An Interdisciplinary Approach: Presentation of the Pediatric Obstructive Sleep Apnea Diagnostic Examination Form (POSADEF).

This report emphasizes the need for interdisciplinary collaboration in diagnosing and treating pediatric obstructive sleep apnea (OSA). OSA, affecting 1% to 4% of children, often results from adenotonsillar hypertrophy, craniofacial disorders, or obesity. While adenotonsillectomy is the primary treatment, about 75% of children, especially those with craniofacial disorders or obesity, continue to experience OSA symptoms post-surgery. To address these cases, several medical fields emphasize the necessity and demand for interdisciplinary collaboration in managing pediatric OSA. Therefore, the authors aimed to develop the Pediatric Obstructive Sleep Apnea Diagnostic Examination Form (POSADEF). This form, based on clinical experience and the literature, captures craniofacial and functional characteristics linked to pediatric OSA. A case study of an eight-year-old girl with OSA, who was unsuccessfully treated with adenotonsillectomy, underlines the importance of the diagnostic examination form. The orthodontic assessment revealed craniofacial disorders and subsequent treatment with maxillary expansion and functional appliance therapy resolved her OSA symptoms. This case demonstrates the value of POSADEF in enabling comprehensive evaluation and treatment across medical disciplines. POSADEF is designed to assist health care professionals in diagnosing craniofacial and orofacial anomalies contributing to pediatric OSA.

[The Inventor of the "Triage": Dominique-Jean Larrey (1766-1842), Napoleon's Chief Military Doctor]. / Der Erfinder der "Triage" ­ Dominique-Jean Larrey (1766­1842), Napoleons oberster Militärchirurg.

During the reign of Emperor Napoleon I, Dominique-Jean Larrey (1766-1842) was chief surgeon in the French army. He has become known as the father of modern military surgery and for the development of the "triage system". Larrey was an outstanding and dedicated physician who provided medical care not only to his own troops but also to those of the enemy. Without reliable analgesia and anaesthesia, speed and skill were the most salient characteristics of a surgeon at that time. Against the opposition of the administration, Larrey is credited with the introduction of first-aid on the battlefield as well as a quick rescue of the wounded with the help of the so-called "flying ambulances". He was considered the soldiers' greatest friend.

[The Road to Discovery of the Pulmonary Gas Exchange - From the "Phlogiston-" to the "Oxygen Theory"]. / Der Weg zur Entdeckung des pulmonalen Gasaustausches.

The discovery of oxygen and pulmonary gas exchange was a major advancement in our understanding of breathing. For centuries it was believed that the lungs were primarily necessary to cool the heart or to "refine" the blood. Richard Lower (1631-1691) observed that the blood had a different colour before and after passage through the lung. His assumption was that breathing must have been added a special substance to the blood. Georg Ernst Stahl (1660-1734) formulated a fire substance "phlogiston" (phlox = flame) with his phlogiston theory. He postulated that phlogiston is contained in all combustible substances and escapes when burned. John Mayow (1641-1679) recognised that about one fifth of the breathing gas is important for the breathing process. He called the gas "spiritus nitro aerius". Oxygen was first discovered in the early 1770 s by the Swedish-German pharmacist Carl Wilhelm Scheele (1742-1786) and the English chemist Joseph Priestley (1733-1804) - independently of each other. Antoine-Laurent Lavoisier (1743-1794) recognised oxygen as element and for the first time described the oxidation process accurately.

Comparison of Efficacy in Patients with Metastatic Melanoma Treated with Ipilimumab and Nivolumab Who Did or Did Not Discontinue Treatment Due to Immune-Related Adverse Events: A Real-World Data Study.

Immune-related adverse events (irAEs) are very prevalent when treating patients with ipilimumab and nivolumab in combination, and 30-40% of patients discontinue the treatment for this reason. It is of high clinical relevance to investigate the consequences of discontinuing the treatment early since combination therapy with ipilimumab and nivolumab is the first line of treatment for many patients with metastatic melanoma. In this follow-up study, with real-world data from the nationwide DAMMED database, we investigated whether there was a difference in progression-free survival (PFS) and overall survival (OS) for patients who discontinued or did not discontinue treatment within the first four doses of treatment due to irAEs. In total, 448 patients were treated with ipilimumab and nivolumab. Of these, 133 patients discontinued due to irAEs in the induction phase. Using the Cox proportional hazards model, there was no significant difference in PFS when comparing the group that discontinued with the group that did not discontinue. The group that discontinued had a significantly longer OS than the group that received the full length of treatment. Therefore, we conclude that there is no significant negative impact on efficacy for patients who discontinue due to irAEs in the induction phase of combination immunotherapy for metastatic melanoma.

Why Do Our Cancer Patients Sleep So Badly? Sleep Disorders in Cancer Patients: A Frequent Symptom with Multiple Causes.

INTRODUCTION: On the one hand, sleep disorders in cancer patients are reported in 30-50% of cancer patients. On the other hand, specific causes for these sleep disorders are little known. This study was done to evaluate factors which may affect sleep of cancer patients. To our knowledge, this is the first study which includes return to work as one factor of sleep disturbance. METHODS: 107 patients with various types of cancer treated in 2 hospitals were interviewed with a battery of questionnaires after having given informed consent. The questionnaires intended to detect abnormalities of sleep and related pain, breathing disorders, restless legs syndrome, depression, rumination, medication, and psychosocial distress. The study was approved by the ethics committee of the University of Marburg. RESULTS: The analysis of the 6 sleep-related questionnaires indicated a sleep disorder of any kind in 68% of all patients. Insomnia symptoms were present in 48 patients (44.9%). Pain, depression, anxiety, and worries about the workplace were significantly related to sleep disorders. CONCLUSION: Sleep disorders are common in cancer patients. The causes are manifold and should be considered by caregivers during diagnosis, therapy, and aftercare of cancer patients. Tumour patients should actively be asked about sleep disorders. If these are present, they should be addressed, and as they have a large impact on quality of life, treatment options should be offered in cooperation with sleep specialists.

High Plasma Cystine Levels Are Associated with Blood Pressure and Reversed by CPAP in Patients with Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) independent of obesity (OBS) imposes severe cardiovascular risk. To what extent plasma cystine concentration (CySS), a novel pro-oxidative vascular risk factor, is increased in OSA with or without OBS is presently unknown. We therefore studied CySS together with the redox state and precursor amino acids of glutathione (GSH) in peripheral blood mononuclear cells (PBMC) in untreated male patients with OSA (apnea-hypopnea-index (AHI) > 15 h-1, n = 28) compared to healthy male controls (n = 25) stratifying for BMI ≥ or < 30 kg m-2. Fifteen OSA patients were reassessed after 3-5-months CPAP. CySS correlated with cumulative time at an O2-saturation <90% (Tu90%) (r = 0.34, p < 0.05) beside BMI (r = 0.58, p < 0.001) and was higher in subjects with "hypoxic stress" (59.4 ± 2.0 vs. 50.1 ± 2.7 µM, p < 0.01) defined as Tu90% ≥ 15.2 min (corresponding to AHI ≥ 15 h-1). Moreover, CySS significantly correlated with systolic (r = 0.32, p < 0.05) and diastolic (r = 0.31, p < 0.05) blood pressure. CPAP significantly lowered CySS along with blood pressure at unchanged BMI. Unexpectedly, GSH antioxidant capacity in PBMC was increased with OSA and reversed with CPAP. Plasma CySS levels are increased with OSA-related hypoxic stress and associated with higher blood pressure. CPAP decreases both CySS and blood pressure. The role of CySS in OSA-related vascular endpoints and their prevention by CPAP warrants further studies.

[Control of Respiratory Symptoms During Sleep in Patients with Stable Bronchial Asthma]. / Nächtliche Symptomkontrolle bei Patienten mit stabilem Asthma bronchiale.

INTRODUCTION: Awareness of respiratory symptoms during day- and night-time is important for asthma control. Acoustic long-term recording offers a possibility to monitor symptoms objectively. In this prospective observational study frequency of night-time cough and wheezing was evaluated in patients with stable asthma. METHODS: Night-time cough and wheezing were monitored by LEOSound lung sound monitor in 40 patients with stable asthma. Patients did not complain of respiratory problems during day- and nighttime, asthma control test was 23 points on average. FEV1 was 84 ±â€Š15 %; MEF 50 71 ±â€Š27 % and Rtot 0,48 ±â€Š0,18 kPas/l. The age of the patients was 35 ±â€Š11 years. All patients had an antiobstructive and/or anti-inflammatory medication. The present study focuses on description of frequency, severity and characteristics of night-time symptoms like cough and wheezing in patients with stable asthma and tries to depict differences in patients who present cough or wheezing. RESULTS: Wheezing was monitored in 2 of the 40 patients. In the first patient duration of wheezing was 19 min, in the second 55 min. Lung function in patient 1 showed a moderate bronchial obstruction, he was still smoking. Patient 2 was a non-smoker with a significant bronchial obstruction (FEV1 49 %; MEF 50 27 % and Rtot 0,52 kPas/l). In 26 patients there was no coughing, 14 patients had 4 ±â€Š3 (2 - 13) cough epochs during the night. By dividing the collective in two groups differentiated by the presence of cough/ no cough we found no significant differences regarding lung function and ACT-scores. Both patients with night-time wheezing presented low ACT- Scores (20 and 21 points). CONCLUSIONS: Nocturnal wheezing and cough episodes were detectable in 2 respectively 14 patients with stable asthma. Long-term recording of normal and adventitious breath sounds offers a practical opportunity to evaluate night-time cough and wheezing objectively.

Description of nighttime cough epochs in patients with stable COPD GOLD II-IV.

PURPOSE: Chronic cough is one of the main symptoms of COPD. Ambulatory objective monitoring provides novel insights into the determinants and characteristics of nighttime cough in COPD. MATERIALS AND METHODS: Nighttime cough was monitored objectively by LEOSound lung sound monitor in patients with stable COPD II-IV. In 30 patients, with 10 patients in each stage group, nighttime cough was analyzed for epoch frequency, epoch severity (epoch length and coughs per epoch), and pattern (productive or nonproductive). RESULTS: Cough was found in all patients ranging from 1 to 294 events over the recording period. In 29 patients, cough epochs were monitored, ranging from 1 to 75 epochs. The highest amount of cough epochs was found in patients with COPD stage III. Active smokers had significantly more productive cough epochs (61%) than nonsmokers (24%). CONCLUSION: We found a high rate of nighttime cough epochs in patients with COPD, especially in those in stage III. Productive cough was predominantly found in patients with persistent smoking. LEOSound lung sound monitor offers a practical and valuable opportunity to evaluate cough objectively.

Long-term Recording of Night-Time Respiratory Symptoms in Patients with Stable COPD II-IV.

INTRODUCTION: Night-time respiratory symptoms have a considerable impact on sleep and life quality in patients with chronic obstructive pulmonary disease (COPD). Lack of awareness of night-time symptoms can lead to worsened COPD control. Automated long-term monitoring of respiratory symptoms with LEOSound enables assessment of nocturnal wheezing and cough. METHODS: In this observational study we investigated the prevalence and severity of cough and wheezing in patients with stable COPD [Global Initiative for Chronic Obstructive Lung Disease (GOLD) II-IV] disease for two consecutive nights with the LEOSound system. 48 patients (30 males, 63%) were eligible for inclusion, median age was 67 years, and body mass index (BMI) was 25.3 kg/m2. RESULTS: In 15 out of 48 patients (31%), we found wheezing periods for at least 10-minute duration. Wheezing periods >30 minutes were monitored in seven patients and wheezing periods >60 minutes were monitored in three patients. The maximum duration of wheezing was 470 minutes in one patient with COPD II. The median wheezing rate differed between the COPD stages and between active and non-active smokers. Cough was found in 42 patients (87.5%) with a range of 1-326 events. The cough-period-index in night one was 0.83 n/hour (P25:0.33||P75: 2.04) and night two 0.97 n/hour (P25:0.25||P75: 1.9). Most of the cough events were non-productive with a median of 0.86. CONCLUSIONS: Night-time symptoms are common in COPD patients. LEOSound offers an opportunity to evaluate objectively night-time symptoms like wheezing and cough in patients with COPD which remain otherwise unnoticed. We found a high incidence of night-time wheezing in these patients, which was related to persistant smoking.

Age-related differences in skeletal muscle microvascular response to exercise as detected by contrast-enhanced ultrasound (CEUS).

BACKGROUND: Aging involves reductions in exercise total limb blood flow and exercise capacity. We hypothesized that this may involve early age-related impairments of skeletal muscle microvascular responsiveness as previously reported for insulin but not for exercise stimuli in humans. METHODS: Using an isometric exercise model, we studied the effect of age on contrast-enhanced ultrasound (CEUS) parameters, i.e. microvascular blood volume (MBV), flow velocity (MFV) and blood flow (MBF) calculated from replenishment of Sonovue contrast-agent microbubbles after their destruction. CEUS was applied to the vastus lateralis (VLat) and intermedius (VInt) muscle in 15 middle-aged (MA, 43.6±1.5 years) and 11 young (YG, 24.1±0.6 years) healthy males before, during, and after 2 min of isometric knee extension at 15% of peak torque (PT). In addition, total leg blood flow as recorded by femoral artery Doppler-flow. Moreover, fiber-type-specific and overall capillarisation as well as fiber composition were additionally assessed in Vlat biopsies obtained from CEUS site. MA and YG had similar quadriceps muscle MRT-volume or PT and maximal oxygen uptake as well as a normal cardiovascular risk factors and intima-media-thickness. RESULTS: During isometric exercise MA compared to YG reached significantly lower levels in MFV (0.123±0.016 vs. 0.208±0.036 a.u.) and MBF (0.007±0.001 vs. 0.012±0.002 a.u.). In the VInt the (post-occlusive hyperemia) post-exercise peaks in MBV and MBF were significantly lower in MA vs. YG. Capillary density, capillary fiber contacts and femoral artery Doppler were similar between MA and YG. CONCLUSIONS: In the absence of significant age-related reductions in capillarisation, total leg blood flow or muscle mass, healthy middle-aged males reveal impaired skeletal muscle microcirculatory responses to isometric exercise. Whether this limits isometric muscle performance remains to be assessed.

Lower hypoxic ventilatory response in smokers compared to non-smokers during abstinence from cigarettes.

BACKGROUND: Carotid body O2-chemosensitivity determines the hypoxic ventilatory response (HVR) as part of crucial regulatory reflex within oxygen homeostasis. Nicotine has been suggested to attenuate HVR in neonates of smoking mothers. However, whether smoking affects HVR in adulthood has remained unclear and probably blurred by acute ventilatory stimulation through cigarette smoke. We hypothesized that HVR is substantially reduced in smokers when studied after an overnight abstinence from cigarettes i.e. after nicotine elimination. METHODS: We therefore determined the isocapnic HVR of 23 healthy male smokers (age 33.9 ± 2.0 years, BMI 24.2 ± 0.5 kg m-2, mean ± SEM) with a smoking history of >8 years after 12 h of abstinence and compared it to that of 23 healthy male non-smokers matched for age and BMI. RESULTS: Smokers and non-smokers were comparable with regard to factors known to affect isocapnic HVR such as plasma levels of glucose and thiols as well as intracellular levels of glutathione in blood mononuclear cells. As a new finding, abstinent smokers had a significantly lower isocapnic HVR (0.024 ± 0.002 vs. 0.037 ± 0.003 l min-1 %-1BMI-1, P = 0.002) compared to non-smokers. However, upon re-exposure to cigarettes the smokers' HVR increased immediately to the non-smokers' level. CONCLUSIONS: This is the first report of a substantial HVR reduction in abstinent adult smokers which appears to be masked by daily smoking routine and may therefore have been previously overlooked. A low HVR may be suggested as a novel link between smoking and aggravated hypoxemia during sleep especially in relevant clinical conditions such as COPD.

[Is daytime sleepiness a sufficient predictor of sleep-disordered breathing during pre-anesthesia consultation?]. / "Tagesschläfrigkeit" als Prädiktor für schlafbezogene Atmungsstörungen (SBAS)--ist eine präoperative Evaluation sinnvoll?

BACKGROUND: Sleep-disordered breathing (SDB) is associated with increased rate of perioperative complications. Daytime sleepiness is a frequent symptom of SDB. Thus, aim of the present study was to evaluate whether preoperative assessment of daytime sleepiness would be eligible for sufficient prediction of SDB. METHODS: Patients before scheduled surgery were prospectively recruited and asked to answer a standardized sleep questionnaire (Epworth Sleepiness Scale; ESS). The night before surgery, sleep polygraphy was performed and the oxygen desaturation index 4% (ODI 4%) was calculated. RESULTS: Data of 363 patients (190 men and 173 women) were finally analyzed. Regarding risk assessment, 42 patients had ASA grade 1, 192 patients had ASA grade 2, 123 patients had ASA grade 3 and 6 patients had ASA grade 4. Mean Body Mass Index was 27.9 ± 5.1 kg/m2, mean age was 59.2 ± 13.3 years and mean ESS score was 5.7 ± 3.4. Clinical relevant daytime sleepiness (ESS ≥ 11) was found in 32 patients (9%). In 11 patients (34%) with ESS ≥ 11, ODI 4% ≥ 5/h was calculated whereas in 21 patients with ESS ≥ 11 (66%), ODI 4% < 5/h was found. Odds ratio between ODI 4% ≥ 5/h and ESS ≥ 11 was 0.919 (CI 0.85-0.99, p = 0.038). CONCLUSION: In non-obese patients, daytime sleepiness is a rare event and is not associated with SDB. Thus, daytime sleepiness is not eligible for the preoperative SDB screening.

Occurrence of rapid eye movement sleep deprivation after surgery under regional anesthesia.

BACKGROUND: Sleep disturbances after general surgery have been described. In this study, we assessed rapid eye movement (REM) sleep in patients undergoing knee replacement surgery using a regional anesthetic technique. METHODS: Ambulatory polysomnography (PSG) was performed on 3 nights: the night before surgery (PSG1), the first night after surgery (PSG2), and the fifth postoperative night (PSG3). Postoperative analgesia was maintained with peripheral nerve catheters for the first 3 days and with oral opioids thereafter. In addition, nonsteroidal antiinflammatory drugs were administered. Postoperative pain was monitored using a visual analog scale. RESULTS: PSG was performed in 12 patients, 6 men and 6 women, with a mean age of 61 (±12) years. REM sleep was reduced from PSG1 (median 16.4%) to PSG2 (median 6.3%; P = 0.02). The Hodges-Lehmann estimate for the median reduction is -7.8% (95% confidence interval -14.8% to -0.7%). During PSG3, significantly more REM sleep was detected (median 15.4%) compared with PSG2 (P = 0.01). The Hodges-Lehmann estimate for this median increase is 10.0% (95% confidence interval 1.7%-25.3%). CONCLUSION: Postoperative reduction of REM sleep also occurs after surgery and regional anesthesia.

[Sleep disordered breathing and nonsustained ventricular tachycardia in patients with chronic heart failure]. / Schlafbezogene Atmungsstörungen und maligne ventrikuläre Arrhythmien bei Patienten mit chronischer Herzinsuffizienz.

BACKGROUND: Patients with chronic heart failure (CHF) have a high incidence of sleep disordered breathing (SDB). It is assumed that patients with the combination of CHF and SDB have more ventricular couplets and nonsustained ventricular tachycardia (NSVT) than patients without SDB. METHODS: In 63 patients, 49 men and 14 women with chronic heart failure (EF < 45%), all-night polysomnography and long-term-ECG were performed. Mean age was 59 ± 15 years, mean BMI 27 ± 5 kg/m(2). 56% had an ischemic, 44% a nonischemic heart disease. 51% had heart insufficiency classification NYHA III. RESULTS: 42 of the 63 patients (67%) had sleep disordered breathing (SDB) with an AHI ≥5/h. In 24 patients (38%) SDB was central, in 18 (29%) obstructive. More patients with SDB than patients without SDB had NSVT (50% vs. 19%). Nocturnal frequency of NSVT in patients with SDB was about twice as high as the rate observed during daytime (0.48/h vs. 0.21/h). In patients without SDB there was no relevant difference between day and night (0.23/h vs. 0.21/h). AHI correlated with NSVT (r = 0.329, p < 0.01). Day/night comparison of couplets was 2.3/h vs. 1.9/h in SDB patients and 2.0/h vs. 1.6/h in patients without SDB. CONCLUSIONS: Patients with chronic heart failure have a high prevalence of SDB. The combination of CHF and SDB predisposes for nocturnal malignant ventricular arrhythmias.