The genetic basis of severe COVID-19 has been thoroughly studied, and many genetic risk factors shared between populations have been identified. However, reduced sample sizes from non-European groups have limited the discovery of population-specific common risk loci. In this second study nested in the SCOURGE consortium, we conducted a genome-wide association study (GWAS) for COVID-19 hospitalization in admixed Americans, comprising a total of 4702 hospitalized cases recruited by SCOURGE and seven other participating studies in the COVID-19 Host Genetic Initiative. We identified four genome-wide significant associations, two of which constitute novel loci and were first discovered in Latin American populations (BAZ2B and DDIAS). A trans-ethnic meta-analysis revealed another novel cross-population risk locus in CREBBP. Finally, we assessed the performance of a cross-ancestry polygenic risk score in the SCOURGE admixed American cohort. This study constitutes the largest GWAS for COVID-19 hospitalization in admixed Latin Americans conducted to date. This allowed to reveal novel risk loci and emphasize the need of considering the diversity of populations in genomic research.

ObjectivesTo develop a consensual definition for the term ‘early axial spondyloarthritis—axSpA’—and ‘early peripheral spondyloarthritis—pSpA’.MethodsThe ASAS (Assessment of SpondyloArthritis international Society-Spondyloarthritis EARly definition) steering committee convened an international working group (WG). Five consecutive steps were followed: (1) systematic literature review (SLR); (2) discussion of SLR results within the WG and ASAS community; (3) a three-round Delphi survey inviting all ASAS members to select the items that should be considered for the definition; (4) presentation of Delphi results to the WG and ASAS community and (5) ASAS voting and endorsement (2023 annual meeting).ResultsFollowing the SLR, consensus was to proceed with an expert-based definition for early axSpA (81% in favour) but not for pSpA (54% against). Importantly, early axSpA should be based on symptom duration taking solely axial symptoms into account. 151–164 ASAS members participated in the Delphi surveys. Consensus was achieved for considering the following items within early axSpA definition: duration of symptoms ≤2 years; axial symptoms defined as cervical/thoracic/back/buttock pain or morning stiffness; regardless of the presence/absence of radiographic damage. The WG agreed that in patients with a diagnosis of axSpA ‘early axSpA’ should be defined as a duration of ≤2 years of axial symptoms. Axial symptoms should include spinal/buttock pain or morning stiffness and should be considered by a rheumatologist as related to axSpA. The ASAS community endorsed this proposal (88% in favour).ConclusionsEarly axSpA has newly been defined, based on expert consensus. This ASAS definition should be adopted in research studies addressing early axSpA.

Prognostic tools in pathological-node (pN) patients after radical cystectomy (RC) are needed. To evaluate the prognostic impact of lymph node (LN)-density on disease-specific survival (DSS) in patients with bladder cancer (BC) undergoing RC with pelvic lymph node dissection. We analyzed a multi-institutional cohort of 1169 patients treated with upfront RC for cT1-4aN0M0 urothelial BCat nine centers. LN-densitywas calculated as the ratio of the number of positive LNs×100% to the number of LNs removed. The optimal LN-density cut-off value was defined by creating a time-dependent receiver operating characteristic (ROC) curve in pN patients. Univariable and multivariable Cox' regression analyses were used to assess the effect of conventional Tumor Nodes Metastasis (TNM) nodal staging system, LN-density and other LN-related variables on DSS in the pN-positive cohort. Of the 1169 patients, 463 (39.6%) patients had LN-involvement. The area under the ROC curve was 0.60 and the cut-off for LN-density was set at 20%, 223 of the pN-positive patients (48.2%) had a LN-density ≥ 20%. In multivariable models, the number of LN-metastases (HR 1.03, p = 0.005) and LN-density, either as continuous (HR 1.01, p = 0.013) or as categorical variable (HR 1.37, p = 0.014), were independently associated with worse DSS, whereas pN-stage was not. LN-density ≥ 20% was an independent predictor of worse DSS in BC patients with LN-involvement at RC. The integration of LN-density and other LN-parameters rather than only conventional pN-stage may contribute to a more refined risk-stratification in BC patients with nodal involvement.

BTK inhibitors have been concurrently administered with anti-CD20 monoclonal antibodies (mAbs) in chronic lymphocytic leukemia (CLL). However, the optimal regimen for combining these two drugs remains pending. This multi-center phase 2 study aimed to analyze whether consolidation with ofatumumab improved the response in patients with CLL receiving front-line treatment with ibrutinib. Patients received 12 cycles of ibrutinib monotherapy. Those who achieved CR after this induction were maintained on ibrutinib. Conversely, those who did not attain CR continued with ibrutinib in addition to a consolidation, which involved 7 doses of ofatumumab. The primary objective was the complete response (CR) rate at cycle 20. This study is registered within the EU Clinical Trials Register (EudraCT 2016-004937-26). Between September 8, 2017, and May 21, 2018, 84 patients (median age, 69 years) were included. After completion of 12 cycles of ibrutinib (n=80), 4 patients (5%) were in CR, 67 (84%) in partial response (PR), and 6 patients (7%) had a PR with lymphocytosis (PRL). After consolidation with ofatumumab, 20 patients improved the response from PR to CR and 6 patients with PRL obtained a PR. Seventy-one patients (85%) completed 20 cycles of treatment, with a CR rate of 24/71 (34%). According to the intention-to-treat analysis at cycle 20, the ORR was 69/84 (82.2%), with a CRR of 24/84 (28.6%). Progression-free survival and overall survival at 48-months were 89.9% (CI: 82.4-95.5) and 92.2% (CI: 85.3-97.1), respectively. These findings underscore the potential for a consolidation strategy in CLL, wherein the addition of a mAb in patients with low tumor burden might enhance the quality of the response. The study was funded by Janssen that also supplied ibrutinib, whereas ofatumumab was supplied by Novartis.

BackgroundSeveral studies have established the safety and efficacy of balloon guide catheters (BGCs) for large vessel occlusions. However, the utility of BGCs remains largely unexplored for distal medium vessel occlusions (DMVOs). In this study, we aim to compare the outcomes of BGC vs. Non-BGC in patients undergoing mechanical thrombectomy (MT) for DMVO.MethodThis retrospective study from the Stroke Thrombectomy and Aneurysm Registry (STAR) encompassed adult patients with acute anterior cerebral artery, posterior cerebral artery, and middle cerebral artery-M2–3–4 occlusions. Procedure times, safety, recanalization, and neurological outcomes were compared between the two groups, with subgroup analysis based on first-line thrombectomy techniques.ResultsA total of 1508 patients were included, with 231 patients (15.3%) in the BGC group and 1277 patients (84.7%) in the non-BGC group. The BGC group had a lower modified Thrombolysis in Cerebral Infarction (mTICI) score ≥2C (43.2% vs 52.7%, P=0.01), longer time from puncture to intracranial access (15 vs 8 min, P<0.01), and from puncture to final recanalization (97 vs 34 min, P<0.01). In the Solumbra subgroup, the first pass effect (FPE) rate was lower in the BGC group (17.4% vs 30.7%, P=0.03). Regarding clinical outcomes, the BGC group had a lower rate of distal embolization (8.8% vs 14.9%, P=0.03).ConclusionOur study found that use of BGC in patients with DMVO was associated with lower mTICI scores, decreased FPE rates, reduced distal embolization, and longer procedure times.

Obstetric forceps play an important role in safe childbirth, yet there is a lack of distinction between various forceps types in clinical practice. This study aimed to evaluate and compare perineal pressure and forces on the baby during nonrotational forceps-assisted births using Simpson-Braun forceps, Kielland forceps, and Thierry spatulas on a simulation model. This experimental study involved six obstetricians conducting 108 forceps-assisted births on a simulation model. Instruments were assessed for their impact on perineal pressure, traction force, and operator-assessed difficulty. Thierry's spatulas exerted the lowest force on the baby, while Kielland forceps exhibited the lowest perineal pressure, though not statistically significant. An experienced obstetrician demonstrated less perineal pressure with Simpson forceps. Notably, no significant differences in difficulty were observed between instruments. This study highlights distinctions in forceps performance, with Thierry spatulas applying the least force on the fetal head, while an experienced obstetrician fared better with Simpson forceps in terms of perineal pressure. Kielland forceps remain a viable alternative for nonrotational forceps births, showing comparable outcomes.

This study aimed to compare outcomes of low Alberta Stroke Program Early Computed Tomography Score (ASPECTS) patients with stroke who underwent mechanical thrombectomy (MT) within 6 hours or 6 to 24 hours after stroke onset. A retrospective cohort study was conducted using data from a large multicenter international registry from 2013 to 2023. Patients with low ASPECTS (2-5) who underwent MT for anterior circulation intracranial large vessel occlusion were included. A propensity matching analysis was conducted for patients presented in the early (<6 hours) vs late (6-24 hours) time window after symptom onset or last known normal. Among the 10 229 patients who underwent MT, 274 met the inclusion criteria. 122 (44.5%) patients were treated in the late window. Early window patients were older (median age, 74 years [IQR, 63-80] vs 66.5 years [IQR, 54-77]; P < .001), had lower proportion of female patients (40.1% vs 54.1%; P = .029), higher median admission National Institutes of Health Stroke Scale score (20 [IQR, 16-24] vs 19 [IQR, 14-22]; P = .004), and a higher prevalence of atrial fibrillation (46.1% vs 27.3; P = .002). Propensity matching yielded a well-matched cohort of 84 patients in each group. Comparing the matched cohorts showed there was no significant difference in acceptable outcomes at 90 days between the 2 groups (odds ratio = 0.90 [95% CI = 0.47-1.71]; P = .70). However, the rate of symptomatic ICH was significantly higher in the early window group compared with the late window group (odds ratio = 2.44 [95% CI = 1.06-6.02]; P = .04). Among patients with anterior circulation large vessel occlusion and low ASPECTS, MT seems to provide a similar benefit to functional outcome for patients presenting <6 hours or 6 to 24 hours after onset.

The development of highly active drugs has improved the survival of melanoma patients, but elevated drug prices place a significant burden on health care systems. In Spain, the public health care system is transferred to the 17 autonomous communities (AACC). The objective of this study is to describe the situation of drug access for melanoma patients in Spain and how this decentralized system is affecting equity. From July to September 2023, a cross-sectional survey was sent to members of the Spanish Multidisciplinary Melanoma Group (GEM Group). The questionnaire consulted about the real access to new drugs in each hospital. The responses were collected anonymously and analyzed according to several variables, including the AACC. The survey was answered by 50 physicians in 15 AACC. No major differences on access between AACC were observed for indications that are reimbursed by the Spanish Health Care System (adjuvant immunotherapy for stage IIIC-IIID and resected stage IV melanoma). Important differences in drug access were observed among AACC and among centers within the same AACC, for most of the EMA indications that are not reimbursed (adjuvant immunotherapy for stages IIB-IIC-IIIA-IIIB) or that are not fully reimbursed (ipilimumab plus nivolumab in advanced stage). Homogeneously, access to adjuvant targeted drugs, TIL therapy and T-VEC, is extremely low or non-existing in all AACC. For most indications that reimbursement is restricted out of the EMA indication, a great diversity on access was found throughout the different hospitals in Spain, including heterogeneity intra-AACC.

In recent years, there has been an increase in Neisseria gonorrhoeae infections in Europe and Spain. Disseminated gonococcal infection is an uncommon clinical presentation that includes gonococcal arthritis. Improved antibiotic treatment has reduced the incidence of gonococcal arthritis. However, the increase in gonococcal infections may have increased the frequency of this clinical entity in recent times. We report five cases of gonococcal arthritis in patients in a tertiary-care hospital in the northern area of Madrid (Spain) from October 2022 to October 2023. Major cases occurred in male patients with unprotected sex and polyarticular symptoms requiring hospital admission and treatment with ceftriaxone and cefixime. The use of molecular techniques has allowed the detection of a greater number of culture-negative cases of gonococcal arthritis, as well as the detection of mutations associated with resistance to fluoroquinolone for switching to oral treatment.

Albuminuria could potentially emerge as a novel marker of congestion in acute heart failure. However, the current evidence linking albuminuria and congestion in patients with congestive heart failure (CHF) remains somewhat scarce. This study aimed to evaluate the prevalence of albuminuria in a cohort of patients with CHF, identify the independent factors associated with albuminuria and analyse the correlation with different congestion parameters. This is a subanalysis of the Spanish Cardiorenal Registry, in which we enrolled 864 outpatients with heart failure and a value of urinary albumin:creatinine ratio (UACR) at the first visit. The median age was 74years, 549 (63.5%) were male and 438 (50.7%) had a reduced left ventricular ejection fraction. A total of 350 patients (40.5%) had albuminuria. Among these patients, 386 (33.1%) had a UACR of 30-300mg/g and 64 (7.4%) had a UACR >300mg/g. In order of importance, the independent variables associated with higher UACR were estimated glomerular filtration rate determined by the Chronic Kidney Disease Epidemiology Collaboration equation (R2=57.6%), systolic blood pressure (R2=21.1%), previous furosemide equivalent dose (FED; R2=7.5%), antigen carbohydrate 125 (CA125; R2=6.1%), diabetes mellitus (R2=5.6%) and oedema (R2=1.9%). The combined influence of oedema, elevated CA125 levels and the FED accounted for 15.5% of the model's variability. In patients with chronic stable heart failure, the prevalence of albuminuria is high. The risk factors of albuminuria in this population are chronic kidney disease and hypertension. Congestion parameters are also associated with increased albuminuria.