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OBJECTIVE: The objective of this study was to investigate variations across hospitals in infection rates and associated costs, the latter reflected in 90-day Medicare payments. Despite high rates and expenditures of healthcare-associated infections associated with durable ventricular assist device implant, few studies have examined inter-hospital variation and associated costs. METHODS: Clinical data on 8688 patients who received primary durable ventricular assist devices from July 2008 to July 2017 from The Society of Thoracic Surgeons Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs) hospitals (n=120) were merged with post-implant 90-day Medicare claims. Terciles of hospital-specific, risk-adjusted infection rates per 100 patient-months were estimated using Intermacs and associated with Medicare payments (among 5440 Medicare beneficiaries). Primary outcomes included infections within 90 days of implant and Medicare payments. RESULTS: There were 3982 infections identified among 27.8% (2,417/8,688) of patients developing an infection. The median (25(th), 75(th) percentile) adjusted incidence of infections (per 100 patient-months) across hospitals was 14.3 (9.3, 19.5) and varied by hospital (range 0.0 – 35.6). Total Medicare payments from implant to 90-days were 9.0% (absolute difference: $13,652) greater in high versus low infection tercile hospitals, p

Objective Infections are among the most common complications in recipients of durable left ventricular assist devices (LVAD). However, existing studies examining infections in LVAD recipients are limited is size and design. Comprehensive, systematic reviews of all types of infections occurring among recipients of contemporary LVADs have not been conducted. The goal of this scoping review was to synthesize all available evidence related to rates of infections (including location and types) in LVAD recipients. Methods In February 2019, 4,581 published studies were identified through searching five bibliographic databases: PubMed, Scopus, EMBASE, CINAHL and Web of Science Core Collection. Inclusion criteria required reporting of infectious complications among LVAD recipients receiving contemporary (HeartMate II, HeartMate 3 and HeartWare HVAD) LVADs. Study key characteristics were extracted by 2 independent reviewers and current literature described narratively. All analyses took place between Feb 2019 and Jan 2021. Results A total of 132 studies met inclusion criteria. Most studies were observational (n=118; 89.4%), single-center (n=93, 70.4%) and from the U.S. (n=88; 66.7%). Only 48 (36.3%) studies used the standardized International Society for Heart and Lung Transplantation (ISHLT) definition for reporting infections. Only 35 (26.5%) studies reported age, gender and racial distribution of their study population. Driveline infections were the most commonly reported infection type. Conclusions Most studies did not utilize standardized infection definitions or provide complete information on infection locations and types. In order to further advance the scientific rigor, published studies should (i) use standardized definitions for reporting infections and (ii) stratify rates by infection location and type.

Failure to rescue (FTR), defined as death after a complication, is recognized as a principal driver of variation in mortality among hospitals. We evaluated FTR as a quality metric in patients who received durable left ventricular assist devices (LVADs) using the Society of Thoracic Surgeons Interagency Registry for Mechanically Assisted Circulatory Support.Data on 13,617 patients who received primary durable LVADs from April 2012 to October 2017 at 131 hospitals that performed at least 20 implants were analyzed from the Society of Thoracic Surgeons Interagency Registry for Mechanically Assisted Circulatory Support. Rates of major complications and FTR were compared across risk-adjusted in-hospital mortality terciles (low, medium, high) and hospital volume. Logistic regression was used to estimate expected FTR rates on the basis of patient factors for each major complication.The overall unadjusted in-hospital mortality rate was 6.96%. Risk-adjusted in-hospital mortality rates varied 3.1-fold across terciles (low, 3.3%; high, 10.3%; P trend.001). Rates of major complications varied 1.1-fold (low, 34.0%; high, 38.8%; P .0001). Among patients with a major complication, 854 died in-hospital for an FTR rate of 17.7%, with 2.8-fold variation across mortality terciles (low, 8.5%; high, 23.9%; P .0001). FTR rates were highest for renal dysfunction requiring dialysis (45.3%) and stroke (36.5%). Higher average annual LVAD volume was associated with higher rates of major complications (10 per year, 26.7%; 10-20 per year, 34.0%; 20-30 per year, 34.0%;30 per year, 40.1%; P trend.0001) whereas hospitals implanting10 per year had the highest FTR rate (10 per year, 23.5%; 10-20 per year, 16.5%; 20-30 per year, 17.0%;30 per year, 17.9%; P = .03).FTR might serve as an important quality metric for durable LVAD implant procedures, and identifying strategies for successful rescue after complications might reduce hospital variations in mortality.

Background As public health personnel and resources are redirected to COVID-19, sexually transmitted diseases (STD) programs have been unable to sustain pre-COVID-19 activities. Methods We used California (CA) surveillance data to describe trends in case reporting for gonorrhea, chlamydia, and syphilis of any stage in the pre- versus post-COVID-19 eras (January-June 2019 and January-June 2020). We also analyzed data from an electronic survey administered by the CA STD Control Branch to local health jurisdictions in April, June, and September of 2020, assessing the impact of COVID-19 on STD programs. Results There were sharp declines in cases of all reportable bacterial STDs occurring in conjunction with the March 19, 2020 CA stay-at-home order, most of which did not return to baseline by July. Comparing January-June 2020 to January-June of 2019, there were decreases in reported cases of chlamydia (31%), late syphilis (19%), primary/secondary syphilis (15%), early nonprimary nonsecondary syphilis (14%), and gonorrhea (13%). The largest percentage declines in STD case reporting were among Hispanic, Asian/Pacific Islander, and Black persons. Seventy-eight percent of local health jurisdiction respondents indicated that half or more of their workforce had been redeployed to COVID-19 by September 2020. Conclusions During the COVID-19 era, STD case reporting and programmatic functions have diminished throughout CA. Because this may contribute to decreases or delays in STD diagnosis and treatment-with resultant increases in STD transmission-providers and public health officials should prepare for potential increases in STD-related morbidity in the months and years to come.

Women with a history of ductal carcinoma in situ (DCIS) have an elevated risk of a subsequent invasive breast cancer, but there are few established potentially modifiable factors known to lower this risk. Bisphosphonates are a commonly used treatment for patients with osteoporosis and have been shown to lower risks of recurrence and mortality in patients with invasive breast cancer; however, their use has not previously been investigated within the context of DCIS. Utilizing a population-based nested case–control design, we compared 301 cases of women diagnosed with DCIS and a subsequent breast cancer and 587 individually matched controls (on age, DCIS diagnosis year, primary treatment, histology, grade, and disease-free survival time) who were diagnosed with DCIS but never a subsequent breast cancer. Information on recency and duration of bisphosphonate use was ascertained from patient interviews and medical record reviews. Current users of bisphosphonates had a reduced risk of developing an invasive breast cancer compared with never users [OR = 0.50; 95% confidence interval (CI): 0.26–0.99]. Users of bisphosphonates for ≥48 months had a similar reduction in risk (OR = 0.45; 95% CI, 0.24–1.06). This is the first study to document that bisphosphonate use is associated with a lower risk of subsequent invasive breast cancer among women with a history of DCIS. This finding is consistent with the protective effect of bisphosphonates observed in other breast cancer settings. If validated by others, bisphosphonates may be an effective risk-reducing approach with the potential added benefits of its positive impacts on bone health and fracture risk. Significance: This study finds that bisphosphonate use among women with a history of DCIS is associated with lower risk of subsequent invasive breast cancer, providing a potential preventative approach for this high-risk population.

Purpose: Basal-like breast cancer (BLBC) is a particularly aggressive intrinsic molecular subtype of breast cancer that lacks targeted therapies. There is also no clinically useful test to risk stratify patients with BLBC. We hypothesized that a transcriptome-based phenotypic characterization of BLBC tumors and their microenvironments may overcome these challenges. Experimental Design: We conducted a retrospective correlative genomic sequencing study using a matched pairs design with validation in five independent cohorts. The study was conducted on a large population-based prospective cohort of the major molecular subtypes of breast cancer conducted in the greater Seattle-Puget Sound metropolitan area. Cases consisted of women 20–69 years of age first diagnosed with invasive breast cancer identified through the population-based Surveillance Epidemiology and End Results program. Patients for this analysis (n = 949) were identified from the 1,408 patients with stage I–III triple-negative breast cancer [estrogen receptor–negative (ER−), progesterone receptor–negative (PR−), HER2−]. Of the 949 women, 248 developed a recurrence after their initial diagnosis. A matched set of 67 recurrent and nonrecurrent BLBC tumors was subjected to transcriptome sequencing. Through RNA sequencing of the matched sets of recurrent and nonrecurrent BLBC tumors, we aimed to identify prognostic phenotypes. To identify nonredundant and uncorrelated prognostic genes, we used an ensemble of variable selection algorithms, which resulted in a ranking of genes on the basis of their expected utility in classification. Using leave-one-out cross-validation, we trained a random forest classifier on the basis of the top 21 genes (BRAVO-DX). Validations were performed in five independent triple-negative or BLBC cohorts, and biomarker robustness and transferability were demonstrated by employing real-time PCR. Results: We found that cancer cell intrinsic and immunologic phenotypes are independent predictors of recurrence. By simultaneously interrogating the tumor and its microenvironment, we developed a compound risk model that stratified patients into low-, medium-, and high-risk groups, with a 14%/56%/74% chance of recurrence, respectively. Biologically, the primary tumors of patients who developed a recurrence had increased growth factor signaling and stem-like features, while nonrecurrent tumors showed high lymphocyte infiltration with clonal expansion of T and B cells, as well as antitumor polarization of macrophages. We validated our model in five independent cohorts, including three large cohorts, where BRAVO-DX was highly informative in identifying patients with disease recurrence [HR, 6.79 (95% confidence interval (CI), 1.89–24.37); HR, 3.45 (95% CI, 2.41–4.93); and HR, 1.69 (95% CI, 1.17–2.46)]. A smaller gene set focused on the tumor immunophenotype, BRAVO-IMMUNE, was highly prognostic in all five cohorts. Conclusions: Together, these results indicate that phenotypic characteristics of BLBCs and their microenvironment are associated with recurrence-free survival and demonstrate the utility of intrinsic and extrinsic phenotypes as independent prognostic biomarkers in BLBC. Pending further evaluation and validation, our prognostic model has the potential to inform clinical decision-making for patients with BLBC as it identifies those at high risk of rapidly progressing on standard chemotherapy, as well as those who may benefit from alternative first-line therapies.

Previous multi-center imaging studies with 18F-FDG PET have established the presence of Parkinson's disease motor- and cognition-related metabolic patterns termed PDRP and PDCP in patients with this disorder. Given that in PD cerebral perfusion and glucose metabolism are typically coupled in the absence of medication, we determined whether subject expression of these disease networks can be quantified in early-phase images from dynamic 18F-FPCIT PET scans acquired to assess striatal dopamine transporter (DAT) binding. Methods: We studied a cohort of early-stage PD patients and age-matched healthy control subjects who underwent 18F-FPCIT at baseline; scans were repeated 4 years later in a smaller subset of patients. The early 18F-FPCIT frames, which reflect cerebral perfusion, were used to compute PDRP and PDCP expression (subject scores) in each subject, and compared to analogous measures computed based on 18F-FDG PET scan when additionally available. The late 18F-FPCIT frames were used to measure caudate and putamen DAT binding in the same individuals. Results: PDRP subject scores from early-phase 18F-FPCIT and 18F-FDG scans were elevated and striatal DAT binding reduced in PD versus healthy subjects. The PDRP scores from 18F-FPCIT correlated with clinical motor ratings, disease duration, and with corresponding measures from 18F-FDG PET. In addition to correlating with disease duration and analogous 18F-FDG PET values, PDCP scores correlated with DAT binding in the caudate/anterior putamen. PDRP and PDCP subject scores using either method rose over 4 years whereas striatal DAT binding declined over the same time period. Conclusion: Early-phase images obtained with 18F-FPCIT PET can provide an alternative to 18F-FDG PET for PD network quantification. This technique therefore allows PDRP/PDCP expression and caudate/putamen DAT binding to be evaluated with a single tracer in one scanning session.

Objective We examined for improvements in preoperative moderate mitral regurgitation following continuous-flow left ventricular assist device (cfLVAD) implantation. Methods From 2006 to 2020, 190 patients with moderate MR underwent cfVLAD implant without concomitant mitral valve (MV) surgery. Cardiac dimensions and contractility, as well as valve function, were assessed with an echocardiogram (echo) pre-cfLVAD, and at approximately 1 month post-cfLVAD. Outcomes were determined by retrospective chart review. Results Median echo follow-up was 0.94 (0.53, 1.38) months. Residual significant moderate or greater MR was present in 30/190 (15.8%) on follow-up. Patients with significant residual MR had larger preoperative left ventricular internal diameters in diastole (74.4 ± 8.7 vs. 71.1.0 ± 9.1 mm, p = .034). Significant residual MR was associated with higher preoperative mean pulmonary artery pressures (OR = 1.055, p = .035) and pulmonary capillary wedge pressures (OR = 1.060, p = .034). Significant residual MR on echo was not associated with any survival difference (p = .325). The 1, 5, and 10 year survival were 89.9%, 55.2%, and 34.2%, respectively. Conclusions For patients with moderate MR undergoing LVAD implantation, the likelihood of significant residual MR is low and mitral intervention in this population is not recommended. However, select patients with larger preoperative left heart dimensions and pulmonary vascular pressures may be at risk for persistent residual MR.

Recent studies on a rodent model of Parkinson’s disease (PD) have raised the possibility of increased blood–brain barrier (BBB) permeability, demonstrated by histology, autoradiography, and positron emission tomography (PET). However, in human PD patients, in vivo evidence of increased BBB permeability is lacking. We examined the hypothesis that levodopa treatment increases BBB permeability in human subjects with PD, particularly in those with levodopa-induced dyskinesia (LID). We used rubidium-82 (82Rb) and PET to quantify BBB influx in vivo in 19 PD patients, including eight with LID, and 12 age- and sex-matched healthy subjects. All subjects underwent baseline 82Rb scans. Seventeen chronically levodopa-treated patients were additionally rescanned during intravenous levodopa infusion. Influx rate constant, K1, by compartmental modeling or net influx transport, Ki, by graphical approach could not be estimated reliably. However, Vd, the “apparent volume of distribution” based on the 82Rb concentration in brain tissue and blood, was estimated with good stability as a local measure of the volume of distribution. Rubidium influx into brain tissue was undetectable in PD patients with or without LID, scanned on and off drug. No significant differences in regional Vd were observed for PD patients with or without LID relative to healthy subjects, except in left thalamus. Moreover, changes in Vd measured off- and on-levodopa infusion were also not significant for dyskinetic and non-dyskinetic subjects. 82Rb PET did not reveal significant changes in BBB permeability in PD patients.

Background: Parkinson’s disease (PD) is characterized by brain metabolic networks, specifically associated with motor and cognitive manifestations. Few studies have investigated network changes in cerebral hemispheres ipsilateral and contralateral to the clinically more affected body side. Objective: We examined hemispheric network abnormalities and their relationship to striatal dopaminergic deficits in PD patients at different stages. Methods: 45 PD patients underwent dual-tracer positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) and 18F-fluorodopa (FDOPA) in a high-resolution PET scanner. In all patients, we computed expression levels for the PD-related motor/cognition metabolic patterns (PDRP/PDCP) as well as putamen/caudate FDOPA uptake values in both hemispheres. Resulting hemispheric measures in the PD group were compared with corresponding healthy control values and assessed across disease stages. Results: Hemispheric PDRP and PDCP expression was significantly elevated contralateral and ipsilateral to the more affected body side in patients with unilateral symptoms (H&Y 1: p

The Systolic Blood Pressure Intervention Trial (SPRINT), a large randomized controlled trial funded by the National Institutes of Health, randomized 9361 patients with hypertension over 50 years of age and at least one cardiovascular risk factor to intensive (SBP

We report an unusual case of a patient with hypertrophic obstructive cardiomyopathy, anomalous aortic origin of a coronary artery, obesity hypoventilation syndrome, and acquired long QT syndrome who was able to defy the odds of sudden cardiac death in the rarest of circumstances. (Level of Difficulty: Advanced.), Graphical abstract, We report an unusual case of a patient with hypertrophic obstructive cardiomyopathy, anomalous aortic origin of a coronary artery, obesity…

Context and Objectives The Controlled Antenatal Thyroid Screening Study I (CATS-I) was a randomized controlled trial investigating the effects of levothyroxine therapy for suboptimal gestational thyroid function (SGTF), comparing outcomes in children of treated (SGTF-T) with untreated (SGTF-U) women during pregnancy. This follow-up study, CATS-II, reports the long-term effects on anthropometric, bone, and cardiometabolic outcomes in mothers and offspring and includes a group with normal gestational thyroid function (NGTF). Design & Participants 332 mothers (197 NGTF, 56 SGTF-U, 79 SGTF-T) aged 41.2±5.3 years (mean±SD) and 326 paired children assessed 9.3±1.0 years after birth for (i) body mass index (BMI); (ii) lean, fat, and bone mass by dual-energy X-ray absorptiometry; (iii) blood pressure, augmentation index, and aortic pulse-wave-velocity; and (iv) thyroid function, lipids, insulin, and adiponectin. The difference between group means was compared using linear regression. Results Offspring’s measurements were similar between groups. Although maternal BMI was similar between groups at CATS-I, after 9 years (at CATS-II) SGTF-U mothers showed higher BMI (median [interquartile ratio] 28.3 [24.6-32.6] kg/m2) compared with NGTF (25.8 [22.9-30.0] kg/m2; P = 0.029), driven by fat mass increase. At CATS-II SGTF-U mothers also had higher thyroid-stimulating hormone (TSH) values (2.45 [1.43-3.50] mU/L) than NGTF (1.54 [1.12-2.07] mU/L; P = 0.015), since 64% had never received levothyroxine. At CATS-II, SGTF-T mothers had BMI (25.8 [23.1-29.8] kg/m2, P = 0.672) and TSH (1.68 [0.89-2.96] mU/L; P = 0.474) values similar to NGTF mothers. Conclusions Levothyroxine supplementation of women with SGTF did not affect long-term offspring anthropometric, bone, and cardiometabolic measurements. However, absence of treatment was associated with sustained long-term increase in BMI and fat mass in women with SGTF.

Objective The optimal screening frequency of sexually transmitted infections (STIs) for MSM and transgender women (TGW) on HIV pre-exposure prophylaxis (PrEP) is unclear, with present guidelines recommending screening every 3-6 months. We aimed to determine the number of STIs for which treatment would have been delayed without quarterly screening. Design The US PrEP Demonstration Project was a prospective, open-label cohort study that evaluated PrEP delivery in STI clinics in San Francisco and Miami, and a community health center in Washington, DC. In all, 557 HIV-uninfected MSM and TGW were offered up to 48 weeks of PrEP and screened quarterly for STIs. Methods The proportion of gonorrhea, chlamydia, and syphilis infections for which treatment would have been delayed had screening been conducted every 6 versus every 3 months was determined by taking the number of asymptomatic STIs at weeks 12 and 36 divided by the total number of infections during the study follow-up period for each STI. Results Among the participants, 50.9% had an STI during follow-up. If screening had been conducted only semiannually or based on symptoms, identification of 34.3% of gonorrhea, 40.0% of chlamydia, and 20.4% of syphilis infections would have been delayed by up to 3 months. The vast majority of participants (89.2%) with asymptomatic STIs reported condomless anal sex and had a mean of 8.1 partners between quarterly visits. Conclusions Quarterly STI screening among MSM on PrEP could prevent a substantial number of partners from being exposed to asymptomatic STIs, and decrease transmission.

Background Various solutions are used for donor heart preservation. We examined the outcomes in our heart transplant population where histidine-tryptophan-ketoglutarate (HTK) solution has been used for heart preservation since 2004. Methods This was a retrospective review of the United Network for Organ Sharing (UNOS) database (2004-2016) comparing our heart transplant outcomes with other national centers. Propensity matching in a 1:3 ratio was performed to adjust for preoperative recipient variables. Results After propensity matching comparing UNOS outcomes (n = 1080) with our institutional data (n = 360), there was no difference in matched preoperative variables. Donor hearts were similar for donor age, sex, donor-to-recipient size ratio, LVEF, and ischemic time. Our HTK cohort had a larger proportion with donor cardiac arrest (26.3% vs 6.1%, P Conclusions Use of HTK solution for donor hearts was associated with a low rate of severe PGD. Overall survival was not significantly different from other institutions using a variety of preservation solutions in the UNOS database during the same period. HTK solution is efficacious for preservation of donor hearts.

Background Structural valve degeneration (SVD) is a major flaw of bioprostheses. An apparent increase in the SVD rate has been observed among patients who received the Trifecta bioprosthesis (Abbott Vascular, Santa Clara, CA). Methods This study retrospectively reviewed 1058 consecutive patients who underwent aortic valve placement with a stented bioprosthesis between January 2011 and December 2015. Patients were grouped into a Trifecta group (508 [48.0%] patients with Trifecta bioprostheses) and a non-Trifecta group (550 [52.0%] patients with other bioprostheses). Results Patients in the Trifecta group were older (69.7 years vs 64.6 years; P = .001), were more likely female (40.4% vs 28.0%; P = .001), more often had aortic stenosis (85.1% vs 77.1%; P = .001), and received smaller valves (23.0 mm vs 25.0 mm; P Conclusions The SVD rate of the Trifecta bioprosthesis has been greater than expected, compared with other bioprostheses, particularly in younger patients. In view of the large number of Trifecta bioprostheses implanted worldwide, further investigation involving other institutions is warranted.

Both routine sexually transmitted disease surveillance and administrative hospital data may be imperfect systems to understand the true morbidity of neurosyphilis within the California Project Area from 2016 to 2018. Supplemental digital content is available in the text., Accurate reporting of neurosyphilis diagnoses is important to quantify and monitor severe outcomes associated with infection of Treponemal pallidum. This analysis compared the demographic distribution of neurosyphilis diagnoses in sexually transmitted disease surveillance data with administrative hospital data in the California Project Area from 2016 to 2018. Although neurosyphilis morbidity was similar, significant differences were noted by sex, age group, race/ethnicity, and region. Both sexually transmitted disease surveillance and administrative hospital data may be imperfect systems to understand the true morbidity of neurosyphilis.

We examined cardiac features associated with residual mitral regurgitation (MR) following continuous-flow left ventricular assist device (cfLVAD) implant. From 2003 to 2017, 134 patients with severe MR underwent cfVLAD implant without mitral valve (MV) intervention. Echocardiographic (echo) assessment occurred pre-cfLVAD, early post-cfLVAD, and at last available echo. Ventricular and atrial volumes were calculated from established formulas and normalized to be predicted. Cluster analysis based on preoperative normalized left ventricular and atrial volumes, and MV height identified grades 1, 2, and 3 with progressively larger cardiac chamber sizes. Median early echo follow-up was 0.92 (0.55, 1.45) months and the last follow-up was 15.12 (5.28, 38.28) months. Mitral regurgitation improved early after cfLVAD by 2.10 ± 1.16 grades (p < 0.01). Mitral regurgitation severity at the last echocardiogram positively correlated with the preoperative left ventricular volume (p = 0.014, R = 0.212), left atrial volume (p = 0.007, R = 0.233), MV anteroposterior height (p = 0.032, R = 0.185), and MV mediolateral diameter (p = 0.043, R = 0.175). Morphologically, smaller grade 1 hearts were correlated with MR resolution at the late follow-up (p = 0.023). Late right ventricular failure (RVF) at the last clinical follow-up was less in grade 1 (4/48 [8.3%]) compared with grades 2 and 3 (26/86 [30.2%]), p = 0.004). Grade 1 cardiac dimensions correlates with improvement in severe MR and had less late RVF.

Brimonidine eye drops are frequently prescribed for the treatment of glaucoma and ocular hypertension in adults. Systemic toxicities including neurological side effects have been reported with its use, especially in the paediatric population. In this report, we present a case of encephalopathy secondary to the use of brimonidine eye drops in a patient with underlying advanced chronic kidney disease, who recovered promptly after drug cessation. Herein, we also review the pharmacokinetics of eye drops leading to their systemic side effects, especially in the context of renal impairment. We also explore the possibility of extracorporeal treatment, such as by haemodialysis, for the treatment of these manifestations. This case demonstrates the need to clarify a patient's drug history and stop offending medications early on in a patient with delirium, while treatments such as antidotes or extracorporeal treatment are being considered.

Objectives We examined for differences in pre–left ventricular assist device (LVAD) implantation myocardial transcriptome signatures among patients with different degrees of mitral regurgitation (MR). Methods Between January 2018 and October 2019, we collected left ventricular (LV) cores during durable LVAD implantation (n = 72). A retrospective chart review was performed. Total RNA was isolated from LV cores and used to construct cDNA sequence libraries. The libraries were sequenced with the NovaSeq system, and data were quantified using Kallisto. Gene Set Enrichment Analysis (GSEA) and Gene Ontology analyses were performed, with a false discovery rate Results Comparing patients with preoperative mild or less MR (n = 30) and those with moderate-severe MR (n = 42), the moderate-severe MR group weighted less (P = .004) and had more tricuspid valve repairs (P = .043), without differences in demographics or comorbidities. We then compared both groups with a group of human donor hearts without heart failure (n = 8). Compared with the donor hearts, there were 3985 differentially expressed genes (DEGs) for mild or less MR and 4587 DEGs for moderate-severe MR. Specifically altered genes included 448 DEGs for specific for mild or less MR and 1050 DEGs for moderate-severe MR. On GSEA, common regulated genes showed increased immune gene expression and reduced expression of contraction and energetic genes. Of the 1050 genes specific for moderate-severe MR, there were additional up-regulated genes related to inflammation and reduced expression of genes related to cellular proliferation. Conclusions Patients undergoing durable LVAD implantation with moderate-severe MR had increased activation of genes related to inflammation and reduction of cellular proliferation genes. This may have important implications for myocardial recovery.

Background Dysfunction and inflammation of hearts subjected to cold ischemic preservation may differ between left and right ventricles, suggesting distinct strategies for amelioration. Methods and Results Explanted murine hearts subjected to cold ischemia for 0, 4, or 8 h in preservation solution were assessed for function during 60 min of warm perfusion and then analyzed for cell death and inflammation by immunohistochemistry and western blotting and total RNA sequencing. Increased cold ischemic times led to greater left ventricle (LV) dysfunction compared to right ventricle (RV). The LV experienced greater cell death assessed by TUNEL+ cells and cleaved caspase‐3 expression (n = 4). While IL‐6 protein levels were upregulated in both LV and RV, IL‐1β, TNFα, IL‐10, and MyD88 were disproportionately increased in the LV. Inflammasome components (NOD‐, LRR‐, and pyrin domain‐containing protein 3 (NLRP3), adaptor molecule apoptosis‐associated speck‐like protein containing a CARD (ASC), cleaved caspase‐1) and products (cleaved IL‐1β and gasdermin D) were also more upregulated in the LV. Pathway analysis of RNA sequencing showed increased signaling related to tumor necrosis factor, interferon, and innate immunity with ex‐vivo ischemia, but no significant differences were found between the LV and RV. Human donor hearts showed comparable inflammatory responses to cold ischemia with greater LV increases of TNFα, IL‐10, and inflammasomes (n = 3). Conclusions Mouse hearts subjected to cold ischemia showed time‐dependent contractile dysfunction and increased cell death, inflammatory cytokine expression and inflammasome expression that are greater in the LV than RV. However, IL‐6 protein elevations and altered transcriptional profiles were similar in both ventricles. Similar changes are observed in human hearts., Increasing duration of murine donor heart storage with subsequent ex‐vivo perfusion using clinically utilized histidine‐tryptophan‐ketoglutarate preservation solution induced progressively higher expression of IL‐1β, MyD88, TNFα, IL‐6, MCP1, and inflammasome components. This inflammatory response was disproportionately greater in the left ventricle compared to the right ventricle. We confirm that LV contractility and relaxation were also degraded to a greater degree in the left ventricle compared to the right ventricle following progressively longer periods of preservation. Murine findings corroborated with results from human preserved donor hearts where we also observed selective upregulation of TNFα, MCP1, and inflammasome components (Nlrp3, cleaved IL‐1β‐p17) in the left ventricle compared to the right ventricle during cold preservation.

Regional changes in brain metabolism upgraded with measurements of specific metabolic brain patterns and automated diagnostic algorithms can help to differentiate among neurodegenerative parkinsonisms, but with few reports on pathological confirmation. Here we describe a parkinsonian patient with atypical presentation and 18F-FDG-PET imaging consistent with idiopathic Parkinson's disease. The latter was confirmed at the pathohistological examination.

Background An ideal imaging biomarker for a neurodegenerative disorder should be able to measure abnormalities in the earliest stages of the disease. Objective We investigated metabolic network changes in two independent cohorts of drug-naive Parkinson's disease (PD) patients who have not been exposed to dopaminergic medication. Methods We scanned 85 de novo, drug-naive PD patients and 85 age-matched healthy control subjects from Italy (n = 96) and the United States (n = 74) with [18 F]-fluorodeoxyglucose PET. All patients had clinical follow-ups to verify the diagnosis of idiopathic PD. Spatial covariance analysis was used to identify and validate de novo PD-related metabolic patterns in the Italian and U.S. cohorts. We compared the de novo PD-related metabolic patterns to the original PD-related pattern that was identified in more advanced patients who had been on chronic dopaminergic treatment. Results De novo PD-related metabolic patterns were identified in each of the two independent cohorts of drug-naive PD patients, and each differentiated PD patients from healthy control subjects. Expression values for these disease patterns were elevated in drug-naive PD patients relative to healthy controls in the identification as well as in each of the validation subgroups. The two de novo PD-related metabolic patterns were topographically very similar to each other and to the original PD-related pattern. Conclusions Reproducible PD-related patterns are expressed in de novo, drug-naive PD patients. In PD, disease-related metabolic patterns have stereotyped topographies that develop independently of chronic levodopa treatment. © 2019 International Parkinson and Movement Disorder Society.

Background: Type II diabetes and certain diabetes treatments have been observed to impact breast cancer risk. However, their associations with different breast cancer molecular subtype defined by estrogen receptor (ER)/progesterone receptor (PR)/HER2 status are unclear. Methods: We conducted a retrospective multi-center population-based case–case study consisting of 4,557 breast cancer cases to evaluate the impact of type II diabetes and diabetes medications on the risk of different breast cancer molecular subtypes [ER+/HER2−, ER+/HER2+, triple negative (ER−/PR−/HER2−), and HER2 overexpressing (H2E, ER−/PR−/HER2+)]. Using ER+/HER2− cases as the reference group, we estimated ORs and corresponding 95% confidence intervals (CI) for each subtype using polytomous logistic regression. Results: Compared with those without a diabetes history, women with type II diabetes had a 38% (95% CI, 1.01–1.89) increased odds of triple-negative breast cancer (TNBC). Current and longer term recent metformin use (13–24 months of treatment within the 24-month period prior to breast cancer diagnosis) was associated with elevated odds of TNBC (OR = 1.54; 95% CI, 1.07–2.22 and OR = 1.80; 95% CI, 1.13–2.85, respectively). Conclusions: The odds of having a triple-negative rather than ER+/HER2− breast cancer is greater for women with type II diabetes, and particularly for those who were users of metformin. This finding is supported by some preclinical data suggesting that diabetes may be more strongly associated with risk of triple-negative disease. Impact: Our study provides novel evidence regarding potential differential effects of type II diabetes and metformin use on risk of different molecular subtypes of breast cancer.

INTRODUCTION: Oral contraceptive use is a well-established risk factor for breast cancer and is common among reproductive-aged women in the United States. Its relationship with less common, more aggressive, molecular subtypes is less clear. METHODS: A population-based case-case analysis was conducted comparing three less common molecular subtypes to luminal A breast cancer among 1701 premenopausal cases aged 21–49 diagnosed with a first primary invasive breast cancer between 2004 and 2015. Medical record reviews and structured interviewer administered questionnaires were used to collect data on oral contraceptive use. Multinomial logistic regression was used to estimate odds ratios (OR) and corresponding 95% confidence intervals (95% CI) for recency of oral contraceptive use for each subtype of breast cancer. RESULTS: Current use of oral contraceptives and use within five years before diagnosis was associated with lower odds of H2E tumors compared to luminal A tumors [odds ratio (OR)=0.5, 95% confidence interval (CI): 0.3, 0.9 and OR=0.5, 95% CI: 0.4, 0.8, respectively] with increasing duration associated with decreasing odds (p for trend

Background HIV-associated neurocognitive disorder (HAND) remains prevalent in the era of combination antiretroviral therapy (cART). The prevalence of HAND in Hong Kong is not known. Methods Between 2013 and 2015, 98 treatment-naïve HIV-1-infected individuals were referred to and screened by the AIDS Clinical Service, Queen Elizabeth Hospital with (1) the International HIV Dementia Scale (IHDS), a screening tool that targets moderate to severe HAND, (2) the Montreal Cognitive Assessment (MoCA), a frequently used cognitive screening test and (3) the Patient Health Questionnare-9 (PHQ-9), a 9-item questionnaire that evaluates depression symptoms. Within the study period, 57 of them completed the second set of IHDS and MoCA at 6 months after baseline assessment. Results Most participants were male (94%), with a median age of 31 years. At baseline, 38 (39%) and 25 (26%) of them scored below the IHDS (≤10) and MoCA (25/26) cut-offs respectively. Poor IHDS performers also scored lower on MoCA (p = 0.039) but the correlation between IHDS and MoCA performance was weak (r = 0.29, p = 0.004). Up to a third of poor IHDS performers (13/38) showed moderate depression (PHQ-9 > 9). In the multivariable analysis, a lower education level (p = 0.088), a history of prior psychiatric illness (p = 0.091) and the presence of moderate depression (p = 0.079) tended to be significantly associated with poor IHDS performance. At follow-up, 54 out of 57 were on cART, of which 46 (85%) had achieved viral suppression. Their blood CD4+ T-lymphocytes and IHDS scores were higher at follow-up compared to baseline values (both p

Outcomes of non-small cell lung cancer (NSCLC) patients with chronic obstructive pulmonary disease (COPD n = 587) and interstitial lung disease (ILD n = 34) treated with curative-intent radiotherapy were retrospectively investigated. Presence of ILD but not decreased forced expiratory volume in 1-second correlated with poor overall survival. Increased breathlessness and oxygen requirements after radiotherapy were observed in severe/very severe COPD and ILD.

PURPOSE: Up to 25% of patients diagnosed as idiopathic Parkinson’s disease (IPD) have an atypical parkinsonian syndrome (APS). We had previously validated an automated image-based algorithm to discriminate between IPD, multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). While the algorithm was accurate with respect to the final clinical diagnosis after long term expert follow-up, its relationship to the initial referral diagnosis and to the neuropathological gold standard is not known. METHODS: Patients with an uncertain diagnosis of parkinsonism were referred for [(18)F]-fluorodeoxyglucose (FDG) PET to classify patients as IPD or as APS based on the automated algorithm. Patients were followed by a movement disorder specialist and subsequently underwent neuropathological examination. The image-based classification was compared to the neuropathological diagnosis in 15 patients with parkinsonism. RESULTS: At the time of referral to PET, the clinical impression was only 66.7% accurate. The algorithm correctly identified 80% of the cases as IPD or APS (p=0.02) and 87.5% of the APS cases as MSA or PSP (p=0.03). The final clinical diagnosis was 93.3% accurate (p

Aim Direct kidney involvement in B-cell lymphoproliferative disease is a rare disorder with only a few studies reported in Caucasian patients. The clinicopathological characteristics and outcome of this entity remain poorly described. Methods We retrospectively studied all adult Chinese patients who had histology-proven renal parenchymal infiltration by malignant B-cells between 1/1/2000 and 31/12/2018 at 2 tertiary hospitals in Hong Kong. Clinical, pathological and radiological data were collected from 20 patients. Follow-up data were analyzed until 31/12/2019. Results Median follow-up duration was 22 (1-171) months. Only 7 patients (35%) had established diagnosis of hematological cancer before kidney biopsy. Diffuse large B-cell lymphoma (DLBCL) was the most common subtype in our cohort (n=5, 25%). Others included low-grade B-cell lymphoma (n=11), intravascular large B-cell lymphoma (n=1), mantle cell lymphoma (n=1) and multiple myeloma (n=2). Fourteen patients (70%) presented with AKI while 12 patients (60%) had proteinuria. Seven patients (35%) had unilateral renal mass, 1 had bilateral renal masses and 1 had bilateral diffuse nephromegaly in computed tomography. Lymphomatous tubulointerstitial infiltration was the prevalent histological finding. Nine patients (45%) had coexisting renal lesions other than direct tumor infiltration. All but 1 patient received chemotherapy. Ten patients died and renal responders had a significantly better survival than non-renal responders (P=0.03). Conclusion Direct tumor infiltration can occur in a wide variety of B-cell lymphoproliferative disorders. Coexisting immunoglobulin-related nephropathy is frequently found. Renal biopsy is required for early diagnosis which allows timely and appropriate treatment. This article is protected by copyright. All rights reserved.

Background The opioid epidemic has seen a drastic increase in the incidence of drug-associated infective endocarditis (IE). No clinical tool exists to predict operative morbidity and mortality in patients undergoing surgery. Methods A multi-institutional database was reviewed between 2011 and 2018. Multivariate logistic regression was fitted in an automated stepwise fashion. The STratification risk analysis in OPerative management of drug-associated IE (STOP) score was constructed. Morbidity was defined as reintubation, prolonged ventilation, pneumonia, renal failure, dialysis, stroke, reoperation for bleeding, and a permanent pacemaker. Cross-validation provided an unbiased estimate of out-of-sample performance. Results A total of 1181 patients underwent surgery for drug-associated IE (median age, 39; interquartile range [IQR], 30-54, 386 women [32.7%], 341 reoperations for prosthetic valve endocarditis [28.9%], 316 patients with multivalve disease [26.8%]). Operative morbidity and mortality were 41.1% and 5.9%, respectively. Predictors of morbidity were dialysis (95% confidence interval [CI], 1.16-2.82), emergent intervention (1.83-4.73), multivalve procedure (1.01-1.98), causative organisms other than Streptococcus (1.09-2.02), and type of valve procedure performed [aortic valve procedure (1.07-2.15), mitral valve replacement (1.03-2.05), tricuspid valve replacement (1.21-2.60)]. Predictors of mortality were dialysis (1.29-5.74), active endocarditis (1.32-83), lung disease (1.25-5.43), emergent intervention (1.69-6.60), prosthetic valve endocarditis (1.24-3.69), aortic valve procedure (1.49-5.92) and multivalve disease (1.00-2.95). Variables maximizing explanatory power were translated into a scoring system. Each point increased odds of morbidity and mortality by 22.0% and 22.4% with an accuracy of 94.0% and 94.1%, respectively. Conclusion Drug-related IE is associated with significant morbidity and mortality. An easily-applied risk stratification score may aid in clinical decision-making.

Purpose To document the epidemiology, presentation, clinical interventions, and outcomes of paediatric glaucoma in Hong Kong. Methods This multicentre territory-wide retrospective study was performed by reviewing charts of patients with paediatric glaucoma in six clusters of the Hong Kong Hospital Authority and The Chinese University of Hong Kong from 2006 to 2015. Results This study included 150 eyes of 98 patients with paediatric glaucoma (presenting age: 5.2±5.7 years). Of them, 35 eyes (23.3%) had primary congenital glaucoma, 22 eyes (14.7%) had juvenile open-angle glaucoma, and 93 eyes (62.0%) had secondary glaucoma. The most prevalent types of secondary glaucoma were lens-related after cataract extraction (18.0%), Axenfeld-Rieger anomaly (5.3%), uveitis (5.3%), Sturge-Weber syndrome (4.7%), and traumatic (3.3%). The most common clinical presentations were parental concerns (20.7%) including cloudy cornea (12.7%) and tearing/photophobia (8.0%), followed by poor visual acuity (18.0%), high intraocular pressure (13.3%), and strabismus (6.0%). The follow-up duration was 8.46±6.51 years. Furthermore, 63.2% of eyes with primary glaucoma and 45.2% of eyes with secondary glaucoma were treated surgically. The final visual acuity was 0.90±0.98 LogMAR; intraocular pressure was 18.4±6.6 mm Hg; and number of glaucoma medications was 2.22±1.61. Conclusion Primary congenital glaucoma was most prevalent, followed by juvenile open-angle glaucoma and aphakic glaucoma. Most eyes with primary glaucoma required surgical treatment. Parental concerns were important clinical presentations. Basic assessments by healthcare providers to identify glaucoma signs (eg, poor visual acuity, high intraocular pressure, and strabismus) warranted prompt referral to an ophthalmologist.

BACKGROUND: Coronavirus disease 2019 (COVID-19) necessitated wide-scale adoption of telemedicine (TM) and restriction of in-person care. The impacts on allergy/immunology (A/I) care delivery are still being studied. OBJECTIVE: To describe the outcomes of rapid transition to TM-based care (video visit followed by in-person visits dedicated to diagnostic and therapeutic procedures when needed) at an academic A/I practice during COVID-19. METHODS: Demographic data were compared for patients originally scheduled for in-person visits between March 10, 2020, and April 30, 2020, who completed a video visit instead between March 10, 2020, and June 30, 2020, and those who did not. Appointment completion, diagnoses, and drug allergy and skin testing completion were compared for visits between March 10, 2020, and June 30, 2020, and 1 year prior (March 10, 2019-June 30, 2019). RESULTS: Sixty-nine percent (265 of 382) of patients originally scheduled between March 10, 2020, and April 30, 2020, were able to complete video visits. Patients who completed video visits were more likely to be white (52% vs 33%; P < .001), English-speaking (96% vs 89%; P = .01), and privately insured (70% vs 54%; P = .004). With TM-based care compared with in-person care, there were significant decreases in environmental and food skin testing completion rates (91% and 92% in 2019 vs 60% and 64% in 2020, respectively, P < .001). Drug allergy testing completed after internal referral remained low but comparable (51% in 2019 vs 52% in 2020). Transitioning nonprocedural visits to video allowed allergen immunotherapy and biologic injection visits to resume at a volume similar to pre-COVID. No COVID-19 infections resulted from in-clinic exposure. CONCLUSIONS: Although transitioning to TM-based care allowed continued A/I care delivery, strategies are needed to achieve higher testing completion rates and ensure video visits do not exacerbate existing health disparities.

Introduction: In heart transplantation, the supply of donor hearts is contributed by the short tolerable preservation period with risk for primary graft dysfunction. Understanding the differential biological responses to preservation between the left ventricle (LV) and right ventricle (RV) may provide critical insights. Methods: Murine donor hearts were infused with cold HTK solution and stored on ice for 0h, 4h and 8h followed by 90minutes perfusion with Krebs Buffer. The LV and RV were collected at the end of reperfusion for gene expression and protein analysis by RNA-sequencing and western blot. Results: Differential gene expression analysis showed that RV has 1092 upregulated genes and 291 downregulated genes compared to LV after cold storage followed by perfusion. GO analysis show that gene sets related to immune response (padj=7e-27), cell responses to interferon-beta (padj=8.90e-19) were enriched in RV upregulated genes (figure). We also confirmed the upregulation of immune response genes such IL1-β, Myd88 by qPCR and western blot. Moreover, we found that active β-catenin, a potential upstream regulator of IL1- β, also upregulated in RV. Wnt/β-catenin downstream target genes were also enriched in human donor RVs during prolonged preservation. Importantly, donor hearts from murine Myd88-/- showed reduced differences in the transcriptome of the LV vs RV (figure) and demonstrated improved heart function after prolonged cold storage with reperfusion. Conclusions: The RV demonstrates more extensive inflammatory response to storage compared to the LV. Selective upregulation of Wnt/β-catenin signaling in the RV may be important for enhancing this inflammatory response to preservation. Deficiency of MyD88 mediated innate immune signaling improved cardiac contractility after prolonged preservation and likely have important clinical implications for transplantation.

Robotic cardiac surgery addressing the mitral and tricuspid valves is a highly developed field offering multiple potential advantages regarding postoperative complications, valve repair rates, hospital length of stay, and rapid functional recovery compared with the conventional sternotomy approach for select patients. The unparalleled stereoscopic view within the heart and precision of robotic arms make robotic surgery a highly attractive minimally invasive approach, facilitating repair of even the most complex valvular pathology. Careful candidate selection and surgical planning are paramount to optimising the outcomes of those who undergo robotic valve surgery. As a team’s experience grows, the technique can be applied to a wider range of patients that may derive even greater benefit, such as those with significant comorbid conditions, ventricular dysfunction, and previous sternotomy. The goal of this review is to provide clinicians with a practical overview of the factors influencing a patient’s candidacy for robotic valve surgery. We discuss key issues such as preoperative diagnostic assessment, concerns regarding demographics and surgical pathology, and additional considerations relating to surgical exposure, cardiopulmonary bypass, and myocardial protection. Diligent patient assessment and a strong team-based approach are paramount to developing and maintaining a successful robotic valve surgery program, with the most seasoned teams being able to safely offer the technique to the vast majority of patients referred for mitral or tricuspid valve repair or replacement.

Background: Evidence-based breast cancer treatment guidelines recommend the most appropriate course of therapy based on tumor characteristics and extent of disease. Evaluating the multilevel factors associated with guideline discordance is critical to identifying strategies to eliminate breast cancer survival disparities. Methods: We identified females diagnosed with a first primary, stage I–III breast cancer between the ages of 20–69 years of age from the population-based Seattle-Puget Sound Surveillance, Epidemiology, and End Results registry. Participants completed a survey about social support, utilization of patient support services, hypothesized barriers to care, and initiation of breast cancer treatment. We used logistic regression to estimate odds ratios and 95% confidence intervals (CI). Results: Among 1,390 participants, 10% reported guideline-discordant care. In analyses adjusted for patient-level sociodemographic factors, individuals who did not have someone to go with them to appointments or drive them home (OR 1.96; 95% CI, 1.09–3.59) and those who had problems talking to their doctors or their staff (OR 2.03; 95% CI, 1.13–3.64) were more likely to be guideline discordant than those with social support or without such problems, respectively. Use of patient support services was associated with a 43% lower odds of guideline discordance (OR 0.57; 95% CI, 0.36–0.88). Conclusions: Although guideline discordance in this cohort of early-stage breast cancer survivors diagnosed Impact: This study supports extending the reach of interventions designed to improve guideline concordance.

Background Music therapy improves neuronal activity and connectivity of healthy persons and patients with clinical symptoms of neurological diseases like Parkinson’s disease, Alzheimer’s disease, and major depression. Despite the plethora of publications that have reported the positive effects of music interventions, little is known about how music improves neuronal activity and connectivity in afflicted patients. Methods For patients suffering from Parkinson’s disease (PD), we propose a daily 25-min music-based synchronous finger tapping (SFT) intervention for 8 weeks. Eligible participants with PD are split into two groups: an intervention group and a control arm. In addition, a third cohort of healthy controls will be recruited. Assessment of finger tapping performances, the Unified Parkinson’s Disease Rating Scale (UPDRS), an n-back test, the Montreal Cognitive Assessment (MoCA), as well as oxygenated hemoglobin (HbO2), deoxygenated hemoglobin (HbR), and total hemoglobin activation collected by functional near-infrared spectroscopy (fNIRS) are measured at baseline, week 4 (during), week 8 (post), and week 12 (retention) of the study. Data collected from the two PD groups are compared to baseline performances from healthy controls. Discussion This exploratory prospective trial study investigates the cortical neuronal activity and therapeutic effects associated with an auditory external cue used to induce automatic and implicit synchronous finger tapping in patients diagnosed with PD. The extent to which the intervention is effective may be dependent on the severity of the disease. The study’s findings are used to inform larger clinical studies for optimization and further exploration of the therapeutic effects of movement-based music therapy on neural activity in neurological diseases. Trial registration ClinicalTrials.gov NCT04212897. Registered on December 30, 2019. The participant recruitment and study protocol have received ethical approval from the First Affiliated Hospital of Dalian Medical University. The hospital Protocol Record number is PJ-KY-2019-123. The protocol was named “fNIRS Studies of Music Intervention of Parkinson’s Disease.” The current protocol is version 1.1, revised on September 1, 2020.

Parkinson’s disease and parkinsonian disorders can present with a variety of symptoms, and there is often a significant overlap between the different disorders. Diagnosis typically relies on clinical examination, especially at follow-up visits, which has limitations. Neuroimaging has played a major role in the elucidation of anatomical and functional abnormalities in different parkinsonian disorders. Various imaging techniques have been investigated for their potential to aid in diagnosis during routine clinical practice. In this chapter, we describe the use of functional imaging with PET and SPECT in the research of atypical parkinsonian syndromes (APS), including multiple system atrophy, progressive supranuclear palsy, and corticobasal degeneration. We focus on the utility of these imaging techniques to facilitate differential diagnosis and assess disease progression in patients with APS, especially in the early stages of disease.

A previously healthy 9-month-old girl presented to the emergency department for fever, rash, and decreased urine output for 3 days. She was in compensated shock: temperature of 39.6°C, heart rate of 168 beats per minute, and blood pressure of 130/63. Her examination was notable for a diffuse blanching rash. Laboratory studies showed an elevated procalcitonin of 21.74 ng/mL, normal white blood cell count of 7.90 K/µL, and elevated creatinine of 0.36 mg/dL. Urinalysis demonstrated large blood, negative nitrites, trace leukocyte esterase, and 30 to 49 white blood cells per high-power field. Renal ultrasound was consistent with pyelonephritis. Because of concern for septic shock, she was given 60 mL/kg of normal saline and ceftriaxone and transferred to the PICU. In the PICU, vancomycin was added on the first day of admission because of worsening clinical status. She required vasopressor support with epinephrine for 2 days. Her initial microbiologic evaluation was unrevealing: urine culture grew 1000 to 9000 colony-forming units of normal flora, blood culture was negative, and respiratory pathogen panel result was positive for rhinovirus. Abdominal ultrasound on hospital day 1 showed developing left perinephric abscesses. Her rash worsened, and she developed lip peeling and conjunctivitis on day 2, concerning for Kawasaki disease or a toxin-mediated process, typically caused by Staphylococcus aureus or Streptococcus pyogenes. Because it is unusual for either pathogen to cause pyelonephritis in infants, and because the patient had persistent fevers, a blood sample was sent for sequencing of microbial cell-free DNA (cfDNA) on day 3. On day 7, testing resulted with evidence of S aureus in the blood. She was switched from vancomycin and ceftriaxone to ceftaroline for methicillin-sensitive …

Objective To present clinicians at the point-of-care with real-world data on the effectiveness of various treatment options in a precision cohort of patients closely matched to the index patient. Materials and Methods We developed disease-specific, machine-learning, patient-similarity models for hypertension (HTN), type II diabetes mellitus (T2DM), and hyperlipidemia (HL) using data on approximately 2.5 million patients in a large medical group practice. For each identified decision point, an encounter during which the patient’s condition was not controlled, we compared the actual outcome of the treatment decision administered to that of the best-achieved outcome for similar patients in similar clinical situations. Results For the majority of decision points (66.8%, 59.0%, and 83.5% for HTN, T2DM, and HL, respectively), there were alternative treatment options administered to patients in the precision cohort that resulted in a significantly increased proportion of patients under control than the treatment option chosen for the index patient. The expected percentage of patients whose condition would have been controlled if the best-practice treatment option had been chosen would have been better than the actual percentage by: 36% (65.1% vs 48.0%, HTN), 68% (37.7% vs 22.5%, T2DM), and 138% (75.3% vs 31.7%, HL). Conclusion Clinical guidelines are primarily based on the results of randomized controlled trials, which apply to a homogeneous subject population. Providing the effectiveness of various treatment options used in a precision cohort of patients similar to the index patient can provide complementary information to tailor guideline recommendations for individual patients and potentially improve outcomes.

Background: Music therapy improves neuronal activity and connectivity of healthy persons and patients with clinical symptoms of neurological diseases like Parkinson’s Disease, Alzheimer’s Disease, and Major Depression. Despite the plethora of publications that have reported the positive effects of music interventions, little is known about how music improves neuronal activity and connectivity in afflicted patients. In this three-part series of studies, each of the three neurological disorders – (1) Parkinson’s Disease, (2) Alzheimer’s Disease, and (3) Major Depression – will be treated individually in detail. Methods: For patients suffering from Parkinson’s Disease (PD), we propose a daily 25-minute music-based synchronous finger tapping (SFT) intervention for 8-weeks. Participants will be each split into two groups: an intervention group and a control arm. Assessment of finger tapping performances, the Unified Parkinson’s Disease Rating Scale (UPDRS), an n-back test, the Montreal Cognitive Assessment (MoCA), as well as oxygenated- (HbO 2 ), deoxygenated- hemoglobin (HbR), and total hemoglobin activation collected by functional near-infrared spectroscopy (fNIRS) will be measured at baseline, week 4 (during), week 8 (post), and week 12 (retention) of the study. Data collected from the two PD groups will be compared to baseline performances from healthy controls.Discussion: The trial study investigates the cortical neuronal activity and therapeutic effects associated with an auditory external cue used to induce automatic and implicit synchronous finger tapping in patients diagnosed with PD. The extent to which the intervention is effective may be dependent on the severity of the disease.

Background Perineural invasion (PNI) is a high-risk feature of cutaneous squamous cell carcinoma (CSCC). Depths at which PNI occurs are unknown. Objective To determine the most superficial depth at which PNI occurs in CSCC and stratify by tumor clinical diameter and body location. Methods and materials Single-institution retrospective review of CSCC specimens reporting PNI on pathology reports between January 2004 and August 2014. Depth was defined as distance from top of granular layer to middle of nerve invaded by CSCC or distance from erosion to middle of nerve affected by CSCC. Results Of 66 specimens identified with PNI, 45 specimens were included. Mean histopathologic depth to PNI was 2.7 mm (SD = 1.8 mm, median depth = 2.2 mm, range 0.5-12 mm). Perineural invasion depth varied by anatomic location, with the head associated with most superficial average PNI depth (2.2 mm) and trunk with greatest average PNI depth (4.3 mm). Perineural invasion depth correlated with clinical tumor diameter. The largest percentage of specimens with PNI were of clinical diameter of at least 2 cm (20/45 = 44%). Conclusion Clinicians encountering lesions suspicious for CSCC have the greatest chance of detecting PNI using biopsy techniques that reach at least 3 to 4 mm deep.

Background Tong-Xie-Yao-Fang (TXYF) is a Chinese herbal formula for treating chronic diarrhoea accompanied by abdominal pain. The results were inconsistent in previous trials examining its effect. Aim To study the efficacy of TXYF granules for treating diarrhoea-predominant irritable bowel syndrome (IBS-D). Methods We performed a double-blind, placebo-controlled randomised trial and enrolled 160 participants with IBS-D. The participants had VAS scores ≥3 cm in IBS-D global symptoms and ≥2 days in a week with abdominal pain and loose stools (Bristol score 5, 6 or 7). They were randomly assigned to received TXYF or placebo during a treatment period of 4 weeks, and they were followed up for 8 weeks after treatment. The primary outcome was adequate relief of IBS-D global symptoms for at least 2 of 4 weeks during weeks 1-4. Secondary outcomes included mean weekly VAS scores of IBS-D major symptoms, mean weekly stool frequency, mean weekly Bristol score, and adverse events. Results 155 of 160 patients completed the trial. We found a significantly higher rate of adequate relief of global symptoms in TXFY group during weeks 1 to 4 (57.5% vs 37.5%, χ2 = 5.6391, P = 0.017); logistic regression analysis showed a similar result (OR 2.2, 95% CI 1.2-4.4, P = 0.016). Most of the secondary outcomes showed superiority of TXYF over placebo in weekly assessment from week 3 to week 7. The adverse event rate was low in both groups (3.8% vs 3.8%, P = 1.000). Conclusion During a 4 week trial, TXFY granules were superior to placebo in controlling symptoms of IBS-D.

Blood-circulating microRNAs (miRNAs) have been reported to be used as potential biomarkers in various cancers. MiR-101 has been found to act as a tumor suppressor in many tumor types, but little is known for osteosarcoma. The purpose of this study was to investigate miR-101 expression in osteosarcoma patients and assess its correlation with clinical features and prognosis. Serum samples from 152 osteosarcoma patients and 70 healthy controls were detected using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The data showed that miR-101 expression levels were remarkably underexpressed in serum samples from osteosarcoma patients compared to controls, and the post-treatment serum miR-101 expression was significantly higher than that in the pre-treatment expression. Low serum miR-101 expression was positively associated with advanced clinical stage and distant metastasis. Receiver operating characteristic (ROC) curve analysis showed that serum miR-101 could serve as a useful marker for osteosarcoma diagnosis, with a high sensitivity and specificity. Moreover, patients with high miR-101 expression had longer overall survival and recurrence free survival than those with low miR-101 expression. In addition, both univariate and multivariate analyses showed that serum miR-101 downregulation was associated with shorter overall survival and recurrence free survival. Our present results implicated serum miR-101 might be a useful biomarker for the clinical diagnosis and prognosis of osteosarcoma.

Background: Incidence rates of in situ breast carcinomas have increased due to widespread adoption of mammography. Very little is known about why some women with in situ breast cancer later develop second primary breast cancers. Methods: In this population-based nested case–control study among in situ breast cancer survivors, including 539 cases with a second primary breast cancer and 994 matched controls, we evaluated the association between first-degree family history of breast cancer and risk of developing a second primary breast cancer. Results: First-degree family history of breast cancer was associated with an increased risk of developing a second primary breast cancer among women with a previous in situ breast cancer [odds ratio (OR) = 1.33, 95% confidence interval (CI), 1.05–1.69] and those with two or more affected first-degree relatives had an even higher risk (OR = 1.94; 95% CI, 1.15–3.28). Those whose relative was diagnosed at less than 50 years old were more likely to develop a second primary breast cancer (OR = 1.78; 95% CI, 1.24–2.57). No difference in risks associated with number or age of affected relatives was observed by menopausal status. Conclusions: Results from this study suggest that first-degree family history of breast cancer may be an important risk factor for development of a second primary breast cancer among women with a previous in situ breast cancer. Impact: Given the growing population of in situ breast cancer survivors, a better understanding of risk factors associated with development of a second primary breast cancer is needed to further understand risk. Cancer Epidemiol Biomarkers Prev; 27(3); 315–20. ©2018 AACR.

Key Clinical Message Termination of pregnancy is indicated for Serratia marcescens bacteremia, a major cause of mortality. Our present case was highly challenging because the patient wished to continue with her pregnancy, and the ultrasonography showed features of a placental abscess. Although the outcomes were good after prolonged antibiotic treatment, this was an exceptional case.