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Silicone breast implants with smooth outer shells are associated with higher rates of capsular contracture, whereas textured implants have been linked to the development of breast implant-associated anaplastic large cell lymphoma. By assessing the gene expression profile of fibrous capsules formed in response to smooth and textured implants, insight into the development of breast implant-associated abnormalities can be gained.Miniature smooth or textured silicone implants were surgically inserted into female rats ( n = 10) and harvested for the surrounding capsules at postoperative week 6. RNA sequencing and quantitative polymerase chain reaction were performed to identify genes differentially expressed between smooth and textured capsules. For clinical correlation, the expression of candidate genes was assayed in implant capsules harvested from human patients with and without capsular contracture.Of 18,555 differentially expressed transcripts identified, three candidate genes were selected: matrix metalloproteinase-3 ( MMP3 ), troponin-T3 ( TNNT3 ), and neuregulin-1 ( NRG1 ). In textured capsules, relative gene expression and immunostaining of MMP3 and TNNT3 was up-regulated, whereas NRG1 was down-regulated compared to smooth capsules [mean relative fold change, 8.79 ( P = 0.0059), 4.81 ( P = 0.0056), and 0.40 ( P0.0001), respectively]. Immunostaining of human specimens with capsular contracture revealed similar gene expression patterns to those of animal-derived smooth capsules.An expression pattern of low MMP3 /low TNNT3 /high NRG1 is specifically associated with smooth implant capsules and human implant capsules with capsular contracture. The authors' clinically relevant breast implant rat model provides a strong foundation to further explore the molecular genetics of implant texture and its effect on breast implant-associated abnormalities.The authors have demonstrated that there are distinct gene expression profiles in response to smooth versus textured breast implants. Since surface texture may be linked to implant-related pathology, further molecular analysis of periprosthetic capsules may yield strategies to mitigate implant-related complications.

BACKGROUND Measuring an accurate blood pressure (BP) in ambulatory patients is critical for therapeutic decisions. An accurate noninvasive device that measures BP continuously could provide a more comprehensive assessment of BP. The aim of this study was to determine whether the LiveOne device, a cuffless wristband that provides continuous BP measurements, is accurate in comparison to an invasive arterial line (A-line). METHODS We enrolled hospitalized patients and healthy volunteers in this multicenter study. All patients had an invasive A-line. Waveforms were simultaneously downloaded from the A-line and LiveOne device. The primary outcome was the correlation between the LiveOne device and the A-line for systolic BP (SBP) and diastolic BP (DBP). RESULTS Thirty-four patients with 233 measurement periods were included. Mean age was 60.7 ± 15.2 years, and 15 (44%) were female. The correlation for SBP was 0.91 and for DBP was 0.85. The mean band error was 0.0 ± 6.9 mm Hg for SBP and 1.2 ± 5.7 mm Hg for DBP. The mean absolute error was 8.2 ± 5.8 mm Hg for SBP and 6.4 ± 3.9 mm Hg for DBP. For SBP, 98% of LiveOne measurements were within 15 mm Hg and for DBP, 92% of LiveOne measurements were within 10 mm Hg. CONCLUSIONS The LiveOne device provides continuous, noninvasive BP measurements that are accurate in comparison to A-line measurements. The portability and unobtrusive nature of this device and the ability to provide continuous BP measurements may offer advantages over currently available BP monitors. CLINICAL TRIALS REGISTRATION Trial Number NCT03919136.

Cryptococcus neoformans is a common fungus found throughout the environment that causes opportunistic disease in immunocompromised individuals. Infection of humans with C neoformans usually manifests as lung disease through inhalation of spores or meningoencephalitis by involvement of the central nervous system. Rarely, dissemination in the form of cutaneous lesions can occur in individuals with long term immunosuppression. We present a patient with C. neoformans manifesting as cellulitis with focal segmental glomerulosclerosis treated with corticosteroids. Because of the mortality associated with disseminated cryptococcosis, early identification, especially of atypical cutaneous presentations is critical from a dermatological perspective.

Pulmonary hypertension (PH) (1) is a recalcitrant disease that is increasingly recognized as a critical contributor of cardiovascular mortality worldwide. While considerable progress has been made in the understanding of pathophysiology of PH, significant knowledge gaps still remain.

Background: The development of aortic insufficiency (AI) following continuous flow left ventricular assist device (CF-LVAD) implantation is common, although the clinical significance remains unclear. We previously described novel echocardiographic (TTE) parameters that outperformed traditional TTE parameters in grading AI severity in these patients. The aim of this study was to evaluate the prognostic performance of these parameters compared to traditional measurements. Methods: CF-LVAD patients with varying degrees of AI (N=57) underwent Doppler TTE of the LVAD outflow cannula. All patients had AI severity graded by our novel parameters (Systolic/Diastolic ratio and the diastolic acceleration of the LVAD outflow cannula) and traditional vena contracta. The prognostic performance of novel and traditional AI parameters was determined by comparing rates of hospital readmission, need for aortic valve intervention and/or urgent transplantation and death (primary endpoints) for each parameter. Results: Grading AI severity using novel AI parameters led to reclassification of 21% of patients from trace/mild AI to moderate or greater AI (N=12). Using traditional AI parameters, there was no difference in the occurrence of the primary endpoint between the trace/mild group and the moderate or greater group (1.08 vs. 0.89 events/person, p=0.39) (Figure 1A). With the novel AI parameters, there were significantly more events in the patients with moderate or greater AI compared to those with trace/mild. (1.11 vs. 0.56 events/person, p=0.02) (Figure 1B). Novel parameters better predicted the need for aortic valve intervention, urgent transplantation or death than traditional methods (p=0.049) (Figure 1C-D). Conclusions: In patients with CF-LVADs, traditional parameters tend to underestimate AI severity and future cardiac events. Novel AI TTE parameters are better able to discriminate AI severity and predict clinically meaningful outcomes.

Arteriovenous malformations are common in patients with Continuous-Flow Left Ventricular Assist Devices (LVAD) and may reflect deregulation of angiogenesis. Angiopoietin-2 (Ang-2) is a stimulator of angiogenesis produced by endothelial cells in response to thrombin. In this study, we evaluate Ang-2 expression in patients with LVAD compared with stable heart failure (HF) or orthotopic heart transplant (OHT) and test the hypothesis that elevated Ang-2 in patients with LVAD leads to increased angiogenesis. Blood samples were taken from 79 patients (n= 21 HF, 41 LVAD, 17 OHT) during routine heart catheterization. Ang-2 was measured by ELISA and thrombin was measured by Western Blot. Cultured human umbilical vein endothelial cells (HUVECs) were incubated with plasma from each patient and Ang-2 expression was measured by RT-PCR. HUVECs were then incubated on Matrigel with serum from each patient in the presence or absence of an Ang-2 blocking antibody and tube formation was measured by microscopy. Also, vena caval endothelial cells were isolated from discarded guide wires used during catheterization and Ang-2 expression was measured by quantitative immunofluorescence. In patients with LVAD vs. HF or OHT, Ang-2 was elevated in both serum (12.3±9.6, 4.5±2.1, and 4.9±2.0 ng/mL respectively, p10 ng/mL was associated with a higher 3 month risk of GI bleeding vs. Ang-2 in vitro . Therefore, Ang-2 overexpression may contribute to AVM formation in patients with LVAD.

Background: Echocardiographic assessment of left ventricular assist devices (LVAD) is used as a screening tool to evaluate the integrity and mechanics of the pump and circuit. We aimed to 1) establish the normal range and upper reference limit of peak velocity of the outflow cannula for the modern era of LVADs and 2) assess the performance of the current reference limit and our new reference limit in patients with continuous flow LVADs as a screening tool for cannula malfunction. Methods: LVAD outflow peak velocities were measured with Doppler echocardiography (TTE) in 57 patients with LVADs (HeartMate II (HMII) = 44, HeartWare (HW) = 13). The average velocity and the upper and lower normal reference limits (defined as +/- two standard deviations from the mean) for each LVAD type was then calculated. The upper reference limit was then used as a screening threshold for cannula malfunction. Results: The average outflow cannula peak velocity for the HMII cohort was 1.94 m/sec +/- 0.42 with an upper and lower reference limit of 2.78 m/sec and 1.10 m/sec, respectively. The average outflow cannula peak velocity for the HW cohort was 2.36 +/- 0.53 with an upper and lower reference limit of 3.42 m/sec and 1.3 m/sec, respectively, which was significantly higher than the HMII cohort (p=0.004). Velocities from both cohorts were dramatically higher than the commonly citied upper reference limit velocities of 2 m/sec. Use of the previously cited reference limit poorly discriminated between normal and malfunctioning LVAD cannulas whereas our new reference limit identified all four patients with outlet cannula malfunction (Figure1). Conclusions: In both HeartMate II and HeartWare LVADs, the average peak outflow velocity and reference limit for the normal population as measured by Doppler-TTE was markedly higher than currently cited LVAD reference limits. Patients with peak outflow velocities above our upper reference limit should be evaluated for LVAD outflow cannula malfunction.

The aim of this study was to develop a technique to measure regurgitant flow throughout the entire cardiac cycle that would more accurately measure aortic insufficiency (AI) severity in patients with continuous-flow left ventricular assist devices (CF-LVADs).AI is a common problem after CF-LVAD implantation. Current echocardiographic evaluation of AI does not take into account the unique flow properties present in patients with CF-LVADs.In this prospective study, patients with LVADs who had varying degrees of AI (N = 20) underwent simultaneous right-sided heart catheterization (RHC) and transthoracic echocardiography (TTE). Regurgitant fraction (RF) across the aortic valve was calculated by subtracting the cardiac output obtained using the Fick method from the total systemic flow measured using the sum of the product of the velocity time integral and the cross-sectional area of the LVAD outflow cannula and aortic valve, respectively. The RFs were then compared with the following: 1) traditional TTE grading parameters; and 2) new TTE parameters unique to LVAD physiology, namely the diastolic flow acceleration and the systolic-to-diastolic peak velocity (S/D) ratio of the LVAD outflow cannula.Patients without evidence of AI had an RF approaching zero (2.4 ± 4.6%). Patients with trace and mild AI had an RF of 31.0 ± 5.4%, whereas patients with moderate or severe AI had an RF of 45.8 ± 3.6%. RF correlated better with pulmonary capillary wedge pressure (PCWP) than with vena contracta (correlation coefficient [R] = 0.73 vs. 0.56). The new TTE parameters (S/D ratio and diastolic acceleration) highly correlated with RF (R = 0.91 and 0.94, respectively) and more strongly correlated with PCWP than did vena contracta (R = 0.82 and 0.65 vs. 0.56).RF measured by simultaneous RHC and TTE better correlates with clinical filling pressures than do traditional TTE parameters and may identify significant AI that could be underestimated using conventional measures. Novel TTE parameters, unique to CF-LVAD physiology, better correlate with RF and filling pressures than do our current TTE measurements.

Hydrophilic polymer coatings were designed to reduce friction between the catheter and vessel wall and facilitate intravascular manipulations during catheterization and placement of drug-eluting stents. One newly reported complication of such hydrophilic coatings is the fragmentation and embolization of the polymer, which can lead to ischemia and infarct by blocking the small vasculature. In this report, we present a patient with a non-healing ulcer on the leg. Biopsy from the ulcer revealed the presence of hydrophilic polymer emboli within the dermal vessels. This is one of the few reports of such a complication involving the skin. Our objective is to emphasize the histopathologic features of this uncommon iatrogenic phenomenon.

Vemurafenib is an inhibitor of BRAF and is used to treat patients with metastatic melanoma who carry a V600E BRAF mutation. Recently, four patients have been described in the literature who developed a neutrophilic panniculitis following treatment with a BRAF inhibitor. We present an additional case and review the clinical findings of the cases reported to date.

A 53-year-old woman presented for evaluation and treatment of discrete, violaceous, annular plaques on the forehead and cheeks. The biopsy specimen and the clinical presentation were consistent with lichen planus actinicus. Lichen planus actinicus is a photosensitive variant of lichen planus that can present with annular, melasma-like, dyschromic, or violaceous plaques in sun-exposed areas. The clinical manifestations of lichen planus actinicus and treatments are discussed.