Prognostic and predictive significance of nuclear HIF1α expression in locally advanced HNSCC patients treated with chemoradiation with or without nimotuzumab

Background Anti-EGFR-based therapies have limited success in HNSCC patients. Predictive biomarkers are greatly needed to identify the patients likely to be benefited from these targeted therapies. Here, we present the prognostic and predictive association of biomarkers in HPV-negative locally advanced (LA) HNSCC patients.Methods Treatment-naive tumour tissue samples of 404 patients, a subset of randomised Phase 3 trial comparing cisplatin radiation (CRT) versus nimotuzumab plus cisplatin radiation (NCRT) were analysed to evaluate the expression of HIF1α, EGFR and pEGFR by immunohistochemistry and EGFR gene copy change by FISH. Progression-free survival (PFS), locoregional control (LRC) and overall survival (OS) were estimated by Kaplan–Meier method. Hazard ratios were estimated by Cox proportional hazard models.Results Baseline characteristics of the patients were balanced between two treatment groups (CRT vs NCRT) and were representative of the trial cohort. The median follow-up was of 39.13 months. Low HIF1α was associated with better PFS [HR (95% CI) = 0.62 (0.42–0.93)], LRC [HR (95% CI) = 0.56 (0.37–0.86)] and OS [HR (95% CI) = 0.63 (0.43–0.93)] in the CRT group. Multivariable analysis revealed HIF1α as an independent negative prognostic biomarker. For patients with high HIF1α, NCRT significantly improved the outcomes [PFS:HR (95% CI) = 0.55 (0.37–0.82), LRC:HR (95% CI) = 0.55 (0.36–0.85) and OS:HR (95% CI) = 0.54 (0.36–0.81)] compared to CRT. While in patients with low HIF1α, no difference in the clinical outcomes was observed between treatments. Interaction test suggested a predictive value of HIF1α for OS (P = 0.008).Conclusions High HIF1α expression is a predictor of poor clinical response to CRT in HPV-negative LA-HNSCC patients. These patients with high HIF1α significantly benefited with the addition of nimotuzumab to CRT.Clinical trial registration Registered with the Clinical Trial Registry of India (Trial registration identifier—CTRI/2014/09/004980).Subject terms: Tumour biomarkers, Head and neck cancer, Tumour biomarkers, Head and neck cancer, Predictive markers     

Obstetric analgesia and anaesthesia in SARS-CoV-2-positive parturients across 10 maternity units in the north-west of England: a retrospective cohort study

Since the start of the COVID-19 pandemic, few studies have reported anaesthetic outcomes in parturients with SARS-CoV-2 infection. We reviewed the labour analgesic and anaesthetic interventions utilised in symptomatic and asymptomatic parturients who had a confirmed positive test for SARS-CoV-2 across 10 hospitals in the north-west of England between 1 April 2020 and 31 May 2021. Primary outcomes analysed included the analgesic/anaesthetic technique utilised for labour and caesarean birth. Secondary outcomes included a comparison of maternal characteristics, caesarean birth rate, maternal critical care admission rate along with adverse composite neonatal outcomes. A positive SARS-CoV-2 test was recorded in 836 parturients with 263 (31.4%) reported to have symptoms of COVID-19. Neuraxial labour analgesia was utilised in 104 (20.4%) of the 509 parturients who went on to have a vaginal birth. No differences in epidural analgesia rates were observed between symptomatic and asymptomatic parturients (OR 1.03, 95%CI 0.64–1.67; p = 0.90). The neuraxial anaesthesia rate in 310 parturients who underwent caesarean delivery was 94.2% (95%CI 90.6–96.0%). The rates of general anaesthesia were similar in symptomatic and asymptomatic parturients (6% vs. 5.7%; p = 0.52). Symptomatic parturients were more likely to be multiparous (OR 1.64, 95%CI 1.19–2.22; p = 0.002); of Asian ethnicity (OR 1.54, 1.04–2.28; p = 0.03); to deliver prematurely (OR 2.16, 95%CI 1.47–3.19; p = 0.001); have a higher caesarean birth rate (44.5% vs. 33.7%; OR 1.57, 95%CI 1.16–2.12; p = 0.008); and a higher critical care utilisation rate both pre- (8% vs. 0%, p = 0.001) and post-delivery (11% vs. 3.5%; OR 3.43, 95%CI 1.83–6.52; p = 0.001). Eight neonates tested positive for SARS-CoV-2 while no differences in adverse composite neonatal outcomes were observed between those born to symptomatic and asymptomatic mothers (25.8% vs. 23.8%; OR 1.11, 95%CI 0.78–1.57; p = 0.55). In women with COVID-19, non-neuraxial analgesic regimens were commonly utilised for labour while neuraxial anaesthesia was employed for the majority of caesarean births. Symptomatic women with COVID-19 are at increased risk of significant maternal morbidity including preterm birth, caesarean birth and peripartum critical care admission.     

Impact and Predictors of Noncircular Left Ventricular Outflow Tract Shapes on Estimating Aortic Stenosis Severity by Means of Continuity Equations

Determining aortic stenosis (AS) severity is clinically important. Calculating aortic valve (AV) area by means of the continuity equation assumes a circular left ventricular outflow tract (LVOT). The full impact of this assumption in calculating AV area is unknown. Predictors of noncircular LVOT shape in patients with AS are undefined.In 109 adult patients with AS who underwent multiplanar transesophageal echocardiography, we calculated AV area by means of the standard continuity method and by a modified method involving planimetric LVOT area.We found 54 circular, 37 horizontal-oval, 8 vertical-oval, and 10 irregular LVOTs. Area derived by direct planimetry correlated better with the modified than the standard continuity method (r=0.89 vs r=0.85; both P=0.0001). Valve areas of patients with mild, moderate, or severe AS by planimetry were more often mischaracterized with use of the standard than modified method (29 vs 18; P <0.0001). Horizontal-oval AV area derived by planimetry (1.28 ± 0.55 cm²) was underestimated by the standard method (1.05 ± 0.47 cm²; P=0.001), but not by the modified method. Congenital AV morphology and low cardiac index were the only multivariate predictors of horizontal-oval shape. Low cardiac index was the only predictor of noncircular shape.More than half our patients with AS had noncircular LVOTs. Using the modified method reduces mischaracterizations of AS severity. Congenital AV morphology and low cardiac index predict horizontal-oval or noncircular shape. These data suggest the value of direct LVOT measurement to calculate AS severity in patients who have congenital AV or a low cardiac index.     

Dermatofibrosarcoma protuberans: Rare cause of head and neck swelling

Dermatofibrosarcoma protuberance of head and neck is a rare neoplasm and accounts for less than one percent of Head and Neck Neoplasm. The objective of this report is to understand etiology, presentation, histopathologic identification and treatment option for this tumour. The goal of current report is to acquaint the clinician with presentation and treatment option for this disease.     

Myocardial perfusion SPECT reconstruction: Receiver operating characteristic comparison of CAD detection accuracy of filtered backprojection reconstruction with all of the clinical imaging information available to readers and solely stress slices iteratively reconstructed with combined compensation

BACKGROUND: Past receiver operating characteristic (ROC) studies have demonstrated that single photon emission computed tomography (SPECT) perfusion imaging by use of iterative reconstruction with combined compensation for attenuation, scatter, and detector response leads to higher area under the ROC curve (A(z)) values for detection of coronary artery disease (CAD) in comparison to the use of filtered backprojection (FBP) with no compensations. A new ROC study was conducted to investigate whether this improvement still holds for iterative reconstruction when observers have available all of the imaging information normally presented to clinical interpreters when reading FBP SPECT perfusion slices. METHODS AND RESULTS: A total of 87 patient studies including 50 patients referred for angiography and 37 patients with a lower than 5% likelihood for CAD were included in the ROC study. The images from the two methods were read by 4 cardiology fellows and 3 attending nuclear cardiologists. Presented for the FBP readings were the short-axis, horizontal long-axis, and vertical long-axis slices for both the stress and rest images; cine images of both the stress and rest projection data; cine images of selected cardiac-gated slices; the CEQUAL-generated stress and rest polar maps; and an indication of patient gender. This was compared with reading solely the iterative reconstructed stress slices with combined compensation for attenuation, scatter, and resolution. With A(z) as the criterion, a 2-way analysis of variance showed a significant improvement in detection accuracy for CAD for the 7 observers (P = .018) for iterative reconstruction with combined compensation (A(z) of 0.895 +/- 0.016) over FBP even with the additional imaging information provided to the observers when scoring the FBP slices (A(z) of 0.869 +/- 0.030). When the groups of 3 attending physicians or 4 cardiology fellows were compared separately, the iterative technique was not statistically significantly better; however, the A(z) for each of the 7 observers individually was larger for iterative reconstruction than for FBP. Compared with results from our previous studies, the additional imaging information did increase the diagnostic accuracy of FBP for CAD but not enough to undo the statistically significantly higher diagnostic accuracy of iterative reconstruction with combined compensation. CONCLUSIONS: We have determined through an ROC investigation that included two classes of observers (experienced attending physicians and cardiology fellows in training) that iterative reconstruction with combined compensation provides statistically significantly better detection accuracy (larger A(z)) for CAD than FBP reconstructions even when the FBP studies were read with all of the extra clinical nuclear imaging information normally available.     

A skin abscess model for teaching incision and drainage procedures

Background  

Skin and soft tissue infections are increasingly prevalent clinical problems, and it is important for health care practitioners to be well trained in how to treat skin abscesses. A realistic model of abscess incision and drainage will allow trainees to learn and practice this basic physician procedure.