Autopsy Findings and Venous Thromboembolism in Patients With COVID-19: A Prospective Cohort Study.

BACKGROUND: The new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused more than 210 000 deaths worldwide. However, little is known about the causes of death and the virus's pathologic features. OBJECTIVE: To validate and compare clinical findings with data from medical autopsy, virtual autopsy, and virologic tests. DESIGN: Prospective cohort study. SETTING: Autopsies performed at a single academic medical center, as mandated by the German federal state of Hamburg for patients dying with a polymerase chain reaction-confirmed diagnosis of COVID-19. PATIENTS: The first 12 consecutive COVID-19-positive deaths. MEASUREMENTS: Complete autopsy, including postmortem computed tomography and histopathologic and virologic analysis, was performed. Clinical data and medical course were evaluated. RESULTS: Median patient age was 73 years (range, 52 to 87 years), 75% of patients were male, and death occurred in the hospital (n = 10) or outpatient sector (n = 2). Coronary heart disease and asthma or chronic obstructive pulmonary disease were the most common comorbid conditions (50% and 25%, respectively). Autopsy revealed deep venous thrombosis in 7 of 12 patients (58%) in whom venous thromboembolism was not suspected before death; pulmonary embolism was the direct cause of death in 4 patients. Postmortem computed tomography revealed reticular infiltration of the lungs with severe bilateral, dense consolidation, whereas histomorphologically diffuse alveolar damage was seen in 8 patients. In all patients, SARS-CoV-2 RNA was detected in the lung at high concentrations; viremia in 6 of 10 and 5 of 12 patients demonstrated high viral RNA titers in the liver, kidney, or heart. LIMITATION: Limited sample size. CONCLUSION: The high incidence of thromboembolic events suggests an important role of COVID-19-induced coagulopathy. Further studies are needed to investigate the molecular mechanism and overall clinical incidence of COVID-19-related death, as well as possible therapeutic interventions to reduce it. PRIMARY FUNDING SOURCE: University Medical Center Hamburg-Eppendorf.

Work of Breathing in Fixed and Pressure Relief Continuous Positive Airway Pressure (C-Flex™): A post hoc Analysis.

BACKGROUND: Expiratory pressure relief continuous positive airway pressure (pressure relief CPAP; C-Flex™) causes increases in inspiratory duty cycle and shortening of expiratory time. It has been suggested that these changes are caused by an increase in work of breathing. OBJECTIVES: We studied the effects of C-Flex on work of breathing and intrinsic positive end-expiratory pressure as compared to fixed CPAP. METHODS: Work of breathing was analyzed in 24 patients with obstructive sleep apnea during treatment with fixed CPAP and C-Flex with 3 different pressure relief settings in a randomized order during rapid-eye-movement (REM) and non-REM sleep. Work of breathing was assessed on a breath-by-breath basis using a piezoelectric esophageal pressure catheter and a pneumotachograph for measuring airflow. RESULTS: We found there was no increase in inspiratory work of breathing observed using C-Flex compared to fixed CPAP. Instead, we found a linear decrease in inspiratory work of breathing with increasing pressure relief, with a mean difference of 1.22 J/min between CPAP and maximum pressure release (C-Flex 3; 90% of the value with nasal CPAP); however, the decrease was not statistically significant. The decrease in inspiratory work of breathing associated with C-Flex has a significant inverse correlation with BMI. CONCLUSIONS: The C-Flex technology does not change work of breathing but shows a tendency towards a reduction of inspiratory work of breathing in patients with a lower BMI using higher C-Flex. The effect is probably caused by diminishing airway resistance generated by the positive end-expiratory pressure. Our findings may lead to additional fields of application of the C-Flex technology, such as chronic obstructive pulmonary disease or muscular dystrophy.

Primary radiotherapy with endobronchial high-dose-rate brachytherapy boost for inoperable lung cancer: long-term results.

BACKGROUND: To retrospectively evaluate the outcome of patients with inoperable non-small-cell lung cancer treated with primary external beam radiotherapy combined with high-dose-rate endobronchial brachytherapy boost. PATIENTS AND METHODS: Between 1988 and 2005, 35 patients with non-small-cell lung cancer (stage I-III) ineligible for surgical resection and/or chemotherapy, were primarily treated with external beam radiotherapy with a median total dose of 50 Gy (range, 46-60). A median of 3 fractions high-dose-rate endobronchial brachytherapy was applied as a boost after external beam radiotherapy, the median total dose was 15 Gy (range, 8-20). High-dose-rate endobronchial brachytherapy was carried out with iridium-192 sources (370 GBq) and prescribed to 1 cm distance from the source axis. RESULTS: With a median follow-up of 26 months from the first fraction of high-dose-rate endobronchial brachytherapy, the 1-, 2- and 5-year overall (local progression-free) survival rates were 76% (76%), 61% (57%) and 28% (42%), respectively. Complete or partial remission rates 6 to 8 weeks after treatment were 57% and 17%, respectively. Significant prognostic favorable factors were a complete remission 6-8 weeks after treatment and a negative nodal status. In patients without mediastinal node involvement, a long-term local control could be achieved with 56% 5-year local progression-free survival. Common Toxicity Criteria grade 3 toxicities were hemoptysis (n = 2) and necrosis (n = 1). One fatal hemoptysis occurred in combination with a local tumor recurrence. CONCLUSIONS: The combination of external beam radiotherapy with high-dose-rate endobronchial brachytherapy boost is an effective primary treatment with acceptable toxicity in patients with non-small-cell lung cancer ineligible for surgical resection and/or chemotherapy.

Clinical features of critically ill patients with Shiga toxin-induced hemolytic uremic syndrome.

OBJECTIVE: In Spring 2011, an unprecedented outbreak of Shiga toxin-producing Escherichia coli serotype O104:H4-associated hemolytic uremic syndrome occurred in Northern Germany. The aim of this study was to describe the clinical characteristics, treatments, and outcomes of critically ill patients with Shiga toxin-producing E. coli-associated hemolytic uremic syndrome during this outbreak. DESIGN, SETTING, AND PATIENTS: Multicenter, retrospective, observational study of critically ill adult patients with Shiga toxin-producing E. coli-associated hemolytic uremic syndrome in six hospitals in Hamburg, Germany, between May 2011 and August 2011. MEASUREMENTS AND MAIN RESULTS: During the study period, 106 patients with Shiga toxin-producing E. coli-associated hemolytic uremic syndrome were admitted to eight ICUs. The median age was 40 years (range, 18-83) with a female:male ratio of 3:1. The median time from onset of clinical symptoms to hospital admission was 3 days and from hospital to ICU admission an additional 3 days. A total of 101 patients (95.3%) had acute renal failure and 78 (73.6%) required renal replacement therapy. Intubation and mechanical ventilation were required in 38 patients (35.8%) and noninvasive ventilation was required in 17 patients (16.0%). The median duration of invasive ventilation was 7 days (range, 1-32 days) and the median ICU stay was 10 days (range, 1-45 days). Fifty-one patients (48.1%) developed sepsis; of these 51 patients, 27 (25.4%) developed septic shock. Seventy patients (66.0%) developed severe neurological symptoms. Ninety-seven patients (91.5%) were treated with plasma exchange and 50 patients (47.2%) received eculizumab (monoclonal anti-C5 antibody). The mortality rate was 4.7%. Mild residual neurological symptoms were present in 21.7% of patients at ICU discharge, and no patient required renal replacement therapy 6 months after ICU admission. CONCLUSIONS: During the 2011 Shiga toxin-producing E. coli-associated hemolytic uremic syndrome outbreak in Germany, critical illness developed rapidly after hospital admission, often in young women. The infection was associated with severe neurological and renal symptoms, requiring mechanical ventilation and renal replacement therapy in a substantial proportion of patients. Overall, recovery was much better than expected.

A novel extracorporeal CO(2) removal system: results of a pilot study of hypercapnic respiratory failure in patients with COPD.

BACKGROUND: Hypercapnic respiratory failure in patients with COPD frequently requires mechanical ventilatory support. Extracorporeal CO2 removal (ECCO2R) techniques have not been systematically evaluated in these patients. METHODS: This is a pilot study of a novel ECCO2R device that utilizes a single venous catheter with high CO2 removal rates at low blood flows. Twenty hypercapnic patients with COPD received ECCO2R. Group 1 (n = 7) consisted of patients receiving noninvasive ventilation with a high likelihood of requiring invasive ventilation, group 2 (n = 2) consisted of patients who could not be weaned from noninvasive ventilation, and group 3 (n = 11) consisted of patients on invasive ventilation who had failed attempts to wean. RESULTS: The device was well tolerated, with complications and rates similar to those seen with central venous catheterization. Blood flow through the system was 430.5 ± 73.7 mL/min, and ECCO2R was 82.5 ± 15.6 mL/min and did not change significantly with time. Invasive ventilation was avoided in all patients in group 1 and both patients in group 2 were weaned; PaCO2 decreased significantly (P < .003) with application of the device from 78.9 ± 16.8 mm Hg to 65.9 ± 11.5 mm Hg. In group 3, three patients were weaned, while the level of invasive ventilatory support was reduced in three patients. One patient in group 3 died due to a retroperitoneal bleed following catheterization. CONCLUSIONS: This single-catheter, low-flow ECCO2R system provided clinically useful levels of CO2 removal in these patients with COPD. The system appears to be a potentially valuable additional modality for the treatment of hypercapnic respiratory failure.

Endobronchial ultrasound: a useful tool in the diagnosis of bronchogenic cyst.

Diagnosis of bronchogenic cysts is possible with computed tomography, where the cysts are seen usually as well-circumscribed lesions of water density. However, many of the cysts have a soft-tissue density thus rendering them indistinguishable from neoplasms. In this article, we describe a case of bronchogenic cyst presenting as soft-tissue mass that was evaluated and diagnosed by endobronchial ultrasound (EBUS). We discuss the ultrasound image characteristics of the cyst and its histopathology findings. EBUS seems to be a valuable tool in the diagnosis of bronchogenic cysts and also enables their complete aspiration.

Combination of narrow band imaging (NBI) and autofluorescence imaging (AFI) videobronchoscopy in endoscopic assessment of lung cancer extension.

Both narrow band imaging (NBI) and autofluorescence imaging (AFI) are new techniques for the assessment of lung cancer. The major aim of this study was to investigate whether the combination of these two techniques improve sensitivity and specificity in the assessment of lung cancer extension. The study prospectively evaluated 118 patients with suspected lung cancer. All of the patients were examined using EVIS LUCERA SPECTRUM videobronchoscopy system. The narrow band imaging preceded autofluorescence imaging examination. In every patient, at least 1 but no more than 4 biopsies were taken from places visualized as pathologic, surrounding primary tumor, and at least 1 biopsy from places that appeared visually normal. Sensitivity, specificity, positive, and negative predictive value for autofluorescence imaging in the assessment of tumor extension were 89.2, 77.8, 87, and 81%, respectively. Sensitivity, specificity, positive, and negative predictive value for narrow band imaging were 90.4, 82.4, 91.8, and 79.7%, respectively. Corresponding values for combination of techniques were 93.7, 86.9, 94.5, and 85.1%. Combination of techniques significantly improves sensitivity (P = 0.034) with borderline effect on specificity (P = 0.056) of autofluorescence imaging. There was no significant improvement for sensitivity and specificity of NBI alone. The combination of techniques shows significantly better sensitivity and specificity in the assessment of lung cancer extension when compared to white light videobronchoscopy alone, but improvement is not so convincing when compared to the each technique alone.

Recurrent respiratory papillomatosis: a rare chronic disease, difficult to treat, with potential to lung cancer transformation: apropos of two cases and a brief literature review.

Recurrent respiratory papillomatosis (RRP), which is caused exclusively by human papilloma virus (HPV), is a rare condition characterized by recurrent growth of benign papillomata in the respiratory tract. The papillomata can occur anywhere in the aerodigestive tract but most frequently in the larynx, affecting both children and adults. The management of this entity remains still challenging since no specific definitive treatment exists. Nevertheless, novel surgical interventions as well as several adjuvant therapies have shown promising results in the long-term palliative management of this debilitating disease. Despite its mostly benign nature, RRP may cause significant morbidity and mortality because of its unpredictable clinical course and especially its tendency, albeit infrequent, for malignant transformation. In this article, we present two patients with RRP; one underwent bronchoscopic laser ablation in combination with inhaled interferon-alpha administration that led to a long-term regression of the disease while the other patient was diagnosed with transformation to squamous cell lung carcinoma with fatal outcome. We include a review of the current literature with special emphasis on RRP management and the potential role of HPV in the development of lung cancer.

Autofluorescence imaging videobronchoscopy in the detection of lung cancer: from research tool to everyday procedure.

Autofluorescence imaging videobronchoscopy (AFI) is one of the new systems of autofluorescence bronchoscopy designed for thorough examination of bronchial mucosa. The integration of autofluorescence and videobronchoscopy provides clear images of normal and pathologically altered bronchial mucosa. Major indications for AFI include evaluation of early-stage lung cancer and detection of precancerous lesions. However, in recent years, the indications for AFI are widening, and this tool might find its place in routine daily bronchoscopic practice. With new indications for AFI, such as evaluation of tumor extension or follow-up after surgical resection, this tool might be more often used by bronchoscopists. A sharp learning curve and clear distinction between healthy and pathologically altered mucosa make this technology acceptable for young and inexperienced bronchoscopists. One of the major disadvantages of AFI is low specificity in the detection of premalignant lesions and early-stage lung cancer. This disadvantage could be overcome with the appearance of new and improved technologies in autofluorescence, such as the addition of backscattered light analysis, ultraviolet spectra, fluorescence-reflectance or dual digital systems. Quantitative image analysis is also one of the ways to improve objectivity and minimize observer errors. However, one of the most appropriate solutions would be the addition of AFI to narrow band imaging, and merging the two technologies into one videobronchoscope.

Bronchoscopic long-term palliation of a recurrent atypical carcinoid tumor.

Bronchial carcinoid tumors account for 1-2% of all primary lung tumors and are separated into 2 subgroups: typical and atypical carcinoids. Atypical carcinoids as intermediate-grade malignancies can metastasize more frequently, thus exhibiting poorer prognosis than the low-grade typical carcinoid tumors. Surgical resection remains the mainstay of treatment for pulmonary carcinoids. Bronchoscopic treatment using ablation techniques is an effective alternative to surgery in selected patients with typical carcinoid tumors. However, evidence is lacking regarding the effect of bronchoscopic resection of atypical carcinoid tumor and its recurrences. We report the case of a 73-year-old male with frequent endobronchial recurrences of a previously surgically resected atypical carcinoid tumor successfully treated using Nd:YAG laser photoresection. Furthermore, the therapeutic and local staging aspects of the disease are discussed emphasizing the efficacy of bronchoscopic resection strategies and the value of novel bronchoscopic imaging techniques in detailed inspection of the structures of the bronchial wall.

Tracheal diverticulum.

Tracheal diverticulum is a rarely encountered entity, usually discovered incidentally as an outpouching at the right side on radiography or computed tomography (CT). We present the case of a male patient with a tracheal diverticulum detected during a work-up for hemoptysis. His thoracic CT scan showed a sac formation on the right dorsolateral wall of the trachea. Flexible bronchoscopy showed a collapsed entrance to the diverticulum, which could be opened by flexible forceps. The mucosal lining of the diverticulum seemed normal, without retained secretions or blood. Although with limited clinical consequences, tracheal diverticulum must be kept in mind as a reservoir for secretions that may cause infection, and also hemoptysis if infected.

Clinical application of virtual bronchoscopic navigation system for peripheral lung lesions.

Transbronchial lung biopsy is an indispensable method for the diagnosis of peripheral lung lesions; however, the diagnostic yield still remains unsatisfactory. Endobronchial ultrasound with guide sheath (EBUS-GS) is an excellent method for the decision of biopsy points and has contributed to improvements in diagnostic yield, but the decision of choosing the proper bronchus depends on the individual ability of each bronchoscopist. To clarify the usefulness of the virtual bronchoscopic navigation system (VBN), we evaluated the diagnostic yield and time required to determine the target lesion. Fifty-seven cases using EBUS-GS with VBN (VBN/EBUS-GS group) and 55 cases using EBUS-GS (EBUS-GS group) were compared. In the VBN/EBUS-GS group, computer software detects the air density in the bronchi from the computed tomography image and imports a detailed virtual Bronchoscopic Image. After inserting the starting position and the peripheral target lesion, the software depicts the most ideal route to the target lesion during the bronchoscopic procedure. EBUS is then used to confirm the accuracy of the route. Diagnostic yield was 84.2% for the VBN/EBUS-GS group and 80.0% for EBUS-GS group. The required time to determine the biopsy position was significantly less in the VBN/EBUS-GS group (5.54 ± 0.57 min in VBN/EBUS-GS group vs. 9.27 ± 0.86 min in EBUS-GS group, P<0.01). In conclusion, VBN proved useful in shortening the time needed to determine the biopsy position.

Bronchoscopy: the past, the present, and the future.

This article discusses bronchoscopy: its history, including development of instruments and techniques and important historical figures; current techniques and issues; and future possibilities and potential controversies.

Autofluorescence imaging videobronchoscopy improves assessment of tumor margins and affects therapeutic strategy in central lung cancer.

OBJECTIVE: Autofluorescence imaging (AFI) videobronchoscopy is a new endoscopic tool that improves visualization of neoplastic changes in the bronchial mucosa. The major aim of our study was to determine sensitivity and specificity of the technique in the assessment of tumor extent (margins). The secondary objective was to evaluate the possible effect of AFI on the change in therapeutic decisions of lung cancer treatment. METHODS: In this prospective trial, we enrolled 104 patients in whom we performed 624 targeted biopsies, 3 from the pathologically altered mucosa (red-brownish or magenta colored) and 3 from randomly picked normal areas. We were using the Olympus BF-F260 videobronchoscope and EVIS LUCERA system. White light videobronchoscopy (WLB) preceded AFI examination and biopsy collection. All biopsy specimens were examined by a pathologist blinded to bronchoscopy findings, and where applicable surgically resected specimens were examined. RESULTS: In 14.4% of the patients, AFI revealed a greater extent of the tumor than WLB, and in 11.5% that finding led to change in therapeutic decision (lesser or greater resection or avoidance of surgery). We found a significant correlation between tumor extent determined by AFI and changes in therapeutic decisions (P < 0.01). Sensitivity, specificity, positive predictive value and negative predictive value for AFI in the assessment of tumor extension were 93%, 92%, 92% and 93%, respectively. Corresponding results for WLB were 84%, 79%, 77% and 85%, respectively. Relative sensitivity of AFI is 1.11. CONCLUSIONS: Our results confirm that AFI videobronchoscopy significantly improves the assessment of central lung cancer extension and influences the therapeutic strategy. This technique has greater sensitivity and specificity, in assessment of tumor margins, than WLB alone.

Treatment of recurrent bronchial carcinoma: the role of high-dose-rate endoluminal brachytherapy.

PURPOSE: This study's aim was to assess outcome and toxicity of high-dose-rate endoluminal brachytherapy (HDREB) for recurrent bronchial carcinoma. METHODS AND MATERIALS: From 1987 to 2005, 41 patients were treated with HDREB for symptomatic recurrent bronchial carcinoma. All patients had previously undergone external beam radiotherapy (EBRT) with a median dose of 56 Gy (range, 30-70 Gy). The median HDREB dose applied was 15 Gy (range, 5-29 Gy). The median time interval between primary EBRT and reirradiation was 9 months (range, 2-54 months). RESULTS: After a median follow-up of 6.7 months, the 6-, 12-, and 24-month overall survival rates were 58%, 18%, and 7%, respectively. The median overall survival time was 6.7 months. Local remission was achieved in 73% of patients (n = 30). A total of 24% of patients (n = 10) showed no response or progressive disease within 8 weeks after treatment. In 1 patient, treatment response was not documented. The 6-, 12-, and 24-month local control rates were 38%, 17%, and 3%, respectively. The median local progression-free survival time was 4 months (range, 1-23 months). Prognostic factors were a total dose of >or=15 Gy of HDREB (p = 0.029) and a Karnofsky performance score of >or=80% (p = 0.0012). The cause of death was locoregional progression in 27% of patients (n = 11), distant metastases in 24% of patients (n = 10), fatal hemorrhage in 15% of patients (n = 6), and other causes in 29% of patients (n = 12). None of the patients with locally controlled disease showed grade 3 or 4 late effects. CONCLUSIONS: Palliative treatment of symptomatic, locally recurrent bronchial carcinoma with HDREB can effectively relieve symptoms in the majority of patients while causing only few complications. Still, time to progression is short.

Narrow band imaging videobronchoscopy improves assessment of lung cancer extension and influences therapeutic strategy.

OBJECTIVE: Narrow band imaging (NBI) videobronchoscopy is a new technique aimed at lung cancer detection. This study investigated its sensitivity and specificity for evaluation of lung cancer extension and its possible influence on therapeutic decision, compared with white light videobronchoscopy. METHODS: In this prospective study, we evaluated 106 patients with suspected lung cancer. All patients were examined using EVIS LUCERA videoendoscopy system. In every patient, at least three biopsies were taken from places visualized as pathologic, surrounding primary tumor, and three biopsies from places that appeared normal. The overall number of biopsies performed in 106 patients was 636. RESULTS: The specificity and sensitivity of NBI in revealing greater lung cancer extension were 85.6% and 95%, respectively; positive and negative predictive values were 84% and 95.6%, respectively. Specificity and sensitivity were significantly better when compared with white light bronchoscopy alone (P < 0.01). NBI led to the change in therapeutic decision in 14 patients. There was statistically significant correlation between NBI assessment of tumor extension and change in therapeutic decision (P < 0.000). CONCLUSIONS: NBI showed significantly better specificity and sensitivity in the assessment of lung cancer extension. NBI proved that it might have potential influence on therapeutic decision, making it more accurate. The procedure is safe and easily deployed in everyday practice.