A retrospective multicenter study on clinical and serological parameters in patients with MuSK myasthenia gravis with and without general immunosuppression.

Introduction: Muscle-specific kinase (MuSK)- myasthenia gravis (MG) is caused by pathogenic autoantibodies against MuSK that correlate with disease severity and are predominantly of the IgG4 subclass. The first-line treatment for MuSK-MG is general immunosuppression with corticosteroids, but the effect of treatment on IgG4 and MuSK IgG4 levels has not been studied. Methods: We analyzed the clinical data and sera from 52 MuSK-MG patients (45 female, 7 male, median age 49 (range 17-79) years) from Italy, the Netherlands, Greece and Belgium, and 43 AChR-MG patients (22 female, 21 male, median age 63 (range 2-82) years) from Italy, receiving different types of immunosuppression, and sera from 46 age- and sex-matched non-disease controls (with no diagnosed diseases, 38 female, 8 male, median age 51.5 (range 20-68) years) from the Netherlands. We analyzed the disease severity (assessed by MGFA or QMG score), and measured concentrations of MuSK IgG4, MuSK IgG, total IgG4 and total IgG in the sera by ELISA, RIA and nephelometry. Results: We observed that MuSK-MG patients showed a robust clinical improvement and reduction of MuSK IgG after therapy, and that MuSK IgG4 concentrations, but not total IgG4 concentrations, correlated with clinical severity. MuSK IgG and MuSK IgG4 concentrations were reduced after immunosuppression in 4/5 individuals with before-after data, but data from non-linked patient samples showed no difference. Total serum IgG4 levels were within the normal range, with IgG4 levels above threshold (1.35g/L) in 1/52 MuSK-MG, 2/43 AChR-MG patients and 1/45 non-disease controls. MuSK-MG patients improved within the first four years after disease onset, but no further clinical improvement or reduction of MuSK IgG4 were observed four years later, and only 14/52 (26.92%) patients in total, of which 13 (93.3%) received general immunosuppression, reached clinical remission. Discussion: We conclude that MuSK-MG patients improve clinically with general immunosuppression but may require further treatment to reach remission. Longitudinal testing of individual patients may be clinically more useful than single measurements of MuSK IgG4. No significant differences in the serum IgG4 concentrations and IgG4/IgG ratio between AChR- and MuSK-MG patients were found during follow-up. Further studies with larger patient and control cohorts are necessary to validate the findings.

Comparing R-Bendamustine vs. R-CHOP Plus Maintenance Therapy as First-Line Systemic Treatment in Follicular Lymphoma: A Multicenter Retrospective GELTAMO Study.

Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and R-bendamustine (R-B) are the most common frontline treatment strategies for advanced-stage follicular lymphoma (FL). After R-CHOP induction therapy, using rituximab for maintenance therapy notably improves outcomes; however, whether this can be achieved by using the same approach after R-B therapy is still being determined. This retrospective analysis compared 476 FL patients from 17 GELTAMO centers who received R-based regimens followed by rituximab maintenance therapy for untreated advanced-stage FL. The complete response rate at the end of induction was higher with R-B and relapses were more frequent with R-CHOP. During induction, cytopenias were significantly more frequent with R-CHOP and so was the use of colony-stimulating factors. During maintenance therapy, R-B showed more neutropenia and infectious toxicity. After a median follow-up of 81 months (95% CI: 77-86), the 6-year rates of progression-free survival (PFS) were 79% (95% CI: 72-86) for R-bendamustine vs. 67% (95% CI: 61-73) for R-CHOP (p = 0.046), and 6-year overall survival (OS) values were 91% (95% CI: 86-96) for R-B vs. 91% (95% CI: 87-94) for R-CHOP (p = 0.49). In conclusion, R-B followed by rituximab maintenance therapy in patients with previously untreated FL resulted in significantly longer PFS than R-CHOP, with older patients also benefiting from this treatment without further toxicity. Adverse events during maintenance were more frequent with R-B without impacting mortality.

Survival Outcomes and Health-Related Quality of Life in Older Adults Diagnosed with Acute Myeloid Leukemia Receiving Frontline Therapy in Daily Practice.

Acute myeloid leukemia has a poor prognosis in older adults, and its management is often unclear due to its underrepresentation in clinical trials. Both overall survival (OS) and health-related quality-of-life (HRQoL) are key outcomes in this population, and patient-reported outcomes may contribute to patient stratification and treatment assignment. This prospective study included 138 consecutive patients treated in daily practice with the currently available non-targeted therapies (intensive chemotherapy [IC], attenuated chemotherapy [AC], hypomethylating agents [HMA], or palliative care [PC]). We evaluated patients' condition at diagnosis (Life expectancy [Lee Index for Older Adults], Geriatric Assessment in Hematology [GAH scale], HRQoL [EQ-5D-5L questionnaire], and fatigue [fatigue items of the QLQ-C30 scale]), OS, early death (ED), treatment tolerability (TT) and change in HRQoL over 12 months follow-up. The median OS was 7.1 months (IC not reached, AC 5.9, HMA 8.8, and PC 1.0). Poor risk AML category and receiving just palliative care, as well as a higher Lee index score in the patients receiving active therapy, independently predicted a shorter OS. The Lee Index and GAH scale were not useful for predicting TT. The white blood cell count was a valid predictor for ED. Patients' HRQoL remained stable during follow-up.

Neoadjuvant photodynamic therapy as a therapeutic alternative in multiple basal cell carcinoma induced by radiotherapy.

INTRODUCTION: Non-melanoma skin cancer within previously irradiated areas presents a common challenge, requiring innovative therapies. Complex scenarios, like XRT-induced basal cell carcinoma (BCC) or Gorlin's syndrome, often involve multiple synchronous tumor lesions where photodynamic therapy (PDT) offers a viable therapeutic alternative. CLINICAL CASE: We present the case of a 49-year-old male with a history of XRT for brain tumors. The patient was undergoing treatment for recurrent basal cell carcinomas (BCCs) in the right temporal irradiated area, unresponsive to conventional treatments. In the latest evaluation, the patient presented a nodular tumor and several peripheral superficial foci. Photodynamic therapy (PDT) was administered using methyl aminolevulinate 160 mg/g in cream (Metvix®) in two sessions spaced 7 days apart before surgery. The photosensitizer was applied 3 h before initiating PDT, and red light exposure was performed with the Aktilite© lamp (wavelength 630 nm, 100 mm distance, voltage 100 to 240 V, frequency 50 Hz, power 180 W) for 7 min. CONCLUSIóN: PDT with methyl aminolevulinate demonstrated efficacy as a neoadjuvant treatment in a case of multiple XRT-induced BCCs before surgery. PDT emerges as a valuable therapeutic alternative for multiple BCCs, particularly in non-responsive cases.

Curso electivo para la formación pedagógica de alumnos ayudantes en la carrera de Medicina

Introducción: El proceso de formación de alumnos ayudantes exige nuevas concepciones teóricas y metodológicas, que permitan el desarrollo integral de los futuros profesionales de la salud. Esto mediante acciones específicas que influyan educativamente en la ejecución de los planes y programas de la carrera de Medicina, desde una proyección científica y pedagógica. Objetivo: Diseñar un curso electivo para la formación pedagógica de los alumnos ayudantes en la carrera de Medicina de la Filial Universitaria de Ciencias Médicas, del municipio Cárdenas. Materiales y métodos: La investigación se sustenta desde la concepción dialéctico materialista. Los métodos teóricos fueron: histórico-lógico, análisis documental, sistematización, sistémico estructural funcional y modelación. Entre los métodos empíricos se emplearon: revisión de documentos, encuestas a alumnos ayudantes y tutores. También se realizó observación al desempeño de los alumnos ayudantes. La población fue conformada por 103 alumnos ayudantes y 38 tutores. Resultados: Las insuficientes acciones pedagógicas para la formación de alumnos ayudantes, se constatan como problema en los tres indicadores de la dimensión cognitiva y en dos de los indicadores de las dimensiones procedimental y actitudinal. En el diseño del programa del curso electivo se abordan los temas a desarrollar, para potenciar la formación pedagógica en los alumnos ayudantes. Conclusiones: Se presenta un curso electivo para la formación pedagógica de alumnos ayudantes en la carrera de Medicina.

Introduction: The process of training assistant students requires new theoretical and methodological concepts that allow the comprehensive development of future health professionals. This by means of specific actions that educationally influence the execution of plans and programs of medicine studies, from a scientific and pedagogical projection. Objective: To design an elective course for the pedagogical training of assistant students in the medicine undergraduate studies of University Campus of Medical Sciences, in the municipality of Cardenas. Materials and methods: The research is based on the dialectical materialist conception. The theoretical methods were: historical-logical, documentary analysis, systematization, systemic structural functional and modeling. Among empirical methods used were: documentary review, surveys of the assistant students and tutors. Observation of the performance of assistant students was also carried out. The population consisted of 103 assistant students and 38 tutors. Results: Insufficient pedagogical actions for the training of assistant students are found as problems in the three indicators of the cognitive dimension and in two of the indicators of the procedural and attitudinal dimensions. In the design of the program of the elective course, the topics to be developed to enhance the pedagogical training of the assistant students are addressed. Conclusions: An elective course for the pedagogical training of assistant students in the Medicine undergraduate studies is presented.

Azathioprine in hidradenitis suppurativa with inflammatory phenotype: a case series of 11 patients.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease that negatively impacts the quality of life of patients. It presents as deep-seated nodules, abscesses, fistulae, sinus tracts, and scars in the axilla, inguinal area, submammary folds, and perianal area. Recently, two phenotypes have been described: a follicular phenotype and an inflammatory phenotype. Numerous medical treatments are available for hidradenitis suppurativa, with particular importance of antitumor necrosis factor antibodies. Due to the association of HS with other conditions with a pro-inflammatory state, particularly Crohn's disease, it has been suggested that azathioprine may have a role in the treatment of HS. OBJECTIVE: To assess the effectiveness of azathioprine monotherapy in patients with moderate-severe HS. METHODS: We retrospectively studied patients with HS treated with azathioprine in monotherapy. We performed both clinical and ultrasound evaluation at baseline as well as in the follow-up visits. Their baseline score on the iHS4 and DLQI scales and 12-16 weeks after starting the treatment were compared. We also registered the number of patients who achieved HiSCR. RESULTS: Six patients presented significant improvement, reducing their score in iHS4 and DLQI scales and achieving HiSCR. Another patient had clinical improvement, meaning reduction in iHS4 and DLQI, but without achieving HiSCR. Two patients stopped the treatment before week 12 because of adverse events. The remaining two patients presented no improvement. The median (Q3-Q1) baseline iHS4 score was 6 (12-6), and follow-up iHS4 score, 4 (6-2), being these differences statistically significant (P = 0.006). Median (Q3-Q1) baseline DLQI scores and 12-16 weeks after treatment were 17 (23-11) and 14 (18-9) although statistically nonsignificant (P = 0.099). CONCLUSION: We present a case series of 11 patients treated with azathioprine with good clinical and ultrasonographic response. We suggest that azathioprine may benefit a certain patient profile with the inflammatory phenotype.

HLA-DQA1*05 Was Not Associated With Primary Nonresponse or Loss of Response to First Anti-TNF in Real-World Inflammatory Bowel Disease Patients.

BACKGROUND: We lack predictors of response to biologics in the management of patients with inflammatory bowel disease (IBD). A recent study has shown a significant association between HLA-DQA1*05 carriers and the development of loss of response to anti-tumor necrosis factor (TNF) mediated by immunogenicity. METHODS: Retrospective single-center cohort study including IBD patients who had received anti-TNF therapy as a first biologic and whose HLA-DQA1*05 had been determined. Primary nonresponse and secondary failure (assessed by survival analysis) have been evaluated as well as safety outcomes. RESULTS: A total of 199 IBD patients (161 [81%] with Crohn's disease and 38 [19%] with ulcerative colitis) were included. A total of 42.4% were HLA-DQA1*05 carriers and 60% received combination therapy at the start of anti-TNF treatment. Median follow-up was 24 (interquartile range, 11-66) months. No statistically significant differences were found in primary nonresponse to anti-TNF (89.3% vs 87.8%; P = .825), depending on HLA carriers and noncarriers. No differences in secondary loss of response according to HLA variant in any of the analyses performed (full cohort, according to IBD or anti-TNF type) were observed. Again, no differences were observed in patients treated with combination therapy. In terms of safety, no significant differences were found in the rate of infusion reactions or serious adverse events. CONCLUSION: In our real-life cohort of IBD patients treated for the first time with anti-TNF, being an HLA-DQA1*05 carrier did not act as a predictor of response failure, either primary or secondary. The safety of anti-TNF treatment has also not been influenced by the variant.

The HLA variant DQA1*05 has been identified as a risk factor for the development of antibodies to anti-tumor necrosis factor drugs. We observed that its presence has no impact on clinical outcomes, such as secondary loss of response. These data suggest that caution is required before making decisions based on this HLA variant.

Brachytherapy in the prevention of recurrence of conjunctival melanoma : Results of a case report in a University Hospital in Valladolid, Spain.

AIM: Describe the results of brachytherapy in the prevention of recurrences in conjunctival melanoma (CM) and describe a dosimetric protocol. METHODS: Retrospective and descriptive case report. Eleven consecutive patients with a confirmed histopathological diagnosis of CM treated with brachytherapy between 1992 and 2023 were reviewed. Demographic, clinical, and dosimetric characteristics as well as recurrences were recorded. Quantitative variables were represented by the mean, median, and standard deviation, and qualitative variables by frequency of distribution. RESULTS: Of a total of 27 patients diagnosed with CM, 11 who were treated with brachytherapy were included in the study (7 female; mean age at time of treatment: 59.4 years). Mean follow-up was 58.82 months (range 11-141 months). Of a total of 11 patients, 8 were treated with ruthenium-106 and 3 with iodine-125. Brachytherapy was performed in 6 patients as adjuvant therapy after biopsy-proven CM on histopathology and in the other 5 patients after recurrence. The mean dose was 85 Gy in all cases. Recurrences outside of the previously irradiated area were observed in 3 patients, metastases were diagnosed in 2 patients, and one case of an ocular adverse event was reported. CONCLUSION: Brachytherapy is an adjuvant treatment option in invasive conjunctival melanoma. In our case report, only one patient had an adverse effect. However, this topic requires further research. Furthermore, each case is unique and should be evaluated by experts in a multidisciplinary approach involving ophthalmologists, radiation oncologists, and physicists.

Clinical outcomes after CPX-351 in patients with high-risk acute myeloid leukemia: A comparison with a matched cohort from the Spanish PETHEMA registry.

BACKGROUND: CPX-351 is approved for the treatment of therapy related acute myeloid leukemia (t-AML) and AML with myelodysplastic related changes (MRC-AML). The benefits of this treatment over standard chemotherapy has not been addressed in well matched cohorts of real-life patients. METHODS: Retrospective analysis of AML patients treated with CPX-351 as per routine practice. A propensity score matching (PSM) was used to compare their main outcomes with those observed in a matched cohort among 765 historical patients receiving intensive chemotherapy (IC), all of them reported to the PETHEMA epidemiologic registry. RESULTS: Median age of 79 patients treated with CPX-351 was 67 years old (interquartile range 62-71), 53 were MRC-AML. The complete remission (CR) rate or CR without recovery (CRi) after 1 or 2 cycles of CPX-351 was 52%, 60-days mortality 18%, measurable residual disease <0.1% in 54% (12 out of 22) of them. Stem cell transplant (SCT) was performed in 27 patients (34%), median OS was 10.3 months, and 3-year relapse incidence was 50%. Using PSM, we obtained two comparable cohorts treated with CPX-351 (n = 52) or IC (n = 99), without significant differences in CR/CRi (60% vs. 54%) and median OS (10.3 months vs. 9.1 months), although more patients were bridged to SCT in the CPX-351 group (35% vs. 12%). The results were confirmed when only 3 + 7 patients were included in the historical cohort. In multivariable analyses, SCT was associated with better OS (HR 0.33 95% CI: 0.18-0.59), p < 0.001. CONCLUSION: Larger post-authorization studies may provide evidence of the clinical benefits of CPX-351 for AML in the real-life setting.

Outcomes after robotic thymectomy in nonthymomatous versus thymomatous patients with acetylcholine-receptor-antibody-associated myasthenia gravis.

The aim of this study was to investigate the surgical and long-term neurological outcomes of patients with acetylcholine-receptor-antibody-associated myasthenia gravis (AChR-MG) who underwent robotic thymectomy (RATS). We retrospectively analyzed the clinical-pathological data of all patients with AChR-MG who underwent RATS using the DaVinci® Robotic System at the MUMC+ between April 2004 and December 2018. Follow-up data were collected from 60 referring Dutch hospitals. In total, 230 myasthenic patients including 76 patients with a thymoma (33.0%) were enrolled in this study. Mean follow-up time, procedure time and hospitalization were, respectively 65.7 ± 43.1 months, 111±52.5 min and 3.3 ± 2.2 days. Thymomatous patients had significantly more frequently and more severe complications than nonthymomatous patients (18.4% vs. 3.9%, p<0.001). Follow up data was available in 71.7% of the included patients. The Myasthenia Gravis Foundation of America postintervention score showed any kind of improvement of MG-symptoms after RATS in 82.4% of the patients. Complete stable remission (CSR) or pharmacological remission (PR) of MG was observed in 8.4% and 39.4% of the patients, respectively. Mean time till CSR/PR remission after thymectomy was 26.2 ± 29.2 months. No statistical difference was found in remission or improvement in MGFA scale between thymomatous and nonthymomatous patients. RATS is safe and feasible in patients with MG. The majority of the patients (82.4%) improved after thymectomy. CSR and PR were observed in 8.4% and 39.4% of the patients, respectively, with a mean of 26.2 months after thymectomy. Thymomatous patients had more frequently and more severe complications compared to nonthymomatous patients.

Epidemiology of Fabry disease in patients in hemodialysis in the Madrid community.

This study screened for Fabry disease (FD) in patients in hemodialysis (HD) in the region of Madrid (CAM) with a cross-sectional design to evaluate HD-prevalent patients, followed by a three-year period prospective design to analyze HD-incident patients. INCLUSION CRITERIA: patients older than 18 years on HD in the CAM, excluding patients diagnosed with any other hereditary disease with renal involvement different from FD, that sign the Informed Consent (IC). EXCLUSION CRITERIA: underaged patients or not agreeing or not being capable of signing the IC. RESULTS: 3470 patients were included, 63% males and with an average age of 67.9±9.7 years. 2357 were HD-prevalent patients and 1113 HD-incident patients. For HD-prevalent patients, average time in HD was 45.2 months (SD 51.3), in HD-incident patients proteinuria was present in 28.4%. There were no statistical differences in plasmatic alpha-galactosidase A (α-GAL-A) activity or Lyso-GL-3 values when comparing HD-prevalent and HD-incident populations and neither between males and females. A genetic study was performed in 87 patients (2.5% of patients): 60 male patients with decreased enzymatic activity and 27 female patients either with a decreased GLA activity, increased Lyso-Gl3 levels or both. The genetic variants identified were: p.Asp313Tyr (4 patients), p.Arg220Gln (3 patients) and M290I (1 patient). None of the identified variants is pathogenic. CONCLUSIONS: 76% of HD Centers of the CAM participated in the study. This is the first publication to describe the prevalence of FD in the HD-population of a region of Spain as well as its average α-GAL-A-activity and plasmatic Lyso-Gl3 levels. It is also the first study that combines a cross-sectional design with a prospective follow-up design. This study has not identified any FD patient.

A 35-year follow-up study of patients admitted to methadone treatment between 1982-1984 in Asturias, Spain. / Estudio de seguimiento de 35 años de pacientes admitidos a tratamiento con metadona entre 1982-1984 en Asturias, España.

The objective was to evaluate outcomes in a heroin-dependent population 35 years after first enrolment in methadone maintenance treatment (MMT).  An ad hoc protocol was used to assess drug misuse, treatment, and drug-related morbidity in the survivor sample. The standardized mortality ratio (SMR) and 95% confidence interval (CI) were calculated.  A total of 214 heroin-dependent patients entered MMT between 1982 and 1984 in the Asturias Public Health Service. Information was received on 195 subjects, of whom 146 were deceased.  Men accounted for 77.5% of the study cohort. Over the 35-year follow-up period, the SMR was 11.75 (95% CI = 9.95 - 13.77). In the survivor sample, 5.7% were still enrolled in MMT; human immunodeficiency virus (HIV) was diagnosed in 38.77% and hepatitis B/C in 73.46%. No differences were found between sexes in mortality or HIV and hepatitis B/C status. None of the female survivors were using heroin at the 35-year follow-up compared with 5.26% of males. In conclusion, our study confirms the high long-term mortality rate of heroin addicts, even after enrollment in MMT.

El objetivo fue evaluar el estado de una población dependiente a la heroína 35 años después de su primera inscripción en un tratamiento de mantenimiento con metadona (TMM). Se utilizó un protocolo ad hoc para evaluar morbilidad, consumo y tratamiento de la adicción en la muestra de supervivientes. Se calculó la razón de mortalidad estandarizada (RME) con un intervalo de confianza (IC) del 95%. Un total de 214 pacientes ingresaron en TMM entre 1982 y 1984 en el Servicio de Salud Pública de Asturias. Se recibió información sobre 195 sujetos, de los cuales 146 habían fallecido. Los hombres representaron el 77,5% de la cohorte del estudio. Durante el período de seguimiento de 35 años, la RME fue de 11,75 (IC 95% = 9,95 ­ 13,77). En la muestra de supervivientes, el 5,7% todavía estaba inscrito en TMM; el virus de inmunodeficiencia humana (VIH) se diagnosticó en un 38,77% y la hepatitis B/C en un 73,46%; el consumo actual de heroína se informó en un 4,1%. No hubo diferencias de género en la mortalidad o la condición de VIH y hepatitis B/C. Ninguna de las mujeres consumía heroína en el seguimiento de 35 años en comparación con el 5,26% de los hombres. En conclusión, nuestro estudio confirma la alta tasa de mortalidad a largo plazo, incluso después de la inscripción en TMM.

The transcriptomic landscape of elderly acute myeloid leukemia identifies B7H3 and BANP as a favorable signature in high-risk patients.

Acute myeloid leukemia (AML) in the elderly remains a clinical challenge, with a five-year overall survival rate below 10%. The current ELN 2017 genetic risk classification considers cytogenetic and mutational characteristics to stratify fit AML patients into different prognostic groups. However, this classification is not validated for elderly patients treated with a non-intensive approach, and its performance may be suboptimal in this context. Indeed, the transcriptomic landscape of AML in the elderly has been less explored and it might help stratify this group of patients. In the current study, we analyzed the transcriptome of 224 AML patients > 65 years-old at diagnosis treated in the Spanish PETHEMA-FLUGAZA clinical trial in order to identify new prognostic biomarkers in this population. We identified a specific transcriptomic signature for high-risk patients with mutated TP53 or complex karyotype, revealing that low expression of B7H3 gene with high expression of BANP gene identifies a subset of high-risk AML patients surviving more than 12 months. This result was further validated in the BEAT AML cohort. This unique signature highlights the potential of transcriptomics to identify prognostic biomarkers in in elderly AML.

Reemergence of pathogenic, autoantibody-producing B cell clones in myasthenia gravis following B cell depletion therapy.

Myasthenia gravis (MG) is an autoantibody-mediated autoimmune disorder of the neuromuscular junction. A small subset of patients (<10%) with MG, have autoantibodies targeting muscle-specific tyrosine kinase (MuSK). MuSK MG patients respond well to CD20-mediated B cell depletion therapy (BCDT); most achieve complete stable remission. However, relapse often occurs. To further understand the immunomechanisms underlying relapse, we studied autoantibody-producing B cells over the course of BCDT. We developed a fluorescently labeled antigen to enrich for MuSK-specific B cells, which was validated with a novel Nalm6 cell line engineered to express a human MuSK-specific B cell receptor. B cells (≅ 2.6 million) from 12 different samples collected from nine MuSK MG patients were screened for MuSK specificity. We successfully isolated two MuSK-specific IgG4 subclass-expressing plasmablasts from two of these patients, who were experiencing a relapse after a BCDT-induced remission. Human recombinant MuSK mAbs were then generated to validate binding specificity and characterize their molecular properties. Both mAbs were strong MuSK binders, they recognized the Ig1-like domain of MuSK, and showed pathogenic capacity when tested in an acetylcholine receptor (AChR) clustering assay. The presence of persistent clonal relatives of these MuSK-specific B cell clones was investigated through B cell receptor repertoire tracing of 63,977 unique clones derived from longitudinal samples collected from these two patients. Clonal variants were detected at multiple timepoints spanning more than five years and reemerged after BCDT-mediated remission, predating disease relapse by several months. These findings demonstrate that a reservoir of rare pathogenic MuSK autoantibody-expressing B cell clones survive BCDT and reemerge into circulation prior to manifestation of clinical relapse. Overall, this study provides both a mechanistic understanding of MuSK MG relapse and a valuable candidate biomarker for relapse prediction.

Caffeine Restores Neuronal Damage and Inflammatory Response in a Model of Intraventricular Hemorrhage of the Preterm Newborn.

Germinal matrix-intraventricular hemorrhage (GM-IVH) is the most frequent intracranial hemorrhage in the preterm infant (PT). Long-term GM-IVH-associated sequelae include cerebral palsy, sensory and motor impairment, learning disabilities, or neuropsychiatric disorders. The societal and health burden associated with GM-IVH is worsened by the fact that there is no successful treatment to limit or reduce brain damage and neurodevelopment disabilities. Caffeine (Caf) is a methylxanthine that binds to adenosine receptors, regularly used to treat the apnea of prematurity. While previous studies support the beneficial effects at the brain level of Caf in PT, there are no studies that specifically focus on the role of Caf in GM-IVH. Therefore, to further understand the role of Caf in GM-IVH, we have analyzed two doses of Caf (10 and 20 mg/kg) in a murine model of the disease. We have analyzed the short (P14) and long (P70) effects of the treatment on brain atrophy and neuron wellbeing, including density, curvature, and phospho-tau/total tau ratio. We have analyzed proliferation and neurogenesis, as well as microglia and hemorrhage burdens. We have also assessed the long-term effects of Caf treatment at cognitive level. To induce GM-IVH, we have administered intraventricular collagenase to P7 CD1 mice and have analyzed these animals in the short (P14) and long (P70) term. Caf showed a general neuroprotective effect in our model of GM-IVH of the PT. In our study, Caf administration diminishes brain atrophy and ventricle enlargement. Likewise, Caf limits neuronal damage, including neurite curvature and tau phosphorylation. It also contributes to maintaining neurogenesis in the subventricular zone, a neurogenic niche that is severely affected after GM-IVH. Furthermore, Caf ameliorates small vessel bleeding and inflammation in both the cortex and the subventricular zone. Observed mitigation of brain pathological features commonly associated with GM-IVH also results in a significant improvement of learning and memory abilities in the long term. Altogether, our data support the promising effects of Caf to reduce central nervous system complications associated with GM-IVH.

Ponatinib, chemotherapy, and transplant in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia.

Promising results have been shown with the combination of ponatinib and chemotherapy in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). The PONALFIL (Ponatinib With Chemotherapy for Young Adults Ph Positive Acute Lymphoblastic Leukemia) trial combined ponatinib (30 mg/d) with standard induction and consolidation chemotherapy followed by allogeneic hematopoietic stem cell transplant (alloHSCT) in newly diagnosed Ph+ ALL patients aged 18 to 60 years. Ponatinib was only given pre-emptively after alloHSCT. Primary end points were hematologic and molecular response before alloHSCT and event-free survival (EFS), including molecular relapse as event. Thirty patients (median age, 49 years; range, 19-59 years) entered the trial. All exhibited hematologic response, and alloHSCT was performed in 26 patients (20 in complete molecular response and 6 in major molecular response). Only 1 patient died (of graft-versus-host disease), and 5 patients exhibited molecular relapse after alloHSCT. No tyrosine kinase inhibitor was given after HSCT in 18 of 26 patients. Twenty-nine patients are alive (median follow-up, 2.1 years; range, 0.2-4.0 years), with 3-year EFS and overall survival (OS) of 70% (95% confidence interval, 51-89) and 96% (95% confidence interval, 89-100), respectively. Comparison of the PONALFIL and the ALLPh08 (Chemotherapy and Imatinib in Young Adults With Acute Lymphoblastic Leukemia Ph [BCR-ABL] Positive; same schedule, using imatinib as the tyrosine kinase inhibitor) trials by propensity score showed significant improvement in OS for patients in PONALFIL (3-year OS, 96% vs 53%; P = .002). The most frequent grade 3 to 4 adverse events were hematologic (42%), infectious (17%), and hepatic (22%), with only one vascular occlusive event. The combination of chemotherapy with ponatinib followed by alloHSCT is well tolerated, with encouraging EFS in adults with newly diagnosed Ph+ ALL. Cross-trial comparison suggests improvement vs imatinib (clinicaltrials.gov identifier #NCT02776605).

Empathy levels among dental students and professors from a dental school in the Dominican Republic / Empatía en estudiantes y profesores de una escuela de odontología de República Dominicana

Abstract Introduction: The concept of empathy has been incorporated as one of the key elements for the achievement of the teaching-learning process goals in health science students. Objective: To estimate and compare the levels of empathy among dental students and professors in the undergraduate dental medicine program at the Universidad Central del Este (Dominican Republic). Materials and methods: Cross-sectional study. The study population (n=264) was divided into two groups: the first consisted of students in their first to fifth year of dental school (N=223; n=215), distributed in two areas (basic-preclinical and clinical courses), while the second group comprised professors working in both areas in the dental school of the university (N=53; n=49). The Jefferson Scale of Empathy (S-Version) was used. The descriptive analysis of the data included the estimation of means, standard deviations and percentages, and the reliability of the data was estimated using Cronbach's alpha. In addition, a two-way ANOVA was performed, calculating the effect size and the statistical power of the test; furthermore, when the Fisher's exact test was significant for any factor, Tukey's test was used to estimate differences between means. A significance level of α<0.05 and β<0.20 was established. Results: Overall empathy scores and compassionate care dimension scores among the professor group did not differ significantly from the scores obtained by the students (basic-preclinical and clinical area), but there were differences between students from both areas (p<0.05). There were no significant differences between the three subgroups in the Perspective Taking and Walking in the Patient's Shoes dimensions (p=0.428 and p=0.866). Conclusion: The levels of empathy and compassionate care dimension of professors are similar to those of students in general (regardless of the area).

Resumen Introducción. El concepto de empatía se ha integrado como uno de los elementos centrales para el logro final del proceso de enseñanza-aprendizaje en estudiantes de ciencias de la salud. Objetivo. Estimar y comparar los niveles de empatía entre estudiantes y profesores de pregrado de odontología de la Universidad Central del Este (República Dominicana). Materiales y métodos. Estudio transversal. La población de estudio (n=264) se dividió en dos grupos: el primero, compuesto por estudiantes de primero a quinto año de la carrera de odontología (N=223; n=215) distribuidos en dos áreas (básica-preclínica y clínica), y el segundo, por los docentes de ambas áreas en la escuela de odontología de la universidad (N=53; n=49). Se utilizó la Escala de Empatía Médica de Jefferson (Versión-S). El análisis descriptivo de los datos incluyó la estimación de medias, desviaciones estándar y porcentajes, y la confiabilidad de los datos se estimó mediante CC de Cronbach; además, se realizó un ANOVA bifactorial, calculándose el tamaño del efecto y la potencia de la prueba, y en los casos en que la prueba exacta de Fisher fue significativa para algún factor, se utilizó la prueba de Tukey para estimar las diferencias entre las medias. El nivel de significancia estadística utilizado fue α<0.05 y β<0.20. Resultados. Los valores globales de empatía y de la dimensión Cuidado con compasión en los profesores no difirieron significativamente con los obtenidos por los estudiantes (área básica-preclínica y clínica), pero sí hubo diferencias entre los estudiantes de ambas áreas (p<0.05). En las dimensiones Adopción de perspectiva y Ponerse en los zapatos del otro no existieron diferencias entre los tres subgrupos (p=0.428 y p=0.866). Conclusión. Los niveles de empatía y de la dimensión Cuidado compasivo de los profesores no difieren de los de los estudiantes en general (ambas áreas).