Persisting Symptomatic Severe Secondary Mitral Regurgitation in Heart Failure Patients.

Aims We aimed to assess the rate of persisting severe symptomatic secondary mitral regurgitation (MR) in a newly diagnosed heart failure (HF) population following optimisation of guideline directed medical therapy (GDMT), cardiac resynchronisation therapy (CRT) and revascularisation. Methods We assessed all new patients referred to our hospital group's HF clinics. We retrospectively reviewed these patients at HF clinic enrolment, HF programme completion, as well as most recent follow up. Results Of the 242 new patients referred to our HF clinics, there were 10 patients (4.1%) who had either persisting symptomatic severe secondary MR at HF programme completion, or had undergone mitral valve surgery. There were no percutaneous mitral valve repairs at the time of these patients' referrals. The rates of ACE/ARB/ARNI, BB and MRA use were 87.8%, 94.1%, and 49.8% in those with mid ranged, or reduced ejection fraction. The rates of ICD and CRT therapy were 15.1% and 4.4% at follow up. Patients with severe MR had higher time adjusted rates of death or hospitalization for heart failure. Conclusion In a well-treated newly diagnosed HF population, repeat assessment at HF programme completion suggests 4.1% of patients have a persisting indication for percutaneous mitral valve repair based on persisting severe symptomatic secondary MR.

Global parental leave in surgical careers: differences according to gender, geographical regions and surgical career stages.

BACKGROUND: There is a lack of information regarding the provision of parental leave for surgical careers. This survey study aims to evaluate the experience of maternity/paternity leave and views on work-life balance globally. METHODS: A 55-item online survey in 24 languages was distributed via social media as per CHERRIES guideline from February to March 2020. It explored parental leave entitlements, attitude towards leave taking, financial impact, time spent with children and compatibility of parenthood with surgical career. RESULTS: Of the 1393 (male : female, 514 : 829) respondents from 65 countries, there were 479 medical students, 349 surgical trainees and 513 consultants. Consultants had less than the recommended duration of maternity leave (43.8 versus 29.1 per cent), no paid maternity (8.3 versus 3.2 per cent) or paternity leave (19.3 versus 11.0 per cent) compared with trainees. Females were less likely to have children than males (36.8 versus 45.6 per cent, P = 0.010) and were more often told surgery is incompatible with parenthood (80.2 versus 59.5 per cent, P < 0.001). Males spent less than 20 per cent of their salary on childcare and fewer than 30 hours/week with their children. More than half (59.2 per cent) of medical students did not believe a surgical career allowed work-life balance. CONCLUSION: Surgeons across the globe had inadequate parental leave. Significant gender disparity was seen in multiple aspects.

When Azoles Cannot Be Used: The Clinical Effectiveness of Intermittent Liposomal Amphotericin Prophylaxis in Hematology Patients.

BACKGROUND: Patients unable to take azoles are a neglected group lacking a standardized approach to antifungal prophylaxis. We evaluated the effectiveness and safety of intermittent liposomal amphotericin B (L-AMB) prophylaxis in a heterogenous group of hematology patients. METHODS: A retrospective cohort of all hematology patients who received a course of intravenous L-AMB, defined as 1 mg/kg thrice weekly from July 1, 2013 to June 30, 2018, were identified from pharmacy records. Outcomes included breakthrough-invasive fungal disease (BIFD), reasons for premature discontinuation, and acute kidney injury. RESULTS: There were 198 patients who received 273 courses of L-AMB prophylaxis. Using a conservative definition, the BIFD rate was 9.6% (n = 19 of 198) occurring either during L-AMB prophylaxis or up to 7 days from cessation in patients who received a course. Probable/proven BIFD occurred in 13 patients (6.6%, 13 of 198), including molds in 54% (n = 7) and non-albicans Candidemia in 46% (n = 6). Cumulative incidence of BIFD was highest in patients with acute myeloid leukemia (6.8%) followed by acute lymphoblastic leukemia (2.7%) and allogeneic stem cell transplantation (2.5%). The most common indication for L-AMB was chemotherapy, or anticancer drug-azole interactions (75% of courses) dominated by vincristine, or acute myeloid leukemia clinical trials, followed by gut absorption concerns (13%) and liver function abnormalities (8.8%). Acute kidney injury, using a modified international definition, complicated 27% of courses but was not clinically significant, accounting for only 3.3% (9 of 273) of discontinuations. CONCLUSIONS: Our findings demonstrate a high rate of BIFD among patients receiving L-AMB prophylaxis. Pragmatic trials will help researchers find the optimal regimen of L-AMB prophylaxis for the many clinical scenarios in which azoles are unsuitable, especially as targeted anticancer drugs increase in use.

Molecular patterns of response and treatment failure after frontline venetoclax combinations in older patients with AML.

The BCL-2 inhibitor venetoclax combined with hypomethylating agents or low-dose cytarabine represents an important new therapy for older or unfit patients with acute myeloid leukemia (AML). We analyzed 81 patients receiving these venetoclax-based combinations to identify molecular correlates of durable remission, response followed by relapse (adaptive resistance), or refractory disease (primary resistance). High response rates and durable remissions were typically associated with NPM1 or IDH2 mutations, with prolonged molecular remissions prevalent for NPM1 mutations. Primary and adaptive resistance to venetoclax-based combinations was most commonly characterized by acquisition or enrichment of clones activating signaling pathways such as FLT3 or RAS or biallelically perturbing TP53. Single-cell studies highlighted the polyclonal nature of intratumoral resistance mechanisms in some cases. Among cases that were primary refractory, we identified heterogeneous and sometimes divergent interval changes in leukemic clones within a single cycle of therapy, highlighting the dynamic and rapid occurrence of therapeutic selection in AML. In functional studies, FLT3 internal tandem duplication gain or TP53 loss conferred cross-resistance to both venetoclax and cytotoxic-based therapies. Collectively, we highlight molecular determinants of outcome with clinical relevance to patients with AML receiving venetoclax-based combination therapies.

Variability in body temperature in healthy adults and in patients receiving chemotherapy: prospective observational cohort study.

Between-individual variability of body temperature has been little investigated, but is of clinical importance: for example, in detection of neutropenic sepsis during chemotherapy. We studied within-person and between-person variability in temperature in healthy adults and those receiving chemotherapy using a prospective observational design involving 29 healthy participants and 23 patients undergoing chemotherapy. Primary outcome was oral temperature. We calculated each patient's mean temperature, standard deviation within each patient (within-person variability), and between patients (between-person variability). Secondary analysis explored temperature changes in the three days before admission for neutropenic sepsis. 1,755 temperature readings were returned by healthy participants and 1,765 by chemotherapy patients. Mean participant temperature was 36.16 C (95% CI 36.07-36.26) in healthy participants and 36.32 C (95% CI 36.18-36.46) in chemotherapy patients. Healthy participant within-person variability was 0.40 C (95% CI 0.36-0.44) and between-person variability was 0.26 C (95% CI 0.16-0.35). Chemotherapy patient within-person variability was 0.39 C (95% CI 0.34-0.44) and between-person variability was 0.34 C (95% CI 0.26-0.48). Thus, use of a population mean rather than personalised baselines is probably sufficient for most clinical purposes as between-person variability is not large compared to within-person variability. Standardised guidance and provision of thermometers to patients might help to improve recording and guide management.

Proteomic analysis reveals greater abundance of complement and inflammatory proteins in subcutaneous adipose tissue from postpartum cows treated with sodium salicylate.

This study aimed to investigate sodium salicylate (SS) treatment effects on the proteome of adipose tissue (AT) in postpartum cows. Twenty Holstein cows were assigned to control (CON, n = 10) or SS (n = 10) provided via drinking water (2.3 g/L) during the first 7 d of lactation. Subcutaneous AT was collected on d 7 of treatment and label-free quantitative shotgun proteomics and immunoblotting were analyzed in a subset of 5 AT per group. Eighty out of 1422 proteins (5.6%) were differentially abundant between CON and SS [fold change ±1.5, P < 0.05]. Top canonical pathways differing between CON and SS (Ingenuity) were complement system, interleukin-10 signaling, and acute phase response signaling. The abundances of complement C1r, C1qC, C1qB and C6 were greater in SS than CON. Regarding IL-10 signaling, the abundances of BLVRB, STAT3, and lipopolysaccharide binding protein (LBP) were greater in SS AT compared to CON. Immunoblots revealed increased abundance of paraoxanase-1 and tumor necrosis factor-alpha, as well as a tendency for greater abundance of cluster differentiation 172a in SS AT, which may indicate of increased macrophage infiltration. SS treatment postpartum likely promotes inflammatory signaling in AT of dairy cows, perhaps due to immune cell recruitment. SIGNIFICANCE: This work demonstrates that treating early lactating cows with sodium salicylate, an anti-inflammatory agent that has been shown to have metabolic effects and increase milk production in dairy cows, affects the proteome of subcutaneous adipose tissue in early lactating dairy cows. Unexpectedly, sodium salicylate treatment enriched inflammatory pathways of the complement system, cytokine signaling, and acute phase response, as revealed by proteomic analysis of subcutaneous adipose tissues from cows at 7 d postpartum. These findings imply that SS treatment during the first 7 d of lactation likely promotes inflammatory signaling in AT of the dairy cow, perhaps due to immune cell recruitment. Tissue-specific impacts of systemic sodium salicylate requires further scrutiny.

Meta-analysis of the prevalence of renal cancer detected by abdominal ultrasonography.

BACKGROUND: The potential for an ultrasound-based screening programme for renal cell carcinoma (RCC) to improve survival through early detection has been the subject of much debate. The prevalence of ultrasound-detected asymptomatic RCC is an important first step to establishing whether a screening programme may be feasible. METHODS: A systematic search of MEDLINE and Embase was performed up to March 2016 to identify studies reporting the prevalence of renal masses and RCC. Two populations of patients were chosen: asymptomatic individuals undergoing screening ultrasonography and patients undergoing ultrasonography for abdominal symptoms not related to RCC. A random-effects meta-analysis was performed. Study quality was evaluated using a validated eight-point checklist. RESULTS: Sixteen studies (413 551 patients) were included in the final analysis. The pooled prevalence of renal mass was 0·36 (95 per cent c.i. 0·23 to 0·52) per cent and the prevalence of histologically proven RCC was 0·10 (0·06 to 0·15) per cent. The prevalence of RCC was more than double in studies from Europe and North America than in those from Asia: 0·17 (0·09 to 0·27) versus 0·06 (0·03 to 0·09) per cent respectively. Data on 205 screen-detected RCCs showed that 84·4 per cent of tumours were stage T1-T2 N0, 13·7 per cent were T3-T4 N0, and only 2·0 per cent had positive nodes or metastases at diagnosis. CONCLUSION: At least one RCC would be detected per 1000 individuals screened. The majority of tumours identified are early stage (T1-T2).

Academic requirements for Certificate of Completion of Training in surgical training: Consensus recommendations from the Association of Surgeons in Training/National Research Collaborative Consensus Group.

BACKGROUND: Surgical trainees are expected to demonstrate academic achievement in order to obtain their certificate of completion of training (CCT). These standards are set by the Joint Committee on Surgical Training (JCST) and specialty advisory committees (SAC). The standards are not equivalent across all surgical specialties and recognise different achievements as evidence. They do not recognise changes in models of research and focus on outcomes rather than process. The Association of Surgeons in Training (ASiT) and National Research Collaborative (NRC) set out to develop progressive, consistent and flexible evidence set for academic requirements at CCT. METHODS: A modified-Delphi approach was used. An expert group consisting of representatives from the ASiT and the NRC undertook iterative review of a document proposing changes to requirements. This was circulated amongst wider stakeholders. After ten iterations, an open meeting was held to discuss these proposals. Voting on statements was performed using a 5-point Likert Scale. Each statement was voted on twice, with ≥80% of votes in agreement meaning the statement was approved. The results of this vote were used to propose core and optional academic requirements for CCT. RESULTS: Online discussion concluded after ten rounds. At the consensus meeting, statements were voted on by 25 delegates from across surgical specialties and training-grades. The group strongly favoured acquisition of 'Good Clinical Practice' training and research methodology training as CCT requirements. The group agreed that higher degrees, publications in any author position (including collaborative authorship), recruiting patients to a study or multicentre audit and presentation at a national or international meeting could be used as evidence for the purpose of CCT. The group agreed on two essential 'core' requirements (GCP and methodology training) and two of a menu of four 'additional' requirements (publication with any authorship position, presentation, recruitment of patients to a multicentre study and completion of a higher degree), which should be completed in order to attain CCT. CONCLUSION: This approach has engaged stakeholders to produce a progressive set of academic requirements for CCT, which are applicable across surgical specialties. Flexibility in requirements whilst retaining a high standard of evidence is desirable.

Renal Squamous Cell Carcinoma of a Native Kidney After Renal Transplant: A Case Report.

BACKGROUND: Renal squamous cell carcinoma is a rare primary tumor of the kidney that rapidly invades local structures and has a poor prognosis. Presentation is usually nonspecific and is associated with renal stone disease and chronic infection. Immunosuppressed renal transplant recipients are more likely to develop a malignancy than the general population. Squamous cell carcinoma of the kidney in the context of a renal transplant and long-term immunosuppression has not previously been described in the literature. CASE REPORT: A 46-year-old white man with previous renal stones and recurrent urinary infections underwent a right nephrectomy and subsequent renal transplantation owing to failure of the remaining kidney. Five years posttransplant, an abdominal ultrasound scan was performed owing to recurrent urinary infections and ongoing pyuria. This was reported as normal, but he later developed a discharging sinus in his left flank. A computed tomography (CT) scan revealed a tracking perinephric abscess with an associated cystic lesion of the left kidney. A left nephrectomy was performed and histologic examination suggested an invasive squamous cell carcinoma of the renal pelvis. The patient later required major surgery for chronic infection, and further imaging revealed metastatic disease, resulting in the decision to manage palliatively. CONCLUSION: Given the nonspecific nature of the symptoms and the poor prognosis, health care professionals should have a lower threshold for diagnostic imaging in these patients. Abdominal ultrasonography was unhelpful and only a later CT scan revealed the underlying malignancy. This should be expedited if there is a persistent abnormality on urinalysis. Once diagnosed, a change in immunosuppressant regime to include sirolimus should be considered.

Adoptive T cell immunotherapy for treatment of ganciclovir-resistant cytomegalovirus disease in a renal transplant recipient.

Cytomegalovirus (CMV) is a significant cause of morbidity, mortality and graft loss in solid organ transplantation (SOT). Treatment options for ganciclovir-resistant CMV are limited. We describe a case of ganciclovir-resistant CMV disease in a renal transplant recipient manifested by thrombotic microangiopathy-associated glomerulopathy. Adoptive T cell immunotherapy using CMV-specific T cells from a donor bank was used as salvage therapy. This report is a proof-of-concept of the clinical and logistical feasibility of this therapy in SOT recipients.

Acute tubulointerstitial nephritis in Scotland.

BACKGROUND AND AIMS: Acute tubulointerstitial nephritis (ATIN) is a potentially reversible cause of acute kidney injury with the majority of cases drug related. Our aims were to examine the incidence profile of patients with ATIN in Scotland and to assess the impact of corticosteroid treatment. DESIGN AND METHODS: All adult patients with biopsy-proven ATIN, diagnosed between 2000 and 2012, presenting to renal units serving 1.9 of Scotland's 5 million population were included. Patient demographics, presenting, aetiologic and pathologic features, treatment given and outcome were extracted from patient records. RESULTS: In total, 171 cases representing 4.7% of native renal biopsies were identified. Median serum creatinine (sCr) was 327 µmol/l at biopsy (106 µmol/l at baseline). Eosinophilia, fever or rash was present in 57% with all 3 in only 1.1%. Active urinary sediment was found in 68%. Aetiology appeared drug induced in 73%. Proton pump inhibitors (PPIs) were likely causative in almost as many cases as antibiotics (35% each) and were more frequently implicated than non-steroidal anti-inflammatory drugs (20%). Number of PPI-related cases paralleled the rising prescription of these drugs. Corticosteroids were prescribed in 59% of drug-induced ATIN (median sCr at biopsy: 356 µmol/l vs. 280 µmol/l in those managed conservatively). There was no difference in sCr at 1, 6 and 12 months, with similar proportions of both groups experiencing complete renal recovery (48% vs. 41%) and becoming dialysis dependent (10% in both). CONCLUSIONS: Incidence of biopsy-proven ATIN in Scotland has been rising over the past decade with the majority of cases drug induced. Evidence supporting corticosteroid treatment is lacking.

Clinical impact of FDG PET-CT on the management of patients with locally advanced cervical carcinoma.

AIM: To evaluate the impact of staging FDG PET-CT on the initial management of patients with locally advanced cervical carcinoma (LACC) and any prognostic variables predicting survival. MATERIALS AND METHODS: Retrospective analysis of consecutive patients undergoing FDG PET-CT for staging of LACC in a single tertiary referral centre, between April 2008 and August 2011. Comparison was made between MRI and PET-CT findings and any subsequent impact on treatment intent or radiotherapy planning was evaluated. RESULTS: Sixty-three patients underwent FDG PET-CT for initial staging of LACC. Major impact on management was found in 20 patients (32%), a minor impact in five (8%), and no impact in 38 (60%). In those patients where PET-CT had a major impact, 12 had more extensive local nodal involvement, five had occult metastatic disease, two had synchronous tumours, and one patient had equivocal lymph nodes on MRI characterized as negative. PET-positive nodal status at diagnosis was found to be a statistically significant predictor of relapse-free survival (p < 0.05). CONCLUSION: Staging FDG PET-CT has a major impact on the initial management of approximately one-third of patients with LACC by altering treatment intent and/or radiotherapy planning. PET-defined nodal status is a poor prognostic indicator.

Consensus guidelines for antifungal prophylaxis in haematological malignancy and haemopoietic stem cell transplantation, 2014.

There is a strong argument for the use of antifungal prophylaxis in high-risk patients given the significant mortality associated with invasive fungal disease, the late identification of these infections, and the availability of safe and well-tolerated prophylactic medications. Clinical decisions about which patients should receive prophylaxis and choice of antifungal agent should be guided by risk stratification, knowledge of local fungal epidemiology, the efficacy and tolerability profile of available agents, and estimates such as number needed to treat and number needed to harm. There have been substantial changes in practice since the 2008 guidelines were published. These include the availability of new medications and/or formulations, and a focus on refining and simplifying patient risk stratification. Used in context, these guidelines aim to assist clinicians in providing optimal preventive care to this vulnerable patient demographic.

Chromosome 9p deletion in clear cell renal cell carcinoma predicts recurrence and survival following surgery.

BACKGROUND: Wider clinical applications of 9p status in clear cell renal cell carcinoma (ccRCC) are limited owing to the lack of validation and consensus for interphase fluorescent in situ hybridisation (I-FISH) scoring technique. The aim of this study was to analytically validate the applicability of I-FISH in assessing 9p deletion in ccRCC and to clinically assess its long-term prognostic impact following surgical excision of ccRCC. METHODS: Tissue microarrays were constructed from 108 renal cell carcinoma (RCC) tumour paraffin blocks. Interphase fluorescent in situ hybridisation analysis was undertaken based on preset criteria by two independent observers to assess interobserver variability. 9p status in ccRCC tumours was determined and correlated to clinicopathological variables, recurrence-free survival and disease-specific survival. RESULTS: There were 80 ccRCCs with valid 9p scoring and a median follow-up of 95 months. Kappa statistic for interobserver variability was 0.71 (good agreement). 9p deletion was detected in 44% of ccRCCs. 9p loss was associated with higher stage, larger tumours, necrosis, microvascular and renal vein invasion, and higher SSIGN (stage, size, grade and necrosis) score. Patients with 9p-deleted ccRCC were at a higher risk of recurrence (P=0.008) and RCC-specific mortality (P=0.001). On multivariate analysis, 9p deletion was an independent predictor of recurrence (hazard ratio 4.323; P=0.021) and RCC-specific mortality (hazard ratio 4.603; P=0.007). The predictive accuracy of SSIGN score improved from 87.7% to 93.1% by integrating 9p status to the model (P=0.001). CONCLUSIONS: Loss of 9p is associated with aggressive ccRCC and worse prognosis in patients following surgery. Our findings independently confirm the findings of previous reports relying on I-FISH to detect 9p (CDKN2A) deletion.

Neuroprotective potential of pleiotrophin overexpression in the striatonigral pathway compared with overexpression in both the striatonigral and nigrostriatal pathways.

Intrastriatal injection of recombinant adeno-associated viral vector serotype 2/1 (rAAV2/1) to overexpress the neurotrophic factor pleiotrophin (PTN) provides neuroprotection for tyrosine hydroxylase immunoreactive (THir) neurons in the substantia nigra pars compacta (SNpc), increases THir neurite density in the striatum (ST) and reverses functional deficits in forepaw use following 6-hydroxydopamine (6-OHDA) toxic insult. Glial cell line-derived neurotrophic factor (GDNF) gene transfer studies suggest that optimal neuroprotection is dependent on the site of nigrostriatal overexpression. The present study was conducted to determine whether enhanced neuroprotection could be accomplished via simultaneous rAAV2/1 PTN injections into the ST and SN compared with ST injections alone. Rats were unilaterally injected in the ST alone or injected in both the ST and SN with rAAV2/1 expressing either PTN or control vector. Four weeks later, all rats received intrastriatal injections of 6-OHDA. Rats were euthanized 6 or 16 weeks relative to 6-OHDA injection. A novel selective total enumeration method to estimate nigral THir neuron survival was validated to maintain the accuracy of stereological assessment. Long-term nigrostriatal neuroprotection and functional benefits were only observed in rats in which rAAV2/1 PTN was injected into the ST alone. Results suggest that superior preservation of the nigrostriatal system is provided by PTN overexpression delivered to the ST and restricted to the ST and SN pars reticulata and is not improved with overexpression of PTN within SNpc neurons.

Protothecosis in hematopoietic stem cell transplantation: case report and review of previous cases.

Prototheca species are achlorophyllus algae. Prototheca wickerhamii and Prototheca zopfii cause human disease. In immunocompetent individuals, they cause soft tissue infections and olecranon bursitis, but in transplant recipients, these organisms can cause disseminated disease. We report a fatal case of disseminated P. zopfii infection in an hematopoietic stem cell transplant (HSCT) recipient with bloodstream infection and involvement of multiple soft tissue sites. We review all previous cases of protothecosis in HSCT reported in the literature. Protothecosis is uncommon after HSCT, but has a disseminated presentation that is frequently fatal. It is commonly misidentified as a yeast. Tumor necrosis factor-alpha inhibitors and contamination of central venous catheters may contribute to development of protothecosis. Optimal treatment approaches are yet to be defined. New agents such as miltefosine may be possible future therapies.

Quantitative proteomics in resected renal cancer tissue for biomarker discovery and profiling.

BACKGROUND: Proteomics-based approaches for biomarker discovery are promising strategies used in cancer research. We present state-of-art label-free quantitative proteomics method to assess proteome of renal cell carcinoma (RCC) compared with noncancer renal tissues. METHODS: Fresh frozen tissue samples from eight primary RCC lesions and autologous adjacent normal renal tissues were obtained from surgically resected tumour-bearing kidneys. Proteins were extracted by complete solubilisation of tissues using filter-aided sample preparation (FASP) method. Trypsin digested proteins were analysed using quantitative label-free proteomics approach followed by data interpretation and pathways analysis. RESULTS: A total of 1761 proteins were identified and quantified with high confidence (MASCOT ion score threshold of 35 and P-value <0.05). Of these, 596 proteins were identified as differentially expressed between cancer and noncancer tissues. Two upregulated proteins in tumour samples (adipose differentiation-related protein and Coronin 1A) were further validated by immunohistochemistry. Pathway analysis using IPA, KOBAS 2.0, DAVID functional annotation and FLink tools showed enrichment of many cancer-related biological processes and pathways such as oxidative phosphorylation, glycolysis and amino acid synthetic pathways. CONCLUSIONS: Our study identified a number of differentially expressed proteins and pathways using label-free proteomics approach in RCC compared with normal tissue samples. Two proteins validated in this study are the focus of on-going research in a large cohort of patients.

Non-steroidal anti-inflammatory drug use and brain tumour risk: a case-control study within the Clinical Practice Research Datalink.

PURPOSE: The aetiology of primary brain tumours is largely unknown; the role of non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin use and glioma risk has been inconclusive, but few population-based studies with reliable prescribing data have been conducted, and the association with meningioma risk has yet to be assessed. METHODS: The UK Clinical Practice Research Datalink was used to assess the association between aspirin and non-aspirin NSAID use and primary brain tumour risk using a nested case-control study design. Conditional logistic regression analysis was performed on 5,052 brain tumour patients aged 16 years and over, diagnosed between 1987 and 2009 and 42,678 controls matched on year of birth, gender and general practice, adjusting for history of allergy and hormone replacement therapy use in the glioma and meningioma models, respectively. RESULTS: In conditional logistic regression analysis, excluding drug use in the year preceding the index date, there was no association with non-aspirin NSAID use (OR 0.96, 95 % CI 0.81-1.13) or glioma risk comparing the highest category of daily defined dose to non-users; however, non-aspirin NSAID use was positively associated with meningioma risk (OR 1.35, 95 % CI 1.06-1.71). No association was seen with high- or low-dose aspirin use irrespective of histology. CONCLUSIONS: This large nested case-control study finds no association between aspirin or non-aspirin NSAID use and risk of glioma but a slight increased risk with non-aspirin NSAIDs and meningioma.