Purpose Several options exist for management of clinically localized renal masses suspicious for cancer, including active surveillance, thermal ablation and radical or partial nephrectomy. We ...summarize evidence on effectiveness and comparative effectiveness of these treatment approaches for patients with a renal mass suspicious for localized renal cell carcinoma. Materials and Methods We searched MEDLINE®, Embase® and the Cochrane Central Register of Controlled Trials from January 1, 1997 through May 1, 2015. Paired investigators independently screened articles to identify controlled studies of management options or cohort studies of active surveillance, abstracted data sequentially and assessed risk of bias independently. Strength of evidence was graded by comparisons. Results The search identified 107 studies (majority T1, no active surveillance or thermal ablation stratified outcomes of T2 tumors). Cancer specific survival was excellent among all management strategies (median 5-year survival 95%). Local recurrence-free survival was inferior for thermal ablation with 1 treatment but reached equivalence to other modalities after multiple treatments. Overall survival rates were similar among management strategies and varied with age and comorbidity. End-stage renal disease rates were low for all strategies (0.4% to 2.8%). Radical nephrectomy was associated with the largest decrease in estimated glomerular filtration rate and highest incidence of chronic kidney disease. Thermal ablation offered the most favorable perioperative outcomes. Partial nephrectomy showed the highest rates of urological complications but overall rates of minor/major complications were similar among interventions. Strength of evidence was moderate, low and insufficient for 11, 22 and 30 domains, respectively. Conclusions Comparative studies demonstrated similar cancer specific survival across management strategies, with some differences in renal functional outcomes, perioperative outcomes and postoperative harms that should be considered when choosing a management strategy.
Purpose Clinical practice varies widely on the diagnostic role of biopsy for clinically localized renal masses suspicious for renal cell carcinoma. Therefore, we performed a systematic review of the ...available literature to quantify the accuracy and rate of adverse events of renal mass biopsy. Materials and Methods MEDLINE®, Embase® and the Cochrane databases were searched (January 1997 to May 2015) for relevant studies. The systematic review process established by the Agency for Healthcare Research and Quality was followed. Nondiagnostic biopsies were excluded from diagnostic accuracy calculations. Results A total of 20 studies with 2,979 patients and 3,113 biopsies were included in the study. The overall nondiagnostic rate was 14.1% with 90.4% of those undergoing surgery found to have malignancy. Repeat biopsy led to diagnosis in 80% of patients. The false-positive rate was low (4.0%), histological and renal cell carcinoma subtype concordance was substantial, and Fuhrman upgrading notable (16%) from low grade (1 to 2) to high grade (3 to 4). Core biopsy was highly sensitive (97.5%, CI 96.5–98.5) and specific (96.2%, CI 90.7–100) when a diagnostic result was obtained, but most patients (∼80%) did not undergo surgery after a benign biopsy. Among patients undergoing extirpation 36.7% with a negative biopsy had malignant disease on surgical pathology (negative predictive value 63.3%, CI 52.4–74.2). Direct complications included hematoma (4.9%), clinically significant pain (1.2%), gross hematuria (1.0%), pneumothorax (0.6%) and hemorrhage (0.4%). Conclusions Diagnostic accuracy was generally high for biopsy of localized renal masses with a low complication rate, but the nondiagnostic rate and negative predictive value were concerning. Renal mass sampling should be used judiciously as further research will determine its true clinical utility.
Testis cancer is the most common solid malignancy in young males. The purpose of this guideline is to provide a useful reference on the effective evidence-based treatment of early stage testicular ...cancer.
The systematic review utilized to inform this guideline was conducted by a methodology team at the Johns Hopkins University Evidence-based Practice Center. The methodology team searched using PubMed®, Embase®, and the Cochrane Central Register of Controlled Trials (CENTRAL) from January 1980 through August 2018. The evidence review team also reviewed relevant systematic reviews and references provided by the panel to identify articles that may have been missed by the database searches.
When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low). Such evidence-based statements are provided as Strong, Moderate, or Conditional Recommendations. In instances of insufficient evidence, additional guidance is provided as Clinical Principles and Expert Opinions.
This guideline attempts to improve a clinician's ability to evaluate and treat patients with testicular cancer, but higher quality evidence in future trials will be essential to improve level of care for these patients.
The past few years have witnessed a notable rise in sedentary tendencies, unveiling a modern era of prolonged stillness and diminished physical engagement. This study sought to assess the feasibility ...of a digital health intervention (DHI) to reduce overall sedentary behavior among university students. The study also identifies distinct subgroups within Indian universities that exhibit a heightened propensity for engaging in unhealthy behaviors.
The research design used was a quasi-experimental (pre-post) design. A total of 500 participants were selected using a simple randomized sampling method (250 belonging to the control group and 250 belonging to the experimental group). These participants actively engaged in the study for 2 weeks. The participants completed the Sedentary Behavior Questionnaire (SBQ) before the intervention to evaluate their level of sedentary behavior. To evaluate the impact of the intervention on subjectively measured sedentary behavior, statistical analyses were conducted using the paired-samples
-test and analysis of covariance (ANCOVA) with the
Bonferroni test.
The findings demonstrated a significant t-value of sedentary behavior for the entire group, with t(249) = 4.88,
< .05. Furthermore, the F-value of 28.787 indicated a statistically significant difference in the sedentary behavior between the experimental and control groups. When considering female university students specifically, the t-value for sedentary behavior was significant at t(105) = 3.22,
< .05, and for male university students, the t-value for sedentary behavior was found to be significant at t(143) = 3.69,
< .05.
Smartphone-based health interventions targeting sedentary behavior reduction demonstrated promising outcomes in facilitating health behavior change among university students.
Background & Aims Nonalcoholic steatohepatitis (NASH) is associated with oxidative stress. We surmised that pharmacologic activation of NF-E2 p45-related factor 2 (Nrf2) using the acetylenic ...tricyclic bis(cyano enone) TBE-31 would suppress NASH because Nrf2 is a transcriptional master regulator of intracellular redox homeostasis. Methods Nrf2 +/+ and Nrf2 -/- C57BL/6 mice were fed a high-fat plus fructose (HFFr) or regular chow diet for 16 weeks or 30 weeks, and then treated for the final 6 weeks, while still being fed the same HFFr or regular chow diets, with either TBE-31 or dimethyl sulfoxide vehicle control. Measures of whole-body glucose homeostasis, histologic assessment of liver, and biochemical and molecular measurements of steatosis, endoplasmic reticulum (ER) stress, inflammation, apoptosis, fibrosis, and oxidative stress were performed in livers from these animals. Results TBE-31 treatment reversed insulin resistance in HFFr-fed wild-type mice, but not in HFFr-fed Nrf2-null mice. TBE-31 treatment of HFFr-fed wild-type mice substantially decreased liver steatosis and expression of lipid synthesis genes, while increasing hepatic expression of fatty acid oxidation and lipoprotein assembly genes. Also, TBE-31 treatment decreased ER stress, expression of inflammation genes, and markers of apoptosis, fibrosis, and oxidative stress in the livers of HFFr-fed wild-type mice. By comparison, TBE-31 did not decrease steatosis, ER stress, lipogenesis, inflammation, fibrosis, or oxidative stress in livers of HFFr-fed Nrf2-null mice. Conclusions Pharmacologic activation of Nrf2 in mice that had already been rendered obese and insulin resistant reversed insulin resistance, suppressed hepatic steatosis, and mitigated against NASH and liver fibrosis, effects that we principally attribute to inhibition of ER, inflammatory, and oxidative stress.
Mice lacking the transcription factor NF-E2 p45-related factor 2 (Nrf2) develop more severe nonalcoholic steatohepatitis (NASH), with cirrhosis, than wild-type (Nrf2
+/+
) mice when fed a high-fat ...(HF) diet for 24 weeks. Although NASH is usually associated with insulin resistance, HF-fed Nrf2
−/−
mice exhibited better insulin sensitivity than HF-fed Nrf2
+/+
mice. In livers of HF-fed mice, loss of Nrf2 resulted in greater induction of lipogenic genes, lower expression of β-oxidation genes, greater reduction in AMP-activated protein kinase (AMPK) levels, and diminished acetyl coenzyme A (CoA) carboxylase phosphorylation than in the wild-type livers, which is consistent with greater fatty acid (FA) synthesis in Nrf2
−/−
livers. Moreover, primary Nrf2
−/−
hepatocytes displayed lower glucose and FA oxidation than Nrf2
+/+
hepatocytes, with FA oxidation partially rescued by treatment with AMPK activators. The unfolded protein response (UPR) was perturbed in control regular-chow (RC)-fed Nrf2
−/−
mouse livers, and this was associated with constitutive activation of NF-κB and JNK, along with upregulation of inflammatory genes. The HF diet elicited an antioxidant response in Nrf2
+/+
livers, and as this was compromised in Nrf2
−/−
livers, they suffered oxidative stress. Therefore, Nrf2 protects against NASH by suppressing lipogenesis, supporting mitochondrial function, increasing the threshold for the UPR and inflammation, and enabling adaptation to HF-diet-induced oxidative stress.
Management strategies for localized renal masses suspicious for renal cell carcinoma include radical nephrectomy, partial nephrectomy, thermal ablation, and active surveillance. Given favorable ...survival outcomes across strategies, renal preservation is often of paramount concern. To inform clinical decision making, we performed a systematic review and meta-analysis of studies comparing renal functional outcomes for radical nephrectomy, partial nephrectomy, thermal ablation, and active surveillance.
We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from January 1, 1997 to May 1, 2015 to identify comparative studies reporting renal functional outcomes. Meta-analyses were performed for change in eGFR, incidence of CKD, and AKI.
We found 58 articles reporting on relevant renal functional outcomes. Meta-analyses showed that final eGFR fell 10.5 ml/min per 1.73 m
lower for radical nephrectomy compared with partial nephrectomy and indicated higher risk of CKD stage 3 or worse (relative risk, 2.56; 95% confidence interval, 1.97 to 3.32) and ESRD for radical nephrectomy compared with partial nephrectomy. Overall risk of AKI was similar for radical nephrectomy and partial nephrectomy, but studies suggested higher risk for radical nephrectomy among T1a tumors (relative risk, 1.37; 95% confidence interval, 1.13 to 1.66). In general, similar findings of worse renal function for radical nephrectomy compared with thermal ablation and active surveillance were observed. No differences in renal functional outcomes were observed for partial nephrectomy versus thermal ablation. The overall rate of ESRD was low among all management strategies (0.4%-2.8%).
Renal functional implications varied across management strategies for localized renal masses, with worse postoperative renal function for patients undergoing radical nephrectomy compared with other strategies and similar outcomes for partial nephrectomy and thermal ablation. Further attention is needed to quantify the changes in renal function associated with active surveillance and nephron-sparing approaches for patients with preexisting CKD.
Vast stretches of open water bodies are gradually becoming hypoxic as a result of depletion of oxygen levels mainly due to various human anthropogenic activities. This problem of hypoxic stress on ...the fish population is likely to be exacerbated soon since the aquatic hypoxic environment is continuously spreading over vast areas worldwide. In recent years, various harmful effects of hypoxia to bony fishes have been reported, such as the restriction of energy-consuming metabolic processes, arrest of the growth of ovary and testes that are associated with endocrine disruption, loss of sperm and egg quality, inhibition of fertilization, hatching success, and also the reduction of larval survivability, thereby impairment of overall reproductive and developmental processes in fish. Disruption of the brain-pituitary-gonad axis, and certain enzymes related to steroidogenesis and vitellogenesis in fish have also been reported as the primary targets for an endocrine malfunction during hypoxia. Hypoxia-sensitive downregulation of key genes responsible for controlling sex hormones' synthesis has been documented in certain bony fishes. Further, continuous exposure to hypoxia was reported to induce early expression of pro-apoptotic/tumor suppressor p53 genes, thereby causing immense cell death in hypoxic embryos. However, the cellular responses to long-term hypoxia exposure and the degree of reproductive impairments in bony fishes are still not adequate to figure out the actual underlying mechanisms. The present review intends to highlight the current knowledge about the detrimental impact of chronic/acute hypoxia at different stages of fish reproduction and the associated underlying molecular mechanisms.
Magnetic hyperthermia cancer therapy has emerged as a promising approach for targeted and localized treatment of cancer. This innovative technique utilizes magnetic nanoparticles to generate ...localized heat within tumor cells, leading to their selective destruction. This study explores the hyperthermic potential of Lanthanum Strontium Manganite (LSMO), which are rare earth metal-based magnetic nanoparticles, for their application in magnetic hyperthermia cancer therapy. A modified citrate sol-gel technique was utilized to create LSMO (La0·7Sr0·3MnO3) nanoparticles, which were then modified by coating with silica. Comprehensive physical characterization of the nanoparticles was performed, and their hyperthermic potential was evaluated in vitro. The biocompatibility and selective cytotoxicity of LSMO nanoparticles were investigated, and the results demonstrated promising outcomes. With its controlled and localized heat generation and enhanced biocompatibility, LSMO offers an encouraging avenue for advancing targeted and effective cancer treatments. Future research in this field may pave the way for transformative improvements in cancer therapy outcomes.
•Silica coated Lanthanum Strontium Manganite magnetic nanoparticles synthesized.•Characterization including Hyperthermic output under Alternating magnetic field.•Biocompatibility and application as a nanoagent for magnetic hyperthermia therapy.•Excellent hyperthermia output and anti cancer efficacy demonstrated in vitro.•Could act as alternative to Iron oxide based nanoparticles for cancer therapy.
Objectives: This retrospective study was conducted to assess and compare the efficacy of oral misoprostol and intravenous oxytocin in the induction of labour after PROM. Materials and method: A total ...of 106 patients with singleton term pregnancy with PROM were included in the misoprostol and oxytocin groups. Misoprostol and oxytocin were administered in the standard doses. Close monitoring of the maternal and fetal status and progress of labour was done. In cases of failed induction, cesarean section was performed. The outcome was recorded. Results and observations: Both the groups were comparable in terms of demographic and baseline parameters. The induction to delivery time was significantly shorter in the misoprostol group (P value <0.001). The cesarean section rates were comparable in both the groups. There was no incidence of intrapartum complications in any group. The fetal outcome, in terms of APGAR scores and NICU admissions, was also comparable. Conclusion: Oral misoprostol is a safe and effective alternative to oxytocin, especially in cases of unfavourable cervix.
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