Periodic limb movements in patients with suspected obstructive sleep apnea without comorbid conditions.

Background: Periodic limb movement disorder (PLMD) and obstructive sleep apnea (OSA) are overlapping clinical syndromes with common risk factors. However, current literature has failed to establish a clear pathophysiological link between them. Thus, little is known about periodic limb movements (PLM) in otherwise healthy patients with suspected OSA. Methods: We performed a retrospective analysis of 112 patients (age: 44.5 ± 12.0 years, 14.3% female) with suspected OSA who underwent full night polysomnography for the first time. Patients with chronic diseases of any kind, recent infections, malignancies, or daily or regular use of any type of medication were excluded. Group comparisons were made based on the severity of OSA (using the apnea hypopnea index, AHI) or the periodic limb movement index (PLMI). Results: Both, PLMI and the total number of periodic limb movements during sleep (PLMS), showed a significant increase in patients with severe OSA. In addition, AHI and apnea index (AI) were significantly higher in patients with PLMI >15/h, with a similar trend for hypopnea index (HI) (p < 0.001, p < 0.001, and p > 0.05, respectively). PLMI was significantly positive correlated with AHI, AI, and HI (r = 0.392, p < 0.001; r = 0.361, p < 0.001; and r = 0.212, p < 0.05, respectively). Patients with PLMI >15/h were significantly older (p < 0.001). There was no significant association between body mass index (BMI) and PLMI >15/h. Conclusion: We found a significant association between the severity of OSA and PLM in our study population with suspected OSA but without other comorbidities. PLMI and PLMS were significantly increased in patients with severe OSA. Future prospective studies with larger collectives should verify the presented results and should include mechanistic aspects in their evaluation.

Symmetrically dotted tympanic membranes.

Key Clinical Message: Color changes of the tympanic membranes without an inflammatory component or perforation are rarely described. They may result from hemorrhage after barotrauma or spontaneously. Other explanatory models include discoloration due to otomycosis. Abstract: This is a case of a 61-year-old patient with an unexplained incidental of black dots located almost symmetrically on the antero-inferior quadrant of both tympanic membranes. This harmless anatomical rarity has not been published before. Underlying pathologies should be excluded in the case of discoloration of the tympanic membranes.

Heart Rate Variability as a Surrogate Marker of Severe Chronic Coronary Syndrome in Patients with Obstructive Sleep Apnea.

BACKGROUND AND OBJECTIVES: Obstructive sleep apnea (OSA) is a known risk factor for chronic coronary syndrome (CCS). CCS and OSA are separately associated with significant changes in heart rate variability (HRV). In this proof-of-concept study, we tested whether HRV values are significantly different between OSA patients with concomitant severe CCS, and OSA patients without known CCS. MATERIAL AND METHODS: The study comprised a retrospective assessment of the historical and raw polysomnography (PSG) data of 32 patients who presented to a tertiary university hospital with clinical complaints of OSA. A total of 16 patients (four females, mean age 62.94 ± 2.74 years, mean body mass index (BMI) 31.93 ± 1.65 kg/m2) with OSA (median apnea-hypopnea index (AHI) 39.1 (30.5-70.6)/h) and severe CCS were compared to 16 patients (four females, mean age 62.35 ± 2.06 years, mean BMI 32.19 ± 1.07 kg/m2) with OSA (median AHI 40 (30.6-44.5)/h) but without severe CCS. The short-long-term HRV (in msec) was calculated based on the data of a single-lead electrocardiogram (ECG) provided by one full-night PSG, using the standard deviation of the NN, normal-to-normal intervals (SDNN) and the heart rate variability triangular index (HRVI) methods, and compared between the two groups. RESULTS: A significant reduction (p < 0.05) in both SDNN and HRVI was found in the OSA group with CCS compared to the OSA group without CCS. CONCLUSIONS: Severe CCS has a significant impact on short-long-term HRV in OSA patients. Further studies in OSA patients with less-severe CCS may shed more light onto the involved mechanistic processes. If confirmed in future larger studies, this physiologic metric has the potential to provide a robust surrogate marker of severe CCS in OSA patients.

Anatomic Features of the Nasal and Pharyngeal Region Do Not Influence PAP Therapy Response.

The objective of this study was to investigate to which extent anatomic features of the nasal and pharyngeal region contribute to the severity of obstructive sleep apnea (OSA) and positive airway pressure (PAP) therapy response. Therefore, 93 patients (mean age 57.5 ± 13.0 years, mean body mass index 32.2 ± 5.80 kg/m2, 75 males, 18 females) diagnosed with OSA who subsequently started PAP therapy were randomly selected from the databank of a sleep laboratory of a tertiary university medical center. Patients were subdivided based on nasal anatomy (septal deviation, turbinate hyperplasia, their combination, or none of the above), pharyngeal anatomy (webbing, tonsillar hyperplasia, their combination, or none of the above), and (as a separate group) tongue base anatomy (no tongue base hyperplasia or tongue base hyperplasia). Then, polysomnographic data (e.g., arousal index, ARI; respiratory disturbance index, RDI; apnea index, AI; hypopnea index, HI; and oxygen desaturation index, ODI) of diagnostic polysomnography (PSG) and PAP therapy control PSG were collected, grouped, and evaluated. Septal deviation, turbinate hyperplasia, or their combination did not significantly affect the assessed PSG parameters or the response to PAP therapy compared with patients without nasal obstruction (p > 0.05 for all parameters). Accordingly, most PSG parameters and the response to PAP therapy were not significantly affected by webbing, tonsil hyperplasia, or their combination compared with patients without pharyngeal obstruction (p > 0.05 for RDI, AI, HI, and ODI, respectively). However, in the pharyngeal anatomy group, ARI was significantly higher in patients with tonsil hyperplasia (p = 0.018). Further, patients with tongue base hyperplasia showed a significantly higher HI in the diagnostic PSG (p = 0.025) compared with patients with normal tongue base anatomy, but tongue base anatomy did not significantly affect the response to PAP therapy (p > 0.05 for all parameters). The influence of anatomic features of the nasal and pharyngeal region on PAP therapy response appears to be small, and generalizability of these results requires further studies.

Drug-Induced Sleep Endoscopy Findings and Hypoglossal Nerve Stimulation Therapy Outcomes.

Hypoglossal-nerve stimulation (HGNS) is an established second-line therapy for patients with obstructive sleep apnea (OSA). Existing studies investigating the effect of preoperative drug-induced sleep endoscopic (DISE) findings on HGNS outcomes have mainly focused on the apnea/hypopnea index (AHI) among polysomnography (PSG) parameters, and have less frequently tested other PSG parameters such as the apnea index (AI), hypopnea index (HI), oxygen desaturation index (ODI), snoring index, and arousal index, or patient-reported excessive daytime sleepiness. The aim of this study was to investigate the correlation between DISE findings and the above-mentioned metrics after HGNS therapy. We only included patients with DISE findings providing detailed information about the degree of the anteroposterior velar (APV), oropharyngeal lateral wall (OPLW), or tongue-base (BT) obstruction based on the velum, oropharynx, base of tongue, and epiglottis (VOTE) classification. The data of 25 patients (9 female (36%)) were retrospectively evaluated. The mean age at the date of implantation was 54.52 ± 9.61 years, and the mean BMI was 29.99 ± 3.97 kg/m2. Spearman's rho correlation coefficients were calculated. Significant correlations were found between the degree of APV obstruction and postoperative HI (r = -0.5, p < 0.05), and between the degree of OPLW obstruction and postoperative snoring index (r = 0.42, p < 0.05). BT obstruction was strongly correlated with postoperative metrics such as AHI (r = -0.57, p < 0.01), AI (r = -0.5, p < 0.05), ODI (r = -0.57, p < 0.01), ∆ AHI (r = 0.58, p < 0.01), ∆ AI (r = 0.54, p < 0.01) and ∆ ODI (r = 0.54, p < 0.01). No significant correlation was found between DISE findings and postoperative Epworth Sleepiness Scale values. These findings suggest that preoperative DISE findings, especially the degree of BT obstruction, are important for predicting an HGNS therapy outcome.

Serum Ferritin Levels in Severe Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) has been associated with various acute and chronic inflammatory diseases, as has serum ferritin, an intracellular iron storage protein. Little is known about the relationship between severity of OSA and serum ferritin levels in otherwise healthy subjects. In this study, all polysomnographic recordings, serum levels of ferritin, C-reactive protein (CRP), and hemoglobin, as well as patient files from 90 consecutive, otherwise healthy individuals with suspected OSA who presented to a tertiary sleep medical center were retrospectively analyzed. For comparison, three groups were formed based on apnea-hypopnea index (AHI; none or mild OSA: <15/h vs. moderate OSA: 15-30/h vs. severe OSA: >30/h). Serum ferritin levels were significantly positively correlated with AHI (r = 0.3240, p = 0.0020). A clear trend of higher serum ferritin levels was found when patients with severe OSA were compared to those without or with mild OSA. Serum CRP and serum hemoglobin levels did not differ significantly among OSA severity groups. Age and body-mass index (BMI) tended to be higher with increasing OSA severity. The BMI was significant higher in patients with severe OSA compared to those without or with mild (p < 0.001). Therefore, serum ferritin levels may provide a biochemical surrogate marker for OSA severity.

Central Apneic Event Prevalence in REM and NREM Sleep in OSA Patients: A Retrospective, Exploratory Study.

Patients with sleep-disordered breathing show a combination of different respiratory events (central, obstructive, mixed), with one type being predominant. We observed a reduced prevalence of central apneic events (CAEs) during REM sleep compared to NREM sleep in patients with predominant obstructive sleep apnea (OSA). The aim of this retrospective, exploratory study was to describe this finding and to suggest pathophysiological explanations. The polysomnography (PSG) data of 141 OSA patients were assessed for the prevalence of CAEs during REM and NREM sleep. On the basis of the apnea-hypopnea index (AHI), patients were divided into three OSA severity groups (mild: AHI < 15/h; moderate: AHI = 15-30/h; severe: AHI > 30/h). We compared the frequency of CAEs adjusted for the relative length of REM and NREM sleep time, and a significantly increased frequency of CAEs in NREM was found only in severely affected OSA patients. Given that the emergence of CAEs is strongly associated with the chemosensitivity of the brainstem nuclei regulating breathing mechanics in humans, a sleep-stage-dependent chemosensitivity is proposed. REM-sleep-associated neuronal circuits in humans may act protectively against the emergence of CAEs, possibly by reducing chemosensitivity. On the contrary, a significant increase in the chemosensitivity of the brainstem nuclei during NREM sleep is suggested.

Insomnia in Patients Undergoing Hypoglossal Nerve Stimulation Therapy for Obstructive Sleep Apnea.

Hypoglossal nerve stimulation (HGNS) is a treatment for obstructive sleep apnea (OSA) patients with intolerance of positive airway pressure therapy. Comorbid insomnia is quite prevalent in OSA patients. We investigated the impact of insomnia and excessive daytime sleepiness (EDS) on polysomnography metrics after HGNS treatment. Data of 27 consecutive patients (9 female; mean age 55.52 ± 8.6 years) were retrospectively evaluated. Insomnia was assessed using the ISI (insomnia severity index) and EDS using the Epworth sleepiness scale (ESS). The median ISI was reduced significantly 3 months after HGNS activation (preoperative: 19; postoperative: 14; p < 0.01). Significant correlations emerged between preoperative ISI and postoperative AHI (apnea/hypopnea index; Spearman's rho = 0.4, p < 0.05), ∆ AHI (r = −0.51, p < 0.01) and ∆ ODI (oxygen desaturation index; r = −0.48, p < 0.05). ISI correlated strongly with EES both preoperatively (r = 0.46; p < 0.02) and postoperatively (r = 0.79; p < 0.001). Therefore, HGNS therapy is associated with a significant reduction of insomnia-related symptoms, in addition to the improvement in respiratory metrics in OSA. Nonetheless, the preoperative severity of patient-reported insomnia symptoms was inversely correlated with the respiratory PSG-outcomes after HGNS. Insomnia should be considered in studies of EDS in OSA patients, especially those treated with HGNS.

Massive nasopharyngeal rhabdomyosarcoma in an adult patient: a rare case report.

Rhabdomyosarcoma (RMS) is a highly invasive malignant soft tissue sarcoma that rarely affects adults. The head and neck region accounts for most adult RMSs. Here, we report a case of a 24-year-old Caucasian woman who was diagnosed with persistent hoarseness and a painless left-sided neck mass. Physical examination and image studies showed a massive tumor of the nasopharynx, extending from the left-sided skull base to supraglottic structures. Histopathologic evaluation revealed the diagnosis of a poorly differentiated RMS. Due to the primary tumor size and involvement of crucial structures, extensive surgical excision was not amenable. Thus, the patient was treated with radiotherapy and chemotherapy. Although very rare, nasopharyngeal RMSs should be considered in the differential diagnosis of neck masses in adult patients. This case report illustrates the difficulty in the diagnosis and treatment of rare head and neck malignancies and encourages its reporting.

Short-Term Outcome of Unilateral Inspiration-Coupled Hypoglossal Nerve Stimulation in Patients with Obstructive Sleep Apnea.

Hypoglossal nerve stimulation (HGNS) is a therapeutic option for patients with obstructive sleep apnea (OSA) and intolerance of positive airway pressure (PAP) therapy. Most reported data are based on multicentre pivotal trials with selected baseline core clinical features. Our aim was to investigate polysomnography (PSG)-based outcomes of HGNS-therapy in a patient cohort with higher average AHI and BMI than previously reported. Data of 29 consecutive patients (nine female; mean age: 55.52 ± 8.6 years, mean BMI 30.13 ± 3.93 kg/m2) were retrospectively evaluated. Numerical values of PSG- based metrics were compared before and after intervention using Wilcoxon's rank-sum test. AHI (38.57/h ± 12.71, 24.43/h ± 13.3, p < 0.001), hypopnea index (24.05/h ± 9.4, 15.27/h ± 8.23, p < 0.001), apnea index (14.5/h ± 12.05, 9.17/h ± 10.86, p < 0.01), snoring index (262.68/h ± 170.35, 143.48/h ± 162.79, p < 0.001), cortical arousal index (20.8/h ± 10.34 vs. 14.9/h ± 8.36, p < 0.01) and cumulative duration of apnea and hypopnea during sleep (79.79 min ± 40.32 vs. 48.62 min ± 30.56, p < 0.001) were significantly lower after HGNS. HGNS provides an effective therapy option for selected patients not tolerating PAP-therapy with higher average AHI and BMI than usually reported. HGNS-therapy appears to suppress central nervous system arousal circuits while not eliciting peripheral autonomous sympathetic activation. Such metrics as the snoring index and the cumulative duration of respiratory events during sleep may be considered in future HGNS studies.

Obstructive Sleep Apnea Disrupts Glycemic Control in Obese Individuals.

The link between obstructive sleep apnea (OSA) and obesity, and their common comorbidities such as diabetes mellitus (DM) or cardiovascular diseases, is not fully understood. The aim of this study was to investigate the possible association of OSA severity in obese individuals with polysomnography-based sleep parameters, as well as C-reactive protein (CRP) and glycated hemoglobin (HbA1c) serum levels. Polysomnographic recordings and blood samples were retrospectively compared between a group of 23 adult obese individuals with mild OSA (apnea-hypopnea index (AHI) = 7.5 (5.5-12.5)/h, age = 42.57 ± 11.44 years, 16 male, 7 female, body mass index (BMI) = 37.35 ± 3.88 kg/m²) and an age-, sex-, and BMI-matched group of individuals with moderate or severe OSA (AHI 41.5 (25.7-71.8)/h, age = 43.43 ± 11.96 years, 16 male, 7 female, BMI = 37.87 ± 4.74 kg/m²). All respiratory sleep-associated parameters were significantly higher in individuals with moderate and severe OSA compared to those with mild OSA. CRP levels did not differ between the two OSA severity groups. However, serum levels of HbA1c were significantly higher in the moderate/severe OSA group. Therefore, OSA severity may have a significant impact on glycemic control in obese individuals. Additionally, OSA severity did not appear to be further associated with systemic inflammation in obese individuals. Obese individuals may benefit not only from lifestyle modification, but also from OSA screening and treatment, particularly to prevent DM-associated disorders and conditions.

Medical and Dental Students' Perception of Interdisciplinary Knowledge, Teaching Content, and Interprofessional Status at a German University: A Cross-Sectional Study.

Although oral health is considered a key indicator of overall health, dentistry is still neglected in medical education at the university level. Interprofessional education (IPE) is an important tool to promote collaboration among health care providers and to reduce barriers to access in health care. In this cross-sectional study, medical and dental students at Mainz University, Germany, were surveyed regarding their perception of interdisciplinary knowledge, teaching content, interprofessional standing, and attitudes toward IPE. Spearman's rank correlation was used to identify associated statements. Structural equation modeling (SEM) was performed to understand how sex, study progress, and prior education might influence student attitudes. In total, 426 medical students and 211 dental students were included in the study. Dental students rated their interdisciplinary knowledge higher than medical students. The relevance of IPE as assessed by the students correlated significantly with their motivation to continue IPE after graduation. Both groups of students valued the other discipline but rejected a combined graduate program. Students with prior professional training valued the synergy of medicine and dentistry more the students without prior training. Interprofessional knowledge and interest in IPE was higher among dental students. Understanding students' attitudes toward IPE is an important prerequisite for adapting university curricula to strengthen students' attitudes and motivation.

Accumulating Comorbidities May Promote Increasing Severity of Obstructive Sleep Apnea with Aging in Males but Not in Females.

Evidence suggests an increasing apnea−hypopnea index (AHI) with aging. However, the effect of aging on sleep-related metrics, especially AHI, has been less frequently investigated within different gender-specific subpopulations by taking prominent confounding factors, e.g., obstructive sleep apnea (OSA)-related comorbidities and body mass index (BMI) into account. Therefore, we retrospectively analyzed 186 first-time polysomnographic (PSG) recordings and medical files of all patients presented to a tertiary university sleep center during a 1-year period. Six groups were formed based on age (over vs. under 55 years) and gender: PSG-related parameters (AHI, apnea-index, and hypopnea-index) were significantly higher in the older mixed-gender cohort (p = 0.0001, p = 0.0011, and p = 0.0015, respectively), and the older female cohort (p = 0.0005, p = 0.0027, and p = 0.001, respectively). Within the older male cohort, the AHI and apnea-index were significantly higher (p = 0.0067, and p = 0.0135, respectively). Inter-group comparison of the BMI showed no significant difference in any subpopulation. Within the older male cohort there were significantly more patients with arterial hypertension, diabetes mellitus, cardiovascular diseases, and chronic mental health disorders (p < 0.0001, p = 0.001, p = 0.0181, and p = 0.0454, respectively). Contrarily, within the female subpopulation there were no significant differences for the aforementioned comorbidities. In conclusion, all investigated sleep PSG-parameters increased among the older subpopulations. We suggest that Osa severity may increase with age due to the increasing accumulation of comorbidities in males, but not in females.

Obstructive Sleep Apnea in Patients with Head and Neck Cancer-More than Just a Comorbidity?

Obstructive sleep apnea is the most common type of sleep-disordered breathing with growing prevalence. Its presence has been associated with poor quality of life and serious comorbidities. There is increasing evidence for coexisting obstructive sleep apnea in patients suffering from head and neck cancer, a condition that ranks among the top ten most common types of cancer worldwide. Routinely, patients with head and neck cancer are treated with surgery, radiation therapy, chemotherapy, immunotherapy or a combination of these, all possibly interfering with the anatomy of the oral cavity, pharynx or larynx. Thus, cancer treatment might worsen already existing obstructive sleep apnea or trigger its occurrence. Hypoxia, the hallmark feature of obstructive sleep apnea, has an impact on cancer biology and its cure. Early diagnosis and sufficient treatment of coexisting obstructive sleep apnea in patients with head and neck cancer may improve quality of life and could also potentially improve oncological outcomes.

A rare case of acute idiopathic colocolic intussusception in an adult patient.

Adult intussusception is a rare condition that is frequently associated with malignancy and requires surgical approach. Symptoms are often non-specific and of subacute or chronic character. Therefore, computerized tomography (CT) scan is the most commonly used modality for identifying adult intussusception. A 51-year-old female presented with a 1-day history of increasing abdominal pain. Abdominal ultrasound and CT scan revealed intussusception. Intra-operatively, colocolic intussusception was present and laparoscopically reduced. A lead point was found neither intra-operatively nor in post-operative ileocolonoscopy and resection of involved bowel segments was not necessary.

The Fibrin Cleavage Product Bß15-42 Channels Endothelial and Tubular Regeneration in the Post-acute Course During Murine Renal Ischemia Reperfusion Injury.

Early and adequate restoration of endothelial and tubular renal function is a substantial step during regeneration after ischemia reperfusion (IR) injury, occurring, e.g., in kidney transplantation, renal surgery, and sepsis. While tubular epithelial cell injury has long been of central importance, recent perception includes the renal vascular endothelium. In this regard, the fibrin cleavage product fibrinopeptide Bß15-42 mitigate IR injury by stabilizing interendothelial junctions through its affinity to VE-cadherin. Therefore, this study focused on the effect of Bß15-42 on post-acute physiological renal regeneration. For this, adult male C57BL/6 mice were exposed to a 30 min bilateral renal ischemia and reperfusion for 24 h or 48 h. Animals were randomized in a non-operative control group, two operative groups each treated with i.v. administration of either saline or Bß15-42 (2.4 mg/kg) immediately prior to reperfusion. Endothelial activation and inflammatory response was attenuated in renal tissue homogenates by single application of Bß15-42. Meanwhile, Bß15-42 did not affect acute kidney injury markers. Regarding the angiogenetic players VEGF-A, Angiopoietin-1, Angiopoietin-2, however, we observed significant higher expressions at mRNA and trend to higher protein level in Bß15-42 treated mice, compared to saline treated mice after 48 h of IR, thus pointing toward an increased angiogenetic activity. Similar dynamics were observed for the intermediate filament vimentin, the cytoprotective protein klotho, stathmin and the proliferation cellular nuclear antigen, which were significantly up-regulated at the same points in time. These results suggest a beneficial effect of anatomical contiguously located endothelial cells on tubular regeneration through stabilization of endothelial integrity. Therefore, it seems that Bß15-42 represents a novel pharmacological approach in the targeted therapy of acute renal failure in everyday clinical practice.