Liposomal bupivacaine interscalene blocks demonstrate a greater proportion of total shoulder arthroplasty patients with clinically tolerable pain: a retrospective quality improvement study of 491 patients.

OBJECTIVE: To evaluate the effects of liposomal bupivacaine use for interscalene blocks on postoperative analgesia in total shoulder arthroplasty patients. METHODS: De-identified total or reverse total shoulder arthroplasty patients between 2018 and 2021 were analyzed. Patients were grouped into single shot interscalene block with liposomal bupivacaine (LB) with plain bupivacaine, other block (OB) with other local anesthetics (mepivacaine, ropivacaine, or plain bupivacaine), or no block (NB). The primary outcome was the proportion of patients with clinically tolerable pain scores (mean VAS ≤4) from 0 to 24 â€‹h in each group. Secondary outcomes included averaged visual analog pain scores (VAS) and opioid consumption measured in morphine milligram equivalents (MMEs) from 0 to 24 â€‹h. We also analyzed the proportion of patients with clinically tolerable pain, mean VAS, and opioid consumption from 0 to 72 â€‹h in those patients with at least a 3-day hospital length of stay. RESULTS: A total of 491 de-identified total shoulder arthroplasty patients, 285 liposomal bupivacaine group (LB), 178 other block group (OB), and 28 no block group (NB), were analyzed. The primary outcome showed a statistically significant different proportion of patients with clinically tolerable pain from 0 to 24 â€‹h in the LB group (69 â€‹%) vs. OB group (39 â€‹%) vs. NB group (11 â€‹%) (<0.001). Secondary outcomes included statistically significant differences in VAS (LB median â€‹= â€‹3.35, OB median â€‹= â€‹4.38, NB median â€‹= â€‹5.25 (p â€‹< â€‹0.001, <0.001)) and total MME opioid consumption (LB median â€‹= â€‹40, OB median â€‹= â€‹60, NB median â€‹= â€‹88 (p â€‹< â€‹0.001, 0.001)) between groups from 0 to 24 â€‹h. For patients who had hospital stays of at least 3 days, a significant association was found with having achieved clinically tolerable pain 0-72 â€‹h and the LB group (51 â€‹%) vs. OB group (21 â€‹%) vs. NB group (11 â€‹%) (P â€‹= â€‹0.006). However, there was no statistical difference in mean VAS or opioid consumption between these groups. CONCLUSION: A greater proportion of total shoulder arthroplasty patients that received liposomal bupivacaine in interscalene block have clinically tolerable pain scores from 0 to 24 â€‹h, lower VAS, and lower MME consumption in patients following total shoulder arthroplasty. LEVEL OF EVIDENCE: Level III - Clinical Study.

Restraint Stress Alters Expression of Glucocorticoid Bioavailability Mediators, Suppresses Nrf2, and Promotes Oxidative Stress in Liver Tissue.

Hepatic glutathione synthesis and antioxidant protection are critically important for efficient detoxification processes in response to metabolic challenges. However, this biosynthetic pathway, regulated by nuclear factor (erythroid-derived 2)-like 2 (Nrf2), previously demonstrated paradoxical repression following exposure to glucocorticoid stress hormones in cultured hepatic cells. Therefore, the present study used an in vivo model of sub-acute psychological stress to investigate the relationship between hepatic corticosteroid regulation and antioxidant systems. Male Wistar rats were kept under control conditions or subjected to six hours of restraint stress applied for 1 or 3 days (n = 8 per group) after which the liver was isolated for assays of oxidative/nitrosative status and expression of corticosteroid regulatory and Nrf2-antioxidant response element pathway members. A single stress exposure produced a significant increase in the expression of corticosterone reactivator, 11-beta-hydroxysteroid dehydrogenase 1 (11ß-Hsd1), while the 11ß-Hsd2 isozyme and corticosteroid-binding globulin were down-regulated following stress, indicative of an elevated availability of active corticosterone. Exposure to restraint significantly decreased hepatic concentrations of total cysteine thiols and the antioxidant reduced glutathione on Day 1 and increased 3-nitrotyrosinated and carbonylated proteins on Day 3, suggestive of oxidative/nitrosative stress in the liver following stress exposure. Conversely, there was a sustained down-regulation of Nrf2 mRNA and protein in addition to significant reductions in downstream glutamate-cysteine ligase catalytic subunit (Gclc), the rate-limiting enzyme in glutathione synthesis, on Day 1 and 3 of stress treatment. Interestingly, other antioxidant genes including superoxide dismutase 1 and 2, and glutathione peroxidase 4 were significantly up-regulated following an episode of restraint stress. In conclusion, the results of the present study indicate that increased expression of 11ß-Hsd1, indicative of elevated tissue glucocorticoid concentrations, may impair the Nrf2-dependent antioxidant response.

Sub-acute restraint stress progressively increases oxidative/nitrosative stress and inflammatory markers while transiently upregulating antioxidant gene expression in the rat hippocampus.

We have previously demonstrated that acute stress decreases neuronal nitric oxide synthase (NOS) expression in the hippocampus despite increased concentrations of nitric oxide which may indicate feedback inhibition of neuronal NOS expression via inducible NOS-derived nitric oxide. Moreover, the hippocampus undergoes an initial oxidative/nitrosative insult that is rapidly followed by upregulation of protective antioxidants, including the zinc-binding metallothioneins, in order to counter this and restore redox balance following acute stress exposure. In the present study, we have utilized indicators of oxidative/nitrosative stress, members of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway, antioxidant metallothioneins, and neuroinflammatory markers to observe the changes occurring in the hippocampus following short term repeated stress exposure. Male Wistar rats were subjected to control conditions or 6 h of restraint stress applied for 1, 2, or 3 days (n = 8 per group) after which the hippocampus was isolated for redox assays and relative gene expression. The hippocampus showed increased oxidative stress, transient dys-homeostasis of total zinc, and increased expression of the Nrf2 pathway members. Moreover, repeated stress increased nitrosative status, nitric oxide metabolites, and 3-nitrotyrosine, indicative of nitrosative stress in the hippocampus. However, levels of neuronal NOS decreased over all stress treatment groups, while increases were observed in inducible NOS and xanthine dehydrogenase. In addition to inducible NOS, mRNA expression of other inflammatory markers including interleukin-6 and interleukin-1ß also increased even in the presence of increased anti-inflammatory glucocorticoids. Together, these results demonstrate that despite increases in antioxidant expression, sub-acute stress causes an inflammatory phenotype in the hippocampus by inducing oxidative/nitrosative stress, zinc dys-homeostasis, and the accumulation of nitrotyrosinated proteins which is likely driven by increased inducible NOS signaling.

Changes in hippocampal inflammatory-related and redox enzyme genes in response to sub-acute restraint stress: Additional dataset.

This data article presents complementary results pertaining to the research article entitled "Sub-acute restraint stress progressively increases oxidative/nitrosative stress and inflammatory markers while transiently upregulating antioxidant gene expression in the rat hippocampus" (Chen et al., 2018). The present article provides additional gene expression data of selected neuroinflammatory markers and regulatory enzymes involved in oxidation-reduction reactions. Male Wistar rats aged 7-8 weeks were exposed to control, 1, 2, or 3 episodes of 6-h restraint stress in the light cycle after which the whole brain was quickly removed and the hippocampus excised for relative gene expression analysis. Specifically, mRNA levels of inflammatory regulators including allograft inflammatory factor 1, class II major histocompatibility complex, integrin alpha M, interferon gamma, and prostaglandin-endoperoxide synthase 2 were analyzed by real-time PCR. The gene expression of redox regulatory enzymes including glutathione peroxidase 1, glutathione peroxidase 4, superoxide dismutase 1, superoxide dismutase 2, myeloperoxidase, and NADPH oxidase subunit P47phox were also determined. These data provide useful insights in the molecular basis of inflammatory and redox regulation in the hippocampus following a short term to repeated psychological challenge in rats.

Neuronal and inducible nitric oxide synthase upregulation in the rat medial prefrontal cortex following acute restraint stress: A dataset.

This data article provides additional evidence on gene expression changes in the neuronal and inducible isoforms of nitric oxide synthase in the medial prefrontal cortex following acute stress. Male Wistar rats aged 6-8 weeks were exposed to control or restraint stress conditions for up to four hours in the dark cycle after which the brain was removed and the medial prefrontal cortex isolated by cryodissection. Following RNA extraction and cDNA synthesis, gene expression data were measured using quantitative real-time PCR. The mRNA levels of the neuronal and inducible nitric oxide synthase isoforms, and the inhibitory subunit of NF-κB, I kappa B alpha were determined using the ΔΔCT method relative to control animals. This data article presents complementary results related to the research article entitled 'Acute restraint stress induces specific changes in nitric oxide production and inflammatory markers in the rat hippocampus and striatum' [1].

A pragmatic and successful approach to treating nonsmall-cell lung carcinoma.

Lung cancer is the single leading cause of cancer deaths for men and women combined. Nonsmall-cell lung carcinoma (NSCLC), which results largely from smoking tobacco, accounts for 87% of all lung cancer cases. Methods of patient selection, preoperative and intraoperative care, and postoperative outcomes for patients with NSCLC who were treated from 1991 through 2003 at Inova Fairfax Hospital are discussed. All patients were treated with surgery, some selectively and progressively with a combination of preoperative neoadjuvant therapy, to try to downstage the disease to make complete resection feasible. Outcomes from this data collection period match or exceed the best results for treatment of late-stage (ie, III and IV) disease reported anywhere to date.