Evaluation of the inflammation-based modified Glasgow Prognostic Score (mGPS) as a prognostic and predictive biomarker in patients with metastatic colorectal cancer receiving first-line chemotherapy: a post hoc analysis of the randomized phase III XELAVIRI trial (AIO KRK0110).

BACKGROUND: The inflammation-based modified Glasgow Prognostic Score (mGPS) combines serum levels of C-reactive protein and albumin and was shown to predict survival in advanced cancer. We aimed to elucidate the prognostic impact of mGPS on survival as well as its predictive value when combined with gender in unselected metastatic colorectal cancer (mCRC) patients receiving first-line chemotherapy in the randomized phase III XELAVIRI trial. PATIENTS AND METHODS: In XELAVIRI, mCRC patients were treated with either fluoropyrimidine/bevacizumab followed by additional irinotecan at first progression (sequential treatment arm; Arm A) or upfront combination of fluoropyrimidine/bevacizumab/irinotecan (intensive treatment arm; Arm B). In the present post hoc analysis, survival was evaluated with respect to the assorted mGPS categories 0, 1 or 2. Interaction between mGPS and gender was analyzed. RESULTS: Out of 421 mCRC patients treated in XELAVIRI, 362 [119 women (32.9%) and 243 men (67.1%)] were assessable. For the entire study population a significant association between mGPS and overall survival (OS) was observed [mGPS = 0: median 28.9 months, 95% confidence interval (CI) 25.9-33.6 months; mGPS = 1: median 21.4 months, 95% CI 17.6-26.1 months; mGPS = 2: median 16.8 months, 95% CI 14.3-21.2 months; P < 0.00001]. Similar results were found when comparing progression-free survival between groups. The effect of mGPS on survival did not depend on the applied treatment regimen (P = 0.21). In female patients, a trend towards longer OS was observed in Arm A versus Arm B, with this effect being clearly more pronounced in the mGPS cohort 0 (41.6 versus 25.5 months; P = 0.056). By contrast, median OS was longer in male patients with an mGPS of 1-2 treated in Arm B versus Arm A (20.8 versus 17.4 months; P = 0.022). CONCLUSION: We demonstrate the role of mGPS as an independent predictor of OS regardless of the treatment regimen in mCRC patients receiving first-line treatment. mGPS may help identify gender-specific subgroups that benefit more or less from upfront intensive therapy.

Patient-reported outcomes in large vessel vasculitis: insights from a retrospective analysis of disease activity and associated factors.

BACKGROUND: Patient-reported outcomes (PROs) play a crucial role in assessing rheumatic diseases, offering insights into disease evaluation and treatment efficacy. This study focuses on PRO assessment in large vessel vasculitides, including Takayasu Arteritis and Giant Cell Arteritis (GCA). METHODS: We retrospectively analyzed routine data from patients treated at our rheumatology clinic over a 10-year span. Patient and physician-rated global disease activity scale (G-DAS) scores, measured on a numeric rating scale (0-10 points), were collected at each visit. Clinical variables like age, sex, body mass index (BMI), disease duration, lab values, pain perception, and questionnaire responses were recorded. Linear regression and generalized additive linear regression (GAM analysis) examined associations between PROs and these factors. RESULTS: The study included 138 patients, primarily diagnosed with GCA (94.4%). Mean follow-up was 2.5 years (0-7.7). Patient and physician G-DAS exhibited a moderate correlation (Pearson R 0.19, CI 0.14-0.24, p < 0.001). Higher patient G-DAS correlated with younger age (CI -3.4 - -1.5, p < 0.001), increased pain (CI 3.5-4, p < 0.001), functional limitations (HAQ, CI 0.5-0.6, p < 0.001), reduced physical (CI 2.3-2.7, p ≤ 0.001) and psychological well-being (CI 2.1-2.5, p < 0.001), and higher BMI (CI 1.3-2.4, p < 0.001). Physician G-DAS correlated with Birmingham Vasculitis Activity Score (V3.0; R 0.42, p 0.046) and were significantly linked to serum CRP elevations (ß = 0.04, CI 0.0-0.08, p 0.028). CONCLUSIONS: These findings underscore the need to integrate PRO measures into vasculitis disease management strategies, enhancing the understanding of disease activity from the patient's perspective.

Predictive factors for obstetric anal sphincter injury in primiparous women: systematic review and meta-analysis.

OBJECTIVES: The primary objective was to perform a systematic review of predictive factors for obstetric anal sphincter injury (OASI) occurrence at first vaginal delivery, with the diagnosis made by ultrasound (US-OASI). The secondary objective was to report on incidence rates of sonographic anal sphincter (AS) trauma, including trauma that was not clinically reported at childbirth, among the studies providing data for our primary objective. METHODS: We conducted a systematic search of MEDLINE, EMBASE, Web of Science, CINAHL, The Cochrane Library and ClinicalTrials.gov databases. Both observational cohort studies and interventional trials were eligible for inclusion. Study eligibility was assessed independently by two authors. Random-effects meta-analyses were performed to pool effect estimates from studies reporting on similar predictive factors. Summary odds ratio (OR) or mean difference (MD) is reported with 95% CI. Heterogeneity was assessed using the I2 statistic. Methodological quality was assessed using the Quality in Prognosis Studies tool. RESULTS: A total of 2805 records were screened and 21 met the inclusion criteria (16 prospective cohort studies, three retrospective cohort studies and two interventional non-randomized trials). Increasing gestational age at delivery (MD, 0.34 (95% CI, 0.04-0.64) weeks), shorter antepartum perineal body length (MD, -0.60 (95% CI, -1.09 to -0.11) cm), labor augmentation (OR, 1.81 (95% CI, 1.21-2.71)), instrumental delivery (OR, 2.13 (95% CI, 1.13-4.01)), in particular forceps extraction (OR, 3.56 (95% CI, 1.31-9.67)), shoulder dystocia (OR, 12.07 (95% CI, 1.06-137.60)), episiotomy use (OR, 1.85 (95% CI, 1.11-3.06)) and shorter episiotomy length (MD, -0.40 (95% CI, -0.75 to -0.05) cm) were associated with US-OASI. When pooling incidence rates, 26% (95% CI, 20-32%) of women who had a first vaginal delivery had US-OASI (20 studies; I2 = 88%). In studies reporting on both clinical and US-OASI rates, 20% (95% CI, 14-28%) of women had AS trauma on ultrasound that was not reported clinically at childbirth (16 studies; I2 = 90%). No differences were found in maternal age, body mass index, weight, subpubic arch angle, induction of labor, epidural analgesia, episiotomy angle, duration of first/second/active-second stages of labor, vacuum extraction, neonatal birth weight or head circumference between cases with and those without US-OASI. Antenatal perineal massage and use of an intrapartum pelvic floor muscle dilator did not affect the odds of US-OASI. Most (81%) studies were judged to be at high risk of bias in at least one domain and only four (19%) studies had an overall low risk of bias. CONCLUSION: Given the ultrasound evidence of structural damage to the AS in 26% of women following a first vaginal delivery, clinicians should have a low threshold of suspicion for the condition. This systematic review identified several predictive factors for this. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Longitudinal Doppler Assessments in Late Preterm Fetal Growth Restriction.

PURPOSE: To assess the longitudinal variation of the ratio of umbilical and cerebral artery pulsatility index (UCR) in late preterm fetal growth restriction (FGR). MATERIALS AND METHODS: A prospective European multicenter observational study included women with a singleton pregnancy, 32+ 0-36+ 6, at risk of FGR (estimated fetal weight [EFW] or abdominal circumference [AC] < 10th percentile, abnormal arterial Doppler or fall in AC from 20-week scan of > 40 percentile points). The primary outcome was a composite of abnormal condition at birth or major neonatal morbidity. UCR was categorized as normal (< 0.9) or abnormal (≥ 0.9). UCR was assessed by gestational age at measurement interval to delivery, and by individual linear regression coefficient in women with two or more measurements. RESULTS: 856 women had 2770 measurements; 696 (81 %) had more than one measurement (median 3 (IQR 2-4). At inclusion, 63 (7 %) a UCR ≥ 0.9. These delivered earlier and had a lower birth weight and higher incidence of adverse outcome (30 % vs. 9 %, relative risk 3.2; 95 %CI 2.1-5.0) than women with a normal UCR at inclusion. Repeated measurements after an abnormal UCR at inclusion were abnormal again in 67 % (95 %CI 55-80), but after a normal UCR the chance of finding an abnormal UCR was 6 % (95 %CI 5-7 %). The risk of composite adverse outcome was similar using the first or subsequent UCR values. CONCLUSION: An abnormal UCR is likely to be abnormal again at a later measurement, while after a normal UCR the chance of an abnormal UCR is 5-7 % when repeated weekly. Repeated measurements do not predict outcome better than the first measurement, most likely due to the most compromised fetuses being delivered after an abnormal UCR.

Metastable CrMnNi steels processed by laser powder bed fusion: experimental assessment of elementary mechanisms contributing to microstructure, properties and residual stress.

The complex thermal history imposed by the laser-based powder bed fusion of metals (PBF-LB/M) process is known to promote the evolution of unique microstructures. In the present study, metastable CrMnNi steels with different nickel contents and, thus, different phase stabilities are manufactured by PBF-LB/M. Results clearly reveal that an adequate choice of materials will allow to tailor mechanical properties as well as residual stress states in the as-built material to eventually redundantize any thermal post-treatment. The chemical differences lead to different phase constitutions in as-built conditions and, thus, affect microstructure evolution and elementary deformation mechanisms upon deformation, i.e., twinning and martensitic transformation. Such alloys designed for additive manufacturing (AM) highlight the possibility to tackle well-known challenges in AM such as limited damage tolerance, porosity and detrimental residual stress states without conducting any post treatments, e.g., stress relieve and hot isostatic pressing. From the perspective of robust design of AM components, indeed it seems to be a very effective approach to adapt the material to the process characteristics of AM.

Scenarios for modeling solar radiation modification.

Making informed future decisions about solar radiation modification (SRM; also known as solar geoengineering)-approaches such as stratospheric aerosol injection (SAI) that would cool the climate by reflecting sunlight-requires projections of the climate response and associated human and ecosystem impacts. These projections, in turn, will rely on simulations with global climate models. As with climate-change projections, these simulations need to adequately span a range of possible futures, describing different choices, such as start date and temperature target, as well as risks, such as termination or interruptions. SRM modeling simulations to date typically consider only a single scenario, often with some unrealistic or arbitrarily chosen elements (such as starting deployment in 2020), and have often been chosen based on scientific rather than policy-relevant considerations (e.g., choosing quite substantial cooling specifically to achieve a bigger response). This limits the ability to compare risks both between SRM and non-SRM scenarios and between different SRM scenarios. To address this gap, we begin by outlining some general considerations on scenario design for SRM. We then describe a specific set of scenarios to capture a range of possible policy choices and uncertainties and present corresponding SAI simulations intended for broad community use.

Limited surface impacts of the January 2021 sudden stratospheric warming.

Subseasonal weather prediction can reduce economic disruption and loss of life, especially during "windows of opportunity" when noteworthy events in the Earth system are followed by characteristic weather patterns. Sudden stratospheric warmings (SSWs), breakdowns of the winter stratospheric polar vortex, are one such event. They often precede warm temperatures in Northern Canada and cold, stormy weather throughout Europe and the United States - including the most recent SSW on January 5th, 2021. Here we assess the drivers of surface weather in the weeks following the SSW through initial condition "scrambling" experiments using the real-time CESM2(WACCM6) Earth system prediction framework. We find that the SSW itself had a limited impact, and that stratospheric polar vortex stretching and wave reflection had no discernible contribution to the record cold in North America in February. Instead, the tropospheric circulation and bidirectional coupling between the troposphere and stratosphere were dominant contributors to variability.

Umbilical venous diameter and flow in monochorionic diamniotic twin pregnancy: association with placental sharing and fetal demise.

OBJECTIVE: To examine the association of umbilical venous diameter and flow in monochorionic diamniotic twin pregnancy with placental sharing and fetal demise. METHODS: This was a prospective longitudinal cohort study of a consecutive series of monochorionic diamniotic twin pregnancies that underwent ultrasound assessments at 12, 16, 20 and 28 weeks' gestation. Fetal biometry (crown-rump length at 12 weeks or estimated fetal weight (EFW) thereafter) and cord insertion sites were recorded at each visit, as well as the diameter of the umbilical vein (UV) in both the intra-abdominal part and a free loop of the umbilical cord. Time-averaged maximum velocity in the intra-abdominal part of the UV was measured to calculate UV-flow. Univariate and multivariate linear regression analyses were performed to assess the relationship between intertwin ratios of these variables and placental sharing at 12, 16, 20 and 28 weeks' gestation. Placental sharing was calculated by dividing the larger by the smaller placental share, as measured on placental injection studies after birth. Additionally, the Mann-Whitney U-test and receiver-operating-characteristics-curve analysis were used to explore the relationship between the occurrence of fetal demise and intertwin differences in fetal biometry, cord insertion sites, UV diameters and flow at 12, 16, 20 and 28 weeks. RESULTS: Of 200 consecutive monochorionic twin pregnancies enrolled, injection studies were performed in 165 (82.5%) placentas. On univariate analysis, intertwin differences in fetal biometry, cord insertions and UV variables were associated significantly with placental sharing at 12, 16, 20 and 28 weeks' gestation. On multivariate analysis, intertwin differences in fetal biometry, cord insertions and all three UV variables remained associated significantly with placental sharing at 12 and 16 weeks. However, at 20 and 28 weeks, only the intertwin EFW ratio was associated consistently with placental sharing. Fetal demise of one or both twins complicated 26 (13.0%) pregnancies. Differences in EFW and cord insertion sites were not associated significantly with fetal demise, while at 16 weeks, differences in intra-abdominal UV diameter and flow were associated with an increased risk of subsequent fetal demise. CONCLUSIONS: At 12 and 16 weeks' gestation, intertwin differences in UV diameter and flow reflect placental sharing more accurately than do differences in fetal growth and cord insertion sites. At 16 weeks, discordance in intra-abdominal UV diameter and flow is also associated with an increased risk of fetal demise. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Diagnostic value of quantitative SPECT/CT in assessing active sacroiliitis in patients with axial spondylarthritis and/or inflammatory low back pain.

BACKGROUND: The diagnostic accuracy of bone scintigraphy (BS) increases with SPECT/CT imaging. It would therefore be appropriate to reassess the diagnostic utility of scintigraphy in sacroiliitis with axial spondyloarthritis (SpA). The aim of this study was to compare the diagnostic performance of MRI, SPECT/CT and a combination of both techniques in sacro-iliitis, and to evaluate the correlation between quantitative SPECT/CT indices and quantitative MRI inflammatory lesion scores. METHODS: Thirty-one patients with active SpA and 22 patients with inflammatory low back pain underwent MRI and SPECT/CT of the sacroiliac joints. The diagnostic accuracy of both techniques was calculated using clinical diagnosis as the gold standard. The correlation between MRI and SPECT/CT was calculated by comparing the SPECT/CT activity indices and the Berlin/SPARCC scoring systems for MRI. RESULTS: The sensitivity and specificity values in quantitative SPECT/CT, taking the sacroiliac/promontory ratio of >1.36 as the cut-off value, were close to those from MRI published in the literature. The combination of both techniques increased sensitivity while maintaining high specificity. There was a moderate correlation between SPECT/CT and MRI total scores. This correlation was improved by using solely the MRI inflammation scores. CONCLUSION: Quantitative SPECT/CT showed better diagnostic accuracy than planar scintigraphy and showed a moderate correlation with MRI scores in active sacroiliitis. The combination of both tests increased the diagnostic accuracy. Quanti-tative SPECT/CT could play a relevant role in the diagnosis of active sacroiliitis in patients with high a suspicion of SpA and a negative/inconclusive MRI test or in patients with whom MRI studies cannot be carried out.

Efficacy of AAV serotypes to target Schwann cells after intrathecal and intravenous delivery.

To optimize gene delivery to myelinating Schwann cells we compared clinically relevant AAV serotypes and injection routes. AAV9 and AAVrh10 vectors expressing either EGFP or the neuropathy-associated gene GJB1/Connexin32 (Cx32) under a myelin specific promoter were injected intrathecally or intravenously in wild type and Gjb1-null mice, respectively. Vector biodistribution in lumbar roots and sciatic nerves was higher in AAVrh10 injected mice while EGFP and Cx32 expression rates and levels were similar between the two serotypes. A gradient of biodistribution away from the injection site was seen with both intrathecal and intravenous delivery, while similar expression rates were achieved despite higher vector amounts injected intravenously. Quantified immune cells in relevant tissues were similar to non-injected littermates. Overall, AAV9 and AAVrh10 efficiently transduce Schwann cells throughout the peripheral nervous system with both clinically relevant routes of administration, although AAV9 and intrathecal injection may offer a more efficient approach for treating demyelinating neuropathies.

Variation of enterohepatic circulation observed with 75SeHCAT images in the first three hours. Scintigraphic patterns and analysis of their association with the diagnosis of bile acid malabsorption.

OBJETIVE: To evaluate the enterohepatic circulation of 75-Selenium turoselecolic acid (75Se-SeHCAT) during the first 3 h and its correlation with the abdominal retention at the 7th day (AR7), as contribution to the clinical study of biliar acid malabsorption (BAM). MATERIALS AND METHODS: 38 patients with chronic diarrhea were retrospectively studied. Acquisition protocol included static abdominal images at 1st, 2nd and 3rd hour and the 7th day after oral administration of the radiopharmaceutical. Images of 1-3 h determined 5 patterns of enterohepatic circulation that, due to their location, were characterized as: 1) gallbladder 2-3 h, 2) gallbladder 3 h, 3) gallbladder-abdomen 2-3 h, 4) abdomen, 5) upper left abdomen. The association of these patterns with the AR7 (Fisher, STATA) were investigated. Patients were classified as Non BAM (AR7 > 15%), mild-BAM (AR7 15-10%), moderate-BAM (AR7 10-5%) or severe-BAM (AR7 < 5%). RESULTS: 19 patients had an AR7 diagnostic of BAM (7 mild-BAM, 5 moderate-BAM, 7 severe-BAM). The pattern "gallbladder at 2-3 h" was statistically associated with Non BAM (p 0,008), while "gallbladder-abdomen at 2-3 h" was correlated with having BAM (p 0,029). CONCLUSION: Variations detected at the abdominal level in images during the first 3 h were associated with changes in intestinal absorption and the incorporation of the radiopharmaceutical into the pool of bile acids, so visual interpretation of the images at 2nd and 3rd hour could be useful in the final assessment of the study.

[Identification of rheumatological health apps in the Apple app store applying the "semiautomatic retrospective app store analysis" method : A longitudinal observation]. / Identifikation rheumatologischer Gesundheits-Apps im Apple App Store mit der Methode der "semiautomatischen retrospektiven App Store-Analyse" : Eine longitudinale Betrachtung.

BACKGROUND: The Apple and Google app stores offer a wide range of health apps. It is still a challenge to find valuable and qualified apps. OBJECTIVE: Can German language apps be identified using the "semiautomated retrospective app store analysis" (SARASA) method for the field of rheumatology? MATERIAL AND METHOD: The SARASA is a semiautomated method to select and characterize apps listed in the app store. After the first application in February 2018 SARASA was applied again to the Apple app store in February 2020. RESULTS: In February 2018 it was possible to acquire metadata for 103,046 apps and in February 2020 data for 94,735 apps that were listed in the category "health and fitness" or "medicine" in Apple's app store frontend for Germany. After applying the search terms 59 apps with a German language app description were identified for the field of rheumatology in 2018 and 53 apps in 2020. For these, more detailed manual reviews seem worthwhile. In 2018, the apps found were more likely to address patients than physicians and this was more balanced in 2020. In addition, it became apparent that for certain diseases there was no app developer activity. The percentage breakdown of matches by search term revealed substantial fluctuations in the app market when comparing 2018 to 2020. DISCUSSION: The SARASA method provides a useful tool to identify apps from app stores that meet predefined, formal criteria. Subsequent manual checks of the quality of the contents are still necessary. Further development of the SARASA method and consensus and standardization of quality criteria are worthwhile. Quality criteria should be considered for offers of mobile health apps in app stores.

SPARC-positive macrophages are the superior prognostic factor in the microenvironment of diffuse large B-cell lymphoma and independent of MYC rearrangement and double-/triple-hit status.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with respect to outcome. Features of the tumor microenvironment (TME) are associated with prognosis when assessed by gene expression profiling. However, it is uncertain whether assessment of the microenvironment can add prognostic information to the most relevant and clinically well-established molecular subgroups when analyzed by immunohistochemistry (IHC). PATIENTS AND METHODS: We carried out a histopathologic analysis of biomarkers related to TME in a very large cohort (n = 455) of DLBCL treated in prospective trials and correlated with clinicopathologic and molecular data, including chromosomal rearrangements and gene expression profiles for cell-of-origin and TME. RESULTS: The content of PD1+, FoxP3+ and CD8+, as well as vessel density, was not associated with outcome. However, we found a low content of CD68+ macrophages to be associated with inferior progression-free survival (PFS) and overall survival (OS; P = 0.023 and 0.040, respectively) at both univariable and multivariable analyses, adjusted for the factors of the International Prognostic Index (IPI), MYC break and BCL2/MYC and BCL6/MYC double-hit status. The subgroup of PDL1+ macrophages was not associated with survival. Instead, secreted protein acidic and cysteine rich (SPARC)-positive macrophages were identified as the subtype of macrophages most associated with survival. SPARC-positive macrophages and stromal cells directly correlated with favorable PFS and OS (both, P[log rank] <0.001, P[trend] < 0.001). The association of SPARC with prognosis was independent of the factors of the IPI, MYC double-/triple-hit status, Bcl2/c-myc double expression, cell-of-origin subtype and a recently published gene expression signature [lymphoma-associated macrophage interaction signature (LAMIS)]. CONCLUSIONS: SPARC expression in the TME detected by a single IHC staining with fair-to-good interobserver reproducibility is a powerful prognostic parameter. Thus SPARC expression is a strong candidate for risk assessment in DLBCL in daily practice.

Liquid-like protein interactions catalyse assembly of endocytic vesicles.

During clathrin-mediated endocytosis, dozens of proteins assemble into an interconnected network at the plasma membrane. As initiators of endocytosis, Eps15 and Fcho1/2 concentrate downstream components, while permitting dynamic rearrangement within the budding vesicle. How do initiator proteins meet these competing demands? Here we show that Eps15 and Fcho1/2 rely on weak, liquid-like interactions to catalyse endocytosis. In vitro, these weak interactions promote the assembly of protein droplets with liquid-like properties. To probe the physiological role of these liquid-like networks, we tuned the strength of initiator protein assembly in real time using light-inducible oligomerization of Eps15. Low light levels drove liquid-like assemblies, restoring normal rates of endocytosis in mammalian Eps15-knockout cells. By contrast, initiator proteins formed solid-like assemblies upon exposure to higher light levels, which stalled vesicle budding, probably owing to insufficient molecular rearrangement. These findings suggest that liquid-like assembly of initiator proteins provides an optimal catalytic platform for endocytosis.

Variation of enterohepatic circulation through the image with 75SeHCAT in the first 3 hours. Scintigraphic patterns and análisis of its association with the diagnosis of bile acid malabsorption. / Variación de la circulación enterohepática a través de la imagen con 75SeHCAT en las 3 primeras horas. Patrones gammagráficos y análisis de su asociación con el diagnóstico de malabsorción de ácidos biliares.

OBJETIVE: To evaluate the enterohepatic circulation of 75-Selenium turoselecolic acid (75Se-SeHCAT) during the first 3 hours and its correlation with the abdominal retention at the 7th day (AR7), as contribution to the clinical study of biliar acid malabsorption (BAM). MATERIALS AND METHODS: 38 patients with chronic diarrhea were retrospectively studied. Acquisition protocol included static abdominal images at 1st, 2nd and 3rd hour and the 7th day after oral administration of the radiopharmaceutical. Images of 1 to 3 hours determined 5 patterns of enterohepatic circulation that, due to their location, were characterized as: 1) gallbladder 2-3 hours, 2) gallbladder 3 hours, 3) gallbladder-abdomen 2-3 hours, 4) abdomen, 5) upper left abdomen. The association of these patterns with the AR7 (Fisher, STATA) were investigated. Patients were classified as Non BAM (AR7>15%), mild-BAM (AR7: 15-10%), moderate-BAM (AR7: 10-5%) or severe-BAM (AR7<5%). RESULTS: 19 patients had an AR7 diagnostic of BAM (7 mild-BAM, 5 moderate-BAM, 7 severe-BAM). The pattern "gallbladder at 2-3 hours" was statistically associated with Non BAM (p 0,008), while "gallbladder-abdomen at 2-3 hours" was correlated with having BAM (p 0,029). CONCLUSION: Variations detected at the abdominal level in images during the first 3 hours were associated with changes in intestinal absorption and the incorporation of the radiopharmaceutical into the pool of bile acids, so visual interpretation of the images at 2nd and 3rd hour could be useful in the final assessment of the study.

Afatinib plus gemcitabine versus gemcitabine alone as first-line treatment of metastatic pancreatic cancer: The randomised, open-label phase II ACCEPT study of the Arbeitsgemeinschaft Internistische Onkologie with an integrated analysis of the 'burden of therapy' method.

BACKGROUND: Targeting the epidermal growth factor receptor pathway remains controversial in pancreatic cancer. Afatinib is an oral irreversible ErbB family blocker approved in non-small-cell lung cancer. This open-label, multicenter, randomised phase II trial evaluated gemcitabine plus afatinib (Gem/afatinib) versus gemcitabine (Gem) alone as first-line treatment for metastatic pancreatic cancer. PATIENTS AND METHODS: Patients were randomised in a 2:1 ratio to either Gem (1000 mg/m2 weekly for three weeks followed by one week of rest, repeated every four weeks) and afatinib (40 mg orally once daily) or Gem alone. Overall survival (OS) was the primary study end-point. The novel BOTh©™ methodology was implemented to derive a quantitative estimate for the 'Burden of Therapy/Toxicity' (BOTh) for each patient on every day during the clinical study. RESULTS: One hundred nineteen patients from 25 centres were randomised, 79 patients for Gem/afatinib and 40 for Gem. Median OS was 7.3 months in the Gem/afatinib arm versus 7.4 months in the Gem-alone arm (hazard ratio [HR]: 1.06, p = 0.80). Median progression-free survival was identical in both arms (3.9 months versus 3.9 months, HR: 0.85, p = 0.43). Adverse events were more frequent in the Gem/afatinib arm, especially diarrhoea (71% vs. 13%) and skin rash (65% vs. 5%). The BOTh©™ analysis revealed a significantly higher burden of toxicity in the combination arm (p = 0.0005). CONCLUSION: The addition of afatinib to Gem did not improve treatment efficacy and was more toxic. The BOTh©™ methodology allowed a detailed insight into the course of treatment-related adverse events over the study period. The trial was registered at clinicaltrials.gov (NCT01728818) and Eudra-CT (2011-004063-77).

Cranial findings detected by second-trimester ultrasound in fetuses with myelomeningocele: a systematic review.

BACKGROUND: Abnormal intracranial findings are often detected at mid-trimester ultrasound (US) in fetuses with myelomeningocele (MMC). It is unclear whether these findings constitute a spectrum of the disease or are an independent finding, which should contraindicate fetal surgery. OBJECTIVE: To ascertain the spectrum and frequency of US-detected cranial findings in fetuses with MMC. SEARCH STRATEGY: MEDLINE, Embase, Web of Science and CENTRAL were searched from January 2000 to June 2020. SELECTION CRITERIA: Study reporting incidence of cranial US findings in consecutive cases of second-trimester fetuses with MMC. DATA COLLECTION AND ANALYSIS: Publication quality was assessed by Newcastle-Ottawa Scale (NOS) and modified NOS. Meta-analysis could not be performed as a result of high clinical diversity and study heterogeneity. MAIN RESULTS: Fourteen cranial US findings were reported in 15 studies. Findings in classic Chiari II malformation (CIIM) spectrum included posterior fossa funnelling (96%), small transcerebellar diameter (82-96%), 'banana' sign (50-100%), beaked tectum (65%) and 'lemon' sign (53-100%). Additional cranial findings were small biparietal diameter (BPD) and head circumference (HC) (<5th centile; 53 and 71%, respectively), ventriculomegaly (45-89%), abnormal pointed shape of the occipital horn (77-78%), thinning of the posterior cerebrum, perinodular heterotopia (11%), abnormal gyration (3%), corpus callosum disorders (60%) and midline interhemispheric cyst (42%). CONCLUSIONS: We identified 14 cranial findings by second-trimester US in fetuses with MMC. The relatively high incidence of these findings and their unclear prognostic significance might not contraindicate fetal surgery in the case of normal fetal genetic testing. Some cranial findings may independently affect postnatal outcome, however. Long-term detailed follow-up is required to investigate this. TWEETABLE ABSTRACT: A high rate of cranial abnormalities found on second-trimester ultrasound in fetuses with myelomeningocele.

[Statement of the German Society for Rheumatology (DGRh) on the use of video consultations in rheumatology]. / Stellungnahme der Deutschen Gesellschaft für Rheumatologie e. V. (DGRh) zur Anwendung der Videosprechstunde in der Rheumatologie.

For several years video consultations have been regarded as a new form of medical healthcare infrastructure, in addition to personal doctor-patient contacts and have also been partly promoted. The COVID-19 pandemic brought unexpected topicality and attention to the use of video consultations. The National Association of Statutory Health Insurance Physicians (Kassenärztliche Bundesvereinigung) decided on special regulations in the context of the COVID-19 pandemic, which reduce previous obstacles to the use of telemedicine and video consultations (and also partly of conventional telephony). The present statement of the German Society of Rheumatology (DGRh) on the use of video consultations is intended to give an overview of in which form and with which limitations video consultations can be used in rheumatology in Germany. It sketches an outlook on how video consultations can undertake which functions in rheumatological care in the future.

[Position paper of the commission on digital rheumatology of the German Society of Rheumatology: tasks, targets and perspectives for a modern rheumatology]. / Positionspapier der Kommission Digitale Rheumatologie der Deutschen Gesellschaft für Rheumatologie e. V.: Aufgaben, Ziele und Perspektiven für eine moderne Rheumatologie.

Digitalization in the healthcare system is a great challenge for rheumatology as for other medical disciplines. The German Society for Rheumatology (DGRh) wants to actively participate in this process and benefit from it. By founding the commission on digital rheumatology, the DGRh has created a committee that deals with the associated tasks, advises the DGRh on questions and positions associated with digital health. For the DGRh, this affects the most diverse areas of digitalization in medicine and rheumatology. This position paper presents the topics and developments currently handled by the commission and the tasks identified.