Predictors of progression of cognitive decline in Alzheimer’s disease: the role of vascular and sociodemographic factors

Rates of disease progression differ among patients with Alzheimer’s disease, but little is known about prognostic predictors. The aim of the study was to assess whether sociodemographic factors, disease severity and duration, and vascular factors are prognostic predictors of cognitive decline in Alzheimer’s disease progression. We conducted a longitudinal clinical study in a specialized clinical unit for the diagnosis and treatment of dementia in Rome, Italy. A total of 154 persons with mild to moderate Alzheimer’s disease consecutively admitted to the dementia unit were included. All patients underwent extensive clinical examination by a physician at admittance and all follow-ups. We evaluated the time-dependent probability of a worsening in cognitive performance corresponding to a 5-point decrease in Mini-Mental State Examination (MMSE) score. Survival analysis was used to analyze risk of faster disease progression in relation to age, education, severity and duration of the disease, family history of dementia, hypertension, hypercholesterolemia, and type 2 diabetes. Younger and more educated persons were more likely to have faster Alzheimer’s disease progression. Vascular factors such as hypertension and hypercholesterolemia were not found to be significantly associated with disease progression. However, patients with diabetes had a 65% reduced risk of fast cognitive decline compared to Alzheimer patients without diabetes. Sociodemographic factors and diabetes predict disease progression in Alzheimer’s disease. Our findings suggest a slower disease progression in Alzheimer’s patients with diabetes. If confirmed, this result will contribute new insights into Alzheimer’s disease pathogenesis and lead to relevant suggestions for disease treatment

Identification of novel chemotherapeutic strategies for metastatic uveal melanoma

Melanoma of the uveal tract accounts for approximately 5% of all melanomas and represents the most common primary intraocular malignancy. Despite improvements in diagnosis and more effective local therapies for primary cancer, the rate of metastatic death has not changed in the past forty years. In the present study, we made use of bioinformatics to analyze the data obtained from three public available microarray datasets on uveal melanoma in an attempt to identify novel putative chemotherapeutic options for the liver metastatic disease. We have first carried out a meta-analysis of publicly available whole-genome datasets, that included data from 132 patients, comparing metastatic vs. non metastatic uveal melanomas, in order to identify the most relevant genes characterizing the spreading of tumor to the liver. Subsequently, the L1000CDS(2) web-based utility was used to predict small molecules and drugs targeting the metastatic uveal melanoma gene signature. The most promising drugs were found to be Cinnarizine, an anti-histaminic drug used for motion sickness, Digitoxigenin, a precursor of cardiac glycosides, and Clofazimine, a fat-soluble iminophenazine used in leprosy. In vitro and in vivo validation studies will be needed to confirm the efficacy of these molecules for the prevention and treatment of metastatic uveal melanoma

Intra-seasonal variation of anthropometrical, conditional, and technical tests in U14 soccer players. [Variación en los parámetros antropométricos, condicionales y test técnicos de jugadores de fútbol SUB-14].

This study aimed to analyze the annual variation of soccer players abilities assessed by means of a field-battery test administered six times during an entire competitive season (from T0 to T5). Anthropometric (i.e., body mass, stature, and body mass index), soccer skill (i.e., touch with the body, touch with the head, passing, shooting, dribbling with pass, and dribbling) and functional capacities (i.e., counter-movement jump with and without free arms, and speed) tests were submitted to 33 Under-14 soccer players. A general improvement across the season as confirmed by the rising effects from 0.3 (T2) to 0.6 (T5) was showed. The technical skills (except touch with the head and dribbling) and functional tests showed significant differences (p < 0.001) between T0 and T5 but they were not dependent by the exposure to training. This study underlined that the skills’ development in youth soccer players are not linear due to the effects of the growth and maturation. In order to optimize this process, in-season assessment are needed. Finally, programs and decisions promoted by coaches and scouts aimed to the development of youth soccer players should be inspired by the potential results that might be achieved by players. Resumen El objetivo del presente estudio consistió en analizar la variación anual de las habilidades de jugadores de fútbol sub-14 (n=33) mediante una batería de test de campo administrados seis veces a lo largo de la temporada (de T0 a T5). Las mediciones registradas se centraron en aspectos antropométricos (i.e., talla, peso e índice de masa corporal), habilidades específicas (i.e., toques con el cuerpo, con la cabeza, pases, lanzamientos, regates con pase y regates) y la condición física (i.e., salto en contra movimiento con y sin movimiento de brazos y velocidad). Los resultados mostraron una mejora a lo largo de la temporada con efectos que pasaron de 0.3 (T2) a 0.6 (T5). Las habilidades técnicas (excepto el toque con la cabeza y el regate) y los test funcionales mostraron diferencias significativas (p<0.001) entre los periodos T0 y T5, pero éstas no fueron dependientes de la exposición al entrenamiento. El presente estudio permite resaltar que el desarrollo de habilidades en jóvenes jugadores de fútbol no es lineal debido a los efectos del desarrollo y la maduración. En relación con el proceso de optimización de entrenamiento se requieren evaluaciones a lo largo de la temporada. Finalmente, los programas específicos y las decisiones de entrenadores y scouters debe centrarse en el desarrollo de los jugadores jóvenes tomando como punto de partida el potencial que pueden alcanzar

Clinical Impact of Pretransplant Multidrug-Resistant Gram-Negative Colonization in Autologous and Allogeneic Hematopoietic Stem Cell Transplantation

Abstract Multidrug-resistant Gram-negative bacteria (MDR-GNB) are an emerging cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Three-hundred forty-eight consecutive patients transplanted at our hospital from July 2012 to January 2016 were screened for a pretransplant MDR-GNB colonization and evaluated for clinical outcomes. A pretransplant MDR-GNB colonization was found in 16.9% of allo-HSCT and in 9.6% of auto-HSCT recipients. Both in auto- and in allo-HSCT, carriers of a MDR-GNB showed no significant differences in overall survival (OS), transplant-related mortality (TRM), or infection-related mortality (IRM) compared with noncarriers. OS at 2 years for carriers compared with noncarriers was 85% versus 81% ( P  = .262) in auto-HSCT and 50% versus 43% ( P  = .091) in allo-HSCT. TRM at 2 years was 14% versus 5% ( P  = .405) in auto-HSCT and 31% versus 25% ( P  = .301) in allo-HSCT. IRM at 2 years was 14% versus 2% ( P  = .142) in auto-HSCT and 23% versus 14% ( P  = .304) in allo-HSCT. In multivariate analysis, only grade III to IV acute graft-versus-host disease was an independent factor for reduced OS ( P P P P  = .207). We conclude that in this extended single-center experience, a pretransplant MDR-GNB colonization did not significantly influence OS, TRM, and IRM both in auto- and allo-HSCT settings and that MDR-GNB attributed mortality can be controlled in carriers when an early pre-emptive antimicrobial therapy is started in case of neutropenic fever

Bologna Guidelines for Diagnosis and Management of Adhesive Small Bowel Obstruction (ASBO): 2010 Evidence-Based Guidelines of the World Society of Emergency Surgery

Contains fulltext : 97685.pdf (publisher's version ) (Open Access)BACKGROUND: There is no consensus on diagnosis and management of ASBO. Initial conservative management is usually safe, however proper timing for discontinuing non operative treatment is still controversial. Open surgery or laparoscopy are used without standardized indications. METHODS: A panel of 13 international experts with interest and background in ASBO and peritoneal diseases, participated in a consensus conference during the 1st International Congress of the World Society of Emergency Surgery and 9th Peritoneum and Surgery Society meeting, in Bologna, July 1-3, 2010, for developing evidence-based recommendations for diagnosis and management of ASBO. Whenever was a lack of high-level evidence, the working group formulated guidelines by obtaining consensus. RECOMMENDATIONS: In absence of signs of strangulation and history of persistent vomiting or combined CT scan signs (free fluid, mesenteric oedema, small bowel faeces sign, devascularized bowel) patients with partial ASBO can be managed safely with NOM and tube decompression (either with long or NG) should be attempted. These patients are good candidates for Water Soluble Contrast Medium (WSCM) with both diagnostic and therapeutic purposes. The appearance of water-soluble contrast in the colon on X-ray within 24 hours from administration predicts resolution. WSCM may be administered either orally or via NGT (50-150 ml) both immediately at admission or after an initial attempt of conservative treatment of 48 hours. The use of WSCM for ASBO is safe and reduces need for surgery, time to resolution and hospital stay.NOM, in absence of signs of strangulation or peritonitis, can be prolonged up to 72 hours. After 72 hours of NOM without resolution surgery is recommended.Patients treated non-operatively have shorter hospital stay, but higher recurrence rate and shorter time to re-admission, although the risk of new surgically treated episodes of ASBO is unchanged. Risk factors for recurrences are age <40 years and matted adhesions. WSCM does not affect recurrence rates or recurrences needing surgery when compared to traditional conservative treatment.Open surgery is the preferred method for surgical treatment of strangulating ASBO as well as after failed conservative management. In selected patients and with appropriate skills, laparoscopic approach can be attempted using open access technique. Access in the left upper quadrant should be safe. Laparoscopic adhesiolysis should be attempted preferably in case of first episode of SBO and/or anticipated single band. A low threshold for open conversion should be maintained.Peritoneal adhesions should be prevented. Hyaluronic acid-carboxycellulose membrane and icodextrin can reduce incidence of adhesions. Icodextrin may reduce the risk of re-obstruction. HA cannot reduce need of surgery

Predicting disease progression in alzheimer's disease: The role of neuropsychiatric syndromes on functional and cognitive decline

Patients with Alzheimer's disease (AD) have heterogeneous rates of disease progression. The aim of the current study is to investigate whether neuropsychiatric disturbances predict cognitive and functional disease progression in AD, according to failure theory. We longitudinally examined 177 memory-clinic AD outpatients (mean age = 73.1, SD = 8.1; 70.6% women). Neuropsychiatric disturbances at baseline were categorized into five syndromes. Patients were followed for up to two years to detect rapid disease progression defined as a loss of >= 1 abilities in Activities of Daily living (ADL) or a drop of >= 5 points on Mini-Mental State Examination (MMSE). Hazard ratios (HR) were calculated with Gompertz regression, adjusting for sociodemographics, baseline cognitive and functional status, and somatic comorbidities. Most patients (74.6%) exhibited one or more neuropsychiatric syndromes at baseline. The most common neuropsychiatric syndrome was Apathy (63.8%), followed by Affective (37.3%), Psychomotor (8.5%), Manic (7.9%), and Psychotic (5.6%) syndromes. The variance between the observed (Kaplen Meier) and predicted (Gompertz) decline for disease progression in cognition (0.30, CI = 0.26-0.35), was higher than the variance seen for functional decline (0.22, CI = 0.18-0.26). After multiple adjustment, patients with the Affective syndrome had an increased risk of functional decline (HR = 2.0; CI = 1.1-3.6), whereas the risk of cognitive decline was associated with the Manic (HR = 3.2, CI = 1.3-7.5) syndrome. In conclusion, specific neuropsychiatric syndromes are associated with functional and cognitive decline during the progression of AD, which may help with the long-term planning of care and treatment. These results highlight the importance of incorporating a thorough psychiatric examination in the evaluation of AD patients

a new clinicobiological scoring system for the prediction of infection related mortality and survival after allogeneic hematopoietic stem cell transplantation

Abstract Infection-related mortality (IRM) is a substantial component of nonrelapse mortality (NRM) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). No scores have been developed to predict IRM before transplantation. Pretransplantation clinical and biochemical data were collected from a study cohort of 607 adult patients undergoing allo-HSCT between January 2009 and February 2017. In a training set of 273 patients, multivariate analysis revealed that age >60 years ( P  = .003), cytomegalovirus host/donor serostatus different from negative/negative ( P P  = .004), and pretransplantation IgM level P  = .028) were independent predictors of increased IRM. Based on these results, we developed and subsequently validated a 3-tiered weighted prognostic index for IRM in a retrospective set of patients (n = 219) and a prospective set of patients (n = 115). Patients were assigned to 3 different IRM risk classes based on this index score. The score significantly predicted IRM in the training set, retrospective validation set, and prospective validation set ( P P P

Infections after Allogenic Transplant with Post-Transplant Cyclophosphamide: Impact of Donor HLA Matching

ABSTRACT Incidence and outcome of infections after allogeneic hematopoietic stem cell transplantation (HSCT) with post-transplant cyclophosphamide (PT-Cy) as graft-versus-host disease (GVHD) prophylaxis are largely unknown. Study aims were to estimate the incidence of pre-engraftment bloodstream infections (PE-BSIs) and viral infections (VIs; cytomegalovirus [CMV], adenovirus [ADV], human herpes virus 6 [HHV6], and BK-polyomavirus hemorrhagic-cystitis [BKPyV-HC]), their predictive factors, and infection-related mortality (IRM) after HSCT with PT-Cy. We analyzed 235 patients: 62%, 21%, and 17% received haploidentical (haplo), matched-unrelated donor (MUD), and matched-related donor, respectively. Overall, 72 patients had 77 PE-BSI episodes at a median time of 13 days after HSCT: cumulative incidence function (CIF) at 28 days was 32%, without differences among donor types (P = .988). By multivariate analysis, CIF of PE-BSI was higher in patients with severe neutropenia before HSCT (adjusted hazard ratio [AHR] = 2.90) and in multidrug-resistant Gram-negative bacteria rectal carriers (AHR = 2.68). IRM at 30 days was 5%, without differences by donor type (P = .106). Overall, 208 patients experienced ≥1 VIs (first occurrence among CMV, HHV6, ADV, BKPyV-HC) at a median time of 20 days after HSCT: CIF at 90 days was 91%, significantly higher in MUD and haplo (P = .0089). By multivariate analysis, also acute GVHD grade ≥2 (AHR = 1.32) and host/donor CMV-serology mismatch (positive/positive versus negative/negative: AHR = 2.95, positive/negative versus negative/negative: AHR = 2.41, negative/positive versus negative/negative: AHR = 2.35) affected VIs occurrence. IRM at 180 days was 8%, without differences among donor types (P = .106). In conclusion, study results did not show a significant impact of donor type on PE-BSI incidence; conversely, MUD and haploidentical transplants retained a higher occurrence of VIs in the early phase after HSCT

Post-transplantation Cyclophosphamide and Sirolimus after Haploidentical Hematopoietic Stem Cell Transplantation Using a Treosulfan-based Myeloablative Conditioning and Peripheral Blood Stem Cells.

Haploidentical hematopoietic stem cell transplantation (HSCT) performed using bone marrow (BM) grafts and post-transplantation cyclophosphamide (PTCy) has gained much interest for the excellent toxicity profile after both reduced-intensity and myeloablative conditioning. We investigated, in a cohort of 40 high-risk hematological patients, the feasibility of peripheral blood stem cells grafts after a treosulfan-melphalan myeloablative conditioning, followed by a PTCy and sirolimus-based graft-versus-host disease (GVHD) prophylaxis (Sir-PTCy). Donor engraftment occurred in all patients, with full donor chimerism achieved by day 30. Post-HSCT recovery of lymphocyte subsets was broad and fast, with a median time to CD4 > 200/mu L of 41 days. Cumulative incidences of grade II to IV and III-IV acute GVHD were 15% and 7.5%, respectively, and were associated with a significant early increase in circulating regulatory T cells at day 15 after HSCT, with values < 5% being predictive of subsequent GVHD occurrence. The 1-year cumulative incidence of chronic GVHD was 20%. Nonrelapse mortality (NRM) at 100 days and 1 year were 12% and 17%, respectively. With a median follow-up for living patients of 15 months, the estimated 1-year overall and disease-free survival (DFS) was 56% and 48%, respectively. Outcomes were more favorable in patients who underwent transplantation in complete remission (1-year DFS 71%) versus patients who underwent transplantation with active disease (DFS, 34%; P = .01). Overall, myeloablative haploidentical HSCT with peripheral blood stem cells (PBSC) and Sir-PTCy is a feasible treatment option: the low rates of GVHD and NRM as well as the favorable immune reconstitution profile pave the way for a prospective comparative trial comparing BM and PBSC in this specific transplantation setting. (C) 2015 American Society for Blood and Marrow Transplantation

Secondary SOLID Tumors after Allogeneic STEM CELL Transplantation: A CROSS-Sectional Evaluation in 260 Adults at 1-Year Follow-up

n/