Evolution and outcomes of aortic dilations in giant cell arteritis.

OBJECTIVES: To identify factors associated with the progression of giant cell arteritis (GCA)-related or associated aortic dilations. METHODS: In this retrospective study, 47 GCA patients with aortic dilation were longitudinally analyzed. Each patient underwent ≥2 imaging scans of the aorta during the follow-up. Three progression statuses of aortic dilations were distinguished: fast-progressive (FP) defined by a progression of the aortic diameter ≥5 mm/year or ≥1 cm/2 years, slow progressive (SP) by a progression of the aortic diameter >1 mm during the follow-up, and not progressive (NP) when aortic diameter remained stable. RESULTS: Among the 47 patients with aortic dilation, the thoracic section was involved in 87 % of patients. Within a total follow-up of 89 [6-272] months, we identified 13 (28 %) patients with FP dilations, and 16 (34 %) and 18 (38 %) patients with SP and NP dilations, respectively. No differences regarding baseline characteristics, cardiovascular risk factors or treatments were observed among the 3 groups. However, FP patients more frequently showed atheromatous disease (p = 0.04), with a more frequent use of statins (p = 0.04) and antiplatelet agents (p = 0.02). Among the 27 (57 %) patients with aortitis, aortic dilation developed on an inflammatory segment in 23 (85 %). Among the FP patients who underwent aortic surgery with available histology (n = 3), all presented active vasculitis. CONCLUSION: This study suggests that aortic inflammation, as well as atheromatous disease, might participate in the fast progression of aortic dilation in GCA.

Interfacility Transfer Teams: A Pilot Study to Assess Viability as a Skill Sustainment Platform.

INTRODUCTION: A US Naval hospital in the remote Pacific region has developed interfacility transfer (IFT) teams staffed by active duty personnel out of necessity due to a large percentage of critically ill patients requiring IFT and a lack of local resources. The IFT program underwent significant improvements in training and quality assurance in 2017. We sought to assess patient safety when transport was performed by our locally sourced and trained IFT teams. En route care (ERC) is a recognized critical capability gap in the US Navy requiring clinicians with current knowledge and skills to maintain competency. IFT programs may be a viable skill sustainment program for ERC clinicians. MATERIALS AND METHODS: A database was created as part of the quality assurance program to collate information on patient demographics, level of care provided, reason for transport, and interventions provided by the transporting team. A retrospective review of these data was conducted with emphasis on the appropriateness of patient management and skill sustainment for active duty personnel. The project was deemed institutional review board exempt. RESULTS: Of the 1,193 patient care reports reviewed, interventions were required in 128 (10.7%) of patients and 58 (4.9%) required ventilator management. Medical deterioration occurred during 22 (1.8%) of the transports, with 20 (90.9%) of the deterioration episodes managed appropriately. No patient harm occurred. CONCLUSIONS: IFT teams with local training were able to safely transport critically ill patients with no adverse outcomes, defined as direct harm to the patients as a result of transport. Patient care during transports included routine interventions, ventilator management, and troubleshooting of patient deteriorations. Our data further suggest IFT programs may be a viable skill sustainment platform for ERC clinicians.

Frequency and characteristics of severe relapse in giant cell arteritis.

OBJECTIVES: To assess the frequency and characteristics of severe relapse in patients with giant cell arteritis (GCA) in a real-life setting. METHODS: In a monocentric database of 530 patients, we retrospectively analysed patients who experienced at least one relapse and distinguished severe from nonsevere relapses. Severe relapse was defined by the occurrence of an ischaemic event (ophthalmologic, neurologic, digestive, limb ischaemia), the occurrence of an aortic complication (i.e. new or worsening of aortic dilation, aortic dissection), or new or worsening of vascular stenosis. RESULTS: From the cohort of 530 patients, 242 (45.7%) patients experienced relapse at least once, including 13 (2.5% of the cohort) who experienced severe relapse. Among the 464 recorded relapses, 14 (3% of all relapses) were severe. Severe relapse corresponded to the following vascular events: a peripheral limb ischaemia in 6 patients, a visual event in 3 patients (including 2 acute anterior ischaemic anterior neuropathies), an aortic complication in 3 patients, a mesenteric ischaemia in one patient and an ischaemic stroke in one patient.When compared with the 229 patients who experienced nonsevere relapses, severe relapse patients were younger at diagnosis (p= 0.02), more frequently showed limb claudication at baseline (p< 0.0001) and fewer GCA-related cranial signs (p< 0.0001). At diagnosis, more large-vessel vasculitis on imaging (82% vs 36%, p= 0.002) were observed in patients with severe relapse. The death rate did not differ between patients with severe and nonsevere relapses. CONCLUSION: In a real-life setting, relapse affects nearly half of GCA patients, but severe relapse is rare.

Baldwin and Whitehead's Manzamine Alkaloids Biosynthesis Hypothesis Involves a Finely Tuned Reactivity of Acrolein: Automated Extraction of Reactivity Patterns from LC-MS2 Data.

Inspired by the multicomponent reaction-type scenario involving fatty dialdehydes, a nitrogen source, and acrolein, as a key C3 unit, put forward by Baldwin and Whitehead to explain the formation of manzamine-type alkaloids, 96 multicomponent reactions were designed, and their analytical readouts were deconvoluted using a herein-provided chemoinformatic workflow. This strategy pinpointed relevant conditions tuning the reactivity of acrolein to fulfill Baldwin and Whitehead's manzamine alkaloids biosynthetic hypothesis. This strategy can become part of a general method for the high-content analysis of multicomponent reactions applied to a natural product biosynthetic scenario.

Duration of analgesia after forefoot surgery compared between an ankle and a sciatic nerve block at the popliteal crease: A randomised controlled single-blinded trial.

BACKGROUND: Forefoot surgery is associated with severe postoperative pain. Ankle and sciatic nerve blocks provide satisfactory postoperative analgesia after forefoot surgery, but little is known on their respective duration of analgesia. OBJECTIVE: This randomised controlled, single-blinded trial tested the hypothesis that after forefoot surgery in the setting of multimodal analgesia, an ankle block provides analgesia superior to that of a sciatic nerve block at the popliteal crease. DESIGN: A randomised controlled study. SETTING: A single centre study in a university hospital in Switzerland, from September 2018 to November 2022. PATIENTS: From 91 patients scheduled for forefoot surgery, 60 met the inclusion criteria of which 56 completed the protocol and their data were available for analysis. Exclusion criteria were existing sciatic nerve deficit, pre-existing peripheral neuropathy, chronic pain diagnosis, pregnancy, or identified contraindications to peripheral nerve block. INTERVENTION: Patients undergoing forefoot surgery were randomly allocated to either a multi-injection ankle block (partly under ultrasound guidance) or a sciatic nerve block at the popliteal crease (under ultrasound guidance) combined with a saphenous nerve block at the ankle. Patients in each group received a total of 30 ml of ropivacaine 0.5% and a multimodal analgesic regimen inclusive of dexamethasone, paracetamol, ketorolac then ibuprofen. MAIN OUTCOME MEASURE: The primary outcome was duration of analgesia, defined as time to first morphine request. RESULTS: Mean ±â€ŠSD duration of analgesia was 15.4 ±â€Š8.0 h in the ankle block group and 20.0 ±â€Š10.3 h in the sciatic nerve block group ( P  = 0.32). Of note, 15 of 26 (58%) and 24 of 30 (80%) patients of the ankle and sciatic nerve block groups did not request any morphine ( P  = 0.09). Other secondary outcomes were similar between groups. CONCLUSION: Compared with the ankle block, the sciatic nerve block at the popliteal crease does not provide a longer duration of analgesia in patients undergoing forefoot surgery in the setting of multimodal analgesia. TRIAL REGISTRATION: Clinicaltrials.com identifier: NCT03683342.

Femoral vs sciatic nerve block to provide analgesia after medial open wedge high tibial osteotomy in the setting of multimodal analgesia: A randomized, controlled, single-blinded trial.

STUDY OBJECTIVE: Medial open wedge high tibial osteotomy (MOW HTO) is associated with moderate to severe postoperative pain. The proximal part of the tibia is innervated by branches from the femoral nerve anteriorly and the sciatic nerve posteriorly. There is a paucity of information regarding the optimal peripheral nerve block for postoperative analgesia with minimal impact on motor function. This study tested the hypothesis that a femoral nerve block provides superior analgesia to a sciatic nerve block after MOW HTO in the setting of multimodal analgesia. DESIGN: Randomized controlled single-blind trial. SETTING: Operating room, postoperative recovery area and ward, up to 6 postoperative months. PATIENTS: Fifty patients undergoing MOW HTO. INTERVENTIONS: Interventions were femoral or sciatic nerve block under ultrasound guidance. For each intervention, a total of 100 mg of ropivacaine was injected. Postoperative pain treatment followed a pre-defined protocol with intravenous patient-controlled analgesia of morphine, paracetamol, and ibuprofen. MEASUREMENTS: The primary outcome was intravenous morphine consumption at 24 h postoperatively. Secondary outcomes included rest and dynamic pain scores (on a numeric rating scale out of 10) at 2, 24 and 48 h postoperatively. Functional outcomes included the Short Form-12, Knee injury and Osteoarthritis Outcome Score, and International Knee Documentation Committee (IKDC) scores measured at 6 months postoperatively. MAIN RESULTS: Mean [95% confidence interval] i.v. morphine consumption at 24 postoperative hours were 24 mg [15 mg,33 mg] in the femoral nerve block group and 24 mg [16 mg,32 mg] in the sciatic nerve block group (p = 0.98). There were no significant differences in the secondary outcomes between groups. CONCLUSIONS: This trial failed to demonstrate that a femoral nerve block provides superior analgesia to a sciatic nerve block after MOW HTO under general anesthesia in the setting of multimodal analgesia. There was no significant difference in quality of life and functional outcomes at 6 months postoperatively between groups. Trial registry number:Clinicaltrials.com - NCT05728294; Kofam.ch - SNCTP000003048 | BASEC2018-01774.

Evolution of the Therapeutic Management of Giant Cell Arteritis: Analysis of Real-Life Practices over Two Timeframes (2014-2017 and 2018-2020).

Objectives: To determine how therapeutic strategies for giant cell arteritis (GCA), especially glucocorticoid (GC) management, evolved between 2014 and 2020. Patients and Methods: Consecutive GCA patients followed for at least 24 months in a single tertiary center were enrolled and separated into two groups: those diagnosed from 2014 to 2017 and those diagnosed from 2018 to 2020. GC doses (mg/kg/day) were analyzed at onset, at Month 3 (M3) and, if continued, at M6, M12, M18 and M24. Physicians' practices were also individually analyzed. Results: Among the 180 patients included, 96 (53%) were diagnosed in 2014-2017 and 84 (47%) in 2018-2020. All patients received GC at diagnosis without a difference in the initial dose between the two groups (p = 0.07). At M3, the daily dose was lower in patients treated after 2017 (p = 0.002). In patients who still received GC at M6 (p = 0.0008), M12 (p = 0.01) and M24 (p = 0.02), the daily GC dose was still lower in patients treated after 2017. The proportion of patients who definitively discontinued GC use before M18 (42% versus 21%, p = 0.003) was higher in those treated after 2017. The rates of immunosuppressant use were not different between the two time periods (31% versus 38%, p = 0.34), but tocilizumab replaced methotrexate. Significant differences were observed among practitioners regarding the GC doses at M6 (p = 0.04) and M12 (p = 0.04), the total GC duration (p = 0.02) and the ability to stop GC before M18 (p = 0.007). Conclusions: This real-life study showed a global change in GC management over time for GCA patients, with important variability among physicians' practices.

Diagnosing and treating pericarditis and myocarditis in the emergency department.

Pericarditis and myocarditis represent a challenging set of diseases to diagnose and treat. These diseases typically present with chest pain and dyspnea in previously healthy young people, often in the weeks following a viral illness, including COVID-19. Nonetheless, the etiologies can be very diverse, including infectious, noninfectious, drug-induced, and autoimmune causes. This review focuses on the evaluation, diagnosis, and management of emergency department patients presenting with pericarditis and myocarditis and summarizes current guidelines and best-practice medical management strategies in order to avoid potential life-threatening cardiac complications.

A critical region of A20 unveiled by missense TNFAIP3 variations that lead to autoinflammation.

A20 haploinsufficiency (HA20) is an autoinflammatory disease caused by heterozygous loss-of-function variations in TNFAIP3, the gene encoding the A20 protein. Diagnosis of HA20 is challenging due to its heterogeneous clinical presentation and the lack of pathognomonic symptoms. While the pathogenic effect of TNFAIP3 truncating variations is clearly established, that of missense variations is difficult to determine. Herein, we identified a novel TNFAIP3 variation, p.(Leu236Pro), located in the A20 ovarian tumor (OTU) domain and demonstrated its pathogenicity. In the patients' primary cells, we observed reduced A20 levels. Protein destabilization was predicted in silico for A20_Leu236Pro and enhanced proteasomal degradation was confirmed in vitro through a flow cytometry-based functional assay. By applying this approach to the study of another missense variant, A20_Leu275Pro, for which no functional characterization has been performed to date, we showed that this variant also undergoes enhanced proteasomal degradation. Moreover, we showed a disrupted ability of A20_Leu236Pro to inhibit the NF-κB pathway and to deubiquitinate its substrate TRAF6. Structural modeling revealed that two residues involved in OTU pathogenic missense variations (i.e. Glu192Lys and Cys243Tyr) establish common interactions with Leu236. Interpretation of newly identified missense variations is challenging, requiring, as illustrated here, functional demonstration of their pathogenicity. Together with functional studies, in silico structure analysis is a valuable approach that allowed us (i) to provide a mechanistic explanation for the haploinsufficiency resulting from missense variations and (ii) to unveil a region within the OTU domain critical for A20 function.

The postoperative analgesic efficacy of liposomal bupivacaine versus long-acting local anaesthetics for peripheral nerve and field blocks: A systematic review and meta-analysis, with trial sequential analysis.

BACKGROUND: Liposomal bupivacaine is claimed by the manufacturer to provide analgesia for up to 72 h postoperatively. OBJECTIVES: To compare the postoperative analgesic efficacy of liposomal bupivacaine versus long-acting local anaesthetics for peripheral nerve or field blocks. DESIGN: A systematic review and meta-analysis with trial sequential analysis. DATA SOURCES: MEDLINE, Embase and Web of Science, among others, up to June 2022. ELIGIBILITY CRITERIA: We retrieved randomised controlled trials comparing liposomal bupivacaine versus bupivacaine, levobupivacaine or ropivacaine for peripheral nerve and field blocks after all types of surgery. Our primary endpoint was rest pain score (analogue scale 0 to 10) at 24 h. Secondary endpoints included rest pain score at 48 and 72 h, and morphine consumption at 24, 48 and 72 h. RESULTS: Twenty-seven trials including 2122 patients were identified. Rest pain scores at 24 h were significantly reduced by liposomal bupivacaine with a mean difference (95% CI) of -0.9 (-1.4 to -0.4), I2  = 87%, P  < 0.001. This reduction in pain scores persisted at 48 h and 72 h with mean differences (95% CI) of -0.7 (-1.1 to -0.3), I2  = 82%, P  = 0.001 and -0.7 (-1.1 to -0.3), I2  = 80%, P  < 0.001, respectively. There were no differences in interval morphine consumption at 24 h ( P  = 0.15), 48 h ( P  = 0.15) and 72 h ( P  = 0.07). The quality of evidence was moderate. CONCLUSIONS: There is moderate level evidence that liposomal bupivacaine reduces rest pain scores by 0.9 out of 10 units, when compared with long-acting local anaesthetics at 24 hours after surgery, and by 0.7 up to 72 hours after surgery.

Efficacy and tolerance of methotrexate in a real-life monocentric cohort of patients with giant cell arteritis.

OBJECTIVES: To assess the indications, efficiency and tolerance profiles of methotrexate (MTX) in patients with giant cell arteritis (GCA) in a real-life setting. METHODS: From a monocentric database of >500 GCA patients, we retrospectively selected 49 patients who received MTX between 2010 and 2020. Cumulative glucocorticoid (GC) doses, the number of relapses and GC-related adverse events were recorded before, during and after MTX. We separately analyzed the 3 main indications of MTX, i.e., disease relapse, GC-sparing strategy, and GCA presentation. RESULTS: With a median follow-up of 84 [10-255] months, 25 (51%) and 18/41 (44%) patients relapsed during MTX treatment and after its discontinuation, respectively. Among the 40 patients who relapsed before MTX, 26 (65%) experienced a new relapse after MTX introduction. Once MTX was introduced, 24 (49%) patients were able to discontinue GC after 20.5 [7-64] months. No significant difference in cumulative GC doses were noted before and after MTX introduction with a total GC dose of 14.7 [1.05-69.4] grams. At the last follow-up, MTX was discontinued in 41 patients, including 13 (32%) due to clinicobiological remission, 12 (30%) due to treatment failure and 15 (36%) due to side effects. CONCLUSION: Our real-life study showed a modest beneficial effect of MTX on relapse in patients with GCA. However, we did not observe any GC-sparing effect in this study. Other studies are needed to assess the GC-sparing effect in patients in whom GC management is adapted from recent recommendations.

Preventive effect of beta-blockers in the development of aortic dilation in giant cell arteritis-related aortitis.

OBJECTIVES: To analyze whether beta-blockers (BBs), in addition to conventional care, can decrease the risk of aortic dilation in giant-cell arteritis (GCA)-related aortitis. METHODS: We conducted in a single medical center retrospective study including 65 consecutive patients with GCA-related aortitis who all underwent aortic morphology control during follow-up. The impact of previous cardiovascular (CV) risk factors and/or events on BB prescription and on the risk for new aortic dilation was analyzed using a weighted (8-point maximum) score between 0 (i.e., 0/8 CV risk factors and events) and 1 (i.e., 8/8). RESULTS: Among the 65 patients with GCA-related aortitis, 15 (23%) were taking BBs before GCA diagnosis and continued them thereafter. The vascular score was significantly higher in patients who received BBs (0.25 [0.125-0.625] vs. 0.125 [0-0.625] in patients without BBs, p < 0.0001). The median follow-up was 91 [25-163] months in GCA patients taking BBs and 61 [14-248] months in patients not taking BBs (p = 0.13). None of the patients taking BBs developed a new aortic dilation, whereas 15 (15/50; 30%) patients not taking BBs did (p = 0.01), as detected at a median time of 38 [6-120] months after the first imaging. Rates of other CV events during follow-up did not differ between the groups (p = 1). CONCLUSIONS: This study is the first to suggest that BBs in addition to conventional care in patients with GCA-related aortitis may help to prevent the risk of aortic dilation during follow-up. Larger-sized studies are required to confirm these results.

Drugs associated with systemic sclerosis: An updated list of suspected drugs using the WHO pharmacovigilance database.

OBJECTIVE: The pathophysiological mechanisms involved in systemic sclerosis (SSc), especially the triggering factor, are poorly understood. The literature supporting the role of drugs in the onset of SSc primarily relies on case reports, short series or previous studies of old drugs. We aimed to update the list of suspected drugs associated with SSc (DASSc). METHODS: Analyzing the World Health Organization (WHO) pharmacovigilance database (Vigibase®), we collected all individual case safety reports (ICSRs) of drugs putatively associated with SSc reported since 1967 using the Medical Dictionary for Regulatory Activities preferred terms "systemic sclerosis" and "scleroderma". For each drug, a disproportionality analysis was performed by calculating the information component (IC). An identified drug was considered significant if the IC025 was >0. RESULTS: A total of 2800 deduplicated ICSRs of DASSc were identified, accounting for 509 ICSRs and 38 suspected DASSc after exclusion of protopathic and indication biases. Anticancer drugs were the most represented drug class, accounting for 16/38 (42%) of DASSc and 317/509 (62.3%) of ICSRs, which occurred mostly in the first years after the introduction of the drugs. Among these, taxane-based agents, bleomycin, vinblastine, imatinib, dacarbazine, pembrolizumab and pemetrexed were associated with the highest disproportionate reporting. Hormone replacement therapy, romiplostim and eculizumab were associated with a significant signal. DASSc was considered a serious adverse drug reaction in 404 (92%, n = 441) cases with 41 (9%) cases resulting in death. CONCLUSION: Several new drugs with significant disproportionality signals were identified as potential drugs implicated the development of SSc, particularly anticancer drugs.

Low total gamma globulin level discovery at diffuse large B-cell lymphoma diagnosis predicts high risk of infection-related death: data from a monocentric retrospective study.

OBJECTIVE: Diffuse large B-cell lymphoma can complicate the course of B-cell primary immunodeficiencies or induce lowering of total gamma globulin levels, whose clinical status as an effective secondary immunodeficiency remains unspecified. This study aimed to assess the frequency, and clinical and prognostic relevance of the low total gamma-globulin levels discovered at diagnosis of diffuse large B-cell lymphoma. RESULTS: In a 2-year monocentric retrospective study, 96 patients diagnosed with diffuse large B-cell lymphoma who had a serum electrophoresis were included. Patients were divided into those with lower (L-TGL and higher (H-TGL) total gamma-globulin levels (total gamma-globulin levels ≤5.5 g/l and >5.5 g/l) and compared for outcomes, including fatal infectious events. Twelve (12.5%; 8 males; age median 68 years, range 55-82 years) exhibited L-TGL. There was no difference between the both groups regarding demographics, Ann Arbor lymphoma stage, inflammatory parameters or chemotherapy regimen. However, overall death rates (10/12, 83.3% versus 22/96, 26.2%; p = 0.03) and infection-related death rates (10/12, 83% versus 6/96, 6.2%; p <0.001) were significantly higher in the L-TGL group. CONCLUSION: We demonstrate for the first time the strong negative impact of L-TGL on overall and infection-related mortality in diffuse large B-cell lymphoma. Prospective studies should distinguish immunodeficiencies secondary to the lymphoma from pre-existing humoral primary immunodeficiencies, using biomolecular testing and post-treatment total gamma-globulin level monitoring, to determine the best management strategy for infectious risk during diffuse large B-cell lymphoma treatment in the context of L-TGL.

Impact of Glucocorticoid Cumulative Doses in a Real-Life Cohort of Patients Affected by Giant Cell Arteritis.

OBJECTIVES: To describe the impact of cumulative glucocorticoid (GC) doses on related adverse events (AEs) in giant cell arteritis (GCA) in a real-life setting. METHODS: The medical charts of the last 139 consecutive GCA patients followed in a tertiary centre were retrospectively analysed. The cumulative GC doses were calculated, and the main GC-related AEs were collected during the follow-up. RESULTS: After a median follow-up duration of 35.6 (2-111) months, the median cumulative GC dose in the 139 patients was 9184 (1770-24,640) mg, and 131 patients (94%) presented at least one GC-related AE. Infections (63%) were the most frequently reported GC-related AE, followed by metabolic events (63%), including weight gain in 51% of them. Cardiovascular and neuropsychiatric events occurred in 51% and 47% of patients, respectively. Osteoporotic fractures, muscular involvement, digestive events, geriatric deterioration, skin fragility, ophthalmologic complications and hypokalaemia were reported in <35% of patients. Cardiovascular events (p = 0.01), osteoporotic fractures (p = 0.004), cataract occurrence (p = 0.03), weight gain (p = 0.04) and infections (p = 0.01) were significantly associated with GC cumulative doses > 9 g. Longer GC durations were associated with cataract occurrence (p = 0.01), weight gain (p = 0.03) and all-grade infections (p = 0.048), especially herpes zoster occurrence (p = 0.003). Neuropsychiatric and metabolic events appeared within the first months after GC introduction, whereas herpes zoster recurred, and most cardiovascular AEs emerged after 1 year. Geriatric events, especially osteoporotic fractures, occurred 2 years after GC introduction. CONCLUSION: This study highlights how frequent GC-related AEs are and the impact of prolonged GC and cumulative doses.

Tolerance of glucocorticoids in giant cell arteritis: a study of patient-reported adverse events.

OBJECTIVE: To assess patients' self-reported glucocorticoid (GC)-related adverse events (AEs) in a GCA population. METHODS: A questionnaire was sent to the 100 patients most recently diagnosed with GCA in a tertiary centre. This questionnaire included open- and close-ended questions on the disease and GC effects. Eight primary AE areas were analysed: cardiovascular, metabolic, muscle, cognitive and psychologic, bone, cutaneous and hairiness, infective and visual complications. Including derivative subitems from preceding areas, a total of 18 GC-related AEs were analysed separately and according to GC duration. RESULTS: Ninety patients were analysed and 89 (99%) reported at least one GC-related AE [median 6 (range 1-11)]. Cognitive and psychological changes, primarily insomnia (72%), affected 90% of patients. Cutaneous changes and muscle loss affected 70% of patients, with frequent impairment of physical autonomy (P = 0.007) associated with this event. Metabolic issues, especially weight gain (40%) and diabetes mellitus (20%), affected 49% of patients. Conversely, vision troubles and bone fractures were mentioned by 42% and 9% of patients, respectively, and more frequently in patients who received GCs for >18 months (P = 0.01 and P = 0.007, respectively). Cardiovascular changes and infections affected 30% and 26% of patients, respectively. CONCLUSION: This real-life study of GC tolerance assessed using a self-evaluation provides pragmatic and updated data reminding us that GC tolerance remains more noteworthy than ever. This study suggests carefully monitoring GC-related AEs during follow-up and encourages GC-sparing strategies in some patients.

Successful pregnancy and fetal outcome following previous treatment with pembrolizumab for relapsed Hodgkin's lymphoma.

BACKGROUND: Classical Hodgkin lymphoma (cHL) is one of the most frequently diagnosed neoplasms in young adults and is curable even in the relapse setting. Many patients seek advice regarding pregnancy once they have a sustained complete remission (CR). PD1 inhibitors are effective in inducing CRs in relapsed cHL, but little is known about their effects on pregnancy, fetal outcomes, or risk of relapse. The PD1/PDL1 axis is vital in the maintenance of pregnancy, allowing for fetal tolerance. This axis is also a key pathway by which Hodgkin Reed Sternberg cells escape immune surveillance. Thus, exposure to PD1 inhibitors in the context of a pregnant cHL survivor could potentially lead to maternal and fetal complications as well as increase the risk of relapse. Pregnancy and fetal outcomes following PD1 inhibitors have been reported in women with melanoma, but not cHL. Such data may help physicians counsel their patients on this topic. CASE: This case describes a 25-year-old woman who was diagnosed with advanced stage cHL that was treated with multiple courses of chemotherapy and autologous stem cell transplant (ASCT) for primary refractory disease. She experienced a relapse eight months following ASCT and was treated with the PD1 inhibitor pembrolizumab. She completed a total of 21 cycles, achieving a CR after cycle five. After 2 years of sustained CR off pembrolizumab, she had an unassisted and uneventful pregnancy. She delivered a healthy baby boy with no significant complications. He reached his normal milestones in his first year. She remains in CR four years following her last dose of pembrolizumab, evoking the possibility of her being cured of cHL. CONCLUSION: Successful pregnancies and fetal outcomes, while maintaining clinical remissions, are possible in women with relapsed cHL treated with pembrolizumab.

Impact of Giant Cell Arteritis and Its Treatment on the Patient's Quality of Life: A Single-Center Self-Assessment Study.

Little is known about the impact of giant cell arteritis (GCA) and its treatment on patient-reported physical, mental, and psychic quality of life (QoL). In this monocentric study, a questionnaire was sent to the 100 last patients diagnosed with GCA and followed-up in a single tertiary center. Their physical, mental and psychic status were self-assessed via close-ended questions, the 12-item short form survey (SF-12) and the 15-item geriatric depression scale (GDS). We aimed to identify parameters that were significantly associated with moderate-to-severe disability in both physical and mental domains. Ninety patients were analyzable. Moderate to severe physical disability was found in 41 (46%) patients. In multivariate analysis, walking difficulties (OR, 95% CI 8.42 [2.98-26.82], p <0.0001), muscle mass and strength reduction (OR, 95% CI 4.38 [1.37-16.31], p = 0.01) and age >80 (OR, 95% CI 4.21 [1.44-13.61], p = 0.008) were independent findings associated with moderate to severe physical disability. Moderate to severe mental disability was found in 30 (33%) patients. In multivariate analysis, depressive mood (OR, 95% CI 11.05 [3.78-37.11], p < 0.0001), felt adverse events attributable to glucocorticoids (OR, 95% CI 10.54 [1.65-213.1], p = 0.01) and use of immune-suppressants (OR, 95% CI 3.50 [1.14-11.87], p = 0.03) were independent findings associated with moderate to severe mental disability. There was a statistically significant negative correlation between GDS and the physical and/or mental disability scores (GDS and PCS-12: r = -0.33, p = 0.0013; GDS and MCS-12: r = -0.36, p = 0.0005). In conclusion, this study identified via a self-assessment of patients with GCA some medical and modifiable findings that significantly affect their physical and mental quality of life. A better knowledge of these factors may help improve the care of GCA patients.

Chronic intestinal pseudo-obstruction with dilated biliary tract as a spectrum of stiff person syndrome in a nondiabetic patient.

Stiff person syndrome (SPS) is a rare and challenging neuromuscular junction disorder with typical musculoskeletal manifestations associated with anti-GAD65 antibodies, extra rheumatological manifestations, including neuropsychiatric symptoms and severe dysautonomic troubles. Chronic intestinal pseudo-obstruction (CIPO) is also a rare condition corresponding to a sub-occlusive syndrome, resulting from the functional or structural impairment of smooth neuromuscular tissues of the intestinal tract. In the clinical spectrum of SPS, CIPO has rarely been described and dilated biliary tract has never been described. This present report is therefore the first in the context of anti-GAD65 antibodies with the additional involvement of the biliary tract. Here, we report the case of a 44-year-old woman hospitalized for a rapidly progressive CIPO associated with dilated biliary tract, revealing a typical SPS with slowly progressive rheumatologic complaints relegated to the background. The concomitant improvement of the neuromuscular function on skeletal, intestinal and biliary tree systems with the good outcomes of anti-GAD65 titer under immunosuppressant drugs, allowed us to link all three organic involvements to the antibody pathogenicity on the respective neuromuscular junctions. Therefore, we discussed their common pathogeny based on our patient's treatment outcome.