Real life experience with mTOR-inhibitors after lung transplantation.

Mammalian target of rapamycin inhibitors (mTORi) are increasingly used after lung transplantation as part of a calcineurin inhibitor sparing regimen, aiming to preserve renal function. The aim of our study was to determine whether immunosuppressive therapy using mTORi in lung transplant recipients (LTR) is feasible in practice, or limited by intolerance and adverse events. Data were retrospectively assessed for all LTR transplanted between July 1991 and January 2020. Patients ever receiving mTORi (monotherapy or in combination with calcineurin inhibitor) as treatment of physicians' choice were included. 149/1184 (13%) of the LTR ever received mTORi. Main reasons to start were renal insufficiency (67%) and malignancy (21%). In 52% of the patients, mTORi was stopped due to side effects or drug toxicity after a median time of 159 days. Apart from death, main reasons for discontinuation were infection (19%) and edema (14%). Early discontinuation (<90 days) was mainly due to edema or gastrointestinal intolerance. As mTORi was stopped due to adverse events or drug intolerance in 52% of LTR, cautious consideration of advantages and disadvantages when starting mTORi is recommended.

Patient-reported outcomes after 10-year follow-up of intensive, multifactorial treatment in individuals with screen-detected type 2 diabetes: the ADDITION-Europe trial.

AIMS: To present the longer-term impact of multifactorial treatment of type 2 diabetes on self-reported health status, diabetes-specific quality of life, and diabetes treatment satisfaction at 10-year follow up of the ADDITION-Europe trial. METHODS: The ADDITION-Europe trial enrolled 3057 individuals with screen-detected type 2 diabetes from four centres [Denmark, the UK (Cambridge and Leicester) and the Netherlands], between 2001 and 2006. Participants were randomized at general practice level to intensive treatment or to routine care . The trial ended in 2009 and a 10-year follow-up was performed at the end of 2014. We measured self-reported health status (36-item Short-Form Health Survey and EQ-5D), diabetes-specific quality of life (Audit of Diabetes-Dependent Quality of Life questionnaire), and diabetes treatment satisfaction (Diabetes Treatment Satisfaction Questionnaire) at different time points during the study period. A mixed-effects model was applied to estimate the effect of intensive treatment (intention-to-treat analyses) on patient-reported outcome measures for each centre. Centre-specific estimates were pooled using a fixed effects meta-analysis. RESULTS: There was no difference in patient-reported outcome measures between the routine care and intensive treatment arms in this 10-year follow-up study [EQ-5D: -0.01 (95% CI -0.03, 0.01); Physical Composite Score (36-item Short-Form Health Survey): -0.27 (95% CI -1.11, 0.57), Audit of Diabetes-Dependent Quality of Life questionnaire: -0.01 (95% CI -0.11, 0.10); and Diabetes Treatment Satisfaction Questionnaire: -0.20 (95% CI -0.70, 0.29)]. CONCLUSIONS: Intensive, multifactorial treatment of individuals with screen-detected type 2 diabetes did not affect self-reported health status, diabetes-specific quality of life, or diabetes treatment satisfaction at 10-year follow-up compared to routine care.

Platelet-Rich plasma Injection Management for Ankle osteoarthritis study (PRIMA): protocol of a Dutch multicentre, stratified, block-randomised, double-blind, placebo-controlled trial.

INTRODUCTION: Platelet-rich plasma (PRP) is a potentially efficacious treatment for ankle osteoarthritis (OA), but its use has not been examined in high-quality studies. Systematic reviews show that PRP injections significantly decrease pain and improve function in patients with knee OA. Ankle OA is more common than hip or knee OA in the young active population; with a prevalence of 3.4%.PRP injections in ankle OA are shown to be safe and improve quality of life over time, but no randomised controlled trial has been conducted. Our randomised controlled trial will evaluate the efficacy of PRP injections for symptom reduction and functional improvement, compared with placebo, in the treatment of ankle (talocrural) OA. METHODS AND ANALYSIS: We will conduct the Platelet-Rich plasma Injection Management for Ankle OA study: a multicentre, randomised, placebo-controlled trial. One hundred patients suffering from ankle OA will be randomised into two treatment groups: PRP injection or placebo (saline) injection. Both groups will receive two injections of PRP or placebo at an interval of 6 weeks. Primary outcome is the American Orthopaedic Foot and Ankle Society score at 26 weeks. Secondary outcomes determined at several follow-up moments up to 5 years, include Ankle Osteoarthritis Score, Foot and Ankle Outcome Score, pain subscale of (0-40), Visual Analogue Scale score (0-100), Ankle Activity Score (0-10), subjective patient satisfaction Short Form Health Survey-36, Global Attainment Scaling and the EuroQol-5 dimensions-3 levels utility score. A cost-effectiveness analysis will be performed at 1 year. ETHICS AND DISSEMINATION: The study is approved by the Medical Ethics Review Committee Amsterdam Medical Center, the Netherlands (ABR 2018-042, approved 23 July 2018) and registered in the Netherlands trial register (NTR7261). Results and new knowledge will be disseminated through the Dutch Arthritis Association (ReumaNederland), Dutch patient federation, conferences and published in a scientific peer-reviewed journal. TRIAL REGISTRATION NUMBER: NTR7261.

No difference in mid-term survival and clinical outcome between patient-specific and conventional instrumented total knee arthroplasty: a randomized controlled trial.

PURPOSE: The purpose of this multicentre prospective randomized controlled trial was to compare the survival rate and clinical outcome in total knee arthroplasty (TKA) after MRI-based patient-specific instruments (PSI) and conventional instruments 5 years after initial surgery. METHODS: At a mean follow-up of 5.1 years (0.4), 163 patients (90.6%) with a mean age of 71.8 years (8.7) were analysed. A survival analysis with revision of the TKA as endpoint was performed. The Knee Society Score (KSS), evaluations on plain radiographs and patient-reported outcome measures (PROMs) were obtained preoperatively and at each FU. RESULTS: At final follow-up, one TKA in the PSI- (1.2%) and 3 TKAs in the conventional group (3.8%) had undergone revision surgery (n.s.). No radiological abnormalities were noted at any time point. Postoperatively, the KSS and PROMs significantly improved within each group compared with the preoperative values. There were no clinically relevant differences for the KSS [PSI: 77.4, 9.8 (95% CI 75.0-79.7) vs. conventional: 77.3 10.5 (95% CI 74.9-79.8)] and the PROMs between both groups (n.s.) at 5 years follow-up. CONCLUSION: There is still a lack of reliable data on the survival of TKA and clinical evidence, when using PSI for TKA. Longer follow-up studies are, therefore, needed. LEVEL OF EVIDENCE: I.

Correction to: No difference in mid-term survival and clinical outcome between patient-specific and conventional instrumented total knee arthroplasty: a randomized controlled trial.

In the original article, one of the co-author's (W. van der Weegen) middle name has been missed in the publication of the article. The correct complete name should be W. van der Weegen.

Prevention of deep sternal wound infection in cardiac surgery: a literature review.

BACKGROUND: Deep sternal wound infection (DSWI) is a dreaded complication of cardiac surgery with considerable consequences in terms of mortality, morbidity and treatment costs. In addition to standard surgical site infection prevention guidelines, multiple specific measures in the prevention of DSWI have been developed and evaluated in the past decades. This review focuses on these specific measures to prevent DSWI. METHODS: An extensive literature search was performed to assess interventions in the prevention of DSWI. Articles describing results of a randomized controlled trial were categorized by type of intervention. Results were yielded and, if possible, pooled. RESULTS: From a total of 743 articles found, 48 randomized controlled trials were selected. Studies were divided into 12 categories, containing pre-, peri- and postoperative preventive measures. Specific measures shown to be effective were: antibiotic prophylaxis with a first-generation cephalosporin for at least 24 h, application of local gentamicin before chest closure, sternal closure with figure-of-eight steel wires, and postoperative chest support using a corset or vest. CONCLUSION: This study identified several measures that prevent DSWI after cardiac surgery that are not frequently applied in current practice. It is recommended that the guidelines on prevention of surgical site infection in cardiac surgery should be updated.

Low incidence of postoperative urinary retention with the use of a nurse-led bladder scan protocol after hip and knee arthroplasty: a retrospective cohort study.

PURPOSE: Postoperative urinary retention (POUR), defined as the inability to empty the bladder voluntary after surgery, is a commonly reported complication. This study reports the incidence and possible risk factors for POUR after elective fast-track hip or knee arthroplasty when using a nurse-led bladder scan protocol. METHODS: This retrospective cohort study included data from 803 patients who underwent unilateral hip or knee arthroplasty. Patients' digital clinical records were reviewed for eligibility. Patients with incomplete data registration, preoperative bladder volume >250 ml, preexisting bladder catheterization, and/or patients following the outpatient pathway were excluded. Bladder volumes were assessed at different moments pre- and postoperatively. The outcome was the incidence of POUR, defined as the inability to void spontaneously with a bladder volume >600 ml, treated with indwelling catheterization. Further analysis between POUR and non-POUR patients was performed to detect possible risk factors for POUR. RESULTS: Six hundred and thirty-eight patients operated on primary unilateral hip or knee arthroplasty were analyzed. The incidence of POUR was 12.9% (n = 82, 95% CI 9.4-15.5). Gender, age, BMI, ASA classification, preoperative bladder volume, type of anesthesia, type of arthroplasty, and perioperative fluid administration were not significant different between POUR and non-POUR patients. Patients with a bladder volume of >200 ml at the recovery room were at higher risk (OR 5.049, 95% CI 2.815-9.054) for POUR. CONCLUSIONS: When using a nurse-led bladder scan protocol in fast-track hip and knee arthroplasty, the incidence of POUR was 12.9%, with a bladder volume of >200 ml at the recovery room as a risk factor for POUR. LEVEL OF EVIDENCE: A retrospective cohort study, Level III.

"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.

No difference in joint awareness after mobile- and fixed-bearing total knee arthroplasty: 3-year follow-up of a randomized controlled trial.

PURPOSE: To compare the patients ability to forget the artificial knee joint in everyday life who were randomized to be operated for mobile- or fixed-bearing total knee arthroplasty (TKA). METHODS: This single-center randomized controlled trial evaluated the 3-year follow-up of the cemented mobile- and fixed-bearing TKA from the same brand in a series of 41 patients. Clinical examination was during the pre-, 6-week, 6-month, 1-, 2- and 3-year follow-up containing multiple patient-reported outcome measures (PROMs) including the 12-item Forgotten Joint Score (FJS-12) at 3 years. Effect size was calculated for each PROM at 3-year follow-up to quantify the size of the difference between both bearings. RESULTS: At 3-year follow-up, general linear mixed model analysis showed that there were no significant or clinically relevant differences between the two groups for all outcome measures. Calculated effect sizes were small (<0.3) for all the PROMs except for the FJS-12; these were moderate (0.5). CONCLUSION: The results of this study demonstrate that joint awareness was slightly lower in patients operated with the MB TKA with comparable improved clinical outcome and PROMs at 3-year follow-up. Measuring joint awareness with the FJS-12 is useful and provides more stringent information at 3-year follow-up compared to other PROMs and should be the PROM of choice at each follow-up after TKA. LEVEL OF EVIDENCE: Level I, randomized controlled trial.

No difference in terms of radiostereometric analysis between fixed- and mobile-bearing total knee arthroplasty: a randomized, single-blind, controlled trial.

PURPOSE: A concern that arises with any new prosthesis is whether it will achieve satisfactory long-term implant stability. The gold standard of assessing the quality of fixation in a new or relatively new implant is to undertake a randomized controlled trial using radiostereometric analysis. It was hypothesized that both mobile-bearing total knee arthroplasty and fixed-bearing total knee arthroplasty have comparable migration patterns at 2-year follow-up. This study investigated two types of cemented total knee arthroplasty, the mobile- or fixed-bearing variant from the same family with use of radiostereometric analysis. METHODS: This prospective, patient-blinded, randomized, controlled trial was designed to investigate early migration of the tibia component after two years of follow-up with use of radiostereometric analysis. A total of 50 patients were randomized to receive a mobile- or fixed-bearing TKA from the same family. Patients were evaluated during 2-year follow-up, including radiostereometric analysis, physical and clinical examination and patient reported outcome measures (PROMs). RESULTS: At two-year follow-up, the mean (±SD) maximum total point motion (MTPM) in the fixed-bearing group was 0.82 (±1.16) versus 0.92 mm (±0.64) in the mobile-bearing group (p = n.s) with the largest migration seen during the first 6 weeks (0.45 ± 0.32 vs. 0.54 ± 0.30). The clinical outcome and PROMs significantly improved within each group, not between both groups. CONCLUSIONS: Measuring early micromotion is useful for predicting clinical loosening that can lead to revision. The results of this study demonstrate that early migration of the mobile-bearing is similar to that of the fixed-bearing component at two years and was mainly seen in the first weeks after implantation. LEVEL OF EVIDENCE: Randomized, single-blind, controlled trial, Level I.

Vaginal high-risk human papillomavirus infection in a cross-sectional study among women of six different ethnicities in Amsterdam, the Netherlands: the HELIUS study.

OBJECTIVE: In the Netherlands the incidence of cervical cancer is higher among ethnic minority populations compared with the general Dutch population. We investigated the prevalence of, and risk factors associated with, vaginal high-risk human papillomavirus (hrHPV) infection in women of six different ethnicities living in Amsterdam. METHODS: For this cross-sectional study we selected women aged 18-34 years old of six ethnicities from the large-scale multiethnic HEalthy LIfe in an Urban Setting study. Self-collected vaginal swabs were tested for HPV DNA and genotyped using a highly sensitive PCR and reverse line blot assay (short PCR fragment (SPF)10-PCR DNA enzyme immunoassay/LiPA25-system version-1, delft diagnostic laboratory (DDL)). Participants completed a questionnaire regarding demographics and sexual behaviour. Logistic regression using generalised estimating equations was used to assess risk factors of hrHPV, and to investigate whether prevalence of hrHPV differed among ethnicities. RESULTS: The study population consisted of 592 women with a median age of 27 (IQR: 23-31) years. Dutch and African Surinamese women reported the highest sexual risk behaviour. HrHPV prevalence was highest in the Dutch (40%) followed by the African Surinamese (32%), Turkish (29%), Ghanaian (26%), Moroccan (26%) and South-Asian Surinamese (18%). When correcting for sexual risk behaviour, the odds to be hrHPV-positive were similar for all non-Dutch groups when compared with that of the Dutch group. CONCLUSIONS: We found an overall higher hrHPV prevalence and higher sexual risk behaviour in the native Dutch population. Further research is needed to unravel the complex problem concerning cervical cancer disparities, such as differences in participation in the cervical cancer screening programme, or differences in clearance and persistence of hrHPV.

Combined or Serial Liver and Lung Transplantation for Epithelioid Hemangioendothelioma: A Case Series.

Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor with variable biological and clinical behavior. There is increasing experience with liver transplantation (LiTx) for hepatic EHE, even in cases of extrahepatic disease localization. Until now, no cases of lung transplantation (LuTx) had been reported for pulmonary EHE. This report describes three cases of EHE with multifocal disease in patients who underwent either serial or combined LiTx and LuTx.

Iron deficiency in the first 6 months of age in infants born between 32 and 37 weeks of gestational age.

BACKGROUND/OBJECTIVES: Preterm infants are at risk of iron deficiency (ID). In the Netherlands, preterm infants born after 32 weeks of gestational age (GA) do not receive iron supplementation on a routine basis. We hypothesized that dietary iron intake in these infants might not be sufficient to meet the high iron requirements during the first 6 months of life. SUBJECTS/METHODS: In a prospective cohort study, we analyzed the prevalence and risk factors of ID in 143 infants born between 32+0 and 36+6 weeks GA who did not receive iron supplementation. RESULTS: ID at the age of 4 and 6 months was present in 27 (18.9%) and 7 (4.9%) infants. Results of a multivariable logistic regression analysis showed that ID was associated with lower birth weight, a shorter duration of formula feeding, more weight gain in the first 6 months of life and lower ferritin concentrations at the age of 1 week. CONCLUSIONS: Preterm infants born after 32 weeks GA have an increased risk of ID compared with those born at term, supporting the need of iron supplementation. Our results suggests that measurement of ferritin at the age of 1 week might be useful to identify those infants at particular risk and could be used in populations without general supplementation programs. However, the efficacy and safety of individualized iron supplementation, based on ferritin concentrations at the age of 1 week, together with other predictors of ID, needs to be further investigated, preferably in a randomized controlled trial.

Azithromycin and the treatment of lymphocytic airway inflammation after lung transplantation.

Lymphocytic airway inflammation is a major risk factor for chronic lung allograft dysfunction, for which there is no established treatment. We investigated whether azithromycin could control lymphocytic airway inflammation and improve allograft function. Fifteen lung transplant recipients demonstrating acute allograft dysfunction due to isolated lymphocytic airway inflammation were prospectively treated with azithromycin for at least 6 months (NCT01109160). Spirometry (FVC, FEV1 , FEF25-75 , Tiffeneau index) and FeNO were assessed before and up to 12 months after initiation of azithromycin. Radiologic features, local inflammation assessed on airway biopsy (rejection score, IL-17(+) cells/mm(2) lamina propria) and broncho-alveolar lavage fluid (total and differential cell counts, chemokine and cytokine levels); as well as systemic C-reactive protein levels were compared between baseline and after 3 months of treatment. Airflow improved and FeNO decreased to baseline levels after 1 month of azithromycin and were sustained thereafter. After 3 months of treatment, radiologic abnormalities, submucosal cellular inflammation, lavage protein levels of IL-1ß, IL-8/CXCL-8, IP-10/CXCL-10, RANTES/CCL5, MIP1-α/CCL3, MIP-1ß/CCL4, Eotaxin, PDGF-BB, total cell count, neutrophils and eosinophils, as well as plasma C-reactive protein levels all significantly decreased compared to baseline (p < 0.05). Administration of azithromycin was associated with suppression of posttransplant lymphocytic airway inflammation and clinical improvement in lung allograft function.

Combined liver and lung transplantation with extended normothermic lung preservation in a patient with end-stage emphysema complicated by drug-induced acute liver failure.

Isolated lung transplantation (LuTx) and liver transplantation are established treatments for irreversible lung and liver failure. Combined liver and lung transplantation (cLiLuTx) is a less common, but approved therapy of combined organ failure, mostly applied in patients suffering from progressive cystic fibrosis and advanced liver disease. We report a patient who was listed for LuTx due to end-stage chronic obstructive pulmonary disease and who developed drug-induced acute hepatic failure. The only therapeutic option was hyper-urgent cLiLuTx. To correct the poor coagulation in order to reduce the per-operative risk of bleeding, the liver was transplanted first. In anticipation of the longer lung preservation time, cold flushed lungs were preserved on a portable lung perfusion device for ex vivo normothermic perfusion for 11 h 15 min, transplanted sequentially off-pump, and reperfused after a total ex vivo time of 13 h 32 min and 16 h for the first and second lung, respectively. Ten months later, the patient is doing well and no rejection occurred. Normothermic ex vivo lung perfusion may help to prolong preservation time, facilitating long-distance transport and combined organ transplantation.

Body mass index in lung transplant candidates: a contra-indication to transplant or not?

BACKGROUND: According to International Society of Heart and Lung Transplantation criteria, high body mass index (BMI; ≥ 30 kg/m(2)) is a relative contraindication for lung transplantation (LT). On the other hand, low BMI may be associated with worse outcome. We investigated the influence of pre-LT BMI on survival after LT in a single-center study. METHODS: Patients were divided according to the World Health Organization criteria into 4 groups: BMI <18.5 kg/m(2) (underweight), BMI 18.5-24.9 kg/m(2) (normal weight), BMI 25-29.9 kg/m(2) (overweight), and BMI ≥ 30 kg/m(2) (obesity). An additional analysis was made per underlying disease. RESULTS: BMI was determined in a cohort of 546 LT recipients, of which 28% had BMI <18.5 kg/m(2). Underweight resulted in similar survival (P = .28) compared with the normal weight group. Significantly higher mortality was found in overweight (P = .016) and obese patients (P = .031) compared with the normal-weight group. Subanalysis of either underweight (P = .19) or obese COPD patients (P = .50) did not reveal worse survival. In patients with interstitial lung disease, obesity was associated with increased mortality (P = .031) compared with the normal-weight group. In cystic fibrosis patients, underweight was not associated with a higher mortality rate (P = .12) compared with the normal-weight group. CONCLUSIONS: Low pre-LT BMI did not influence survival rate in our cohort, independently from underlying disease.

The value of Ret-Hb and sTfR in the diagnosis of iron depletion in healthy, young children.

OBJECTIVES: Reticulocyte hemoglobin (Ret-Hb) content and soluble transferrin receptor (sTfR) are described as promising biomarkers in the analysis of iron status. However, the value of Ret-Hb and sTfR in the early detection of iron depletion, as frequently observed in children in high-income countries, is unclear. We hypothesized that young children to iron depletion, using the WHO cutoff of ferritin <12 µg/l, would have lower Ret-Hb and higher sTfR concentrations compared to children with a ferritin ⩾level 12 µg/l. SUBJECTS/METHODS: In this cross-sectional study, we analyzed mean concentrations of Ret-Hb and sTfR in 351 healthy children aged 0.5-3 years in a high-income country. The Student's t-test was used to compare Ret-Hb and sTfR concentrations between groups. RESULTS: We showed that concentrations of Ret-Hb and sTfR are similar in children with and without iron depletion. A decrease in Ret-Hb concentration was present only when ferritin concentrations were <8 µg/l. sTfR concentrations were similar in children with ferritin concentrations <6 µg/l and ⩾12 µg/l. CONCLUSIONS: Our results showed that the discriminative value of Ret-Hb and sTfR for the detection of iron depletion is limited. Our findings suggest that ferritin is the most useful biomarker in the screening of iron depletion in healthy children in high-income countries. However, ideally, reference ranges of iron status biomarkers should be based on studies showing that children with concentrations outside reference ranges have poor neurodevelopmental outcomes.

Symptoms from treatment with sunitinib or sorafenib: a multicenter explorative cohort study to explore the influence of patient-reported outcomes on therapy decisions.

PURPOSE: Optimal long-lasting treatment with sunitinib and sorafenib is limited by dose modifications (DMs) due to adverse events (AEs). These AEs may be underrecognized and their influence on health-related quality of life (HRQL) underestimated. Improved insight into the relationship between AEs and therapy decisions is needed. To improve decision making around managing symptoms and reduce DMs, this study was set up to explore the influence of patient-reported symptoms on therapy decisions. METHODS: In this multicenter cohort study, patient characteristics, reasons for and different forms of used dose modifications, and AEs were prospectively obtained from cancer patients on sunitinib/sorafenib treatment. Used instruments to get insight into AEs were the patient-scored Utrecht Symptom Diary (USD) and the professional-scored Common Terminology Criteria for AEs version 3.0. RESULTS: Median total treatment duration in 42 patients was 16 weeks. Median time till dose modification was 10 weeks. DMs occurred mostly due to multiple mild AEs. By using the USD, a higher prevalence of most AEs was found compared to the literature. Sixty percent of the patients experienced a decreased HRQL due to multiple AEs. CONCLUSIONS: Because severe AEs due to sunitinib/sorafenib treatment seldom occur, it is more important to focus on treating and preventing multiple mild AEs with higher impact on HRQL, when trying to avoid dose modifications. Using patient self-reported measurement methods helps to early recognize symptoms and to differentiate among symptom intensities. This systematic approach might help to achieve the optimal dosing, which might improve PFS and OS.

Pirfenidone: a potential new therapy for restrictive allograft syndrome?

This case report describes the evolution of pulmonary function findings (FVC, FEV1 and TLC) and CT features with pirfenidone treatment for restrictive allograft syndrome following lung transplantation. Furthermore, we herein report hypermetabolic activity on (18) F-FDG PET imaging in this setting, which could indicate active fibroproliferation and pleuroparenchymal remodeling. These findings may warrant further investigation.

Influence of a neurokinin-1 receptor antagonist (aprepitant) on gastric sensorimotor function in healthy volunteers.

BACKGROUND: Substance P (SP) is a member of the neurokinin (NK) family and is one of the established neurotransmitters in the mammalian central and enteric nervous system. It is unclear whether NK1 receptors are involved in the control of gastric sensorimotor function in man. METHODS: We studied the effects of aprepitant, an NK1 receptor antagonist used in the treatment of chemotherapy-induced emesis, on gastric sensorimotor function in healthy volunteers. Sixteen healthy volunteers (six males, 32.4 ± 2.7 years) were studied on three separate occasions after placebo, aprepitant 80 or 125 mg in randomized double-blind study to assess gastric compliance, perception to isobaric distensions, and gastric accommodation with a gastric barostat. KEY RESULTS: Compared to placebo, both doses of aprepitant did not influence gastric compliance or sensitivity to gastric distension. Aprepitant 80 and 125 mg did not have any significant effects on gastric accommodation compared with placebo (mean postprandial gastric volume increase, respectively, 83.4 ± 28.4 vs 35.3 ± 16.2 vs 83.9 ± 30.4 mL, NS). Postprandial gastric compliance and sensitivity to distention were also not altered. CONCLUSIONS & INFERENCES: In health, NK1 receptors do not appear to be involved in the control of gastric compliance, accommodation or sensitivity to distention in man.