization. The pre-travel consultation group did have a shorter duration of hospitalization and reduced need for gastroenterology consultation for prolonged or severe symptoms, which are positive outcomes that reflect reduced morbidity of travelers' diarrhea., Competing Interests: Given that this was a retrospective chart review with no patient contact or intervention, the risk to our study subjects was deemed minimal, and a consent waiver was obtained from the Mayo Clinic Institutional Review Board.Consent for publication is not applicable as protected health information did not accompany this manuscript.The authors have no conflicts of interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: Multiple antigen miniarrays used for detecting autoantibodies to tumor-associated antigens (TAAs) can be a useful approach for cancer detection and diagnosis. We here address a very specific question: might there be autoimmune responses to TAAs which precede clinical detection of hepatocellular carcinoma (HCC) in HBV and HCV chronic liver disease patients under continuous medical surveillance, and if so, could these anti-TAAs be added to the armamentarium of diagnostic tests?, Methods: We here examine the utility of a panel of 12 TAAs for the diagnosis of hepatocellular carcinoma (HCC). We derived a predictive rule for the presence of HCC based on the panel, from a cohort comprising 160 HCC patients and 90 normals. We then applied this rule to sequential anti-TAA data from a cohort of 17 HCC patients, from whom this information was available prior to diagnosis., Results: The predictors (autoantibodies to HCC1, P16, P53, P90, and survivin) indicated the presence of HCC prior to diagnosis in 16 of the 17 patients, at a median lead time of 0.75 year., Conclusions: We believe these findings warrant further study of anti-TAA profiles as biomarkers for primary or early diagnosis of HCC.

Introduction: Multiple formulae have been proposed for calculating orotracheal depth for paediatric intubation. However, literature on the validation of these formulae in the emergency department setting is limited. Three methods described in the local Advanced Paediatric Life Support curriculum include the Broselow tape, endotracheal tube (ETT) size x 3, and the age-based formula of age divided by 2, add 12. We aimed to determine their accuracy., Materials and Methods: Patients with intubation performed in the Children's Emergency from 1 January 2009 to 31 December 2013 were included in this retrospective observational study. The depths of ETT placement based on the formulae were calculated from the actual depth of ETT. ETT position between T2 to T4 vertebral bodies of the chest radiograph was taken as the reference position for radiological accuracy., Results: ETT size x 3 has the highest accuracy of 76.5%, as compared to 67.9% for age-based formula and 63.5% for Broselow tape. When the formulae were inaccurate, Broselow tape often predicted a depth that was too shallow as compared to ETT size x 3 ( P = 0.006) and age-based formula ( P = 0.011). The accuracy of Broselow tape was not uniform across the age groups, with highest accuracy in patients 1 to 8 years old. ETT size x 3 had the highest accuracy in patients weighing more than 25 kg., Conclusion: ETT size x 3 was superior for determining orotracheal intubation depth but cannot preclude the confirmation of appropriate placement of ETT by auscultation and chest radiograph.

Background: Patients with limited English proficiency (LEP) and type 2 diabetes mellitus (T2DM) have several health disparities, including suboptimal patient-provider interactions, poorer glycemic control, and T2DM complications. Understanding existing interventions for improving T2DM outcomes in this population is critical for reducing disparities., Methods: We performed a systematic review of randomized controlled trials (RCTs) and observational studies examining the effectiveness of interventions in improving T2DM outcomes among patients with LEP in North America. Quality was assessed using the Cochrane risk of bias tool for RCTs and the Newcastle-Ottawa Scale for non-RCT studies. Meta-analysis was conducted using the random-effects model., Results: Fifty-four studies, 39 of which reported sufficient data for meta-analysis of glycemic control, were included. The interventions were associated with a statistically significant reduction in hemoglobin A 1c (HbA 1c ) (weighted difference in means, -0.84% [95% CI, -0.97 to -0.71]) that was, however, very heterogeneous across studies (I 2  = 95.9%). Heterogeneity was explained by study design (lower efficacy in RCTs than non-RCTs) and by intervention length and delivery mode (greater reduction in interventions lasting <6 months or delivered face-to-face); P < 0.05 for all three covariates. The interventions were also associated in most studies with improvement in knowledge, self-efficacy in diabetes management, quality of life, blood pressure, and low-density lipoprotein cholesterol., Discussion: Multiple types of interventions are available for T2DM management in patients with LEP. Multicomponent interventions delivered face-to-face seem most effective for glycemic control. More research is needed to better understand other aspects of multicomponent interventions that are critical for improving important outcomes among patients with T2DM and LEP.

Background: Botulism is a rare, potentially severe illness, often fatal if not appropriately treated. Data on treatment are sparse. We systematically evaluated the literature on botulinum antitoxin and other treatments., Methods: We conducted a systematic literature review of published articles in PubMed via Medline, Web of Science, Embase, Ovid, and Cumulative Index to Nursing and Allied Health Literature, and included all studies that reported on the clinical course and treatment for foodborne botulism. Articles were reviewed by 2 independent reviewers and independently abstracted for treatment type and toxin exposure. We conducted a meta-analysis on the effect of timing of antitoxin administration, antitoxin type, and toxin exposure type., Results: We identified 235 articles that met the inclusion criteria, published between 1923 and 2016. Study quality was variable. Few (27%) case series reported sufficient data for inclusion in meta-analysis. Reduced mortality was associated with any antitoxin treatment (odds ratio [OR], 0.16; 95% confidence interval [CI], .09-.30) and antitoxin treatment within 48 hours of illness onset (OR, 0.12; 95% CI, .03-.41). Data did not allow assessment of critical care impact, including ventilator support, on survival. Therapeutic agents other than antitoxin offered no clear benefit. Patient characteristics did not predict poor outcomes. We did not identify an interval beyond which antitoxin was not beneficial., Conclusions: Published studies on botulism treatment are relatively sparse and of low quality. Timely administration of antitoxin reduces mortality; despite appropriate treatment with antitoxin, some patients suffer respiratory failure. Prompt antitoxin administration and meticulous intensive care are essential for optimal outcome., (Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Erysipelothrix rhusiopathiae is a facultatively anaerobic Gram-positive bacillus found mostly in swine, fish and sheep. E. rhusiopathiae classically causes cutaneous eruptions in butchers, fish handlers and veterinarians. Based solely on case reports, 90% of E. rhusiopathiae bloodstream infections (BSI) have been associated with infective endocarditis (IE). To assess the true frequency of IE in E. rhusiopathiae BSI as well as other clinical associations, we performed a retrospective cohort analysis of E. rhusiopathiae BSI at Mayo Clinic. This is a single-centre, retrospective study conducted between 1/1/1994 and 20/6/2016 at Mayo Clinic in Rochester, MN. Medical records were reviewed for demographics, E. rhusiopathiae BSI, anti-microbial susceptibilities, incidence of IE, patient comorbidities, intensive care unit (ICU) admission and duration of antibiotics. Five cases of E. rhusiopathiae BSI were identified. Risk factors included animal exposures, immunosuppression, diabetes and kidney disease. All cases involved penicillin-sensitive strains and high-grade BSI. Four cases showed no signs of IE on transesophageal echocardiogram. All patients recovered fully with intravenous antibiotics. Our retrospective review illustrates that E. rhusiopathiae can cause invasive BSI in the absence of IE and that the previously reported 90% association between BSI and IE may be overestimated due to reporting bias. E. rhusiopathiae should be suspected in any patient with Gram-positive bacilli in blood cultures and the aforementioned risk factors. A limitation of our study was the low sample size, and future studies may involve multicentre collaborations and the use of polymerase chain reaction (PCR) or serologic testing to increase the number of diagnoses.., (© 2017 Blackwell Verlag GmbH.)

Purpose: Cardiovascular implantable electronic device infection (CIEDI) rates are rising. To improve outcomes, our institution developed an online care process model (CPM) and a specialized inpatient heart rhythm service (HRS)., Methods: This retrospective review compared hospital length of stay (LOS), mortality, and times to subspecialty consultation and procedures before and after CPM and HRS availability., Results: CPM use was associated with shortened time to surgical consultation (median 2 days post-CPM vs. 3 days pre-CPM, p = 0.0152), pocket closure (median 4 vs. 5 days, p < 0.0001), and days to new CIED implant (median 7 vs. 8 days, p = 0.0126). Post-HRS patients were more likely to have a surgical consultation (OR 7.01, 95% CI 1.56-31.5, p = 0.011) and shortened time to pocket closure (coefficient - 2.21 days, 95% CI - 3.33 to - 1.09, p < 0.001), compared to pre-HRS., Conclusions: The CPM and HRS were associated with favorable outcomes, but further integration of CPM features into hospital workflow is needed.

Nonpurulent lower extremity cellulitis (NLEC) is a common clinical diagnosis, with β-hemolytic streptococci and Staphylococcus aureus considered to be the most frequent causes. In 1999, the US Public Health Service alerted clinicians to the presence of community-acquired methicillin-resistant S aureus (CA-MRSA) infections in 4 children in the upper Midwest. Since then, it has become a well-recognized cause of skin and soft-tissue infections, in particular, skin abscess. A previous population-based study of NLEC in Olmsted County, Minnesota, reported an unadjusted incidence rate of 199 per 100,000 person-years in 1999, but it is unknown whether CA-MRSA subsequently has affected NLEC incidence. We, therefore, sought to determine the population-based incidence of NLEC since the emergence of CA-MRSA. Age- and sex-adjusted incidence (per 100,000 persons) of NLEC was 176.6 (95% CI, 151.5-201.7). Incidence differed significantly between sexes with age-adjusted sex-specific rates of 133.3 (95% CI, 104.1-162.5) and 225.8 (95% CI, 183.5-268.0) in females and males, respectively. Seasonal incidence differed, with rates of 224.6 (95% CI, 180.9-268.4) in warmer months (May-September) compared with 142.3 (95% CI, 112.8-171.9) in colder months (January-April and October-December). Despite emergence and nationwide spread of CA-MRSA since 1999 in the United States, the incidence of NLEC in Olmsted County was lower in 2013 than in 1999, particularly in females. This suggests that CA-MRSA is not a significant cause of NLEC and that NLEC cases are seasonally distributed. These findings may be important in formulation of empirical therapy for NLEC and in patient education because many patients with NLEC are prone to recurrent bouts of this infection., (Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background.: Most cardiovascular implantable electronic device (CIED) recipients are elderly, have multiple comorbid conditions, and are at increased risk of CIED infection (CIEDI). Current guidelines recommend complete device removal in patients with CIEDI to prevent relapse and mortality. However, comorbidities or other factors may preclude device removal, thus prompting a nonsurgical approach that includes chronic antibiotic suppression (CAS). There are limited data on outcomes of patients receiving CAS for CIEDI., Methods.: We retrospectively screened 660 CIEDI cases from 2005 to 2015 using electronic health records and a CIEDI institutional database and identified 48 patients prescribed CAS. Primary outcomes were infection relapse and survival., Results.: The median age was 78 years, and 73% (35/48) were male. The median Charlson comorbidity index was 4. Common pathogens were coagulase-negative staphylococci (21%, 10/48) and methicillin-sensitive Staphylococcus aureus (19%, 9/48). At 1 month after hospitalization, 25% (12/48) of patients had died, of whom only 1 initiated CAS; 67% (8/12) of these had staphylococcal infections. Of the 37 patients who initiated CAS, the most common antimicrobials were trimethoprim-sulfamethoxazole, penicillin, and amoxicillin (22%, 8/37 each). Estimated median overall survival was 1.43 years (95% confidence interval, 0.27-2.14), with 18% (6/33 survivors) developing relapse within 1 year. Of the 6 patients who relapsed, 2 (33%) subsequently underwent CIED extraction., Conclusion.: CAS is reasonable in select patients who are not candidates for complete device removal for attempted cure of CIEDI. Nevertheless, 1-month mortality in our sample of CAS-eligible patients was high and reflective of high rates of comorbid conditions., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com)

Mycobacterium iranicum is a newly reported nontuberculous mycobacterial (NTM) species that has been previously isolated in twelve patients. Our report presents the thirteenth known case of M. iranicum , which caused septic arthritis of the right third proximal interphalangeal joint and associated tenosynovitis in a 39-year-old female following a rose thorn injury., (© 2017 The Authors.)

Given the limitations of current therapeutic options for postmenopausal osteoporosis, there is a need for alternatives with minimal adverse effects. In this study, we evaluated the effects of icaritin (ICT), a natural prenylflavonoid, on osteoclastogenesis both in vitro and in an ovariectomized (OVX) rat model and investigated its underlying molecular mechanism(s) of action. ICT inhibited osteoclast formation in two osteoclast precursor models, RAW 264.7 mouse monocyte cell line and human PBMC. ICT also inhibited sealing zone and resorption pit formation in a dose-dependent manner. Mechanistically, ICT inhibited RANKL-induced NF-κB and MAPK/AP-1 pathways to suppress gene expression of nuclear factor of activated T cells (NFAT)c1, the master transcription regulator of osteoclast differentiation. ICT, by inhibiting the TRAF6/c-Src/PI3K pathway, suppressed NADPH oxidase-1 activation to attenuate intracellular ROS production and downregulate calcineurin phosphatase activity. As a result, NFATc1 nuclear translocation and activity was suppressed. Crucially, ICT promoted proteasomal degradation of TRAF6, the critical adaptor protein that transduces RANKL/RANK signaling, and the inhibitory effect of ICT on osteoclastogenesis was reversed by the proteasomal inhibitor MG 132. ICT administration inhibited OVX-induced bone loss and resorption by suppressing osteoclast formation and activity. Consistent with cellular studies, ICT downregulated TRAF6 and NFATc1 protein expression in CD11b + /Gr-1 -/low osteoclast precursors isolated from OVX rats. Put together, we present novel findings that ICT, by downregulating TRAF6, coordinates inhibition of NF-κB, MAPK/AP-1, and ROS signaling pathways to reduce expression and activity of NFATc1. These results demonstrate the potential of ICT for treatment of postmenopausal osteoporosis and point to TRAF6 as a promising target for novel anti-osteoporotic drugs. © 2017 American Society for Bone and Mineral Research., (© 2017 American Society for Bone and Mineral Research.)

Identification of biomarkers for early detection of lung cancer (LC) is important, in turn leading to more effective treatment and reduction of mortality. Serological proteome analysis (SERPA) was used to identify proteins around 34 kD as ECH1 and HNRNPA2B1, which had been recognized by serum autoantibody from 25 LC patients. In the validation study, including 90 sera from LC patients and 89 sera from normal individuals, autoantibody to ECH1 achieved an area under the curve (AUC) of 0.799 with sensitivity of 62.2% and specificity of 95.5% in discriminating LC from normal individuals, and showed negative correlation with tumor size ( r s = -0.256, p = 0.023). Autoantibody to HNRNPA2B1 performed an AUC of 0.874 with sensitivity of 72.2% and specificity of 95.5%, and showed negative correlation with lymph node metastasis ( r s = -0.279, p = 0.012). By using longitudinal preclinical samples, autoantibody to ECH1 showed an AUC of 0.763 with sensitivity of 60.0% and specificity of 89.3% in distinguishing early stage LC from matched normal controls, and elevated autoantibody levels could be detected greater than 2 y before LC diagnosis. ECH1 and HNRNPA2B1 are autoantigens that elicit autoimmune responses in LC and their autoantibody can be the potential biomarkers for the early detection of LC.

Aim: We investigated the expression of neuropeptide Y (NPY), NPY receptor 1 (NPYR1) and NPY receptor 2 (NPYR2) in infantile haemangiomas (IHs)., Methods: Immunohistochemical (IHC) staining was performed on proliferating IHs from six patients aged 4-13 (mean 8.7) months and involuted IHs from six patients aged 5-59 (mean 18.7) years, for the expression of NPY, NPYR1 and NPYR2. Protein and messenger ribonucleic acid expression corresponding to these proteins was investigated by Western blotting and NanoString analysis, respectively., Results: IHC staining, Western blotting and NanoString analysis demonstrated the presence of NPYR1, but not NPYR2, within proliferating and involuted IHs. IHC staining showed NPYR1 was expressed by B and T lymphocytes expressing CD45 and mast cells expressing tryptase. IHC staining demonstrated the presence of NPY on the NPYR1 + cells, but it was not detected by Western blotting or NanoString analysis., Conclusion: NPYR1, but not NPYR2, was present in IHs. The localisation of NPYR1 to B and T lymphocytes and mast cells suggests its role in the biology of IHs. The demonstration of NPY on the NPYR1 + cells, without active transcription, suggests that NPY was not being produced within IHs., (©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

We examined the prevalence of cardiovascular risk factors among Somali refugees at a midwestern hospital in the U.S. This was a retrospective cohort study of 1007 adult Somali patients and an age and frequency-matched cohort of non-Somali patients actively empanelled to a large, academic primary care practice network in the Midwest United States between January 1, 2011 and December 31, 2012. Cardiovascular risk factors were obtained by chart review and compared between the two cohorts using a Chi squared test. Median age was 35 years (Q1, Q3; 27, 50). The prevalence of diabetes was significantly higher among Somali versus non-Somali patients (12.1 vs 5.3 %; p = 0.0001), as was prediabetes (21.3 vs 17.2 %; p < 0.02) and obesity (34.6 vs 32.1 %; p = 0.047). After adjusting for age, sex, body mass index, education and employment, among the Somali patients, the odds ratio (95 % confidence interval) for diabetes was 2.78 (1.76-4.40) and 1.57 (1.16-2.13) for pre-diabetes. There was a significantly higher prevalence of diabetes, pre-diabetes and obesity among Somali patients compared with non-Somali patients. Further research into the specific causes of these disparities and development of targeted effective and sustainable interventions to address them is needed.

When studies on rheumatoid arthritis (RA) that were made many decades ago and could be considered "historical" in nature are analyzed in the context of recent observations, important insights on RA and on the function of rheumatoid factor (RF) become apparent. RF in the role of antibody to immune complexes (ICs) appears to be involved in activation of the complement system and in the production of chemotactic and inflammatory mediators, creating a condition that can be sustained and reinitiated. In the synovial cavity, a state of nonresolving inflammation is produced with the formation of citrullinated protein antigen-antibody complexes or other forms of ICs. This is followed by a second wave of IC production in the form of RF acting as antibody reactive with the initial ICs. Both of these processes are associated with complement consumption and production of inflammatory mediators. We present a model of an initiation phase of RA that might represent an example of repetitive formation of ICs and complement-mediated inflammation. Targeting therapy at this phase of RA to break the cycles of recurrent inflammation might be a novel approach to aid in further control of the disease., (© 2016 Tan and Smolen.)

Objectives: Autoantibodies against tumor-associated antigens (TAAs) identified in patients with advanced lung cancer may be detected in subjects with early lung cancer or even predate the diagnosis. The purpose of this study is to address the temporal relationship between lung cancer development and serum autoantibody response., Materials and Methods: Two cohorts of patients with newly diagnosed lung cancer were included. The first cohort included 90 sera from patients with lung cancer (Stages I-III) and 89 normal control sera. In the second cohort, 93 serial serum samples from 25 patients with CT-scan screen-detected stage I lung cancer were collected before the diagnosis of lung cancer (average 32 months) and 56 controls were matched on age, gender, and smoking. Autoantibody levels were measured by immunoassay., Results: Measurement of autoantibodies against seven TAAs (14-3-3ζ, c-Myc, MDM2, NPM1, p16, p53 and cyclin B1) individually could discriminate lung cancer patients from normal individuals in the first cohort and the area under curve (AUC) was 0.863 based on a panel of seven autoantibodies, with sensitivity of 68.9% and specificity of 79.5%. Autoantibodies in serial pre-diagnostic serum samples against the same panel of seven TAAs were detected prior to lung cancer diagnosis with sensitivity of 76.0% and specificity of 73.2% (AUC) (95%CI): 0.885 (0.797-0.973)). Elevated autoantibody levels could be detected greater than four years prior to lung cancer diagnosis., Conclusion: A panel of seven TAAs may enhance the early detection of lung cancer, consistent with a humoral immune response to TAAs that can be detected months to years prior to the diagnosis., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Universal human immunodeficiency virus (HIV) screening remains low in many clinical practices despite published guidelines recommending screening for all patients between ages 13-65. Electronic clinical decision support tools have improved screening rates for many chronic diseases. We designed a quality improvement project to improve the rate of universal HIV screening of adult patients in a Midwest primary care practice using a clinical decision support tool., Methods: We conducted this quality improvement project in Rochester, Minnesota from January 1, 2014 to December 31, 2014. Baseline primary care practice HIV screening data were acquired from January 1, 2014 to April 30, 2014. We surveyed providers and educated them about current CDC recommended screening guidelines. We then added an HIV screening alert to an existing electronic clinical decision support tool and post-intervention HIV screening rates were obtained from May 1, 2014 to December 31, 2014. The primary quality outcome being assessed was change in universal HIV screening rates., Results: Twelve thousand five hundred ninety-six unique patients were eligible for HIV screening in 2014; 327 were screened for HIV. 6,070 and 6,526 patients were seen before and after the intervention, respectively. 1.80 % of eligible patients and 3.34 % of eligible patients were screened prior to and after the intervention, respectively (difference of -1.54 % [-2.1 %, -0.99 %], p < 0.0001); OR 1.89 (1.50, 2.38). Prior to the intervention, African Americans were more likely to have been screened for HIV (OR 3.86 (2.22, 6.71; p < 0.001) than Whites, but this effect decreased significantly after the intervention (OR 1.90 (1.12, 3.21; p = 0.03)., Conclusions: These data showed that an electronic alert almost doubled the rates of universal HIV screening by primary care providers in a Midwestern practice and reduced racial disparities, but there is still substantial room for improvement in universal screening practices. Opportunities for universal HIV screening remain abundant, as many providers either do not understand the importance of screening average risk patients or do not remember to discuss it. Alerts to remind providers of current guidelines and help identify screening opportunities can be helpful.

Neuroendocrine prostate cancer (NEPC) has a poor prognosis, with a median survival of less than 1 year after diagnosis. Following androgen deprivation therapy, prostate adenocarcinoma cells have been observed to develop an androgen receptor-negative, terminally differentiated and indolent neuroendocrine-like phenotype. However, several molecular events, including interleukin 6 (IL-6) stimulation, in the prostate microenvironment result in the appearance of aggressive, highly proliferative castrate-resistant NEPC. In this study, we examined the mechanistic effects of a natural prenylflavonoid, icaritin (ICT), on neuroendocrine differentiation in IL-6-induced LNCaP cells and NEPC development in the male transgenic adenocarcinoma of the mouse prostate (TRAMP) model. TRAMP mice received daily intraperitoneal injection of ICT or vehicle. ICT induced apoptosis in prostate tumor, suppressed NEPC development and, accordingly, improved overall survival in TRAMP mice. Expression of neuroendocrine markers (synaptophysin) and androgen receptor in TRAMP mice and neuroendocrine-like LNCaP cells were inhibited by ICT. Suppression of neuroendocrine and NEPC development by ICT was associated with dose-dependent inhibitory effects on abnormally elevated IL-6/STAT3 and Aurora kinase A in vitro and in vivo Since ICT demonstrated favorable pharmacokinetic and safety profiles with marked enrichment in prostate tissues, our study provides evidence for the development of prenylflavonoid as a multimodal therapeutic agent against NEPC., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose: CAPERα, a tumor-associated antigen, was identified from a cDNA clone with autoantibody from a patient with hepatocellular carcinoma (HCC). It has been implicated, by way of alternative splicing of VEGF pre-mRNA, in the regulation of microvessel formation in Ewing's sarcoma. In this study, we looked for possible association of alterations in CAPERα with microvessel density in HCC., Methods: Enzyme-linked immunosorbent assay using recombinant CAPERα as antigen were used to detect antibody against CAPERα. Immunohistochemistry (IHC) on liver sections was performed to analyze expression profiles of CAPERα, VEGF and CD34 in HCC and control tissues and was further used to assess the correlation of expression among CAPERα, VEGF and CD34 in HCC development., Results: Autoantibody to CAPERα was highest in HCC (22/76, 28.9%), not detected in prostate cancer (0/79) and at 3.4% (3/88) in breast cancer. In immunohistochemical analysis of grades II and III HCC tissues, significantly decreased immunostaining for CAPERα was observed and this correlated directly with decreased immunostaining for VEGF (R=0.534, P=0.0003). Using CD34 immunostaining for detecting newly formed microvessels, strong staining was observed in grades II and III HCC. Normal liver sections, all of which have high expression of CAPERα were totally negative for CD34 immunostaining. A significant inverse correlation was seen between CAPERα and CD34 immunostaining (R=-0.481, P=0.0012)., Conclusions: Decreased expression of CAPERα appears to be correlated with appearance of microvessels. It would be of interest to elucidate the cause of altered CAPERα since new formation of microvessels is important in progression of HCC.

Background: Risk factors for and optimal surveillance of renal dysfunction in patients on tenofovir disoproxil fumarate (TDF) remain unclear. We investigated whether a urine protein-osmolality (P/O) ratio would be associated with renal dysfunction in HIV-infected persons on TDF., Methods: This retrospective, single-center study investigated the relationship between parameters of renal function (estimated glomerular filtration rate (eGFR) and P/O-ratio) and risk factors for development of kidney dysfunction. Subjects were HIV-infected adults receiving TDF with at least one urinalysis and serum creatinine performed between 2010 and 2013. Regression analyses were used to analyze risk factors associated with abnormal P/O-ratio and abnormal eGFR during TDF therapy., Results: Patients were predominately male (81%); (65%) were Caucasian. Mean age was 45.1(±11.8) years; median [IQR] TDF duration was 3.3 years. [1.5-7.6]. Median CD4+ T cell count and HIV viral load were 451 cells/μL [267.5-721.5] and 62 copies/mL [0-40,150], respectively. Abnormal P/O-ratio was not associated with low eGFR. 68% of subjects had an abnormal P/O-ratio and 9% had low eGFR. Duration of TDF use, age, diabetes and hypertension were associated with renal dysfunction in this study. After adjustment for age, subjects on TDF > 5 years had almost a four-fold increased likelihood of having an abnormal P/O-ratio than subjects on TDF for < 1yr (OR 3.9; 95% CI 1.2-14.0; p = 0.024)., Conclusion: Abnormal P/O-ratio is common in HIV-infected patients on TDF but was not significantly associated with low eGFR, suggesting that abnormal P/O-ratio may be a very early biomarker of decreased renal function in HIV infected patients.

Hepatitis C virus (HCV) genotype 4 accounts for 8-13% of all chronic HCV infections worldwide. Patients with HCV genotype 4 have been reported to have poor treatment responses to PEGylated interferon and ribavirin regimens. Recently a single tablet, fixed-dose combination of sofosbuvir, an RNA-directed RNA polymerase (NS5B) inhibitor, and ledipasvir, a nonstructural protein 5A (NS5A) inhibitor, has been approved for treatment of chronic HCV infection. Two studies using the fixed-dose combination in chronic HCV genotype 4 for 12 weeks reported sustained virologic response rates at 12 weeks (SVR12) of 93-95%. Data also support the use of ledipasvir/sofosbuvir in chronic HCV genotype 4 and HIV co-infection. Administered as a single once-daily oral regimen, this ribavirin- and interferon-free regimen is well tolerated, with low potential for adverse effects and represents a significant advancement in the treatment of chronic HCV genotype 4 infection., (Copyright 2016 Prous Science, S.A.U. or its licensors. All rights reserved.)

A 39-year-old male, who recently underwent a composite valve graft of the aortic root and ascending aorta for bicuspid aortic valve and aortic root aneurysm, was hospitalized for severe sepsis, rhabdomyolysis (creatine kinase 29000 U/L), and severe liver dysfunction (AST > 7000 U/L, ALT 4228 U/L, and INR > 10). Cardiac magnetic resonance imaging (MRI) findings were consistent with sternal osteomyelitis with a 1.5 cm abscess at the inferior sternotomy margin, which was contiguous with pericardial thickening. Aspiration and culture of this abscess did not yield any organisms, so he was treated with vancomycin and cefepime empirically for 4 weeks. Because this patient was improving clinically on antibiotics and did not show external signs of wound infection, there was no compelling indication for sternectomy. This patient's unusual presentation with osteomyelitis and rhabdomyolysis has never been reported and is crucial for clinicians to recognize in order to prevent delays in diagnosis.

Case: A 73-year-old immunocompromised male presented with recurrent left elbow swelling due to Mycobacterium avium intracellulare complex (MAC) olecranon bursitis. 3 years after completing MAC treatment, he underwent right total knee arthroplasty (TKA). 1 year later, he developed TKA pain and swelling and was diagnosed with MAC prosthetic joint infection (PJI). He underwent TKA resection, reimplantation, and 12 months of anti-MAC therapy. This patient is the seventh case report of MAC olecranon bursitis and the third case report of MAC PJI. He is the only report of both MAC olecranon bursitis and PJI occurring in the same patient., Informed Consent: This patient was informed and agreed to the publication of this material., (© 2015 Published by Elsevier Ltd.)

Aims: Interstitial CD45+ cells and T lymphocytes have previously been demonstrated within infantile haemangioma (IH). This study investigated the expression of B and T lymphocyte markers by the CD45+ population, and the expression of Thy-1, a marker of thymocyte progenitors, which have the ability to give rise to both B and T cells., Methods: Immunohistochemical (IHC) staining was performed on proliferating and involuted IHs for the expression of CD45, CD3, CD20, CD79a, Thy-1 and CD34. The presence of mRNA corresponding to CD45, CD3G, CD20 and Thy-1 was confirmed by reverse transcriptase-polymerase chain reaction in snap-frozen IH tissues. Cell counting of 3,3-diaminobenzidine IHC-stained slides was performed on CD45+ only cells and dually stained CD45+/CD3+ cells or CD45+/CD20+ cells and analysed statistically. In situ hybridisation and mass spectrometry were also performed to confirm the presence and abundance of Thy-1, respectively., Results: IHC staining showed a subpopulation of CD45+ interstitial cells that expressed the T lymphocyte marker, CD3, and another subpopulation that expressed the B lymphocyte marker, CD20, in proliferating and diminished in involuted IHs. The abundant expression of Thy-1 on the endothelium of proliferating, but not involuted IH, was demonstrated by IHC staining and confirmed by in situ hybridisation and mass spectrometry., Conclusions: Both B and T lymphocytes are present within the interstitium of proliferating and involuted IH. The expression of Thy-1 by the endothelium suggests that B and T cells in IH may have originated from within the lesion, rather than migrating from the peripheral circulation., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Aims: Cells expressing markers of mast cells, macrophages and dendritic cells have previously been demonstrated within the interstitium of infantile haemangioma (IH). This study characterised these myeloid cellular subpopulations within IH., Methods: Immunohistochemical staining was performed on proliferating and involuted IHs for the expression of Nanog, tryptase, CD163, DC-SIGN and CD45. The presence of mRNA corresponding to Nanog, tryptase α/β-1, tryptase β-2, CD163 and DC-SIGN was confirmed by NanoString and RT-PCR in snap-frozen IH tissues., Results: Immunohistochemical staining showed expression of Nanog by interstitial phenotypical mast cells within proliferating IH, which were separate from the interstitial M2-polarised macrophages that also expressed DC-SIGN, a dendritic cell marker. These two myeloid cellular subpopulations in IH did not express the pan-haematopoietic marker, CD45., Conclusions: There are two interstitial subpopulations of myeloid cells within IH: phenotypical mast cells which also express Nanog, indicating a primitive phenotype; and M2-polarised macrophages which also express DC-SIGN., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

A 26-year-old woman with paranoid schizophrenia was admitted to the medical intensive care unit with septic shock requiring intubation and mechanical ventilation. The source of septic shock was not identified despite obtaining CT of the chest/abdomen/pelvis, bronchoalveolar lavage and microbiological results for tracheal secretions, blood, urine and cervix. An indium-111 tagged white cell count scan was subsequently performed, revealing increased right anterior deltoid uptake. Owing to serial increases (up to 1310 U/L) in serum creatine kinase and a history of local intramuscular paliperidone injections for management of schizophrenia, surgical exploration was performed and identified necrotising skeletal muscle inflammation and extensive fat necrosis with an organising abscess, consistent with pyomyositis. A gram stain of purulent fluid revealed gram-positive cocci, but no organisms grew in culture. The patient recovered after 10 days of daptomycin and 7 weeks of wound care. Paliperidone injections were discontinued and oral risperidone was initiated., (2015 BMJ Publishing Group Ltd.)

A 68-year-old avid deer hunter with ischemic cardiomyopathy underwent left ventricular assist device (LVAD) implantation for destination therapy two years ago. He was living an active lifestyle, tracking deer and fishing in a Midwestern forest in November. His wife removed an engorged tick on his thorax. A few days later, he experienced fever, confusion, and ataxia and was hospitalized with septic shock and ventricular fibrillation. The LVAD site had no signs of trauma, drainage, warmth, or tenderness. A peripheral blood smear revealed intraleukocytic anaplasma microcolony inclusions. After completing 14 days of doxycycline, he recovered. Typical non-device-associated infections in LVAD recipients include pneumonia, urinary tract infection, or Clostridium difficile colitis. Human granulocytic anaplasmosis (HGA) is a very atypical non-LVAD infection, and the incidence of tickborne illnesses in LVAD recipients is unknown.