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Archives of Gynecology and Obstetrics Aug 2022Endometrial hyperplasia (EH) is the precursor lesion for endometrioid adenocarcinoma of the endometrium (EC), which represents the most common malignancy of the female... (Review)
Review
Endometrial hyperplasia (EH) is the precursor lesion for endometrioid adenocarcinoma of the endometrium (EC), which represents the most common malignancy of the female reproductive tract in industrialized countries. The most important risk factor for the development of EH is chronic exposure to unopposed estrogen. Histopathologically, EH can be classified into EH without atypia (benign EH) and atypical EH/endometrial intraepithelial neoplasia (EIN). Clinical management ranges from surveillance or progestin therapy through to hysterectomy, depending on the risk of progression to or concomitant EC and the patient´s desire to preserve fertility. Multiple studies support the efficacy of progestins in treating both benign and atypical EH. This review summarizes the evidence base regarding risk factors and management of EH. Additionally, we performed a systematic literature search of the databases PubMed and Cochrane Controlled Trials register for studies analyzing the efficacy of progestin treatment in women with EH.
Topics: Endometrial Hyperplasia; Endometrial Neoplasms; Endometrium; Female; Humans; Progestins; Risk Factors
PubMed: 35001185
DOI: 10.1007/s00404-021-06380-5 -
A systematic review of the effect of L-tryptophan supplementation on mood and emotional functioning.Journal of Dietary Supplements 2021L-tryptophan (TRP), one of the essential amino acids in humans, is a precursor of serotonin, and hence its intake is closely related to the suppression of depressed and...
L-tryptophan (TRP), one of the essential amino acids in humans, is a precursor of serotonin, and hence its intake is closely related to the suppression of depressed and anxious moods. We did a systematic review of RCTs to examine the effects of tryptophan intake on the mood of healthy adults by searching PubMed, the Cochrane Library, and Ichu-shi according to PRISMA guidelines. As a result, 11 RCTs met the criteria and were accepted. Four RCTs showed the effects of tryptophan intake on negative feelings and happy feelings in healthy individuals, with significant differences between the treatment and the control groups. This suggests that TRP intake may be an effective approach to decrease anxiety and increase positive mood in healthy individuals. On the other hand, the effectiveness of TRP for aggressive feelings was not recognized. Reviewing these 11 RCTs, we concluded that taking 0.14-3g of TRP per day in addition to the usual meal can be expected to improve the mood of healthy individuals. In order to estimate the optimum amount of TRP intake more accurately, further studies need to be conducted with more appropriate settings of intake period, intake frequency, and intake method.
Topics: Adult; Affect; Dietary Supplements; Emotions; Humans; Randomized Controlled Trials as Topic; Serotonin; Tryptophan
PubMed: 32272859
DOI: 10.1080/19390211.2020.1746725 -
Annual Review of Clinical Psychology 2015Postpartum depression (PPD) adversely affects the health and well being of many new mothers, their infants, and their families. A comprehensive understanding of... (Review)
Review
Postpartum depression (PPD) adversely affects the health and well being of many new mothers, their infants, and their families. A comprehensive understanding of biopsychosocial precursors to PPD is needed to solidify the current evidence base for best practices in translation. We conducted a systematic review of research published from 2000 through 2013 on biological and psychosocial factors associated with PPD and postpartum depressive symptoms. Two hundred fourteen publications based on 199 investigations of 151,651 women in the first postpartum year met inclusion criteria. The biological and psychosocial literatures are largely distinct, and few studies provide integrative analyses. The strongest PPD risk predictors among biological processes are hypothalamic-pituitary-adrenal dysregulation, inflammatory processes, and genetic vulnerabilities. Among psychosocial factors, the strongest predictors are severe life events, some forms of chronic strain, relationship quality, and support from partner and mother. Fully integrated biopsychosocial investigations with large samples are needed to advance our knowledge of PPD etiology.
Topics: Depression, Postpartum; Endocrine System Diseases; Female; Humans; Pregnancy; Psychology; Risk Factors
PubMed: 25822344
DOI: 10.1146/annurev-clinpsy-101414-020426 -
Clinical Lymphoma, Myeloma & Leukemia Jan 2021Philadelphia-like (Ph-like) acute lymphoblastic leukemia (ALL) is a subgroup of B-cell precursor ALL (BCP-ALL) with a gene expression profile analogous to... (Review)
Review
Philadelphia-like (Ph-like) acute lymphoblastic leukemia (ALL) is a subgroup of B-cell precursor ALL (BCP-ALL) with a gene expression profile analogous to Philadelphia-positive ALL and recurrent IKAROS Family Zinc Finger 1 (IKZF1) gene deletion despite lacking BCR-ABL1 (Breakpoint cluster region-ABL protooncogene) translocation. Although recognized to occur at all ages, the proportion of cases among BCP-ALL varies (< 10% in children and up to 30% in adolescents). In all age groups, males are more commonly affected. Generally, Ph-like ALL is associated with adverse clinical features and an increased risk of treatment failure with conventional approaches. Genetic alterations such as aberrant expression, point mutations, or fusion translocations lead to activation of cytokine receptors and signaling kinases, which affect the ABL1 (ABL class fusion) or Janus Kinase (JAK) signaling pathways. Several clinical trials are being conducted to understand whether specific tyrosine kinase inhibitor therapy can improve cure rates. This review summarizes the current literature available about this entity.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Philadelphia Chromosome; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Young Adult
PubMed: 33485429
DOI: 10.1016/j.clml.2020.08.011 -
Cureus Oct 2022Psilocybin is a plant alkaloid that is derived from precursors of tryptamine and is present in many different types of mushrooms. It has been utilized by indigenous... (Review)
Review
Psilocybin is a plant alkaloid that is derived from precursors of tryptamine and is present in many different types of mushrooms. It has been utilized by indigenous peoples of Central and South America for centuries in a ceremonial setting to promote spiritual experiences. Indigenous societies have long employed psilocybin and other 5-HT 2A agonist classic psychedelics in their rites. They were a focus in psychiatry in the middle of the 20th century as both experimental medicines and tools for studying brain function. Due to the fact that traditional psychedelics were being used for purposes other than medical research and in connection with the burgeoning counterculture by the late 1960s and early 1970s, these scientific investigations fell out of favor. However, thanks to a number of encouraging studies that validated the earlier research, interest in traditional psychedelics has surged among scientists in the 21st century. In this review, we examine therapeutic studies on psilocybin, the traditional psychedelic that has received the lion's share of recent attention. According to three controlled studies, psilocybin may reduce symptoms of depression and anxiety in the context of cancer-related psychological discomfort for at least six months after a single acute treatment for mood and anxiety disorders. Three months after two acute doses, individuals in a small, open-label study with treatment-resistant depression reported fewer depressive and anxiety symptoms. Small, open-label pilot studies on addiction have demonstrated encouraging success rates for alcohol and cigarette addiction. The review also briefly discusses the synthesis, mechanism of action, effects, molecular pharmacology, adverse effects, and contraindications of psilocybin.
PubMed: 36381758
DOI: 10.7759/cureus.30214 -
Experimental Gerontology Apr 2020Nicotinamide adenine dinucleotide (NAD+) is an essential pyridine nucleotide that is present in all living cells. NAD+ acts as an important cofactor and substrate for a...
Nicotinamide adenine dinucleotide (NAD+) is an essential pyridine nucleotide that is present in all living cells. NAD+ acts as an important cofactor and substrate for a multitude of biological processes including energy production, DNA repair, gene expression, calcium-dependent secondary messenger signalling and immunoregulatory roles. The de novo synthesis of NAD+ is primarily dependent on the kynurenine pathway (KP), although NAD+ can also be recycled from nicotinic acid (NA), nicotinamide (NAM) and nicotinamide riboside (NR). NAD+ levels have been reported to decline during ageing and age-related diseases. Recent studies have shown that raising intracellular NAD+ levels represents a promising therapeutic strategy for age-associated degenerative diseases in general and to extend lifespan in small animal models. A systematic review of the literature available on Medline, Embase and Pubmed was undertaken to evaluate the potential health and/or longevity benefits due to increasing NAD+ levels. A total of 1545 articles were identified and 147 articles (113 preclinical and 34 clinical) met criteria for inclusion. Most studies indicated that the NAD+ precursors NAM, NR, nicotinamide mononucleotide (NMN), and to a lesser extent NAD+ and NADH had a favourable outcome on several age-related disorders associated with the accumulation of chronic oxidative stress, inflammation and impaired mitochondrial function. While these compounds presented with a limited acute toxicity profile, evidence is still quite limited and long-term human clinical trials are still nascent in the current literature. Potential risks in raising NAD+ levels in various clinical disorders using NAD+ precursors include the accumulation of putative toxic metabolites, tumorigenesis and promotion of cellular senescence. Therefore, NAD+ metabolism represents a promising target and further studies are needed to recapitulate the preclinical benefits in human clinical trials.
Topics: Aging; Animals; Humans; Inflammation; Mice; NAD; Neurodegenerative Diseases; Niacinamide; Nicotinamide Mononucleotide; Oxidative Stress; Pyridinium Compounds; Rats; Risk Assessment
PubMed: 31917996
DOI: 10.1016/j.exger.2020.110831 -
The Cochrane Database of Systematic... Oct 2017Acute respiratory infections (ARIs) comprise of a large and heterogeneous group of infections including bacterial, viral, and other aetiologies. In recent years,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Acute respiratory infections (ARIs) comprise of a large and heterogeneous group of infections including bacterial, viral, and other aetiologies. In recent years, procalcitonin (PCT), a blood marker for bacterial infections, has emerged as a promising tool to improve decisions about antibiotic therapy (PCT-guided antibiotic therapy). Several randomised controlled trials (RCTs) have demonstrated the feasibility of using procalcitonin for starting and stopping antibiotics in different patient populations with ARIs and different settings ranging from primary care settings to emergency departments, hospital wards, and intensive care units. However, the effect of using procalcitonin on clinical outcomes is unclear. This is an update of a Cochrane review and individual participant data meta-analysis first published in 2012 designed to look at the safety of PCT-guided antibiotic stewardship.
OBJECTIVES
The aim of this systematic review based on individual participant data was to assess the safety and efficacy of using procalcitonin for starting or stopping antibiotics over a large range of patients with varying severity of ARIs and from different clinical settings.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE, and Embase, in February 2017, to identify suitable trials. We also searched ClinicalTrials.gov to identify ongoing trials in April 2017.
SELECTION CRITERIA
We included RCTs of adult participants with ARIs who received an antibiotic treatment either based on a procalcitonin algorithm (PCT-guided antibiotic stewardship algorithm) or usual care. We excluded trials if they focused exclusively on children or used procalcitonin for a purpose other than to guide initiation and duration of antibiotic treatment.
DATA COLLECTION AND ANALYSIS
Two teams of review authors independently evaluated the methodology and extracted data from primary studies. The primary endpoints were all-cause mortality and treatment failure at 30 days, for which definitions were harmonised among trials. Secondary endpoints were antibiotic use, antibiotic-related side effects, and length of hospital stay. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable hierarchical logistic regression adjusted for age, gender, and clinical diagnosis using a fixed-effect model. The different trials were added as random-effects into the model. We conducted sensitivity analyses stratified by clinical setting and type of ARI. We also performed an aggregate data meta-analysis.
MAIN RESULTS
From 32 eligible RCTs including 18 new trials for this 2017 update, we obtained individual participant data from 26 trials including 6708 participants, which we included in the main individual participant data meta-analysis. We did not obtain individual participant data for four trials, and two trials did not include people with confirmed ARIs. According to GRADE, the quality of the evidence was high for the outcomes mortality and antibiotic exposure, and quality was moderate for the outcomes treatment failure and antibiotic-related side effects.Primary endpoints: there were 286 deaths in 3336 procalcitonin-guided participants (8.6%) compared to 336 in 3372 controls (10.0%), resulting in a significantly lower mortality associated with procalcitonin-guided therapy (adjusted OR 0.83, 95% CI 0.70 to 0.99, P = 0.037). We could not estimate mortality in primary care trials because only one death was reported in a control group participant. Treatment failure was not significantly lower in procalcitonin-guided participants (23.0% versus 24.9% in the control group, adjusted OR 0.90, 95% CI 0.80 to 1.01, P = 0.068). Results were similar among subgroups by clinical setting and type of respiratory infection, with no evidence for effect modification (P for interaction > 0.05). Secondary endpoints: procalcitonin guidance was associated with a 2.4-day reduction in antibiotic exposure (5.7 versus 8.1 days, 95% CI -2.71 to -2.15, P < 0.001) and lower risk of antibiotic-related side effects (16.3% versus 22.1%, adjusted OR 0.68, 95% CI 0.57 to 0.82, P < 0.001). Length of hospital stay and intensive care unit stay were similar in both groups. A sensitivity aggregate-data analysis based on all 32 eligible trials showed similar results.
AUTHORS' CONCLUSIONS
This updated meta-analysis of individual participant data from 12 countries shows that the use of procalcitonin to guide initiation and duration of antibiotic treatment results in lower risks of mortality, lower antibiotic consumption, and lower risk for antibiotic-related side effects. Results were similar for different clinical settings and types of ARIs, thus supporting the use of procalcitonin in the context of antibiotic stewardship in people with ARIs. Future high-quality research is needed to confirm the results in immunosuppressed patients and patients with non-respiratory infections.
Topics: Acute Disease; Anti-Bacterial Agents; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Cause of Death; Humans; Protein Precursors; Randomized Controlled Trials as Topic; Respiratory Tract Infections; Treatment Failure
PubMed: 29025194
DOI: 10.1002/14651858.CD007498.pub3 -
Clinical Infectious Diseases : An... Jan 2020Because of the diverse etiologies of community-acquired pneumonia (CAP) and the limitations of current diagnostic modalities, serum procalcitonin levels have been... (Meta-Analysis)
Meta-Analysis
Because of the diverse etiologies of community-acquired pneumonia (CAP) and the limitations of current diagnostic modalities, serum procalcitonin levels have been proposed as a novel tool to guide antibiotic therapy. Outcome data from procalcitonin-guided therapy trials have shown similar mortality, but the essential question is whether the sensitivity and specificity of procalcitonin levels enable the practitioner to distinguish bacterial pneumonia, which requires antibiotic therapy, from viral pneumonia, which does not. In this meta-analysis of 12 studies in 2408 patients with CAP that included etiologic diagnoses and sufficient data to enable analysis, the sensitivity and specificity of serum procalcitonin were 0.55 (95% confidence interval [CI], .37-.71; I2 = 95.5%) and 0.76 (95% CI, .62-.86; I2 = 94.1%), respectively. Thus, a procalcitonin level is unlikely to provide reliable evidence either to mandate administration of antibiotics or to enable withholding such treatment in patients with CAP.
Topics: Anti-Bacterial Agents; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Community-Acquired Infections; Humans; Pneumonia; Pneumonia, Bacterial; Procalcitonin; Protein Precursors
PubMed: 31241140
DOI: 10.1093/cid/ciz545 -
Critical Reviews in Oncology/hematology Aug 2020Children with acute lymphoblastic leukemia (ALL) experience detrimental effects on motor function during and after chemotherapy. The objective of this systematic review...
The effect of exercise and motor interventions on physical activity and motor outcomes during and after medical intervention for children and adolescents with acute lymphoblastic leukemia: A systematic review.
BACKGROUND
Children with acute lymphoblastic leukemia (ALL) experience detrimental effects on motor function during and after chemotherapy. The objective of this systematic review was to evaluate the effect of exercise and motor interventions on physical activity and motor outcomes of children with ALL during and after chemotherapy.
METHODS
Ten databases were searched. Nineteen studies were included: 11 randomized clinical trials (RCT), 2 controlled clinical trials (CCT), and 6 cohort studies.
RESULTS
Participants included 508 children with ALL. Between-group results from RCTs and CCTs supported that exercise and motor intervention improved: fatigue during acute chemotherapy; physical activity, range of motion (ROM), strength, bone mineral density, aerobic capacity, and fatigue during maintenance chemotherapy; functional mobility, ROM, strength, and aerobic capacity during post-treatment survivorship; and participation, physical activity, ROM, strength, and coordination during multiple-phase interventions.
CONCLUSION
Low quality evidence supports the efficacy of motor and exercise interventions for children and adolescents with ALL.
Topics: Adolescent; Bone Density; Child; Exercise; Exercise Tolerance; Fatigue; Humans; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 32580035
DOI: 10.1016/j.critrevonc.2020.103004 -
Clinical Lymphoma, Myeloma & Leukemia Apr 2021Acute lymphoblastic leukemia (ALL) typically responds better when treated with multiagent chemotherapy in the pediatric and young adolescent populations. Treatment of... (Meta-Analysis)
Meta-Analysis
Systematic Review and Meta-analysis of CD19-Specific CAR-T Cell Therapy in Relapsed/Refractory Acute Lymphoblastic Leukemia in the Pediatric and Young Adult Population: Safety and Efficacy Outcomes.
Acute lymphoblastic leukemia (ALL) typically responds better when treated with multiagent chemotherapy in the pediatric and young adolescent populations. Treatment of relapsed/refractory (RR) ALL remains a challenge. Even after stem-cell transplantation and intensive chemotherapy, the prognosis of RR-ALL remains grave. The advent of chimeric antigen receptors has demonstrated promising results in RR-ALL. Chimeric antigen receptor-modified T cells (CAR-T) and engineered T cells are used to target cancer cells. In 2017, the US Food and Drug Administration approved CD19-specific CAR-T (tisagenlecleucel) therapy for RR-B-cell ALL in patients under 25 years old. In this systematic review, we discuss the efficacy and safety of CD19-specific CAR-T therapy in RR-B-cell ALL in the pediatric and young adult population. We searched the PubMed, Embase, Web of Science, Cochrane Library, and clinical trials databases. A total of 448 patients received a CD19-specific CAR-T product, and 446 patients had evaluable data. The age range was 0 to 30 years. The incidence rate of complete remission was 82%. The cumulative incidence of relapse after CD19-specific CAR-T therapy is 36%. Similarly, the incidence rate of grade 3 or higher adverse events of neutropenia, thrombocytopenia, neurotoxicity, infections, and cytokine release syndrome were 38%, 23%, 18%, 29%, and 19%, respectively. Our subgroup analysis shows the incidence rate of minimal residual negative complete remission was 69% with the CD28z costimulatory domain, 81% with the 4-1BB domain, and 77% with fourth-generation CD19-specific CAR-T therapy.
Topics: Adolescent; Antigens, CD19; Child; Cytokine Release Syndrome; Drug Resistance, Neoplasm; Humans; Immunotherapy, Adoptive; Neoplasm Recurrence, Local; Neurotoxicity Syndromes; Neutropenia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Progression-Free Survival; Receptors, Antigen, T-Cell; Receptors, Chimeric Antigen; Remission Induction; Thrombocytopenia; Young Adult
PubMed: 33573914
DOI: 10.1016/j.clml.2020.12.010