Nintedanib for Systemic Sclerosis-Associated Interstitial Lung Disease

BACKGROUND: Interstitial lung disease (ILD) is a common manifestation of systemic sclerosis and a leading cause of systemic sclerosis-related death. Nintedanib, a tyrosine kinase inhibitor, has been shown to have antifibrotic and antiinflammatory effects in preclinical models of systemic sclerosis and ILD. METHODS: We conducted a randomized, double-blind, placebo-controlled trial to investigate the efficacy and safety of nintedanib in patients with ILD associated with systemic sclerosis. Patients who had systemic sclerosis with an onset of the first non-Raynaud's symptom within the past 7 years and a high-resolution computed tomographic scan that showed fibrosis affecting at least 10% of the lungs were randomly assigned, in a 1:1 ratio, to receive 150 mg of nintedanib, administered orally twice daily, or placebo. The primary end point was the annual rate of decline in forced vital capacity (FVC), assessed over a 52-week period. Key secondary end points were absolute changes from baseline in the modified Rodnan skin score and in the total score on the St. George's Respiratory Questionnaire (SGRQ) at week 52. RESULTS: A total of 576 patients received at least one dose of nintedanib or placebo; 51.9% had diffuse cutaneous systemic sclerosis, and 48.4% were receiving mycophenolate at baseline. In the primary end-point analysis, the adjusted annual rate of change in FVC was 1252.4 ml per year in the nintedanib group and 1293.3 ml per year in the placebo group (difference, 41.0 ml per year; 95% confidence interval [CI], 2.9 to 79.0; P=0.04). Sensitivity analyses based on multiple imputation for missing data yielded P values for the primary end point ranging from 0.06 to 0.10. The change from baseline in the modified Rodnan skin score and the total score on the SGRQ at week 52 did not differ significantly between the trial groups, with differences of 120.21 (95% CI, 120.94 to 0.53; P=0.58) and 1.69 (95% CI, 120.73 to 4.12 [not adjusted for multiple comparisons]), respectively. Diarrhea, the most common adverse event, was reported in 75.7% of the patients in the nintedanib group and in 31.6% of those in the placebo group. CONCLUSIONS: Among patients with ILD associated with systemic sclerosis, the annual rate of decline in FVC was lower with nintedanib than with placebo; no clinical benefit of nintedanib was observed for other manifestations of systemic sclerosis. The adverse-event profile of nintedanib observed in this trial was similar to that observed in patients with idiopathic pulmonary fibrosis; gastrointestinal adverse events, including diarrhea, were more common with nintedanib than with placebo

Acute diverticulitis management: evolving trends among Italian surgeons. A survey of the Italian Society of Colorectal Surgery (SICCR)

Acute diverticulitis (AD) is associated with relevant morbidity/mortality and is increasing worldwide, thus becoming a major issue for national health systems. AD may be challenging, as clinical relevance varies widely, ranging from asymptomatic picture to life-threatening conditions, with continuously evolving diagnostic tools, classifications, and management. A 33-item-questionnaire was administered to residents and surgeons to analyze the actual clinical practice and to verify the real spread of recent recommendations, also by stratifying surgeons by experience. CT-scan remains the mainstay of AD assessment, including cases presenting with recurrent mild episodes or women of child-bearing age. Outpatient management of mild AD is slowly gaining acceptance. A conservative management is preferred in non-severe cases with extradigestive air or small/non-radiologically drainable abscesses. In severe cases, a laparoscopic approach is preferred, with a non-negligible number of surgeons confident in performing emergency complex procedures. Surgeons are seemingly aware of several options during emergency surgery for AD, since the rate of Hartmann procedures does not exceed 50% in most environments and damage control surgery is spreading in life-threatening cases. Quality of life and history of complicated AD are the main indications for delayed colectomy, which is mostly performed avoiding the proximal vessel ligation, mobilizing the splenic flexure and performing a colorectal anastomosis. ICG is spreading to check anastomotic stumps’ vascularization. Differences between the two experience groups were found about the type of investigation to exclude colon cancer (considering the experience only in terms of number of colectomies performed), the size of the peritoneal abscess to be drained, practice of damage control surgery and the attitude towards colovesical fistula

) Maceil, C. E.; In The Encyclopedia of Nuclear Magnetic Resonance

Evanescent-wave cavity ring-down spectroscopy has been applied to a planar fused-silica surface covered with crystal violet (CV + ) cations to characterize the silanol groups indirectly. A radiation-polarization dependence of the adsorption isotherm of CV + at the CH 3 CN/silica interface is measured and fit to a two-site Langmuir equation to determine the relative populations of two different types of isolated silanol groups. CV + binding at type I sites yields a free energy of adsorption of -29.9 ( 0.2 kJ/mol and a saturation surface density of (7.4 ( 0.5) × 10 12 cm -2 , whereas the values of -17.9 ( 0.4 kJ/mol and (3.1 ( 0.4) × 10 13 cm -2 are obtained for the type II sites. The CV + cations, each with a planar area of ∼120 Å 2 , seem to be aligned randomly while lying over the SiOtype I sites, thereby suggesting that this type of site may be surrounded by a large empty surface area (>480 Å 2 ). In contrast, the CV + cations on a type II sites are restricted with an average angle of ∼40°tilted off the surface normal, suggesting that the CV + cations on these sites are grouped closely together. The average tilt angle increases with increasing concentration of crystal violet so that CV + cations may be separated from each other to minimize the repulsion of nearby CV + and SiOH sites. Adsorption behavior of organic molecules on silica surfaces has been the major theme of interface studies for improving the efficiency of chromatographic separations. When cationic molecules are involved, the strong electrostatic interaction with the negatively charged silanol (SiOH) groups on the surface of the stationary-phase silica may cause unwanted peak broadening and tailing, mainly from a slow kinetic response of the electrostatic adsorption. [1][2][3][4][5][6] The surface charge density is one of the primary factors influencing the strength of electrostatics. Accordingly, insight into how the cationic molecules interact with the local silanol groups of the silica surface should aid in the improvement of the design of surface modifications. Silanol groups play the main role in influencing the interfacial adsorption behavior, possessing an average surface density of ∼4.9 × 10 14 cm -2 on the silica surface 7-9 or an average surface area of 20.4 Å 2 per silanol group. As compared to silica sol particles, which have higher surface areas of (0.1-5) × 10 22 Å 2 /g, 7-9 only a few studies focus on characterization of silanol groups on a planar silica surface. 10-12 Ong et al. 10 first reported that isolated and vicinal silanol groups both exist at the water/silica interface possessing different pK a values of 4.9 and 8.5, with corresponding surface populations of 19 and 81%, respectively. These results were confirmed by means of cross-polarization magic angle spinning NMR 13 and fluorescence microscopy. 14 The isolated silanol groups with pK a ) 4.9 are anticipated to be separated far from each other (>5.5 Å), permitting proton dissociation. The vicinal silanol groups are located so closely as to form hydrogen bonds directly with their neighbors (<3.3 Å), which share 46% of the surface population, or through a water-molecule bridge (3.5-5.5 Å), which covers ∼35% of the surface population. 12,[15][16][17] By using second harmonic generation (SHG) with a cationic crystal violet (CV + ) molecular probe to investigate the local density distribution of the isolated silanols (pK a ) 4.9) on the planar fusedsilica surface, Xu and co-workers 12 classified them into two types. The first type of silanol group is anticipated to be surrounded by a large empty surface area (g120 Å 2 ) with a surface density o

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity > 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI