Independent risk factors for an increased incidence of thromboembolism after lung transplantation.

BACKGROUND Thromboembolism (TE) after lung transplantation (LTX) is associated with increased morbidity and mortality. The aim of this study is to analyze the incidence and outcome of venous and arterial thromboembolic complications and to identify independent risk factors. PATIENTS AND METHODS We retrospectively analyzed the medical records of 221 patients who underwent LTX at our institution between 2002 and 2021. Statistical analysis was performed using SPSS and GraphPad software. RESULTS 74 LTX recipients (33%) developed TE. The 30-days incidence and 12-months incidence were 12% and 23%, respectively. Nearly half of the patients (48%) developed pulmonary embolism, 10% ischemic stroke. Arterial hypertension (p = 0.006), a body mass index (BMI) > 30 (p = 0.006) and diabetes mellitus (p = 0.041) were independent predictors for TE. Moreover, a BMI of > 25 at the time of transplantation was associated with an increased risk for TE (43% vs. 32%, p = 0.035). At the time of LTX, 65% of the patients were older than 55 years. An age > 55 years also correlated with the incidence of TE (p = 0.037) and these patients had reduced overall post-transplant survival when the event occurred within the first postoperative year (59% vs. 72%, p = 0.028). CONCLUSIONS The incidence of TE after LTX is high, especially in lung transplant recipients with a BMI > 25 and an age > 55 years as well as cardiovascular risk factors closely associated with the metabolic syndrome. As these patients comprise a growing recipient fraction, intensified research should focus on the risks and benefits of regular screening or a prolonged TE prophylaxis in these patients. Trial registration number DKRS: 00021501

ECMO for COVID-19 patients in Europe and Israel

Since March 15th, 2020, 177 centres from Europe and Israel have joined the study, routinely reporting on the ECMO support they provide to COVID-19 patients. The mean annual number of cases treated with ECMO in the participating centres before the pandemic (2019) was 55. The number of COVID-19 patients has increased rapidly each week reaching 1531 treated patients as of September 14th. The greatest number of cases has been reported from France (n = 385), UK (n = 193), Germany (n = 176), Spain (n = 166), and Italy (n = 136) .The mean age of treated patients was 52.6 years (range 16–80), 79% were male. The ECMO configuration used was VV in 91% of cases, VA in 5% and other in 4%. The mean PaO2 before ECMO implantation was 65 mmHg. The mean duration of ECMO support thus far has been 18 days and the mean ICU length of stay of these patients was 33 days. As of the 14th September, overall 841 patients have been weaned from ECMO support, 601 died during ECMO support, 71 died after withdrawal of ECMO, 79 are still receiving ECMO support and for 10 patients status n.a. . Our preliminary data suggest that patients placed on ECMO with severe refractory respiratory or cardiac failure secondary to COVID-19 have a reasonable (55%) chance of survival. Further extensive data analysis is expected to provide invaluable information on the demographics, severity of illness, indications and different ECMO management strategies in these patients

Pervasive Platelet Secretion Defects in Patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

Critically ill COVID-19 patients suffer from thromboembolic as well as bleeding events. Endothelial dysfunction, spiking of von Willebrand factor (vWF), and excessive cytokine signaling result in coagulopathy associated with substantial activation of plasmatic clotting factors. Thrombocytopenia secondary to extensive platelet activation is a frequent finding, but abnormal platelet dysfunction may also exist in patients with normal platelet counts. In this study, we performed analyses of platelet function and of von Willebrand factor in critically ill COVID-19 patients (n = 13). Platelet aggregometry was performed using ADP, collagen, epinephrin, and ristocetin. VWF and fibrinogen binding of platelets and CD62 and CD63 expression after thrombin stimulation were analyzed via flow cytometry. In addition, VWF antigen (VWF:Ag), collagen binding capacity (VWF:CB), and multimer analysis were performed next to routine coagulation parameters. All patients exhibited reduced platelet aggregation and decreased CD62 and CD63 expression. VWF binding of platelets was reduced in 12/13 patients. VWF:CB/VWF:Ag ratios were pathologically decreased in 2/13 patients and elevated in 2/13 patients. Critically ill COVID-19 patients exhibit platelet secretion defects independent of thrombocytopenia. Platelet exhaustion and VWF dysfunction may result in impaired primary hemostasis and should be considered when treating coagulopathy in these patients

Intramuscular deposit of calcium is a potential reason for hypocalcaemia in COVID-19

Despite some common pathogenic themes, the association of hidradenitis suppurativa (HS) and rheumatoid arthritis (RA) has been poorly investigated. We aimed to evaluate the bidirectional association between HS and RA. A population-based study was conducted to compare HS patients (n = 6779) with age-, sex- and ethnicity-matched control subjects (n = 33,260) with regard to the incidence of new-onset and the prevalence of preexisting RA. Adjusted hazard ratios (HRs) and adjusted odds ratios (ORs) were estimated. The prevalence of preexisting RA was greater among patients with HS relative to controls (0.5% vs 0.3%. respectively; p = 0.019). The odds of being diagnosed with HS were 1.6-fold higher in patients with a history of RA (fully-adjusted OR, 1.66; 95% CI, 1.11-2.49; p = 0.014). The incidence rate of new-onset RA was estimated at 4.3 (95% CI, 2.5-6.8) and 2.4 (95% CI, 1.8-3.2) cases per 10,000 person-years among patients with HS and controls, respectively. The risk of RA was comparable between patients with HS and controls (fully-adjusted HR, 1.45; 95% CI, 0.77-2.72; p = 0.249). Compared to other patients with HS, those with HS and comorbid RA were older, had a higher prevalence of diabetes mellitus, hypertension, and hyperlipidemia, and had a comparable risk of all-cause mortality. In conclusions, a preexisting diagnosis of RA predisposes individuals to develop HS. Clinicians managing patients with HS and RA should be aware of this association. Further research is required to delineate the underlying pathomechanism of this observation

“Do no further harm” – Why shall we sedate unresponsive patients?

Ziel: Adipositas ist hochprävalent und mit einer Reihe von Folgeerkrankungen und einem erhöhten Mortalitätsrisiko assoziiert. Die Entstehung und Aufrechterhaltung der Adipositas wurde dabei mit einer veränderten Reaktion auf Nahrungsmittelreize, der sogenannten Reizreaktivität, in Verbindung gebracht. Die funktionelle Kernspintomographie stellt ein innovatives Verfahren zur Untersuchung der neurobiologischen Grundlage der Reizreaktivität auf Nahrungsmittelreize dar und ermöglicht zudem eine Prüfung der Zusammenhänge der neuralen Reizreaktivtät mit der klinisch beobachteten Symptomatik und erlaubt es zudem Parallelen zu Abhängigkeitserkrankungen zu untersuchen. Methode, Ergebnisse und Schlussfolgerungen: In diesem narrativen Review werden die Befunde zur neuralen Reizreaktivität auf Nahrungsmittelreize sowie deren Zusammenhang mit Essverhalten und dem Erfolg gewichtsreduzierender Maßnahmen zusammenfassend dargestellt und ebenso Befunde zu Determinanten der neuralen Reizreaktivität erörtert. Darüber hinaus werden die Limitationen der bisherigen Studien und der genutzten Bildgebungs-Methodik diskutiert

Subjektives Befinden und Arbeitsfähigkeit nach SARS-CoV-2-Immunisierung mit dem Vektor-Impfstoff ChAdOx1-S (AstraZeneca COVID-19–Vakzin)

Background!#!The SARS coronavirus 19 vaccine ChAdOx1‑S (Vaxzevria, AstraZeneca) has been licensed since January 2021 by the Paul Ehrlich Institute for Germany. In several campaigns, healthcare workers and medical students were offered this vaccine on a voluntary basis.!##!Aim!#!The primary endpoint of the study was to assess the rate and duration of the incapacity to work as a result of initial immunization with ChAdOx1‑S. Secondary endpoints were type and severity of adverse events and self-perceived tolerability.!##!Material and methods!#!Anonymized online questionnaire to be completed once by all vaccinated individuals after receiving the first dose of ChAdOx1‑S. The severity of side effects was queried using an ordinal numerical rating scale with values ranging from 0 to 10. Other key data points were age, sex, and occupational group. Ability to work in the days following the injection was also assessed by self-reporting.!##!Results!#!Data from 1988 respondents were analyzed. The mean age was 37.13 years (standard deviation 13.7 years). Of the respondents 69.8% were female, 48.1% belonged to therapeutic and technical professions with patient contact, 38% were students, 10.6% were nursing personnel and 4% were physicians. Only 14.4% of respondents reported having tolerated the vaccination without side effects. The most common side effect was fatigue, followed by pain at the injection site. This was followed in descending frequency by headache, aching limbs, and chills. After vaccination 18% of respondents felt able to return to work immediately, 51% of all respondents had to report themselves unfit for work for at least 1 day after vaccination. Side effects were more prevalent in male and younger respondents.!##!Conclusion!#!Vaccination with ChAdOx1‑S frequently resulted in side effects. These resulted in 37% of respondents reporting sick. Nevertheless, 89.6% of all respondents would choose coronavirus vaccination with ChAdOx1‑S again

Protocol based evaluation for feasibility of extubation compared to clinical scoring systems after major oral cancer surgery safely reduces the need for tracheostomy: a retrospective cohort study

Abstract Background Despite risks, complications and negative impact to quality of life, tracheostomy is widely used to bypass upper airway obstruction after major oral cancer surgery (MOCS). Decision to tracheostomy is frequently based on clinical scoring systems which mainly have not been validated by different cohorts. Delayed extubation in the Intensive Care Unit (ICU) may be a suitable alternative in selected cases. We hypothesize that delayed routine ICU extubation after MOCS instead of scoring system based tracheostomy is safe, feasible and leads to lower tracheostomy rates. Methods We retrospectively analyzed our clinical protocol which provides routine extubation of patients after MOCS in the ICU. The primary outcome measure was a composite of early reintubation within 24 h or secondary tracheostomy. Secondary outcome measures included airway obstruction related morbidity and mortality. Predictor variables included tumor localisation, surgical procedure and reconstruction method, length of operation and pre-existing morbidity. Furthermore we assessed the ability of four clinical scoring systems to identify patients requiring secondary tracheostomy. Statistical processing includes basic descriptive statistics, Chi-squared test and multivariate logistic regression analysis. Results Two hundred thirty four cases were enclosed to this retrospective study. Fourteen patients (6%) required secondary tracheostomy, Ten patients (4%) required reintubation within 24 h after extubation. No airway obstruction associated mortality, morbidity and cannot intubate cannot ventilate situation was observed. Seventy five percent of the patients were extubated within 17 h after ICU admission. All evaluated scores showed a poor positive predictive value (0.08 to 0.18) with a sensitivity ranged from 0.13 to 0.63 and specificity ranged from 0.5 to 0.93. Conclusions Our data demonstrate that common clinical scoring systems fail to prevent tracheostomy in patients after MOCS. Application of scoring systems may lead to a higher number of unnecessary tracheostomies. Delayed routine extubation in the ICU after MOCS seems an appropriate and safe approach to avoid tracheostomy and the related morbidity

Predictive markers related to local and systemic inflammation in severe COVID-19-associated ARDS: a prospective single-center analysis

Abstract Background As the COVID-19 pandemic strains healthcare systems worldwide, finding predictive markers of severe courses remains urgent. Most research so far was limited to selective questions hindering general assumptions for short- and long-term outcome. Methods In this prospective single-center biomarker study, 47 blood- and 21 bronchoalveolar lavage (BAL) samples were collected from 47 COVID-19 intensive care unit (ICU) patients upon admission. Expression of inflammatory markers toll-like receptor 3 (TLR3), heme oxygenase-1 (HO-1), interleukin (IL)-6, IL-8, leukocyte counts, procalcitonin (PCT) and carboxyhemoglobin (CO-Hb) was compared to clinical course. Clinical assessment comprised acute local organ damage, acute systemic damage, mortality and outcome after 6 months. Results PCT correlated with acute systemic damage and was the best predictor for quality of life (QoL) after 6 months (r = − 0.4647, p = 0.0338). Systemic TLR3 negatively correlated with impaired lung function (ECMO/ECLS: r = − 0.3810, p = 0.0107) and neurological short- (RASS mean: r = 0.4474, p = 0.0023) and long-term outcome (mRS after 6 m: r = − 0.3184, p = 0.0352). Systemic IL-8 correlated with impaired lung function (ECMO/ECLS: r = 0.3784, p = 0.0161) and neurological involvement (RASS mean: r = − 0.5132, p = 0.0007). IL-6 in BAL correlated better to the clinical course than systemic IL-6. Using three multivariate regression models, we describe prediction models for local and systemic damage as well as QoL. CO-Hb mean and max were associated with higher mortality. Conclusions Our predictive models using the combination of Charlson Comorbidity Index, sex, procalcitonin, systemic TLR3 expression and IL-6 and IL-8 in BAL were able to describe a broad range of clinically relevant outcomes in patients with severe COVID-19-associated ARDS. Using these models might proof useful in risk stratification and predicting disease course in the future. Trial registration The trial was registered with the German Clinical Trials Register (Trial-ID DRKS00021522, registered 22/04/2020)

Does volatile sedation with sevoflurane allow spontaneous breathing during prolonged prone positioning in intubated ARDS patients? A retrospective observational feasibility trial

Abstract Background Lung-protective ventilation and prolonged prone positioning (PP) are presented as essential in treating acute respiratory distress syndrome (ARDS). The optimal respirator mode, however, remains controversial. Pressure-supported spontaneous breathing (PS) during ARDS provides several advantages, but is difficult to achieve during PP because of respiratory depression as a side effect of sedative drugs. This study was designed to evaluate the feasibility and safety of PS during PP in ARDS patients sedated with inhaled sevoflurane. Results Overall, we have observed 4339 h of prone positioning in 62 patients who had a median of four prone episodes during treatment. Within 3948 h (91%), patients were successfully brought into a pressure-supported spontaneous breathing mode. The median duration of each prone episode was 17 h (IQR 3). Median duration of pressure-supported spontaneous breathing per episode was 16 h (IQR 5). Just one self-extubation occurred during 276 episodes of PP. Conclusions and implications Pressure-supported spontaneous breathing during prolonged prone positioning in intubated ARDS patients with or without ECMO can be achieved during volatile sedation with sevoflurane. This finding may provide a basis upon which to question the latest dogma in ARDS treatment. Our concept must be further investigated and compared to controlled ventilation with regard to driving pressure, lung-protective parameters, muscle weakness and mortality before it can be routinely applied

Pervasive Platelet Secretion Defects in Patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

Critically ill COVID-19 patients suffer from thromboembolic as well as bleeding events. Endothelial dysfunction, spiking of von Willebrand factor (vWF), and excessive cytokine signaling result in coagulopathy associated with substantial activation of plasmatic clotting factors. Thrombocytopenia secondary to extensive platelet activation is a frequent finding, but abnormal platelet dysfunction may also exist in patients with normal platelet counts. In this study, we performed analyses of platelet function and of von Willebrand factor in critically ill COVID-19 patients (n = 13). Platelet aggregometry was performed using ADP, collagen, epinephrin, and ristocetin. VWF and fibrinogen binding of platelets and CD62 and CD63 expression after thrombin stimulation were analyzed via flow cytometry. In addition, VWF antigen (VWF:Ag), collagen binding capacity (VWF:CB), and multimer analysis were performed next to routine coagulation parameters. All patients exhibited reduced platelet aggregation and decreased CD62 and CD63 expression. VWF binding of platelets was reduced in 12/13 patients. VWF:CB/VWF:Ag ratios were pathologically decreased in 2/13 patients and elevated in 2/13 patients. Critically ill COVID-19 patients exhibit platelet secretion defects independent of thrombocytopenia. Platelet exhaustion and VWF dysfunction may result in impaired primary hemostasis and should be considered when treating coagulopathy in these patients