Association between preoperative lumbar skeletal muscle index and postoperative nausea and vomiting in patients undergoing pylorus-preserving pancreatoduodenectomy: a retrospective study.

BACKGROUND: Sarcopenia is associated with postoperative complications; however, its impact on the quality of postoperative recovery, such as postoperative nausea and vomiting (PONV) and pain, remains unclear. We investigated the association of preoperative lumbar skeletal muscle mass index (LSMI) with PONV, postoperative pain, and complications. METHODS: Medical records of 756 patients who underwent pylorus-preserving pancreatoduodenectomy (PPPD) were retrospectively reviewed. The skeletal muscle areas were measured on abdominal computed tomography (CT) images. LSMI was calculated by dividing the skeletal muscle area by the square of the patient's height. We analyzed the correlations between preoperative LSMI calibrated with confounding variables and PONV scores, PONV occurrence, pain scores, rescue analgesic administration, postoperative complications, and length of hospital stay. RESULTS: The median (1Q, 3Q) LSMI was 47.72 (40.74, 53.41) cm2/m2. The incidence rates of PONV according to time period were as follows: post-anesthesia care unit, 42/756 (5.6%); 0-6 h, 54/756 (7.1%); 6-24 h, 120/756 (15.9%); 24-48 h, 46/756 (6.1%); and overall, 234/756 (31.0%). The incidence of PONV was inversely correlated with LSMI 24-48 h post-surgery and overall. LSMI and PONV scores were negatively associated 6-24 h and 24-48 h post-surgery. There was no association between LSMI and postoperative pain scores, rescue analgesic administration, complications, or length of hospital stay. CONCLUSIONS: Preoperative LSMI was associated with PONV in patients undergoing PPPD. Therefore, LSMI measured on preoperative abdominal CT can be a predictive indicator of PONV. Appropriate PONV prophylaxis is necessary in patients with low LSMI before PPPD.

Enhanced Recovery After Surgery for Craniotomies: A Systematic Review and Meta-analysis.

The efficacy of the enhanced recovery after surgery (ERAS) protocols in neurosurgery has not yet been established. We performed a systematic review and meta-analysis of randomized controlled trials to compare the effects of ERAS protocols and conventional perioperative care on postoperative outcomes in patients undergoing craniotomy. The primary outcome was postoperative length of hospital stay. Secondary outcomes included postoperative pain visual analog pain scores, incidence of postoperative nausea and vomiting (PONV), postoperative complications, all-cause reoperation, readmission after discharge, and mortality. A literature search up to August 10, 2023, was conducted using PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus databases. Five studies, including 871 patients, were identified for inclusion in this review. Compared with conventional perioperative care, ERAS protocols reduced the length of postoperative hospital stay (difference of medians, -1.52 days; 95% CI: -2.55 to -0.49); there was high heterogeneity across studies (I2, 74%). ERAS protocols were also associated with a lower risk of PONV (relative risk, 0.79; 95% CI: 0.69-0.90; I2, 99%) and postoperative pain with a visual analog scale score ≥4 at postoperative day 1 (relative risk, 0.37; 95% CI: 0.28-0.49; I2, 14%). Other outcomes, including postoperative complications, did not differ between ERAS and conventional care groups. ERAS protocols may be superior to conventional perioperative care in craniotomy patients in terms of lower length of hospital stay, lower incidence of PONV, and improved postoperative pain scores. Further randomized trials are required to identify the impact of ERAS protocols on the quality of recovery after craniotomy.

8-Methoxypsoralen Induces Apoptosis by Upregulating p53 and Inhibits Metastasis by Downregulating MMP-2 and MMP-9 in Human Gastric Cancer Cells.

Furanocoumarin 8-methoxypsoralen (8-MOP) is the parent compound that naturally occurs in traditional medicinal plants used historically. 8-MOP has been employed as a photochemotherapeutic component of Psoralen + Ultraviolet A (PUVA) therapy for the treatment of vitiligo and psoriasis. Although the role of 8-MOP in PUVA therapy has been studied, little is known about the effects of 8-MOP alone on human gastric cancer cells. In this study, we observed anti-proliferative effect of 8-MOP in several human cancer cell lines. Among these, the human gastric cancer cell line SNU1 is the most sensitive to 8-MOP. 8-MOP treated SNU1 cells showed G1-arrest by upregulating p53 and apoptosis by activating caspase-3 in a dose-dependent manner, which was confirmed by loss-of-function analysis through the knockdown of p53-siRNA and inhibition of apoptosis by Z-VAD-FMK. Moreover, 8-MOPinduced apoptosis is not associated with autophagy or necrosis. The signaling pathway responsible for the effect of 8-MOP on SNU1 cells was confirmed to be related to phosphorylated PI3K, ERK2, and STAT3. In contrast, 8-MOP treatment decreased the expression of the typical metastasis-related proteins MMP-2, MMP-9, and Snail in a p53-independent manner. In accordance with the serendipitous findings, treatment with 8-MOP decreased the wound healing, migration, and invasion ability of cells in a dose-dependent manner. In addition, combination treatment with 8-MOP and gemcitabine was effective at the lowest concentrations. Overall, our findings indicate that oral 8-MOP has the potential to treat early human gastric cancer, with fewer side effects.

Light-Stimulated Carbon Dot Hydrogel: Targeting and Clearing Infectious Bacteria In Vivo.

Infectious bacteria evolve fast into resistance to conventional antimicrobial agents, whereas treatments for drug resistance bacteria progress more slowly. Here, we report a universally applicable photoactivated antimicrobial modality through light-responsive carbon dot-embedding soft hyaluronic acid hydrogel (CDgel). Because of the innate nature of the infectious bacteria that produce hyaluronidase, applied hyaluronic acid-based CDgel breaks down via bacteria and releases carbon dots (CDs) into the infectious sites. The released CDs possess photodynamic capabilities under light irradiation, inducing 1O2 generation and growth inhibition of the infectious bacteria, S. aureus and E. coli (∼99% and ∼97%, respectively), in vitro. In particular, these photodynamic effects of CDs from CDgel have been shown to accelerate the healing of infected wounds in vivo, showing a higher wound regeneration rate as compared to that of untreated wounds. Our work demonstrates that the biocompatible and shape-controllable CDgel possesses therapeutic potential as a treatment modality for the light-driven control of drug-resistant bacterial infections.

G-749 Promotes Receptor Tyrosine Kinase TYRO3 Degradation and Induces Apoptosis in Both Colon Cancer Cell Lines and Xenograft Mouse Models.

G-749 is an FLT3 kinase inhibitor that was originally developed as a treatment for acute myeloid leukemia. Some FLT3 kinase inhibitors are dual kinase inhibitors that inhibit the TAM (Tyro3, Axl, Mer) receptor tyrosine kinase family and are used to treat solid cancers such as non-small cell lung cancer (NSCLC) and triple-negative breast cancer (TNBC). AXL promotes metastasis, suppression of immune response, and drug resistance in NSCLC and TNBC. G-749, a potential TAM receptor tyrosine kinase inhibitor, and its derivative SKI-G-801, effectively inhibits the phosphorylation of AXL at nanomolar concentration (IC50 = 20 nM). This study aimed to investigate the anticancer effects of G-749 targeting the TAM receptor tyrosine kinase in colon cancer. Here, we demonstrate the potential of G-749 to effectively inhibit tumorigenesis by degrading TYRO3 via regulated intramembrane proteolysis both in vitro and in vivo. In addition, we demonstrated that G-749 inhibits the signaling pathway associated with cell proliferation in colon cancer cell lines HCT15 and SW620, as well as tumor xenograft mouse models. We propose G-749 as a new therapeutic agent for the treatment of colon cancer caused by abnormal TYRO3 expression or activity.

Anoctamin1 Induces Hyperproliferation of HaCaT Keratinocytes and Triggers Imiquimod-Induced Psoriasis-Like Skin Injury in Mice.

Psoriasis, a long-lasting and multifactorial skin disease, is related to comorbidities such as metabolic disease, depression, and psoriatic arthritis. Psoriasis occurs due to a variety of factors including keratinocyte hyperproliferation, inflammation, and abnormal differentiation. Proinflammatory cytokines upregulated by increased activation of keratinocytes and immune cells in the skin trigger progression of psoriasis. This study aimed to investigate the effects of anoctamin1 (ANO1) on psoriasis development in vitro and in vivo. We analyzed the proliferation of HaCaT keratinocytes and ANO1-related ERK and AKT signaling pathways after ANO1 inhibitor (T16Ainh-A01 and Ani9) treatment and knock-down of ANO1. Furthermore, after applying imiquimod (IMQ) cream or coapplying IMQ cream and T16Ainh-A01 on mouse ears, we not only observed psoriatic symptoms, including ear thickening, but also quantified the effects of treatment on ERK and AKT signaling-involved proteins and proinflammatory cytokines. Inhibition of ANO1 attenuated the proliferation of HaCaT cells and induced reduction of pERK1/2. Coapplication of IMQ and T16Ainh-A01 on ears of mice reduced not only symptoms of IMQ-induced psoriasis such as thickening and erythema, but also expression of ANO1 and pERK1/2 compared to that of application of IMQ alone. In addition, the expression levels of IL-17A, IL-17F, IL-22, IL-23, IL-6, IL-1ß, and TNF-α increased after applying IMQ and were significantly reduced by coapplying IMQ and T16Ainh-A01. These results aid in understanding the underlying mechanisms of ANO1 in epidermal layer keratinocyte hyperproliferation and suggest the potential of ANO1 as a target to treat psoriasis.

Co-treatment of birinapant with TRAIL synergistically induces apoptosis by downregulating cFLIP(L) in MDA-MB-453 cell lines.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has received much attention owing to its ability to specifically induce cell death in cancer. However, several types of cancer, including some forms of breast cancer, are resistant to TRAIL. Various chemotherapeutic agents, phytochemicals, and TRAIL combination therapies have been proposed to resolve TRAIL resistance. Here, we explored the sensitization effect of birinapant on TRAIL-induced apoptosis in the MDA-MB-453 cell line. Although neither birinapant nor TRAIL showed any cytotoxic effect when used alone, apoptosis was induced when birinapant and TRAIL were used together. Our data suggest that the combination of birinapant and TRAIL induces downregulation of FLICE-like inhibitory protein (cFLIP) (L) protein expression. Interestingly, cFLIP(L) overexpression reversed apoptosis caused by co-treatment with TRAIL. Taken together, our results indicate that a combination of birinapant and TRAIL may be a promising treatment for TRAIL-resistant breast cancer.

Temporal trends in incidence of pediatric type 1 diabetes in Alabama: 2000-2017.

OBJECTIVE: The incidence of type 1 diabetes has increased in the United States and worldwide. We hypothesized that trends in the annual incidence rates of childhood-onset type 1 diabetes in the state of Alabama would be different by race and sex. METHODS: We performed a retrospective observational cohort study, analyzing children with type 1 diabetes (n = 3770) managed at the Children's Hospital of Alabama between 2000 and 2017. We compared crude incidence rates using negative binomial regression models and analyzed differences in annual trends of age-adjusted incidence by race and sex using joinpoint regression. RESULTS: The crude type 1 diabetes incidence rate was estimated at 16.7 per 100 000 children <19 years of age in Alabama. Between 2000 and 2007, there was an increase in age-adjusted incidence of type 1 diabetes with an annual percent change (APC) of 10% from 2000 to 2007 and a 1.7% APC decrease from 2007 to 2017. The age-adjusted incidence for Whites and Blacks increased with an average annual percentage change (AAPC) of 4.4% and 2.8%, respectively. A nearly 11% increasing trend in age-adjusted incidence was observed for both races, though the increase plateaued in 2006 for Whites and 2010 for Blacks. CONCLUSIONS: Following significantly increasing annual trends for both races, the age-adjusted rate remained statistically stable for Whites and decreased significantly for Blacks. Longer-sustained trend increases for Blacks resulted in type 1 diabetes incidence tripling compared to the doubling of the rate for Whites.

Extranasopharyngeal angiofibroma mimicking choanal polyp in patients with chronic paranasal sinusitis.

Extranasopharyngeal angiofibroma (ENA) is an angiofibroma that occurs in the extranasopharynx. It shows pathologic findings, such as juvenile angiofibroma (JNA), which accounts for 0.5% of head and neck mass. However, compared with JNA, the prevalence, affected site, and clinical characteristics are completely different, which leads some physicians to classify ENA as a disease different from JNA. ENA of the nasal turbinate origin are rarely reported in the literature. In addition, choanal polyp originating from the posterior part of the nasal turbinate is uncommonly reported. Recently, we encountered two cases of ENA, which were not diagnosed by intraoperative frozen section examination, but were histopathologically diagnosed post-operatively. Although we were unable to diagnose and perform embolization pre-operatively, ENA has been successfully treated by endoscopic surgery, without profuse bleeding.

Differential impact of circulating tumor cells on disease recurrence and survivals in patients with head and neck squamous cell carcinomas: An updated meta-analysis.

PURPOSE: The prognostic impact of circulating tumor cells (CTC) on disease recurrence, progression and survivals in patients with head and neck squamous cell carcinoma (HNSCC) has not been adequately described. The objective of this study was to determine the impacts of the presence of CTC on loco-regional recurrence and survival of HNSCC patients by conducting a systematic review and meta-analysis. METHODS: A comprehensive search for articles published between 1990 and 2016 was conducted and data from these studies were extracted, using the MEDLINE, Cochrane Library, and EMBASE databases. The main outcomes were overall survival (OS) and recurrence-free survival (RFS) of HNSCC patients. Pooled hazard ratio (HR) and 95% confidence intervals (95%CI) were calculated using the random effect model for outcomes. The quality of the studies, heterogeneity and publication bias were assessed with the appropriate statistical methods. RESULTS: Six eligible studies with 429 patients were identified. The presence of CTC was significantly associated shorter RFS (HR = 4.88 [95%CI: 1.93-12.35], P < 0.001). However, it could not predict patients' OS (HR = 1.92 [95%CI: 0.93-3.96], P = 0.078). The following analyses using univariable values of each study also made the similar results (HR = 1.70 [95%CI: 0.83-3.45] for OS, HR = 3.79 [95%CI: 2.02-7.13] for RFS). Heterogeneity and publication bias were not significant, except one enrolled study. CONCLUSIONS: The presence of CTC is not a significant prognostic indicator for OS of patients with HNSCC, although it could reflect the outcomes of loco-regional disease.

Interleukin-1 beta injected intracisternally inhibited NMDA-evoked behavioral response in the orofacial area of freely moving rats.

The brain-derived interleukin-1beta (IL-1beta) has been involved in the modulation of nociceptive processing. The direction of the effects, however, analgesia or hyperalgesia, is controversial. Here, we report the role of IL-1beta injected intracisternally in orofacial pain transmission. Experiments were carried out on 90 male SD rats and surgical procedures were performed under pentobarbital sodium. Intracisternal injection of 0.3 or 0.6 microg of N-methyl-d-aspartic acid (NMDA) produced intense scratching behavioral responses including vocalization, agitation and a desire to escape in a dose-related manner. The intracisternal injection of 1 or 10 ng IL-1beta significantly decreased the NMDA-evoked scratching behavioral responses. Pretreatment with an IL-1 receptor antagonist or naloxone, an opioid receptor antagonist, blocked the IL-1beta-induced antinociceptive response. These results suggest that cytokine injected intracisternally seems to produce antinociceptive effects in the NMDA-evoked pain model of the orofacial area and the antinociceptive effect seems to be mediated by an opioid pathway.