Thomas Brack

Disability and survival in Duchenne muscular dystrophy

Background: Duchenne muscular dystrophy (DMD) leads to progressive impairment of muscle function, respiratory failure and premature death. Longitudinal data on the course of physical disability and respiratory function are sparse. Objectives: To assess prospectively physical impairment and disability, respiratory function and survival in patients with DMD over several years to describe the course of the disease with current care. Methods: In 43 patients with DMD, aged 5–35 years, yearly assessments of physical disability by the Duchenne muscular dystrophy physical Impairment and Dependence on care (DID) score, ranging from 9 (no disability) to 80 (complete dependence), and forced vital capacity (FVC), were obtained over a mean time interval of 5.4 (SD 2.1) years. Results: DID scores were correlated with age according to a hyperbolic function (f = 85.3×age/(10.05+age), R = 0.62, p<0.0001). FVC declined exponentially with age (f = 139.1×exp(−0.08×age), R = 0.52, p<0.0001). Mean age at which patients lost their ambulation was 9.4 (SD 2.4) years and they became dependent on an electric wheelchair at 14.6 (4.0) years. Age at the beginning of assisted ventilation was 19.8 (3.9) years, Three patients died during the observation period. The estimated probability of survival to age 30 years was 85% (median survival was 35 years). Conclusions: Our detailed observations of the progression of physical disability, dependence on care and respiratory impairment in patients with DMD from childhood to adult life is valuable for predicting the clinical course with current medical care. Compared with historical data, survival has improved considerably.

Bronchoscopic radioisotope injection for sentinel lymph-node mapping in potentially resectable non-small-cell lung cancer

OBJECTIVE Prospective study to evaluate the feasibility of a preoperative bronchoscopic radioisotope application, followed by conventional sentinel lymph-node (SLN) identification and to investigate the occurrence and distribution of micrometastases in relation to SLN activity. METHODS Twenty patients with a mean age of 63 years and proven clinical stage T1-3 N0-1 non-small-cell lung cancer (NSCLC) were included. A dosage of 80MBq radiolabeled technetium-99m nanocolloid was endoscopically administrated on intubated patients in the operation theatre. At thoracotomy, scintigraphic readings of both the primary tumor and hilar and mediastinal lymph-node stations were obtained with a hand-held gamma-counter. Patients underwent lung resection and mediastinal lymphadenectomy. Radiolabeled nodes were also examined separately on back-table. SLNs were defined as the hottest nodes or nodes with at least one-tenth of the radioactivity of the hottest nodes. SLNs pathologic assessment included standard examination using hematoxylin and eosin staining on step sections and immunohistochemistry (ICH) for cytokeratins. RESULTS Identification of SLNs was possible in 19/20 (95%) patients after bronchoscopic radioisotope application. In 7/19 (37%) patients, a unique SLN was identified, whereas in 12/19 (63%) patients, nodes from two different stations could be classified as SLNs. Metastatic nodal disease was found in 9/19 (47%) patients. ICH revealed micrometastases in 2/12 (17%) patients, initially classified nodal negative. Pathologic negative SLNs were a predictor for absence of metastatic nodal disease after mediastinal lymphadenectomy. No complication related to the procedure was observed. CONCLUSION Our preliminary results suggest that preoperative bronchoscopic radioisotope injection for SLN identification is a safe and simple method, improving accuracy of SLN detection in comparison to intraoperative technique. The absence of metastases in the SLNs seems to predict a negative nodal status accurately.

Cheyne-Stokes Respiration in Patients with Heart Failure: Prevalence, Causes, Consequences and Treatments

Cheyne-Stokes respiration (CSR) is characterized by a pattern of cyclic oscillations of tidal volume and respiratory rate with periods of hyperpnea alternating with hypopnea or apnea in patients with heart failure. CSR harms the failing heart through intermittent hypoxia brought about by apnea and hypopnea and recurrent sympathetic surges. CSR impairs the quality of life and increases cardiac mortality in patients with heart failure. Thus, CSR should actively be pursued in patients with severe heart failure. When CSR persists despite optimal therapy of heart failure, noninvasive adaptive servoventilation is currently the most promising treatment.

Definition, discrimination, diagnosis and treatment of central breathing disturbances during sleep

The complexity of central breathing disturbances during sleep has become increasingly obvious. They present as central sleep apnoeas (CSAs) and hypopnoeas, periodic breathing with apnoeas, or irregular breathing in patients with cardiovascular, other internal or neurological disorders, and can emerge under positive airway pressure treatment or opioid use, or at high altitude. As yet, there is insufficient knowledge on the clinical features, pathophysiological background and consecutive algorithms for stepped-care treatment. Most recently, it has been discussed intensively if CSA in heart failure is a “marker” of disease severity or a “mediator” of disease progression, and if and which type of positive airway pressure therapy is indicated. In addition, disturbances of respiratory drive or the translation of central impulses may result in hypoventilation, associated with cerebral or neuromuscular diseases, or severe diseases of lung or thorax. These statements report the results of an European Respiratory Society Task Force addressing actual diagnostic and therapeutic standards. The statements are based on a systematic review of the literature and a systematic two-step decision process. Although the Task Force does not make recommendations, it describes its current practice of treatment of CSA in heart failure and hypoventilation. Description of the actual approach to differential diagnosis and treatment options in central breathing disturbances http://ow.ly/QsE9304Jt8f

Hermansky-Pudlak syndrome type 4 in a patient from Sri Lanka with pulmonary fibrosis

Hermansky–Pudlak syndrome (HPS) is a rare autosomal recessive disorder characterized by oculocutaneous albinism and a platelet storage pool deficiency. Some patients also develop fatal pulmonary fibrosis and some have granulomatous colitis. Six human genes HPS1, ADB3A, HPS3, HPS4, HPS5, and HPS6 have been identified as cause of the six known subtypes of HPS. While there exist nearly 500 Puerto Rican and non‐Puerto Rican HPS‐1 patients, very few HPS‐4 patients have been reported, and most of these have not been described in detail. We now delineate the clinical characteristics of an HPS‐4 patient homozygous for a novel HPS‐4 mutation, P685delC. The patient, the first individual with HPS reported from Sri Lanka, had severe pulmonary fibrosis, typical of HPS‐1 disease, without granulomatous colitis. We conclude that pulmonary fibrosis occurs as part of HPS‐4 and that HPS should be considered in all ethnic groups.

Diffuse Idiopathic Neuroendocrine Cell Hyperplasia Causing Severe Airway Obstruction in a Patient with a Carcinoid Tumor

We report a 57-year-old female with severe airway obstruction who underwent resection of a tumor of unknown dignity during lung volume reduction surgery. The nodule consisted of a well-differentiated neuroendocrine tumor (carcinoid), and severe chronic obstructive lung disease was due to diffuse idiopathic pulmonary neuroendocrine cell hyperplasia, a very rare cause of obliterative bronchiolitis. Radionuclide ablative therapy of the neuroendocrine tissue was considered but not found to be feasible due to a low lung/background ratio of the radiotracer.

Impact of comorbidities on physical activity in COPD.

Both comorbidities and physical inactivity have been shown to impair quality of life and contribute to hospital admissions and mortality in chronic obstructive pulmonary disease (COPD) patients. We hypothesized that the comorbid status predicts the level of daily physical activity (PA) in COPD.

Periodic whole body acceleration: a novel therapy for cardiovascular disease.

BACKGROUND Periodic whole body acceleration in the spinal axis (pGz) applied by a motion platform is a novel treatment modality that induced endothelial nitric oxide release into the circulation of animals, healthy subjects and patients with inflammatory diseases during single treatment sessions in previous studies. We hypothesized that patients with advanced arteriosclerotic diseases who are not candidates for a surgical intervention would clinically benefit from repeated pGz treatments over several weeks through improvement of endothelial function. PATIENTS AND METHODS 11 patients, 5 men (37 to 71 y) with stable ischemic heart disease, LVEF < 35%, NYHA stage > II, and 6 patients (51 to 83 y, 1 woman) with intermittent leg claudication, Fontaine stage II, were enrolled after optimization of pharmacological therapy. PGz was applied for 40 min, 5 days/week during 5 weeks. Quality of life (SF-36 questionnaire), exercise performance, and endothelial function were assessed at baseline, during the treatment period, and 4 weeks after discontinuation of pGz. RESULTS PGz was well tolerated. In heart failure paitents, pGz therapy improved quality of life, increased 6 min walking distance by a mean +/- SE of 105 +/- 24 m, and improved postischemic skin hyperemia (p < .05 in all instances). In 4 of 6 patients with intermittent claudication, quality of life, treadmill walking distance and post-ischemic skin hyperemia improved with pGz therapy (p < .05). Four weeks after discontinuation of pGz, most therapeutic effects had vanished in both patient groups. CONCLUSIONS In patients with severe heart failure and with leg claudication who remain symptomatic despite maximal medical therapy and who were not candidates for surgery, periodic acceleration applied over several weeks improved quality of life and exercise capacity. The clinical benefits appear to be mediated through improved endothelial function.

Determinants of annual change in physical activity in COPD

Daily physical activity (PA) is reduced in patients with COPD. Previous cross‐sectional analyses indicate various predictors for a low level of PA including airway obstruction, exacerbations and co‐morbidities. However, information from longitudinal studies evaluating PA in the context of disease progression, survival and co‐morbidities is scant.

Accuracy of the Hospital Anxiety and Depression Scale for Identifying Depression in Chronic Obstructive Pulmonary Disease Patients

Psychological morbidity is common in chronic respiratory diseases. The diagnostic accuracy of the Hospital Anxiety and Depression Scale (HADS) and risk factors for comorbid depression in chronic obstructive pulmonary disease (COPD) are addressed. Consecutive COPD patients (GOLD stage I–IV, 40–75 years old) were enrolled in a multicentre, cross-sectional cohort study. Diagnosis of depression was ascertained through clinical records. Lung function, HADS score, 6-minute walking test (6-MWT), MRC dyspnoea score, and COPD Assessment Test (CAT) were evaluated. Two hundred fifty-nine COPD patients (mean age 62.5 years; 32% female; mean FEV1 48% predicted) were included. Patients diagnosed with depression (29/259; 11.2%) had significantly higher HADS-D and HADS-Total scores than nondepressed patients (median (quartiles) HADS-D 6 [4; 9] versus 4 [2; 7], median HADS-Total 14 [10; 20] versus 8 [5; 14]). Receiver-operating characteristic plots showed moderate accuracy for HADS-D, AUC 0.662 (95%CI 0.601–0.719), and HADS-Total, AUC 0.681 (95%CI 0.620–0.737), with optimal cut-off scores of >5 and >9, respectively. Sensitivity and specificity were 62.1% and 62.6% for HADS-D compared to 75.9% and 55.2% for HADS-Total. Age, comorbidities, sex, and lower airflow limitation predicted depression. The HADS exhibits low diagnostic accuracy for depression in COPD patients. Younger men with comorbidities are at increased risk for depression.