Treatment experience with continuous local antibiotic perfusion for periprosthetic joint infection.

BACKGROUND: Antibiotic concentrations 100-1000 times higher than the minimum inhibitory concentration are necessary for eradicating biofilms in periprosthetic joint infections (PJI). Achieving this with intravenous antibiotics is challenging, but continuous local antibiotic perfusion (CLAP) can increase the local concentration of antibiotics. Although there are several reports on CLAP therapy in the fracture-related infection, there are only few reports on its application in PJI. Here, we report our experience with CLAP therapy for PJI. METHODS: Eight patients with PJI (two males and six females, with mean age of 73.5 years [±11.6]) were treated at our department, and their clinical characteristics were analyzed. The parameters considered were the classification of PJI, surgical procedure, duration of CLAP, duration of transvenous antibiotic administration, time of CRP-negative status, whether the infection resolved or recurred, and whether there were complications due to CLAP. RESULTS: Initial surgery included total knee arthroplasty in five cases, unicompartmental knee arthroplasty in one case, and total hip arthroplasty in two cases. There were four cases of early postoperative infection, two of acute delayed infection, and two of chronic delayed infection. The surgical procedures performed were two-stage revision for two patients, and debridement, antibiotics, and implant retention (DAIR) for the other six. The mean durations of CLAP and transvenous antibiotic administration were 8.5 (±2.4) and 22.4 days (±13.7), respectively, and the mean time to CRP-negative status was 23.3 days (±10.7). All eight patients successfully resolved without additional irrigation or debridement, and no recurrence was observed at the last follow-up after discontinuation of oral antibiotics. No systemic side effects of gentamicin or other complications associated with CLAP were observed. CONCLUSION: All patients achieved infection resolution with the combined use of CLAP. This suggests that CLAP is a useful treatment option for PJI.

Survey of Osteoarthritis of the Shoulder in Patients who Underwent Knee Arthroplasty for Knee Osteoarthritis.

The relationship between osteoarthritis (OA) of the lower extremity and shoulder OA has not been established. This study evaluated the prevalence of shoulder OA in patients with knee OA. We collected contrast-enhanced computed tomography (CECT) images of the shoulder joints of 105 patients with knee OA that were taken 1 week after they underwent primary knee arthroplasty to check for venous thromboembolism (VTE). The images were compared with CECT images of 110 control-group patients that were taken for the purpose of differentiating VTE. Shoulder OA was present in a significantly higher percentage of patients with knee arthroplasty than controls (29% versus 15%), and the difference was particularly pronounced in patients in their 70s (33%) compared to age-matched controls (11%). Patients with knee OA often use arm support to stand up or walk due to knee joint pain and muscle weakness, which places the weight-bearing shoulder at risk of developing OA.

Subchondral fatigue fracture of the femoral head with acetabular dysplasia treated by transposition osteotomy of the acetabulum: a case report.

Introduction: Subchondral insufficiency fracture of the femoral head commonly occurs in older women with osteoporosis. However, subchondral fatigue fracture of the subchondral femoral head is rare. We present a rare case of fatigue fracture of the subchondral femoral head with acetabular dysplasia. Case Report: The patient was a 16-year-old male, height 180 cm, weight 112 kg, and body mass index 34.6 kg/m2. Continuous right hip pain appeared after club activity of table tennis a month before admission to our department. Pain was observed on deep flexion of the right hip joint. The FADIR test was positive. X-ray images showed a depressed deformity of the right femoral head loading portion. In addition, the center-edge angle was 10° on the right and 21° on the left, tear drop distance was 12 mm on the right and 8 mm on the left, and bilateral acetabular dysplasia was noted. In magnetic resonance imaging, the T1-weighted image shows low-intensity signal and the T2-weighted image shows high-intensity signal, indicating a fatigue fracture of the femoral head with subchondral depression. Thus, transposition osteotomy of the acetabulum was performed in this case. Postoperatively, the depression portion showed gradual remodeling, and the patient returned to sports after 6 months. Because this patient was highly obese with acetabular dysplasia, a large shear force was applied to the loading portion of the femoral head relative to the acetabular rim. The femoral head was repeatedly forced, resulting in a fatigue fracture. We believe that the stress applied to the depressed portion was dispersed by the transposition osteotomy of the acetabulum, resulting in remodeling. Conclusion: This is the first report of the transposition osteotomy of the acetabulum for a subchondral fatigue fracture of the femoral head with acetabular dysplasia. Thus, this may serve as a reference in the management of such rare occurrences and pave the way for further understanding of this condition.

Goishi tea leaf powder affects lower body weight and visceral fat accumulation during energy restriction in obese rats.

Goishi tea is a unique Japanese post-fermented tea produced in Kochi prefecture. The aim of this study was to investigate whether the supplementation of energy-restricted diet with Goishi tea leaves affects body weight, visceral fat accumulation, and fecal lipids in diet-induced obese rats. 18 male Wistar rats were fed a high-fat diet for 12 weeks. Subsequently, the diet-induced obese rats were fed a low-energy diet containing 1% (G1 group) or 3% (G3 group) of Goishi tea leaf powder, or without any tea extracts (C group) for 4 weeks. After 4 weeks, body weight and body fat ratio were significantly lower in the G3 group than in the C group. Plasma insulin levels were significantly higher in the C group than in the G1 and G3 groups, whereas plasma leptin levels were significantly lower in the G3 group than in the C group. In addition, the lipid absorption rate was significantly lower in the G3 group than in the C and G1 groups. In conclusion, the administration of Goishi tea leaves under dietary restrictions might contribute to body weight reduction and inhibition of lipid absorption, as a diet therapy to help prevent obesity and metabolic syndrome. J. Med. Invest. 70 : 60-65, February, 2023.

Long-term effectiveness and safety of high dose chemotherapy followed by autologous stem cell transplantation in daily practice in patients with diffuse large B-cell lymphoma.

We retrospectively evaluated long-term outcomes of high dose chemotherapy followed by autologous stem cell transplant (HDC/ASCT) in patients with diffuse large B-cell lymphoma (DLBCL). Between 2004 and 2020, 46 DLBCL patients received HDC/ASCT in our institution, including 12 patients (26.1%), who received as an upfront setting (UFS). At a median follow-up time of 69 months (range, 2-169 months), the 5-year progression-free survival (PFS) rates were 82.5% (95%CI, 46.1-95.3%) in the UFS, and 57.8% (95%CI, 38.1-73.2%) in the relapsed or refractory (R/R) patients (n=34), respectively. The 5-year PFS rates were 62.3% (95%CI, 34.0-81.3%) in primary resistant (n=13) or early relapsing (within 1 year from the initial diagnosis) patients (n=4), and 53.3% (95%CI, 25.9-74.6%) in those relapsing >1 year after the initial diagnosis (n=17), with no statistically significant difference (p=0.498). In R/R patients, multivariate analysis showed that the remission status before HDC/ASCT was an independent poor prognostic factor for progression-free survival (hazard ratio [HR], 17.0; 95%CI, 3.35-86.6; p=0.000630) and high-risk category in the international prognostic index for OS (HR, 9.39; 95%CI, 1.71-51.6; p=0.0100). The incidence of non-relapse mortality by 5 years, and 10 years were 12.2%, and 15.2%, respectively. Eleven patients (23.9%) developed second malignancies, which was the most frequent late complication after HDC/ASCT, with 5-year, and 10-year cumulative incidence of 16.9%, 22.5%, respectively. In conclusion, HDC/ASCT is effective for chemo-sensitive R/R DLBCL regardless of the timing and lines of therapy. However, careful observation is required, considering the long-term complications such as secondary malignancies.

Comparison of tibial implant positioning between symmetrical and anatomical design implants in unicompartmental knee arthroplasty for Japanese patients.

PURPOSE: In unicompartmental knee arthroplasty (UKA) procedures, maximizing the bone coverage of the tibial implant and eliminating the medial and posterior overhang would be optimal. We commonly used Physica ZUK® (ZUK), which is a symmetrical design. Alternatively, since Persona Partial Knee® (PPK) was developed in 2017 with an anatomical design to improve bone coverage, we started PPK. We hypothesized that the PPK facilitated better bone coverage than the ZUK without obvious overhangs. This study evaluated the bone coverage and the medial and posterior overhang of these differently designed tibial implants. METHODS: Seventy-nine knees from 68 patients who underwent UKA were evaluated. Cases were categorized into the ZUK (41 knees) and PPK (38 knees) groups. CT images were acquired before surgery and 1 week after surgery. We measured the tibial bone coverage, and the medial and posterior overhang by 3D software. RESULTS: The bone coverages were 103.8 ± 4.8% and 102.0 ± 3.0%, the medial overhangs were 2.2 ± 1.2 mm and 1.4 ± 1.1 mm, and the posterior overhangs were 0.6 ± 1.3 mm and 0.4 ± 1.2 mm for the ZUK and PPK groups, respectively. The bone coverage and medial overhang were significantly different between the groups, with ZUK being larger. CONCLUSION: Patients who received PPK had significantly smaller medial overhangs and better bone coverage. PPK is more likely to give better results than ZUK.

Factors Associated with Surgical Field Bacterial Detection during Total Hip Arthroplasty.

Total hip arthroplasty (THA) provides relief from hip pain and improves hip function. However, periprosthetic joint infection (PJI) remains an area of concern. We examined the detection rate of bacteria from surgical fields in wound closure, along with the relationship between bacterial detection rate and type of antiseptic, surgery time, and surgeon experience for 500 patients who underwent THA at our department. The mean age at surgery was 64.3 (± 27.3) years. The bacterial detection rate was 4.6%. None of the cases revealed PJI. No significant association between the detection rate and type of antiseptic used or surgery time was observed. However, for patients treated by surgeons with < 10 years of orthopedic experience, a detection rate of 7.3% was found, while a rate of 1.3% was observed for those treated by surgeons with ≥ 10 years of orthopedic experience. This finding indicated that orthopedic experience of less than 10 years was significantly associated with an increased bacterial detection rate (chi-square test, p=0.002). The detection rate was associated with surgeon experience but not with antiseptic type or surgery time. It is possible that intraoperative handling may increase the number of bacteria in surgical fields in wound closure.

Upregulation of OASIS/CREB3L1 in podocytes contributes to the disturbance of kidney homeostasis.

Podocyte injury is involved in the onset and progression of various kidney diseases. We previously demonstrated that the transcription factor, old astrocyte specifically induced substance (OASIS) in myofibroblasts, contributes to kidney fibrosis, as a novel role of OASIS in the kidneys. Importantly, we found that OASIS is also expressed in podocytes; however, the pathophysiological significance of OASIS in podocytes remains unknown. Upon lipopolysaccharide (LPS) treatment, there is an increase in OASIS in murine podocytes. Enhanced serum creatinine levels and tubular injury, but not albuminuria and podocyte injury, are attenuated upon podocyte-restricted OASIS knockout in LPS-treated mice, as well as diabetic mice. The protective effects of podocyte-specific OASIS deficiency on tubular injury are mediated by protein kinase C iota (PRKCI/PKCι), which is negatively regulated by OASIS in podocytes. Furthermore, podocyte-restricted OASIS transgenic mice show tubular injury and tubulointerstitial fibrosis, with severe albuminuria and podocyte degeneration. Finally, there is an increase in OASIS-positive podocytes in the glomeruli of patients with minimal change nephrotic syndrome and diabetic nephropathy. Taken together, OASIS in podocytes contributes to podocyte and/or tubular injury, in part through decreased PRKCI. The induction of OASIS in podocytes is a critical event for the disturbance of kidney homeostasis.

Survey of Shoulder Osteoarthritis in Patients who Underwent Total Hip Arthroplasty for Hip Osteoarthritis.

To the best of our knowledge, no previous studies have reported a relationship between osteoarthritis (OA) of the lower limbs and OA of the shoulder joints. We evaluated the correlation between shoulder OA and hip OA. We collected contrast-enhanced computed tomography (CECT) images of the shoulder joints of 159 patients with hip OA who underwent primary total hip arthroplasty (THA). The images, taken 1 week after THA to monitor venous thromboembolism (VTE), were used to examine the prevalence of shoulder OA. They were compared with those of 103 controls who underwent CECT during the same period to monitor VTE. Shoulder OA was observed in 15% of the controls and 24% of the THA patients. Although the rate was somewhat higher in the THA group, the difference was not significant. However, in the THA group, significantly more patients with bilateral hip OA (33%) had shoulder OA than those with unilateral hip OA (17%). In summary, the prevalence of shoulder OA was significantly higher in patients with bilateral hip OA. In these patients, pain and instability in the hip joints require them to use arm support to stand up or walk, putting the weight-bearing shoulder at risk of developing OA.

CXCL10 is a novel anti-angiogenic factor downstream of p53 in cardiomyocytes.

Tumor suppressor protein p53 plays crucial roles in the onset of heart failure. p53 activation results in cardiac dysfunction, at least partially by suppressing angiogenesis. Though p53 has been reported to reduce VEGF production by inhibiting hypoxia-inducible factor, the anti-angiogenic property of p53 remains to be fully elucidated in cardiomyocytes. To explore the molecular signals downstream of p53 that regulate vascular function, especially under normoxic conditions, DNA microarray was performed using p53-overexpressing rat neonatal cardiomyocytes. Among genes induced by more than 2-fold, we focused on CXCL10, an anti-angiogenic chemokine. Real-time PCR revealed that p53 upregulated the CXCL10 expression as well as p21, a well-known downstream target of p53. Since p53 is known to be activated by doxorubicin (Doxo), we examined the effects of Doxo on the expression of CXCL10 and found that Doxo enhanced the CXCL10 expression, accompanied by p53 induction. Importantly, Doxo-induced CXCL10 was abrogated by siRNA knockdown of p53, indicating that p53 activation is necessary for Doxo-induced CXCL10. Next, we examined the effect of hypoxic condition on p53-mediated induction of CXCL10. Interestingly, CXCL10 was induced by hypoxia and its induction was potentiated by the overexpression of p53. Finally, the conditioned media from cultured cardiomyocytes expressing p53 decreased the tube formation of endothelial cells compared with control, analyzed by angiogenesis assay. However, the inhibition of CXCR3, the receptor of CXCL10, restored the tube formation. These data indicate that CXCL10 is a novel anti-angiogenic factor downstream of p53 in cardiomyocytes and could contribute to the suppression of vascular function by p53.

An Avulsion Fracture of the Lesser Trochanter of the Femur with Prodromal Symptoms in an adult: A Case Report and Review of Literature.

Introduction: An avulsion fracture of the lesser trochanter of the femur in adults is rare and should be differentiated from neoplastic lesions. We present a rare case of avulsion fracture of the lesser trochanter of the femur with prodromal symptoms in an adult. Case Report: A right-handed 40-year-old man with gradual-onset left hip joint pain resulting from baseball pitching consulted a neighborhood doctor. X-ray images did not show any obvious anomalies; however, the pain persisted. Two months after the onset of pain, he stumbled when getting into a car, and the pain worsened. He was then brought into our hospital's emergency unit, and an avulsion fracture of the lesser trochanter of the left femur was detected. Due to mild displacement (<20 mm) and no neoplastic lesions by gadolinium-enhanced magnetic resonance imaging and the technetium scintigraphy, he was managed conservatively. During the final follow-up, 1 year after the onset of symptoms, non-union of the lesser trochanteric fracture was noticed. However, there were no pain and no limited range of motion at the hip joint; therefore, he had no problems with daily activities and sports. Conclusion: The avulsion fracture of the lesser trochanter of the femur in our patient may have been caused by repeated flexion, adduction, and internal rotation of the hip joint during baseball pitching. Although bone union was not achieved, his condition was managed successfully using conservative treatment. Our experience offers a few key learning points to manage such rare fracture occurrences in adults and suggests that conservative treatment is often sufficient for mild displacement (<20 mm) of the fracture.

PKNOX2 regulates myofibroblast functions and tubular cell survival during kidney fibrosis.

The number of patients with chronic kidney disease (CKD) is increasing worldwide. When kidneys are exposed to severe injury, tubular cell death occurs and kidney fibrosis progresses by activating fibroblasts and myofibroblasts (referred to as (myo)fibroblasts), leading to CKD; however, the pathological and molecular mechanisms underlying CKD, including kidney fibrosis, remain obscure. In the present study, we focused on a transcription factor PBX/Knotted Homeobox 2 (PKNOX2) in kidney fibrosis. The transcript and protein expression of PKNOX2 was upregulated in fibrotic kidneys after unilateral ureteral obstruction (UUO). Importantly, immunofluorescence microscopic analysis revealed that the number of PKNOX2-expressing myofibroblasts was increased, whereas the expression of PKNOX2 was decreased in proximal tubular epithelial cells after UUO. In (myo)fibroblasts, PKNOX2 was induced by TGF-ß1. Knockdown of PKNOX2 using shRNA lentiviral system reduced the viability of (myo)fibroblasts either in the presence or absence of TGF-ß1, accompanied by increased apoptosis. Moreover, PKNOX2 knockdown decreased TGF-ß1-induced migration of myofibroblasts and differentiation of fibroblasts into myofibroblasts. Significantly, knockdown of PKNOX2 also decreased the viability and increased apoptosis of tubular epithelial cells. Collectively, PKNOX2 regulates the function of (myo)fibroblasts and the viability of proximal tubular epithelial cells in progression of kidney fibrosis.

Maresin-1 induces cardiomyocyte hypertrophy through IGF-1 paracrine pathway.

The resolution of inflammation is closely linked with tissue repair. Recent studies have revealed that macrophages suppress inflammatory reactions by producing lipid mediators, called specialized proresolving mediators (SPMs); however, the biological significance of SPMs in tissue repair remains to be fully elucidated in the heart. In this study, we focused on maresin-1 (MaR1) and examined the reparative effects of MaR1 in cardiomyocytes. The treatment with MaR1 increased cell size in cultured neonatal rat cardiomyocytes. Since the expression of fetal cardiac genes was unchanged by MaR1, physiological hypertrophy was induced by MaR1. SR3335, an inhibitor of retinoic acid-related orphan receptor α (RORα), mitigated MaR1-induced cardiomyocyte hypertrophy, consistent with the recent report that RORα is one of MaR1 receptors. Importantly, in response to MaR1, cardiomyocytes produced IGF-1 via RORα. Moreover, MaR1 activated phosphoinositide 3-kinase (PI3K)/Akt signaling pathway and wortmannin, a PI3K inhibitor, or triciribine, an Akt inhibitor, abrogated MaR1-induced cardiomyocyte hypertrophy. Finally, the blockade of IGF-1 receptor by NVP-AEW541 inhibited MaR-1-induced cardiomyocyte hypertrophy as well as the activation of PI3K/Akt pathway. These data indicate that MaR1 induces cardiomyocyte hypertrophy through RORα/IGF-1/PI3K/Akt pathway. Considering that MaR1 is a potent resolving factor, MaR1 could be a key mediator that orchestrates the resolution of inflammation with myocardial repair.

Transcription factor old astrocyte specifically induced substance is a novel regulator of kidney fibrosis.

Prevention of kidney fibrosis is an essential requisite for effective therapy in preventing chronic kidney disease (CKD). Here, we identify Old astrocyte specifically induced substance (OASIS)/cAMP responsive element-binding protein 3-like 1 (CREB3l1), a CREB/ATF family transcription factor, as a candidate profibrotic gene that drives the final common pathological step along the fibrotic pathway in CKD. Although microarray data from diseased patient kidneys and fibrotic mouse model kidneys both exhibit OASIS/Creb3l1 upregulation, the pathophysiological roles of OASIS in CKD remains unknown. Immunohistochemistry revealed that OASIS protein was overexpressed in human fibrotic kidney compared with normal kidney. Moreover, OASIS was upregulated in murine fibrotic kidneys, following unilateral ureteral obstruction (UUO), resulting in an increase in the number of OASIS-expressing pathological myofibroblasts. In vitro assays revealed exogenous TGF-ß1 increased OASIS expression coincident with fibroblast-to-myofibroblast transition and OASIS contributed to TGF-ß1-mediated myofibroblast migration and increased proliferation. Significantly, in vivo kidney fibrosis induced via UUO or ischemia/reperfusion injury was ameliorated by systemic genetic knockout of OASIS, accompanied by reduced myofibroblast proliferation. Microarrays revealed that the transmembrane glycoprotein Bone marrow stromal antigen 2 (Bst2) expression was reduced in OASIS knockout myofibroblasts. Interestingly, a systemic anti-Bst2 blocking antibody approach attenuated kidney fibrosis in normal mice but not in OASIS knockout mice after UUO, signifying Bst2 functions downstream of OASIS. Finally, myofibroblast-restricted OASIS conditional knockouts resulted in resistance to kidney fibrosis. Taken together, OASIS in myofibroblasts promotes kidney fibrosis, at least in part, via increased Bst2 expression. Thus, we have identified and demonstrated that OASIS signaling is a novel regulator of kidney fibrosis.

CCN2 as a novel molecule supporting energy metabolism of chondrocytes.

CCN2/connective tissue growth factor (CTGF) is a unique molecule that promotes both chondrocytic differentiation and proliferation through its matricellular interaction with a number of extracellular biomolecules. This apparently contradictory functional property of CCN2 suggests its certain role in basic cellular activities such as energy metabolism, which is required for both proliferation and differentiation. Comparative metabolomic analysis of costal chondrocytes isolated from wild-type and Ccn2-null mice revealed overall impaired metabolism in the latter. Among the numerous metabolites analyzed, stable reduction in the intracellular level of ATP, GTP, CTP, or UTP was observed, indicating a profound role of CCN2 in energy metabolism. Particularly, the cellular level of ATP was decreased by more than 50% in the Ccn2-null chondrocytes. The addition of recombinant CCN2 (rCCN2) to cultured Ccn2-null chondrocytes partly redeemed the cellular ATP level attenuated by Ccn2 deletion. Next, in order to investigate the mechanistic background that mediates the reduction in ATP level in these Ccn2-null chondrocytes, we performed transcriptome analysis. As a result, several metabolism-associated genes were found to have been up-regulated or down-regulated in the mutant mice. Up-regulation of a number of ribosomal protein genes was observed upon Ccn2 deletion, whereas a few genes required for aerobic and anaerobic ATP production were down-regulated in the Ccn2-null chondrocytes. Among such genes, reduction in the expression of the enolase 1 gene was of particular note. These findings uncover a novel functional role of CCN2 as a metabolic supporter in the growth-plate chondrocytes, which is required for skeletogenesis in mammals.

Hexanoyl-lysine as an oxidative-injured marker - application of development of functional food.

We could proposed that N(ε)-(hexanoy)lysine, HEL, become a useful biomarker for detection of oxidative stress damage occurred by exhaustive exercise. We examined the preventive effect of flavonoid compound, eriocitrin, against exercise-induced oxidative damage in rat liver. Eriocitrin administration prior to exercise significantly suppressed the increases in thiobarbituric acid-reactive substance caused by lipid peroxidation during exhaustive exercise. The increase in the contents of HEL in rat liver was also abolished by eriocitrin administration. The concentration of oxidized glutathione was significantly increased by exercise, but the eriocitrin administration suppressed this increase. These results suggested that eriocitrin administration prior to exercise prevented oxidative damages caused by exhaustive exercise-induced oxidative stress. Therefore, it was suggested that HEL could be a good biomarker for oxidative stress, especially at earlier stage when oxidative damage was occurred by lipid peroxidation than a stage of harmful aldehyde formation. Moreover, it was suggested that eriocitrin metabolites, eriodictyol and 3, 4 - dihydroxyhydrocinnamic, might scavenge free radicals and reactive oxygen species, resulting in suppression of lipid peroxidation and reactive proteins with radicals to form HEL. These findings implied that eriocitrin might be useful as an anti-oxidative compound to protect oxidative stress damages.

A novel trans-4-hydroxycinnamic acid derivative from Meyer lemon (Citrus meyeri).

Isolation and structural elucidation of a new trans-4-hydroxycinnamic acid derivative from Meyer lemon (Citrus meyeri hort. ex Y. Tanaka) was carried out. The derivative exhibited the antioxidative activity by ORAC (oxygen radical absorbance capacity) assay and was found in the flavedo and alvedo of Meyer lemon peel.