Safety, Tolerability and Pharmacokinetics of Half-Life Extended Severe Acute Respiratory Syndrome Coronavirus 2 Neutralizing Monoclonal Antibodies AZD7442 (Tixagevimab-Cilgavimab) in Healthy Adults.

BACKGROUND: AZD7442 is a combination of extended half-life, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific neutralizing monoclonal antibodies (tixagevimab and cilgavimab). METHODS: This phase 1, first-in-human, randomized, double-blind, placebo-controlled, dose-escalation study evaluated AZD7442 administered intramuscularly (300 mg) or intravenously (300, 1000, or 3000 mg) in healthy adults (aged 18-55 years). The primary end point was safety and tolerability. Secondary end points included pharmacokinetics and antidrug antibodies. RESULTS: Between 18 August and 16 October 2020, a total of 60 participants were enrolled; 50 received AZD7442, and 10 received placebo. Adverse events (all of mild or moderate intensity) occurred in 26 participants (52.0%) in the AZD7442 groups and 8 (80.0%) in the placebo group. No infusion or injection site or hypersensitivity reactions occurred. Tixagevimab and cilgavimab had mean half-lives of approximately 90 days (range, 87.0-95.3 days for tixagevimab and 79.8--91.1 days for cilgavimab) and similar pharmacokinetic profiles over the 361-day study period. SARS-CoV-2-specific neutralizing antibody titers provided by AZD7442 were maintained above those in plasma from convalescent patients with coronavirus disease 2019 (COVID-19). CONCLUSIONS: AZD7442 was well tolerated in healthy adults, showing a favorable safety profile across all doses. Depending on the SARS-CoV-2 variant, pharmacokinetic analyses suggest the AZD7442 could offer protection for ≥6 months against symptomatic COVID-19 after a single 300-mg intramuscular administration. CLINICAL TRIALS REGISTRATION: NCT04507256.

Antibodies are proteins produced by the body in response to infections caused by microbes, including viruses. AZD7442 is a combination of 2 human antibodies, with an extended duration of effect, sourced from people who had recovered from coronavirus disease 2019 (COVID-19). These antibodies recognize a specific part (spike protein) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, and prevent the virus from infecting cells in the body. The current study evaluated the safety of AZD7442 in healthy volunteers. Sixty adults were given AZD7442 or placebo (salt solution) as injections into the muscle (300-mg dose) or infusions into a vein (300­3000-mg doses). The study did not find any safety issues with AZD7442, including at the highest dose. AZD7442 was measured in the blood 12 months after dosing, suggesting a long duration of protection. Following this study, AZD7442 was tested in larger clinical trials to investigate its potential in preventing and treating COVID-19. AZD7442 is currently authorized as treatment for outpatients with COVID-19 and as a preventive drug in people who may not respond well to COVID-19 vaccines and need additional protection (eg, those taking medications that dampen the immune system).

Targeting the Endothelin-1 pathway to reduce invasion and chemoresistance in gallbladder cancer cells.

BACKGROUND: Gallbladder cancer (GBC) is a prevalent and deadly biliary tract carcinoma, often diagnosed at advanced stages with limited treatment options. The 5-year survival rate varies widely from 4 to 60%, mainly due to differences in disease stage detection. With only a small fraction of patients having resectable tumors and a high incidence of metastasis, advanced GBC stages are characterized by significant chemoresistance. Identification of new therapeutic targets is crucial, and recent studies have shown that the Endothelin-1 (ET-1) signaling pathway, involving ETAR and/or ETBR receptors (ETRs), plays a crucial role in promoting tumor aggressiveness in various cancer models. Blocking one or both receptors has been reported to reduce invasiveness and chemoresistance in cancers like ovarian, prostate, and colon. Furthermore, transcriptomic studies have associated ET-1 levels with late stages of GBC; however, it remains unclear whether its signaling or its inhibition has implications for its aggressiveness. Although the role of ET-1 signaling in gallbladder physiology is minimally understood, its significance in other tumor models leads us to hypothesize its involvement in GBC malignancy. RESULTS: In this study, we investigated the expression of ET-1 pathway proteins in three GBC cell lines and a primary GBC culture. Our findings demonstrated that both ETAR and ETBR receptors are expressed in GBC cells and tumor samples. Moreover, we successfully down-regulated ET-1 signaling using a non-selective ETR antagonist, Macitentan, which resulted in reduced migratory and invasive capacities of GBC cells. Additionally, Macitentan treatment chemosensitized the cells to Gemcitabine, a commonly used therapy for GBC. CONCLUSION: For the first time, we reveal the role of the ET-1 pathway in GBC cells, providing insight into the potential therapeutic targeting of its receptors to mitigate invasion and chemoresistance in this cancer with limited treatment options. These findings pave the way for further exploration of Macitentan or other ETR antagonists as potential therapeutic strategies for GBC management. In summary, our study represents a groundbreaking contribution to the field by providing the first evidence of the ET 1 pathway's pivotal role in modulating the behavior and aggressiveness of GBC cells, shedding new light on potential therapeutic targets.

Knowledge, Attitudes, and Behavior in the administration of medication in the home care setting: Cross-cultural Spanish adaptation.

OBJECTIVE: The aim of the study is to validate and adapt the "Knowledge Attitute and Behaviour in the administration of medication in the home care setting questionnaire" in the home care setting in Cordoba, Spain, through a cross-validation process. DESIGN: Cross-sectional study SAMPLE: 106 community nurses provide home care in Cordoba, and are involved in the management of the medication process in the patient's home. MEASUREMENTS: Community nurses' knowledge, attitudes, and behaviors toward medication error prevention strategies in-home care. RESULTS: For the evaluation of psychometric properties, Cronbach's α was calculated, which returned a value of 0.639, showing good internal consistency. Most participants agreed that the home care setting increases the risk of medication errors. CONCLUSION: The study, underscores the importance of analyzing the phenomenon of medication errors in the home care setting. The characteristics and peculiarities of a home care setting are different from a hospital setting, which means that factors such as the environment, the figures involved in the care process (caregivers and/or family members), and the way in which they communicate with the rest of the multi-professional team can influence both the type of errors and the likelihood of their occurrence.

CHRONOFALLS: A multicentre nurse-led intervention in the chronoprevention of in-hospital falls in adults.

BACKGROUND: Falls are among the most common and serious adverse events for hospitalised patients. In-hospital falls pose a major medical and economic challenge for public health worldwide. Nevertheless, the issue is often addressed without regard to certain relevant variables such as the time of the fall. The aim of this study was to determine the effect of the implementation of a nurse-led intervention based on the temporal patterns of falls and their aetiology on the occurrence of falls. METHODS: A mixed-method research design was carried out in three phases: a) a longitudinal prospective study (audits, chronobiological analyses and implementation of a multicentre nurse-led intervention based on temporal patterns of falls); b) a retrospective study of fall records; and c) a qualitative study based on focus groups. The protocol was published in 2021. RESULTS: A difference was observed in the number of fall records before and after the chronopreventive intervention (retrospective: 64.4% vs. 35.6%; p < 0,001). According to the interrupted series analysis, considering the influence of the COVID-19 pandemic, a reduction in falls of 2.96% (95% CI 1.70%-4.17%) was observed. The concepts of falls, the COVID-19 pandemic and the causes of non-registration have emerged as categories for qualitative analysis. CONCLUSIONS: A multicentric nurse-led program based on tailored organisational, educational and behavioural chronopreventive measures seems to lead to a reduction in the number of in-hospital falls. The findings of the present study, highlighting the implementation of chronopreventive measures, can serve as a basis for future health policies. TRIAL REGISTRATION: The project was registered on the Clinical Trials Registry NCT04367298 (29/04/2020).

Formal and Informal Services Used by Women Who Suffer Intimate Partner Violence in Spain.

Intimate partner violence (IPV) is an important public health problem. Female victims of IPV do not always use the institutional resources available to them. We conducted a cross-sectional study using data from the Spanish 2014 Macro-Survey on Violence Against Women. The findings show that 15% of the survey participants suffered from IPV in the last year. The factors associated with a higher probability of suffering IPV are being of non-Spanish nationality, being a student, having a low-educational level, having no income, being the household head, and not having a current partner. Regarding the resources used by women subjected to IPV, almost half resorted to informal sources, such as female friends and/or their own mothers. The use of formal resources was low. Therefore, IPV continues to be a problem in Spain that seems to remain in the private domain. Consequently, it is necessary to increase the availability of and access to legal resources.

Impact of sound levels on physiological and consciousness state of cardiovascular patients.

BACKGROUND: Patients treated in intensive care units (ICUs) experience life-threatening medical conditions but some external factors in ICUs do not help or even adversely affect and complicate their evolution. Among others, such factors include noise pollution due to alarms and medical clinical equipment, as well as the activities of the health care personnel themselves. AIM: This study aimed to evaluate the influence of elevated sound levels on physiological variables and the consciousness state of patients treated in a cardiovascular area in an ICU. DESIGN: A longitudinal study with several observations was carried out during 1 month in the cardiovascular area of an ICU of a third-level hospital in southern Spain. METHODS: Sound levels were monitored in different work shifts and patients' physiological data and consciousness status were recorded. Generalized additive mixed models (GAMMs) were developed to detect the variability of the sound levels together with the vital parameters of the patients in the ICU. RESULTS: Thirty-eight patients were included. The mean sound level was 54.09 dBA. The GAMM sound levels analysis showed a significant increase in sound levels from 4:30 p.m. to 8:00 p.m. (1.83 dBA; P < .001) and 8:00 p.m. to 11:30 p.m. (3.06 dBA; P < .001). An increase in heart rate (3.66 bpm; P < .001), respiratory rate (2.62 rpm; P < .001) and the Glasgow Coma Scale (0.50 units; P = .002) was detected during the 4:30 p.m.-8:30 p.m. CONCLUSIONS: Elevated sound levels in cardiovascular ICUs seem to influence positively the physiological and consciousness status of patients. Given the importance of the findings for patient safety, future intervention studies are recommended. RELEVANCE TO CLINICAL PRACTICE: The finding of this study could translate into structural changes in ICU facilities, as well as the development of clinical practice guidelines that influence the behaviour of health care professionals.

Measurement of aggression in older adults.

Aggressive behaviors are prevalent in late-life and are associated with important consequences for older adults, caregivers, and healthcare providers. Age-related changes in the manifestation of aggression are precipitated in part by the rise of cognitive impairment. Such changes necessitate the use of psychometrically sound measures. The present article identifies existing measures of aggression for older adults, highlights the strengths and limitations of these measures, and proposes avenues for future research in this area. Five full-scale measures of aggression, as well as five subscales of aggression embedded within larger non-aggression measures in older adults were identified. Overall, measures of aggression specific to late-life are predominately observational and limited to individuals with dementia or older adults living in long-term care settings. The psychometric properties of aggression scales in late-life generally indicate adequate internal consistency, interrater reliability, and concurrent validity. In contrast, the reliability and validity of subscales of aggression contained within larger neuropsychiatric measures are more difficult to ascertain due to limited research. Future investigations would benefit from examining the psychometric properties of widely-used self-report measures of aggression among older adults, further evaluating the psychometric properties of aggression subscales, and developing additional measures which are predictive of aggressive behaviors.

Chronoprevention in hospital falls of older people: protocol for a mixed-method study.

BACKGROUND: Accidental falls in hospitals are serious events concerning the safety of the patients. Recent studies demonstrated that the time of falls is a key factor to be considered in prevention. It has been shown that the time of day, the day of the week and the month of the year impact on the occurrence of falls. The aim of the study is to determine the effect of the application of a programme of preventive measures based on the temporal patterns of the risk factors on the hospital fall occurrence. METHODS: A mixed-method research design. The following three phases will be carried out: 1) Longitudinal prospective study in two parts: (a) audits and seminars of healthcare professionals focused on an effective and efficient hospital falls register. Multi-Component and Single Cosinor analyses will be performed to obtain the temporal patterns of hospital falls and their related variables and (b) implementation of a based-temporal patterns, multidimensional prevention programme. 2) Retrospective study of falls registered in institutional databases. 3) Qualitative study based on focus groups (physicians, nurses and nursing assistants). The study protocol was approved in 2018. DISCUSSION: With regard to the safety of patients, hospital falls are serious events. Recent studies have demonstrated that the time of falls is a key factor to be considered in prevention. It has been shown that the time of day, the day of the week and the month of the year impact on the occurrence of falls. It is imperative to study temporal patterns of hospital falls to effectively and comprehensively define the aetiology of falls and, therefore, design preventive strategies. A reduction of the number of in-hospital falls and related injuries is expected, as well as an improvement in the quality of life of patients. Considering temporal patterns and levels of mood and sleep of healthcare professionals will achieve an improvement in patient safety. TRIAL REGISTRATION: Retrospectively registered in ClinicalTrials.gov ID: NCT04367298.

[Clinical and epidemiological characteristics of the Philadelphia negative myeloproliferative neoplasms in Chile]. / Características clínicas y epidemiológicas de las neoplasias mieloproliferativas Philadelphia negativas en el sistema público de salud de Chile.

BACKGROUND: Philadelphia-negative myeloproliferative neoplasms (Ph-MPN) are chronic hematological disorders characterized by the overproduction of one or more mature myeloid blood cell lineages. Classical Ph-MPN are polycythemia vera (PV), essential thrombocytopenia (ET) and primary myelofibrosis (PMF). AIM: To assess the epidemiological, clinical and diagnostic characteristics of Ph-MPN in Chile. MATERIAL AND METHODS: Retrospective review of medical records of all patients referred as MPN from 2012 to 2017. Patients with (9;21) translocation were excluded. RESULTS: Data of 462 cases with a median age of 69 years from 10 public hospitals was reviewed. ET was the most frequently Ph-MNP found. The incidence of Ph-MPN was 1.5 x 100.000 cases. The JAK2 V617F mutation study was performed in 96% of patients and only 30% had a bone marrow biopsy. Thrombotic events were observed in 29% of patients. Bleeding events were observed in 7%. Five-year overall survival was 87%. CONCLUSIONS: ET is the most frequent Ph-MPN. The mean incidence was lower than reported in the literature, in part because of a sub diagnosis.

[Clinical and epidemiological characteristics of the Philadelphia negative myeloproliferative neoplasms in Chile]. / Características clínicas y epidemiológicas de las neoplasias mieloproliferativas Philadelphia negativas en el sistema público de salud de Chile.

BACKGROUND: Philadelphia-negative myeloproliferative neoplasms (Ph-MPN) are chronic hematological disorders characterized by the overproduction of one or more mature myeloid blood cell lineages. Classical Ph-MPN are polycythemia vera (PV), essential thrombocytopenia (ET) and primary myelofibrosis (PMF). AIM: To assess the epidemiological, clinical and diagnostic characteristics of Ph-MPN in Chile. MATERIAL AND METHODS: Retrospective review of medical records of all patients referred as MPN from 2012 to 2017. Patients with (9;21) translocation were excluded. RESULTS: Data of 462 cases with a median age of 69 years from 10 public hospitals was reviewed. ET was the most frequently Ph-MNP found. The incidence of Ph-MPN was 1.5 x 100.000 cases. The JAK2 V617F mutation study was performed in 96% of patients and only 30% had a bone marrow biopsy. Thrombotic events were observed in 29% of patients. Bleeding events were observed in 7%. Five-year overall survival was 87%. CONCLUSIONS: ET is the most frequent Ph-MPN. The mean incidence was lower than reported in the literature, in part because of a sub diagnosis.

Severe trauma patients and nursing practice-associated infections.

AIMS: Our study examined factors influencing the development of healthcare-associated infections in the intensive care unit (ICU) of a tertiary hospital in southern Spain. BACKGROUND: Healthcare-associated infections are a frequent adverse event, significantly lengthening patient stays in the ICU. Nursing practice is a key factor in the infection control process. DESIGN: A retrospective longitudinal study with two observation periods (admission and discharge) was performed in an ICU of a tertiary hospital. METHODS: We analysed patient records for those admitted to this unit coded as CIE 800-959.9 from 2012 to 2016. Using binomial logistic regression analysis, we analysed factors associated with healthcare-associated infections. RESULTS: We analysed 375 records (men: 78.1%; average age: 46.63 years). Of these, 9.2% patients acquired a healthcare-associated infection during their stay. Nursing practice-related factors significantly associated with the development of infection were the number of days connected to mechanical ventilation and the number of days in the ICU. CONCLUSION: Healthcare-associated infections in patients with severe trauma admitted to the ICU are mainly associated with the management of invasive techniques. A multidisciplinary approach should focus on the review of action and care plans.

Association between Physical Activity, Food Consumption and Depressive Symptoms Among Young Adults in Spain: Findings of a National Survey.

Young adults have a significant prevalence of mental disorders, which could lead to dysfunctional quality of life. Records of 1,645 Spanish adolescents were examined and multiple logistic regressions were performed. Being a woman, being older and having a sedentary life were all associated with a higher psychological vulnerability, whereas a low frequency of fresh fruit and bread/cereals consumption, as well as regular intense physical activity, were considered protective against such susceptibility. Regular physical activity and a diet with a high consumption of fruit and cereals may help reduce depressive symptoms, but sociodemographic features are as much as important as lifestyle habits.

An improved catalogue of putative synaptic genes defined exclusively by temporal transcription profiles through an ensemble machine learning approach.

BACKGROUND: Assembly and function of neuronal synapses require the coordinated expression of a yet undetermined set of genes. Previously, we had trained an ensemble machine learning model to assign a probability of having synaptic function to every protein-coding gene in Drosophila melanogaster. This approach resulted in the publication of a catalogue of 893 genes which we postulated to be very enriched in genes with a still undocumented synaptic function. Since then, the scientific community has experimentally identified 79 new synaptic genes. Here we use these new empirical data to evaluate our original prediction. We also implement a series of changes to the training scheme of our model and using the new data we demonstrate that this improves its predictive power. Finally, we added the new synaptic genes to the training set and trained a new model, obtaining a new, enhanced catalogue of putative synaptic genes. RESULTS: The retrospective analysis demonstrate that our original catalogue was significantly enriched in new synaptic genes. When the changes to the training scheme were implemented using the original training set we obtained even higher enrichment. Finally, applying the new training scheme with a training set including the 79 new synaptic genes, resulted in an enhanced catalogue of putative synaptic genes. Here we present this new catalogue and announce that a regularly updated version will be available online at: http://synapticgenes.bnd.edu.uy CONCLUSIONS: We show that training an ensemble of machine learning classifiers solely with the whole-body temporal transcription profiles of known synaptic genes resulted in a catalogue with a significant enrichment in undiscovered synaptic genes. Using new empirical data provided by the scientific community, we validated our original approach, improved our model an obtained an arguably more precise prediction. This approach reduces the number of genes to be tested through hypothesis-driven experimentation and will facilitate our understanding of neuronal function. AVAILABILITY: http://synapticgenes.bnd.edu.uy.

Cluster Locator, online analysis and visualization of gene clustering.

Summary: Genes sharing functions, expression patterns or quantitative traits are not randomly distributed along eukaryotic genomes. In order to study the distribution of genes that share a given feature, we present Cluster Locator, an online analysis and visualization tool. Cluster Locator determines the number, size and position of all the clusters formed by the protein-coding genes on a list according to a given maximum gap, the percentage of gene clustering of the list and its statistical significance. The output includes a visual representation of the distribution of genes and gene clusters along the reference genome. Availability and implementation: Cluster Locator is freely available at http://clusterlocator.bnd.edu.uy/. Supplementary information: Supplementary data are available at Bioinformatics online.

Use of beta-blockers and risk of aseptic loosening in total hip and knee arthroplasty: a nested case - control study.

OBJECTIVES: To analyze the effect of beta-blockers on the risk of aseptic loosening (AL) in Total Hip (THA) or Knee (TKA) Arthroplasty. METHODS: A nested case-control study was conducted. Cases were patients who underwent revision surgery for THA or TKA due to AL. Controls were patients who sustained primary THA or TKA and were matched to cases in respect to age, sex, type of prostheses and follow-up in a 4:1 ratio. The use of beta-blockers was achieved. A logistic regression analysis adjusted to potential confounders was performed to determine the risk of AL. Analysis was also adjusted to cardioselectivity of the beta-blocker and the adherence to treatment, measured as Proportion of Days Covered (PDC). RESULTS: 24 cases and 96 controls were selected. Compared to non-users, any use of beta-blockers was associated with a reduced risk of AL [adjusted OR 0.141 (Confidence Interval (CI) 95% 0.04-0.86)]. Use of selective beta-blockers showed significant lower risk of AL [adjusted OR 0.112 (CI95% 0.01-0.91)]. PDC ≥50% was associated with reduced risk of AL compared to non-users [adjusted OR 0.083 (CI95% 0.01-0.66)]. CONCLUSION: The first clinical evidence showing an association between the use of beta-blockers and lower risk of aseptic loosening in THA and TKA is provided.

Chronotype, nursing activity, and gender: A systematic review.

AIM: To synthesize evidence about the effect of individual circadian preference (chronotype) and gender in the development of sleep and mood problems in nursing professionals. BACKGROUND: Shift workers are more prone to having unhealthy habits and unfavourable clinical conditions than nonshift workers. These associations are mediated by chronotype and gender differences have also been detected. DESIGN: A quantitative systematic review. DATA SOURCES: Electronic searches were performed in MEDLINE, Scopus, ScienceDirect, and Web of Science from 1 July 2012 - 1 July 2017. REVIEW METHODS: A systematic review was conducted using the Cochrane Collaboration guidelines and two quality assessment tools: the National Heart, Lung and Blood Institute and GRADE. Inclusion criteria were quantitative studies where the sample consists entirely of nurses, analysing circadian rhythms or individual chronotype or gender and sleep/mood disturbances in nursing activity. The review was reported using the PRISMA statement. RESULTS: A total of 23 studies were included in the review (five cohort studies and 18 cross-sectional studies). Data on gender-specific attention were scarce (two studies) and showed a higher incidence of sleep problems. Female nurses with eveningness-oriented personality seem to be more prone to having sleep disorders, insomnia, fatigue, and anxiety than male and morningness ones. CONCLUSIONS: Evidence seems to show that female nurses with an evening-oriented preference suffer more problems of insomnia, sleepiness, fatigue, and anxiety. The impact of our results may affect nurses, patient safety and the quality of clinical practice.

Gender, socioeconomic, medical, and environmental factors related to domestic accidents of the elderly in Spain. Findings of a national survey.

Domestic accidents pose serious threats to the independence of the elderly. We explored associations between domestic accidents and gender, socioeconomic, medical, and environmental factors using data from the European Health Survey 2014 for elderly Spanish female and male nationals. Records of 5960 participants (mean age ± SD: 75.9 ± 7.6 years), 59.8% of whom were women, were examined. Domestic accidents occurred in 460 (7.1%) seniors, predominately in women (78.5%). Age (adjusted odds ratio [aOR]: 1.02 [95% confidence interval [CI]: 1.00-1.03, p = .003], female gender (aOR 2.04 [95% CI 1.60-2.60, p < .001]), difficulty managing 12 stairs (reference: none) (some: aOR 2.03 [95% CI 1.53-2.68, p < .001]; much: aOR 2.88 [95% CI 2.15-3.87, p < .001]; inability: aOR 3.09 [95% CI 2.14-4.45, p < .001]), and depressive symptoms severity (reference: absent) (mild: aOR 1.44 [95% CI 1.10-1.89, p = .008]; moderate: aOR 1.91 [95% CI 1.35-2.71, p < .001];. Very severe: aOR 2.53 [95% CI 1.72-3.71, p < .001]; extremely severe: aOR 2.38 [95% CI 1.45-3.93, p = .001]) were independently associated with domestic accidents. Severity of depressive symptoms was the most prominent feature for women, while inability to manage 12 stairs was the most prominent for men. Our results suggest important gender differences in factors associated with domestic accidents that are relevant to intervention and preventive programs.

[Response rates to first-line treatment in eligible patients to autologous stem transplantation in Chile]. / Mieloma múltiple en Chile: Respuesta a tratamiento en pacientes con mieloma múltiple elegibles para trasplante autólogo de progenitores hematopoyéticos.

Background The treatment of choice of newly diagnosed multiple myeloma (NDMM) is an induction with proteasome inhibitors followed autologous stem cell transplantation (HSCT). Since 2013, the treatment of these patients in the public system is based on CTD (cyclophosphamide, thalidomide, and dexamethasone). Aim To evaluate the response rates achieved with CTD, and the results of HSCT in patients with NDMM in the public setting. Material and Methods Data from patients considered as candidates for HSCT from different centers of the National Adult Antineoplastic Drug Program (PANDA, for its acronym in Spanish), diagnosed between 2013 and 2017, was analyzed. The response to treatment of first and second lines of treatment was evaluated, in addition to the results of HSCT. An optimal Response was defined as the sum of strict complete remission, complete remission and very good partial response (sCR, CR and VGPR). Results One hundred and seventy-seven patients were analyzed, 54% women, and 53% with IgG multiple myeloma. Information about the international staging system was retrieved in 127 patients (71%). Seventeen percent were ISS I, 22% in ISS II and 32% ISS III. CTD was used as first treatment in 106 patients (60%), and cyclophosphamide, bortezomib and dexamethasone (CyBorD) in 13 (7%). As first line, CTD had an overall response of 50.9%, and CyBorD of 76.9%. Thirty patients were treated with bortezomib as second line treatment. Forty patients (22%) underwent HSCT. The 5-year Overall Survival (OS) in transplanted patients and non-transplanted patients was 100 and 62% respectively (p < 0.01). Conclusions The response rate achieved by CTD in these patients is suboptimal. The response to CyBorD was better.

AL amyloidosis in the Chilean public health system: a pending debt. Multicenter study of the Chilean Monoclonal Gammopathies Cooperative Group.

BACKGROUND: Immunoglobulin light chain (AL) amyloidosis is a rare and underdiagnosed entity. AIM: To characterize patients with AL amyloidosis in Chilean public health centers. MATERIAL AND METHODS: We conducted a retrospective, multicenter study. Public centers of the Chilean Monoclonal Gammopathies Cooperative Group were asked to search for patients with AL amyloidosis in their databases. Epidemiological, clinical and laboratory characteristics were evaluated. RESULTS: Forty-two patients aged 22 to 84 years were found. Twenty four percent had localized AL amyloidosis; 64% had a lambda light chain clone; 47% were associated with multiple myeloma and 9% with non-Hodgkin lymphoma. The most commonly involved organ was the kidney (76%). Serum free light chains were measured in 31% and an echocardiogram was performed in 74% of patients. Seventeen percent of patients received only palliative care, 17% were treated with bortezomib, 21% with thalidomide, and 40% with melphalan. No patient was transplanted. The mean overall survival (OS) of the group was 19 months. The 5-year OS was 28%. CONCLUSIONS: It is important to obtain these realistic, national data to initiate strategies to improve early diagnosis and proper management of this disease.

Avulsion Fractures of Posterior Calcaneal Tuberosity: Identification of Prognostic Factors and Classification.

Avulsion fractures of the posterior calcaneal tuberosity are rare injuries, and little is known about the underlying factors, outcomes, and prognosis. Furthermore, classifications described previously focus on fracture morphology, with uncertain clinical utility. We present the results of a retrospective study of 21 patients treated for this pathology from January 2002 to December 2015. Features analyzed were age; sex; mechanism of injury; medical comorbidities; type of fracture, as proposed by Beavis; fracture displacement; fragment size; type of treatment; complications; need for secondary surgery; and the American Orthopaedic Foot and Ankle Society score after treatment and follow-up care. Mean age was 56.95years. A total of 61.9% were females, and 71.4% were secondary to low-energy trauma. In addition, 19% were diabetic. Mean follow-up was 57.24 months. Surgery was performed in 81%. Complications rate was 61.9%, and secondary surgery was needed in 38.1%. Mean fracture displacement was significantly higher when complications occurred (25.91mm versus 7.61 mm) (p = .03) and when soft tissues complications appeared (30.65mm versus 14.68 mm) (p = .02). Female gender was associated with the secondary loss of reduction (p = .04). The Beavis classification was not related significantly with any outcome variable. When fracture displacement was ≥2cm, complication rate increased from 30% to 90.9% (p = .008) and soft tissue compromise increased from 0% to 45.45% (p = .035). A new classification system with prognostic value is described, based on fracture displacement. We present 1 of the largest series published to date; fracture displacement is a major variable that influences the outcomes of these injuries, and a new classification attending to a prognostic factor is developed.