Plasma-Based Scaffold Containing Bone-Marrow Mononuclear Cells Promotes Wound Healing in a Mouse Model of Pressure Injury.

Pressure injuries, or pressure ulcers, are a common problem that may lead to infections and major complications, besides being a social and economic burden due to the costs of treatment and hospitalization. While surgery is sometimes necessary, this also has complications such as recurrence or wound dehiscence. Among the newer methods of pressure injury treatment, advanced therapies are an interesting option. This study examines the healing properties of bone marrow mononuclear cells (BM-MNCs) embedded in a plasma-based scaffold in a mouse model. Pressure ulcers were created on the backs of mice (2 per mouse) using magnets and assigned to a group of ulcers that were left untreated (Control, n = 15), treated with plasma scaffold (Plasma, n = 15), or treated with plasma scaffold containing BM-MNC (Plasma + BM-MNC, n = 15). Each group was examined at three time points (3, 7, and 14 days) after the onset of treatment. At each time point, animals were subjected to biometric assessment, bioluminescence imaging, and tomography. Once treatment had finished, skin biopsies were processed for histological and wound healing reverse transcription polymerase chain reaction (RT-PCR) array studies. While wound closure percentages were higher in the Plasma and Plasma + BM-MNC groups, differences were not significant, and thus descriptive data are provided. In all individuals, the presence of donor cells was revealed by immunohistochemistry on posttreatment onset Days 3, 7, and 14. In the Plasma + BM-MNC group, less inflammation was observed by positron emission tomography-computed tomography (PET/CT) imaging of the mice at 7 days, and a complete morphometabolic response was produced at 14 days, in accordance with histological results. A much more pronounced inflammatory process was observed in controls than in the other two groups, and this persisted until Day 14 after treatment onset. RT-PCR array gene expression patterns were also found to vary significantly, with the greatest difference noted between both treatments at 14 days when 11 genes were differentially expressed.

Stem cell and tissue engineering approaches in pressure ulcer treatment.

CONTEXT: Pressure ulcers or injuries, arise from ischemic damage to soft tissues induced by unrelieved pressure over a bony prominence. They are usually difficult to treat with standard medical therapy and often they recur. In the search for better treatment options, promising alternative forms of treatment are today emerging. Within the field of regenerative medicine, ongoing research on advanced therapies seeks to develop medicinal products based on gene therapy, somatic cell therapy, tissue-engineering and combinations of these. OBJECTIVE: The main objective is to perform an overview of experimental and clinical developments in somatic cell therapy and tissue engineering targeting the treatment of pressure injuries. METHODS: Searching terms as "PRESSURE ULCER", "STEM CELL THERAPY", "TISSUE ENGINEERING" or "WOUND HEALING" were used in combination or alone, including publications refered to basic and clinical research and focusing on articles showing results obtained in a clinical context. A total of 80 references are cited, including 23 references published in the 3 last years. RESULTS: The results suggest that this form of treatment could be an interesting option in patients with difficult-to-treat ulcers as spinal cord injury patients. CONCLUSION: This field of regenerative medicine is very broad and further research is warranted.

Philadelphia-negative chronic myeloproliferative neoplasm follow-up: when the phone rings. Changes during the COVID-19 pandemic and patient satisfaction. Experience in 30 health centers in Spain.

The SARS-CoV-2 pandemic has favored the expansion of telemedicine. Philadelphia-negative chronic myeloproliferative neoplasms (Ph-MPN) might be good candidates for virtual follow-up. In this study, we aimed to analyze the follow-up of patients with Ph-MPN in Spain during COVID-19, its effectiveness, and acceptance among patients. We present a multicenter retrospective study from 30 centers. Five hundred forty-one patients were included with a median age of 67 years (yr). With a median follow-up of 19 months, 4410 appointments were recorded. The median of visits per patient was 7 and median periodicity was 2.7 months; significantly more visits and a higher frequency of them were registered in myelofibrosis (MF) patients. 60.1% of visits were in-person, 39.5% were by telephone, and 0.3% were videocall visits, with a predominance of telephone visits for essential thrombocythemia (ET) and polycythemia vera (PV) patients over MF, as well as for younger patients (< 50 yr). The proportion of phone visits significantly decreased after the first semester of the pandemic. Pharmacological modifications were performed only in 25.7% of the visits, and, considering overall management, ET patients needed fewer global treatment changes. Telephone contact effectiveness reached 90% and only 5.4% required a complementary in-person appointment. Although 56.2% of the cohort preferred in-person visits, 90.5% of our patients claimed to be satisfied with follow-up during the pandemic, with an 83% of positive comments. In view of our results, telemedicine has proven effective and efficient, and might continue to play a complementary role in Ph-MPN patients' follow-up.

Use of eltrombopag for patients 65 years old or older with immune thrombocytopenia.

BACKGROUND: Eltrombopag is useful for immune thrombocytopenia (ITP). However, results of clinical trials may not accurately mirror clinical practice reality. Here we evaluated eltrombopag for primary and secondary ITP in our ≥65-year-old population. METHODS: A total of 106 primary ITP patients (16 with newly diagnosed ITP, 16 with persistent ITP, and 74 with chronic ITP) and 39 secondary ITP patients (20 with ITP secondary to immune disorders, 7 with ITP secondary to infectious diseases, and 12 with ITP secondary to lymphoproliferative disorders [LPD]) were retrospectively evaluated. RESULTS: Median age of our cohort was 76 (interquartile range, IQR, 70-81) years. 75.9% of patients yielded a platelet response including 66.2% complete responders. Median time to platelet response was 14 (IQR, 8-21) days. Median time on response was 320 (IQR, 147-526) days. Sixty-three adverse events (AEs), mainly grade 1-2, occurred. The most common were hepatobiliary laboratory abnormalities (HBLAs) and headaches. One transient ischemic attack in a newly diagnosed ITP and two self-limited pulmonary embolisms in secondary ITP were the only thrombotic events observed. CONCLUSION: Eltrombopag showed efficacy and safety in ITP patients aged ≥65 years with primary and secondary ITP. However, efficacy results in LPD-ITP were poor. A relatively high number of deaths were observed.

Efficacy and safety of eltrombopag in persistent and newly diagnosed ITP in clinical practice.

Eltrombopag is safe and effective in primary chronic ITP. However, lack of clinical trials avoids a clear demonstration of its utility in newly diagnosed and persistent ITP. Our aim here is to report Spanish results for this type of patients. We retrospectively evaluated 220 adult primary ITP patients. According to standard definition, patients were allocated to newly diagnosed (n = 30), persistent (n = 30), and chronic (n = 160) ITP. Groups were homogenous regarding most relevant parameters. 180 (90%) of 220 patients achieved a platelet response (R) with 167 (75.9%) complete responses (CR) after a 15-month follow-up. No statistical significant differences among groups but a trend towards a greater efficacy in newly diagnosed ITP were observed (93.3% of responses with 86.7% of CR). Efficacy in persistent ITP (83.3% of responses with 80.0% of CR) and chronic ITP (79.4% of responses with 73.1% of CR) was similar. 70 patients (31.8%) experienced adverse events. 15 of them were grade 3-4. Most common adverse effects were headache and hepatobiliary laboratory abnormalities (HBLAs). One persistent ITP had a venous thrombosis and one chronic ITP had grade II myelofibrosis. We consider Eltrombopag use for the early stage ITP as effective and safe as it is in chronic ITP.

Eltrombopag safety and efficacy for primary chronic immune thrombocytopenia in clinical practice.

BACKGROUND: Eltrombopag is effective and safe in chronic immune thrombocytopenia (ITP). However, clinical trials may not accurately reflect what happens in clinical practice. We evaluated the efficacy and safety of eltrombopag in primary chronic ITP in a real-world setting. METHODS: A total of 164 primary patients with chronic ITP from 40 Spanish centers, who had been treated with eltrombopag, were retrospectively evaluated. RESULTS: The median age of our cohort (72% women) was 63 yr (interquartile range, IQR, 45-75 yr). The median time with ITP diagnosis was 81 months (IQR, 30-192 months). The median number of therapies prior to eltrombopag was 3 (IQR, 2-4). At the time of eltrombopag start, 45 patients (30%) were receiving concomitant treatment for ITP. Forty-six patients (30%) had bleeding signs/symptoms the month before the treatment started. The median platelet count at eltrombopag initiation was 22 × 10(9) /L (IQR, 8-39 × 10(9) /L). A total of 135 patients (88.8%) achieved a platelet response. The median time to platelet response was 12 d (95% CI, 9-13 d). Maintained platelet response rate during the 15-month period under examination was 75.2%. Twenty-eight patients (18.4%) experienced adverse events, mainly grades 1-2. CONCLUSION: Eltrombopag is highly effective and well tolerated in unselected patients with primary chronic ITP.

Successful discontinuation of eltrombopag after complete remission in patients with primary immune thrombocytopenia.

Eltrombopag is effective and safe in immune thrombocytopenia (ITP). Some patients may sustain their platelet response when treatment is withdrawn but the frequency of this phenomenon is unknown. We retrospectively evaluated 260 adult primary ITP patients (165 women and 95 men; median age, 62 years) treated with eltrombopag after a median time from diagnosis of 24 months. Among the 201 patients who achieved a complete remission (platelet count >100 × 10(9) /l), eltrombopag was discontinued in 80 patients. Reasons for eltrombopag discontinuation were: persistent response despite a reduction in dose over time (n = 33), platelet count >400 × 10(9) /l (n = 29), patient's request (n = 5), elevated aspartate aminotransferase (n = 3), diarrhea (n = 3), thrombosis (n = 3), and other reasons (n = 4). Of the 49 evaluable patients, 26 patients showed sustained response after discontinuing eltrombopag without additional ITP therapy, with a median follow-up of 9 (range, 6-25) months. These patients were characterized by a median time since ITP diagnosis of 46.5 months, with 4/26 having ITP < 1 year. Eleven patients were male and their median age was 59 years. They received a median of 4 previous treatment lines and 42% were splenectomized. No predictive factors of sustained response after eltrombopag withdrawal were identified. Platelet response following eltrombopag cessation may be sustained in an important percentage of adult primary ITP patients who achieved CR with eltrombopag. However, reliable markers for predicting which patients will have this response are needed.

Vitamin K antagonist-associated intracerebral hemorrhage: lessons from a devastating disease in the dawn of the new oral anticoagulants.

BACKGROUND: Intracerebral hemorrhage (ICH) is the most feared complication associated with vitamin K antagonists (VKAs). We performed a retrospective study on the clinicoradiologic characteristics that influence its outcome. METHODS: We reviewed the clinical histories and neuroimaging studies of all patients attended at the Hospital Universitario Central de Asturias in 2010-2011 who had an ICH while being on VKA and analyzed the differential characteristics between patients with acceptable versus poor outcomes attending to 3 end points: death, poor outcome (modified Rankin Scale [mRS] score ≥ 4) at discharge, and poor outcome 3 months later. Additionally, CHA2DS2-VASc and HAS-BLED scores (validated tools for prediction of the risk of stroke and major hemorrhage, respectively, in patients with atrial fibrillation) were calculated to assess a priori risk-benefit balance for anticoagulant therapy. RESULTS: Eighty patients entered the sample (median age of 79 years). A priori annual risk of major bleeding surpassed ischemic stroke risk-without anticoagulation-only in 4. Fifty percent of the patients had an initial Glasgow Coma Scale (GCS) score lower than 13; in 51.3%, initial international normalized ratio was above their therapeutic range. Median hematoma size was 24.75 cc(3); relevant growth (≥33%) occurred in 29.4% of patients with a second computed tomography scan. On multivariable analysis, overall in-hospital mortality (47.5%) was related to prior antiplatelet therapy (P = .008), GCS (P = .001), and perilesional edema size (P = .036). Baseline mRS (P = .058) and National Institutes of Health Stroke Scale (NIHSS) scores (P = .008) were associated with poor outcome at discharge (77.5%). Initial NIHSS (P = .005) and glycemia (P = .038) predicted 3-month poor outcome (68.3%). VKA reversal was performed in almost all patients, which prevented assessment of its therapeutic value. CONCLUSIONS: VKA-associated ICH presents in a particularly vulnerable population and has a poor prognosis that may be reliably predicted by several clinicoradiologic features.