Accelerated DNA replication fork speed due to loss of R-loops in myelodysplastic syndromes with SF3B1 mutation.

Myelodysplastic syndromes (MDS) with mutated SF3B1 gene present features including a favourable outcome distinct from MDS with mutations in other splicing factor genes SRSF2 or U2AF1. Molecular bases of these divergences are poorly understood. Here we find that SF3B1-mutated MDS show reduced R-loop formation predominating in gene bodies associated with intron retention reduction, not found in U2AF1- or SRSF2-mutated MDS. Compared to erythroblasts from SRSF2- or U2AF1-mutated patients, SF3B1-mutated erythroblasts exhibit augmented DNA synthesis, accelerated replication forks, and single-stranded DNA exposure upon differentiation. Importantly, histone deacetylase inhibition using vorinostat restores R-loop formation, slows down DNA replication forks and improves SF3B1-mutated erythroblast differentiation. In conclusion, loss of R-loops with associated DNA replication stress represents a hallmark of SF3B1-mutated MDS ineffective erythropoiesis, which could be used as a therapeutic target.

Association of Tryptophan: Kynurenine Metabolites with Healing in Chronic Venous Leg Ulcers.

OBJECTIVE: Chronic wound healing is a complex process that is still not well understood. The tryptophan (TRP)-L-Kynurenine (KYN) pathway has recently been under increased scrutiny in regards to wound healing. The study applied metabolomics to elucidate the TRP-L- KYN pathway associated with wound healing in chronic venous leg ulcers (CVLUs). APPROACH: This study used a longitudinal comparative design of 60 serum samples collected from 30 older adult patients with CVLUs, receiving weekly sharp debridement at a wound clinic. The serum samples were collected at baseline and week 4 (healed wounds) or week 8 (non-healed wounds). Liquid chromatography-mass spectrometry (LC-MS) metabolomics was used to analyze targeted metabolites. A Bayesian approach was employed to examine robust correlations between changes in metabolite values and linear healing slope and to compare by group. RESULTS: The mean age was 71.13 (±9.46). Half of the sample were female and the minority (17%) were Black. The mean values of evaluated metabolites for the non-healed group were consistently lower than those for the healed group. The healed group (n=12) had higher KYN values; Those on a healing trajectory (n=23) had lower KYN levels and higher TRP levels at baseline and over time. There was moderate support (Bayes Factor = 3.70) for a negative association between change in Kynurenic Acid and linear healing slope (r = -0.35, CrI = -0.62, -0.04, PD= 98%). Results suggest KYN and TRP may be markers for healing in individuals with CVLUs. INNOVATION AND CONCLUSION: Gaining a better understanding of the associations between the TRP-L- KYN pathway and the healing of CVLUs may help to clarify the links of inflammation with the rate and success of wound healing. Biomarker development focused on the TRP-L- KYN pathway could be pursued, if the associations are further supported by focused research studies.

Sleep, Fatigue, and Inflammatory Biomarkers in Older Adults with Chronic Venous Leg Ulcers Receiving Intensive Outpatient Wound Care.

Objective: Chronic venous ulcers are a relatively common and distressing condition that disproportionately affects older individuals. Along with multiple concomitant issues such as wound drainage, pain, and mobility impairments, individuals with chronic venous leg ulcers (CVLUs) commonly report sleep disturbances and fatigue; however, limited research has examined these symptoms in relation to inflammatory biomarkers in this population over the intensive wound care treatment trajectory. This study aimed at describing the symptoms of sleep and fatigue in older adults with CVLUs receiving intensive wound treatment with weekly debridement and exploring the relationships between these symptoms and tumor necrosis factor-alpha (TNF-α), c-reactive protein (CRP), and interleukin (IL)-6. Approach: Demographics, clinical characteristics, Pittsburgh Sleep Quality Index (PSQI) scores, Brief Fatigue Inventory (BFI), TNF-α, CRP, and IL-6 levels were collected from 84 older adults with CVLUs at three time points (baseline, week 4, and week 8). Data analysis included descriptive statistics and Bayesian estimation of associations. Results: Findings showed a consistent pattern of poor sleep quality and mild fatigue among these individuals. Lower IL-6 levels at week 4 and higher CRP levels at week 8 were linked to poor sleep quality. Higher CRP levels were linked to greater fatigue at baseline and week 8. Sleep and fatigue were correlated at all time points. Innovation and Conclusion: This study highlights the importance of clinicians evaluating sleep and fatigue in those with CVLUs. Further research is needed to validate circulating inflammatory biomarkers to enhance our understanding of sleep and fatigue's role in wound healing.

Retrospective View of Four Cases of Cutaneous Manifestations in COVID-19 Patients in an Acute Care Setting.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the etiologic agent of coronavirus disease 2019 (COVID-19), causes an excessive inflammatory response and hemostatic abnormalities in the lungs, kidney, and skin. Four patients with COVID-19 admitted to an acute care community hospital developed nonblanchable purpuric macules, patches, and retiform purpura-like lesions at the sacrum, buttocks, lower extremities, and upper back. These lesions can be misdiagnosed as deep tissue pressure injuries. One patient also developed a vesicular-like rash at the upper back and another one developed pernio (chilblains)-like lesions to the third toe of the left foot. Previous studies suggest that the vascular hyperinflammation status and microthrombosis may be responsible for the cutaneous manifestations in patients with SARS-CoV-2. These cutaneous manifestations observed in patients with SARS-CoV-2 may be related to progression of the disease.

Associação entre variáveis clínicas e demográficas de pacientes internados em unidade de terapia intensiva oncológica e a carga de trabalho de enfermagem / Asociación entre variables clínicas y demográficas de pacientes en unidad de terapia intensiva oncológica y la carga de trabajo de enfermería / Association between Clinical and Demographic Variables in Patients in an Oncology Intensive Care Unit and the Nursing Workload

Introdução: O uso do Nursing Activity Score permite correlacionar a carga de trabalho de enfermagem com os índices de avaliação prognóstica na unidade de terapia intensiva e auxiliar no desenvolvimento do processo de trabalho dos enfermeiros por meio do dimensionamento adequado da equipe. Objetivo: Analisar a associação entre variáveis clínicas e demográficas de pacientes com carga de trabalho de enfermagem em uma Unidade de Terapia Intensiva Oncológica. Métodos: Coorte prospectiva, realizada no Instituto Nacional de Câncer José Alencar Gomes da Silva, no período de setembro a dezembro de 2016. A coleta de dados inclui a mensuração da carga de trabalho por meio do Escore de Atividades de Enfermagem. Foi realizada análise estatística descritiva dos dados. Em seguida, a associação das variáveis qualitativas com o NAS foi testada pelo teste de Kruskal-Wallis e as variáveis quantitativas foram analisadas por análise de regressão múltipla. Para o tratamento dos dados, foram consideradas significância p = 0,05 e 95 porcento de confiança. Resultado: A carga total de trabalho encontrada (79,04 porcento) corresponde a 18 horas e 57 minutos de assistência a cada paciente em 24 horas. A média da condição de saída do paciente é dividida em sobreviventes e não sobreviventes, com uma pontuação de 74,19 porcento (DP = 11,54) e 126,64 porcento (DP = 17,62), respectivamente. Conclusão: Apenas as variáveis status de desempenho de Karnofsky e condição de saída foram significativamente associadas à carga de trabalho(AU)

Introducción: El uso del Puntaje de Actividades de Enfermería permite correlacionar la carga de trabajo de enfermería con los índices de evaluación pronóstica en la unidad de cuidados intensivos y ayuda en el desarrollo del proceso de trabajo de las enfermeras a través del dimensionamiento del personal apropiado. Objetivo: Analizar la asociación entre variables clínicas y demográficas de pacientes con carga de trabajo de enfermería en una Unidad de Cuidados Intensivos de Oncología. Métodos: Estudio de cohorte prospectiva, realizada en Instituto Nacional del Câncer José Alencar Gomes da Silva de septiembre a diciembre de 2016. La recolección de datos incluye la medición de la carga de trabajo a través del Puntaje de Actividades de Enfermería. Se realizó un análisis estadístico descriptivo de los datos. Después, se probó la asociación de variables cualitativas con NAS mediante la prueba de Kruskal-Wallis y se analizaron las variables cuantitativas mediante análisis de regresión múltiple. Para el tratamiento de los datos, se consideró una significancia p = 0,05 y un 95 por ciento de confianza. Resultado: La carga de trabajo total encontrada (79,04 por ciento) corresponde a 18 horas y 57 minutos de asistencia a cada paciente dentro de las 24 horas. La media para la condición de salida de los pacientes se divide en sobrevivientes y no sobrevivientes, con un puntaje de 74,19 por ciento (SD = 11,54) y 126,64 por ciento (SD = 17,62), respectivamente. Conclusión: Solo las variables de estado de rendimiento de Karnofsky y la condición de salida se asociaron significativamente con la carga de trabajo(AU)

Introduction: The use of the Nursing Activity Score (NAS) makes it possible to correlate the nursing workload with prognostic evaluation indices in the intensive care unit and helps in the development of the nurses' work process through the sizing of the appropriate personnel. Objective: To analyze the association between clinical and demographic variables about patients with a nursing workload in an oncology intensive care unit. Methods: Prospective cohort study carried out at José Alencar Gomes da Silva National Cancer Institute, from September to December 2016. The data collection includes the measurement of the workload through the Nursing Activities Score. A descriptive statistical analysis of the data was performed. Afterwards, the association between qualitative variables and the NAS was tested using the Kruskal-Wallis test and the quantitative variables were analyzed using multiple regression analysis. For data treatment, significance was considered (P = 0.05; confidence interval 95 percent). Result: The total workload found (79.04 percent) corresponds to 18 hours and 57 minutes of assistance to each patient within 24 hours. The mean for the discharge condition of the patients is divided into survivors and non-survivors, with a score of 74.19 percent (SD=11.54) and 126.64 percent (SD=17.62), respectively. Conclusion: Only Karnofsky performance state variables and discharge condition were significantly associated with workload(AU)

Medication Errors in the Context of Hematopoietic Stem Cell Transplantation: A Systematic Review.

BACKGROUND: There have been numerous efforts by health institutions and professionals to prevent and reduce medication errors. OBJECTIVES: The aim of this study was to identify in the literature the incidence, related factors, consequences, and prevention mechanisms of medication errors in the context of hematopoietic stem cell transplantation. METHODS: This is a systematic review carried out in the databases LILACS, PubMed, PMC, EMBASE, and CINAHL databases, from January 11 to 13, 2017. RESULTS: Eleven studies were included in this review and presented in 4 categories of analysis. (1) occurrence-most of the medication errors were related to administration and prescription; (2) related factors-multicausal, highlighting issues including polypharmacy, lack of double checking, and similarity between the medications' names; (3) consequences-the main ones were associated with adverse reactions, with prolonged hospitalization time as outcome; (4) preventive measures-related to safe practices in pharmacotherapy, such as double check and application of the 10 rights of medication administration. CONCLUSION: Medication administration is an activity of great responsibility for nursing; however, in order to achieve a decrease in medication errors, prevention strategies are necessary for the whole health team. IMPLICATIONS FOR PRACTICE: Practice improvements are needed including establishing institutional drug administration protocols and keeping them updated, using a computerized prescription system, and promoting patient safety with staff.

A Meta-analysis to Compare Four-layer to Short-stretch Compression Bandaging for Venous Leg Ulcer Healing.

Compression therapy is the standard of care for venous leg ulcers (VLUs), and some evidence suggests 4-layer compression is more effective than short-stretch bandages. A meta-analysis was conducted to compare the effectiveness of these 2 compression bandages for venous ulcer healing. In March 2016, a systematic review of the literature was conducted to identify randomized controlled trials. Databases used included Pubmed/MEDLINE, EMBASE, Cochrane Central, the Cumulative Index of Nursing and Allied Health Literature, and the Latin American and Caribbean of Health Sciences Information System. Search terms were varicose ulcer, venous leg ulcer, venous ulceration, leg ulcer, compression bandages, compressive therapy, multilayer system, four-layer system, elastic bandages, short-stretch bandage, short-stretch system, and inelastic bandage. No publication time or language restrictions were imposed, but findings subjected to analysis were limited to results of research that reported healing and healing time using 4-layer and short-stretch compression only. The quality of the studies was assessed using the Jadad scale. Data extracted included study design, country, target population demographics, VLU clinical aspects at baseline, sample size, interventions applied, follow-up period, complete healing, and healing time as outcomes. Relative risk was calculated considering a 95% confidence interval for dichotomous variables (complete healing), and heterogeneity was statistically assessed among the studies using the chi-squared test assuming random effect when I2 ≥50%. The search yielded 557 papers; 21 met the study criteria for full-text analysis, and 7 met the meta-analysis inclusion criteria. The studies included 1437 patients, average age 70 (range 23-97) years with 1446 venous leg ulcers. Most (5) studies were classified as being at low risk of bias. At 12 and 16 weeks, 259 ulcers (51.08%) healed completely in the 4-layer and 234 (46.34%) in the short-stretch bandage groups, respectively (P = .41). At 24 weeks, 268 ulcers (69.07%) in the 4-layer and 257 (62.23%) in the short-stretch bandage groups, respectively, had healed (P = .16). The 2 bandage systems evaluated were similar in achieving complete healing at their respective study endpoints. The average time for healing was 73.6 ± 14.64 days in the 4-layer and 83.8 ± 24.89 days in the short-stretch bandage groups; no meta-analysis was done for this outcome due the inability to retrieve all the individual patient data for each study. The choice of compression system remains at the discretion of the clinicians based on evidence of effectiveness, patient tolerability, and preference. Additional randomized controlled trials to compare various wound and patient outcomes between different compression systems are warranted.

All about compression: A literature review.

Lower extremity ulcers represent a significant public health problem as they frequently progress to chronicity, significantly impact daily activities and comfort, and represent a huge financial burden to the patient and the health system. The aim of this review was to discuss the best approach for venous leg ulcers (VLUs). Online searches were conducted in Ovid MEDLINE, Ovid EMBASE, EBSCO CINAHL, and reference lists and official guidelines. Keywords considered for this review were VLU, leg ulcer, varicose ulcer, compressive therapy, compression, and stocking. A complete assessment of the patient's overall health should be performed by a trained practitioner, focusing on history of diabetes mellitus, hypertension, dietetic habits, medications, and practice of physical exercises, followed by a thorough assessment of both legs. Compressive therapy is the gold standard treatment for VLUs, and the ankle-brachial index should be measured in all patients before compression application.

Comparison of outcomes in patients with venous leg ulcers treated with compression therapy alone versus combination of surgery and compression therapy: a systematic review.

BACKGROUND: Venous leg ulcers (VLUs) are the most prevalent type of lower extremity ulcers and can be difficult to manage. Clinicians are challenged to provide care and recommendations that promote timely healing, minimize the risk of recurrence, and are cost-effective. Compression therapy is generally considered the primary intervention for both ulcer management and prevention of recurrence. However, recent studies suggest that surgical correction of venous insufficiency may enhance healing of venous ulcers or help prevent recurrence. PURPOSE: The objective of this systematic review was to compare wound healing and recurrence rates in patients managed with compression therapy alone versus compression therapy plus surgery. SEARCH STRATEGY: The author conducted a literature review selecting primary studies published between 2002 and 2012, using the electronic databases MEDLINE/PubMed and CINAHL/EBSCOhost. The following key words were applied: leg ulcer; varicose ulcer; bandage; "stockings, compression," venous ulceration; venous ulcer; compressive therapy; compression therapy; stocking; venous surgery. Inclusion criteria included randomized controlled trials that compared VLU healing rates and recurrence rates among patients receiving compression therapy alone, and patients receiving both compression therapy and surgical intervention to correct venous incompetence. Studies published in English, Spanish, or Portuguese were included. RESULTS: Sixty-seven studies were retrieved and 4 were identified that met inclusion criteria. In 3 of the studies, researchers reported no differences in healing rates for patients managed with compression plus surgery when compared to patients managed with compression alone. One study reported higher healing rates in the surgical group. Most studies revealed lower recurrence rates in patients who were managed with surgery plus compression, but these differences were not statistically significant. CONCLUSIONS: Existing evidence supports compression therapy as the most critical element in the management of venous leg ulcers. However, evidence also suggests that surgical obliteration of incompetent perforator veins may promote longer ulcerfree periods and lower rates of recurrence.