The influence of fixation and cryopreservation of cerebrospinal fluid on antigen expression and cell percentages by flow cytometric analysis.

The pauci-cellular nature of cerebrospinal (CSF), particularly ventricular CSF, and the rapid cell death following sampling, incumbers the use of flow cytometric analysis of these samples in the investigation of central nervous system (CNS) pathologies. Developing a method that allows long-term storage and batched analysis of CSF samples without compromising cell integrity is highly desirable in clinical research, given that CSF is often sampled after hours creating logistical difficulties for fresh processing. We examined percentages and relative proportion of peripheral and brain-derived immune cells in cryopreserved and transfix-treated CSF, compared to freshly processed CSF. Cell proportions were more comparable between Fresh and Cryopreserved CSF (mean of differences = 3.19), than between fresh and transfix-treated CSF (mean of differences = 14.82). No significant differences in cell percentages were observed in fresh versus cryopreserved CSF; however significantly lower cell percentages were observed in transfix-treated CSF compared to Fresh CSF [(CD11b++ (p = 0.01), CD4+ (p = 0.001), CD8+ (p = 0.007), NK cells (p = 0.04), as well as CD69+ activation marker (p = 0.001)]. Furthermore, loss of marker expression of various lymphocyte sub-populations were observed in transfix-treated CSF. Cryopreservation is a feasible option for long-term storage of ventricular CSF and allows accurate immunophenotyping of peripheral and brain-derived cell populations by flow cytometry.

Estimates of protection levels against SARS-CoV-2 infection and severe COVID-19 in Germany before the 2022/2023 winter season: the IMMUNEBRIDGE project.

PURPOSE: Despite the need to generate valid and reliable estimates of protection levels against SARS-CoV-2 infection and severe course of COVID-19 for the German population in summer 2022, there was a lack of systematically collected population-based data allowing for the assessment of the protection level in real time. METHODS: In the IMMUNEBRIDGE project, we harmonised data and biosamples for nine population-/hospital-based studies (total number of participants n = 33,637) to provide estimates for protection levels against SARS-CoV-2 infection and severe COVID-19 between June and November 2022. Based on evidence synthesis, we formed a combined endpoint of protection levels based on the number of self-reported infections/vaccinations in combination with nucleocapsid/spike antibody responses ("confirmed exposures"). Four confirmed exposures represented the highest protection level, and no exposure represented the lowest. RESULTS: Most participants were seropositive against the spike antigen; 37% of the participants ≥ 79 years had less than four confirmed exposures (highest level of protection) and 5% less than three. In the subgroup of participants with comorbidities, 46-56% had less than four confirmed exposures. We found major heterogeneity across federal states, with 4-28% of participants having less than three confirmed exposures. CONCLUSION: Using serological analyses, literature synthesis and infection dynamics during the survey period, we observed moderate to high levels of protection against severe COVID-19, whereas the protection against SARS-CoV-2 infection was low across all age groups. We found relevant protection gaps in the oldest age group and amongst individuals with comorbidities, indicating a need for additional protective measures in these groups.

[Chylous ascites in NSCLC: It is not always malignant]. / Chylöser Aszites bei NSCLC: Nicht alles ist maligne, was maligne aussieht.

The etiology of chylous ascites is multifactorial. Malignant diseases, cirrhosis, trauma, lymphomatic abnormalities and mycobacteriosis are the most common causes. In NSCLC, chylous ascites is observed with peritoneal metastasis or abdominal lymph node metastases.RET alterations occur in 1-2% of NSCLC patients and since recently they can be treated in a targeted fashion.Our case report shows that new targeted therapies revolutionize prognosis, but confront us with the challenge of new and partly unknown side effects.

Immunity Against SARS-CoV-2 in the German Population.

BACKGROUND: Early during the SARS-CoV-2 pandemic, national population-based seroprevalence surveys were conducted in some countries; however, this was not done in Germany. In particular, no seroprevalence surveys were planned for the summer of 2022. In the context of the IMMUNEBRIDGE project, the GUIDE study was carried out to estimate seroprevalence on the national and regional levels. METHODS: To obtain an overview of the population-wide immunity against SARS-CoV-2 among adults in Germany that would be as statistically robust as possible, serological tests were carried out using self-sampling dried blood spot cards in conjunction with surveys, one by telephone and one online. Blood samples were analyzed for the presence of antibodies to the S and N antigens of SARS-CoV-2. RESULTS: Among the 15 932 participants, antibodies to the S antigen were detected in 95.7%, and to the N antigen in 44.4%. In the higher-risk age groups of persons aged 65 and above and persons aged 80 and above, anti-S antibodies were found in 97,4% and 98.8%, respectively. Distinct regional differences in the distribution of anti-S and anti-N antibodies emerged. Immunity gaps were found both regionally and in particular subgroups of the population. High anti-N antibody levels were especially common in eastern German states, and high anti-S antibody levels in western German states. CONCLUSION: These findings indicate that a large percentage of the adult German population has formed antibodies against the SARS-CoV-2 virus. This will markedly lower the probability of an overburdening of the health care system by hospitalization and high occupancy of intensive care units due to future SARS-CoV-2 waves, depending on the viral characteristics of then prevailing variants.

[Acute dyspnea]. / Akute Dyspnoe.

ACUTE DYSPNEA: The leading symptom "acute dyspnea" and the causal underlying diseases have a high risk potential for an unfavorable course of treatment with a high letality. This overview of possible causes, diagnostic procedures and guideline-based therapy is intended to help implement a targeted and structured emergency medical care in the emergency department. The leading symptom "acute dyspnea" is present in 10% of prehospital and 4-7% of patients in the emergency department. The most common conditions in the emergency department with the leading symptom "acute dyspnea" are heart failure in 25%, COPD in 15%, pneumonia in 13%, respiratory disorders in 8%, and pulmonary embolism in 4%. In 18% of cases, the leading symptom "acute dyspnea" is sepsis. The in-hospital letality is high and amounts to 9%. In critically ill patients in the non-traumatologic resuscitation room, respiratory disorders (B-problems) are present in 26-29%. In addition to cardiovascular disease, noncardiovascular disease may underlie "acute dyspnea" and requires differential diagnostic consideration. A structured approach can contribute to a high degree of certainty in the clarification of the leading symptom "acute dyspnea".

[Do we need Respiratory Care Units or Respiratory Emergency Centers?] / Brauchen wir Respiratory Care Units oder Atemnotfallzentren?

Although lung and heart diseases often occur together, the focus in acute medical emergency care frequently lies on the treatment of the cardiological symptoms only. This leads to a repeated patient visit and an impaired quality of life. How can this treatment gap be closed?

Effect of antimicrobial therapy on progression-free survival of immunotherapy and chemo-/immunotherapy in patients with non-small cell lung cancer.

BACKGROUND: The choice between immunotherapy with a checkpoint inhibitor (CPI) and chemo-/immunotherapy (CIT) in patients with NSCLC stage IV is often discussed. There are some data that the effect of CPI therapy is impaired by antimicrobial therapy (AMT). Little is known about the influence of AMT on CIT. PATIENTS AND METHODS: We retrospectively analysed 114 patients (age 68 ± 8.5 years) with NSCLC stage IV. Patients were treated according to the guidelines with either CPI alone (pembrolizumab, nivolumab, atezolizumab, cemiplimab) or CIT (Carboplatin/Pemetrexed/Pembrolizumab, Carboplatin/Paclitaxel/Pembrolizumab). We registered patients' characteristics including presence and timing of AMT. Group 1 consisted of 42 patients with AMT in the month before CPI or CIT, group 2 were 49 patients with AMT during CPI or CIT, and group 3 were 64 patients without AMT and CPI or CIT. RESULTS: Group 1-3 showed comparable patients characteristics. Using cox-regression analysis, we found that AMT in the month before CPI resulted in a decreased progression-free survival (PFS) compared to patients with CPI and no AMT (14 ± 1.02 vs. 4 ± 1.02 months, p = 0.002, 95% CI 1.88-9). In patients, who were treated with CIT, there was no difference in PFS in those with or without AMT in the month before therapy (10 ± 2.5 vs. 6 ± 1.2 months, p = 0.7). Interestingly, AMT during CIT or CPI therapy showed no effect on PFS. CONCLUSIONS: In a real-life setting, we found that AMT reduces PFS when given in the month before CIT therapy. AMT before or during CIT does not seem to influence PFS. As a consequence, AMT before start of therapy might be a factor that could lead to a preference of CIT instead of CPI in NSCLC stage IV patients.

Older patients with EGFR mutation-positive non-small cell lung cancer treated with afatinib in clinical practice: A subset analysis of the non-interventional GIDEON study.

INTRODUCTION: Lung cancer is most common in older patients; despite this, older patients are historically under-represented in clinical studies. Here we present data from GIDEON, a study undertaken in Germany in patients with epidermal growth factor receptor mutation-positive (EGFRm+) non-small cell lung cancer (NSCLC) receiving first-line afatinib. GIDEON enrolled a high proportion of patients aged ≥70 years, providing an opportunity to study afatinib use in older patients. MATERIALS AND METHODS: In GIDEON (NCT02047903), a prospective non-interventional study, patients with EGFRm+ NSCLC received first-line afatinib in routine clinical practice until disease progression, death or intolerable adverse events. Key objectives were twelve-month progression-free survival (PFS) rate and objective response rate (ORR). Overall survival (OS) and safety were also assessed. This post hoc analysis explores outcomes of patients grouped by age (≥70 and <70 years). RESULTS: In the 152 patients enrolled in GIDEON (69.7% female, 64.5%/22.4%/13.2% with Del19/L858R/other exon 18-21 mutations, 33.6% with brain metastases), the median age was 67 years (range 38-89) and 43.4% were aged ≥70 years. In the ≥70 years age group and the <70 years age group, twelve-month PFS rate was 58.9% and 43.9%, median PFS was 17.2 months and 10.6 months, ORR was 72.0% and 76.5%, twelve-month OS rate was 79.1% and 79.2%, 24-month OS rate was 52.0% and 61.7%, and median OS was 30.4 months and 27.4 months, respectively. In the ≥70 years age group and the <70 years age group, grade ≥3 adverse drug reactions (ADRs) were observed in 34.8% and 40.7% of patients, respectively; the most common were diarrhea (13.6% and 14.0%), acneiform dermatitis (7.6% and 7.0%), stomatitis (1.5% and 4.7%) and maculopapular rash (1.5% and 4.7%). DISCUSSION: Patients with EGFRm+ NSCLC aged ≥70 years showed clinical benefit from first-line afatinib with no unexpected safety signals, supporting the use of afatinib in this setting.

Nintedanib plus docetaxel after progression on first-line immunochemotherapy in patients with lung adenocarcinoma: Cohort C of the non-interventional study, VARGADO.

Background: Immune checkpoint inhibitors (ICIs) with or without chemotherapy represent first-line standard of care for patients with advanced non-small cell lung cancer (NSCLC) without targetable driver mutations. The most appropriate second-line therapy after failing immunochemotherapy remains an open question. Nintedanib, an oral triple angiokinase inhibitor that targets the vascular endothelial growth factor receptor, fibroblast growth factor receptor, and, platelet-derived growth factor receptor, in combination with docetaxel, is approved for treatment of advanced NSCLC (adenocarcinoma histology) following progression on first-line chemotherapy. Methods: VARGADO (NCT02392455) is an ongoing, prospective, non-interventional study investigating the efficacy and safety of nintedanib plus docetaxel following first-line chemotherapy with or without ICIs in patients with locally advanced, metastatic, or locally recurrent NSCLC of adenocarcinoma histology. This analysis focuses on Cohort C, which enrolled patients who had received prior first line chemotherapy with ICIs. Patients received second-line docetaxel (75 mg/m2) by intravenous infusion on Day 1, plus oral nintedanib (200 mg twice daily) on Days 2-21 of each 21-day cycle during routine clinical care. The primary endpoint is overall survival (OS) rate 1 year after the start of treatment with nintedanib plus docetaxel. Secondary endpoints include progression-free survival (PFS), OS, and disease control rate (DCR). Safety was also assessed. Results: Among 137 patients treated, the median age was 63 years (range, 37-84); 57 patients (41.6%) were female, most patients had Eastern Cooperative Oncology Group performance status of 0 (28.5%) or 1 (43.1%); 118 (86.1%) had stage IV NSCLC and 27 (19.7%) had brain metastases. Most (n=120, 87.6%) patients had received pembrolizumab/pemetrexed/platinum-based chemotherapy as first-line treatment. In 80 patients with available response data, the DCR was 72.5% (complete response: 1.3%; partial response: 36.3%; stable disease: 35.0%). Median progression-free survival was 4.8 months (95% confidence interval: 3.7-6.6). OS data were immature. Grade ≥3 treatment-emergent adverse events (TEAEs), serious TEAEs, and TEAEs leading to treatment discontinuation were reported in 62 (45.3%), 50 (36.5%), and 40 patients (29.2%), respectively. Conclusions: This analysis indicates that nintedanib plus docetaxel represents an effective second-line treatment option in patients with advanced adenocarcinoma NSCLC following progression on first-line immunochemotherapy. The safety profile was manageable with no unexpected signals.

[Viral meningitis: a rare cause of hyperventilation]. / Virale Meningoenzephalitis: eine seltene Ursache der Hyperventilation.

The etiology of hyperventilation is multifactorial. When excluding somatic causes, neurogenic hyperventilation must always be considered. Since hyperventilation itself causes neuromuscular symptoms such as paresthesia, vertigo, cephalgia, and nausea, the differential diagnosis of viral meningitis in the presence of hyperventilation is not always obvious and can easily be overlooked. Our case report shows that somatogenic causes of hyperventilation should be carefully excluded.

Clinical and neurophysiological patterns of impairments to emotion attention and empathy in multiple sclerosis.

Patients suffering from multiple sclerosis experience various cognitive and affective impairments, resulting in a negative impact on social behavior and personal independence to differing degrees. According to these often clinically subtle but conflicting cognitive-affective impairments, recordings of these socially relevant issues are still of demand to stratifying clinical and social support in a sophisticated way. Therefore, we studied specific cognitive and affective capacities in eleven patients with a predominant relapsing-remitting type of multiple sclerosis by applying paradigms of event-related potentials and a well-selected neuropsychological test protocol. Thus far, distinct cognitive disturbances of executive and attentional domains and the Wechsler Memory Test's four memory indices were found in multiple sclerosis patients. Concerning affective domains, patients showed discrete impairments of affect discrimination and affected naming as proved by specific testing (Tuebinger Affect Battery). Neurophysiologically, event-related potentials recordings in multiple sclerosis patients, were associated with decreased implicit emotion processing to cues of different emotion arousal at the early processing stage depending on attentional capacities and alterations of implicit emotion modulation at late processing stages. These clinical neurophysiological and neuropsychological data were correlated in part to quantitative magnetic resonance imaging brain lesions. Summarizing our data, our data indicate certain neurocognitive and neuroaffective dysfunctions in patients with multiple sclerosis, thus highlighting the validity of sensitive recording of less apparent neurologic disturbances in multiple sclerosis for optimizing the individual care management in patients.

Effect of antimicrobial therapy on progression-free survival of patients with non-small cell lung cancer receiving checkpoint inhibitor- and chemotherapy.

BACKGROUND: Checkpoint inhibitor therapy (CPI) has significantly changed therapy in non-small cell lung cancer (NSCLC) in recent years. There are some data that the effect of CPI therapy is influenced by the microbiome. Little is known about the influence and timing of antimicrobial therapy (AMT) on the microbiome-mediated effect on CPI therapy. PATIENTS AND METHODS: We retrospectively analysed 70 patients (age 68 ± 9.2 years) with NSCLC stage IV. Patients were treated according to the guidelines with either CPI alone (pembrolizumab, nivolumab, atezolizumab) or chemotherapy (platin doublet or docetaxel/nintedanib or pemetrexed). We registered patient's characteristics including presence and timing of AMT. Group 1 consisted of 27 patients with AMT in the month before CPI- or chemotherapy, group 2 was 30 patients with AMT during CPI- or chemotherapy, and group 3 was 43 patients without AMT. RESULTS: Groups 1-3 showed comparable patient characteristics. Using cox-regression analysis, we found that AMT in the month before CPI resulted in a decreased progression-free survival (PFS) compared to patients with CPI and no AMT (14 ± 1.56 vs. 5 ± 0.99, p = 0.005, 95% CI: 0.13-0.67). In patients, who were treated with chemotherapy alone, there was no difference in PFS in those with or without AMT in the month before therapy (5 ± 0.99 vs. 6 ± 0.81 months, p = 0.3). Interestingly, AMT during chemotherapy or CPI therapy showed no effect on PFS. CONCLUSIONS: In a real-life setting, we found that AMT reduces PFS when given in the month before CPI therapy. AMT before chemotherapy and during CPI and chemotherapy seems not to influence PFS. The best PFS was seen in patients without AMT before CPI therapy. This implies the need for an even more restrictive use of AMT in the context of patients with NSCLC stage IV disease.

Impact of COVID-19-adapted guidelines on resuscitation quality in out-of-hospital-cardiac-arrest: a manikin study.

BACKGROUND: The aim of this study is to evaluate the effects of European Resuscitation Council (ERC) COVID-19-guidelines on resuscitation quality emphasizing advanced airway management in out-of-hospital-cardiac-arrest. METHODS: In a manikin study paramedics and emergency physicians performed advanced cardiac life support in three settings: ERC guidelines 2015 (control), COVID-19-guidelines as suggested with minimum staff (COVID-19-minimal-personnel); COVID-19-guidelines with paramedics and an emergency physician (COVID-19-advanced-airway-manager). Main outcome measures were no-flow-time, quality metrics as defined by ERC and time intervals to first chest compression, oxygen supply, intubation and first rhythm analysis. Data were presented as mean±standard deviation. RESULTS: Thirty resuscitation scenarios were completed. No-flow-time was markedly prolonged in COVID-19-minimal-personnel (113±37 s) compared to control (55±9 s) and COVID-19-advanced-airway-manager (76±38s; P<0.001 each). In both COVID-19-groups chest compressions started later (COVID-19-minimal-personnel: 32±6 s; COVID-19-advanced-airway-manager: 37±7 s; each P<0.001 vs. control [21±5 s]), but oxygen supply (COVID-19-minimal-personnel: 29±5 s; COVID-19-advanced-airway-manager: 34±7 s; each P<0.001 vs. control [77±19 s]) and first intubation attempt (COVID-19-minimal-personnel: 111±14 s; COVID-19-advanced-airway-manager: 131±20 s; each P<0.001 vs. control [178±44 s]) were performed earlier. However, time interval to successful intubation was similar (control: 198±48 s; COVID-19-minimal-personnel: 181±42 s; COVID-19-advanced-airway-manager: 130±25 s) due to a longer intubation time in COVID-19-minimal-personnel (61±35 s) compared to COVID-19-advanced-airway-manager (P=0.002) and control (19±6 s; P<0.001). Time to first rhythm analysis was more than doubled in COVID-19-minimal-personnel (138±96 s) compared to control (50±12 s; P<0.001). CONCLUSIONS: Delayed chest compressions and prolonged no-flow-time markedly reduced the quality of resuscitation. These negative effects were attenuated by increasing the number of staff and by adding an experienced airway manager. The use of endotracheal intubation for reducing aerosol release during resuscitation should be discussed critically as its priorization is associated with an increase in no-flow-time.

Afatinib as first-line treatment in patients with EGFR-mutated non-small cell lung cancer in routine clinical practice.

BACKGROUND: Lung cancer is a leading cause of cancer-related death in Germany and worldwide. Non-small cell lung cancer (NSCLC) comprises ~80% of lung cancer diagnoses; in White patients, around 10% of NSCLC cases are epidermal growth factor receptor mutation-positive (EGFRm+). Head-to-head clinical trials have demonstrated superior efficacy with second-/third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) versus first-generation EGFR TKIs in EGFRm+ NSCLC. Data from routine clinical practice are necessary to confirm that clinical trial findings are transferable to real-world populations. METHODS: In NCT02047903, a prospective non-interventional study in Germany, patients with EGFRm+ NSCLC received first-line afatinib until disease progression or intolerable adverse events. Key objectives were progression-free survival (PFS) rate at 12 months, objective response rate (ORR) and overall survival (OS). Safety/tolerability was also assessed. RESULTS: Of 152 patients, 106 (69.7%) were female, 20 (13.1%) patients had an uncommon EGFR mutation and 51 patients (33.6%) had brain metastases. A starting dose of <40 mg was received by 39 (25.7%) patients. Overall, the 12-month PFS rate was 50.2% while the median PFS was 12.2 months. The ORR was 74.6% and the median OS was 30.4 months. In patients with brain metastases and uncommon mutations, the median PFS was 10.5 and 10.7 months, and the ORR was 77.3% and 83.3%, respectively. Treatment effectiveness was similar in patients with a starting dose of <40 mg (median PFS: 16.4 months; ORR, 81.3%) and a starting dose of 40 mg (median PFS: 10.8 months; ORR, 72.1%). Adverse drug reactions were manageable and consistent with the known afatinib safety profile. CONCLUSION: The results support clinical trial data for afatinib in routine clinical practice, including in patients generally excluded from clinical trials. Outcomes were positive in patients with uncommon EGFR mutations and in those with brain metastases. Treatment benefit was also seen in patients receiving a <40 mg afatinib starting dose, supporting patient-tailored dosing.

Axenfeld-Rieger Anomaly and Neuropsychiatric Problems-More than Meets the Eye.

OBJECTIVE: The main purpose of this article is to demonstrate the co-occurrence of Axenfeld-Rieger anomaly and neuropsychiatric problems as clinical signs of genetically determined cerebral small vessel disease in two patients. CASE STUDY: We report on two adolescent individuals with ocular anterior segment dysgenesis (Axenfeld-Rieger anomaly) presenting with neuropsychiatric symptoms. Both patients underwent cerebral magnetic resonance imaging showing white matter T2-hyperintensities involving different brain regions, suspective of cerebral small vessel disease. Genetic analysis revealed pathogenic mutations in the FOXC1 gene (patient 1) and the COL4A1 gene (patient 2), respectively. CONCLUSION: We report on the co-occurrence of ocular anterior segment dysgenesis (Axenfeld-Rieger anomaly) and neuropsychiatric symptoms as clinical signs of genetically determined cerebral small vessel disease in two patients. In both patients, the cerebral lesions involved the frontotemporal regions, brain regions that control social behavior as well as executive and cognitive function, highlighting the fact that neuropsychiatric symptoms may be early clinical presentations of cerebral small vessel disease. We further provide a review of monogenic causes of pediatric cerebral small vessel disease, emphasizing the links to childhood-onset neuropsychiatric disease.

Patients with severe aortic stenosis and coexisting pulmonary hypertension treated by transapical transcatheter aortic valve replacement-Is there a need for increased attention?

OBJECTIVES: Aim of this study is to elucidate the impact of pulmonary hypertension on patients treated with a transapical aortic valve replacement. BACKGROUND: In patients with aortic stenosis (AS) the coexistence of pulmonary hypertension (PH) is associated with increased peri-operative risk for surgical aortic valve replacement. For transcatheter aortic valve replacement (TAVR), it is unknown whether transapical TAVR (TA-TAVR) is associated with increased peri-interventional risk in PH patients. METHODS: We performed a single center analysis in 189 patients with severe AS with (AS + PH) or without PH (AS - PH) undergoing TA-TAVR. PH was defined by mean pulmonary artery pressure ≥25 mmHg assessed by right heart catheterization (exclusion of 64 patients due to missing results). As the primary endpoint a combination of 30-day mortality or cardiopulmonary resuscitation (CPR) was analyzed. RESULTS: Seventy three patients (58.4%) had PH. Increased peri-interventional risk in AS + PH patients was reflected by an increased rate of the primary endpoint in comparison to AS - PH patients (24.7 vs. 3.8%; p = .002). A higher proportion of acute kidney injury (34.2 vs. 15.7%; p = .025) was found in AS + PH patients while AS - PH patients showed a higher rate of bleeding in comparison AS + PH patients (18.5 vs. 6.8% p = .050). CONCLUSION: Patients with AS + PH treated by TA-TAVR are at increased peri-interventional risk for severe complications in comparison to AS - PH patients. Therefore, the identification of preventive therapeutic strategies is needed. CLASSIFICATIONS: TAVR, transapical, pulmonary hypertension, aortic stenosis.

Reduction of sleep-disordered breathing following effective percutaneous mitral valve repair with the MitraClip system.

PURPOSE: This study tested the hypothesis that a reduction of pulmonary congestion achieved by a reduction of mitral regurgitation (MR) severity in heart failure (HF) patients is associated with reduced event lengths of sleep-disordered breathing (SDB). METHODS: We prospectively enrolled 20 consecutive HF patients who underwent MitraClip implantation. Patients underwent cardiorespiratory polygraphic recording prior to and after percutaneous mitral valve repair (PMVR). Beyond routinely established indicators of apneas and hypopneas per hour (respiratory event index), we manually analyzed apnea event lengths. RESULTS: MitraClip implantation led to marked reduction of MR severity and a reduction in left atrial pressure. These hemodynamic changes were accompanied by changes in SDB: the subtype of SDB switched from CSA to OSA in 4 patients. Likewise, quantitative indicators of SDB were altered in both forms of SDB with a reduction in circulatory delay (CSA 38 ± 14 vs. 33 ± 15 s.; p = 0.002 and OSA 34 ± 9 vs. 28 ± 6 s.; p = 0.02) and a corresponding reduction in ventilation lengths in CSA patients (42 ± 15 vs. 37 ± 13 s.; p = 0.05). CONCLUSION: A reduction of pulmonary congestion as achieved by a decrease of left atrial pressure through successful MitraClip implantation is associated with a reduction in respiratory event lengths, further pointing towards a relation between SDB and HF.

Sleep-disordered breathing in patients with newly diagnosed lung cancer.

BACKGROUND: There are currently no data on the prevalence of sleep-disordered breathing (SDB) in patients with newly-diagnosed lung cancer. This might be of interest given that SDB is associated with increased cancer incidence and mortality. Furthermore, intermittent hypoxia has been linked with tumor growth and progression. The aim of the current study was to investigate the prevalence of SDB in patients with newly-diagnosed lung cancer. METHODS: Patients with newly-diagnosed lung cancer from three centers in Germany were screened for SDB using a two-channel screening system (ApneaLink™). SDB was defined as an apnea-hypopnea index of > 5/h, and was classified as mild if the AHI was 5-15/h whereas an AHI ≥15/h was classified as severe SDB. The presence of SDB-related symptoms was assessed using the Epworth Sleepiness Scale (ESS) and the Pittsburgh Sleep Quality Index (PSQI). RESULTS: A total of 100 patients were included. The overall prevalence of SDB was 49%; 32 patients (32%) had mild SDB with a median AHI of 7.7/h (quartile [Q1 5.4/h, Q3 10.4/h]) and a median oxygen desaturation index of 8.5 [Q1 4.2/h; Q3 13.4/h] and seventeen patients (17%) had moderate to severe SDB with a median AHI of 25.2 [Q1 18/h, Q3 45.5/h] and a median oxygen desaturation index of 20.6/h [Q1 9.6/h, Q3 36.6/h]. Patients with moderate to severe SDB had mild daytime sleepiness (ESS score 8.24 ± 3.96 vs. 5.74 ± 3.53 in those without SDB vs. 6.22 ± 2.72 in those with mild SDB; p = 0.0343). The PSQI did not differ significantly between the three groups (p = 0.1137). CONCLUSIONS: This study showed a high prevalence of SDB in patients with newly-diagnosed lung cancer. In these patients SDB was associated with intermittent hypoxia and increased daytime sleepiness. Additional research is needed to determine whether SDB influences prognosis and morbidity in patients with lung cancer. TRIAL REGISTRATION: NCT02270853 (ClinicalTrials.gov), date of registration: 14th October 2014.

Testing the applicability of a benthic foraminiferal-based transfer function for the reconstruction of paleowater depth changes in Rhodes (Greece) during the early Pleistocene.

We present paleo-water depth reconstructions for the Pefka E section deposited on the island of Rhodes (Greece) during the early Pleistocene. For these reconstructions, a transfer function (TF) using modern benthic foraminifera surface samples from the Adriatic and Western Mediterranean Seas has been developed. The TF model gives an overall predictive accuracy of ~50 m over a water depth range of ~1200 m. Two separate TF models for shallower and deeper water depth ranges indicate a good predictive accuracy of 9 m for shallower water depths (0-200 m) but far less accuracy of 130 m for deeper water depths (200-1200 m) due to uneven sampling along the water depth gradient. To test the robustness of the TF, we randomly selected modern samples to develop random TFs, showing that the model is robust for water depths between 20 and 850 m while greater water depths are underestimated. We applied the TF to the Pefka E fossil data set. The goodness-of-fit statistics showed that most fossil samples have a poor to extremely poor fit to water depth. We interpret this as a consequence of a lack of modern analogues for the fossil samples and removed all samples with extremely poor fit. To test the robustness and significance of the reconstructions, we compared them to reconstructions from an alternative TF model based on the modern analogue technique and applied the randomization TF test. We found our estimates to be robust and significant at the 95% confidence level, but we also observed that our estimates are strongly overprinted by orbital, precession-driven changes in paleo-productivity and corrected our estimates by filtering out the precession-related component. We compared our corrected record to reconstructions based on a modified plankton/benthos (P/B) ratio, excluding infaunal species, and to stable oxygen isotope data from the same section, as well as to paleo-water depth estimates for the Lindos Bay Formation of other sediment sections of Rhodes. These comparisons indicate that our orbital-corrected reconstructions are reasonable and reflect major tectonic movements of Rhodes during the early Pleistocene.