Purpose: Histopathologic analysis of femoral head specimens following total hip arthroplasty (THA) is a routine practice that represents a significant use of health care resources. However, it occasionally results in discovery of undiagnosed hematopoietic malignancy and other discrepant diagnoses such as avascular necrosis. The purpose of this study was to determine the rate of discordant and discrepant diagnoses discovered from routine histopathological evaluation of femoral heads following THA and perform a cost analysis of this practice. Materials and Methods: A review of patients undergoing primary THA between 2004-2017 was conducted. A comparison of the surgeon’s preoperative and postoperative diagnosis, and the histopathologic diagnosis was performed. In cases where the clinical and histopathology differed, a review determined whether this resulted in a change in clinical management. Medicare reimbursement and previously published cost data corrected for inflation were utilized for cost calculations. Results: A review of 2,134 procedures was performed. The pathologic diagnosis matched the postoperative diagnosis in 96.0% of cases. Eighty-three cases (4.0%) had a discrepant diagnosis where treatment was not substantially altered. There was one case of discordant diagnosis where lymphoma was diagnosed and subsequently treated. The cost per discrepant diagnosis was $141,880 and per discordant diagnosis was $1,669 when using 100% Medicare reimbursement and Current Procedural Terminology (CPT) code combination 88304+88311. Conclusion Histopathologic analysis of femoral head specimens in THAs showed an association with high costs given the rarity of discordant diagnoses. Routine use of the practice should be at the discretion of individual hospitals with consideration for cost and utility thresholds.

Background: Antibiotic-loaded bone cement (ALBC) is commonly used in total knee arthroplasty (TKA), especially among high-risk patients. While previous studies have reported on the efficacy of ALBC in reducing the rate of periprosthetic joint infection (PJI), its impact on antibiotic resistance has not been determined. The purpose of this study was to investigate antibiotic resistance among organisms causing PJIs after TKA in which ALBC was utilized. Methods: A retrospective review from December 1998 through December 2017 identified 36 PJIs that met inclusion criteria. Patients with culture-negative infection and unknown cement type were excluded. Patient characteristics, infecting organism, and antibiotic susceptibilities were recorded. ABLC included an aminoglycoside in all cases. Results: There was no difference in the type of PJI between the 2 groups. Staphylococcus species was the most commonly isolated, with 9 of 16 cases (56.3%) using non-ALBC and 14 of 20 (65.0%) cases using ALBC. Of those infected with Staphylococcus, there was no significant difference in antibiotic susceptibilities between groups. Overall, there were only 3 cases where the infecting organism was aminoglycoside resistant (standard cement, 1; ALBC, 2). Conclusions These results suggest that the use of ALBC does not increase the risk of antibiotic resistance or affect the pattern of infection, even as the use of ALBC continues to increase, particularly among high-risk patients.

This study was aimed to investigate the relevance of nilotinib in combination with tetrandrine (Tet) on reversing multidrug resistance and inducing apoptosis of K562/A02 cell line and its mechanism. Methyl-thiazol tetrazolium (MTT) assay was employed to examine the pharmacological effect of nilotinib or Tet alone on K562/A02 cell line, the IC(50) of daunorubicin (DNR) on K562/A02 cell line treated with nilotinib and Tet was calculated; the flow cytometry (FCM) was employed to detect the apoptosis rate of K562/A02. The expression of bax/survivin mRNA was determined by RT-PCR, and the expression of bax/survivin protein was assayed by Western blot. The results showed that after being treated by 5 nmol/L nilotinib or 1.0 µml/L Tet for 48 hours, IC(50) of DNR to K562/A02 was 5.71 ± 0.72 mg/L or 6.52 ± 0.43 mg/L, respectively, while in their combined treatment, IC(50) decreased to 3.12 ± 0.13 mg/L. Nilotinib or Tet alone could increase DNR-inducing apoptosis rate of K562/A02 cell, while the apoptosis rate of K562/A02 increased remarkably in combination treatment of nilotinib with Tet. After being treated with 5 nmol/L nilotinib or 1.0 µml/L Tet alone for 48 hours, the expressions of bax mRNA and BAX protein was up-regulated, while both effects were more obvious in combination treatment of nilotinib with Tet. Treatment with 5 nmol/L nilotinib or 1.0 µmol/L Tet alone for 48 hours down-regulated the expression of survivin mRNA and its protein, while treatment of nilotinib in combination with Tet had more significant effect on down-regulation of their expression. It is concluded that the K562/A02 cells are resistant to DNR, nilotinib or Tet alone both can partially reverse resistance of K562/A02 cells to DNR, increase the apoptosis rate of K562/A02 cells. Combination of nilotinib with Tet shows obvious synergistic action, mechanism of which may associate with up-regulation of bax mRNA and BAX protein expressions and down-regulation of survivin mRNA and its protein expressions.
Apoptosis ; drug effects ; Benzylisoquinolines ; administration & dosage ; pharmacology ; Daunorubicin ; pharmacology ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Gene Expression Regulation, Leukemic ; Humans ; Inhibitor of Apoptosis Proteins ; genetics ; K562 Cells ; Pyrimidines ; administration & dosage ; pharmacology ; bcl-2-Associated X Protein ; genetics

OBJECTIVETo investigate the reversible effect of nilotinib, BrTet (5-bromotetrandrine) and their combination on multidrug resistance cell line K562/A02 and its mechanism.

METHODSCell proliferation inhibition was assessed by MTT method and cell apoptosis by flow cytometry (FCM). The expression of mdr1 mRNA was determined by RT-PCR, and the expression of P-gp was assessed by Western blot.

RESULTSAfter 48 h 5 nmol/L nilotinib or 0.5 µmol/L BrTet treatment, IC(50) of daunorubicin (DNR) to K562/A02 was 4.52 mg/L or 5.41 mg/L respectively; While on combinative treatment, its IC(50) decreased to 2.98 mg/L. Nilotinib or BrTet alone was not able to increase the DNR induced apoptosis rate of K562/A02 cell (P > 0.05), while on combination treatment the apoptosis rate increased remarkably. After 48 h 5 nmol/L nilotinib or 0.5 µmol/L BrTet treatment alone, gray-scale value of mdr1 mRNA was 0.48 ± 0.04 or 0.64 ± 0.01, respectively; while on combinative treatment the value decreased to 0.35 ± 0.04. The P-gp expression level in K562/A02 cells was 0.61 ± 0.05, or 0.52 ± 0.02 when treated with 5 nmol/L nilotinib or 0.5 µmol/L BrTet alone for 48 h, but on combination treatment, the level decreased to 0.44 ± 0.03.

CONCLUSIONNilotinib or BrTet alone can partially reverse drug resistance of K562/A02 cells. The mechanism may be associated with the decrease of mdr1 mRNA and P-gp expression and increase of the apoptosis rate. And there is a synergistic action with these two agants in combination.

ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Daunorubicin ; pharmacology ; Drug Resistance, Multiple ; drug effects ; Drug Resistance, Neoplasm ; drug effects ; Humans ; K562 Cells

This study was aimed to explore the effects and mechanisms of transplantation tolerance induced by "TBI + cyclophosphamide (CTX)" regimen combined with intra-bone marrow injection of allogenic BMCs. On day 0 C57BL/6 (H-2(b), B6) mice received sublethal dose of total body irradiation (TBI) ((60)Co gamma-ray) followed by intrabone marrow-bone marrow transplantation (IBM-BMT) of 3 x 10(7) cells/30 microl BMCs from BALB/c (H-2(d)) mice. The recipient mice were given CTX intraperitoneally 2 days after IBM-BMT. On day 7 skin grafting was performed and the skin survival was observed. The tolerance mechanism was investigated by mixed lymphocyte reaction (MLR), IL-2 reverse test, adoptive transfer assay in vitro. The results showed that the mean survival time (MST) of skin allografts in group treated with TBI + CTX + BMT was significantly longer, compared with that of other groups (P < 0.01). On day 90 after IBM-BMT, the phenotypic character of the recipient mice (black color) began to convert to that of the donor mice (white color). The MLR demonstrated that the immune responses of recipient mice were donor-specific tolerance. Suppressive activity in the spleen cells of tolerant B6 mice was observed in adoptive transfer assay in vitro. IL-2 reversal and the phenotypic conversion showed that the tolerance mechanisms were involved in clonal anergy and the development of chimerism. It is concluded that the nonmyeloablative regimen combined with IBM-BMT can induce a long-term tolerance, and the multiple mechanisms including clonal anergy, suppressor cells and chimerism were involved in transplantation immune tolerance.
Animals ; Bone Marrow Transplantation ; immunology ; methods ; Cyclophosphamide ; administration & dosage ; Female ; Immunosuppressive Agents ; Interleukin-2 ; administration & dosage ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Time Factors ; Transplantation Tolerance ; drug effects ; immunology ; Whole-Body Irradiation

BACKGROUND: As a result of improved and novel treatment strategies, the spectrum of patients with cardiovascular disease is consistently changing. Overall, those patients are typically older and characterized by increased burden with comorbidities. Limited data on the prognostic impact of age in cardiogenic shock (CS) is available. Therefore, this study investigates the prognostic impact of age in patients with CS. METHODS: From 2019 to 2021, consecutive patients with CS of any cause were included. The prognostic value of age (i.e., 60-80 years and > 80 years) was investigated for 30-day all-cause mortality. Spearman's correlations, Kaplan-Meier analyses, as well as multivariable Cox proportional regression analyses were performed for statistics. Subsequent risk assessment was performed based on the presence or absence of CS related to acute myocardial infarction (AMI). RESULTS: 223 CS patients were included with a median age of 77 years (interquartile range: 69-82 years). No significant difference in 30-day all-cause mortality was observed for both age-groups (54.6% vs. 63.4%, log-rank P = 0.169; HR = 1.273, 95% CI: 0.886-1.831, P = 0.192). In contrast, when analyzing subgroups stratified by CS-etiology, AMI-related CS patients of the group > 80 years showed an increased risk of 30-day all-cause mortality (78.1% vs. 60.0%, log-rank P = 0.032; HR = 1.635, 95% CI: 1.000-2.673, P = 0.050), which was still evident after multivariable adjustment (HR = 2.072, 95% CI: 1.174-3.656, P = 0.012). CONCLUSIONS Age was not associated with 30-day all-cause mortality in patients with CS of mixed etiology. However, increasing age was shown to be a significant predictor of increased mortality-risk in the subgroup of patients presenting with AMI-CS.