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Blood Jul 2024Myelodysplastic syndromes/neoplasms (MDS) are clonal hematologic disorders characterized by morphologic abnormalities of myeloid cells and peripheral cytopenias. While...
Myelodysplastic syndromes/neoplasms (MDS) are clonal hematologic disorders characterized by morphologic abnormalities of myeloid cells and peripheral cytopenias. While genetic abnormalities underlie the pathogenesis of these disorders and their heterogeneity, current classifications of MDS rely predominantly on morphology. We performed genomic profiling of 3,233 patients with MDS or related disorders to delineate molecular subtypes and define their clinical implications. Gene mutations, copy-number alterations (CNAs), and copy-neutral loss of heterozygosity (cnLOH) were derived from targeted sequencing of a 152-gene panel, with abnormalities identified in 91, 43, and 11% of patients, respectively. We characterized 16 molecular groups, encompassing 86% of patients, using information from 21 genes, 6 cytogenetic events, and LOH at the TP53 and TET2 loci. Two residual groups defined by negative findings (molecularly not-otherwise specified, absence of recurrent drivers) comprised 14% of patients. The groups varied in size from 0.5% to 14% of patients and were associated with distinct clinical phenotypes and outcomes. The median bone marrow blast percentage across groups ranged from 1.5 to 10%, and the median overall survival from 0.9 to 8.2 years. We validated 5 well-characterized entities, added further evidence to support 3 previously reported subsets, and described 8 novel groups. The prognostic influence of bone marrow blasts depended on the genetic subtypes. Within genetic subgroups, therapy-related MDS and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) had comparable clinical and outcome profiles to primary MDS. In conclusion, genetically-derived subgroups of MDS are clinically relevant and may inform future classification schemas and translational therapeutic research.
PubMed: 38958467
DOI: 10.1182/blood.2023023727 -
PM & R : the Journal of Injury,... Jul 2024Patients' interactions with health care providers influence back pain-related outcomes. The Health Care Providers' Pain and Impairment Relationship Scale (HC-PAIRS) is... (Review)
Review
OBJECTIVES
Patients' interactions with health care providers influence back pain-related outcomes. The Health Care Providers' Pain and Impairment Relationship Scale (HC-PAIRS) is an instrument that assesses providers' attitudes and beliefs about patients with persistent back pain, with lower scores implying that persistent pain does not indicate disability or limitation of activities. This scoping review aims to explore the extent of research involving the HC-PAIRS.
LITERATURE SURVEY
PubMed, Embase, and PEDro databases were searched from inception to April 2022.
METHODS
Extracted HC-PAIRS scores were standardized to 15-item scores and categorized by profession, student or professional status, and pre/post-educational intervention to evaluate scores. Psychometric properties and educational interventions of the HC-PAIRS were described.
RESULTS
After screening, 51 studies representing 10,416 participants were included. Student and professional scores were investigated in 24 and 29 studies, respectively. Twenty-one studies included educational interventions, with heterogenous follow-up. Psychometric properties of the HC-PAIRS were assessed in 10 studies and demonstrated acceptable reliability and validity. The overall baseline mean score among all participants was 55.34 (95% CI: 53.54-57.14) (students: 56.54 [56.54-60.87]; professionals: 51.67 [49.08-54.27]). Nurses (61.99 [55.66-68.31]) and non-health care professionals (65.30 [57.33-73.28]) had the highest overall baseline mean scores, whereas chiropractors (51.69 [33.73-69.66]), MDs/PAs (52.64 [47.27-58.00]), physical therapists (53.42 [50.67-56.17]), and exercise professionals (57.36 [49.39-65.33]) had lower scores.
CONCLUSIONS
The HC-PAIRS has been used across many disciplines in both students and professionals and demonstrated acceptable reliability and validity. Professionals commonly treating back pain had lower HC-PAIRS scores. Future research could benefit from standardization of interventions and timing of follow-up assessments.
PubMed: 38958442
DOI: 10.1002/pmrj.13186 -
Alzheimer's & Dementia : the Journal of... Jul 2024Sodium-glucose cotransporter 2 (SGLT2) inhibitors exhibit potential benefits in reducing dementia risk, yet the optimal beneficiary subgroups remain uncertain.
INTRODUCTION
Sodium-glucose cotransporter 2 (SGLT2) inhibitors exhibit potential benefits in reducing dementia risk, yet the optimal beneficiary subgroups remain uncertain.
METHODS
Individuals with type 2 diabetes (T2D) initiating either SGLT2 inhibitor or sulfonylurea were identified from OneFlorida+ Clinical Research Network (2016-2022). A doubly robust learning was deployed to estimate risk difference (RD) and 95% confidence interval (CI) of all-cause dementia.
RESULTS
Among 35,458 individuals with T2D, 1.8% in the SGLT2 inhibitor group and 4.7% in the sulfonylurea group developed all-cause dementia over a 3.2-year follow-up, yielding a lower risk for SGLT2 inhibitors (RD, -2.5%; 95% CI, -3.0% to -2.1%). Hispanic ethnicity and chronic kidney disease were identified as the two important variables to define four subgroups in which RD ranged from -4.3% (-5.5 to -3.2) to -0.9% (-1.9 to 0.2).
DISCUSSION
Compared to sulfonylureas, SGLT2 inhibitors were associated with a reduced risk of all-cause dementia, but the association varied among different subgroups.
HIGHLIGHTS
New users of sodium-glucose cotransporter 2 (SGLT2) inhibitors were significantly associated with a lower risk of all-cause dementia as compared to those of sulfonylureas. The association varied among different subgroups defined by Hispanic ethnicity and chronic kidney disease. A significantly lower risk of Alzheimer's disease and vascular dementia was observed among new users of SGLT2 inhibitors compared to those of sulfonylureas.
PubMed: 38958394
DOI: 10.1002/alz.14048 -
Arquivos Brasileiros de Cirurgia... 2024Despite the preference for multimodal treatment for gastric cancer, abandonment of chemotherapy treatment as well as the need for upfront surgery in obstructed patients...
PERIOPERATIVE CHEMOTHERAPY, ADJUVANT CHEMOTHERAPY AND ADJUVANT CHEMORADIOTHERAPY IN THE SURGICAL TREATMENT OF GASTRIC CANCER IN A HOSPITAL OF THE BRAZILIAN UNIFIED HEALTH SYSTEM.
BACKGROUND
Despite the preference for multimodal treatment for gastric cancer, abandonment of chemotherapy treatment as well as the need for upfront surgery in obstructed patients brings negative impacts on the treatment. The difficulty of accessing treatment in specialized centers in the Brazilian Unified National Health System (SUS) scenario is an aggravating factor.
AIMS
To identify advantages, prognostic factors, complications, and neoadjuvant and adjuvant therapies survival in gastric cancer treatment in SUS setting.
METHODS
The retrospective study included 81 patients with gastric adenocarcinoma who underwent treatment according to INT0116 trial (adjuvant chemoradiotherapy), CLASSIC trial (adjuvant chemotherapy), FLOT4-AIO trial (perioperative chemotherapy), and surgery with curative intention (R0 resection and D2 lymphadenectomy) in a single cancer center between 2015 and 2020. Individuals with other histological types, gastric stump, esophageal cancer, other treatment protocols, and stage Ia or IV were excluded.
RESULTS
Patients were grouped into FLOT4-AIO (26 patients), CLASSIC (25 patients), and INT0116 (30 patients). The average age was 61 years old. More than 60% of patients had pathological stage III. The treatment completion rate was 56%. The pathological complete response rate of the FLOT4-AIO group was 7.7%. Among the prognostic factors that impacted overall survival and disease-free survival were alcoholism, early postoperative complications, and anatomopathological status pN2 and pN3. The 3-year overall survival rate was 64.9%, with the CLASSIC subgroup having the best survival (79.8%).
CONCLUSIONS
The treatment strategy for gastric cancer varies according to the need for initial surgery. The CLASSIC subgroup had better overall survival and disease-free survival. The INT0116 regimen also protected against mortality, but not with statistical significance. Although FLOT4-AIO is the preferred treatment, the difficulty in carrying out neoadjuvant treatment in SUS scenario had a negative impact on the results due to the criticality of food intake and worse treatment tolerance.
Topics: Humans; Stomach Neoplasms; Middle Aged; Male; Female; Chemotherapy, Adjuvant; Retrospective Studies; Brazil; Aged; Chemoradiotherapy, Adjuvant; Adenocarcinoma; Adult; Prognosis; National Health Programs; Gastrectomy; Neoadjuvant Therapy; Treatment Outcome; Neoplasm Staging; Perioperative Care
PubMed: 38958346
DOI: 10.1590/0102-6720202400017e1810 -
Arquivos Brasileiros de Cirurgia... 2024Advanced megaesophagus predisposes to risks of malnutrition infections and cancer, in addition to having a significant impact on quality of life. There is currently no... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Advanced megaesophagus predisposes to risks of malnutrition infections and cancer, in addition to having a significant impact on quality of life. There is currently no consensus in the literature regarding the best surgical option for advanced megaesophagus, although there is a predilection for esophagectomy, despite this surgery being associated with significant morbidity and mortality. Other surgical procedures, such as esophageal mucosectomy and Heller cardiomyotomy, have been proposed with good results.
AIMS
To conduct a systematic review and meta-analysis of the literature on the surgical treatment of advanced megaesophagus.
METHODS
Databases used included PubMed, Latin American and Caribbean Health Sciences Literature (Lilacs), Embase and Medical Literature Analysis and Retrieval System Online (MedLine), as well as reference research. Two reviewers selected the articles independently.
RESULTS
A total of 14 articles were chosen, which included 1,862 patients. The studies were divided into two groups: laparoscopic cardiomyotomy with fundoplication (213 patients) and major surgeries (1,649 patients). The studies yielded mostly good or excellent results regarding late outcomes in both groups. However, there was significant morbidity associated with the major surgeries group.
CONCLUSIONS
Laparoscopic Heller myotomy can be performed on patients with advanced megaesophagus, with lower rates of complications and mortality compared to major surgeries, with reservations regarding late outcomes results.
Topics: Humans; Esophageal Achalasia; Treatment Outcome
PubMed: 38958345
DOI: 10.1590/0102-6720202400016e1809 -
Arquivos Brasileiros de Cirurgia... 2024Deep penetrating endometriosis (DE) can affect abdominal and pelvic organs like the bowel and bladder, requiring treatment to alleviate symptoms.
BACKGROUND
Deep penetrating endometriosis (DE) can affect abdominal and pelvic organs like the bowel and bladder, requiring treatment to alleviate symptoms.
AIMS
To study and investigate clinical and surgical outcomes in patients diagnosed with DE involving the intestines, aiming to analyze the effectiveness of surgical treatments.
METHODS
All cases treated from January 2021 to July 2023 were included, focusing on patients aged 18 years or older with the disease affecting the intestines. Patients without intestinal involvement and those with less than six months of post-surgery follow-up were excluded. Intestinal involvement was defined as direct invasion of the intestinal wall or requiring adhesion lysis for complete resection. Primary outcomes were adhesion lysis, rectal shaving, disc excision (no-colectomy group), and segmental resection (colectomy group) along with surgical complications like anastomotic leak and fistulas, monitored for up to 30 days.
RESULTS
Out of 169 patients with DE surgically treated, 76 met the inclusion criteria. No colectomy treatment was selected for 50 (65.7%) patients, while 26 (34.2%) underwent rectosigmoidectomy (RTS). Diarrhea during menstruation was the most prevalent symptom in the RTS group (19.2 vs. 6%, p<0.001). Surgical outcomes indicated longer operative times and hospital stays for the segmental resection group, respectively 186.5 vs. 104 min (p<0.001) and 4 vs. 2 days, (p<0.001). Severe complications (Clavien-Dindo ≥3) had an overall prevalence of 6 (7.9%) cases, without any difference between the groups. There was no mortality reported. Larger lesions and specific symptoms like dyschezia and rectal bleeding were associated with a higher likelihood of RTS. Bayesian regression highlighted diarrhea close to menstruation as a strong predictor of segmental resection.
CONCLUSIONS
In patients with DE involving the intestines, symptoms such as dyschezia, rectal bleeding, and menstrual period-related diarrhea predict RTS. However, severe complication rates did not differ significantly between the segmental resection group and no-colectomy group.
Topics: Humans; Female; Endometriosis; Adult; Treatment Outcome; Retrospective Studies; Intestinal Diseases; Postoperative Complications; Middle Aged; Colectomy; Young Adult
PubMed: 38958344
DOI: 10.1590/0102-6720202400013e1806 -
Acta Cirurgica Brasileira 2024To evaluate using a biocellulose-based hydrogel as an adjuvant in the healing process of arterial ulcers.
PURPOSE
To evaluate using a biocellulose-based hydrogel as an adjuvant in the healing process of arterial ulcers.
METHODS
A prospective single group quasi-experimental study was carried out with chronic lower limb arterial ulcer patients. These patients received biocellulose-based hydrogel dressings and outpatient guidance on dressing and periodic reassessments. The primary outcomes were the ulcer-healing rate and product safety, which were assessed by ulcer area measured in photographic records of pre-treatment and posttreatment after 7, 30, and 60 days. Secondary outcomes were related to clinical assessment by the quality-of-life scores (SF-36 and EQ-5D) and pain, evaluated by the visual analogue scale (VAS).
RESULTS
Seventeen participants were included, and one of them was excluded. Six patients (37%) had complete wound healing, and all patients had a significant reduction in the ulcer area during follow-up (233.6mm2 versus 2.7mm2) and reduction on the score PUSH 3.0 (p < 0.0001). The analysis of the SF-36 and EQ-5D questionnaires showed a statistically significant improvement in almost all parameters analyzed and with a reduction of pain assessed by the VAS.
CONCLUSIONS
The biocellulose-based hydrogel was safe and showed a good perspective to promoting the necessary conditions to facilitate partial or complete healing of chronic arterial ulcers within a 60-day follow-up. Quality of life and pain were positively affected by the treatment.
Topics: Humans; Male; Female; Wound Healing; Prospective Studies; Middle Aged; Aged; Quality of Life; Treatment Outcome; Chronic Disease; Cellulose; Leg Ulcer; Bandages; Aged, 80 and over; Pain Measurement; Hydrogels
PubMed: 38958305
DOI: 10.1590/acb392924 -
International Journal of Cancer Jul 2024The overall survival (OS) improvement after the advent of several novel systemic therapies, designed for treatment of metastatic urothelial carcinoma of the urinary...
The overall survival (OS) improvement after the advent of several novel systemic therapies, designed for treatment of metastatic urothelial carcinoma of the urinary bladder (mUCUB), is not conclusively studied in either contemporary UCUB patients and/or non-UCUB patients. Within the Surveillance, Epidemiology, and End Results database, contemporary (2017-2020) and historical (2000-2016) systemic therapy-exposed metastatic UCUB and, subsequently, non-UCUB patients were identified. Separate Kaplan-Meier and multivariable Cox regression (CRM) analyses first addressed OS in mUCUB and, subsequently, in metastatic non-UCUB (mn-UCUB). Of 3443 systemic therapy-exposed patients, 2725 (79%) harbored mUCUB versus 709 (21%) harbored mn-UCUB. Of 2725 mUCUB patients, 582 (21%) were contemporary (2017-2020) versus 2143 (79%) were historical (2000-2016). In mUCUB, median OS was 11 months in contemporary versus 8 months in historical patients (Δ = 3 months; p < .0001). After multivariable CRM, contemporary membership status (2017-2020) independently predicted lower overall mortality (OM; hazard ratio [HR] = 0.68, 95% confidence interval [CI] = 0.60-0.76; p < .001). Of 709 mn-UCUB patients, 167 (24%) were contemporary (2017-2020) and 542 (76%) were historical (2000-2016). In mn-UCUB, median OS was 8 months in contemporary versus 7 months in historical patients (Δ = 1 month; p = .034). After multivariable CRM, contemporary membership status (2017-2020) was associated with HR of 0.81 (95% CI = 0.66-1.01; p = .06). In conclusion, contemporary systemic therapy-exposed metastatic patients exhibited better OS in UCUB. However, the magnitude of survival benefit was threefold higher in mUCUB and approximated the survival benefits recorded in prospective randomized trials of novel systemic therapies.
PubMed: 38958288
DOI: 10.1002/ijc.35077 -
The Journal of Antimicrobial... Jul 2024The risk factors and outcomes associated with persistent bacteraemia in Gram-negative bloodstream infection (GN-BSI) are not well described. We conducted a follow-on...
OBJECTIVES
The risk factors and outcomes associated with persistent bacteraemia in Gram-negative bloodstream infection (GN-BSI) are not well described. We conducted a follow-on analysis of a retrospective population-wide cohort to characterize persistent bacteraemia in patients with GN-BSI.
METHODS
We included all hospitalized patients >18 years old with GN-BSI between April 2017 and December 2021 in Ontario who received follow-up blood culture (FUBC) 2-5 days after the index positive blood culture. Persistent bacteraemia was defined as having a positive FUBC with the same Gram-negative organism as the index blood culture. We identified variables independently associated with persistent bacteraemia in a multivariable logistic regression model. We evaluated whether persistent bacteraemia was associated with increased odds of 30- and 90-day all-cause mortality using multivariable logistic regression models adjusted for potential confounders.
RESULTS
In this study, 8807 patients were included; 600 (6.8%) had persistent bacteraemia. Having a permanent catheter, antimicrobial resistance, nosocomial infection, ICU admission, respiratory or skin and soft tissue source of infection, and infection by a non-fermenter or non-Enterobacterales/anaerobic organism were associated with increased odds of having persistent bacteraemia. The 30-day mortality was 17.2% versus 9.6% in those with and without persistent bacteraemia (aOR 1.65, 95% CI 1.29-2.11), while 90-day mortality was 25.5% versus 16.9%, respectively (aOR 1.53, 95% CI 1.24-1.89). Prevalence and odds of developing persistent bacteraemia varied widely depending on causative organism.
CONCLUSIONS
Persistent bacteraemia is uncommon in GN-BSI but is associated with poorer outcomes. A validated risk stratification tool may be useful to identify patients with persistent bacteraemia.
PubMed: 38958258
DOI: 10.1093/jac/dkae211 -
Child: Care, Health and Development Jul 2024Early executive functioning (EF) skills are foundational capabilities that predict school readiness, academic development and psychiatric risk. Early interventions...
BACKGROUND
Early executive functioning (EF) skills are foundational capabilities that predict school readiness, academic development and psychiatric risk. Early interventions enhancing these capabilities could have critical import in improving outcomes. However, to develop interventions, it is necessary to identify specific EF skills that will vary with child age. Thus, we aimed to examine the characteristics and efficacy of interventions targeting EF in infancy and early childhood up to age 3.
METHODS
A comprehensive search of PubMed, Embase, CINAHL and APA PsycINFO databases was performed for studies published before December 2022. Randomized and non-randomized studies of interventions designed to improve at least one EF skill in children ≤3 years were included. EF skills included attentional control, inhibition/self-regulation, activity initiation, working memory, cognitive flexibility, planning ability, problem-solving and performance monitoring. We independently extracted data, used the revised Cochrane Risk-of-Bias tool to assess the quality of the evidence and conducted Synthesis Without Meta-analysis (SWiM). The overall quality of the evidence and the strength of recommendations was determined using elements of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
RESULTS
Thirty-five studies met inclusion criteria (original n = 7467). Studies were highly variable in the EF skill targeted, target subject (i.e., child, parent and teacher), nature and dosage of the intervention, and timing of outcome assessment. Most interventions focused on improving impulse control and self-regulation. The overall quality of evidence was low to moderate with a high risk of bias, though six studies had low risk of bias but yielded mixed findings of efficacy.
CONCLUSIONS
The relatively small number of early EF intervention studies uses such variable methods that there is currently no converging evidence of efficacy to recommend a specific intervention. Thus, findings support the need for a more systematic, targeted approach to the design and implementation of early EF interventions for target populations.
Topics: Humans; Executive Function; Child, Preschool; Infant; Child Development; Early Intervention, Educational
PubMed: 38958229
DOI: 10.1111/cch.13298