Reproductive and pregnancy control in Wilson disease patients in Spain.

BACKGROUND AND AIM: Recommendations on pregnancy, lactation, and contraception in women with Wilson disease are briefly stated in international guidelines but are not entirely homogeneous. Data regarding the management of these special events among patients with Wilson disease in Spain are lacking. We used the Wilson Registry platform of the Spanish Association for the Study of the Liver to question patients on their reproductive and gestational lives. METHODS: This was a multicentre ambispective study including adult women with Wilson disease in the Spanish Wilson Registry interviewed about their contraception, childbearing, pregnancy, and lactation experiences. Clinical and analytical data were extracted from the registry. RESULTS: The study included 92 women from 17 centres in Spain. Most (63%) reported having a previous pregnancy history. The rate of spontaneous miscarriages was 21.6%, mainly occurring in the first trimester and up to one third among undiagnosed patients. Most pregnant women received chelator therapy during pregnancy, but dose reduction was recommended in less than 10%. After delivery, artificial lactation predominated (60.3%) and its use was mainly based on physician's recommendations (68%). Up to 40% of the women included reported some concerns about their reproductive lives, mainly related to the potential drug toxicity to their children. Most of the patients considered the information given by specialists to be sufficient. CONCLUSION: Gestational management among women with Wilson disease in Spain was found to be highly heterogeneous and frequently different from what is described in international guidelines. Education on rare liver diseases should be a priority for scientific societies in order to homogenize patient follow-up and recommendations.

Telemedicine With Wearable Technologies in Patients Undergoing Hematopoietic Cell Transplantation and Chimeric Antigen Receptor T-Cell Therapy (TEL-HEMATO Study): Prospective Noninterventional Single-Center Study.

BACKGROUND: Patients with hematological malignancies receiving hematopoietic cell transplantation (HCT) or chimeric antigen receptor (CAR) T-cell therapy are at risk of developing serious clinical complications after discharge. OBJECTIVE: The aim of the TEL-HEMATO study was to improve our telehealth platform for the follow-up of patients undergoing HCT or CAR T-cell therapy during the first 3 months after discharge with the addition of wearable devices. METHODS: Eleven patients who received autologous (n=2) or allogeneic (n=5) HCT or CAR T-cell therapy (n=4) for hematological malignancies were screened from November 2022 to July 2023. Two patients discontinued the study after enrollment. The telehealth platform consisted of the daily collection of vital signs, physical symptoms, and quality of life assessment up to 3 months after hospital discharge. Each patient received a clinically validated smartwatch (ScanWatch) and a digital thermometer, and a dedicated smartphone app was used to collect these data. Daily revision of the data was performed through a web-based platform by a hematologist or a nurse specialized in HCT and CAR T-cell therapy. RESULTS: Vital signs measured through ScanWatch were successfully collected with medium/high adherence: heart rate was recorded in 8/9 (89%) patients, oxygen saturation and daily steps were recorded in 9/9 (100%) patients, and sleeping hours were recorded in 7/9 (78%) patients. However, temperature recorded manually by the patients was associated with lower compliance, which was recorded in 5/9 (55%) patients. Overall, 5/9 (55%) patients reported clinical symptoms in the app. Quality of life assessment was completed by 8/9 (89%) patients at study enrollment, which decreased to 3/9 (33%) at the end of the third month. Usability was considered acceptable through ratings provided on the System Usability Scale. However, technological issues were reported by the patients. CONCLUSIONS: While the addition of wearable devices to a telehealth clinical platform could have potentially synergic benefits for HCT and CAR T-cell therapy patient monitoring, noncomplete automation of the platform and the absence of a dedicated telemedicine team still represent major limitations to be overcome. This is especially true in our real-life setting where the target population generally comprises patients of older age with a low digital education level.

Clinical Impact of Supplementation with Pasteurized Donor Human Milk by High-Temperature Short-Time Method versus Holder Method in Extremely Low Birth Weight Infants: A Multicentre Randomized Controlled Trial.

Nosocomial infections are a frequent and serious problem in extremely low birth weight (ELBW) infants. Donor human milk (DHM) is the best alternative for feeding these babies when mother's own milk (MOM) is not available. Recently, a patented prototype of a High-Temperature Short-Time (HTST) pasteurizer adapted to a human milk bank setting showed a lesser impact on immunologic components. We designed a multicentre randomized controlled trial that investigates whether, in ELBW infants with an insufficient MOM supply, the administration of HTST pasteurized DHM reduces the incidence of confirmed catheter-associated sepsis compared to DHM pasteurized with the Holder method. From birth until 34 weeks postmenstrual age, patients included in the study received DHM, as a supplement, pasteurized by the Holder or HTST method. A total of 213 patients were randomized; 79 (HTST group) and 81 (Holder group) were included in the analysis. We found no difference in the frequency of nosocomial sepsis between the patients of the two methods-41.8% (33/79) of HTST group patients versus 45.7% (37/81) of Holder group patients, relative risk 0.91 (0.64-1.3), p = 0.62. In conclusion, when MOM is not available, supplementing during admission with DHM pasteurized by the HTST versus Holder method might not have an impact on the incidence of catheter-associated sepsis.

State of affairs and future challenges in laboratory medicine in Spain: an analysis of the Spanish Society of Laboratory Medicine (SEQCML).

Objectives: Laboratory Medicine is a crucial discipline that contributes to the diagnosis, management and monitoring of patients. This branch of medicine faces two major challenges: New technologies and increased demand. There is limited information available of the state of affairs in Laboratory Medicine in Spain. This study provides a picture of clinical laboratories and clinical laboratory professionals. Methods: The Spanish Society of Laboratory Medicine distributed a questionnaire among the 250 most representative centers (the ones with the largest volume of determinations and training programs), of which 174 (69.6%) returned the questionnaire providing data for 2019. Results: Laboratories were classified according to the number of determinations. In total, 37% identified themselves as small (<1 million determinations per year); 40% considered themselves medium-sized (1-5 million determinations per year) and 23% considered they were large laboratories (>5 million determinations). The level of specialization of laboratory physicians and laboratory performance were higher in large laboratories. Most requests (87%) and determinations (93%) corresponded to biochemistry and hematology. As many as 63% of physicians had an indefinite contract, and 23% were older than 60 years. Conclusions: Laboratory medicine is a consolidated discipline that is gaining relevance in Spain. It adds value to the diagnosis, prognosis and follow-up of diseases, and to treatment response monitoring. The results of this study will help us address challenges such as the need for specialized training for laboratory professionals; the emergence of technological innovations; exploitation of Big Data; optimization of quality management systems and patient safety.

"Cut and Paste" Processes in the Search of Bioactive Products: One-Pot, Metal-free O-Radical Scission-Oxidation-Addition of C, N or P-Nucleophiles.

Hypervalent iodine reagents have been applied in many metal-free, efficient synthesis of natural products and other bioactive compounds. In particular, treatment of alcohols, acetals and acids with hypervalent iodine reagents and iodine results in O-radicals that can undergo a ß-scission reaction. Under these oxidative conditions, derivatives of amino acids, peptides or carbohydrates are converted into cationic intermediates, which can subsequently undergo inter- or intramolecular addition of nucleophiles. Most reported papers describe the addition of oxygen nucleophiles, but this review is focused on the addition of carbon, nitrogen and phosphorous nucleophiles. The resulting products (nucleoside and alkaloid analogs, unnatural amino acids, site-selectively modified peptides) are valuable intermediates or analogs of bioactive compounds.

Intramolecular Metal-Free C(sp3)-H Activation Enables a Selective Mono O-Debenzylation of Fully Protected Aminosugars.

Carbamate-bearing benzylated aminosugars undergo an I2/I(III)-promoted intramolecular hydrogen atom transfer (IHAT) followed by a nucleophilic attack to provide polycyclic structures. Thus, suitably positioned benzyl ethers are surgically oxidized into the corresponding mixed N/O-benzylidene acetals, which can be conveniently deprotected under mild acidic conditions to grant access to selectively O-deprotected aminosugars amenable for further derivatization. The scope of this strategy has been proven with a series of furanosic and pyranosic scaffolds. Preliminary mechanistic studies, including Hammett LFER and KIE analyses, support a reaction pathway with nucleophilic cyclization as the rate-determining step.

Socioeconomic Factors and Quality of Life Perceived by Parents and Children with Complex Chronic Conditions in Spain.

Health-related quality of life of children with complex chronic conditions could be affected by sociodemographic factors. Most studies focus exclusively on the parents' perceptions of quality of life. This study aimed to determine the health-related quality of life of these children, according to their parents and the children themselves. A cross-sectional study was developed on children aged over five years with complex chronic conditions. Health-related quality of life, educational attainment, and social status were evaluated. A total of 101 children were included with a mean age of 10.48 years, and 35.6% were female. The most frequent disease was oncological (28.7%). Children perceived a better health-related quality of life, compared to their parents' assessment: median difference -8.4 (95%CI: -9.2 to -3.8). Moreover, differences were observed by socioeconomic factors. Parents and children with complex chronic conditions perceive differently the health-related quality of life. Social determinants associate with an uneven perceived quality of life.

Tumor de glándula lacrimal: a propósito de un caso / Lacrimal gland tumor: a case proposal

INTRODUCCIÓN: El carcinoma adenoide quístico (CAQ) es conocido por su lento crecimiento, su tendencia a la recurrencia local y al desarrollo de metástasis a distancia incluso décadas después del diagnóstico inicial, y a pesar de terapias agresivas. OBJETIVO: Presentar el caso de una paciente con CAQ de la glándula lagrimal, tumor muy infrecuente que representa casi el 10% de las lesiones orbitarias ocupantes de espacio. De éstas el 20-30% son de origen epitelial, de las cuales el 55% son lesiones benignas y el 45% malignas. El CAQ es el más común de los tumores epiteliales malignos de la glándula lagrimal (65%). CASO CLÍNICO: Presentamos el caso clínico de una paciente con CAQ de glándula lacrimal diagnosticado de forma incidental tras la realización de TAC desde la consulta de psiquiatría. RESULTADOS Y CONCLUSIONES: El síntoma de presentación más frecuente suele ser la proptosis, acompañada o no de dolor, aunque también puede presentarse como ptosis mecánica, reducción de visión y diplopía. La cirugía radical no ha demostrado mejorar la supervivencia o reducir la recurrencia local en comparación con un abordaje quirúrgico, más conservador en pacientes con tumores de menor tamaño y sin afectación ósea. Las mayores tasas de supervivencia se han conseguido, en pacientes tratados con quimioterapia, con quimioterapia citorreductiva intra-arterial seguida de exenteración orbital y radioterapia.

INTRODUCTION:The adenoid cystic carcinoma (ACC) is known for its slow growth, a tendency to local recurrence and the development of distant metastases even decades after the initial diagnosis, and despite aggressive therapies. AIM:We present the case of a patient with a lacrimal gland tumor. They are very rare tumors that represent almost 10% of space-occupying orbital lesions, of which 20-30% are of epithelial origin, of these, 55% are benign and 45% are malignant. The ACC is the most common malignant epithelial tumor (65%). CASE REPORT :We present the clinical case of a patient with ACC of the lacrimal gland incidentally diagnosed after performing a CT scan from the psychiatric office. RESULTS AND CONCLUSIONS:The most frequent presentation symptom is usually proptosis, accompanied or not accompanied by pain, although it can also occur as mechanical ptosis, vision reduction, and diplopia. Radical surgery has not been shown to improve survival or reduce local recurrence compared to a more conservative surgical approach in patients with smaller tumors and without bone involvement. The highest survival rates have been achieved, in patients treated with chemotherapy, with intra-arterial cytoreductors (IACC) followed by orbital exenteration and radiotherapy.

Outcomes of surgical resection after neoadjuvant chemoimmunotherapy in locally advanced stage IIIA non-small-cell lung cancer.

OBJECTIVES: This analysis aimed to evaluate perioperative outcomes of surgical resection following neoadjuvant treatment with chemotherapy plus nivolumab in resectable stage IIIA non-small-cell lung cancer. METHODS: Eligible patients received neoadjuvant chemotherapy (paclitaxel + carboplatin) plus nivolumab for 3 cycles. Reassessment of the tumour was carried out after treatment and patients with at least stable disease as best response underwent pulmonary resection. After surgery, patients received adjuvant treatment with nivolumab for 1 year. Surgical data were collected from the NADIM database and patient charts were reviewed for additional surgical details. RESULTS: Among 46 patients who received neoadjuvant treatment, 41 (89.1%) underwent surgery. Two patients rejected surgery and 3 did not fulfil resectability criteria. There were 35 lobectomies (85.3%), 3 of which were sleeve lobectomies (9.4%), 3 bilobectomies (7.3%) and 3 pneumonectomies (7.3%). Video-assisted thoracoscopy was the initial approach in 51.2% of cases, with a conversion rate of 19% (n = 4). There was no operative mortality at either 30 or 90 days. The most common complications were prolonged air leak (n = 8), pneumonia (n = 5) and arrhythmia (n = 4). Complete resection (R0) was achieved in all patients who underwent surgery, downstaging was observed in 37 patients (90.2%) and major pathological response in 34 patients (82.9%). CONCLUSIONS: Surgical resection following induction therapy with chemotherapy plus nivolumab appears to be safe and offers appropriate oncological outcomes. Perioperative morbidity and mortality rates in our study were no higher than previously reported in this setting. A minimally invasive approach is, therefore, feasible.

Tandem Radical Fragmentation/Cyclization of Guanidinylated Monosaccharides Grants Access to Medium-Sized Polyhydroxylated Heterocycles.

The fragmentation of anomeric alkoxyl radicals (ARF) and the subsequent cyclization promoted by hypervalent iodine provide an excellent method for the synthesis of guanidino-sugars. The methodology described herein is one of the few existing general methodologies for the formation of medium-sized exo- and endoguanidine-containing heterocycles presenting a high degree of oxygenation in their structure.

Paciente con amputación transfemoral derecha, clavo gamma y síndrome hemimotor derecho: valoración y manejo del proceso de protetización / Patient with a right transfemoral amputation, gamma nail, and right Hemi-motor syndrome: assessment and management of the prosthetic fitting

Introducción: la decisión de protetizar a un paciente amputado depende de: la etiología, nivel de amputación, uni o bilateralidad, comorbilidades, soporte sociofamiliar, capacidad funcional y motivación del paciente. Observación clínica: varón, 83 años, diabético, cardiopatía isquémica, accidente cerebrovascular con paresia braquial derecha residual en año 2000. Clavo gamma por fractura pertro-cantérea derecha en 2012 y amputación transfemoral derecha en 2018 de causa vascular. Se protetiza mediante encaje de contención isquiática CAT-CAM, sistema de suspensión tipo Kiss, rodilla de bloqueo a la extensión con adaptación del sistema de desbloqueo en porción antero-interna del encaje y pie Sach. Tras tratamiento fisioterápico, consigue deambulación autónoma con ayuda de un bastón y tercera persona por dificultad para agarre de MSD. Conclusión: los médicos rehabilitadores debemos apostar por dotar a nuestros pacientes de autonomía y funcionalidad, siempre que sea viable.

Introduction: prosthesis, an amputee patient, depends on etiology, level, uni or bilaterality, comorbidities, socio-family support, functional capacity, and motivation of the patient. Clinical observation: male, 83 years old, diabetic, ischemic heart disease, stroke with residual upper right limb (URL) paresis in 2000. Gamma nail due to the right trochanteric fracture in 2012, and right transfemoral amputation in 2018 of vascular cause. Prosthetic fitting CAD-CAM socket/interface, Kiss type suspension system, extension locking knee with an adaptation of the unlocking system in the antero-internal portion of the socket, and Sach foot. After physiotherapeutic treatment, he achieves independent walking with the help of 1 cane and third-person due to difficulty in the URL grip. Conclusion: rehabilitation doctors must bet on providing our patients with independency, and better function, whenever it is viable.

Prenatal screening and diagnosis of genetic abnormalities: SEGO, SEQCML, AEDP consensus recommendations.

In this paper, the scientific societies SEGO, SEQCML and AEDP provide a series of consensus-based recommendations for prenatal screening and diagnosis of genetic abnormalities. A set of evaluation indicators are also proposed as a means to improve the quality of the biochemical, ultrasound, and genetic processes involved in prenatal screening and diagnosis of genetic anomalies. Some recommendations are also proposed in relation to invasive prenatal diagnostic procedures, more specifically regarding sample collection and genetic testing. The purpose of this proposal is to unify performance criteria and quality indicators at national level, with audits performed on a regular basis. It is strongly recommended that a national prenatal screening strategy be established and provided with the resources necessary to evaluate the performance of quality indicators and diagnostic procedures under the supervision of health authorities. Protocols should be revised on a regular basis to consider the incorporation of new cost-effective technologies.

Skin Autofluorescence of Pregnant Women With Diabetes Predicts the Macrosomia of Their Children.

Advanced glycation end products (AGEs) accumulated during long-term hyperglycemia are involved in diabetes complications and can be estimated by skin autofluorescence (sAF). During pregnancy, hyperglycemia exposes women to the risk of having a macrosomic newborn. The aim of this study was to determine whether sAF of women with diabetes during a singleton pregnancy could predict macrosomia in their newborns. Using an AGE Reader, we measured the sAF at the first visit of 343 women who were referred to our diabetology department during years 2011-2015. Thirty-nine women had pregestational diabetes, 95 early gestational diabetes mellitus (GDM), and 209 late GDM. Macrosomia was defined as birth weight ≥4,000 g and/or large for gestational age ≥90th percentile. Forty-six newborns were macrosomic. Their mothers had 11% higher sAF compared with other mothers: 2.03 ± 0.30 arbitrary units (AUs) vs. 1.80 ± 0.34 (P < 0.0001). Using multivariate logistic regression, the relation between sAF and macrosomia was significant (odds ratio 4.13 for 1-AU increase of sAF [95% CI 1.46-11.71]) after adjusting for several potential confounders. This relation remained significant after further adjustment for HbA1c (among 263 women with available HbA1c) and for women with GDM only. sAF of pregnant women with diabetes, a marker of long-term hyperglycemic exposure, predicts macrosomia in their newborns.

Synthesis of Chiral Polyhydroxylated Benzimidazoles by a Tandem Radical Fragmentation/Cyclization Reaction: A Straight Avenue to Fused Aromatic-Carbohydrate Hybrids.

The synthesis of benzimidazole-fused iminosugars through a tandem ß-fragmentation-intramolecular cyclization reaction is described. The use of the benzimidazole ring as the internal nucleophile and the use of phenyliodosophthalate (PhI(Phth)), a new metal-free and low toxic hypervalent iodine reagent, are the most remarkable novelties of this synthetic strategy. With this approach, we have demonstrated the usefulness of the fragmentation of anomeric alkoxyl radicals promoted by the PhI(Phth)/I2 system for the preparation of new compounds with potential interest for both medicinal and synthetic chemists.