[Pathophysiology, diagnosis, prognosis and treatment of pulmonary hypertension associated with chronic lung disease]. / Pulmonale Hypertonie bei Lungenerkrankungen und/oder Hypoxie.

The pathophysiology of pulmonary hypertension associated with chronic lung disease (PH-CLD) is complex, multifactorial, and not consistent among pulmonary diseases. However, pulmonary vasculopathy triggered by various factors, such as chronic alveolar hypoxia or cigarette smoking, seems to play a central role in the pathogenesis of PH-CLD. While the initial workup of PH-CLD is usually complicated by an overlap of symptoms of PH and the underlying lung disease, PH-CLD should be considered when there is a discrepancy between symptoms (especially exertional dyspnea) and pulmonary function tests. Clinical suspicion of PH-CLD can be strengthened by noninvasive diagnostic tools such as transthoracic echocardiography (TTE) or N-terminal pro-B-type natriuretic peptide (NT-pro-BNP). However, a right heart catheterization should only be performed in specialized centers to establish the diagnosis if therapeutic consequences for the patient were expected.The basic treatment of PH-CLD is optimal management of the underlying lung disease. Among the existing interventional and registry-based studies, only a small number of data suggests favorable outcomes when treating PH-CLD patients with PAH-specific medications. Some publications even suggest negative effects. Nevertheless, recent data on inhaled vasoactive therapy in PH-CLD showed positive results for inhaled Treprostinil, although long-term data for this therapeutic approach are still lacking. Treatment of PH-CLD patients with PAH-specific drugs should only be performed in specialized centers and preferably in the context of clinical trials.

Eight Patients With Pilonidal Carcinoma in One Decade-Is the Incidence Rising?

INTRODUCTION: Carcinoma secondary to pilonidal disease is very rare with fewer than 130 reported cases so far. It is presumed that underreporting and underpublishing contribute to the low reported incidence. METHODS: A post was published on a closed Facebook group with about 30,000 Syrian doctors asking if anyone had ever seen a patient with pilonidal carcinoma before. The patients' data were collected retrospectively from the treating physicians. RESULTS: Between 2010 and 2019, we identified eight patients with pilonidal carcinoma. All patients were males with a mean age of 55.5 years. The mean interval between diagnosis of pilonidal disease and diagnosis of carcinoma was 6.9 years. A growing ulcer on the background of a pilonidal sinus disease was the presenting complaint in 50% of cases. Three patients were lost from follow-up after the diagnosis due to referral. All other five patients underwent surgical resection and three of them received postoperative chemoradiation. Four patients were followed for six months or longer: two died of metastases, one survived after recurrence and re-excision, and one survived with no recurrence. CONCLUSION: This paper presents the largest cohort of pilonidal carcinoma so far and the first that describes the disease in the Syrian population. Due to underreporting, the real incidence of pilonidal carcinoma exceeds what is reported so far in the literature.

Mathematical Arterialization of Capillary Blood for Blood Gas Analysis in Critically Ill Patients.

BACKGROUND: In clinical practice, capillary blood taken from hyperemized earlobes (CBGE) or fingertips (CBGF) is frequently used as substitute for arterial blood (ABG) for blood gas analysis. While there is a close agreement between ABG and CBGE/CBGF regarding pH and pCO2, pO2 is often underestimated by CBG. Recently, a software tool (v-TAC®; Roche Diagnostics, Risch-Rotkreuz, Switzerland) has been developed to calculate ABG values based on a peripheral venous blood gas analysis supplemented with peripheral oxygen saturation. OBJECTIVE: Here we investigate whether v-TAC can also be used to calculate ABG values from capillary blood samples. METHODS: Patients (n = 85) with an indwelling arterial line were included in the study. A reference ABG sample (ABG1) was obtained, followed by CBGE, CBGF, and finally a second ABG (ABG2). Results of CBGE/CBGF before and after mathematical arterialization by v-TAC (aCBGE/aCBGF) were compared to ABG1. RESULTS: After mathematical arterialization by v-TAC, the mean bias in pO2 between ABG1 and CBGE went down from 5.24 mm Hg (95% limit of agreement [95% LoA]: -14.19 to 24.67) to 0.18 mm Hg (95% LoA: -11.84 to 12.20) and was in a similar range as the mean bias between ABG1 and ABG2 (0.39 mm Hg [95% LoA: -13.46 to 14.24]). Differences in pH and pCO2 between arterial and capillary samples were small before and after mathematical arterialization. Very similar results were obtained when using fingertip instead of earlobe capillary blood. CONCLUSION: In summary, v-TAC can be used for mathematical arterialization of capillary blood samples for blood gas analysis resulting in increased diagnostic accuracy for pO2.

Successful treatment of prolonged COVID-19 with Bamlanivimab in a patient with severe B-Cell aplasia due to treatment with an anti-CD20 monoclonal antibody: A case report.

A 71-year-old female patient with B-cell depletion due to treatment with an anti-CD20 monoclonal antibody was admitted for worsening COVID-19. Overall, she had persistent viral shedding, worsening respiratory failure, and progressive pneumonia that did not improve despite dexamethasone and antibiotic therapy. After administration of bamlanivimab, a monoclonal antibody with high affinity for the receptor-binding domain of the SARS-CoV-2 spike protein, inflammatory markers rapidly decreased, SARS-CoV2 RT-PCR became negative, and the patient improved clinically and radiologically. In conclusion, we demonstrated successful treatment of prolonged COVID-19 in a patient with severe B-cell aplasia with a virus-neutralizing monoclonal antibody.

Effects of Transcatheter Mitral Valve Repair Using MitraClip® Device on Sleep Disordered Breathing in Patients with Mitral Valve Regurgitation.

Sleep disordered breathing (SDB) is common among patients with valvular heart disease, and successful valve surgery could reduce SDB severity. However, data about the effects of transcatheter mitral valve repair on SDB are scarce. Therefore, mitral regurgitation (MR) patients undergoing MitraClip-placement were prospectively enrolled. Before MitraClip-placement, daytime sleepiness and sleep quality were assessed using the Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI), respectively; and all patients underwent SDB screening using five-channel respiratory polygraphy. After 3-6 months, patients had a similar reassessment including: ESS, PSQI, and respiratory polygraphy. 67 patients were included (77 ± 8years). Despite normal sleepiness scores, 41 patients (61%) had SDB with apnea-hypopnea-index (AHI) ≥ 15 h before MitraClip-placement, of whom only three patients had known SDB previously. Compared to patients without SDB, patients with SDB had similar sleepiness scores but higher NT-proBNP values at baseline (4325 vs. 1520 pg/mL, p < 0.001). At follow-up, there were significant AHI improvements among patients with SDB (p = 0.013). However, there were no significant sleepiness score changes. In conclusion, the prevalence of SDB among MitraClip candidates is very high even in those without daytime sleepiness. MR patients with SDB have higher NT-proBNP values, which may reflect a worse prognosis. MitraClip-placement may improve the underlying SDB, which could be an additional benefit of the procedure.

Early risk markers for severe clinical course and fatal outcome in German patients with COVID-19.

BACKGROUND: Some patients with Corona Virus Disease 2019 (COVID-19) develop a severe clinical course with acute respiratory distress syndrome (ARDS) and fatal outcome. Clinical manifestations and biomarkers in early stages of disease with relevant predictive impact for outcomes remain largely unexplored. We aimed to identify parameters which are significantly different between subgroups. DESIGN: 125 patients with COVID-19 were analysed. Patients with ARDS (N = 59) or non-ARDS (N = 66) were compared, as well as fatal outcome versus survival in the two groups. KEY RESULTS: ARDS and non-ARDS patients did not differ with respect to comorbidities or medication on developing a fatal outcome versus survival. Body mass index was higher in patients with ARDS versus non-ARDS (p = 0.01), but not different within the groups in survivors versus non-survivors. Interleukin-6 levels on admission were higher in patients with ARDS compared to non-ARDS as well as in patients with fatal outcome versus survivors, whereas lymphocyte levels were lower in the different subgroups (all p<0.05). There was a highly significant 3.5-fold difference in fever load in non-survivors compared to survivors (p<0.0001). Extrapulmonary viral spread was detected more often in patients with fatal outcome compared to survivors (P = 0.01). Further the detection of SARS-CoV-2 in serum showed a significantly more severe course and an increased risk of death (both p<0.05). CONCLUSIONS: We have identified early risk markers for a severe clinical course, like ARDS or fatal outcome. This data might help develop a strategy to address new therapeutic options early in patients with COVID-19 and at high risk for fatal outcome.

The bidirectional relationship between chronic obstructive pulmonary disease and coronary artery disease.

Chronic obstructive pulmonary disease (COPD) and coronary artery disease (CAD) not only have smoking as a common risk factor, they also share epidemiological relationships and important mutual effects. There is good evidence to suggest that COPD is highly prevalent but underdiagnosed among CAD patients and vice versa. The symptoms of the two diseases can overlap, making differential diagnosis challenging. This highlights the importance of pulmonary function tests (PFTs) in patients with CAD but also a cardiological assessment in patients with COPD. Chronic obstructive pulmonary disease is a risk factor for the development of CAD independent of other cardiovascular risk factors, and the presence of COPD worsens prognosis in patients with CAD. Mechanisms underlying the associations between COPD and CAD have been less well studied, but inflammation is increasingly being recognized as an important factor linking the two diseases. Other potential contributors include increased oxidative stress, platelet activation, and arterial stiffness. The influence of medications used to treat one condition on the other one needs to be understood and taken into account in patient management. Physicians need to be aware of the important links between COPD and CAD, both of which are commonly encountered in clinical practice. This should help to optimize the management of both conditions to improve patient outcomes.

Characterization and Triggers of Dyspnea in Patients with Chronic Obstructive Pulmonary Disease or Chronic Heart Failure: Effects of Weather and Environment.

BACKGROUND AND OBJECTIVES: Dyspnea is one of the most disturbing symptoms for patients with chronic obstructive pulmonary disease (COPD) or heart failure (HF). This study investigated dyspnea triggers and factors associated with worsening dyspnea in patients with COPD or HF. METHODS: COPD support group members and HF patients with reduced ejection fraction (HFrEF) and no airway obstruction answered a questionnaire describing different weather conditions (rising/falling air pressure, sunny, foggy, rainy, windy, snowy, hazy, high ozone levels, and airborne pollen) and environmental circumstances (cooking, grilling, perfumes, cigarette smoke, gasoline odor, and flower scents) and were asked to estimate the occurrence and severity of dyspnea under these conditions using predefined scales. RESULTS: 230 patients with COPD and 90 with HFrEF (left ventricular ejection fraction 34 ± 10%, Tiffeneau index > 70%) were analyzed. COPD patients reported dyspnea more often than HF patients in almost all weather and environmental conditions (p = 0.004 to p < 0.001), with the exception of outdoor floral scents and cigarette smoke. Severe to very severe dyspnea was reported more in COPD versus HF in all weather and environmental conditions except sunny weather (p = 0.01 to p < 0.001). COPD was associated with more severe dyspnea than HF in all conditions (all p < 0.001). CONCLUSIONS: Dyspnea was triggered by a variety of weather and other environmental triggers in patients with COPD and occurred more often than in HF patients under the same conditions. Foggy weather and exposure to perfumes were associated with severe dyspnea in the majority of COPD patients, but only a minority of HF patients.

Whole-Body Plethysmography and Blood Gas Analysis in Patients with Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and coronary heart disease (CHD) often occur together. However, COPD is underdiagnosed among CHD patients. OBJECTIVES: This study investigated the prevalence of COPD and relevant pulmonary function test (PFT) impairments in patients with acute myocardial infarction (AMI). METHODS: Patients undergoing coronary angiography for AMI were prospectively included. Body plethysmography, lung diffusing capacity, blood gas analysis, and echocardiography were performed. The following patient subgroups were compared: with versus without COPD, ST elevation myocardial infarction (STEMI) versus non-STEMI (NSTEMI). The prevalence of PFT impairments was also recorded. RESULTS: A total of 100 patients (51 with NSTEMI, 49 with STEMI) were included. Twenty patients had diagnosed COPD, of whom 15 were diagnosed for the first time; 80% of all COPD patients were not receiving COPD therapy. Patients with COPD had higher maximum creatine kinase (p = 0.008) and troponin T (p = 0.054) levels than those without COPD. Hypoxaemia was more common in COPD patients (lower oxygen saturation [p = 0.008] and partial pressure of oxygen [PaO2] [p = 0.005]). PaO2 was significantly lower in STEMI compared with NSTEMI (p = 0.017). Independent of a COPD diagnosis, 65 patients had relevant PFT impairments. CONCLUSIONS: The high prevalence of undiagnosed COPD and relevant pulmonary function impairments in this cohort of patients with AMI, and the fact that pulmonary disease was untreated in the majority of COPD patients, highlight the importance of a general pulmonary workup of patients with AMI. Furthermore, patients with CHD should undergo screening for COPD, given the fact that COPD patients had larger infarction size.

Serum phosphate and phosphate-regulatory hormones in COPD patients.

BACKGROUND: Fibroblast growth factor 23 (FGF23) regulates phosphate metabolism by increasing renal phosphate excretion and decreasing 1.25-dihydroxyvitamin D synthesis. Reports about hypophosphatemia in patients with chronic obstructive pulmonary disease (COPD) suggest altered phosphate metabolism. Therefore, we hypothesized that disturbances in phosphate-regulatory hormones such as FGF23 and parathyroid hormone (PTH) are present in COPD patients. METHODS: We investigated 40 COPD patients (63.5 ± 9.9 years, 27 male), each matched with two age- and sex-matched controls without any primary lung disease. COPD patients underwent lung function testing in advance. All patients had a glomerular filtration rate (GFR) > 60 mL/min/1.73m2. We measured concentrations of intact FGF23 (iFGF23) and c-terminal FGF23 (c-term FGF23), phosphate, parathyroid hormone (PTH) and C-reactive protein (CRP) levels in COPD patients and controls. RESULTS: Phosphate (1.0 ± 02 vs. 1.1 ± 0.2 mmol/L; p = 0.027), PTH (54.2 ± 29.4 vs. 68.7 ± 31.8 pg/mL; p = 0.002) and iFGF23 (46.3 ± 29.0 vs. 57.5 ± 33.5 pg/mL; p = 0.026 ) levels were significantly lower in COPD patients compared with controls. There was a significant negative correlation between c-term FGF23 and total lung capacity (r = - 0.4; p = 0.01), and between c-term FGF23 and CRP in COPD patients (r = 0.48; p = 0.002). iFGF23 and c-term FGF23 were positively correlated with phosphate and PTH in the control group. CONCLUSION: We confirmed lower average serum phosphate levels in COPD patients compared with controls. However, our data do not suggest a causative role for FGF23 or PTH in COPD because levels of both phosphate-lowering hormones appear to be adaptively decreased as well. Therefore, further investigations are needed to identify the pathogenesis of low phosphate levels in patients with COPD and the relationship between phosphate-regulatory hormones and disease progression.