High intensity focused ultrasound in the treatment of breast fibroadenomata (HIFU-F trial)

Background: High intensity focused ultrasound (HIFU) is a non-invasive ablative technique utilising the application of high frequency ultrasound (US) pressure waves to cause tissue necrosis. This emerging technology is currently limited by prolonged treatment times. The aim of the HIFU-F trial was to perform circumferential HIFU treatment as a means of shortening treatment times. Methods: A prospective trial was set up to treat 50 consecutive patients ≥18 years of age. Eligible patients possessed symptomatic fibroadenomata, visible on US. Patients ≥25 years of age required histological confirmation of the diagnosis. Primary outcome measures were reduction in treatment time, reduction in volume on US after 12 months and complication rates. Results: HIFU treatment was performed in 51 patients (53 treatments) with a mean age of 29.8 years (SD 7.2 years) and diameter of 2.6 cm (SD 1.4 cm). Circumferential ablation reduced treatment times by an estimated 19.9 minutes (SD 25.1 minutes), which is a 29.4% (SD 15.2%) reduction compared to whole lesion ablation. Volume reduction of 43.2% (SD 35.4%; p<0.005, paired t-test) was observed on US at 12 months post-treatment. Local complications completely resolved at one month apart from skin hyper-pigmentation, which persisted in nine cases at three months, six cases at six months and six at 12 months. Conclusion: Circumferential HIFU treatment for breast fibroadenomata is feasible to reduce both lesion size and treatment time. HIFU is a non-invasive alternative technique for the treatment of breast fibroadenomata

A Cure for HIV Infection: "Not in My Lifetime" or "Just Around the Corner"?

With the advent and stunning success of combination antiretroviral therapy (ART) to prolong and improve quality of life for persons with HIV infection, HIV research has been afforded the opportunity to pivot towards studies aimed at finding "a cure." The mere idea that cure of HIV might be possible has energized researchers and the community towards achieving this goal. Funding agencies, both governmental and private, have targeted HIV cure as a high priority; many in the field have responded to these initiatives and the cure research agenda is robust. In this "salon" two editors of Pathogens and Immunity, Michael Lederman and Daniel Douek ask whether curing HIV is a realistic, scalable objective. We start with an overview perspective and have asked a number of prominent HIV researchers to add to the discussion

The use of machine learning to reduce overtreatment of the axilla in breast cancer: retrospective cohort study

Background: Patients with early breast cancer undergoing primary surgery, who have low axillary nodal burden, can safely forego axillary node clearance (ANC). However, routine use of axillary ultrasound (AUS) leads to 43% of patients in this group having ANC unnecessarily, following a positive AUS. The intersection of machine learning with medicine can provide innovative ways to understand specific risks within large patient data sets, but this has not yet been trialed in the arena of axillary node management in breast cancer. Objective: The objective of this study was to assess if machine learning techniques could be used to improve preoperative identification of patients with low and high axillary metastatic burden. Methods: A single-center retrospective analysis was performed on patients with breast cancer who had a preoperative AUS, and the specificity and sensitivity of AUS were calculated. Standard statistical methods and machine learning methods, including artificial neural network, naive Bayes, support vector machine, and random forest, were applied to the data to see if they could improve the accuracy of preoperative AUS to better discern high and low axillary burden. Results: The study included 459 patients; 142 (31%) had a positive AUS; among this group, 88 (62%) had 2 or fewer macrometastatic nodes at ANC. Logistic regression outperformed AUS (specificity 0.950 vs 0.809). Of all the methods, the artificial neural network had the highest accuracy (0.919). Interestingly, AUS had the highest sensitivity of all methods (0.777), underlining its utility in this setting. Conclusions: We demonstrated that machine learning improves identification of the important subgroup of patients with no palpable axillary disease, positive ultrasound, and more than 2 metastatically involved nodes. A negative ultrasound in patients with no palpable lymphadenopathy is highly indicative of low axillary burden, and it is unclear whether sentinel node biopsy adds value in this situation. Further studies with larger patient numbers focusing on specific breast cancer subgroups are required to refine these techniques in this setting

Material Decomposition in Spectral CT using deep learning: A Sim2Real transfer approach

The state-of-the art for solving the nonlinear material decomposition problem in spectral computed tomography is based on variational methods, but these are computationally slow and critically depend on the particular choice of the regularization functional. Convolutional neural networks have been proposed for addressing these issues. However, learning algorithms require large amounts of experimental data sets. We propose a deep learning strategy for solving the material decomposition problem based on a U-Net architecture and a Sim2Real transfer learning approach where the knowledge that we learn from synthetic data is transferred to a real-world scenario. In order for this approach to work, synthetic data must be realistic and representative of the experimental data. For this purpose, numerical phantoms are generated from human CT volumes of the KiTS19 Challenge dataset, segmented into specific materials (soft tissue and bone). These volumes are projected into sinogram space in order to simulate photon counting data, taking into account the energy response of the scanner. We compared projection- and image-based decomposition approaches where the network is trained to decompose the materials either in the projection or in the image domain. The proposed Sim2Real transfer strategies are compared to a regularized Gauss-Newton (RGN) method on synthetic data, experimental phantom data and human thorax data

Improved coronary calcium detection and quantification with low-dose full field-of-view photon-counting CT:a phantom study

OBJECTIVE: The aim of the current study was to systematically assess coronary artery calcium (CAC) detection and quantification for spectral photon-counting CT (SPCCT) in comparison to conventional CT and, in addition, to evaluate the possibility of radiation dose reduction. METHODS: Routine clinical CAC CT protocols were used for data acquisition and reconstruction of two CAC containing cylindrical inserts which were positioned within an anthropomorphic thorax phantom. In addition, data was acquired at 50% lower radiation dose by reducing tube current, and slice thickness was decreased. Calcifications were considered detectable when three adjacent voxels exceeded the CAC scoring threshold of 130 Hounsfield units (HU). Quantification of CAC (as volume and mass score) was assessed by comparison with known physical quantities. RESULTS: In comparison with CT, SPCCT detected 33% and 7% more calcifications for the small and large phantoms, respectively. At reduced radiation dose and reduced slice thickness, small phantom CAC detection increased by 108% and 150% for CT and SPCCT, respectively. For the large phantom size, noise levels interfered with CAC detection. Although comparable between CT and SPCCT, routine protocols CAC quantification showed large deviations (up to 134%) from physical CAC volume. At reduced radiation dose and slice thickness, physical volume overestimations decreased to 96% and 72% for CT and SPCCT, respectively. In comparison with volume scores, mass score deviations from physical quantities were smaller. CONCLUSION: CAC detection on SPCCT is superior to CT, and was even preserved at a reduced radiation dose. Furthermore, SPCCT allows for improved physical volume estimation. KEY POINTS: • In comparison with conventional CT, increased coronary artery calcium detection (up to 156%) for spectral photon-counting CT was found, even at 50% radiation dose reduction. • Spectral photon-counting CT can more accurately measure physical volumes than conventional CT, especially at reduced slice thickness and for high-density coronary artery calcium. • For both conventional and spectral photon-counting CT, reduced slice thickness reconstructions result in more accurate physical mass approximation

Are Endovascular Interventions for Central Vein Obstructions due to Cardiac Implanted Electronic Devices Effective?

&lt;b&gt;Objective:&lt;/b&gt; One of the late-onset complications of cardiac implanted electronic devices (CIEDs) is central venous obstruction (CVO). The aim of this study was to investigate the feasibility, efficacy, and safety of endovascular treatment of CIED-related CVOs. &lt;b&gt;Methods:&lt;/b&gt; Eighteen patients who underwent endovascular management of their device-related CVO were reviewed. Patients were classified into three groups: Group I patients were asymptomatic and needed lead replacement; Group II patients presented with symptomatic CVO without lead dysfunction, and Group III patients were referred with both symptomatic CVO and lead dysfunction. A treatment strategy involved recanalization and balloon angioplasty for Group I and angioplasty/stents for Groups II and III. Technical success, clinical success, complications, and long-term follow-up were assessed. &lt;b&gt;Results:&lt;/b&gt; Thirteen patients were in Group I, four in Group II, and one in Group III. Technical and clinical success was achieved in 17 patients (94%). No major complications were reported. Restenosis was observed in two patients at 40 and 42 weeks of follow-up, and these patients were successfully treated with angioplasty. &lt;b&gt;Conclusion:&lt;/b&gt; Endovascular management of CVO due to CIED is a safe and efficient technique. Plain balloon angioplasty is sufficient for lead replacement purposes, while stenting is needed for symptomatic CVO to achieve good long-term patency

Autocrine Production of β-Chemokines Protects CMV-Specific CD4+ T Cells from HIV Infection

Induction of a functional subset of HIV-specific CD4+ T cells that is resistant to HIV infection could enhance immune protection and decrease the rate of HIV disease progression. CMV-specific CD4+ T cells, which are less frequently infected than HIV-specific CD4+ T cells, are a model for such an effect. To determine the mechanism of this protection, we compared the functional response of HIV gag-specific and CMV pp65-specific CD4+ T cells in individuals co-infected with CMV and HIV. We found that CMV-specific CD4+ T cells rapidly up-regulated production of MIP-1α and MIP-1β mRNA, resulting in a rapid increase in production of MIP-1α and MIP-1β after cognate antigen stimulation. Production of β-chemokines was associated with maturational phenotype and was rarely seen in HIV-specific CD4+ T cells. To test whether production of β-chemokines by CD4+ T cells lowers their susceptibility to HIV infection, we measured cell-associated Gag DNA to assess the in vivo infection history of CMV-specific CD4+ T cells. We found that CMV-specific CD4+ T cells which produced MIP-1β contained 10 times less Gag DNA than did those which failed to produce MIP-1β. These data suggest that CD4+ T cells which produce MIP-1α and MIP-1β bind these chemokines in an autocrine fashion which decreases the risk of in vivo HIV infection

Pulse Oximetry as an Aid to Rule Out Pneumonia among Patients with a Lower Respiratory Tract Infection in Primary Care.

Guidelines recommend chest X-rays (CXRs) to diagnose pneumonia and guide antibiotic treatment. This study aimed to identify clinical predictors of pneumonia that are visible on a chest X-ray (CXR+) which could support ruling out pneumonia and avoiding unnecessary CXRs, including oxygen saturation. A secondary analysis was performed in a clinical trial that included patients with suspected pneumonia in Swiss primary care. CXRs were reviewed by two radiologists. We evaluated the association between clinical signs (heart rate &gt; 100/min, respiratory rate ≥ 24/min, temperature ≥ 37.8 °C, abnormal auscultation, and oxygen saturation &lt; 95%) and CXR+ using multivariate analysis. We also calculated the diagnostic performance of the associated clinical signs combined in a clinical decision rule (CDR), as well as a CDR derived from a large meta-analysis (at least one of the following: heart rate &gt; 100/min, respiratory rate ≥ 24/min, temperature ≥ 37.8 °C, or abnormal auscultation). Out of 469 patients from the initial trial, 107 had a CXR and were included in this study. Of these, 26 (24%) had a CXR+. We found that temperature and oxygen saturation were associated with CXR+. A CDR based on the presence of either temperature ≥ 37.8 °C and/or an oxygen saturation level &lt; 95% had a sensitivity of 69% and a negative likelihood ratio (LR-) of 0.45. The CDR from the meta-analysis had a sensitivity of 92% and an LR- of 0.37. The addition of saturation &lt; 95% to this CDR increased the sensitivity (96%) and decreased the LR- (0.21). In conclusion, this study suggests that pulse oximetry could be added to a simple CDR to decrease the probability of pneumonia to an acceptable level and avoid unnecessary CXRs