Minimal residual disease (MRD) is an important prognostic factor in adults with acute lymphoblastic leukemia (ALL) and may be used for treatment decisions. The Programa Español de Tratamientos en ...Hematología (PETHEMA) ALL-AR-03 trial (Treatment of High Risk Adult Acute Lymphoblastic Leukemia LAL-AR/2003) assigned adolescent and adult patients (age 15 to 60 years) with high-risk ALL (HR-ALL) without the Philadelphia (Ph) chromosome to chemotherapy or to allogeneic hematopoietic stem-cell transplantation (allo-HSCT) according to early cytologic response (day 14) and flow-MRD level after consolidation.
Patients with good early cytologic response (< 10% blasts in bone marrow at day 14 of induction) and a flow-MRD level less than 5 × 10(-4) at the end of consolidation were assigned to delayed consolidation and maintenance therapy, and allo-HSCT was scheduled in patients with poor early cytologic response or flow-MRD level ≥ 5 × 10(-4).
Complete remission was attained in 282 (87%) of 326 patients, and 179 (76%) of 236 patients who completed early consolidation were assigned by intention-to treat to receive allo-HSCT (71) or chemotherapy (108). Five-year disease-free survival (DFS) and overall survival (OS) probabilities were 37% and 35% for the whole series, 32% and 37% for patients assigned to allo-HSCT, and 55% and 59% for those assigned to chemotherapy. Multivariable analysis showed poor MRD clearance (≥ 1 × 10(-3) after induction and ≥ 5 × 10(-4) after early consolidation) as the only prognostic factor for DFS and OS.
Prognosis for Ph-negative HR-ALL in adolescents and adults with good early response to induction and low flow-MRD levels after consolidation is quite favorable when allo-HSCT is avoided. In this study, the pattern of MRD clearance was the only prognostic factor for DFS and OS.
Objective: Although increased central fat mass is characteristic of active Cushing’s syndrome (CS), little is known about body composition and secretion of adipokines after long-term recovery of CS. ...The aim of this study was to evaluate central fat mass and its correlation with adipokines and cardiovascular risk factors in patients after long-term remission of CS.
Methods: Thirty-seven women with CS in remission (27 of pituitary and 10 of adrenal origin; mean age, 50 ± 14 yr; mean time of hormonal cure, 11 ± 6 yr) were enrolled and compared to 14 women with active CS and 85 gender-, age-, and body mass index-matched healthy controls. Total and trunk fat mass were measured by dual-energy x-ray absorptiometry scanning. Laboratory parameters and adipokine levels including adiponectin, visfatin, soluble TNFα-receptor 1 (sTNF-R1), sTNF-R2, and IL-6 were measured.
Results: Cured CS patients had more total and trunk fat mass than controls. Cured and active CS had higher levels of sTNF-R1 and IL-6 and lower adiponectin levels than controls. Higher insulin levels and blood pressure in both groups of CS patients and higher apolipoprotein B in cured CS were observed compared to controls. sTNF-R1 correlated positively with percentage of trunk fat mass and remained significant after adjusting for anthropometric parameters.
Conclusion: Despite long-term cure, patients who have suffered CS exhibit persistent accumulation of central fat, as in active hypercortisolemia, with the consequent unfavorable adipokine profile, leading to a state of low-grade inflammation. This situation determines a persistent and increased cardiovascular risk in these patients.
Despite long-term cure, Cushing′s syndrome determines persistent accumulation of central fat, an unfavorable adipokine profile, low-grade inflammation, and increased cardiovascular risk, as in active hypercortisolemia.
The outcome of colorectal cancer is mostly based on TNM classification. There are several factors determining that patients with the same tumoral stage present different outcomes. The nutritional ...status has been related to the immunological response and may affect the oncologic results. The purpose of this study was to determine if preoperative nutritional parameters may predict the oncologic outcome in patients with early colorectal cancer.
A prospective observational study of patients undergoing elective surgery for colorectal cancer was performed with stage I. Preoperative nutritional assessment included glycemic and lipid profiles, total proteins, and albumin levels. These parameters were correlated with tumoral recurrence during a follow-up of at least 24 months.
During the period of study, 744 patients were operated on and 228 (30.6%) followed the inclusion criteria for this study. Recurrence rate was 5.7% (13 patients). Patients with hypoproteinemia showed a 7.8-fold greater risk of recurrence during the first 24 months after surgery OR 7.8 (CI95% 1.3-48),
= 0.012. Patients with glycated hemoglobin levels (HbA1c) > 6.2% showed a 2.3 increased risk of recurrence OR 2.3 (CI95% 1.1-4.7;
= 0.01.
Preoperative values of total proteins and HbA1c correlate with the recurrence rate in early colorectal cancer.
Genomic studies have yielded important insights into the pathogenesis of obesity. Circulating microRNAs (miRNAs) are valuable biomarkers of systemic diseases and potential therapeutic targets. We ...sought to define the circulating pattern of miRNAs in obesity and examine changes after weight loss.
We assessed the genomewide circulating miRNA profile cross-sectionally in 32 men and after surgery-induced weight loss in 6 morbidly obese patients. The most relevant miRNAs were cross-sectionally validated in 80 men and longitudinally in 22 patients (after surgery-induced weight loss). We evaluated the effects of diet-induced weight loss in 9 obese patients. Thirty-six circulating miRNAs were associated with anthropometric variables in the initial sample.
In the validation study, morbidly obese patients showed a marked increase of miR-140-5p, miR-142-3p (both P < 0.0001), and miR-222 (P = 0.0002) and decreased levels of miR-532-5p, miR-125b, miR-130b, miR-221, miR-15a, miR-423-5p, and miR-520c-3p (P < 0.0001 for all). Interestingly, in silico targets leukemia inhibitory factor receptor (LIFR) and transforming growth factor receptor (TGFR) of miR-140-5p, miR-142-3p, miR-15a, and miR-520c-3p circulated in association with their corresponding miRNAs. Moreover, a discriminant function of 3 miRNAs (miR-15a, miR-520c-3p, and miR-423-5p) was specific for morbid obesity, with an accuracy of 93.5%. Surgery-induced (but not diet-induced) weight loss led to a marked decrease of miR-140-5p, miR-122, miR-193a-5p, and miR-16-1 and upregulation of miR-221 and miR-199a-3p (P < 0.0001 for all).
Circulating miRNAs are deregulated in severe obesity. Weight loss-induced changes in this profile and the study of in silico targets support this observation and suggest a potential mechanistic relevance.
Epidemiological studies show that adherence to a Mediterranean diet (MD) increases longevity; however, few studies are restricted to Mediterranean populations or explore the effect of a MD pattern ...that directly incorporates olive oil. Therefore the relationship between adherence to the MD and mortality was studied within the the Spanish cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Spain). The EPIC-Spain analysis included 40 622 participants (37·7 % males) aged 29–69 years who were recruited from five Spanish regions in 1992–1996. During a mean follow-up of 13·4 years, 1855 deaths were documented: 913 from cancer, 399 from CVD, 425 from other causes and 118 from unknown causes of death. Risk of all-cause and cause-specific mortality was assessed according to the level of adherence to a relative MD (rMED) score, measured using an 18-unit scale incorporating nine selected dietary components. A high compared with a low rMED score was associated with a significant reduction in mortality from all causes (hazard ratio (HR) 0·79; 95 % CI 0·69, 0·91), from CVD (HR 0·66; 95 % CI 0·49, 0·89), but not from overall cancer (HR 0·92; 95 % CI 0·75, 1·12). A 2-unit increase in rMED score was associated with a 6 % (P < 0·001) decreased risk of all-cause mortality. A high olive oil intake and moderate alcohol consumption contributed most to this association. In this Spanish cohort, following an olive oil-rich MD was related to a significant reduction in all-cause mortality, and reduced the risk of mortality from CVD. These results support the important role that the MD pattern has on reducing mortality in Mediterranean countries.
The COVID-19 pandemic has led to an increased workload for nurses and organisational and structural changes, which have been necessary to meet the needs of inpatients in isolation. Aim: To describe ...the impact of the COVID-19 pandemic on levels of adherence to the completion of nursing records that document the risk of developing pressure ulcers, falling, and social vulnerability among hospitalised patients in isolation. Methods: Observational pre-post comparison study. Comparison between nursing records (the Braden, Downton, and Gijón scales) belonging to 1205 inpatients took place in two phases. Phase 1: 568 patients admitted in February 2020, prior to the COVID-19 pandemic, vs. phase 2: 637 patients hospitalised with COVID-19 in March–April 2020, during the peak of the first wave of the pandemic. This research adheres to the STROBE guidelines for the reporting of observational studies. Results: The degree of completion of the Braden, Downton, and Gijón scales decreased significantly in phase 2 vs. phase 1 (p < 0.001). The mean Downton and Gijón scale scores for patients admitted in phase 1 were higher compared to those of patients admitted in phase 2 (p < 0.001). The mean Braden scale score in phase 2 was higher than in phase 1 (p < 0.05). Conclusion: During the COVID-19 pandemic, there was a decrease in the completion of nursing records in the clinical records of patients in isolation. The levels of risk of developing PUs, falling, and social vulnerability of patients admitted to hospital were lower during the first wave of the pandemic.
Background
Metabolic dysfunction‐associated steatotic liver disease (MASLD) is a leading cause of end‐stage liver disease associated with increased mortality and cardiovascular disease. Obesity and ...diabetes are the most important risk factors of MASLD. It is well‐established that obesity‐associated insulin resistance leads to a situation of tissue lipotoxicity characterized by an accumulation of excess fat in non‐fat tissues such as the liver, promoting the development of MASLD, and its progression into metabolic dysfunction‐associated steatohepatitis.
Methods
Here, we aimed to review the impact of disrupted intestinal permeability, antimicrobial proteins and bacterial endotoxin in the development and progression of MASLD.
Results and Conclusion
Recent studies demonstrated that obesity‐ and obesogenic diets‐associated alterations of intestinal microbiota along with the disruption of intestinal barrier integrity, the alteration in antimicrobial proteins and, in consequence, an enhanced translocation of bacterial endotoxin into bloodstream might contribute to this pathological process through to impacting liver metabolism and inflammation.
Recent studies demonstrated that obesity‐ and obesogenic diets‐associated alterations of intestinal microbiota along with the disruption of intestinal barrier integrity, the alteration in antimicrobial proteins and, in consequence, an enhanced translocation of bacterial endotoxin into bloodstream might contribute to metabolic dysfunction‐associated steatotic liver disease (MASLD) through to impacting liver metabolism and inflammation. Here, we aimed to review the impact of disrupted intestinal permeability, antimicrobial proteins and bacterial endotoxin in the development and progression of MASLD.
The automation of the Wilderness Search and Rescue (WiSAR) task aims for high levels of understanding of various scenery. In addition, working in unfriendly and complex environments may cause a time ...delay in the operation and consequently put human lives at stake. In order to address this problem, Unmanned Aerial Vehicles (UAVs), which provide potential support to the conventional methods, are used. These vehicles are provided with reliable human detection and tracking algorithms; in order to be able to find and track the bodies of the victims in complex environments, and a robust control system to maintain safe distances from the detected bodies. In this paper, a human detection based on the color and depth data captured from onboard sensors is proposed. Moreover, the proposal of computing data association from the skeleton pose and a visual appearance measurement allows the tracking of multiple people with invariance to the scale, translation and rotation of the point of view with respect to the target objects. The system has been validated with real and simulation experiments, and the obtained results show the ability to track multiple individuals even after long-term disappearances. Furthermore, the simulations present the robustness of the implemented reactive control system as a promising tool for assisting the pilot to perform approaching maneuvers in a safe and smooth manner.
Background
Disease recurrence occurs in 20% to 40% of adults with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL) who are treated with chemotherapy and tyrosine kinase ...inhibitors (TKIs). In the current study, the authors report the incidence, treatment, and outcome after first disease recurrence in young and older adults treated in the ALL Ph08 trial (ClinicalTrials.gov identifier NCT01491763).
Methods
Patients aged 18 to 55 years with de novo Ph+ ALL were treated with imatinib concurrently with standard‐dose induction and consolidation therapy followed by allogeneic hematopoietic stem cell transplantation (allo‐HSCT) when possible. In patients with first disease recurrence, the authors analyzed the type of recurrence, timing, location, presence of kinase domain mutations, type of treatment, and outcomes.
Results
Of the 125 patients, 28 patients (22%) developed disease recurrence before (4 patients) or after (24 patients) HSCT, with the recurrences being molecular in 11 patients (39%) and overt in 17 patients (61%). T315I was the most common mutation noted at the time of disease recurrence. Change in TKI was the most frequent treatment for patients with molecular disease recurrence whereas rescue chemotherapy and TKI change followed by second allo‐HSCT when possible were performed for the most part in patients with overt disease recurrence. A total of 20 patients (71%) achieved response. The median disease‐free survival (DFS) and overall survival (OS) were 8.5 months and 15.3 months, respectively. A trend for better DFS and OS was observed in patients with molecular recurrence compared with those with overt recurrence (median of 16.9 months vs 6.3 months P = .05 and 28.7 months vs 11.5 months P = .05 for DFS and OS, respectively).
Conclusions
Disease recurrence was frequent in young and older adults with Ph+ ALL who were treated with imatinib and chemotherapy with HSCT. Although the majority of patients responded to rescue therapy, their outcomes were poor, especially with regard to overt disease recurrence.
Outcomes after first disease recurrence in adults with Philadelphia chromosome–positive acute lymphoblastic leukemia are poor. Patients with overt disease recurrence appear to have a worse prognosis compared with those with molecular recurrence.
Diabetes is a common cause of shortened life expectancy. We aimed to assess the association between diabetes and cause-specific death.
We used the pooled analysis of individual data from 12 Spanish ...population cohorts with 10-year follow-up. Participants had no previous history of cardiovascular diseases and were 35-79 years old. Diabetes status was self-reported or defined as glycemia >125 mg/dL at baseline. Vital status and causes of death were ascertained by medical records review and linkage with the official death registry. The hazard ratios and cumulative mortality function were assessed with two approaches, with and without competing risks: proportional subdistribution hazard (PSH) and cause-specific hazard (CSH), respectively. Multivariate analyses were fitted for cardiovascular, cancer, and noncardiovascular noncancer deaths.
We included 55,292 individuals (15.6% with diabetes and overall mortality of 9.1%). The adjusted hazard ratios showed that diabetes increased mortality risk: 1) cardiovascular death, CSH = 2.03 (95% CI 1.63-2.52) and PSH = 1.99 (1.60-2.49) in men; and CSH = 2.28 (1.75-2.97) and PSH = 2.23 (1.70-2.91) in women; 2) cancer death, CSH = 1.37 (1.13-1.67) and PSH = 1.35 (1.10-1.65) in men; and CSH = 1.68 (1.29-2.20) and PSH = 1.66 (1.25-2.19) in women; and 3) noncardiovascular noncancer death, CSH = 1.53 (1.23-1.91) and PSH = 1.50 (1.20-1.89) in men; and CSH = 1.89 (1.43-2.48) and PSH = 1.84 (1.39-2.45) in women. In all instances, the cumulative mortality function was significantly higher in individuals with diabetes.
Diabetes is associated with premature death from cardiovascular disease, cancer, and noncardiovascular noncancer causes. The use of CSH and PSH provides a comprehensive view of mortality dynamics in a population with diabetes.
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