New variants expand the neurological phenotype of COQ7 deficiency.

The protein encoded by COQ7 is required for CoQ10 synthesis in humans, hydroxylating 3-demethoxyubiquinol (DMQ10) in the second to last steps of the pathway. COQ7 mutations lead to a primary CoQ10 deficiency syndrome associated with a pleiotropic neurological disorder. This study shows the clinical, physiological, and molecular characterization of four new cases of CoQ10 primary deficiency caused by five mutations in COQ7, three of which have not yet been described, inducing mitochondrial dysfunction in all patients. However, the specific combination of the identified variants in each patient generated precise pathophysiological and molecular alterations in fibroblasts, which would explain the differential in vitro response to supplementation therapy. Our results suggest that COQ7 dysfunction could be caused by specific structural changes that affect the interaction with COQ9 required for the DMQ10 presentation to COQ7, the substrate access to the active site, and the maintenance of the active site structure. Remarkably, patients' fibroblasts share transcriptional remodeling, supporting a modification of energy metabolism towards glycolysis, which could be an adaptive mechanism against CoQ10 deficiency. However, transcriptional analysis of mitochondria-associated pathways showed distinct and dramatic differences between patient fibroblasts, which correlated with the extent of pathophysiological and neurological alterations observed in the probands. Overall, this study suggests that the combination of precise genetic diagnostics and the availability of new structural models of human proteins could help explain the origin of phenotypic pleiotropy observed in some genetic diseases and the different responses to available therapies.

Frontline Therapy in Chronic Lymphocytic Leukemia.

BACKGROUND: The treatment landscape of chronic lymphocytic leukemia (CLL) has tremendously evolved in the last decades, thanks to the introduction of more effective therapies. SUMMARY: Frontline therapy for patients with CLL includes chemoimmunotherapy (CIT) and pathway inhibitors (PIs) (i.e., bruton tyrosine kinase inhibitors and BCL2 inhibitors); the latter has proved to be more effective than CIT mainly in patients with high-risk features (e.g., TP53 aberrations and unmutated IGHV) with acceptable toxicity. Combinations of PIs are playing the protagonist role as frontline therapy for CLL. KEY MESSAGES: In this article, the management of treatment-naïve patients with CLL is discussed.

Evolution in the frontline treatment of patients with chronic lymphocytic leukemia: experience from one European center.

Treatment of chronic lymphocytic leukemia (CLL) has dramatically evolved over the last decades thanks to the introduction of targeted therapies. We aimed to describe retrospectively the evolution in the frontline prescription in the CLL patients from our institution. As a secondary objective, the impact of frontline therapy on the time-to-next-treatment (TTNT) and overall survival (OS). After a median of 6.4 years (0.1-36.4) of follow-up from diagnosis, 323 of 780 CLL patients (41.4%) required therapy. Alkylating agents in monotherapy (chlorambucil) were the most used until 2012, and from then, chemoimmunotherapy. Since 2018, targeted therapies were the most common therapeutic strategy (74.1%). Patients who received targeted therapies had significantly longer TTNT compared to other regimens. In the multivariable analyses, mutated IGHV genes targeted therapies and chemoimmunotherapy regimens were related to longer TTNT, and sex female, age younger than 65, and mutated IGHV genes were associated with better OS.

Hidratación combinada y efectos en la salud vocal en estudiantes de logopedia / Combined hydration and effects on the vocal health in speech language pathology students

Objetivo: Evaluar si la hidratación combinada (sistémico y superficial) disminuye síntomas vocales y mejora la eficiencia glótica en una muestra de estudiantes de Logopedia. Material y Métodos: Estudio cuasi-experimental con grupo Hidratación (N=20) y grupo Control (N=19) con valoración pre y post-hidratación (ingesta de agua 1.500 ml/día e inhalaciones dos veces/día durante una semana). Se analizaron factores deshidratantes relacionados con la voz (uso vocal, tabaco, alcohol, café, respiración bucal), síntomas vocales y eficiencia glótica a través del Tiempo Máximo Fonación, Fo, Jitter % y Shimmer %, usando Multi-Dimensional Voice Program (MDVP). Resultados: Grupo Hidratación disminuyó significativamente sequedad (p = 0,013), carraspeo (p = 0,005), fatiga vocal (p = 0,015), dolor faríngeo (p = 0,009), Shimmer % (p = 0,048) frente al grupo Control que sólo disminuyó el carraspeo (p = 0,02). Conclusiones: La hidratación combinada puede ser una medida útil para mejorar la salud vocal de los futuros logopedas. (AU

Objective: To evaluate if a combined hydration (systemic and superficial) decreases the vocal symptoms and improves the glottic efficiency in a sample of university students of Speech therapist. Material and Methods: Quasi-experimental study with Hydration group (N=20) and Control group (N=19) with pre and post-hydration assessment (water intake 1.500 ml/day and steam twice/day for a week). Voice-related dehydrating factors (vocal use, tobacco, alcohol, coffee, oral breathing), vocal symptoms and glottic efficiency through Maximum Phonation Time, Fo, Jitter % and Shimmer %, using Multi-Dimensional Voice Program (MDVP) were analyzed. Results: Hydration group significantly decreased dryness (p = .013=, throat clearing (p = .005), vocal fatigue (p = .015), pain throat (p = .009) and Shimmer % (p = .048) compared to the Control group, which only decreased throat clearing (p = .02). Discussion: The combined hydration may be a useful measure to improve vocal health for future speech-language-pathologists. (AU)

Sequence matters: Total body irradiation (TBI)-based myeloablative conditioning with post-transplant cyclophosphamide may reduce the early nonrelapse mortality compared with pretransplant cyclophosphamide plus TBI.

OBJECTIVES: High-dose total body irradiation (TBI) is considered a cornerstone of myeloablative conditioning for allogeneic stem cell transplantation (allo-SCT). We retrospectively compared the main outcomes of an HLA matched or 1-allele mismatched related or unrelated allo-SCT in adult patients affected by acute leukemia (AL) or myelodysplastic syndromes (MDS). METHODS: Fifty-nine patients received cyclophosphamide (Cy)-TBI (13.5 Gy) and graft-versus-host disease (GVHD) prophylaxis with a calcineurin-inhibitor plus methrotrexate (CyTBI group) and 28 patients received fludarabine-TBI (8.8-13.5 Gy) and GVHD prophylaxis with PTCy and tacrolimus (FluTBI-PTCy group). RESULTS: Median follow-up for survivors was 82 and 22 months. The 12-month probability of overall survival and progression-free survival were similar (p = .18, p = .7). The incidence of Grades 2-4 and 3-4 acute GVHD, and the incidence of moderate-to-severe chronic GVHD were higher in the CyTBI group (p = .02, p < .01and p = .03). Nonrelapse mortality (NRM) at 12 months posttransplant was higher in the CyTBI group (p = 0.05), while the incidence of relapse was similar in both groups (p = 0.7). The number of GVHD-free and relapse-free patients without systemic immunosuppression (GRFS) at 1-year posttransplant was higher in the FluTBI-PTCy group (p = 0.01). CONCLUSIONS: The study confirms the safety and efficacy of a novel FluTBI-PTCy platform with reduced incidence of severe acute and chronic GVHD, and early improvement of NRM.

Successful Outcome in Patients with Myelofibrosis Undergoing Allogeneic Donor Hematopoietic Cell Transplantation Using Reduced Doses of Post-Transplantation Cyclophosphamide: Challenges and Review of the Literature.

Engraftment and nonrelapse mortality (NRM) after allogeneic hematopoietic cell transplantation (allo-HCT) depend greatly on the transplantation platform in patients with myelofibrosis (MF). We report outcomes of 14 consecutive MF patients who received reduced doses of post-transplantation cyclophosphamide (PTCy; 60 mg/kg total dose) and tacrolimus as graft-versus-host disease (GVHD) prophylaxis as part of a new standardized allo-HCT protocol. The median patient age at allo-HCT was 59 years (range, 41 to 67 years), and the median interval from diagnosis to HCT was 19 months (range, 2 to 114 months). All patients received ruxolitinib before HCT, and 71% had no response. Most patients (78%) had symptomatic splenomegaly at HCT. Eighty-six percent received reduced-intensity conditioning, and 64% underwent allo-HCT from an unrelated donor. There were no graft failures, and neutrophil and platelet recovery occurred at a median of 21 days and 31 days, respectively. The cumulative incidence of grade II-IV acute GVHD was 28.6%, and that of grade III-IV acute GVHD was 7%. The 2-year incidence of overall and moderate-severe chronic GVHD was 36% and 14%, respectively. Only 1 patient relapsed after transplantation, and NRM was 7% at 100 days and 14% at 2 years. The GVHD-free/relapse-free and immunosuppression-free incidence at 1 year was 41%. With a median follow-up for survivors of 28 months (range, 8 to 55 months), the 2-year overall survival and progression-free survival were 86% and 69%, respectively. Reduced doses of PTCy as GVHD prophylaxis for high-risk MF patients showed promising results by reducing the incidence of GVHD without any cases of graft failure.

Análisis de la variabilidad del resultado del cultivo para «Streptococcus agalactiae» entre la semana 35-37 de gestación y el ingreso en sala de partos / Analysis of the variability of the culture outcome for «Streptococcus agalactiae» between week 35-37 of gestation and admission to delivery

Objetivo: Analizar la variabilidad del resultado del cultivo para Streptococcus agalactiae entre la semana 35-37 de gestación y el ingreso en sala de partos, así como las posibles variables influyentes en este cambio. Metodología: Estudio observacional, descriptivo y transversal. Se realizó un análisis descriptivo e inferencial, uni y bivariante. Técnica de muestreo no probabilística accidental. Resultados: Participaron 304 mujeres gestantes (608 muestras). La prevalencia de S. agalactiae se situó en el 15,1 % (preingreso) y el 15,6 % (ingreso). El 7,2 % de las mujeres (22) presentaron variabilidad de resultado entre el primer y el segundo cultivos. El 4,2 % (8) positivizó y un 3 % (14) negativizó. El 22,9 % (29) de los casos positivos presentaron cepas resistentes a clindamicina.Un antecedente de cultivo positivo aumentó la probabilidad de positividad cuatro veces durante la gestación actual. Los principales factores que influyeron en el cambio del resultado del cultivo aumentando su probabilidad fueron: la etnia (6,155 veces), el primer cultivo positivo (15,203 veces), la presencia de infecciones de transmisión sexual (3,8 veces), la edad (x2 0,005) y el peso (x2 0,044) con resultados estadísticamente relevantes. (AU)

Purpose: To investigate the variability of the culture result for Streptococcus agalactiae between weeks 35-37 of gestation and admissions to the delivery room and the possible variables influencing this change. Material and methods: An observational, descriptive, cross-sectional study of a series of cases was conducted with 304 (608 cultures) pregnant women. An accidental non-probabilistic sampling technique was used. Results: The results’ variability occurred in 7.2% (22) of the sample, where 4% (9) changed from positive to negative, and 26% (14) changed from negative to positive. The prevalence of pregnant women with positive Streptococcus agalactiae was 50 positives in the first culture (15.6%) and 46 (15.1%) in a second time. 4.2% (8) were positive and 3% (14) were negative. 22.9% (29) of the positive cases presented strains resistant to clindamycin.Presenting a history of positive culture in another pregnancy increased the probability of positivity four times during the current pregnancy. Likewise, obtaining a positive result in the first culture registered the probability of continuing to be positive in subsequent determinations in 9.5 times. The presence of a history of sexually transmitted infections increased the probability of suffering a change in result by 3.8 times. (AU)

Outcomes from a Spanish Expanded Access Program on cannabidiol treatment in pediatric and adult patients with epilepsy.

AIM: To evaluate the effectiveness and tolerability of cannabidiol (CBD) in patients with developmental and epileptic encephalopathies, including Dravet syndrome (DS), and Lennox-Gastaut syndrome (LGS), in a Spanish Expanded Access Program (EAP). METHODS: This was a multicenter, retrospective, observational study of patients treated with purified CBD in 14 hospitals across Spain. Patients with (1) written informed consent and (2) at least 6 months follow-up before the closure of the database were included. Primary effectiveness endpoints included reductions (100 %, ≥75 %, ≥50 %, ≥25 %, or 0 %) or worsening in seizure frequency (all seizure types and most disabling seizures) at 1-, 3-, 6-, and 12-month visits and at the last visit, and median relative seizure reduction between baseline and last visit. Secondary effectiveness endpoints included retention rate, reduction in seizure severity, status epilepticus, healthcare utilization, and quality of life. Primary safety endpoints included rates of adverse events (AEs) and AEs leading to discontinuation. RESULTS: One hundred and two patients (DS 12 %; LGS 59 %; other epilepsy syndromes 29 %) with a mean age of 15.9 years were enrolled. Patients were highly refractory to antiseizure medications (ASMs); mean number of prior failed ASMs was 7.5 (SD 3.7). The mean CBD dose was 13.0 mg/kg/day at the last visit. The proportion of patients with ≥50 % reduction in the total number of seizures from baseline was 44.9 % at 6 months and 38.9 % at 12 months. The median number of total seizures per month reduced by 47.6 % from baseline to the last visit. At 12 months, seizure severity was lower in 33/54 patients (61.1 %) and unchanged in 17/54 patients (31.5 %). Quality of life, based on the CAVE scale, increased from a mean score of 17.9 ± 4.7 (n = 54) at baseline to 21.7 ± 5.5 (n = 51) at the last patient visit (21.2 % improvement). The mean treatment retention time was 10.3 months. There were no statistically significant changes in the number of status epilepticus episodes, but lower healthcare utilization was observed. Adverse events occurred in sixty-eight patients (66.7 %), and the most common were somnolence (34.3 %) and diarrhea (12.7 %). Cannabidiol was discontinued exclusively due to AEs in 7.8 % of patients, increasing to 25.5 % when both lack of efficacy and AEs were considered together. CONCLUSIONS: Cannabidiol demonstrated promising effectiveness and tolerability in patients with developmental and epileptic encephalopathies taking part in a Spanish EAP.

Effectiveness of proprioceptive neuromuscular facilitation therapy and strength training among post-menopausal women with thumb carpometacarpal osteoarthritis. A randomized trial.

BACKGROUND: Thumb carpometacarpal osteoarthritis (CMC OA) greatly affects post-menopausal women. It is characterized by pain and functional deficits that limit the performance of activities of daily life and affect quality of life. PURPOSE: Analyze the effects of 4/weeks strength training, with and without proprioceptive neuromuscular facilitation (PNF) on the disability among post-menopausal women with thumb CMC OA. Secondly, analyze the effects on pain, mobility, and strength. STUDY DESIGN: Superiority randomized clinical trial. METHODS: 42 women were randomly allocated to strength training program (SEG, n = 21) and to a strength training plus PNF therapy program (PNFG, n = 21). The Disability (disabilities of the arm, shoulder and hand questionnaire), pain (visual analogue scale), mobility (Kapandji Test), and hand strength were evaluated pre, post intervention (at 4 weeks) and follow-up (at 8 weeks). RESULTS: Disability was significantly reduced in both groups after intervention, but reduction was statistically superior in PNFG (between-group mean difference [MD] = -16.69 points; CI = -21.56:-11.82; P<.001; d = 2.14). Similar results were observed for secondary outcomes: pain (MD = -2.03; CI = -2.83:-1.22; P<.001; d = 1.58), mobility (MD = 0.96; CI = 0.52:1.38; P<.001; d = 1.40) and strength (grip: MD = 3.47kg; CI = 1.25:5.69; P = .003; d = 0.97, palmar: MD = 0.97kg; CI = 0.14:1.80; P = .024; d = 0.72, tip: MD = 1.12kg; CI = 0.41:1.83; P = .003; d = 0.99 and key pinch: MD = 0.85kg; CI = 0.001:1.70; P = .049; d = 0.62). These improvements were maintained at follow-up. CONCLUSIONS: The combination of PNF exercises and strength training is more effective for reducing disability pain and improve mobility and strength in post-menopausal women with CMC OA than a programme based solely on strength.

Infecciones de transmisión sexual e influencia en la positividad y/o modificación del resultado del cultivo para Streptococcus agalactiae durante la gestación / Sexually transmitted infections and influence on positivity and/or modification of culture results for Streptococcus agalactiae during gestation

Objetivo: Analizar la relación entre las infecciones de transmisión sexual (ITS) y la positividad para Streptococcus agalactiae (SGB) y/o la modificación del resultado del cultivo para SGB durante el tercer trimestre de gestación. Metodología: Estudio observacional, descriptivo y transversal de serie de casos en gestantes durante el periodo 2016-2018. Muestreo no probabilístico, accidental consecutivo, con un análisis descriptivo e inferencial y una recogida de datos ambispectiva. Resultados: La muestra del estudio fue de 304 gestantes (608 cultivos). La prevalencia de SGB en gestantes fue de 48 (15,3%). Existió una variabilidad de resultados entre los cultivos de 22 (7,2%). Un total de 25 gestantes (8,2%) presentaron antecedentes de ITS, lo que multiplicó el riesgo en 3,8 veces (p= 0,01) para la modificación y/o positividad del cultivo. No se halló asociación entre el tipo de ITS y el cultivo positivo para SGB y/o modificación de éste. Conclusiones: El estudio actualiza la prevalencia de SGB en nuestro medio en el 15,1-15,6%, y muestra una variabilidad del resultado del cultivo para SGB durante el tercer trimestre de gestación del 7,2%.El antecedente de ITS se asoció con una mayor probabilidad de modificación del cultivo para SGB (p= 0,01), así como de positividad del cultivo para SGB (p= 0,01) durante el tercer trimestre de gestación.Se debería considerar el antecedente de ITS, dada su influencia en el resultado final y/o positividad del cultivo rectovaginal. Se precisarían estudios de mayor amplitud y prospectivos para optimizar el cribado para SGB durante la gestación. (AU)

Objective: To analyze the relationship between sexually transmitted infections (STIs) and positivity for Streptococcus agalactiae (GBS) and/or the modification of the culture result during third trimester of pregnancy.Methodology: Observational, descriptive, cross-sectional study of a series of cases in pregnancy women during the years 2016-2018. Non probabilistic, accidental and consecutive sampling with a descriptive and inferential analysis.Results: The study sample was 304 pregnant women (608 cultures). The prevalence of GBS was 48 (15.3%). There was a variability of results between the cultures of 22 (7.2%). 25(8.2%) of the pregnant women had a history of STIs, multiplying the risk by 3.8 times (p= 0.01) for the modification and/or positivity of the culture. There was no association between the type of STIs and the positive culture for GBS and/or its modification.Conclusions: The study updates the prevalence of GBS in our environment and shows a variability of between 15.1-15.6% and variability for the result of the culture during the third trimester of pregnancy of 7.2%.The history of STI was also associated with a greater probability of modification (p= 0.01) and positivity (p= 0.01) of the culture for GBS during the third trimester of gestation.A history of STI should be considered given its influence on the result and positivity of the vaginal-rectal culture. A larger study is required to optimize screening for GBS in pregnancy. (AU)

El sujetador mamario como herramienta de salud en la mujer / The breast bra as a health tool for women

Objetivo: Estudiar la literatura existente sobre el sujetador mamario como herramienta de bienestar y/o salud en la mujer.Metodología: Revisión bibliográfica en las bases de datos Turning Research Into Practice, Biblioteca Cochrane Plus, PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), BMJ Best Practice, Cuiden, Cuidatge y UpToDate en inglés y español de los últimos 10 años. Ultima búsqueda en septiembre de 2021.Resultados: De las 150 referencias bibliográficas halladas, 130 cumplían los criterios de selección. Se seleccionaron 12 artículos: 8 originales, 2 guías de actuación y 2 revisiones sistemáticas. Los principales resultados hacían referencia al dolor de mama y sus causas, procesos dolorosos relacionados con el sujetador y su uso (talla, copa...), situaciones especiales (gestación, lactancia, deportes de impacto o cirugías en la mama), alteraciones biomecánicas e influencia en la calidad de vida relacionada con la depresión y la ansiedad.Conclusiones: No se halló evidencia de que la flacidez de los senos esté causada por no usar sujetador mamario. Tampoco se halló relación entre el uso de sostén y un mayor riesgo de cáncer de mama. Se relacionó el correcto uso del sujetador mamario con mejoras en la mastalgia, alteraciones locales o irradiadas, osteomusculares y nerviosas, alteraciones biomecánicas y del estado de ánimo. Parece que el uso del sujetador es beneficioso en determinadas situaciones, como la gestación y la lactancia, las intervenciones quirúrgicas de la mama y la práctica de deportes de impacto. Se evalúa la prenda del sujetador mamario como una herramienta más de salud en la mujer. (AU)

Objective: To study the existing literature on the bra as a tool for well-being in women.Methodology: Review of the Turning Research into Practice, Cochrane Library Plus, PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), BMJ Best Practice and UpToDate databases in English and Spanish for the last 10 years. Last search in September 2021.Results: Of the 150 bibliographic references, 130 met the selection criteria. 12 articles were selected: 8 originals, 2 guidelines for action and 2 systematic review. The main results found were breast pain and causes, painful processes related to the bra, special situations such as pregnancy, lactation or breast surgeries, biomechanical alterations and the influence on quality of life related to depression and anxiety.Conclusions: There is no evidence that sagging breasts are caused by not wearing a bra. Nor is it between wearing a bra and an increased risk of breast cancer. Correct use of the bra was related to improvements in breast pain, biomechanical alterations and mood, breastfeeding, breast surgery and practice of impact sports. The bra garment is evaluated as a health tool in women. (AU)

The road to chemotherapy-free treatment in chronic lymphocytic leukaemia.

PURPOSE OF REVIEW: The treatment landscape of chronic lymphocytic leukaemia (CLL) has tremendously evolved in the last decades, from chemo to chemoimmunotherapy (CIT) and, eventually, to pathway inhibitors that target critical pathways for leukaemic cells survival. Also, treatment goals are moving towards achieving undetectable minimal residual disease with little toxicity. RECENT FINDINGS: We performed a thorough review of the history of treatment approvals by both the Food and Drug Administration (FDA) and the European Medicines Agency (EMA). This review especially focuses on therapies that are currently approved by both agencies. The indications and particular characteristics of each drug are examined. SUMMARY: Currently available treatment approaches for CLL offer the opportunity to individualize therapy for every single patient with CLL. Inhibitors of B-cell receptor (BCR) signalling pathways and antiapoptotic proteins are nowadays the treatment of choice for most CLL patients, but CIT can be an option for younger and fit patients with low-risk disease [mutated IGHV, no del(11q) or del(17p)/TP53 mutations].

Utilidad del SPECT-CT en la biopsia del ganglio centinela tras quimioterapia neoadyuvante en cáncer de mama y axila positiva / The usefulness of SPECT-CT in sentinel lymph nodes identification after neoadjuvant chemotherapy in patients with breast cancer and axillary involvement

Objetivo Valorar la utilidad de los estudios híbridos SPECT-CT en la biopsia del ganglio centinela (BGC) post quimioterapia neoadyuvante (QNA) en pacientes cN+. Método Estudio transversal de los resultados obtenidos en un grupo de 25 pacientes tratadas en la Unidad Funcional de Mama del HUGTIP desde marzo de 1918 a septiembre de 2020. La metodología específica para este estudio incluye: 1)ecografía axilar y colocación de marcador ecovisible en el ganglio afecto antes de iniciar la QNA; 2)tras QNA, colocación de marcador ferromagnético (Magseed®) en ganglio marcado previamente (GM); 3)valoración del estado axilar tras la QNA, que incluye estudio linfogammagráfico axilar con SPECT-CT; BGC y exéresis del ganglio marcado (GM) si es distinto al ganglio centinela (GC), y vaciado ganglionar axilar (VGA). Resultados La valoración de los SPECT-CT permitió verificar la coincidencia entre el GM y el GC en 14 casos (56%). En 3 casos no se encontró GC y en 8 casos el marcador magnético no estaba en un GC. La biopsia selectiva de los ganglios (GC y/o GM) fue negativa en 12 pacientes (2 con VGA positivo) y positiva en 13 (4 con VGA positivo). Conclusión El estudio SPECT-CT aportó información adicional sobre la localización y la concordancia del ganglio marcado y el ganglio centinela previa a la cirugía, mejorando la planificación de la misma. (AU)

Objective To evaluate the usefulness of SPECT-CT hybrid studies in the biopsy of sentinel lymph node (SLNB) after neoadjuvant chemotherapy (NAC) in patients with axillary metastatic disease (N+). Methods Cross-sectional study of 25 patients treated in the HUGTIP Breast Functional Unit from March 2018 to September 2020. All patients included in the study were submitted to: (1)axillary ultrasound (US) and US visible marker placement in the affected node before starting the NAC; (2)placement of a ferromagnetic marker in the previously marked lymph node (MLN) after NAC; (3)assessment of axillary status after NAC: it includes SPECT-CT lymphoscintigraphy; SLNB and excision of the MLN whether different from the sentinel lymph node (SLN); and axillary lymph node dissection (ALND). Results In 14 patients (56%) the MLN corresponded with the SLN. In 3 cases it was not possible identify the SLN and in 8 cases the MLN was not a SLN. The biopsy of MLN and SLN was negative for metastasis in 12 patients (2 of them had a positive ALND) and was positive for metastasis in 13 patients (4 of them had a positive ALND). Conclusion The SPECT-CT study provided additional information about the identification and the concordance of the MLN and the SLN improving the surgical planning. (AU)

Factores relacionados con la adherencia al tratamiento antirretroviral en mujeres con VIH: Un estudio mixto con diseño secuencial / Factors affecting adherence to antiretroviral treatment in women with HIV: A sequential mixed model research design

INTRODUCCIÓN: El VIH/Sida afecta cada vez a más mujeres. La adherencia al tratamiento antirretroviral es decisiva en la calidad de vida de las personas infectadas. OBJETIVOS: El objetivo del estudio es determinar el grado de adherencia manifestada en un grupo de mujeres con VIH/Sida, con TAR e identificar los factores y circunstancias que influyen en su adherencia. METODOLOGÍA: Se ha realizado un estudio con diseño mixto secuencial explicativo. Los sujetos de estudio son 86 mujeres diagnosticadas con VIH/Sida en tratamiento con TARGA. RESULTADOS: Se recogieron datos cualitativos de 18 de ellas. El 59,3% de las participantes son no adherentes. Los factores determinantes de la no adherencia son el grado académico, edad, ingresos, así como factores personales, interpersonales como el apoyo sociofamiliar, estigma percibido y autoestigma y factores relativos a la enfermedad y tratamiento. CONCLUSIÓN: Los cuidados de enfermería deben abordar con enfoque de género aquellos factores psicosociales e individuales del proceso de adherencia

BACKGROUND: HIV/AIDS is affecting more and more women. Adherence to antiretroviral treatment (ART) is decisive for those infected to achieve quality of life. PURPOSE: The aim of the present study is to determine the degree of adherence displayed by a group of women with HIV/AIDS and to identify those factors and circumstances which might influence their adherence to ART. METHOD: A sequential mixed model research design was applied. The subjects studied consisted of 86 women diagnosed with HIV/AIDS and treated with ART. Findings and discussion: Qualitative data were collected from 18 of these women. 59.3% of participants were non-adherents. The determining factors for non-adherence were level of education, age, income, as well as personal and/or interpersonal factors such as socio-familial support, perceived stigma, self-stigma and factors related to disease and treatment. Nursing care should take a gender-focused approach towards those psychological and personal factors inherent in the adherence process

Advantages of preoperative localization and surgical resection of metastatic axillary lymph nodes using magnetic seeds after neoadjuvant chemotherapy in breast cancer.

PURPOSE: To assess the safety and effectiveness of magnetic seeds in preoperative localization and surgical dissection of metastatic axillary lymph nodes (LN+) in breast cancer patients with axillary involvement, after neoadjuvant chemotherapy (NAC). In addition, to assess the impact of targeted axillary dissection (TAD) in reducing the rate of false negatives (FN) in sentinel lymph node biopsy (SLNB). MATERIALS AND METHODS: A cross-sectional prospective cohort study was conducted from April 2017 to September 2019, including breast cancer patients with axillary lymph node involvement treated with NAC. Prior to NAC, the LN+ were marked by ultrasound-guided clip insertion. After NAC, a magnetic seed (Magseed®) was inserted in the clip-marked lymph node (MLN). During surgery, the MLN was located and removed with the aid of a magnetic detection probe (Sentimag®) and the sentinel lymph node was removed. Axillary lymph node dissection (ALND) was used to determine the rate of FN for SLNB alone and the combination of SLNB and MLN dissection, called TAD. RESULTS: The study included 29 patients (mean age, 55; range, 30-78 years). Selective preoperative localization and surgical dissection were successful for all 30 MLNs (100%). The MLN corresponded to the SLN in 50% of cases. After ALND, there were 21.4% (3/14) FN with SLNB alone and 5.9% (1/17) with TAD. CONCLUSIONS: Following NAC, selective surgical removal of MLN by preoperative localization using magnetic seeds is a safe and effective procedure with a success rate of 100%. Adding TAD reduces the rate of FN associated with SLNB alone.

Hidden etiology of cerebral palsy: genetic and clinical heterogeneity and efficient diagnosis by next-generation sequencing.

Cerebral palsy (CP) is a heterogeneous neurodevelopmental disorder that causes movement and postural disabilities. Recent research studies focused on genetic diagnosis in patients with CP of unknown etiology. The present study was carried out in 20 families with one family member affected with idiopathic CP. Chromosomal microarray and exome sequencing techniques were performed in all patients. Chromosomal microarray analysis did not show any pathological or probable pathological structural variant. However, the next-generation sequencing study showed a high diagnostic yield. We report 11/20 patients (55%) with different pathogenic or potentially pathogenic variants detected by exome sequencing analysis: five patients with mutations in genes related to hereditary spastic paraplegia, two with mutations in genes related to Aicardi-Goutières syndrome, three with mutations in genes related to developmental/epileptic encephalopathies, and one with a mutation in the PGK1 gene. The accurate and precise patients' selection, the use of a high-throughput genetic platform, the selection of adequate target genes, and the application of rigorous criteria for the clinical interpretation are the most important elements for a good diagnostic performance. Based on our findings, next-generation sequencing should be considered in patients with cryptogenic CP as the first line of genetic workup. IMPACT: Sequencing techniques in CP of uncertain etiology provides a diagnostic yield of 55%. The appropriate selection of cases optimizes the diagnostic yield. NGS facilitate better understanding of new phenotypes of certain genetic diseases.

Pneumoendoscopic single port approach to breast cancer. How we do it?

Endoscopic procedures have not become the gold standard in breast surgery. In order to improve today's outcomes we have developed a pilot study in the Breast Pathology Unit of Hospital Germans Trias i Pujol. A surgical procedure was performed creating a pneumoendoscopic cavity by using a Single Incision Laparoscopic Surgery (Single port) approach with a follow up of four years. Four patients underwent pneumoendoscopic single-port breast surgery receiving skin-sparing quadrantectomy and axillary surgery requiring lymphadenectomy in all of them. All patients had immediate reconstruction with a Latisimus Dorsi flap. No perioperative complications appeared. Mean operative time was 290 min (range 240-315 min) and mean hospital stay was 3,2 days. Surgical margins of all cases were pathologically negative and all patients were disease free after four years of monitoring. All patients were satisfied with the cosmetic outcome in the immediate postoperative and during the follow up. Although all innovative techniques generate hesitation on their beginnings and are liable to improve, we believe that pneumoendoscopic single-port breast surgery can be suitable for breast cancer, offering better cosmetic outcomes with oncological safety.

A very mild phenotype of Charcot-Marie-Tooth disease type 4H caused by two novel mutations in FGD4.

BACKGROUND: Mutations in the FGD4 gene cause an autosomal recessive demyelinating peripheral neuropathy referred to as CMT4H, characterized by its onset in infancy or early-childhood and its slow progression. METHODS: The clinical and genetic status of two patients with CMT4H was studied, performing genetic testing with a panel of genes and analysing FGD4 mRNA expression by quantitative PCR. RESULTS: Two novel FGD4 variants (c.514delG and c.2211dupA) were identified in two mildly affected Spanish siblings with CMT4H, and with disease onset in late adolescence/adulthood (one of them remaining asymptomatic at 20). On examination, foot deformity was observed without weakness or sensory involvement, and in the muscles of the lower extremities magnetic resonance imaging showed no fat replacement. Further analysis of FGD4 expression in peripheral blood suggested that neither mutation affected splicing, nor did they affect the dosage of FGD4 mRNA (compared to a healthy control). It was predicted that each allele would produce a truncated protein, p.Ala172Glnfs*28 (c.514delG) and p.Ala738Serfs*5 (c.2211dupA), the latter containing all the functional domains of the native protein. CONCLUSIONS: The conservation of functional domains in the proteins produced from the FGD4 gene of two patients with CMT4H, could explain both the milder phenotype and the later disease onset in these patients. These results expand the clinical and mutational spectrum of FGD4-related peripheral neuropathies.

Clinical and molecular diagnosis of non-phosphomannomutase 2 N-linked congenital disorders of glycosylation in Spain.

The congenital disorders of glycosylation (CDG) are defects in glycoprotein and glycolipid glycan synthesis and attachment. They affect multiple organ/systems, but non-specific symptoms render the diagnosis of the different CDG very challenging. Phosphomannomutase 2 (PMM2)-CDG is the most common CDG, but advances in genetic analysis have shown others to occur more commonly than previously thought. The present work reports the clinical and mutational spectrum of 25 non-PMM2 CDG patients. The most common clinical symptoms were hypotonia (80%), motor or psychomotor disability (80%) and craniofacial dysmorphism (76%). Based on their serum transferrin isoform profile, 18 were classified as CDG-I and 7 as CDG-II. Pathogenic variations were found in 16 genes (ALG1, ALG6, ATP6V0A2, B4GALT1, CCDC115, COG7, DOLK, DPAGT1, DPM1, GFPT1, MPI, PGM1, RFT1, SLC35A2, SRD5A3, and SSR4). Overall, 27 variants were identified, 12 of which are novel. The results highlight the importance of combining genetic and biochemical analyses for the early diagnosis of this heterogeneous group of disorders.