Feasibility of a New Model of Care for Allogeneic Stem Cell Transplantation Recipients Facilitated by eHealth: The MY-Medula Pilot Study.

The use of allogeneic stem cell transplantation (allo-SCT) for the treatment of hematologic diseases is steadily increasing; however, allo-SCT has the downside of causing considerable treatment-related morbidity and mortality. Mobile technology applied to healthcare (mHealth) has proven to be a cost-effective strategy to improve care and offer new services to people with multimorbidity, but there are little data on its usefulness in allo-SCT recipients. Here we describe a new integrated healthcare model facilitated by an mHealth platform, EMMASalud-MY-Medula, and to report the results of a feasibility and usability pilot study. The MY-Medula platform was developed in 4 phases. First, patient and healthcare professional needs were identified, and technological development and pretesting tests were conducted (phases 1 to 3, January 2016 to March 2021). Then a nonrandomized, prospective, observational, single-center pilot study was conducted (October 2021 to January 2022) at the adult SCT unit of a tertiary university hospital. Twenty-eight volunteer allo-SCT recipients were included in the pilot study, of whom one-half were outpatients in the first-year post-SCT and one-half were affected by steroid-dependent graft-versus-host disease (SR-GVHD). All patients used the MY-Medula app during the 2-month follow-up period, with a median number of visits to the app of 143 (range, 6 to 477). A total of 2067 self-monitoring records were created, and 205 text messages were received, most of them related to symptoms description (47%) and doubts about medication (21%). In 3.4% of the cases, drug dosage was adjusted by the pharmacist because of dosing errors or interactions. At the end of the study, a 6-question Likert-type questionnaire for patients and a 22-question test for healthcare professionals showed a high degree of satisfaction (95% and 100%, respectively) with the new healthcare pathway. Reengineering the follow-up of allo-SCT recipients into an integrated, multidisciplinary model of care facilitated by mHealth tools is feasible and has been associated with high usability and a high degree of satisfaction by patients and healthcare professionals. A randomized trial aiming to determine the cost-effectiveness of MY-Medula-based follow-up post-SCT is currently enrolling participants.

Experimental transmission of Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) to SCID-hu Thy/Liv mice.

Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) is a novel human lymphotropic herpesvirus linked to several human neoplasms. To date, no animal model for infection by this virus has been described. We have examined the susceptibility of C.B-17 scid/scid mice implanted with human fetal thymus and liver grafts (SCID-hu Thy/Liv mice) to KSHV infection. KSHV virions were inoculated directly into the implants, and viral DNA and mRNA production was assayed using real-time quantitative polymerase chain reaction. This revealed a biphasic infection, with an early phase of lytic replication accompanied and followed by sustained latency. Ultraviolet irradiation of the inoculum abolished all DNA- and mRNA-derived signals, and infection was inhibited by ganciclovir. Viral gene expression was most abundant in CD19(+) B lymphocytes, suggesting that this model faithfully mimics the natural tropism of this virus. Short-term coinfection with HIV-1 did not alter the course of KSHV replication, nor did KSHV alter levels of HIV-1 p24 during the acute phase of the infection. Although no disease was evident in infected animals, SCID-hu Thy/Liv mice should allow the detailed study of KSHV tropism, latency, and drug susceptibility.

Assessment of Confirmed Clinical Hypersensitivity to Rituximab in Patients Affected with B-Cell Neoplasia.

Rituximab hypersensitivity reactions are rare but are one of the main causes of rituximab elimination from antilymphoma immunochemotherapy treatments. While the clinical picture may be indistinguishable from other infusion-related reactions, hypersensitivity reactions (HSR) do not disappear and instead become more intense with subsequent administrations. Objective. To describe the use of the 12-step protocol for desensitization to intravenous rituximab in clinical practice and the complementary study of a possible IgE-mediated HSR in the context of B-cell lymphoma treatment. Methods. A 12-step rituximab desensitization protocol was performed prospectively within clinical practice in 10 patients with a history of severe infusion reactions or in patients who had a repeated reaction at subsequent doses despite taking more intense preventive measures. Skin prick tests were performed at the time of reaction and at a later time to eliminate false negatives due to possible drug interference. Results. Overall, with the desensitization protocol, 70% of patients were able to complete the scheduled immunochemotherapy. Two patients had to discontinue the therapy due to clinical persistence and the third due to lymphoma progression. Intradermal tests with 0.1% rituximab were positive in only 20% of cases, demonstrating a mechanism of hypersensitivity. Conclusions. The 12-step desensitization protocol is very effective and assumable within healthcare practice. There is a need to determine the mechanism underlying the infusion reaction in a large proportion of cases due to the risk of future drug exposure.

Prevalence of M. tuberculosis infection and tuberculosis disease among HIV-infected people in Spain.

OBJECTIVE: To study the prevalence of Mycobacterium tuberculosis infection (MTBI) and past/current tuberculosis (TB) among human immunodeficiency virus (HIV) infected persons in Spain. DESIGN: Longitudinal study conducted between 2000 and 2003 at 10 HIV hospital-based clinics. Data were drawn from clinical records. Associations were measured using odds ratios (ORs) and their 95% confidence intervals (95%CI). RESULTS: Of the 1242 persons who met the eligibility criteria, most were male (75%), aged <40 years (75%) and unemployed (40%). HIV infection occurred through intravenous drug use (53%), heterosexual sex (29%) and sex between men (16%). In the initial evaluation, 315 subjects had evidence of MTBI: 84 (6.8%) had a history of TB, 23 (1.8%) current TB and 208 (16.8%) latent tuberculosis infection (LTBI). MTBI was associated with male sex, age 30-49 years, contact with a TB case, homelessness, poor education, and negatively with CD4 <100 cells/mm(3). Among subjects with MTBI, past/current TB was associated with retirement/disability (OR 6, 95%CI 1.6-22.5), CD4 <200 cells/mm(3) (OR 9.7, 95%CI 3.8-24.6), viral load >55,000 copies (OR 5.3, 95%CI 1.4-20.0), and negatively, with skilled work (OR 0.4, 95%CI 0.1-1.0) or administrative/managerial/professional work (OR 0.05, 95%CI 0.01-0.4). CONCLUSION: Social context has an impact on the effectiveness of HIV and TB control programmes even in industrialised countries with free access to health care.

CD8-positive lymphocytes in graft-versus-host disease of humanized NOD.Cg-Prkdc(scid)Il2rg(tm1Wjl)/SzJ mice.

Immunocompromised mice that can support a human immune system are an increasingly important model for the investigation of haemopoietic stem/progenitor cell (HSPC) development and human infectious disease. NOD-SCID IL-2Rγ(-/-) (NSG) mice engrafted with human fetal liver and thymus prior to HSPC engraftment, commonly known as NSG-bone marrow-liver-thymus (NSG-hu-BLT) mice, are one such model and have robust reconstitution of human leucocytes within the peripheral blood and tissues. Four NSG-hu-BLT mice were submitted for diagnostic necropsy examination following the development of alopecia, pruritus and lethargy after HSPC engraftment. Histopathology revealed multifocal to coalescing single keratinocyte cell death in the epidermis and follicles with dermatitis and mild dermal fibrosis. Single-cell hepatocyte cell death was present in three cases, with various degrees of portal fibrosis. In the skin and liver, cell death was associated with lymphocytes that reacted with anti-human CD45, CD3 and CD8 antibodies, consistent with a diagnosis of graft-versus-host disease (GvHD). This study expands on recently reported microscopical features of GvHD in NSG-hu-BLT mice and suggests a role for CD8(+) T lymphocytes in the progression of the disease. NSG-hu-BLT mice represent an excellent model of GvHD, but its prevalence may compromise their use in other fields of biomedical research.

HLA-DR2, a marker for class I antigen sensitization.

After analysis of 423 hemodialysis patients in a transfusion program and 461 cadaver-donor renal transplants, we found that HLA-DR2 frequency was significantly higher in the responder (36%) than in the nonresponder patient group (19%), according to the percentage of PRA (panel reactive antibodies). Among DR2+ patients, the percentage of hypersensitized patients was twice that of DR2- patients. Graft survival curves in cadaver-donor renal transplants indicated a significantly lower survival when recipients were DR2+, even in recipient-donor pairs identical for class II antigens but mismatched for class I antigens. The prognostic probability of low response to transfusions by a stepwise logistic regression analysis showed the influence of sex and DR2 phenotype. By multivariant discriminant analysis, we found that the DR2 phenotype was one of the most influential transfusion sensitization risk factors. Our preliminary conclusion is that DR2 can be related to immune responsiveness to class I antigens.

Characterization of an HLA-DR15 DQ5 haplotype found in the Spanish Caucasoid population.

HLA class II typing by RFLP and PCR-SSOP has been performed on HLA-DR2-positive individuals as a part of a study on MHC in a Spanish Caucasoid population. The results of this study reveal that HLA-DR15 (DRB1*1501 DRB5*0101) and DQ5 (DQA1*0102 DQB1*0501/0502) are not uncommonly associated in such a population. Family segregation has been assessed and allogeneic reactivity against some classic DR2 haplotypes has been tested; a stimulatory capability of DQ6 antigen in this situation is shown. It is suggested that the reported association is not uncommon in European Caucasoids as well as in other populations and it should be considered in matching for transplantation and in DR2-associated diseases.

Molecular cloning and polymerase chain reaction-sequence-specific oligonucleotide detection of the allele encoding the novel allospecificity HLA-Cw6.2 (Cw*1502) in Spanish gypsies.

A proposed novel allospecificity, HLA-Cw6.2, has been reported to be commonly found (approximately 25%) in Spanish Gypsies. Full-length cDNAs of the allele (Cw*1502) coding for this antigen have been cloned in this study. A simple PCR-SSO method for its detection has been standardized and a correlation with the serologic Cw6.2 phenotype has been established. This specificity has been also detected in the homozygous typing cell RML. Although the primary structures of Cw*1502 and Cw*0601 are not closely related, they share specific motifs that may account for their serologic cross-reactivity. Two novel HLA-C alleles (Cw*12022 and Cw*0602) are also reported.

Molecular characterization of a novel, serologically detectable, HLA-C allele: Cw*1602.

Cw*1602, a novel HLA-C allele belonging to the newly assigned Cw*16 group, has been cloned and sequenced from a Spanish Caucasoid cell expressing a "Cw6.2" phenotype. Some of the polymorphic substitutions of the new allele, and linkage disequilibrium to B51, had been predicted on the basis of previously published studies. The primary structure of Cw*1602 is in agreement with its serologic reactivity and, in comparison with that of Cw*1601, underlines the dimorphism of HLA-C molecules at residues 77 and 80 of the alpha 1-domain alpha helix.

Prospective randomized clinical trial comparing high-dose ifosfamide + GM-CSF vs high-dose cyclophosphamide + GM-CSF for blood progenitor cell mobilization.

Between August 1994 and June 1999, 56 patients were prospectively randomized to receive ifosfamide 10 g/m2 + GM-CSF 5 microg/kg/day (IFO+GM-CSF n = 28) and cyclophosphamide 4 g/m2 + GM-CSF 5 microg/kg/day (CY+GM-CSF n = 28). Both groups were comparable for age, gender, diagnosis, disease stage and previous chemotherapy. The IFO+GM-CSF group demonstrated a shorter median interval between therapy and apheresis (10 days (8-14) vs 13 days (8-25) P = 0.002), median number of doses of GM-CSF (9 (7-13) vs 15 (9-31) P = 0.001), median of days with aplasia (0.5 (0-10) vs 6 (0-21) P = 0.001), median days with fever (0 (0-6) vs 3 (0-9) P = 0.006) and median of days using i.v. antibiotics (0 (0-11) vs 7.5 (0-19) P = 0.002). The median MNC yield was similar in both groups. The CD34+ cell yield was better in the CY+GM-CSF group (3.14 (0.9-11.8) vs 5.33 (0. 08-32)) but not at significant levels (P = 0.1). White blood cell hematopoietic recovery was more rapid in the CY+GM-CSF group (16 (10-22) vs 13 (10-24) P = 0.02). Platelet engraftment was similar in both groups. Costs of mobilization and transplantation were almost the same: $28 570 ($18 527-$47 028) and $30 020 ($17 281-$67 591), respectively (P = 0.9). There were no differences in disease-free survival and overall survival between both groups. Mild and transient non-hematological toxicity (hemorrhagic cystitis, decrease in serum creatinine clearance and CNS dysfunction) was seen most frequently in the IFO+GM-CSF group.

A randomized double-blind clinical trial of two antivenoms in patients bitten by Bothrops atrox in Colombia. The Regional Group on Antivenom Therapy Research (REGATHER).

A randomized double-blind clinical trial in 39 patients envenomed by Bothrops atrox in Antioquia and Chocó, Colombia, was performed to compare the efficacy and safety of 2 equine-derived antivenoms prepared at Instituto Clodomiro Picado, University of Costa Rica. Twenty patients received a monovalent anti-B. atrox antivenom (group A) and 19 patients were treated with a polyvalent (Crotalinae) antivenom (group B). Both antivenoms were equally efficient in the neutralization of the most relevant signs of envenoming (haemorrhage and blood clotting time alteration). Fourteen patients (36%) presented early adverse reactions to antivenoms and no significant difference between the 2 groups was observed. Urticaria (18%) was the most frequent early adverse reaction and there was no life-threatening anaphylactic reaction. Based on clinical criteria and serum venom levels, estimated by an enzyme immunoassay, 15 patients were classified into 2 groups: mild and moderate/severe envenoming. With the antivenom doses used in this study (3, 6 and 9 vials for mild, moderate and severe envenoming, respectively), both antivenoms were equally efficient in clearing serum venom levels within the first hour of treatment, and the levels remained below the lower limit of venom detection for 24 h. Antivenom concentration in serum remained high for up to 24 h after antivenom infusion, suggesting that an excess of antibody in relation to circulating antigen had been administered.

Antibodies to lens crystallins after endocapsular cataract surgery.

Levels of serum antibodies against lens alpha, beta H and beta L crystallins were determined in 15 patients before and after endocapsular cataract extraction. The most abundant antibody at the time of surgery was anti-beta L, followed by anti-beta H and anti-alpha. An increase in the basal levels of these antibodies was seen after surgery in 93 percent of the cases. Relative increase was highest for anti-alpha, followed by anti-beta H and anti-beta L. There were individual variations both in the shape of the time-dependent antibody response after surgery and in the relative intensity of the response to the different antigens. The endocapsular technique therefore leads to the release of crystallins into the anterior chamber in sufficient amounts to provoke in many patients a humoral immune response.

[Myasthenia and thymoma in a seven year old girl]. / Miastenia y timoma en una niña de 7 años.

INTRODUCTION: Myasthenia is an autoimmune disease, being generalized muscular weakness, with important participation of facial muscles, a prominent feature. Signs of muscular fatigue arise, worsened by exercise and alleviated by rest. Clinical symptoms are less marked before noon, and get worse as the day advances, through the afternoon and evening. A clear relationship between myasthenia and thymic abnormalities does exist, being glandular hyperplasia and tumours the commonest underlying pathologic findings. Initial treatment is based on anticholinesterase drugs and steroids. Non respondents should be treated with immunoglobulins, immunosuppresses, plasmapheresis and surgical removal of the thymus, according to the symptoms control. CASE REPORT: We present the case of a seven years old girl with generalized muscular weakness, worsening through the day, being the diagnosis of myasthenia confirmed by the high level of acetylcholine antireceptors antibodies and the neurophysiologic study. Imaging study of the mediastinum showed a thymic mass located in the right lobe. CONCLUSION: It is therefore most important to rule out these conditions when myasthenia is suspected.

[Basis for the elaboration of nutritional guidelines]. / Bases para la elaboracion de guías nutricionales.

The work herein described proposes certain essential methodological baselines in preparing nutritional guidelines for the population. Based on the general statement concerning the social and nutritional conditions of Colombia--which point out the general tendencies for Latin America--the author presents some of the actual relations between food habits and local epidemiology. The establishment of nutritional guides for the community requires a general conception of the food system and concurrent and concerted actions in the production, distribution and consumption sub-systems. The economic and sociocultural factors that must be taken into account when designing these guides, are defined in the present document. Among such factors, it is unavoidable to be fully cognizant of the food habits and practices of the population. Consequently, the development of surveys and qualitative studies that maintain actual diagnostics constitutes an indispensable tool for the adequate preparation of nutritional guides.

[Bone mineral density in a population with severe infantile cerebral palsy]. / Densidad mineral ósea en la población con afectación severa por parálisis cerebral infantil.

OBJECTIVE: To determine the bone mineral density (BMD) values in children and adolescents with moderate and severe infantile cerebral palsy (ICP) in our catchment area, and compare these values with a healthy population. MATERIAL AND METHOD: A prognostic study of cases and controls for the assessment of BMD in patients from 2 to 18 years old with infantile cerebral palsy belonging to the Gross Motor Function Classification System (GMFCS) Groups IV and V. The BMD measurements were performed at distal femur level, dividing this region into 3 areas following the forearm protocol. RESULTS: The BMD for each of the three areas studied results in the final sample of 69 patients were much lower than the reference levels. There was a statistically significant difference (P<.05) between the BMD values in the two sub-groups studied. DISCUSSION: The greater the involvement, from a neurological point of view, in patients classified as Group V shows a very low BMD compared to patients of similar sex and age. The acquisition of bone capital in patients with ICP does not follow the normal pattern of the healthy population.

[Radial head and neck fractures in children]. / Fracturas pediátricas de cabeza y cuello de radio.

OBJECTIVE: To analyse cases of radial head and neck fractures in children and compare them with the literature. METHOD: Retrospective and descriptive study of 21 children with radial head and neck fractures. The following parameters were collected: demographics, comorbidity, classification, treatment, need for rehabilitation, lack of range of motion (ROM), time for recovery and complications. RESULTS: The series included 11 males, and the mean age was 8.3 years. The right side was affected in 14 patients. Twelve cases had an associated ipsilateral elbow injury. According to the Chambers classification, 15 cases belonged to group A, while in the Steele-Graham classification, 12 cases were in group I. Eleven patients were treated with immobilization only, 4 percutaneously, and 6 by open reduction and internal fixation (ORIF). Eleven of them needed rehabilitation and despite this, 8 did not achieve full mobility. The mean time to obtain the greatest ROM was 4.71 months. Eight patients had complications, with the most common being neuroapraxia and valgus deformity of the elbow. DISCUSSION AND CONCLUSIONS: Treatment of paediatric radius head and neck fractures must be step-wise, from immobilization only, manual and/or percutaneous reduction, to ORIF, whichever is less indicated. In this respect, both the transcapital needle and/or removal the radius head should be avoided. The most common complication is lack of supination, especially in cases treated by ORIF. The posterior interosseous neuroapraxia was the most common of the rest of complications.

Continuous peripheral nerve blockade in lower extremity surgery.

Peripheral nerve blocks afford numerous benefits for lower extremity surgery. There is growing interest in continuous peripheral nerve blocks, mainly for treatment of postoperative pain, a field that represents a challenge to the anaesthesiologist. This paper seeks to review the efficacy of continuous lower limb blocks for postoperative pain relief. Not only do continuous peripheral nerve blocks afford specificity of analgesic area but current research has shown that they enhance postoperative analgesia and patient satisfaction. New techniques and devices are increasingly appearing, and catheters are constantly being developed and improved; an example being the stimulating catheter, which represents one of the newest advances in this area. The above techniques show that continuous postoperative analgesia with catheters in the lower extremities is not only possible, but indeed provides sustained effective postoperative analgesia, reduces use of opioids, and improves rehabilitation and patient well-being with minimal side-effects. These techniques could prove an alternative to postoperative pain treatment following ambulatory surgery.