Unselected donor-derived hematopoietic stem cells boost for Chimeric Antigen Receptor T-cell associated hematotoxicity.

Hematological toxicity following Chimeric Antigen Receptor-T therapy in a patient with a prior allogeneic stem cell transplantation was resolved by the infusion of unselected donor-derived stem cell boost. Due to the donor's lymphocytes, the patient experienced a well-controlled flare-up of acute graft versus host disease.

Hyposalivation and periodontal disease as oral non-articular characteristics in rheumatoid arthritis.

OBJECTIVE: To investigate the association among rheumatoid arthritis (RA), saliva production, and periodontal status. METHODS: An observational study was carried out on 103 subjects with RA and 103 without RA matched by sex and age. Rheumatologic evaluation included serological and clinical variables. A full mouth periodontal examination was performed according to the American Academy of Periodontology (1999). Resting and stimulated whole salivary flows were determined after spiting during 5 min. RESULTS: RA was associated with a higher prevalence of severe periodontitis (12% vs. 4%), with a marked reduction in resting and stimulated saliva production, and with a higher prevalence of resting (19% vs. 0%) and also stimulated hyposalivation (54% vs. 10%), compared with the control group. The differences in mean resting and stimulated salivary flows between RA and control groups persisted after the exclusion of people with hyposalivation. Saliva production was not associated with the presence or the severity of periodontal disease, or with the rheumatic clinical characteristics of the patients. CONCLUSIONS: More than 50% of people with RA have some degree of reduction in their salivary flows, an affection not associated with the periodontal status or rheumatic activity, which are the expression of the two related inflammatory diseases. The influence of autonomic dysfunction on hyposalivation can be considered. While periodontitis would be a disease-associated comorbidity of RA, poor saliva production should be included among the extra-articular manifestations. Key Points • Rheumatoid arthritis patients are more prone to suffer from periodontitis and/or hyposalivation. • Periodontal disease is more prevalent in people with rheumatoid arthritis and also an association was found between the severities of both pathologies. • More than 50% of people with RA would have some degree of reduction in their salivary flows, an affection not associated with the periodontal status or rheumatic activity. • Reduced saliva production in rheumatoid arthritis patients should be included among the extra-articular manifestations.

The application of a multidisciplinary approach in the diagnosis of Castleman disease and Castleman-like lymphadenopathies: A 20-year retrospective analysis of clinical and pathological features.

BACKGROUND: Castleman disease (CD) comprises a group of rare and heterogeneous haematological disorders, including unicentric (UCD) and multicentric (MCD) forms, the latter further subdivided into HHV8-MCD, POEMS-MCD and idiopathic-MCD (iMCD). However, according to the Castleman Disease Collaborative Network guidelines, the diagnosis of CD can only be achieved through collaboration between clinicians and pathologists. METHODS: We applied these clinical and pathological criteria and implement with clonality testing to a retrospective cohort of 48 adult and paediatric Italian patients diagnosed with reactive lymphadenitis with CD-like histological features. RESULTS: We confirmed the diagnosis of CD in 60% (29/48) of the cases, including 12 (41%) UCD and 17 (59%; five HHV8-MCD, three POEMS-MCD and nine iMCD) MCD. Of the remaining 19 cases (40%) with multiple lymphadenopathy, 5 (26%) were classified as autoimmune diseases, 1 (5%) as autoimmune lymphoproliferative disorder, 1 (5%) as IgG4-related disease, 11 (83%) as reactive lymphadenitis and 1 (5%) as nodal marginal zone lymphoma. CONCLUSIONS: Our study emphasizes the importance of the multidisciplinary approach to reactive lymphadenitis with CD-like features in order to achieve a definitive diagnosis and choose the appropriate treatment.

Curcumin nanocrystals-in-nanofibres as a promising platform for the management of periodontal disease.

It is estimated that nearly a half of the world's population over 30 years old suffer from some kind of periodontal disease (PD). Although preventable, PD can pose a significant health burden to patients, causing from pain and discomfort to disfigurement and death. The management of PD often requires surgical procedures accompanied of systemic antibiotic and anti-inflammatory treatments. Curcumin (CUR), a potent anti-inflammatory and antimicrobial active, has shown great promise in the management of PD; however, its effects are often limited by its low bioavailability. In this work, we report the development of electrospun nanofibres (NFs) loaded with CUR nanocrystals (NCs) for the management of PD. NCs of 100 nm were obtained by media milling and loaded into dissolving polyvinyl alcohol NFs using electrospinning. The resultant NCs-in-NFs dissolved in water spontaneously, releasing NCs with a particle size of âˆ¼120 nm. The physiochemical characterisation of the systems indicated the absence of chemical interactions between drug and polymer, and nanofibres with an amorphous nature. In vitro release profiles demonstrated that the NCs had a significantly higher dissolution rate (∼100 % at day 40) than the control group (approximately 6 % at day 40), which consisted of NFs containing a physical mixture of the drug and stabiliser. Finally, mucosal deposition studies demonstrated a 10-fold higher capacity of the novel NCs-in-NFs system to deposit CUR ex vivo using excised neonatal porcine mucosal tissue, when compared to the control group.

Correction: Bocci et al. Remarkable Remission Rate and Long-Term Efficacy of Upfront Metronomic Chemotherapy in Elderly and Frail Patients, with Diffuse Large B-Cell Lymphoma. J. Clin. Med. 2022, 11, 7162.

In the original publication [...].

Allogenic Cord Blood Transfusion in Preterm Infants.

Repeated red blood cell (RBC) transfusions in preterm neonates cause the progressive displacement of fetal hemoglobin (HbF) by adult hemoglobin. The ensuing increase of oxygen delivery may result at the cellular level in a dangerous condition of hyperoxia, explaining the association between low-HbF levels and retinopathy of prematurity or bronchopulmonary dysplasia. Transfusing preterm neonates with RBC concentrates obtained from allogeneic umbilical blood is a strategy to increase hemoglobin concentration without depleting the physiologic HbF reservoir. This review summarizes the mechanisms underlying a plausible beneficial impact of this strategy and reports clinical experience gathered so far in this field.

Hypnosis to reduce fear of falling in hospitalized older adults: a feasibility randomized controlled trial.

BACKGROUND: Fear of falling is associated with numerous negative health outcomes in older adults and can limit the rehabilitation process. Hypnosis is now recognized as an effective treatment for a variety of conditions, especially anxiety and pain, which can be integrated safely with conventional medicine. The objective of this study was to assess the feasibility and acceptability of a hypnosis intervention in hospitalized older adults to reduce fear of falling. METHODS: In this feasibility randomized controlled trial, 32 older patients, hospitalized in geriatric rehabilitation wards, were randomly allocated (1:1 ratio) to either an intervention group (hypnosis, 2 sessions, one per week, plus usual rehabilitation program) or a control group (usual rehabilitation program only). Clinical assessors and statistician were blinded to group allocation. Primary outcomes were recruitment rate, retention rate, and adherence to the intervention. Exploratory outcomes, analyzed according to the intention-to-treat principle, included impact of hypnosis on fear of falling (assessed by a new scale perform-FES), functional status, in-hospital falls, and length of hospital stay. RESULTS: Recruitment rate was 1.3 patients per week. The recruitment of the population sample was achieved in 5.5 months. The retention rate did not differ significantly between groups and a good adherence to the hypnosis intervention was achieved (77% of patients received the full intervention). No adverse event related to the hypnosis intervention was observed. Regarding exploratory clinical outcomes, no differences were found between groups on any outcome. CONCLUSION: Hypnosis is feasible and well accepted in a geriatric hospitalized population undergoing rehabilitation. Further pilot work should be conducted, with an increased number of hypnosis sessions, before conducting a full-scale trial to conclude whether, or not, hypnosis is effective to reduce fear of falling. TRIAL REGISTRATION: NCT04726774.

IMT504 protects beta cells against apoptosis and maintains beta cell identity, without modifying proliferation.

We have demonstrated that oligodeoxynucleotide IMT504 promotes significant improvement in the diabetic condition in diverse animal models. Based on these results, here we evaluated whether these effects observed in vivo could be due to direct effects on ß-cells. We demonstrate by immunofluorescence that IMT504 enters the cell and locates in cytoplasm where it induces GSK-3ß phosphorylation that inactivates this kinase. As GSK-3ß tags Pdx1 for proteasomal degradation, by inactivating GSK-3ß, IMT504 induces an increase in Pdx1 protein levels, demonstrated by Western blotting. Concomitantly, an increase in Ins2 and Pdx1 gene transcription was observed, with no significant increase in insulin content or secretion. Enhanced Pdx1 is promising since it is a key transcription factor for insulin synthesis and is also described as an essential factor for the maintenance ß-cell phenotype and function. Dose-dependent inhibition of H2 O2 -induced apoptosis determined by ELISA as well as decreased expression of Bax was also observed. These results were confirmed in another ß-cell line, beta-TC-6 cells, in which a cytokine mix induced apoptosis that was reversed by IMT504. In addition, an inhibitor of IMT504 entrance into cells abrogated the effect IMT504. Based on these results we conclude that the ß-cell recovery observed in vivo may include direct effects of IMT504 on ß-cells, by maintaining their identity/phenotype and protecting them from oxidative stress and cytokine-induced apoptosis. Thus, this work positions IMT504 as a promising option in the framework of the search of new therapies for type I diabetes treatment.

Transesophageal Echocardiography Guidance to Prevent and Manage Pitfalls from Abdominal Normothermic Regional Perfusion and Optimize Timing during Organ Retrieval from a Donor after Circulatory Death.

An essential means of collecting more abdominal donor organs is controlled donation after circulatory death (cDCD). The organs are typically preserved during cDCD using the abdominal normothermic regional perfusion (A-NRP) technique to recirculate oxygenated blood flow following cardiac arrest and the withdrawal of life support. One of the challenges of A-NRP is ensuring the correct vascular devices' positionings, specifically extracorporeal membrane oxygenation cannulae and aortic balloons, typically achieved through fluoroscopy with or without contrast agents. Here, we present a case report in which transesophageal echocardiography (TEE) helped the transplant team to effectively procure viable abdominal organs from a cDCD donor in the shortest time frame, as minimizing time is one of the most crucial factors in maintaining organ viability. TEE use leads to a more effective and efficient A-NRP procedure with limited complications. In addition, it allows us to observe the circulation of both the thoracic and part of the abdominal organs using one fast exam. This case is the first report describing TEE as a primary guide and useful tool for DCD donors. However, prospective studies are needed to confirm that TEE could be used as standard practice during all DCD organ retrieval procedures.

Potential of agro-industrial residues from the Amazon region to produce activated carbon.

Thousands of tons of residual lignocellulosic biomass are produced and discarded by agroindustries in the Amazon. These biomasses could be harnessed and used in the preparation of activated carbon, in view of the growing demand for this product with high added value, however, little is known about their characteristics, in addition to their potential as precursors of activated carbon. Therefore, the aim of this work was to evaluate the potential of four different biomasses in the preparation and quality of activated carbon. Residues from the processing of the fruits of acai, babassu, Brazil nut, and oil palm were collected, characterized, carbonized, physically activated with CO2, and characterized. The contents of the total extractives, insoluble lignin, minerals, holocellulose, and elemental (CHNS-O) were analyzed. The surface area and surface morphology were determined from the AC produced, and adsorption tests for methylene blue and phenol were performed. The four biomasses showed potential for use in the preparation of CA; the residues presented high contents of lignin (21.83-55.76%) and carbon (46.49-53.79%). AC were predominantly microporous, although small mesopores could be observed. The AC had a surface area of 569.65-1101.26 m2 g-1, a high methylene blue (93-390 mg g-1), and phenol (159-595 mg g-1) adsorption capacities. Babassu-AC stood out compared to the AC of the other analyzed biomasses, reaching the best results.

Efficacy of Residual Site Radiation Therapy (ISRT) in Patients with Primary Mediastinal Lymphoma with Deauville Score 4 Following R-CHT: Results of a Retrospective Mono Institutional Study.

BACKGROUND: In order to evaluate the efficacy of residual site radiation therapy (RSRT) in terms of progression-free survival (PFS) and overall survival (OS) in patients with primary mediastinal lymphoma (PMBCL) with Deauville Score 4 (DS 4) following rituximab and chemotherapy treatment (R-ICHT). METHODS: Thirty-one patients with PMBCL were recruited. After completion of R-ICHT, patients were staged with 18F-fluorodeoxyglucose positron-emission tomography, showing DS 4, and were treated with adjuvant RSRT. The chosen techniques for RT delivery were intensity-modulated radiation therapy (IMRT) or three-dimensional conformal RT (3D-CRT). Most patients underwent the first one using cone-beam computed tomography (CBCT). All patients were evaluated every 3 months for the first 2 years and every 6 months afterwards for a period of at least 5 years, with clinical and radiological procedures as required. RESULTS: All patients received RSRT with a dose of 30 Gy in 15 fractions. The median follow-up time of 52.7 months (IQR: 26-64.1 months). The 5-year OS rate was 100%. The 2-year and 5-year PFS rates were 96.7% and 92.5%, respectively. Patients with relapsed disease had been treated with high-dose chemotherapy (HDC) and autologous stem cell transplantation (auto-SCT). CONCLUSION: RSRT in patients with PMBCL treated with ICHT and DS 4 did not impact unfavorably on patient survival.

Beneficial effects of metformin on mice female fertility after a high-fat diet intake.

Female fertility is highly dependent on energy balance. High fat diet (HFD) intake entails a risk of infertility and ovulatory disorders. Considering the increase in the prevalence of overweight and obesity over the last decades, it is crucial to understand the mechanisms involved in overweight-associated infertility. In this study, we evaluated the reproductive performance of female mice fed with a HFD and the effects of metformin administration on ovarian function in these mice. We hypothesized that one of the mechanisms involved in subfertility due to a HFD intake is the alteration of ovarian blood vessel formation. We found that mice fed with HFD had altered estrous cycles and steroidogenesis, increased ovarian fibrosis, fewer pups per litter and require more time to achieve pregnancy. HFD-fed mice also presented dysregulated ovarian angiogenesis and an increase in nuclear DNA damage in ovarian cells. Ovulation rates were lower in these animals, as evidenced both in natural mating and after ovulation induction with gonadotropins. Metformin ameliorated ovarian angiogenesis, improved steroidogenesis, fibrosis, and ovulation, decreased the time to pregnancy and increased litter sizes in HFD-fed mice. We conclude that ovarian angiogenesis is one of the mechanisms detrimentally affected by HFD intake. Since metformin could improve ovarian microvasculature, it may be an interesting strategy to study in women to shed light on new targets for patients with metabolic disturbances.

1. Victims of Enforced Disappearances: Absent Bodies, Inner Presences: 1. Victims of Enforced Disappearances: Absent Bodies, Inner Presences1.

Enforced disappearance represents the quintessence of human rights violations with a strong psychological component. Bodies vanishing have a deterrent effect by terrorizing and paralyzing the entire society. However, the absence of those bodies is overly present in the inner experience of the families of the disappeared, who are victims in their turn. A state of severe psychological deterioration affects the relatives of the disappeared: depression, anxiety, powerlessness, guilt, post-traumatic stress disorder, inability to mourn, even suicide are the consequences of the unbearable uncertainty about the fate of the loved one. But the disappeared persons, notwithstanding the absence of their bodies, continue to be more present than ever in the inner experience of those who have loved them. For the families of the disappeared, to regain psychological equilibrium is a fine balance between the need to remember and the necessity to forget. The author affirms that, at a social and political level, to cultivate a collective memory of enforced disappearance is an ethical duty which validates the actual occurrence of the atrocities, helps prevent repetition and alleviates the transgenerational transmission of trauma.

Les disparitions forcées représentent la quintessence des violations des droits humains avec une forte composante psychologique. Les corps que l'on ne retrouve pas sont un moyen de dissuasion qui opère en terrorisant et paralysant la société toute entière. L'absence de ces corps est excessivement présente dans l'expérience intérieure des familles de ces disparus ; elles deviennent des victimes à leur tour. Un état de détérioration psychologique aigu affecte les membres de la famille du disparu : dépression, angoisse, sentiment d'impuissance, culpabilité, syndrome post-traumatique, incapacité à faire le deuil, et même le suicide sont les conséquences de l'insupportable incertitude concernant le destin de la personne aimée. Les personnes disparues, du fait de l'absence de leur dépouille, continuent d'être plus que jamais présentes dans l'expérience intérieure de ceux qui les ont aimées. Pour les familles des disparus, retrouver une stabilité psychologique se trouve dans un équilibre délicat entre le besoin de se souvenir et la nécessité d'oublier. L'auteur soutient qu'au niveau social et politique, cultiver une mémoire collective des disparitions forcées est un devoir éthique qui confirme que des atrocités ont bien eu lieu, qui aide à en prévenir la répétition et qui allège la transmission transgénérationnelle du traumatisme.

La desaparición forzada representa la quintaesencia de las violaciones de derechos humanos con un fuerte componente psicológico. La desaparición de cuerpos tiene un efecto disuasorio al aterrorizar y paralizar a toda la sociedad. Sin embargo, la ausencia de esos cuerpos está excesivamente presente en la experiencia interior de las familias de los desaparecidos, que son víctimas a su vez. Un estado de grave deterioro psicológico afecta a los familiares de los desaparecidos: depresión, ansiedad, impotencia, culpabilidad, trastorno de estrés postraumático, incapacidad para el duelo, incluso suicidio son las consecuencias de la insoportable incertidumbre sobre la suerte del ser querido. Pero las personas desaparecidas, a pesar de la ausencia de sus cuerpos, siguen estando más presentes que nunca en la experiencia interior de quienes las han amado. Para las familias de los desaparecidos, recuperar el equilibrio psicológico es un delicado equilibrio entre la necesidad de recordar y la necesidad de olvidar. La autora afirma que, a nivel social y político, cultivar una memoria colectiva de la desaparición forzada es un deber ético que valida la ocurrencia real de las atrocidades, ayuda a prevenir su repetición y alivia la transmisión transgeneracional del trauma.

Diagnostic Process of an Ancient Colonnade Using 3D High-Resolution Models with Non-Invasive Multi Techniques.

Here, an avant-garde study of three ancient Doric columns of the precious, ancient Romanesque church of Saints Lorenzo and Pancrazio in the historical town center of Cagliari (Italy) is presented based on the integrated application of different non-destructive testing methods. The limitations of each methodology are overcome by the synergistic application of these methods, affording an accurate, complete 3D image of the studied elements. Our procedure begins with a macroscopic in situ analysis to provide a preliminary diagnosis of the conditions of the building materials. The next step is laboratory tests, in which the porosity and other textural characteristics of the carbonate building materials are studied by optical and scanning electron microscopy. After this, a survey with a terrestrial laser scanner and close-range photogrammetry is planned and executed to produce accurate high-resolution 3D digital models of the entire church and the ancient columns inside. This was the main objective of this study. The high-resolution 3D models allowed us to identify architectural complications occurring in historical buildings. The 3D reconstruction with the above metric techniques was indispensable for planning and carrying out the 3D ultrasonic tomography, which played an important role in detecting defects, voids, and flaws within the body of the studied columns by analyzing the propagation of the ultrasonic waves. The high-resolution 3D multiparametric models allowed us to obtain an extremely accurate picture of the conservation state of the studied columns in order to locate and characterize both shallow and internal defects in the building materials. This integrated procedure can aid in the control of the spatial and temporal variations in the materials' properties and provides information on the process of deterioration in order to allow adequate restoration solutions to be developed and the structural health of the artefact to be monitored.

Dysfunctional antioxidant capacity of high-density lipoprotein in rheumatoid arthritis.

BACKGROUND: High-density lipoprotein (HDL) presents atheroprotective functions not readily reflected by plasma HDL-cholesterol levels. The aim of this study was to investigate HDL antioxidant function in patients with rheumatoid arthritis (RA). METHODS: This pilot and cross-sectional study included 50 RA patients and 50 controls matched by age, gender, cardiovascular risk factors and drug therapy. The antioxidant capacity of HDL was assessed by the total radical-trapping antioxidative potential test (TRAP-assay) and the susceptibility of low-density lipoprotein (LDL) to oxidation by the Conjugated Dienes Assay (Dmax ). A carotid ultrasound was performed in all participants to detect subclinical atherosclerosis. RESULTS: High-density lipoprotein from RA patients showed lower antioxidant capacity than those from controls [oxidized-LDL%: 35.8 (27-42) vs. 24.4 (20-32), p < .001] when analysed with the TRAP-assay. In addition, the time to achieve 50% of maximal LDL oxidation (Lag-time) was shorter in RA-patients than in matched controls [57.2 (42-71) vs. 69.5 (55-75) minutes, (p = .003)]. RA patients showed a higher atherosclerotic burden than controls. The pro-oxidant pattern in RA was irrespective of the presence of carotid atherosclerosis. On the contrary, there was a positive correlation between inflammatory parameters (erythrocyte sedimentation rate, ultrasensitive C-reactive protein and fibrinogen) and the loss of HDL-anti-oxidant capacity measured by the TRAP-assay (rho = .211, p = .035; rho = .231, p = .021 and rho = .206, p = .041, respectively). Furthermore, the glucocorticoid dose at recruitment was negatively associated with the Lag-time in RA patients (rho = -.387, p = .026). CONCLUSION: Rheumatoid arthritis patients present reduced HDL antioxidant capacity and a lower resistance of LDL particles to oxidation, mainly related to the degree of inflammation.

Early MRI termination with major impact on the radiological interpretation: The experience of a large university hospital.

PURPOSE: To report the incidence of early magnetic resonance imaging (MRI) terminations and analyse their risk factors in a large university hospital. METHOD: All consecutive patients aged > 16 years who underwent an MRI over a 14-month period were included. The following parameters were collected: demographics, in- or outpatient, history of claustrophobia, anatomical region investigated, and early MRI termination along with its cause. The potential link between these parameters and early MRI termination was statistically analysed. RESULTS: Overall, 22,566MRIs were performed (10,792 [48%] men and 11,774[52%] women, mean age: 57 [range: 16-103] years). Early MRI termination was reported in 183 (0.8%) patients (99 men and 84 women, mean age: 63 years). Of these early terminations, 103 (56%) were due to claustrophobia and 80 (44%) to other causes. Early terminations were more common in inpatients than outpatients (1.2% vs. 0.6%, p < 0.001), for both claustrophobia- and non-claustrophobia-related reasons. A prior history of claustrophobia was strongly associated with claustrophobia-related early termination (6.6% vs. 0.2%, p = 0.0001). Non-claustrophobia-related early terminations were significantly more common (0.6% vs. 0.2%) in elderly patients (>65 years old) than in younger ones. No other parameter was significantly associated with early termination. CONCLUSIONS: Early MRI termination is currently rare. The main risk factors for claustrophobia-related terminations comprised a prior history of claustrophobia, and examinations in inpatients. Non-claustrophobia-related early terminations were more common in both elderly patients and inpatients.