Radiological artificial intelligence - predicting personalized immunotherapy outcomes in lung cancer.

Personalized medicine has revolutionized approaches to treatment in the field of lung cancer by enabling therapies to be specific to each patient. However, physicians encounter an immense number of challenges in providing the optimal treatment regimen for the individual given the sheer complexity of clinical aspects such as tumor molecular profile, tumor microenvironment, expected adverse events, acquired or inherent resistance mechanisms, the development of brain metastases, the limited availability of biomarkers and the choice of combination therapy. The integration of innovative next-generation technologies such as deep learning-a subset of machine learning-and radiomics has the potential to transform the field by supporting clinical decision making in cancer treatment and the delivery of precision therapies while integrating numerous clinical considerations. In this review, we present a brief explanation of the available technologies, the benefits of using these technologies in predicting immunotherapy response in lung cancer, and the expected future challenges in the context of precision medicine.

Distribution of Aeration and Pulmonary Blood Volume in Healthy, ARDS and COVID-19 Lungs: A Dual-Energy Computed Tomography Retrospective Cohort Study.

RATIONALE AND OBJECTIVES: Few reports have studied lung aeration and perfusion in normal lungs, COVID-19, and ARDS from other causes (NC-ARDS) using dual-energy computed tomography pulmonary angiograms (DE-CTPA). To describe lung aeration and blood-volume distribution using DE-CTPAs of patients with NC-ARDS, COVID-19, and controls with a normal DE-CTPA ("healthy lungs"). We hypothesized that each of these conditions has unique ranges of aeration and pulmonary blood volumes. MATERIALS AND METHODS: This retrospective, single-center study of DE-CTPAs included patients with COVID-19, NC-ARDS (Berlin criteria), and controls. Patients with macroscopic pulmonary embolisms were excluded. The outcomes studied were the (1) lung blood-volume in areas with different aeration levels (normal, ground glass opacities [GGO], consolidated lung) and (2) aeration/blood-volume ratios. RESULTS: Included were 20 patients with COVID-19 (10 milds, 10 moderate-severe), six with NC-ARDS, and 12 healthy-controls. Lung aeration was lowest in patients with severe COVID-19 24% (IQR13%-31%) followed by those with NC-ARDS 40%(IQR21%-46%). Blood-volume in GGO was lowest in patients with COVID-19 [moderate-severe:-28.6 (IQR-33.1-23.2); mild: -30.1 (IQR-33.3-23.4)] and highest in normally aerated areas in NC-ARDS -37.4 (IQR-52.5-30.2-) and moderate-severe COVID-19 -33.5(IQR-44.2-28.5). The median aeration/blood-volume ratio was lowest in severe COVID-19 but some values overlapped with those observed among patients with NC-ARDS. CONCLUSION: Severe COVID-19 disease is associated with low total aerated lung volume and blood-volume in areas with GGO and overall aeration/blood volume ratios, and with high blood volume in normal lung areas. In this hypothesis-generating study, these findings were most pronounced in severe COVID disease. Larger studies are needed to confirm these preliminary findings.

The Added Value of a High CT Coronary Artery Calcium Score in the Management of Patients Presenting with Acute Chest Pain vs. Stable Chest Pain.

Background: Contrast computerized tomography (CT) scan is occasionally aborted due to a high coronary artery calcium score (CACS). For the same CACS in our clinical practice, we observed a higher occurrence of severe coronary artery disease (CAD) in patients with acute chest pain (ACP) compared to patients with stable chest pain (SCP). Since it is known that ACP differs in many ways from SCP, the aim of this study was to compare the predictive value of a high CACS for the diagnosis of severe CAD between ACP and SCP patients. Methods: This single center observational retrospective study included consecutive patients who underwent cardiac CT for chest pain and were found to have a CACS of >200 Agatston units. Patients were divided into two groups, ACP and SCP. Severe CAD was defined as ≥70% stenosis on coronary CT angiography or invasive coronary angiography. Baseline characteristics and final diagnosis of severe CAD were compared. Results: The cohort included 220 patients, 106 with ACP and 114 with SCP. ACP patients had higher severe CAD rates (60.4% vs. 36.8%; p < 0.001). On multivariate analysis including cardiac risk factors, CACS > 400 au (OR = 2.34 95% CI [1.32−4.15]; p = 0.004) and ACP (OR = 2.54 95% CI [1.45−4.45]; p = 0.001) were independent predictors of severe CAD. The addition of the clinical setting of ACP added significant incremental predictive value for severe stenosis. Conclusion: A high CACS is more associated with severe CAD in patients presenting with ACP than SCP. The findings suggest that the CACS could impact the management of patients during the scan.

Loss of left ventricular rotation is a significant determinant of functional mitral regurgitation.

AIM: To evaluate insufficient rotational movement of the left ventricle (LV) as a potential novel mechanism for functional regurgitation of the mitral valve (FMR). METHODS AND RESULTS: We compared reference subjects and patients with LV dysfunction (LVD, ejection fraction EF < 50%) with and without FMR (regurgitant volume RVol>10 ml). Subjects without structural mitral valve pathology undergoing cardiac MRI were evaluated. Delayed enhancement, global LV remodeling parameters, systolic twist and torsion were measured (using manual and novel automated cardiac MRI tissue-tracking). The study included 117 subjects with mean ± SD age 50.4 ± 17.8 years, of which 30.8% were female. Compared to subjects with LVD without FMR (n = 31), those with FMR (n = 37) had similar clinical characteristics, diagnoses, delayed enhancement, EF, and longitudinal strain. Subjects with FMR had significantly larger left ventricles (EDVi:136.6 ± 41.8 vs 97.5 ± 26.2 ml/m, p < 0.0001) with wider separation between papillary muscles (21.1 ± 7.6 vs 17.2 ± 5.7 mm, p = 0.023). Notably, they had lower apical (p < 0.0001) but not basal rotation and lower peak systolic twist (3.1 ± 2.4° vs 5.5 ± 2.5°, p < 0.0001) and torsion (0.56 ± 0.38°/cm vs 0.88 ± 0.52°/cm, p = 0.004). In a multivariate model for RVol including age, gender, twist, LV end-diastolic volume, sphericity index and separation between papillary muscles, only gender, volume and twist were significant. Twist was the most powerful correlate (beta -2.23, CI -3.26 to -1.23 p < 0.001). In patients with FMR, peak systolic twist negatively correlates with RVol (r = -0.73, p < 0.0001). CONCLUSION: Reduced rotational systolic LV motion is significantly and independently associated with RVol among patients with FMR, suggesting a novel pathophysiological mechanism and a potential therapeutic target.

Diffuse pulmonary calcifications: A case series and review of literature.

Pulmonary calcifications are usually incidental asymptomatic findings discovered on x-rays or computed tomography scans that can be easily overlooked, and their significance undermined, especially in a seemingly asymptomatic person. Calcifications can be a marker of chronicity or disease severity, and thus have diagnostic value. Rarely, calcification can be the direct cause of morbidity. Calcifications can be either localized or diffuse. Many diseases, in particular infectious diseases, can cause localized calcifications. Diffuse calcifications are less common and usually secondary to a handful of conditions such as dystrophic pulmonary calcifications, metastatic pulmonary calcifications, disseminated pulmonary ossifications and pulmonary alveolar microlithiasis. We describe three cases of diffuse pulmonary calcifications, review the different causes of diffuse pulmonary calcifications and provide some indicators on how to differentiate between them. Differentiating between the different types of pulmonary calcifications has significant implications on the management and prognosis of the patients, and thus it is important to distinguish between them.

COVID-19 classification of X-ray images using deep neural networks.

OBJECTIVES: In the midst of the coronavirus disease 2019 (COVID-19) outbreak, chest X-ray (CXR) imaging is playing an important role in diagnosis and monitoring of patients with COVID-19. We propose a deep learning model for detection of COVID-19 from CXRs, as well as a tool for retrieving similar patients according to the model's results on their CXRs. For training and evaluating our model, we collected CXRs from inpatients hospitalized in four different hospitals. METHODS: In this retrospective study, 1384 frontal CXRs, of COVID-19 confirmed patients imaged between March and August 2020, and 1024 matching CXRs of non-COVID patients imaged before the pandemic, were collected and used to build a deep learning classifier for detecting patients positive for COVID-19. The classifier consists of an ensemble of pre-trained deep neural networks (DNNS), specifically, ReNet34, ReNet50¸ ReNet152, and vgg16, and is enhanced by data augmentation and lung segmentation. We further implemented a nearest-neighbors algorithm that uses DNN-based image embeddings to retrieve the images most similar to a given image. RESULTS: Our model achieved accuracy of 90.3%, (95% CI: 86.3-93.7%) specificity of 90% (95% CI: 84.3-94%), and sensitivity of 90.5% (95% CI: 85-94%) on a test dataset comprising 15% (350/2326) of the original images. The AUC of the ROC curve is 0.96 (95% CI: 0.93-0.97). CONCLUSION: We provide deep learning models, trained and evaluated on CXRs that can assist medical efforts and reduce medical staff workload in handling COVID-19. KEY POINTS: • A machine learning model was able to detect chest X-ray (CXR) images of patients tested positive for COVID-19 with accuracy and detection rate above 90%. • A tool was created for finding existing CXR images with imaging characteristics most similar to a given CXR, according to the model's image embeddings.

Is There a Need for a Pulmonary Artery Catheter in Cardiac Surgery Today?

Pulmonary artery catheters are a useful tool for hemodynamic monitoring in high-risk patients during surgery and while in intensive care. However, there are major risks inherent to the device, and with modern day technology, their routine use has decreased. We discuss the need for routine insertion of pulmonary artery catheters in cardiac surgery. We also present a case of a left ventricular assist device implantation complicated by serious pulmonary hemorrhage due to pulmonary artery catheter insertion, highlighting the potentially life-threatening risks involved.

Bilateral Adrenal Hemorrhage in Coronavirus Disease 2019 Patient: A Case Report.

CONTEXT: Bilateral adrenal hemorrhage is a rare condition with potentially life-threatening consequences such as acute adrenal insufficiency. Early adrenal axis testing, as well as directed imaging, is crucial for immediate diagnosis and treatment. Coronavirus disease 2019 (COVID-19) has been associated with coagulopathy and thromboembolic events. CASE DESCRIPTION: A 66-year-old woman presented with acute COVID-19 infection and primary adrenal insufficiency due to bilateral adrenal hemorrhage (BAH). She also had a renal vein thrombosis. Her past medical history revealed primary antiphospholipid syndrome (APLS). Four weeks after discharge she had no signs of COVID-19 infection and her polymerase chain reaction test for COVID-19 was negative, but she still needed glucocorticoid and mineralocorticoid replacement therapy. The combination of APLS and COVID-19 was probably responsible of the adrenal event as a "two-hit" mechanism. CONCLUSIONS: COVID-19 infection is associated with coagulopathy and thromboembolic events, including BAH. Adrenal insufficiency is life threatening; therefore, we suggest that early adrenal axis testing for COVID-19 patients with clinical suspicion of adrenal insufficiency should be carried out.

Ibrutinib-associated invasive fungal diseases in patients with chronic lymphocytic leukaemia and non-Hodgkin lymphoma: An observational study.

BACKGROUND: Invasive fungal diseases (IFD) are life-threatening infections most commonly diagnosed in acute leukaemia patients with prolonged neutropenia and are uncommonly diagnosed in patients with lymphoproliferative diseases. OBJECTIVES: Following the initial report of aspergillosis diagnosed shortly after beginning ibrutinib for chronic lymphocytic leukaemia, a survey was developed to seek additional cases of IFD during ibrutinib treatment. METHODS: Local and international physicians and groups were approached for relevant cases. Patients were included if they met the following criteria: diagnosis of chronic lymphocytic leukaemia/non-Hodgkin lymphoma; proven or probable IFD; and ibrutinib treatment on the date IFD were diagnosed. Clinical and laboratory data were captured using REDCap software. RESULT: Thirty-five patients with IFD were reported from 22 centres in eight countries: 26 (74%) had chronic lymphocytic leukaemia. The median duration of ibrutinib treatment before the onset of IFD was 45 days (range 1-540). Aspergillus species were identified in 22 (63%) of the patients and Cryptococcus species in 9 (26%). Pulmonary involvement occurred in 69% of patients, cranial in 60% and disseminated disease in 60%. A definite diagnosis was made in 21 patients (69%), and the mortality rate was 69%. Data from Israel regarding ibrutinib treated patients were used to evaluate a prevalence of 2.4% IFD. CONCLUSIONS: The prevalence of IFD among chronic lymphocytic leukaemia/non-Hodgkin lymphoma patients treated with ibrutinib appears to be higher than expected. These patients often present with unusual clinical features. Mortality from IFD in this study was high, indicating that additional studies are urgently needed to identify patients at risk for ibrutinib-associated IFD.

The management of cardiac implantable electronic device lead perforations: a multicentre study.

AIMS: Lead perforation is a rare, well-known complication of cardiac implantable electronic device (CIED) implants, whose management is mostly not evidence-based. Main management strategies include conservative approach based on clinical and lead function follow-up vs. routine invasive lead revision approach. This study compared the complications of both strategies by composite endpoint, including recurrent perforation-related symptoms, recurrent pericardial effusion (PEf), lead dysfunction, and device infection during 12 month follow-up. METHODS AND RESULTS: Multicentre retrospective analysis, inquiring data from imaging studies, device interrogation, pericardiocentesis, and clinical charts of patients with suspected perforating leads between 2007 and 2014 in five hospitals. All cases were reviewed by electrophysiologist and defined as definite perforations by suggestive symptoms along with lead perforation on imaging, bloody PEf on pericardiocentesis shortly after implant, or right ventricular (RV) lead non-capture along with diaphragmatic stimulation upon bipolar pacing. Clinical outcomes associated with both management approaches were compared, with respect to the composite endpoint. The study included 48 definitive perforation cases: 22 managed conservatively and 26 via lead revision. Conservative management was associated with an increased composite endpoint compared with lead revision (8/22 vs. 1/26; P = 0.007). The dominant complication among the conservative cohort was appearance of cardiac tamponade during follow-up; 5/6 occurring in cases which presented with no or only mild PEf and were treated by antiplatelets/coagulants during or shortly after CIED implantation. CONCLUSION: A conservative management of CIED lead perforation is associated with increased complications compared with early lead revision. Lead revision may be the preferred management particularly in patients receiving antiplatelets/coagulants.

The radiological myometrial appearance after cesarean section: is it associated with postpartum complications and subsequent delivery outcome?

PURPOSE: To evaluate whether the characteristics of the radiological uterine myometrial discontinuity (RMD) is associated with maternal-neonatal outcomes and post-cesarean section (CS) complications. A secondary aim was to describe the evolution of the CT uterine surgical incision and the related outcome of a subsequent trial of labor after cesarean (TOLAC). METHODS: Single center retrospective cohort study of CT scans was performed within 6 weeks from cesarean delivery. Demographic characteristics of patients were recorded (age, intrapartum fever, CS data, and hospital stay length). Abdominopelvic CT scans were performed using a multidetector CT (16 or 256 slice) with intravenous contrast material. CT analysis was performed by two radiologists in consensus. The RMD seen as low attenuation gap in expected incision site was assessed for: visualization, thickness, and presence of gas. Logistic regression analysis was fitted to assess the relationship of the delivery-CT time interval with the presence of RMD and gas. RESULTS: Of a total of 75,791 births during the study period there were 8775 CS (11.6%). The study group consisted of 101 CTs in 84 woman after CS. RMD defined in 73 (72.2%) of all CT exams; the mean RMD thickness was 7 mm ± 3.9, "RMD gas" observed in 15 (17.9%) of CT exams. RMD thickness or gas presence were strongly associated with a CS-1st CT exam time interval of less than 7 days, OR 5.8 [CI 1.5-22.6], p = 0.010, but not with maternal, delivery, or neonatal characteristics. A subsequent successful vaginal birth was achieved in 75% of the patients with no uterine rupture, regardless of the RMD gas presence. CONCLUSION: RMD gas visualization on CT is not associated with febrile morbidity, cesarean characteristics, and subsequent TOLAC results. RMD gas is a normal post-operative finding and should not lead to changes in the postpartum delivery complication management or recommendations for the future mode of delivery.

Dual-energy computed tomography as a diagnostic tool for gout during intercritical periods.

AIM: The aim of this study is to evaluate the diagnostic yield of dual-energy computed tomography (DECT) in detection of uric acid accumulation in joints or periarticular structures in patients suspected of having gout, in their intercritical period. METHODS: Patients with a history of recurrent, short-lived mono- or oligo-arthralgia or arthritis, referred to the rheumatology clinic for diagnosis of their condition, were included in this retrospective evaluation. RESULTS: DECT confirmed the diagnosis of gout in 30 of 50 patients (60%). A positive DECT was present in 12 of 16 cases (75%) with serum uric acid > 8.5 mg/dL, compared to seven of 13 cases (54%) and two of five cases (40%) with levels of 6.1-8.5 mg/dL and ≤ 6 mg/dL, respectively. The diagnostic impact of screening hands and feet were highest (78% and 56%, respectively). Follow-up data were available for 24 of the 30 patients with urate deposits identified by DECT. Twenty-one were treated with urate-lowering agents, all responded with lowering of serum uric acid and cessation of flares. Follow-up data were available for 16 of the 20 patients with no urate deposits identified by DECT. Gout was diagnosed in two of them by synovial fluid examination during subsequent flares. Both positive and negative predictive values of DECT for diagnosing gout in this patient population were 87%. Following DECT, treatment regimen was modified to gout-specific therapy in 52% of the patients. DISCUSSION: The ability to make a definite diagnosis of gout by DECT imaging in a substantial number of asymptomatic patients in the intercritical period should help in treatment decision-making and improve patient adherence to long-term urate-lowering therapy.

MEK inhibitor treatment is effective in a patient with metastatic carcinoma of the ampulla of Vater with BRAF and NRAS mutations shown by next-generation sequencing.

Here, we present a case of an 84-year-old woman who developed obstructive jaundice and was diagnosed with nonoperable adenocarcinoma originating from the ampulla of Vater, a lethal disease with a median overall survival of less than a year. Her tumor was examined by next-generation sequencing, which showed BRAF and NRAS mutations. To target these mutations, a MEK inhibitor was chosen for treatment. The patient has been treated with a MEK inhibitor for the last 12 months since diagnosis, with clinical and laboratory improvement and manageable side effects. PET-computed tomography imaging has shown stable disease or improvement in the primary and metastatic lesions. This is the first case report of an ampulla of a Vater cancer patient with NRAS and BRAF mutations, identified in next-generation sequencing, and treated successfully with a MEK inhibitor.

Ectopic pancreatic pseudocyst and cyst presenting as a cervical and mediastinal mass: case report and review of the literature.

Ectopic pancreas in the mediastinum is extremely rare. We are reporting on a case of a twenty two year old woman who presented to our clinic with a large cervical mass. The CT scan revealed a cystic lesion in the anterior mediastinum. The patient underwent surgical resection by cervical approach. A Cystic mass with pseudocysts, cysts and complete pancreatic tissue were found in pathology. There were no signs of pancreatitis or malignancy. No recurrence was observed after a follow up of four years. We reviewed the case reports describing this rare condition in the medical literature.We conclude that the possibility of ectopic pancreatic tissue should be included in the differential diagnosis of anterior mediastinal cystic mass, though as a remote possibility. Surgery is probably needed for the diagnosis and treatment. Posterior mediastinal pseudocyst is a different entity associated with acute pancreatitis. In those cases surgery is not recommended. Our third conclusion is that pancreatic tissue should be actively sought, if a structure resembling a pseudocyst is found in an unexpected location. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1849369005957671.