Evaluation of pure-tone audiometric protocols in vestibular schwannoma screening

The objective was to evaluate the pure-tone audiogram-based screening protocols in VS diagnostics. We retrospectively analyzed presenting symptoms, pure tone audiometry and MRI finding from 246 VS patients and 442 controls were collected to test screening protocols (AAO-HNS, AMCLASS-A/B, Charing Cross, Cueva, DOH, Nashville, Oxford, Rule3000, Schlauch, Seattle, Sunderland) for sensitivity and specificity. Results were pooled with data from five other studies, and analysis of sensitivity, specificity and positive likelihood ratio (LR+) for each protocol was performed. Our results show that protocols with significantly higher sensitivity (AMCLASS-A/B, Nashville) show also significantly lowest specificity, and tend to have low association (positive likelihood ratio, LR+) to the VS. The highest LR+ was found for protocols AAO-HNS, Rule3000 and Seattle. In conclusions, knowing their properties, screening protocols are simple decision-making tools in VS diagnostic. To use the advantage of the highest sensitivity, protocols AMCLASS-A + B or Nashville can be of choice. For more reasonable approach, applying the protocols with high LR+ (AAO-HNS, Rule3000, Seattle) may reduce the overall number of MRI scans at expense of only few primarily undiagnosed VS.     

Labyrinthine malformation in the 22q11.2 deletion syndrome

Velocardiofacial syndrome and DiGeorge syndrome, integrating to form the 22q11.2 deletion syndrome, manifest frequently with hearing loss. Instead, a labyrinthine anomaly is only occasionally described in velocardiofacial syndrome/DiGeorge syndrome. We report a vestibular labyrinthine malformation demonstrated with computed tomographic scan in a patient with a palatal cleft and a 22q11.2 deletion presenting as velocardiofacial syndrome.     

Off-pump versus on-pump coronary artery bypass surgery in patients aged 80 years and older: institutional results and meta-analysis

Patients aged ≥80 years are at high risk of adverse events after coronary artery bypass grafting. This study was performed to evaluate whether off-pump coronary artery bypass surgery (OPCAB) is superior to conventional surgery (CCAB) in these high-risk patients. The outcome of 185 patients aged ≥80 years who underwent OPCAB or CCAB at our institution was reviewed and a meta-analysis on this issue was performed. Similar immediate postoperative results were observed after OPCAB and CCAB at our institution, despite significantly different operative risk (mean logistic EuroSCORE, OPCAB 20.3% vs CCAB 13.4%, P = 0.003). Among 56 propensity score matched pairs a trend toward lower postoperative stroke (0%, 95% CI 0–0 vs 3.6%, 95% CI 0–10.0, P = 0.50) was observed after OPCAB. No significant differences were observed in the other outcome end points. Five-year survival was 81.0% after OPCAB and 78.1% after CCAB (P = 0.239). Pooled analysis of eight studies including 3416 patients showed a significantly higher risk of postoperative stroke after CCAB (pooled rates: 4.2%, 95% confidence interval (95% CI) 2.4–7.1 vs 1.5%, 95% CI 0.9–2.5, risk ratio (RR) 2.15, 95% CI 1.17–3.96, P = 0.01). A trend toward higher immediate postoperative mortality was observed after CCAB (15 studies including 4409 patients, pooled rates: 6.5%, 95% CI 5.2–8.0 vs 5.6%, 95% CI 4.2–7.4, RR 1.29, 95% CI 0.86–1.93, P = 0.21). Generic inverse variance analysis showed similar intermediate survival after CCAB and OPCAB (RR 1.31, 95% CI 0.85–2.01, P = 0.22). At 2 years, survival was 82.8% (95% CI 76.4–89.2) after CCAB and 88.3% (95% CI 82.9–93.7) after OPCAB. Current results indicate that OPCAB compared with CCAB in patients aged ≥80 years is associated with significantly lower postoperative stroke and with a trend toward better early survival. However, suboptimal quality of the available studies, particularly the lack of comparability of the study groups, prevents conclusive results on this controversial issue.     

Long-term outcomes after ascending aortic replacement and aortic root replacement for type A aortic dissection

 Open in a separate windowOBJECTIVESWe investigated whether the selective use of supracoronary ascending aorta replacement achieves late outcomes comparable to those of aortic root replacement for acute Stanford type A aortic dissection (TAAD).METHODSPatients who underwent surgery for acute type A aortic dissection from 2005 to 2018 at the Helsinki University Hospital, Finland, were included in this analysis. Late mortality was evaluated with the Kaplan–Meier method and proximal aortic reoperation, i.e. operation on the aortic root or aortic valve, with the competing risk method.RESULTSOut of 309 patients, 216 underwent supracoronary ascending aortic replacement and 93 had aortic root replacement. At 10 years, mortality was 33.8% after aortic root replacement and 35.2% after ascending aortic replacement (P = 0.806, adjusted hazard ratio 1.25, 95% confidence interval, 0.77–2.02), and the cumulative incidence of proximal aortic reoperation was 6.0% in the aortic root replacement group and 6.2% in the ascending aortic replacement group (P = 0.65; adjusted subdistributional hazard ratio 0.53, 95% confidence interval 0.15–1.89). Among 71 propensity score matched pairs, 10-year survival was 34.4% after aortic root replacement and 36.2% after ascending aortic replacement surgery (P = 0.70). Cumulative incidence of proximal aortic reoperation was 7.0% after aortic root replacement and 13.0% after ascending aortic replacement surgery (P = 0.22). Among 102 patients with complete imaging data [mean follow-up, 4.7 (3.2) years], the estimated growth rate of the aortic root diameter was 0.22 mm/year, that of its area 7.19 mm²/year and that of its perimeter 0.43 mm/year.CONCLUSIONSWhen stringent selection criteria were used to determine the extent of proximal aortic reconstruction, aortic root replacement and ascending aortic replacement for type A aortic dissection achieved comparable clinical outcomes.     

SARS‐CoV‐2 and human milk: What is the evidence?

The novel coronavirus SARS‐CoV‐2 has emerged as one of the most compelling and concerning public health challenges of our time. To address the myriad issues generated by this pandemic, an interdisciplinary breadth of research, clinical and public health communities has rapidly engaged to collectively find answers and solutions. One area of active inquiry is understanding the mode(s) of SARS‐CoV‐2 transmission. Although respiratory droplets are a known mechanism of transmission, other mechanisms are likely. Of particular importance to global health is the possibility of vertical transmission from infected mothers to infants through breastfeeding or consumption of human milk. However, there is limited published literature related to vertical transmission of any human coronaviruses (including SARS‐CoV‐2) via human milk and/or breastfeeding. Results of the literature search reported here (finalized on 17 April 2020) revealed a single study providing some evidence of vertical transmission of human coronavirus 229E; a single study evaluating presence of SARS‐CoV in human milk (it was negative); and no published data on MERS‐CoV and human milk. We identified 13 studies reporting human milk tested for SARS‐CoV‐2; one study (a non‐peer‐reviewed preprint) detected the virus in one milk sample, and another study detected SARS‐CoV‐2 specific IgG in milk. Importantly, none of the studies on coronaviruses and human milk report validation of their collection and analytical methods for use in human milk. These reports are evaluated here, and their implications related to the possibility of vertical transmission of coronaviruses (in particular, SARS‐CoV‐2) during breastfeeding are discussed.     

VEGF Pathways in the Lymphatics of Healthy and Diseased Heart

Cardiac lymphatic system is a rare focus of the modern cardiovascular research. Nevertheless, the growing body of evidence is depicting lymphatic endothelium as an important functional unit in healthy and diseased myocardium. Since the discovery of angiogenic VEGF‐A in 1983 and lymphangiogenic VEGF‐C in 1997, an increasing amount of knowledge has accumulated on the essential roles of VEGF ligands and receptors in physiological and pathological angiogenesis and lymphangiogenesis. Tissue adaptation to several stimuli such as hypoxia, pathogen invasion, degenerative process and inflammation often involves coordinated changes in both blood and lymphatic vessels. As lymphatic vessels are involved in the initiation and resolution of inflammation and regulation of tissue edema, VEGF family members may have important roles in myocardial lymphatics in healthy and in cardiac disease. We will review the properties of VEGF ligands and receptors concentrating on their lymphatic vessel effects first in normal myocardium and then in cardiac disease.     

Spatial aspects of oncogenic signalling determine the response to combination therapy in slice explants from Kras‐driven lung tumours

A key question in precision medicine is how functional heterogeneity in solid tumours informs therapeutic sensitivity. We demonstrate that spatial characteristics of oncogenic signalling and therapy response can be modelled in precision‐cut slices from Kras‐driven non‐small‐cell lung cancer with varying histopathologies. Unexpectedly, profiling of in situ tumours demonstrated that signalling stratifies mostly according to histopathology, showing enhanced AKT and SRC activity in adenosquamous carcinoma, and mitogen‐activated protein kinase (MAPK) activity in adenocarcinoma. In addition, high intertumour and intratumour variability was detected, particularly of MAPK and mammalian target of rapamycin (mTOR) complex 1 activity. Using short‐term treatment of slice explants, we showed that cytotoxic responses to combination MAPK and phosphoinositide 3‐kinase–mTOR inhibition correlate with the spatially defined activities of both pathways. Thus, whereas genetic drivers determine histopathology spectra, histopathology‐associated and spatially variable signalling activities determine drug sensitivity. Our study is in support of spatial aspects of signalling heterogeneity being considered in clinical diagnostic settings, particularly to guide the selection of drug combinations. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.