A prospective, randomized trial of liposomal bupivacaine compared to conventional bupivacaine on pain control and postoperative opioid use in adults receiving adductor canal blocks for total knee arthroplasty.

BACKGROUND: Total knee arthroplasty (TKA) is a commonly performed procedure to alleviate pain and improve functional limitations caused by end-stage joint damage. Effective management of postoperative pain following TKA is crucial to the prevention of complications and enhancement of recovery. Adductor canal blocks (ACB) with conventional bupivacaine (CB) provide adequate analgesia after TKA, but carry a risk of rebound pain following block resolution. Liposomal bupivacaine (LB) is an extended-release local anesthetic that can provide up to 72 h of pain relief. The objective of this study was to compare postoperative outcomes between ACBs using LB and CB after TKA. METHODS: This single institution, prospective, randomized, clinical trial enrolled patients scheduled for TKA. Participants were randomized to receive ACB with either LB or CB. Pain scores up to 72 h postoperatively were assessed as the primary outcome. Opioid consumption and length of stay were evaluated as secondary outcomes. RESULTS: A total of 80 patients were enrolled. Demographic and clinical characteristics were similar between the two groups. LB group showed significantly lower cumulative opioid use during the 72 h evaluated (P = 0.016). There were no differences in pain scores or length of stay between the groups. CONCLUSION: The study demonstrated that LB ACBs led to significantly lower opioid consumption in the days following TKA without affecting pain scores or length of stay. This finding has important implications for improving postoperative outcomes and reducing opioid use in TKA patients. Previous studies have reported inconsistent results regarding the benefits of LB, highlighting the need for further research. TRIAL REGISTRATION: This project was retrospectively registered with clinicaltrials.gov ( NCT05635916 ) on 2 December 2022.

A Comprehensive Review of Celiac Disease/Gluten-Sensitive Enteropathies.

Celiac disease is a complex immune-mediated gluten-sensitive enteropathy with protean clinical manifestations. It is manifest in genetically predisposed individuals who ingest gluten in varying amounts. In broad terms, it is thought to affect 1% of the population in the USA. More specifically, the prevalence increases drastically from 1:133 in patients not-at-risk, to 1:56 in symptomatic patients, to 1:39 in patients with a second-degree relative with the diagnosis, and to 1:22 in patients with a first-degree relative with the diagnosis. It may be associated with several immune-mediated phenomena, autoimmune diseases, and complicated by vitamin and other trace element deficiencies, bone disease, and malignancy. Our understanding of celiac disease has evolved rapidly over the past two decades. This has led to several lines of enquiry on the condition and potential treatment options. More recently, several entities including gluten intolerance, non-celiac gluten sensitivity, and seronegative celiac disease have been described. These conditions are distinct from allergies or intolerance to wheat or wheat products. There are challenges in defining some of these entities since a large number of patients self-report these conditions. The absence of confirmatory diagnostic tests poses an added dilemma in distinguishing these entities. The differences in spectrum of symptoms and highlights of the variability between the pediatric and adult populations have been studied in some detail. The role of screening for celiac disease is examined in both the general population and "at risk" populations. Diagnostic strategies including the best available serologic testing, utility of HLA haplotypes DQ2 and DQ8 which are seen in over 90% of patients with celiac disease as compared with approximately 40% of the general population, and endoscopic evaluation are also reviewed. Comprehensive nutritional management after diagnosis is key to sustained health in patients with celiac disease. Simple algorithms for care based on a comprehensive multidisciplinary approach are proposed. Refractory and non-responsive celiac diseases in the setting of a gluten-free diet are examined as are novel non-dietary therapies. Finally, the association of other disease states including psychiatric illness, infertility, lymphoproliferative malignancy, and mortality is explored with special attention paid to autoimmune and atopic disease.

Hit or a miss: Concordance between histopathologic-endoscopic findings in gastric mucosal biopsies.

BACKGROUND: Current literature shows a variable degree of concordance between endoscopic and histopathologic findings in gastric mucosal biopsies. Most prior studies have focused on specific gastric entities such as gastritis in patients with high prevalence of Helicobacter pylori (H. pylori). In this study, we assess concordance between histologic and endoscopic findings in a wide spectrum of targeted as well as non-targeted gastric endoscopic biopsies. METHODS: We retrospectively reviewed pathology database and slides at Hershey Medical Center to identify 630 gastric mucosal biopsies obtained from 525 consecutive patients. The corresponding clinical and endoscopic findings were retrieved from the electronic medical record. RESULTS: The rate of abnormal endoscopic and histologic findings was 72.9% and 74.4%, respectively, with Cohen's ĸ coefficient of 0.24. There were 444 (70.5%) concordant cases and 186 (29.5%) discordant cases (88 cases with abnormal endoscopy but normal histology, and 98 cases with normal endoscopy but abnormal histology). Some endoscopic findings, in particular, mass, polyp, ulcer, and nodule/papule were highly concordant with abnormal histopathologic findings; while other endoscopic findings such as inflammatory changes, normal and prominent folds were associated with normal and a variety of abnormal histopathology. Multivariate analysis showed no significant association between intestinal metaplasia and H. pylori in this study. CONCLUSIONS: Histopathologic-endoscopic correlation in gastric biopsies varies depending on endoscopic mucosal patterns. Intestinal metaplasia may not have a significant association with H. pylori infection in populations with low prevalence of H. pylori.

Terminal Ileitis as a Feature of Henoch-Schönlein Purpura Masquerading as Crohn Disease in Adults.

Henoch-Schönlein purpura (HSP), more recently termed immunoglobulin A (IgA) vasculitis, is a systemic small-vessel vasculitis characterized by perivascular IgA deposition. This disease manifests clinically as palpable purpura, arthralgia, gastrointestinal symptoms, and renal dysfunction. Although ileitis can be seen in HSP, terminal ileitis is virtually pathognomonic for Crohn disease. We present a comprehensive review of the literature on this association, including 2 cases of our own, to demonstrate the importance of considering HSP in the differential diagnosis of ileitis suggestive of Crohn disease. We review the growing body of literature suggesting a pathophysiologic link between the conditions, possibly through an IgA-mediated mechanism.

Lung lining fluid glutathione attenuates IL-13-induced asthma.

GGT(enu1) mice, deficient in gamma-glutamyl transferase and unable to metabolize extracellular glutathione, develop intracellular glutathione deficiency and oxidant stress. We used intratracheal IL-13 to induce airway inflammation and asthma in wild-type (WT) and GGT(enu1) mice to determine the effect of altered glutathione metabolism on bronchial asthma. WT and GGT(enu1) mice developed similar degrees of lung inflammation. In contrast, IL-13 induced airway epithelial cell mucous cell hyperplasia, mucin and mucin-related gene expression, epidermal growth factor receptor mRNA, and epidermal growth factor receptor activation along with airway hyperreactivity in WT mice but not in GGT(enu1) mice. Lung lining fluid (extracellular) glutathione was 10-fold greater in GGT(enu1) than in WT lungs, providing increased buffering of inflammation-associated reactive oxygen species. Pharmacologic inhibition of GGT in WT mice produced similar effects, suggesting that the lung lining fluid glutathione protects against epithelial cell induction of asthma. Inhibiting GGT activity in lung lining fluid may represent a novel therapeutic approach for preventing and treating asthma.

Histamine 4 receptor activation induces recruitment of FoxP3+ T cells and inhibits allergic asthma in a murine model.

Histamine has an important role in regulation of immune response which is mediated by differential expression of four distinct receptors, H1R-H4R. H1R and HR2 have previously been shown to be involved with modulation of lung inflammation. H4R is also expressed on inflammatory cells; therefore, we investigated the potential role of H4R in development of allergic asthma in a murine model. We determined that the H4R agonist 4-methylhistamine when delivered intratracheally before Ag challenge mitigated airway hyperreactivity and inflammation. This was associated with an increase in IL-10 and IFN-gamma, but not TGF-beta or IL-16, as well as a decrease in IL-13 in the bronchoalveolar lavage fluid. We also observed that H4R agonist instillation resulted in accumulation of FoxP3(+) T cells suggesting a direct effect on T regulatory cell recruitment. To investigate this further, we determined the in vitro effect of H4R stimulation on human T cell migration. The H4R agonist induced a 2- to 3-fold increase in T cell migration, similar to that seen for H1R agonists. Cells transmigrating to the H4R agonist, but not H1R, were skewed toward a CD4 cell expressing CD25 and intracellular FoxP3. H4R-responsive cells suppressed proliferation of autologous T cells, an effect that was dependent on IL-10 production. We conclude that H4R stimulation enriches for a regulatory T cell with potent suppressive activity for proliferation. These findings identify a novel function for H4R and suggest a potential therapeutic approach to attenuation of asthmatic inflammation.

Early life exposure to environmental levels of the aromatase inhibitor tributyltin causes masculinisation and irreversible sperm damage in zebrafish (Danio rerio).

To determine whether early life exposure to tributyltin (TBT), an aromatase inhibitor, impaired reproductive function in fish, Danio rerio were exposed to environmentally realistic levels (0.01-100 ng l(-1)) of TBT from 0 to 30, 30 to 60, and 0 to 70 days post-hatch, and the sex ratio and sperm motility of the adults examined 3-5 months after cessation of exposure. Fish exposed for 70 days to 0.1 ng l(-1) of TBT, a concentration presently below the detection limit in water, showed a male biased population which produced a high incidence of sperm lacking flagella. At 1 ng l(-1), the motility of sperm was significantly lower than that of control fish, while at 10 ng l(-1), all sperm lacked flagella and, at 100 ng l(-1), milt volume had increased. The effect of exposure on sex ratio was similar after exposure from 0 to 70 and 0 to 30 days, but even 100 ng l(-1) gave only 65% males after exposure from 30 to 60 days. Effects on sperm motility and morphology and on milt volume were less pronounced after 30 day than 70 day exposure. Our data suggest that screening for aromatase inhibiting activity and assessment of its risks in early life to human and wildlife fertility needs to be urgently addressed, and that the reproductive toxicity of TBT may presently be underestimated.