Parametric modelling of prevalent cohort data with uncertainty in the measurement of the initial onset date.

In prevalent cohort studies with follow-up, if disease duration is the focus, the date of onset must be obtained retrospectively. For some diseases, such as Alzheimer's disease, the very notion of a date of onset is unclear, and it can be assumed that the reported date of onset acts only as a proxy for the unknown true date of onset. When adjusting for onset dates reported with error, the features of left-truncation and potential right-censoring of the failure times must be modeled appropriately. Under the assumptions of a classical measurement error model for the onset times and an underlying parametric failure time model, we propose a maximum likelihood estimator for the failure time distribution parameters which requires only the observed backward recurrence times. Costly and time-consuming follow-up may therefore be avoided. We validate the maximum likelihood estimator on simulated datasets under varying parameter combinations and apply the proposed method to the Canadian Study of Health and Aging dataset.

Antibody-mediated thyroid dysfunction during T-cell checkpoint blockade in patients with non-small-cell lung cancer.

Background: Programmed cell death protein-1 (PD-1) blockade therapies have demonstrated durable responses and prolonged survival in a variety of malignancies. Treatment is generally well tolerated although immune-related adverse events (irAEs) can occur. Autoimmune thyroid dysfunction is among the most common irAE, but an assessment of the clinical, mechanistic, and immunologic features has not been previously described. Patient and methods: Patients with advanced non-small-cell lung cancer (NSCLC) treated with pembrolizumab at Memorial Sloan Kettering Cancer Center (n = 51) as part of KEYNOTE-001 (NCT01295827) were included. Thyroid function test and anti-thyroid antibodies were assessed prospectively at each study visit, beginning before the first treatment. Frequency of development of thyroid dysfunction, association with anti-thyroid antibodies, clinical course, and relationship with progression-free survival and overall survival to treatment with pembrolizumab was evaluated. Results: Of 51 patients treated, 3 were hypothyroid and 48 were not at baseline. Ten of 48 [21%, 95% confidence interval (CI) 10% to 35%] patients developed thyroid dysfunction requiring thyroid replacement. Anti-thyroid antibodies were present in 8 of 10 patients who developed thyroid dysfunction, compared with 3 of 38 who did not (80% versus 8%, P < 0.0001). Thyroid dysfunction occurred early (median, 42 days) in the pembrolizumab course, and a majority (6 of 10 patients) experienced brief, transient hyperthyroidism preceding the onset of hypothyroidism; no persistent hyperthyroidism occurred. Both hyperthyroidism and hypothyroidism were largely asymptomatic. Overall survival with pembrolizumab was significantly longer in subjects who developed thyroid dysfunction (hazard ratio, 0.29; 95% CI 0.09-0.94; P = 0.04). Conclusions: Thyroid dysfunction during pembrolizumab treatment of NSCLC is common and is characterized by early-onset, frequently preceded by transient hyperthyroidism, closely associated with anti-thyroid antibodies, and may be associated with improved outcomes. The presence of antibody-mediated toxicity in T-cell-directed therapy suggests an under-recognized impact of PD-1 biology in modulating humoral immunity.

Pediatric intestinal transplant listing criteria - a call for a change in the new era of intestinal failure outcomes.

Current listing indications used for intestinal transplantation (IT) were proposed in 2001. We undertook the present single center study to see if these criteria are still valid. The 2001 criteria (advanced cholestasis, loss of >50% central venous catheter (CVC) sites, ≥2 sepsis/year, ultrashort bowel) were compared in children with intestinal failure in old era-1998-2005 (N = 99) to current era-2006-2012 (N = 91) to predict the need for IT using sensitivity, specificity, NPV and PPV. Two 2001 criteria had poorer predictive value in the current era: Advanced cholestasis (PPV 64% old vs. 40% current era; sensitivity 84% vs. 65%, respectively) and ultrashort bowel (PPV 100% old vs. 9% current era; sensitivity 10% vs. 4%, respectively). Three newly proposed criteria had high predictive value: ≥2 ICU admissions (p = 0.0001, OR 23.6, 95% CI 2.7-209.8), persistent bilirubin >75 mmol/L despite lipid strategies (p = 0.0005, OR 24.0, 95% CI 3.2-177.4), and loss of ≥3 CVC sites (p = 0.0003, OR 33.3, 95% CI 18.8-54.0). There was 98% probability of needing IT when two of these new criteria were present. The 2001 IT criteria have limited predictive ability in the current era and should be revised. A multicenter study is required to validate the findings of this single center experience.

Testosterone regulates bone response to inflammation.

This study evaluated the alveolar bone response to testosterone and the impact of Resolvin D2 (RvD2) on testosterone-induced osteoblast function. For the in vivo characterization, 60 male adult rats were used. Treatments established sub-physiologic (L), normal (N), or supra-physiologic (H) concentrations of testosterone. Forty rats were subjected to orchiectomy; 20 rats received periodical testosterone injections while 20 rats received testicular sham-operation. Four weeks after the surgeries, 10 rats in each group received a subgingival ligature around the lower first molars to induce experimental periodontal inflammation and bone loss. In parallel, osteoblasts were differentiated from neonatal mice calvariae and treated with various doses of testosterone for 48 h. Cell lysates and conditioned media were used for the determination of alkaline phosphatase, osteocalcin, RANKL, and osteoprotegerin. Micro-computed tomography linear analysis demonstrated that bone loss was significantly increased for both L and H groups compared to animals with normal levels of testosterone. Gingival IL-1ß expression was increased in the L group (p<0.05). Ten nM testosterone significantly decreased osteocalcin, RANKL, and OPG levels in osteoblasts; 100 nM significantly increased the RANKL:OPG ratio. RvD2 partially reversed the impact of 10 nM testosterone on osteocalcin, RANKL, and OPG. These findings suggest that both L and H testosterone levels increase inflammatory bone loss in male rats. While low testosterone predominantly increases the inflammatory response, high testosterone promotes a higher osteoblast-derived RANKL:OPG ratio. The proresolving mediator RvD2 ameliorates testosterone-derived downregulation of osteocalcin, RANKL, and OPG in primary murine osteoblasts suggesting a direct role of inflammation in osteoblast function.

Environmental survival of Neisseria meningitidis.

Neisseria meningitidis is transmitted through the inhalation of large human respiratory droplets, but the risk from contaminated environmental surfaces is controversial. Compared to Streptococcus pneumoniae and Acinetobacter baumanni, meningococcal viability after desiccation on plastic, glass or metal surfaces decreased rapidly, but viable meningococci were present for up to 72 h. Encapsulation did not provide an advantage for meningococcal environmental survival on environmental surfaces.

SURgical interventions with FEIBA (SURF): international registry of surgery in haemophilia patients with inhibitory antibodies.

Factor VIII Inhibitor Bypassing Activity (FEIBA) can effectively achieve haemostasis in haemophilia patients with inhibitors. Further evaluation of FEIBA in surgical settings is of significant interest considering the relatively limited prospective data published to date. The aim of the study is to evaluate the perioperative efficacy and safety of FEIBA in haemophilia patients with inhibitors. Haemophilia patients with inhibitors who underwent surgical procedures and received FEIBA for perioperative haemostatic control were prospectively enrolled in an open-label, noninterventional, postauthorization study [SURgical interventions with FEIBA (SURF)]. Outcome measures included haemostatic efficacy, safety, FEIBA exposure and blood loss associated with the perioperative use of FEIBA. Thirty-five surgical procedures were performed at 19 centres worldwide in patients with congenital haemophilia A, congenital haemophilia B, or acquired haemophilia A. Haemorrhagic risk was severe in 37.1% (13 of 35) of the procedures, moderate in 25.7% (9 of 35) and mild in 37.1% (13 of 35). One moderate risk surgery was excluded from the efficacy analyses because it did not meet all protocol requirements. Haemostasis was judged to be 'good' or 'excellent' in 91.2% (31 of 34) of surgical procedures and 'fair' in 8.8% (3 of 34). Among the 12 adverse events, three were serious adverse events (SAEs), two of which were unrelated to FEIBA therapy; one SAE, a clot in an arteriovenous fistula, was deemed to be possibly related to therapy. This prospective investigation confirms that FEIBA can be safely and effectively used when performing surgical procedures in haemophilia patients with inhibitors.

Patients' experiences of negative pressure wound therapy for the treatment of wounds: a review.

OBJECTIVE: To review the research on patients' experiences of undergoing negative pressure wound therapy (NPWT). METHOD: A literature search was carried out using the following databases: Academic Search Complete, CINAHL, PsychINFO, MEDLINE, PubMed and PsyARTICLES. The search covered the period from 2001 to 2012, using the key words: ['negative pressure wound therapy' OR 'vacuum-assisted closure' OR 'topical negative therapy'] AND ['patients' experiences' OR 'psychological' OR 'stress' OR 'anxiety' OR 'wellbeing' OR 'pain' OR 'quality of life' OR 'physical']. RESULTS: Twenty-five relevant articles were included. NPWT is generally considered to be successful in reducing wound depth and facilitating healing. However, studies have highlighted a number of issues that need to be considered. For example, the type of dressing used during treatment can have a significant effect on patients' experience of pain. Furthermore, the NPWT system can cause patients to feel anxious due to both the patient and the health professional being unfamiliar with this form of treatment. It can also restrict patients' daily care and wider social life, which may result in a negative self-image and low self-esteem. Despite this, some studies have reported positive improvements to patients' quality of life. Additionally, since NPWT can lead to faster healing, any detrimental impact upon patients' wellbeing may be short-term and less prolonged than that of other treatments. CONCLUSION: Compared with other treatments, there is evidence to show that NPWT can lead to faster wound healing, and a reduced frequency of dressing changes and other treatments. However, there are a number of challenges with the use of NPWT, which need to be explored further so that improvements can be made. Specifically, certain aspects of NPWT may impact negatively on patients' wellbeing, albeit short-term. Therefore, research needs to explore patients' experience of NPWT throughout the treatment process and to consider how this can be improved to minimise any negative effects.

Dehiscence of the posterior and superior semicircular canal presenting in pregnancy.

OBJECTIVE: We present an interesting case of superior and posterior semicircular canal dehiscence in pregnancy. METHOD: We present a case report and a review of the world literature concerning semicircular canal dehiscence. CASE REPORT: A 34-year-old woman presented with sound and pressure induced vertigo at 22 weeks gestation. A thinly sliced computed tomography (CT) scan of the petrous temporal bones viewed with coronal reconstructions was performed post-partum. This showed the presence of both left superior canal and posterior canal dehiscence. CONCLUSION: To our knowledge this is the first reported case of semicircular canal dehiscence in pregnancy. The diagnosis of semicircular canal dehiscence should be suspected in pregnant patients with sound induced vertigo.

Report of consensus panel 5 from the 11th international workshop on Waldenstrom's macroglobulinemia on COVID-19 prophylaxis and management.

Consensus Panel 5 (CP5) of the 11th International Workshop on Waldenstrom's Macroglobulinemia (IWWM-11; held in October 2022) was tasked with reviewing the current data on the coronavirus disease-2019 (COVID-19) prophylaxis and management in patients with Waldenstrom's Macroglobulinemia (WM). The key recommendations from IWWM-11 CP5 included the following: Booster vaccines for SARS-CoV-2 should be recommended to all patients with WM. Variant-specific booster vaccines, such as the bivalent vaccine for the ancestral Wuhan strain and the Omicron BA.4.5 strain, are important as novel mutants emerge and become dominant in the community. A temporary interruption in Bruton's Tyrosine Kinase-inhibitor (BTKi) or chemoimmunotherapy before vaccination might be considered. Patients under treatment with rituximab or BTK-inhibitors have lower antibody responses against SARS-CoV-2; thus, they should continue to follow preventive measures, including mask wearing and avoiding crowded places. Patients with WM are candidates for preexposure prophylaxis, if available and relevant to the dominant SARS-CoV-2 strains in a specific area. Oral antivirals should be offered to all symptomatic WM patients with mild to moderate COVID-19 regardless of vaccination, disease status or treatment, as soon as possible after the positive test and within 5 days of COVID-19-related symptom onset. Coadministration of ibrutinib or venetoclax with ritonavir should be avoided. In these patients, remdesivir offers an effective alternative. Patients with asymptomatic or oligosymptomatic COVID-19 should not interrupt treatment with a BTK inhibitor. Infection prophylaxis is essential in patients with WM and include general preventive measures, prophylaxis with antivirals and vaccination against common pathogens including SARS-CoV-2, influenza, and S. pneumoniae.

Report of consensus panel 7 from the 11th international workshop on Waldenström macroglobulinemia on priorities for novel clinical trials.

Recent advances in the understanding of Waldenström macroglobulinemia (WM) biology have impacted the development of effective novel agents and improved our knowledge of how the genomic background of WM may influence selection of therapy. Consensus Panel 7 (CP7) of the 11th International Workshop on WM was convened to examine the current generation of completed and ongoing clinical trials involving novel agents, consider updated data on WM genomics, and make recommendations on the design and prioritization of future clinical trials. CP7 considers limited duration and novel-novel agent combinations to be the priority for the next generation of clinical trials. Evaluation of MYD88, CXCR4 and TP53 at baseline in the context of clinical trials is crucial. The common chemoimmunotherapy backbones, bendamustine-rituximab (BR) and dexamethasone, rituximab and cyclophosphamide (DRC), may be considered standard-of-care for the frontline comparative studies. Key unanswered questions include the definition of frailty in WM; the importance of attaining a very good partial response or better (≥VGPR), within stipulated time frame, in determining survival outcomes; and the optimal treatment of WM populations with special needs.

The IMAGEN study: reinforcement-related behaviour in normal brain function and psychopathology.

A fundamental function of the brain is to evaluate the emotional and motivational significance of stimuli and to adapt behaviour accordingly. The IMAGEN study is the first multicentre genetic-neuroimaging study aimed at identifying the genetic and neurobiological basis of individual variability in impulsivity, reinforcer sensitivity and emotional reactivity, and determining their predictive value for the development of frequent psychiatric disorders. Comprehensive behavioural and neuropsychological characterization, functional and structural neuroimaging and genome-wide association analyses of 2000 14-year-old adolescents are combined with functional genetics in animal and human models. Results will be validated in 1000 adolescents from the Canadian Saguenay Youth Study. The sample will be followed up longitudinally at the age of 16 years to investigate the predictive value of genetics and intermediate phenotypes for the development of frequent psychiatric disorders. This review describes the strategies the IMAGEN consortium used to meet the challenges posed by large-scale multicentre imaging-genomics investigations. We provide detailed methods and Standard Operating Procedures that we hope will be helpful for the design of future studies. These include standardization of the clinical, psychometric and neuroimaging-acquisition protocols, development of a central database for efficient analyses of large multimodal data sets and new analytic approaches to large-scale genetic neuroimaging analyses.

The patient journey of adults with hearing impairment: the patients' views.

OBJECTIVE: The term 'patient journey' refers to the experiences and processes the patient goes through during the course of a disease and its treatment. The study explores the perspectives of adults with acquired hearing impairment and to further develop the patient journey template based on the Ida model. DESIGN: Qualitative approach using thematic analysis and process mapping. SETTING: Support groups of people with hearing impairment. PARTICIPANTS: Thirty-two adults with acquired hearing impairment from two hearing impaired groups in Wales. All were hearing aid users. MAIN OUTCOME MEASURE: Participants worked in small groups to describe their experiences through hearing loss. These data were used to develop a template of the patients' perspective of the journey. This was then compared with the perspective of professionals, and a 'patient journey template for adults with acquired hearing impairment' was developed. RESULTS: This template identifies seven main phases as follows: (i) pre-awareness; (ii) awareness; (iii) movement; (iv) diagnostics; (v) rehabilitation; (vi) self-evaluation; and (vii) resolution. The study identified a number of new components. The self-evaluation component was not defined by professionals and reflects the need for patients to consider the costs, benefits and alternatives to the approach provided by audiologists. It is important for audiologists to be aware of this. CONCLUSION: The study highlighted the differences and commonalities in perspectives of professionals and patients. Use of the patient journey can help clinicians to understand the unique experiences their patients go through help them to develop patient-centred treatment.

Tinnitus complaint behaviour in long-standing Menière's disorder: its association with the other cardinal symptoms.

OBJECTIVE: To explore factors that determines tinnitus complaint behaviour in patients with chronic long-standing Menière's disorder. DESIGN AND SETTING: A questionnaire-based cross-sectional investigation. This included the Oto-neurological questionnaire, the Hearing Disability and Handicap Scale (HDHS), Hearing Measurement Scale (HMS) on sound localisation and the Dizziness Handicap Questionnaire (DHQ). PARTICIPANTS: Randomly selected 183 members of the Finnish Menière's Federation. INTERVENTION: Postal questionnaire. MAIN OUTCOME MEASURE: International Tinnitus Inventory and impact of tinnitus. RESULTS: The 183 patients,[36 men and 147 women; mean age, 63 years] had their Meniere's disorder-like symptoms, with a mean of 18 years [range, 1-43], 19% of patients ranked tinnitus as their most severe symptom, and 10% experienced tinnitus as causing a severe or very severe impact. Regression analysis indicated that 41% of International Tinnitus Inventory variance and 28% of tinnitus impact variance were explained by the cardinal symptoms of Menière's disorder. Furthermore, 40% of International Tinnitus Inventory and 25% of tinnitus impact variance were explained by symptom-related disabilities (HDHS, HMS and DHQ). Aural pressure, hearing loss and gait problems were the most important predictors of tinnitus complaint. Understanding what people say and limitation of activities because of vertigo were the most important related disabilities. CONCLUSION: Tinnitus shares a significant variance with the other cardinal symptoms in patients with long-standing Menière's disorder. As the impact is significantly related to activity limitations based on hearing disability and vertigo, the results suggest that therapeutic efforts to reduce tinnitus in Menière's disorder should include the alleviation of balance and hearing problems.

Hybridisation between dingoes and domestic dogs in proximity to Indigenous communities in northern Australia.

In northern Australia, wild dog populations potentially interact with domestic dogs from remote communities, which would create opportunities for disease transmission at the wild-domestic interface. An example is rabies, in the event of an incursion into northern Australia. However, the likelihood of such wild-domestic interactions is ambiguous. Hybridisation analyses based on 23 microsatellite DNA markers were performed on canine-origin scats collected in bushland areas around remote Indigenous communities in the Northern Peninsula Area, Queensland. Sufficient DNA was extracted from 6 of 41 scats to assess the percentage of dingo purity. These scats most likely originated from two 'pure' domestic dogs (0% dingo purity), one hybrid (20% dingo purity) and three 'pure' dingoes (92%-98% dingo purity). The two domestic dog samples were collected in the vicinity of communities. The location of two of the dingo-origin samples provides genetic evidence that dingoes are present in areas close to the communities. The availability of anthropogenic food resources likely creates opportunities for interactions with domestic dogs in the region. The hybrid sample demonstrates the occurrence of antecedent contacts between both populations by means of mating and supports the likelihood of a spatio-temporal overlap at the wild-domestic interface. This represents the first genetic survey involving a wild dog population of equatorial northern Queensland, with evidence of dingo purity. Our results have implications for potential disease transmission within a priority area for biosecurity in northern Australia.

Changes in Gut Bacterial Translation Occur before Symptom Onset and Dysbiosis in Dextran Sodium Sulfate-Induced Murine Colitis.

Longitudinal studies on the gut microbiome that follow the effect of a perturbation are critical in understanding the microbiome's response and succession to disease. Here, we use a dextran sodium sulfate (DSS) mouse model of colitis as a tractable perturbation to study how gut bacteria change their physiology over the course of a perturbation. Using single-cell methods such as flow cytometry, bioorthogonal noncanonical amino acid tagging (BONCAT), and population-based cell sorting combined with 16S rRNA sequencing, we determine the diversity of physiologically distinct fractions of the gut microbiota and how they respond to a controlled perturbation. The physiological markers of bacterial activity studied here include relative nucleic acid content, membrane damage, and protein production. There is a distinct and reproducible succession in bacterial physiology, with an increase in bacteria with membrane damage and diversity changes in the translationally active fraction, both, critically, occurring before symptom onset. Large increases in the relative abundance of Akkermansia were seen in all physiological fractions, most notably in the translationally active bacteria. Performing these analyses within a detailed, longitudinal framework determines which bacteria change their physiology early on, focusing therapeutic efforts in the future to predict or even mitigate relapse in diseases like inflammatory bowel diseases. IMPORTANCE Most studies on the gut microbiome focus on the composition of this community and how it changes in disease. However, how the community transitions from a healthy state to one associated with disease is currently unknown. Additionally, common diversity metrics do not provide functional information on bacterial activity. We begin to address these two unknowns by following bacterial activity over the course of disease progression, using a tractable mouse model of colitis. We find reproducible changes in gut bacterial physiology that occur before symptom onset, with increases in the proportion of bacteria with membrane damage, and changes in community composition of the translationally active bacteria. Our data provide a framework to identify possible windows of intervention and which bacteria to target in microbiome-based therapeutics.

Conservation concerns associated with low genetic diversity for K'gari-Fraser Island dingoes.

The dingo population on world heritage-listed K'gari-Fraser Island (K'gari) is amongst the most well-known in Australia. However, an absence of population genetic data limits capacity for informed conservation management. We used 9 microsatellite loci to compare the levels of genetic diversity and genetic structure of 175 K'gari dingo tissue samples with 264 samples from adjacent mainland regions. Our results demonstrated that the K'gari population has significantly lower genetic diversity than mainland dingoes (AR, HE, PAR; p < 0.05) with a fourfold reduction in effective population size (Ne = 25.7 vs 103.8). There is also strong evidence of genetic differentiation between the island and mainland populations. These results are in accordance with genetic theory for small, isolated, island populations, and most likely the result of low initial diversity and founder effects such as bottlenecks leading to decreased diversity and drift. As the first study to incorporate a large sample set of K'gari dingoes, this provides invaluable baseline data for future research, which should incorporate genetic and demographic monitoring to ensure long-term persistence. Given that human-associated activities will continue to result in dingo mortality, it is critical that genetic factors are considered in conservation management decisions to avoid deleterious consequences for this iconic dingo population.

The effective coupling coefficient for a completed PIN-PMN-PT array.

The computation of the electromechanical coupling coefficient (EMCC) of a fully assembled medical ultrasound transducer array is directly computed with closed form expressions. The Levenberg-Marquardt non-linear regression algorithm (LMA) is employed to help confirm the EMCC calculated prediction (kEFF) and provide statistical insights. The complex electrical impedance spectra of a 1-3 composite array with two matching layers operating at a 3.75 MHz center frequency using PIN-PMN-PT single crystal material is measured in air both before and after oven heating at 160 °C for 15 min. The oven heating produces changes in the EMCC of -4.9%, clamped dielectric constant of -11%, and effective transducer longitudinal velocity of -2.5%. Utilizing the pre- and post-heating array impedance data, the calculated EMCC values from the new closed form expressions agree well with the complete KLM model based LMA, and also exhibit approximately one tenth the error as compared to the formulas for a flat, unloaded transducer.

Pili of Neisseria meningitidis. Analysis of structure and investigation of structural and antigenic relationships to gonococcal pili.

To provide information useful for the design of a pilus vaccine effective for the prevention of both meningococcal and gonococcal disease, the electron microscopic morphology of meningococcal pili and the structural and antigenic relationships of meningococcal pili to gonococcal pili were investigated. Meningococcal pili were 4-6 nm in width, extended 500-6,000 nm from the organism surface, and occurred singly or in bundles composed of 8-10 pili per bundle. Meningococcal pilin varied between 17,250 and 20,600 daltons. Pilin was present in outer membrane preparations of some meningococcal isolates that were nonpiliated by electron microscopic examination. Antibodies to gonococcal pili, cyanogen bromide cleavage fragments of gonococcal pilin, or synthetic peptide analogues corresponding to regions of the gonococcal pilin sequence, were used to detect common meningococcal and gonococcal antigenic determinants that might indicate the existence of a conserved sequence beyond residue 29. Antibody to intact gonococcal pili or to the variable CNBR-3 region of gonococcal pilin detected little shared antigenicity with meningococcal pilin. However, pilin from all tested meningococcal isolates reacted with antibody to the CNBR-2 fragment of gonococcal pilin, a region highly conserved among gonococcal strains. Meningococcal pilins were also broadly crossreactive with antibody to a synthetic peptide corresponding to residues 69-84 of the gonococcal sequence, a part of the CNBR-2 region that appears to be critical for gonococcal receptor-binding function. If a sequence similar to 69-84 is also important for receptor-binding function in meningococcal pili, a peptide corresponding to this region may elicit antibodies that block the adherence function of pili elaborated by both Neisseria gonorrhoeae and N. meningitidis.

Exploring beyond viral load testing for EBV lymphoproliferation: role of serum IL-6 and IgE assays as adjunctive tests.

We examined serum IL-6 and IgE assays as adjuncts to VL monitoring for PTLD. Paediatric solid organ transplant recipients were followed with VL monitoring. VL, IL-6, and IgE assays were compared between PTLD cases and non-cases at <3, 3-6 and >6 months after transplantation. Median IL-6 levels in PTLD cases were 15.5 (2.0-87.1) and 23.3 (2.1-276) pg/mL compared with 3.25 (0.92-114) and 3.5 (0.75-199.25) pg/mL in non-cases at 3-6 and >6 months, respectively (p = 0.006 and p = 0.005). At >6 months, IL-6 levels correlated with VL and PTLD occurrence (Spearman's coefficients = 0.40; p = 0.001 and 0.32; p = 0.003) in univariate analyses. No benefit was derived from performance of IgE levels. The sensitivity and specificity of high VL as a test of PTLD were 76.3% and 92.5%, while the negative predictive value and PPV of VL were 94.9% and 68.4%, respectively. Combining elevated IL-6 with high VL increased the PPV and specificity to 80% and 96.2%, respectively, and improved the receiver operating characteristic curve. Serum IL-6 levels can improve the clinician's ability to identify PTLD, among patients with elevated EBV viral loads.