Thi Dan Linh Nguyen-Kim

TAVI in a low left main coronary artery ostium and wide aortic sinus of Valsava

A very short distance between the aortic annulus and the left main coronary artery (LMCA) ostium is typically a contraindication for transcatheter aortic valve implantation (TAVI) given concerns of potential coronary obstruction following their deployment. We report the case of an 85-year-old patient admitted to our hospital with acute cardiac decompensation. Transthoracic echocardiography demonstrated …

Brief Report: Pulmonary Function Tests: High Rate of False-Negative Results in the Early Detection and Screening of Scleroderma-Related Interstitial Lung Disease.

Validated methods for the screening and early diagnosis of systemic sclerosis (SSc; scleroderma)–related interstitial lung disease (ILD) are needed. The aim of this study was to evaluate the performance of pulmonary function tests (PFTs) compared with that of high‐resolution computed tomography (HRCT) of the chest for the detection of SSc‐related ILD in clinical practice, and to identify predictors of lung involvement that is functionally occult but significant on HRCT.

Evaluation of clinicopathological factors in PD-1 response: derivation and validation of a prediction scale for response to PD-1 monotherapy.

Background:Anti-PD-1 therapy has shown significant clinical activity in advanced melanoma. We developed and validated a clinical prediction scale for response to anti- PD-1 monotherapy.Methods:A total of 315 patients with advanced melanoma treated with pembrolizumab (2 or 10 mg kg−1 Q2W or Q3W) or nivolumab (3 mg kg−1 Q2W) at four cancer centres between 2011 to 2013 served as the setting for the present cohort study. Variables with significant association to response on a univariate analysis were entered into a forward stepwise logistic regression model and were given a score based on ORs to calculate a clinical prediction scale.Results:The developed clinical prediction scale included elevated LDH (1 point), age <65 years (1 point), female sex (1 point), history of ipilimumab treatment (2 points) and the presence of liver metastasis (2 points). The scale had an area under the receiver-operating curve (AUC) of 0.73 (95% CI 0.67, 0.80) in predicting response to therapy. The predictive performance of the score was maintained in the validation cohort (AUC 0.70 (95% CI 0.58, 0.81)) and the goodness-to-fit model demonstrated good calibration.Conclusions:Based on a large cohort of patients, we developed and validated a simple five-factor prediction scale for the clinical activity of PD-1 antibodies in advanced melanoma patients. This scale can be used to stratify patients participating in clinical trials.

Evaluation of pulmonary nodules and infection on chest CT with radiation dose equivalent to chest radiography: Prospective intra-individual comparison study to standard dose CT

PURPOSE To compare prospectively, in patients undergoing chest computed tomography (CT) for pulmonary-nodules or infection, image-quality and accuracy of standard dose (SD) and reduced dose (RD) CT with tin-filtration. MATERIAL AND METHODS This IRB-approved study included 100 consecutive patients (36 female;median age 56 years) referred for follow-up of pulmonary-nodules (n=43) or suspicion of infection (n=57) undergoing single-energy CT with SD and RD using tin-filtration at 100 kVp (CTDIvol 2.47 mGy and 0.07 mGy, respectively). Images were reconstructed with advanced modeled iterative reconstruction (ADMIRE) at strength 3 and 5. Image-noise was measured. Two independent readers evaluated nodules and pulmonary-infection. SD CT served as reference standard. RESULTS No significant difference was found in noise between RD with ADMIRE5 and SD with ADMIRE3 (118HU ± 14 vs. 120HU ± 17; p=0.08). Sensitivity for detection of atelectasis and interstitial lung changes was higher in images reconstructed with ADMIRE5 (93% and 88%; respectively) than in those reconstructed with ADIMRE3 (77% and 78%; respectively). Sensitivity for detection of consolidations was 90% for ADMIRE3 and 89% for ADMIRE5. Sensitivity for nodule detection was 71% for ADMIRE3 and 81% for ADMIRE5. Specificity for detection of atelectasis and interstitial lung changes was 99% and 96% with ADMIRE5 and 99% and 96% with ADMIRE3. Specificity for detection of consolidations was 99% for ADMIRE3 and 5. Specificity for detection of nodules was 87% for both ADMIRE3 and 5. CONCLUSION Chest CT with a radiation dose equivalent to conventional radiography is feasible and allows for detection of pulmonary infection with high sensitivity, whereas the accuracy for detecting nodules is only moderate.

A New Prognostic Score Supporting Treatment Allocation for Multimodality Therapy for Malignant Pleural Mesothelioma: A Review of 12 Years' Experience

Introduction: Treatment of malignant pleural mesothelioma (MPM) remains a clinical challenge. The aim of this study was to identify selection factors for allocation of MPM patients to multimodal therapy based on survival data from 12 years of experience. Methods: Eligible patients had MPM of all histological subtypes with clinical stage T1–3 N0–2 M0. Induction chemotherapy consisted of cisplatin/gemcitabine (cis/gem) or cisplatin/pemetrexed (cis/pem), followed by extrapleural pneumonectomy (EPP). Multivariate analysis was performed to assess independent prognosticators for overall survival (OS). A Multimodality Prognostic Score was developed based on clinical variables available before surgery. Results: From May 1999 to August 2011, 186 MPM patients were intended to be treated with induction chemotherapy followed by EPP. Hematologic toxicity was significantly less frequent after cis/pem compared to cis/gem, but there was no difference in response or OS between the regimens. One hundred and twenty-eight patients underwent EPP with a 30-day mortality of 4.7%. Fifty-two percent of the patients received adjuvant radiotherapy. The median OS of patients undergoing EPP was significantly longer with 22 months (95% confidence interval: 20–24) when compared to 11 months (9–12) for patients treated without EPP. A prognostic score was defined considering tumor volume, histology, C-reactive protein level, and response to chemotherapy that identified patient groups not benefitting from multimodality treatment which was confirmed in an independent cohort. Conclusion: Patients receiving induction chemotherapy followed by EPP for MPM of all histological subtypes and irrespective of nodal status showed a median survival of 22 months. A prognostic score is proposed to help patient allocation for surgery after validation in an independent cohort.

Assessment of bronchial and pulmonary blood supply in non-small cell lung cancer subtypes using computed tomography perfusion.

ObjectivesThe aim of this study was to investigate the dual blood supply of non–small cell lung cancer (NSCLC) and its association with tumor subtype, size, and stage, using computed tomography perfusion (CTP). Materials and MethodsA total of 54 patients (median age, 65 years; range, 42–79 years; 15 women, 39 men) with suspected lung cancer underwent a CTP scan of the lung tumor. Pulmonary and bronchial vasculature regions of interest were used to calculate independently CTP parameters (blood flow [BF], blood volume [BV], and mean transit time [MTT]) of the tumor tissue. The mean and maximum pulmonary and bronchial perfusion indexes (PImean and PImax) were calculated. The tumoral volume and the largest tumoral diameter were assessed. Differences in CTP parameters and indexes among NSCLC subtypes, tumor stages and tumor dimensions were analyzed using non-parametric tests. ResultsAccording to biopsy, 37 patients had NSCLC (22 adenocarcinomas [ACs], 8 squamous cell carcinomas [SCCs], 7 large-cell carcinomas [LCC]). The mean bronchial BF/pulmonary BF, bronchial BV/pulmonary BV, and bronchial MTT/pulmonary MTT was 41.2 ± 30.0/36.9 ± 24.2 mL/100 mL/min, 11.4 ± 9.7/10.4 ± 9.4 mL/100 mL, and 11.4 ± 4.3/14.9 ± 4.4 seconds, respectively. In general, higher bronchial BF than pulmonary BF was observed in NSCLC (P = 0.014). Using a tumoral volume cutoff of 3.5 cm3, a significant difference in pulmonary PImax was found (P = 0.028). There was a significantly higher mean pulmonary BF in LCCs and SCCs compared with ACs (P = 0.018 and P = 0.044, respectively), whereas the mean bronchial BF was only significantly higher in LCCs compared with ACs (P = 0.024). Correspondingly, the PImax was significantly higher in LCCs and SCCs than in ACs (P = 0.001 for both). Differences between bronchial and pulmonary PImean and PImax among T stages and Union Internationale Contre le Cancer stages were not statistically significant (P values ranging from 0.691 to 0.753). ConclusionsThe known dual blood supply of NSCLC, which depends on tumor size and histological subtype, is reflected in CTP parameters, with parameters depending both on tumor size and histological subtype. This has to be accounted for when analyzing NSCLC with CTP.

Lumbar Facet Joint Arthritis Is Associated with More Coronal Orientation of the Facet Joints at the Upper Lumbar Spine

We retrospectively analyzed CT scans of 620 individuals, who presented to our traumatology department between 2008 and 2010. Facet joint (FJ) arthritis was present in 308 (49.7%) individuals with a mean grade of 1. It was seen in 27% of individuals ≤40 years and in 75% of individuals ≥41 years (P < 0.0001) as well as in 52% of females and 49% of males (P = 0.61). Mean FJ orientation was 30.4° at L2/3, 38.7° at L3/4, 47° at L4/5, and 47.3° at L5/S1. FJ arthritis was significantly associated with more coronal (increased degree) FJ orientation at L2/3 (P = 0.03) with a cutoff point at ≥32°. FJs were more coronally oriented (48.8°) in individuals ≤40 years and more sagittally oriented (45.6°) in individuals ≥41 years at L5/S1 (P = 0.01). Mean FJ asymmetry was 4.89° at L2/3, 6.01° at L3/4, 6.67° at L4/5, and 7.27° at L5/S1, without a significant difference for FJ arthritis. FJ arthritis is common, increases with age, and affects both genders equally. More coronally oriented FJs (≥32°) in the upper lumbar spine may be an individual risk factor for development of FJ arthritis.

How much liver needs to be transected in ALPPS? A translational study investigating the concept of less invasiveness.

BACKGROUND ALPPS induces rapid liver hypertrophy after stage‐1 operation, enabling safe, extended resections (stage‐2) after a short period. Recent studies have suggested that partial transection at stage‐1 might be associated with a better safety profile. The aim of this study was to assess the amount of liver parenchyma that needs to be divided to achieve sufficient liver hypertrophy in ALPPS. METHODS In a bi‐institutional, prospective cohort study, nonfibrotic patients who underwent ALPPS with complete (n = 22) or partial (n = 23) transection for colorectal liver metastases were analyzed and compared with an external ALPPS cohort (n = 23). A radiologic tool was developed to quantify the amount of parenchymal transection. Liver hypertrophy and clinical outcome were compared between both techniques. The relationship of partial transection and hypertrophy was investigated further in an experimental murine model of partial ALPPS. RESULT The median amount of parenchymal transection in partial ALPPS was 61% (range, 34–86%). The radiologic method correlated poorly with the intraoperative surgeons estimation (rS = 0.258). Liver hypertrophy was equivalent for the partial ALPPS, ALPPS, and external ALPPS cohort (64% vs 60% vs. 64%). Experimental data demonstrated that partial transection of at least 50% induced comparable hypertrophy (137% vs 156%) and hepatocyte proliferation compared to complete transection. CONCLUSION The study provides clinical and experimental evidence that partial liver partition of at least 50% seems to be equally effective in triggering volume hypertrophy as observed with complete transection and can be re recommended as less invasive alternative to ALPPS.

Urinary Biomarkers at Early ADPKD Disease Stage

Background Autosomal dominant polycystic kidney disease (ADPKD) is characterized by a decline in renal function at late disease stage when the majority of functional renal parenchyma is replaced by cystic tissue. Thus, kidney function, assessed by estimated glomerular filtration rate (eGFR) does not well represent disease burden in early disease. Here, we investigated various urinary markers for tubular injury and their association with disease burden in ADPKD patients at early disease course. Methods ADPKD patients between 18 and 40 years with an eGFR greater or equal to 70 ml per min per 1.73m2 were eligible for this cross-sectional study. Urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL), Kidney Injury Molecule-1 (KIM-1), and Uromodulin (UMOD) were investigated by Enzyme-Linked Immunosorbent Assay. Clara Cell Protein 16 (CC16) was investigated by Latex Immuno Assay. Cryoscopy was performed to assess urine osmolality and Urinary Albumin-to-Creatinine Ratio (UACR) was calculated. The association and the predictive properties of the markers on eGFR and height adjusted total kidney volume (htTKV) was evaluated using multiple regression analysis, incorporating different control variables for adjustment. Internal bootstrapping validated the obtained results. Results In 139 ADPKD patients (age 31 ±7 years, mean eGFR of 93 ± 19 ml per min per 1.73 m2) the total kidney volume was negatively correlated with eGFR and UMOD and positive associated with age, UACR, KIM-1 and urine osmolality after adjustment for possible confounders. Urine osmolality and htTKV were also associated with eGFR, whereas no association of CC16, NGAL and UMOD with eGFR or htTKV was found. Conclusion UACR and urinary KIM-1 are independently associated with kidney size but not with renal function in our study population. Urine osmolality was associated with eGFR and kidney volume following adjustment for multiple confounders. Despite statistical significance, the clinical value of our results is not yet conceivable. Further studies are needed to evaluate the property of the aforementioned biomarkers to assess disease state at early ADPKD stage.

Prognostic value of aortic regurgitation after TAVI in patients with chronic kidney disease

BACKGROUND Aortic regurgitation (AR) after transcatheter aortic valve implantation (TAVI) for severe aortic valve stenosis results in major haemodynamic changes. Influence of post-implant AR and aortic valve calcification on outcome in patients with chronic kidney disease (CKD) is unclear. METHODS Short-term outcome was defined as a combined 30-day endpoint, long-term outcome as survival. Post-implant AR was classified as none/mild or moderate/severe using transthoracic echocardiography. Aortic valve calcification was calculated by computed tomography. Logistic regression analyses were performed in patients with none/mild (estimated glomerular filtration rate [eGFR]≥30ml/min/1.73m(2)) and advanced (eGFR<30ml/min/1.73m(2)) CKD to evaluate predictors of outcome and post-implant AR. RESULTS TAVI was performed in 546 consecutive patients. Moderate/severe post-implant AR was the only independent predictor of the 30-day endpoint in patients with advanced (OR 7.091, 95% CI 1.144-43.962, p=0.035), but not in patients with none/mild CKD. Similarly, moderate/severe AR predicted impaired survival only in patients with advanced CKD (p<0.001). NT-proBNP (OR 1.023 per 500ng/l increase, 95% CI 1.003-1.043; p=0.026) before intervention was the only independent predictor of the 30-day endpoint in patients with none/mild CKD. Aortic valve calcification was comparable in patients with none/mild versus advanced CKD and was an independent predictor of moderate/severe post-implant AR in the overall population as well as in the subgroups with none/mild or advanced CKD. CONCLUSIONS Moderate/severe AR after TAVI predicts outcome in patients with advanced CKD, but not in patients with none/mild CKD. Aortic valve calcification is an important predictor of post-implant AR independent of kidney function.