The establishment of a multiple myeloma clinical registry in the Asia-Pacific region: The Asia-Pacific Myeloma and Related Diseases Registry (APAC MRDR).

BACKGROUND: Multiple myeloma (MM) is the second most common haematological cancer worldwide. Along with related diseases including monoclonal gammopathy of undetermined significance (MGUS), plasma cell leukaemia (PCL) and plasmacytoma, MM incidence is rising, yet it remains incurable and represents a significant disease burden. Clinical registries can provide important information on management and outcomes, and are vital platforms for clinical trials and other research. The Asia-Pacific Myeloma and Related Diseases Registry (APAC MRDR) was developed to monitor and explore variation in epidemiology, treatment regimens and their impact on clinical outcomes across this region. Here we describe the registry's design and development, initial data, progress and future plans. METHODS: The APAC MRDR was established in 2018 as a multicentre collaboration across the Asia-Pacific, collecting prospective data on patients newly diagnosed with MM, MGUS, PCL and plasmacytoma in Korea, Singapore, Malaysia and Taiwan, with China recently joining. Development of the registry required a multidisciplinary team of clinicians, researchers, legal and information technology support, and financial resources, as well as local clinical context from key opinion leaders in the APAC region. Written informed consent is obtained and data are routinely collected throughout treatment by hospital staff. Data are stored securely, meeting all local privacy and ethics requirements. Data were collected from October 2018 to March 2024. RESULTS: Over 1700 patients from 24 hospitals have been enrolled onto the APAC MRDR to date, with the majority (86%) being newly diagnosed with MM. Bortezomib with an immunomodulatory drug was most frequently used in first-line MM therapy, and lenalidomide-based therapy was most common in second-line. Establishment and implementation challenges include regulatory and a range of operational issues. CONCLUSION: The APAC MRDR is providing 'real-world' data to participating sites, clinicians and policy-makers to explore factors influencing outcomes and survival, and to support high quality studies. It is already a valuable resource that will continue to grow and support research and clinical collaboration in MM and related diseases across the APAC region.

Multicenter Survey on Staff Understanding of Preoperative Fasting Guidelines.

PURPOSE: To assess the knowledge of nursing staff regarding pediatric preoperative fasting in a tertiary pediatric center and a general hospital. DESIGN: Anonymous electronic survey with nine questions modified to each institution. METHODS: This was a prospective quantitative study. Nursing staff at a tertiary pediatric center and pediatric nursing staff at a general hospital with pediatric services were eligible for participation. An anonymous electronic survey with nine questions via Survey Monkey was used over a 2-month period. FINDINGS: There were 295 participants from the tertiary pediatric center and 24 from the general hospital which represented 10% of overall nursing staff at the tertiary pediatric center and approximately 50% of pediatric nursing staff at the general hospital. At both the tertiary pediatric center and the general hospital, 50 to 80% of participants correctly answered most questions. More participants were correct for the fasting times for infants less than 6 month of age than for those over 6 months old. For clear fluids, 61 (20.7%) and 13 (4.4%) considered jelly and breast milk as clear fluids respectively at the tertiary pediatric center. CONCLUSIONS: Preoperative fasting continues to be a core area of pediatric care that is not completely understood. Our survey showed that although the majority of staff claim to be able to access the hospital guidelines, knowledge of these guidelines can be improved. In light of ongoing changing evidence, it is clear that education is a key factor in reducing morbidity and improving patient experience related to preoperative fasting.

Differences in Drug-Susceptibility Patterns between Mycobacterium avium, Mycobacterium intracellulare, and Mycobacterium chimaera Clinical Isolates: Prospective 8.5-Year Analysis by Three Laboratories.

Background: It has been suggested that Mycobacterium avium, Mycobacterium intracellulare, and M. chimaera have differential drug susceptibility patterns. We prospectively analyzed and compared the drug susceptibility patterns among these species over an 8.5-year period. Methods: A microdilution method (Slomyco®) was performed for drug susceptibility testing of 402 M. avium, 273 M. intracellulare, and 139 M. chimaera clinical isolates. Results: M. avium showed significantly higher resistance to moxifloxacin, ciprofloxacin, rifampicin, ethambutol, streptomycin, linezolid, cotrimoxazole, and clarithromycin. M. avium also showed higher minimum inhibitory concentrations (MIC) than M. intracellulare and M. chimaera against all drugs except ethionamide, to which M. intracellulare and M. chimaera showed greater resistance. Conclusions: Our series demonstrated differential drug resistance patterns among the most frequent M. avium complex species. M. avium was more resistant than M. intracellulare and M. chimaera versus eight antibiotics and showed greater MIC values to most of the antibiotics studied. These data suggest that knowledge of the local distribution and susceptibility profiles of these pathogens is essential for adequate clinical management.

The effectiveness of conservative interventions for the management of syndromic hypermobility: a systematic literature review.

INTRODUCTION: 'Syndromic hypermobility' encompasses heritable connective tissue disorders such as hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorders which are characterised by excessive joint range of motion and pain. Conservative interventions such as exercise are the cornerstone of management, yet their effectiveness is unclear. AIM: To systematically appraise the effectiveness of conservative management for people with syndromic hypermobility. METHOD: A systematic online database search was conducted (AMED, BND, CINAHL Plus, MEDLINE, PEDro, PsychINFO and SportDiscus). Potential articles were assessed for eligibility by two researchers against the following criteria: adults and children with a hEDS/HSD diagnosis (or equivalent diagnosis using specific criteria); non-pharmacological or non-surgical interventions; outcomes related to pain, physical function, psychological well-being or quality of life. Controlled trials and cohort studies were included. Critical Appraisal Skills Programme checklists were used to assess methodological quality. RESULTS: Eleven studies were included, comprising eight controlled trials and three cohort studies. All studies investigated interventions that had exercise as the primary component. Three small controlled studies demonstrated superior effects of conservative management relative to a control group. However, those studies only focused on a single area of the body, only recruited women, and had no long-term follow-up. All studies reported improvements in a wide range of outcomes over time. CONCLUSION: Controlled trial evidence for the superiority of conservative management over comparators is weak. There is some evidence that people improve over time. Robust randomised controlled trial research of the long-term effectiveness of 'whole-body' (rather than individual joints or body areas) conservative management is required. Key Points • Conservative management is the cornerstone of management of syndromic hypermobility. • The review found that evidence for the effectiveness of conservative management relative to no treatment or other conservative comparators was weak. • However, there was consistent evidence for effectiveness from pre- to post-treatment. • Further robust randomised controlled trial evidence is required.

Epidemiological distribution of genotypes of Giardia duodenalis in humans in Spain.

BACKGROUND: Although the distribution of Giardia duodenalis genotypes in humans has been increasingly reported in recent years, data on possible differences in pathogen transmission between age groups and virulence between genotypes are scarce. The purpose of this study is to investigate the genetic diversity of G. duodenalis in humans in Spain and compare the distribution of G. duodenalis assemblages A and B between children and adults and clinical presentations between the two genotypes. METHODS: In the present study, 125 microscopy-positive fecal samples were collected from humans in Spain over a 7-year period. PCR and sequence analyses of the triosephosphate isomerase, ß-giardin and glutamate dehydrogenase genes were used to identify the multilocus genotypes of G. duodenalis. RESULTS: Sequence analysis of three genetic loci identified both G. duodenalis assemblages A (29) and B (66), with co-infections of the two in two patients. Among the sequences obtained in this study, four multilocus genotypes (MLGs) of the sub-assemblage AII were observed within assemblage A. In contrast, 19 MLGs were detected within assemblage B due to the high sequence diversity at each locus. One MLG, however, was found in 51.9% (27/52) of assemblage B samples. Children were more commonly infected by assemblage B (44/53 or 83%) than adults (22/42 or 52.4%; χ2 = 10.371, df = 1, P = 0.001). Asymptomatic infection was more common in patients with assemblage A (4/29 or 13.8%) than in those with assemblage B (1/66 or 1.5%; χ2 = 6.091, df = 1, P = 0.029), and the frequency of abdominal pain occurrence was higher in assemblage B patients (65/66 or 98.5%) than assemblage A patients (25/29 or 86.2%; χ2 = 6.091, df = 1, P = 0.029). CONCLUSIONS: These results illustrate the existence of differences in genotype distribution between children and adults and clinical presentations between G. duodenalis genotypes. They are useful in understanding the transmission of G. duodenalis in humans in Spain.

Can invasive breast carcinoma with close or positive margins be managed without a new surgery?

We present the long-term outcome (FU 127 months) of a prospective study with 248 breast cancer patients with close or positive surgical margin, treated with 50 Gy whole breast irradiation plus high-dose-rate boost, 3 × 4.4 Gy. Actuarial breast failure at 10/15 years was 6.5%/11.6%; with positive margin (120) 6.8%/14.8%, with margin ≤2 mm (76) 9.8%/9.8%, with margin >2 mm <5 mm (52) 2%/2%. In 90 patients aged ≤50 was 11.9%/17.8%, between 51 and 70, 3.8%/8.2%, >70, 0%. Fibrosis appeared in 26.7%. Cosmetic outcome was excellent/good in 85.8%. This approach avoids a second surgery in women >50 with positive surgical margin, or with close margins in all ages.

Benznidazole Nanoformulates: A Chance to Improve Therapeutics for Chagas Disease.

This article describes the characterization of various encapsulated formulations of benznidazole, the current first-line drug for the treatment of Chagas disease. Given the adverse effects of benznidazole, safer formulations of this drug have a great interest. In fact, treatment of Chagas disease with benznidazole has to be discontinued in as much as 20% of cases due to side effects. Furthermore, modification of delivery and formulations could have potential effects on the emergence of drug resistance. The trypanocidal activity of new nanostructured formulations of benznidazole to eliminate Trypanosoma cruzi was studied in vitro as well as their toxicity in two cultured mammalian cell lines (HepG2 and Fibroblasts). Nanoparticles tested included nanostructured lipid carriers, solid lipid nanoparticles, liposomes, quatsomes, and cyclodextrins. The in vitro cytotoxicity of cyclodextrins-benznidazole complexes was significantly lower than that of free benznidazole, whereas their trypanocidal activity was not hampered. These results suggest that nanostructured particles may offer improved therapeutics for Chagas disease.

High-dose-rate interstitial brachytherapy boost in inoperable locally advanced tongue carcinoma.

PURPOSE: Locally advanced tongue carcinomas (LATCs) in inoperable lesions are managed with external beam radiation therapy (EBRT) and chemotherapy. In our institution, the boost to the gross tumor volume is delivered with high-dose-rate brachytherapy (HDR-BT) after EBRT. We review the outcome of these patients when HDR-BT is added as a boost. METHODS AND MATERIALS: From May 2000 to December 2014, a total of 24 patients with LATC, nonsurgical oral tongue, and base of tongue carcinomas were treated with EBRT and with interstitial plastic tubes for brachytherapy; median dose was 18-24 Gy in 6-8 fractions after 50-60 Gy of EBRT. Mean age was 60 years, 20 men and 4 women. The distribution by stages was 11 patients in Stage III and 13 patients in Stage IV. All cases but one received chemotherapy. RESULTS: With a median followup of 44 months, local control (LC) rate at 4 years was 80% for the entire group, 78% in Stage III, and 90% in Stage IV. The cause-specific survival was 68% at 4 years; the regional control was 76%. Four patients developed distant metastasis with disease free from distant metastasis of 77% at 4 years. The overall survival was 68% at 4 years. CONCLUSIONS: HDR-BT yields similar results to low dose rate in treatment of patients with LATC, with better results than those reported with exclusive EBRT. HDR-BT allows to increase the local dose, with good LC rates. In patients with large tumors requiring very mutilating surgery and patients who refuse surgery, EBRT with HDR-BT boost is a good option to increase the LC and cause-specific survival while keeping a better functional outcome.

[Risk of depression in 75 years or older persons, comprehensive geriatric assessment and associated factors in primary care: cross sectional study]. / Riesgo de depresión en personas de 75 años o más, valoración geriátrica integral y factores de vulnerabilidad asociados en Atención Primaria.

OBJECTIVES: To determine the prevalence of the risk of depression, major defining characteristics and factors associated with. DESIGN: Sub-study of comprehensive geriatric assessment cross-study. SETTING: Primary health center. PARTICIPANTS: For an estimated 14% prevalence we need a sample of 288 people. From 3854, 290 people ≥75 years were selected. Excluding terminals, chemotherapy, recent surgery, temporary residence, mental retardation, serious psychiatric illness, or under home care. OUTCOME: risk of depression (≥2 points on the Goldberg depression subscale. DEPENDENT VARIABLES: Sociodemographic and five study areas of the Comprehensive Geriatric Assessment: medical -comorbidity, polypharmacy, falls and hospital admissions-, functional -Up&Go Test, Lawton-Brody and Barthel Index-, nutritional -Mini Nutritional Assessment (MNA)-, mental-affective -Pfeiffer Questionnaire and Goldberg scale-, and social. Descriptive analysis and logistic regression. RESULTS: We obtained 290 interviews, with 102 (35.1%) male and mean age of 79.4 years (SD:3.2). The prevalence of the risk of depression was 37.2%, 26.5% in men and 43.1% in women (p=0.005). Association of risk of depression is observed with arterial hypertension (OR:3.87 95% CI:1.61-9.34), cancer (OR:4.12 95%, CI:1.58-10.76), lack of leisure activity (OR:2.75 95%, CI:1.33-5.67), increase of anxiety scale (OR:1.87 95%, CI:1.57-2.22) and decrease in MNA (OR:0.78 95%, CI:0.68-0.9). CONCLUSIONS: The prevalence of risk of depression is higher than expected, although overestimated until being confirmed with a diagnostic test. We appreciate new associations of comorbidity variables with risk of depression and corroborate other known. The studied factors that were associated with the risk of depression should be included in future studies of geriatric depression.

Incorporation of mesoporous silica particles in gelatine gels: effect of particle type and surface modification on physical properties.

The aim of this work was to investigate the impact of mesoporous silica particles (MSPs) on the physicochemical properties of filled protein gels. We have studied the effect of the addition of different mesoporous silica particles, either bare or functionalized with amines or carboxylates, on the physical properties of gelatine gels (5% w/v). Textural properties of the filled gels were investigated by uniaxial compression, while optical properties were investigated by turbidity. The MSPs were characterized with the objective of correlating particle features with their impact on the corresponding filled-gel properties. The addition of MSPs (both with and without functionalization) increased the stiffness of the gelatine gels. Furthermore, functionalized MSPs showed a remarkable increase in the strength of the gels and a slight reduction in the brittleness of the gels, in contrast with nonfunctionalized MSPs which showed no effect on these two properties. The turbidity of the gels was also affected by the addition of all tested MSPs, showing that the particles that formed smaller aggregates resulted in a higher contribution to turbidity. MSPs are promising candidates for the development of functional food containing smart delivery systems, also being able to modulate the functionality of protein gels.

Identification and characterization of nucleolin as a COUP-TFII coactivator of retinoic acid receptor ß transcription in breast cancer cells.

INTRODUCTION: The orphan nuclear receptor COUP-TFII plays an undefined role in breast cancer. Previously we reported lower COUP-TFII expression in tamoxifen/endocrine-resistant versus sensitive breast cancer cell lines. The identification of COUP-TFII-interacting proteins will help to elucidate its mechanism of action as a transcriptional regulator in breast cancer. RESULTS: FLAG-affinity purification and multidimensional protein identification technology (MudPIT) identified nucleolin among the proteins interacting with COUP-TFII in MCF-7 tamoxifen-sensitive breast cancer cells. Interaction of COUP-TFII and nucleolin was confirmed by coimmunoprecipitation of endogenous proteins in MCF-7 and T47D breast cancer cells. In vitro studies revealed that COUP-TFII interacts with the C-terminal arginine-glycine repeat (RGG) domain of nucleolin. Functional interaction between COUP-TFII and nucleolin was indicated by studies showing that siRNA knockdown of nucleolin and an oligonucleotide aptamer that targets nucleolin, AS1411, inhibited endogenous COUP-TFII-stimulated RARB2 expression in MCF-7 and T47D cells. Chromatin immunoprecipitation revealed COUP-TFII occupancy of the RARB2 promoter was increased by all-trans retinoic acid (atRA). RARß2 regulated gene RRIG1 was increased by atRA and COUP-TFII transfection and inhibited by siCOUP-TFII. Immunohistochemical staining of breast tumor microarrays showed nuclear COUP-TFII and nucleolin staining was correlated in invasive ductal carcinomas. COUP-TFII staining correlated with ERα, SRC-1, AIB1, Pea3, MMP2, and phospho-Src and was reduced with increased tumor grade. CONCLUSIONS: Our data indicate that nucleolin plays a coregulatory role in transcriptional regulation of the tumor suppressor RARB2 by COUP-TFII.

Criptococosis en pacientes con síndrome de inmunodeficiencia adquirida (SIDA) / Cryptococcosis in patients with acquired immunodeficiency syndrome (AIDS)

La criptococosis, enfermedad poco habitual hasta hace unos años, es ahora más frecuente por la presencia de una población inmunodeprimida susceptible. Si bien la puerta de entrada es respiratoria, la forma de expresión clínica más común es la meningoencefálica. La falla de los mecanismos de defensa locales explican la localización predominante de la enfermedad en el sistema nervioso central (SNC). A este nivel la confirmación diagnóstica suele ser fácil. El pulmón es el segundo órgano más comprometido y en ocasiones la única localización. Es más frecuente que el diagnóstico de criptococosis pulmonar sea secundario al de meningoencefalitis. En pacientes inmunodeprimidos la reacción inflamatoria meníngea puede ser escasa o nula y el síndrome meníngeo estar ausente, debiendo pensarse en criptococosis en todo paciente infectado con el VIH que tenga un cuadro febril prolongado sin causa evidente que lo explique. Se aconseja frente a esta eventualidad el estudio microbiológico del líquido céfalo-raquídeo (LCR) con tinción especial que permita visualizar el germen