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.

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.

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.

[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.

[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.

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.

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.

Complementary DNA sequence of the HLA-B*3924 allele.

We have isolated the complete coding region of HLA-B*39 from a Spanish Caucasoid, using a new PCR primer for its 5' untranslated region. The cDNA matched partial genomic sequences of B*3924, an allele whose distribution appears to be restricted to Mediterranean and Arabian Caucasoids. A single amino acid change exclusive to B*3924 (threonine-98) distinguishes it from B*3903.

[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.

Complementary DNA sequence of the novel HLA-B*3704 allele.

The novel HLA-B*3704 allele was identified by polymerase chain reaction with sequence specific oligoneucletides (PCR-SSO) in a Spanish Caucasoid individual whose T-lymphocytes showed an ambiguous HLA-B phenotype. The nucleotide sequence of B*3704 was determined after reverse transcription-polymerase chain reaction (RT-PCR) amplification and molecular cloning of its complete coding region. B*3704 differs from B*3701 by a single nucleotide replacement that induces the substitution of histidine for tyrosine 171. Residue 171 is located in the alpha-helix of the alpha-2 domain, lining the A pocket of the peptide-binding site. Therefore, the His171 substitution seen in HLA-B*3704 is likely to affect its antigen-presenting properties and is probably responsible for the differentiated serological phenotype of this allele in comparison with B*3701.

SCH-C (SCH 351125), an orally bioavailable, small molecule antagonist of the chemokine receptor CCR5, is a potent inhibitor of HIV-1 infection in vitro and in vivo.

We describe here the identification and properties of SCH-C (SCH 351125), a small molecule inhibitor of HIV-1 entry via the CCR5 coreceptor. SCH-C, an oxime-piperidine compound, is a specific CCR5 antagonist as determined in multiple receptor binding and signal transduction assays. This compound specifically inhibits HIV-1 infection mediated by CCR5 in U-87 astroglioma cells but has no effect on infection of CXCR4-expressing cells. SCH-C has broad and potent antiviral activity in vitro against primary HIV-1 isolates that use CCR5 as their entry coreceptor, with mean 50% inhibitory concentrations ranging between 0.4 and 9 nM. Moreover, SCH-C strongly inhibits the replication of an R5-using HIV-1 isolate in SCID-hu Thy/Liv mice. SCH-C has a favorable pharmacokinetic profile in rodents and primates with an oral bioavailability of 50-60% and a serum half-life of 5-6 h. On the basis of its novel mechanism of action, potent antiviral activity, and in vivo pharmacokinetic profile, SCH-C is a promising new candidate for therapeutic intervention of HIV infection.

Coinfection of SCID-hu Thy/Liv mice with human herpesvirus 6 and human immunodeficiency virus type 1.

Human herpesvirus 6 (HHV-6) has been proposed as a potential cofactor in the progression of human immunodeficiency virus type 1 (HIV-1) disease. We used the SCID-hu Thy/Liv mouse model to evaluate the in vivo interactions between HHV-6 and HIV-1. Our results demonstrate that HHV-6 and HIV-1 can simultaneously replicate in the human thymus in vivo. In this model, however, the presence of one virus appears not to modify the replication or cytopathicity of the other.

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.

Antiviral activity of 2'-deoxy-3'-oxa-4'-thiocytidine (BCH-10652) against lamivudine-resistant human immunodeficiency virus type 1 in SCID-hu Thy/Liv mice.

Oral administration of 2'-deoxy-3'-oxa-4'-thiocytidine (BCH-10652), a nucleoside analog structurally similar to lamivudine (3TC), caused dose-dependent inhibition of viral replication in SCID-hu Thy/Liv mice infected with human immunodeficiency virus type 1 NL4-3 and with an NL4-3 clone containing the M184V mutation in reverse transcriptase that confers resistance to 3TC. These experiments demonstrate the utility of this mouse model for evaluating drug resistance and for performing direct comparisons between antiviral compounds in vivo.

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.

R5 strains of human immunodeficiency virus type 1 from rapid progressors lacking X4 strains do not possess X4-type pathogenicity in human thymus.

Some individuals infected with only R5 strains of human immunodeficiency virus type 1 progress to AIDS as quickly as individuals harboring X4 strains. We determined that three R5 viruses were much less pathogenic than an X4 virus in SCID-hu Thy/Liv mice, suggesting that R5 virus-mediated rapid disease progression is associated with host, not viral, factors.

CCR5- and CXCR4-utilizing strains of human immunodeficiency virus type 1 exhibit differential tropism and pathogenesis in vivo.

CCR5-utilizing (R5) and CXCR4-utilizing (X4) strains of human immunodeficiency virus type 1 (HIV-1) have been studied intensively in vitro, but the pathologic correlates of such differential tropism in vivo remain incompletely defined. In this study, X4 and R5 strains of HIV-1 were compared for tropism and pathogenesis in SCID-hu Thy/Liv mice, an in vivo model of human thymopoiesis. The X4 strain NL4-3 replicates quickly and extensively in thymocytes in the cortex and medulla, causing significant depletion. In contrast, the R5 strain Ba-L initially infects stromal cells including macrophages in the thymic medulla, without any obvious pathologic consequence. After a period of 3 to 4 weeks, Ba-L infection slowly spreads through the thymocyte populations, occasionally culminating in thymocyte depletion after week 6 of infection. During the entire time of infection, Ba-L did not mutate into variants capable of utilizing CXCR4. Therefore, X4 strains are highly cytopathic after infection of the human thymus. In contrast, infection with R5 strains of HIV-1 can result in a two-phase process in vivo, involving apparently nonpathogenic replication in medullary stromal cells followed by cytopathic replication in thymocytes.