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To present the successful resolution of a type Ia endoleak in a patient previously treated with a fenestrated Anaconda endograft using a custom-made branched endograft. The limited working length and the retrograde orientation of the renal arteries due to caudal migration of the previous fenestrated endograft required a unique custom-made 5-branched graft configuration designed by COOK Medical (Bloomington, Indiana). This design featured 2 short (10-mm) retrograde branches for the renal arteries, along with an additional branch extending from the main body of the graft to accommodate the contralateral limb of the previous endograft. A .014″ wire was used as a stabilizing "pull-through wire" for the Fustar sheath, providing adequate stability for the challenging catheterization of the target vessels. Custom-made branched endovascular aneurysm repair after failed fenestrated Anaconda device is a feasible solution. Thorough planning and complex endovascular techniques may be necessary.Clinical ImpactThis technical report highlights the significant challenges associated with endovascular reintervention following failure of fenestrated endografts. Such reoperations often require customized grafts and advanced endovascular skills. Our experience demonstrates that with appropriate planning, branched endovascular repair (bEVAR) can be a feasible and effective solution for managing failed fenestrated endovascular aneurysm repair (fEVAR) apart from open conversion.

Chile has been training specialists since the 19th century, which was strengthened in the 20th century with the creation of institutions and the National Health Services System, which diversified specialties. As of November 2024, Chile has 93 specialties taught in 21 training centres. To analyse the number and distribution of medical specialties in Chile in 2024, including characteristics by age group, sex and geographical distribution. Cross-sectional descriptive study using data on specialists registered with the Superintendence of Health in 2023 and 2024. Demographic variables, certification, speciality and region of work were analysed, using National Institute of Statistics (INE) 2023 population projections for comparison. Comparatively, the 2024 registers showed an increase of 4.40% in the number of specialist doctors and an increase of 5.83% in the number of specialties registered, given that a doctor can have more than one specialty. The analysis focused on specialties with a representation of more than 1% of the total. Of the total of 41,132 specialties as of June 2024, the main ones were General Surgery, Internal Medicine, Gynaecology and Obstetrics, and Paediatrics. With regard to the proportion by sex, there were specialties with a high proportion of women, such as Paediatric and Adolescent Psychiatry (78%) and others with a high proportion of men, such as Urology (92%). The rate of specialists presents a national average of 20/10,000 inhabitants, with the regions of Ñuble, Metropolitana and Libertador Bernardo O'Higgins exceeding this average. The higher proportion of women in certain areas suggests socio-cultural factors. The centralised distribution of specialists in Chile makes it difficult for the health system to respond, especially affecting remote regions. Currently, there are strategies for equitable distribution, taking into account regional needs and gender equity, which seek to guarantee timely and quality access to the whole country.

Granular cell tumors of the neurohypophysis are rare, benign neoplasms originating from pituicytes that often pose diagnostic challenges due to their resemblance to other sellar lesions. We report the case of a 26-year-old man with a 2-year history of headache, polyuria, and hypopituitarism. Magnetic resonance imaging revealed a 21 × 23×30 mm suprasellar mass compressing the optic chiasm and hypothalamus. Hormonal evaluation showed hypogonadotropic hypogonadism, central hypothyroidism, and arginine vasopressin deficiency. The patient underwent partial tumor resection. Histopathology confirmed a grade I granular cell tumor, positive for thyroid transcription factor 1, S100, and vimentin. Granular cell tumors are slow-growing lesions with nonspecific clinical and radiologic features. Diagnosis relies on histologic and immunohistochemical findings. Complete resection is often limited by tumor vascularity and proximity to vital structures. Granular cell tumors should be considered in the differential diagnosis of suprasellar tumors. Early recognition and multidisciplinary management may improve patient outcomes.

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Psoriatic arthritis (PsA) is a chronic inflammatory disease with a complex clinical spectrum. Sphingosine-1-phosphate (S1P) and its receptor (S1PR) are key lipid mediators involved in immunity and bone remodelling. This study evaluates the inter-relationship between serum levels of S1P and S1PR and clinical activity, radiological findings and different stages of PsA. A cross-sectional observational study was conducted including 64 subjects: 21 healthy controls and 43 patients with PsA: 16 with recent-onset PsA and 27 with established PsA (EPsA). Clinical variables such as disease activity in PsA (DAPSA), bone mineral density (BMD), Trabecular Bone Score, 3D-Shaper and inflammatory activity by Doppler ultrasound and MRI were assessed. S1P and S1PR levels were measured by ELISA. S1P levels were significantly higher in the PsA group compared with controls (p=0.013), with the highest values observed in the EPsA subgroup (p=0.009). Although no significant correlation was observed with the DAPSA Score, S1PR levels were significantly higher in patients with Achilles enthesitis detected by ultrasound (p=0.046) and in those with bone proliferation/structural damage (p=0.03). Patients with EPsA showed significantly higher cortical volumetric BMD compared with controls (p=0.027). The S1P/S1PR axis is dysregulated in PsA and is associated with disease progression. Its correlation with ultrasound findings of enthesitis and new bone formation suggests that S1P acts as a critical mediator in the osteoimmunology of the enthesis, positioning it as a potential biomarker of structural damage and a novel therapeutic target.

Dogs are common companion animals, often infested by fleas that can transmit zoonotic pathogens in rural tropical areas. In Colombia, studies on flea-borne agents in dogs are limited. Understanding the presence of these ectoparasites and associated microorganisms is crucial. To assess flea infestation and detect and identify Rickettsia and Bartonella spp. in fleas collected from dogs in Cundinamarca, Colombia. Between 2019 and 2020, fleas were collected from rural domestic dogs in 24 municipalities of western Cundinamarca. Fleas were morphologically identified and pooled for DNA extraction. Molecular screening of Rickettsia and Bartonella spp. was performed by qPCR. Positive samples underwent further characterization by conventional PCR. Rickettsia was additionally analyzed using RFLP, while Bartonella was evaluated through phylogenetic analysis. Of the 116 dogs examined across 24 municipalities, 39.7% were infested with fleas. A total of 138 fleas were collected and grouped into 46 pools, with Ctenocephalides felis felis identified in 94% of them. Rickettsia was detected in 83% of pools, with Rickettsia asembonensis and Rickettsia felis identified in most positive samples. Bartonella was found in 28% of pools; however, sequencing success was limited, and no species-level identification could be achieved. This study documents flea infestation in domestic dogs in Cundinamarca, predominantly by C. felis felis. High detection of R. asembonensis and presence of R. felis confirm widespread rickettsial circulation in fleas. Bartonella was detected less frequently, but species-level identification was not achieved.

Identifying individuals with tuberculosis infection (TBI) at increased risk of progressing to active TB remains challenging. The World Health Organization recommends both the tuberculin skin test (TST) and the interferon-gamma release assay (IGRA), including QuantiFERON-TB Gold Plus (QFT®-Plus), for the detection of TBI. QIAreach®, a novel IGRA assay designed for resource-limited settings, has shown strong concordance with QFT®-Plus. However, data on immunosuppressed individuals are limited. To address this gap, we assessed the diagnostic performance of QIAreach® compared with QFT®-Plus in a high TB/HIV-burden setting. We prospectively evaluated QIAreach® at an HIV reference center in Manaus, Brazil. Blood samples from PLHIV aged ≥ 18 years with CD4 cell counts ≥ 350 cells/mm³ or with unavailable CD4 results at enrollment were tested using both assays per manufacturer instructions. Diagnostic performance (sensitivity, specificity, and predictive values) was assessed using QFT®-Plus as the reference standard. Cohen's kappa coefficient determined test agreement. Among 266 participants (median age 37 years; 70% men; median CD4 537 cells/mm³), QIAreach® sensitivity, specificity, and negative predictive value (95% CI) were 0.97 (0.90-1.00), 0.73 (0.66-0.78), and 0.99 (0.96-0.99), respectively. Concordance (Cohen's kappa) was 0.36. QIAreach® demonstrated high sensitivity and negative predictive value (NPV) in PLHIV. However, its increased false-positive rate affected specificity. Given its high NPV, further studies are needed to determine its role as a point-of-care triage test for TBI.

Infertility is a globally prevalent disease affecting approximately 1 in 6 people at some stage in their lives. Despite its profound personal significance, access to fertility care remains uneven, shaped by legal, financial, cultural and infrastructural barriers. While declining fertility rates have prompted some policymakers to frame medically assisted reproduction within demographic strategies, we argue that fertility care must be fundamentally understood as a matter of individual rights, reproductive autonomy and self‑fulfilment. International human rights instruments increasingly recognize equitable access to fertility treatment as a core component of reproductive health, yet country-level disparities in eligibility, public funding and available treatment options persist. These inequalities disproportionately affect marginalized groups, leading many to delay or abandon treatment or to seek cross‑border care. The fertility journey is further burdened by emotional strain, stigma, workplace challenges and financial and psychological uncertainty. Individuals who remain involuntarily childless after treatment may require long‑term psychosocial support, underscoring the need for patient‑centred, rights‑based policies that extend beyond medical intervention. Ensuring fair access to fertility care, improving outcome reporting and integrating psychological and social support are essential to addressing infertility as both a private struggle and a broader public health issue.

The ethical conflicts involved in the medical indication of early serological diagnosis in Alzheimer's disease, for clinical contexts where a medical indication is required to perform the intervention, have been scarcely analyzed. The prescription of early serological diagnosis in Alzheimer's disease violates more principles than it supports. To carry out an analysis regarding the ethical conflicts associated with the indication of early serological diagnosis of Alzheimer's disease and to offer a clinical practice recommendation based on said analysis. Ethical analysis, in which the logical consequences of prescribing early serological diagnosis will be explained in terms of the ethical principles of autonomy, justice, beneficence and non-maleficence. The intervention presents marginal benefit in terms of autonomy and beneficence, while it violates the principles of beneficence, non-maleficence and justice. The intervention is not ethically recommended. This could change if its cost diminishes and if disease-modifying therapies with an adequate safety profile are developed.

Dyspnea and other exertional symptoms are cornerstone elements in clinical practice, essential for diagnostic processes, risk stratification, and the effective management of respiratory diseases. To investigate the intensity of dyspnea and leg discomfort during physical exercise and their relationships with multi-organ functional variables. A multicenter study involving 948 adult patients evaluated via integrated cardiopulmonary exercise testing (CPET). Dyspnea at peak exercise showed a mean value of 6.1±3.1 and a median of 7 (IQR, 5). Leg discomfort presented a mean value of 6.3±3.1 and a median of 7 (IQR, 5). Symptoms of dyspnea and leg discomfort reached maximal intensity (i.e., 10 points) in 23% and 30% of patients, respectively, while the remaining participants exhibited submaximal symptom levels. Four phenotypes were identified at peak exercise: paucisymptomatic, peripheral, mixed, and dyspneic. These phenotypes were associated with a sequential and progressive impairment of peak work rate (Wpeak) and peak oxygen consumption (VO2peak), initially exhibiting a bimodal trend for leg discomfort and a subsequent linear inverse relationship with dyspnea. Four distinct phenotypes exist based on predominant exertional symptoms: paucisymptomatic, peripheral, mixed, and dyspneic. These are sequentially associated with increasingly severe grades of functional impairment. These findings warrant the orientation of rehabilitation strategies toward the specific limiting system predominantly responsible for the symptoms, thereby enhancing the therapeutic value of the intervention.

We describe a case of Sweet syndrome, an acute neutrophilic dermatosis that may occur as a paraneoplastic manifestation. A 25-year-old man presented with recurrent abdominal pain and painful erythematous plaques on the trunk and upper limbs, without symptoms of catecholamine excess. Imaging revealed a retroperitoneal mass and extensive hypermetabolic lymphadenopathy on positron emission tomography/computed tomography using fluorine-18 fluorodeoxyglucose (18F-FDG) and gallium-68 DOTA-Tyr3-octreotate (68Ga-DOTATATE), raising concern for metastatic disease. Skin biopsy confirmed Sweet syndrome, while lymph node biopsies demonstrated reactive lymphoid hyperplasia. A computed tomography-guided biopsy of the retroperitoneal mass established the diagnosis of paraganglioma, but was complicated by hypertensive crisis. Subsequent biochemical evaluation revealed markedly elevated plasma normetanephrine levels despite normotension. The patient underwent preoperative alpha-adrenergic blockade followed by surgical resection. Cutaneous lesions resolved rapidly after tumor removal, and plasma normetanephrines normalized, confirming biochemical cure. This case highlights an association between Sweet syndrome and succinate dehydrogenase complex iron-sulfur subunit B (SDHB)-related paraganglioma and underscores the risk of false-positive metastatic findings on functional imaging and reinforces the importance of biochemical exclusion of paraganglioma before biopsy of vascularized retroperitoneal masses.

Chronic Chagas cardiomyopathy (CCC) remains a major cause of heart failure (HF)-related mortality in Latin America and is increasingly recognized as a global health concern. Prognostic models developed in non-Chagas populations often perform poorly in CCC, highlighting the need for etiology-specific risk stratification. We applied high-throughput plasma proteomics to evaluate 2-year mortality risk in CCC compared with other HF etiologies. Baseline plasma from 1,212 adults with heart failure with reduced ejection fraction (HFrEF; LVEF <50%) was analyzed to quantify 734 circulating proteins. CCC was confirmed in 191 participants (16%) by dual Trypanosoma cruzi serology. Two-year mortality was higher in CCC than in the overall HF cohort (26% vs. 16%, p&#x2009;<&#x2009;0.01). Feature-selection methods identified a nine-protein panel (P9: C1QA, CCL4, REN, EGLN1, COL9A1, GP1BA, ITM2A, CNPY2, NT-proBNP) that improved risk classification compared with NT-proBNP alone, increasing F1-macro by 20% (0.674 vs. 0.560) and integrated time-dependent discrimination for 2-year mortality (iAUC) by 6%. Performance gains varied by HF etiology. Improvements were greatest in hypertensive (+40%) and ischemic (+21%) HF, whereas in CCC the P9 panel underperformed NT-proBNP alone (-16%), suggesting distinct underlying disease biology. External validation in the UK Biobank confirmed generalizability: compared with NT-proBNP, P9 improved F1-macro by 18% and iAUC by 7.4%, reaching an F1-macro of 0.612 in the highest-risk tertile. Pathway enrichment identified 14 CCC-specific pathways, mainly related to fibrosis, integrin signaling, immune dysregulation, and impaired protein trafficking. Exploratory analyses also highlighted potential pathway-linked therapeutic targets consistent with distinct CCC mechanisms. The P9 proteomic panel improved mortality risk prediction beyond NT-proBNP and the MAGGIC clinical score across most HF etiologies and showed consistent performance in an independent population-based cohort. In contrast, in CCC P9 underperformed NT-proBNP alone, highlighting the distinct biological features of this disease. These findings underscore the limitations of universal biomarker models in CCC and support the need for etiology-specific risk stratification strategies.

Sporotrichosis is a globally distributed subcutaneous mycosis caused by fungi of the Sporothrix complex, and is associated with worse outcomes in immunocompromised individuals, including those with diabetes mellitus. The impact of diabetes mellitus on the clinical presentation and outcomes of sporotrichosis remains poorly characterized. We conducted a systematic review of individual participant data to assess this association. Eight databases (Cochrane Library, Embase, LILACS, MEDLINE/PubMed, Scopus, Global Index Medicus/WHO, SciELO, and Web of Science) were searched without restrictions on publication date, country, language, sex, or age. The retrieved case data were divided into two groups: (1) localized disease and (2) systemic disease. We identified 122 cases of sporotrichosis in patients with diabetes mellitus from 64 articles and from 28 unpublished cases from Brazil and Mexico. Most patients were male (62.3%), with a mean age of 56.6 years, and 73% were from hyperendemic countries. Among cutaneous presentations, lymphocutaneous and fixed cutaneous forms were most frequent (41%), while osteoarticular multifocal disease was the leading extracutaneous manifestation (22.1%). Alcohol use disorder was independently associated with systemic disease (adjusted OR 4.76, 95% CI 1.45-18.05; P&#xa0;=&#xa0;.014). Compared with localized disease, systemic disease more commonly presented with joint symptoms (40.6% vs. 13.5%; P&#xa0;<&#xa0;.001), lesions with lower limb involvement (80% vs. 20%; P&#xa0;<&#xa0;.001), head involvement (81.3% vs. 18.8%; P&#xa0;<&#xa0;.001), and trunk involvement (84.6% vs. 15.4%; P&#xa0;<&#xa0;.001). Itraconazole monotherapy was the main treatment (45.9%), followed by amphotericin B-based regimens (33.6%). There were better outcomes for patients with localized disease than for those with systemic disease (cure rate 86.6% vs. 56.4%; P&#xa0;<&#xa0;.001). Systemic disease carried a 20% mortality rate in this population. These findings underscore the challenges posed by sporotrichosis in patients with diabetes mellitus and highlight the need for further research on risk factors for systemic disease and optimal treatment strategies for this population. Diabetes mellitus is associated with more severe sporotrichosis disease and outcomes. A review of 122 diabetic cases found systemic disease carried 20% mortality. Diabetes and alcohol use increased systemic risk 5-fold. Early diagnosis and tailored treatment are critical for diabetic population.

The sodium-hydrogen exchanger isoform 3 (NHE3) is a critical mediator of proximal tubule and thick ascending limb Na+ reabsorption and H+/NH4+ secretion, yet the physiological implications of its upregulation during low K+ intake remain poorly understood. We hypothesized that renal NHE3 is important for the acid-base response during K+ depletion. To test this, we utilized kidney-specific NHE3 knockout (NHE3KS-KO) mice. Following 10 days of a K+-deficient diet (<&#x2009;30 ppm), NHE3KS-KO mice exhibited exacerbated hypokalemia compared to control mice, despite near complete elimination of urinary K+ excretion and comparable levels of ROMK and BK&#x3b1; protein abundance in both genotypes. Control and NHE3KS-KO mice developed hypernatremia secondary to a urinary concentrating defect; however, this was associated with a&#x2009;~&#x2009;2-fold greater fluid intake in NHE3KS-KO mice. These effects occurred without changes in glomerular filtration rate. Both genotypes developed metabolic acidosis, which was significantly more severe in NHE3KS-KO mice. This exacerbated acidosis correlated with a&#x2009;~&#x2009;60% lower mRNA expression of glutamine synthetase and a lower urinary NH4+/creatinine ratio. Furthermore, early histopathological signs of hypokalemic nephropathy were observed exclusively in some of the NHE3KS-KO mice. Our findings demonstrate that renal NHE3 attenuates the severity of hypokalemia and metabolic acidosis during K+ restriction, possibly via NH4+ formation/transport, which might accelerate the development of hypokalemic nephropathy.

to evaluate humoral immune response to recombinant zoster vaccine(RZV) in immunosuppressed patients with systemic sclerosis(SSc) compared with healthy controls, to identify factors influencing vaccine response, and to assess RZV safety and impact on patient-reported outcome measures(PROMs) and disease activity(DA). A sub-analysis of a randomized, double-blind, placebo-controlled trial included 76 immunosuppressed SSc patients and 304 healthy controls(CG) receiving two RZV doses. SSc patients were randomized to receive two initial doses of RZV or placebo; after unblinding, the placebo group received two doses of RZV. Anti-glycoprotein-E antibodies were measured at baseline and six-weeks post-second dose. Geometric mean concentrations(GMCs) and factor increase(FI) were calculated. Cell-mediated immunogenicity (CMI) was evaluated. DA and PROMs were assessed using standardized instruments. Body mass index(BMI) defined nutritional status. SSc patients(47.4%diffuse/52.6%limited) were younger(53.0 vs 55.0&#x2009;years, p= 0.002) and had lower BMI(p= 0.005) than CG. Humoral response were significantly lower in SSc compared with controls(92.6% vs 99.7%,p= 0.001). SSc patients showed significantly lower GMC(5.81 vs 12.6, p< 0.001) and FI(31.0 vs 59.4, p< 0.001) than controls, with comparable CMI(p> 0.05). Disease subtypes, demographic factors, immunosuppressive therapies or nutritional status did not predict impaired vaccine response(p> 0.05). Local adverse events were reduced in SSc patients(73.7% vs 86.5%,p= 0.024), while systemic reactions were comparable overall(59.2% vs 61.5%,p= 0.712). DA and PROMs outcomes remained stable(p> 0.05). RZV was well tolerated. Despite the high seroconversion rate, the immune response was significantly lower in magnitude compared with controls, without triggering DA or worsening PROMs. &#x223c;50% lower antibody concentrations in SS raise concerns about long-term protection, underscoring the need for ongoing monitoring. ClinicalTrials.gov; NCT05879419.

Recently, it has been reported that dual agonists of the glucagon-like peptide-1 (GLP-1) receptor and the glucagon receptor (GCGR) have important functions in regulating glucose metabolism and energy expenditure. However, the usefulness of these dual agonists for the treatment of type 2 diabetes remains unclear. This systematic review and meta-analysis of randomized controlled trials aimed to assess the impact of GLP-1/GCGR dual agonists on glycemic markers. The search process was performed in PubMed, Scopus, ClinicalTrials.gov, and Cochrane Library databases. Randomized controlled trials assessing the impact of GLP-1/GCGR agonists on glycemic parameters were included. The meta-analysis was performed with the random-effects model and the generic inverse variance method, and the leave-one-out method was used for the sensitivity analysis. The meta-analysis of 14 randomized controlled trials demonstrated that GLP-1/GCGR agonists significantly decrease fasting glucose (WMD: -0.79 mmol/l, 95% CI: -1.14, -0.45, p<0.0001, I2 = 92%) and HbA1c (WMD: -0.50%, 95% CI: -0.67, -0.32, p<0.0001, I2 = 93%). However, these dual agonists had no significant impact on insulin levels (WMD: -14.78 pmol/l, 95% CI: -35.89, 6.34, p=0.17, I2 = 87%). The subgroup analysis by treatment duration exhibited that GLP-1/GCGR agonists significantly reduced fasting glucose and HbA1c in randomized controlled trials &#x2264;12 weeks and >12 weeks, as well as insulin levels in those studies >12 weeks of treatment. In conclusion, the results of our meta-analysis indicated that GLP-1/GCGR dual agonists have a positive effect by decreasing fasting glucose and HbA1c concentrations.

Given that mobile health (mHealth) technology offers a feasible solution for early hearing loss (HL) screening, the purpose of this study was to determine the diagnostic accuracy and acceptability of an mHealth intervention for HL screening in people over 65 years old across four primary health care (PHC) centers. It was hypothesized that the mHealth app would have higher diagnostic accuracy compared with other index tests. Using a multicenter diagnostic accuracy comparative study design, 203 adults over 65 years old (Mdn = 72 years) were assessed using pure-tone audiometry as the reference-standard test, with mild (> 25 dB) and moderate (&#x2265; 40 dB) HL as cutoffs. Index tests included the following: mHealth hearing screening app, preventive medical examination assessment, diagnostic hearing assessments, and self-reported HL measures. Sensitivity, specificity, and area under the curve (AUC) values were estimated. Acceptability was determined using a validated Likert-type questionnaire. The results of the mHealth HL screening showed the highest sensitivity for mild (90.06%) and moderate (98.44%) HL. The AUC for the mHealth intervention was significantly higher (p < .001) for mild HL compared with all index tests, and it was significantly higher (p < .001) for moderate HL compared with the preventive medical examination assessment. Acceptability of the mHealth intervention was rated as highly acceptable by older adults and professionals. mHealth screening is a sensitive, user-friendly, and acceptable tool for HL screening in older adults. Integration within preventive medical examination programs is feasible and could enhance early HL detection and management within PHC contexts. https://doi.org/10.23641/asha.32536584.

Microtubules are essential cytoskeleton polymers composed of &#x3b1;/&#x3b2;-tubulin heterodimers that play a central role in the regulation of various cellular processes, including cell division, cell shape, cell polarity, motility and intracellular trafficking. The expression of different tubulin genes results in a variety of isotypes that, combined with post-translational modifications (PTMs), define a "tubulin code" that generates microtubule diversity. Growing evidence has shown promising links between tubulin isotypes and PTMs with several cancer properties, leading to the emergence of the concept of a "cancer tubulin code". In this review, we focus on dissecting the impact of tubulin acetylation, detyrosination and polyglutamylation on microtubule properties and functions, and how these PTMs, together with specific tubulin isotypes, affect cancer cell division, invasion and metastasis. Because conventional chemotherapy with microtubule-targeting drugs often leads to resistance and accounts for a high mortality rate among cancer patients, we discuss possible directions that explore the potential of the cancer tubulin code and respective microtubule diversity in improving drug response, while overcoming resistance. Lastly, we address the therapeutic value of small-molecule inhibitors of tubulin-modifying enzymes in cancer treatment. Overall, this review showcases the potential of exploring the cancer tubulin code to open new avenues in diagnostic, prognostic and therapeutic applications for precision oncology.

Varnimcabtagene autoleucel (var-cel) is an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy administered using an adaptive, fractionated dosing strategy. We conducted a multicenter retrospective study to evaluate the safety and efficacy of var-cel in patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL) treated at four Spanish centers, including patients enrolled in the CART19-BE-01 trial and a subsequent compassionate use program. Thirty patients underwent leukapheresis; 27 received var-cel following lymphodepletion and fractionated infusion in three escalating doses (0.1 to 5 &#xd7; 106 CAR T cells/kg). Any-grade cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 93% and 4%, respectively, with Grade &#x2265;3 CRS and/or ICANS observed in a single patient (4%). The overall response rate among infused patients was 89% (95% CI, 71-98), including 78% complete responses (95% CI, 58-91). Median duration of response and progression-free survival were 17.1 and 15.4 months, respectively. With a median follow-up of 21.7 months, median overall survival was 35.2 months. In this multicenter academic experience, var-cel demonstrated high antitumor activity with low rates of severe CRS and ICANS, supporting its use within a coordinated national network.