Interleukin (IL)-1 inhibitors have been suggested as possible therapeutic options in a large number of old and new clinical entities characterized by an IL-1 driven pathogenesis.
To perform a ...nationwide snapshot of the on-label and off-label use of anakinra (ANA) and canakinumab (CAN) for different conditions both in children and adults.
We retrospectively collected demographic, clinical, and therapeutic data from both adult and pediatric patients treated with IL-1 inhibitors from January 2008 to July 2016.
Five hundred and twenty-six treatment courses given to 475 patients (195 males, 280 females; 111 children and 364 adults) were evaluated. ANA was administered in 421 (80.04%) courses, CAN in 105 (19.96%). Sixty-two (32.1%) patients had been treated with both agents. IL-1 inhibitors were employed in 38 different indications (37 with ANA, 16 with CAN). Off-label use was more frequent for ANA than CAN (p < 0.0001). ANA was employed as first-line biologic approach in 323 (76.7%) cases, while CAN in 37 cases (35.2%). IL-1 inhibitors were associated with corticosteroids in 285 (54.18%) courses and disease modifying anti-rheumatic drugs (DMARDs) in 156 (29.65%). ANA dosage ranged from 30 to 200 mg/day (or 1.0-2.0 mg/kg/day) among adults and 2-4 mg/kg/day among children; regarding CAN, the most frequently used posologies were 150mg every 8 weeks, 150mg every 4 weeks and 150mg every 6 weeks. The frequency of failure was higher among patients treated with ANA at a dosage of 100 mg/day than those treated with 2 mg/kg/day (p = 0.03). Seventy-six patients (14.4%) reported an adverse event (AE) and 10 (1.9%) a severe AE. AEs occurred more frequently after the age of 65 compared to both children and patients aged between 16 and 65 (p = 0.003 and p = 0.03, respectively).
IL-1 inhibitors are mostly used off-label, especially ANA, during adulthood. The high frequency of good clinical responses suggests that IL-1 inhibitors are used with awareness of pathogenetic mechanisms; adult healthcare physicians generally employ standard dosages, while pediatricians are more prone in using a weight-based posology. Dose adjustments and switching between different agents showed to be effective treatment strategies. Our data confirm the good safety profile of IL-1 inhibitors.
A few studies have reported the safety profile of interleukin (IL)-1 blockers from real life. The aim of this study is to describe anakinra (ANA) and canakinumab (CAN) safety profile in children and ...adults, based on data from a real-life setting. Demographic, clinical, and therapeutic data from patients treated with ANA and CAN were retrospectively collected and analyzed. Four hundred and seventy five patients were enrolled; ANA and CAN were prescribed in 421 and 105 treatment courses, respectively. During a mean follow-up of 24.39 ± 27.04 months, 89 adverse events (AE) were recorded; 13 (14.61%) were classified as serious AE (sAE). The overall estimated rate of AE and sAE was 8.4 per 100 patients/year. Safety concerns were more frequent among patients aged ≥ 65 years compared with patients < 16 years (
p
= 0.002). No differences were detected in the frequency of safety concerns between monotherapy and combination therapy with immunosuppressants (
p
= 0.055), but a significant difference was observed when injection site reactions were excluded from AE (
p
= 0.01). No differences were identified in relation to gender (
p
= 0.462), different lines of biologic therapy (
p
= 0.775), and different dosages (
p
= 0.70 ANA;
p
= 0.39 CAN). The overall drug retention rate was significantly different according to the occurrence of safety concerns (
p
value < 0.0001); distinguishing between ANA and CAN, significance was maintained only for ANA (
p
< 0.0001 ANA;
p >
0.05 CAN). Treatment duration was the only variable associated with onset of AE (OR = 0.399 C.I. 0.250–0.638,
p
= 0.0001). ANA and CAN have shown an excellent safety profile; the risk for AE and sAE tends to decrease over time from the start of IL-1 inhibition.
This study was designed to assess the feasibility and safety of a single-step combined therapy using radiofrequency ablation and transarterial chemoembolization (RFA + TACE) in patients with ...hepatocellular carcinoma (HCC) and uncontrolled coagulopathy. The study also aimed to compare the effectiveness of this approach with TACE alone, performed in a control group.
One hundred and forty-three consecutive cirrhotic patients having a single HCC < 8 cm were enrolled in this observational prospective single-center study from January 2010 to June 2017 and were divided, according to coagulation tests, into three groups (A: low risk; B: intermediate risk and C: high risk of bleeding). The feasibility and safety of a single-step combined treatment (RFA followed by TACE) were evaluated in terms of technical success rate, periprocedural complications, and laboratory values variations. Tumor response obtained at 1-month CT follow-up for group C was compared with that of control group, composed by 16 matched patients with severe coagulopathy and single HCC < 8 cm, who underwent only TACE in a previous period, performed by the same operator.
Technical success was achieved in all patients, without any major complications. Minor complications rate was significantly higher in group C after RFA; however, the patients were successfully treated with subsequent TACE therapy, without any differences between pre- and post-procedural laboratory values. One-month complete response rates were similar in all the three groups; however, the response rates of group C were significantly higher as compared to that of the control TACE Group (p < .001).
The single-step RFA plus TACE therapy allows expansion of the indication for percutaneous thermal ablation, allowing to also include cases previously contraindicated due to the procedural high-risk of complications associated with bleeding, thus improving short-term patient outcome.
Background and aims
The COVID‐19 pandemic represents a source of stress and potential burnout for many physicians. This single‐site survey aimed at assessing perceived stress and risk to develop ...burnout syndrome among physicians operating in COVID wards.
Methods
This longitudinal survey evaluated stress and burnout in 51 physicians operating in the COVID team of Gemelli Hospital, Italy.
Participants were asked to complete the Maslach Burnout Inventory (MBI) and the Perceived Stress Questionnaire on a short run (PSQs) (referring to the past 7 days) at baseline (T0) and then for four weeks (T1‐T4). Perceived Stress Questionnaire on a long run (PSQl) (referring to the past 2 years) was completed only at T0.
Results
Compared with physicians board‐certified in internal medicine, those board‐certified in other disciplines showed higher scores for the Emotional Exhaustion (EE) score of the MBI scale (P < .001). Depersonalisation (DP) score showed a reduction over time (P = .002). Attending physicians scored lower than the resident physicians on the DP scale (P = .048) and higher than resident physicians on the Personal Accomplishment (PA) scale (P = .04). PSQl predicted higher scores on the EE scale (P = .003), DP scale (P = .003) and lower scores on the PA scale (P < .001). PSQs showed a reduction over time (P = .03). Attending physicians had a lower PSQs score compared with the resident physicians (P = .04).
Conclusions
Medical specialty and clinical position could represent risk factors for the development of burnout in a COVID team. In these preliminary results, physicians board‐certified in internal medicine showed lower risk of developing EE during the entire course of the study.
Interleukin (IL)-1 plays a crucial role in the pathogenesis of Adult onset Still's disease (AOSD).
To evaluate the efficacy and safety of anakinra (ANA) and canakinumab (CAN) in a large group of AOSD ...patients.
Data on clinical, serological features, and concomitant treatments were retrospectively collected at baseline and after 3, 6, and 12 months from AOSD patients (Yamaguchi criteria) referred by 18 Italian centers. Pouchot's score was used to evaluate disease severity.
One hundred forty patients were treated with ANA; 4 were subsequently switched to CAN after ANA failure. The systemic pattern of AOSD was identified in 104 (74.2%) of the ANA-treated and in 3 (75%) of the CAN-treated groups; the chronic-articular type of AOSD was identified in 48 (25.8%) of the ANA-treated and in 1 (25%) of the CAN-treated groups. Methotrexate (MTX) was the most frequent disease modifying anti-rheumatic drug (DMARD) used before beginning ANA or CAN 91/140 (75.8%), 2/4 (50%), respectively. As a second-line biologic DMARD therapy in 29/140 (20.7%) of the patients, ANA was found effective in improving all clinical and serological manifestations (
< 0.0001), and Pouchot's score was found to be significantly reduced at all time points (
< 0.0001). No differences in treatment response were identified in the ANA-group when the patients were stratified according to age, sex, disease pattern or mono/combination therapy profile. ANA primary and secondary inefficacy at the 12-month time point was 15/140 (10.7%) and 11/140 (7.8%), respectively. Adverse events (AEs) mainly represented by in situ (28/47, 59.5%) or diffuse (12/47, 25.5%) skin reactions and infections (7/47, 14.8%) were the main causes for discontinuation. Pouchot's score and clinical and serological features were significantly ameliorated at all time points (
< 0.0001) in the CAN-group, and no AEs were registered during CAN therapy. Treatment was suspended for loss of efficacy only in one case (1/4, 25%).
This is the largest retrospective observational study evaluating the efficacy and safety of IL-1 inhibitors in AOSD patients. A good response was noted at 3 months after therapy onset in both the ANA- and CAN-groups. Skin reaction may nevertheless represent a non-negligible AE during ANA treatment.
•This study reports a comprehensive evidence of the overall morbidity of HDV patients.•The majority of HDV-positive patients have advanced liver disease.•A holistic approach is needed due to ...comorbidities present in 47.4% of patients.•Peg-IFN may not be a therapeutic option in over 53% of the patients.•Anti-HDV and HDV-RNA testing were missed in 24% and 30% of patients respectively.
We aimed to characterize the epidemiologic and comorbidities profiles of patients with chronic Hepatitis D (CHD) followed in clinical practice in Italy and explored their interferon (IFN) eligibility.
This was a cross-sectional study of the PITER cohort consisting of consecutive HBsAg-positive patients from 59 centers over the period 2019-2023. Multivariable analysis was performed by logistic regression model.
Of 5492 HBsAg-positive enrolled patients, 4152 (75.6%) were screened for HDV, 422 (10.2%) were anti-HDV positive. Compared with HBsAg mono-infected, anti-HDV positive patients were more often younger, non-Italians, with a history of drug use, had elevated alanine transaminase (ALT), cirrhosis, or hepatocellular carcinoma (HCC). Compared with Italians, anti-HDV positive non-Italians were younger (42.2% age ≤ 40 years vs. 2.1%; P < 0.001), more often females (males 43.0% vs. 68.6%; P < 0.001) with less frequent cirrhosis and HCC. HDV-RNA was detected in 63.2% of anti-HDV-positive patients, who were more likely to have elevated ALT, cirrhosis, and HCC. Extrahepatic comorbidities were present in 47.4% of anti-HDV positive patients and could affect the eligibility of IFN-containing therapies in at least 53.0% of patients in care.
CHD affects young, foreign-born patients and older Italians, of whom two-thirds had cirrhosis or HCC. Comorbidities were frequent in both Italians and non-Italians and impacted eligibility for IFN.
The evolution of modern human reproductive scheduling is an aspect of our life history that remains vastly uncomprehended. The present work aims to address this gap by validating a non-destructive ...cutting-edge methodology to infer adult life-history events on modern teeth with known life history and then applying it to fossil specimens. We use phase-contrast synchrotron X-ray microtomography to visualize the dental cementum of 21 specimens: nine contemporary humans; 10 Neanderthals from Krapina (Croatia, 130-120 kyr); one Neolithic
from Ajmana (Serbia); and one Mesolithic
from Vlasac (Serbia). We were able to correctly detect and time (root mean square error = 2.1 years;
= 0.98) all reproductive (menarche, parturition, menopause) and other physiologically impactful events in the modern sample. Nonetheless, we could not distinguish between the causes of the events detected. For the fossil specimens, we estimated age at death and age at occurrence of biologically significant events. Finally, we performed an exploratory analysis regarding possible sexual dimorphism in dental cementum microstructure, which allowed us to correctly infer the sex of the Neolithic specimen, for which the true value was known via DNA analysis.
Growth of Neanderthal infants from Krapina (120-130 ka), Croatia Mahoney, Patrick; McFarlane, Gina; Smith, B Holly ...
Proceedings - Royal Society. Biological sciences/Proceedings - Royal Society. Biological Sciences,
11/2021, Letnik:
288, Številka:
1963
Journal Article
Recenzirano
Odprti dostop
Modern humans have a slow and extended period of childhood growth, but to what extent this ontogenetic pathway was present in Neanderthals is debated. Dental development, linked to the duration of ...somatic growth across modern primates, is the main source for information about growth and development in a variety of fossil primates, including humans. Studies of Neanderthal permanent teeth report a pace of development either similar to recent humans or relatively accelerated. Neanderthal milk teeth, which form and emerge before permanent teeth, provide an opportunity to determine which pattern was present at birth. Here we present a comparative study of the prenatal and early postnatal growth of five milk teeth from three Neanderthals (120 000-130 000 years ago) using virtual histology. Results reveal regions of their milk teeth formed quickly before birth and over a relatively short period of time after birth. Tooth emergence commenced towards the earliest end of the eruption schedules displayed by extant human children. Advanced dental development is consistent with expectations for Neanderthal infant feeding.
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