COVID-19 impact on the management of head and neck cancer: a French single-centre experience.

INTRODUCTION: The COVID-19 pandemic has caused unprecedented pressure on medical care resources and access. The aim of this study was to evaluate the time between the cancer symptoms' onset and the first ENT specialist consultation for patients with head and neck (HNC) and salivary glands cancers during the pandemic. METHODS: The outcome measures evaluated were time to diagnosis, and time to treatment onset, as well as the COVID-19 impact on the proportion of both cancer patient groups: asymptomatic and advanced stages. This is single-centre retrospective cross-sectional study, including 473 patients who were treated in our University Hospital for HNC and salivary gland cancers, 171 in the COVID-19 pandemic group (C +), and 302 patients in the pre-pandemic group (C-). RESULTS: There were no significant between-group differences in the delays between cancer symptoms' onset and ENT consultation, diagnostic workup and initial treatment onset, respectively. There was a suggestive reduction in the number of diagnostic panendoscopy performed in the C + group (62%) compared to the C- group (73%) as well as a suggestive increase in the delay to adjuvant radiotherapy onset. CONCLUSION: The median delay between cancer symptoms' onset and ENT specialist consultation was not affected by the COVID-19 pandemic in our centre. Our results suggest an 11% decrease in diagnostic procedures performed independently, a decrease in the delay between the ENT consultation and surgical treatment onset and a 10-day increase in the delay to adjuvant radiotherapy onset.

Effect of Different Modalities of Purgative Preparation on the Diagnostic Yield of Small Bowel Capsule for the Exploration of Suspected Small Bowel Bleeding: A Multicenter Randomized Controlled Trial.

INTRODUCTION: The aim of our study was to compare clear liquid diet with 2 different polyethylene glycol (PEG)-based bowel preparation methods regarding diagnostic yield of small bowel capsule endoscopy (SBCE) in patients with suspected small bowel bleeding (SBB). METHODS: In this prospective multicenter randomized controlled trial, consecutive patients undergoing SBCE for suspected SBB between September 2010 and February 2016 were considered. Patients were randomly assigned to standard regimen, that is, clear fluids only (prep 1), standard regimen plus 500 mL PEG after SBCE ingestion (prep 2), or standard regimen plus 2 L PEG plus 500 mL PEG after SBCE ingestion (prep 3). The primary outcome was the detection of at least one clinically significant lesion in the small bowel. The quality of small bowel cleansing was assessed. A questionnaire on the clinical tolerance was filled by the patients. RESULTS: We analyzed 834 patients. No significant difference was observed for detection of P1 or P2 small bowel lesions between prep1 group (40.5%), prep 2 group (40.2%), and prep 3 group (38.5%). Small bowel cleansing was improved in prep 2 and 3 groups compared with that in prep 1 group. Compliance to the preparation and tolerance was better in prep 2 group than in prep 3 group. DISCUSSION: Small bowel purgative before SBCE allowed better quality of cleansing. However, it did not improve diagnostic yield of SBCE for suspected SBB.

Consideration Regarding the Analysis of Randomized Controlled Trials in the Era of Evidence-based Medicine.

ABSTRACT: Analysis of randomized controlled trials (RCTs) is the cornerstone of evidence-based medicine, therapeutic guidelines and ultimately daily practice. However, 2 issues contribute to cloud the analysis of RCTs. Industry-sponsored RCTs aim at capturing as large indications as possible and clinicians rely excessively on P value statistical significance for the evaluation of the findings. To be most valuable to practitioners, analysis of RCTs needs to provide absolute risk reduction, number of patients needed to treat, fragility index along with the estimation of lost to follow-up patients, and outcome postponement (gain in survival time). We analyzed few major cardiovascular RCTs and assessed the robustness of their findings. Our suggested analytic parameters may be further used in future systematic reviews and meta-analyses.

Mid-term outcomes of mastoid obliteration with biological hydroxyapatite versus bioglass: a radiological and clinical study.

PURPOSE: Radiological assessment of osseointegration of mastoid grafts: biological hydroxyapatite (Bio-Oss®) (BHA) versus bioglass S53P4 (Bonalive®) (BG). METHODS: Retrospective (10 ± 4 months post-surgery) monocentric high resolution computed tomography (CT) scan assessment (November 2018 and October 2020) by two independent radiologists (R1, R2), blinded to patient allocation. All patients who had undergone a total mastoid obliteration were eligible. Excluded: complications namely otological acute or chronic infections, unbalanced metabolic disease, long-term cortico-steroid therapy, auto-immune disease, history of allergy to grafting materials and post-surgery CT scan in other centers (n = 8). PRIMARY OUTCOMES: the ratio between two regions of interests (ROI) (graft to otic capsule). SECONDARY OUTCOMES: resorption of mastoid grafts and assessment of clinical tolerance. RESULTS: Included 21 patients (mean age: 29 ± 21 years; 5 females, 16 males). Significantly higher osseointegration for BHA vs. BG (R1 p = 0.043; R2 p = 0.004); almost perfect inter-reader agreement k = 0.922). The ROI ratios for BHA and BG to that of the otic capsule were 0.57 ± 0.11 (R1) and 0.59 ± 0.14 (R2); 0.43 ± 0.11 (R1) and 0.43 ± 0.08 (R2), respectively. Density increased significantly by 399 ± 261 Hounsfield units (HU) (p = 0.008) and decreased by 464 ± 161 HU (p < 0.001) for BHA vs. BG. Resorption rates were 24.1 ± 21.0% and 66.7 ± 15.1% (p = 0.076), respectively. No significant difference in clinical tolerance was observed. CONCLUSION: Post-operative CT scan of mastoid obliteration seems reliable in assessment of biomaterial graft's mid-term feasibility and stability: BHA seems to provide a more optimal osseointegration versus BG with no significant differences in graft resorption and clinical tolerance.

Thyroid dysfunction induced by immune checkpoint inhibitors is associated with a better progression-free survival and overall survival in non-small cell lung cancer: an original cohort study.

BACKGROUND: The objective of this study was to investigate the association between the onset of TD and treatment efficacy in NSCLC patients who initiated anti-PD-1 blockade (Nivolumab®) and to assess the impact of TD severity and subtype on nivolumab efficacy. MATERIALS AND METHODS: This study was performed at a referral oncology center between July 20, 2015 and June 30, 2018. Patients with histologically confirmed stage IIIB/IV NSCLC in progression after one or two lines of treatment and who initiated Nivolumab were included. Thyroid function (TSH ± fT4, fT3) was monitored and patients were classified according to TD status [TD(+) versus TD(-)], severity [moderate thyroid dysfunction: TSH level between 0.1 and 0.4 or 4.0 and 10 mIU/L and severe thyroid dysfunction: TSH ≤ 0.1 or ≥ 10mUI/L) and subtype (isolated hypothyroidism, isolated hyperthyroidism and hyperthyroidism then hypothyroidism)]. Clinical endpoints were overall survival (OS) and progression-free survival (PFS). RESULTS: Among 194 eligible patients, 134 patients (median age, 63 yo; 70.1% male) were included. Forty (29.9%) patients were classified in TD(+) and had a longer OS of 29.8 months (95% CI 18.8-NR) versus 8.1 months (95% CI 5.5-11.5) in TD(-) group (p < 0.001). PFS was also longer (8.7 months (95% CI 5.3-15.1) in TD(+) versus 1.7 months (95% CI 1.6-1.9) in TD(-) group (p < 0.001). In Cox proportional hazards analysis, TD remained an independent predictive factor of OS/PFS. Severity and subtype of TD were not correlated with OS/PFS. CONCLUSIONS: This study suggested that TD induced by Nivolumab appears to be an independent predictive factor of survival, irrespective of TD severity and subtype.

Diagnostic value of positron-emission tomography textural indices for malignancy of 18F-fluorodeoxyglucose-avid adrenal lesions.

BACKGROUND: PET Textural indices could have an add-on diagnostic value for diagnosis of malignancy in patients with FDG-avid adrenal lesions. METHODS: Consecutive patients referred for a FDG-PET/CT to our nuclear medicine department from June 2012 to June 2017 were retrospectively screened. Inclusion criteria were: patients with a FDG-avid adrenal lesion (uptake≥liver background); malignant/benign lesion confirmed histologically or with follow-up imaging examination. Pheochromocytomas were not included in the analysis. For each adrenal lesion, 5 quantitative PET parameters (SUVmax, MTV, TLG, TLRmax and TLRmean) were calculated. Thirty-seven textural indices were extracted using LIFEx software®. Diagnostic performance to determine malignancy was assessed with a ROC analysis. Parameters with a significantly AUC>0.5 were selected and groups of highly correlated (r>0.8) parameters were created. A scoring system combining PET and textural indices was examined. RESULTS: PET textural indices were calculated for 53 lesions (37 malignant, 16 benign). Three PET metabolic parameters (SUVmax, TLRmax, TLRmean) and 13 textural indices had an AUC>0.5. Seven groups of highly correlated parameters (r>0.8) were extracted. For PET parameters, SUVmax had the best AUC (0.89 95% CI [0.79-0.98]; cut-off=7.0). For textural indices, ZLNU had the best AUC (0.87 95% CI [0.78-0.96]; cut-off=34.7) and specificity of 100%. Three scores combining the best four textural indices alone (ContrastGLCM, LRHGE, SZE and ZLNU) or with one PET parameters (SUVmax, TLRmax) were developed but did not increase the diagnostic performance (AUC≤0.89). ZLNU was the best parameter to distinguish primary adrenal cancer from adrenal metastases in malignant lesions (P<0.001). CONCLUSIONS: Our study highlighted excellent diagnostic performance of several PET textural indices comparable to that of PET metabolic parameters. However, our results did not find any additional diagnostic value of textural indices when combined with metabolic parameters.

Hydroxychloroquine may be beneficial in preeclampsia and recurrent miscarriage.

Recurrent miscarriage (RM) and vasculoplacental disorders, such as preeclampsia (PE), affect women of childbearing age worldwide. Vascular endothelial dysfunction and immunological impairment are associated with both RM and PE. To date, there is no effective or optimal therapeutic approach for these conditions. Notably, aspirin use is only partially effective in the prevention of PE. Hydroxychloroquine (HCQ) has demonstrated beneficial effects on disease flares, pregnancy outcomes and cardiovascular impairment in systemic erythaematosus lupus (SLE) through its immunomodulatory, vasculoprotective and antithrombotic properties. Here, in the context of the underlying physiological dysregulation associated with PE and RM, the beneficial properties and potential therapeutic efficacy of HCQ are reviewed in anticipation of the results of current and future trials. Two related trials addressing RM in the absence of maternal autoimmune disease are ongoing. Other trials addressing pregnancy outcomes in the presence of maternal autoimmune disease are forthcoming. In this review, we hypothesise that the immunological and endothelial effects of HCQ may be beneficial in the context of PE and RM, regardless of the maternal autoimmune status.

Feasibility of use of medical dual energy scanner for forensic detection and characterization of explosives, a phantom study.

OBJECTIVE: Detection of explosives is a challenge due to the use of improvised and concealed bombs. Post-bomb strike bodies are handled by emergency and forensic teams. We aimed to determine whether medical dual-energy computed tomography (DECT) algorithm and prediction model can readily detect and distinguish a range of explosives on the human body during disaster victim identification (DVI) processes of bombings. MATERIALS AND METHODS: A medical DECT of 8 explosives (Semtex, Pastex, Hexamethylene triperoxide diamine, Acetone peroxide, Nitrocellulose, Pentrite, Ammonium Nitrate, and classified explosive) was conducted ex-vivo and on an anthropomorphic phantom. Hounsfield unit (HU), electron density (ED), effective atomic number (Zeff), and dual energy index (DEI),were compared by Wilcoxon signed rank test. Intra-class (ICC) and Pearson correlation coefficients (r) were computed. Explosives classification was performed through a prediction model with test-retest samples. RESULTS: Except for DEI (p = 0.036), means of HU, ED, and Zeff were not statistically different (p > 0.05) between explosives ex-vivo and on the phantom (r > 0.80). Intra- and inter-reader ICC were good to excellent: 0.806 to 0.997 and 0.890, respectively. Except for the phantom DEI, all measurements from each individual explosive differed significantly. HU, ED, Zeff, and DEI differed depending on the type of explosive. Our decision tree provided Zeff and ED for explosives classification with high accuracy (83.7%) and excellent reliability (100%). CONCLUSION: Our medical DECT algorithm and prediction model can readily detect and distinguish our range of explosives on the human body. This would avoid possible endangering of DVI staff.

Relationship between baseline and post-bronchodilator interrupter resistance and specific airway resistance in preschool children.

BACKGROUND: The assessment of airway function in preschool children can be done using simple measurement techniques such as interrupter resistance (Rint) or specific airway resistance (sRaw). OBJECTIVE: The aim of the study was to assess the relationship and the agreement between Rint and sRaw baseline measurements expressed in z-score and bronchodilator response (BDR) in accordance with the latest reference equations and recommended procedures. METHODS: One hundred thirty children aged 3 to 6 years old, referred to our pediatric pulmonary function test unit for assessment of airway function were consecutively included. Children performed baseline and post-bronchodilator measurements of Rint and sRaw. RESULTS: One hundred twenty baseline measurements were obtained (98.7%) with both techniques. At baseline there was a strong correlation between Rint and sRaw z-score (r = 0.5, P < .01) despite the poor agreement (Cohen Kappa coefficient 0.09 [-0.08; 0.26]). The agreement for BDR was fair, with Cohen Kappa coefficient (95% IC) = 0.33 (0.13; 0.54). Children with poorly or partially controlled asthma had both higher baseline Rint and sRaw (P < .01), and higher post-bronchodilator mean change (P < .01), than children with well-controlled asthma. CONCLUSION: The poor agreement between the Rint and sRaw reference measurements demonstrates the lack of reliability of sole Rint or sRaw technique for airway obstruction diagnosis and the need to perform each technique concomitantly with BDR test. Other longitudinal and larger sample studies are needed to confirm the threshold value for a positive BDR, especially for sRaw.

Video clip assessment of a salivary gland ultrasound scoring system in Sjögren's syndrome using consensual definitions: an OMERACT ultrasound working group reliability exercise.

OBJECTIVE: To develop ultrasound (US) definitions and a US novel scoring system for major salivary gland (SG) lesions in patients with primary Sjögren's syndrome (pSS) and to test their intrareader and inter-reader reliability using US video clips. METHODS: Twenty-five rheumatologists were subjected to a three-round, web-based Delphi process in order to agree on (1) definitions and scanning procedure of salivary gland ultrasonography (SGUS): parotid, submandibular and sublingual glands (PG, SMG and SLG); (2) definitions for the elementary SGUS lesions in patients with Sjögren's syndrome; (3) scoring system for grading changes. The experts rated the statements on a 1-5 Likert scale. In the second step, SGUS video clips of patients with pSS and non-pSS sicca cases were collected containing various spectrums of disease severity followed by an intrareader and inter-reader reliability exercise. Each video clip was evaluated according to the agreed definitions. RESULTS: Consensual definitions were developed after three Delphi rounds. Among the three selected SGs, US assessment of PGs and SMGs was agreed on. Agreement was reached to score only greyscale lesions and to focus on anechoic/hypoechoic foci in a semiquantitative matter or, if not possible on a qualitatively (present/absent) evaluation of fatty or fibrous lesions. Intrareader reliability for detecting and scoring these lesions was excellent (Cohen's kappa 0.81) and inter-reader reliability was good (Light's kappa 0.66). CONCLUSION: New definitions for developing a novel semiquantitative US score in patients with pSS were developed and tested on video clips. Inter-reader and intrareader reliabilities were good and excellent, respectively.

Blood anti-Müllerian hormone is a possible determinant of recurrent early miscarriage, yet not conclusive in predicting a further miscarriage.

RESEARCH QUESTION: Is blood anti-Müllerian hormone (AMH) concentration a strong determinant of unexplained recurrent early miscarriage (REM)? DESIGN: In the first part of the study, AMH concentrations measured using an Immunotech ELISA Kit were compared between 188 unselected (mostly fertile) women consecutively referred for three or more miscarriages in the first trimester of pregnancy and 376 age-matched parous women without pregnancy loss. Cases and controls were previously enrolled in an incident case-control study on thrombophilic mutations. Blood samples were collected >2 months after any recognized obstetric event or hormonal treatment. In the second part of the study, a prospective 2-year follow-up of cases was performed. RESULTS: When considering all women irrespective of age, AMH concentration did not significantly differ between cases and controls. However, in the subgroup ≥25 years old (176 cases versus 358 controls of ∼33.5 years), the cases had significantly lower AMH concentrations than the controls (median [interquartile range]: 2.8 [1.4-4.7] versus 3.25 [1.7-5.5], P = 0.046) and the proportion of cases with an AMH concentration <1 ng/ml was significantly higher (17.6% versus 10.6%; odds ratio 1.80; 95% confidence interval 1.07-3.00, P = 0.028). With regard to the subsequent pregnancy, AMH concentration was not correlated with either the conception delay or the miscarriage occurrence. However, increased age and number of previous miscarriages were significantly predictive of a subsequent miscarriage (P = 0.046 and 0.03, respectively). CONCLUSION: An altered ovarian reserve is a possible determinant of unexplained REM. However, AMH blood concentration predicts neither the delay nor the outcome of a subsequent pregnancy.

Post-mortem X-ray computed tomography (PMCT) identification using ante-mortem CT-scan of the sphenoid sinus.

PURPOSE: To evaluate forensic identification of individuals through visual comparison of sphenoid sinus anatomical configuration using ante- and post-mortem CT-scans. METHOD AND MATERIALS: Ante- and post-mortem head CT-scan of 33 individuals were retrospectively collected. Ten head CT-scans were randomly selected from various neurological contexts and added to the ante-mortem group. Ten other head CT-scans were randomly selected from our post-mortem PACS and added to the post-mortem group. These CT-scans were assigned into 2 groups for analysis: an ante-mortem group (33 + 10) and a post-mortem group (33 + 10). For ethics and to avoid identification bias, CT-scans were anonymized - not showing any head structure but only sphenoid sinuses. An anatomical based classification system using the sphenoid sinuses anatomical variations was created according to anatomical and surgical literature. This classification was used by readers to identify in two different steps a maximum of matched and then unmatched scans. RESULTS: The first reader had a sensitivity of 100% [CI: 89.4%-100%] and a specificity of 100% [CI: 99.8%-100%]. Sensitivity and specificity were respectively 93.9% [CI: 79.8%-99.3%] and 99.9% [CI: 99.6%-100%] for the second reader. Positive and negative predictive values were respectively 100% [CI: 89.4%-100%] and 100% [CI: 99.8%-100%] for the first reader. Positive and negative values were respectively 96.9% [CI: 83.8%-99.9%] and 99.9% [CI: 99.7%-100%] for the second reader. Inter-reader variability was estimated by Cohen's kappa and an excellent agreement was found. CONCLUSION: We reported an excellent validity and reliability of subjective visual comparison of ante- and post-mortem CT-data using an anatomical based classification of the sphenoid sinus.

Comparison between preprandial vs. postprandial insulin aspart in patients with type 1 diabetes on insulin pump and real-time continuous glucose monitoring.

BACKGROUND: The objective was to compare glycemic control between preprandial and postprandial bolus administration (15 min before [PRE] or immediately after the meal [POST]) in patients with type 1 diabetes using insulin pump and real-time continuous glucose monitoring. METHODS: Between September 2015 and February 2016, a single-centre, open randomized, 2-way crossover study of patients on bolus insulin aspart administration was conducted during two 14-day periods and according to 2 administration regimen schedules (PRE/POST or POST/PRE). Inclusion criteria were as follows: patients with type 1 diabetes, ≥18 and ≤ 65 years old, treated with insulin aspart using a Medtronic® insulin pump and trained on functional insulin therapy. Patients were randomly assigned to either regimen schedule. At the beginning of each period, each patient was provided with a standardized high fat meal. Primary outcome was the area under the curve for interstitial glucose above 140 mg/dL per minute (AUC > 140 mg/dL/min) during each period. Secondary outcomes were time spent in hypo/eu/hyperglycemia, glycemic variability indices, and AUC during 4 hours after high fat meal calculated with continuous glucose monitoring data. RESULTS: Twenty-two patients were included. Mean AUC > 140 mg/dL/min was statistically higher in patients on POST (43.70 mg/dL/min; 95%CI: 34.08 to 53.31) versus PRE insulin aspart regimen (37.24 mg/dL/min 95%CI: 27.63 to 46.85) (P = 0.03). Mean interstitial glycemia and glycemic variability indices were also increased (P < 0.05) on POST regimen. The mean AUC 4 hours after the high fat meal was higher on POST regimen but not statistically different (P = 0.06). CONCLUSIONS: In our study, postprandial administration of insulin aspart appears to mildly increase glycemic excursion and glycemic variability.

Normal sonoanatomy of small joints in healthy children: changes in cartilage and vascularisation according to age and gender.

OBJECTIVES: The metacarpophalangeal (MCP) and metatarsophalangeal (MTP) joints may be involved in juvenile idiopathic arthritis. Our goal was to describe their normal sonoanatomy in healthy children, according to age and gender. METHODS: We studied 41 consecutive healthy children (20 girls, 21 boys; age 2-15 years) divided into four age groups: 2-4 years (n=9), 5-7 years (n=11), 8-12 years (n=12), and 13-15 years (n=9). Longitudinal ultrasound axis of the MCP and MTP joints were obtained. The evolution of the cartilage thickness and vascularisation of these joints were studied according to age and gender. The MCP or MTP joints were the statistical unit. RESULTS: At all sites, on B-mode images, cartilage thickness was associated with age (p<0.0001). Cartilage thickness at different sites was significantly greater in boys than in girls (p≤0.05). Blood vessels were seen within the cartilage, with differences across age groups. CONCLUSIONS: This study provides children's age- and gender-specific sonoanatomy data of MCP and MTP and confirms the importance of using colour Doppler or Power Doppler to study cartilage vascularisation.

Actigraphy is not a reliable method for measuring sleep patterns in neonates.

AIM: Polysomnography is the gold standard for studying sleep, but it is complex to use, and this can be problematic in clinically unstable preterm infants. We evaluated the reliability of actigraphy and polysomnography in detecting sleep-wake patterns in newborn infants. METHODS: A prospective, monocentric study was conducted that measured the sleep patterns of 48 infants: 24 late preterm neonates born at 34-36 weeks of gestational age and 24 term neonates. We used both polysomnography and the Actiwatch Mini during a three-hour period and then compared the results from the two methods. RESULTS: The baseline measurements for the preterm and terms groups were as follows: gestational age (34.5 weeks and 39.2 weeks), birthweight (2368 g and 3393 g) and age (6.4 days and 0.72 days). With the Actiwatch Mini, sensitivity for the late preterm and full-term infants was 78% and 87% for the leg actigraph and 78% and 93% for the arm actigraph. For specificity, the respective figures were 42% and 31% for the leg and 34% and 20% for the arm. CONCLUSION: Actigraphy using the Actiwatch Mini was not a reliable method for measuring sleep patterns in healthy late preterm and term neonates a few days after birth.

Interest towards human, animal and object in children with autism spectrum disorders: an ethological approach at home.

Autistic spectrum disorders (ASD) are characterised by attention deficits in communication and social interactions and a lack of interest in people. Data are mostly based on clinical situations. However, recent studies have shown a more mixed situation where children with ASD (ASD children) displayed interest towards humans, in both experimental and natural settings. The aim of this study was to assess the interest of ASD children in a natural standardised home setting. Here, we hypothesised that ASD children would display more interest towards animate stimuli-human and pet-when in the child's home than in the lab experimental setting. We used an ethological approach involving observations, a methodological alternative to lab static techniques, to investigate the behaviour of ninety 6- to 12-year-old ASD and typical development (TD) children. Our results were consistent with those of the literature revealing that the ASD children displayed interest towards animate stimuli as did children with TD children. Interestingly, while the ASD children showed higher interest towards humans, e.g. their parent, than the TD children did, they showed less interest towards pet compared to the TD children. Our results suggested that animals are not inherently easy to decode for ASD children, in contrast with previous experiences where a pet was regarded as a more attractive partner, easier to be understood. At last, the ASD children changed more frequently their focus point than the TD children did. These differences may be explained by the reduced attention skills in ASD or the study's context. To conclude, larger exploratory studies in natural settings conducted beyond ordinary human to human interactions are crucial for better understanding of the underlying mechanisms involved in social interactions in ASD.

Finegoldia magna, not a well-known infectious agent of bacteriemic post-sternotomy mediastinitis.

Post-sternotomy mediastinitis, a nosocomial infection mostly caused by staphylococci, can be life-threatening. A case of mediastinitis due to Finegoldia magna after a coronary artery bypass graft surgery was reviewed. Although this bacterium is difficult to be isolated from routine blood cultures, a F. magna bacteriemia associated with mediastinitis was diagnosed.