Leveraging 3D convolutional neural network and 3D visible-near-infrared multimodal imaging for enhanced contactless oximetry.

Significance: Monitoring oxygen saturation ( SpO 2 ) is important in healthcare, especially for diagnosing and managing pulmonary diseases. Non-contact approaches broaden the potential applications of SpO 2 measurement by better hygiene, comfort, and capability for long-term monitoring. However, existing studies often encounter challenges such as lower signal-to-noise ratios and stringent environmental conditions. Aim: We aim to develop and validate a contactless SpO 2 measurement approach using 3D convolutional neural networks (3D CNN) and 3D visible-near-infrared (VIS-NIR) multimodal imaging, to offer a convenient, accurate, and robust alternative for SpO 2 monitoring. Approach: We propose an approach that utilizes a 3D VIS-NIR multimodal camera system to capture facial videos, in which SpO 2 is estimated through 3D CNN by simultaneously extracting spatial and temporal features. Our approach includes registration of multimodal images, tracking of the 3D region of interest, spatial and temporal preprocessing, and 3D CNN-based feature extraction and SpO 2 regression. Results: In a breath-holding experiment involving 23 healthy participants, we obtained multimodal video data with reference SpO 2 values ranging from 80% to 99% measured by pulse oximeter on the fingertip. The approach achieved a mean absolute error (MAE) of 2.31% and a Pearson correlation coefficient of 0.64 in the experiment, demonstrating good agreement with traditional pulse oximetry. The discrepancy of estimated SpO 2 values was within 3% of the reference SpO 2 for ∼ 80 % of all 1-s time points. Besides, in clinical trials involving patients with sleep apnea syndrome, our approach demonstrated robust performance, with an MAE of less than 2% in SpO 2 estimations compared to gold-standard polysomnography. Conclusions: The proposed approach offers a promising alternative for non-contact oxygen saturation measurement with good sensitivity to desaturation, showing potential for applications in clinical settings.

Adverse Events with Hypoglossal Nerve Stimulation in the Treatment of Obstructive Sleep Apnea-A Systematic Review of Clinical Trials and Real-World Data.

Background/Objectives: Hypoglossal nerve stimulation (HNS) emerged as an alternative treatment for patients with obstructive sleep apnea (OSA) a decade ago. Long-term clinical trials and real-world data show that HNS treatment provides significant and sustained improvements in both OSA disease control and quality-of-life measures over time. Given the nature of HNS treatment, with the requirement of using an implantable neurostimulation system, patient safety is a critical domain in the assessment of this technology. The objective of this review was to evaluate adverse events (AEs) and complications with HNS therapy in a systematic review of published evidence. Methods: Medline, Cochrane, and Web of Science were systematically searched to identify randomized controlled and real-world observational studies reporting relevant outcomes with HNS therapy for treatment of OSA that included procedure-, device-, and treatment-related AEs. Results: Out of 418 articles screened, 27 were reviewed for eligibility, and 17 studies, the majority found to have low-to-moderate risk of bias, with data on 1962 patients were included for further analysis. Across included studies, reporting of AEs was heterogeneous with regard to the classifications used and the extent of reporting. Over an average follow-up duration of 17.5 ± 16.9 months, the pooled mortality rate was 0.01% (95% CI = 0.0 to 0.2%), with all reported deaths being unrelated to HNS treatment. The HNS system survival probability over the follow-up time of 60 months was 0.9834 (95% CI = 0.9768 to 0.9882), with infections and request for removal by patients being the most common indications. The pooled surgical revision rate was 0.08% (95% CI 0.0 to 0.2%). Most reported treatment-related side effects were transient stimulation-related discomfort (0.08%, 95% CI = 0.0 to 0.2%) and tongue abrasions (0.07%, 95% CI = 0.0 to 0.2%). Based on the systematic review, a standardized set of endpoints was defined, aiming to harmonize safety data relevant to HNS therapy. Conclusions: In this systematic review, HNS therapy for treatment of OSA is associated with a positive patient safety profile. AEs occur mainly at device implantation and during the treatment acclimatization period. Due to a lack of available evidence, partially implantable HNS systems are underrepresented in this review, which limits the generalizability of the results. Significant heterogeneity was found for adverse event reporting. A framework for reporting HNS outcomes that includes AEs and side effects is proposed to facilitate comparability of the reported data.

The effects of a digital lifestyle intervention in patients with hypertension: Results of a pilot randomized controlled trial.

In this pilot study, the authors investigated the preliminary effectiveness of the digital lifestyle intervention, actensio (mementor DE GmbH), in treating arterial hypertension. Adults with arterial hypertension were randomly assigned to an intervention group (actensio + standard care) or a control group (waiting list + standard care) in a 1:1 ratio. Primary and secondary endpoints were assessed at baseline (t0) and 3 months post-randomization (t1). The primary endpoint was average systolic blood pressure, measured at home for 1 week. Secondary endpoints included patient engagement (measured using the "patient activation measure"; PAM-13), average diastolic blood pressure, and heart rate. All endpoints were analyzed using ANCOVA models, following an intention-to-treat approach, while adjusting for baseline values. Missing data were estimated using multiple imputation models. A total of N = 102 participants (f = 59, age = 52.94 ± 9.01) were randomized to either the intervention (IG; N = 52) or the control group (CG; N = 50), of which N = 80 completed the blood pressure diary, and N = 81 the PAM-13 at t1. Between-group comparisons showed an average group difference in systolic blood pressure of -5.06 mm Hg (95% CI = -8.71 to -1.41, p = .013) between the intervention group (M = 137.37 ± 10.13) and the control group (M = 142.35 ± 11.23). Average group difference for patient engagement was 3.35 points with a trend towards statistical significance (95% CI = -018 to 6.89, p = .064), favoring the intervention group (MIG = 79.38 ± 9.44 vs. MCG = 75.45 ± 10.62). There were no group differences in diastolic blood pressure (-1.78 mm Hg; 95% CI = -4.50 to 0.95, p = .402) and heart rate (-0.684; 95% CI = -3.73 to 2.36, p = 0.683). The results of the present pilot study confirm the preliminary effectiveness of the digital lifestyle intervention, actensio, in reducing high blood pressure in patients with hypertension.

Introduction of ICD-11 in Germany: Seizing opportunities together. / ICD-11 Einführung in Deutschland: Gemeinsam die Chance nutzen.

With the new ICD-11 developed by the WHO and translated into German for use in Germany by the Federal Institute for Drugs and Medical Devices, the German healthcare system is facing a change that is more than a simple change of a medical coding system. The ICD-11 modernises the coding system, for example, by including new, separate health conditions such as sleep-wake disorders and conditions related to sexual health, thus making the corresponding diseases more visible. The ICD-11 is more precise than the ICD-10: it allows cross-referencing between diagnoses, symptoms, functionality and locations and partially abandons the strict hierarchy of the ICD-10. In addition, a greater number of rare diseases are represented with their own specific code than was previously possible with ICD-10. Finally, the ICD-11 is also significantly more "modern" than the ICD-10 (which dates back to pre-digital times) in that it enables new, digitally-supported processes, such as keywords flexibility and sustainability when updating the system as well as actual coding at the point of care. The switch to ICD-11 can be a great opportunity for the German healthcare system that should not be missed. It will benefit health service research, which at best will be able to work with much more detailed and correct data sets. But medical care will also benefit because the ICD-11 reflects current medical knowledge. In addition, certain illnesses will be removed from the psychiatric category, meaning that those affected will no longer be stigmatised by their classification in the ICD. The improved coding of diagnoses will ultimately also support guideline-based treatments. However, the changeover is only the first step. The challenges - also for health service research - include in particular the latency of introduction and uniform use as well as the necessary change in coding habits. For ICD-11 to be a success in Germany, authorities, the medical profession, payers and patients must work together on strategies to ensure not only a rapid but also a comprehensive implementation that maximises the potential of ICD-11.

Drivers and barriers of patients' acceptance of video consultation in cancer care.

Background: Due to digitization in the medical sector, many healthcare interactions are switched to online services. This study assessed the acceptance of video consultations (VCs) in cancer care, and determined drivers and barriers of acceptance. Methods: A cross-sectional online-based survey study was conducted in Germany from February 2022 to February 2023. Recruitment took place at oncology outpatient clinics, general practitioners, oncology practices and via cancer-related social media channels. Inclusion criteria were a cancer diagnosis, cancer treatment and internet access. Sociodemographic, medical data, eHealth-related data were acquired via an online assessment. The Unified Theory of Acceptance and Use of Technology (UTAUT) model was used to determine the acceptance of VC and its predictors. Results: Of N = 350 cancer patients, 56.0% (n = 196) reported high acceptance of VC, 28.0% (n = 98) stated moderate acceptance and 16.0% (n = 56) indicated low acceptance. Factors influencing acceptance were younger age (ß = -.28, p < .001), female gender (ß = .35, p = .005), stage of disease (ß = .11, p = .032), high digital confidence (ß = .14, p = .010), low internet anxiety (ß = -.21, p = .001), high digital overload (ß = -.12, p = .022), high eHealth literacy (ß = .14, p = .028), personal trust (ß = -.25, p < .001), internet use (ß = .17, p = .002), and the UTAUT predictors: performance expectancy (ß = .24, p < .001), effort expectancy (ß = .26, p < .001), and social influence (ß = .34, p < .001). Conclusions: Patients' acceptance of VC in cancer care is high. Drivers and barriers to acceptance identified should be considered for personalized applications. Considering the growing demand for cancer care establishing digital healthcare solutions is justified.

Concurrent hypoglossal and phrenic nerve stimulation in patients with obstructive and treatment emergent central sleep apnea.

BACKGROUND: Patients with obstructive or central sleep apnea are primarily treated with positive airway pressure treatment. There are novel implantable options targeting either obstructive sleep apnea using hypoglossal nerve stimulation (HNS) or central sleep apnea using phrenic nerve stimulation (PNS). METHODS: Patients with sleep apnea were implanted with both HNS and PNS devices, and their response to each therapy was monitored using home sleep tests as well as Epworth Sleepiness scale (ESS). RESULTS: We evaluated our concurrent neurostimulation approach in two patients. Both patients were implanted with two neuromodulation devices: The first case suffered from treatment emergent central sleep apnea after HNS activation for primarily obstructive sleep apnea (apnea-hypopnea index/AHI 54/h). The central portion resolved under PNS (AHI 23.7/h). The second case suffered from predominantly central sleep apnea (AHI 82/h). Here, the PNS device was implanted first, resulting in a subsequent reduction of the central portion. The residual obstructive sleep apnea was addressed using HNS (AHI 5.4/h). No interaction between the HNS and PNS systems was noticed in either of the two patients. CONCLUSIONS: In selected cases, a concurrent treatment with hypoglossal and phrenic nerve stimulation may lead to improvement of sleep apnea and patient satisfaction in a safe manner.

Effect of phrenic nerve stimulation on patients with central sleep apnea: A meta-analysis.

Patients with central sleep apnea (CSA) have a lower quality of life and higher morbidity and mortality. Phrenic nerve stimulation (PNS) is a novel treatment for CSA that has been shown to be safe. However, the effects of PNS on sleep changes are still under debate. This meta-analysis was performed to evaluate the efficacy of PNS in patients with CSA. PubMed, Scopus, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL) and Web of Science databases were searched for relevant studies published. We performed random-effects meta-analyses of the changes in apnea-hypopnea index (AHI), central apnea index (CAI), Arousal Index, percent of sleep with O2 saturation <90% (T90), Epworth Sleepiness Scale (ESS) and sleep efficiency. Ten studies with a total of 580 subjects were analyzed. Overall meta-analysis showed AHI [SMD: -2.24, 95% confidence interval (CI): was -3.11 to -1.36(p＜0.00001)], CAI [SMD: -2.32, 95% CI: -3.17 to -1.47 (p＜0.00001)] and Arousal Index (p = 0.0002, SMD (95% CI) -1.79 (-2.74 to -0.85)) significantly reduced after PNS. No significant changes were observed in T90, ESS and sleep efficiency (p > 0.05). Meta-analysis of observational studies demonstrated AHI, CAI and Arousal Index had a decreasing trend between before and after PNS (all, p＜0.05). However, ESS and T90 did not change significantly after PNS (p > 0.05). Meta-analysis of RCTs showed that CSA patients had trends of a lower AHI (I2 = 0%), CAI (I2 = 74%), Arousal Index (I2 = 0%), T90 (I2 = 0%) and ESS (I2 = 0%) after PNS (all, p＜0.05). The use of PNS appears to be safe and feasible in patients with CSA. However, larger, independent RCTs are required to investigate the efficacy and long-term effect of PNS and more attention should be paid to T90 and ESS.

Clinical validation of a contactless respiration rate monitor.

Respiratory rate (RR) is an often underestimated and underreported vital sign with tremendous clinical value. As a predictor of cardiopulmonary arrest, chronic obstructive pulmonary disease (COPD) exacerbation or indicator of health state for example in COVID-19 patients, respiratory rate could be especially valuable in remote long-term patient monitoring, which is challenging to implement. Contactless devices for home use aim to overcome these challenges. In this study, the contactless Sleepiz One+ respiration monitor for home use during sleep was validated against the thoracic effort belt. The agreement of instantaneous breathing rate and breathing rate statistics between the Sleepiz One+ device and the thoracic effort belt was initially evaluated during a 20-min sleep window under controlled conditions (no body movement) on a cohort of 19 participants and secondly in a more natural setting (uncontrolled for body movement) during a whole night on a cohort of 139 participants. Excellent agreement was shown for instantaneous breathing rate to be within 3 breaths per minute (Brpm) compared to thoracic effort band with an accuracy of 100% and mean absolute error (MAE) of 0.39 Brpm for the setting controlled for movement, and an accuracy of 99.5% with a MAE of 0.48 Brpm for the whole night measurement, respectively. Excellent agreement was also achieved for the respiratory rate statistics over the whole night with absolute errors of 0.43, 0.39 and 0.67 Brpm for the 10th, 50th and 90th percentiles, respectively. Based on these results we conclude that the Sleepiz One+ can estimate instantaneous respiratory rate and its summary statistics at high accuracy in a clinical setting. Further studies are required to evaluate the performance in the home environment, however, it is expected that the performance is at similar level, as the measurement conditions for the Sleepiz One+ device are better at home than in a clinical setting.

[Hair or air: clinical snapshot of an alopecia areata under NIV interface]. / Haare oder Luft ­ klinischer Schnappschuss einer Alopezie unter NIV-Maske.

An alopecia areata developed under NIV interface.

Effects of sacubitril-valsartan on central and obstructive apneas in heart failure patients with reduced ejection fraction.

OBJECTIVE: This study aimed to evaluate the effect of sacubitril-valsartan (SV) on central apneas (CA) and obstructive apneas (OA) in patients with heart failure with reduced ejection fraction (HFrEF). METHODS: In patients with HFrEF, SV initiation was titrated to the highest tolerable dosage. Patients were evaluated with portable apnea monitoring, echocardiography, and cardiopulmonary exercise testing at baseline and 3 months later. RESULTS: Of a total of 18 patients, 9 (50%) had OA, 7 (39%) had CA, and 2 (11%) had normal breathing. SV therapy was related to a reduction in NT-pro BNP and an improvement in LV function after 3 months. Portable apnea monitoring revealed a significant decrease of the respiratory event index (REI) after treatment with SV (20 ± 23 events/h to 7 ± 7 events/h, p = 0.003). When subgrouping according to type of apneas, REI, and time spent below 90% saturation (T90) decreased in patients with CA and OA (all p < 0.05). CONCLUSION: In this prospective study, SV treatment for 3 months in patients with CA and OA is associated with a significant decrease in REI.

Phrenic nerve stimulation for the treatment of central sleep apnea in patients with heart failure.

OBJECTIVE: Central sleep apnea (CSA) is associated with increased morbidity and mortality in patients with heart failure (HF). We aimed to explore the effectiveness of phrenic nerve stimulation (PNS) on CSA in patients with HF. METHODS: This was a prospective and non-randomized study. The stimulation lead was inserted into the right brachiocephalic vein and attached to a proprietary neurostimulator. Monitoring was conducted during the implantation process, and all individuals underwent two-night polysomnography. RESULTS: A total of nine subjects with HF and CSA were enrolled in our center. There was a significant decrease in the apnea-hypopnea index (41 ± 18 vs 29 ± 25, p = 0.02) and an increase in mean arterial oxygen saturation (SaO2) (93% ± 1% vs 95% ± 2%, p = 0.03) after PNS treatment. We did not observe any significant differences of oxygen desaturation index (ODI) and SaO2 < 90% (T90) following PNS. Unilateral phrenic nerve stimulation might also categorically improve the severity of sleep apnea. CONCLUSION: In our non-randomized study, PNS may serve as a therapeutic approach for CSA in patients with HF.

Adherence Monitoring Using Telemonitoring Techniques.

Telemonitoring is a frequently used tool in the long-term management of many chronic diseases, such as chronic obstructive pulmonary disease or chronic heart failure. The use of new sensors and telemedical tools will shape medical practice in the future, particularly in sleep medicine. During the last decades, the number of people with sleep disordered breathing has been increasing.Telemedicine (TM) approaches could be used in various ways in sleep medicine: telediagnostics, teleconsultation, teletherapy, and telemonitoring of patients being treated with positive pressure devices.This chapter aims to summarize the recent scientific progresses of these techniques as well as their potential clinical applications and tries to give consideration to the remaining problems with TM applications.

Management of Obstructive Sleep Apnea in Patients With Heart Failure.

Sleep apnea is traditionally classified as obstructive sleep apnea (OSA), which occurs when the upper airway collapses due to the relaxation of oropharyngeal musculature, and central sleep apnea occurs when the brainstem cannot stimulate breathing. Most sleep apnea in patients with heart failure (HF) results from coexisting OSA and central sleep apnea (CSA), or complex sleep apnea syndrome. OSA and CSA are common in HF and can be involved in its progression by exposure to the heart to intermittent hypoxia, increased preload and afterload, activating sympathetic, and decreased vascular endothelial function. A majority of treatments have been investigated in patients with CSA and HF; however, less or short-term randomized trials demonstrated whether treating OSA in patients with HF could improve morbidity and mortality. OSA could directly influence the patient's recovery. This review will focus on past and present studies on the various therapies for OSA in patients with HF and summarize CSA treatment options for reasons of reference and completeness. More specifically, the treatment covered include surgical and non-surgical treatments and reported the positive and negative consequences for these treatment options, highlighting possible implications for clinical practice and future research directions.

Investigation of respiratory rate in patients with cystic fibrosis using a minimal-impact biomotion system.

BACKGROUND: In this study we tested the hypothesis that in patients with cystic fibrosis (pwCF) respiratory rate (RR) is associated with antibiotic treatment, exacerbation status, forced expiratory volume in one second (FEV1) and C-reactive protein (CRP). METHODS: Between June 2018 and May 2019, we consecutively enrolled pwCF who were referred to our hospital. We determined RR and heart rate (HR) by using the minimal-impact system VitaLog during the hospital stay. Furthermore, we performed spirometry and evaluated CRP. RESULTS: We included 47 patients: 20 with pulmonary exacerbation and 27 without. RR decreased in patients with exacerbation (27.5/min (6.0/min) vs. 24.4/min (6.0/min), p = 0.004) and in patients with non-exacerbation (22.5/min (5.0/min) vs. 20.9/min (3.5/min), p = 0.024). Patients with exacerbation showed higher RR than patients with non-exacerbation both at the beginning (p = 0.004) and at the end of their hospital stay (p = 0.023). During the hospital stay, HR did not change in the total cohort (66.8/min (11.0/min) vs. 66.6/min (12.0/min), p = 0.440). Furthermore, we did not find significant differences between patients with exacerbation and patients with non-exacerbation (67.0/min (12.5/min) vs. 66.5/min (10.8/min), p = 0.658). We observed a correlation of ρ = -0.36 between RR and FEV1. Moreover, we found a correlation of ρ = 0.52 between RR and CRP. CONCLUSION: In pwCF requiring intravenous therapy, respiratory rate is higher at their hospital admittance and decreased by the time of discharge; it is also associated with C-reactive protein. Monitoring RR could provide important information about the overall clinical conditions of pwCF.

[Experiences with digital care of patients with chronic and acute lung diseases during the SARS-CoV-2 pandemic]. / Erfahrungen mit der digitalen Versorgung von Patienten mit chronischen und akuten Lungenerkrankungen während der SARS-CoV-2-Pandemie.

BACKGROUND: Management of patients with respiratory disorders, such as asthma or chronic obstructive pulmonary disease (COPD), became challenging during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic due to infection prevention measures. To maintain care, a remote monitoring program was initiated, comprising a smartphone app and a Bluetooth spirometry device. OBJECTIVE: To assess patient- and physician-related experience with remote monitoring. MATERIAL AND METHODS: Structured questionnaires were developed to rate experiences from the patient or physician perspective on six-level Likert scales. Interactions between patients and physicians via the digital platform and overall utilization was analyzed. RESULTS: A total of 745 patients with asthma, COPD, post-coronavirus disease 2019 (COVID-19) and other respiratory diseases were enrolled from 31 centers in Germany. Mean follow-up was 49.4 ± 12.6 weeks. Each participant submitted on average 289 measurements. Patient-reported experience with the remote monitoring program was positive, with the highest satisfaction reported for "Experience with home measurement" (1.4 ± 0.5; 99% positive), followed by "Communication/interaction" (1.8 ± 0.9; 83% positive) and "Overall satisfaction with program" (1.8 ± 0.8; 87% positive). In all, 70% reported subjective quality of life improvements related to participation in the program. Physician satisfaction with the program was also high with a mean rating of 2.2 ± 1.2. DISCUSSION: App-based remote monitoring was successfully implemented in routine care during the SARS-CoV­2 pandemic and demonstrated potential for improvements in care. Patient-relevant experience was positive in all dimensions and remote monitoring was well accepted. Physicians who participated in the program also expressed positive experiences, as demonstrated by a high level of interaction with the platform and positive evaluations of effects from the program.

Non Invasive Ventilation's Effectiveness (NIV) in Patients with Interstitial Lung Disease and Hypercapnic Respiratory Failure.

Background: The therapeutic options for patients with interstitial lung disease (ILD) are limited. On the other hand, the role of noninvasive ventilation (NIV) in ILD management is not clear. This study investigated the effect of nighttime NIV in hypercapnic ILD patients. Materials and Methods: In this unblinded randomized clinical trial, we included a total of 20 ILD patients admitted in a specialized center with hypoxia, PaCO2>45, and HCO3>27. Participants were randomly allocated into two groups; intervention (nighttime NIV plus standard treatment) and control (standard treatment). The severity of dyspnea and the quality of life (QoL) was evaluated at beginning of the trial and after 30 days through Modified medical research council (mMRC) dyspnea scale and the SF-36 health survey questionnaire. Paired or Wilcoxon Signed rank tests and independent samples t-test or Mann-Whiney U test were used for between and within groups analyses, respectively. Results: The mean age of 20 patients enrolled was 62.57±6.67 and 40% were male. Although, a clinical significant improvement of dyspnea was detected in NIV group (P=0.046) after intervention, it was not statistically different from control group. Significant improvement was observed in physical functioning (P<0.001), social functioning (P=0.004) and pain (P=0.003) detected after 30 days in NIV group and the observed improvement in QoL was significantly higher than control group for physical functioning (P=0.042) and general health (0.049). Conclusion: Our results suggest NIV treatment in patients with ILD and hypercapnic respiratory failure could be advised in order to improve physical functioning.

New Paths in Respiratory Sleep Medicine: Consumer Devices, e-Health, and Digital Health Measurements.

Sleep health and tracking sleep with contemporary wearables have become more popular. Sleep disorders, in particular, sleep-disordered breathing, have a higher prevalence than estimated previously. Many patients with apnea and hypopnea events suffer whereas others do not report complaints or show cardiovascular consequences. Assessment with wearables may support efforts to distinguish which type of apnea is related to aging and which to cardiovascular comorbidities. Innovative methods offer smart solutions for problems that are insufficiently addressed. Telemedical concepts help bring patients to sleep medicine expertise at an early stage. To use these methods clinically, they must be certified as medical devices.

Long-Term SARS-CoV-2 Specific Immunity Is Affected by the Severity of Initial COVID-19 and Patient Age.

The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently the greatest medical challenge. Although crucial to the future management of the pandemic, the factors affecting the persistence of long-term SARS-CoV-2 immunity are not well understood. Therefore, we determined the extent of important correlates of SARS-CoV-2 specific protection in 200 unvaccinated convalescents after COVID-19. To investigate the effective memory response against the virus, SARS-CoV-2 specific T cell and humoral immunity (including virus-neutralizing antibodies) was determined over a period of one to eleven months. SARS-CoV-2 specific immune responses were present in 90% of individual patients. Notably, immunosuppressed patients did not have long-term SARS-CoV-2 specific T cell immunity. In our cohort, the severity of the initial illness influenced SARS-CoV-2 specific T cell immune responses and patients' humoral immune responses to Spike (S) protein over the long-term, whereas the patients' age influenced Membrane (M) protein-specific T cell responses. Thus, our study not only demonstrated the long-term persistence of SARS-CoV-2 specific immunity, it also determined COVID-19 severity and patient age as significant factors affecting long-term immunity.

A randomized clinical trial on the short-term effects of 12-week sacubitril/valsartan vs. enalapril on peak oxygen consumption in patients with heart failure with reduced ejection fraction: results from the ACTIVITY-HF study.

AIMS: ACTIVITY-HF was a randomized, double-blind, active-controlled study, which assessed the short-term effect of sacubitril/valsartan compared with the active comparator enalapril on improving maximal exercise capacity in patients with heart failure with reduced ejection fraction (HFrEF). METHODS AND RESULTS: A total of 201 ambulatory patients with HFrEF (left ventricular ejection fraction ≤ 40%, New York Heart Association class III) across 34 centres in Germany were randomized (1:1) to receive sacubitril/valsartan 97/103 mg bid (n = 103) or enalapril 10 mg bid (n = 98). The primary endpoint of the study was the change from baseline in peak oxygen consumption (VO2 ; adjusted to body weight) after 12 weeks, and the key secondary endpoint was change from baseline in peak VO2 after 6 weeks. The study population was predominantly male (81.1%) with a mean age of 66.9 years and a body mass index of 29.4 kg/m2 . Change in peak VO2 from baseline to Week 12 was similar between sacubitril/valsartan and enalapril groups [least squares mean difference: 0.32 mL/min/kg; 95% confidence interval (CI) -0.21, 0.85; P = 0.2327]. Similarly, no significant differences were observed between the two treatment groups in minute ventilation to carbon dioxide production slope, exercise capacity at first ventilatory threshold or Borg scale at either Week 6 or Week 12. Change in heart rate at first ventilatory threshold was lower in the sacubitril/valsartan group compared with the enalapril group at Week 12 (mean -3.75 bpm; 95% CI -7.03, -0.48; P = 0.0248). The safety of sacubitril/valsartan was comparable to enalapril. CONCLUSION: In patients with HFrEF, short-term treatment with sacubitril/valsartan for 12 weeks did not result in significant benefits on peak VO2 when compared with enalapril.