Peripheral Involvement Research Articles

Leukostasis Twist in Mantle Cell Lymphoma: Systematic Review and Case Report

Introduction: Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma. Patients often present with lymphadenopathy, early satiety, and B-symptoms. Despite up to 92% of MCL patients having peripheral blood involvement by flow cytometry, presentation with leukemic involvement and hyperleukocytosis are uncommon. Hyperleukocytosis, marked by a white blood count (WBC) >100 x 10 9/L, often leads to symptomatic leukostasis due to tissue hypoxia, generally found in acute leukemias. We conducted a systematic review of leukostasis in MCL, and present a case we encountered in our clinical practice of a non-nodal MCL variant showing leukostasis, spontaneous tumour lysis syndrome (TLS), and severe anemia to identify treatment strategies and outcomes. Methods: We searched PubMed for peer-reviewed articles and abstracts on “mantle cell lymphoma,” “hyperleukocytosis,” and “leukostasis.” All articles and abstracts that discuss hyperleukocytosis leading to leukostasis in MCL were included. Results: The search yielded eight results. After exclusions, five case reports and abstracts were included. These studies featured different MCL variants, presenting WBCs ranging from 121 to 1227 x 10 9/L, and various leukostasis symptoms. Leukapheresis was used in all five published cases, leading to lower WBCs and symptom improvement. Results are summarized in Table 1. Our patient was found to have the small lymphocyte variant of MCL, with WBC of 543.3 x 10 9/L on presentation. Our facility does not have leukapheresis capability. As a result, our initial treatment consisted of only supportive care and escalating doses of corticosteroids, with close monitoring for TLS. To our knowledge, this report is the first demonstration that IV methylprednisolone, without leukapheresis, is effective for acute management of leukostasis. Our patient's WBC reduced from 543.3 x 10 9/L to 230 x 10 9/L, leading to improved neurological function and oxygenation. Steroids were particularly useful in our patient with secondary, MCL-related warm autoimmune hemolytic anemia. Conclusion: This review highlights the importance of recognizing non-specific leukostasis symptoms, even in patients with mature B-cell lymphoproliferative disorders. Leukapheresis is effective in treating leukostasis in MCL patients. In hospitals without leukapheresis, escalating doses of IV methylprednisolone can be considered as a safe and effective strategy.

The Mini-Teddi-R Treatment Demonstrated a High Rate of Remission in Patients with DLBCL Involving the CNS Who Had Previously Been Exposed to BTK Inhibitors

Background: Secondary CNS B-cell lymphomas (SCNSL) are aggressive lymphomas with a bleak prognosis. TEDDI-R has been successful in achieving lasting remission in relapsed/refractory primary DLBCL of the CNS (PCNSL), but the effectiveness of ibrutinib-responsive tumors in SCNSL remains unknown. This study presents initial findings from the use of mini-TEDDi-R in SCNSL. Methods: Efficacy and safety data of mini-TEDDi-R were retrospectively analyzed for patients with DLBCL involving the CNS. All patients experienced relapse in the CNS or/and peripheral region after initial therapy. Brain parenchyma involvement allowed for treatment with MTX, Ara-c, and/or BTK inhibitors. The dosage of the drugs used in the original regimen was reduced, leading to the adoption of the term “mini-TEDDi-R.” Each 21-day cycle involved the following treatments: intravenous rituximab at a dose of 375 mg/m 2/day on days 1-2, oral temozolomide at a dose of 150 mg/m 2/day on days 2-5, intravenous infusion of 30 mg/m 2/day etoposide on days 2-5, intravenous infusion of 25 mg/m 2 of pegylated liposomal doxorubicin on day 2, intravenous infusion of dexamethasone at a dose of 10 mg/m 2/BID on days 1-5, and oral zanubrutinib at a dose of 200mg/BID or oral orelabrutinib at a dose of 150mg/qd or oral ibrutinib at a dose of 560mg/qd from day 1 until neutrophil count <0.5*10^9/L or platelet count <30*10^9/L. Additionally, intrathecal administration of 70 mg of cytarabine occurred on days 1 and 5, All remissions observed on MRI were confirmed through FDG-PET and CSF analysis. Results: Between December 2019 and June 2023, 24 patients with a median age of 53 (range 28-69) received mini-TEDDi-R treatment. All patients had DLBCL, comprising 16 (66.7%) non-GCB, 6 (25%) GCB, and 2 (8.3%) transformed from FL. All patients experienced relapse in the CNS system after a median of 6 (range 1-17) prior therapies, and all (100%) patients received prior anthracycline treatment. A total of 21 patients (87.5%) had received multiple lines of therapy before mini-TEDDi-R. Among them, 19 patients (79.2%) had received HD-MTX based salvage therapy, 11 patients (45.8%) had received HD-Ara-c based salvage therapy, and 14 patients (58.3%) had been exposed to BTK inhibitors. Seven patients (29.2%) showed triple resistance to MTX, Ara-c, and BTK inhibitors. Six patients had previously undergone transplantation, and four patients had experienced failure of CD19 CART treatment. Thirteen patients (54.2%) had isolated CNS disease, while 11 patients (45.8%) had both CNS and peripheral disease. Thirteen patients (54.2%) underwent 1 cycle of mini-TEDDi-R, 8 patients (33.3%) completed 2 cycles, 2 patients (8.3%) finished 3 cycles, and 1 patient (4.2%) completed 4 cycles. The objective remission rate (ORR) was determined to be 70.8%, with a complete remission (CR) rate of 58.3%. Notably, patients (N=14) exposed to BTK inhibitors previously exhibited a similar CR rate compared to patients (N=10) who had not received prior BTK inhibitor treatment (50% vs. 70%, p = 0.348). Patients (N=19) who had undergone HD-MTX based salvage therapy achieved an ORR of 74% and a CR rate of 58%. No significant difference in response rate was observed between patients with peripheral and non-peripheral secondary CNS involvement. In patients who achieved complete remission, only one patient experienced a second CNS relapse. Four patients bridged to auto-HSCT, 2 patients bridged to CART treatment, and 4 patients underwent auto-HSCT combined with CART treatment for consolidation. The median overall survival and median PFS have not been reached within the 11.8-month follow-up period. Toxicity was evaluated over 39 cycles. Grade 3 and 4 neutropenia occurred in 51% and 16% of cycles, respectively, while febrile neutropenia was observed in 10% of cycles. The median duration of neutropenia was 6 days (range 4-10). Three cycles (8%) were complicated by infections graded as ≥G3, but no opportunistic infections (including Aspergillus) were observed. Grade 3 and 4 thrombocytopenia occurred in 26% and 14% of cycles, respectively. The median duration of neutropenia was 7 days (range 3-14). Conclusions: The mini-TEDDi-R regimen demonstrated a favorable remission rate in patients with DLBCL involving the CNS. The treatment was well-tolerated, and patients with tumors that were previously exposed to BTK inhibitors and HD-MTX treatment also showed positive responses to mini-TEDDi-R.

The effect of polypharmacy on rheumatoid and psoriatic arthritis treatment: retrospective study.

Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are chronic, progressive inflammatory diseases that can be accompanied by other diseases. In recent years, with the increase in the lifespan of individuals, the concept of polypharmacy has become more prominent. We aimed to show the prevalence of polypharmacy and the effects of polypharmacy on disease activity in RA and PsA. This study included PsA patients who had peripheral joint involvement and, RA patients. Since PsA has a heterogeneous clinical picture, only patients with peripheral joint involvement were included in the study and patients with inflammatory low back pain or radiological sacroiliitis or spondylitis, dactylitis or enthesitis were not included in the study due to homogeneity concerns. The numbers of medications used by the patients at the onset of their treatment and at sixth months into their treatment were recorded. Polypharmacy was accepted as the simultaneous use of at least five medications by the person. The Disease Activity Score 28 joints C-Reactive Protein (DAS-28 CRP) was used to assess disease activity for both disease. The modified Charlson Comorbidity Index (CCI) scores of the patients were calculated based on their chronic diseases. The sample of the study included 232 RA and 73 PsA patients. Polypharmacy was present at the treatment onset in 115 (49.6%) of the RA patients and 28 (38.4%) of the PsA patients. At the sixth month of treatment, polypharmacy was present in the sixth month of the treatment in 217 (93.5%) RA and 61 (83.6%) PsA patients. The mean ages of the RA and PsA patients who were receiving polypharmacy treatment at the beginning were significantly older than the mean ages of those who were not receiving polypharmacy treatment. In both the RA and PSA groups, the patients with polypharmacy at the beginning had statistically significantly higher DAS-28 CRP scores at six months of treatment than those without polypharmacy at the beginning (p<0.001). Polypharmacy was present both at the time of diagnosis and in the treatment process in the RA and PsA patients, and the presence of polypharmacy at the beginning of the treatment was among the factors that affected the treatment of these patients by significantly affecting their 6th-month DAS-28 CRP values.

What is the association of depression with clinical response to therapy in patients with psoriatic arthritis treated with biologic disease-modifying antirheumatic drugs?

Psoriatic arthritis (PsA) is a chronic, progressive inflammatory joint disease that is associated with higher prevalence of depression. There is limited literature about the impact of depression, particularly regarding the response to therapy. A retrospective cohort study with PsA patients that started their first biologic disease-modifying antirheumatic drugs (bDMARD) was conducted. In the majority of cases, a cutoff score of ≥ 8 in Hospital Anxiety and Depression Scale (HADS) was used to define cases of depression. In cases where patients did not complete the questionnaire, a previous diagnosis made by a psychiatrist was used to establish the presence of depression. Response to therapy 12 months after the start of bDMARD was evaluated and the switch rate to another bDMARD due to inefficacy was assessed at month 12. A total of 129 patients (66 females, 51.2%; mean age of 47.7 ± 11.0 years and mean disease duration of 10.0 ± 7.7 years) with PsA were included. Thirty-two (24.8%) patients had depression. Patients with depression and peripheral involvement had a significantly lower ACR20/50/70 responses (p = 0.001, p = 0.002, and p = 0.001 respectively) after 12 months of therapy and a significantly worse EULAR response (p = 0.002). Furthermore, patients with depression and axial involvement had a significantly worse response based on ASDAS response criteria (p = 0.031). Switch due to ineffectiveness in the first 12 months was significantly higher in patients with depression (p = 0.002). Depression in PsA is a frequent yet often understudied comorbidity. The causal relationship between depression and PsA is difficult to decrypt and further research is needed. Recognition of depressive symptoms is crucial and a multidisciplinary approach should be provided to individuals with this comorbidity. Key Points • Depression in PsA is a frequent yet often understudied comorbidity. In our study, the prevalence of depression was 24.8%. • Depression in PsA seems to be associated to lower response to therapy and higher discontinuation rates of bDMARD. • Recognition of depressive symptoms is crucial and a multidisciplinary approach should be provided to individuals with this comorbidity.

Difficult-to-treat axial spondyloarthritis is associated with psoriasis, peripheral involvement and comorbidities: results of an observational nationwide study

ObjectivesTo determine the cumulative incidence and identify the factors associated with difficult-to-treat axial spondyloarthritis (D2T-axSpA) in French patients newly benefiting from the French ‘long-term illness’ (LTI) social security scheme for...

Abstract 19 — Treat-to-Target in Spondyloarthritis (SpA): Are There Sex-Related Differential Responses?

Background: Studies have reported that female patients with spondyloarthritis have different disease courses and treatment responses compared to male patients. Whether patients’ sex is associated with a different outcome after receiving one-year of tight control, treat-to-target (T2T) strategy remains uncertain. Thus, this study aimed to evaluate the differences in the clinical response between male and female patients from the APLAR SpA Registry. Methods: Patients who fulfilled the CASPAR 2006 classification criteria for PsA and 2009 ASAS classification for axSpA were recruited. They received 1 year of protocolized treatment aiming at 1) MDA or DAPSA-LDA for PsA patients, and 2) ASDAS-LDA for axSpA patients. Patients were assessed every 3-monthly and treatment was escalated if target was not reached. Results: Ninety-one male (age: 45.6±16.1, 43 PsA, 48 axSpA) and 52 female (age: 49.2±13.4, 36 PsA, 16 axSpA) patients were included. There was no significant difference between the 2 sexes at baseline, except a higher ESR and more severe enthesitis in female patients. During the study period, the use of csDMARDs and NSAIDs decreased slightly, whilst the use of bDMARDs significantly increased across both sexes (Fig. 1a). Considering the whole cohort, there were significant improvement in disease activity in PsA after 1-year and disease activity in axSpA remained low. Despite similar bDMARDs use at 1-year, female PsA patients had a lower MDA achievement rate (36% in female vs 51% in male). Female patients also remained to have a higher physician global assessment score (2.61±1.76 in female vs 1.98±1.57 in male, p=0.03), greater functional impairment (HAQ: 0.54±0.57 in female vs 0.32±0.46 in male, p=0.01) and more severe enthesitis (SPARCC: 0.83±1.67 in female vs 0.16±1.09 in male, p=0.005) at 1-year. There was also a trend of higher perceived disease burden and peripheral involvement in female (Fig. 1b). Conclusion: There may be differential treat-to-target responses between male and female SpA patients. The causes of such differential characteristics should be further explored to potentially implement a sex-specific treat-to-target strategy for spondyloarthritis.

Bilateral fibro-osseous TMJ ankylosis in Marie-Strumpell disease: a case report

Reporting a case of bilateral fibro-osseous TMJ ankylosis in Marie-Strumpell disease. Managed with interposition gap arthroplasty with temporalis myofacial flap. Marie-Strumpell disease or ankylosing spondylitis is a chronic inflammatory disorder affecting predominantly the axial skeleton although peripheral joint involvement may be a significant feature. Temporo-mandibular joint involvement in ankylosing spondylitis varies from 4% to 35%. A 53-year-old male patient reported to our department with a chief complaint of difficulty in opening his mouth and difficulty in eating food. The case was diagnosed as a case of bilateral fibro-osseous TMJ ankylosis associated with ankylosing spondylitis. The individual was managed with aggressive resection of ankylotic segments and inter-position of the temporalis myofascial flap bilaterally with early mobilization and aggressive physiotherapy. Aggressive resection of the ankylotic mass with inter-positional gap arthroplasty with early mobilization and aggressive physiotherapy is a highly effective and safe surgical management option for the management of TMJ ankylosis and with acceptable immediate and long-term outcome with minimum re-ankylosis and have produced satisfactory mandibular movements.

Comparison of Computed Tomography Findings between Adult and Pediatric COVID-19 Patients.

This study aims to compare chest computed tomography (CT) findings between adult and pediatric patients with coronavirus disease-19 (COVID-19) pneumonia. This study included 30 pediatric patients aged 1 to 17 years and 30 adult patients over 18 years of age with COVID-19 pneumonia confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) who have findings related to COVID-19 on Chest Computed Tomography. The CT findings of adult and pediatric patients were compared with a z-test. Bilateral involvement (p:0.00056), involvement in all five lobes (p<0.00001), and central and peripheral involvement (p:0.01928) were significantly higher in the adult group compared to the pediatric group. In the pediatric group, the frequency of unilateral involvement (p:0.00056), involvement of solitary lobe (p:0.00132), and peripheral involvement (p: 0.01928) were significantly higher than in the adult group. The most common parenchymal finding in adults and pediatric patients was ground-glass opacities (100% and 83%, respectively). Among the parenchymal findings in adults, ground-glass opacities with consolidation (63%) were the second most common finding, followed by air bronchogram (60%) in adults, while in pediatric patients, halo sign (27%) and nodule (27%) were the second most common, followed by the ground-glass opacities with consolidation (23%). The CT findings of pediatric COVID-19 patients must be well-known as the course of the disease is usually less severe, and the radiological findings are uncertain when compared with adults.

Upadacitinib effectiveness and factors associated with minimal disease activity achievement in patients with psoriatic arthritis: preliminary data of a real-life multicenter study

BackgroundUpadacitinib (UPA) is a selective JAK inhibitor recently approved for the treatment of psoriatic arthritis (PsA). In this post-approval study, we aimed to evaluate the effectiveness and safety of UPA over 24 weeks and identify clinical predictors of response, in a multicentric cohort of patients affected by PsA.MethodsOne hundred and twenty-six patients with PsA treated with UPA were enrolled in 10 Italian centres. UPA effectiveness outcomes, such as the proportion of patients with MDA status, DAPSA remission, and low disease activity, ASDAS-CRP inactive and low disease activity, and change from baseline in DAPSA and ASDAS-CRP scores, were evaluated every 12 weeks until week 24. The proportion of DAPSA minor, moderate, and major improvement, and ASDAS clinically important improvement (CII) and major improvement (MI) were considered as well. All treatment-related adverse events were collected during the observation period. Clinical predictors of MDA response at week 24 were evaluated through multivariate analysis.ResultsAt baseline, 124/126 (98%) and 54/126 (43%) patients showed peripheral and axial involvement, respectively; 110 (87%) patients were intolerant or resistant to biologic DMARDs. At 24 weeks, MDA status, DAPSA remission, and ASDAS-CRP inactive disease were achieved in 47%, 23%, and 48% of patients, respectively. Minor, moderate, and major DAPSA improvement was observed in 67%, 39%, and 23%, respectively; while 65% and 35% achieved ASDAS-CRP CII and MI, respectively. The mean change from baseline was 15.9 ± 13.5 (p < 0.001) for DAPSA and 1.21 ± 0.97 (p < 0.001) for ASDAS-CRP. Thirteen patients (10%) discontinued UPA due to a lack of efficacy or non-serious adverse events. No serious adverse events were observed. Male gender (OR 2.54, 95% CI 1.03–6.25 p = 0.043), being naïve to biological DMARDs (OR 4.13, 95% CI 1.34–12.71, p = 0.013) and elevated baseline CRP (OR 2.49, 95% CI 1.02–6.12, p = 0.046) were associated with MDA response at week 24.ConclusionsThis is one of the first real-life studies supporting the effectiveness of UPA and its safety profile in PsA patients. Furthermore, the study identifies predictors of MDA response to UPA treatment at 6 months.

Exploring the links among peripheral immunity, biomarkers, cognition, and neuroimaging in Alzheimer's disease.

We analyzed relationships among peripheral immunity markers, cognition, Alzheimer's disease (AD)-related biomarkers, and neuroimaging to understand peripheral immunity involvement in AD. Peripheral immunity markers were assessed in AD, non-AD neurodegenerative disorders, and controls, examining their connections with cognition, AD-related biomarkers, and neuroimaging using multiple regression models. The study included 1579 participants. Higher levels of white blood cell, neutrophil, monocyte, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and lower lymphocyte-to-monocyte ratio (LMR) were associated with cognitive decline and more severe anxiety and depression. The impact of lower LMR, lymphocyte count, and higher NLR on cognitive decline is mediated through cerebrospinal fluid amyloid beta (Aβ) levels. Additionally, increased PLR, NLR, and SII were associated with brain atrophy and hippocampal Aβ deposition (amyloid positron emission tomography). Peripheral immunity markers offer a non-invasive and cost-effective means of studying AD-related pathophysiological changes, providing valuable insights into its pathogenesis and treatment. Peripheral immunity markers linked to cognitive decline and anxiety/depression.Low LMR, LYM, and high NLR linked to reduced CSF Aβ, impacting cognition.High PLR, NLR, SII associated with brain atrophy and hippocampal Aβ deposition.

Mucocutaneous lesions associated with lymphoproliferative disorder: a case report

Introduction: Leukemia is a type of blood cancer characterized by the accumulation of mature or immature cells in the bone marrow (BM), peripheral blood, lymph nodes, and lymphoid tissues. These cells can cause extranodal infiltration in tissues such as skin (leukemia cutis [LC]) and mucous membranes, being these locations rare. Case presentation: The patient was referred to a university hospital, where BM and computed tomography tests were performed, showing peripheral lymphatic involvement and maxillary paranasal sinus (PNS) opacity. Subsequently, functional endoscopic sinus surgery (FESS) of the PNS was performed and biopsies were taken from the skin lesion and PNS mucosa. Based on the results of the BM tests, the patient was diagnosed with B-cell acute lymphoblastic leukemia, so chemotherapy (CT) was initiated. The biopsy report described infiltration of leukemoid neoplastic cells in both locations (skin lesion and PNS mucosa), confirmed by immunohistochemistry. During CT, the patient developed bone marrow aplasia, tumor lysis syndrome and septic and hypovolemic shock, which eventually led to his death. Conclusion: LC is a rare condition associated with poor prognosis, so once detected it is necessary to initiate systemic treatment and look for possible extramedullary metastases. PNS opacity in patients with oncologic immunosuppression is usually considered as nasosinusal infection; however, it may also be secondary to an unusual infiltrative involvement of leukemia.

The clinical characteristics and prognosis of patients with SAPHO syndrome--a real-world cohort study.

We aimed to analyze the clinical characteristics and outcomes of patients with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. The clinical records of 64 patients with SAPHO syndrome were collected, and the treatment and outcomes of 27 patients were followed up. The patients were divided into three groups according to the site of bone lesions: only anterior chest wall (ACW) involvement, only spinal involvement, and bone lesion involvement at both sites. The clinical characteristics and outcomes were compared. The clinical characteristics of the patients with and without peripheral joint involvement were compared. Among all patients, 31.25% (20/64) had only ACW involvement, 15.63% (10/64) had only spinal involvement, and 53.12% (34/64) had both ACW and spinal involvement. Peripheral joint involvement was observed in 25.00% (16/64) of the patients. Patients with only spinal involvement were older than those with only ACW involvement (p = 0.006). Patients with both ACW and spinal involvement were olderthan those with only ACW involvement (p = 0.002) and had a longerdiagnosis delay (p = 0.015). Patients with peripheral joint involvement were younger than those without peripheral joint involvement (p = 0.028). During follow-up, 88.89% (24/27) of patients had good outcomes. Twenty-two patients were treated with non-steroidal anti-inflammatory drugs + Iguratimod (IGU), and the outcomes of 90.91% (20/22) improved. A relationship may exist between the sites of bone lesions and clinical characteristics of patients with SAPHO syndrome. The clinical outcomes of these patients may be good, and IGU may be effective in treating SAPHO syndrome. Key Points • This study is the first long-term follow-up on the effectiveness of iguratimod in treating patients with SAPHO. • This study revealed that patients with SAPHO and different bone lesion sites may present with different clinical characteristics.

Evaluation of facial nerve perineural spread from cutaneous squamous cell carcinoma using 3T MR neurography.

Perineural spread (PNS) is a rare but potentially fatal consequence of cutaneous squamous cell carcinoma (cSCC) of the head and neck. We aimed to evaluate the accuracy of 3T MR neurography in detecting and defining the extent of facial nerve (VII) PNS from cSCC, and highlight characteristic radiological features in peripheral branches to improve early diagnosis. Single-institution retrospective review of 38 patients with clinical, radiological, and/or histopathological findings consistent with VII PNS from cSCC who underwent pre-operative 3T MR neurography. Compared to histopathology (gold standard), 3T MR neurography had a sensitivity of 89% and positive predictive value of 97%. In true-positive cases (n = 33), zonal extent was correctly identified in 100%. Seventy-nine% had simultaneous trigeminal nerve (V) PNS, mostly involving the auriculotemporal branch of the mandibular nerve (64%). When the causative lesion was absent (n = 23), the extra-temporal VII demonstrated asymmetrical enhancement alone (n = 6), bulky expansion (n = 8), or extra-neural spread (n = 9). Peripheral VII branch involvement, particularly the buccal and zygomatic, was readily identified using known anatomical landmarks. 3T MR neurography is highly accurate in evaluating VII PNS from cSCC, and thus should be specifically requested by physicians if suspicious for disease. Coexistent V PNS was common, highlighting the need to examine V branches to allow complete treatment planning. The unique radiological patterns identified showcases disease progression. As early detection improves patient outcomes, the radiologist must look for peripheral VII involvement inspecific anatomical areas, which is within the capabilities of 3T MR neurography.

Cause analysis of conversion to biologics in spondyloarthritis patients with poor response to conventional treatment.

We sought to investigate the reasons why spondyloarthritis (SpA) patients failed to respond to non-steroidal anti-inflammatory drugs (NSAIDs) and conventional synthetic disease-modifying antirheumatic drugs (cDMARDs) and the influences of different initial cDMARDs on the likelihood of a switch to biologics. SpA patients were divided into a conventional drug maintenance group and a biologics conversion group to determine the causes of conversion to biologics. Then, we divided all patients into three groups according to different initial cDMARDs, NSAID monotherapy, NSAID + (sulfasalazine or thalidomide) double combination, and NSAID + sulfasalazine + thalidomide triple combination therapy groups, to clarify the influence of initial treatment on later conversion to biologics. This study includes 202 patients, including 97 patients in the conventional drug maintenance group and 105 patients in the biologics conversion group. The mean age of the conventional drug maintenance group was higher than that of the biologics conversion group (40.8 ± 14.3 vs. 33.8 ± 12.3 years, P < 0.05). Uveitis (OR 5.356, P < 0.05) is positively correlated with conversion to biological therapy, while age (OR 0.940, P < 0.05) is negatively correlated. The proportion of NSAID monotherapy, double combination, and triple combination groups converted to biological agents was 80%, 51.1%, and 23.2%, respectively (P < 0.05). Age and uveitis are related to conversion to biologics therapy. The early combination of sulfasalazine and thalidomide with NSAIDs may lower the probability of conversion to biologics therapy in the later stage and offer a new option for patients with limited use of biologics in SpA patients. Key Points • Patients' move to biologics may be caused mostly by inadequate disease control by conventional oral medications. • Regardless of axial vs. peripheral joint involvement, combination drug therapy was superior to single drug therapy in controlling SpA and decreasing the probability of conversion to a biological agent. • For SpA patients who are not candidates for biologics due to contraindications or other reasons, early combination application of NSAIDs, sulfasalazine, and thalidomide may be a new choice.

Cluster Analysis to Explore Clinical Subphenotypes of Eosinophilic Granulomatosis With Polyangiitis.

Previous studies suggested that distinct phenotypes of eosinophilic granulomatosis with polyangiitis (EGPA; formerly known as Churg-Strauss syndrome) could be determined by the presence or absence of antineutrophil cytoplasmic antibodies (ANCA), reflecting predominant vasculitic or eosinophilic processes, respectively. This study explored whether ANCA-based clusters or other clusters can be identified in EGPA. This study used standardized data of 15 European centers for patients with EGPA fulfilling widely accepted classification criteria. We used multiple correspondence analysis, hierarchical cluster analysis, and a decision tree model. The main model included 10 clinical variables (musculoskeletal [MSK], mucocutaneous, ophthalmological, ENT, cardiovascular, pulmonary, gastrointestinal, renal, central, or peripheral neurological involvement); a second model also included ANCA results. The analyses included 489 patients diagnosed between 1984 and 2015. ANCA were detected in 37.2% of patients, mostly perinuclear ANCA (85.4%) and/or antimyeloperoxidase (87%). Compared with ANCA-negative patients, those with ANCA had more renal (P < 0.001) and peripheral neurological involvement (P = 0.04), fewer cardiovascular signs (P < 0.001), and fewer biopsies with eosinophilic tissue infiltrates (P = 0.001). The cluster analyses generated 4 (model without ANCA) and 5 clusters (model with ANCA). Both models identified 3 identical clusters of 34, 39, and 40 patients according to the presence or absence of ENT, central nervous system, and ophthalmological involvement. Peripheral neurological and cardiovascular involvement were not predictive characteristics. Although reinforcing the known association of ANCA status with clinical manifestations, cluster analysis does not support a complete separation of EGPA in ANCA-positive and -negative subsets. Collectively, these data indicate that EGPA should be regarded as a phenotypic spectrum rather than a dichotomous disease.

La actividad de la artritis psoriásica con afectación axial se correlaciona con el PsAID12

ObjectiveTo determine the impact of the disease in patients with PsA in daily clinical practice and to evaluate its relationship with its axial activity. MethodsA cross-sectional study was conducted in consecutive patients attended from January 2021 to December 2021 who met the CASPAR criteria, with clinical of inflammatory back pain and positive axial imaging, with or without peripheral involvement. Demographic, clinical, analytical data, HAQ index, PsAID12 and activity index (BASDAI and ASDAS-PCR) were also collected. Patients were divided into two groups, those with high impact and those with low impact according to PsAID results. Continuous variables are shown as median (Q1-Q3) and categorical variables as percentages and frequencies. ResultsOf the 269 patients evaluated with PsA, 72 patients with axial involvement were included, 40 men (55.6%), with a median age of 54.1 years and disease duration of 7 years. 28.3% of the patients were obese and serum CRP level was 0.45mg/dl (0.08-1.10). BASDAI was 4.2 (2.0-6.2) and ASDAS-PCR was 2.4 (1.5-3.2), which translates into 39.6% of patients in low activity or remission. The median PsAID total score was 3.9 (1.6–5.4), evaluated in 61 patients. The patients who achieved a PsAID12≤4 were 63%, mostly men and with lower CRP levels than PsAID≥4 patients. In addition, low impact measured by the PsAID12 was associated with low results in BASDAI and ASDAS-PCR. ConclusionsAxial involvement reflected lower impact of the disease measured by PsAID12 and it is correlated with low activity measured by BASDAI and ASDAS-PCR.

COVID-19 severity stratification using quantitative computed tomography analysis

Aim: This study aimed to examine the utility of computer-assisted quantitative assessment of chest&#x0D; computed tomography (CT) images in the stratification of Coronavirus Disease 2019 (COVID-19)&#x0D; severity.&#x0D; Materials and Methods: This study was designed as a retrospective, single-center study and&#x0D; included a total of 142 RT-PCR-confirmed COVID-19 patients. CT findings were visually evaluated&#x0D; and noted for their morphology and distribution characteristics. Visual semi-quantitative score (VSS)&#x0D; and computer-aided quantitative score (CQS) were calculated. The utility of the approach was&#x0D; assessed based on its ability to predict the patients who would require intensive care.&#x0D; Results: The presence of underlying fibrosis, air bubble sign, and co-occurrence of central and&#x0D; peripheral lung area involvement were the CT findings that were significantly more commonly&#x0D; encountered in patients with intensive care requirements during the follow-up period. We found a&#x0D; significant positive correlation between total VSS and CQS (p

Cluster Analysis To Explore Clinical Subphenotypes Of Eosinophilic Granulomatosis With Polyangiitis (Churg-Strauss).

Previous studies suggested that distinct phenotypes of eosinophilic granulomatosis with polyangiitis (EGPA) could be determined by presence or absence of antineutrophil cytoplasmic antibodies (ANCA), reflecting predominant vasculitic or eosinophilic processes, respectively. This study explored whether ANCA-based clusters or other clusters can be identified in EGPA. This study used standardized data of 15 European centers for patients with EGPA fulfilling widely accepted classification criteria. We used multiple correspondence analysis, hierarchical cluster analysis, and a decision tree model. The main model included 10 clinical variables (musculoskeletal, mucocutaneous, ophthalmological, ENT, cardiovascular, pulmonary, gastrointestinal, renal, central or peripheral neurological involvement); a second model also included ANCA results. The analyses included 489 patients diagnosed in 1984-2015. ANCA were detected in 37.2% of patients, mostly P-ANCA (85.4%) and/or anti-myeloperoxidase (87.0%). Compared with ANCA-negative patients, those with ANCA had more renal (P<0.001) and peripheral neurological involvement (P=0.04), fewer cardiovascular signs (P<0.001) and fewer biopsies with eosinophilic tissue infiltrates (P=0.001). The cluster analyses generated four (model without ANCA) and five clusters (model with ANCA). Both models identified three identical clusters of 34, 39 and 40 patients according to the presence or absence of ENT, CNS and ophthalmological involvement. Peripheral neurological and cardiovascular involvement were not predictive characteristics. Although reinforcing the known association of ANCA status with clinical manifestations, cluster analysis does not support a complete separation of EGPA in ANCA-positive and -negative subsets. Collectively, these data indicate that EGPA should be regarded as a phenotypic spectrum rather than a dichotomous disease.

Role of HLA class I and II alleles in susceptibility to ankylosing spondylitis in Chinese Han.

The objective of the study was to clarify the associations of HLA class I and II alleles with ankylosing spondylitis (AS) among Chinese Han. We performed HLA genotyping and Sanger sequencing for 68 HLA-B*27(-), 62 HLA-B*27(+) AS patients, and 70 controls. Case-control analyses and separate analyses of HLA-B*27(-) patients were performed. One-way ANOVA and Kruskal-Wallis multiple comparisons test were used to analyze the effects of HLA-A\B\C\DRB1\DQB1 alleles on clinical characteristics of HLA-B*27(-) and HLA-B*27(+) patients. In the HLA-B*27(+) group, positive associations were seen with A*11:02, B*27:04, B*27:05, C*02:02, C*12:02, and DRB1*04:01 and negative associations were seen with A*33:03, B*07:02, B*57:01, and C*07:02. The age at onset was greater in HLA-B*27(-) patients than in HLA-B*27(+) patients (30.03 ± 15.15 vs. 23.08 ± 7.79 years). In the HLA-B*27(-) group, those with A*01:01, B*13:01, B*13:02, C*01:02, C*04:01, DQB1*02:01, DQB1*06:01, and DRB1*03:01 had an earlier onset than those without these alleles, while patients carrying B*40:02, C*07:02, C*12:02, C*15:02, DQB1*05:02, and DQB1*05:03 had a delayed onset. In the HLA-B*27(-) group, A*32:01(+), C*08:01(+), and DRB1*04:05(-) women were likely to develop AS. In the HLA-B*27(+) group, DQB1*03:02(+) women may be more likely to develop AS. DRB1*12:02 and HLA-B*27 interacted with the distribution of AS-affected sites. In the HLA-B*27(+) group, DRB1*12:02(+) patients were likely to have peripheral joint involvement. HLA class I and II alleles other than HLA-B*27 contribute to AS predisposition and characteristics among Chinese Han patients.

Trastuzumab Deruxtecan‒Related Interstitial Lung Disease/Pneumonitis: Computed Tomography Imaging Patterns to Guide Diagnosis and Management

PURPOSE Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate approved for the treatment of several advanced cancers; however, severe or fatal interstitial lung disease/pneumonitis can occur. We characterized the computed tomography (CT) patterns of T-DXd‒related pneumonitis as a marker for its clinical severity. MATERIALS AND METHODS Ninety patients with advanced cancers who developed T-DXd‒related pneumonitis in two completed single-arm clinical trials were included. Three radiologists independently characterized the CT patterns of pneumonitis at diagnosis, for analyses of those patterns' relationships with clinical severity and pneumonitis outcome. RESULTS T-DXd‒related pneumonitis most commonly presented with cryptogenic organizing pneumonia (COP) pattern, observed in 65 patients (72%), followed by a newly identified COP/hypersensitivity pneumonitis (HP) pattern (13%), acute interstitial pneumonia (AIP)/acute respiratory distress syndrome (ARDS) pattern (11%), and HP pattern (3%). A subset of cases with COP pattern demonstrated an atypical distribution with upper and peripheral lung involvement (6/65; 9%). CT patterns were associated with Common Terminology Criteria for Adverse Events severity grades of pneumonitis, with the AIP/ARDS pattern having higher grades compared with others ( P &lt; .0001). Fatal pneumonitis was more common in the AIP/ARDS pattern than in others ( P = .005). The onset of pneumonitis was earlier in the AIP/ARDS pattern compared with others (median time to onset: at 17.9 v 32.7 weeks of therapy; P = .019). Pneumonitis was treated by withholding T-DXd with or without corticosteroids in most patients (78/90; 87%). CONCLUSION T-DXd‒related pneumonitis most commonly demonstrated a COP pattern, with a subset having an atypical distribution. The AIP/ARDS pattern was indicative of severe, potentially fatal pneumonitis, and requires immediate clinical attention to mitigate serious adverse events.