Pasi I. Nevalainen

Obesity, diabetes, and preoperative hyperglycemia as predictors of periprosthetic joint infection: a single-center analysis of 7181 primary hip and knee replacements for osteoarthritis.

BACKGROUND Diabetes and obesity are common in patients undergoing joint replacement. Studies analyzing the effects of diabetes and obesity on the occurrence of periprosthetic joint infection have yielded contradictory results, and the combined effects of these conditions are not known. METHODS The one-year incidence of periprosthetic joint infections was analyzed in a single-center series of 7181 primary hip and knee replacements (unilateral and simultaneous bilateral) performed between 2002 and 2008 to treat osteoarthritis. The data regarding periprosthetic joint infection (defined according to Centers for Disease Control and Prevention criteria) were collected from the hospital infection register and were based on prospective, active surveillance. Patients diagnosed with diabetes were identified from the registers of the Social Insurance Institution of Finland. The odds ratios (ORs) for infection and the accompanying 95% confidence intervals (CIs) were calculated with use of binary logistic regression with adjustment for age, sex, American Society of Anesthesiologists risk score, arthroplasty site, body mass index, and diabetic status. RESULTS Fifty-two periprosthetic joint infections occurred during the first postoperative year (0.72%; 95% CI, 0.55% to 0.95%). The infection rate increased from 0.37% (95% CI, 0.15% to 0.96%) in patients with a normal body mass index to 4.66% (95% CI, 2.47% to 8.62%) in the morbidly obese group (adjusted OR, 6.4; 95% CI, 1.7 to 24.6). Diabetes more than doubled the periprosthetic joint infection risk independent of obesity (adjusted OR, 2.3; 95% CI, 1.1 to 4.7). The infection rate was highest in morbidly obese patients with diabetes; this group contained fifty-one patients and periprosthetic infection developed in five (9.8%; 95% CI, 4.26% to 20.98%). In patients without a diagnosis of diabetes at the time of the surgery, there was a trend toward a higher infection rate in association with a preoperative glucose level of ≥6.9 mmol/L (124 mg/dL) compared with <6.9 mmol/L. The infection rate was 1.15% (95% CI, 0.56% to 2.35%) in the former group compared with 0.28% (95% CI, 0.15% to 0.53%) in the latter, and the adjusted OR was 3.3 (95% CI, 0.96 to 11.0). The type of diabetes medication was not associated with the infection rate. CONCLUSIONS Diabetes and morbid obesity increased the risk of periprosthetic joint infection following primary hip and knee replacement. The benefits of joint replacement should be carefully weighed against the incidence of postoperative infection, especially in morbidly obese patients. LEVEL OF EVIDENCE Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Preoperative hyperglycemia predicts infected total knee replacement

BACKGROUND Diabetes increases the risk of surgical site infections. In many patients undergoing total knee replacement, however, diabetes has not been diagnosed. The purpose of this study was to analyze the applicability of preoperative screening for hyperglycemia in identifying patients predisposed to infected knee replacement. METHODS A recent series of 1565 primary total knee replacements performed due to osteoarthritis in a specialized, publicly funded hospital for joint replacement was reviewed. RESULTS Preoperative hyperglycemia was significantly associated with infected knee replacement: during the 1-year follow-up infection occurred in 0.44%, 0.93% and 2.42% of patients with preoperative plasma glucose <6.1 mmol/l (<110 mg/dl), 6.1-6.9 mmol/l (110-125 mg/dl) and > or =7.0 mmol/l (> or =126 mg/dl). In age- and gender-adjusted analysis the patients with the highest glucose levels had a 4-fold risk for infected knee replacement compared to the patients with the lowest glucose. Obesity increased the risk of infected knee replacement, but the effect of hyperglycemia on the infection rates remained significant also after adjustment for body mass index. None of the patients with normal but 2.8% of patients with increased glycosylated hemoglobin (>6.5%) experienced infected knee replacement. CONCLUSION Obesity and hyperglycemia associate with a higher risk of infected knee replacement. Preoperative screening of plasma glucose is an efficient way to identify patients in increased risk of infection following primary total knee replacement.

Expression profiling of claudins in the human gastrointestinal tract in health and during inflammatory bowel disease

Abstract Background. Claudins, being part of the tight junction protein family, partially determine the integrity and paracellular permeability of the intestinal epithelium. The aim of this study was twofold. First, the authors set out to create an overview of claudin mRNA expression along the proximal-distal axis of the healthy human intestine. Second, the authors aimed to analyze expression levels of claudins in patients with active and inactive inflammatory bowel diseases (IBD) such as Crohns disease or ulcerative colitis (UC). Methods. mRNA expression levels of claudins were determined in gastrointestinal biopsies from healthy patients as well as patients diagnosed with IBD using SybrGreen real-time PCR. Results. Claudins show distinct expression patterns throughout the gastrointestinal tract. Some claudins show a proximal expression pattern, such as CLDN18 which is solely expressed in the stomach, and CLDN2 and -15 that are predominantly expressed in the proximal parts of the gastrointestinal tract. Other claudins, such as CLDN3, -4, -7 and -8, are predominantly expressed in the distal parts of the gastrointestinal tract or show a ubiquitous expression pattern throughout the entire gastrointestinal tract, which is the case for CLDN12. In addition, we show that changes in claudin expression in IBD are dependent on gastrointestinal location and inflammatory activity. Conclusions. This study provides detailed mRNA expression patterns of various claudins throughout the human gastrointestinal tract. Analysis of expression levels of claudins in patients with CD, active and inactive UC shows that changes in expression are confined to specific intestinal segments and strongly depend on inflammatory activity.

Segmental transport of Ca2+ and Mg2+ along the gastrointestinal tract

Calcium (Ca(2+)) and magnesium (Mg(2+)) ions are involved in many vital physiological functions. Since dietary intake is the only source of minerals for the body, intestinal absorption is essential for normal homeostatic levels. The aim of this study was to characterize the absorption of Ca(2+) as well as Mg(2+) along the gastrointestinal tract at a molecular and functional level. In both humans and mice the Ca(2+) channel transient receptor potential vanilloid subtype 6 (TRPV6) is expressed in the proximal intestinal segments, whereas Mg(2+) channel transient receptor potential melastatin subtype 6 (TRPM6) is expressed in the distal parts of the intestine. A method was established to measure the rate of Mg(2+) absorption from the intestine in a time-dependent manner by use of (25)Mg(2+). In addition, local absorption of Ca(2+) and Mg(2+) in different segments of the intestine of mice was determined by using surgically implanted intestinal cannulas. By these methods, it was demonstrated that intestinal absorption of Mg(2+) is regulated by dietary needs in a vitamin D-independent manner. Also, it was shown that at low luminal concentrations, favoring transcellular absorption, Ca(2+) transport mainly takes place in the proximal segments of the intestine, whereas Mg(2+) absorption predominantly occurs in the distal part of the gastrointestinal tract. Vitamin D treatment of mice increased serum Mg(2+) levels and 24-h urinary Mg(2+) excretion, but not intestinal absorption of (25)Mg(2+). Segmental cannulation of the intestine and time-dependent absorption studies using (25)Mg(2+) provide new ways to study intestinal Mg(2+) absorption.

Diabetes is associated with persistent pain after hip and knee replacement

Background and purpose — In some patients, for unknown reasons pain persists after joint replacement, especially in the knee. We determined the prevalence of persistent pain following primary hip or knee replacement and its association with disorders of glucose metabolism, metabolic syndrome (MetS), and obesity. Patients and methods — The incidence of pain in the operated joint was surveyed 1–2 years after primary hip replacement (74 patients (4 bilateral)) or primary knee replacement (119 patients (19 bilateral)) in 193 osteoarthritis patients who had participated in a prospective study on perioperative hyperglycemia. Of the 155 patients who completed the survey, 21 had undergone further joint replacement surgery during the follow-up and were excluded, leaving 134 patients for analysis. Persistent pain was defined as daily pain in the operated joint that had lasted over 3 months. Factors associated with persistent pain were evaluated using binary logistic regression with adjustment for age, sex, and operated joint. Results — 49 of the134 patients (37%) had a painful joint and 18 of them (14%) had persistent pain. A greater proportion of knee patients than hip patients had a painful joint (46% vs. 24%; p = 0.01) and persistent pain (20% vs. 4%; p = 0.007). Previously diagnosed diabetes was strongly associated with persistent pain (5/19 vs. 13/115 in those without; adjusted OR = 8, 95% CI: 2–38) whereas MetS and obesity were not. However, severely obese patients (BMI ≥ 35) had a painful joint (but not persistent pain) more often than patients with BMI < 30 (14/21 vs. 18/71; adjusted OR = 5, 95% CI: 2–15). Interpretation — Previously diagnosed diabetes is a risk factor for persistent pain in the operated joint 1–2 years after primary hip or knee replacement.

Risk factors for perioperative hyperglycemia in primary hip and knee replacements

Background and purpose — Perioperative hyperglycemia has been associated with adverse outcomes in several fields of surgery. In this observational study, we identified factors associated with an increased risk of hyperglycemia following hip and knee replacement. Patients and methods — We prospectively monitored changes in glucose following primary hip and knee replacements in 191 patients with osteoarthritis. Possible associations of patient characteristics and operation-related factors with hyperglycemia (defined as glucose > 7.8 mmol/L in 2 consecutive measurements) and severe hyperglycemia (glucose > 10 mmol/L) were analyzed using binary logistic regression with adjustment for age, sex, operated joint, and anesthesiological risk score. Results — 76 patients (40%) developed hyperglycemia, and 48 of them (25% of the whole cohort) had severe hyperglycemia. Glycemic responses were similar following hip replacement and knee replacement. Previously diagnosed diabetes was associated with an increased risk of hyperglycemia and severe hyperglycemia, compared to patients with normal glucose metabolism, whereas newly diagnosed diabetes and milder glucose metabolism disorders had no effect. In patients without previously diagnosed diabetes, increased values of preoperative glycosylated hemoglobin (HbA1c) and fasting glucose on the day of operation were associated with hyperglycemia. Higher anesthesiological risk score—but none of the operation-related factors analyzed—was associated with an increased risk of hyperglycemia. Interpretation — Perioperative hyperglycemia is common in primary hip and knee replacements. Previously diagnosed diabetes is the strongest risk factor for hyperglycemia. In patients with no history of diabetes, preoperative HbA1c and fasting glucose on the day of operation can be used to stratify the risk of hyperglycemia.