Prognostic factors, disease course, and treatment efficacy in Duchenne muscular dystrophy: A systematic review and meta-analysis.

INTRODUCTION/AIMS: Prognostic factors in Duchenne muscular dystrophy (DMD) predict the disease course and may help individualize patient care. The aim was to summarize the evidence on prognostic factors that may support treatment decisions. METHODS: We searched six databases for prospective studies that each included ≥50 DMD patients with a minimum follow-up of 1 y. Primary outcomes were age at loss of ambulation (LoA), pulmonary function (forced vital capacity percent of predicted, FVC%p), and heart failure. RESULTS: Out of 5074 references, 59 studies were analyzed. Corticosteroid use was associated with a delayed LoA (pooled effect hazard ratio [HR] 0.42, 95% confidence interval [CI] 0.23-0.75, I2 94%), better pulmonary function tests (higher peak FVC%, prolonged time with FVC%p > 50%, and reduced need for assisted ventilation) and delayed cardiomyopathy. Longer corticosteroid treatment was associated with later LoA (>1 y compared to <1 y; pooled HR: 0.50, 95% CI 0.27-0.90) and early treatment start (aged <5 y) may be associated with early cardiomyopathy and higher fracture risk. Genotype appeared to be an independent driver of LoA in some studies. Higher baseline physical function tests (e.g., 6-minute walk test) were associated with delayed LoA. Left ventricular dysfunction and FVC <1 L increased and the use of angiotensin-converting enzyme (ACE) inhibitors reduced the risk of heart failure and death. Fusion surgery in scoliosis may potentially preserve pulmonary function. DISCUSSION: Prognostic factors that may inform clinical decisions include age at corticosteroid treatment initiation and treatment duration, ACE-inhibitor use, baseline physical function tests, pulmonary function, and cardiac dysfunction.

Nocturnal cerebral tissue oxygenation in lowlanders with chronic obstructive pulmonary disease travelling to an altitude of 2,590 m: Data from a randomised trial.

Altitude exposure induces hypoxaemia in patients with chronic obstructive pulmonary disease (COPD), particularly during sleep. The present study tested the hypothesis in patients with COPD staying overnight at high altitude that nocturnal arterial hypoxaemia is associated with impaired cerebral tissue oxygenation (CTO). A total of 35 patients with moderate-to-severe COPD, living at <800 m (mean [SD] age 62.4 [12.3] years, forced expiratory volume in 1 s [FEV1 ] 61 [16]% predicted, awake pulse oximetry ≥92%) underwent continuous overnight monitoring of pulse oximetry (oxygen saturation [SpO2 ]) and near-infrared spectroscopy of prefrontal CTO, respectively, at 490 m and 2,590 m. Regression analysis was used to evaluate whether nocturnal arterial desaturation (COPDDesat , SpO2 <90% for >30% of night-time) at 490 m predicted CTO at 2,590 m when controlling for baseline variables. At 2,590 m, mean nocturnal SpO2 and CTO were decreased versus 490 m, mean change -8.8% (95% confidence interval [CI] -10.0 to -7.6) and -3.6% (95% CI -5.7 to -1.6), difference in change ΔCTO-ΔSpO2 5.2% (95% CI 3.0 to 7.3; p < .001). Moreover, frequent cyclic desaturations (≥4% dips/hr) occurred in SpO2 and CTO, mean change from 490 m 35.3/hr (95% CI 24.9 to 45.7) and 3.4/hr (95% CI 1.4 to 5.3), difference in change ΔCTO-ΔSpO2 -32.8/hr (95% CI -43.8 to -21.8; p < .001). Regression analysis confirmed an association of COPDDesat with lower CTO at 2,590 m (coefficient -7.6%, 95% CI -13.2 to -2.0; p = .007) when controlling for several confounders. We conclude that lowlanders with COPD staying overnight at 2,590 m experience altitude-induced hypoxaemia and periodic breathing in association with sustained and intermittent cerebral deoxygenation. Although less pronounced than the arterial deoxygenation, the altitude-induced cerebral tissue deoxygenation may represent a risk of brain dysfunction, especially in patients with COPD with nocturnal hypoxaemia at low altitude.

Altered cardiac repolarisation in highlanders with high-altitude pulmonary hypertension during wakefulness and sleep.

High-altitude pulmonary hypertension (HAPH) is an altitude-related illness associated with hypoxaemia that may promote sympathetic excitation and prolongation of the QT interval. The present case-control study tests whether QT intervals, markers of malignant cardiac arrhythmias, are prolonged in highlanders with HAPH (HAPH+) compared to healthy highlanders (HH) and healthy lowlanders (LL). The mean pulmonary artery pressure (mPAP) was measured by echocardiography in 18 HAPH+ (mPAP, 34 mmHg) and 18 HH (mPAP, 23 mmHg) at 3,250 m, and 18 LL (mPAP, 18 mmHg) at 760 m, Kyrgyzstan (p < .05 all mPAP comparisons). Groups were matched for age, sex and body mass index. Electrocardiography and pulse oximetry were continuously recorded during nocturnal polysomnography. The heart rate-adjusted QT interval, QTc, was averaged over consecutive 1-min periods. Overall, a total of 26,855 averaged 1-min beat-by-beat periods were semi-automatically analysed. In HAPH+, maximum nocturnal QTc was longer during sleep (median 456 ms) than wakefulness (432 ms, p < .05) and exceeded corresponding values in HH (437 and 419 ms) and LL (430 and 406 ms), p < .05, respectively. The duration of night-time QTc >440 ms was longer in HAPH+ (median 144 min) than HH and LL (46 and 14 min, p < .05, respectively). HAPH+ had higher night-time heart rate (median 78 beats/min) than HH and LL (66 and 65 beats/min, p < .05, respectively), lower mean nocturnal oxygen saturation than LL (88% versus 95%, p < .05) and more cyclic oxygen desaturations (median 24/hr) than HH and LL (13 and 3/hr, p < .05, respectively). In conclusion, HAPH was associated with higher night-time heart rate, hypoxaemia and longer QTc versus HH and LL, and may represent a substrate for increased risk of malignant cardiac arrhythmias.

Health Preference Measures in Patients with Obstructive Sleep Apnea Syndrome Undergoing Continuous Positive Airway Pressure Therapy: Data from a Randomized Trial.

BACKGROUND: In patients with obstructive sleep apnea syndrome (OSAS), the preference-based, health-related quality of life in terms of utility has not been extensively studied. OBJECTIVE: To address this point, we compared the performance of different instruments assessing utility in patients with OSAS undergoing continuous positive airway pressure (CPAP) therapy. MATERIALS AND METHODS: Data of 208 patients with OSAS (28 women, mean ± SE age 54.4 ± 0.7 years, apnea-hypopnea index (AHI) 51.9 ± 1.8/h, Epworth sleepiness score 13.4 ± 0.2) participating in a randomized trial of different CPAP modalities over 2 years were analyzed. Evaluations included sleep studies, Epworth sleepiness scale, and several utility instruments that measure subjective health preference on a scale ranging from 1 (most preferred and perfect health) to 0 (least preferred and very poor health). RESULTS: After 2 years of CPAP therapy, the mean ± SE AHI was 6.7 ± 1.5/h and Epworth score 7.9 ± 0.4, both p < 0.001 versus baseline. Baseline utilities and changes (95% confidence interval) after 2 years of CPAP therapy were EuroQol 5-dimensions 0.79 ± 0.01, 0.02 (0.00-0.05, p = 0.064); short-form 6-dimension medical outcome questionnaire 0.72 ± 0.01, 0.06 (0.04-0.08, p < 0.001); Euro-thermometer visual analog scale 0.70 ± 0.01, 0.09 (0.07-0.12, p < 0.001); time trade-off 0.82 ± 0.01, 0.03 (0.01-0.06, p = 0.002); and standard gamble 0.82 ± 0.01, -0.01 (-0.03 to 0.02, p = 0.712). CONCLUSION: The short-form 6-dimensions questionnaire, the Euro-thermometer, and the time trade-off instruments reflected the major clinical improvements in OSAS, while the EuroQoL 5-dimensions and standard gamble tests were not sensitive to CPAP effects. These results indicate that the evaluation of utility of a treatment for OSAS depends critically on the instrument used, which is important from an individual and societal perspective.

Right and Left Heart Function in Lowlanders with COPD at Altitude: Data from a Randomized Study.

BACKGROUND: Changes in pulmonary hemodynamics and cardiac function in patients with chronic obstructive pulmonary disease (COPD) traveling to altitude have not been assessed despite an increasing prevalence of the disease. OBJECTIVES: We hypothesized that pulmonary artery pressure (PAP) significantly increases and cardiac function deteriorates during exposure to hypobaric hypoxia as encountered by traveling to moderate altitude or air flight. METHODS: A total of 37 patients (17 female; median age [quartiles] 66 years [60; 69] with COPD GOLD grade 2-3 [FEV1 57% predicted (49; 71)]) living < 800 m underwent echocardiography in Zurich (490 m) and after 1 night at Davos Jakobshorn (2,590 m) in a randomized order of allocation. RESULTS: The transtricuspid pressure gradient increased from 23 mm Hg (18; 29) to 32 mm Hg (25; 41) (p < 0.0001; Δmedian [95% CI] 7.5 [2.0; 13.0]), the right ventricular fractional area change decreased from 45% (39; 49) to 38% (33; 43) (p = 0.002), while the heart rate and systolic blood pressure increased from 70 bpm (64; 78) to 82 bpm (70; 86) (p < 0.0001) and from 133 mm Hg (123; 141) to 136 mm Hg (126; 148) (p = 0.002), respectively, and left ventricular diastolic dysfunction was more prevalent (24-54%, p = 0.02). CONCLUSIONS: This is a first study assessing changes in pulmonary hemodynamics and cardiac function in patients with COPD during a short altitude sojourn. Despite the increase in PAP and indications of change in cardiac function, the exposure was well tolerated. None of the patients had to descend to lower altitude for symptomatic altitude-related disease.

Acquired Resistance to Bedaquiline and Delamanid in Therapy for Tuberculosis.

Treatment of multidrug-resistant Mycobacterium tuberculosis is a challenge. This letter describes the emergence of resistance to new therapies, bedaquiline and delamanid.

Autoadjusted versus fixed CPAP for obstructive sleep apnoea: a multicentre, randomised equivalence trial.

BACKGROUND: The obstructive sleep apnoea syndrome (OSAS) is conventionally treated by continuous positive airway pressure set at a fixed level (fCPAP). Automatic mask pressure adjustment (autoCPAP) is increasingly used during home therapy. We investigated whether autoCPAP is equivalent to fCPAP in improving sleepiness in patients with OSAS in the long-term. METHODS: In this multicentre equivalence trial, 208 patients with OSAS, with median Epworth sleepiness score (ESS) 13, apnoea/hypopnoea index 48.4/hour, were randomised to treatment with autoCPAP (5-15 mbar) or fCPAP (pressure set at the 90th percentile applied by autoCPAP during 2-4 weeks adaptation). Coprimary outcomes were changes in subjective and objective sleepiness from baseline to 2 years after treatment. Equivalence ranges were ±2 points in ESS and ±3 min sleep resistance time evaluated by recording responses to light signals. RESULTS: At 2 years, in the intention to treat analysis, the reduction in sleepiness versus pretreatment baseline was similar in patients using autoCPAP (n=113, mean ESS-change -6.3, 95% CI -7.1 to -5.5; sleep resistance time +8.3 min, +6.9 to +9.7) and fCPAP (n=95, mean ESS-change -6.2, 95% CI -7.0 to -5.3; sleep resistance time +6.3 min, +4.7 to +7.8). The 95% CI of difference in ESS-reduction between autoCPAP and fCPAP was -0.9 to +1.4 and the 95% CI of difference in increase in sleep resistance time was -2.6 to +1.0 min. Blood pressure reduction and OSAS-related costs were similar between groups. CONCLUSIONS: AutoCPAP and fCPAP are equivalent within prespecified ranges in improving subjective and objective sleepiness in patients with OSAS over the course of 2 years. Costs of these treatments are similar. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT00280800.

Exercise Performance of Lowlanders with COPD at 2,590 m: Data from a Randomized Trial.

BACKGROUND: Effects of hypobaric hypoxia at altitude on exercise performance of lowlanders with chronic obstructive pulmonary disease (COPD) have not been studied in detail. OBJECTIVES: To quantify changes in exercise performance and associated physiologic responses in lowlanders with COPD travelling to moderate altitude. METHODS: A total of 31 COPD patients with a median age (quartiles) of 66 years (59; 69) and FEV1 of 56% predicted (49; 69) living below 800 m performed a constant-load bicycle exercise to exhaustion at 60% of the maximal work rate at 490 m (Zurich) and at an identical work rate at 2,590 m (Davos) in randomized order. Pulmonary gas exchange, pulse oximetry (SpO2), cerebral tissue oxygenation (CTO; near-infrared spectroscopy), and middle cerebral artery peak blood flow velocity (MCAv) by Doppler ultrasound during 30 s at end exercise were compared between altitudes. RESULTS: With ascent from 490 to 2,590 m, the median endurance time (quartiles) was reduced from 500 s (256; 795) to 205 s (139; 297) by a median (95% CI) of 303 s (150-420) (p < 0.001). End exercise SpO2 decreased from 92% (89; 94) to 81% (77; 84) and CTO from 62% (56; 66) to 55% (50; 60); end exercise minute ventilation increased from 40.6 L/min (35.5; 47.8) to 47.2 L/min (39.6; 58.7) (p < 0.05; all comparisons 2,590 vs. 490 m). MCAv increased similarly from rest to end exercise at 490 m (+25% [17; 36]) and at 2,590 m (+21% [14; 30]). However, the ratio of MCAv increase to SpO2 drop during exercise decreased from +6%/% (3; 12) at 490 m to +3%/% (2; 5) at 2,590 m (p < 0.05). CONCLUSIONS: In lowlanders with COPD travelling to 2,590 m, exercise endurance is reduced by more than half compared to 490 m in association with reductions in systemic and cerebral oxygen availability.

Diagnosis, Prevention and Treatment of Stable COPD and Acute Exacerbations of COPD: The Swiss Recommendations 2018.

The Swiss National Guidelines 2013 for chronic obstructive pulmonary disease have been revised in order to acknowledge recent progress in diagnosis and management of this disease. The resulting new Swiss recommendations are based on best evidence from the literature, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2018 report and other published national guidelines. Misdiagnosis of chronic obstructive pulmonary disease is common and means that patients do not always receive optimal treatment. To improve the management of patients with chronic obstructive pulmonary disease in Switzerland, these recommendations encourage a more comprehensive assessment of patients, based on the combined assessment of symptoms, degree of airflow limitation, risk of exacerbation and the presence of comorbidities. Recommendations for evidence-based preventive measures, as well as pharmacological and non-pharmacological strategies for the management of both stable and acute exacerbations of chronic obstructive pulmonary disease are provided in this update.

Association between sleep apnoea and pulmonary hypertension in Kyrgyz highlanders.

This case-control study evaluates a possible association between high altitude pulmonary hypertension (HAPH) and sleep apnoea in people living at high altitude.Ninety highlanders living at altitudes >2500 m without excessive erythrocytosis and with normal spirometry were studied at 3250 m (Aksay, Kyrgyzstan); 34 healthy lowlanders living below 800 m were studied at 760 m (Bishkek, Kyrgyzstan). Echocardiography, polysomnography and other outcomes were assessed. Thirty-six highlanders with elevated mean pulmonary artery pressure (mPAP) >30 mmHg (31-42 mmHg by echocardiography) were designated as HAPH+. Their data were compared to that of 54 healthy highlanders (HH, mPAP 13-28 mmHg) and 34 healthy lowlanders (LL, mPAP 8-24 mmHg).The HAPH+ group (median age 52 years (interquartile range 47-59) had a higher apnoea-hypopnoea index (AHI) of 33.8 events·h-1 (26.9-54.6) and spent a greater percentage of the night-time with an oxygen saturation <90% (T<90; 78% (61-89)) than the HH group (median age 39 years (32-48), AHI 9.0 events·h-1 (3.6-16), T<90 33% (10-69)) and the LL group (median age 40 years (30-47), AHI 4.3 events·h-1 (1.4-12.6), T<90 0% (0-0)); p<0.007 for AHI and T<90, respectively, in HAPH+ versus others. In highlanders, multivariable regression analysis confirmed an independent association between mPAP and both AHI and T<90, when controlled for age, gender and body mass index.Pulmonary hypertension in highlanders is associated with sleep apnoea and hypoxaemia even when adjusted for age, gender and body mass index, suggesting pathophysiologic interactions between pulmonary haemodynamics and sleep apnoea.

Mechanisms of Improved Exercise Performance under Hyperoxia.

BACKGROUND: The impact of hyperoxia on exercise limitation is still incompletely understood. OBJECTIVES: We investigated to which extent breathing hyperoxia enhances the exercise performance of healthy subjects and which physiologic mechanisms are involved. METHODS: A total of 32 healthy volunteers (43 ± 15 years, 12 women) performed 4 bicycle exercise tests to exhaustion with ramp and constant-load protocols (at 75% of the maximal workload [Wmax] on FiO2 0.21) on separate occasions while breathing ambient (FiO2 0.21) or oxygen-enriched air (FiO2 0.50) in a random, blinded order. Workload, endurance, gas exchange, pulse oximetry (SpO2), and cerebral (CTO) and quadriceps muscle tissue oxygenation (QMTO) were measured. RESULTS: During the final 15 s of ramp exercising with FiO2 0.50, Wmax (mean ± SD 270 ± 80 W), SpO2 (99 ± 1%), and CTO (67 ± 9%) were higher and the Borg CR10 Scale dyspnea score was lower (4.8 ± 2.2) than the corresponding values with FiO2 0.21 (Wmax 257 ± 76 W, SpO2 96 ± 3%, CTO 61 ± 9%, and Borg CR10 Scale dyspnea score 5.7 ± 2.6, p < 0.05, all comparisons). In constant-load exercising with FiO2 0.50, endurance was longer than with FiO2 0.21 (16 min 22 s ± 7 min 39 s vs. 10 min 47 s ± 5 min 58 s). With FiO2 0.50, SpO2 (99 ± 0%) and QMTO (69 ± 8%) were higher than the corresponding isotime values to end-exercise with FiO2 0.21 (SpO2 96 ± 4%, QMTO 66 ± 9%), while minute ventilation was lower in hyperoxia (82 ± 18 vs. 93 ± 23 L/min, p < 0.05, all comparisons). CONCLUSION: In healthy subjects, hyperoxia increased maximal power output and endurance. It improved arterial, cerebral, and muscle tissue oxygenation, while minute ventilation and dyspnea perception were reduced. The findings suggest that hyperoxia enhanced cycling performance through a more efficient pulmonary gas exchange and a greater availability of oxygen to muscles and the brain (cerebral motor and sensory neurons).

Effect of rituximab on pulmonary function in patients with rheumatoid arthritis.

BACKGROUND: Rituximab (RTX), a B-cell depleting monoclonal antibody is increasingly used in several antibody-mediated diseases. It has been reported to cause pulmonary toxicity, though mainly during polychemotherapy of malignant lymphoma. Prospective data on RTX-induced pulmonary complications in patients with rheumatoid arthritis (RA) are lacking. METHODS AND METHODS: Serial spirometries and measurements of diffusion capacity of the lung for carbon monoxide (DLCO) in patients with RA before and 2, 4, 8, and 26 weeks after treatment with RTX were performed. A reduction from baseline of forced vital capacity (FVC) of ≥10%, or ≥15% of DLCO was defined as indicative for pulmonary toxicity. RESULTS: Thirty-three patients (mean (SD) age 59 (12) years, 27% males) were included. Mean (SD) FVC predicted and DLCO predicted at baseline were 108% (18%) and 88% (18%), respectively. In contrast to FVC, DLCO showed a progressive decline during follow-up with a maximum reduction of 6.1% (95%CI 2.5%, 9.7%; p = 0.001) at 26 weeks compared with baseline. After 26 weeks, 22% of the patients had a ≥15% DLCO decline. None of the patients reported increased dyspnea during follow-up. Risk factors for pulmonary function changes after treatment with RTX were cigarette smoking, repeated administration of the drug, and co-medication with Prednisone. CONCLUSION: Although no cases of symptomatic lung injury were observed, the progressive DLCO decline seems to indicate the presence of subclinical RTX-induced pulmonary toxicity.

Sleep respiratory disturbances and arousals at moderate altitude have overlapping electroencephalogram spectral signatures.

An ascent to altitude has been shown to result in more central apneas and a shift towards lighter sleep in healthy individuals. This study employs spectral analysis to investigate the impact of respiratory disturbances (central/obstructive apnea and hypopnea or periodic breathing) at moderate altitude on the sleep electroencephalogram (EEG) and to compare EEG changes resulting from respiratory disturbances and arousals. Data were collected from 51 healthy male subjects who spent 1 night at moderate altitude (2590 m). Power density spectra of Stage 2 sleep were calculated in a subset (20) of these participants with sufficient artefact-free data for (a) epochs with respiratory events without an accompanying arousal, (b) epochs containing an arousal and (c) epochs of undisturbed Stage 2 sleep containing neither arousal nor respiratory events. Both arousals and respiratory disturbances resulted in reduced power in the delta, theta and spindle frequency range and increased beta power compared to undisturbed sleep. The similarity of the EEG changes resulting from altitude-induced respiratory disturbances and arousals indicates that central apneas are associated with micro-arousals, not apparent by visual inspection of the EEG. Our findings may have implications for sleep in patients and mountain tourists with central apneas and suggest that respiratory disturbances not accompanied by an arousal may, none the less, impact sleep quality and impair recuperative processes associated with sleep more than previously believed.

Severe metabolic acidosis in adult patients with Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) leads to progressive paresis, respiratory failure and premature death. Long-term positive pressure ventilation can improve quality of life and survival, but previously unrecognized complications may arise. We analyzed the characteristics of severe metabolic acidosis occurring in 8 of 55 DMD patients, of 20-36 years of age, observed over a 5-year period. All patients were on positive pressure ventilation and were being treated for chronic constipation. Before admission, they had had a reduced intake of fluids and food. Upon examination, they were severely ill, dyspneic and suffering from abdominal discomfort. Metabolic acidosis with a high anion gap was noted in 5 of the 8 patients and with a normal anion gap in the other 3. They all recovered after the administration of fluids and nutrition, the regulation of bowel movements and treatment with antibiotics, as appropriate. Metabolic acidosis is a life-threatening, potentially preventable complication in older DMD patients. Early recognition, subsequent administration of fluids, nutrition and antibiotics and regulation of bowel movements seem to be essential.

Circulating levels of cell-derived microparticles are reduced by mild hypobaric hypoxia: data from a randomised controlled trial.

PURPOSE: Hypoxia is known to induce the release of microparticles in vitro. However, few publications have addressed the role of hypoxia in vivo on circulating levels of microparticles. This randomised, controlled, crossover trial aimed to determine the effect of mild hypoxia on in vivo levels of circulating microparticles in healthy individuals. METHODS: Blood was obtained from 51 healthy male volunteers (mean age of 26.9 years) at baseline altitude (490 m) and after 24 and 48 h at moderate altitude (2,590 m). The order of altitude exposure was randomised. Flow cytometry was used to assess platelet-poor plasma for levels of circulating microparticles derived from platelets, endothelial cells, leucocytes, granulocytes, monocytes, red blood cells and procoagulant microparticles. RESULTS: Mean (standard deviation) oxygen saturation was significantly lower on the first and second day after arrival at 2,590 m, 91.0 (2.0) and 92.0 (2.0) %, respectively, compared to 490 m, 96 (1.0) %, p < 0.001 for both comparisons. A significant decrease in the levels of procoagulant microparticles (annexin V+ -221/µl 95 % CI -370.8/-119.0, lactadherin+ -202/µl 95 % CI -372.2/-93.1), platelet-derived microparticles (-114/µl 95 % CI -189.9/-51.0) and red blood cell-derived microparticles (-81.4 µl 95 % CI -109.9/-57.7) after 48 h at moderate altitude was found. Microparticles derived from endothelial cells, granulocytes, monocytes and leucocytes were not significantly altered by exposure to moderate altitude. CONCLUSIONS: In healthy male individuals, mild hypobaric hypoxia, induced by a short-term stay at moderate altitude, is associated with lower levels of procoagulant microparticles, platelet-derived microparticles and red blood cell-derived microparticles, suggesting a reduction in thrombotic potential.

[New manifestation of a type 2-inflammation in the upper respiratory tract with nasal polyposis under treatment with an asthma biologic]. / Neumanifestation einer Typ-2-Inflammation im Bereich der oberen Atemwege mit Polyposis nasi unter einem Asthmabiologikum.

INTRODUCTION: For 7 years we gained experience of how asthma and chronic rhinosinusitis with nasal polyposis respond to biologics. In contrast, it is much less known, how ASA/NSAID intolerance (Widal's disease) behaves under biologicals. We therefore describe the case of a patient with both clinical conditions who reacted with a severe intolerance reaction under perioperative metamizole administration.

Sleep medicine in the Kyrgyz Republic: past, present, and future.

STUDY OBJECTIVES: As in many other Low and Middle Income Countries (LMICs) around the world, sleep disorders in the Kyrgyz Republic remain mostly undiagnosed and untreated. This article aims to describe the current state of practice of sleep medicine in the Kyrgyz Republic from the perspective of local and international health care workers who are active in the field and to propose a strategy to challenge the status quo. METHODS: We performed a policy analysis and interviewed local doctors working in the field. RESULTS: We identified 3 major barriers to the practice of sleep medicine and namely education and training, financial constraints and infrastructure and equipment. We then propose a multistep strategy to improve the current situation based on 3 pillars: knowledge sharing, implementation research activities and policy changes. CONCLUSIONS: Despite being at its early days and facing major challenges, sleep health in the Kyrgyz Republic is being recognized as a priority by health care workers in the field and now requires attention at local and government level. Furthermore, north-south academic partnerships represent an effective tool for knowledge sharing and should be further incentivised. CITATION: Cirri L, Bolotbek uulu A, Shakiev N, et al. Sleep medicine in the Kyrgyz Republic: past, present, and future. J Clin Sleep Med. 2024;20(7):1213-1216.

Artificial intelligence (AI)-assisted chest computer tomography (CT) insights: a study on intensive care unit (ICU) admittance trends in 78 coronavirus disease 2019 (COVID-19) patients.

Background: The global coronavirus disease 2019 (COVID-19) pandemic has posed substantial challenges for healthcare systems, notably the increased demand for chest computed tomography (CT) scans, which lack automated analysis. Our study addresses this by utilizing artificial intelligence-supported automated computer analysis to investigate lung involvement distribution and extent in COVID-19 patients. Additionally, we explore the association between lung involvement and intensive care unit (ICU) admission, while also comparing computer analysis performance with expert radiologists' assessments. Methods: A total of 81 patients from an open-source COVID database with confirmed COVID-19 infection were included in the study. Three patients were excluded. Lung involvement was assessed in 78 patients using CT scans, and the extent of infiltration and collapse was quantified across various lung lobes and regions. The associations between lung involvement and ICU admission were analysed. Additionally, the computer analysis of COVID-19 involvement was compared against a human rating provided by radiological experts. Results: The results showed a higher degree of infiltration and collapse in the lower lobes compared to the upper lobes (P<0.05). No significant difference was detected in the COVID-19-related involvement of the left and right lower lobes. The right middle lobe demonstrated lower involvement compared to the right lower lobes (P<0.05). When examining the regions, significantly more COVID-19 involvement was found when comparing the posterior vs. the anterior halves and the lower vs. the upper half of the lungs. Patients, who required ICU admission during their treatment exhibited significantly higher COVID-19 involvement in their lung parenchyma according to computer analysis, compared to patients who remained in general wards. Patients with more than 40% COVID-19 involvement were almost exclusively treated in intensive care. A high correlation was observed between computer detection of COVID-19 affections and the rating by radiological experts. Conclusions: The findings suggest that the extent of lung involvement, particularly in the lower lobes, dorsal lungs, and lower half of the lungs, may be associated with the need for ICU admission in patients with COVID-19. Computer analysis showed a high correlation with expert rating, highlighting its potential utility in clinical settings for assessing lung involvement. This information may help guide clinical decision-making and resource allocation during ongoing or future pandemics. Further studies with larger sample sizes are warranted to validate these findings.

Does venous blood gas analysis provide accurate estimates of hemoglobin oxygen affinity?

Alterations in hemoglobin oxygen affinity can be detected by exposing blood to different PO2 and recording oxygen saturation, a method termed tonometry. It is the gold standard to measure the PO2 associated with 50 % oxygen saturation, the index used to quantify oxygen affinity (P50Tono). P50Tono is used in the evaluation of patients with erythrocytosis suspected to have hemoglobin with abnormal oxygen affinity. Since tonometry is labor intensive and not generally available, we investigated whether accurate estimates of P50 could also be obtained by venous blood gas analysis, co-oximetry, and standard equations (P50Ven). In 50 patients referred for evaluation of erythrocytosis, pH, PO2, and oxygen saturation were measured in venous blood to estimate P50Ven; P50Tono was measured for comparison. Agreement among P50Ven and P50Tono was evaluated (Bland-Altman analysis). Mean P50Tono was 25.8 (range 17.4-34.1) mmHg. The mean difference (bias) of P50Tono-P50Ven was 0.5 mmHg; limits of agreement (95 % confidence limits) were -5.2 to +6.1 mmHg. The sensitivity and specificity of P50Ven to identify the 25 patients with P50Tono outside the normal range of 22.9-26.8 mmHg were 5 and 77 %, respectively. We conclude that estimates of P50 based on venous blood gas analysis and standard equations have a low bias compared to tonometry. However, the precision of P50Ven is not sufficiently high to replace P50Tono in the evaluation of individual patients with suspected disturbances of hemoglobin oxygen affinity.

["Literally torn apart by coughing"]. / "Vom Husten buchstäblich zerrissen".

The present case reports on a 53-year-old patient with severe chronic obstructive pulmonary disease (COPD) and acute pneumonia who complained of massive right-sided chest pain and hemoptysis after a severe coughing fit. To the authors' great surprise, further clinical and radiological investigations revealed a rupture of the right intercostal muscles caused by the coughing fit, with herniation of parts of the right lower lobe of the lung down to the subcutaneous and below the M. latissimus dorsi. The patient was presented to the colleagues in thoracic surgery and needed to be operated twice, finally with a mesh insert.