Bedeutsame Veränderungen in der Entwicklung der oberen pharyngealen und nasalen, neonatalen Atem- und Luftwege in Abhängigkeit vom Gestationsalter und dem Geschlecht

Detailgenaue anatomische Kenntnisse des respiratorischen Systems sind insbesondere in der Atemwegssicherung Früh- und Neugeborener essenziell. Hierzu zählen neben der endotrachealen Intubation auch die an Bedeutung zunehmenden nicht invasiven Beatmungsmöglichkeiten, beispielsweise mittels supraglottischer Atemwegshilfen (Larynxmaske, Larynxtubus) und CPAP- NIPPV- BIPAP oder HHHFNC-Beatmung. Es ist allgemeiner Konsens, dass sich die Anatomie Früh- und Neugeborener von der Anatomie Erwachsener unterscheidet und die Intubation dieser Altersgruppe einen besonderen Anspruch darstellt (2, 3). Aufgrund mangelnder anatomisch korrekter Abbildungen des fetalen Atemweges, fehlendem Zugang zu früh- und neugeborenen Präparaten sowie Mangel an klinischen Studien an Früh- und Neugeborenen, fehlt es AnästhesistInnen und IntensivmedizinerInnen häufig an Fachwissen über die tatsächliche Anatomie dieser Altersgruppe (4-6). In dieser Studie werden die oberen neonatalen pharyngealen und nasalen Atemwege analysiert. Ziel ist es neben der Verbesserung des Wissensstandes zur frühkindlichen Anatomie auch einen möglichen Zusammenhang zwischen der Entwicklung der makroskopischen Anatomie des frühkindlichen Atemweges und dem Gestationsalter sowie dem Geschlecht zu untersuchen. Die Untersuchungen werden an 22 Präparaten, dankenswerter Weise bereitgestellt vom Anatomischen Institut der Universität zu Köln, durchgeführt. Die Präparate sind zwischen 25+0 Wochen (175 Tage, 5,8 Monate) und 43+2 Wochen (303 Tage, 9,9 Monate) alt. Das Durchschnittsalter liegt bei 30+5 Wochen (215 Tage, 7,1 Monate). Nach erfolgreicher anatomischer Präparation des nasalen und pharyngealen Atemweges, sowie der Trachea und des Ösophagus erfolgt die Ausmessung anatomisch relevanter Landmarken und Messgrößen an den Präparaten selbst, sowie anhand fotografischer Datei. Im Anschluss werden die gewonnenen Daten in statistische Analysen eingeschlossen. Im Rahmen der Studie konnte keine statistisch signifikante Korrelation zwischen den von uns ausgewählten Winkeln und dem Gestationsalter festgestellt werden. Bei den Abständen hingegen zeigen sowohl der „Abstand Palatum durum oral“ (R2 = 0,293, p = 0,009) und „Abstand Palatum molle 1 oral“ (R2 = 0,205, p = 0,034), „Abstand palatum molle 2 oral (R2 = 0,228, p = 0,025) und „Abstand palatum molle 3 oral“ (R2 = 0,298, p = 0,009) positive Korrelationen. Diese Abstände befinden sich im vorderen Pharynxbereich. Sie liegen zwischen dem harten Gaumen und der Zunge, sowie zwischen dem vorderen, mittleren und hinteren Teil des weichen Gaumens und der Zunge und vergrößern sich mit steigendem Gestationsalter. 9 Der „Winkel epsilon oral“, welcher zwischen dem Eingang in die Trachea und dem Ösophagus liegt, ist bei männlichen Präparaten signifikant größer als bei weiblichen (p = 0,052). Dieser Winkel ist insbesondere in der endotrachealen Intubation relevant. Er hat Einfluss darauf, ob der Tubus während der Intubation in die Trachea oder fälschlicher Weise in den Ösophagus gleitet. Nach Unterteilung der Stichprobe in drei altersspezifische Untergruppierungen weisen noch weitere Winkel und auch einige der ausgemessenen Abstände geschlechtsspezifische Unterschiede auf. Stets sind Winkel und Abstände der männlichen Präparate größer als die der weiblichen. Auffallend ist dabei, dass sich in der jüngsten Gruppe unter 28 Wochen wesentlich deutlichere geschlechtsrelevante Unterschiede nachweisen lassen als in den beiden älteren Gruppen (Gruppe zwei 28+0 bis 36+6 Schwangerschaftswoche, Gruppe drei ab der 37. Schwangerschaftswoche), in denen die Messgrößen weniger weit auseinander reichen. Zweizeitig erfolgt auch der Einschluss der von uns gefertigten Präparate in die Studie „Anatomic accuracy, physiologic characteristics, and fidelity of very low birth weight infant airway simulators“ der KollegInnen Lengua Hinojosa et al. des Universitätsklinikum Eppendorf, 2021 (1), In dieser Studie dienen die Präparate als Grundlage zur Überprüfung der anatomischen Genauigkeit von vier bereits bestehenden Intubationssimulatoren der Neonatologie

HIV-1 heterosexual transmission and association with sexually transmitted infections in the era of treatment as prevention

Objectives: HIV-1 heterosexual transmission among individuals on antiretroviral treatment (ART) with undetectable viremia is extremely rare. The aim of this study was to evaluate the risk of sexual HIV-1 transmission and other sexually transmitted infections (STIs) in HIV-1 serodifferent couples while the index partner is on ART. Methods: HIV transmission was evaluated in 200 HIV-1 heterosexual serodifferent couples in a stable relationship (≥3 months). All HIV-positive individuals had been on ART for ≥3 months and had been followed up for a median preceding time of 4.5 years (range 0.3–16 years) at the HIV couples clinic at Hospital Nossa Senhora da Conceição in Porto Alegre, Brazil. Following written informed consent, participants responded to demographic/behavioral questionnaires. Quantitative PCR for HIV RNA, T-cell subsets, and STI testing (syphilis, herpes, human papillomavirus, gonorrhea, and bacterial vaginosis) were performed. Self-collected vaginal swabs were obtained for quantitative HIV genital viral load testing. Results: Among 200 couples, 70% of index partners were female. Five seroconversions were observed; the HIV infection incidence was 2.5% (95% confidence interval 0.8% to 5.7%). Mean plasma viral load results were higher in HIV transmitters compared to non-transmitters (p = 0.02). The presence of STIs was significantly greater in couples who seroconverted (60.0% vs. 13.3%; odds ratio 9.75, 95% confidence interval 1.55–61.2; p = 0.023). The duration of undetectable HIV viremia and presence of STIs were associated with HIV transmission. Conclusions: Undetectable viremia was the main factor associated with non-transmissibility of HIV in this setting

Antiretroviral adherence and virologic suppression in partnered and unpartnered HIV-positive individuals in southern Brazil

Background: An undetectable serum HIV-1 load is key to effectiveness of antiretroviral (ARV) therapy, which depends on adherence to treatment. We evaluated factors possibly associated with ARV adherence and virologic response in HIV-infected heterosexual individuals. Methods: A cross-sectional study was conducted in 200 HIV-1 serodiscordant couples and 100 unpartnered individuals receiving ARV treatment at a tertiary hospital in southern Brazil. All subjects provided written informed consent, answered demographic/behavioral questionnaires through audio computer-assisted self-interviews (ACASI), and collected blood and vaginal samples for biological markers and assessment of sexually transmitted infections (STIs). HIV-negative partners were counseled and tested for HIV-1. Results: The study population mean age was 39.9 years, 53.6% were female, 62.5% were Caucasian, 52.6% had incomplete or complete elementary education, 63.1% resided in Porto Alegre. Demographic, behavioral and biological marker characteristics were similar between couples and single individuals. There was an association between adherence reported on ACASI and an undetectable serum viral load (P<0.0001). Logistic regression analysis demonstrated that single-tablet ARV-regimens were independently associated with adherence (OR = 2.3; 95CI%: 1.2–4.4; P = 0.011) after controlling for age, gender, education, marital status, personal income, ARV regimen, and median time of ARV use. A positive correlation between genital secretion PCR results and serum viral load was significant in the presence of STIs (r = 0.359; P = 0.017). Although HIV PCR detection in vaginal secretions was more frequent in women with detectable viremia (9/51, 17.6%), it was also present in 7 of 157 women with undetectable serum viral loads (4.5%), p = 0.005. Conclusions: ARV single tablet regimens are associated with adherence. Detectable HIV-1 may be present in the genital secretions of women with undetectable viremia which means there is potential for HIV transmission in adherent individuals with serologic suppression

Primary resistance of HIV to antiretrovirals among individuals recently diagnosed at voluntary counselling and testing centres in the metropolitan region of Recife, Pernambuco

Determining the prevalence and type of antiretroviral (ARV) resistance among ARV-naïve individuals is important to assess the potential responses of these individuals to first-line regimens. The prevalence of primary resistance and the occurrence of recent infections among individuals with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) were identified among recently diagnosed patients at five sexually transmitted disease/AIDS testing and counselling centres in the metropolitan region of Recife (RMR), Pernambuco, Brazil, between 2007-2009. One-hundred and eight samples were analysed using the Calypte® BED assay. Males predominated (56%), as did patients aged 31-50 years. Twenty-three percent presented evidence of a recent HIV infection. The median CD4+ T lymphocyte count was 408 cells/mm³ and the median viral load was 3.683 copies/mL. The prevalence of primary resistance was 4.6% (confidence interval 95% = 1-8.2%) based on criteria that excluded common polymorphisms in accordance with the surveillance drug resistance mutation criteria. The prevalence of resistance to non-nucleoside reverse transcriptase, nucleoside/nucleotide reverse transcriptase and protease inhibitors were 3.8%, 1.5% and 0.8%, respectively. Fifty-seven percent of strains were from clade B, 37.7% were clade F and 3.1% were clade C; there were no statistically significant differences with respect to resistance between clades. Recent infection tended to be more common in men (p = 0.06) and in municipalities in the south of the RMR (Jaboatão dos Guararapes and Cabo de Santo Agostinho) (p = 0.046). The high prevalence of recent infection and the high prevalence of non-B strains in this poor Brazilian region merit further attention.Laboratório Central de Saúde Pública de Pernambuco Setor de VirologiaUniversidade Federal de Pernambuco Programa de Pós-Graduação em Medicina TropicalFiocruz Centro de Pesquisa Aggeu MagalhãesCentro de Testagem e Aconselhamento Herbert de SouzaUniversidade Federal de São Paulo (UNIFESP) Laboratório de RetrovirologiaUNIFESP, Laboratório de RetrovirologiaSciEL

Abatacept, Cenicriviroc, or Infliximab for Treatment of Adults Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial

IMPORTANCE: Immune dysregulation contributes to poorer outcomes in COVID-19. OBJECTIVE: To investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-masked, placebo-controlled clinical trial using a master protocol to investigate immunomodulators added to standard care for treatment of participants hospitalized with COVID-19 pneumonia. The results of 3 substudies are reported from 95 hospitals at 85 clinical research sites in the US and Latin America. Hospitalized patients 18 years or older with confirmed SARS-CoV-2 infection within 14 days and evidence of pulmonary involvement underwent randomization between October 2020 and December 2021. INTERVENTIONS: Single infusion of abatacept (10 mg/kg; maximum dose, 1000 mg) or infliximab (5 mg/kg) or a 28-day oral course of cenicriviroc (300-mg loading dose followed by 150 mg twice per day). MAIN OUTCOMES AND MEASURES: The primary outcome was time to recovery by day 28 evaluated using an 8-point ordinal scale (higher scores indicate better health). Recovery was defined as the first day the participant scored at least 6 on the ordinal scale. RESULTS: Of the 1971 participants randomized across the 3 substudies, the mean (SD) age was 54.8 (14.6) years and 1218 (61.8%) were men. The primary end point of time to recovery from COVID-19 pneumonia was not significantly different for abatacept (recovery rate ratio [RRR], 1.12 [95% CI, 0.98-1.28]; P = .09), cenicriviroc (RRR, 1.01 [95% CI, 0.86-1.18]; P = .94), or infliximab (RRR, 1.12 [95% CI, 0.99-1.28]; P = .08) compared with placebo. All-cause 28-day mortality was 11.0% for abatacept vs 15.1% for placebo (odds ratio [OR], 0.62 [95% CI, 0.41-0.94]), 13.8% for cenicriviroc vs 11.9% for placebo (OR, 1.18 [95% CI 0.72-1.94]), and 10.1% for infliximab vs 14.5% for placebo (OR, 0.59 [95% CI, 0.39-0.90]). Safety outcomes were comparable between active treatment and placebo, including secondary infections, in all 3 substudies. CONCLUSIONS AND RELEVANCE: Time to recovery from COVID-19 pneumonia among hospitalized participants was not significantly different for abatacept, cenicriviroc, or infliximab vs placebo. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04593940

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials

Anatomical investigations on the upper airway in premature and newborn babies

Safe intubation of newborns remains a challenge. This investigates the upper airway anatomy of (pre-)term infants was investigated to improve airway management and the development of airway devices. Angles and diameters of both oral and nasal intubation pathways of 22 cadavers of premature and term stillborn infants were measured, relative to their gestational age (GA) and tested for statistical significance. The systematic influence of sex on the distribution of values was examined. Cast models of the oral and nasal intubation pathway were (produced using a silicone dental impression material) 3D-scanned. No significant correlation with GA was seen in the angles studied. However, four distances around the hard and soft palate did show statistically significant positive correlations with GA. Regarding differences between the sexes, only the angle between the entrance of the trachea and the esophagus was greater for male cadavers. The angles of the ventilation pathway of (pre-)term infants do not depend systematically on GA. Anatomically, laryngeal masks might therefore also be well-suited ventilators for preterm infants. Alterations in the size but not the shape of laryngeal masks for small preterm infants is recommended. The data obtained may thus be used as a basis for the development of airway devices and airway simulators for medical education and clinical training

Prevalência de obesidade e risco cardiovascular em pacientes com HIV/AIDS em Porto Alegre, Brasil

Objetivo: Conhecer a prevalência de sobrepeso, obesidade e risco cardiovascular em nossos pacientes ambulatoriais com HIV/AIDS de acordo com o sexo, tratamento antirretroviral e outras variáveis. Sujeitos e métodos: Os pacientes foram submetidos à avaliação antropométrica. O índice de massa corporal e a medida da circunferência da cintura foram utilizados para classificar o estado nutricional e o risco cardiovascular. Resultados: A maior parte dos 345 pacientes (58,8%) era do sexo masculino. A obesidade foi detectada em 8,3% deles; 34,2% tinham sobrepeso e 5,2%, desnutrição. Quase a metade (51,3%) apresentou algum risco cardiovascular, com risco elevado em 24,6% e muito elevado em 26,7%. Conclusões: O sobrepeso e a obesidade têm elevada prevalência. As mulheres são mais frequentemente obesas (OR = 3,53; IC 95%, 1,47 < OR < 8,69) e seu risco cardiovascular é frequentemente mais alto (OR = 6,97; IC 95%, 4,16 < OR < 11,76). A prevalência de obesidade e de risco cardiovascular não se alterou conforme o tratamento antirretroviral ou outras variáveis.Objective: The aim of this study was to discover the prevalence of overweight, obesity and cardiovascular risk in our HIV/AIDS outpatients according to sex, antiretroviral therapy and other variables. Subjects and methods: Patients underwent an anthropometric assessment. Body mass index and waist circumference were used to classify their nutritional status and their cardiovascular risk. Results: The majority of the 345 patients (58.8%) were males. Obesity was detected in 8.3% of them; 34.2% were overweight, and 5.2% malnourished. Near half of them (51.3%) had some cardiovascular risk, with increased risk in 24.6% of them, and substantially increased risk in 26.7% of them. Conclusions: Overweight and obesity were highly prevalent. Women were more frequently obese (OR = 3.53; IC 95%, 1.47 < OR < 8.69), and their cardiovascular risk was often higher (OR = 6.97; IC 95%, 4.16 < OR < 11.76). The prevalence of obesity and cardiovascular risk did not change according to antiretroviral therapy or other variables