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Purpose: To determine whether Macklin effect (a linear collection of air contiguous to the bronchovascular sheath) on baseline CT imaging is an accurate predictor for subsequent pneumomediastinum (PMD)/pneumothorax (PNX) development in invasively ventilated patients with COVID-19-related acute respiratory distress syndrome (ARDS). Materials and methods: This is an observational, case-control study. From a prospectively acquired database, all consecutive invasively ventilated COVID-19 ARDS patients who underwent at least one baseline chest CT scan during the study time period (February 25th, 2020–December 31st, 2020) were identified; those who had tracheal lesion or already had PMD/PNX at the time of the first available chest imaging were excluded. Results: 37/173 (21.4%) patients enrolled had PMD/PNX; specifically, 20 (11.5%) had PMD, 10 (5.8%) PNX, 7 (4%) both. 33/37 patients with subsequent PMD/PNX had Macklin effect on baseline CT (89.2%, true positives) 8.5 days [range, 1–18] before the first actual radiological evidence of PMD/PNX. Conversely, 6/136 patients without PMD/PNX (4.4%, false positives) demonstrated Macklin effect (p < 0.001). Macklin effect yielded a sensitivity of 89.2% (95% confidence interval [CI]: 74.6–96.9), a specificity of 95.6% (95% CI: 90.6–98.4), a positive predictive value (PV) of 84.5% (95% CI: 71.3–92.3), a negative PV of 97.1% (95% CI: 74.6–96.9) and an accuracy of 94.2% (95% CI: 89.6–97.2) in predicting PMD/PNX (AUC:0.924). Conclusions: Macklin effect accurately predicts, 8.5 days in advance, PMD/PNX development in COVID-19 ARDS patients.

Objective Pituitary neuroendocrine tumours (PitNET)s can be aggressive, thus presenting local invasion, postsurgical recurrence and/or resistance to treatment, responsible for significant morbidity. The study aimed at identifying prognostic factors of postsurgical outcome using data-driven classification of patients.Design Retrospective observational study.Methods Clinicopathological and radiological data of patients with PitNET treated via endoscopic endonasal surgery were collected. Tumour recurrence/progression and progression-free survival were assessed by classification tree analysis (CTA) and Kaplan-Meier curves, respectively. Histological subtype, cavernous/sphenoid sinus invasion, mitosis, Ki-67, p53, Trouillas' grading, degree of tumour exeresis and postsurgery disease activity were also evaluated.Results A total of 1066 (466 gonadotroph, 287 somatotroph, 148 lactotroph, 157 corticotroph and 8 thyrotroph) tumours were included; 21.7% invaded the cavernous/sphenoid sinus. Based on Trouillas' classification, 64.3% were grade 1a, 14.2% 1b, 16.1% 2a, and 5.4% 2b; 18.3% had >2/10 HPF mitoses, 24.9% had Ki-67 >= 3%; 15.8% were positive for p53. Exeresis was radical in 81.2% of the cases. Median follow-up was 59.2 months. At last evaluation, 79.4% of the patients were cured; 20.6% had disease persistence, controlled by medical treatment in 18.3% of them. Disease recurrence/progression was recorded in 10.9% of the cases. CTA identified 5 distinct patient subgroups with different risk of disease recurrence/progression. Grade 2 of the Trouillas' grading, >2/10 HPF mitoses, Ki-67 >= 3%, p53 protein expression (P < .001), tumour invasion (P = .002) and ACTH-subtype (P = .003) were identified as risk factors of disease recurrence/progression.Conclusions The combined evaluation of Trouillas' grading, proliferation indexes and immunohistochemistry appears promising in the prediction of surgical outcome in PitNET.

Purpose Biochemical remission (BR), gross total resection (GTR), and intraoperative cerebrospinal fluid (CSF) leaks are important metrics in transsphenoidal surgery for acromegaly, and prediction of their likelihood using machine learning would be clinically advantageous. We aim to develop and externally validate clinical prediction models for outcomes after transsphenoidal surgery for acromegaly. Methods Using data from two registries, we develop and externally validate machine learning models for GTR, BR, and CSF leaks after endoscopic transsphenoidal surgery in acromegalic patients. For the model development a registry from Bologna, Italy was used. External validation was then performed using data from Zurich, Switzerland. Gender, age, prior surgery, as well as Hardy and Knosp classification were used as input features. Discrimination and calibration metrics were assessed. Results The derivation cohort consisted of 307 patients (43.3% male; mean [SD] age, 47.2 [12.7] years). GTR was achieved in 226 (73.6%) and BR in 245 (79.8%) patients. In the external validation cohort with 46 patients, 31 (75.6%) achieved GTR and 31 (77.5%) achieved BR. Area under the curve (AUC) at external validation was 0.75 (95% confidence interval: 0.59–0.88) for GTR, 0.63 (0.40–0.82) for BR, as well as 0.77 (0.62–0.91) for intraoperative CSF leaks. While prior surgery was the most important variable for prediction of GTR, age, and Hardy grading contributed most to the predictions of BR and CSF leaks, respectively. Conclusions Gross total resection, biochemical remission, and CSF leaks remain hard to predict, but machine learning offers potential in helping to tailor surgical therapy. We demonstrate the feasibility of developing and externally validating clinical prediction models for these outcomes after surgery for acromegaly and lay the groundwork for development of a multicenter model with more robust generalization.

Background Coronavirus disease 2019 acute respiratory distress syndrome (COVID‐19 ARDS) is a disease that often requires invasive ventilation. Little is known about COVID‐19 ARDS sequelae. We assessed the mid‐term lung status of COVID‐19 survivors and investigated factors associated with pulmonary sequelae. Methods All adult COVID‐19 patients admitted to the intensive care unit from 25th February to 27th April 2020 were included. Lung function was evaluated through chest CT scan and pulmonary function tests (PFT). Logistic regression was used to identify predictors of persisting lung alterations. Results Forty‐nine patients (75%) completed lung assessment. Chest CT scan was performed after a median (interquartile range) time of 97 (89–105) days, whilst PFT after 142 (133–160) days. The median age was 58 (52–65) years and most patients were male (90%). The median duration of mechanical ventilation was 11 (6–16) days. Median tidal volume/ideal body weight (TV/IBW) was 6.8 (5.71–7.67) ml/Kg. 59% and 63% of patients showed radiological and functional lung sequelae, respectively. The diffusion capacity of carbon monoxide (DLCO) was reduced by 59%, with a median per cent of predicted DLCO of 72.1 (57.9–93.9) %. Mean TV/IBW during invasive ventilation emerged as an independent predictor of persistent CT scan abnormalities, whilst the duration of mechanical ventilation was an independent predictor of both CT and PFT abnormalities. The extension of lung involvement at hospital admission (evaluated through Radiographic Assessment of Lung Edema, RALE score) independently predicted the risk of persistent alterations in PFTs. Conclusions Both the extent of lung parenchymal involvement and mechanical ventilation protocols predict morphological and functional lung abnormalities months after COVID‐19.

Background: In several countries, extended interval COVID-19 vaccination regimens are now used to accelerate population coverage, but the relative immunogenicity of different vaccines in older people remains uncertain. In this study we aimed to assess the antibody and cellular responses of older people after a single dose of either the BNT162b2 vaccine (tozinameran; Pfizer-BioNTech) or ChAdOx1 nCoV-19 vaccine (Oxford University-AstraZeneca). Methods: Participants aged 80 years or older, who did not live in a residential or care home or require assisted living, and had received a single dose of either the BNT162b2 vaccine or ChAdOx1 nCoV-19 vaccine were eligible to participate. Participants were recruited through local primary care networks in the West Midlands, UK. Blood samples and dried blood spots were taken 5-6 weeks after vaccination to assess adaptive immune responses using Elecsys electrochemiluminescence immunoassay and cellular responses by ELISpot. Primary endpoints were percentage response and quantification of adaptive immunity. Findings: Between Dec 29, 2020, and Feb 28, 2021, 165 participants were recruited and included in the analysis. 76 participants had received BNT162b2 (median age 84 years, IQR 82-89; range 80-98) and 89 had received ChAdOx1 nCoV-19 (median age 84 years, 81-87; 80-99). Antibody responses against the spike protein were detectable in 69 (93%) of 74 BNT162b2 vaccine recipients and 77 (87%) of 89 ChAdOx1 nCoV-19 vaccine recipients. Median antibody titres were of 19·3 U/mL (7·4-79·4) in the BNT162b2 vaccine recipients and 19·6 U/mL (6·1-60·0) in the ChAdOx1 nCoV-19 vaccine recipients (p=0·41). Spike protein-specific T-cell responses were observed in nine (12%) of 73 BNT162b2 vaccine recipients and 27 (31%) of 88 ChAdOx1 nCoV-19 vaccine recipients, and median responses were three-times higher in ChAdOx1 nCoV-19 vaccine recipients (24 spots per 1 × 106 peripheral blood mononuclear cells) than BNT162b2 vaccine recipients (eight spots per 1 × 106 peripheral blood mononuclear cells; p

Dental care professionals (DCPs) are thought to be at enhanced risk of occupational exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, robust data to support this from large-scale seroepidemiological studies are lacking. We report a longitudinal seroprevalence analysis of antibodies to SARS-CoV-2 spike glycoprotein, with baseline sampling prior to large-scale practice reopening in July 2020 and follow-up postimplementation of new public health guidance on infection prevention control (IPC) and enhanced personal protective equipment (PPE). In total, 1,507 West Midlands DCPs were recruited into this study in June 2020. Baseline seroprevalence was determined using a combined IgGAM enzyme-linked immunosorbent assay and the cohort followed longitudinally for 6 mo until January/February 2021 through the second wave of the coronavirus disease 2019 pandemic in the United Kingdom and vaccination commencement. Baseline seroprevalence was 16.3%, compared to estimates in the regional population of 6% to 7%. Seropositivity was retained in over 70% of participants at 3- and 6-mo follow-up and conferred a 75% reduced risk of infection. Nonwhite ethnicity and living in areas of greater deprivation were associated with increased baseline seroprevalence. During follow-up, no polymerase chain reaction–proven infections occurred in individuals with a baseline anti–SARS-CoV-2 IgG level greater than 147.6 IU/ml with respect to the World Health Organization international standard 20-136. After vaccination, antibody responses were more rapid and of higher magnitude in those individuals who were seropositive at baseline. Natural infection with SARS-CoV-2 prior to enhanced PPE was significantly higher in DCPs than the regional population. Natural infection leads to a serological response that remains detectable in over 70% of individuals 6 mo after initial sampling and 9 mo from the peak of the first wave of the pandemic. This response is associated with protection from future infection. Even if serological responses wane, a single dose of the Pfizer-BioNTech 162b vaccine is associated with an antibody response indicative of immunological memory.

Summary Coronavirus 19 (COVID‐19) has been associated with both transient and persistent systemic symptoms that do not appear to be a direct consequence of viral infection. The generation of autoantibodies has been proposed as a mechanism to explain these symptoms. To understand the prevalence of autoantibodies associated with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, we investigated the frequency and specificity of clinically relevant autoantibodies in 84 individuals previously infected with SARS‐CoV‐2, suffering from COVID‐19 of varying severity in both the acute and convalescent setting. These were compared with results from 32 individuals who were on the intensive therapy unit (ITU) for non‐COVID reasons. We demonstrate a higher frequency of autoantibodies in the COVID‐19 ITU group compared with non‐COVID‐19 ITU disease control patients and that autoantibodies were also found in the serum 3–5 months post‐COVID‐19 infection. Non‐COVID patients displayed a diverse pattern of autoantibodies; in contrast, the COVID‐19 groups had a more restricted panel of autoantibodies including skin, skeletal muscle and cardiac antibodies. Our results demonstrate that respiratory viral infection with SARS‐CoV‐2 is associated with the detection of a limited profile of tissue‐specific autoantibodies, detectable using routine clinical immunology assays. Further studies are required to determine whether these autoantibodies are specific to SARS‐CoV‐2 or a phenomenon arising from severe viral infections and to determine the clinical significance of these autoantibodies., Acute infection with COVID is associated with a pattern of autoantibodies including a high proportion with epidermal antibodies. This autoantibody pattern is more common in severe COVID and is persistent up to 6 months.

L’introduzione nella pratica clinica del dosaggio della copeptina come marcatore surrogato di arginin-vasopressina sta modificando radicalmente l’approccio diagnostico alle sindromi poliurico-polidipsiche, rendendo sempre meno utilizzato il test indiretto dell’assetamento. Un semplice dosaggio di copeptina al mattino a digiuno e in grado di diagnosticare con elevata accuratezza diagnostica il diabete insipido nefrogenico, mentre per distinguere il diabete insipido centrale dalla poliuria primaria e necessario ricorrere al dosaggio della copeptina stimolata con infusione di soluzione ipertonica 3% NaCl. Recentemente, e stato proposto di sostituire l’infusione di soluzione ipertonica con l’infusione di arginina e i primi dati sono certamente incoraggianti, ma si rimane in attesa di conferme da studi prospettici su vasta scala. L’impiego del dosaggio di copeptina nella diagnostica dell’iponatremia non e ancora entrato nella pratica clinica quotidiana. Tuttavia, alcuni studi indicano che il dosaggio di copeptina potrebbe essere utile, ad esempio, per distinguere alcuni sottogruppi di sindrome da inappropriata antidiuresi (SIAD) e, in associazione con la sodiuria, per individuare i pazienti ipovolemici. Mancano, comunque, conferme basate su evidenze piu nette.

During the COVID-19 outbreak, reports have surfaced of children who present with features of a multisystem inflammatory syndrome with overlapping features of Kawasaki disease and toxic shock syndrome - Paediatric Inflammatory Multisystem Syndrome- temporally associated with SARS-CoV-2 pandemic (PIMS-TS). Initial reports find that many of the children are PCR-negative for SARS-CoV-2, so it is difficult to confirm whether this syndrome is a late complication of viral infection in an age group largely spared the worst consequences of this infection, or if this syndrome reflects enhanced surveillance.Children hospitalised for symptoms consistent with PIMS-TS between 28 April and 8 May 2020, and who were PCR-negative for SARS-CoV-2, were tested for antibodies to viral spike glycoprotein using an ELISA test.Eight patients (age range 7-14 years, 63% male) fulfilled case-definition for PIMS-TS during the study period. Six of the eight patients required admission to intensive care. All patients exhibited significant IgG and IgA responses to viral spike glycoprotein. Further assessment showed that the IgG isotypes detected in children with PIMS-TS were of the IgG1 and IgG3 subclasses, a distribution similar to that observed in samples from hospitalised adult COVID-19 patients. In contrast, IgG2 and IgG4 were not detected in children or adults. IgM was not detected in children, which contrasts with adult hospitalised adult COVID-19 patients of whom all had positive IgM responses.Strong IgG antibody responses can be detected in PCR-negative children with PIMS-TS. The low detection rate of IgM in these patients is consistent with infection having occurred weeks previously and that the syndrome onset occurs well after the control of SARS-CoV-2 viral load. This implies that the disease is largely immune-mediated. Lastly, this indicates that serology can be an appropriate diagnostic tool in select patient groups.

Background Patients with chronic kidney disease (CKD) are more prone to severe infection. Vaccination is a key strategy to reduce this risk. Some studies suggest vaccine efficacy may be reduced in patients with CKD, despite preserved maintenance of long-term responses to some pathogens and vaccines. Here, we investigated immune responses to 2 vaccines in patients with CKD to identify predictors of immunological responsiveness. Methods Individuals >65 years old, with or without nondialysis CKD (n = 36 and 29, respectively), were vaccinated with a nonadjuvanted seasonal influenza vaccine (T-dependent) and Pneumovax23 (23-valent pneumococcal polysaccharide [PPV23], T-independent). Humoral responses were measured at baseline, day 28, and 6 months. Lymphocyte subset and plasma cell/blast analyses were performed using flow cytometry. Cytomegalovirus (CMV) serotyping was assessed by enzyme-linked immunosorbent assay. Results Only modest responsiveness was observed to both vaccines, independent of CKD status (25% adequate response in controls vs. 12%–18% in the CKD group). Unexpectedly, previous immunization with PPV23 (median 10-year interval) and CMV seropositivity were associated with poor PPV23 responsiveness in both study groups (P < .001 and .003, respectively; multivariable linear regression model). Patients with CKD displayed expanded circulating populations of T helper 2 and regulatory T cells, which were unrelated to vaccine responses. Despite fewer circulating B cells, patients with CKD were able to mount a similar day 7 plasma cell/blast response to controls. Conclusion Patients with nondialysis CKD can respond similarly to vaccines as age- and sex-matched healthy individuals. CKD patients display an immune signature that is independent of vaccine responsiveness. Prior PPV23 immunization and CMV infection may influence responsiveness to vaccination. Clinical Trials Registration. NCT02535052, Patients with nondialysis Chronic Kidney Disease (CKD) can mount similar responses to vaccination as controls. Subtle changes in lymphocyte phenotype are seen in CKD when controlled for effect of Cytomegalovirus (CMV). Latent CMV infection and previous PPV23 vaccination are associated with poorer vaccine responses.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections have a devastating effect on patients receiving hemodialysis. To what extent infection-induced antibody responses are maintained, or protective, is unknown. This study describes the evolution of antibodies against the SARS-CoV-2 spike protein in a cohort of 990 patients on hemodialysis. During the first wave of the pandemic, 26% of patients had developed antispike SARS-CoV-2 antibodies. Fewer PCR-confirmed second-wave infections were observed in patients with pre-existing antibodies (4.2%) than those without antibodies (11.4%). This study shows that SARS-CoV-2 antibodies in patients on hemodialysis are well maintained and associate with reduced risk of subsequent SARS-CoV-2 infection.

The control of magnetic properties at the nanoscale is a current topic of intense research. It was shown that combining both magnetic and plasmonic nanoparticles (NPs) led to the improvement of their magneto-optical signal. In this context, common strategies consist of the design of bimetallic NPs. However, the understanding of the physics leading to the coupling between magnetic and plasmonic NPs is lacking, preventing any significant progress for the development of future photonic devices. In this article, we propose to focus our attention on an efficient and commonly used magnetic metal, cobalt, and evaluate its plasmonic properties at the nanoscale through the use of NP regular arrays, as a potential candidate combining both optical and magnetic functionalities within the same metal. We show that such NPs display plasmonic properties within a large spectral range from the UV to the NIR spectral range, with efficient quality factors, when the inter-particle distance is properly selected. These as-fabricated simple materials could find applications in integrated photonic devices for telecommunications.

Dried blood spot (DBS) samples can be used for the detection of severe acute respiratory syndrome coronavirus 2 spike antibodies. DBS sampling is comparable to matched serum samples with a relative 98.1% sensitivity and 100% specificity. Thus, DBS sampling offers an alternative for population-wide serologic testing in the coronavirus pandemic.

Objective and design A clinicopathological score has been proposed by Trouillas et al. to predict the evolution of pituitary adenomas. Aim of our study was to perform an independent external validation of this score and identify other potential predictor of post-surgical outcome. Methods The study sample included 566 patients with pituitary adenomas, specifically 253 FSH/LH-secreting, 147 GH-secreting, 85 PRL-secreting, 72 ACTH-secreting and 9 TSH-secreting tumours with at least 3-year post-surgical follow-up. Results In 437 cases, pituitary adenomas were non-invasive, with low (grade 1a: 378 cases) or high (grade 1b: 59 cases) proliferative activity. In 129 cases, tumours were invasive, with low (grade 2a: 87 cases) or high (grade 2b: 42 cases) proliferative activity. During the follow-up (mean: 5.8 years), 60 patients developed disease recurrence or progression, with a total of 130 patients with pituitary disease at last follow-up. Univariate analysis demonstrated a significantly higher risk of disease persistence and recurrence/progression in patients with PRL-, ACTH- and FSH/LH-secreting tumours as compared to those with somatotroph tumours, and in those with high proliferative activity (grade 1b and 2b) or >1 cm diameter. Multivariate analysis confirmed tumour type and grade to be independent predictors of disease-free-survival. Tumour invasion, Ki-67 and tumour type were the only independent prognostic factors of disease-free survival. Conclusions Our data confirmed the validity of Trouillas’ score, being tumour type and grade independent predictors of disease evolution. Therefore, we recommend to always consider both features, together with tumour histological subtype, in the clinical setting to early identify patients at higher risk of recurrence.

ObjectiveTo determine the rates of asymptomatic viral carriage and seroprevalence of SARS-CoV-2 antibodies in healthcare workers.DesignA cross-sectional study of asymptomatic healthcare workers undertaken on 24/25 April 2020.SettingUniversity Hospitals Birmingham NHS Foundation Trust (UHBFT), UK.Participants545 asymptomatic healthcare workers were recruited while at work. Participants were invited to participate via the UHBFT social media. Exclusion criteria included current symptoms consistent with COVID-19. No potential participants were excluded.InterventionParticipants volunteered a nasopharyngeal swab and a venous blood sample that were tested for SARS-CoV-2 RNA and anti-SARS-CoV-2 spike glycoprotein antibodies, respectively. Results were interpreted in the context of prior illnesses and the hospital departments in which participants worked.Main outcome measureProportion of participants demonstrating infection and positive SARS-CoV-2 serology.ResultsThe point prevalence of SARS-CoV-2 viral carriage was 2.4% (n=13/545). The overall seroprevalence of SARS-CoV-2 antibodies was 24.4% (n=126/516). Participants who reported prior symptomatic illness had higher seroprevalence (37.5% vs 17.1%, χ2=21.1034, pConclusions and relevanceWe identify differences in the occupational risk of exposure to SARS-CoV-2 between hospital departments and confirm asymptomatic seroconversion occurs in healthcare workers. Further investigation of these observations is required to inform future infection control and occupational health practices.

58 anos) e modelo para doenca hepatica final de 12 pontos; houve predominância de homens. A etiologia mais comum (60,4%) foi o virus da hepatite C. Os valores de corte foram MAMC ≤ 25,09 cm para a massa muscular, PT ≤ 93,4 Nm para a forca muscular e 6MWT ≤ 459 m para a funcao muscular. e as precisoes usadas para determinar a massa muscular, forca e funcao pelo MAMC, PT e 6MWT foram ≤ 25,09 cm e 77,9%, ≤ 93,4Nm e 72,72% e ≤ 459 me 75%, respectivamente.

BACKGROUND: COVID-19 disease can lead to severe functional impairments after discharge. We assessed the quality of life of invasively ventilated COVID-19 ARDS survivors. METHODS: We carried out a prospective follow-up study of the patients admitted to the Intensive Care Units (ICUs) of a teaching hospital. Patients affected by COVID-19 ARDS who required invasive ventilation and were successfully discharged home were assessed through the telephone administration of validated tests. We explored survival, functional outcomes, return to work, quality of life, cognitive and psychological sequelae. The main variables of interest were the following: demographics, severity scores, laboratory values, comorbidities, schooling, working status, treatments received during ICU stay, complications, and psychological, cognitive, functional outcomes. RESULTS: Out of 116 consecutive invasively ventilated patients, overall survival was 65/116 (56%) with no death occurring after hospital discharge. Forty-two patients were already discharged home with a median follow-up time of 61 (51-71) days after ICU discharge and 39 of them accepted to be interviewed. Only one patient (1/39) experienced cognitive decline. The vast majority of patients reported no difficulty in walking (32/35:82%), self-care (33/39:85%), and usual activities (30/39:78%). All patients were either malnourished (15/39:38%) or at risk for malnutrition (24/39:62%). Exertional dyspnea was present in 20/39 (51%) patients. 19/39 (49%) reported alterations in senses of smell and/or taste either before or after hospitalization. CONCLUSIONS: Invasively ventilated COVID-19 ARDS survivors have an overall good recovery at a 2-months follow-up which is better than what was previously reported in non-COVID-19 ARDS patients.

Objective To determine the incidence, predictors, and outcome of pneumothorax (PNX)/pneumomediastinum (PMD) in coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS). Design Observational study. Setting Tertiary-care university hospital. Participants One hundred sixteen consecutive critically ill, invasively ventilated patients with COVID-19 ARDS. Interventions The authors collected demographic, mechanical ventilation, imaging, laboratory, and outcome data. Primary outcome was the incidence of PNX/PMD. Multiple logistic regression analyses were performed to identify predictors of PNX/PMD. Measurements and Main Results PNX/PMD occurred in a total of 28 patients (24.1%), with 22 patients developing PNX (19.0%) and 13 developing PMD (11.2%). Mean time to development of PNX/PMD was 14 ± 11 days from intubation. The authors found no significant difference in mechanical ventilation parameters between patients who developed PNX/PMD and those who did not. Mechanical ventilation parameters were within recommended limits for protective ventilation in both groups. Ninety-five percent of patients with PNX/PMD had the Macklin effect (linear collections of air contiguous to the bronchovascular sheaths) on a baseline computed tomography scan, and tended to have a higher lung involvement at intensive care unit (ICU) admission (Radiographic Assessment of Lung Edema score 32.2 ± 13.4 v 18.7 ± 9.8 in patients without PNX/PMD, p = 0.08). Time from symptom onset to intubation and time from total bilirubin on day two after ICU admission were the only independent predictors of PNX/PMD. Mortality was 60.7% in patients who developed PNX/PMD versus 38.6% in those who did not (p = 0.04). Conclusion PNX/PMD occurs frequently in COVID-19 patients with ARDS requiring mechanical ventilation, and is associated with increased mortality. Development of PNX/PMD seems to occur despite use of protective mechanical ventilation and has a radiologic predictor sign.

The real estimate of the infection fatality rate of SARS-CoV-2 is a pivotal aspect of the COVID-19 pandemic. However, this number is still debated, since both the numerator and the denominator are uncertain. Data analysis from the most affected areas in the world minimizes computational errors and represents a unique approach for estimating infection fatality rate. We first extracted data from PubMed/Medline, Google, traditional media and social media to obtain the rate of SARS-CoV-2 antibodies seroprevalence in the most affected and best-studied areas in the world: Val Seriana (Italy), Ischgl (Austria) and Manaus (Brasil). We then searched mortality data from national institutes of statistics and calculated excess mortality. We estimated the infection fatality rate considering several scenarios according to the mortality attributable to COVID-19 and the proportion of the population infected with the virus. We found that the seropositivity was surprisingly close to 40% in all the considered areas. We calculated the SARS-CoV-2 infection fatality rate for Val Seriana, using from half to the entire excess mortality (1208 deaths) and considering from 40% to 80% of the population as being infected with SARS-CoV-2. In the most conservative scenario, infection fatality rate was as low as 0.55%, while in the worst-case one it was 2.2%. We found that the seroconversion rate in the most affected areas worldwide is about 40%. We consequently estimated the infection fatality rate to be between 0.55% and 2.2% in an area with a relatively elderly population. © 2021 The Author(s). Published by MRE Press.

BackgroundProspective population-based studies investigating multiple determinants of pre-vaccination antibody responses to SARS-CoV-2 are lacking.MethodsWe did a prospective population-based study in SARS-CoV-2 vaccine-naive UK adults recruited between May 1 and November 2, 2020, without a positive swab test result for SARS-CoV-2 prior to enrolment. Information on 88 potential sociodemographic, behavioural, nutritional, clinical and pharmacological risk factors was obtained through online questionnaires, and combined IgG/IgA/IgM responses to SARS-CoV-2 spike glycoprotein were determined in dried blood spots obtained between November 6, 2020 and April 18, 2021. We used logistic and linear regression to estimate adjusted odds ratios (aORs) and adjusted geometric mean ratios (aGMRs) for potential determinants of SARS-CoV-2 seropositivity (all participants) and antibody titres (seropositive participants only), respectively.Results1696 (15.2%) of 11,130 participants were seropositive. Factors independently associated with increased risk of SARS-CoV-2 seropositivity included frontline health/care occupation (aOR 1.86, 95% CI 1.48–2.33), international travel (1.20, 1.07–1.35), number of visits to shops and other indoor public places (≥5 vs. 0/week: 1.29, 1.06-1.57, P-trend=0.01), body mass index (BMI) ≥25 vs 2 (1.24, 1.11–1.39), Asian/Asian British vs White ethnicity (1.65, 1.10–2.49), and alcohol consumption ≥15 vs 0 units/week (1.23, 1.04–1.46). Light physical exercise associated with decreased risk (0.80, 0.70–0.93, for ≥10 vs 0–4 h/week). Among seropositive participants, higher titres of anti-Spike antibodies associated with factors including BMI ≥30 vs 2 (aGMR 1.10, 1.02–1.19), Asian/Asian British vs White ethnicity (1.22, 1.04–1.44), frontline health/care occupation (1.24, 95% CI 1.11–1.39), international travel (1.11, 1.05–1.16), and number of visits to shops and other indoor public places (≥5 vs. 0/week: 1.12, 1.02-1.23, P-trend=0.01); these associations were not substantially attenuated by adjustment for COVID-19 disease severity.ConclusionsHigher alcohol consumption and reduced light physical exercise represent new modifiable risk factors for SARS-CoV-2 infection. Recognised associations between Asian/Asian British ethnic origin and obesity and increased risk of SARS-CoV-2 seropositivity were independent of other sociodemographic, behavioural, nutritional, clinical and pharmacological factors investigated. Among seropositive participants, higher titres of anti-Spike antibodies in people of Asian ancestry and in obese people were not explained by greater COVID-19 disease severity in these groups.FundingBarts Charity, Health Data Research UK.

Introduction/Background* Sentinel node biopsy (SNB) is the standard of care for vulvar cancer patients clinically N0 (cN0) at preoperative assessment, with unifocal primary tumor, Methodology According to the Grosnapet study design, lymph node status was assessed by pre-operative PET/CT scan and cN0 patients were enrolled on the base of the following criteria: a) Tumor > 4 cm, b) Multifocal tumors, c) previous complete excision; d) contralateral nodal involvement, e) previous RTCT treatment or f) vulvar recurrence. Vulvar surgery was performed according to current recommendations, as appropriate. Sentinel lymph node was detected by radiotracer and blue dye to reach the maximum detection rate. Radical lymphadenectomy was always provided after SNB, according to the standard of care. Both PET/CT scan and SNB were compared to final pathology report. Patients were followed up quarterly, undergoing clinical visit, groin ultrasound and PET/CT scan. Result(s)* During the study period, 72 patients were considered eligible for a total of 111 groins included. Median patient’s age was 73yrs. Histopathology revealed 16 (14.4%) groins with metastatic sentinel nodes (SLNs). Only one case had further involved non SLNs. Overall, 18/274 (6.5%) SLN excised were positive at histology. Median metastasis diameter was 4.8 (1.5-12). One false negative SN was identified (NPV 99%). PET/CT showed an NPV of 92%. After a median follow-up of 38 months (range 1-97 months), 19 recurrences and 6 deaths were registered. The 3-year disease-free survival (DFS) was 72.6%. Conclusion* This is the largest series that strongly support the use of SNB in cN0 patients currently excluded. A careful preoperative study could safely select eligible patients. Further validation is advisable.

Age is the major risk factor for mortality after SARS-CoV-2 infection and older people have received priority consideration for COVID-19 vaccination. However, vaccine responses are often suboptimal in this age group and few people over the age of 80 years were included in vaccine registration trials. We determined the serological and cellular response to spike protein in 100 people aged 80–96 years at 2 weeks after the second vaccination with the Pfizer BNT162b2 mRNA vaccine. Antibody responses were seen in every donor with high titers in 98%. Spike-specific cellular immune responses were detectable in only 63% and correlated with humoral response. Previous SARS-CoV-2 infection substantially increased antibody responses after one vaccine and antibody and cellular responses remained 28-fold and 3-fold higher, respectively, after dual vaccination. Post-vaccine sera mediated strong neutralization of live Victoria infection and although neutralization titers were reduced 14-fold against the P.1 variant first discovered in Brazil they remained largely effective. These data demonstrate that the mRNA vaccine platform delivers strong humoral immunity in people up to 96 years of age and retains broad efficacy against the P.1 variant of concern.

Detecting antibody responses during and after SARS‐CoV‐2 infection is essential in determining the seroepidemiology of the virus and the potential role of antibody in disease. Scalable, sensitive and specific serological assays are essential to this process. The detection of antibody in hospitalized patients with severe disease has proven relatively straightforward; detecting responses in subjects with mild disease and asymptomatic infections has proven less reliable. We hypothesized that the suboptimal sensitivity of antibody assays and the compartmentalization of the antibody response may contribute to this effect. We systematically developed an ELISA, optimizing different antigens and amplification steps, in serum and saliva from non‐hospitalized SARS‐CoV‐2‐infected subjects. Using trimeric spike glycoprotein, rather than nucleocapsid, enabled detection of responses in individuals with low antibody responses. IgG1 and IgG3 predominate to both antigens, but more anti‐spike IgG1 than IgG3 was detectable. All antigens were effective for detecting responses in hospitalized patients. Anti‐spike IgG, IgA and IgM antibody responses were readily detectable in saliva from a minority of RT‐PCR confirmed, non‐hospitalized symptomatic individuals, and these were mostly subjects who had the highest levels of anti‐spike serum antibodies. Therefore, detecting antibody responses in both saliva and serum can contribute to determining virus exposure and understanding immune responses after SARS‐CoV‐2 infection., This manuscript describes the development of a highly sensitive ELISA, optimizing different antigens and amplification steps, in serum and saliva from non‐hospitalized SARS‐CoV‐2‐infected subjects. Using a trimeric spike glycoprotein, rather than nucleocapsid, enabled detection of responses in individuals with mild‐to‐moderate infection. The detection of antibodies in both serum and saliva can contribute to determining virus exposure and understanding immune responses to SARS‐CoV‐2.

BackgroundVitamin D has numerous mechanistic roles within the immune system. There is increasing evidence to suggest Vitamin D deficiency may increase individuals’ risk of COVID-19 infection and susceptibility. We aimed to determine the relationship between severity of vitamin D deficiency and sufficiency and COVID-19 infection within healthcare workers.MethodsThe study included an observational cohort of healthcare workers who isolated due to COVID-19 symptoms from 12th to 22nd May 2020, from the University Hospitals Birmingham NHS Foundation Trust (UHBFT). This was part of the COVID-19 convalescent immunity study (COCO). Data collected included SARS-CoV-2 seroconversion status, serum 25(OH)D3 levels as well as age, body mass index (BMI), sex, ethnicity, job role, and co-morbidities. Participants were grouped into four vitamin D (VD) categories. 1) Severe VD deficiency (VD ResultsWhen VD levels were compared against COVID-19 seropositivity rate, a U-shaped curve was identified in the total population. This trend repeated when split into subgroups of age, sex, ethnicity, BMI, and co-morbidity status. Significant difference was identified in the COVID-19 seropositivity rate between VD groups between multiple VD groups in the total population, males, females, BAME, BMI2), 0 and +1 comorbidities; the majority of which were differences when the severely VD deficient category were compared to the other group. A significantly larger proportion of those within the Black, Asian, minority ethnic (BAME) group (vs. white ethnicity) were severely vitamin D deficient (P <0.00001). A significantly higher proportion of the 0-comorbidity subgroup were vitamin D deficient in comparison to the 1+ comorbidity subgroup (P = 0.046).ConclusionsFurther investigation of the U-shaped curves is required to determine whether high VD levels can have a detrimental effect on susceptibility to COVID-19 infection. Future randomised clinical trials of VD supplementation could potentially identify ‘optimal’ VD levels. This would allow for targeted therapeutic treatment for those at-risk such as in the BAME group.

Background In the last years, few reports have shown the feasibility of the endoscopic endonasal approach (EEA) for craniopharyngiomas in pediatric patients. For these tumors, recent studies have suggested less aggressive surgery, favoring the preservation of the patient's quality of life. Objective The aim of this study was to assess the outcome of the EEA in a large series with specific attention on the long-term functional sequelae. Materials All consecutive pediatric craniopharyngiomas operated on through this approach since 2000 were included in the study. Preoperative and postoperative operative clinical, radiologic, and pathologic features were retrieved from patient records (mean follow-up, 72 ± 67 months). Results The series included 25 patients (12 female; mean age, 8.9 ± 4.1 years). Most of the tumors presented with a supradiaphragmatic extension (88%). Removal was radical in 23 patients (92%). Complications consisted of 6 cerebrospinal fluid leaks (24%). One patient (4%) died of postoperative respiratory complications. Most patients (92%) developed panhypopituitarism and visual disturbances normalized or improved in 6 patients (43%). At follow-up, 9 patients (36%) were overweight/obese (6 were already overweight before surgery). The tumor recurrence rate was 19%. Conclusions EEA can be an effective approach for midline craniopharyngiomas in children older than 3 years. It gives a satisfactory exposure of the suprasellar region and an adequate assessment of the brain–tumor interface. Its main limitations are age-related anatomic features of nasal/paranasal sinuses and the risk of cerebrospinal fluid leak.

Myasthenia gravis (MG) is an autoimmune disease affecting neuromuscular transmission that manifests with muscle weakness and typically involves the eye muscles, often producing diplopia and ptosis. Recent studies suggest that hyperprolactinaemia may have a role in the development of MG, although its association with prolactinoma is extremely rare. We report the unusual case of a 71-year-old male affected with macroprolactinoma, who presented at our Center 2 weeks after starting cabergoline treatment because of acute onset of headache, diplopia, and ptosis. On admission, he presented with drowsiness, dropped head, swallowing impairment and bilateral ptosis, which rapidly worsened. Based on clinical manifestation and history, emergency surgery was performed on suspicion of pituitary apoplexy (PA), the typical complication occurring in patients with macroadenomas who present these symptoms. No pituitary haemorrhage was found. The symptoms initially resolved after surgery, but soon returned and worsened day by day, especially in the evening, despite the increase of cortisone replacement doses. MG was thus suspected and confirmed by the detection of antibodies to the acetylcholine receptor. Pyridostigmine was started with prompt improvement of neurological symptoms. In conclusion, although very rare, MG should be considered in the differential diagnosis of patients with macroprolactinomas and suggestive neurological symptoms in order to provide early and appropriate treatment. The role of hyperprolactinaemia in MG onset and evolution is also discussed.

We aimed to evaluate patients' perspectives on a progesterone subcutaneous formulation for endometrial preparation for frozen-thawed blastocyst transfer. In this prospective study, women with at least one experience with vaginal progesterone, undergone endometrial preparation with oral estradiol valerate and daily subcutaneous progesterone administered from the fifth day before the transfer until the day of the beta-hCG test. Patients completed three questionnaires, at enrollment (Q1), for gathering information on the experience with vaginal treatment and expectations about the subcutaneous route and then at the time of the transfer (Q2) and eight days later (Q3). Main outcome measures were patients' opinions on comfort, ease of use, convenience, overall satisfaction, level of anxiety and pain associated with the administration of subcutaneous progesterone in comparison with their previous experience. Sixty-nine women completed the questionnaires. All vaginal versus subcutaneous comparisons were significantly in favor of the subcutaneous route. When comparing patients' expectations at Q1 with patients' opinions at Q2 and Q3, all evaluations, except for one, demonstrated that the patient's positive expectation was confirmed after 5 and 13 days of treatment. In conclusion, in women with previous experience with vaginal progesterone, the subcutaneous route was associated with significantly increased acceptance.

In the last three decades, we assisted in a shift in the dairy product preferences in developed countries, with an increase in goat-derived products consumption. As already seen in the bovine sector, the diffusion of goat milk consumption has led to an abandonment of the local breeds in favor of the more productive cosmopolitan breeds, with an intense reduction in the livestock biodiversity. However, in several studies, it has been shown that local breeds present unique features such as a robust behavior towards the local climate and a high quality of their dairy products. This study aims to assess the differences between the basic lactation variables (milk yield, fat %, protein %, lactose % and somatic cell count) in the Alpine goat and the local breed Verzasca goat from a Bayesian point of observation. Results indicate that the Nera di Verzasca goat has overall lactation characteristics similar toa cosmopolite breed such as the Alpine goat, except for the milk daily yield reduced with respect to Alpine goats (1.68 ± 0.84 and 2.14 ± 1.03, respectively). Moreover, the Verzasca goat showed a tendency to maintain a lower level of somatic cell count along with lactation (798 ± 1734 and 1216 ± 2828, respectively). These findings help to increase the knowledge about the Italian local goat breeds and are important in the optic of biodiversity conservation.

International audience; Due to their high porosity and chemical versatility, metal-organic frameworks (MOFs) exhibit physical properties appealing for photonic-based applications. While several MOF photonic structures have been reported, examples of applications thereof are mainly limited to chemical sensing. Herein, the range of application of photonic MOFs is extended to local thermal and photothermal sensing by integrating them into a new architecture: MOF photonic balls. Micrometric-sized photonic balls are made of monodispersed MOFs colloids that are self-assembled via spray-drying, a low-cost, green, and high-throughput method. The versatility of the process allows tuning the morphology and the composition of photonic balls made of several MOFs and composites with tailored optical properties. X-ray nanotomography and environmental hyperspectral microscopy enable analysis of single objects and their evolution in controlled atmosphere and temperature. Notably, in presence of vapors, the MOF photonic balls act as local, label-free temperature probes. Importantly, compared to other thermal probes, the temperature detection range of these materials can be adjusted "on-demand." As proof of concept, the photonic balls are used to determine local temperature profiles around a concentrated laser beam. More broadly, this work is expected to stimulate new research on the physical properties of photonic MOFs providing new possibilities for device fabrication.

Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening disease occurring several weeks after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Deep immune profiling showed acute MIS-C patients had highly activated neutrophils, classical monocytes and memory CD8+ T-cells, with increased frequencies of B-cell plasmablasts and double-negative B-cells. Post treatment samples from the same patients, taken during symptom resolution, identified recovery-associated immune features including increased monocyte CD163 levels, emergence of a new population of immature neutrophils and, in some patients, transiently increased plasma arginase. Plasma profiling identified multiple features shared by MIS-C, Kawasaki Disease and COVID-19 and that therapeutic inhibition of IL-6 may be preferable to IL-1 or TNF-α. We identified several potential mechanisms of action for IVIG, the most commonly used drug to treat MIS-C. Finally, we showed systemic complement activation with high plasma C5b-9 levels is common in MIS-C suggesting complement inhibitors could be used to treat the disease., Graphical abstract, Genomics; Immune response; Immune system disorder; Immunology

Study question Can PGT-A reduce the anxiety generally experienced by infertile women undergoing IVF in the waiting period between embryo transfer and the pregnancy test? Summary answer PGT-A reduces anxiety in infertile women after embryo transfer, probably due to a gain of confidence in their treatment route. What is known already The waiting period, i.e. the time between embryo-transfer and the pregnancy-test, is considered unpredictable and unmanageable, thus figuring amongst the most stressful steps of an IVF treatment. This is mainly imputable to women’s lost sense of control over the outcome. Uncertainty is in fact a source of fear and elevated distress. PGT-A has been shown to improve live birth rate per embryo transfer and reduce miscarriage rate per clinical pregnancy across several trials and observational studies worldwide, especially in advanced maternal age (AMA) women. Here, we investigated if euploid embryo transfer does involve also lower emotional burden over untested one. Study design, size, duration Prospective observational study evaluating the level of anxiety in the waiting period among women undergoing euploid or untested embryo transfer. Data were collected between September 2019 and September 2020 in a public hospital. A total of 48 infertile women were recruited: 25 undergoing euploid single embryo transfer after trophectoderm biopsy and NGS, and 23 undergoing untested single embryo transfer. Participants/materials, setting, methods To measure the level of anxiety, the two groups completed the STAI (State Trait Anxiety Inventory) questionnaire at two time points: before starting the ovarian stimulation (T0), and at day 8 after embryo transfer (T1). The chosen questionnaire has been previously validated to capture the level of patients’ anxiety during the waiting period. Outcomes of T0 were used to control for individual level state of anxiety at T1. Main results and the role of chance The two groups showed similar reproductive history and sociodemographic characteristics except for female age, which was higher in the PGT-A group (37.7±3.2 yr versus 32.3±2.2 yr in the control). This is due to AMA (maternal age >35 yr) being the main indication to PGT-A. Conversely, the duration of infertility was similar in the two groups (3.8±2.2 yr versus 3.7±1.9 in the control). At T0 all patients showed similar levels of anxiety (46.4 points versus 49.9 in the control, 95%CI of the difference: from –9.97 to 3.03 points, p = 0.3). Remarkably, at T1 instead, the women undergoing euploid embryo transfer showed a significantly decreased level of anxiety with respect to the control (39.9 points versus 53.4; 95% CI of the difference: from –18.26 to –8.69, p Limitations, reasons for caution The sample size is small, yet the study resulted powered enough to reveal the considerable advantage of PGT-A toward the primary outcome. We analysed only the waiting period here. Therefore, data will be collected in the future at subsequent gestational stages, such as when prenatal genetic diagnosis is usually conducted. Wider implications of the findings: Women undergoing PGT-A seem reassured by the technique. This is probably due to the gain of confidence and control derived from an increased expectation of success. From this perspective, assessing women’s wellbeing and attitude towards all different clinical procedures should become a critical part of their treatment. Trial registration number None

Background Frequently SARS-CoV-2 results in mild or moderate disease with potentially lower concentrations of antibodies compared to those that are hospitalised. Here, we validated an ELISA using SARS-CoV-2 trimeric spike glycoprotein, with targeted detection of IgG, IgA and IgM (IgGAM) using serum and dried blood spots (DBS) from adults with mild or moderate disease. Methods Targeting the SARS-CoV-2 trimeric spike, a combined anti-IgG, IgA and IgM serology ELISA assay was developed using 62 PCR-confirmed non-hospitalised, mild or moderate COVID-19 samples, ≥14 days post symptom onset and 624 COVID-19 negative samples. The assay was validated using 73 PCR-confirmed non-hospitalised, mild or moderate COVID-19 samples, ≥14 days post symptom onset and 359 COVID-19 negative serum samples with an additional 81 DBSs. The assay was further validated in 226 PCR-confirmed non-hospitalised, mild or moderate COVID-19 samples, ≥14 days post symptom onset and 426 COVID-19 negative clinical samples. Results A sensitivity and specificity of 98.6% (95% CI, 92.6–100.0), 98.3% (95% CI, 96.4–99.4), respectively, was observed following validation of the SARS-CoV-2 ELISA. No cross-reactivities with endemic coronaviruses or other human viruses were observed, and no change in results were recorded for interfering substances. The assay was stable at temperature extremes and components were stable for 15 days once opened. A matrix comparison showed DBS to correlate with serum results. Clinical validation of the assay reported a sensitivity of 94.7% (95% CI, 90.9–97.2%) and a specificity of 98.4% (95% CI, 96.6–99.3%). Conclusions The human anti-IgGAM SARS-CoV-2 ELISA provides accurate and sensitive detection of SARS-CoV-2 antibodies in non-hospitalised adults with mild or moderate disease. The use of dried blood spots makes the assay accessible to the wider community.

This study aimed to quantify 24 h body core temperature (BcT°) and sleep-wake cycle rhythm alterations in craniopharyngioma (CP) patients and to identify markers related to the postsurgical outcomes. Ten consecutive CP patients underwent neuroradiological, endocrinological and ophthalmological evaluations, 24 h BcT° and sleep-wake cycle recordings before and after endoscopic endonasal surgery. The sample included four women and six men. Nocturnal sleep efficiency was pathologically reduced in eight patients before surgery. Seven out of ten patients presented one to three daytime naps. 24 h BcT° rhythm was pathological in six out of ten cases. Post-surgery sleep efficiency normalized in four out of eight patients, whereas nine out of ten patients presented with two to six longer daytime naps. Diurnal naps were mainly present in patients showing pre-operative involvement of the third ventricle floor. 24 h BcT° remained pathological in only one out of six cases, returned to normal in two and improved in three. 24 h BcT° rhythm improved more in papillary CPs than in adamantomatous CPs. Our data confirmed that both CP and surgery frequently disrupt the sleep-wake cycle and BcT° rhythms. Tumour location and histotype may be related to a worse postsurgical outcome. Therefore, in-depth investigation including circadian monitoring is crucial for surgical outcome.

Introduction: Endobronchial ultrasound (EBUS) is an endoscopic diagnostic procedure combining flexible fibrobronchoscopy with ultrasound techniques; it allows transbronchial needle aspiration biopsy for the diagnosis and staging of mediastinal masses. We present our preliminary experience with the use of the i-gel O2 supraglottic airway device for management of EBUS procedures. Methods: An observational study on 39 patients who underwent EBUS under general anesthesia was performed. Airways were managed with i-gel O2 by anesthesiologists unfamiliar with it. Data collected included patient characteristics, i-gel O2 positioning, mechanical ventilation, procedure, and complications occurring during and after the EBUS. Results: The i-gel airway was successfully positioned during the first attempt in 34/39 cases (87.2%). No failed positioning was recorded. The EBUS scope easily passed through the i-gel in all patients and in 14 (35.6%) cases it was also inserted through the esophagus allowing the examination or fine needle aspiration of paraesophageal lymph nodes. In one case, during the EBUS procedure, the i-gel was dislocated but easily put in place again. During EBUS, air leakages were significant in 2 cases (5.1%) and minimal in 14 cases (35.9%). A brief self-solved laryngospasm and a bronchospasm during bronchoscopy were recorded. After recovery, no patients had dysphagia; mild odynophagia and pharyngodinia were referred by 2 (5.1%) and 12 (30.1%) patients, respectively. Conclusions: The i-gel O2 airway is easy to position and manage even for anesthesiologists unfamiliar with it. This supraglottic airway device is suitable for a complete endosonographic evaluation of the mediastinum.

There is large epidemiological evidence on the short-term health effects of O3 and NO2. These gaseous pollutants induce oxidative stress through their oxidative potential. Therefore, the evaluation of their combined oxidative capacity (Ox) has been proposed rather than studying the effect of either gas individually. To study the short-term effects of daily concentrations of O3, NO2, and Ox on mortality in Rome, in 2002–2015, daily deaths from the city mortality registry were analyzed along with O3 and NO2 levels observed in Rome and with estimated Ox and Owt (Ox, weighted by the redox potential of O3 and NO2). A Poisson regression model was used considering trends, and meteorological and population changes. The effects on mortality were estimated at lag 0–1 and 0–5 for 10 μg/m3. O3 and NO2 were associated with mortality, with the highest effects at lag 0–5, 0.81% (0.45–1.17) and 2.72% (2.07–3.37), respectively. Ox had an intermediate effect between the two gases. After adjusting for PM10, Owt had a stronger effect (1.72%; 1.14–2.30) than either gas, 0.86% (0.50–1.22) for O3 and 1.61% (1.15–2.06) for NO2. Both Ox and Owt were associated with cerebrovascular, respiratory and, to a lesser extent, cardiac mortality more than either gas. These results suggest that the use of Ox (or Owt) can provide a better assessment of the combined role of O3 and NO2 on mortality and can avoid the uncertainty of the threshold level for ozone. The brain and lungs seem to be the main targets of O3 and NO2.

We thank M.M. Speeckaert and co-workers for their interest in our paper about vitamin D status and seroconversion for coronavirus disease 2019 (COVID-19) in UK healthcare workers [1]. We agree with the authors that vitamin D binding protein (DBP) is important in determining serum 25(OH)D3 levels. The majority of vitamin D in the circulation is bound to DBP, also known as gc-globulin, which has actin-binding and immunomodulatory functions independent of vitamin D carriage [2]. DBP levels may be particularly relevant to determining 25(OH)D3 levels in severely ill COVID-19 patients with acute respiratory distress syndrome (ARDS), as we have previously demonstrated that DBP is a negative acute phase protein with levels dropping by about a third in patients with ARDS [3]. This tends to lower circulating total vitamin D but releases free 25(OH)D that can be taken up by cells of the immune system and epithelial cells. The consequences of changes in serum 25(OH)D during illness are, therefore, complex and difficult to interpret [4]. Genome-wide association analyses have shown that single nucleotide polymorphisms (SNPs) in the gene for DBP (GC) are important contributors to the genetic component of circulating 25D concentrations, but this is still a relatively small proportion of overall serum 25D levels, and it is unclear how these SNPs impact DBP/25D homeostasis in the setting of disease., This work outlines the potential importance of vitamin D binding protein and vitamin D in immune function and COVID-19 infection https://bit.ly/3byTaO5

COVID-19 has been associated with both transient and persistent systemic symptoms that do not appear to be a direct consequence of viral infection. The generation of autoantibodies has been proposed as a mechanism to explain these symptoms. To understand this phenomenon in more detail, we investigated the frequency and specificity of clinically relevant autoantibodies in 84 individuals previously infected with SARS-CoV-2, suffering from COVID-19 of varying severity in both the acute and convalescent setting. These were compared with results from 32 individuals who were on ITU for non COVID reasons. We demonstrate a higher frequency of autoantibodies in the COVID-19 ITU group compared with non-COVID-19 ITU disease control patients and that autoantibodies were also found in the serum 3-5 months post COVID-19 infection. Non-COVID patients displayed a diverse pattern of autoantibodies; in contrast, the COVID-19 groups had a more restricted panel of autoantibodies including skin, skeletal muscle and cardiac antibodies. Our results demonstrate that severe COVID-19 induces a pattern of autoantibodies that may correlate with and contribute to the immune pathology associated with the long-term sequelae of infection.

Background Parkinson’s disease (PD) is characterized by the loss of nigral dopaminergic neurons leading to impaired striatal dopamine signaling, α-synuclein- (α-syn-) rich inclusions, and neuroinflammation. Degenerating neurons are surrounded by activated microglia with increased secretion of interleukin-1β (IL-1β), driven largely by the NLRP3 inflammasome. A critical role for microglial NLRP3 inflammasome activation in the progression of both dopaminergic neurodegeneration and α-syn pathology has been demonstrated in parkinsonism mouse models. Fibrillar α-syn activates this inflammasome in mouse and human macrophages, and we have shown previously that the same holds true for primary human microglia. Dopamine blocks microglial NLRP3 inflammasome activation in the MPTP model, but its effects in this framework, highly relevant to PD, remain unexplored in primary human microglia and in other in vivo parkinsonism models. Methods Biochemical techniques including quantification of IL-1β secretion and confocal microscopy were employed to gain insight into dopamine signaling-mediated inhibition of the NLRP3 inflammasome mechanism in primary human microglia and the SYN120 transgenic mouse model. Dopamine and related metabolites were applied to human microglia together with various inflammasome activating stimuli. The involvement of the receptors through which these catecholamines were predicted to act were assessed with agonists in both species. Results We show in primary human microglia that dopamine, l-DOPA, and high extracellular K+, but not norepinephrine and epinephrine, block canonical, non-canonical, and α-syn-mediated NLRP3 inflammasome-driven IL-1β secretion. This suggests that dopamine acts as an inflammasome inhibitor in human microglia. Accordingly, we provide evidence that dopamine exerts its inhibitory effect through dopamine receptor D1 and D2 (DRD1 and DRD2) signaling. We also show that aged mice transgenic for human C-terminally truncated (1–120) α-syn (SYN120 tg mice) display increased NLRP3 inflammasome activation in comparison to WT mice that is diminished upon DRD1 agonism. Conclusions Dopamine inhibits canonical, non-canonical, and α-syn-mediated activation of the NLRP3 inflammasome in primary human microglia, as does high extracellular K+. We suggest that dopamine serves as an endogenous repressor of the K+ efflux-dependent microglial NLRP3 inflammasome activation that contributes to dopaminergic neurodegeneration in PD, and that this reciprocation may account for the specific vulnerability of these neurons to disease pathology.

The aim of the study was to assess the short-term consequences of SARS-CoV-2-related pneumonia, also in relation to radiologic/laboratory/clinical indices of risk at baseline. This prospective follow-up cohort study included 94 patients with confirmed COVID-19 admitted to a medical ward at the Montichiari Hospital, Brescia, Italy from February 28th to April 30th, 2020. Patients had COVID-19 related pneumonia with respiratory failure. Ninety-four patients out of 193 survivors accepted to be re-evaluated after discharge, on average after 4 months. In ¼ of the patients an evidence of pulmonary fibrosis was detected, as indicated by an altered diffusing capacity of the lung for carbon monoxide (DLCO); in 6–7% of patients the alteration was classified as of moderate/severe degree. We also evaluated quality of life thorough a structured questionnaire: 52% of the patients still lamented fatigue, 36% effort dyspnea, 10% anorexia, 14% dysgeusia or anosmia, 31% insomnia and 21% anxiety. Finally, we evaluated three prognostic indices (the Brixia radiologic score, the Charlson Comorbidity Index and the 4C mortality score) in terms of prediction of the clinical consequences of the disease. All of them significantly predicted the extent of short-term lung involvement. In conclusion, our study demonstrated that SARS-CoV-2-related pneumonia is associated to relevant short-term clinical consequences, both in terms of persistence of symptoms and in terms of impairment of DLCO (indicator of a possible development of pulmonary fibrosis); some severity indices of the disease may predict short-term clinical outcome. Further studies are needed to ascertain whether such manifestations may persist long-term.

We demonstrated recently a record 19.9%-efficient GaAs solar cell with an absorber thickness of only 200 nm. Our next step is to optimize the device to reach a 25% efficiency. In this contribution we will present our latest simulation and experimental results based on an extensive analysis of the optical and electrical losses. The benefits brought by the contacts optimization and the improvement of the nanostructured design at the rear side of the solar cell will be emphasized.

BackgroundThe threshold of protection for anti-SARS-CoV-2 spike glycoprotein antibodies and their longevity are not known. Interpretation of serological results in with respect to international reference material can inform this essential question.Methods1,507 West Midlands dental care professionals were recruited into this study in June 2020. Baseline seroprevalence of antibodies directed against the SARS-CoV-2 spike glycoprotein was determined and the cohort was followed longitudinally for 6 months until January/February 2021 through the second wave of the COVID-19 pandemic in the United Kingdom, and commencement of vaccination.ResultsBaseline seroprevalence was 16.3% in this cohort, compared to estimates in the general population of between 6-7%. Seropositivity was retained in over 70% of participants at 3 and 6-month follow up and conferred a 74% reduced risk of infection. During follow-up, no PCR-proven infections occurred in individuals with a baseline anti-SARS-CoV-2 IgG level greater than 147.6 IU/ml with respect to the World Health Organization international standard 20-136. Post-vaccination, antibody responses were more rapid and of higher magnitude in individuals with who were seropositive at baseline.ConclusionNatural infection leads to a serological response that remains detectable in over 70% of individuals 6 months after initial sampling and 9 months from the peak of the first wave of the pandemic. This response is associated with protection from future infection. Even if serological responses wane, a single dose of the Pfizer-BioNTech vaccine is associated with an antibody response indicative of immunological memory.FundingThe Association of Clinical Biochemistry and Laboratory Medicine and The Institute for Global Innovation (IGI) of the University of Birmingham.

Background Cervical cancer is the fourth most common cancer globally among women in incidence and mortality. Women living with HIV (WLHIV) are disproportionately at a higher risk of developing the disease. Aim To determine the knowledge, attitude, and practice of cervical cancer screening among WLHIV in the Kilimanjaro region, northern Tanzania, following the integration of these services in routine HIV care in the country. Methods and results A cross‐sectional study was conducted in the Kilimanjaro region among 297 WLHIV attending care and treatment centers (CTC) in Hai district and Mawenzi regional hospitals in northern Tanzania between 21 August and 3 September 2020. A questionnaire was used for data collection using face‐to‐face interviews. Data were analyzed using SPSS version 20.0. Frequencies and percentages summarized categorical variables and numerical variables summarized using median and interquartile range (IQR). About half (50.2%) of 297 WLHIV in this study had ever screened for cervical cancer, and 64% screened within the past 12 months preceding the survey. Although 90% ever heard of cervical cancer screening, only 20.5% knew when WLHIV should start screening. Over half (52.5%) had adequate knowledge of prevention, 38.4% on risk factors, and 27.9% of cervical cancer signs and symptoms. Two‐thirds (66.7%) had positive attitudes toward cervical cancer screening. A major source of cervical cancer screening information was the health care providers (80.1%) and the mass media (66%), particularly radio. Conclusions The WLHIV in this study had inadequate knowledge but favorable attitudes toward cervical cancer screening, while half had screened for cervical cancer. Efforts should be directed to capacity building of health care providers at CTC and scaling up the mass media campaigns as relevant interventions to promote the uptake of cervical cancer screening programs among WLHIV in Tanzania.

Arthritis is a common clinical feature of systemic lupus erythematosus (SLE) and is usually non-erosive as opposed to rheumatoid arthritis (RA). While RA synovial pathology has been extensively studied, little is known about the pathophysiology of lupus arthritis. Here, we aimed to explore the cytokine and cellular compartments in synovial fluids of SLE patients with arthritic manifestations. Acellular synovial fluid and paired serum samples from SLE patients (n=17) were analyzed with cytokine bead array for T helper associated cytokines. From two SLE patients, synovial fluid mononuclear cells (SFMC) were analyzed by multiparameter flow cytometry to dissect T cell, B cell, monocyte and dendritic cell phenotypes. SLE-derived SFMC were further stimulated in vitro to measure their capacity for producing IFN and IL-17A. All patients fulfilled the ACR 1982 classification criteria for SLE. Clinical records were reviewed to exclude the presence of comorbidities such as osteoarthritis or overlap with RA. IL-17A and IL-6 levels were high in SLE synovial fluid. A clear subset of the synovial CD4+ T cells expressed CCR6+, a marker associated with Th17 cells. IL-17-production was validated amongst CD4+CCR6+ T cells following in vitro stimulation. Furthermore, a strong IFN production was observed in both CD4+ and CD8+ cells. Our study shows high IL-17A and IL-6 levels in synovial fluids of patients with lupus arthritis. The Th17 pathway have been implicated in several aspects of SLE disease pathogenesis and our data points to Th17 involvement also for lupus arthritis.

Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening disease occurring several weeks after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Deep immune profiling showed acute MIS-C patients had highly activated neutrophils, classical monocytes and memory CD8+ T-cells; increased frequencies of B-cell plasmablasts and double-negative B-cells. Post treatment samples from the same patients, taken when symptoms were resolving, identified recovery-associated immune features including CD163+ monocytes, emergence of a new population of immature neutrophils and, in some patients, a transient increase in arginase. Plasma profiling identified multiple features shared by MIS-C, Kawasaki Disease and COVID-19 and that therapeutic inhibition of IL6 may be preferable to IL1 or TNF-a. We identified potential new mechanisms of action for IVIG, the most commonly used drug to treat MIS-C. Finally, we showed systemic complement activation with high plasma C5b-9 levels is common in MIS-C, suggesting complement inhibitors could be used to treat the disease. Funding Information: Birmingham Women’s and Children’s Hospital Charity funded the single cell RNA sequencing analysis. No other external funding was received. Declaration of Interests: None declared. Ethics Approval Statement: Reviewed and approved by South of Birmingham Research Ethics Committee (REC: 17/WM/0453, IRAS: 233593).

Summary Arthritis is a common clinical feature of systemic lupus erythematosus (SLE) and is usually non‐erosive, as opposed to rheumatoid arthritis (RA). While RA synovial pathology has been extensively studied, little is known about the pathophysiology of lupus arthritis. Here, we aimed to explore the cytokine and cellular compartments in synovial fluids of SLE patients with arthritic manifestations. Acellular synovial fluid and paired serum samples from SLE patients (n = 17) were analyzed with cytokine bead array for T helper‐associated cytokines. From two SLE patients, synovial fluid mononuclear cells (SFMC) could also be captured and were analyzed by multiparameter flow cytometry to dissect T cell, B cell, monocyte and dendritic cell phenotypes. SLE‐derived SFMC were further stimulated in vitro to measure their capacity for producing interferon (IFN)‐γ and interleukin (IL)‐17A. All patients fulfilled the ACR 1982 classification criteria for SLE. Clinical records were reviewed to exclude the presence of co‐morbidities such as osteoarthritis or overlap with RA. IL‐17A and IL‐6 levels were high in SLE synovial fluid. A clear subset of the synovial CD4+ T cells expressed CCR6+, a marker associated with T helper type 17 (Th17) cells. IL‐17A‐production was validated among CD4+CCR6+ T cells following in‐vitro stimulation. Furthermore, a strong IFN‐γ production was observed in both CD4+ and CD8+ cells. Our study shows high IL‐17A and IL‐6 levels in synovial fluids of patients with lupus arthritis. The Th17 pathway has been implicated in several aspects of SLE disease pathogenesis and our data also point to Th17 involvement for lupus arthritis., IL‐17A and IL‐6 are elevated in synovial fluid of SLE arthritis patients. The Th17 pathway have been implicated in several aspects of SLE disease pathogenesis and our data points to Th17 involvement also for lupus arthritis.

The neonatal response to stress was reported to be related to the type of delivery, that is elective or emergency cesarean sections (ELCS and EMCS, respectively). Nitric oxide (NO) is also reported to be related to uterine inertia, and high levels of NO metabolites (NOs) are associated with physical and emotional stress. The study aimed to assess the concentrations of cortisol (C) and NOs in the amniotic fluid of puppies delivered by ELCS or EMCS. In total, 32 puppies were delivered by ELCS and 22 by EMCS. ANCOVA showed an effect of the ELCS vs. EMCS on both amniotic NOs (p &lt, 0.001) and C (p &lt, 0.001) concentrations. Lower amniotic C concentrations were found at increasing Apgar score (p &lt, 0.001). Higher amniotic NOs concentrations were associated to increasing mother’s parity (p &lt, 0.001), puppies’ birthweight (p &lt, 0.001), and time of labor within the EMCS group (p &lt, 0.05). A positive correlation between birthweight and amniotic NOs concentrations was also found (p &lt, 0.05) in the EMCS group. Due to the possible concurrence of several compartments (maternal, maybe placental, and fetal) to the final amniotic fluid composition, the definition of the role played by the three compartments in the higher C and NOs concentrations found in amniotic fluids collected from puppies delivered by EMCS than ELCS needs further clarification.

Background Immune suppression is a clinical feature of chronic lymphocytic leukaemia (CLL), and patients show increased vulnerability to SARS-CoV-2 infection and suboptimal antibody responses. Method We studied antibody responses in 500 patients following dual COVID-19 vaccination to assess the magnitude, correlates of response, stability and functional activity of the spike-specific antibody response with two different vaccine platforms. Results Spike-specific seroconversion post-vaccine was seen in 67% of patients compared to 100% of age-matched controls. Amongst responders, titres were 3.7 times lower than the control group. Antibody responses showed a 33% fall over the next 4 months. The use of an mRNA (n = 204) or adenovirus-based (n = 296) vaccine platform did not impact on antibody response. Male gender, BTKi therapy, prophylactic antibiotics use and low serum IgA/IgM were predictive of failure to respond. Antibody responses after CD20-targeted immunotherapy recovered 12 months post treatment. Post-vaccine sera from CLL patients with Spike-specific antibody response showed markedly reduced neutralisation of the SARS-CoV-2 delta variant compared to healthy controls. Patients with previous natural SARS-CoV-2 infection showed equivalent antibody levels and function as healthy donors after vaccination. Conclusions These findings demonstrate impaired antibody responses following dual COVID-19 vaccination in patients with CLL and further define patient risk groups. Furthermore, humoural protection against the globally dominant delta variant is markedly impaired in CLL patients and indicates the need for further optimisation of immune protection in this patient cohort.