Statistical learners are leading towards auto-epistemic logic, but is it the right way to progress in artificial intelligence (AI)? Ways to discover AI fit the senses and the intellect. The structure ...of symbols–the operations by which the intellectual solution is realized–and the search for strategic reference points evoke essential issues in the analysis of AI. Studying how knowledge can be represented through methods of theoretical generalization and empirical observation is only the latest step in a long process of evolution. In this paper, we try to outline the origin of knowledge and how modern artificial minds have inherited it.
Cancer treatments can often adversely affect the quality of life of young women. One of the most relevant negative impacts is the loss of fertility. Cyclophosphamide is one of the most detrimental ...chemotherapeutic drugs for the ovary. Cyclophosphamide may induce the destruction of dormant follicles while promoting follicle activation and growth. Herein, we demonstrate the in vivo protective effect of the allosteric Bcr-Abl tyrosine kinase inhibitor Asciminib on signaling pathways activated by cyclophosphamide in mouse ovaries. We also provide evidence that Asciminib does not interfere with the cytotoxic effect of cyclophosphamide in Michigan Cancer Foundation (MCF)7 breast cancer cells. Our data indicate that concomitant administration of Asciminib mitigates the cyclophosphamide-induced ovarian reserve loss without affecting the anticancer potential of cyclophosphamide. Taken together, these observations are relevant for the development of effective ferto-protective adjuvants to preserve the ovarian reserve from the damaging effects of cancer therapies.
Extremely low gestational age neonates (ELGANs, i.e., neonates born before 28 weeks of gestation) are at high risk of developing retinopathy of prematurity (ROP), with potential long-life visual ...impairment. Due to concomitant anemia, ELGANs need repeated red blood cell (RBC) transfusions. These produce a progressive replacement of fetal hemoglobin (HbF) by adult hemoglobin (HbA). Furthermore, a close association exists between low levels of HbF and severe ROP, suggesting that a perturbation of the HbF-mediated oxygen release may derange retinal angiogenesis and promote ROP.
BORN (umBilical blOod to tRansfuse preterm Neonates) is a multicenter double-blinded randomized controlled trial in ELGANs, to assess the effect of allogeneic cord blood RBC transfusions (CB-RBCs) on severe ROP development. Recruitment, consent, and randomization take place at 10 neonatology intensive care units (NICUs) of 8 Italian tertiary hospitals. ELGANs with gestational age at birth comprised between 24+0 and 27+6 weeks are randomly allocated into two groups: (1) standard RBC transfusions (adult-RBCs) (control arm) and (2) CB-RBCs (intervention arm). In case of transfusion need, enrolled patients receive transfusions according to the allocation arm, unless an ABO/RhD CB-RBC is unavailable. Nine Italian public CB banks cooperate to make available a suitable amount of CB-RBC units for all participating NICUs. The primary outcome is the incidence of severe ROP (stage 3 or higher) at discharge or 40 weeks of postmenstrual age, which occurs first.
BORN is a groundbreaking trial, pioneering a new transfusion approach dedicated to ELGANs at high risk for severe ROP. In previous non-randomized trials, this transfusion approach was proven feasible and able to prevent the HbF decrease in patients requiring multiple transfusions. Should the BORN trial confirm the efficacy of CB-RBCs in reducing ROP severity, this transfusion strategy would become the preferential blood product to be used in severely preterm neonates.
ClinicalTrials.gov NCT05100212. Registered on October 29, 2021.
Carmustine (BCNU), etoposide, cytarabine, and melphalan (BEAM) are a widely used high-dose chemotherapy regimen for autologous stem cell transplantation transplant (ASCT) in lymphoid malignancies. ...During BCNU shortages, some centers switched to fotemustine-substituted BEAM (FEAM). Neutropenic enterocolitis (NEC) is a life-threatening complication occurring after intestinal mucosa damage related to intensive chemotherapy. NEC mortality may be up to 30%-50%. In our study, we compared NEC incidence, symptoms, mortality, and transplant outcome in terms of overall survival (OS) and progression-free survival (PFS) in the BEAM
. FEAM groups. Furthermore, we compared the cost of hospitalization of patients who did
. patients who did not experience a NEC episode (NECe).
A total of 191 patients were enrolled in this study (N = 129 and N = 62 were conditioned with BEAM and FEAM, respectively). All patients received bed-side high-resolution ultrasound (US) for NEC diagnosis.
NEC incidence and NEC-related mortality were similar in the BEAM and FEAM groups (31% and 40.3%, p = 0.653, and 5% and 8%, p = 0.627, respectively). At a median follow-up of 116 months, no difference was noted between BEAM
. FEAM groups in terms of OS and PFS (p = 0.181 and p = 0.978, respectively). BEAM appeared equivalent to FEAM in terms of NEC incidence and efficacy. The high incidence of NEC and the low mortality is related to a timely US diagnosis and prompt treatment. US knowledge in NEC diagnosis allows to have comparable days of hospitalization of patients NECpos
. patients NECneg. The cost analysis of NECpos
. NECneg has been also performed.
Introduction
Neutropenic enterocolitis (NEC) is a life-threatening complication reported in patients with acute myeloid leukemia (AML) following chemotherapy (CHT). Intensive induction and ...consolidation CHT may damage intestinal mucosa leading to a NEC episode (NECe). NEC reported mortality may be up to 30-60%. Early US-guided bed-side diagnosis and prompt treatment may substantially improve the survival. An emerging worldwide concern is the intestinal colonization by multi-drug-resistant bacteria especially when patients are exposed to chemotherapy regimens potentially correlated to mucosal damage.
Methods
In our study we prospectively enrolled all AML patients admitted in our leukemia unit to receive intensive induction and consolidation chemotherapy and experiencing chemotherapy-induced-neutropenia (CHTN).
Results and discussion
Overall, we enrolled N=213 patients from 2007 to March 2023. We recorded N=465 CHTN, and N=42 NECe (9.0% incidence). The aim of our study was to assess which chemotherapy regimens are more associated with NEC. We found that ALM1310, followed by 7 + 3 (daunorubicin), 7 + 3 (idarubicin), 5 + 3 + 3 (cytarabine, etoposide, idarubicin), and AML1310 (consolidation) were associated with a statistically higher incidence of NEC. We did not detect NEC episodes in patients treated with CPX-351, 5 + 2 (cytarabine, idarubicine), and high-dose cytarabine. Thus, we found that cytarabine could determine mucosal damage when associated with an anthracycline but not if delivered either alone or as dual-drug liposomal encapsulation of daunorubicin/cytarabine. We also describe NEC mortality, symptoms at diagnosis, intestinal sites involvement, and prognostic significance of bowel wall thickening.
In this paper, we consider impulse control problems involving conditional McKean–Vlasov jump diffusions, with the common noise coming from the
σ
-algebra generated by the first components of a ...Brownian motion and an independent compensated Poisson random measure. We first study the well-posedness of the conditional McKean–Vlasov stochastic differential equations (SDEs) with jumps. Then, we prove the associated Fokker–Planck stochastic partial differential equation (SPDE) with jumps. Next, we establish a verification theorem for impulse control problems involving conditional McKean–Vlasov jump diffusions. We obtain a Markovian system by combining the state equation with the associated Fokker–Planck SPDE for the conditional law of the state. Then we derive sufficient variational inequalities for a function to be the value function of the impulse control problem, and for an impulse control to be the optimal control. We illustrate our results by applying them to the study of an optimal stream of dividends under transaction costs. We obtain the solution explicitly by finding a function and an associated impulse control, which satisfy the verification theorem.
Diabetic foot infection is frequent in diabetic patients and is due to neuropathy, trauma or peripheral arterial disease. The presence of an abscess requires urgent drainage and specific antibiotic ...therapy. Patients with critical limb ischemia need revascularization and, subsequently the intervention of a plastic surgeon is often required in cases of exposure of tendons and ligaments. During the COVID-19 pandemic, a patient was refered to our department with an abscess on the dorsum of the left foot. After urgent drainage with tendon exposure, he started specific antibiotic therapy and underwent tibial vessels angioplasty. After infection healing cord blood platelet gel was applied, accelerating the healing process, with injection of its liquid part into the exposed tendons, thus retaining the vital functions of the tendons.
Surgical site dehiscence after lower limb revascularization through bypass represents a serious postoperative complication, especially in diabetic and obese patients, with subsequent risk of early ...graft failure, infection, sepsis, hemorrhage, major amputation and sometimes death. To prevent bypass exposure and subsequent complications, physicians recur to reoperation, antibiotic therapy, advanced dressing and vacuum-assisted closure therapy. To improve the process of wound healing, cord blood platelet gel can be used to fill deep and large wounds. Growth factors released from platelets in the cord blood platelet gel stimulate the process of healing and allow patients to be followed up in Outpatient Surgery, thus reducing hospital stay and costs, while providing excellent results.
•PBSCs are the preferred source of stem and progenitor cells harvested for AlloSCT.•G-CSF treatment can lead to side effects.•Mobilization failure is 1 of the most common problems during PBSC ...collection.•We have developed a model for predicting the probability of performing PBSC collection.•Only 2 variables, basal CD34+ and Plt counts, are required for evaluation in this model.
A longitudinal, prospective, observational, single-center cohort study on healthy donors was designed to identify predictors of CD34+ cell mobilization on day 4 after granulocyte colony-stimulating factor (G-CSF) administration. As potential predictors of mobilization, age, sex, body weight, height, blood volume, WBC count, peripheral blood (PB) mononuclear cell count, platelet (Plt) count, and hematocrit and hemoglobin levels were considered. Two different evaluations of CD34+ cell counts were determined for each donor: baseline (before G-CSF administration) and in PB on day 4 after G-CSF administration. One hundred twenty-two consecutive healthy donors with a median age of 47.5 years were enrolled. The median value of CD34+ on day 4 was 43 cells/µL (interquartile range, 23 to 68), and 81.1% of donors had ≥20 cells/µL. Basal WBC count, Plt count, and CD34+ were significantly higher for the subjects with CD34+ levels over median values on day 4. A multivariate quartile regression analysis, adjusted by sex, age, basal CD34+, and basal Plt count, showed a progressively stronger relationship between baseline CD34+ and Plt levels and the CD34+ levels on day 4. The basal CD34+ cut-off level to predict the levels of CD34+ on day 4 was either ≤2 cells/μL or ≥3 cells/μL and that of basal Plt count was ≤229 × 109/L or ≥230 × 109/L, respectively, to determine whether mobilization therapy should or should not be attempted. PB stem cell mobilization with G-CSF was highly effective on day 4, and herein we describe a model for predicting the probability of performing PB stem cell collection after a short course of G-CSF.
The efficacy of umbilical cord blood platelet gel (CBPG) application on healing foot ulcers was analyzed in 10 diabetic patients treated for critical lower limb ischemia by surgical or endovascular ...arterial revascularization. During a 9-month period, 20 diabetic patients affected by critical lower limb ischemia with tissue loss were enrolled in this nonblinded, consecutive series, randomized clinical trial. After clinical evaluation, patients underwent endovascular or surgical revascularization of the affected limb, followed by minor amputations or surgical debridement of ischemic lesions. Patients were then randomly divided into two groups: 10 patients in Group A treated with standard wound care and 10 patients in Group B treated with topic application of CBPG. The CBPG protocol consisted of platelet gel application twice a week for 4 weeks and then once a week for an additional 4 weeks. Healing was assessed by direct ulcer dimension tracing onto clear plastic sheet and subsequent computerized planimetry. The mean pretreatment and post-treatment ulcer areas at 30 days for Group A were 15.1 cm2 and 8.1 cm2, respectively, and for Group B were 15.7 cm2 and 3.25 cm2, respectively; resulting in a mean ulcer area reduction of 46% for Group A and 79% for Group B patients (P < .01). These observations suggest CBPG application can promote more rapid wound healing than standard care, and indicate the need for a randomized, multicenter trial to confirm clinical efficacy.
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