Radiological Analysis of Unused Donor Lungs: A Tool to Improve Donor Acceptance for Transplantation?

Despite donor organ shortage, a large proportion of possible donor lungs are declined for transplantation. Criteria for accepting/declining lungs remain controversial because of the lack of adequate tools to aid in decision-making. We collected, air-inflated, and froze a large series of declined/unused donor lungs and subjected these lung specimens to CT examination. Affected target regions were scanned by using micro-CT. Lungs from 28 donors were collected. Two lungs were unused, six were declined for non-allograft-related reasons (collectively denominated nonallograft declines, n = 8), and 20 were declined because of allograft-related reasons. CT scanning demonstrated normal lung parenchyma in only four of eight nonallograft declines, while relatively normal parenchyma was found in 12 of 20 allograft-related declines. CT and micro-CT examinations confirmed the reason for decline in most lungs and revealed unexpected (unknown from clinical files or physical inspection) CT abnormalities in other lungs. CT-based measurements showed a higher mass and density in the lungs with CT alterations compared with lungs without CT abnormalities. CT could aid in the decision-making to accept or decline donor lungs which could lead to an increase in the quantity and quality of lung allografts.

Parametric Response Mapping of Bronchiolitis Obliterans Syndrome Progression After Lung Transplantation.

Bronchiolitis obliterans syndrome (BOS) remains a major complication after lung transplantation. Air trapping and mosaic attenuation are typical radiological features of BOS; however, quantitative evaluation remains troublesome. We evaluated parametric response mapping (PRM, voxel-to-voxel comparison of inspiratory and expiratory computed tomography [CT] scans) in lung transplant recipients diagnosed with BOS (n = 20) and time-matched stable lung transplant recipients (n = 20). Serial PRM measurements were performed prediagnosis, at time of BOS diagnosis, and postdiagnosis (Tpre , T0 , and Tpost , respectively), or at a postoperatively matched time in stable patients. PRM results were correlated with pulmonary function and confirmed by microCT analysis of end-stage explanted lung tissue. Using PRM, we observed an increase in functional small airway disease (fSAD), from Tpre to T0 (p = 0.006) and a concurrent decrease in healthy parenchyma (p = 0.02) in the BOS group. This change in PRM continued to Tpost , which was significantly different compared to the stable patients (p = 0.0002). At BOS diagnosis, the increase in fSAD was strongly associated with a decrease in forced expiratory volume in 1 s (p = 0.011). Micro-CT confirmed the presence of airway obliteration in a sample of a BOS patient identified with 67% fSAD by PRM. We demonstrated the use of PRM as an adequate output to monitor BOS progression in lung transplant recipients.

Prophylactic Azithromycin Therapy After Lung Transplantation: Post hoc Analysis of a Randomized Controlled Trial.

Prophylactic azithromycin treatment has been demonstrated to improve freedom from bronchiolitis obliterans syndrome (BOS) 2 years after lung transplantation (LTx). In the current study, we re-evaluated the long-term effects of this prophylactic approach in view of the updated classification system for chronic lung allograft dysfunction (CLAD). A retrospective, intention-to-treat analysis of a randomized controlled trial comparing prophylactic treatment with placebo (n = 43) versus azithromycin (n = 40) after LTx was performed. Graft dysfunction (CLAD), graft loss (retransplantation, mortality), evolution of pulmonary function and functional exercise capacity were analyzed 7 years after inclusion of the last study subject. Following LTx, 22/43 (51%) patients of the placebo group and 11/40 (28%) patients of the azithromycin group ever developed CLAD (p = 0.043). CLAD-free survival was significantly longer in the azithromycin group (p = 0.024). No difference was present in proportion of obstructive versus restrictive CLAD between both groups. Graft loss was similar in both groups: 23/43 (53%) versus 16/40 (40%) patients (p = 0.27). Long-term pulmonary function and functional exercise capacity were significantly better in the azithromycin group (p < 0.05). Prophylactic azithromycin therapy reduces long-term CLAD prevalence and improves CLAD-free survival, pulmonary function, and functional exercise capacity after LTx.

Genetic variation in immunoglobulin G receptor affects survival after lung transplantation.

Chronic rejection remains the most important complication after lung transplantation (LTx). There is mounting evidence that both rheumatoid arthritis and chronic rejection share similar inflammatory mechanisms. As genetic variants in the FCGR2A gene that encodes the immunoglobulin gamma receptor (IgGR) have been identified in rheumatoid arthritis, we investigated the relationship between a genetic variant in the IgGR gene and chronic rejection and mortality after LTx. Recipient DNA from blood or explant lung tissue of 418 LTx recipients was evaluated for the IgGR (rs12746613) polymorphism. Multivariate analysis was carried out, correcting for several co-variants. In total, 216 patients had the CC-genotype (52%), 137 had the CT-genotype (33%) and 65 had the TT-genotype (15%). Univariate analysis demonstrated higher mortality in the TT-genotype compared with both other genotypes (p < 0.0001). Multivariate analysis showed that the TT-genotype had worse survival compared with the CC-genotype (hazard ratio [HR] = 2.26, p = 0.0002) but no significance was observed in the CT-genotype (HR = 1.32, p = 0.18). No difference was seen for chronic rejection. The TT-genotype demonstrated more respiratory infections (total, p = 0.037; per patient, p = 0.0022) compared with the other genotypes. A genetic variant in the IgGR is associated with higher mortality and more respiratory infections, although not with increased prevalence of chronic rejection, after LTx.

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.

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.

[Rivaroxaban: Xarelto--recommendations for pharmacists]. / Le Rivaroxaban (Xarelto): guide de la pratique officinale.

Rivaroxaban is one of the new oral anticoagulants (NOACs). It has many potential advantages in comparison with Vitamin K Antagonists (VKA). It has a predictable anticoagulant effect and does not theoretically require biological monitoring. It is also characterized by less food and drug interactions. However, due to major risks associated with over- and under-dosage, its optimal use in patients should be carefully followed by health care professionals. The aim of this article is to provide recommendations for pharmacists on the practical use of Xarelto in its different approved indications. This document is adapted from the practical user guide of rivaroxaban which was developed by an independent group of Belgian experts in the field of thrombosis and haemostasis.

Medication in the perioperative period: stop or continue? A review.

Preoperative evaluation of medication is important as part of the anesthetic plan. The aim of this manuscript is to evaluate and compare through literature review the existing evidence to support optimal perioperative medication management.

131 treatment in dogs with hyperthyroidism caused by a non-resectable ectopic thyroid tumour: 5 cases (2008-2019).

OBJECTIVES: This study aimed to describe the clinical and diagnostic characteristics, as well as outcomes of radioiodine treatment in dogs with hyperthyroidism caused by a non-resectable ectopic thyroid tumour. MATERIALS AND METHODS: This retrospective study reviewed the medical records between 2008 and 2018 of dogs diagnosed with hyperthyroidism secondary to a non-resectable ectopic thyroid tumour and treated with radioiodine. RESULTS: Five dogs were included in the study. Three dogs had sublingual ectopic tumours, of which one also had a unilateral cervical thyroid tumour. The remaining two dogs were diagnosed with an ectopic thyroid tumour at the level of the caudal pharynx and the heart base, respectively. All cases were treated with radioiodine. The size of the ectopic masses decreased after radioiodine treatment. Total thyroxine concentrations returned to reference ranges in all dogs. Further, clinical signs of hyperthyroidism disappeared after treatment in all patients. One dog developed myelosuppression secondary to radioiodine treatment. The dog with metastasis had a very short survival compared to the four dogs without metastasis (3 months compared to 7, 36, 50 and 24 months, respectively) and succumbed most likely to thyroid-related problems. In the remaining four dogs, their quality of life improved. They died due to diseases unrelated to the ectopic thyroid tumour. CLINICAL SIGNIFICANCE: Radioiodine therapy should be considered as a treatment option in dogs diagnosed with hyperthyroidism due to a non-resectable ectopic thyroid tumour.

Serum hyaluronic acid, a marker for improved liver perfusion after gradual surgical attenuation of extrahepatic portosystemic shunt closure in dogs.

Current liver function tests used in dogs do not consistently normalise after successful surgical attenuation of portosystemic shunts (PSS). Serum hyaluronic acid (sHA) concentrations in dogs with PSS are reported to be higher at diagnosis than in healthy dogs. The objective of this study was to assess sHA as a marker of liver perfusion by measuring sHA concentrations in dogs before and after gradual surgical attenuation of extrahepatic (EH)PSS and by determining whether sHA concentrations could differentiate closed EHPSS from persistent shunting. Specificity of sHA was assessed by comparing sHA concentrations in dogs with EHPSS to those in dogs with other liver diseases. Twenty dogs with EHPSS had sHA concentrations measured at diagnosis, 1, 3, and 6 months postoperatively. In addition, sHA concentrations were determined in 10 dogs with other liver diseases. At EHPSS diagnosis, median sHA concentration was 335.6 ng/mL (43.0-790.7 ng/mL). All dogs had a significant decrease in sHA concentrations from 1 month postoperatively onwards (P < 0.05), regardless of surgical outcome. At all postoperative follow-up visits, there was a significant difference between the median sHA concentration in dogs with closed EHPSS vs. those with persistent shunting (P < 0.05). Median sHA concentration in dogs with other liver diseases was 89.8 ng/mL (22.9-160.0 ng/mL), which was significantly lower than dogs with EHPSS at diagnosis (P < 0.001). In conclusion, sHA is a promising non-invasive biomarker that can help to determine liver perfusion after surgical attenuation of EHPSS. In addition, sHA could potentially be used to differentiate dogs with EHPSS from dogs with other liver diseases.

Periprocedural bridging of anticoagulation.

When deciding to preoperatively interrupt--and potentially substitute--a chronic treatment with antithrombotics or not, the surgical or anesthetic bleeding risk of continuing or substituting treatment should be balanced against the risk of thrombosis in case treatment is not interrupted or substituted. The decision will primarily be based upon the initial indication to antithrombotic treatment and the nature of the planned procedure.

Recombinant human thyrotropin administration enhances thyroid uptake of radioactive iodine in hyperthyroid cats.

BACKGROUND: Hyperthyroidism is the most diagnosed endocrine disorder in cats and radioiodine (131I) is the treatment of choice. The dose emission rate and radioactivity in urine, saliva, and on hair and paws are determined by the dose of administered 131I. A dose reduction of therapeutic 131I could possibly be achieved after recombinant human thyrotropin (rhTSH) administration as in humans with nodular goiter. HYPOTHESIS: rhTSH will increase radioiodine uptake in hyperthyroid cats. ANIMALS: Five hyperthyroid cats. METHODS: Twenty-five micrograms rhTSH (day 1) or 2 mL 0.9% sodium chloride (NaCl) (day 9) was injected IV. One hour later, 11.4 +/- 4.1 (mean +/- SD) MBq 123I was injected IV. Radioactive iodine uptake (RAIU) was measured 6, 12, and 24 hours after rhTSH (RAIU-rhTSH) or NaCl (RAIU-blanco) injection. Blood samples for measurement of TT4 were taken before injection of rhTSH or NaCl (TT4(0)) and at the time of imaging. RESULTS: Percentages of RAIU-rhTSH (and RAIU-blanco) at 6, 12, and 24 hours after administration of rhTSH were 34 +/- 18 (31 +/- 21), 46 +/- 20 (38 +/- 18), and 47 +/- 15 (36 +/- 14). There was a statistically significant effect of rhTSH administration on RAIU (P = .043) but not on serum TT4 concentration. Baseline serum TT4(0) concentration influenced RAIU-rhTSH significantly at 6 hours (P = .037). CONCLUSION AND CLINICAL IMPORTANCE: The increased RAIU observed after rhTSH administration in hyperthyroid cats could lead to a lower therapeutic dose of 131I after rhTSH administration in hyperthyroid cats and decreased risk of environmental and owner contamination during and after hospitalization.

A single sample method for evaluating 51chromium-ethylene diaminic tetraacetic acid clearance in normal and hyperthyroid cats.

BACKGROUND: Chronic kidney failure is frequently seen in middle-aged and elderly cats. 51Chromium-ethylene diaminic tetraacetic acid (51Cr-EDTA) clearance and single blood sample (SBS) method are used in several species to estimate the glomerular filtration rate (GFR). HYPOTHESIS: The hypothesis of this study was that 51Cr-EDTA clearance could be determined using an SBS method in normal and hyperthyroid cats. ANIMALS: Forty-six cats were included in this study, with an average age of 9.5 years. Of these cats, 27 had hyperthyroidism; 19 were healthy. METHODS: After IV injection of 51Cr-EDTA (average dose: 4.25 MBq), 7 blood samples were obtained between 5 and 240 minutes. Reference clearance was calculated in mL/min and mL/min/kg body weight, using a 2-compartment model. Optimal time for clearance measurement with SBS was then determined by systematically comparing each individual plasma concentration to the reference multisample clearance. RESULTS: The average reference plasma clearance of 51Cr-EDTA for all cats was 14.9 mL/min (3.7 mL/min/kg). The clearance in hyperthyroid cats averaged 16.4 mL/min (4.3 mL/min/kg) and in normal cats averaged 10.3 mL/min (2.4 mL/min/kg). The optimal time for the SBS was 48 minutes after injection of tracer 51Cr-EDTA (R2= 0.9414), giving the following converting equation: clearance = (0.0066 x DV48 minutes) - 0.9277 (in mL/min). CONCLUSIONS AND CLINICAL IMPORTANCE: In this study, the single sample 51Cr-EDTA clearance method was used to estimate the global GFR in cats. The method identified differences in clearance between normal and hyperthyroid cats. The optimal time for an SBS was 48 minutes.

Contrast-Enhanced Ultrasound Examination for the Assessment of Renal Perfusion in Cats with Chronic Kidney Disease.

BACKGROUND: Contrast-enhanced ultrasound examination (CEUS) is a functional imaging technique allowing noninvasive assessment of tissue perfusion. Studies in humans show that the technique holds great potential to be used in the diagnosis of chronic kidney disease (CKD). However, data in veterinary medicine are currently lacking. OBJECTIVES: To evaluate renal perfusion using CEUS in cats with CKD. ANIMALS: Fourteen client-owned cats with CKD and 43 healthy control cats. METHODS: Prospective case-controlled clinical trial using CEUS to evaluate renal perfusion in cats with CKD compared to healthy control cats. Time-intensity curves were created, and perfusion parameters were calculated using off-line software. A linear mixed model was used to examine differences between perfusion parameters of cats with CKD and healthy cats. RESULTS: In cats with CKD, longer time to peak and shorter mean transit times were observed for the renal cortex. In contrast, a shorter time to peak and rise time were seen for the renal medulla. The findings for the renal cortex indicate decreased blood velocity and shorter total duration of enhancement, likely caused by increased vascular resistance in CKD. Increased blood velocity in the renal medulla has not been described before and may be because of a different response to regulatory factors in cortex and medulla. CONCLUSIONS AND CLINICAL IMPORTANCE: Contrast-enhanced ultrasound examination was capable of detecting perfusion changes in cats with CKD. Further research is warranted to assess the diagnostic capabilities of CEUS in early stage of the disease process.

Catastrophizing, pain and traumatic stress symptoms following burns: A prospective study.

BACKGROUND: Pain and posttraumatic stress disorder (PTSD) symptoms are significant problems in the aftermath of a burn injury and they often co-occur. Catastrophizing has been linked to both phenomena. The aim of this study was to investigate the underlying role of catastrophizing in PTSD symptoms and pain following burns. METHODS: This prospective study included 216 patients with burns. PTSD symptoms and pain were measured during hospitalization (T1) and 6 (T2) and 12 months (T3) postburn. The Impact of Event Scale-Revised (IES-R) indexed PTSD symptoms. Acute pain (T1) was the mean pain during the first two weeks of hospitalization measured using an 11-point graphic numeric rating scale. Chronic pain was indexed using the single item 'average' pain from the Brief Pain Inventory (BPI). Catastrophizing was measured at T1 and T2 using the Cognitive Emotion Regulation Questionnaire (CERQ). Data were analysed using structural equation modelling (SEM). RESULTS: The results showed that T2 catastrophizing mediated between acute and chronic PTSD symptoms, and T3 pain. Furthermore, the study revealed significant associations between catastrophizing, PTSD symptoms and pain at the respective measurements, and significant longitudinal associations between the constructs. CONCLUSION: A negative cognitive-affective response to a burn event, such as catastrophizing, mediated the relationship between acute and chronic PTSD symptoms and later chronic pain. Screening for catastrophizing and acute PTSD symptoms is recommended to identify persons at risk for chronic PTSD symptoms and pain. SIGNIFICANCE: The identification of individuals who have the tendency to catastrophize may assist in finding those at risk for development of both chronic PTSD symptoms and chronic pain. Individuals may benefit from early psychological therapy focussing on catastrophizing and acute PTSD symptoms that may ameliorate both chronic PTSD symptoms and pain.

Associations between traumatic stress symptoms, pain and bio-active components in burn wounds.

OBJECTIVE: Pain and traumatic stress symptoms often co-occur. Evidence suggests that the neuropeptide oxytocine and pro-inflammatory cytokines are associated with both stress and pain. The aim of this pilot study was to explore relations between self-reported pain and traumatic stress, oxytocin and three cytokines in burn wounds. METHODS: An observational study in three burn centres was performed. Patients were invited to participate in the study when deep dermal injury was suspected. Patients completed the Impact of Event Scale (IES), a self-report questionnaire assessing traumatic stress symptoms, and they rated their pain the day prior to surgery. During surgery, eschar (i.e., burned tissue) was collected and stored at -80 ° C until analysis. When the data collection was complete, oxytocin and cytokine levels were analysed. RESULTS: Eschar from 53 patients was collected. Pain and stress scores were available from 42 and 36 patients respectively. Spearman correlational analyses showed an association between lower oxytocin levels at wound site and a higher total IES score (r = -0.37) and pain (r = -0.32). Mann-Whitney U tests comparing groups scoring high or low on pain or stress confirmed these associations. CONCLUSION: These analyses lend support to a hormonal pathway that may explain how psychological distress affects pain at skin level in patients with traumatic stress symptoms.

Comparison and reproducibility of plasma clearance of exogenous creatinine, exo-iohexol, endo-iohexol, and 51Cr-EDTA in young adult and aged healthy cats.

BACKGROUND: Important characteristics determining the usefulness of a method for glomerular filtration rate (GFR) measurement are convenience, availability, and reproducibility. HYPOTHESIS: The use of different plasma clearance methods could lead to different results and differences in reproducibility. ANIMALS: Twelve healthy cats: 6 young adult cats (age 7-12 months), and 6 aged cats (age 9-12 years) were included in this study. METHODS: A cross-over design was used to compare the plasma clearance of exogenous creatinine (PECCT), exo-iohexol (PexICT), endo-iohexol (PenICT), and chromium-51 ethylenediaminetetraacetic acid (51Cr-EDTA), and to investigate reproducibility of these methods. Cats of different ages were included to determine if differences in GFR in young adult versus aged cats would be detected with these methods. The PECCT, PexICT, and PenICT were performed in a combined manner. Plasma data were subjected to noncompartmental (creatinine, exo-iohexol, and endo-iohexol) or bicompartmental (51Cr-EDTA) analysis with a statistical moment approach. Area under the concentration-time curve was calculated using the trapezoidal rule with extrapolation to infinity. Statistical analyses were carried out using a random effects model. RESULTS: Globally, the 4 methods differed significantly (P < .0001) in GFR assessment. Clearance of exo-iohexol and chromium-51 ethylenediaminetetraacetic acid (51Cr -EDTA) showed the highest and lowest reproducibility, respectively. Only plasma clearance of creatinine differed significantly between young adult and aged cats. CONCLUSION AND CLINICAL IMPORTANCE: We found considerable differences in reproducibility of different GFR measurements. These findings should be taken into account not only in practice but also in future studies involving GFR measurement.

Evaluation of Renal Perfusion in Hyperthyroid Cats before and after Radioiodine Treatment.

BACKGROUND: Hyperthyroidism and chronic kidney disease (CKD) are common in elderly cats. Consequently, both diseases often occur concurrently. Furthermore, renal function is affected by thyroid status. Because changes in renal perfusion play an important role in functional renal changes in hyperthyroid cats, investigation of renal perfusion may provide novel insights. OBJECTIVES: To evaluate renal perfusion in hyperthyroid cats with contrast-enhanced ultrasound (CEUS). ANIMALS: A total of 42 hyperthyroid cats was included and evaluated before and 1 month after radioiodine treatment. METHODS: Prospective intrasubject clinical trial of contrast-enhanced ultrasound using a commercial contrast agent (SonoVue) to evaluate renal perfusion. Time-intensity curves were created, and perfusion parameters were calculated by off-line software. A linear mixed model was used to examine differences between pre- and post-treatment perfusion parameters. RESULTS: An increase in several time-related perfusion parameters was observed after radioiodine treatment, indicating a decreased blood velocity upon resolution of the hyperthyroid state. Furthermore, a small post-treatment decrease in peak enhancement was present in the renal medulla, suggesting a lower medullary blood volume. CONCLUSIONS AND CLINICAL IMPORTANCE: Contrast-enhanced ultrasound indicated a higher cortical and medullary blood velocity and higher medullary blood volume in hyperthyroid cats before radioactive treatment in comparison with 1-month post-treatment control.

Systemic analgesia and co-analgesia.

Potent opioids are excellent painkillers but their use is hampered by side-effects such as nausea, vomiting, bowel dysfunction, urinary retention, pruritus, sedation and respiratory depression. Co-analgesics are often combined with opioids to reduce the prevalence of these unwanted effects while maintaining or even improve the quality of analgesia. A search of the recent literature demonstrated that peripheral opioid antagonists are able to reduce opioid-induced bowel dysfunction without interfering with analgesia. Dexmedetomidine, gabapentin, and ketamine significantly reduce opioid consumption but have no effect on the incidence of opioid side-effects. In contrast, intravenous lidocaine and corticosteroids not only produce an opioid-sparing but also a significant reduction in the occurrence of postoperative ileus and nausea and vomiting. It remains unclear whether the perioperative use gabapentin, ketamine and corticosteroids has an effect on the development of postsurgical chronic pain states.