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Management of intracoronary calcium (ICC) continues to be a challenge for interventional cardiologists. There have been significant advances in calcium treatment devices. However, there still exists a knowledge gap regarding which devices to choose for the treatment of ICC. The purpose of this manuscript is to review the principles of intravascular lithotripsy (IVL) and clinical data. The technique of IVL will then be compared to alternative calcium treatment devices. Clinical data will be reviewed concerning the treatment of coronary, peripheral artery and valvular calcifications. Controversies to be discussed include how to incorporate IVL into your practice, what is the best approach for treating calcium subtypes, how to approach under-expanded stents, what is the ideal technique for performing IVL, how safe is IVL, whether imaging adds value when performing IVL, and how IVL fits into a treatment program for peripheral arteries and calcified valves.

Circulating IL-6, an activator of JAK/STAT signaling, is associated with poor prognosis and aromatase inhibitor (AI) resistance in hormone-receptor positive (HR+) breast cancer. Here we report the results of a phase 2 single-arm Simon 2-stage trial combining Ruxolitinib, an oral selective inhibitor of JAK1/2, with exemestane, a steroidal AI, in patients with HR+ metastatic breast cancer (MBC) after progression on non-steroidal AI (NSAI). Safety and efficacy were primary objectives, and analysis of inflammatory markers as predictors of response was a key secondary objective. Twenty-five subjects enrolled. The combination of ruxolitinib and exemestane was safe, though anemia requiring transfusion in 5/15 (33%) at the 25 mg dose in stage 1 led to a reduction to 15 mg twice daily in stage 2 (with no additional transfusions). Clinical benefit rate (CBR) in the overall study population was 24% (95% CI 9.4-45.1); 6/25 patients demonstrated stable disease for ≥6 months. Median progression-free survival was 2.8 months (95% CI 2.6-3.9). Exploratory biomarkers revealed high levels of systemic inflammation and 60% harbored a high-risk IL-6 genotype. Pharmacodynamics demonstrated modest on-target inhibition of phosphorylated-STAT3 by ruxolitinib at a tolerable dose. Thus, ruxolitinib combined with exemestane at a tolerable dose was safe but minimally active in AI-resistant tumors of patients with high levels of systemic inflammation. These findings highlight the need for more potent and specific therapies targeting inflammation in MBC.

BackgroundThe COVID-19 pandemic has caused a global mechanical ventilator shortage for treatment of severe acute respiratory failure. Development of novel breathing devices has been proposed as a low cost, rapid solution when full-featured ventilators are unavailable. Here we report the design, bench testing and preclinical results for an 'Automated Bag Breathing Unit' (ABBU). Output parameters were validated with mechanical test lungs followed by animal model testing.ResultsThe ABBU design uses a programmable motor-driven wheel assembled for adult resuscitation bag-valve compression. ABBU can control tidal volume (200-800 ml), respiratory rate (10-40 bpm), inspiratory time (0.5-1.5 s), assist pressure sensing (- 1 to - 20 cm H2O), manual PEEP valve (0-20 cm H2O). All set values are displayed on an LCD screen. Bench testing with lung simulators (Michigan 1600, SmartLung 2000) yielded consistent tidal volume delivery at compliances of 20, 40 and 70 (mL/cm H2O). The delivered fraction of inspired oxygen (FiO2) decreased with increasing minute ventilation (VE), from 98 to 47% when VE was increased from 4 to 16 L/min using a fixed oxygen flow source of 5 L/min. ABBU was tested in Berkshire pigs (n = 6, weight of 50.8 ± 2.6 kg) utilizing normal lung model and saline lavage induced lung injury. Arterial blood gases were measured following changes in tidal volume (200-800 ml), respiratory rate (10-40 bpm), and PEEP (5-20 cm H2O) at baseline and after lung lavage. Physiological levels of PaCO2 (≤ 40 mm Hg [5.3 kPa]) were achieved in all animals at baseline and following lavage injury. PaO2 increased in lavage injured lungs in response to incremental PEEP (5-20 cm H2O) (p

This Perspective presents a case study of multidimensional clinical transformation in an academic general internal medicine practice. In the face of increasing internal and external pressures, health systems and individual medical practices have pursued multiple strategies to improve quality, patient experience, and efficiency, while reducing staff and provider stress and burnout. We describe a Lean-informed approach that emphasizes the importance of organizational alignment in goals, evidence-based problem solving, and leadership behaviors to support a culture of continuous improvement. Our aim in this Perspective is to provide a real-world example of a feasible process for the planning, preparation, and execution of effective transformation, and to present lessons that may be useful to other academic health center practices seeking to develop innovative models to achieve the quadruple aim.

BackgroundMentorship plays an essential role in enhancing the success of junior faculty. Previous evaluation tools focused on specific types of mentors or mentees. The main objective was to develop and provide validity evidence for a Mentor Evaluation Tool (MET) to assess the effectiveness of one-on-one mentoring for faculty in the academic health sciences.MethodsEvidence was collected for the validity domains of content, internal structure and relationship to other variables. The 13 item MET was tested for internal structure evidence with 185 junior faculty from Schools of Dentistry, Medicine, Nursing, and Pharmacy. Finally, the MET was studied for additional validity evidence by prospectively enrolling mentees of three different groups of faculty (faculty nominated for, or winners of, a lifetime achievement in mentoring award; faculty graduates of a mentor training program; and faculty mentors not in either of the other two groups) at the University of California San Francisco (UCSF) and asking them to rate their mentors using the MET. Mentors and mentees were clinicians, educators and/or researchers.ResultsThe 13 MET items mapped well to the five mentoring domains and six competencies described in the literature. The standardized Cronbach's coefficient alpha was 0.96. Confirmatory factor analysis supported a single factor (CFI = 0.89, SRMR = 0.05). The three mentor groups did not differ in the single overall assessment item (P = 0.054) or mean MET score (P = 0.288), before or after adjusting for years of mentoring. The mentorship score means were relatively high for all three groups.ConclusionsThe Mentor Evaluation Tool demonstrates evidence of validity for research, clinical, educational or career mentors in academic health science careers. However, MET did not distinguish individuals nominated as outstanding mentors from other mentors. MET validity evidence can be studied further with mentor-mentee pairs and to follow prospectively the rating of mentors before and after a mentorship training program.

Objective  Sinonasal undifferentiated carcinoma (SNUC) is an aggressive neoplasm, with conflicting existing literature regarding prognosis and treatment due to the rarity of disease. Characterization of optimal SNUC management is necessary for improved outcomes. Study Design  Case series with planned data collection and analysis. Setting  Hospital of the University of Pennsylvania and Pennsylvania Hospital. Participants  Patients with pathologically confirmed SNUC treated within a 15-year period were identified, and records were obtained and evaluated for several demographic characteristics. Main Outcomes Measures  Disease-specific survival from diagnosis was the primary endpoint, while disease recurrence was a secondary endpoint of the study. Results  Twenty-seven patients with established SNUC were included in this cohort, with a median age of 55 years. Eighty-five percent of patients were surgically treated, and 85% of patients presented with stage IV disease. Two-year disease-specific survival was 66% and 5-year disease-specific survival was 46%. Ninety-six percent of patients received both chemotherapy and radiation as adjuvant treatment. Nodal disease at presentation and disease recurrence both significantly decreased patient survival ( p

BackgroundCardiovascular diseases are among the leading causes of mortality and morbidity in sub-Saharan Africa, including Zambia, where cardiovascular diseases account for 8% of the mortality rates. Despite an increasing number of cardiovascular disease-related studies in Zambia, qualitative studies exploring how cardiovascular diseases and their risk factors are understood in the socioeconomic and cultural contexts are still few. This study, therefore, aimed to analyze the beliefs, perceptions, and behaviors related to cardiovascular diseases and their risk factors among the local residents of Zambia.MethodsThis qualitative study was conducted from August to September 2014 among healthy residents aged 40 years and above in a rural community in Mumbwa District. We investigated the beliefs, perceptions, and behaviors related to cardiovascular diseases and their potential risk factors in the sociocultural context of Zambia by conducting in-depth interviews and focus group interviews. Audio-recorded interviews were transcribed and analyzed using thematic analysis with investigator triangulation.ResultsWe conducted 34 in-depth interviews and 6 focus group interviews with 27 males and 40 females. Most participants were aware of the prevalence of cardiovascular diseases around them and correctly identified hypertension, excessive salt, sugar, and cooking oil intakes, poor quality cooking oil, consumption of meat or vegetables contaminated with chemicals, obesity, stress ["thinking too much"], lack of physical exercise, and heredity as potential risk factors of cardiovascular diseases, while smoking and alcohol were mentioned by only a few participants. However, they claimed that many of these risk factors were difficult to avoid due to ingrained taste preferences for high salt and sugar, increasingly busy lives that force them to use cooking oil to reduce preparation time, cultural preference for big body size or fatness, especially for women, stigmatized body image attached to HIV, stressful life or life events related to poverty, and financial barriers to affording quality foods and healthcare services. Limited health screening opportunities and the negative impact of HIV-related stigma on health-seeking behavior also emerged as important risk factors for cardiovascular diseases.ConclusionsThis study revealed that participants are relatively well aware of cardiovascular diseases and their risk factors. However, they engage in high-risk health behaviors, due to ingrained taste preferences, limited knowledge, and unavoidable socioeconomic and cultural circumstances. Results suggest that prevention interventions addressing cardiovascular diseases in rural Zambia should target gaps in knowledge and socioeconomic and cultural barriers.

Higher precision surgical devices are needed for tumor resections near critical brain structures. The goal of this study is to demonstrate feasibility of a system capable of precise and bloodless tumor ablation. An image-guided laser surgical system is presented for excision of brain tumors in vivo in a murine xenograft model. The system combines optical coherence tomography (OCT) guidance with surgical lasers for high-precision tumor ablation (Er:YAG) and microcirculation coagulation (Thulium (Tm) fiber laser). Methods: A fluorescent human glioblastoma cell line was injected into mice and allowed to grow four weeks. Craniotomies were performed and tumors were imaged with confocal fluorescence microscopy. The mice were subsequently OCT imaged prior, during and after laser coagulation and/or ablation. The prior OCT images were used to compute three-dimensional tumor margin and angiography images, which guided the coagulation and ablation steps. Histology of the treated regions was then compared to post-treatment OCT images. Results: Tumor sizing based on OCT margin detection matched histology to within experimental error. Although fluorescence microscopy imaging showed the tumors were collocated with OCT imaging, margin assessment using confocal microscopy failed to see the extent of the tumor beyond ~ 250 µm in depth, as verified by OCT and histology. The two-laser approach to surgery utilizing Tm wavelength for coagulation and Er:YAG for ablation yielded bloodless resection of tumor regions with minimal residual damage as seen in histology. Conclusion: Precise and bloodless tumor resection under OCT image guidance is demonstrated in the murine xenograft brain cancer model. Tumor margins and vasculature are accurately made visible without need for exogenous contrast agents.

IntroductionSeveral methods have been developed to electronically monitor patients for severe sepsis, but few provide predictive capabilities to enable early intervention; furthermore, no severe sepsis prediction systems have been previously validated in a randomised study. We tested the use of a machine learning-based severe sepsis prediction system for reductions in average length of stay and in-hospital mortality rate.MethodsWe conducted a randomised controlled clinical trial at two medical-surgical intensive care units at the University of California, San Francisco Medical Center, evaluating the primary outcome of average length of stay, and secondary outcome of in-hospital mortality rate from December 2016 to February 2017. Adult patients (18+) admitted to participating units were eligible for this factorial, open-label study. Enrolled patients were assigned to a trial arm by a random allocation sequence. In the control group, only the current severe sepsis detector was used; in the experimental group, the machine learning algorithm (MLA) was also used. On receiving an alert, the care team evaluated the patient and initiated the severe sepsis bundle, if appropriate. Although participants were randomly assigned to a trial arm, group assignments were automatically revealed for any patients who received MLA alerts.ResultsOutcomes from 75 patients in the control and 67 patients in the experimental group were analysed. Average length of stay decreased from 13.0 days in the control to 10.3 days in the experimental group (p=0.042). In-hospital mortality decreased by 12.4 percentage points when using the MLA (p=0.018), a relative reduction of 58.0%. No adverse events were reported during this trial.ConclusionThe MLA was associated with improved patient outcomes. This is the first randomised controlled trial of a sepsis surveillance system to demonstrate statistically significant differences in length of stay and in-hospital mortality.Trial registrationNCT03015454.

BackgroundThere has been a global increase in HIV infection in persons 50 years of age and older. This group is at risk for development of chronic illness that may be exacerbated by socio-behavioral risk factors such as smoking, unhealthy alcohol use, and sedentary lifestyle. However, socio-behavioral risk factors in this older HIV infected population are not well described. The current study aims to describe and document factors related to alcohol use, tobacco smoking, and physical exercise in older adults living with HIV (OALHIV).MethodsThis cross-sectional quantitative study was conducted between August and September 2015, and enrolled HIV-infected participants aged 50 years and older from 12 community hospitals in Chiang Mai Province, Northern Thailand.ResultsOf the 364 participants recruited in the study, 57.1% were female, and 67.3% were between 50-59 years of age. Respectively, 15.1%, 59.1%, and 18.7% were current smokers, currently engaged in physical exercises, and reported ever drank alcohol in the past year. 22.1% of those who drank alcohol reported experience of heavy episodic drinking. Male gender was one of the strongest predictors of ever drank alcohol in the past year (AOR, 4.66; CI, 2.28-9.49; P 20,000 Baht: AOR, 5.34; CI, 1.28-22.25; P = 0.021). Lower educational level was associated with decreased odds of physical exercises (no education versus secondary and higher: AOR, 0.22; CI, 0.08-0.55; P = 0.001).ConclusionSmoking and alcohol use is common among OALHIV, with a substantial proportion not engaging in physical exercises. Interventions for OALHIV should particularly target males and those of lower socio-economic status to deter smoking and alcohol use and to promote physical exercises.

Intravascular optical coherence tomography (IVOCT) images are recorded by detecting light backscattered within coronary arteries. We hypothesize that non-thin-capped fibroatheroma (TCFA) causes may scatter light to create the false appearance of IVOCT TCFA. Ten human cadaver hearts were imaged with IVOCT (n=14 coronary arteries). IVOCT and histological TCFA images were coregistered and compared. Of 21 IVOCT TCFAs (fibrous cap 1 quadrant), only 8 were true histological TCFA. Foam cell infiltration was responsible for 70% of false IVOCT TCFA and caused both thick-capped fibroatheromas to appear as TCFA, and the appearance of TCFAs when no lipid core was present. Other false IVOCT TCFA causes included smooth muscle cell-rich fibrous tissue (12%) and loose connective tissue (9%). If the lipid arc >1 quadrant (obtuse) criterion was disregarded, 45 IVOCT TCFAs were identified, and sensitivity of IVOCT TCFA detection increased from 63% to 87%, and specificity remained high at 92%. We demonstrate that IVOCT can exhibit 87% (95% CI, 75%-93%) sensitivity and 92% specificity (95% CI, 86%-96%) to detect all lipid arcs (both obtuse and acute, 1 quadrant requirement enhances the ability of IVOCT to detect TCFA.

BackgroundDue to the clinical challenges of treatment-resistant depression (TRD), we evaluated the efficacy of mindfulness-based cognitive therapy (MBCT) relative to a structurally equivalent active comparison condition as adjuncts to treatment-as-usual (TAU) pharmacotherapy in TRD.MethodsThis single-site, randomized controlled trial compared 8-week courses of MBCT and the Health Enhancement Program (HEP), comprising physical fitness, music therapy and nutritional education, as adjuncts to TAU pharmacotherapy for outpatient adults with TRD. The primary outcome was change in depression severity, measured by percent reduction in the total score on the 17-item Hamilton Depression Rating Scale (HAM-D17), with secondary depression indicators of treatment response and remission.ResultsWe enrolled 173 adults; mean length of a current depressive episode was 6.8 years (SD = 8.9). At the end of 8 weeks of treatment, a multivariate analysis showed that relative to the HEP condition, the MBCT condition was associated with a significantly greater mean percent reduction in the HAM-D17 (36.6 vs. 25.3%; p = 0.01) and a significantly higher rate of treatment responders (30.3 vs. 15.3%; p = 0.03). Although numerically superior for MBCT than for HEP, the rates of remission did not significantly differ between treatments (22.4 vs. 13.9%; p = 0.15). In these models, state anxiety, perceived stress and the presence of personality disorder had adverse effects on outcomes.ConclusionsMBCT significantly decreased depression severity and improved treatment response rates at 8 weeks but not remission rates. MBCT appears to be a viable adjunct in the management of TRD.

The ability to distinguish macrophage subtypes noninvasively could have diagnostic potential in cancer, atherosclerosis, and diabetes, where polarized M1 and M2 macrophages play critical and often opposing roles. Current methods to distinguish macrophage subtypes rely on tissue biopsy. Optical imaging techniques based on light scattering are of interest as they can be translated into biopsy-free strategies. Because mitochondria are relatively strong subcellular light scattering centers, and M2 macrophages are known to have enhanced mitochondrial biogenesis compared to M1, we hypothesized that M1 and M2 macrophages may have different angular light scattering profiles. To test this, we developed an in vitro angle-resolved forward light scattering measurement system. We found that M1 and M2 macrophage monolayers scatter relatively unequal amounts of light in the forward direction between 1.6 deg and 3.2 deg with M2 forward scattering significantly more light than M1 at increasing angles. The ratio of forward scattering can be used to identify the polarization state of macrophage populations in culture.

ObjectiveTo identify factors associated with participant consent to record visits; to estimate effects of recording on patient-clinician interactions.MethodsSecondary analysis of data from a randomized trial studying communication about depression; participants were asked for optional consent to audio record study visits. Multiple logistic regression was used to model likelihood of patient and clinician consent. Multivariable regression and propensity score analyses were used to estimate effects of audio recording on 6 dependent variables: discussion of depressive symptoms, preventive health, and depression diagnosis; depression treatment recommendations; visit length; visit difficulty.ResultsOf 867 visits involving 135 primary care clinicians, 39% were recorded. For clinicians, only working in academic settings (P=0.003) and having worked longer at their current practice (P=0.02) were associated with increased likelihood of consent. For patients, white race (P=0.002) and diabetes (P=0.03) were associated with increased likelihood of consent. Neither multivariable regression nor propensity score analyses revealed any significant effects of recording on the variables examined.ConclusionFew clinician or patient characteristics were significantly associated with consent. Audio recording had no significant effect on any of the 6 dependent variables examined.Practice implicationsBenefits of recording clinic visits likely outweigh the risks of bias in this setting.

New optical imaging techniques that provide contrast to study both the anatomy and composition of atherosclerotic plaques can be utilized to better understand the formation, progression and clinical complications of human coronary artery disease. We present a dual-modality fiber-based optical imaging system for simultaneous microstructural and molecular analysis of atherosclerotic plaques that combines optical coherence tomography (OCT) and two-photon luminescence (TPL) imaging. Experimental results from ex vivo human coronary arteries show that OCT and TPL optical contrast in recorded OCT-TPL images is complimentary and in agreement with histological analysis. Molecular composition (e.g., lipid and oxidized-LDL) detected by TPL imaging can be overlaid onto plaque microstructure depicted by OCT, providing new opportunities for atherosclerotic plaque identification and characterization.

Accuracy of IVOCT for measurement of neointimal thickness and effect of neointima in the appearance of metallic struts in IVOCT images was investigated. Phantom vessels were constructed and coronary stents were deployed and covered with thick (250-400 μm) and thin (30-70 μm) phantom neointima. High resolution Micro-CT images of the stent struts were recorded as a gold standard. IVOCT images of the phantom vessels were acquired with various luminal blood scattering strengths and measured neointimal thicknesses from IVOCT and Micro-CT images were compared. In transparent lumen, comparison of IVOCT and Micro-CT neointima thickness measurements found no significant difference (p > 0.05) in the thick neointima phantom but a significant difference (p < 0.05) in the thin neointima phantom. For both thick and thin neointima, IVOCT neointimal thickness measurements varied from Micro-CT values by as much as ±35%. Increased luminal scattering due to presence of blood at concentrations