Comparison of water- vs. land-based exercise for improving functional capacity and quality of life in patients living with and beyond breast cancer (the AQUA-FiT study): a randomized controlled trial.

BACKGROUND: Patients living with and beyond breast cancer frequently exhibit several side effects that can impact quality of life and physical functioning way beyond diagnosis and cancer therapies. Traditional on-land exercise has shown to be effective in reducing several symptoms of BC but little is known about the role of water-based exercise in improving physical and psychological well-being. OBJECTIVES: To compare land- vs. water-based exercise training for BC survivors to improve Health-Related Quality of Life (HRQoL), cancer-related fatigue (CRF), physical functioning, body composition and physical activity in patients with BC. METHODS: A randomised, parallel group (1:1) controlled trial was conducted between 2020 and 2022. Patients were randomly allocated to complete a similar exercise training twice weekly during 12 weeks either on land (LG) using traditional gym equipment or in a swimming pool (WG) using body-weight exercises and water-suitable accessories. Both groups were supervised and monitored by an experienced physiotherapist. Main outcome was HRQoL (EORTC QLQ C30 and B23 module) and CRF measured with the Piper Scale. Secondary variables included functional capacity with the 6 Minutes Walking Test (6MWT), upper and lower body strength (handgrip strength and 30″ Sit-to-Stand (STS) test), body composition and objectively measured physical activity. RESULTS: 28 patients were assessed and randomised during the study period. One patient did not receive the allocated intervention due to skin issues and one patient was dropped out during the intervention. A significant effect of time was found for both symptom severity (F(2,52) = 6.46, p = 0.003) and overall functioning (F1.67,43.45 = 5.215, p =0 .013) but no interaction was found between group and time. No effects were reported for CRF. Similar findings were reported for functional capacity (time effect F1.231,32.019 = 16.818, p < 0.001) and lower body strength (time effect F2,52 = 15.120, p < 0.001) as well as fat mass (time effect F2,52 = 4.38, p = 0.017). Notably, a significant time per group interaction was reported for physical activity (F2,52 = 6.349, p =0.003) with patients in the WG significantly improving PA levels over time while patients in the LG exhibited a marked decreased. CONCLUSIONS: Exercise training either in water or on land can decrease symptom severity and improve functionality and body composition. Water-based training seems more effecting than land-based exercise to improve physical activity patterns over time.

Outpatient Surgery and Unplanned Overnight Admission in Bilateral Inguinal Hernia Repair: A Population-based Study.

PURPOSE: The use of outpatient surgery in inguinal hernia is heterogeneous despite clinical recommendations. This study aimed to analyze the utilization trend of outpatient surgery for bilateral inguinal hernia repair (BHIR) in Spain and identify the factors associated with outpatient surgery choice and unplanned overnight admission. METHODS: A retrospective observational study of patients undergoing BIHR from 2016 to 2021 was conducted. The clinical-administrative database of the Spanish Ministry of Health RAE-CMBD was used. Patient characteristics undergoing outpatient and inpatient surgery were compared. A multivariable logistic regression analysis was performed to identify factors associated with outpatient surgery choice and unplanned overnight admission. RESULTS: A total of 30,940 RHIBs were performed; 63% were inpatient surgery, and 37% were outpatient surgery. The rate of outpatient surgery increased from 30% in 2016 to 41% in 2021 (p < 0.001). Higher rates of outpatient surgery were observed across hospitals with a higher number of cases per year (p < 0.001). Factors associated with outpatient surgery choice were: age under 65 years (OR: 2.01, 95% CI: 1.92-2.11), hospital volume (OR: 1.59, 95% CI: 1.47-1.72), primary hernia (OR: 1.89, 95% CI: 1.71-2.08), and laparoscopic surgery (OR: 1.47, 95% CI: 1.39-1.56). Comorbidities were negatively associated with outpatient surgery. Open surgery was associated (OR: 1.26, 95% CI: 1.09-1.47) with unplanned overnight admission. CONCLUSIONS: Outpatient surgery for BHIR has increased in recent years but is still low. Older age and comorbidities were associated with lower rates of outpatient surgery. However, the laparoscopic repair was associated with increased outpatient surgery and lower unplanned overnight admission.

Totally extraperitoneal repair of groin hernia in liver transplant patients: a case series study (TOHER).

PURPOSE: The present study aims to describe the feasibility and the postoperative results of groin hernia repair in liver transplant patients using a totally extra-peritoneal (TEP) repair approach. METHODS: From May 2022 to March 2023, liver transplant patients with groin hernia underwent TEP groin hernia repair, by the single common senior experimented surgeon. Background information, intraoperative findings, postoperative complications, postoperative pain, health, and well-being were registered. RESULTS: Thirteen TEP approach groin hernioplasties were performed in 10 patients, completing the procedure in all cases without the need for conversion either to open or transabdominal preperitoneal approaches. 70% of surgical explorations revealed multiple hernia defects: lateral hernias in all patients, medial defects in 62%, and femoral defects in 30.8%. Median hospital stay was 1 day [range (0.3)], with 30% treated as outpatients. Post-surgical complications occurred in 30% of cases: 1 hematoma and 2 seromas. Postoperative pain and physical functioning scored 100 (IQR 44) and 90 (IQR 15), respectively. CONCLUSION: TEP groin hernioplasty is safe and feasible for liver transplant patients, with low complication rates, short hospital stays, and a significant proportion treated as outpatients. The posterior approach allows comprehensive repair of myopectineal defects, crucial due to associated hernial defects.

A hybrid approach: a safe option for surgical treatment of early-stage cervical cancer.

OBJECTIVE: The aim of the study was to describe the surgical treatment of early-stage cervical cancer (CC) via minimally invasive surgery (MIS) and a sequential hybrid approach combining MIS and mini-Pfannenstiel. Evaluate sentinel lymph node (SLN) detection using a hybrid tracer (ICG-99m Tc nanocolloid). PATIENTS AND METHODS: Prospective, observational, descriptive, single-center study conducted at Son Espases University Hospital between January 2019 and September 2021. Patients with early-stage CC (FIGO 2018 IA1 with ILV-IIA1) who underwent surgical treatment with a follow-up of at least one year were included. RESULTS: Thirty early-stage CC patients were included, of whom four (13.3%) were upstaged due to positive SLNs. In these cases, laparotomy was avoided, and paraaortic lymphadenectomy was performed via MIS approach. Twenty-six patients had a radical hysterectomy: 15 underwent a hybrid approach, 10 laparoscopy, and one laparotomy. Patients undergoing laparoscopic surgery had a smaller estimated tumor size than those undergoing the hybrid approach. The overall SLN detection rate was 96.1%, with 88.5% of cases occurring bilaterally. Five out of 26 patients (19.2%) presented SLN macrometastases, and five (19.2%) had atypical drainage. Surgery refined staging in 33.3% (10/30) of cases. No recurrences were reported after an average follow-up of 32 months. CONCLUSIONS: MIS for SLN avoids laparotomy leading to rapid recovery and early adjuvant treatment initiation in nodal metastasis. In our study, tumor size is an important clinical implication in the surgical approach to be used. The hybrid tracer provided a high detection rate and combined the advantages of the two tracers. The hybrid approach has a quick recovery and optimal results.

MUC1 inhibition leads to decrease in PD-L1 levels via upregulation of miRNAs.

The PD-L1/PD-1 pathway is a critical component of the immunosuppressive tumor microenvironment in acute myeloid leukemia (AML), but little is known about its regulation. We investigated the role of the MUC1 oncoprotein in modulating PD-L1 expression in AML. Silencing of MUC1 in AML cell lines suppressed PD-L1 expression without a decrease in PD-L1 mRNA levels, suggesting a post-transcriptional mechanism of regulation. We identified the microRNAs miR-200c and miR-34a as key regulators of PD-L1 expression in AML. Silencing of MUC1 in AML cells led to a marked increase in miR-200c and miR-34a levels, without changes in precursor microRNA, suggesting that MUC1 might regulate microRNA-processing. MUC1 signaling decreased the expression of the microRNA-processing protein DICER, via the suppression of c-Jun activity. NanoString (Seattle, WA, USA) array of MUC1-silenced AML cells demonstrated an increase in the majority of probed microRNAs. In an immunocompetent murine AML model, targeting of MUC1 led to a significant increase in leukemia-specific T cells. In concert, targeting MUC1 signaling in human AML cells resulted in enhanced sensitivity to T-cell-mediated lysis. These findings suggest MUC1 is a critical regulator of PD-L1 expression via its effects on microRNA levels and represents a potential therapeutic target to enhance anti-tumor immunity.

National registry of hemoglobinopathies in Spain (REPHem).

BACKGROUND: Although highly prevalent throughout the world, the accurate prevalence of hemoglobinopathies in Spain is unknown. PROCEDURE: This study presents data on the national registry of hemoglobinopathies of patients with thalassemia major (TM), thalassemia intermedia (TI), and sickle cell disease (SCD) in Spain created in 2014. Fifty centers reported cases retrospectively. Data were registered from neonatal screening or from the first contact at diagnosis until last follow-up or death. RESULTS: Data of the 715 eligible patients were collected: 615 SCD (497 SS, 64 SC, 54 SBeta phenotypes), 73 thalassemia, 9 CC phenotype, and 18 other variants. Most of the SCD patients were born in Spain (65%), and 51% of these were diagnosed at newborn screening. Median age at the first diagnosis was 0.4 years for thalassemia and 1.0 years for SCD. The estimated incidence was 0.002 thalassemia cases and 0.03 SCD cases/1,000 live births. Median age was 8.9 years (0.2-33.7) for thalassemia and 8.1 years (0.2-32.8) for SCD patients. Stroke was registered in 16 SCD cases. Transplantation was performed in 43 TM and 23 SCD patients at a median age of 5.2 and 7.8 years, respectively. Twenty-one patients died (3 TM, 17 SCD, 1 CC) and 200 were lost to follow-up. Causes of death were related to transplantation in three patients with TM and three patients with SCD. Death did not seem to be associated with SCD in six patients, but nine patients died secondary to disease complications. Overall survival was 95% at 15 years of age. CONCLUSIONS: The registry provides data about the prevalence of hemoglobinopathies in Spain and will permit future cohort studies and the possibility of comparison with other registries.

Neutrophil gelatinase-associated lipocalin is a biomarker of acute-on-chronic liver failure and prognosis in cirrhosis.

BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) is a syndrome that occurs in cirrhosis characterized by organ failure(s) and high mortality rate. There are no biomarkers of ACLF. The LCN2 gene and its product, neutrophil gelatinase-associated lipocalin (NGAL), are upregulated in experimental models of liver injury and cultured hepatocytes as a result of injury by toxins or proinflammatory cytokines, particularly Interleukin-6. The aim of this study was to investigate whether NGAL could be a biomarker of ACLF and whether LCN2 gene may be upregulated in the liver in ACLF. METHODS: We analyzed urine and plasma NGAL levels in 716 patients hospitalized for complications of cirrhosis, 148 with ACLF. LCN2 expression was assessed in liver biopsies from 29 additional patients with decompensated cirrhosis with and without ACLF. RESULTS: Urine NGAL was markedly increased in ACLF vs. no ACLF patients (108(35-400) vs. 29(12-73)µg/g creatinine; p<0.001) and was an independent predictive factor of ACLF; the independent association persisted after adjustment for kidney function or exclusion of variables present in ACLF definition. Urine NGAL was also an independent predictive factor of 28day transplant-free mortality together with MELD score and leukocyte count (AUROC 0.88(0.83-0.92)). Urine NGAL improved significantly the accuracy of MELD in predicting prognosis. The LCN2 gene was markedly upregulated in the liver of patients with ACLF. Gene expression correlated directly with serum bilirubin and INR (r=0.79; p<0.001 and r=0.67; p<0.001), MELD (r=0.68; p<0.001) and Interleukin-6 (r=0.65; p<0.001). CONCLUSIONS: NGAL is a biomarker of ACLF and prognosis and correlates with liver failure and systemic inflammation. There is remarkable overexpression of LCN2 gene in the liver in ACLF syndrome. LAY SUMMARY: Urine NGAL is a biomarker of acute-on-chronic liver failure (ACLF). NGAL is a protein that may be expressed in several tissues in response to injury. The protein is filtered by the kidneys due to its small size and can be measured in the urine. Ariza, Graupera and colleagues found in a series of 716 patients with cirrhosis that urine NGAL was markedly increased in patients with ACLF and correlated with prognosis. Moreover, gene coding NGAL was markedly overexpressed in the liver tissue in ACLF.

Clinical Evolution After Enzyme Replacement Therapy in Twins with the Severe Form of Maroteaux-Lamy Syndrome.

Mucopolysaccharidosis type VI (MPS VI) is a progressive, autosomal, recessive lysosomal disorder. This disorder, due to a deficiency in N-acetylgalactosamine-4-sulfatase (ASB), results in an accumulation of glycosaminoglycan (GAG), causing multiple organ failures. In this study, monochorionic biamniotic twins with the severe form of MPS VI underwent enzyme replacement therapy (ERT) with weekly infusions of recombinant human ASB (galsulfase) at 1 mg/kg. After 9 years of ERT, a comprehensive clinical examination was performed. Several types of biochemical, immunological, and genetic investigations were also conducted. Both twins showed the typical symptoms and signs of MPS VI at baseline, including short stature, progressive dysmorphic facial features, and dysostosis multiplex. Twin 2 presented stronger multisystemic involvement, with marked musculoskeletal, neurological, and odontological components. She also developed an ischemic spinal cord lesion after surgery, which is the first case described in the literature in Maroteaux-Lamy syndrome. However, the extent of disease was found to be equally stabilized in the two sisters, concretely the cardiac and respiratory functions and body length. The early diagnosis and treatment of MPS VI are critical for an optimal clinical outcome, and further evidence for the new treatment strategies is needed.

GM2 gangliosidoses in Spain: analysis of the HEXA and HEXB genes in 34 Tay-Sachs and 14 Sandhoff patients.

The GM2 gangliosidoses are autosomal recessive lysosomal storage diseases caused by a deficiency of the ß-hexosaminidase A enzyme. This enzyme is composed of two polypeptide chains designated the α- and ß- subunits and it interacts with the GM2 activator protein. The HEXA and HEXB genes encode the α-subunit and the ß-subunit, respectively. Mutations in these genes are causative of Tay-Sachs disease (HEXA) and Sandhoff disease (HEXB). We analyzed the complete HEXA gene in 34 Spanish patients with Tay-Sachs disease and the HEXB gene in 14 Spanish patients with Sandhoff disease. We identified 27 different mutations, 14 of which were novel, in the HEXA gene and 14 different mutations, 8 of which unreported until now, in the HEXB gene, and we attempted to correlate these mutations with the clinical presentation of the patients. We found a high frequency of c.459+5G>A (IVS4+5G>A) mutation in HEXA affected patients, 22 of 68 alleles, which represent the 32.4%. This is the highest percentage found of this mutation in a population. All patients homozygous for mutation c.459+5G>A presented with the infantile form of the disease and, as previously reported, patients carrying mutation p.R178H in at least one of the alleles presented with a milder form. In HEXB affected patients, the novel deletion c.171delG accounts for 21.4% of the mutant alleles (6/28). All patients with this deletion showed the infantile form of the disease. The Spanish GM2 gangliosidoses affected patients show a great mutational heterogeneity as seen in other inherited lisosomal diseases in this country.

Health changes in fishermen 2 years after clean-up of the Prestige oil spill.

BACKGROUND: In 2002, the oil tanker Prestige spilled more than 67,000 tons of bunker oil, heavily contaminating the coast of northwestern Spain. OBJECTIVE: To assess respiratory effects and chromosomal damage in clean-up workers of the oil spill 2 years after the exposure. DESIGN: Cross-sectional study. SETTING: Fishermen cooperatives in coastal villages. PARTICIPANTS: Local fishermen who were highly exposed (n = 501) or not exposed (n = 177) to oil 2 years after the spill. MEASUREMENTS: Respiratory symptoms; forced spirometry; methacholine challenge; markers of oxidative stress (8-isoprostane), airway inflammation (interleukins, tumor necrosis factor-α, and interferon-γ), and growth factor activity in exhaled breath condensate; and chromosomal lesions and structural alterations in circulating lymphocytes. RESULTS: Compared with nonexposed participants, persons exposed to oil were at increased risk for lower respiratory tract symptoms (risk difference, 8.0 [95% CI, 1.1 to 14.8]). Lung function did not significantly differ between the groups. Among nonsmoking participants, exposed individuals had higher exhaled 8-isoprostane levels than nonexposed individuals (geometric mean ratio, 2.5 [CI, 1.7 to 3.7]), and exposed individuals with lower respiratory tract symptoms had higher 8-isoprostane levels than those of exposed individuals without symptoms. Exposed nonsmoking participants also had higher levels of exhaled vascular endothelial growth factor (risk difference, 44.8 [CI, 27.9 to 61.6]) and basic fibroblast growth factor (risk difference, 16.0 [CI, 3.5 to 28.6]). A higher proportion of exposed participants had structural chromosomal alterations (risk difference, 27.4 [CI, 10.0 to 44.8]), predominantly unbalanced alterations. The risk for elevated levels of exhaled 8-isoprostane, vascular endothelial growth factor, and basic fibroblast growth factor and structural chromosomal alterations seemed to increase with intensity of exposure to clean-up work. LIMITATIONS: The clinical significance of exhaled biomarkers and chromosomal findings are uncertain. The association between oil exposure and the observed changes may not be causal. The findings may not apply to spills involving other types of oil or to different populations of oil spill workers. CONCLUSION: Participation in clean-up of a major oil spill was associated with persistent respiratory symptoms, elevated markers of airway injury in breath condensate, and chromosomal damage.

Mathematical modeling of cadmium(II) solvent extraction from neutral and acidic chloride media using Cyanex 923 extractant as a metal carrier.

This paper describes experimental work and the mathematical modeling of solvent extraction of cadmium(II) from neutral and acidic aqueous chloride media with a Cyanex 923 extractant in Exxol D-100. Solvent extraction experiments were carried out to analyze the influence of variations in the composition of the aqueous and organic phases on the efficiency of cadmium(II) extraction. In neutral and acidic chloride conditions, the extraction of cadmium(II) by the organophosphorous extractant Cyanex 923 (L) is based on the solvation mechanism of neutral H(n)CdCl((2+n)) species and the formation of H(n)CdCl((2+n))L(q) complexes in the organic phase, where n=0, 1, 2 and q=1, 2. The mathematical model of cadmium(II) extraction was derived from the mass balances and chemical equilibria involved in the separation system. The model was computed with the Matlab software. The equilibrium parameters for metal extraction, i.e. the stability constants of the aqueous Cd-Cl complexes, the formation constants of the acidic Cd-Cl species and the metal equilibrium extraction constants, were proposed. The optimized constants were appropriate, as there was good agreement when the model was fitted to the experimental data for each of the experiments.

Molecular analysis of mucopolysaccharidosis type IIIB in Portugal: evidence of a single origin for a common mutation (R234C) in the Iberian Peninsula.

Mucopolysaccharidosis type IIIB (Sanfilippo B disease) is a rare autosomal recessive disorder caused by defective alpha-N-acetylglucosaminidase (NAGLU). We examined the NAGLU gene in 11 MPS IIIB Portuguese patients, having identified five novel (M1K, W147X, G304V, S522P, and R533X) and four previously reported mutations (W168X, R234C, R565W and R643C). R234C attained the high prevalence of 32% of the mutated alleles. Because R234C had already been reported to be common in Spanish patients, a haplotypic analysis was conducted to address the question of its origin in the Iberian Peninsula. Three neutral markers were studied that allowed for the identification of the probable founder haplotype (174-234-G) on which R234C arose. The sharing of the ancestral haplotype by Portuguese and Spanish patients clearly implied a common origin of the mutation in Iberia, through an event that was inferred to have been rather recent. Therefore, the reconstructed history of R234C explains the high incidence of the mutation in Iberian patients with Sanfilippo B disease.

Reg genes are CCK2 receptor targets in ElasCCK2 mice pancreas.

We previously demonstrated that expression of the gastrin receptor, CCK2R, in pancreatic acini of transgenic ElasCCK2 mice induced alteration of acinar morphology and differentiation, increased sensitivity to a carcinogen and development of preneoplastic lesions and tumours. Reg proteins are suggested to be involved in pancreatic cancer and in regeneration of endocrine pancreas. Reg I gene is a known target of gastrin. We examined whether an expression of CCK2R in the pancreatic acini of ElasCCK2 mice is linked to induction of Reg proteins expression. We analyzed Reg expression by Western-blot and immunohistochemistry in pancreas from ElasCCK2 and control mice. Islet neogenesis, glucose homeostasis, insulin secretion and content were also evaluated. Reg I is exclusively produced in acini in ElasCCK2 and control mice. In tumoral pancreas, Reg I and Reg III proteins are expressed in duct-like cells in preneoplastic lesions or in the periphery of tumours and in adjacent acini. The expression of Reg III proteins is increased in ElasCCK2 pancreas before the development of preneoplastic lesions in a subpopulation of islet cells and in small islet-like cell clusters dispersed within the acinar tissue. Several criteria of an enhanced neogenesis are fulfilled in ElasCCK2 pancreas. Moreover, ElasCCK2 mice have an improved response to glucose load, an increased insulin secretion and a doubling of insulin content compared to control mice. We show that Reg proteins are targets of CCK2R activation and are induced during early steps of carcinogenesis in ElasCCK2 mice pancreas. Alterations of exocrine tissue homeostasis in ElasCCK2 pancreas concomitantly activate regenerative responses of the endocrine pancreas possibly linked to paracrine actions of Reg III proteins.

Protocol biopsies in renal transplantation: insights into patient management and pathogenesis.

A 1-day symposium on the application of protocol biopsies in renal transplantation was held in Boston, 21 July 2006. Representatives from centers with extensive experience in the use of protocol biopsies for routine patient care and research reported results on the pathological findings and their value in patient management. The consensus was that protocol biopsies, in experienced hands, are a safe and valuable means of detecting subclinical disease that can benefit from modification of therapy. Furthermore, molecular studies reveal evidence of activity or progression not readily appreciated by histological techniques. Wider application is expected in multicenter clinical trials to predict and validate outcomes. The principal barrier to wider use of protocol biopsies is knowledge of the benefits of intervention.

The systemic absorption of etoposide after intravaginal administration in patients with cervical intraepithelial lesions associated with human papillomavirus infection.

PURPOSE: The purpose of this study was to determine the systemic absorption and the release of etoposide in cervical tissue administered via a vaginal ovule to women diagnosed with cervical intraepithelial lesions associated with human papillomavirus (HPV). METHODS: Fifteen women with low- and high-grade intraepithelial neoplasia confirmed by colposcopic test received a 50-mg intravaginal etoposide dose three times a week for 3 weeks. At the end of the study period, paralleled with the last ovule administered, blood samples were collected over a period of 24 h, and in situ cervical samples were obtained at 3 and 10 h after drug administration. Etoposide concentrations were determined in plasma and in in situ cervical samples using the high-performance liquid chromatography method with electrochemical detection. RESULTS: Pharmacokinetic analyses of plasma data indicated low or lack of systemic exposure of etoposide after the vaginal administration. Nevertheless, high concentrations of etoposide were found in all in situ cervical samples, indicating that etoposide could be released from its pharmaceutical formulation. CONCLUSIONS: The results of the study suggest that the etoposide administered as intravaginal ovule is safe and tolerable and apparently could be a suitable option in patients with cervical intraepithelial neoplasia. Clinical results and the true impact on HPV infection and evolution of dysplasia need to be confirmed.

Genetic abnormalities associated with the t(12;21) and their impact in the outcome of 56 patients with B-precursor acute lymphoblastic leukemia.

The ETV6/RUNX1 rearrangement is found in 20-30% of children with B-cell precursor acute lymphoblastic leukemia and is associated with a good outcome. To determine the cytogenetic and molecular abnormalities associated with the ETV6/RUNX1 rearrangement and the influence of this rearrangement in patients' evolution, we analyzed the molecular cytogenetic profiles of 56 children with this rearrangement and B-cell precursor acute lymphoblastic leukemia. Secondary changes detected with conventional cytogenetics and with fluorescence in situ hybridization were found in 71.4% of cases, the most frequent being the loss of the normal ETV6 allele, 12p aberrations, duplication of the fusion gene, and trisomy 21, as in replicating the results of previous studies. In this preliminary series, with a mean follow-up of 69.3 months, secondary abnormalities did not influence patients' outcome. It seems therefore that the prognostic value of the t(12;21) does not vary and that ETV6/RUNX1 rearrangement is an independent indicator of good prognosis.

[Outcome of two patients with Hurler's syndrome under enzyme replacement therapy with human recombinant alpha-L-iduronidase]. / Evolución de dos pacientes con síndrome de Hurler en tratamiento con enzima recombinante humana alpha-L-iduronidasa.

We performed a prospective study of two patients with Hurler's syndrome (aged 4.8 years and 17 months at the beginning of the intervention) under enzyme replacement therapy with human recombinant alpha-L-iduronidase for 452 and 28 weeks respectively. The aim of this study was to analyze the safety and efficacy of the intervention during the treatment periods. Several diagnostic imaging tests, clinical examinations, and serial laboratory determinations were performed to demonstrate the effectiveness of the therapy in both patients. In patient 1 (a boy aged 4.8 years, homozygote W402X), the treatment was always intended to be palliative because of the advanced stage of the disease. In patient 2 (a 17-month-old girl, heterozygote W402X) the treatment was initiated early with subsequent clinical stabilization without acquisition of regressive factors. Bone marrow transplantation from an unrelated donor was successful. Currently, because of the lack of histocompatible bone marrow donors, transplantation of hematopoietic stem cells from umbilical cord blood or peripheral blood are being performed with satisfactory results. In the future, gene therapy may be able to prevent the diseases associated with Hurler's syndrome and halt the neurocognitive deterioration characteristic of these patients.

[The DISEHTAC II study: diagnosis and follow-up of hypertension in Catalonia. comparison with 1996 data]. / Estudio DISEHTAC II: diagnóstico y seguimiento de la hipertensión arterial en Cataluña. Comparación con los datos de 1996.

OBJECTIVE: To evaluate the changes in the diagnosis and follow-up of hypertension, and in the evaluation of cardiovascular risk, in a population served by primary care centers in Catalonia (northeastern Spain). Management was evaluated with indicators published in the Guidelines for Hypertension for Primary Care (Guía de Hipertensión Arterial para la Atención Primaria). DESIGN: Multicenter, observational, before-after design (1996-2001). SETTING: Primary care. PARTICIPANTS: Twelve primary care centers chosen from among the 31 centers that took part in the DISEHTAC I study (1996), with a total of 990 patient records. MAIN MEASURES: We analyzed age, sex, date of diagnosis of hypertension, number of blood pressure measurements needed for diagnosis, use of the mean value of duplicate blood pressure determinations, values for all blood pressure measurements in 2001, blood pressure determinations during the preceding 6 months, screening for and diagnosis of diabetes, dyslipidemia, smoking, obesity, and left ventricular hypertrophy. RESULTS: Of the 171 new cases of hypertension, 16.7% were diagnosed from at least 3 duplicate blood pressure measurements or as a result of acute episodes of hypertension. About one third (32.4%) of the patients with hypertension had blood pressure values below 140 and 90 mm Hg (25.7% in 1996), and the difference between the 2 sets of survey results was statistically significant. In three fourths (75.4%) of the patients, blood pressure had been measured during the preceding 6 months; this percentage was not significantly different in comparison to the figure found in 1996. Screening to detect cardiovascular risk factors was done in 50.4% of the patients (63.1% in 1996). CONCLUSIONS: Follow-up for hypertension in Catalonia has improved notably since 1996, but there was no improvement in the diagnosis of risk factors or in the integral evaluation of cardiovascular risk.