Automatic Detection of Post-Operative Clips in Mammography Using a U-Net Convolutional Neural Network.

BACKGROUND: After breast conserving surgery (BCS), surgical clips indicate the tumor bed and, thereby, the most probable area for tumor relapse. The aim of this study was to investigate whether a U-Net-based deep convolutional neural network (dCNN) may be used to detect surgical clips in follow-up mammograms after BCS. METHODS: 884 mammograms and 517 tomosynthetic images depicting surgical clips and calcifications were manually segmented and classified. A U-Net-based segmentation network was trained with 922 images and validated with 394 images. An external test dataset consisting of 39 images was annotated by two radiologists with up to 7 years of experience in breast imaging. The network's performance was compared to that of human readers using accuracy and interrater agreement (Cohen's Kappa). RESULTS: The overall classification accuracy on the validation set after 45 epochs ranged between 88.2% and 92.6%, indicating that the model's performance is comparable to the decisions of a human reader. In 17.4% of cases, calcifications have been misclassified as post-operative clips. The interrater reliability of the model compared to the radiologists showed substantial agreement (κreader1 = 0.72, κreader2 = 0.78) while the readers compared to each other revealed a Cohen's Kappa of 0.84, thus showing near-perfect agreement. CONCLUSIONS: With this study, we show that surgery clips can adequately be identified by an AI technique. A potential application of the proposed technique is patient triage as well as the automatic exclusion of post-operative cases from PGMI (Perfect, Good, Moderate, Inadequate) evaluation, thus improving the quality management workflow.

Association of Thoracic Skeletal Muscle Index with Clinical Outcome and Response to Nutritional Interventions in Patients at Risk of Malnutrition-Secondary Analysis of a Randomized Trial.

BACKGROUND: Measurement of skeletal muscle index (SMI) in computed tomography has been suggested to improve the objective assessment of muscle mass. While most studies have focused on lumbar vertebrae, we examine the association of SMI at the thoracic level with nutritional and clinical outcomes and response to nutritional intervention. METHODS: We conducted a secondary analysis of EFFORT, a Swiss-wide, multicenter, randomized trial. We investigated the association of low SMI at the 12th thoracic vertebra (T12) with adverse outcome within 30 days after hospital admission (primary endpoint). RESULTS: 663 of 2028 patients from the EFFORT trial had available CT scans for T12, and 519 among them also had available L3 scans. Mean SMI at T12 was 22.4 ± 5.8 cm2/m2 and 19.6 ± 5.5 cm2/m2 in male and female patients, respectively, and correlated well with nutritional parameters, including nutritional risk based on NRS 2002 (adjusted coefficient -0.63, 95%CI -1.25 to -0.01, p = 0.047), BMI (adjusted coefficient 0.74, 95%CI 0.66 to 0.82, p < 0.001) and handgrip strength (adjusted coefficient 0.15, 95%CI 0.11 to 0.2, p < 0.001). In multivariate regression analyses, low SMI was not a significant predictor for either clinical outcome or for treatment response. Results for SMI measured at L3 were similar, with only little prognostic value. CONCLUSIONS: Within medical patients at risk for malnutrition, SMI at thoracic vertebra provided low prognostic information regarding clinical outcomes and nutritional treatment response.

Association of CT-based diagnosis of sarcopenia with prognosis and treatment response in patients at risk of malnutrition - A secondary analysis of the Effect of early nutritional support on Frailty, Functional Outcomes, and Recovery of malnourished medical inpatients Trial (EFFORT) trial.

BACKGROUND & AIM: CT-derived measures of muscle mass may help to identify patients with sarcopenia. We investigated the prognostic significance of CT-derived sarcopenia and muscle attenuation with nutritional markers, clinical outcomes and response to nutritional support in medical in-patients at nutritional risk. METHOD: Within this secondary analysis of the randomized-controlled Effect of early nutritional support on Frailty, Functional Outcomes, and Recovery of malnourished medical inpatients Trial (EFFORT) comparing individualized nutritional support with usual care nutrition in medical inpatients, we investigated associations of CT-based sarcopenia and muscle attenuation at the level L3 with different nutritional and clinical outcomes, and the response to the nutritional intervention. The primary composite endpoint was adverse clinical outcome within 30 days of hospital admission. RESULTS: We included 573 of 2028 EFFORT patients with available CT scans, of which 68.4% met the CT-based definition of sarcopenia and 72.9% had low muscle attenuation. In multivariate analysis, low skeletal muscle index was associated with higher nutritional risk (coefficient per NRS class -0.94 (95%CI -1.87 to -0.01) p = 0.049) and higher risk for adverse clinical outcomes (adjusted odds ratio 1.59 (95% CI 1.06 to 2.38), p = 0.024). Low muscle attenuation was also associated with adverse clinical outcome (adjusted odds ratio 1.67 (95%CI 1.08 to 2.58), p = 0.02). Nutritional support tended to be more effective in reducing mortality in non-sarcopenic patients compared to patients with CT-based sarcopenia (p for interaction 0.058). CONCLUSIONS: Within a population of medical patients at nutritional risk, CT-based sarcopenia and muscle attenuation were associated with several nutritional parameters and predicted adverse clinical outcomes. Information from CT scans, thus may help to better characterize these patients, and may be helpful in guiding therapeutic interventions.

Nicotine Replacement Therapy for Smokers with Acute Aneurysmal Subarachnoid Hemorrhage: An International Survey.

INTRODUCTION: Smoking prevalence is twice as high among patients admitted to hospital because of the acute condition of aneurysmal subarachnoid hemorrhage (aSAH) as in the general population. Smoking cessation may improve the prognosis of aSAH, but nicotine replacement therapy (NRT) administered at the time of aSAH remains controversial because of potential adverse effects such as cerebral vasospasm. We investigated the international practice of NRT use for aSAH among neurosurgeons. METHODS: The online SurveyMonkey software was used to administer a 15-question, 5-min online questionnaire. An invitation link was sent to those 1425 of 1988 members of the European Association of Neurosurgical Societies (EANS) who agreed to participate in surveys to assess treatment strategies for withdrawal of tobacco smoking during aSAH. Factors contributing to physicians' posture towards NRT were assessed. RESULTS: A total of 158 physicians from 50 nations participated in the survey (response rate 11.1%); 68.4% (108) were affiliated with university hospitals and 67.7% (107) practiced at high-volume neurovascular centers with at least 30 treated aSAH cases per year. Overall, 55.7% (88) of physicians offered NRT to smokers with aSAH, 22.1% (35) offered non-NRT support including non-nicotine medication and counselling, while the remaining 22.1% (35) did not actively support smoking cessation. When smoking was not possible, 42.4% (67) of physicians expected better clinical outcomes when prescribing NRT instead of nicotine deprivation, 36.1% (57) were uncertain, 13.9% (22) assumed unaffected outcomes, and 7.6% (12) assumed worse outcomes. Only 22.8% (36) physicians had access to a local smoking cessation team in their practice, of whom half expected better outcomes with NRT as compared to deprivation. CONCLUSIONS: A small majority of the surveyed physicians of the EANS offered NRT to support smoking cessation in hospitalized patients with aSAH. However, less than half believed that NRT could positively impact clinical outcome as compared to deprivation. This survey demonstrated the lack of consensus regarding use of NRT for hospitalized smokers with aSAH.

Unsupervised Domain Adaptation for Vertebrae Detection and Identification in 3D CT Volumes Using a Domain Sanity Loss.

A variety of medical computer vision applications analyze 2D slices of computed tomography (CT) scans, whereas axial slices from the body trunk region are usually identified based on their relative position to the spine. A limitation of such systems is that either the correct slices must be extracted manually or labels of the vertebrae are required for each CT scan to develop an automated extraction system. In this paper, we propose an unsupervised domain adaptation (UDA) approach for vertebrae detection and identification based on a novel Domain Sanity Loss (DSL) function. With UDA the model's knowledge learned on a publicly available (source) data set can be transferred to the target domain without using target labels, where the target domain is defined by the specific setup (CT modality, study protocols, applied pre- and processing) at the point of use (e.g., a specific clinic with its specific CT study protocols). With our approach, a model is trained on the source and target data set in parallel. The model optimizes a supervised loss for labeled samples from the source domain and the DSL loss function based on domain-specific "sanity checks" for samples from the unlabeled target domain. Without using labels from the target domain, we are able to identify vertebra centroids with an accuracy of 72.8%. By adding only ten target labels during training the accuracy increases to 89.2%, which is on par with the current state-of-the-art for full supervised learning, while using about 20 times less labels. Thus, our model can be used to extract 2D slices from 3D CT scans on arbitrary data sets fully automatically without requiring an extensive labeling effort, contributing to the clinical adoption of medical imaging by hospitals.

Incidence and clinical impact of vertebral endplate changes after limited lumbar microdiscectomy and implantation of a bone-anchored annular closure device.

BACKGROUND: An annular closure device (ACD) could potentially prevent recurrent herniation by blocking larger annular defects after limited microdiscectomy (LMD). The purpose of this study was to analyze the incidence of endplate changes (EPC) and outcome after LMD with additional implantation of an ACD to prevent reherniation. METHODS: This analysis includes data from a) RCT study-arm of patients undergoing LMD with ACD implantation and b) additional patients undergoing ACD implantation at our institution. Clinical findings (VAS, ODI), radiological outcome (reherniation, implant integrity, volume of EPC) and risk factors for EPC were assessed. RESULTS: Seventy-two patients (37 men, 47 ± 11.63yo) underwent LMD and ACD implantation between 2013-2016. A total of 71 (99%) patients presented with some degree of EPC during the follow-up period (14.67 ± 4.77 months). In the multivariate regression analysis, localization of the anchor was the only significant predictor of EPC (p = 0.038). The largest EPC measured 4.2 cm3. Reherniation was documented in 17 (24%) patients (symptomatic: n = 10; asymptomatic: n = 7). Six (8.3%) patients with symptomatic reherniation underwent rediscectomy. Implant failure was documented in 19 (26.4%) patients including anchor head breakage (n = 1, 1.3%), dislocation of the whole device (n = 5, 6.9%), and mesh dislocation into the spinal canal (n = 13, 18%). Mesh subsidence within the EPC was documented in 15 (20.8%) patients. Seven (9.7%) patients underwent explantation of the entire, or parts of the device. CONCLUSION: Clinical improvement after LMD and ACD implantation was proven in our study. High incidence and volume of EPC did not correlate with clinical outcome. The ACD might prevent disc reherniation despite implant failure rates. Mechanical friction of the polymer mesh with the endplate is most likely the cause of EPC after ACD.

sEVD-smartphone-navigated placement of external ventricular drains.

BACKGROUND: Currently, the trajectory for insertion of an external ventricular drain (EVD) is mainly determined using anatomical landmarks. However, non-assisted implantations frequently require multiple attempts and are associated with EVD malpositioning and complications. The authors evaluated the feasibility and accuracy of a novel smartphone-guided, angle-adjusted technique for assisted implantations of an EVD (sEVD) in both a human artificial head model and a cadaveric head. METHODS: After computed tomography (CT), optimal insertion angles and lengths of intracranial trajectories of the EVDs were determined. A smartphone was calibrated to the mid-cranial sagittal line. Twenty EVDs were placed using both the premeasured data and smartphone-adjusted insertion angles, targeting the center of the ipsilateral ventricular frontal horn. The EVD positions were verified with post-interventional CT. RESULTS: All 20 sEVDs (head model, 8/20; cadaveric head, 12/20) showed accurate placement in the ipsilateral ventricle. The sEVD tip locations showed a mean target deviation of 1.73° corresponding to 12 mm in the plastic head model, and 3.45° corresponding to 33 mm in the cadaveric head. The mean duration of preoperative measurements on CT data was 3 min, whereas sterile packing, smartphone calibration, drilling, and implantation required 9 min on average. CONCLUSIONS: By implementation of an innovative navigation technique, a conventional smartphone was used as a protractor for the insertion of EVDs. Our ex vivo data suggest that smartphone-guided EVD placement offers a precise, rapidly applicable, and patient-individualized freehand technique based on a standard procedure with a simple, cheap, and widely available multifunctional device.

Hybrid Operating Room Settings for Treatment of Complex Dural Arteriovenous Fistulas.

OBJECTIVE: Dural arteriovenous fistulas (dAVFs) are abnormal direct shunts between the occipital or meningeal artery and a meningeal vein or dural venous sinus. Treatment strategies include endovascular, microsurgical, stereotactic radiosurgical, or combined interventions. With few previous reports focused on dAVF treatment in a hybrid operating room (hOR), the authors reviewed their 6-year experience in this unique setting for these complex fistulas. METHODS: Patients with complex cerebral dAVFs underwent endovascular and microsurgical treatment in the hOR. In this retrospective review, 8 consecutive patients with cerebral dAVFs (Borden type 2 or higher) underwent endovascular and microsurgical treatment. Demographic characteristics, symptoms related to the dAVF, preoperative angiographic features, preinterventional therapies, intraoperative digital subtraction angiography (iDSA), and postoperative clinical and radiologic findings were reviewed. RESULTS: Of these 8 patients, 5 patients underwent multiple embolizations (up to 3) and hybrid procedures, with no procedure-related complications. After microsurgical resection, iDSA revealed remnants of the fistula, which was then immediately re-resected, in 2 patients. At closing of the hybrid procedure, iDSA revealed no fistula remnants in 7 patients (88%). At mean follow-up examination (58 months), 5 patients (62%) had cure of the dAVF, confirmed by noninvasive angiography. Two patients (25%) experienced a recurrence of the dAVF within 5 months. CONCLUSIONS: Our hybrid techniques achieved high rates of dAVF obliteration, with all 8 patients achieving good or excellent outcomes and symptom relief. Angiographic follow-up within 6 months after the hybrid procedure is recommended for all patients even when intraoperative findings do not show remnants.

Longitudinal Imaging of Tumor Volume, Diffusivity, and Perfusion After Preoperative Endovascular Embolization in Supratentorial Hemispheric Meningiomas.

OBJECTIVE: To describe longitudinal image changes in supratentorial hemispheric meningiomas based on magnetic resonance imaging after preoperative embolization using calibrated microspheres. METHODS: A total of 14 patients with symptomatic supratentorial meningiomas were included in a prospective, mono-centric, mono-arm study. Magnetic resonance imaging changes on diffusion-weighted imaging, dynamic contrast susceptibility-perfusion-weighted imaging, susceptibility-weighted imaging, and magnetization-prepared rapid acquisition gradient-echo sequence T1-weighted postcontrast sequences 6 and 48 hours after embolization were evaluated and correlated with angiographic and clinical data. RESULTS: The mean age of the patients was 63 ± 12.7 years with an equal female/male ratio. Twelve meningiomas were World Health Organization grade I and II tumors. After embolization, baseline apparent diffusion coefficient (901 ± 166 mm2/s) decreased significantly within 6 hours (696 ± 115 mm2/s, P = 0.0008) as well within 48 hours (752 ± 134 mm2/s; P = 0.0147). Baseline mean ratio of relative cerebral blood volume (rCBV)tumor/rCBVwhite matter (3.67 ± 1.83) and relative cerebral blood flow (rCBF)tumor/rCBFwhite matter (2.89 ± 1.57) significantly decreased after embolization within 6 hours (rCBVtumor/rCBVwhite matter of 1.45 ± 0.9; P = 0.0007, rCBF of 1.16 ± 0.68; P = 0.0029) and 48 hours (rCBV of 1.50 ± 1.07; P = 0.0009, rCBFtumor/rCBFwhite matter of 1.19 ± 0.8; P = 0.003). The viable enhanced baseline mean tumor volume (54.3 ± 34.9 mm3) was sustainably and significantly diminished within 6 hours (26.6 ± 20.8 mm3; P = 0.02) and 48 hours (29.7 ± 22.5 mm3; P = 0.035) after embolization. There was a good correlation between angiographic devascularization rate and the embolized tumor volume at 6 hours (r = 0.7; P = 0.03) and 48 hours (r = 0.78; P = 0.041). CONCLUSIONS: Preoperative meningioma embolization with calibrated microspheres is safe and effectively induces a significant and sustainable tissue transformation over 48 hours.

Oxygen-transfer performance of a newly designed, very low-volume membrane oxygenator.

OBJECTIVES: Oxygenation of blood and other physiological solutions are routinely required in fundamental research for both in vitro and in vivo experimentation. However, very few oxygenators with suitable priming volumes (<2-3 ml) are available for surgery in small animals. We have designed a new, miniaturized membrane oxygenator and investigated the oxygen-transfer performance using both buffer and blood perfusates. METHODS: The mini-oxygenator was designed with a central perforated core-tube surrounded by parallel-oriented microporous polypropylene hollow fibres, placed inside a hollow shell with a lateral-luer outlet, and sealed at both extremities. With this design, perfusate is delivered via the core-tube to the centre of the mini-oxygenator, and exits via the luer port. A series of mini-oxygenators were constructed and tested in an in vitro perfusion circuit by monitoring oxygen transfer using modified Krebs-Henseleit buffer or whole porcine blood. Effects of perfusion pressure and temperature over flows of 5-60 ml × min(-1) were assessed. RESULTS: Twelve mini-oxygenators with a mean priming volume of 1.5 ± 0.3 ml were evaluated. With buffer, oxygen transfer reached a maximum of 14.8 ± 1.0 ml O2 × l(-1) (pO2: 450 ± 32 mmHg) at perfusate flow rates of 5 ml × min(-1) and decreased with an increase in perfusate flow to 7.8 ± 0.7 ml ml O2 × l(-1) (pO2: 219 ± 24 mmHg) at 60 ml × min(-1). Similarly, with blood perfusate, oxygen transfer also decreased as perfusate flow increased, ranging from 33 ± 5 ml O2 × l(-1) at 5 ml × min(-1) to 11 ± 2 ml O2 × l(-1) at 60 ml × min(-1). Furthermore, oxygen transfer capacity remained stable with blood perfusion over a period of at least 2 h. CONCLUSIONS: We have developed a new miniaturized membrane oxygenator with an ultra-low priming volume (<2 ml) and adequate oxygenation performance. This oxygenator may be of use in overcoming current limitations in equipment size for effective oxygenation in low-volume perfusion circuits, such as small animal extracorporeal circulation and ex vivo organ perfusion.

Targeting the bHLH transcriptional networks by mutated E proteins in experimental glioma.

Glioblastomas (GB) are aggressive primary brain tumors. Helix-loop-helix (HLH, ID proteins) and basic HLH (bHLH, e.g., Olig2) proteins are transcription factors that regulate stem cell proliferation and differentiation throughout development and into adulthood. Their convergence on many oncogenic signaling pathways combined with the observation that their overexpression in GB correlates with poor clinical outcome identifies these transcription factors as promising therapeutic targets. Important dimerization partners of HLH/bHLH proteins are E proteins that are necessary for nuclear translocation and DNA binding. Here, we overexpressed a wild type or a dominant negative form of E47 (dnE47) that lacks its nuclear localization signal thus preventing nuclear translocation of bHLH proteins in long-term glioma cell lines and in glioma-initiating cell lines and analyzed the effects in vitro and in vivo. While overexpression of E47 was sufficient to induce apoptosis in absence of bHLH proteins, dnE47 was necessary to prevent nuclear translocation of Olig2 and to achieve similar proapoptotic responses. Transcriptional analyses revealed downregulation of the antiapoptotic gene BCL2L1 and the proproliferative gene CDC25A as underlying mechanisms. Overexpression of dnE47 in glioma-initiating cell lines with high HLH and bHLH protein levels reduced sphere formation capacities and expression levels of Nestin, BCL2L1, and CDC25A. Finally, the in vivo induction of dnE47 expression in established xenografts prolonged survival. In conclusion, our data introduce a novel approach to jointly neutralize HLH and bHLH transcriptional networks activities, and identify these transcription factors as potential targets in glioma.