Gastrointestinal toxicities of proteasome inhibitor therapy.

PURPOSE: Proteasome inhibitors (PIs), which cause cell death via tumor suppressor and pro-apoptotic proteins, are integral to treatment of many hematologic malignancies but are limited by their gastrointestinal adverse effects. Evidence regarding these PI-related adverse effects is scant. In this study, we evaluated gastrointestinal adverse events caused by PIs and compared gastrointestinal toxicities between bortezomib, carfilzomib, and ixazomib. METHODS: We conducted a retrospective study of cancer patients treated with PIs at a tertiary care cancer center to investigate the clinical characteristics of PI-related gastrointestinal adverse events. RESULTS: Our sample comprised 973 patients with PI exposure and stool studies ordered between January 2017 and December 2022. Of these, 193 patients (20%) had PI-related gastrointestinal toxicity based on clinical symptoms and stool study results. The most common symptom was diarrhea, present in 169 (88% of those with gastrointestinal toxicity). Twenty-two (11%) required hospitalization, and 71 (37%) developed recurrence of symptoms. Compared to bortezomib or carfilzomib, ixazomib had a longer interval from PI initiation to the onset of gastrointestinal symptoms (313 days vs 58 days vs 89 days, p = 0.002) and a significantly lower percentage of diarrhea-predominant presentation of gastrointestinal toxicity (71% vs 96% vs 91%, p = 0.048). CONCLUSION: While PI-related gastrointestinal toxicities have various presentations and courses based on different regimens, the vast majority of patients presented with milder disease behavior. Despite a considerably high rate of hospitalization and recurrence after treatment necessitating optimization of clinical management, our cohort demonstrates favorable outcomes without long-term consequences.

Post-mastectomy Pain Syndrome: A Review Article and Emerging Treatment Modalities.

Post-mastectomy pain syndrome (PMPS) is a syndrome broadly applied to the development of chronic pain after surgical breast intervention (i.e., lumpectomy and mastectomy). The incidence of PMPS is likely underreported, and this has contributed to a paucity of high-level evidence related to the treatment of the aforementioned condition. A drive to reduce the burden of opioid use has led to pain management physicians trialing a variety of strategies to help patients manage PMPS. This review discusses the latest evidence behind treatment options for PMPS, exploring medications as well as interventional techniques (e.g., nerve blocks, radiofrequency ablation, neuromodulation, and intrathecal drug delivery systems). Recent advances in neuromodulation technology are of particular interest here due to the well-localized nature of PMPS-related pain and the specificity with which modern neuromodulation techniques can generate an effect. Finally, the review proposes a framework with which to approach the care of patients with PMPS, with a specific emphasis on the early consideration of neuromodulation techniques along with functional and physical therapy to reduce patient medication burden and improve overall quality of life.

Early Detection of Myeloid-Derived Suppressor Cells in the Lung Pre-Metastatic Niche by Shortwave Infrared Nanoprobes.

Metastatic breast cancer remains a significant source of mortality amongst breast cancer patients and is generally considered incurable in part due to the difficulty in detection of early micro-metastases. The pre-metastatic niche (PMN) is a tissue microenvironment that has undergone changes to support the colonization and growth of circulating tumor cells, a key component of which is the myeloid-derived suppressor cell (MDSC). Therefore, the MDSC has been identified as a potential biomarker for PMN formation, the detection of which would enable clinicians to proactively treat metastases. However, there is currently no technology capable of the in situ detection of MDSCs available in the clinic. Here, we propose the use of shortwave infrared-emitting nanoprobes for the tracking of MDSCs and identification of the PMN. Our rare-earth albumin nanocomposites (ReANCs) are engineered to bind the Gr-1 surface marker of murine MDSCs. When delivered intravenously in murine models of breast cancer with high rates of metastasis, the targeted ReANCs demonstrated an increase in localization to the lungs in comparison to control ReANCs. However, no difference was seen in the model with slower rates of metastasis. This highlights the potential utility of MDSC-targeted nanoprobes to assess PMN development and prognosticate disease progression.

Body-Mounted MR-Conditional Robot for Minimally Invasive Liver Intervention.

MR-guided microwave ablation (MWA) has proven effective in treating hepatocellular carcinoma (HCC) with small-sized tumors, but the state-of-the-art technique suffers from sub-optimal workflow due to the limited accuracy provided by the manual needle insertions. This paper presents a compact body-mounted MR-conditional robot that can operate in closed-bore MR scanners for accurate needle guidance. The robotic platform consists of two stacked Cartesian XY stages, each with two degrees of freedom, that facilitate needle insertion pose control. The robot is actuated using 3D-printed pneumatic turbines with MR-conditional bevel gear transmission systems. Pneumatic valves and control mechatronics are located inside the MRI control room and are connected to the robot with pneumatic transmission lines and optical fibers. Free-space experiments indicated robot-assisted needle insertion error of 2.6 ± 1.3 mm at an insertion depth of 80 mm. The MR-guided phantom studies were conducted to verify the MR-conditionality and targeting performance of the robot. Future work will focus on the system optimization and validations in animal trials.

A Validated Risk Stratification That Incorporates MAGIC Biomarkers Predicts Long-Term Outcomes in Pediatric Patients with Acute GVHD.

Acute graft versus host disease (GVHD) is a common and serious complication of allogeneic hematopoietic cell transplantation (HCT) in children but overall clinical grade at onset only modestly predicts response to treatment and survival outcomes. Two tools to assess risk at initiation of treatment were recently developed. The Minnesota risk system stratifies children for risk of nonrelapse mortality (NRM) according to the pattern of GVHD target organ severity. The Mount Sinai Acute GVHD International Consortium (MAGIC) algorithm of 2 serum biomarkers (ST2 and REG3α) predicts NRM in adult patients but has not been validated in a pediatric population. We aimed to develop and validate a system that stratifies children at the onset of GVHD for risk of 6-month NRM. We determined the MAGIC algorithm probabilities (MAPs) and Minnesota risk for a multicenter cohort of 315 pediatric patients who developed GVHD requiring treatment with systemic corticosteroids. MAPs created 3 risk groups with distinct outcomes at the start of treatment and were more accurate than Minnesota risk stratification for prediction of NRM (area under the receiver operating curve (AUC), .79 versus .62, P = .001). A novel model that combined Minnesota risk and biomarker scores created from a training cohort was more accurate than either biomarkers or clinical systems in a validation cohort (AUC .87) and stratified patients into 2 groups with highly different 6-month NRM (5% versus 38%, P < .001). In summary, we validated the MAP as a prognostic biomarker in pediatric patients with GVHD, and a novel risk stratification that combines Minnesota risk and biomarker risk performed best. Biomarker-based risk stratification can be used in clinical trials to develop more tailored approaches for children who require treatment for GVHD.

A case of image-guided hematometrocolpos drainage requiring tissue plasminogen activator in a pediatric patient.

Hematometrocolpos (HMC) is a rare disorder that occurs when an anatomical anomaly like imperforate hymen causes menstrual blood to be retained in the uterus and vagina. There is no standard of care established for HMC beyond urgent vaginoplasty which requires a demanding post-operative course that may not be suited for all pediatric patients. This is a case report of successful use of image-guided percutaneous drainage of HMC with tissue plasminogen activator (TPA) followed by vaginoplasty in a 13-year-old female with lower vaginal atresia. Additionally, this case explores the role of menstrual suppression and the need for individualized guidelines. It emphasizes the potential of image-guided percutaneous drainage with TPA as a promising, less-invasive treatment option for pediatric HMC as well as the impact on follow-up surgery.

Upper partial sternal split for pediatric cardiac surgery.

OBJECTIVES: We introduced the use of an upper partial sternal split for pediatric cardiac surgical procedures in our unit in 2016. We report the outcomes of our experience in 51 patients using this approach. METHODS: From February 2016 to September 2022, 51 patients underwent congenital cardiac surgical procedures using an upper partial sternal split including vascular ring repair (n = 20), subaortic membrane (n = 12), ventricular septal defect closure with aortic valve resuspension (n = 9), aortic arch repair (n = 4), pulmonary artery band (n = 2), pulmonary artery sling (n = 1), supravalvular aortic stenosis (n = 1), aortic valve replacement (n = 1), and pulmonary artery plasty (n = 1). The surgical approach involved a midline skin incision, based on the manubrium, followed by an upper manubriotomy. No special surgical instrumentation was required. Median patient age was 2.9 years (IQR 1.3, 6.0); median body weight was 15 kg (IQR 9.8, 20). RESULTS: There was no mortality and no patient required intraoperative conversion to full sternotomy. One patient required re-exploration for bleeding when the incision was converted to a full sternotomy. There were no wound complications in any patient. Twenty-one patients (41%) were extubated on the table and of the remaining 30 patients, 23 patients (76%) were extubated within 24 h of surgery. Eleven patients did not require intensive care unit (ICU) admission. Median ICU and hospital stay was 1 day (IQR 1, 1.25) and 5 days (IQR 4, 8) ,respectively. CONCLUSION: An upper partial sternal split approach is straightforward and can be performed safely with a preferable cosmetic result in selected pediatric cardiac operations.

Practice Changes in Checkpoint Inhibitor-Induced Immune-Related Adverse Event Management at a Tertiary Care Center.

Understanding of immune-related adverse events (irAEs) has evolved rapidly, and management guidelines are continually updated. We explored temporal changes in checkpoint inhibitor-induced irAE management at a tertiary cancer care center to identify areas for improvement. We conducted a single-center retrospective study of patients who developed a gastrointestinal, pulmonary, renal, or cardiac irAE between July and 1 October in 2019 or 2021. We collected patient demographic and clinical information up to 1 year after toxicity. Endoscopic evaluation and specialty follow-up after discharge for patients with gastrointestinal irAEs declined between the 2019 and 2021 periods. Symptom duration and steroid taper attempts also declined. For pulmonary irAEs, rates of specialty consultation, hospital admission and readmission, and mortality improved in 2021 compared with 2019. Follow-up rates after hospital discharge were consistently low (<50%) in both periods. For cardiac irAEs, consultation with a cardiologist was frequent and prompt in both periods. Outpatient treatment and earlier specialty consultation improved outcomes with gastrointestinal irAEs. Our study exploring irAE practice changes over time identified areas to improve management; specifically, timely specialty consultation was associated with better outcomes for gastrointestinal irAEs. These findings can help improve the quality of management algorithms at our institution and may inform policies in other institutions.

Clinical Characteristics of Primary Snoring vs Mild Obstructive Sleep Apnea in Children: Analysis of the Pediatric Adenotonsillectomy for Snoring (PATS) Randomized Clinical Trial.

Importance: It is unknown whether children with primary snoring and children with mild obstructive sleep apnea (OSA) represent populations with substantially different clinical characteristics. Nonetheless, an obstructive apnea-hypopnea index (AHI) of 1 or greater is often used to define OSA and plan for adenotonsillectomy (AT). Objective: To assess whether a combination of clinical characteristics differentiates children with primary snoring from children with mild OSA. Design, Setting, and Participants: Baseline data from the Pediatric Adenotonsillectomy Trial for Snoring (PATS) study, a multicenter, single-blind, randomized clinical trial conducted at 6 academic sleep centers from June 2016 to January 2021, were analyzed. Children aged 3.0 to 12.9 years with polysomnography-diagnosed (AHI <3) mild obstructive sleep-disordered breathing who were considered candidates for AT were included. Data analysis was performed from July 2022 to October 2023. Main Outcomes and Measures: Logistic regression models were fitted to identify which demographic, clinical, and caregiver reports distinguished children with primary snoring (AHI <1; 311 patients [67.8%]) from children with mild OSA (AHI 1-3; 148 patients [32.2%]). Results: A total of 459 children were included. The median (IQR) age was 6.0 (4.0-7.5) years, 230 (50.1%) were female, and 88 (19.2%) had obesity. A total of 121 (26.4%) were Black, 75 (16.4%) were Hispanic, 236 (51.5%) were White, and 26 (5.7%) were other race and ethnicity. Black race (odds ratio [OR], 2.08; 95% CI, 1.32-3.30), obesity (OR, 1.80; 95% CI, 1.12-2.91), and high urinary cotinine levels (>5 µg/L) (OR, 1.88; 95% CI, 1.15-3.06) were associated with greater odds of mild OSA rather than primary snoring. Other demographic characteristics, clinical examination findings, and questionnaire reports did not distinguish between primary snoring and mild OSA. A weighted combination of the statistically significant clinical predictors had limited ability to differentiate children with mild OSA from children with primary snoring. Conclusions and Relevance: In this analysis of baseline data from the PATS randomized clinical trial, primary snoring and mild OSA were difficult to distinguish without polysomnography. Mild OSA vs snoring alone did not identify a clinical group of children who may stand to benefit from AT for obstructive sleep-disordered breathing. Trial Registration: ClinicalTrials.gov Identifier: NCT02562040.

Impact of ambient air pollution and socio-environmental factors on the health of children younger than 5 years in India: a population-based analysis.

Background: Ambient air pollution and household environmental factors affect child health, particularly in low-income and middle-income countries. This study aimed to investigate the association between ambient air pollution (PM2·5) levels, socio-environmental factors (including household wealth, housing quality measures, smoking status), and the occurrence of respiratory illness in Indian children. Methods: In this retrospective and observational study, we analysed data from India's National Family Health Survey (NFHS-5, 2019-2021) combined with NASA's Global Annual PM2·5 Grids database. Bivariate and multivariable generalized additive models were employed to examine associations between key social-environmental factors and respiratory illness in children younger than 5 years. Findings: We analysed data from 224,214 children younger than 5 years, representing 165,561 families from 29,757 geographic clusters. Our results showed extremely high annual PM2·5 levels throughout India (median 63·4·g/m3, IQR 41·9-81·6), with higher exposure for rural and impoverished families. In bivariate analyses, PM2·5 was significantly associated with reported respiratory illness (p < 0·001). Using generalized additive models and after accounting for key social and environmental factors, a monotonic increasing and non-linear relationship was observed between PM2·5 and respiratory illness (p < 0·001), with increased likelihood of illness observed even at values near and below India's National Ambient Air Quality Standards of 40 µg/m3. Interpretation: The study highlights the significant association of social-environmental conditions with health outcomes among young children in India. Efforts specifically targeting ambient air pollution and child health during monsoon season could have significant health benefits among this population and help achieve the goal of ending preventable deaths of children younger than 5 years. Funding: National Institutes of Health (NIH T-32-HL139443-3).

Adenotonsillectomy for Snoring and Mild Sleep Apnea in Children: A Randomized Clinical Trial.

Importance: The utility of adenotonsillectomy in children who have habitual snoring without frequent obstructive breathing events (mild sleep-disordered breathing [SDB]) is unknown. Objectives: To evaluate early adenotonsillectomy compared with watchful waiting and supportive care (watchful waiting) on neurodevelopmental, behavioral, health, and polysomnographic outcomes in children with mild SDB. Design, Setting, and Participants: Randomized clinical trial enrolling 459 children aged 3 to 12.9 years with snoring and an obstructive apnea-hypopnea index (AHI) less than 3 enrolled at 7 US academic sleep centers from June 29, 2016, to February 1, 2021, and followed up for 12 months. Intervention: Participants were randomized 1:1 to either early adenotonsillectomy (n = 231) or watchful waiting (n = 228). Main Outcomes and Measures: The 2 primary outcomes were changes from baseline to 12 months for caregiver-reported Behavior Rating Inventory of Executive Function (BRIEF) Global Executive Composite (GEC) T score, a measure of executive function; and a computerized test of attention, the Go/No-go (GNG) test d-prime signal detection score, reflecting the probability of response to target vs nontarget stimuli. Twenty-two secondary outcomes included 12-month changes in neurodevelopmental, behavioral, quality of life, sleep, and health outcomes. Results: Of the 458 participants in the analyzed sample (231 adenotonsillectomy and 237 watchful waiting; mean age, 6.1 years; 230 female [50%]; 123 Black/African American [26.9%]; 75 Hispanic [16.3%]; median AHI, 0.5 [IQR, 0.2-1.1]), 394 children (86%) completed 12-month follow-up visits. There were no statistically significant differences in change from baseline between the 2 groups in executive function (BRIEF GEC T-scores: -3.1 for adenotonsillectomy vs -1.9 for watchful waiting; difference, -0.96 [95% CI, -2.66 to 0.74]) or attention (GNG d-prime scores: 0.2 for adenotonsillectomy vs 0.1 for watchful waiting; difference, 0.05 [95% CI, -0.18 to 0.27]) at 12 months. Behavioral problems, sleepiness, symptoms, and quality of life each improved more with adenotonsillectomy than with watchful waiting. Adenotonsillectomy was associated with a greater 12-month decline in systolic and diastolic blood pressure percentile levels (difference in changes, -9.02 [97% CI, -15.49 to -2.54] and -6.52 [97% CI, -11.59 to -1.45], respectively) and less progression of the AHI to greater than 3 events/h (1.3% of children in the adenotonsillectomy group compared with 13.2% in the watchful waiting group; difference, -11.2% [97% CI, -17.5% to -4.9%]). Six children (2.7%) experienced a serious adverse event associated with adenotonsillectomy. Conclusions: In children with mild SDB, adenotonsillectomy, compared with watchful waiting, did not significantly improve executive function or attention at 12 months. However, children with adenotonsillectomy had improved secondary outcomes, including behavior, symptoms, and quality of life and decreased blood pressure, at 12-month follow-up. Trial Registration: ClinicalTrials.gov Identifier: NCT02562040.

Pediatric Transplant Interventions.

The field of pediatric organ transplantation has grown significantly in recent decades, with interventional radiology (IR) playing an essential role in managing pre and post-transplant complications. Pediatric transplant patients face unique challenges compared to adults, including donor-recipient size mismatch, and complications of a growing child with changing physiology. Interventional radiologists play a major role in pediatric renal and liver transplant. IR interventions begin early in the child's pretransplant journey, with diagnostic procedures such as biopsies, angiograms, and cholangiograms. These procedures are essential for understanding the etiology of organ failure and identifying potential transplant candidates. Minimally invasive therapeutic procedures may serve as bridges to transplant and may include vascular access optimization for hemodialysis, transjugular intrahepatic portosystemic shunts (TIPS) creation, and tumor embolization or ablation. After transplant, image-guided biopsies for the surveillance of graft rejection and treatment of vascular or luminal stenoses, pseudoaneurysms, and anastomotic leaks can maintain the function and longevity of the transplant organ. Careful consideration must be given to patient size and evolving anatomy, radiation exposure, and the need for deeper sedation for pediatric patients. Despite these challenges, the integration of IR in pediatric transplant care has proven beneficial, offering minimally invasive alternatives to surgery, faster recovery times, and improved outcomes.

Neuromodulation for Adjunctive Treatment in Postmastectomy Pain Syndrome.

Postmastectomy pain syndrome (PMPS) affects nearly half of patients who undergo mastectomy to treat breast cancer. As the survival rate of breast cancer increases with advancements in treatment, the incidence of PMPS is also increasing. Patients with PMPS can experience unrelenting, chronic pain refractory to traditional management with oral pharmacotherapy in conjunction with nonpharmacologic treatment (physical therapy, transcutaneous electrical nerve stimulation (TENS)). Neuromodulation is an emerging treatment modality for numerous chronic pain conditions. This case report highlights the tremendous success of spinal cord stimulator placement for a patient with PMPS.

The effect of cisplatin-based neoadjuvant chemotherapy on the renal function of patients undergoing radical cystectomy.

INTRODUCTION: Cisplatin-based neoadjuvant chemotherapy (NAC) is the standard of care for patients with muscle-invasive bladder cancer (MIBC) undergoing radical cystectomy (RC). Cisplatin, however, can induce renal toxicity. Furthermore, RC is an independent risk factor for renal injury, with decreases in estimated glomerular filtration rate (eGFR) of up to 6 mL/min/1.73 m2 reported at one year postoperatively. Our objective was to evaluate the effect of cisplatin-based NAC and RC on the renal function of patients undergoing both. METHODS: We analyzed a multicenter database of patients with MIBC, all of whom received cisplatin-based NAC prior to RC. eGFR values were collected at time points T1 (before NAC), T2 (after NAC but before RC), and T3 (one year post-RC). eGFR and proportion of patients with eGFR <60 ml/min/1.73m2 (chronic kidney disease [CKD] stage ≥3) were compared between these time points. As all patients in this dataset had received NAC, we identified a retrospective cohort of patients from one institution who had undergone RC during the same time period without NAC for context. RESULTS: We identified 234 patients with available renal function data. From T1 to T3, there was a mean decline in eGFR of 17% (13 mL/min/1.73 m2) in the NAC cohort and an increase in proportion of patients with stage ≥3 CKD from 27% to 50%. The parallel cohort of patients who did not receive NAC was comprised of 236 patients. The mean baseline eGFR in this cohort was lower than in the NAC cohort (66 vs. 75 mL/min/1.73 m2). The mean eGFR decline in this non-NAC cohort from T1 to T3 was 6% (4 mL/min/1.73 m2), and the proportion of those with stage ≥3 CKD increased from 37% to 51%. CONCLUSIONS: Administration of NAC prior to RC was associated with a 17% decline in eGFR and a nearly doubled incidence of stage ≥3 CKD at one year after RC. Patients who underwent RC without NAC had a higher rate of stage ≥3 CKD at baseline but appeared to have less renal function loss at one year.

Evidence for an association of serum microanalytes and myofascial pain syndrome.

BACKGROUND: Myofascial Pain Syndrome (MPS) is a common pain disorder. Diagnostic criteria include physical findings which are often unreliable or not universally accepted. A precise biosignature may improve diagnosis and treatment effectiveness. The purpose of this study was to assess whether microanalytic assays significantly correlate with characteristic clinical findings in people with MPS. METHODS: This descriptive, prospective study included 38 participants (25 women) with greater than 3 months of myofascial pain in the upper trapezius. Assessments were performed at a university laboratory. The main outcome measures were the Beighton Index, shoulder range of motion, strength asymmetries and microanalytes: DHEA, Kynurenine, VEGF, interleukins (IL-1b, IL-2, IL-4, IL-5, IL-7, IL-8, IL-13), growth factors (IGF-1, IGF2, G-CSF, GM-CSF), MCP-1, MIP-1b, BDNF, Dopamine, Noradrenaline, NPY, and Acetylcholine. Mann-Whitney test and Spearman's multivariate correlation were applied for all variables. The Spearman's analysis results were used to generate a standard correlation matrix and heat map matrix. RESULTS: Mean age of participants was 32 years (20-61). Eight (21%) had widespread pain (Widespread Pain Index ≥ 7). Thirteen (34%) had MPS for 1-3 years, 14 (37%) 3-10 years, and 11 (29%) for > 10 years. The following showed strong correlations: IL1b,2,4,5,7,8; GM-CSF and IL 2,4,5,7; between DHEA and BDNF and between BDNF and Kynurenine, NPY and acetylcholine. The heat map analysis demonstrated strong correlations between the Beighton Index and IL 5,7, GM-CSF, DHEA. Asymmetries of shoulder and cervical spine motion and strength associated with select microanalytes. CONCLUSION: Cytokine levels significantly correlate with selected clinical assessments. This indirectly suggests possible biological relevance for understanding MPS. Correlations among some cytokine clusters; and DHEA, BDNF kynurenine, NPY, and acetylcholine may act together in MPS. These findings should be further investigated for confirmation that link these microanalytes with select clinical findings in people with MPS.

Peripheral Activation of Formyl Peptide Receptor 2/ALX by Electroacupuncture Alleviates Inflammatory Pain by Increasing Interleukin-10 Levels and Catalase Activity in Mice.

In the context of the electroacupuncture (EA) neurobiological mechanisms, we have previously demonstrated the involvement of formyl peptide receptor 2 (FPR2/ALX) in the antihyperalgesic effect of EA. The present study investigated the involvement of peripheral FPR2/ALX in the antihyperalgesic effect of EA on inflammatory cytokines levels, oxidative stress markers and antioxidant enzymes in an animal model of persistent inflammatory pain. Male Swiss mice underwent intraplantar (i.pl.) injection with complete Freund's adjuvant (CFA). Mechanical hyperalgesia was assessed with von Frey monofilaments. Animals were treated with EA (2/10 Hz, ST36-SP6, 20 minutes) for 4 consecutive days. From the first to the fourth day after CFA injection, animals received i.pl. WRW4 (FPR2/ALX antagonist) or saline before EA. Levels of inflammatory cytokines (TNF, IL-6, IL-4 and IL-10), antioxidant enzymes (catalase and superoxide dismutase), oxidative stress markers (TBARS, protein carbonyl, nitrite/nitrate ratio), and myeloperoxidase activity were measured in paw tissue samples. As previously demonstrated, i.pl. injection of the FPR2/ALX antagonist prevented the antihyperalgesic effect induced by EA. Furthermore, animals treated with EA showed higher levels of IL-10 and catalase activity in the inflamed paw, and these effects were prevented by the antagonist WRW4. EA did not change levels of TNF and IL-6, SOD and MPO activity, and oxidative stress markers. Our work demonstrates that the antihyperalgesic effect of EA on CFA-induced inflammatory pain could be partially associated with higher IL-10 levels and catalase activity, and that these effects may be dependent, at least in part, on the activation of peripheral FPR2/ALX.

Baseline Quality of Life in Pediatric Patients With Low-flow Vascular Malformations.

OBJECTIVE: The aim of this study was to quantify and describe baseline patient and parent-proxy health-related quality of life scores in patients with low-flow vascular malformations at a single, tertiary-care vascular anomalies clinic. STUDY DESIGN: This is a retrospective study of data collected on patients with low-flow vascular malformations between the ages of 2 to 25 who were seen at a single, tertiary-care center vascular anomalies clinic. A total of 266 patients are included in this study. RESULTS: Patients with lymphatic malformations report decreased quality of life scores as compared with venous malformations in the emotional, psychological, school, and social domains. Patients with lower extremity malformation report decreased quality of life scores as compared with head/neck, trunk, upper extremity, and multifocal malformations; most notably in the physical domain. CONCLUSIONS: Treatment of low-flow vascular malformations should aim to improve patient quality of life. The use of standardized health-related quality of life measures in this study quantifies baseline quality of life scores among patients with low-flow vascular malformations.

The Warburg effect: a score for many instruments in the concert of cancer and cancer niche cells.

Although Warburg's discovery of intensive glucose uptake by tumors, followed by lactate fermentation in oxygen presence of oxygen was made a century ago, it is still an area of intense research and development of new hypotheses that, layer by layer, unravel the complexities of neoplastic transformation. This seemingly simple metabolic reprogramming of cancer cells reveals an intriguing, multi-faceted nature that may link various phenomena including cell signaling, cell proliferation, ROS generation, energy supply, macromolecules synthesis/biosynthetic precursor supply, immunosuppression, or cooperation of cancerous cells with cancer-associated fibroblasts (CAFs), known as reversed Warburg effect. According to the current perception of the causes and consequences of the Warburg effect, PI3K/Akt/mTOR are the main signaling pathways that, in concert with the transcription factors HIF-1, p53, and c-Myc, modulate the activity/expression of key regulatory enzymes, including PKM2, and PDK1 to tune in the most optimal metabolic setting for the cancer cell. This in turn secures adequate levels of biosynthetic precursors, NADPH, NAD+, and rapid ATP production to meet the increased demands of intensively proliferating tumor cells. The end-product of "aerobic glycolysis", lactate, an oncometabolite, may provide fuel to neighboring cancer cells, and facilitate metastasis and immunosuppression together enabling cancer progression. The importance and possible applicability of the presented issue are best illustrated by numerous trials with various agents targeting the Warburg effect, constituting a promising strategy in future anti-cancer regimens. In this review, we present the key aspects of this multifactorial phenomenon, depicting the mechanisms and benefits behind the Warburg effect, and also pointing to selected aspects in the field of anticancer therapy.