Conservative management of distal leg necrosis in lung transplant recipients.

Critical limb ischemia (CLI) with distal leg necrosis in lung transplant recipients (LTR) is associated with a high risk for systemic infection and sepsis. Optimal management of CLI has not been defined so far in LTR. In immunocompetent individuals with leg necrosis, surgical amputation would be indicated and standard care. We report on the outcome of four conservatively managed LTR with distal leg necrosis due to peripheral arterial disease (PAD) with medial calcification of the distal limb vessels. Time interval from lung transplantation to CLI ranged from four years (n = 1) to more than a decade (n = 3). In all cases a multimodal therapy with heparin, acetylsalicylic acid, iloprost and antibiotic therapy was performed, in addition to a trial of catheter-based revascularization. Surgical amputation of necrosis was not undertaken due to fear of wound healing difficulties under long-term immunosuppression and impaired tissue perfusion. Intensive wound care and selective debridement were performed. Two patients developed progressive gangrene followed by auto-amputation during a follow-up of 43 and 49 months with continued ambulation and two patients died of unrelated causes 9 and 12 months after diagnosis of CLI. In conclusion, we report a conservative treatment strategy for distal leg necrosis in LTR without surgical amputation and recommend this approach based on our experience.

Exposure to moxifloxacin and cytomegalovirus replication is associated with skin squamous cell carcinoma development in lung transplant recipients.

BACKGROUND: Lung transplant recipients (LTR) are at increased risk for squamous cell carcinoma of the skin (SCC), but risk factors (RF) are incompletely understood. OBJECTIVE: To assess associations between exposure to certain medications and viral infections, and subsequent SCC development. METHODS: Retrospective study examining incidence and potential RF for SCC in LTR transplanted from 1992 to 2010 followed up at one centre. Cumulative incidence and Cox proportional hazards regression models were used to evaluate RF in the first year post-transplant for SCC formation during the follow-up. RESULTS: In 205 analysed LTR, 46 patients were diagnosed with SCC during a median follow-up of 4.9 years. The cumulative incidences of first SCC were 16.7% and 34.1%, for 5 and 10 years post-transplantation respectively. Multivariable analysis identified CMV replication (HR 7.69, 95% CI 2.93-20.2, P < 0.001) and moxifloxacin exposure (HR 2.35, 95% CI 1.15-4.81, P = 0.020) during the first year post-transplantation as independent RF for SCC development during follow-up. CONCLUSION: In our cohort, moxifloxacin use and CMV replication during the first year post-transplantation were associated with increased risk for SCC. These two factors could be indicators of over-immunosuppression. Their role in SCC development requires investigations in larger cohorts and prospective studies.

Clinical features and outcomes of influenza infections in lung transplant recipients: a single-season cohort study.

BACKGROUND: For lung transplant recipients (LTRs) influenza infections pose a considerable risk for complications. These infections have mainly been described in hospitalized patients. The aim of this study was to describe characteristics of predominantly outpatient-treated influenza infections. METHODS: We conducted a single-season (2010/2011) retrospective observational study using database information of our cohort. Patients with evidence for respiratory tract infection received empirical oseltamivir and an oral antibiotic, pending results from nasopharyngeal swab analysis. In laboratory-confirmed influenza infection, treatment was continued and serial weekly swabs were performed until virologic results were negative. RESULTS: We identified 22 infections in 21 of 173 patients followed up; influenza A virus was diagnosed in 13 and influenza B virus in 9 infections. Leading presenting symptoms were cough and rhinorrhea. Oseltamivir was given within 48 h of symptom onset in 13 infections and within 72 h in 21 infections. Prolonged viral shedding (PVS) for ≥ 7 days was detected in 15 infections; median shedding duration for influenza A was 21 days. In univariable analysis, viral load (VL) at diagnosis was associated with extended duration of shedding (P = 0.006). Multivariable analysis confirmed this association. Bronchiolitis obliterans syndrome stage increased in 3 patients at 6-month follow-up. CONCLUSION: In this study, PVS of influenza virus was detected in the majority of LTRs and high VL at diagnosis was predictive for prolonged shedding, which occurred despite extended antiviral therapy.

Smoking prevention intervention with school classes in university hospital by thoracic surgeon und pulmonologist. The Zurich prevention project.

Smoking prevention in schoolchildren to inform and prevent smoking initiation has been widely studied; however, the potential effect of interventions provided in a hospital setting is unknown. An intervention program named "Schoolchildren smoking prevention in the hospital" was developed in which the health aspects of smoking and its individual consequences were presented in an interactive informational event provided by a thoracic surgeon and a pulmonologist. We aimed to assess the feasibility and the short-term effect of smoking-related knowledge improvement in schoolchildren in a hospital setting. Scholars of 45 classes in Canton of Zurich in Switzerland filled in an anonymous 5-item questionnaire with questions on general knowledge about smoking. The answers were evaluated in this prospective observational cohort study. The primary endpoint was to compare the knowledge improvement by interpretation of answers before-and-after the smoking prevention intervention. Additionally, the performance of children was compared after setting up an overall score and specific subgroups according to gender and school-level. Between Jan 2010, and Oct 2019, schoolchildren aged 10 to 16 years participated in this intervention program and completed the questionnaire before (N = 1270) and after (N = 1264) the intervention. The amount of correctly answered questions increased from 40% (±20) before to 81% (±17), p < 0·0001 after the educational session. An intervention program on health effects of smoking provided by lung specialists in the hospital is feasible, well received, leads to a substantial increase of knowledge, and hopefully can be further explored in the development of smoking prevention programs for schoolchildren.

Electronic cigarettes and vaping associated pulmonary illness (VAPI): A narrative review.

BACKGROUND: Electronic (e-) cigarettes are used to heat liquids producing aerosols for inhalation. Recently there have been reports of a large number of adverse outcomes relating to e-cigarette consumption (vaping), which has been referred to as "vaping associated pulmonary illness" (VAPI). AIM: This review provides an overview of clinical, radiological and pathological features of VAPI in the literature. We also describe a case of VAPI, presenting with symptoms of bronchiolitis, responding well to azithromycin in addition to the usual treatments provided for such cases. METHODS: We searched original papers, observational studies, case reports, and meta-analyses published between 2000 and 2019 in English in PubMed database using the keywords: e-cigarette, "vaping associated pulmonary illness", VAPI, EVALI, vaping AND "lung injury". We also used data of the Centers of Disease Control (CDC) website. RESULTS: From an initial search of PubMed, 62 potential articles were identified, and another 9 studies were identified from the bibliographies of retrieved articles. In this search we found 7 case series and 16 case reports, which were included in the review. In this search we also found 4 review articles. CONCLUSION: VAPI is a syndrome presenting with isolated pulmonary or combined pulmonary, gastrointestinal and constitutional symptoms and can be rapidly progressive, leading to respiratory failure, often requiring invasive respiratory support. There is an urgent need for more research on VAPI especially relating to etiology, treatment and prevention.

Patients' representations of their end-stage renal disease: relation with mortality.

BACKGROUND: Self-regulation theory explains how patients' illness perceptions influence self-management behaviour (e.g. via adherence to treatment). Following these assumptions, we explored whether illness perceptions of ESRD-patients are related to mortality rates. METHODS: Illness perceptions of 182 patients participating in the NECOSAD-2 study in the period between December 2004 and June 2005 were assessed. Cox proportional hazard models were used to estimate whether subsequent all-cause mortality could be attributed to illness perception dimensions. RESULTS: One-third of the participants had died at the end of the follow-up. Mortality rates were higher among patients who believed that their treatment was less effective in controlling their disease (perceived treatment control; RR = 0.71, P = 0.028). This effect remained stable after adjusting for sociodemographic and clinical variables (RR = 0.65, P = 0.015). CONCLUSIONS: If we consider risk factors for mortality, we tend to rely on clinical parameters rather than on patients' representations of their illness. Nevertheless, results from the current exploration may suggest that addressing patients' personal beliefs regarding the effectiveness of treatment can provide a powerful tool for predicting and perhaps even enhancing survival.

Esophagopericardial fistula, septic shock and intracranial hemorrhage with hydrocephalus after lung transplantation.

A 57-year old woman underwent lung transplantation for non-specific interstitial pneumonia. Primary graft dysfunction was diagnosed requiring continued use of extracorporeal membrane oxygenation (ECMO). Within three days she developed recurring hemothoraces requiring two surgical evacuations. After ECMO removal a series of complications occurred within four months: femoral thrombosis, persisting tachycardic atrial fibrillation, pneumopericardium with an esophagopericardial fistula and purulent pericarditis, septic shock, multiorgan failure and intracerebral hemorrhage with ventricular involvement requiring external ventricular drainage. Interdisciplinary management coordinated by the intensive care specialist, transplant surgeon and pulmonologist with various interventions by the respective specialists followed by intensive physical rehabilitation allowed for discharge home on day 235 post transplant. Subsequently quality of life was considered good by the patient and family.

Reliability of five rapid D-dimer assays compared to ELISA in the exclusion of deep venous thrombosis.

Studies measuring the fibrin degradation product D-Dimer (DD) using enzyme-linked immunosorbent assays (ELISA) in patients with venographically proven deep venous thrombosis (DVT) suggest that it is possible to exclude DVT when DD level is below a certain cut-off level. However, ELISA methods are time-consuming and not available in all laboratories. Different rapid latex-agglutination assays have been investigated, but their sensitivity is considerably lower. In the present study we compared the value of four novel latex DD tests (Tinaquant, Minutex, Ortho and SimpliRed) and one rapid ELISA (VIDAS) to a classical ELISA DD assay (Organon Mab Y18) in 132 patients suspected of DVT. The VIDAS, a new quantitative automated ELISA, had a sensitivity of 100% and a negative predictive value of 100% for both proximal and distal DVT at a cut-off level of 500 ng/ml. The Tinaquant assay, a new quantitative latex method, had a sensitivity of 99% and a negative predictive value of 93% for both proximal and distal DVT at a cut-off level of 500 ng/ml. For proximal DVT only, both assays had a sensitivity and negative predictive value of 100%. VIDAS and Tinaquant correlated well with ELISA (correlation of r = 0.96 and r = 0.98 respectively). Sensitivities of the semi-quantitative latex assays Minutex, Ortho and SimpliRed were considerably lower (77%, 51% and 61% respectively). These results suggest that VIDAS and Tinaquant may be used instead of ELISA DD in the exclusion of DVT. Tinaquant can be performed within 20 min and VIDAS within 35 min. Both assays might be used as a routine screening test and should be evaluated in large clinical management studies.

Whipple's disease and the central nervous system. A case report and a review of the literature.

A 65-year-old man was suffering from recurrent manic psychosis accompanied by weight loss. He also had a history of pleural effusion, aspecific migratory non-deforming seronegative polyarthritis, sensorineural hearing loss and semicircular canal paresis. Whipple's disease (WD) had been diagnosed at the age of 63 years. On admission to hospital) he had weight loss, diarrhoea in combination with an organic brain syndrome, hemiparesis and ophthalmoplegia, including internuclear ophthalmoplegia (INO). A clinical diagnosis of central nervous system (CNS) WD was made. MRI revealed a thalamus lesion that halved in size during sulfamethoxazole-trimethoprim treatment. The organic brain syndrome and ophthalmoplegia diminished also, as did the cerebrospinal fluid (CSF) IgG level. A review of CNS WD is presented and implications for treatment are discussed.

[Diagnostic image (129). A woman who collapsed upon catheterisation. Air embolism]. / Diagnose in beeld (129). Een vrouw die bij katheterisatie collabeerde. Luchtembolie.

A subclavian catheter was introduced in a 72-year-old woman whereupon she collapsed due to air embolism. The emboli were seen in the superior V. cava, the right atrium and the left pulmonary artery.

[Non-cystic fibrosis bronchiectasis: diagnosis and treatment]. / Non-CF-Bronchiektasen: Diagnostik und Therapie.

Bronchiectasis is the term used for irreversibly dilated airways. Exact epidemiological information on the frequency of bronchiectasis is not available, but the morphological findings are increasingly detected and the associated syndrome is more frequently diagnosed due to improved imaging techniques and increased awareness among chest physicians. The workup of these patients includes a wide panel of investigations guided by patient history and clinical presentation. Despite thorough evaluation the aetiology frequently remains unclear. Chronic infection with Pseudomonas aeruginosa is associated with a severe course of the disease and its detection has impacts on the therapeutic management. Chest physiotherapy, mucoactive substances and antibiotics are the mainstay of therapy. In this review the evaluation of bronchiectasis and the recent therapeutic insights for non-cystic fibrosis bronchiectasis are discussed.

Early tracheal stenosis causing extubation failure and prolonged ventilator dependency.

Postintubation stenosis is the most frequent cause of benign tracheal stenosis and may cause reintubation and delay in weaning of intensive care unit patients. This case study describes typical patients with tracheal stenosis and the management of these patients. Five patients requiring reintubation and mechanical ventilation due to early intubation-related stenosis are discussed. Stridor developed in three cases after extubation. In these cases, bronchoscopy revealed tracheal stenosis. Dilatation and silicone stent placement were performed using rigid bronchoscopy. The other two patients were on ventilators when they were admitted to the intensive care unit and their stenoses were also treated by rigid bronchoscopy. Hypercapnia and hypoxia resolved after intervention in three cases. Of the remaining two patients, one had the tracheostomy closed and in the other patient ventilation was stopped but the tracheostomy was maintained. Tracheal stenosis developing in the subglottic region after extubation, especially after exposure to cuff pressure, may lead to reintubation. A tracheostomy may hinder the diagnosis of progressive stenosis and may lead to unnecessary maintenance of ventilator treatment. Early intubation-related tracheal stenosis should therefore be considered in cases of weaning or extubation failure and prompt appropriate investigation and treatment.

Solitary pulmonary nodule evaluation with 99mTc-methoxy isobutyl isonitrile in a tuberculosis-endemic area.

High prevalence of tuberculosis increases the odds for nonmalignant solitary pulmonary nodules (SPNs). Positron emission tomography (PET) using (18)F-fluorodeoxyglucose is the method of choice for the identification of malignant SPNs requiring curative surgery. However, PET is not widely available. Technetium-99m methoxy isobutyl isonitrile (MIBI) is inexpensive, widely available and shows increased uptake in malignant SPNs. The aim of the present study was to prospectively evaluate the diagnostic value of MIBI single photon emission computed tomography to distinguish between benign and malignant SPNs in a tuberculosis-endemic area. In total, 49 patients with radiologically indeterminate SPNs (single lesion < or =6 cm in diameter) were prospectively evaluated with MIBI. The final diagnosis was established with bronchoscopy, fine-needle aspiration, surgical resection or clinical follow-up for > or =2 yrs. A total of 12 (92%) out of 13 malignant lesions showed increased uptake of MIBI, while no uptake was observed in 33 (92%) out of 36 benign lesions. MIBI uptake indicated malignancy with a sensitivity and specificity of 92% and a negative predictive value of 97%. In this tuberculosis-endemic area, technetium-99m methoxy isobutyl isonitrile single photon emission computed tomography evaluation of solitary pulmonary nodules had a high negative predictive value. Therefore, it has the potential to prevent unnecessary surgical resections of benign nodules and serve as a low-cost alternative when positron emission tomography is not available.

Transbronchial needle aspirates: how many passes per target site?

Transbronchial needle aspiration is a bronchoscopic sampling method for a variety of bronchial and pulmonary lesions. The present study investigated whether and how serial needle passes contribute to the yield of transbronchial needle aspiration at specific target sites. A total of 1,562 needle passes, performed at 374 target sites in 245 patients with neoplastic disease (82%), non-neoplastic disease (15%) or undiagnosed lesions (3%), were prospectively recorded and rated for anatomical location, size, bronchoscopic appearance and underlying disease. Positive aspirates were obtained in 75% of patients and at 68% of target sites. A diagnosis was established with the first, second, third and fourth needle pass at 64, 87, 95 and 98% of targets, respectively. The absolute yield varied strongly with target site features, but the stepwise increment to the maximum yield provided by serial passes was similar across target sites. In conclusion, three transbronchial needle passes per site are appropriate when only a tissue diagnosis is sought and when alternative sites or sampling modalities are available. At least four or five passes should be carried out at lymph node stations critical for the staging of lung cancer.

Acute porphyrias: pathogenesis of neurological manifestations.

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.

Mutation hotspots in the human porphobilinogen deaminase gene: recurrent mutations G111R and R173Q occurring at CpG motifs.

Acute intermittent porphyria (AIP) is an inherited disorder in the haem biosynthetic pathway caused by a partial deficiency of porphobilinogen (PBG) deaminase. To date, more than 200 different mutations have been identified in the PBG deaminase gene (PBGD) in AIP patients from various countries and ethnic groups. While the majority of the PBGD gene mutations, including most of the mutations occurring at CpG dinucleotides, are family-specific, a few CpG mutations have been observed in a number of AIP patients of European origin. To study the origin of these common CpG mutations, eight intragenic single-nucleotide polymorphisms (SNPs) in the PBGD gene, as well as eight microsatellites flanking the gene in chromosome 11 were used to construct haplotypes in six AIP families of German, Polish and Swiss origins who carried either G111R (4707G>A) or R173Q (6391G>A) mutations. Among the three R173Q families, three distinct haplotypes were found to be cosegregated with the mutation. One Swiss and one German G111R family shared partially an intragenic and its extended microsatellite haplotype, whereas the Polish G111R family showed a unique haplotype. These results indicated that the recurrent CpG mutations that exist in the European AIP population can be either of ancestral origins or derived from de novo events.

Zinc mesoporphyrin represses induced hepatic 5-aminolevulinic acid synthase and reduces heme oxygenase activity in a mouse model of acute hepatic porphyria.

Zinc mesoporphyrin (ZnMP) is a potent inhibitor of heme oxygenase (HO) and represses 5-aminolevulinic acid synthase (ALAS). These properties make it a potential candidate for treatment of inducible acute hepatic porphyrias, diseases characterized by neurovisceral symptoms, and massive ALAS induction. Effects of intraperitoneal ZnMP (2.5-10 micromol/kg/d) and heme arginate (3-6 mg/kg/d) on plasma levels of 5-aminolevulinic acid (ALA), on messenger RNA (mRNA), and activity of hepatic ALAS and HO were studied in porphobilinogen deaminase-deficient mice treated with phenobarbital (100 mg/kg/d) to induce ALAS. ZnMP (5 micromol/kg/d) led to a significant reduction of plasma ALA levels to 31% of controls (P < .01) by lowering the activity of hepatic mitochondrial and cytosolic ALAS to 29% and 25% of controls, respectively (P < .03). ZnMP decreased the mRNA levels of hepatic ALAS to 53% (P < .03) of controls and this repression was more pronounced than that achieved with heme arginate. In contrast to heme arginate, ZnMP led to a significant reduction of HO activity. We conclude that the combined effect of ZnMP on highly induced ALAS and on HO may be of potential benefit for human acute hepatic porphyrias and therefore merits further in vivo investigations addressing questions raised by this study.

Safety and yield of ultrasound-assisted transthoracic biopsy performed by pulmonologists.

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 > or =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 > or =20 mm in diameter is safe in the hands of pulmonologists. The yield for neoplastic disease including mesothelioma is high.