Racial differences in systemic sclerosis disease presentation: a European Scleroderma Trials and Research group study

Objectives. Racial factors play a significant role in SSc. We evaluated differences in SSc presentations between white patients (WP), Asian patients (AP) and black patients (BP) and analysed the effects of geographical locations.Methods. SSc characteristics of patients from the EUSTAR cohort were cross-sectionally compared across racial groups using survival and multiple logistic regression analyses.Results. The study included 9162 WP, 341 AP and 181 BP. AP developed the first non-RP feature faster than WP but slower than BP. AP were less frequently anti-centromere (ACA; odds ratio (OR) = 0.4, P < 0.001) and more frequently anti-topoisomerase-I autoantibodies (ATA) positive (OR = 1.2, P = 0.068), while BP were less likely to be ACA and ATA positive than were WP [OR(ACA) = 0.3, P < 0.001; OR(ATA) = 0.5, P = 0.020]. AP had less often (OR = 0.7, P = 0.06) and BP more often (OR = 2.7, P < 0.001) diffuse skin involvement than had WP.AP and BP were more likely to have pulmonary hypertension [OR(AP) = 2.6, P < 0.001; OR(BP) = 2.7, P = 0.03 vs WP] and a reduced forced vital capacity [OR(AP) = 2.5, P < 0.001; OR(BP) = 2.4, P < 0.004] than were WP. AP more often had an impaired diffusing capacity of the lung than had BP and WP [OR(AP vs BP) = 1.9, P = 0.038; OR(AP vs WP) = 2.4, P < 0.001]. After RP onset, AP and BP had a higher hazard to die than had WP [hazard ratio (HR) (AP) = 1.6, P = 0.011; HR(BP) = 2.1, P < 0.001].Conclusion. Compared with WP, and mostly independent of geographical location, AP have a faster and earlier disease onset with high prevalences of ATA, pulmonary hypertension and forced vital capacity impairment and higher mortality. BP had the fastest disease onset, a high prevalence of diffuse skin involvement and nominally the highest mortality

Clinical Results of Mean GTV Dose Optimized Robotic-Guided Stereotactic Body Radiation Therapy for Lung Tumors

Introduction We retrospectively evaluated the efficacy and toxicity of gross tumor volume (GTV) mean dose optimized stereotactic body radiation therapy (SBRT) for primary and secondary lung tumors with and without robotic real-time motion compensation. Materials and methods Between 2011 and 2017, 208 patients were treated with SBRT for 111 primary lung tumors and 163 lung metastases with a median GTV of 8.2 cc (0.3–174.0 cc). Monte Carlo dose optimization was performed prioritizing GTV mean dose at the potential cost of planning target volume (PTV) coverage reduction while adhering to safe normal tissue constraints. The median GTV mean biological effective dose (BED)10 was 162.0 Gy10 (34.2–253.6 Gy10) and the prescribed PTV BED10 ranged 23.6–151.2 Gy10 (median, 100.8 Gy10). Motion compensation was realized through direct tracking (44.9%), fiducial tracking (4.4%), and internal target volume (ITV) concepts with small (≤5 mm, 33.2%) or large (>5 mm, 17.5%) motion. The local control (LC), progression-free survival (PFS), overall survival (OS), and toxicity were analyzed. Results Median follow-up was 14.5 months (1–72 months). The 2-year actuarial LC, PFS, and OS rates were 93.1, 43.2, and 62.4%, and the median PFS and OS were 18.0 and 39.8 months, respectively. In univariate analysis, prior local irradiation (hazard ratio (HR) 0.18, confidence interval (CI) 0.05–0.63, p = 0.01), GTV/PTV (HR 1.01–1.02, CI 1.01–1.04, p < 0.02), and PTV prescription, mean GTV, and maximum plan BED10 (HR 0.97–0.99, CI 0.96–0.99, p < 0.01) were predictive for LC while the tracking method was not (p = 0.97). For PFS and OS, multivariate analysis showed Karnofsky Index (p < 0.01) and tumor stage (p ≤ 0.02) to be significant factors for outcome prediction. Late radiation pneumonitis or chronic rip fractures grade 1–2 were observed in 5.3% of the patients. Grade ≥3 side effects did not occur. Conclusion Robotic SBRT is a safe and effective treatment for lung tumors. Reducing the PTV prescription and keeping high GTV mean doses allowed the reduction of toxicity while maintaining high local tumor control. The use of real-time motion compensation is strongly advised, however, well-performed ITV motion compensation may be used alternatively when direct tracking is not feasible

Clinical Results of Mean GTV Dose Optimized Robotic-Guided Stereotactic Body Radiation Therapy for Lung Tumors

IntroductionWe retrospectively evaluated the efficacy and toxicity of gross tumor volume (GTV) mean dose optimized stereotactic body radiation therapy (SBRT) for primary and secondary lung tumors with and without robotic real-time motion compensation.Materials and methodsBetween 2011 and 2017, 208 patients were treated with SBRT for 111 primary lung tumors and 163 lung metastases with a median GTV of 8.2 cc (0.3–174.0 cc). Monte Carlo dose optimization was performed prioritizing GTV mean dose at the potential cost of planning target volume (PTV) coverage reduction while adhering to safe normal tissue constraints. The median GTV mean biological effective dose (BED)10 was 162.0 Gy10 (34.2–253.6 Gy10) and the prescribed PTV BED10 ranged 23.6–151.2 Gy10 (median, 100.8 Gy10). Motion compensation was realized through direct tracking (44.9%), fiducial tracking (4.4%), and internal target volume (ITV) concepts with small (≤5 mm, 33.2%) or large (&gt;5 mm, 17.5%) motion. The local control (LC), progression-free survival (PFS), overall survival (OS), and toxicity were analyzed.ResultsMedian follow-up was 14.5 months (1–72 months). The 2-year actuarial LC, PFS, and OS rates were 93.1, 43.2, and 62.4%, and the median PFS and OS were 18.0 and 39.8 months, respectively. In univariate analysis, prior local irradiation (hazard ratio (HR) 0.18, confidence interval (CI) 0.05–0.63, p = 0.01), GTV/PTV (HR 1.01–1.02, CI 1.01–1.04, p &lt; 0.02), and PTV prescription, mean GTV, and maximum plan BED10 (HR 0.97–0.99, CI 0.96–0.99, p &lt; 0.01) were predictive for LC while the tracking method was not (p = 0.97). For PFS and OS, multivariate analysis showed Karnofsky Index (p &lt; 0.01) and tumor stage (p ≤ 0.02) to be significant factors for outcome prediction. Late radiation pneumonitis or chronic rip fractures grade 1–2 were observed in 5.3% of the patients. Grade ≥3 side effects did not occur.ConclusionRobotic SBRT is a safe and effective treatment for lung tumors. Reducing the PTV prescription and keeping high GTV mean doses allowed the reduction of toxicity while maintaining high local tumor control. The use of real-time motion compensation is strongly advised, however, well-performed ITV motion compensation may be used alternatively when direct tracking is not feasible

Value of systolic pulmonary arterial pressure as a prognostic factor of death in the systemic sclerosis EUSTAR population

Objective. The aim of this study was to assess the prognostic value of systolic pulmonary artery pressure (sPAP) estimated by echocardiography in the multinational European League Against Rheumatism Scleroderma Trial and Research (EUSTAR) cohort. Methods. Data for patients with echocardiography documented between 1 January 2005 and 31 December 2011 were extracted from the EUSTAR database. Stepwise forward multivariable statistical Cox pulmonary hypertension analysis was used to examine the independent effect on survival of selected variables. Results. Based on our selection criteria, 1476 patients were included in the analysis; 87% of patients were female, with a mean age of 56.3 years (s.d. 13.5) and 31% had diffuse SSc. The mean duration of follow-up was 2.0 years (s.d. 1.2, median 1.9). Taking index sPAP of 50 mmHg. In a multivariable Cox model, sPAP and the diffusing capacity for carbon monoxide (DLCO) were independently associated with the risk of death [HR 1.833 (95% CI 1.035, 3.247) and HR 0.973 (95% CI 0.955, 0.991), respectively]. sPAP was an independent risk factor for death with a HR of 3.02 (95% CI 1.91, 4.78) for sPAP ≥36 mmHg. Conclusion. An estimated sPAP >36 mmHg at baseline echocardiography was significantly and independently associated with reduced survival, regardless of the presence of pulmonary hypertension based on right heart catheterizatio

Mapping and predicting mortality from systemic sclerosis

Objectives To determine the causes of death and risk factors in systemic sclerosis (SSc). Methods Between 2000 and 2011, we examined the death certificates of all French patients with SSc to determine causes of death. Then we examined causes of death and developed a score associated with all-cause mortality from the international European Scleroderma Trials and Research (EUSTAR) database. Candidate prognostic factors were tested by Cox proportional hazards regression model by single variable analysis, followed by a multiple variable model stratified by centres. The bootstrapping technique was used for internal validation. Results We identified 2719 French certificates of deaths related to SSc, mainly from cardiac (31%) and respiratory (18%) causes, and an increase in SSc-specific mortality over time. Over a median follow-up of 2.3 years, 1072 (9.6%) of 11 193 patients from the EUSTAR sample died, from cardiac disease in 27% and respiratory causes in 17%. By multiple variable analysis, a risk score was developed, which accurately predicted the 3-year mortality, with an area under the curve of 0.82. The 3-year survival of patients in the upper quartile was 53%, in contrast with 98% in the first quartile. Conclusion Combining two complementary and detailed databases enabled the collection of an unprecedented 3700 deaths, revealing the major contribution of the cardiopulmonary system to SSc mortality. We also developed a robust score to risk-stratify these patients and estimate their 3-year survival. With the emergence of new therapies, these important observations should help caregivers plan and refine the monitoring and management to prolong these patients' survival

Mapping and predicting mortality from systemic sclerosis

To determine the causes of death and risk factors in systemic sclerosis (SSc).status: publishe

Antibiotic therapy in acute pancreatitis: From global overuse to evidence based recommendations

Background & objectives: Unwarranted administration of antibiotics in acute pancreatitis presents a global challenge. The clinical reasoning behind the misuse is poorly understood. Our aim was to investigate current clinical practices and develop recommendations that guide clinicians in prescribing antibiotic treatment in acute pancreatitis. Methods Four methods were used. 1) Systematic data collection was performed to summarize current evidence; 2) a retrospective questionnaire was developed to understand the current global clinical practice; 3) five years of prospectively collected data were analysed to identify the clinical parameters used by medical teams in the decision making process, and finally; 4) the UpToDate Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system was applied to provide evidence based recommendations for healthcare professionals. Results The systematic literature search revealed no consensus on the start of AB therapy in patients with no bacterial culture test. Retrospective data collection on 9728 patients from 22 countries indicated a wide range (31–82%) of antibiotic use frequency in AP. Analysis of 56 variables from 962 patients showed that clinicians initiate antibiotic therapy based on increased WBC and/or elevated CRP, lipase and amylase levels. The above mentioned four laboratory parameters showed no association with infection in the early phase of acute pancreatitis. Instead, procalcitonin levels proved to be a better biomarker of early infection. Patients with suspected infection because of fever had no benefit from antibiotic therapy. Conclusions The authors formulated four consensus statements to urge reduction of unjustified antibiotic treatment in acute pancreatitis and to use procalcitonin rather than WBC or CRP as biomarkers to guide decision-making

Digital ulcers predict a worse disease course in patients with systemic sclerosis

none120noneMihai, Carina*; Landewé, Robert; Van Der Heijde, Désirée; Walker, Ulrich A.; Constantin, Paul I.; Gherghe, Ana Maria; Ionescu, Ruxandra; Rednic, Simona; Allanore, Yannick; Avouac, Jéroˆme; Czirják, László; Hachulla, Eric; Riemekasten, Gabriela; Cozzi, Franco; Airò, Paolo; Cutolo, Maurizio; Mueller-Ladner, Ulf; Matucci-Cerinic, Marco; Launay, David; Dobrota, Rucsandra; Sfrent-Cornateanu, Roxana; Zingarelli, Stefania; Pigatto, Erika; Cuomo, Giovanna; Caramaschi, Paola; Ananieva, Lidia; Ullman, Susanne; Iversen, Line; Gurman, Alexandra Balbir; Braun-Moscovici, Yolanda; Carreira, Patricia E.; Joven, Beatriz E.; Minier, Tünde; Guiducci, Serena; Bellando-Randone, Silvia; Pellerito, Raffaele; Hunzelmann, Nicolas; Tarner, Ingo H.; Radominski, Sebastião Cezar; De Souza Müller, Carolina; Iannone, Florenzo; Henes, Jörg; Bancel, Dominique Farge; Damjanov, Nemanja; Ostojic, Predrag; Pozzi, Maria Rosa; Hesselstrand, Roger; Denton, Christopher; Krasowska, Dorota; Tikly, Mohammed; Riccieri, Valeria; Cantatore, Francesco Paolo; Corrado, Ada; Da Silva, José Antonio Pereira; Salvador, Maria João; Tyndall, Alan; Gabrielli, Armando; Distler, Oliver; Jordan, Suzan; Heitmann, Stefan; Burkhardt, Harald; Himsel, Andrea; Rozman, Blaz; Smith, Vanessa; Keyser, Filip De; Kalitena, Dusanka Martinovic; Radic, Mislav; Filipescu, Ileana; Petcu, Ana; Vlachoyiannopoulos, Panayiotis; Kucharz, Eugene J.; Widuchowska, Malgorzata; Kopec-Medrek, Magdalena; Kotulska, Anna; Szücs, Gabriella; Stankovic, Aleksandra; Stamenkovic, Bojana; Selmi, Carlo Francesco; Santis, Maria De; Marasini, Bianca; Coleiro, Bernard; Santamaria, Vera Ortiz; Westhovens, René; Becvár, Radim; Novak, Srdan; Engelhart, Merete; Meroni, Pierluigi; Ingegnoli, Francesca; Zeni, Silvana; Sulli, Alberto; Distler, Jörg; Yavuz, Sule; Montecucco, Carlomaurizio; Eyerich, Kilian; Krummel-Lorenz, Brigitte; Zenone, Thierry; Midtvedt, Øyvind; Chizzolini, Carlo; Seidel, Matthias; Oleszowsky, Mara; Üprus, Maria; Opriş, Daniela; Groseanu, Laura; Bielecka, Otylia Kowal; Antonio, Zea Mendoza; Szechinski, Jacek; Morovic-Vergles, Jadranka; Scorza, Raffaella; Puppo, Francesco; Mathieu, Alessandro; Anic, Branimir; Stork, Jiri; Stebbings, Simon; Inanc, Murat; Hasler, Paul; Von Mühlen, Carlos Alberto; Aringer, Martin; Popa, Sergei; Li, Mengtao; Rosato, EdoardoMihai, Carina; Landewé, Robert; Van Der Heijde, Désirée; Walker, Ulrich A.; Constantin, Paul I.; Gherghe, Ana Maria; Ionescu, Ruxandra; Rednic, Simona; Allanore, Yannick; Avouac, Jéroˆme; Czirják, László; Hachulla, Eric; Riemekasten, Gabriela; Cozzi, Franco; Airò, Paolo; Cutolo, Maurizio; Mueller-Ladner, Ulf; Matucci-Cerinic, Marco; Launay, David; Dobrota, Rucsandra; Sfrent-Cornateanu, Roxana; Zingarelli, Stefania; Pigatto, Erika; Cuomo, Giovanna; Caramaschi, Paola; Ananieva, Lidia; Ullman, Susanne; Iversen, Line; Gurman, Alexandra Balbir; Braun-Moscovici, Yolanda; Carreira, Patricia E.; Joven, Beatriz E.; Minier, Tünde; Guiducci, Serena; Bellando-Randone, Silvia; Pellerito, Raffaele; Hunzelmann, Nicolas; Tarner, Ingo H.; Radominski, Sebastião Cezar; De Souza Müller, Carolina; Iannone, Florenzo; Henes, Jörg; Bancel, Dominique Farge; Damjanov, Nemanja; Ostojic, Predrag; Pozzi, Maria Rosa; Hesselstrand, Roger; Denton, Christopher; Krasowska, Dorota; Tikly, Mohammed; Riccieri, Valeria; Cantatore, Francesco Paolo; Corrado, Ada; Da Silva, José Antonio Pereira; Salvador, Maria João; Tyndall, Alan; Gabrielli, Armando; Distler, Oliver; Jordan, Suzan; Heitmann, Stefan; Burkhardt, Harald; Himsel, Andrea; Rozman, Blaz; Smith, Vanessa; Keyser, Filip De; Kalitena, Dusanka Martinovic; Radic, Mislav; Filipescu, Ileana; Petcu, Ana; Vlachoyiannopoulos, Panayiotis; Kucharz, Eugene J.; Widuchowska, Malgorzata; Kopec-Medrek, Magdalena; Kotulska, Anna; Szücs, Gabriella; Stankovic, Aleksandra; Stamenkovic, Bojana; Selmi, Carlo Francesco; DE SANTIS, MARIA LINA; Marasini, Bianca; Coleiro, Bernard; Santamaria, Vera Ortiz; Westhovens, René; Becvár, Radim; Novak, Srdan; Engelhart, Merete; Meroni, Pierluigi; Ingegnoli, Francesca; Zeni, Silvana; Sulli, Alberto; Distler, Jörg; Yavuz, Sule; Montecucco, Carlomaurizio; Eyerich, Kilian; Krummel-Lorenz, Brigitte; Zenone, Thierry; Midtvedt, Øyvind; Chizzolini, Carlo; Seidel, Matthias; Oleszowsky, Mara; Üprus, Maria; Opriş, Daniela; Groseanu, Laura; Bielecka, Otylia Kowal; Antonio, Zea Mendoza; Szechinski, Jacek; Morovic-Vergles, Jadranka; Scorza, Raffaella; Puppo, Francesco; Mathieu, Alessandro; Anic, Branimir; Stork, Jiri; Stebbings, Simon; Inanc, Murat; Hasler, Paul; Von Mühlen, Carlos Alberto; Aringer, Martin; Popa, Sergei; Li, Mengtao; Rosato, Edoard