Bilirubin increases viability and decreases osteoclast apoptosis contributing to osteoporosis in advanced liver diseases.

Bilirubin and bile acids have deleterious effects on osteoblasts, which may explain the low bone formation of liver diseases with cholestasis. Although there is some clinical evidence of increased bone resorption in this condition, the effects of these substances on osteoclasts are unknown. The objective was to analyze the effects of bilirubin and bile acids -lithocholic acid (LCA) and ursodeoxycholic acid (UDCA)- on osteoclast viability and apoptosis, and on the expression of osteoclast-related microRNAs (miRNAs). RAW 264.7 cells and human PBMCs were differentiated into osteoclasts. Success in differentiation was assessed by TRAP stain and osteoclast-specific gene expression; osteoclast activity was detected by the resorption pits in Corning® Osteo Assay Surface Plates. Cells were treated with camptothecin (CAM) or with bilirubin, LCA or UDCA, at several concentrations and combinations, including non-treated cells as control. Cell viability was measured using WST-1 assay and apoptosis assessing Caspase-3 by Western blot. Expression of miR-21a, miR-29b, miR-31, miR-148a, miR-155 and miR-223 were analyzed by Real Time. Viability increased gradually in osteoclasts differentiated from RAW 264.7 cells, as the concentration of bilirubin increased, being particularly high with bilirubin 100 µM (61 %) as compared to the untreated control (p < 0.007). Viability decreased significantly with CAM, LCA and UDCA (80 %, 62 % and 27 %, respectively), effects which were abolished by bilirubin. Moreover, bilirubin increased viability in osteoclasts derived from human PBMCs (p < 0.03). Caspase-3 decreased by 46 % with bilirubin 50 µM and increased 10-fold with LCA 100 µM and CAM (p < 0.01). Bilirubin increased miR-21 and miR-148a expression as compared to controls (115 % and 59 %, respectively; p < 0.007). In conclusion, bilirubin increases viability and decreases apoptosis of osteoclasts, and overexpresses the osteoclastogenic miR-21 and miR-148a. The effects of bilirubin counteract the actions of LCA and UDCA. Therefore, bilirubin may contribute to the increased bone resorption and to the development of osteoporosis in advanced liver diseases.

Fluorescent tetracycline bone labeling as an intraoperative tool to debride necrotic bone during septic hip revision: a preliminary case series.

A plausible cause of persistent infection after septic hip revision may be the presence of nonviable osteomyelitic bone. Since surgical excision of these necrotic fragments is often challenging, the use of fluorescent tetracycline bone labeling (FTBL) as an intraoperative tool may pose an additional assessment aid to provide a visual index of surgical debridement. Methods: We present a single-center study performed in a university hospital from January 2018 to June 2020, in which all consecutive cases of chronic hip periprosthetic joint infection (PJI) undergoing revision using FTBL were retrospectively reviewed. In all cases, the patient was under treatment with tetracyclines at the moment of the revision surgery. During the surgery, all bone failing to fluoresce was considered nonviable and thus removed and sent for both culture and histology. Results: We include three cases in which the FTBL technique was used. In all cases, the histopathological examinations of the nonfluorescent removed bone were consistent with chronic osteomyelitis. Conclusion: The intraoperative use of FTBL successfully aided the surgeon to detect the presence of nonviable bone in all the presented cases of chronic prosthetic hip infection.

Outcomes of hip arthroplasty with concomitant hardware removal: influence of the type of implant retrieved and impact of positive intraoperative cultures.

INTRODUCTION: The impact of residual internal fixation devices on subsequent procedures about the hip has not been clearly well defined. The objective of the current study is to evaluate the outcome of hip arthroplasty after hardware retrieval as a one-stage replacement, to analyze possible differences related to the type of removed implant, and to assess the impact of unexpected intraoperative cultures during implant retrieval. MATERIALS AND METHODS: We present a retrospective study including all those cases undergoing hip arthroplasty with concomitant hardware removal (cannulated screws, intramedullary nail, or dynamic hip screw) from 2005 to 2018. We evaluated demographics, intraoperative cultures, early infection rate, and other complications. RESULTS: A total of 55 cases were included in the study. The median time between the implant surgery and the hip arthroplasty was 113 days. The removed devices included 6 cannulated screws, 34 intramedullary nails, and 15 dynamic hip screws. Up to 74.5% of the failed osteosynthesis belonged to intertrochanteric femoral fractures. Dislocation rate was 9.1% (1.8% requiring revision surgery), 25.5% of the cases needed further new surgeries after the hip arthroplasty, and 49.1% died during the follow-up period. Any-cause revision surgery and mortality rates were significantly increased after intramedullary nail removal. Intraoperative cultures were performed in 46 cases, and in 9 (16.4%), there was bacterial contamination: 6 cases (10.9%) presented one single positive culture and 3 (5.5%) presented ≥ 2 positive cultures for the same microorganism. A total of five cases (9.1%) presented early prosthetic joint infection that required debridement. None of these five cases had presented positive cultures at the implant removal. CONCLUSION: According to our results, hip arthroplasty with concomitant hardware removal is related to a high 5-year mortality rate, mainly when intramedullary nail is retrieved. Whereas a high risk of early prosthetic joint infection is associated, it seems not to be related to the elevated presence of unexpected positive cultures.

Bilirubin and bile acids in osteocytes and bone tissue. Potential role in the cholestatic-induced osteoporosis.

BACKGROUND AND AIMS: Osteoporosis is a common complication in patients with primary biliary cholangitis. Both bilirubin and lithocholic acid (LCA) result in detrimental effects on osteoblastic cells, and ursodeoxycholic acid (UDCA) counteracts these outcomes. However, there is no information on the consequences of these retained substances of cholestasis and sera from cholestatic patients in osteocytes. METHODS: The impact of bilirubin, LCA, UDCA and serum from jaundiced patients on viability, differentiation, mineralization and apoptosis has been assessed in MLO-Y4 and MLO-A5 osteocyte cell lines. Effects on gene expression were assessed in these cells and in human bone fragments. RESULTS: Lithocholic acid 10 µmol/L and bilirubin 50 µmol/L decreased viability in MLO-Y4 and MLO-A5 cells (11% and 53% respectively; P ≤ .01). UDCA alone or combined with LCA or bilirubin increased cell viability. Jaundiced sera decreased cell viability (56%), an effect which was reverted by UDCA. Bilirubin decreased differentiation by 47% in MLO-Y4 (P ≤ .01) and mineralization (87%) after 21 days in MLO-A5 (P ≤ .03). Both bilirubin and LCA increased apoptosis in MLO-Y4, and UDCA diminished the apoptotic effect. Moreover, bilirubin down-regulated RUNX2 and up-regulated RANKL gene expression in bone tissue, MLO-Y4 and MLO-A5 cells, and LCA up-regulated RANKL expression in bone tissue. UDCA 100 µmol/L increased the gene expression of all these genes in bone tissue and MLO-Y4 cells and neutralized the decreased RUNX2 expression induced by bilirubin. CONCLUSION: Bilirubin and LCA have damaging consequences in osteocytes by decreasing viability, differentiation and mineralization, increasing apoptosis and modifying gene expression, effects that are neutralized by UDCA.

Compresión medular por inestabilidad atlantoaxoidea en artritis reumatoide / Medullar compression due to an atlantoaxial instability in rheumatoid arthritis

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Intraoperative Transfusion of Red Blood Cell Units Stored >14 Days is Associated with an Increased Risk of Prosthetic Joint Infection.

Background: The aim of the present study was to evaluate the association between prosthetic joint infection (PJI) after joint arthroplasty and the length of red blood cell (RBC) storage, timing of RBC transfusion, and the number of RBC units transfused. Study design and Methods: All patients who underwent a primary or revision joint artrhoplasty between January 2000 and December 2012 were retrospectively reviewed. For this study, only patients who received RBC transfusions during the day of the surgery (early transfusion group) or within the first 4 days after surgery (late transfusion group) were included. Results: A total of 9906 patients were reviewed. In the early transfusion group (n=1153, 11.6%), patients receiving 1 or 2 RBC units (3.5% vs 6.3%, P=0.041), 3 or 4 RBC (1.3% vs 13.3%, P=0.004) or ≥5 RBC units (5.0% vs 37.5%, P=0.026) had a higher PJI rate only when >50% of RBC units transfused had been stored >14 days. In the late transfusion group (n=920, 9.3%) these differences were not significant. Early transfusion of RBCs stored >14 days was an independent variable associated with an increased risk of PJI (OR:2.50, 95%CI:1.44-4.33) Conclusion: Transfusion of RBC within the first 6h after joint arthroplasty was an independent variable associated with PJI risk when RBC units are stored >14 days. The rate of PJI increased with the number of old RBC units transfused within this critical period.

Clinical results and complications of a two-stage procedure in hip infection using preformed antibiotic-loaded cement spacers.

Antibiotic-loaded cement spacers are used in two- stage hip replacement. The aim of our study was to compare our results using a Spacer-G with previous results reported in the literature. From June 2002 to April 2010, all patients treated with a two-stage revision were retrospectively reviewed. On the basis of the results of the first-stage procedure, 52 patients underwent the second stage, six developed a dislocation, in eight the spacer was maintained, and five patients developed an acute infection of the spacer or the infection was not resolved. With regard to the second-stage procedure the revision was successful in 44 patients, a re-infection developed in four patients and the definitive prosthesis presented a mechanical complication in four more. The literature results reported that 97.5% of the spacers were reimplanted, although 12.09% of them developed a dislocation. Surgeons must assess several aspects so as to avoid mechanical complications like dislocation and re- infections during the two stages of the procedure.

Controversies in the Surgical Management of Shoulder Instability: Open vs Arthroscopic Procedures.

BACKGROUND: Traumatic anterior instability of the shoulder is a common condition associated with a high recurrence rate in young adults. Operative treatment reduces the risk of recurrence. Several studies have compared arthroscopic and open shoulder instability repair. The purpose of this paper is to perform a review of the literature where both techniques are compared in the repair of the anterior shoulder instability without bone loss. METHODS: Prior to arthroscopy, recurrent dislocations were managed by open repair. There have been many studies documenting low recurrence rates after open Bankart stabilization. Initially, arthroscopic fixation reported high failure rates. RESULTS: In the last 20 years, the development of arthroscopic stabilization for recurrent anterior instability has improved failure rates. In comparison with open techniques, arthroscopic procedures have the advantages of decreased morbidity rate, early functional rehabilitation and improved range of motion. CONCLUSION: The available evidence does not show a statistically significant difference in outcome measures between arthroscopic and open repair for the treatment of recurrent anterior shoulder instability. Given the similar results between the 2 groups, differences in length of hospital stay and cost to the patient and society point to arthroscopic repair as the more judicious treatment approach.

Withholding Preoperative Antibiotic Prophylaxis in Knee Prosthesis Revision: A Retrospective Analysis on Culture Results and Risk of Infection.

BACKGROUND: A significant amount of patients undergoing revision surgery of a prosthetic joint turn out to have an infection. Withholding preoperative antibiotic prophylaxis in these patients to optimize culture yield during revision surgery remains a matter of debate. The aim of our study was to determine (1) the rate of positive intraoperative cultures with or without preoperative antibiotic prophylaxis and (2) the incidence of a prosthetic joint infection (PJI) during the follow-up in the 2 groups. METHODS: Medical files of patients in whom preoperative antibiotic prophylaxis was withheld until culture samples were taken (2007-2010, n = 284) and in whom antibiotic prophylaxis was given during the induction of anesthesia (2010-2013, n = 141) were retrospectively reviewed. RESULTS: The percentage of ≥1 positive cultures was the same in the group without (26%) and with preoperative prophylaxis (27%; P value, .7). PJI was diagnosed during revision surgery according to the Musculoskeletal Infection Society criteria in 6.7% patients not receiving preoperative prophylaxis and in 7.0% receiving it (P value, .79). We found no important differences in the type of microorganisms that were isolated in both groups. During a 3-month follow-up, an early PJI developed in patients undergoing total revision surgery in 6.4% of the nonpreoperative prophylaxis group vs 1.6% in the preoperative prophylaxis group (P value, .1). CONCLUSION: Preoperative antibiotic prophylaxis does not reduce culture yield in patients undergoing knee revision surgery. Our data show a trend toward a higher PJI rate in the postoperative period of total revision surgery when preoperative prophylaxis is withheld.

Relationship between femoral offset and dislocation in preformed antibiotic-loaded cement spacers (Spacer-G®).

INTRODUCTION: A reduction in femoral offset may decrease muscle tension and lead to spacer dislocations even though proximal femur, musculature and acetabulum remain intact. In this study, we aimed to determine whether postoperative lateral femoral offset (LFO) and modified vertical femoral offset (MVFO) values affect the risk of dislocation of a hip spacer. MATERIALS AND METHODS: We measured LFO and MVFO in properly centred, postoperative, anteroposterior radiographs of the pelvis in 66 patients (71 spacers). We then compared the operated and non-operated sides and recorded any dislocations. RESULTS: Although LFO decreased (p<0.001), the reduction was not associated with dislocation (p = 0.471). MVFO remained unchanged after spacer implantation (p = 0.277) and was not associated with dislocation (p = 0.418). CONCLUSIONS: In conclusion, the preformed spacer decreased LFO but not MVFO compared with the contralateral hip. The variations did not significantly affect the dislocation rate.

Una infrecuente causa de disfagia / An uncommon cause of dysphagia

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The use of a "rim cutter" device and a flanged cup for improving the mantle of the acetabular component of a cemented Exeter total hip arthroplasty.

A retrospective study was performed to evaluate the cement mantle in two groups of patients treated with the acetabular components of cemented Exeter total hip arthroplasties (THAs). Two groups of 20 patients were compared: Group 1 received non-flanged acetabular cemented cups (Contemporary, Stryker) and Group 2 received flanged acetabular cemented cups (X3 Rim Fit, Stryker). Cups in Group 2 were implanted after using a rim cutter device. Group 2 showed better penetration of cement in zone 1 (10.76 mm compared with 2.93 mm; p = 0.008) and a thicker cement mantle in zone 1 (3.57 mm compared with 2.89 mm; p = 0.04). More cups in Group 2 had a cement mantle thickness less than 3 mm (30 % in Group 1 compared with 70 % in Group 2; p = 0.0039). No other radiological differences were observed. These results favor the use of a rim cutter device and flanged cup to improve the cement mantle for the acetabular components of cemented Exeter THAs. However, the improvements were less than expected. In view of the results of previous studies, further research is therefore needed to assess the value of this approach in improving the acetabular cement mantle.

Trabecular TitaniumTM cups and augments in revision total hip arthroplasty: clinical results, radiology and survival outcomes.

BACKGROUND: Large acetabular defects remain a challenge in hip revision arthroplasty. Experience with Trabecular Titanium™ (TT) cups (Limacorporate S.p.a.) has not been widely reported. Therefore, we assessed the survivorship and clinical and radiological outcomes of patients receiving TT cups, with or without supplementary trabecular titanium hemispherical modules for acetabular reconstruction, in primary and revision total hip arthroplasty (THA). METHODS: Between January 2009 and July 2014, we performed 67 revisions and 5 primary THAs using TT cups in 69 patients. To achieve stability and/or restore the hip's centre of rotation, hemispherical modules were used in 17 cases based on preoperative templating and/or intraoperative findings. Mean follow-up was 30.5 months. Acetabular bone defects were classified according to the Paprosky classification. Survivorship, functional outcomes (Merle d'Aubigné) and radiological outcomes were analysed. RESULTS: 8 patients underwent cup revision: 2 for loosening, 3 for infection, and 3 for hip dislocation. The remaining cases did not present radiological signs of loosening. None of the cases with Paprosky type I classifications needed revision, while 4 with type II and 4 with type III needed revision (p = 0.028). The respective mean values for pain, walking, and range of motion (Merle d'Aubigné scores ± standard deviation) were 3.6 ± 1.4, 3.7 ± 0.7, and 3.8 ± 0.6 preoperatively, and 5.7 ± 0.7, 5.3 ± 0.7, and 5.6 ± 0.7 at the latest follow-up (p<0.001). CONCLUSIONS: In the short term, results with TT cups appear to be encouraging, with satisfactory survival rates for both simple and complex cases.

Importance of selection and duration of antibiotic regimen in prosthetic joint infections treated with debridement and implant retention.

OBJECTIVES: Early prosthetic joint infections (PJIs) are managed with debridement, implant retention and antibiotics (DAIR). Our aim was to evaluate risk factors for failure after stopping antibiotic treatment. METHODS: From 1999 to 2013, early PJIs managed with DAIR were prospectively collected and retrospectively reviewed. The main variables potentially associated with outcome were gathered, and the minimum follow-up was 2 years. For the present study, only patients who were in remission after one debridement and without long-term antibiotic suppression were included. The primary endpoint was implant removal or the need to reintroduce antibiotic treatment due to failure. RESULTS: One-hundred-and-forty-three patients met the inclusion criteria. The failure rate after a median duration of oral antibiotic treatment of 69 days (IQR 45-95 days) was 11.8%. In 92 cases, PJI was due to Gram-positive microorganisms, in 21 cases PJI was due to Gram-negative microorganisms and in 30 cases PJI was due to a polymicrobial infection with both Gram-positive and Gram-negative microorganisms. In Gram-positive infections, rifampicin administered in combination with linezolid, co-trimoxazole or clindamycin was associated with a higher failure rate (27.8%, P = 0.026) than that in patients receiving a combination of rifampicin with levofloxacin, ciprofloxacin or amoxicillin (8.3%) or monotherapy with linezolid or co-trimoxazole (0%). Among patients with a Gram-negative infection, the use of fluoroquinolones was associated with a lower failure rate (7.1% versus 37.5%, P = 0.044). CONCLUSIONS: The only factor associated with failure was the oral antibiotic selection, not the duration of treatment. Linezolid, co-trimoxazole and clindamycin, but not levofloxacin, serum concentrations are reduced by rifampicin; a fact that could explain our findings. Further studies monitoring serum concentration could help to improve the efficacy of these antibiotics when administered in combination with rifampicin.

Calidad de vida y supervivencia tras el tratamiento quirúrgico de las fracturas metastásicas del fémur / Quality of life and survival after surgical treatment of metastatic femoral fractures

Fundamento y objetivo: Analizar los resultados obtenidos en tratamiento quirúrgico de pacientes con fractura de fémur secundaria a enfermedad metastásica ósea, sobre la base de la calidad de vida y la supervivencia. Material y método: Se efectuó un estudio transversal y prospectivo en un período de 15 meses, en el que se incluyeron 20 fracturas de fémur en 19 pacientes, que correspondieron a 10 fracturas inminentes (FI) y 10 fractura establecidas (FE). Como variables de resultado se analizaron las complicaciones asociadas, el tipo de deambulación en el momento del alta hospitalaria y los cambios en la escala de Karnofsky respecto al ingreso. Se registró asimismo la mortalidad perioperatoria y la supervivencia tras la intervención. Resultados: El tratamiento quirúrgico realizado fue osteosíntesis (72%) y protetización (28%). Como complicaciones destacaron: 1 fallecimiento perioperoperatorio y 1 fallo del sistema de osteosíntesis. Respecto a la situación al ingreso, se observó una mejoría en la calidad de vida, sobre la base de la escala de Karnofsky (p=0,017). La supervivencia tras la cirugía fue de 2 meses en el grupo de pacientes con FI y de 5 meses en el grupo de las FE (p=0,816).Conclusiones: Los pacientes intervenidos por fractura secundaria a metástasis ósea en el fémur presentaron una mejoría de calidad de vida según la escala de Karnofsky. A pesar de tratarse de un grupo de pacientes con una reducida supervivencia, el control del dolor y la mejoría funcional justifican el procedimiento (AU)

Background and objectives: To analyze the results of the surgical treatment of proximal femoral fractures secondary to metastatic bone disease, in terms of quality of life improvement and survival. Results: Surgical procedures performed were osteosynthesis (72%) and femoral arthroplasty (28%). With regard to complications, 1 patient died during the intra-operatory period and there was 1 failure of ostesyntesis that required re-operation. There was an improvement in the quality of life measured according to the Karnofsky scale after the surgery (P=.017). Survival after surgery was 2 months in the group of patients with impending fracture and 5 months in the group of patients with established fracture (P=.816).Conclusions: Patients who underwent surgery for a femoral fracture secondary to a metastatic disease showed an improvement in the quality of life, according to the Karnofsky scale. Although they represent a group of patients with a short survival, the control of pain and functional improvement justifiy the procedure (AU)

[Quality of life and survival after surgical treatment of metastatic femoral fractures]. / Calidad de vida y supervivencia tras el tratamiento quirúrgico de las fracturas metastásicas del fémur.

BACKGROUND AND OBJECTIVES: To analyze the results of the surgical treatment of proximal femoral fractures secondary to metastatic bone disease, in terms of quality of life improvement and survival. MATERIAL AND METHOD: A transversal prospective study was carried out during a period of 15 months in which 20 fractures of femur from 19 patients were included, corresponding to 10 imminent fractures (IF) and 10 established fractures. Assessed final outcomes were associated complications, walking type at discharge and change in Karnofsky's scale after surgery. Mortality and survival after operation were also registered. RESULTS: Surgical procedures performed were osteosynthesis (72%) and femoral arthroplasty (28%). With regard to complications, 1 patient died during the intra-operatory period and there was 1 failure of ostesyntesis that required re-operation. There was an improvement in the quality of life measured according to the Karnofsky scale after the surgery (P=.017). Survival after surgery was 2 months in the group of patients with impending fracture and 5 months in the group of patients with established fracture (P=.816). CONCLUSIONS: Patients who underwent surgery for a femoral fracture secondary to a metastatic disease showed an improvement in the quality of life, according to the Karnofsky scale. Although they represent a group of patients with a short survival, the control of pain and functional improvement justifiy the procedure.

Malignant melanoma with metastasis into the capitate.

Metastases to the hand and wrist are rare, with fewer than 200 cases reported in the literature. Phalanges are more commonly involved than metacarpal and wrist. The lung, breast and kidneys are the more common sites of primary lesions than metastasize in the hand. We present an exceptional case of melanoma that metastasized to the capitate. Melanoma can give bone metastases, but we are not aware of reports of this tumour metastatising to the carpal bones. In our knowledge, we have only found a report of metastases in the capitate, a clear-cell sarcoma of the right foot, a tumour close to melanoma with some cytogenetic differences. Hand metastases in a patient who is suffered melanoma should be ruled out if a lytic aggressive lesion appears on x-ray film or positive technetium bone scan is demonstrated.

Leiomyosarcoma of sacrum: imaging and histopathologic findings.

A rare case of low-grade primary leiomyosarcoma of the sacrum is described in a young woman who suffered from pain in the right sacroiliac region. A lytic sacral mass was observed on conventional radiology and CT studies. Magnetic resonance imaging clearly showed Gd-DTPA enhancement in the entire mass demonstrating its hypervascularity, which was later confirmed by angiography. Histopathology and immunohistochemical results of biopsy and curettage of the lesion confirmed the diagnosis. We report on the features of a rare tumor entity through imaging and diagnostic methods.