SuperPath® vs. direct anterior approach : A retrospective comparison between two minimally invasive approaches in total hip arthroplasty.

OBJECTIVE: Minimally invasive approaches are subject to controversy in orthopedic surgery. The aim of the current study was to compare the radiographic parameters between two minimally invasive approaches in total hip arthroplasty. MATERIAL AND METHODS: Between January 2018 and February 2019, the radiographic parameters of 80 patients undergoing total hip arthroplasty via minimally invasive approaches (DAA: n = 40; SuperPath® SP: n = 40) have been measured. The radiographic analysis was performed with digital software tool mediCad® (HECTEC™ GmbH, Landshut, Germany). RESULTS: Patients treated with DAA showed significantly higher inclination (SP: 39.7°â€¯± 7.3° vs. DAA: 44.7°â€¯± 5.3°) and significantly lower cup anteversion values (SP: 31.2°â€¯± 7.9° vs. DAA: 27. 5°â€¯± 5.3°, p < 0.001) than patients undergoing THA via SP postoperatively. The horizontal femoral offset was neither preoperatively nor postoperatively higher in DAA than in SP cohort (preoperative: p = 0.71, postoperative: p = 0.25) (preoperative: SP:37.2 mm ± 7.3 vs. DAA 38.2 mm ± 7.5; postoperative: SP: 38.0 mm ± 7.2 vs. DAA: 40.5 mm ± 7.0). At both times, the acetabular offset was significantly higher in DAA cohort than in SP cohort (preoperative: SP: 32.9 mm ± 5.9 vs. DAA: 36.8 mm ± 4.9; postoperative: SP: 28.9 mm ± 4.2 vs. DAA: 33.4 mm ± 3.8) (preoperative: 0.001; postoperative: p < 0.001). The vertical height was preoperatively and postoperatively not significantly higher in SP cohort than in DAA cohort (preoperative: SP: 16.1 mm ± 4.1 vs. DAA: 15.5 mm ± 4.9; postoperative: SP: 16.6 mm ± 4.6 vs. DAA: 16.1 mm ± 4.6) (preoperative: p = 0.77; postoperative: p = 0.58). The preoperatively existing leg length discrepancy of the affected leg could be compensated via surgery without showing significant differences between the two cohorts (preoperative: SP: -3.2 mm ± 5.4 vs. DAA: 1.9 mm ± 4.9; postoperative: SP: 1.5 mm ± 5.4 vs. DAA: 4.8 mm ± 5.6) (preoperative: p = 0.34; postoperative: p = 0.09). CONCLUSION: The current study demonstrates suitable cup positioning and stem alignment in the coronal plane using minimal-invasive approaches DAA and Superpath®.

Metal Artefact Reduction Sequences (MARS) in Magnetic Resonance Imaging (MRI) after Total Hip Arthroplasty (THA) : A non-invasive approach for preoperative differentiation between periprosthetic joint infection (PJI) and aseptic complications?

BACKGROUND: In the past, radiographic imaging was of minor relevance in the diagnosis of periprosthetic joint infections (PJI). Since metal artefact reduction sequences (MARS) are available, magnetic resonance imaging (MRI) has become a promising diagnostic tool for the evaluation of hip arthroplasty implants. The purpose of the present study was to evaluate the efficacy of MARS-MRI in comparison to established diagnostic tools to distinguish between aseptic failure and PJI. METHODS: From July 2018 to September 2019, 33 patients classified as having an aseptic joint effusion were recruited into the study. The group included 22 women and 11 men with a mean age of 70.4 ± 13.7 (42-88) years. In the same period, 12 patients were classified as having a PJI. The group consisted of 9 women and 3 men with a mean age of 72.5 ± 10.6 (54-88) years. MARS-MRI was conducted using the optimized parameters at 1.5 T in a coronal and axial STIR (short-tau-inversion recovery), a non-fat-saturated T2 in coronal view and a non-fat-saturated T1 in transverse view in 45 patients with painful hip after total hip arthroplasty (THA). Normally distributed continuous data were shown as mean ± standard deviation (SD) and compared using student's t-test. Non-normally distributed continuous data were shown as mean and compared using the Mann-Whitney U test. RESULTS: Synovial layering and muscle edema were significant features of periprosthetic joint infection, with sensitivities of 100% and specifities of 63.0-75.0%. The combined specifity and sensitivity levels of synovial layering and muscular edema was 88.0% and 90.0%. Granulomatous synovitis was a significant feature for aseptic failure, with 90.0% sensitivity and 57.0% specifity. CONCLUSION: MARS-MRI is as suitable as standard diagnostic tools to distinguish between aseptic failure and PJI in patients with THA. Further studies with larger patient numbers have to prove whether MARS-MRI could be integral part of PJI diagnostic.

Incidence, impact and risk factors for multidrug-resistant organisms (MDRO) in patients with major trauma: a European Multicenter Cohort Study.

INTRODUCTION: The burden of MDRO in health systems is a global issue, and a growing problem. We conducted a European multicenter cohort study to assess the incidence, impact and risk factors for multidrug-resistant organisms in patients with major trauma. We conducted this study because the predictive factors and effects of MDRO in severely injured patients are not yet described. Our hypothesis is that positive detection of MDRO in severely injured patients is associated with a less favorable outcome. METHODS: Retrospective study of four level-1 trauma centers including all patients after major trauma with an injury severity score (ISS) ≥ 9 admitted to an intensive care unit (ICU) between 2013 and 2017. Outcome was measured using the Glasgow outcome scale (GOS). RESULTS: Of 4131 included patients, 95 (2.3%) had a positive screening for MDRO. Risk factors for MDRO were male gender (OR 1.73 [95% CI 1.04-2.89]), ISS (OR 1.01 [95% CI 1.00-1.03]), PRBC's given (OR 1.73 [95% CI 1.09-2.78]), ICU stay > 48 h (OR 4.01 [95% CI 2.06-7.81]) and mechanical ventilation (OR 1.85 [95% CI 1.01-3.38]). A positive MDRO infection correlates with worse outcome. MDRO positive cases GOS: good recovery = 0.6%, moderate disability = 2.1%, severe disability = 5.6%, vegetative state = 5.7% (p < 0.001). CONCLUSIONS: MDRO in severely injured patients are rare but associated with a worse outcome at hospital discharge. We identified potential risk factors for MDRO in severely injured patients. Based on our results, we recommend a standardized screening procedure for major trauma patients.

Diagnostic Accuracy of Synovial Neopterin, TNF-α and Presepsin in Periprosthetic Joint Infection: A Prospective Study.

BACKGROUND: Due to the lack of specificity of conventional diagnostic tools, the prediction of periprosthetic joint infections (PJI) remains challenging. The purpose of this study was to evaluate the accuracy of synovial fluid neopterin, presepsin, and TNF-α as diagnostic parameters and to compare it to the biomarkers recommended in the 2018 definition of periprosthetic hip and knee infection. METHODS: Between August 2018 and July 2019, a prospective cohort study was conducted in 80 patients with painful hip, shoulder, and knee arthroplasty. In addition to medical history, clinical and laboratory data were gathered. PJI was diagnosed based on the 2018 definition of periprosthetic hip and knee infection. Synovial joint fluid was analyzed for biomarker measurement using standard quantitative enzyme immunoassay kits. RESULTS: Fifty-three patients (66%) were classified as the aseptic group and twenty-seven patients (34%) as the PJI group. The mean levels of synovial fluid neopterin were significantly higher (p < 0.01) in the PJI group than those in the aseptic group (aseptic 8.3 ± 6.9 vs. PJI 20.9 ± 21.4 nmol/L). The average values of synovial fluid TNF-α and presepsin were not significantly higher in the PJI group than those in the aseptic group (presepsin: aseptic 0.13 ± 0.19 vs. PJI 0.11 ± 0.32 ng/mL, p = 0.08; TNF-α: aseptic 6.6 ± 7.3 vs. PJI 46.3 ± 123.2 pg/mL, p = 0.17). Synovial fluid neopterin was 59% specific and 74% sensitive with a cut-off value of 7.2 nmol/L. The sensitivity and specificity of synovial fluid TNF-α were 63 and 51% with a cut-off value of 3.9 pg/mL. Synovial fluid presepsin was 51% specific and 29% sensitive with a cut-off value above 0.06 ng/mL. CONCLUSION: Synovial fluid neopterin appears to a reliable diagnostic marker for detection of PJI. In contrast, synovial fluid TNF-α and presepsin are not suitable to exclude or diagnose PJI.

[Shoulder arthroplasty]. / Schulterendoprothetik.

Arthroplasty of the shoulder joint leads to excellent clinical results if the indications are valid and the implantation is technically correct. Taking anatomical requirements and mechanical functions as well as material properties and developments in surgical techniques into account, articulations and anchoring systems have been developed which, as modular systems enable successful restoration of the biomechanics and consider the importance of the surrounding soft tissues. Scientific data show promising medium-term and long-term results in terms of functionality and pain reduction. Nevertheless, due to the limited bone stock for implant anchoring, especially loosening of the prosthesis or instability of the glenoid joint component, revision arthroplasty remains challenging. This review article summarizes the relevant aspects of shoulder arthroplasty.

Synovial Alpha-defensin at Reimplantation in Two-stage Revision Arthroplasty to Rule Out Persistent Infection.

BACKGROUND/AIM: Owing to the lack of a diagnostic gold standard, ruling out persistent periprosthetic joint infection (PJI) before second-stage surgery in the setting of two-stage revision arthroplasty constitutes a major challenge. We evaluated if the alpha-defensin-1 (AD-1) test could predict successful infection eradication before reimplantation of a new prosthesis. PATIENTS AND METHODS: Our prospective study included 20 patients who underwent two-stage revision arthroplasty for treatment of PJI. A standard quantitative enzyme AD-1 immunoassay of synovial fluid, the synovial leukocyte esterase test and routine laboratory blood testing were performed prior to explantation and reimplantation. Treatment failure was defined according to the Delphi-based consensus criteria after a minimum follow-up of 1 year. RESULTS: A 15% of our patients met the Delphi Criteria within 1 year. None of the markers investigated were significantly different in patients with and without reinfection. CONCLUSION: Further research is necessary to identify biomarkers more suitable for indicating persistent infection before reimplantation.

Bone Substitutes in Orthopaedic Surgery: Current Status and Future Perspectives.

Bone replacement materials have been successfully supplied for a long time. But there are cases, especially in critical sized bone defects, in which the therapy is not sufficient. Nowadays, there are multiple bone substitutes available. Autologous bone grafts remain the "gold standard" in bone regeneration. Yet, donor-site morbidity and the available amount of sufficient material are limitations for autologous bone grafting. This study aimed to provide information about the current status in research regarding bone substitutes. We report on the advantages and drawbacks of several bone substitutes. At the end, we discuss the current developments of combining ceramic substitutes with osteoinductive substances.

First ray alignment in Lapidus arthrodesis - Effect on plantar pressure distribution and the occurrence of metatarsalgia.

BACKGROUND: Lapidus arthrodesis is an established treatment option for severe hallux valgus deformity especially in patients suffering from instability of the first tarsometatarsal joint. Surgery related metatarsalgia is known to be associated with persistent elevation of the first ray after realignment surgery. Nevertheless, detailed information on ideal positioning of the first ray in Lapidus surgery is missing so far. This study was designed to determine any correlations between radiographic and pedobarographic outcome following the Lapidus procedure with regard to clinical outcome and the occurrence of metatarsalgia. METHODS: Thirty feet (28 patients) after Lapidus surgery were available for follow-up at 42.5±21.0 months. All subjects had radiographic and pedobarographic evaluation of the operated foot and patient satisfaction was recorded using questionnaires. RESULTS: Metatarsalgia was associated with a poorer outcome in FADI and AOFAS scores (p<0.005). A lateral shift of plantar pressure distribution to the third metatarsal head in these cases could be observed. Although Lapidus surgery resulted in significant shortening of the first metatarsal, no correlation to the occurrence of metatarsalgia was detectable. Likewise, axial plane malalignment showed no influence, whereas elevation of the first ray was highly correlated to surgery related metatarsalgia (p=0.007). Subjects suffering from metatarsalgia had a higher BMI (body mass index), but its effect on metatarsalgia turned out not to be significant (p=0.090). CONCLUSION: In Lapidus surgery realignment of the first metatarsal in the sagittal plane seems to be decisive for good clinical outcome. Failing to plantarflex the arthrodesis resulted in a lateral shift of plantar loading with overload of the lesser metatarsals and the occurrence of metatarsalgia.

Trauma induced clotting factor depletion in severely injured children: a single center observational study.

BACKGROUND: Coagulopathy following severe trauma contributes significantly to mortality. Impaired clotting factors have been observed in adult trauma patients, but in pediatric trauma victims their activity has not yet been investigated. METHODS: Sixteen pediatric trauma patients were evaluated according to the ISS and assigned to two cohorts. An additional control group (CO; n = 10) was formed. Routine coagulation parameters and the soluble clotting factors (F) were tested. Nonparametric data was analyzed using the Mann-Whitney U test. Results are reported as median and interquartile range. RESULTS: The ISS of severely (SI, n = 8) and mildly (MI, n = 8) injured children differed significantly (25 [19-28] vs. 5 [4-6]; p < 0.001). INR was elevated in the SI cohort only when compared to the CO (1.21 [1.04-1.58] vs. 0.96 [0.93-1.00]; p = 0.001). Differences between SI and MI were found for FII (67 [53-90] vs. 82 [76-114] %; p = 0.028), FV (76 [47-88] vs. 92 [82-99] %; p = 0.028), and FXIII (67 [62-87] vs. 90 [77-102] %; p = 0.021). Comparison of the SI with the CO (FII 122 [112-144] %; p < 0.001; FV 123 [100-142] %; p = 0.002; and FXIII 102 [79-115] %; p = 0.006) also revealed a reduction in the activity of these factors. Furthermore, fibrinogen (198 [80-242] vs. 296 [204-324] mg/dl; p = 0.034), FVII (71 [63-97] vs. 114 [100-152] %; p = 0.009), FIX (84 [67-103] vs. 110 [90-114] %; p = 0.043), and FX (70 [61-85] vs. 122 [96-140] %; p = 0.001) were reduced in the SI in comparison with the CO. Finally, FVIII was considerably, yet not significantly, increased in both patient cohorts (235 [91-320] % and 197 [164-238] %, respectively). CONCLUSIONS: This study proves that children suffer a depletion of clotting factors following severe injury which basically reflects the findings for adult trauma patients. Attempts to correct the impaired clotting factor activity could be based on a specific hemostatic therapy involving administration of coagulation factors. Nevertheless, therapeutic implications need to be investigated in future studies.

Synovial bone sialoprotein indicates aseptic failure in total joint arthroplasty.

BACKGROUND: Until today, a reliable diagnostic discrimination between periprosthetic joint infections (PJI) and aseptic failure (AF) after total joint arthroplasty (TJA) remains challenging. Nearly all recent research focused on synovial markers to be elevated in PJI rather than in AF patients. In this study, synovial bone sialoprotein (sBSP) was investigated in PJI and AF arthroplasty patients before revision surgery. METHODS: sBSP and C-reactive protein (CRP) were determined in synovial fluid samples of PJI (n = 13) patients fulfilling the MSIS criteria and AF (n = 25) patients. Beside descriptive analysis and comparison, computed statistics determined the area under the receiver operating characteristics curve (AUC) to evaluate the discrimination ability of the tested synovial markers. RESULTS: In patients with PJI according to the MSIS criteria, mean sBSP was significantly lower: 14.8 ng/ml (95% CI 5.5-24.1) vs. 38.2 ng/ml in the AF group (95% CI 31.1-45.3), p ≤ 0.001. Conversely, mean sCRP was significantly higher in PJI patients: 8.4 µg/ml (95% CI 0-17.2) vs. 1.8 µg/ml in the AF group (95% CI 0.9-2.8), p = 0.032. The AUC of sCRP in PJI patients was 0.71. The AUC of sBSP in AF revision arthroplasty patients was 0.83. The detection of osteolyses was not associated with higher sBSP concentrations. CONCLUSIONS: Considering the MSIS criteria, significantly higher sBSP concentrations were found in synovial fluid samples of AF compared to PJI patients. sCRP showed only fair, sBSP good discrimination potential. If it is not clear whether PJI is present or not, sBSP may be considered as an add-on synovial marker.

Is Procalcitonin (PCT) a reliable biomarker for preoperative diagnosing of low grade periprosthetic joint infection? A prospective study.

BACKGROUND: Since a "gold-standard" is missing, diagnosing periprosthetic joint infection (PJI) remains a challenge in orthopedic surgery. The purpose of this study was to evaluate the accuracy of serum and synovial fluid Procalcitonin (S-PCT and SF-PCT) as a diagnostic parameter and to compare it to the biomarkers recommended in the 2018 Definition of periprosthetic hip and knee infection. METHODS: Between August 2018 and July 2019, a prospective cohort study was conducted in 70 patients with painful hip, shoulder and knee arthroplasty. Besides medical history, clinical and laboratory data was gathered. PJI was diagnosed based on the 2018 Definition of periprosthetic hip and knee infection. Preoperative blood and synovial joint fluid were taken for PCT measurement. S-PCT and SF-PCT levels were measured using standard quantitative PCT enzyme immunoassays. RESULTS: Twenty three patients (33%) were classified as the PJI group and fourty seven patient (67%) as the aseptic group. The mean levels of S-PCT were significantly (p <  0.001) higher in the PJI group than those in the aseptic group (PJI 0.05 ± 0.21 ng/mL (0.0-1.03) vs. aseptic 0.02 ± 0.03 ng/mL (0.0-0.18)). In synovial fluid, the mean PCT values in the aseptic group were significantly higher (p <  0.001) than those of PJI group (PJI 2.7 ± 1.4 ng/mL (0.53-9.7) vs. aseptic 8.7 ± 2.5 ng/mL (0.25-87.9)). S- PCT, with a cut-off level of 0.5 ng/mL, had a sensitivity of 13.0% and a specificity of 91.0%. SF-PCT, with a cut-off level of 5.0 ng/mL, had a sensitivity of 13.0% and a specificity of 52.0%. CONCLUSION: S-PCT and SF-PCT appeared to be no reliable biomarkers in the differential diagnosis of PJI from aseptic loosening in total joint arthroplasty.

Long-term results of the reverse Total Evolutive Shoulder System (TESS).

INTRODUCTION: Latest trends in shoulder replacement aim at bone stock preservation. Long-term results of stemless anatomical total shoulder implants compare favourably with stemmed designs in terms of function and survivorship. The Total Evolutive Shoulder System (TESS) has been one of the first designs offering a stemless implant not only for anatomical but also for reverse total shoulder arthroplasty with optional short stem attachment in cases with poor bone quality. The aim of the present study was to evaluate long-term results of the reverse Total Evolutive Shoulder System (TESS). MATERIALS AND METHODS: Between 2006 and 2009, 49 shoulders in 47 patients were replaced using the Biomet reverse Total Evolutive Shoulder System (TESS). 29 shoulders in 27 patients who were aged 72.4 ± 6.7 (53-88) years were available for review at a mean follow-up of 101.6 ± 24.6 (75-142) months. RESULTS: The implant survival rate was 93.1% at 101 months (8.4 years). The overall revision rate of the TESS implant was 17.2%. No implant associated complications to the reverse corolla implant could be observed. All reverse corolla implants showed solid fixation at follow-up. Scapular notching was found in 72.3% of the shoulders. Clinical scores significantly improved at long-term follow-up (VAS from 7.5 ± 1.2 to 1.4 ± 1.5, p < 0.001; quick-DASH from 70.9 ± 12.0 to 28.9 ± 22.9, p < 0.001 and Constant score from 13.0 ± 3.7 to 60.5 ± 16.8, p < 0.001). CONCLUSIONS: In terms of clinical scores, radiographic loosening, complication rates and implant survivorship the reverse Total Evolutive Shoulder System provides results comparable to those of conventional stemmed reverse shoulder arthroplasty.

Does Human Experimental Endotoxemia Impact Negative Cognitions Related to the Self?

A role of inflammatory processes in the pathophysiology of depression is increasingly recognized. Experimental endotoxemia offers an established model to induce transient systemic inflammation in healthy humans, and has been proposed as an experimental paradigm of depression. Indeed, different symptoms of depression can be observed during experimental endotoxemia, including negative mood or dysthymia as key symptoms of depression. Hopelessness and low self-esteem constitute common cognitive symptoms in depression, but have not been specifically assessed during endotoxemia. Thus, we pooled data from healthy volunteers who received low-dose endotoxin (i.e., 0.4 or 0.8 ng/kg lipopolysaccharide, LPS) or placebo in three randomized, controlled studies to investigate the effects of LPS on cognitive schemata related to depression. Validated questionnaires were used to assess self-esteem, hopelessness and the vulnerability factor intolerance of uncertainty after intravenous injection of LPS or placebo. Plasma tumor necrosis factor (TNF)-α and interleukin (IL)-6 were repeatedly assessed, along with self-reported mood. Because not all questionnaires were available from primary studies, data were analyzed in two separate data sets: In data set 1, self-esteem and intolerance of uncertainty were assessed in N = 87 healthy volunteers, who randomly received either 0.4 or 0.8 ng/kg LPS or placebo. In data set 2, hopelessness was measured in N = 59 volunteers who randomly received either LPS (0.8 ng/kg) or placebo. In both data sets, LPS-application led to significant increases in TNF-α and IL-6, reflecting systemic inflammation. Positive mood was significantly decreased in response to LPS, in line with inflammation-induced mood impairment. General self-esteem, intolerance of uncertainty and hopelessness did not differ between LPS- and placebo groups, suggesting that these negative cognitive schemata are not responsive to acute LPS-induced systemic inflammation. Interestingly, LPS-treated volunteers reported significantly lower body-related self-esteem, which was associated with increased TNF-α concentration. Thus, certain aspects of self-esteem related to physical attractiveness and sportiness were reduced. It is conceivable that this effect is primarily related to physical sickness symptoms and reduced physical ability during experimental endotoxemia. With respect to cognitive symptoms of depression, it is conceivable that LPS affects cognitive processes, but not negative cognitive schemata, which are rather based on learning and repeated experiences.

Long-term survivorship of stemless anatomical shoulder replacement.

PURPOSE: Like in many other joints, current shoulder replacement designs aim at bone preservation. According to the literature available, stemless total shoulder arthroplasty (TSA) compares favourably with stemmed designs in terms of function and survivorship of the implant. However, long-term results of stemless shoulder arthroplasty are still missing. Therefore, the aim of the present study was to evaluate long-term results of stemless anatomical TSA. METHODS: Between 2006 and 2009, 51 shoulders in 46 patients were resurfaced using the Biomet Total Evolutive Shoulder System (TESS). Thirty-one shoulders in 26 patients who were aged 66.7 ± 10.0 (range 34-82) years were available for review at a mean follow-up of 94.7 ± 11.3 (76-124) months. RESULTS: The implant survival rate was 93.5% at eight years. The overall revision rate of the TESS implant was 9.7%. Radiolucent lines were found on the glenoid side of the TESS arthroplasty in 90.9% of the cases. All stemless humeral corolla implants showed solid fixation at follow-up. Clinical scores significantly improved at long-term follow-up (VAS from 8.1 ± 0.9 to 1.0 ± 1.2, p < 0.001; Quick-DASH from 67.9 ± 13.5 to 18.7 ± 16.5, p < 0.001 and Constant score from 14.7 ± 6.1 to 68.8 ± 13.2, p < 0.001). CONCLUSIONS: Stemless TSA has stood the test of time at eight years in terms of clinical scores, radiographic loosening, complication rates and implant survivorship.

Sex differences in the pro-inflammatory cytokine response to endotoxin unfold in vivo but not ex vivo in healthy humans.

Clinical data indicate that inflammatory responses differ across sexes, but the mechanisms remain elusive. Herein, we assessed in vivo and ex vivo cytokine responses to bacterial endotoxin in healthy men and women to elucidate the role of systemic and cellular factors underlying sex differences in inflammatory responses. Participants received an i.v. injection of low-dose endotoxin (0.4 ng/kg body mass), and plasma TNF-α and IL-6 responses were analyzed over a period of 6 h. In parallel, ex vivo cytokine production was measured in endotoxin-stimulated blood samples obtained immediately before in vivo endotoxin administration. As glucocorticoids (GCs) play an important role in the negative feedback regulation of the inflammatory response, we additionally analyzed plasma cortisol concentrations and ex vivo GC sensitivity of cytokine production. Results revealed greater in vivo pro-inflammatory responses in women compared with men, with significantly higher increases in plasma TNF-α and IL-6 concentrations. In addition, the endotoxin-induced rise in plasma cortisol was more pronounced in women. In contrast, no sex differences in ex vivo cytokine production and GC sensitivity were observed. Together, these findings demonstrate major differences in in vivo and ex vivo responses to endotoxin and underscore the importance of systemic factors underlying sex differences in the inflammatory response.

Men and women differ in inflammatory and neuroendocrine responses to endotoxin but not in the severity of sickness symptoms.

Impaired mood and increased anxiety represent core symptoms of sickness behavior that are thought to be mediated by pro-inflammatory cytokines. Moreover, excessive inflammation seems to be implicated in the development of mood/affective disorders. Although women are known to mount stronger pro-inflammatory responses during infections and are at higher risk to develop depressive and anxiety disorders compared to men, experimental studies on sex differences in sickness symptoms are scarce. Thus, the present study aimed at comparing physiological and psychological responses to endotoxin administration between men and women. Twenty-eight healthy volunteers (14 men, 14 women) were intravenously injected with a low dose (0.4 ng/kg) of lipopolysaccharide (LPS) and plasma concentrations of cytokines and neuroendocrine factors as well as negative state emotions were measured before and until six hours after LPS administration. Women exhibited a more profound pro-inflammatory response with significantly higher increases in tumor necrosis factor (TNF)-α and interleukin (IL)-6. In contrast, the LPS-induced increase in anti-inflammatory IL-10 was significantly higher in men. The cytokine alterations were accompanied by changes in neuroendocrine factors known to be involved in inflammation regulation. Endotoxin injection induced a significant increase in noradrenaline, without evidence for sex differences. The LPS-induced increase in cortisol was significantly higher in woman, whereas changes in dehydroepiandrosterone were largely comparable. LPS administration also increased secretion of prolactin, but only in women. Despite these profound sex differences in inflammatory and neuroendocrine responses, men and women did not differ in endotoxin-induced alterations in mood and state anxiety or non-specific sickness symptoms. This suggests that compensatory mechanisms exist that counteract the more pronounced inflammatory response in women, preventing an exaggerated sickness response. Disturbance of these compensatory mechanisms by environmental factors such as stress may promote the development of affective disorders in women.

Inflammation-induced pain sensitization in men and women: does sex matter in experimental endotoxemia?

A role of the innate immune system is increasingly recognized as a mechanism contributing to pain sensitization. Experimental administration of the bacterial endotoxin lipopolysaccharide (LPS) constitutes a model to study inflammation-induced pain sensitization, but all existing human evidence comes from male participants. We assessed visceral and musculoskeletal pain sensitivity after low-dose LPS administration in healthy men and women to test the hypothesis that women show greater LPS-induced hyperalgesia compared with men. In this randomized, double-blind, placebo-controlled crossover study, healthy men (n = 20) and healthy women using oral contraceptives (n = 20) received an intravenous injection of 0.4 ng/kg body weight LPS or placebo. Pain sensitivity was assessed with established visceral and musculoskeletal pain models (ie, rectal pain thresholds; pressure pain thresholds for different muscle groups), together with a heartbeat perception (interoceptive accuracy) task. Plasma cytokines (tumor necrosis factor-α and interleukin-6) were measured along with state anxiety at baseline and up to 6-hour postinjection. Lipopolysaccharide application led to significant increases in plasma cytokines and state anxiety and decreased interoceptive awareness in men and women (P < 0.001, condition effects), with more pronounced LPS-induced cytokine increases in women (P < 0.05, interaction effects). Although both rectal and pressure pain thresholds were significantly decreased in the LPS condition (all P < 0.05, condition effect), no sex differences in endotoxin-induced sensitization were observed. In summary, LPS-induced systemic immune activation leads to visceral and musculoskeletal hyperalgesia, irrespective of biological sex. These findings support the broad applicability of experimental endotoxin administration as a translational preclinical model of inflammation-induced pain sensitization in both sexes.

Neural circuitry mediating inflammation-induced central pain amplification in human experimental endotoxemia.

BACKGROUND & AIMS: To elucidate the brain mechanisms underlying inflammation-induced visceral hyperalgesia in humans, in this functional magnetic resonance imaging (fMRI) study we tested if intravenous administration of lipopolysaccharide (LPS) involves altered central processing of visceral pain stimuli. METHODS: In this randomized, double-blind, placebo-controlled fMRI study, 26 healthy male subjects received either an intravenous injection of low-dose LPS (N=14, 0.4 ng/kg body weight) or placebo (N=12, control group). Plasma cytokines (TNF-α, IL-6), body temperature, plasma cortisol and mood were assessed at baseline and up to 6 h post-injection. At baseline and 2 h post-injection (test), rectal pain thresholds and painful rectal distension-induced blood oxygen level-dependent (BOLD) responses in brain regions-of-interest were assessed. To address specificity for visceral pain, BOLD responses to non-painful rectal distensions and painful somatic stimuli (i.e., punctuate mechanical stimulation) were also analyzed as control stimuli. RESULTS: Compared to the control group, LPS-treated subjects demonstrated significant and transient increases in TNF-α, IL-6, body temperature and cortisol, along with impaired mood. In response to LPS, rectal pain thresholds decreased in trend, along with enhanced up-regulation of rectal pain-induced BOLD responses within the posterior insula, dorsolateral prefrontal (DLPFC), anterior midcingulate (aMCC) and somatosensory cortices (all FWE-corrected p<0.05). Within the LPS group, more pronounced cytokine responses correlated significantly with enhanced rectal pain-induced neural activation in DLPFC and aMCC. No significant LPS effects were observed on neural responses to non-painful rectal distensions or mechanical stimulation. CONCLUSIONS: These findings support that peripheral inflammatory processes affect visceral pain thresholds and the central processing of sensory-discriminative aspects of visceral pain.

Inflammation-induced hyperalgesia: effects of timing, dosage, and negative affect on somatic pain sensitivity in human experimental endotoxemia.

BACKGROUND: Inflammation-induced pain amplification and hypersensitivity play a role in the pathophysiology of numerous clinical conditions. Experimental endotoxemia has recently been implemented as model to analyze immune-mediated processes in human pain. In this study, we aimed to analyze dose- and time-dependent effects of lipopolysaccharide (LPS) on clinically-relevant pain models for musculoskeletal and neuropathic pain as well as the interaction among LPS-induced changes in inflammatory markers, pain sensitivity and negative affect. METHODS: In this randomized, double-blind, placebo-controlled study, healthy male subjects received an intravenous injection of either a moderate dose of LPS (0.8 ng/kg Escherichiacoli), low-dose LPS (0.4 ng/kg), or saline (placebo control group). Pressure pain thresholds (PPT), mechanical pain sensitivity (MPS), and cold pain sensitivity (CP) were assessed before and 1, 3, and 6h post injection to assess time-dependent LPS effects on pain sensitivity. Plasma cytokines (TNF-α, IL-6, IL-8, IL-10) and state anxiety were repeatedly measured before, and 1, 2, 3, 4, and 6h after injection of LPS or placebo. RESULTS: LPS administration induced a systemic immune activation, reflected by significant increases in cytokine levels, body temperature, and negative mood with pronounced effects to the higher LPS dose. Significant decreases of PPTs were observed only 3h after injection of the moderate dose of LPS (0.8 ng/kg). MPS and CP were not affected by LPS-induced immune activation. Correlation analyses revealed that decreased PPTs were associated with peak IL-6 increases and negative mood. CONCLUSIONS: Our results revealed widespread increases in musculoskeletal pain sensitivity in response to a moderate dose of LPS (0.8 ng/kg), which correlate both with changes in IL-6 and negative mood. These data extend and refine existing knowledge about immune mechanisms mediating hyperalgesia with implications for the pathophysiology of chronic pain and neuropsychiatric conditions.

Fixation method does not affect restoration of rotation center in hip replacements: a single-site retrospective study.

BACKGROUND: Aseptic loosening is one of the greatest problems in hip replacement surgery. The rotation center of the hip is believed to influence the longevity of fixation. The aim of this study was to compare the influence of cemented and cementless cup fixation techniques on the position of the center of rotation because cemented cup fixation requires the removal of more bone for solid fixation than the cementless technique. METHODS: We retrospectively compared pre- and post-operative positions of the hip rotation center in 25 and 68 patients who underwent artificial hip replacements in our department in 2007 using cemented or cementless cup fixation, respectively, with digital radiographic image analysis. RESULTS: The mean horizontal and vertical distances between the rotation center and the acetabular teardrop were compared in radiographic images taken pre- and post-operatively. The mean horizontal difference was -2.63 mm (range: -11.00 mm to 10.46 mm, standard deviation 4.23 mm) for patients who underwent cementless fixation, and -2.84 mm (range: -10.87 to 5.30 mm, standard deviation 4.59 mm) for patients who underwent cemented fixation. The mean vertical difference was 0.60 mm (range: -20.15 mm to 10.00 mm, standard deviation 3.93 mm) and 0.41 mm (range: -9.26 mm to 6.54 mm, standard deviation 3.58 mm) for the cementless and cemented fixation groups, respectively. The two fixation techniques had no significant difference on the position of the hip rotation center in the 93 patients in this study. CONCLUSIONS: The hip rotation center was similarly restored using either the cemented or cementless fixation techniques in this patient cohort, indicating that the fixation technique itself does not interfere with the position of the center of rotation. To completely answer this question further studies with more patients are needed.