The composition of the choice set modulates probability weighting in risky decisions.

Probability distortion-the tendency to underweight larger probabilities and overweight smaller ones-is a robust empirical phenomenon and an important driver of suboptimal choices. We reveal a novel contextual effect on probability distortion that depends on the composition of the choice set. Probability distortion was larger in a magnitude-diverse choice set (in which participants encountered more unique magnitudes than probabilities) but declined, resulting in more veridical weighting, in a probability-diverse choice set (more unique probabilities than magnitudes). This effect was consistent in two, large, independent datasets (N = 481, N = 100) and held for a subset of lotteries that were identical in the two contexts. It also developed gradually as a function of exposure to the choice set, was independent of attentional biases to probability versus magnitude information, and was specific to probability weighting, leaving risk attitudes unaffected. The results highlight the importance of context when processing probabilistic information.

International multicentre observational study to assess the efficacy and safety of a 0·5 mg kg-1 per day starting dose of oral corticosteroids to treat bullous pemphigoid.

BACKGROUND: European guidelines propose a 0·5 mg kg-1 per day dose of oral prednisone as initial treatment for bullous pemphigoid (BP). We assessed the safety and efficacy of this regimen depending on BP extent and general condition of the patients. METHODS: In a prospective international study, we consecutively included all patients diagnosed with BP. Patients received a 0·5 mg kg-1 per day dose of prednisone, which was then gradually tapered 15 days after disease control, with the aim of stopping prednisone or maintaining minimal treatment (0·1 mg kg-1 per day) within 6 months after the start of treatment. The two coprimary endpoints were control of disease activity at day 21 and 1-year overall survival. Disease severity was assessed according to the Bullous Pemphigoid Disease Area Index (BPDAI) score. RESULTS: In total, 198 patients were included between 2015 and 2017. The final analysis comprised 190 patients with a mean age of 80·9 (SD 9·1) years. Control of disease activity was achieved at day 21 in 119 patients [62·6%, 95% confidence interval (CI) 55·3-69.5]; 18 of 24 patients (75%, 95% CI 53·3-90·2), 75 of 110 patients (68·8%, 95% CI 59·2-77·3) and 26 of 56 patients (46.4%, 95% CI 33·0-60·3) had mild, moderate and severe BP, respectively (P = 0·0218). A total of 30 patients died during the study. The overall Kaplan-Meier 1-year survival was 82·6% (95% CI 76·3-87·4) corresponding to 90·9%, 83·0% and 80·0% rates in patients with mild, moderate and severe BP, respectively (P = 0·5). Thresholds of 49 points for BPDAI score and 70 points for Karnofsky score yielded maximal Youden index values with respect to disease control at day 21 and 1-year survival, respectively. CONCLUSIONS: A 0·5 mg kg-1 per day dose of prednisone is a valuable therapeutic option in patients with mild or moderate BP whose general condition allows them to be autonomous.

[Oxygen Therapy in Lung Transplantation Candidates - A Single Center Retrospective Analysis of 807 Patients]. / Sauerstofftherapie bei Kandidaten zur Lungentransplantation − eine monozentrische retrospektive Analyse von 807 Patienten.

BACKGROUND: Long-term oxygen treatment (LTOT) is frequently used in patients with advanced pulmonary diseases and respiratory failure. Oxygen treatment influences donor lung allocation for patients and is associated with increased mortality. This study investigates oxygen therapy in lung transplantation candidates. METHODS: A retrospective study at a large German transplantation centre between 09/2011 and 01/2019 was performed. Data regarding oxygen therapy was analyzed and LTOT-indication verified by titrated blood gas analysis. The study period splits into 2 periods before and after the introduction of oxygen titration (3rd quarter of 2015). Univariate and multivariate analysis for the endpoint "admission to waiting list" was performed. RESULTS: 807 patients were included in the analysis, 396 in the first and 411 patients in the second period. Of those 293 patients (36.3 %) were transplanted. Six hundred thirty (78 %) patients stated using oxygen for more than 12 hours per day. After implementing oxygen titration in period 2, in 212 (57 %) of 372 patients LTOT indication could be confirmed. Titrated oxygen flow was lower in period 2 (0.5 l/min [IQR 0.0 - 2.0] versus 2 l/min [IQR 0.5 - 3.0]). In multivariate analysis oxygen flow was associated with admission to waiting list as an independent variable. CONCLUSION: Patients referred to lung transplantation use oxygen therapy in the vast majority. Indication for LTOT should be carefully reassessed in candidates. Confirmed LTOT-indication seems to be associated with the likelihood for admission to the waiting list for lung transplantation and could therefore be a selection criterium in the future.

[Lung transplantation : Histomorphological diagnosis and clinical aspects]. / Lungentransplantation : Histomorphologische Diagnostik und klinische Aspekte.

The function of pulmonary allografts is regularly impaired by alloimmune reactions with quite variable clinical outcomes, different involved effector cells and molecules, as well as affected anatomical compartments. Acute rejection of grafts after lung transplantation (LuTx) is not only associated with the subsequent development of acute graft dysfunction, but can also contribute - among other immunological and nonimmunological factors - to the development of chronic lung allograft dysfunction (CLAD), which is the main reason for the limited long-term survival after LuTx. In addition to ACR and analogous to other solid organ transplants, the importance of antibody-mediated (humoral) rejection (AMR) in LuTx has also been recognized. There are currently no specific laboratory, radiological, or clinical tests available for either ACR or AMR. Only by the synoptic examination of histopathological changes and interpretation against the background of microbiological, virological, serological, and functional findings, can adequate sensitivity and specificity be achieved in the diagnostics of rejection. In this article, the current criteria for histopathological diagnostics of rejection following LuTx are summarized and the most important differential diagnoses are discussed.

[Waiting List Management and Organ Allocation for Lung Transplantation 2018]. / Wartelistenführung und Organvermittlung zur Lungentransplantation 2018 ­ Aktuelles für den Pneumologen.

In 2017 an amendment to the German transplant law concerning organ allocation and waiting list management became effective. This implies important consequences on lung transplant centers. Crucial innovations concern the transplant conference, indications for lung transplantation and waiting list management. Certain medical conditions now imply a restriction of waiting list enrollment for patients and there are new options for size-matching of donor lung and recipient. Moreover, the new amendment describes in detail how the clinical parameters, on which the lung allocation score (LAS) is based, are defined and how the essential physical examinations have to be performed. Furthermore, the current article provides a summary of the process of organ allocation by the organ exchange organization.

Detection of chronic lung allograft dysfunction using ventilation-weighted Fourier decomposition MRI.

Chronic lung allograft dysfunction (CLAD) remains the leading cause of morbidity and mortality after lung transplantation. Diagnosis requires spirometric change, which becomes increasingly difficult with advancing CLAD. Fourier decomposition magnetic resonance imaging (FD-MRI) permits acquisition of ventilated-weighted images during free-breathing. This study evaluates FD-MRI in detecting CLAD in selected patients after bilateral lung transplantation (DLTx). DLTx recipients demonstrating CLAD at various stages participated. Radiologists remained blinded to clinical status until completion of image analysis. Image acquisition used a 1.5-T MR scanner using a spoiled gradient echo sequence. After FD processing and regional fractional ventilation (RFV) quantification, the volume defect percentage at 2 thresholds (VDP1,2 ), median lung RFV and quartile coefficient of dispersion (QCD) were calculated. Sixty-two patients participated. CLAD was present in 29/62 (47%) patients, of whom 17/62 (27%) had forced expiratory volume in 1 second ≤65% at image acquisition. VDP1 was higher among these participants compared to other groups (P < .001). Increased VDP1 was associated with subsequent graft loss, with values >2% showing reduced survival, independent of degree of graft dysfunction (P = .005). VDP2 discriminated between presence or absence of CLAD (area under the curve = 0.71; P = .03). QCD increased significantly with advancing disease (P < .001). In conclusion, FD-MRI-derived parameters demonstrate potential in quantitative CLAD diagnosis and assessment after DLTx.

Single lung transplantation from a donor 8 months after double lung transplantation.

Scarcity of donors leads transplant surgeons to consider extended-criteria lungs and occasionally to accept the unlikely. Here we report a case of successful single lung transplantation from a donor 8 months after double lung transplantation.

Human orf complicated by epidermolysis bullosa acquisita.

Orf is a DNA parapoxvirus transmitted to humans by contact with infected goats and sheep. Many complications have been reported after orf infection, including erythema multiforme. A few cases of autoimmune bullous dermatosis complicating orf disease have been reported to date. They are usually characterized by tense blister eruptions with or without mucosal involvement; linear deposition of C3, IgG and/or IgA along the basement membrane; and negativity of indirect immunofluorescence analysis and enzyme-linked immunosorbent assay (ELISA) (performed in four of 11 reported cases). These analyses have targeted antigens of bullous pemphigoid, mucous membrane pemphigoid or epidermolysis bullosa acquisita, except one case of mucosal pemphigoid with antilaminin-332 antibodies. We describe the case of a patient who presented with an ulceration on his finger 10 days after direct contact with a lamb during Eid al-Adha. Four weeks later he developed a severe tense blistering eruption associated with mucous membrane erosions. Indirect immunofluorescence analysis using the patient's serum revealed circulating antibasement membrane IgG that bound the dermal side of salt-split skin. ELISA was positive for recombinant immunodominant NC1 domain of type VII collagen. We finally diagnosed epidermolysis bullosa acquisita complicating probable human orf infection.

Endobronchial Ultrasound in Suspected Non-Malignant Mediastinal Lymphadenopathy.

BACKGROUND: Endobronchial ultrasound (EBUS) bronchoscopy with transbronchial needle aspiration (TBNA) is a well-established tool in mediastinal staging in lung cancer and gains importance in exploration of non-malignant lymphadenopathy. The aim of this study was to evaluate the role of EBUS-TBNA in suspected non-malignant diseases. METHODS: A retrospective, single-center, observation analysis of endobronchial ultrasound bronchoscopy procedures was performed in a university medical center between March 2013 and July 2015. All patients with suspected non-malignant mediastinal lymphadenopathy were included. Cytopathological and microbiological results of EBUS were compared to clinical diagnosis 6 months after procedure and performance of EBUS was contrasted to malignant indications. RESULTS: During study period, 333 EBUS bronchoscopies in 315 patients with mediastinal lymphadenopathy were performed. 111 out of 315 (35 %) patients had neither primary signs nor history of a malignant disease, categorised as patients with suspected non-malignant disease. 245 lymph nodes were sampled (median size 15 mm [IQR10 - 19]). Preferred station for TBNA was lymph node station 7 (38 %). Cytopathological findings revealed non-specific inflammation (n = 81; 70 %), carcinoma (n = 7; 6 %), epithelioid cell granulomas (n = 20; 17 %). 7 samples (6 %) were non-representative. Microbiologic testing of lymph nodes identified 3 infections (Mycobacteria tuberculosis [n = 2] and Nocardia nova [n = 1]) relevant to antibiotic therapy. Minor adverse events were observed in 9 out of 115 (8 %) patients. Sensitivity of EBUS-TBNA intervention in suspected non-malignant disease was 76 % and specificity 96 %. CONCLUSIONS: EBUS-TBNA revealed a specific cause for suspected non-malignant lymphadenopathy in one-third of cases and was associated with excellent specificity. Predominant specific causes were granuloma, besides from tumor. In 3 patients pathogen could be isolated by TBNA.

"White-Out" After Lung Transplantation: A Multicenter Cohort Description of Late Acute Graft Failure.

Graft failure represents a leading cause of mortality after organ transplantation. Acute late-onset graft failure has not been widely reported. The authors describe the demographics, CT imaging-pathology findings, and treatment of patients presenting with the latter. A retrospective review was performed of lung transplant recipients at two large-volume centers. Acute late-onset graft failure was defined as sudden onset of bilateral infiltrates with an oxygenation index <200 without identifiable cause or concurrent extrapulmonary organ failure. Laboratory, bronchoalveolar lavage (BAL), radiology, and histology results were assessed. Between 2005 and 2016, 21 patients were identified. Median survival was 19 (IQR 13-36) days post onset. Twelve patients (57%) required intensive care support at onset, 12 (57%) required mechanical ventilation, and 6 (29%) were placed on extracorporeal life support. Blood and BAL analysis revealed elevated neutrophilia, with CT demonstrating diffuse ground-glass opacities. Transbronchial biopsy samples revealed acute fibrinoid organizing pneumonia (AFOP), organizing pneumonia, and diffuse alveolar damage (DAD). Assessment of explanted lungs confirmed AFOP and DAD but also identified obliterative bronchiolitis. Patients surviving to discharge without redo transplantation (n = 2) subsequently developed restrictive allograft syndrome. This study describes acute late-onset graft failure in lung allograft recipients, without known cause, which is associated with a dismal prognosis.

Cognitive-behaviour therapy for post-traumatic stress in schizophrenia. A randomized controlled trial.

BACKGROUND: There is limited evidence for effective interventions in the treatment of post-traumatic stress symptoms within individuals diagnosed with schizophrenia. Clinicians have concerns about using exposure treatments with this patient group. The current trial was designed to evaluate a 16-session cognitive restructuring programme, without direct exposure, for the treatment of post-traumatic stress symptoms specifically within individuals diagnosed with schizophrenia. METHOD: A multicentre randomized controlled single-blinded trial with assessments at 0 months, 6 months (post-treatment) and 12 months (follow-up) was conducted. A total of 61 participants diagnosed with schizophrenia and exhibiting post-traumatic stress symptoms were recruited. Those randomized to treatment were offered up to 16 sessions of cognitive-behaviour therapy (CBT, including psychoeducation, breathing training and cognitive restructuring) over a 6-month period, with the control group offered routine clinical services. The main outcome was blind rating of post-traumatic stress symptoms using the Clinician Administered PTSD Scale for Schizophrenia. Secondary outcomes were psychotic symptoms as measured by the Positive and Negative Symptom Scale and the Psychotic Symptom Rating Scale. RESULTS: Both the treatment and control groups experienced a significant decrease in post-traumatic stress symptoms over time but there was no effect of the addition of CBT on either the primary or secondary outcomes. CONCLUSIONS: The current trial did not demonstrate any effect in favour of CBT. Cognitive restructuring programmes may require further adaptation to promote emotional processing of traumatic memories within people diagnosed with a psychotic disorder.

Idiopathic linear IgA bullous dermatosis: prognostic factors based on a case series of 72 adults.

BACKGROUND: Linear IgA bullous dermatosis (LABD) is a clinically and immunologically heterogeneous, subepidermal, autoimmune bullous disease (AIBD), for which the long-term evolution is poorly described. OBJECTIVES: To investigate the clinical and immunological characteristics, follow-up and prognostic factors of adult idiopathic LABD. METHODS: This retrospective study, conducted in our AIBD referral centre, included adults, diagnosed between 1995 and 2012, with idiopathic LABD, defined as pure or predominant IgA deposits by direct immunofluorescence. Clinical, histological and immunological findings were collected from charts. Standard histology was systematically reviewed, and indirect immunofluorescence (IIF) on salt-split skin (SSS) and immunoblots (IBs) on amniotic membrane extracts using anti-IgA secondary antibodies were performed, when biopsies and sera obtained at diagnosis were available. Prognostic factors for complete remission (CR) were identified using univariate and multivariate analyses. RESULTS: Of the 72 patients included (median age 54 years), 60% had mucous membrane (MM) involvement. IgA IIF on SSS was positive for 21 of 35 patients tested; 15 had epidermal and dermal labellings. Immunoelectron microscopy performed on the biopsies of 31 patients labelled lamina lucida (LL) (26%), lamina densa (23%), anchoring-fibril zone (AFz) (19%) and LL+AFz (23%). Of the 34 IgA IBs, 22 were positive, mostly for LAD-1/LABD97 (44%) and full-length BP180 (33%). The median follow-up was 39 months. Overall, 24 patients (36%) achieved sustained CR, 19 (29%) relapsed and 35% had chronic disease. CR was significantly associated with age > 70 years or no MM involvement. No prognostic immunological factor was identified. CONCLUSIONS: Patients with LABD who are < 70 years old and have MM involvement are at risk for chronic evolution.

Solar insolation in springtime influences age of onset of bipolar I disorder.

OBJECTIVE: To confirm prior findings that the larger the maximum monthly increase in solar insolation in springtime, the younger the age of onset of bipolar disorder. METHOD: Data were collected from 5536 patients at 50 sites in 32 countries on six continents. Onset occurred at 456 locations in 57 countries. Variables included solar insolation, birth-cohort, family history, polarity of first episode and country physician density. RESULTS: There was a significant, inverse association between the maximum monthly increase in solar insolation at the onset location, and the age of onset. This effect was reduced in those without a family history of mood disorders and with a first episode of mania rather than depression. The maximum monthly increase occurred in springtime. The youngest birth-cohort had the youngest age of onset. All prior relationships were confirmed using both the entire sample, and only the youngest birth-cohort (all estimated coefficients P < 0.001). CONCLUSION: A large increase in springtime solar insolation may impact the onset of bipolar disorder, especially with a family history of mood disorders. Recent societal changes that affect light exposure (LED lighting, mobile devices backlit with LEDs) may influence adaptability to a springtime circadian challenge.

Everolimus Versus Mycophenolate Mofetil De Novo After Lung Transplantation: A Prospective, Randomized, Open-Label Trial.

The role of mammalian target of rapamycin (mTOR) inhibitors in de novo immunosuppression after lung transplantation is not well defined. We compared Everolimus versus mycophenolate mofetil in an investigator-initiated single-center trial in Hannover, Germany. A total of 190 patients were randomly assigned 1:1 on day 28 posttransplantation to mycophenolate mofetil (MMF) or Everolimus combined with cyclosporine A (CsA) and steroids. Patients were followed up for 2 years. The primary endpoint was freedom from bronchiolitis obliterans syndrome (BOS). The secondary endpoints were incidence of acute rejections, infections, treatment failure and kidney function. BOS-free survival in intention-to-treat (ITT) analysis was similar in both groups (p = 0.174). The study protocol was completed by 51% of enrolled patients. The per-protocol analysis shows incidence of bronchiolitis obliterans syndrome (BOS): 1/43 in the Everolimus group and 8/54 in the MMF group (p = 0.041). Less biopsy-proven acute rejection (AR) (p = 0.005), cytomegalovirus (CMV) antigenemia (p = 0.005) and lower respiratory tract infection (p = 0.003) and no leucopenia were seen in the Everolimus group. The glomerular filtration rate (GFR) decreased in both groups about 50% within 6 months. Due to a high withdrawal rate, the study was underpowered to prove a difference in BOS-free survival. The dropout rate was more pronounced in the Everolimus group. Secondary endpoints indicate potential advantages of Everolimus-based protocols but also a potentially higher rate of drug-related serious adverse events.

Phenotyping Chronic Lung Allograft Dysfunction Using Body Plethysmography and Computed Tomography.

Restrictive subtype of chronic lung allograft dysfunction (CLAD) was recently described after lung transplantation. This study compares different definitions of a restrictive phenotype in CLAD patients and impact on survival. Eighty-nine CLAD patients out of 1191 screened patients (September 1987 to July 2012) were included as complete longitudinal lung volume measurements and chest computed tomography (CT) after CLAD onset was available. CT findings and lung volumes were quantified and survival was calculated for distinctive groups and predictive factors for worse survival were investigated. Graft survival in patients with total lung capacity (TLC) between 90% and 81% of baseline (BL) (n = 13, 15%) in CLAD course was similar to those with TLC >90% BL (n = 64, 56%; log-rank test p = 0.9). Twelve patients (13%) developed a TLC ≤80% BL and 10 (11%) had significant parenchymal changes on CT, of whom 6 (46%) also had TLC ≤80% BL. CT changes correlated with TLC ≤80% BL (Φ-coefficient = 0.48, p = 0.001). Patients with either TLC ≤80% or significant CT changes (n = 16, 18%) had a significantly reduced survival (log-rank p < 0.001). Forced vital capacity loss at CLAD onset was associated with poorer survival but did not correlate with the TLC or CT changes. A restrictive subtype of CLAD may be defined by either TLC ≤80% BL or severe parenchymal changes on chest CT.

Prolonged Mechanical Ventilation After Lung Transplantation-A Single-Center Study.

This single-center study examines the incidence, etiology, and outcomes associated with prolonged mechanical ventilation (PMV), defined as time to definite spontaneous ventilation >21 days after double lung transplantation (LTx). A total of 690 LTx recipients between January 2005 and December 2012 were analyzed. PMV was necessary in 95 (13.8%) patients with decreasing incidence during the observation period (p < 0.001). Independent predictors of PMV were renal replacement therapy (odds ratio [OR] 11.13 [95% CI, 5.82-21.29], p < 0.001), anastomotic dehiscence (OR 8.74 [95% CI 2.42-31.58], p = 0.001), autoimmune comorbidity (OR 5.52 [95% CI 1.86-16.41], p = 0.002), and postoperative neurologic complications (OR 5.03 [95% CI 1.98-12.81], p = 0.001), among others. Overall 1-year survival was 86.0% (90.4% for LTx between 2010 and 2012); it was 60.7% after PMV and 90.0% in controls (p < 0.001). Conditional long-term outcome among hospital survivors, however, did not differ between the groups (p = 0.78). Multivariate analysis identified renal replacement therapy (hazard ratio [HR] 3.55 [95% CI 2.40-5.25], p < 0.001), post-LTx extracorporeal membrane oxygenation (HR 3.47 [95% CI 2.06-5.83], p < 0.001), and prolonged inotropic support (HR 1.95 [95% CI 1.39-2.75], p < 0.001), among others, as independent predictors of mortality. In conclusion, PMV complicated 14% of LTx procedures and, although associated with increased in-hospital mortality, outcomes among patients surviving to hospital discharge were unaffected.

[Cutaneous tuberculosis of the ear due to Mycobacterium bovis]. / Tuberculose cutanée de l'oreille à Mycobacterium bovis.

INTRODUCTION: Isolated cutaneous tuberculosis is uncommon, accounting for only 0.14 to 5% of Mycobacterium tuberculosis infections. We report a rare case of ear cutaneous tuberculosis due to Mycobacterium bovis in an immunocompetent woman. CASE REPORT: A 59-year-old woman presented an erythematous and scaly lesion of the ear present for two years. The histological findings were compatible with a diagnosis of sarcoidosis, with non-necrotic granuloma. After failure of dermal corticosteroid therapy, a further biopsy identified M. bovis; the patient was cured following anti-tubercular treatment. DISCUSSION: Ear lesions are predominantly associated with tumors, fungal infections, chondritis, lupus and sarcoidosis. The ear, like the face in general, is a classic localization of lupus vulgaris, a chronic form of confined tuberculosis infection with progressive evolution. The paucibacillary nature of these lesions is the reason why their diagnosis is based in some cases on clinical, histological and immunological findings without bacteriological evidence. However, given the potential therapeutic implications, it is important to push the microbiological analysis as far as possible. In our case, culture and identification provided evidence of M. bovis infection, enabling suitable and effective therapy to be given.

[Allocation systems in transplantation medicine: Advantages and disadvantages]. / Allokationssysteme in der Transplantationsmedizin: Vor- und Nachteile.

Donor organs for transplantations are a scarce commodity; therefore, allocation systems are needed that guarantee an ethically acceptable distribution to patients on the waiting list (equal treatment and fairness) but also take the probability of survival of the transplant in each recipient into consideration. In this article the allocation systems for lung, liver, kidney and pancreas transplants are presented.For lung transplantations an allocation system based on the lung allocation score (LAS) is currently used. The LAS predicts the probability of survival on the waiting list and the survival rate following transplantation. Organs with a limited range of utilization are distributed in a so-called mini-match procedure.For post-mortem kidney and pancreas transplantations a relatively complex but transparent allocation system has been created in which patients are subdivided into groups, each of which has its own allocation rules. The allocation is principally carried out according to criteria of fairness of distribution and according to the prospects of success. The probability of a mismatch also plays a role. The urgency is important for children and for patients who do not have the possibility of dialysis. Combined pancreas and kidney transplantations have priority over kidney transplantations alone.The criterion for the urgency of liver transplantation in Germany is currently the model for end-stage liver disease (MELD), which aims to reduce the waiting list mortality and to prioritize transplantations for those most in need. Because the system insufficiently describes the priority of transplantation for patients with tumors or genetic liver diseases, there is an additional set of rules for so-called standard exceptions.