Four types of hepatic porphyria (acute intermittent porphyria; hereditary coprophorphyria; variegate porphyria; delta-aminolevulinate dehydratase deficiency porphyria) present clinically with an identical neurological syndrome. Symptoms include severe abdominal pain, vomiting, constipation, hypertension, tachycardia, and bladder dysfunction. These symptoms have been ascribed to autonomic neuropathy. Other symptoms are motor weakness and sensory involvement, which correlate with peripheral axonal neuropathy, and mental symptoms occurring without clear morphological findings in the cerebrum. The pathogenetic mechanisms which lead to the neurological dysfunction have remained poorly understood, partly due to the lack of a suitable animal model of these rare disorders. Two hypotheses, the possible neurotoxicity of delta-aminolevulinate (ALA) and heme deficiency in nervous tissue are discussed and corresponding data from porphobilinogen-deaminase deficient mice are presented. The present evidence suggests that multiple mechanisms interact in causing the varied symptoms, including ALA interaction with GABA receptors, altered tryptophan metabolism, and possibly heme depletion in nerve cells.

We conducted a single-center, randomized, placebo-controlled trial to determine whether streptokinase instillations adjunctive to chest tube drainage reduce the need for surgery and improve outcome in patients with pleural empyema. Fifty-three patients (frank pus aspirated, 81%; microbiological agent cultured, 62%; mean effusion pH, 6.6 ± 0.4) received antibiotic treatment, chest tube drainage, and once-daily pleural rinses with either normal saline or normal saline with streptokinase (250,000 IU). Nine patients were excluded for various reasons before pleural rinses were started. Streptokinase (n = 22) was instilled over 4.5 ± 2 days and saline (n = 22) was instilled over 3 ± 1.3 days. One patient in each group died during treatment. Clinical treatment success and need for referral to surgery were the main outcome measures. No difference was observed after 3 days. After 7 days, streptokinase-treated patients had a higher clinical success rate (82 vs. 48%, p = 0.01) and fewer referrals for surgery (45 vs. 9%, p = 0.02). No significant radiologic or functional differences were observed between groups during follow-up over 6 months. We conclude that intrapleural streptokinase adjunctive to chest tube drainage reduces the need for surgery and improves the clinical treatment success in patients with pleural empyema.

Background: Rapid on-site evaluation has been proposed as a method to improve the yield of transbronchial needle aspiration. Objectives: This study investigated whether on-site analysis facilitates routine diagnostic bronchoscopy in terms of sampling, yield and cost. Methods: Patients with lesions accessible for transbronchial needle aspiration on computed tomography were investigated. A cytopathologist screened the needle aspirates on site for the presence of diagnostic material. The bronchoscopic sampling process was adjusted according to the results. In 90 consecutive patients with neoplastic disease (n = 70; 78%), non-neoplastic disease (n = 16; 18%) or undiagnosed lesions (n = 4; 4%) we aspirated 162 lung lesions (paratracheal tumours or lymph nodes: 7%; tracheobronchial lymph nodes: 68%; other: 25%). Results: The diagnostic yield of needle aspiration was 77 and 25% in patients with neoplastic and non-neoplastic lesions, respectively. Sampling could be terminated in 64% of patients after needle aspiration had been performed as the only diagnostic modality, and on-site analysis identified diagnostic material from the first site aspirated in 50% of patients. Only in 2 patients (2%) diagnostic aspirates were not recognized on site. On-site analysis was cost effective due to savings for disposable diagnostic tools, which exceeded the extra expense for the on-site cytology service provided. Conclusions: Rapid on-site analysis of transbronchial aspirates is a highly useful, accurate and cost-effective addition to routine diagnostic bronchoscopy.

Background: Transthoracic ultrasound (US) has gained popularity as a tool for visualizing pleural effusions and assisting thoracentesis or chest drain placement. In the absence of effusion, US just as well demonstrates solid masses involving or abutting the pleura, yet biopsy of such lesions is not widely performed by chest physicians. Objective: To assess the feasibility and the safety of US-assisted cutting needle biopsy performed by chest physicians in routine practice. Methods: Lesions involving or abutting the pleura ≧20 mm in diameter on US were sampled with a 14-gauge cutting needle under local anesthesia. Biopsy site, needle direction and depth of penetration were determined with US. The procedure was performed without direct US guidance in ‘free-hand’ technique. Results: Ninety-one patients underwent 96 cutting-needle biopsies for suspected peripheral lung tumors (n = 44, 46%), pleural-based (n = 39, 41%), mediastinal (n = 10, 10%), or chest wall lesions (n = 3, 3%), which were single in 71%, multiple in 6% and diffuse in 23%. Sensitivity for malignant neoplasms (n = 65) was 85.5% and 100% for mesothelioma (n = 10). Pneumothorax occurred in 4%. Conclusions: US-assisted cutting-needle biopsy of lesions ≧20 mm in diameter is safe in the hands of pulmonologists. The yield for neoplastic disease including mesothelioma is high.

Immunocompromised patients may be at increased risk for complications of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. However, comprehensive data of SARS‐CoV‐2 infection in solid organ transplant (SOT) recipients are still lacking. We performed a multicenter nationwide observational study within the Swiss Transplant Cohort Study (STCS) to describe the epidemiology, clinical presentation, treatment and outcomes of the first microbiologically documented SARS‐CoV‐2 infection among SOT recipients. Overall, 21 patients were included with a median age of 56 years (10 kidney, 5 liver, 1 pancreas, 1 lung, 1 heart and 3 combined transplantations). The most common presenting symptoms were fever (76%), dry cough (57%), nausea (33%) and diarrhea (33%). Ninety‐five percent and 24% of patients required hospital and ICU admission, respectively, and 19% were intubated. After a median of 33 days of follow‐up, 16 patients were discharged, 3 were still hospitalized and 2 patients died. These data suggest that clinical manifestations of SARS‐CoV‐2 infection in middle‐aged SOT recipients appear to be similar to the general population without an apparent higher rate of complications. These results need to be confirmed in larger cohorts.

Lung transplant patients are a vulnerable group of immunosuppressed patients that are prone to frequent respiratory infections. We studied 60 episodes of respiratory symptoms in 71 lung transplant patients. Almost half of these episodes were of unknown infectious etiology despite extensive routine diagnostic testing. We re-analyzed respiratory samples of all episodes with undetermined etiology in order to detect potential viral pathogens missed/not accounted for in routine diagnostics. Respiratory samples were enriched for viruses by filtration and nuclease digestion, whole nucleic acids extracted and randomly amplified before high throughput metagenomic virus sequencing. Viruses were identified by a bioinformatic pipeline and confirmed and quantified using specific real-time PCR. In completion of routine diagnostics, we identified and confirmed a viral etiology of infection by our metagenomic approach in four patients (three Rhinovirus A, one Rhinovirus B infection) despite initial negative results in specific multiplex PCR. Notably, the majority of samples were also positive for Torque teno virus (TTV) and Human Herpesvirus 7 (HHV-7). While TTV viral loads increased with immunosuppression in both throat swabs and blood samples, HHV-7 remained at low levels throughout the observation period and was restricted to the respiratory tract. This study highlights the potential of metagenomic sequencing for virus diagnostics in cases with previously unknown etiology of infection and in complex diagnostic situations such as in immunocompromised hosts.