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    The clinical acceptability of short versus long duration acquisitions for head and neck cancer using long-axial field-of-view PET/CT: a retrospective evaluation.

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    PURPOSE To evaluate the utility of long duration (10 min) acquisitions compared to standard 4 min scans in the evaluation of head and neck cancer (HNC) using a long-axial field-of-view (LAFOV) system in 2-[18F]FDG PET/CT. METHODS HNC patients undergoing LAFOV PET/CT were included retrospectively according to a predefined sample size calculation. For each acquisition, FDG avid lymph nodes (LN) which were highly probable or equivocal for malignancy were identified by two board certified nuclear medicine physicians in consensus. The aim of this study was to establish the clinical acceptability of short-duration (4 min, C40%) acquisitions compared to full-count (10 min, C100%) in terms of the detection of LN metastases in HNC. Secondary endpoints were the positive predictive value for LN status (PPV) and comparison of SUVmax at C40% and C100%. Histology reports or confirmatory imaging were the reference standard. RESULTS A total of 1218 records were screened and target recruitment was met with n = 64 HNC patients undergoing LAFOV. Median age was 65 years (IQR: 59-73). At C40%, a total of 387 lesions were detected (highly probable LN n = 274 and equivocal n = 113. The total number of lesions detected at C100% acquisition was 439, of them 291 (66%) highly probable LN and 148 (34%) equivocal. Detection rate between the two acquisitions did not demonstrate any significant differences (Pearson's Chi-Square test, p = 0.792). Sensitivity, specificity, PPV, NPV and accuracy for C40% were 83%, 44%, 55%, 76% and 36%, whilst for C100% were 85%, 56%, 55%, 85% and 43%, respectively. The improved accuracy reached borderline significance (p = 0.057). At the ROC analysis, lower SUVmax was identified for C100% (3.5) compared to C40% (4.5). CONCLUSION In terms of LN detection, C40% acquisitions showed no significant difference compared to the C100% acquisitions. There was some improvement for lesions detection at C100%, with a small increment in accuracy reaching borderline significance, suggestive that the higher sensitivity afforded by LAFOV might translate to improved clinical performance in some patients

    SAKK57/16 Nab-paclitaxel and Gemcitabine in Soft Tissue Sarcoma (NAPAGE): a phase I/II trial.

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    BACKGROUND To determine whether the combination of nab-paclitaxel with gemcitabine has activity in patients with pretreated soft tissue sarcoma (STS). PATIENTS AND METHODS NAPAGE is a phase Ib/II clinical trial investigating the combination of nab-paclitaxel (nab-pc) with gemcitabine employing two cohorts. One of a dose-de-escalation phase and one of expansion. In phase I, nab-pc was given at 150 mg/m2 in combination with gemcitabine 1000 mg/m2 every two weeks, until disease progression or unacceptable toxicity. This dose was recommended for phase II (RP2D), as there was no dose limiting toxicity (DLT) or discontinuations due to adverse events (AEs). The primary endpoint of the phase II was progression-free rate (PFR) at 3 months (H0: 20%, H1:40%). The secondary endpoints included progression free survival (PFS), overall survival (OS), AEs, objective response and patient-reported outcomes (PRO). Efficacy analysis was by intention to treat. RESULTS The 3-month PFR was 56.4% (95% confidence interval CI: 39.6-72.2%). The 3-month and 6-month PFS were 58.4% (95% CI: 41.3-72.1%) and 44.6% (95% CI: 28.4-59.5%), respectively. Median PFS was 5.3 months (95% CI: 1.4-8.2) and median OS was 12.8 months (95% CI: 10.5-39.2). The most common treatment-related grade ≥ 3 AE were neutropenia (18%), followed by anemia (2.6%), hypertension (2.6%) and alanine aminotransferase increase (2.6%). Grade 1 and grade 2 peripheral sensory neuropathy (PNP) occurred in 15.4% and 20.5%, respectively. No grade 3-4 PNP was reported. CONCLUSIONS Combining nab-pc and gemcitabine is safe. Promising activity is observed in pretreated STS patients with manageable toxicity. This regimen should be considered for further exploration

    Author Correction: Optical coherence tomography in coronary atherosclerosis assessment and intervention.

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    Patient global assessment and inflammatory markers in patients with idiopathic inflammatory myopathies - A longitudinal study.

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    AIM To explore if patient global assessment (PGA) is associated with inflammation over time and if associations are explained by other measures of disease activity and function in patients with idiopathic inflammatory myopathies (IIM). METHODS PGA and systemic inflammatory markers prospectively collected over five years were retrieved from the International MyoNet registry for 1200 patients with IIM. Associations between PGA, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and creatine kinase (CK) were analyzed using mixed models. Mediation analysis was used to test if the association between PGA and inflammatory markers during the first year of observation could be explained by measures of disease activity and function. RESULTS PGA improved, and inflammatory markers decreased during the first year of observation. In the mixed models, high levels of inflammatory markers were associated with worse PGA in both men and women across time points during five years of observation. In men, but not in women, the association between elevated ESR, CRP and poorer PGA was explained by measures of function and disease activity. With a few exceptions, the association between improved PGA and reduced inflammatory markers was partially mediated by improvements in all measures of function and disease activity. CONCLUSION Increased levels of systemic inflammation are associated with poorer PGA in patients with IIM. In addition to known benefits of lowered inflammation, these findings emphasize the need to reduce systemic inflammation to improve subjective health in patients with IIM. Furthermore, the results demonstrate the importance of incorporating PGA as an outcome measure in clinical practice and clinical trials

    Long-term ice mass changes in Greenland and Antarctica derived from satellite laser ranging

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    Time-variable gravity field models obtained from satellite gravimetric techniques allow for the assessment of ice sheet mass changes in remote polar regions, such as Greenland and Antarctica. So far, GRACE has been the primary mission for obtaining the global time-variable gravity field models. However, GRACE was launched in 2002, thus very little is known about the global mass changes before this data, as well as between GRACE and its successor – GRACE Follow-On. We derive a method of gravity field recovery based on Satellite Laser Ranging (SLR) data to geodetic satellites that allows for obtaining direct ice mass change estimates for a period longer by 10 years than that provided by the GRACE missions. The developed method is based on splitting normal equation systems and re-stacking the solutions which allow for stable inversion, reduces the correlations between obtained parameters, stabilizes the ice mass estimates in polar regions, and reduces the noise over oceans by a factor of four. The secular trends obtained from SLR are equal to −113.5 and −82.8 Gt/year, whereas these are −119.1 and −83.3 Gt/year from GRACE and GRACE-FO to degree and order 10 for Greenland and West Antarctica, respectively, for the common period of 2002–2021 and after removing the post-glacial rebound effect. Despite the conformity of the trend and patterns, an underestimation is observed in the solutions expanded to degree and order 10. Therefore, scaling factors between GRACE/GRACE-FO expanded up to a degree and order 10 × 10 and 60 × 60 were derived and applied to SLR solutions to account for the differences in mass estimates due to the truncation of the models. SLR data revealed that in Greenland the smallest ice mass trends are for 1995–2000, 2000–2005, and 2015–2020 which are equal to +54.3, −15.5, and −75.9 Gt/year. The largest ice mass depletion periods took place in 2005–2010, 2010–2015, and recently in 2019–2021 with trends of −213.9, −287.2, and −276.1 Gt/year, respectively. For Greenland and West Antarctica, the period 2010–2015 is characterized by the most enormous ice depletion events, whereas the later 5-year period of 2015–2020 provided a near mass-equilibrium for Antarctica reducing the negative trend and returning to the situation from the ‘90s when no significant ice mass changes were observed

    Training Performance Assessment for Intracranial Aneurysm Clipping Surgery Using a Patient-Specific Mixed-Reality Simulator: A Learning Curve Study.

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    BACKGROUND AND OBJECTIVES The value of simulation-based training in medicine and surgery has been widely demonstrated. This study investigates the introduction and use of a new mixed-reality neurosurgical simulator in aneurysm clipping surgery, focusing on the learning curve and performance improvement. METHODS Five true-scale craniotomy head models replicating patient-specific neuroanatomy, along with a mixed-reality simulator, a neurosurgical microscope, and a set of microsurgical instruments and clips, were used in the operation theater to simulate aneurysm microsurgery. Six neurosurgical residents participated in five video-recorded simulation sessions over 4 months. Complementary learning modalities were implemented between sessions. Thereafter, three blinded analysts reported on residents' use of the microscope, quality of manipulation, aneurysm occlusion, clipping techniques, and aneurysm rupture. Data were also captured regarding training time and clipping attempts. RESULTS Over the course of training, clipping time and number of clipping attempts decreased significantly (P = .018, P = .032) and the microscopic skills improved (P = .027). Quality of manipulation and aneurysm occlusion scoring improved initially although the trend was interrupted because the spacing between sessions increased. Significant differences in clipping time and attempts were observed between the most and least challenging patient models (P = .005, P = .0125). The least challenging models presented higher rates of occlusion based on indocyanine green angiography evaluation from the simulator. CONCLUSION The intracranial aneurysm clipping learning curve can be improved by implementing a new mixed-reality simulator in dedicated training programs. The simulator and the models enable comprehensive training under the guidance of a mentor

    Understanding the factors affecting global political priority for controlling sexually transmitted infections: a qualitative policy analysis.

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    INTRODUCTION Sexually transmitted infections (STIs) are a significant public health challenge, but there is a perceived lack of political priority in addressing STIs as a global health issue. Our study aimed to understand the determinants of global political priority for STIs since the 1980s and to discern implications for future prioritisation. METHODS Through semistructured interviews from July 2021 to February 2022, we engaged 20 key stakeholders (8 women, 12 men) from academia, United Nations agencies, international non-governmental organisations, philanthropic organisations and national public health agencies. A published policy framework was employed for thematic analysis, and findings triangulated with relevant literature and policy documents. We examined issue characteristics, prevailing ideas, actor power dynamics and political contexts. RESULTS A contrast in perspectives before and after the year 2000 emerged. STI control was high on the global health agenda during the late 1980s and 1990s, as a means to control HIV. A strong policy community agreed on evidence about the high burden of STIs and that STI management could reduce the incidence of HIV. The level of importance decreased when further research evidence did not find an impact of STI control interventions on HIV incidence. Since 2000, cohesion in the STI community has decreased. New framing for broad STI control has not emerged. Interventions that have been funded, such as human papillomavirus vaccination and congenital syphilis elimination have been framed as cancer control or improving newborn survival, rather than as STI control. CONCLUSION Globally, the perceived decline in STI control priority might stem from discrepancies between investment choices and experts' views on STI priorities. Addressing STIs requires understanding the intertwined nature of politics and empirical evidence in resource allocation. The ascent of universal health coverage presents an opportunity for integrated STI strategies but high-quality care, sustainable funding and strategic coordination are essential

    Magnetic resonance imaging in acute meningoencephalitis of viral and unknown origin: frequent findings and prognostic potential

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    Background: Magnetic resonance imaging (MRI) findings in meningoencephalitis have mainly been described in terms of their diagnostic value rather than their prognostic potential, except for herpes simplex virus (HSV) encephalitis. The aims of our study were to describe frequency and anatomic locations of MRI abnormalities specific to limbic, circadian and motor systems in a cohort of meningoencephalitis patients, as well as to investigate the prognostic value of these MRI findings. Methods: A secondary, selective analysis of a retrospective database including all meningitis, meningoencephalitis and encephalitis cases treated between 2016 and 2018 in the University hospital of Bern, Switzerland was performed. Patients with meningitis of any cause, bacterial or autoimmune causes of encephalitis were excluded. Results: MRI scans and clinical data from 129 meningoencephalitis cases found that the most frequent causes were tick-borne encephalitis (TBE, 42%), unknown pathogens (40%), VZV (7%), and HSV1 (5%). At discharge, median modified Rankin Score (mRS) was 3 (interquartile range, IQR, 1), 88% of patients had persisting signs and symptoms. After a median of 17 months, median Glasgow Outcome Score (GOS) was 5 (IQR 1), 39% of patients still had residual signs or symptoms. All patients with HSV, 27% with TBE and 31% of those with meningoencephalitis of unknown etiology had fluid-attenuated inversion recovery (FLAIR) and to a lesser extent diffusion-weighted imaging (DWI) lesions in their initial MRI, with highly overlapping anatomical distribution. In one fifth of TBE patients the limbic system was affected. Worse outcome was associated with presence of DWI and/or FLAIR lesions and lower normalized apparent diffusion coefficient (ADC) signal intensities. Conclusion: Presence of FLAIR lesions, restricted diffusion as well as the extent of ADC hypointensity in initial MRI are parameters which might be of prognostic value regarding the longterm clinical outcome for patients with meningoencephalitis of viral and of unknown origin. Although not described before, affection of limbic structures by TBE is possible as shown by our results: A substantial proportion of our TBE patients had FLAIR signal abnormalities in these regions

    Prostate cancer and elective nodal radiation therapy for cN0 and pN0-a never ending story? : Recommendations from the prostate cancer expert panel of the German Society of Radiation Oncology (DEGRO).

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    For prostate cancer, the role of elective nodal irradiation (ENI) for cN0 or pN0 patients has been under discussion for years. Considering the recent publications of randomized controlled trials, the prostate cancer expert panel of the German Society of Radiation Oncology (DEGRO) aimed to discuss and summarize the current literature. Modern trials have been recently published for both treatment-naïve patients (POP-RT trial) and patients after surgery (SPPORT trial). Although there are more reliable data to date, we identified several limitations currently complicating the definitions of general recommendations. For patients with cN0 (conventional or PSMA-PET staging) undergoing definitive radiotherapy, only men with high-risk factors for nodal involvement (e.g., cT3a, GS ≥ 8, PSA ≥ 20 ng/ml) seem to benefit from ENI. For biochemical relapse in the postoperative situation (pN0) and no PSMA imaging, ENI may be added to patients with risk factors according to the SPPORT trial (e.g., GS ≥ 8; PSA > 0.7 ng/ml). If PSMA-PET/CT is negative, ENI may be offered for selected men with high-risk factors as an individual treatment approach

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