Intestinal Alkaline Phosphatase Attenuates Alcohol-Induced Hepatosteatosis in Mice.

BACKGROUND AND AIMS: Bacterially derived factors from the gut play a major role in the activation of inflammatory pathways in the liver and in the pathogenesis of alcoholic liver disease. The intestinal brush-border enzyme intestinal alkaline phosphatase (IAP) detoxifies a variety of bacterial pro-inflammatory factors and also functions to preserve gut barrier function. The aim of this study was to investigate whether oral IAP supplementation could protect against alcohol-induced liver disease. METHODS: Mice underwent acute binge or chronic ethanol exposure to induce alcoholic liver injury and steatosis ± IAP supplementation. Liver tissue was assessed for biochemical, inflammatory, and histopathological changes. An ex vivo co-culture system was used to examine the effects of alcohol and IAP treatment in regard to the activation of hepatic stellate cells and their role in the development of alcoholic liver disease. RESULTS: Pretreatment with IAP resulted in significantly lower serum alanine aminotransferase compared to the ethanol alone group in the acute binge model. IAP treatment attenuated the development of alcohol-induced fatty liver, lowered hepatic pro-inflammatory cytokine and serum LPS levels, and prevented alcohol-induced gut barrier dysfunction. Finally, IAP ameliorated the activation of hepatic stellate cells and prevented their lipogenic effect on hepatocytes. CONCLUSIONS: IAP treatment protected mice from alcohol-induced hepatotoxicity and steatosis. Oral IAP supplementation could represent a novel therapy to prevent alcoholic-related liver disease in humans.

A novel approach to maintain gut mucosal integrity using an oral enzyme supplement.

OBJECTIVE: To determine the role of intestinal alkaline phosphatase (IAP) in enteral starvation-induced gut barrier dysfunction and to study its therapeutic effect as a supplement to prevent gut-derived sepsis. BACKGROUND: Critically ill patients are at increased risk for systemic sepsis and, in some cases, multiorgan failure leading to death. Years ago, the gut was identified as a major source for this systemic sepsis syndrome. Previously, we have shown that IAP detoxifies bacterial toxins, prevents endotoxemia, and preserves intestinal microbiotal homeostasis. METHODS: WT and IAP-KO mice were used to examine gut barrier function and tight junction protein levels during 48-hour starvation and fed states. Human ileal fluid samples were collected from 20 patients postileostomy and IAP levels were compared between fasted and fed states. To study the effect of IAP supplementation on starvation-induced gut barrier dysfunction, WT mice were fasted for 48 hours +/- IAP supplementation in the drinking water. RESULTS: The loss of IAP expression is associated with decreased expression of intestinal junctional proteins and impaired barrier function. For the first time, we demonstrate that IAP expression is also decreased in humans who are deprived of enteral feeding. Finally, our data demonstrate that IAP supplementation reverses the gut barrier dysfunction and tight junction protein losses due to a lack of enteral feeding. CONCLUSIONS: IAP is a major regulator of gut mucosal permeability and is able to ameliorate starvation-induced gut barrier dysfunction. Enteral IAP supplementation may represent a novel approach to maintain bowel integrity in critically ill patients.

An Unusual Pathologic Ulna Fracture Induced by Intraosseous Tumoral Calcium Pyrophosphate Dihydrate Crystal Deposition Disease.

In this case report, we describe a novel occurrence of tumoral calcium pyrophosphate dihydrate crystal deposition disease (TCPPDCD) in a 76-year-old man that presented as an unusual, intraosseous, metadiaphyseal lesion of a long bone causing a pathologic fracture. A routine intralesional biopsy was performed, demonstrating granular deposits composed of polarizing, overlapping rhomboid crystals consistent with TCPPDCD. With limited numbers of reported cases of TCPPDCD, and the atypical intraosseous origin seen in this case, it is paramount to thoroughly evaluate all cases of TCPPDCD to clearly differentiate key findings that are essential in diagnosing and managing TCPPDCD.

The Association of Immediate-Use Steam Sterilization with the Incidence of Orthopaedic Surgical Site Infections: A Propensity Score-Matched Cohort Study.

BACKGROUND: Immediate-use steam sterilization (IUSS), formerly termed "flash" sterilization, has been historically used to sterilize surgical instruments in emergency situations. Strict guidelines deter its use, as IUSS has been theorized to increase the risk of surgical site infections (SSIs), leading to increased health-care costs and poor patient outcomes. We sought to examine the association between the use of IUSS and the rate of orthopaedic SSIs. METHODS: The cases of 70,600 patients who underwent orthopaedic surgery-total knee or hip arthroplasty, laminectomy, or spinal fusion-from January 2014 to December 2020, were retrospectively reviewed for IUSS use. Of this group, 3,526 patients had had IUSS used during surgery. A propensity score-matched (PSM) analysis was conducted to account for known predictors of SSIs and included a total of 7,052 patients. The risk difference (RD), relative risk (RR), odds ratio (OR), and McNemar test compared the SSI risk for patients whose procedure had included the use of IUSS and those whose procedure had not included IUSS. RESULTS: After propensity score matching, 111 (1.57%) of the 7,052 matched patients developed an SSI. Of the 111 patients, 61 (54.95%) were in the IUSS group and 50 (45.05%) were in the non-IUSS group. The estimated probability for developing an SSI was 1.42% for the patients in the non-IUSS group versus 1.73% for the patients in the IUSS group (RR = 0.82 [95% confidence interval (CI)]: 0.57 to 1.19], RD = -0.3% [95% CI: -0.9% to 0.27%]).There was no evidence that the proportion of SSI was greater in the IUSS group (McNemar test, p > 0.29). CONCLUSIONS: SSI rates were not significantly different between IUSS and non-IUSS patients undergoing orthopaedic surgery. Future prospective studies are warranted to further explore the utility of IUSS during orthopaedic procedures. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Zinc deficiency: A cause of opioid-induced physical dependence and addiction in post-operative total hip arthroplasty patients.

OBJECTIVES: Recently, opioid abuse and related overdoses have increased warranting the need for research directed against the opioid epidemic. Previous studies identified that patients on opioid therapy may become zinc deficient and that zinc, in a murine model, may antagonistically affect the opioid receptor.13 Further understanding the relationship between opioid use and zinc deficiency may mitigate the opioid epidemic. METHODS: A retrospective study was conducted to identify zinc (Zn2+) deficiencies among post-operative total hip arthroplasty (THA) patients. On post-operative day one, patients had routine blood tests, including Zn2+ plasma levels. Patients were considered Zn2+-deficient if their Zn2+ plasma was < 56 µg/dL (Reference: 56-134 µg/dL). Upon discharge from the hospital, the patients' inpatient opioid medication consumption per day was determined by dividing total morphine milligram equivalents (MMEs) by length of stay. A Student's t-test was performed to compare the total MMEs for Zn2+-deficient patients versus Zn2+-normal patients. A univariate analysis followed by multiple linear regression was performed to identify demographic or surgical predictors of MMEs/day. RESULTS: For Zn2+-deficient patients, the total MMEs/day was 33.62 ( ± 27.06), as compared to Zn2+-normal patients who consumed 16.22 ( ±16.01) MMEs/day (p = 0.031). The univariate analysis and multiple linear regression showed that patients' Zn2+ status had a significant contribution toward predicting MMEs/day, with p = 0.022 and p = 0.04, re-spectively. CONCLUSION: The results of this study suggest that Zn2+ deficiency may potentiate opioid consumption. Thus, Zn2+ sup-plementation may be a simple approach to reducing opioid addiction and dependence.