Treatment of axial spondyloarthritis patients with biologic disease-modifying anti-rheumatic drugs in 2022 - data from the Romanian Registry of Rheumatic Diseases

Objective. The objective of this cross-sectional study was to analyze data available in the Romanian Registry of Rheumatic Diseases (RRBR) in 2022 for axial spondyloarthritis (axSpA) patients treated with biologic disease modifying anti-rheumatic drugs (bDMARDs). Methods. From the RRBR electronic database were collected multiple variables, including patient’s demographic and clinical characteristics, treatment characteristics, patterns of treatment use (initiations, continuations, switching, tapering), and treatment efficacy data of axSpA patients, from 1 January 2022 to 31 December 2022. Results. In 2022, a total of 4315 axSpA patients were registered in the RRBR database: 70% were men, 48.4 years mean age, 13.3 years mean disease duration, 90% with radiographic axSpA, with high prevalence of extra-musculoskeletal manifestations and cardiovascular comorbidities. Most patients (88%) were treated with a tumor necrosis factor inhibitor (TNFi), usually in monotherapy. The most frequently prescribed bDMARDs were adalimumab (36%), etanercept (32%) and secukinumab (12%). The uptake of biosimilars reached one third of patients from molecules with available biosimilars in 2022. Most patients had a good clinical response, irrespective of clinical form, disease duration, type of medication or line of treatment. Medication switching was needed in 10% of patients, the main reason for switching was secondary loss of efficacy. Medication tapering was implemented in 11% of patients, and it was successful in 90% of cases. Conclusion. Data from RRBR provide a valuable real-world view of clinical practice at the national level regarding biologic treatment of axSpA patients

The AO Spine Thoracolumbar Injury Classification System and Treatment Algorithm in Decision Making for Thoracolumbar Burst Fractures Without Neurologic Deficit

STUDY DESIGN: Prospective Observational Study. OBJECTIVE: To determine the alignment of the AO Spine Thoracolumbar Injury Classification system and treatment algorithm with contemporary surgical decision making. METHODS: 183 cases of thoracolumbar burst fractures were reviewed by 22 AO Spine Knowledge Forum Trauma experts. These experienced clinicians classified the fracture morphology, integrity of the posterior ligamentous complex and degree of comminution. Management recommendations were collected. RESULTS: There was a statistically significant stepwise increase in rates of operative management with escalating category of injury (P \u3c .001). An excellent correlation existed between recommended expert management and the actual treatment of each injury category: A0/A1/A2 (OR 1.09, 95% CI 0.70-1.69, P = .71), A3/4 (OR 1.62, 95% CI 0.98-2.66, P = .58) and B1/B2/C (1.00, 95% CI 0.87-1.14, P = .99). Thoracolumbar A4 fractures were more likely to be surgically stabilized than A3 fractures (68.2% vs 30.9%, P \u3c .001). A modifier indicating indeterminate ligamentous injury increased the rate of operative management when comparing type B and C injuries to type A3/A4 injuries (OR 39.19, 95% CI 20.84-73.69, P \u3c .01 vs OR 27.72, 95% CI 14.68-52.33, P \u3c .01). CONCLUSIONS: The AO Spine Thoracolumbar Injury Classification system introduces fracture morphology in a rational and hierarchical manner of escalating severity. Thoracolumbar A4 complete burst fractures were more likely to be operatively managed than A3 fractures. Flexion-distraction type B injuries and translational type C injuries were much more likely to have surgery recommended than type A fractures regardless of the M1 modifier. A suspected posterior ligamentous injury increased the likelihood of surgeons favoring surgical stabilization

The Diagnostic Process of Spinal Post-Traumatic Deformity: An Expert Survey of 7 Cases, Consensus on Clinical Relevance Does Exist

STUDY DESIGN: Survey of cases. OBJECTIVE: To evaluate the opinion of experts in the diagnostic process of clinically relevant Spinal Post-traumatic Deformity (SPTD). SUMMARY OF BACKGROUND DATA: SPTD is a potential complication of spine trauma that can cause decreased function and quality of life impairment. The question of when SPTD becomes clinically relevant is yet to be resolved. METHODS: The survey of 7 cases was sent to 31 experts. The case presentation was medical history, diagnostic assessment, evaluation of diagnostic assessment, diagnosis, and treatment options. Means, ranges, percentages of participants, and descriptive statistics were calculated. RESULTS: Seventeen spinal surgeons reviewed the presented cases. The items\u27 fracture type and complaints were rated by the participants as more important, but no agreement existed on the items of medical history. In patients with possible SPTD in the cervical spine (C) area, participants requested a conventional radiograph (CR) (76%-83%), a flexion/extension CR (61%-71%), a computed tomography (CT)-scan (76%-89%), and a magnetic resonance (MR)-scan (89%-94%). In thoracolumbar spine (ThL) cases, full spine CR (89%-100%), CT scan (72%-94%), and MR scan (65%-94%) were requested most often. There was a consensus on 5 out of 7 cases with clinically relevant SPTD (82%-100%). When consensus existed on the diagnosis of SPTD, there was a consensus on the case being compensated or decompensated and being symptomatic or asymptomatic. CONCLUSIONS: There was strong agreement in 5 out of 7 cases on the presence of the diagnosis of clinically relevant SPTD. Among spine experts, there is a strong consensus to use CT scan and MR scan, a cervical CR for C-cases, and a full spine CR for ThL-cases. The lack of agreement on items of the medical history suggests that a Delphi study can help us reach a consensus on the essential items of clinically relevant SPTD. LEVEL OF EVIDENCE: Level V

Expert Opinion, Real-World Classification, and Decision-Making in Thoracolumbar Burst Fractures Without Neurologic Deficits?

STUDY DESIGN: Retrospective analysis of prospectively collected data. OBJECTIVES: To compare decision-making between an expert panel and real-world spine surgeons in thoracolumbar burst fractures (TLBFs) without neurological deficits and analyze which factors influence surgical decision-making. METHODS: This study is a sub-analysis of a prospective observational study in TL fractures. Twenty two experts were asked to review 183 CT scans and recommend treatment for each fracture. The expert recommendation was based on radiographic review. RESULTS: Overall agreement between the expert panel and real-world surgeons regarding surgery was 63.2%. In 36.8% of cases, the expert panel recommended surgery that was not performed in real-world scenarios. Conversely, in cases where the expert panel recommended non-surgical treatment, only 38.6% received non-surgical treatment, while 61.4% underwent surgery. A separate analysis of A3 and A4 fractures revealed that expert panel recommended surgery for 30% of A3 injuries and 68% of A4 injuries. However, 61% of patients with both A3 and A4 fractures received surgery in the real world. Multivariate analysis demonstrated that a 1% increase in certainty of PLC injury led to a 4% increase in surgery recommendation among the expert panel, while a .2% increase in the likelihood of receiving surgery in the real world. CONCLUSION: Surgical decision-making varied between the expert panel and real-world treating surgeons. Differences appear to be less evident in A3/A4 burst fractures making this specific group of fractures a real challenge independent of the level of expertise

First record of Rhabdoceras suessi (Ammonoidea, Late Triassic) from the Transylvanian Triassic Series of the Eastern Carpathians (Romania) and a review of its biochronology, paleobiogeography and paleoecology

Abstract The occurrence of the heteromorphic ammonoid Rhabdoceras suessi Hauer, 1860, is recorded for the first time in the Upper Triassic limestone of the Timon-Ciungi olistolith in the Rarău Syncline, Eastern Carpathians. A single specimen of Rhabdoceras suessi co-occurs with Monotis (Monotis) salinaria that constrains its occurrence here to the Upper Norian (Sevatian 1). It is the only known heteromorphic ammonoid in the Upper Triassic of the Romanian Carpathians. Rhabdoceras suessi is a cosmopolitan species widely recorded in low and mid-paleolatitude faunas. It ranges from the Late Norian to the Rhaetian and is suitable for high-resolution worldwide correlations only when it co-occurs with shorter-ranging choristoceratids, monotid bivalves, or the hydrozoan Heterastridium. Formerly considered as the index fossil for the Upper Norian (Sevatian) Suessi Zone, by the latest 1970s this species lost its key biochronologic status among Late Triassic ammonoids, and it generated a controversy in the 1980s concerning the status of the Rhaetian stage. New stratigraphic data from North America and Europe in the subsequent decades resulted in a revised ammonoid biostratigraphy for the uppermost Triassic, the Rhaetian being reinstalled as the topmost stage in the current standard timescale of the Triassic. The geographic distribution of Rhabdoceras is compiled from published worldwide records, and its paleobiogeography and paleoecology are discussed

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Specific Associations Between Clinical Signs, Immune Cells, Disease Genetic Background and Burden in a Group of Patients with B-Cell Chronic Lymphocytic Leukemia

Traficul limfocitelor maligne și normale prin sângele periferic (PB) către ganglioni, splina și ficat este guvernat de modificări specifice ale nivelelor de expresie de suprafață/ intracelulară a unor molecule. Studiul își propune să investigheze asocierea dintre diferite subseturi limfocitare, receptori pentru chemokine sau aberații genetice și anumite simptome clinice la pacienți cu LLC-B. Patruzeci și trei de pacienți au fost incluși în studiu. Prin citometrie în flux multiparametrică a fost testată expresia pentru CCR7, CXCR5, CXCR3, CCR4, CD3, CD4, CD8, CD27, CD28, CD45RA, CD25, CD127, CD38. Defectele genetice au fost determinate prin MLPA. Am observat o frecvență crescută a celulelor CD38+ clonale corelată cu infiltrarea ganglionilor>5cm. CXCR5 si CCR7 sunt omogen exprimați de celulele de LLC-B. Frecvența celulelor B CCR4+ este redusă la pacienții cu un anumit tip de infiltrare ganglionară. Am detectat aberații genetice heterogene și complexe și trisomia 12 este mai frecventă la pacienții ce nu prezintă ganglioni axilari. Deasemenea, frecvența limfocitelor T totale și a unor subseturi (memorie efector și centrală, T reglatorii, T helper foliculare, diferite subseturi funcționale CD8+) este crescută doar concomitent cu prezența anumitor manifestări clinice. Expresia receptorilor pentru chemokine la nivelul limfocitelor T CD4+ este crescută în conexiune cu anumite localizări ganglionare. În concluzie, manifestările clinice la pacienții cu LLC-B sunt în strânsă legatură atât cu factori intrinseci limfocitelor B clonale, cât și de influențe externe, furnizate de semnale provenite din micromediu

Using Equipoise to Determine the Radiographic Characteristics Leading to Agreement on Best Treatment for Thoracolumbar Burst Fractures Without Neurologic Deficits.

STUDY DESIGN Retrospective analysis of prospectively collected data. OBJECTIVES Our goal was to assess radiographic characteristics associated with agreement and disagreement in treatment recommendation in thoracolumbar (TL) burst fractures. METHODS A panel of 22 AO Spine Knowledge Forum Trauma experts reviewed 183 cases and were asked to: (1) classify the fracture; (2) assess degree of certainty of PLC disruption; (3) assess degree of comminution; and (4) make a treatment recommendation. Equipoise threshold used was 77% (77:23 distribution of uncertainty or 17 vs 5 experts). Two groups were created: consensus vs equipoise. RESULTS Of the 183 cases reviewed, the experts reached full consensus in only 8 cases (4.4%). Eighty-one cases (44.3%) were included in the agreement group and 102 cases (55.7%) in the equipoise group. A3/A4 fractures were more common in the equipoise group (92.0% vs 83.7%, P < .001). The agreement group had higher degree of certainty of PLC disruption [35.8% (SD 34.2) vs 27.6 (SD 27.3), P < .001] and more common use of the M1 modifier (44.3% vs 38.3%, P < .001). Overall, the degree of comminution was slightly higher in the equipoise group [47.8 (SD 20.5) vs 45.7 (SD 23.4), P < .001]. CONCLUSIONS The agreement group had a higher degree of certainty of PLC injury and more common use of M1 modifier (more type B fractures). The equipoise group had more A3/A4 type fractures. Future studies are required to identify the role of comminution in decision making as degree of comminution was slightly higher in the equipoise group

The AO Spine Thoracolumbar Injury Classification System and Treatment Algorithm in Decision Making for Thoracolumbar Burst Fractures Without Neurologic Deficit.

STUDY DESIGN Prospective Observational Study. OBJECTIVE To determine the alignment of the AO Spine Thoracolumbar Injury Classification system and treatment algorithm with contemporary surgical decision making. METHODS 183 cases of thoracolumbar burst fractures were reviewed by 22 AO Spine Knowledge Forum Trauma experts. These experienced clinicians classified the fracture morphology, integrity of the posterior ligamentous complex and degree of comminution. Management recommendations were collected. RESULTS There was a statistically significant stepwise increase in rates of operative management with escalating category of injury (P < .001). An excellent correlation existed between recommended expert management and the actual treatment of each injury category: A0/A1/A2 (OR 1.09, 95% CI 0.70-1.69, P = .71), A3/4 (OR 1.62, 95% CI 0.98-2.66, P = .58) and B1/B2/C (1.00, 95% CI 0.87-1.14, P = .99). Thoracolumbar A4 fractures were more likely to be surgically stabilized than A3 fractures (68.2% vs 30.9%, P < .001). A modifier indicating indeterminate ligamentous injury increased the rate of operative management when comparing type B and C injuries to type A3/A4 injuries (OR 39.19, 95% CI 20.84-73.69, P < .01 vs OR 27.72, 95% CI 14.68-52.33, P < .01). CONCLUSIONS The AO Spine Thoracolumbar Injury Classification system introduces fracture morphology in a rational and hierarchical manner of escalating severity. Thoracolumbar A4 complete burst fractures were more likely to be operatively managed than A3 fractures. Flexion-distraction type B injuries and translational type C injuries were much more likely to have surgery recommended than type A fractures regardless of the M1 modifier. A suspected posterior ligamentous injury increased the likelihood of surgeons favoring surgical stabilization