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In COVID-19 related end stage lung disease, there are two distinct phenotypes. The first phenotype is the COVID-19 related acute respiratory distress syndrome (CARDS) showing a classical histopathological pattern of fibrotic diffuse alveolar damage (DAD). The second phenotype is the post-COVID pulmonary fibrosis (PCPF), in which the diagnosis is based on the combined clinical, radiological and (if available) pathological information. Both phenotypes have different clinical features, risk factors, biomarkers and pathophysiology. The exact prognosis in these two phenotypes as well as optimal treatment needs further studies.Key messagesTwo different phenotypes exist for COVID-19 related pulmonary fibrosis. The CARDS phenotype has a worse prognosis compared to the PCPF phenotype, which requires longer-term follow-up and evolves without ARDS picture. The best treatment options for the two different phenotypes, such as anti-fibrotic drugs or lung transplantation, still needs to be defined in future studies.

We identified determinants of SARS-CoV-2 mRNA vaccine antibody response in people with HIV (PWH). Antibody response was higher among PWH less than 60 years, with CD4+ cell count superior to 350 cells/μl and vaccinated with mRNA-1273 by Moderna compared with BNT162b2 by Pfizer-BioNTech. Preinfection with SARS-CoV-2 boosted the antibody response and smokers had an overall lower antibody response. Elderly PWH and those with low CD4+ cell count should be prioritized for booster vaccinations., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Development of chronic lung allograft dysfunction is a limiting factor for post-lung transplant survival. We evaluated whether the dose of the immunosuppressant mycophenolate mofetil or plasma concentrations of the active metabolite mycophenolic acid affect the development of chronic lung allograft dysfunction., Methods: In this retrospective cohort study we recruited 71 patients with a lung transplant between 2010 and 2014 which survived the first year after transplantation up to 1 July 2021. An event-time-analytical Cox proportional-hazards regression model with time-varying-covariates (18,431 measurements for MPA, mycophenolate mofetil dosage, lymphocytes) was used to predict chronic lung allograft dysfunction, with adjustment for sociodemographic factors and lung function at baseline., Results: 37 patients did not develop chronic lung allograft dysfunction (age 41.3 ± 15.6 years, baseline FEV1 95.5 ± 19.1% predicted) and 34 patients developed chronic lung allograft dysfunction (age 50.9 ± 13.3 years, baseline FEV1 102.2 ± 25.4% predicted). Mean mycophenolic acid did not differ significantly between the groups (2.8 ± 1.7 and 3.0 ± 2.3 mg/l; p = 0.724). In the first 4 post-transplant years the death rate was 25%. A total of 50% of the patients died by the ninth post-transplant year. There was a dose-effect relationship between mycophenolate mofetil dosage, mycophenolic acid (r2 = 0.02, p <0.001), as well as lymphocyte levels (r2 = -0.007, p <0.001), but only the traditional risk factor age predicted chronic lung allograft dysfunction. Continuously measured mycophenolic acid did not predict chronic lung allograft dysfunction (hazard ratio 0.98, 95% confidence interval 0.90-1.06, p = 0.64 over a period of 382.97 patient-years)., Conclusion: Mycophenolate mofetil dosage and mycophenolic acid were not associated with chronic lung allograft dysfunction development. Thus, the mycophenolate mofetil dose or mycophenolic acid plasma concentration are not a primary factor related to organ rejection, but chronic lung allograft dysfunction may be influenced by other components of immunosuppression or other factors.

After hospitalization due to acute COPD exacerbations, patient-manageable behaviors influence rehospitalization frequency. This study's aim was to develop a hospital-ward-initiated Behaviour-Change-Wheel (BCW)-based intervention targeting patients' key health behaviors, with the aim to increase quality of life and reduce rehospitalization frequency. Intervention development was performed by University Hospital Zurich working groups and followed the three BCW stages for each of the three key literature-identified problems: insufficient exacerbation management, lack of physical activity and ongoing smoking. In stage one, by analyzing published evidence - including but not limited to patients' perspective - and health professionals' perspectives regarding these problems, we identified six target behaviors. In stage two, we identified six corresponding intervention functions. As our policy category, we chose developing guidelines and service provision. For stage three, we defined eighteen basic intervention packages using 46 Behaviour Change Techniques in our basic intervention. The delivery modes will be face-to-face and telephone contact. In the inpatient setting, this behavioral intervention will be delivered by a multi-professional team. For at least 3 months following discharge, an advanced nursing practice team will continue and coordinate the necessary care package via telephone. The intervention is embedded in a broader self-management intervention complemented by integrated care components. The BCW is a promising foundation upon which to develop our COPD intervention. In future, the interaction between the therapeutic care team-patient relationships and the delivery of the behavioral intervention will also be evaluated., Competing Interests: Claudia Steurer-Stey: reports receiving grants from AstraZeneca Schweiz, GSK Schweiz, consulting fees as an advisory board member and speaker honoraria from AstraZeneca Schweiz, GSK Schweiz and Novartis Schweiz. Paul Chadwick: received speakers honoraria for talks delivered to Roche. Christian Clarenbach: received advisory fees from Roche, Novartis, Boehringer, GSK, Astra Zeneca, Sanofi, Vifor, OM Pharma, Grifols, Daiichi Sankyo and Mundipharma. The authors report no other conflicts of interest in this work. Paul Chadwick and Christian Clarenbach share the senior authorship., (© 2022 Schmid-Mohler et al.)

Since candidates with comorbidities are increasingly referred for lung transplantation, knowledge about comorbidities and their cumulative effect on outcomes is scarce. We retrospectively collected pretransplant comorbidities of all 513 adult recipients transplanted at our center between 1992-2019. Multiple logistic- and Cox regression models, adjusted for donor-, pre- and peri-operative variables, were used to detect independent risk factors for primary graft dysfunction grade-3 at 72 h (PGD3-T72), onset of chronic allograft dysfunction grade-3 (CLAD-3) and survival. An increasing comorbidity burden measured by Charleston-Deyo-Index was a multivariable risk for survival and PGD3-T72, but not for CLAD-3. Among comorbidities, congestive right heart failure or a mean pulmonary artery pressure >25 mmHg were independent risk factors for PGD3-T72 and survival, and a borderline risk for CLAD-3. Left heart failure, chronic atrial fibrillation, arterial hypertension, moderate liver disease, peptic ulcer disease, gastroesophageal reflux, diabetes with end organ damage, moderate to severe renal disease, osteoporosis, and diverticulosis were also independent risk factors for survival. For PGD3-T72, a BMI>30 kg/m2 was an additional independent risk. Epilepsy and a smoking history of the recipient of >20packyears are additional independent risk factors for CLAD-3. The comorbidity profile should therefore be closely considered for further clinical decision making in candidate selection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ehrsam, Schuurmans, Laager, Opitz and Inci.)

Meningitis/encephalitis (ME) syndromic diagnostic assays can be applied for the rapid one-step detection of the most common pathogens in cerebrospinal fluid (CSF). However, the comprehensive performance of multiplex assays is still under evaluation. In our multisite university hospital of eastern Paris, France, ME syndromic testing has been gradually implemented since 2017 for patients with neurological symptoms presenting to an adult or pediatric emergency unit. We analyzed the results from the BioFire FilmArray ME panel versus standard routine bacteriology and virology techniques, together with CSF cytology and clinical data, over a 2.5-year period to compare the diagnostic accuracy of the FilmArray ME panel to that of the reference methods. In total, 1,744 CSF samples from 1,334 pediatric and 336 adult patients were analyzed. False-positive (mostly bacterial) and false-negative (mostly viral) cases were deciphered with the help of clinical data. The performance of the FilmArray ME panel in our study was better for bacterial detection (specificity >99%, sensitivity 100%) than viral detection (specificity >99%, sensitivity 75% for herpes simplex virus 1 [HSV-1] and 89% for enterovirus), our study being one of the largest, to date, concerning enteroviruses. The use of a threshold of 10 leukocytes/mm 3 considerably increased the positive agreement between the results of the FilmArray ME panel and the clinical features, especially for bacterial pathogens, for which agreement increased from 58% to 87%, avoiding two-thirds of inappropriate testing. Based on this analysis, we propose an algorithm for the use of both syndromic and specific assays for the optimal management of suspected meningitis/encephalitis in adult and pediatric patients. IMPORTANCE Based on our comparative analysis of performances of the diagnostic assays, we propose an algorithm for the use of both syndromic and specific assays, for an optimal care of the meningitis/encephalitis threat in adult and pediatric patients.

(1) Background: The way tobacco and tea spread among virgin populations is of major interest our understanding of how ancient economic and cultural practices could have influenced current habits. (2) Methods: hair concentrations of theobromine, theophylline, caffeine, nicotine, and cotinine were measured in hair samples from 47 frozen bodies of people from eastern Siberia, dated from the contact with Europeans to the assimilation of people into Russian society. (3) Results: hair concentration of theobromine, theophylline, and caffeine vary with the type of beverage consumed: green, black, or local herbal teas. Shortly after the first contacts, a few heavy consumers of tobacco were found among light or passive consumers. Tobacco-related co-morbidities began to be recorded one century after and heavy tea users were only found from the 19th century (4) Conclusions: Economic factors and social and family contacts seem to have played a decisive role in tobacco consumption very early on. Behavioral evolution governed the process of substance integration into Siberian culture and was a determinant for the continuity of its use across long periods of time. Analyzing the respective contributions of social and economic processes in the use of these substances opens avenues of investigation for today's public health.

Aims: Chronic lung allograft dysfunction (CLAD) after lung transplantation (Tx) is the clinical result of chronic airway rejection lesions (CARL), histomorphologically described as either obliterative remodeling of small airways or alveolar fibroelastosis, or as a combination of both. We here investigated the CD26-inhibitory effect on CD26-expressing CARL., Main Methods: CARL were induced by BALB/c → C57BL/6 mouse Tx under mild immunosuppression. CARL-related pro-fibrotic mediators were determined by RT-qPCR and western blotting (WB), EMT and ERK markers by WB. CD26 co-expression by immunofluorescence. CD26 was inhibited by Vildagliptin, gene depleted by CD26 -/- mice. Primary lung fibroblasts were employed for ex vivo analyses. Samples from lung transplant patients with CLAD were analyzed by immunohistochemistry., Key Findings: CARL revealed a significantly higher expression of profibrotic proteins vs. normal lungs (p < 0.05). CD26 and EMT co-expressed in CARL with significantly higher Vimentin, Slug, Hif-1α, α-SMA expression vs. normal lungs (p < 0.05). Vildagliptin decreased the expression of α-SMA and N-cadherin in wild type (WT) lung fibroblasts (p < 0.05). Primary lung fibroblasts from WT and CD26 -/- mice treated with TGF-β1, IFN-γ, and FGF showed a reduction of EMT protein expression, proliferation, and reduced activation of ERK in CD26 -/- mice vs. WT mice. CD26-positive cells were found in patient samples with CLAD in areas of loose fibrosis, but not in areas of dense fibrosis., Significance: CD26 is expressed in CARL-developing lung transplants and CD26-inhibition downregulates fibrosis-forming mediators and fibroblast proliferation. CD26 thus qualifies as a target to attenuate the development of CARL mainly via modulation of ERK and the EMT pathway., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Combined pulmonary fibrosis and emphysema (CPFE) is an underrecognized syndrome characterized by chronic, progressive disease with a dismal prognosis. Frequent co-morbidities with a higher incidence than in idiopathic pulmonary fibrosis or emphysema alone are pulmonary hypertension (WHO group 3) in 47-90% of the patients and lung cancer in 46.8% of the patients., Objective: Review current evidence and knowledge concerning diagnosis, risk factors, disease evolution and treatment options of CPFE., Methods: We searched studies reporting CPFE in original papers, observational studies, case reports, and meta-analyses published between 1990 and August 2020, in the PubMed, Embase, Cochrane Library, Wiley Online Library databases and Google Scholar using the search terms [CPFE], [pulmonary fibrosis] OR [IPF] AND [emphysema]. Bibliographies of retrieved articles were searched as well. Further inclusion criteria were publications in English, French, German and Italian, with reference to humans. In vitro data and animal data were not considered unless they were mentioned in studies reporting predominantly human data., Results: Between May 1, 1990, and September 1, 2020, we found 16 studies on CPFE from the online sources and bibliographies. A total of 890 patients are described in the literature. Although male/female ratio was not reported in all studies, the large majority of patients were male (at least 78%), most of them were current or former heavy smokers., Conclusion: CPFE is a syndrome presenting with dyspnea on exertion followed by disruptive cough and recurrent exacerbations. The disease may progress rapidly, be aggravated by pulmonary hypertension WHO group 3 and is associated with an increased risk of lung cancer. Smoking and male sex are important risk factors. There is a need for more research on CPFE especially relating to etiology, influence of genetics, treatment and prevention options. Antifibrotic therapy might be an interesting treatment option for these patients., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Hage et al.)

Competing Interests: None.

Clinical prediction scores support the assessment of patients in the emergency setting to determine the need for further diagnostic and therapeutic steps. During the current COVID-19 pandemic, physicians in emergency rooms (ER) of many hospitals have a considerably higher patient load and need to decide within a short time frame whom to hospitalize. Based on our clinical experiences in dealing with COVID-19 patients at the University Hospital in Zurich, we created a triage score with the acronym "AIFELL" consisting of clinical, radiological and laboratory findings. The score was then evaluated in a retrospective analysis of 122 consecutive patients with suspected COVID-19 from March until mid-April 2020. Descriptive statistics, Student's t-test, ANOVA and Scheffe's post-hoc analysis confirmed the diagnostic power of the score. The results suggest that the AIFELL score has potential as a triage tool in the ER setting intended to select probable COVID-19 cases for hospitalization in spontaneously presenting or referred patients with acute respiratory symptoms., (Copyright © 2020 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: Tobacco smoke worsens COPD and asthma. For healthy individuals, quantifying active and second-hand smoke (SHS) exposure clarifies the epidemiology of tobacco consumption and the efficacy of nonsmoking measures. Identifying tobacco exposure biomarkers and cut-offs might allow the creation of sensitive and specific tests., Aim: We describe the state-of-the-art serum, urinary cotinine and exhaled carbon monoxide (CO) cut-offs for assessing smoking status and SHS exposure in adult patients with COPD or asthma, and healthy controls., Methodology: After a keyword research in the PubMed database, we included papers reporting on the cut-offs of the investigated biomarkers in one of the populations of interest. Papers published before 2000, not in English, or reporting only data on nonadult subjects or on pregnant women were excluded from the analysis. 14 papers were included in the final analysis. We summarised diagnostic cut-offs for smoking status or SHS exposure in COPD, asthmatic and healthy control cohorts, reporting sensitivity and specificity when available., Conclusion: Serum and urinary cotinine and exhaled CO are easy-to-standardise, affordable and objective tests for assessing smoking status and SHS exposure. Evidence on cut-offs with good sensitivity and specificity values is available mainly for healthy controls. For COPD and asthmatic patients, most of the currently available evidence focuses on exhaled CO, while studies on the use of cotinine with definite sensitivity and specificity values are still missing. Solid evidence on SHS exposure is available only for healthy controls. An integrated approach with a combination of these markers still needs evaluation., Competing Interests: Conflict of interest: M. Bradicich has nothing to disclose. Conflict of interest: M.M. Schuurmans has nothing to disclose., (Copyright ©ERS 2020.)

Efforts to conserve marine mammals are often constrained by uncertainty over their population history. Here, we examine the evolutionary history of a harbour seal ( Phoca vitulina ) population in the Moray Firth, northeast Scotland using genetic tools and microsatellite markers to explore population change. Previous fine-scale analysis of UK harbour seal populations revealed three clusters in the UK, with a northeastern cluster that included our Moray Firth study population. Our analysis revealed that the Moray Firth cluster is an independent genetic group, with similar levels of genetic diversity across each of the localities sampled. These samples were used to assess historic abundance and demographic events in the Moray Firth population. Estimates of current genetic diversity and effective population size were low, but the results indicated that this population has remained at broadly similar levels following the population bottleneck that occurred after post-glacial recolonization of the area., Competing Interests: The authors declare there are no competing interests., (©2020 Nikolic et al.)

Vaping-Associated Pulmonary Illness Abstract. Electronic cigarettes are hand-held devices used to vaporize liquids by heating and thus allowing inhalation of aerosols. Recently, cases of patients have been published which presented with a syndrome associated with e-cigarette consumption, also known as vaping. The syndrome designated 'vaping-associated pulmonary illness' (VAPI) features either isolated respiratory, or combined respiratory gastro-intestinal or constitutional symptoms. VAPI can be rapidly progressive and lead to severe respiratory failure requiring intensive care treatment. Despite the as yet very incomplete understanding of the causative agents and pathogenesis we review the current knowledge of the clinical, pathological and radiological aspects in VAPI and summarise the current therapeutic strategies.

Purpose: Utilization of donation after circulatory death (DCD) donors has the potential to decrease donor shortage in lung transplantation (LTx). This study reviews the long-term outcome of LTx from DCD donors., Methods: We included all consecutive DCD (Maastricht Category III) and all donations after brain death (DBD) donor lung transplants at our Center performed between January 2012 and February 2017. Data were analyzed comparing the two groups in regard of survival after LTx as primary outcome., Results: Median withdrawal to cardiac arrest time was 17 min (interquartile range [IQR]: 11.5-20.5). Median cardiac arrest to cold perfusion was 32 min (IQR: 24.5-36.5). Primary graft dysfunction (PGD) grade 3 at T72 occurred in three recipients. Chronic lung allograft dysfunction (CLAD) led to death in two cases. In DCD group, there was no 90-day mortality. In DCD, group 1- and 3-year survival rates were 100% and 80%. In DBD group, 1- and 3-year survival rates were 85% and 69% (p = 0.4)., Conclusions: Our report confirmed the comparable outcome from DCD donors compared with DBD donors. Utility of DCD donors is a safe option to overcome donor shortage.

Objectives: Human leucocyte antigen (HLA) mismatch between donor and recipient has a differential impact on the outcome after transplant (Tx) among transplantable solid organs. Although the lung is considered a highly antigenic organ, the impact of HLA matching between the donor and the recipient has been shown to be heterogeneous on lung Tx outcome. To provide further evidence that HLA matching should be considered in the decision process prior to lung Tx, we evaluated the impact of donor/recipient HLA mismatch on the outcome after lung Tx at our institution., Methods: All patients who underwent lung Tx were analysed in this retrospective single-cohort study between 1994 and 2013 for HLA (-A, -B or -DR) matching between the donor and the recipient and their association with overall survival, the incidence of acute cellular rejection (ACR) and the development of chronic lung allograft dysfunction (CLAD)., Results: In total, 371 (197 men) patients were included. Of these, 117 patients had no HLA match (0/6), 143 had a 1/6 match, 77 had 2/6 matches, 28 had 3/6 matches and 6 had 4/6 matches. One hundred and twenty-two (33%) patients experienced at least 1 episode of ACR and 172 (46%) patients developed CLAD. Univariate analysis showed a significant correlation between HLA mismatch and the development of CLAD, whereas multivariate analysis revealed that the number of HLA matches (hazard ratio 0.76; P = 0.002), antibodies to cytomegalovirus in either donors or recipients (hazard ratio 1.52; P = 0.036) and donor age (hazard ratio 1.03; P < 0.001) were independent risk factors for the development of CLAD. On the other hand, HLA matches did not correlate with the incidence of ACR and with the overall survival rate., Conclusions: The number of HLA mismatches between donors and recipients after lung Tx did not correlate with ACR or with the overall survival. In contrast, HLA mismatch correlated with the development of CLAD and should therefore be considered a risk factor.

Background: Post-transplant lymphoproliferative disorder (PTLD) is a potentially life-threatening complication of transplantation occurring in the setting of immunosuppression and oncogenic viral infections. However, little is known about the cumulative incidence, histological subtypes, risk determinants and outcome of PTLD in solid organ transplant (SOT) recipients in Switzerland., Methods: This retrospective observational study investigated adult SOT recipients from two sequential cohorts, the pre-SCTS (Swiss Transplant Cohort Study) series, with data collected from January 1986 to April 2008, and the STCS series, with data collected from May 2008 to December 2014 in Switzerland. SOT recipients were cross-referenced with the data of all the patients with a lymphoma diagnosis in each transplant centre and with the data of the Swiss Transplant Cohort Study (STCS) to determine the cumulative incidence of PTLD, pre-therapeutic clinical features, clinical course and outcome. Kaplan-Meier analysis was performed for overall survival after PTLD., Results: We identified 79 cases of PTLD during the study period in the two cohorts: pre-STCS from 1986 to 2008 (n = 62) and STCS from 2008 to 2014 (n = 17). Histological subgroups included: early lesions (pre-STCS n = 2, STCS n = 0); polymorphic PTLD (pre-STCS n = 8, STCS n = 7); monomorphic PTLD (pre-STCS n = 47, STCS n = 10), and Hodgkin's lymphoma (pre-STCS n = 5, STCS n = 0). Median time to PTLD diagnosis was 90 months (range 3-281 months) and 14 months (range 2-59 months) in the pre-STCS and STCS cohorts, respectively. Median follow-up after transplantation was 141 months for the pre-STCS patients and 33 months for the STCS patients. Cumulative incidences of PTLD during the STCS period at 0.5, 1 and 5 years were 0.17% (95% confidence interval 0.07-0.46%), 0.22% (0.09-0.53%) and 0.96% (0.52-1.80%), respectively. For the pre-STCS case series, it was not possible to estimate the incidence rate of PTLD. Survival after PTLD diagnosis was 80% (68-87%) at 1 year and 56% (42-68%) at 5 years for the pre-STCS and STCS cohorts combined., Conclusions: At 5 years, the cumulative incidence of PTLD, regardless of the organ transplanted, was only 0.96% in the STCS cohort, which is lower than that reported in the literature.

Foil Smoking/Heroin Inhalation Abstract. Foil smoking is generally heroin consumption by inhalation. By heating an aluminum foil with a fire lighter the heroin on top of the foil starts melting and the smoke is then inhaled using a straw. Foil smoking is the second most common form of heroin consumption after the intravenous use. In contrast to the IV administration, heroin inhalation effects are delayed by a few minutes and the risk of transmission of HIV, Hepatitis or other infectious diseases is not relevant. Severe bronchospasms can occur in patients with or without prior pulmonary disease such as asthma bronchiale. One cerebral consequence of foil smoking is leukoencephalopathy, a spongiform degeneration of the white matter. This is likely triggered by the pyrolysate generated during the heating process. Multiple drug use and concomitant cigarette smoking in heroin addicts make cause-effect relationships difficult to assess. In general, the history of inhalative heroin consumption should be considered in patients presenting with any unkown pulmonary disease with severe bronchospasms as may happen in a severe asthma exacerbation.

Background: Extracorporeal photopheresis (ECP) has been reported to be safe and the ultimate treatment option in lung transplant recipients with chronic lung allograft dysfunction (CLAD), the main overall cause of mortality in lung transplant recipients. However, ECP is not reimbursed in selected health jurisdictions, and reimbursement by health insurance providers is a major issue. In Switzerland, ECP is not recognised by the health authorities as a therapy option for CLAD; thus by the end of 2014, ECP had to be stopped in the majority of adult lung transplant recipients cared for at the University Hospital Zurich because of lack of continuous funding., Objective: To describe the outcome of lung transplant recipients after forced cessation of ECP treatment., Method: We retrospectively analysed outcome of 12 lung transplant recipients undergoing ECP for different phenotypes of CLAD (bronchiolitis obliterans syndrome, restrictive allograft syndrome) at our centre followed-up for 12 months after forced cessation of ECP., Results: Within the 12 months after treatment cessation, seven patients (58%) died with a median survival of 207 days (range 6-365 days). Lung function (FEV1, forced expiratory volume in 1 second) declined significantly 6 months after ECP cessation (p = 0.003)., Conclusion: Our data support the role of ECP as valuable treatment option in lung transplant recipients with CLAD.

Introduction and Aims: Gastrointestinal (GI) complications such as gastric retention (GR) and constipation are common after lung transplantation (LT). Abdominal plain films (APFs) are a low-cost diagnostic tool to detect impaired GI function. The goal of our study was to assess the prevalence of GI pathology seen on APF in lung transplant recipients (LTRs) and to identify associated risk factors., Methods: Retrospective analysis of consecutive LTRs followed up between 2001 and 2013. Demographic, radiographic and clinical data were assessed., Results: 198 patients were included in the study, 166 thereof had more than 1 APF with a mean number of 5 APFs per patient. 163 patients had a detectable radiographic pathology on APF. The proportion of LTR with GR was highest among cystic fibrosis patients (48.5%). Multivariate regression analysis showed a significant association of diabetes with GR with a trend for age and use of opiates as risk factors. Similarly, female sex, advanced age and diabetes showed a trend to be associated with lower GI tract complications. Almost all patients had suffered from at least 1 episode of lower GI dysmotility during a median follow-up of 5.7 years. No clear correlation between GI events and the development of chronic lung allograft dysfunction could be identified., Conclusions: We found a statistically significant association of diabetes with GR and a progressive increase in the prevalence of GR over time after LT. Lower GI complications affected >80% of LTR and increased over time. Future studies correlating GI transit with APF findings are needed., Competing Interests: Conflicts of Interest: None declared.

Lung transplantation (LTx) is an accepted therapy in children with end-stage lung diseases. Pediatric-specific experience is considered important in pediatric LTx. We present our institutional experience and its outcome since the year 2000, asking whether different treatment strategies produce comparable outcomes in pediatric lung transplant recipients at our predominantly adult center. This is a retrospective analysis of children and adolescents aged ≤20 years, undergoing LTx between January 2001 and December 2013. Minimum follow-up was 12 months. Primary endpoints were re-transplantation or death. We performed 33 lung transplant procedures in 29 patients. Survival 1 month post-operatively was 96.6%, at 3 months 93.1% and at 12 months 82.8%, respectively. At the end of our follow up, 72.4% of our pediatric cohort was still alive - median post-transplant survival was 59 months (range 0-159). 72.4% of the children were transplanted with support of extracorporeal membrane oxygenation (ECMO), size-reduced donor grafts were used in 69.0%. The differences between post-transplant survival of the "non-ECMO-group" versus the "ECMO-group" (137 vs. 28 months, P=0.7) and "full size" versus "size-reduced bilateral transplants" (61 vs. 28 months, P = 0.7) were not significant, though. There were no anastomotic complications, also not in size-reduced lungs. Our results are well comparable to the international data and show excellent short- and mid-term outcomes. We advocate ECMO-bridge to be considered as a valuable treatment option to prolong time on the waiting list in highly selected patients, as well as size reduction and lobar transplants as a strong strategy to increase the donor pool and reduce donor-recipient size-mismatches. Pediatr Pulmonol. 2016;51:1222-1228. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Human metapneumovirus (hMPV) causes serious respiratory tract infections in lung transplant recipients (LTRs). We evaluated the characteristics and adverse drug reactions (ADR) of oral ribavirin therapy for hMPV infections in LTRs. LTRs with respiratory symptoms or suspected infection of unknown origin were routinely sampled with nasopharyngeal swabs (NPS) for virological and bacteriological analysis as part of a diagnostic workup. Medical records of hMPV polymerase chain reaction (PCR)-positive LTRs at the University Hospital of Zurich were reviewed retrospectively. Between January 2012 and June 2014, 12 (80%) of 15 consecutive patients with documented hMPV infection received oral ribavirin therapy (800 mg/d, after 48 h: 400 mg/d). Mean duration of therapy was 28.6 days (range: 11-54). Mean duration of viral shedding was 16.3 days (range: 5-48). In general, oral ribavirin was well tolerated in LTRs. The most common ADR was moderate anaemia. All patients recovered from infection without immediate serious sequelae within 3 months of infection.

Background: We aim to assess the incidence, current treatment, and outcome of diverticulitis in highly immunosuppressed lung transplant recipients., Methods: Retrospective analysis of a prospective database of 403 lung transplant recipients transplanted between 1992 and 2013 with a mean follow-up of 100 months (SD 58.0)., Results: 4.46% of lung transplant recipients (n=18) developed diverticulitis. Eight lung transplant recipients developed uncomplicated diverticulitis, which were all treated successfully with antibiotics. Three patients (37.5%) underwent elective sigmoid resection with severe Grade 3b complications after two of five (40%) surgical procedures. Diverticulitis recurrence occurred in five patients (60%). In total, 10 lung transplant recipients presented with 11 episodes of perforated diverticulitis with a 30-day mortality rate of 9.1%. Hartmann procedure was performed in eight lung transplant recipients. Sigmoid resection with primary anastomosis and protective ileostomy was performed in three patients with Hinchey I. Two of these patients developed anastomotic leakage with a secondary Hartmann procedure., Conclusion: Due to high leakage rate after resection with primary anastomosis and protective ileostomy in our cohort of lung transplant recipients with perforated diverticulitis, the Hartmann procedure seems to be the safer option. In contrast, in uncomplicated diverticulitis, non-operative treatment can be considered as a safe and highly successful treatment option, even for recurrences., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In this retrospective, single-center data analysis, we audited our clinical practice to treat Stenotrophomonas maltophilia in asymptomatic lung transplant recipients (LTRs). Eighteen LTRs with confirmed isolation of S. maltophilia were identified. Twelve of these LTRs have been treated with antibiotics, while 6 were managed without treatment. Treatment was based on antibiograms (trimethoprim/sulfamethoxazole [TMP/SMX] (8/12), levofloxacin (1/12), or both (3/12). Clearance (12/12 vs 6/6), eradication (10/12 vs 3/6, P=.27), and freedom from S. maltophilia recurrence (83%±11% vs 40%±22% after one year, log-rank P=.09) were not found to differ significantly between treated and untreated patients. None of the patient groups showed significant changes in lung function or biochemical variables. Creatinine levels at the end of the study period were found to be higher in treated patients compared to the untreated group (P=.049). De novo acquired TMP/SMX resistance in S. maltophilia strains was not observed. These results indicate no evidence that antibiotic treatment for S. maltophilia in asymptomatic LTRs alters lung function or the clinical outcome., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Diagnosis of acute lung allograft rejection is currently based on transbronchial lung biopsies. Additional methods to detect acute allograft dysfunction derived from plasma and bronchoalveolar lavage samples might facilitate diagnosis and ultimately improve allograft survival. This review article gives an overview of the cell profiles of bronchoalveolar lavage and plasma samples during acute lung allograft rejection. The value of these cells and changes within the pattern of differential cytology to support the diagnosis of acute lung allograft rejection is discussed. Current findings on the topic are highlighted and trends for future research are identified.

Background: The evaluation of solitary pulmonary lesions (SPL) requires a balance between procedure-related morbidity and diagnostic yield, particularly in areas where tuberculosis (TB) is endemic. Data on ultrathin bronchoscopy (UB) for this purpose is limited. To evaluate feasibility and safety of UB compared to SB for diagnosis of SPL in a TB endemic region., Methods: In this prospective randomised trial we compared diagnostic yield and adverse events of UB with standard-size bronchoscopy (SB), both combined with fluoroscopy, in a cohort of patients with SPL located beyond the visible range of SB., Results: We included 40 patients (mean age 55.2 years, 45 % male) with malignant SPL (n = 16; 40 %), tuberculous SPL (n = 11; 27.5 %) and other benign SPL (n = 13; 32.5 %). Mean procedure time in UB and SB was 30.6 and 26.0 min, respectively (p = 0.15). By trend, adverse events were recorded more often with UB than with SB (30.0 vs. 5.0 %, p = 0.091), including extensive coughing (n = 2), blocked working channel (n = 2), and arterial hypertension requiring therapeutic intervention (n = 1), all with UB. The overall diagnostic yield of UB compared to SB was 55.0 % vs. 80.0 %, respectively (p = 0.18). Sensitivity for the diagnosis of malignancy of UB and SB was 50.0 % and 62.5 %, respectively (p = 0.95)., Conclusion: UB is not superior to SB for the evaluation of SPL in a region endemic with tuberculosis, when combined with fluoroscopic guidance only., Trial Registration: ClinicalTrials.gov (Identifier: NCT02490059 ).

Questions Under Study: To (1) assess distinct clusters of psychological distress and health-related quality of life during the first 6 months following lung transplantation; (2) identify patients with poor psychosocial outcomes; and (3) determine potential predictors regarding psychological distress and health-related quality (HRQoL) of life at 6 months post-transplant., Methods: A total of 40 patients were examined for psychological distress (Symptom Checklist short version-9) and quality of life (EuroQOL five-dimension health-related quality of life questionnaire) during their first 6 months post-transplant. Hierarchical cluster analyses were performed to identify specific types of post-transplant outcomes in terms of psychological distress and HRQoL over the first six post-transplant months. Correlational analyses examined medical and psychosocial predictors of the outcome at 6 months post-transplant., Results: Three distinctive clusters were identified, summarizing either groups of patients with (1) optimal (35%), (2) good (42%), and (3) poor outcome-clusters (23%). The latter tended to be older, to suffer from more severe disease, to have more co-morbidities, to have had a prolonged intensive care unit and/or hospital stay, to have more hospital admissions and were more frequently treated with antidepressants post-transplant. Disease severity, length of stay, quality of life two weeks post-transplant, hospital admissions and use of antidepressants were strong predictors of psychological distress and impaired health-related quality of life at six months of follow-up., Conclusion: Almost a quarter of the investigated patients suffered from elevated distress and substantially impaired HRQoL, with no improvements over time. Results underscore the psychosocial needs of patients with poor post-transplant outcomes.

Objectives: Overall, emphysema (EMP) is the most common indication for lung transplantation. The majority of patients present with chronic obstructive pulmonary disease (COPD) and less frequently with alpha-1 antitrypsin deficiency (A1ATD). We analysed the results of lung transplants performed for EMP in order to identify the impact of age on short- and long-term outcome., Methods: A retrospective analysis was undertaken of the 108 consecutive lung transplants for EMP performed at our institution from November 1992 to August 2013 (77 COPD, 31 A1ATD). Retransplantations were excluded., Results: The median age was 56 years (range 31-68). Thirty-day mortality rate was 3.7%. One- and 5-year survival rates in COPD and A1ATD recipients were comparable (P = 0.8). The 1- and 5-year survival rates for recipients aged <60 years old were significantly better than the age group of ≥60 years (91 and 79 vs 84 and 54%, P = 0.05). Since 2007, the 1- and 5-year survival for these two age groups were 96 and 92 vs 86 and 44%, respectively, P = 0.04, log-rank test). For the following parameters, we were not able to find any difference to affect survival rates: use of intraoperative extracorporeal membrane oxygenation, waiting list time, sex, graft size reduction, body mass index and diagnosis. In multivariate analysis, age at transplantation (≥60 years old) (HR 2.854; 95% confidence interval (CI) 1.338-6.08, P = 0.008) and unilateral lung transplantation (HR 15.2; 95% CI 3.2-71.9, P = 0.009) were independent risk factors for mortality., Conclusions: COPD and A1ATD recipients have similar overall long-term survival. Recipients aged ≥60 years and unilateral lung transplants were risk factors for mortality., (© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Multiplex PCR assays for respiratory viruses are widely used in routine diagnostics, as they are highly sensitive, rapid, and cost effective. However, depending on the assay system, cross-reactivity between viruses that share a high sequence homology as well as detection of rare virus isolates with sequence variations can be problematic. Virus sequence-independent metagenomic high-throughput sequencing allows for accurate detection of all virus species in a given sample, as we demonstrate here for human Enterovirus and Rhinovirus in a lung transplant patient. While early in infection a commercial PCR assay recorded Rhinovirus, high-throughput sequencing correctly identified human Enterovirus C104 as the source of infection, highlighting the potential of the technology and the benefit of applying open assay formats in complex diagnostic situations., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Electronic cigarettes (e-cigarettes) are vaporisers of liquids often containing nicotine. In the inhaled aerosol carcinogens, ultrafine and metal particles are detected usually in concentrations below those measured in tobacco smoke. Therefore, these products are expected to be less harmful. This has not yet been proven. The long-term safety of e-cigarettes is unknown. Short duration use leads to airway irritation and increased diastolic blood pressure. So far only two randomised controlled trials have investigated efficacy and safety of e-cigarettes for smoking cessation: No clear advantage was shown in comparison to smoking cessation medication. Due to insufficient evidence, e-cigarettes cannot be recommended for smoking cessation. Problematic are the lack of regulation and standardisation of e-cigarette products, which makes general conclusions impossible.

Background: An atherosclerotic disease burden sufficient to put lung transplant candidates at risk for end-organ disease after transplantation is considered to be a relative contraindication for lung transplantation., Objectives: The aim of this study was to assess our current practice of cardiac workup by coronary angiography in lung transplant candidates ≥50 years of age., Methods: We retrospectively analyzed 50 consecutive lung transplant candidates ≥50 years of age in which coronary angiography was performed at the University Hospital Zurich (2009-2013). For every patient, the risk of developing an acute coronary event was estimated by using a recalibrated version of the PROCAM study calculator for the Swiss population., Results: The median estimated risk of developing an acute coronary event within 10 years in the study cohort (n = 50) was 4.2% (interquartile range 1.9-7.6), which is considered to be a low risk. Sixteen percent of patients were considered to be at intermediate risk. In 66% of patients, coronary angiography showed no coronary artery disease (CAD). In 28% of patients, CAD without significant stenosis was diagnosed. In 6% of patients, significant coronary stenosis was detected requiring percutaneous coronary intervention. No correlation between the coronary status and the risk score or cardiovascular risk profile was found., Conclusions: The high prevalence of asymptomatic CAD in lung transplant candidates without correlation to a common clinical risk score supports the important role of coronary angiography for the assessment of coronary artery status. This approach might prevent cardiovascular events and improve long-term survival after transplantation., (© 2015 S. Karger AG, Basel.)

Lung transplant recipients have a life-long profound immunosuppression which makes them prone to respiratory tract infections, in particular viral infections during the winter season. Since the respiratory tract infections may have potentially severe consequences, we recommend early diagnosis and treatment. We obtain nasopharyngeal swabs for viral and bacteriological examination and then treat pre-emptively with antivirals, broad-band antibiotics and often also with intravenous immunoglobulins. Treatment duration is often longer than in immunocompetent patients. As preventive measures we provide vaccination against seasonal influenza and recommend specific daily hygiene measures.

Lung transplantation is an established therapeutic option for end-stage lung disease in selected patients. During the last 30 years more than 34,000 transplantations have been performed worldwide. Emphysema, pulmonary fibrosis, cystic fibrosis and primary pulmonary hypertension are the most common indications. This type of surgical treatment is increasingly successful, with better early and late survival rates. However, lung transplantation is still hampered by persisting problems such as donor organ shortage, primary graft dysfunction, late graft dysfunction and morbidity related to long-term immunosuppression. The first lung transplantation in Switzerland was performed the 10th November 1992 at Zurich University Hospital. Since then the lung transplant programme has progressively increased its yearly transplant volume. Since the beginning of our lung transplantation programme, overall patient survival has increased steadily and has been at benchmark levels since the year 2000. The most important factors influencing this result are presumably good teamwork among all involved specialists, improved surgical techniques, and close and long-term patient follow-up by the transplant pulmonologists. In this paper we present our programme structure, managing strategies for some specific problems and outcome after lung transplantation. The results presented here are from recipients who underwent lung transplantation up to the end of 2011.

Meticulous attention to detail during the early postoperative period after lung transplantation is crucial for the overall success of the procedure. It starts in the intensive care unit with the initiation of immunosuppression, implementation of anti-infective strategies and stabilisation of respiratory function. The subsequent days and weeks on the regular ward focus on titration of immunosuppressive drugs, vigilant fluid management, early mobilisation and initiation of physiotherapy. In parallel, the lung transplant recipients are actively taught about self-monitoring and self-management strategies to allow for a smooth transition to outpatient follow-up care. This article intends to communicate the practical aspects and principles of the patient management used at the authors' centre on a daily basis by a multi-disciplinary transplant team, having at its core both a transplant pulmonologist and a thoracic surgeon. It focuses on the first month after lung transplantation, but does not cover surgical techniques, rare complications or long-term management issues of lung transplant recipients. The target audience of this practical guide are advanced trainees of pulmonology, thoracic surgery, intensive care, anaesthesiology and other clinicians involved in the early postoperative care of lung transplant recipients either in the intensive care unit or on the peripheral ward.

We present the case of a lung transplant recipient with disseminated crystal precipitation, and granulomatous and fibrinous inflammation after therapy with foscarnet (Foscavir; AstraZeneca, Zug, Switzerland) for recurring ganciclovir-resistant cytomegalovirus (CMV) reactivation. This is the first description of systemic crystal precipitation and granulomatous inflammation associated with foscarnet therapy with predominant involvement of the heart, kidneys and lungs., (Copyright © 2012 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: On 22 June 2011, 8 patients with hemolytic uremic syndrome (HUS) or bloody diarrhea were reported in France. All 8 were attendees of a community center event on 8 June near Bordeaux. Three Escherichia coli cases were confirmed by isolation of Shiga toxin-producing E. coli O104:H4 stx2 aggR producing a cefotaximase (CTX-M) β-lactamase (STEC O104:H4); the same rare serotype caused the outbreak in Germany in May-July 2011. An investigation was initiated to describe the outbreak, identify the vehicle for infection, and guide control measures., Methods: We conducted a retrospective cohort study among all adults attending the event, including food handlers. A standardized questionnaire was administered to participants. A case was an attendee who developed HUS or diarrhea between 8 and 24 June. Cases were confirmed by isolation of STEC O104:H4 or O104 serology. Relative risks (RRs) and 95% confidence intervals (CIs) by exposure were calculated using a Poisson regression model., Results: Twenty-four cases were identified (14% attack rate). Of these, 18 (75%) were women, 22 (92%) were adults, 7 (29%) developed HUS, 5 (21%) developed bloody diarrhea, and 12 (50%) developed diarrhea. Ten (42%) cases were confirmed. Fenugreek was the only sprout type with an independent association to illness (RR, 5.1; 95% CI, 2.3-11.1) in multivariable analysis., Conclusions: This investigation identified a point-source STEC O104:H4 outbreak associated with consumption of fenugreek sprouts. Comparison of results from French and German STEC O104:H4 outbreak investigations enabled identification of a common food vehicle, fenugreek sprouts, and resulted in implementation of Europe-wide control measures in July 2011.

Lung transplant recipients (LTRs) are prone to medical complications and emergencies due to the transplanted organ being in constant direct contact with the environment and the need for life-long profound immunosuppression (IS). As a result of these specific circumstances, the medical and surgical management of LTRs frequently differs from usual standard care. Therefore, we outline here some of the principles we take into account when dealing with the most frequent medical emergencies encountered in our lung transplant cohort in Zurich. The main topics dealt with are: diagnostics and treatment of infections, gastrointestinal emergencies, IS and other medication issues as well as work-up of unclear inflammatory signs and peri-operative precautions in LTRs. Early post-operative transplant complications, rare medical emergencies and surgical problems are not covered. Our report is intended to help internists and pulmonologists new to the field to obtain a better understanding of the peculiarities of LTRs and their management., (Copyright © 2012 S. Karger AG, Basel.)

Perceptual processes play an important role in motor learning. While it is evident that visual information greatly contributes to learning new movements, much less is known about provision of prescriptive proprioceptive information. Here, we investigated whether passive (proprioceptively-based) movement training was comparable to active training for learning a new bimanual task. Three groups practiced a bimanual coordination pattern with a 1:2 frequency ratio and a 90° phase offset between both wrists with Lissajous feedback over the course of four days: 1) passive training; 2) active training; 3) no training (control). Retention findings revealed that passive as compared to active training resulted in equally successful acquisition of the frequency ratio but active training was more effective for acquisition of the new relative phasing between the limbs in the presence of augmented visual feedback. However, when this feedback was removed, performance of the new relative phase deteriorated in both groups whereas the frequency ratio was better preserved. The superiority of active over passive training in the presence of augmented feedback is hypothesized to result from active involvement in processes of error detection/correction and planning.

Genome-wide association studies for complex traits are based on the common disease/common variant (CDCV) and common disease/rare variant (CDRV) assumptions. Under the CDCV hypothesis, classical genome-wide association studies using single-marker tests are powerful in detecting common susceptibility variants, but under the CDRV hypothesis they are not as powerful. Several methods have been recently proposed to detect association with multiple rare variants collectively in a functional unit such as a gene. In this paper, we compare the relative performance of several of these methods on the Genetic Analysis Workshop 17 data. We evaluate these methods using the unrelated individual and family data sets. Association was tested using 200 replicates for the quantitative trait Q1. Although in these data the power to detect association is often low, our results show that collapsing methods are promising tools. However, we faced the challenge of assessing the proper type I error to validate our power comparisons. We observed that the type I error rate was not well controlled; however, we did not find a general trend specific to each method. Each method can be conservative or nonconservative depending on the studied gene. Our results also suggest that collapsing and the single-locus association approaches may not be affected to the same extent by population stratification. This deserves further investigation.

Purpose: To decipher the biological pathways involved in keratoconus pathophysiology by determining the patterns of differential gene expression between keratoconus and control corneas., Methods: RNA was extracted from surgically removed corneas of 10 keratoconus patients and from normal corneas of 10 control patients who had undergone enucleation of an eye for ocular melanoma. Several hundred thousand RNA transcripts were assessed using exon microarrays. Statistical comparison and identification of differentially regulated and differentially spliced RNA transcripts was performed by comparing keratoconus cases and controls. In addition, relevant biological pathways were identified by information extraction using network biology., Results: Eighty-seven genes showed significant differences in expression levels. Among these, 69 were downregulated in keratoconus patients, particularly partners of the transcription factor AP-1. The 18 overexpressed genes include mucins, keratins, and genes involved in fibroblast proliferation. In addition, 36 genes were shown to be differentially spliced, including 9 among those that were differentially expressed. Network biology and analysis using Gene Ontology descriptors suggest that many members of both groups belong to pathways of apoptosis and regulation of the balance between cellular differentiation and proliferation., Conclusions: This work constitutes the first genome-wide transcriptome analysis of keratoconus patient corneas that include all currently known genes and exons. Differential expression suggests that mechanisms of cell loss resulting from antiproliferative and hyperapoptotic phenotypes may be responsible for the pathogenesis of keratoconus. Array information, experimental design, raw intensities, and processed log(2) ratios were deposited at the European Bioinformatic Institute's ArrayExpress database (http://www.ebi.ac.uk/arrayexpress/). The accession number is E-MEXP-2777.

Unexplained cough for more than 2 - 3 weeks or patients considered to be at high risk for tuberculosis (TB) should be investigated in a timely manner: Chest radiography and 3 sputum examinations for detection acid-fast bacilli and TB cultures are essential first diagnostic steps. Pending sputum results an antibiotic trial (avoiding fluorochinolones) is warranted and if symptoms do not resolve and the diagnosis remains unclear then additional investigations are required to confirm or rule out pulmonary tuberculosis: sputum provocation by inhalation of hypertonic saline or alternatively bronchoscopy may provide samples to confirm TB or lead to an alternative diagnosis. Immunologic and molecular tests are useful in specific situations to identify previous contact with specific mycobacteria or identify drug-resistant strains. Prompt diagnosis and treatment are important epidemiologic measures to prevent transmission of mycobacteria to contacts including the medical personnel. Isolation measures take into account the transmission by aerosol and the viability of the mycobacteria and specific criteria need to be met before these precautions can be abandoned.

Background: Pandemic 2009 H1N1 influenza virus (H1N1) infection is considered harmful to lung transplant recipients (LTRs). Vaccination against this virus is recommended for LTRs, but little is known about associated benefits and risks. Our aim in this study is to document the safety and clinical effectiveness of the H1N1 vaccine in LTRs., Methods: All LTRs received an informational letter on the H1N1 pandemic that included hygiene and vaccination recommendations. After completing a questionnaire, volunteering LTRs received Pandemrix (H1N1 2009 Monovalent AS03-Adjuvanted Vaccine; GSK). Adverse events (AEs) were documented at short-term follow-up visits and by telephone. Any flu-like symptoms were reported and a low threshold for performing nasal/pharyngeal swabs for virus detection was maintained., Results: Of 168 eligible LTRs (107 already vaccinated for 2009 seasonal influenza), 148 (88%) received at least one vaccination with the H1N1 vaccine and 115 received a second dose. After the first vaccination, 44% had no AEs. Six self-limiting, severe AEs occurred, and the remainder were minor to moderate, predominantly injection-site reactions. After the second vaccination, AEs were clearly less frequent. All AEs resolved completely. Documented H1N1 infection occurred in 2 of 148 vaccinated LTRs, in contrast to 5 infections in 20 non-vaccinated LTRs., Conclusions: H1N1 vaccination is generally well tolerated with mild to moderate, predominantly local AEs in most LTRs and few self-limiting severe events. Clinical effectiveness is good., (Copyright © 2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Purpose: High myopia is a public health problem because of its high prevalence and is a major cause of blindness. The physiopathology of myopia remains unknown and mechanisms causing the disease are most probably complex, combining acquired environmental and genetic factors. The most recent data suggest that genetic determinisms of high myopia could be highly dependent on subject phenotype. The aim of this study was to analyse the ocular components of a high myopic population to verify whether high myopia corresponds to a homogeneous phenotype., Patients and Methods: We analysed the biometric characteristics of 718 myopic eyes with a spherical equivalent of less than -5 diopters. The biometric parameters (corneal radius, axial length, and intraocular pressure) were compared controlling for sex and the degree of myopia., Results: We found a difference between the phenotype of males and females. For men, axial length was the only determinant of the myopic phenotype, whereas for women, the myopic phenotype was determined by axial length and corneal radius. This difference between the phenotypes was more evident for myopia with a spherical equivalent greater than -10 diopters (moderate myopia). This difference between males and females disappeared in myopia less than -15 diopters., Conclusion: There are intersex differences considering the high myopia phenotype at a spherical equivalent less than -5 diopters. However, this difference disappears for extremely high myopia with a spherical equivalence of less than -15 diopters., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Genotypic algorithms for prediction of HIV-1 coreceptor usage need to be evaluated in a clinical setting. We aimed at studying (i) the correlation of genotypic prediction of coreceptor use in comparison with a phenotypic assay and (ii) the relationship between genotypic prediction of coreceptor use at baseline and the virological response (VR) to a therapy including maraviroc (MVC). Antiretroviral-experienced patients were included in the MVC Expanded Access Program if they had an R5 screening result with Trofile (Monogram Biosciences). V3 loop sequences were determined at screening, and coreceptor use was predicted using 13 genotypic algorithms or combinations of algorithms. Genotypic predictions were compared to Trofile; dual or mixed (D/M) variants were considered as X4 variants. Both genotypic and phenotypic results were obtained for 189 patients at screening, with 54 isolates scored as X4 or D/M and 135 scored as R5 with Trofile. The highest sensitivity (59.3%) for detection of X4 was obtained with the Geno2pheno algorithm, with a false-positive rate set up at 10% (Geno2pheno10). In the 112 patients receiving MVC, a plasma viral RNA load of <50 copies/ml was obtained in 68% of cases at month 6. In multivariate analysis, the prediction of the X4 genotype at baseline with the Geno2pheno10 algorithm including baseline viral load and CD4 nadir was independently associated with a worse VR at months 1 and 3. The baseline weighted genotypic sensitivity score was associated with VR at month 6. There were strong arguments in favor of using genotypic coreceptor use assays for determining which patients would respond to CCR5 antagonist.