Results of the Diaphragmatic Plication Database: 10 Years' Experience.

BACKGROUND: Unilateral diaphragmatic paralysis or paresis (UDP) in adults is an often overlooked disease which relevantly impairs the patient's lung function and quality of life. Particularly in idiopathic UDP, there is no evidence for conservative therapy and only little evidence for surgical therapy. METHODS: The method involves retrospective single-center analysis of patients with UDP persistent for at least 1 year who were operated by diaphragmatic resection, plication, and augmentation with a polypropylene mesh. The patients were tested for lung and diaphragmatic function, six-minute walk test (6MWT), and blood gas analysis before, 3 and 12 months after surgery. RESULTS: In total, 85 patients received surgery for UDP. The most frequent reasons for UDP were idiopathic (67%), iatrogenic (mainly cardiac and cervical spine surgery; 24%), and trauma (9%). The mean operation time was 84 ± 24 minutes, the length of hospital stay 8.4 ± 3.9 days, chest tubes were removed after 11.7 ± 4.1 days. Overall morbidity was 42%, mortality 0%. Forced expiratory volume in one second (FEV1) in supine position improved by 12.4% absolute, vital capacity by 11.8% absolute, and sniff nasal inspiratory pressure by 1.4 kPa 12 months after surgery (p <0.001 each). Total lung capacity increased by 6.8% absolute at 12 months (p = 0.001) The 6MWT distance improved by 45.9 m at 3 months and 50.9 m at 12 months (p = 0.001, each). CONCLUSION: Surgical therapy for UDP is highly effective in the long term. The superiority over conservative treatments needs to be evaluated prospectively with standardized physiotherapeutic protocols. FEV1 in supine position and 6MWT are easy to perform tests and represent statistically and patient-relevant outcomes.

[Neuralgic amyotrophy: a common cause of unilateral and bilateral diaphragmatic pareses]. / Die neuralgische Amyotrophie: eine häufige Ursache uni- oder bilateraler Zwerchfellparesen.

There are several causes for unilateral or bilateral diaphragmatic paresis. The most common cause is an (intraoperative) injury to the phrenic nerve.However, in up to 20% of cases, no explanation can be found despite extensive workup. Neuralgic amyotrophy (NA, also known as Parsonage-Turner syndrome) is a common underdiagnosed multifocal autoimmune-inflammatory disease that predominantly affects proximal nerve segments of the upper extremities. Classic symptoms include acute onset of severe pain in the shoulder girdle with delayed onset of paresis of the shoulder and arm muscles. In at least 7% of cases, the phrenic nerve is also affected. Based on the annual incidence of NA of 1:1000, the entity as a cause of diaphragmatic dysfunction is probably not as uncommon as previously thought. However, clinical experience shows that this diagnosis is often not considered, and diaphragmatic paresis gets wrongly classified as idiopathic.This is particularly disastrous because in the early stage of NA, medical therapy with corticosteroids is mostly not considered and the possibility that surgical repair of the diaphragm may be performed prematurely, given that the condition may resolve spontaneously many months after symptom onset.The aim of the present article is to raise awareness of the entity of NA as a cause of diaphragmatic paresis and to establish a standardized approach to diagnosis and treatment.

Home Non-Invasive Positive Pressure Ventilation in Chronic Obstructive Pulmonary Disease: Why, Who, and How?

Advanced chronic obstructive pulmonary disease (COPD) might result in chronic hypercapnic ventilatory failure. Similar to neuromuscular and restrictive chest wall diseases, long-term non-invasive positive pressure ventilation (NPPV) is increasingly used in chronic hypercapnic COPD. This review describes the methods, patient selection, ventilatory strategies, and therapeutic effects of long-term Home-NPPV based on randomized controlled clinical trials published since 1985 in English language retrieved from the databases PubMed and Scopus. Long-term NPPV is feasible and effective in stable, non-exacerbated COPD patients with daytime hypercapnia with arterial pressure of carbon dioxide (PaCO2) levels ≥50 mm Hg (6.6 kPa), if the applied ventilatory pressures and application times improve baseline hypercapnia by at least 20%. Patients who survived an acute hypercapnic exacerbation might benefit from long-term NPPV if hypercapnia persists 2-4 weeks after resolution of the exacerbation. Pressure-controlled ventilation or pressure-support ventilation with adequate minimum backup breathing frequencies, in combination with nasal masks or oronasal masks have been successfully used in all larger clinical trials. Ventilatory strategies with mean inspiratory pressures of up to 28 cm H2O are well-tolerated by patients, but limitations exist in patients with impaired cardiac performance. Home-NPPV with a PaCO2-reductive approach might be considered as an additional treatment option in patients with stable chronic hypercapnic COPD.

Evolution of Web-Based Training Videos Provided by the German Respiratory League for the Correct Inhalation Technique.

BACKGROUND/OBJECTIVE: To assess whether and how the use of scientifically established Web-based training videos for teaching correct inhalation technique in patients with chronic airway diseases has become accepted among the wider population. METHODS: The viewing trends of 141 freely available YouTube videos (full playing time, 01:31-04:37 min:s) provided by the German Respiratory League, covering a broad range of internationally prescribed devices, were analyzed over a 10-year period. Specific emphasis was placed both on German and international videos. RESULTS: The total number of views was 3,350,678. Non-German videos (English, Russian, Turkish, Greek, Arabic, Farsi, and Slovakian) accounted for 23.2% of the views. The number of views steadily increased between 2011 and 2020 with a mean annual increase of 54.0% (range 24.5/119.9%) compared to the respective previous year. By 2020, the incidence of views per 100,000 German inhabitants was 725 for German videos only and 1,030 for all videos. In terms of the annual trend, there were two peak viewing periods, namely in spring and late fall, while the lowest amount of views occurred in summer. CONCLUSION: This study highlights the rising impact of Web-based training videos used for teaching the correct use of inhalation devices, with a steady increase in the number of annual views and a clear seasonal peaking of views in spring and late fall.

The Italian Version of the Severe Respiratory Insufficiency Questionnaire.

BACKGROUND: The Severe Respiratory Insufficiency Questionnaire (SRI) is a multidimensional instrument for health-related quality of life (HRQL) assessment in patients with chronic respiratory failure (CRF). The SRI has originally been developed in German in 2003, but 15 translated versions have been created during the last 18 years with the exclusion of the Italian translation. AIMS OF THE STUDY: The present project was aimed at creating an Italian version of the SRI. METHODS: Professional forward-translation and back-translation procedures have been provided based on the original German version by independent translators, and this was followed by final reconciliation. RESULTS: The Italian SRI contains 49 items covering 7 different subscales which can summarize to one Summary Score. CONCLUSIONS: The Italian SRI is a multidimensional instrument, which can be used for HRQL assessment in Italian-speaking patients with CRF. Validation of the Italian version of the questionnaire is formally required in the future.

[Quality of Care in Home Mechanical Ventilation]. / Versorgungsqualität in der außerklinischen Beatmung.

Home mechanical ventilation has developed rapidly over the last 20 years. Today's most common positive pressure ventilation can be performed either non-invasively via face masks or invasively via endotracheal intubation or tracheal cannula. Non-invasive ventilation (NIV) in particular has gained in importance in recent years as positive evidence for a variety of indications for home mechanical ventilation has become increasingly available. In order to ensure a high quality of treatment for the steadily increasing number of patients, specific guidelines for different patient groups have been developed and regularly updated. The appropriate care structures for these partly multimorbid patient cohorts are strongly discussed, since the capacity limits of the existing care structure are reached by the rapid development in home mechanical ventilation. This development shows, that a critical evaluation of the existing care structures is necessary in order to develop a patient-centered, customized and resource-saving healthcare structure on the basis of the existing structures and taking into account the national characteristics of the German healthcare system.

[The digitalization of pneumology and the role of medical societies]. / Die Digitalisierung der Pneumologie und die Rolle der Fachgesellschaften.

BACKGROUND: Medicine is becoming increasingly digitalized. Digital applications are finding their way into health care. The aim of the study was to record the attitudes of members of the German Respiratory Society (DGP) towards digitalization. METHODS: The study was conducted in cooperation with the DGP, the German Respiratory League and the Health Innovation Hub (HIH) of the German Federal Ministry of Health. Data were gathered with the help of an online questionnaire (July/August 2021), analyzed descriptively and supplemented with a subgroup comparison regarding proactivity of the members. RESULTS: 284 questionnaires were complete and included in the analysis (31% female); 76.4% believed that digitalization would change their daily professional life within five years. 47.2% had prescribed or planned to prescribe Digital Health Applications (DiGA). Lack of technology skills of patients and the time required for health professionals were seen as critical (49.3 and 47.5%). Regarding DiGA, scientific proof of efficacy (48.9%) and ease of use for patients (47.9%) were rated as most important. The subgroup comparison showed that 42.7% actively informed themselves about digital medicine and that this group saw more opportunities for meaningful use of DiGA. CONCLUSION: The members of the DGP have mostly a positive view about the profound changes expected from digital medicine. The more active the role of DGP members and other professional societies, the more digital elements can add value to practice.

The Severe Respiratory Insufficiency Application (SRI App): a pilot randomised controlled trial.

An application (app) for the Severe Respiratory Insufficiency Questionnaire (SRI) has been designed and developed for mobile devices. In a randomised controlled trial comprising 60 patients with chronic respiratory failure, the app was compared with the classic paper SRI. Thereby, it was shown that the SRI app is a practical tool that is well accepted. Missing values can be completely avoided by using the SRI app. Finally, reliability, convergent and discriminant validities were established. Accordingly, for the individual SRI subscales, Cronbach's alpha ranged between 0.56 and 0.81 (app) and between 0.54 and 0.83 (paper), respectively. The multilingual SRI app is accessible free of charge for non-profit research purposes.

Portable NIV for patients with moderate to severe COPD: two randomized crossover trials.

BACKGROUND: Long-term non-invasive ventilation (NIV) is as an established treatment option for chronic hypercapnic COPD patients. Beneficial effects have also been shown during exercise, but this is restricted to rehabilitation programs. New portable NIV (pNIV) devices may now enable NIV application during walking at home. STUDY DESIGN AND METHODS: In two randomized crossover trials, the impact of pNIV on dyspnea and endurance capacity was investigated in patients with moderate to severe COPD. Participants performed a standardized 6-min walking test, with and without pNIV, using a pre-set inspiratory/expiratory positive airway pressure of 18/8 cmH2O. The first study was performed in NIV-naïve patients (Study I), while the second study was performed in those already established on long-term NIV (Study II). RESULTS: 38 patients (66.9 ± 7.4 years, mean FEV1: 30.3 ± 8%pred) and 23 patients (67.6 ± 8.7 years, mean FEV1: 29.8 ± 10.4%pred) participated in Study I and II, respectively. In Study I, the mean difference in the Borg Dyspnea Scale (BDS, primary outcome) score following walking was 3.2 (IQR 2-4) without pNIV, compared to 2.6 (IQR 1-4) with pNIV (ΔBDS 0.65, P = 0.04), while walking distance increased from 311.8 m (95%CI 276.9-346.6 m) to 326.3 m (95%CI 291.5-361.2 m) (P = 0.044) when pNIV was used. Accordingly, in Study II, the mean difference in BDS was 4.4 (IQR 3-6) without pNIV, compared to 4.5 (IQR 3-6) with pNIV (ΔBDS 0.09, P = 0.54), while walking distance decreased from 291.5 m (95%CI 246.1-336.9 m) to 258.4 m (95%CI 213-303.8 m) (P ≤ 0.001). INTERPRETATION: The use of a pNIV device during walking can improve dyspnea and walking distance in patients with moderate to severe COPD. Patients who do not already receive long-term NIV therapy are more likely to benefit compared to those undergoing long-term NIV. Careful patient selection is mandatory. Clinical Trial Register: DRKS00013203; DRKS00012913 registered October 20th 2017 and October 16th 2017; https://www.drks.de/drks_web/.

Long-Term Auscultation in Chronic Obstructive Pulmonary Disease: Renaissance of an Ideograph of Medical Care.

BACKGROUND: Electronic auscultation technology has advanced dramatically in the last few years. Therefore, long-term pulmonary auscultation could provide additional information about respiratory system by monitoring acute chronic obstructive pulmonary disease (AECOPD) exacerbations or by identifying wheezing phenotypes amongst stable COPD patients. OBJECTIVES: Comparison of respiratory sounds in stable versus AECOPD patients recorded with a portable respiratory sound monitor over a period of 24 h. METHODS: This prospective trial evaluated cough and wheezing events using an auscultation monitor specially developed for this purpose with 4 integrated highly sensitive microphones, in stable and severely AECOPD patients for a period of 24 h in an inpatient setting. RESULTS: Twenty stable COPD patients (12 male, 60%) and 20 severely exacerbated COPD patients (14 male, 70%) were analyzed. In AECOPD patients, long-term auscultation revealed a significantly higher number of wheezing epochs than stable COPD patients (591 [IQR: 145-1,645] vs. 152 [IQR: 90-400]; p = 0.021). Conversely, cough epochs did not differ between AECOPD and stable COPD patients (213 [IQR: 140-327] vs. 162 [IQR: 123-243]; p = 0.256). The Borg-dyspnea scale, CAT score, and total CCQ score each showed no correlation with wheezing frequency, while CAT and CCQ scores did correlate with coughing frequency. CONCLUSION: Wheezing, but not coughing, occurs more frequently in AECOPD patients than in stable COPD patients, indicating that severe wheezing is an important clinical sign of exacerbation, while coughing is not. Therefore, the patterns of wheezing and coughing, as assessed by long-term auscultation, differ in stable versus exacerbated COPD patients.

Living conditions and autonomy levels in COPD patients receiving non-invasive ventilation: impact on health related quality of life.

BACKGROUND: Research on health-related quality of life (HRQL) has become increasingly important in recent decades. However, the impact of both living conditions and the level of autonomy impairments on HRQL in COPD patients receiving non-invasive ventilation (NIV) is still unclear. METHODS: The Severe Respiratory Insufficiency Questionnaire (SRI) was used to measure HRQL in a prospective cohort of COPD patients in whom home NIV was already established. Data on sociodemographics, clinical characteristics and standardized levels of autonomy impairment were evaluated. A multiple linear regression analysis was performed to identify the factors associated with a reduced HRQL. RESULTS: A total of 137 patients (67.0 ± 7.8 years, 45% female) were assessed. The mean SRI Summary Score was 54.1 ± 16.9 (95%CI: 51.1-57.1; N = 127). Regular ambulatory care was provided in 76% of patients, but only 37% underwent pulmonary rehabilitation. Overall, 69% of patients lived with family members, while 31% lived alone (family situation). Autonomy impairment levels were most serious in 3%, serious in 14%, and significant in 29% of patients, while 54% had no impairments at all. Of note, higher levels of autonomy impairment were markedly associated with lower SRI scores (regression coefficient - 6.5 ± 1.1 per level; P < 0.001). In contrast, family situation (0.2 ± 3.0; P = 0.959), ambulatory care by a respiratory specialist (1.7 ± 3.6; P = 0.638), and pulmonary rehabilitation (- 0.8 ± 3.1; P = 0.802) did not appear to influence HRQL. Possible subgroup effects were evident for the factors "impaired autonomy" and "living in a nursing home" (P = 0.016). CONCLUSION: A higher level of autonomy impairment has been identified as the major determinant of reduced HRQL in COPD-patients receiving long-term NIV, particularly in those living in a nursing home. Trial Registration German Clinical Trials Register (DRKS00008759).

Placental Endocrine Activity: Adaptation and Disruption of Maternal Glucose Metabolism in Pregnancy and the Influence of Fetal Sex.

The placenta is an endocrine fetal organ, which secretes a plethora of steroid- and proteo-hormones, metabolic proteins, growth factors, and cytokines in order to adapt maternal physiology to pregnancy. Central to the growth of the fetus is the supply with nutrients, foremost with glucose. Therefore, during pregnancy, maternal insulin resistance arises, which elevates maternal blood glucose levels, and consequently ensures an adequate glucose supply for the developing fetus. At the same time, maternal ß-cell mass and function increase to compensate for the higher insulin demand. These adaptations are also regulated by the endocrine function of the placenta. Excessive insulin resistance or the inability to increase insulin production accordingly disrupts physiological modulation of pregnancy mediated glucose metabolism and may cause maternal gestational diabetes (GDM). A growing body of evidence suggests that this adaptation of maternal glucose metabolism differs between pregnancies carrying a girl vs. pregnancies carrying a boy. Moreover, the risk of developing GDM differs depending on the sex of the fetus. Sex differences in placenta derived hormones and bioactive proteins, which adapt and modulate maternal glucose metabolism, are likely to contribute to this sexual dimorphism. This review provides an overview on the adaptation and maladaptation of maternal glucose metabolism by placenta-derived factors, and highlights sex differences in this regulatory network.

[Invasive and Non-Invasive Home Mechanical Ventilation in Germany - A Rapid Development with Large Regional Differences]. / Invasive und nicht-invasive außerklinische Beatmung in Deutschland.

BACKGROUND: The number of patients using home mechanical ventilation (HMV) is steadily increasing in Germany. Detailed data on inpatient initiation and control of HMV are not available. This, however, is absolutely necessary in order to optimize the medical care structures in Germany. Regional diversities must be taken into consideration in order to provide care structures that reflect the local needs. METHOD: The data sets of the German Federal Statistical Office on the OPS (Operation and Procedure Classification System) for HMV from 2008 to 2019 were analysed (N = 572,494). RESULTS: Between 2008 and 2019 there was a doubling of the number of HMV initiations and controls. The number of initiations (N = 17,958) and controls (N = 49,140) was highest in 2019. Furthermore, at the state level, the development of HMV is very heterogeneous. Finally, the increases were particularly due to an increase in non-invasively ventilated patients. CONCLUSION: The rapid increase in HMV is reaching capacity limits of the existing healthcare structure. New healthcare structures should provide an integrated approach between outpatient and inpatient care in order to ensure a high quality of care for patients receiving HMV without compromising the human and economic resources of the system.

[Role of Non-Invasive Strategies in the Treatment of Acute Hypoxemic Respiratory Failure Related to COVID-19]. / Bedeutung nicht-invasiver Verfahren in der Therapie des akuten hypoxämischen Versagens bei COVID-19.

Non-invasive strategies such as HFOT (high-flow oxygen therapy), CPAP (continuous positive airway pressure) and NIV (non-invasive ventilation) are increasingly being used during the COVID-19 pandemics in order to treat acute hypoxemic respiratory failure related to COVID-19, and this is aimed at avoiding intubation. This review article summarizes the current evidence by also emphasizing its heterogeneity. Importantly, current evidence suggests that these non-invasive strategies can be successfully used even in case of severe respiratory failure and are, thus, indeed capable of avoiding intubation, and consequently, tube-related complications. In contrast, it also remains to be emphasized that prolonged spontaneous breathing supported by non-invasive treatment strategies is also prone to complications. In particular, late NIV failure is associated with substantially deteriorated outcome, which is suggested to be meaningful in view of NIV failure rates still being high in Germany. Finally, the current article also refers to a parallel article that addresses the discussion being held in the public media in Germany concerning this topic. Here, its textual questionability, but also its negative consequences for both the research community and the general society are elaborated. In this context, the importance of national and regularly updated guidelines is emphasized.

Obesity hypoventilation syndrome treated with non-invasive ventilation: Is a switch to CPAP therapy feasible?

BACKGROUND AND OBJECTIVE: Obesity hypoventilation syndrome (OHS) can be treated with either continuous positive airway pressure (CPAP) or non-invasive ventilation (NIV) therapy; the device choice has important economic and operational implications. METHODS: This multicentre interventional trial investigated the safety and short-term efficacy of switching stable OHS patients who were on successful NIV therapy for ≥3 months to CPAP therapy. Patients underwent an autotitrating CPAP night under polysomnography (PSG); if the ensuing parameters were acceptable, they were sent home on a fixed CPAP for a 4-6-week period. It was hypothesized that blood gas analysis, PSG parameters and lung function tests would remain unchanged. RESULTS: A total of 42 OHS patients were recruited, of whom 37 patients were switched to CPAP therapy. All patients had a history of severe obstructive sleep apnoea syndrome; chronic obstructive pulmonary disease (COPD) (Global Initiative for Obstructive Lung Disease (GOLD) I/II) was present in 52%. Regarding the primary outcome, 30 of 42 patients (71%, 95% CI: 55-84%) maintained daytime partial pressure of carbon dioxide (PaCO2 ) levels ≤45 mm Hg after the home CPAP period. There was no further impairment in quality of life, sleep parameters or lung function. Interestingly, 24 patients (65%) preferred CPAP as their long-term therapy, despite the high pressure levels used (mean: 13.8 ± 1.8 mbar). After the CPAP period, 7 of 37 patients were categorized as CPAP failure, albeit only due to mild hypercapnia (mean: 47.9 ± 2.7 mm Hg). CONCLUSION: It is feasible to switch most stable OHS patients from NIV to CPAP therapy, a step that could significantly reduce health-related costs. The auto-adjusted CPAP device, used in combination with the analysis of the PSG and capnometry, is a valid titration method in OHS patients.

Vpx overcomes a SAMHD1-independent block to HIV reverse transcription that is specific to resting CD4 T cells.

Early after entry into monocytes, macrophages, dendritic cells, and resting CD4 T cells, HIV encounters a block, limiting reverse transcription (RT) of the incoming viral RNA genome. In this context, dNTP triphosphohydrolase SAM domain and HD domain-containing protein 1 (SAMHD1) has been identified as a restriction factor, lowering the concentration of dNTP substrates to limit RT. The accessory lentiviral protein X (Vpx) proteins from the major simian immunodeficiency virus of rhesus macaque, sooty mangabey, and HIV-2 (SIVsmm/SIVmac/HIV-2) lineage packaged into virions target SAMHD1 for proteasomal degradation, increase intracellular dNTP pools, and facilitate HIV cDNA synthesis. We find that virion-packaged Vpx proteins from a second SIV lineage, SIV of red-capped mangabeys or mandrills (SIVrcm/mnd-2), increased HIV infection in resting CD4 T cells, but not in macrophages, and, unexpectedly, acted in the absence of SAMHD1 degradation, dNTP pool elevation, or changes in SAMHD1 phosphorylation. Vpx rcm/mnd-2 virion incorporation resulted in a dramatic increase of HIV-1 RT intermediates and viral cDNA in infected resting CD4 T cells. These analyses also revealed a barrier limiting HIV-1 infection of resting CD4 T cells at the level of nuclear import. Single amino acid changes in the SAMHD1-degrading Vpx mac239 allowed it to enhance early postentry steps in a Vpx rcm/mnd-2-like fashion. Moreover, Vpx enhanced HIV-1 infection of SAMHD1-deficient resting CD4 T cells of a patient with Aicardi-Goutières syndrome. These results indicate that Vpx, in addition to SAMHD1, overcomes a previously unappreciated restriction for lentiviruses at the level of RT that acts independently of dNTP concentrations and is specific to resting CD4 T cells.

Control of respiratory drive by extracorporeal CO2 removal in acute exacerbation of COPD breathing on non-invasive NAVA.

BACKGROUND: Veno-venous extracorporeal CO2 removal (vv-ECCO2R) and non-invasive neurally adjusted ventilator assist (NIV-NAVA) are two promising techniques which may prevent complications related to prolonged invasive mechanical ventilation in patients with acute exacerbation of COPD. METHODS: A physiological study of the electrical activity of the diaphragm (Edi) response was conducted with varying degrees of extracorporeal CO2 removal to control the respiratory drive in patients with severe acute exacerbation of COPD breathing on NIV-NAVA. RESULTS: Twenty COPD patients (SAPS II 37 ± 5.6, age 57 ± 9 years) treated with vv-ECCO2R and supported by NIV-NAVA were studied during stepwise weaning of vv-ECCO2R. Based on dyspnea, tolerance, and blood gases, weaning from vv-ECCO2R was successful in 12 and failed in eight patients. Respiratory drive (measured via the Edi) increased to 19 ± 10 µV vs. 56 ± 20 µV in the successful and unsuccessful weaning groups, respectively, resulting in all patients keeping their CO2 and pH values stable. Edi was the best predictor for vv-ECCO2R weaning failure (ROC analysis AUC 0.95), whereas respiratory rate, rapid shallow breathing index, and tidal volume had lower predictive values. Eventually, 19 patients were discharged home, while one patient died. Mortality at 90 days and 180 days was 15 and 25%, respectively. CONCLUSIONS: This study demonstrates for the first time the usefulness of the Edi signal to monitor and guide patients with severe acute exacerbation of COPD on vv-ECCO2R and NIV-NAVA. The Edi during vv-ECCO2R weaning was found to be the best predictor of tolerance to removing vv-ECCO2R.

Cryopreservation of Canine Primary Dorsal Root Ganglion Neurons and Its Impact upon Susceptibility to Paramyxovirus Infection.

Canine dorsal root ganglion (DRG) neurons, isolated post mortem from adult dogs, could provide a promising tool to study neuropathogenesis of neurotropic virus infections with a non-rodent host spectrum. However, access to canine DRG is limited due to lack of donor tissue and the cryopreservation of DRG neurons would greatly facilitate experiments. The present study aimed (i) to establish canine DRG neurons as an in vitro model for canine distemper virus (CDV) infection; and (ii) to determine whether DRG neurons are cryopreservable and remain infectable with CDV. Neurons were characterized morphologically and phenotypically by light microscopy, immunofluorescence, and functionally, by studying their neurite outgrowth and infectability with CDV. Cryopreserved canine DRG neurons remained in culture for at least 12 days. Furthermore, both non-cryopreserved and cryopreserved DRG neurons were susceptible to infection with two different strains of CDV, albeit only one of the two strains (CDV R252) provided sufficient absolute numbers of infected neurons. However, cryopreserved DRG neurons showed reduced cell yield, neurite outgrowth, neurite branching, and soma size and reduced susceptibility to CDV infection. In conclusion, canine primary DRG neurons represent a suitable tool for investigations upon the pathogenesis of neuronal CDV infection. Moreover, despite certain limitations, cryopreserved canine DRG neurons generally provide a useful and practicable alternative to address questions regarding virus tropism and neuropathogenesis.

Is Outpatient Control of Long-Term Non-Invasive Ventilation Feasible in Chronic Obstructive Pulmonary Disease Patients?

BACKGROUND: Long-term non-invasive ventilation (NIV) is an established and increasingly used treatment option for patients with chronic hypercapnic chronic obstructive pulmonary disease (COPD). Following inpatient NIV establishment, inpatient control visits regularly occur thereafter. However, it remains unclear whether such control visits can also be performed in an outpatient setting, which, in turn, would reduce costs, patient burden and the complications related to hospitalization. OBJECTIVES: To investigate an outpatient setting with predefined criteria for hospitalization for patients with chronic hypercapnic COPD. METHODS: An outpatient clinic located within the hospital in the vicinity of the respiratory care unit provided predefined criteria for hospitalization of COPD patients receiving long-term NIV therapy. The results of this setting were retrospectively analysed. RESULTS: A total of 130 outpatient visits (80 patients) were analysed. In 93 cases (71.5%), hospital admission was not necessary, while hospitalization was performed in 37 cases (28.5%). Out of these, 7 cases with acute conditions required prompt hospitalization. Patients without hospitalization had better PaCO2 values (45.40 ± 5.27 vs. 50.05 ± 8.04, p = 0.002) and Severe Respiratory Insufficiency Questionnaire Summary scores (55.54 ± 19.74 vs. 41.82 ± 19.59, p = 0.012). CONCLUSION: Outpatient control of long-term NIV in a hospital setting is feasible and has the capacity to identify stable COPD patients in whom NIV therapy is sufficient according to predefined criteria. These patients may not require hospitalization and may account for more than two thirds of cases.

Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors.

UNLABELLED: Type I interferons (IFNs), including IFN-α, upregulate an array of IFN-stimulated genes (ISGs) and potently suppress Human immunodeficiency virus type 1 (HIV-1) infectivity in CD4(+) T cells, monocyte-derived macrophages, and dendritic cells. Recently, we and others identified ISG myxovirus resistance 2 (MX2) as an inhibitor of HIV-1 nuclear entry. However, additional antiviral blocks exist upstream of nuclear import, but the ISGs that suppress infection, e.g., prior to (or during) reverse transcription, remain to be defined. We show here that the HIV-1 CA mutations N74D and A105T, both of which allow escape from inhibition by MX2 and the truncated version of cleavage and polyadenylation specific factor 6 (CPSF6), as well as the cyclophilin A (CypA)-binding loop mutation P90A, all increase sensitivity to IFN-α-mediated inhibition. Using clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 technology, we demonstrate that the IFN-α hypersensitivity of these mutants in THP-1 cells is independent of MX2 or CPSF6. As expected, CypA depletion had no additional effect on the behavior of the P90A mutant but modestly increased the IFN-α sensitivity of wild-type virus. Interestingly, the infectivity of wild-type or P90A virus could be rescued from the MX2-independent IFN-α-induced blocks in THP-1 cells by treatment with cyclosporine (Cs) or its nonimmunosuppressive analogue SDZ-NIM811, indicating that Cs-sensitive host cell cyclophilins other than CypA contribute to the activity of IFN-α-induced blocks. We propose that cellular interactions with incoming HIV-1 capsids help shield the virus from recognition by antiviral effector mechanisms. Thus, the CA protein is a fulcrum for the dynamic interplay between cell-encoded functions that inhibit or promote HIV-1 infection. IMPORTANCE: HIV-1 is the causative agent of AIDS. During acute HIV-1 infection, numerous proinflammatory cytokines are produced, including type I interferons (IFNs). IFNs can limit HIV-1 replication by inducing the expression of a set of antiviral genes that inhibit HIV-1 at multiple steps in its life cycle, including the postentry steps of reverse transcription and nuclear import. This is observed in cultured cell systems, as well as in clinical trials in HIV-1-infected patients. The identities of the cellular antiviral factors, their viral targets, and the underpinning mechanisms are largely unknown. We show here that the HIV-1 Capsid protein plays a central role in protecting the virus from IFN-induced inhibitors that block early postentry steps of infection. We further show that host cell cyclophilins play an important role in regulating these processes, thus highlighting the complex interplay between antiviral effector mechanisms and viral survival.