Measures of Longitudinal Immune Dysfunction and Risk of AIDS and Non-AIDS Defining Malignancies in Antiretroviral-Treated People With Human Immunodeficiency Virus.

BACKGROUND: Human immunodeficiency virus (HIV) infection leads to chronic immune activation/inflammation that can persist in virally suppressed persons on fully active antiretroviral therapy (ART) and increase risk of malignancies. The prognostic role of low CD4:CD8 ratio and elevated CD8 cell counts on the risk of cancer remains unclear. METHODS: We investigated the association of CD4:CD8 ratio on the hazard of non-AIDS defining malignancy (NADM), AIDS-defining malignancy (ADM) and most frequent group of cancers in ART-treated people with HIV (PWH) with a CD4 and CD8 cell counts and viral load measurements at baseline. We developed Cox proportional hazard models with adjustment for known confounders of cancer risk and time-dependent cumulative and lagged exposures of CD4:CD8 ratio to account for time-evolving risk factors and avoid reverse causality. RESULTS: CD4:CD8 ratios below 0.5, compared to above 1.0, were independently associated with a 12-month time-lagged higher risk of ADM and infection-related malignancies (adjusted hazard ratio 2.61 [95% confidence interval {CI }1.10-6.19] and 2.03 [95% CI 1.24-3.33], respectively). CD4 cell counts below 350 cells/µL were associated with an increased risk of NADMs and ADMs, as did infection, smoking, and body mass index-related malignancies. CONCLUSIONS: In ART-treated PWH low CD4:CD8 ratios were associated with ADM and infection-related cancers independently from CD4 and CD8 cell counts and may alert clinicians for cancer screening and prevention of NADM.

Twelve-month effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide in people with HIV: Real-world insights from BICSTaR cohorts.

BACKGROUND: Real-world evidence is an essential component of evidence-based medicine. The aim of the BICSTaR (BICtegravir Single Tablet Regimen) study is to assess effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in antiretroviral treatment-naïve (TN) and treatment-experienced (TE) people with HIV. METHODS: BICSTaR is a prospective, observational cohort study. Participants (≥18 years) are being followed for 24 months. A pooled analysis is presented at 12 months, with the primary endpoint of effectiveness (HIV-1 RNA <50 copies/mL) and secondary endpoints of safety and tolerability (as per protocol). An exploration of patient-reported outcome measures using standardized questionnaires is included. RESULTS: Between June 2018 and May 2021, 1552 people with HIV were enrolled across 12 countries. The analysed population comprised 1509 individuals (279 TN, 1230 TE); most were white (76%), male (84%) and had one or more comorbid conditions (68%). Median age was 47 years. After 12 months of B/F/TAF treatment, HIV-1 RNA was <50 copies/mL in 94% (221/236) of TN participants and 97% (977/1008) of TE participants. Median CD4 cell count increased by 214 cells/µL (p < 0.001) in TN participants and 13 cells/µL (p = 0.014) in TE participants; median CD4/CD8 ratios increased by 0.30 and 0.03, respectively (both p < 0.001). Persistence was high at 12 months (TN, 97%; TE, 95%). No resistance to B/F/TAF emerged. Study drug-related adverse events occurred in 13% of participants through 12 months, leading to B/F/TAF discontinuation in 6%. CONCLUSIONS: The findings of this study provide robust real-world evidence to support the broad use of B/F/TAF in both TN and TE people with HIV.

Performance Analysis of Six Semi-Automated Tumour Delineation Methods on [18F] Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG PET/CT) in Patients with Head and Neck Cancer.

Background. Head and neck cancer (HNC) is the seventh most common neoplastic disorder at the global level. Contouring HNC lesions on [18F] Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) scans plays a fundamental role for diagnosis, risk assessment, radiotherapy planning and post-treatment evaluation. However, manual contouring is a lengthy and tedious procedure which requires significant effort from the clinician. Methods. We evaluated the performance of six hand-crafted, training-free methods (four threshold-based, two algorithm-based) for the semi-automated delineation of HNC lesions on FDG PET/CT. This study was carried out on a single-centre population of n=103 subjects, and the standard of reference was manual segmentation generated by nuclear medicine specialists. Figures of merit were the Sørensen-Dice coefficient (DSC) and relative volume difference (RVD). Results. Median DSC ranged between 0.595 and 0.792, median RVD between -22.0% and 87.4%. Click and draw and Nestle's methods achieved the best segmentation accuracy (median DSC, respectively, 0.792 ± 0.178 and 0.762 ± 0.107; median RVD, respectively, -21.6% ± 1270.8% and -32.7% ± 40.0%) and outperformed the other methods by a significant margin. Nestle's method also resulted in a lower dispersion of the data, hence showing stronger inter-patient stability. The accuracy of the two best methods was in agreement with the most recent state-of-the art results. Conclusions. Semi-automated PET delineation methods show potential to assist clinicians in the segmentation of HNC lesions on FDG PET/CT images, although manual refinement may sometimes be needed to obtain clinically acceptable ROIs.

The incidence of thrombocytopenia in adult patients receiving chemotherapy for solid tumors or hematologic malignancies.

OBJECTIVES: To estimate the risk of thrombocytopenia in various cancers and chemotherapy regimens. METHODS: Structured patient-level data from the Flatiron Health Electronic Health Record database were used to identify adult patients who received chemotherapy for a solid tumor or hematologic malignancy from 2012 to 2017. Three-month cumulative incidence of thrombocytopenia was assessed based on platelet counts, overall and by grade of thrombocytopenia. Co-occurrence of anemia, neutropenia, and leukopenia was evaluated. RESULTS: Of 15,521 patients with solid tumors, 13% had thrombocytopenia within 3 months (platelet count < 100 × 109 /L); 4% had grade 3 (25 to < 50 × 109 /L), and 2% grade 4 (<25 × 109 /L) thrombocytopenia. Of 2537 patients with hematologic malignancies, 28% had any thrombocytopenia, 16% with grade 3, and 12% with grade 4. Among patients with thrombocytopenia, it occurred without another cytopenia in 18% of solid tumors and 7% of hematologic malignancies. CONCLUSIONS: In a large, US-representative sample of patients undergoing chemotherapy in clinical practice, thrombocytopenia incidence varied across tumor and regimen types. Despite recommendations to alter chemotherapy to avoid severe thrombocytopenia, 4% of patients with solid tumors and 16% with hematologic malignancies experienced grade 3 thrombocytopenia. Prediction and prevention of thrombocytopenia may help oncologists avoid dose modifications and their adverse effects on survival.

Neck lymph node metastasis detection in patients with differentiated thyroid carcinoma (DTC) in long-term follow-up: a 131I-SPECT/CT study.

BACKGROUND: The identification of neck lymph node (LN) metastases represents a very important issue in the management of patients with differentiated thyroid carcinoma (DTC). To this purpose, in the present study, we used 131I-SPECT/CT as a diagnostic imaging procedure. METHODS: A consecutive series of 224 DTC patients with ascertained neck radioiodine-avid foci at 131I-SPECT/CT during long-term follow-up was evaluated. All patients had already undergone total thyroidectomy and radioiodine therapy and had been classified as follows: 62 at high risk (H), 64 at low risk (L) and 98 at very low risk (VL). 131I-Whole body scan (WBS) followed by SPECT/CT was performed in all cases. RESULTS: In the 224 patients, 449 neck iodine avid foci were ascertained at SPECT/CT, while 322 were evidenced at WBS in 165/224 patients. WBS classified as residues 263/322 foci and as unclear 59/322 foci; among the former foci SPECT/CT correctly characterized 8 LN metastases and 3 physiologic uptakes and among the latter, it pinpointed 26 LN metastases, 18 residues, and 15 physiologic uptakes. SPECT/CT also classified 127 foci occult at WBS as 59 LN metastases and 68 residues. Globally, SPECT/CT identified 93 LN metastases in 59 patients (26 H, 20 L, 13 VL), while WBS evidenced 34 in 25 cases. All 13 VL patients, T1aN0M0, 5 of whom with LN near sub-mandibular glands, had thyroglobulin undetectable or < 2.5 ng/ml. Globally, SPECT/CT obtained an incremental value than WBS in 45.5% of patients, a more correct patient classification changing therapeutic approach in 30.3% of cases and identified WBS false-positive findings in 8% of cases. CONCLUSIONS: 131I-SPECT/CT proved to correctly detect and characterize neck LN metastases in DTC patients in long-term follow-up, improving the performance of planar WBS. SPECT/CT routine use is thus suggested; its role is particularly relevant in patients with WBS inconclusive, VL, T1aN0M0 and with undetectable or very low thyroglobulin levels.

Are welders more at risk of respiratory infections? Findings from a cross-sectional survey and analysis of medical records in shipyard workers: the WELSHIP project.

BACKGROUND: Exposure to welding fume increases the risk of pneumococcal infection; whether such susceptibility extends to other respiratory infections is unclear. We report findings from a survey and from medical consultation data for workers in a large shipyard in the Middle East. METHODS: Between January 2013 and December 2013, we collected cross-sectional information from 529 male workers variously exposed to welding fume. Adjusted ORs for respiratory symptoms (cough, phlegm, wheezing, shortness of breath and 'chest illness') were estimated using multivariable logistic regression. Subsequently, we examined consultation records from 2000 to 2011 for 15 954 workers who had 103 840 consultations for respiratory infections; the associations between respiratory infections and levels of welding exposure were estimated using a count regression model with a negative binomial distribution. RESULTS: 13% of surveyed workers reported respiratory symptoms with a higher prevalence in winter, particularly among welders. The adjusted OR in welders versus other manual labourers was 1.72 (95% CI 1.02 to 3.01) overall and 2.31 (1.05 to 5.10) in winter months; no effect was observed in summer. The risk of consultation for respiratory infections was higher in welders than in manual labourers, with an adjusted incidence rate ratio of 1.45 (1.59 to 1.83) overall, 1.47 (1.42 to 1.52) in winter and 1.33 (1.23 to 1.44) in summer (interaction, p<0.001). CONCLUSIONS: The observation that respiratory symptoms and consultations for respiratory infection in welders are more common in winter may indicate an enhanced vulnerability to a broad range of infections. If confirmed, this would have important implications for the occupational healthcare of a very large, global workforce.

Minimal Extrathyroid Extension (mETE) as the Only Risk Factor in Patients with Papillary Thyroid Carcinoma (PC): Its Clinical Impact on Recurrence and Outcome during Long-Term Follow-Up.

Minimal extrathyroid extension (mETE) effect on papillary thyroid carcinoma (PC) prognosis is still debated even more so now that this factor has been removed in the 8th AJCC Edition, supporting the hypothesis that mETE is not associated with aggressive tumors. We retrospectively enrolled 91 PC patients (Group 1) submitted to total thyroidectomy and radioiodine ablation. At the time of the primary tumor surgery, mETE was ascertained in all patients with no other risk factors, such as multifocality, vascular invasion, neck and distant metastases, and aggressive histological variants. As controls, 205 consecutive matched PC patients (Group 2) without mETE and the aforementioned risk factors were enrolled. During the follow-up (average 8 years), 16/91 (17.58%) Group 1 patients and 15/205 (7.32%) Group 2 patients developed metastases (p = 0.0078). Cox regression analysis showed an increased risk of metastases in patients with mETE (HR: 2.58 (95% CI 1.28-5.22) p = 0.008). Disease-free survival (DFS) was significantly lower in patients with mETE than in controls (p = 0.0059). The present study seems to demonstrate that mETE can be associated with an aggressive PC and can be considered, even alone without other risk factors, an independent factor of unfavorable DFS. Thus, by excluding mETE in the 8th AJCC Edition, patient care and management could be compromised.

Twelve-month effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide in people with HIV from the Canadian cohort of the observational BICSTaR study.

The BICSTaR (BICtegravir Single Tablet Regimen) study is investigating the effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in people with human immunodeficiency virus (HIV) treated in routine clinical practice. BICSTaR is an ongoing, prospective, observational cohort study across 14 countries. Treatment-naïve (TN) and treatment-experienced (TE) people with HIV (≥18 years of age) are being followed for 24 months. We present an analysis of the primary endpoint (HIV-1 RNA < 50 copies/mL; missing-equals-excluded [M = E]) at month 12 in the BICSTaR Canada cohort, including secondary (CD4 count, CD4/CD8 ratio, safety/tolerability) and exploratory (persistence, treatment satisfaction) endpoints. In total, 201 participants were enrolled in the BICSTaR Canada cohort. The analysis population included 170 participants (TN, n = 10; TE, n = 160), with data collected between November 2018 and September 2020. Of the participants, 88% were male, 72% were White, and 90% had ≥ 1 comorbid condition(s). Median (quartile [Q]1-Q3) age was 50 (39-58) years and baseline CD4 count was 391.5 (109.0-581.0) cells/µL in TN participants and 586.0 (400.0-747.0) cells/µL in TE participants. After 12 months of B/F/TAF treatment, HIV-1 RNA was < 50 copies/mL in 100% (9/9) of TN-active participants and 97% (140/145) of TE-active participants (M = E analysis). Median (Q1-Q3) CD4 cell count increased by +195 (125-307) cells/µL in TN participants and by + 30 (-50 to 123) cells/µL in TE participants. Persistence on B/F/TAF was high through month 12 with 10% (1/10) of TN and 7 % (11/160) of TE participants discontinuing B/F/TAF within 12 months of initiation of treatment. No resistance to B/F/TAF emerged. Study drug-related adverse events occurred in 7% (12/169) of participants, leading to B/F/TAF discontinuation in 4 of 169 participants. Improvements in treatment satisfaction were observed in TE participants. B/F/TAF demonstrated high levels of effectiveness, persistence, and treatment satisfaction, and was well tolerated through month 12 in people with HIV treated in routine clinical practice in Canada.

Infections with spore-forming bacteria in persons who inject drugs, 2000-2009.

Since 2000 in the United Kingdom, infections caused by spore-forming bacteria have been associated with increasing illness and death among persons who inject drugs (PWID). To assess temporal and geographic trends in these illnesses (botulism, tetanus, Clostridium novyi infection, and anthrax), we compared rates across England and Scotland for 2000-2009. Overall, 295 infections were reported: 1.45 per 1,000 PWID in England and 4.01 per 1,000 PWID in Scotland. The higher rate in Scotland was mainly attributable to C. novyi infection and anthrax; rates of botulism and tetanus were comparable in both countries. The temporal and geographic clustering of cases of C. novyi and anthrax into outbreaks suggests possible contamination of specific heroin batches; in contrast, the more sporadic nature of tetanus and botulism cases suggests that these spores might more commonly exist in the drug supply or local environment although at varying levels. PWID should be advised about treatment programs, injecting hygiene, risks, and vaccinations.

Hashimoto's Thyroiditis and Papillary Thyroid Carcinoma: A Follow-Up Study in Patients with Absence of Aggressive Risk Factors at the Surgery of the Primary Tumor.

Hashimoto's thyroiditis (HT) is often associated with papillary thyroid carcinoma (PC); it is still a matter of controversy whether the behavior of carcinoma is more aggressive or not. During the follow-up, we retrospectively enrolled 97 patients with PC/HT after thyroidectomy without risk factors at the surgery of the primary tumor, such as multifocality/multicentricity, extrathyroid tumor extension, vascular invasion, neck and distant metastases, and aggressive histological variants. HT diagnosis was confirmed by histology and serum thyroid antibodies. Tumor size was ≤10 mm in 64 cases (microcarcinomas); 206 matched PC patients after thyroidectomy without HT and risk factors were enrolled as controls, totaling 122 microcarcinomas. During follow-up, metastases occurred in 15/97 (15.5%) PC/HT cases, eight microcarcinomas, and in 16/206 (7.8%) without HT, eight microcarcinomas (p = 0.04). Considering both PC/HT and PC patients without HT who developed metastases, univariate analysis showed an increased risk of metastases in patients with HT coexistence, OR: 2.17 (95% CI 1.03-4.60) p = 0.043. Disease-free survival (DFS) was significantly (p = 0.0253) shorter in PC/HT than in the controls. The present study seems to demonstrate that HT is not a cancer protective factor in PC patients given the less favorable outcomes and significantly shorter DFS. HT may also represent an independent recurrence predictor without other risk factors.

Qualitative and Semiquantitative Parameters of 18F-FDG-PET/CT as Predictors of Malignancy in Patients with Solitary Pulmonary Nodule.

This study aims to evaluate the reliability of qualitative and semiquantitative parameters of 18F-FDG PET-CT, and eventually a correlation between them, in predicting the risk of malignancy in patients with solitary pulmonary nodules (SPNs) before the diagnosis of lung cancer. A total of 146 patients were retrospectively studied according to their pre-test probability of malignancy (all patients were intermediate risk), based on radiological features and risk factors, and qualitative and semiquantitative parameters, such as SUVmax, SUVmean, TLG, and MTV, which were obtained from the FDG PET-CT scan of such patients before diagnosis. It has been observed that visual analysis correlates well with the risk of malignancy in patients with SPN; indeed, only 20% of SPNs in which FDG uptake was low or absent were found to be malignant at the cytopathological examination, while 45.45% of SPNs in which FDG uptake was moderate and 90.24% in which FDG uptake was intense were found to be malignant. The same trend was observed evaluating semiquantitative parameters, since increasing values of SUVmax, SUVmean, TLG, and MTV were observed in patients whose cytopathological examination of SPN showed the presence of lung cancer. In particular, in patients whose SPN was neoplastic, we observed a median (MAD) SUVmax of 7.89 (±2.24), median (MAD) SUVmean of 3.76 (±2.59), median (MAD) TLG of 16.36 (±15.87), and a median (MAD) MTV of 3.39 (±2.86). In contrast, in patients whose SPN was non-neoplastic, the SUVmax was 2.24 (±1.73), SUVmean 1.67 (±1.15), TLG 1.63 (±2.33), and MTV 1.20 (±1.20). Optimal cut-offs were drawn for semiquantitative parameters considered predictors of malignancy. Nodule size correlated significantly with FDG uptake intensity and with SUVmax. Finally, age and nodule size proved significant predictors of malignancy. In conclusion, considering the pre-test probability of malignancy, qualitative and semiquantitative parameters can be considered reliable tools in patients with SPN, since cut-offs for SUVmax, SUVmean, TLG, and MTV showed good sensitivity and specificity in predicting malignancy.

Evaluation of Bone Scan Index as a Prognostic Tool in Breast Cancer Patients with Bone Metastasis.

BACKGROUND: Bone metastatic involvement represents a leading cause of death in patients with advanced breast cancer (BC). At present, it is not clear whether the bone metastatic load might impact Overall Survival (OS) in patients with bone metastatic BC at diagnosis. For this purpose, we used the Bone Scan Index (BSI), which is a reproducible and quantitative expression of tumor load observed at bone scintigraphy. OBJECTIVE: The aim of this study was to associate BSI with OS in bone metastatic BC patients. METHODS: In this retrospective study, we enrolled BC patients with bone metastases at the scintigraphic bone scan performed for staging purposes. The BSI was calculated through the DASciS software, and statistical analysis was carried out. Other clinical variables relevant to OS analysis were taken into account. RESULTS: Of a total of 94 patients, 32% died. In most cases, the histotype was ductal infiltrating carcinoma. The median OS from diagnosis was 72 months (CI 95%: 62-NA). The univariate analysis with COX regression showed that only hormone therapy significantly correlates with OS (HR 0.417, CI 95%: 0.174-0.997, p < 0.049). As concerning BSI, the statistical analysis showed that it does not predict OS in BC patients (HR 0.960, 95% CI: 0.416-2.216, p < 0.924). CONCLUSION: Although the BSI significantly predicts OS in prostate cancer and in other tumors, we observed that the metastatic load of bone disease has not a key role in prognostic stratification in our population.

First-, Second-, and Third-Generation Radiolabeled Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Positron Emission Tomography: State of the Art, a Systematic Review.

Introduction: Lung cancer (LC) is a leading cause of death among men and women, with non-small cell LC (NSCLC) accounting for a substantial portion of the histopathological spectrum and epidermal growth factor receptor (EGFR) mutations being correlated with its manifestation and evolution. Positron emission tomography (PET)/computed tomography has been the most widely used instrument to assess and monitor LC in a noninvasive way, including EGFR-mutated NSCLC, and its course during therapy, indicating to the referring physician the response to ongoing treatment or the lack of it. This systematic review aims to evaluate the feasibility and safety of radiolabeled EGFR tyrosine kinase inhibitors (TKis) in PET in clinical practice. Materials and Methods: From 1999 to April 2022 a Medline search was conducted on four different databases such as PubMed, Cochrane Library, Scopus, and Web of Sciences. Clinical studies were assessed by Quality Assessment of Diagnostic accuracy Studies-2 (QUADAS-2) and preclinical studies were also reported in this review. Results: Nine clinical studies were QUADAS-2 assessed and risk-of-bias assessment, and it turned out acceptable as two out of eight studies had low risk of bias in all four domains for risk-of-bias assessment, and the other four studies had three low-risk domains. The overall assessment for applicability risks was low. Conclusions: Radiolabeled EGFR-TKis in PET are a valid tool in identifying patients who may benefit from TKi therapy and who may not as a means to start an effective treatment. Although the number of clinical studies conducted so far is meager, these new PET tracers are already proving to be very useful in clinical settings as patient prognosis can be better assessed.

Role of Functional Neuroimaging with 123I-MIBG and 123I-FP-CIT in De Novo Parkinson's Disease: A Multicenter Study.

BACKGROUND: Parkinson's disease is a progressive neurodegenerative disorder, with incidence and prevalence rates of 8-18 per 100,000 people per year and 0.3-1%, respectively. As parkinsonian symptoms do not appear until approximately 50-60% of the nigral DA-releasing neurons have been lost, the impact of routine structural imaging findings is minimal at early stages, making Parkinson's disease an ideal condition for the application of functional imaging techniques. The aim of this multicenter study is to assess whether 123I-FP-CIT (DAT-SPECT), 123I-MIBG (mIBG-scintigraphy) or an association of both exams presents the highest diagnostic accuracy in de novo PD patients. METHODS: 288 consecutive patients with suspected diagnoses of Parkinson's disease or non- Parkinson's disease syndromes were analyzed in the present Italian multicenter retrospective study. All subjects were de novo, drug-naive patients and met the inclusion criteria of having undergone both DAT-SPECT and mIBG-scintigraphy within one month of each other. RESULTS: The univariate analysis including age and both mIBG-SPECT and DAT-SPECT parameters showed that the only significant values for predicting Parkinson's disease in our population were eH/M, lH/M, ESS and LSS obtained from mIBG-scintigraphy (p < 0.001). CONCLUSIONS: mIBG-scintigraphy shows higher diagnostic accuracy in de novo Parkinson's disease patients than DAT-SPECT, so given the superiority of the MIBG study, the combined use of both exams does not appear to be mandatory in the early phase of Parkinson's disease.

The DASciS Software for BSI Calculation as a Valuable Prognostic Tool in mCRPC Treated with 223RaCl2: A Multicenter Italian Study.

BACKGROUND/AIM: Radium-223 dichloride (223RaCl2) represents a therapeutic option for metastatic castration-resistant prostate cancer (mCRPC) patients dealing with symptomatic bone metastases. The identification of baseline variables potentially affecting the life-prolonging role of 223RaCl2 is still ongoing. Bone scan index (BSI) defines the total load of bone metastatic disease detected on a bone scan (BS) and is expressed as a percentage value of the whole bone mass. The aim of this multicenter study was to assess the impact of baseline BSI on overall survival (OS) in mCRPC patients treated with 223RaCl2. For this purpose, the DASciS software developed by the Sapienza University of Rome for BSI calculation was shared between six Italian Nuclear Medicine Units. METHODS: 370 pre-treatment BS were analyzed through the DASciS software. Other clinical variables relevant to OS analysis were taken into account for the statistical analysis. RESULTS: Of a total of 370 patients, 326 subjects had died at the time of our retrospective analysis. The median OS time from the first cycle of 223RaCl2 to the date of death from any cause or last contact was 13 months (95%CI 12-14 months). The mean BSI value resulted in 2.98% ± 2.42. The center-adjusted univariate analysis showed that baseline BSI was significantly associated with OS as an independent risk factor (HR 1.137, 95%CI: 1.052-1.230, p = 0.001), meaning that patients with higher BSI values had worse OS. When adjusting for other measures on multivariate analysis, in addition to Gleason score and baseline values of Hb, tALP, and PSA, baseline BSI was confirmed to be a statistically significant parameter (HR 1.054, 95%CI: 1.040-1.068, p < 0.001). CONCLUSIONS: Baseline BSI significantly predicts OS in mCRPC treated with 223RaCl2. The DASciS software was revealed to be a valuable tool for BSI calculation, showing rapid processing time and requiring no more than a single demonstrative training for each participating center.

Male IDUs who have sex with men in England, Wales and Northern Ireland: are they at greater risk of bloodborne virus infection and harm than those who only have sex with women?

OBJECTIVES: In the UK, although transmission of HIV among injecting drug user (IDUs) has been limited since the 1980s, IDUs and men who have sex with men (MSM) have higher HIV and hepatitis C virus (HCV) prevalences than the general population. MSM who are also IDUs (MSM-IDUs) may therefore have a higher risk of infection than male IDUs who only have sex with women. METHODS: Analysis of data from a national survey of IDUs attending services (England, Wales and Northern Ireland) between 1998 and 2007, which collected demographic and behavioural data and oral fluid samples for HIV and HCV antibody testing. RESULTS: Of the 8671 men who reported injecting drugs and having sex during the preceding year, 96% (8354) were men who only had sex with women (MSW). MSM-IDUs and MSW-IDUs had similar age and number of years of injecting. MSM-IDUs had a higher prevalence of HIV (adjusted OR=4.08, 95% CI 1.9 to 8.5) and of HCV (adjusted OR =1.34, 95% CI 1.1 to 1.8) and were about four times (adjusted OR =3.78, 95% CI 2.9 to 4.9) more likely to have unprotected sex with multiple partners. Among those who injected in the 4 weeks prior to participation, the MSM-IDUs had a higher level of needle/syringe sharing (adjusted OR =1.72, 95% CI 1.3 to 2.2). DISCUSSION: MSM-IDUs have a fourfold higher risk of HIV; HCV prevalence in MSM-IDUs is a third higher than among MSW-IDUs, suggesting elevated risk from injecting and possibly sexual transmission. These findings emphasise the need for public health interventions specifically targeted at MSM-IDUs.

A decade of spore-forming bacterial infections among European injecting drug users: pronounced regional variation.

The recent anthrax outbreak among injecting drug users (IDUs) in Europe has highlighted an ongoing problem with severe illness resulting from spore-forming bacteria in IDUs. We collated the numbers of cases of 4 bacterial illnesses (botulism, tetanus, Clostridium novyi, and anthrax) in European IDUs for 2000 to 2009 and calculated population rates. Six countries reported 367 cases; rates varied from 0.03 to 7.54 per million people. Most cases (92%) were reported from 3 neighboring countries: Ireland, Norway, and the United Kingdom. This geographic variation needs investigation.

Initiation of bone-targeted agents in patients with bone metastases and breast or castrate-resistant prostate cancer actively treated in routine clinical practice in Europe.

BACKGROUND: Guidelines recommend starting bone-targeted agents (BTA), such as zoledronic acid and denosumab, as soon as bone metastases (BMs) are definitively diagnosed in all patients with breast cancer (BC) or castration-resistant prostate cancer (CRPC) whether they are symptomatic or not. METHODS: Data were analyzed from 1364 patients with BC and 1161 patients with CRPC who had BMs and were receiving anti-cancer therapy in hospitals across six European countries (Belgium, France, Germany, Italy, Spain and the UK). The 731 physicians (medical oncologists or urologists) provided insights in the decision-making factors driving their management of bone health for these patients, and the patient medical records indicated how these decisions were reflected in routine clinical practice. RESULTS: Within three months of a BM diagnosis, 74% of BC and 51% of CRPC patients had initiated treatment with a BTA. Around 12% of BC and 23% of CRPC patients did not receive a BTA following BM diagnosis. Irrespective of the tumour type (BC or CRPC), most physicians prescribed either denosumab or zoledronic acid as first BTA therapy. Physicians reported bone pain as a major decision-making factor to initiate a BTA. The presence of bone complications at BM diagnosis and bone pain at BM diagnosis were found to be significant predictive factors for a BTA initiation, irrespective of tumour type. CONCLUSIONS: Despite European Society for Medical Oncology (ESMO) guidance on bone protection irrespective of symptomatic disease, not all patients with BMs received a BTA following a BM diagnosis. This suggests that clinical judgements and patients' communication of their pain to their physicians contributed to the decision to prescribe bone protection therapy in cancer patients.

A Comparative Follow-Up Study of Patients with Papillary Thyroid Carcinoma Associated or Not with Graves' Disease.

Whether papillary carcinoma (PC) behavior is more aggressive in Graves' disease (GD) patients than PC cases without GD is controversial. We retrospectively enrolled 33 thyroidectomized PC/GD patients during long-term follow-up, 23/33 without risk factors at surgery, and 18/33 microcarcinomas; 312 PC euthyroid-matched patients without risk factors served as controls. A total of 14/33 (42.4%) PC/GD patients, 4 with and 10 without risk factors at diagnosis, 6 with microcarcinoma, underwent metastases during follow-up. In controls, metastases in 21/312 (6.7%) were ascertained. Considering 10/23 PC/GD patients and 21/312 controls without risk factors who developed metastases, univariate analysis showed that there was an increased risk of metastasis appearance for PC/GD cases (p < 0.001). Disease-free survival (DFS) was significantly (p < 0.0001, log-rank test) shorter in PC/GD patients than in controls. Significantly more elevated aggressiveness in 6/18 PC/GD patients with microcarcinoma than in controls was also ascertained with shorter DFS. Thus, in the present study, PC/GD had aggressive behavior during follow-up also when carcinoma characteristics were favorable and some cases were microcarcinomas. GD and non-GD patient comparison in the cases without risk factors at diagnosis showed an increased risk to develop metastases in GD during follow-up, suggesting that GD alone might be a tumor aggressiveness predictive factor in these cases.

Patient-reported pain severity and health-related quality of life in patients with multiple myeloma in real world clinical practice.

BACKGROUND: The association between patient self-reported pain severity and health-related quality-of-life (HRQoL) is poorly understood. AIMS: This real-world study of symptomatic multiple myeloma (MM) patients sought to determine how pain severity from a single question asked during routine clinical consultation was associated with HRQoL. METHODS AND RESULTS: Point-in-time data on HRQoL of 330 patients with MM (median age 70 years) receiving anti-myeloma therapy in Germany and Italy from November 2017 through February 2018 were analyzed. HRQoL was assessed using validated questionnaires (Work Productivity and Activity Impairment [WPAI], European Organization for Research and Treatment of Cancer Quality of Life Questionnaire -C30 and -MY20). Physical pain severity was assessed during clinical consultation by a single question, asking patients to describe their pain as "no pain," "mild," "moderate," or "severe." Associations between patient-reported pain severity and HRQoL scores were assessed by analysis of variance or χ2 tests. Ninety-six of the 330 patients (29.1%) reported moderate to severe pain. Increase in pain severity, from "no" to "severe" pain, was associated with significantly decreased overall HRQoL (mean score 70.2 to 33.3); significant decreases in levels of physical (82.7 to 35.1), social (81.1 to 44.4), emotional (78.1 to 48.3), and role functioning (79.5 to 38.9); and increased levels of WPAI usual activity impairment (35.4 to 71.4), and fatigue burden (26.0 to 68.9) (all p < .001). CONCLUSION: Higher pain severity, based on a single self-report question, was associated with poorer HRQoL in patients with MM, thereby supporting the clinical relevance of directly asking patients to self-evaluate their pain severity.