Validity of a preoperative scoring system for surgical management of periprosthetic hip infection: one-stage vs. two-stage revision.

INTRODUCTION: There are no widely accepted algorithms for determining optimal treatment for periprosthetic joint infection (PJI). Our study aimed to confirm the validity of a previously published scoring system in a larger number of patients to support a rational surgical treatment strategy for periprosthetic hip infection. MATERIALS AND METHODS: Between February 2001 and December 2020, we performed 155 consecutive revision total hip arthroplasties (THAs) for PJI, with mean follow-up of 6 years. One-stage revision THA was performed in 56 hips and two-stage revision THA in 99 hips. Prosthesis survival from recurrent infection was determined by Kaplan-Meier analysis, using implant removal as the endpoint. The pre-operative scoring system (full score of 12 points), including 6 essential elements, was retrospectively evaluated. RESULTS: The 10-year survival rates were 98% for one-stage (95% confidence interval [CI], 94-100) and 87% (95% CI, 79-96) for two-stage revision THA. Multivariate Cox regression analysis provided a total preoperative score as an independent risk factor for implant removal (hazard ratio, 0.17; 95% CI, 0.06-0.49; p < 0.001). The sensitivity and specificity at the cut-off of 4 points on the scoring system were 80% and 91%, respectively. The average score for one-stage revision THA in successful and failed cases were 8.9 and 6.0, and for two-stage revision THA were 6.5 and 3.9, respectively. We found significant differences between successful cases in one- and two-stage revision THA (p < 0.05). CONCLUSIONS: The preoperative scoring system was useful for managing PJI. One-stage revision THA is recommended in patients scoring ≥ 9 points, and meticulously performed two-stage revision THA is encouraged for patients scoring ≥ 4 points.

Experimental periprosthetic fractures with collarless polished tapered cemented stems.

PURPOSE: After cemented total hip arthroplasty, the risk of periprosthetic fracture (PPF) of taper-slip stems is higher than that of composite-beam stems. We aimed to assess the conditions resulting in PPFs of taper-slip stems using a falling weight. METHODS: Taper-slip stems were fixed to five types of simulated bone models using bone cement, and the fractures were evaluated by dropping stainless-steel weights from a predetermined height onto the heads. The periprosthetic fracture height in 50% of the bone models (PPFH50) was calculated using the staircase method. RESULTS: For the fixation with 0° of flexion, the values for PPFH50 were 61 ± 11, 60 ± 13, above 110, 108 ± 49, and 78 ± 12 cm for the cobalt-chromium-molybdenum alloy, stainless steel alloy (SUS), titanium alloy (Ti), smooth surface, and thick cement mantle models, respectively; for the fixation with 10° of flexion (considering flexure), the PPFH50 values were 77 ± 5, 85 ± 9, 90 ± 2, 89 ± 5, and 81 ± 11 cm, respectively. The fracture rates of the polished-surface stems were 78.6 and 35.7% at the proximal and distal sites, respectively (p < 0.05); the fracture rates of the smooth-surface stems were 14.2 and 100%, respectively (p < 0.05). CONCLUSION: The impact tests demonstrated that the conditions that were less likely to cause PPFs were use of Ti, a smooth surface, a thick cement mantle, and probably, use of SUS.

Evaluation of a joint workshop on study design for hospital and community pharmacists: a retrospective cross-sectional survey.

BACKGROUND: Although pharmacists often identify numerous clinical questions, they face several barriers, including the lack of mentors for research activities in clinical settings. Therefore, a workshop for the appropriate selection of a study design, which is a fundamental first step, may be necessary. The purpose of this study was to evaluate the effectiveness of a workshop on study design for hospital and community pharmacists. Moreover, the characteristics of pharmacists with little involvement in research activities were extracted using decision-tree analysis to guide the design of future workshops. METHODS: A workshop was conducted on October 1, 2023. It comprised three parts: lectures, group work, and presentations. Questionnaire-based surveys were conducted with workshop participants regarding their basic information, their background that influenced research activities, their satisfaction, and their knowledge/awareness. For the questions on knowledge/awareness, the same responses were requested before and after the workshop using a five-scale scoring system. Multivariate logistic regression analysis was conducted to identify independent factors influencing research activities. Decision tree analysis was performed to extract low-effort characteristics of the research activities. RESULTS: Of the 40 workshop attendees, the overall satisfaction score for the workshop was 4.38 of 5, and the score for each question was 4 or higher. Significant increases were observed in the scores of knowledge/awareness after the workshop. Moreover, 95% of the pharmacists answered that it would be highly useful to conduct a joint workshop between hospitals and community pharmacists. Although independent influencing factors were not detected in the multivariate logistic regression analysis, the decision tree analysis revealed that pharmacists who were no member of an academic society (85%, 11/13) or members without any certifications or accreditations related to pharmacy practice (80%, 4/5) were the least active in clinical research. In contrast, those belonging to academic societies and holding certifications or accreditations related to pharmacy practice frequently conducted clinical research. CONCLUSION: The present study revealed that a joint workshop on study design may have the potential to change pharmacists' knowledge and awareness of research activities. Moreover, future workshops should be conducted with pharmacists who do not belong to academic societies.

The modified Spitzy shelf acetabuloplasty for the dysplastic hip.

Aims: Although there are various pelvic osteotomies for acetabular dysplasia of the hip, shelf operations offer effective and minimally invasive osteotomy. Our study aimed to assess outcomes following modified Spitzy shelf acetabuloplasty. Methods: Between November 2000 and December 2016, we retrospectively evaluated 144 consecutive hip procedures in 122 patients a minimum of five years after undergoing modified Spitzy shelf acetabuloplasty for acetabular dysplasia including osteoarthritis (OA). Our follow-up rate was 92%. The mean age at time of surgery was 37 years (13 to 58), with a mean follow-up of 11 years (5 to 21). Advanced OA (Tönnis grade ≥ 2) was present preoperatively in 16 hips (11%). The preoperative lateral centre-edge angle ranged from -28° to 25°. Survival was determined by Kaplan-Meier analysis, using conversions to total hip arthroplasty as the endpoint. Risk factors for joint space narrowing less than 2 mm were analyzed using a Cox proportional hazards model. Results: The mean Merle d'Aubigné clinical score improved from 11.6 points (6 to 17) preoperatively to 15.9 points (12 to 18) at the last follow-up. The survival rates were 95% (95% confidence interval (CI) 91 to 99) and 86% (95% CI 50 to 97) at ten and 15 years. Multivariate Cox regression identified three factors associated with radiological OA progression: age (hazard ratio (HR) 2.85, 95% CI 1.05 to 7.76; p = 0.0398), preoperative joint space (HR 2.41, 95% CI 1.35 to 4.29; p = 0.0029), and preoperative OA (HR 8.34, 95% CI 0.94 to 73.77; p = 0.0466). Conclusion: Modified Spitzy shelf acetabuloplasty is an effective joint-preserving surgery with a wide range of potential indications.

Trochanteric Claw Plate Fixation for Greater Trochanteric Fracture or Osteotomy in Total Hip Arthroplasty.

This study retrospectively evaluated 41 consecutive open reductions and internal fixations following primary or revision total hip arthroplasty, which required trochanteric claw plate fixation for greater trochanteric fracture or osteotomy between January 2008 and December 2020. The mean duration of clinical follow-up was 4.2 years (range, 1-13 years). The patients included 13 men and 28 women, with a mean age of 68 years (range, 32-87 years). The indications for intervention included trochanteric osteotomy, intraoperative fracture, and non-union including postoperative fracture in 6, 9, and 26 cases, respectively. The mean Merle d'Aubigné Clinical Score improved from 9.4 points (range, 5-15 points) pre-operatively, to 14.3 points (range, 9-18 points) at the last follow-up. Bone union occurred in 35 cases (85%), while implant breakage occurred in four cases. At the last follow-up, the mean Merle d'Aubigné Clinical Scores of bone union and non-union were 15.3 and 14.1, respectively (p=0.48). The Kaplan-Meier survival rate, with the endpoint being revision surgery for pain, non-union, dislocation, or implant breakage, at 10 years was 80.0% (95% confidence interval: 62.6-97.4%). Greater trochanteric fixation using a trochanteric claw plate yielded successful results.

Trunnionosis in Metal-on-Polyethylene Total Hip Arthroplasty With Periprosthetic Infection: A Case Report.

A 67-year-old man who underwent right hemiarthroplasty and left total hip arthroplasty (THA) experienced left hip pain two years previously. No previous diagnosis was made at other hospitals. Radiography revealed left hip trunnionosis because of stem-neck shortening, with periprosthetic joint infection (PJI) spreading to both hips. Bilateral revision THA was performed, but the treatment was difficult due to the delayed diagnosis, necessitating the extraction of the well-fixed stem for PJI. Trunnionosis is caused by implant-related, surgical, and patient factors, and early diagnosis is important because of its association with PJI. Furthermore, even implants with few reports of trunnionosis can lead to this complication. Surgeons should always consider that performing THA using a large-diameter head predisposes the patient to trunnionosis.

Alkali-treated titanium dioxide promotes formation of proteoglycan layer and altered calcification and immunotolerance capacity in bone marrow stem cell.

Introduction: In this study, we report that a proteoglycans (PGs)-layer between the bone and titanium dioxide (TiO2) surface after osseointegration improved the calcification capacity and immunotolerance of human bone marrow mesenchymal stem cells (hBMSCs) on TiO2. Alkaline treatment of TiO2 is a method for promoting osteogenesis in hBMSCs. We hypothesized that promotion of osteogenesis due to alkaline treatment was caused by changing PGs-layer on TiO2. Objective: This study aimed to analyze whether alkaline treatment of TiO2 affects PGs-layer formation and immunotolerance in hBMSCs. Methods: The topology and wettability of the alkaline-treated titanium (Ti-Al) and unprocessed titanium (Ti-MS) surfaces were characterized. Initial cell attachment, cell proliferation, calcification capacity, alkaline phosphatase activity, PGs-layer formation, PGs function, and the expression of osteogenic and immunotolerance-related genes were analyzed. The conditioned medium (CM) from hBMSCs grown on Ti-Al and Ti-MS was added to macrophages (hMps) and Jurkat cells, and immunotolerance gene expression in these cells was analyzed. Results: hBMSCs cultured on Ti-Al showed increased initial cell attachment, cell proliferation, PG-layer formation, and osteogenic capacity compared with hBMSCs on Ti-MS. Gene expression of indoleamine 2,3-dioxygenase (IDO) in the hBMSCs cultured on Ti-Al was higher than that in the hBMSCs on Ti-MS. CM from hBMSCs did not affect markers of M1 and M2 macrophages in hMps. CM from hBMSCs cultured on Ti-Al altered the gene expression of Foxp3 in Jurkat cells compared to that of CM from hBMSCs on Ti-MS. Significance: These results suggest that alkaline treatment of TiO2 altered PGs-layer formation, and changed the osteogenesis and immunotolerance of hBMSCs.

Can serum C-reactive protein determine the timing of reimplantation in two-stage revised arthroplasty for periprosthetic hip infection?

BACKGROUND: There are no definitive guides to determine the timing of reimplantation in two-stage revision total hip arthroplasties (THA) for periprosthetic joint infection (PJI). This study was to design to support a rational strategy of surgical treatment using serum C-reactive protein (CRP). METHODS: We analyzed a total of 75 hips for PJI in the process of performing two-stage and multiple-stage revision THAs. CRP level was retrospectively evaluated every week and transformed to log2 (CRP) using a logistic regression model. Prosthesis survival from recurrent infection was determined by Kaplan-Meier analysis, using implant removal as the endpoint. Receiver operating characteristic curves were calculated using each log2 (CRP) to assess predictions of recurrent infection. RESULTS: The 10-year survival rates were 85% (95% confidence interval, 76-95) and 100% for two-stage and multiple-stage revision THAs, respectively. Preoperatively, at 1, 2, 3, and 5 weeks, log2 (CRP) was not associated with recurrent infection. In failed two-stage revision THAs, log2 (CRP) at 3 weeks divided by that at 2 weeks showed a significant difference. Failure was associated with a ratio of >4.0 for the CRP level between 3 and 2 weeks. CONCLUSION: In two-stage revision THA for PJI, patients with CRP elevation from 2 weeks to 3 weeks, especially 4-fold elevation, suggests the need for further debridement and postponement of second-staged reimplantation.

Presenilin 1 deficiency impairs Aß42-to-Aß40- and angiotensin-converting activities of ACE.

Introduction: Alzheimer's disease (AD) is associated with amyloid ß-protein 1-42 (Aß42) accumulation in the brain. Aß42 and Aß40 are the major two species generated from amyloid precursor protein. We found that angiotensin-converting enzyme (ACE) converts neurotoxic Aß42 to neuroprotective Aß40 in an ACE domain- and glycosylation-dependent manner. Presenilin 1 (PS1) mutations account for most of cases of familial AD and lead to an increased Aß42/40 ratio. However, the mechanism by which PSEN1 mutations induce a higher Aß42/40 ratio is unclear. Methods: We over expressed human ACE in mouse wild-type and PS1-deficient fibroblasts. The purified ACE protein was used to analysis the Aß42-to-Aß40- and angiotensin-converting activities. The distribution of ACE was determined by Immunofluorescence staining. Result: We found that ACE purified from PS1-deficient fibroblasts exhibited altered glycosylation and significantly reduced Aß42-to-Aß40- and angiotensin-converting activities compared with ACE from wild-type fibroblasts. Overexpression of wild-type PS1 in PS1-deficient fibroblasts restored the Aß42-to-Aß40- and angiotensin-converting activities of ACE. Interestingly, PS1 mutants completely restored the angiotensin-converting activity in PS1-deficient fibroblasts, but some PS1 mutants did not restore the Aß42-to-Aß40-converting activity. We also found that the glycosylation of ACE in adult mouse brain differed from that of embryonic brain and that the Aß42-to-Aß40-converting activity in adult mouse brain was lower than that in embryonic brain. Conclusion: PS1 deficiency altered ACE glycosylation and impaired its Aß42-to-Aß40- and angiotensin-converting activities. Our findings suggest that PS1 deficiency and PSEN1 mutations increase the Aß42/40 ratio by reducing the Aß42-to-Aß40-converting activity of ACE.

Treatment strategies for recurrent dislocation following total hip arthroplasty: relationship between cause of dislocation and type of revision surgery.

BACKGROUND: There are many therapeutic options for dislocation following total hip arthroplasty (THA). The aim of this study was to evaluate the results of revision surgery for dislocated hips. METHODS: Between November 2001 and December 2020, 71 consecutive revision hip surgeries were performed at our institution for recurrent dislocation following THA. We conducted a retrospective study of all 65 patients (71 hips), who were followed for a mean of 4.7 ± 3.2 years (range, 1-14). The cohort included 48 women and 17 men, with a mean age of 71 ± 12.3 years (range, 34-92). The mean number of previous surgeries was 1.6 ± 1.1 (range, 1-5). From intraoperative findings, we created six categories of revision hip surgery for recurrent dislocation following THA: open reduction and internal fixation (2 hips); head change or liner change only (6 hips); cup change with increased head size only (14 hips); stem change only (7 hips); cup and stem change (24 hips); and conversion to constrained cup (18 hips). Prosthesis survival was analyzed by the Kaplan-Meier method, with repeat revision surgery for re-dislocation or implant failure as the endpoint. A cox proportional hazards model was used for risk factors of re-revision surgery. RESULTS: Re-dislocation occurred in 5 hips (7.0%) and implant failure in 1 hip (1.4%). The 10-year survival rate was 81.1% (95% confidence interval, 65.5-96.8). A Dorr classification of "positional" was a risk factor for re-revision surgery due to re-dislocation. CONCLUSION: Clear understanding of the cause of dislocation is essential for optimizing revision procedures and improving the rate of successful outcomes.

Aß42 treatment of the brain side reduced the level of flotillin from endothelial cells on the blood side via FGF-2 signaling in a blood-brain barrier model.

Our previous study showed that the flotillin level is decreased in the blood of patients with Alzheimer's disease (AD) when compared to that of patients with non-AD and vascular dementia; however, the molecular mechanism remains to be determined. In this study, to elucidate whether Aß accumulation in the brain has an effect on the blood flotillin level, we used our previously established blood-brain barrier (BBB) culture model using microvascular endothelial cells obtained from human induced pluripotent stem cells (iBMECs) and astrocytes prepared from rat cortex. In this BBB model with iBMECs plated on the upper compartment (blood side) and astrocytes plated on the lower compartment (brain side), the trans-endothelial electrical resistance values are high (over 1500 Ωm2) and stable during experiments. We found that the addition of Aß42 (0.5 and 2 µM) to the brain side significantly reduced the level of flotillin secreted by iBMECs on the blood side. The level of basic fibroblast growth factor (FGF-2) in the brain side was significantly reduced by Aß42 treatment, and was accompanied by a reduction in the level of phosphorylation of the fibroblast growth factor receptor in iBMECs. The brain-side Aß42 treatment-induced reduction of flotillin secretion into the blood side was restored in a dose-dependent manner by the addition of FGF-2 into the brain side. These results indicated that Aß accumulation in the brain side reduced FGF-2 release from astrocytes, which attenuated FGF-2-mediated iBMECs signaling via the FGF-2 receptor, and thereby reduced flotillin secretion from iBMECs on the blood side. Our findings revealed a novel signaling pathway crossing the BBB from the brain side to the blood side, which is different from the classical intramural periarterial drainage or lymphatic-system-to-blood pathway.

Apolipoprotein E4 inhibits γ-secretase activity via binding to the γ-secretase complex.

The mechanisms of amyloid accumulation in familial Alzheimer's disease (FAD) and sporadic AD (SAD) are controversial. In FAD, mutations in presenilin (PSEN) impair γ-secretase activity and lead to abnormal amyloid ß-protein (Aß) production, thereby increasing the Aß42/40 ratio. SAD is postulated to be caused by decreased Aß clearance of apolipoprotein E4 (APOE4), the strongest risk factor for SAD. However, whether intracellular APOE4 affects Aß production is unclear. Using APOE3 and APOE4 knock-in (KI) mouse brain and primary cultured fibroblasts from these mice, in this study, we demonstrated that APOE3 and APOE4 bind to the γ-secretase complex and isoform-dependently regulate its activity and Aß production. We found that Aß40 levels and γ-secretase activity were higher in APOE knockout mouse brain than in wild-type mouse brain. APOE4-KI fibroblasts had significant lower Aß levels and γ-secretase activity but higher Aß42/40 ratio compared with APOE3-KI cells, indicating that APOE4-KI reduces Aß production by inhibiting γ-secretase activity. Interestingly, the levels of γ-secretase complex bound to APOE4 are higher than those bound to APOE3, and the levels of γ-secretase complex in the brain and fibroblasts of APOE4-KI mice were higher than those of APOE3-KI mice. Taken together, our findings demonstrate that intracellular APOE4 inhibits Aß production, more preferentially inhibits Aß40 production, and thereby induces an increase in the Aß42/40 ratio via binding to the γ-secretase complex. These results suggest a novel mechanism in which intracellular APOE4 contributes to the pathogenesis of SAD by inhibiting γ-secretase activity.

Ongoing vascular inflammation evaluated by 18F-fluorodeoxyglucose positron emission tomography in patients long after Kawasaki disease.

BACKGROUND: This study aimed to determine whether ongoing vascular inflammation presents in patients who had coronary artery aneurysms (CAAs) caused by Kawasaki disease (KD). METHODS: Subjects were 26 patients with a history of KD; 15 had giant CAA (gCAA) ≥ 8.0 mm and 11 had smaller CAA (smCAA) < 8 mm in the acute phase. They underwent X-ray computed tomography and 18F-fluorodeoxyglucose positron emission tomography. We determined the maximum coronary target-to-background ratio (CaTBR) and the mean thoracic aorta TBR (TaTBR) in each patient. They were compared between groups, and their correlation with various variables was determined. RESULTS: CaTBR and TaTBR were significantly higher in gCAA than in smCAA (P < .005 for both values) and were significantly higher even in patients without any metabolic risk factor (P < .05 for both values). The CAA size in acute phase significantly positively correlated with CaTBR (R2 = 0.32) as well as TaTBR (R2 = 0.28). Also, TaTBR significantly positively correlated with CaTBR (R2 = 0.32) as well as cumulative number of metabolic risk factors (trend, P = .03). CONCLUSIONS: Ongoing vascular inflammation may present long after KD, especially in patients with severe inflammation expressed as gCAA in the acute phase.

Chronic Expanding Hematoma With Progressive Osteolysis After Total Hip Arthroplasty: A Case Report.

A 31-year-old man without any other medical history developed severe hip pain seven years after right primary total hip arthroplasty (THA). Radiography revealed extensive progressive osteolysis around the cup and stem. Periprosthetic infections and adverse reactions to the metal debris were absent. Right revision THA was performed, and chronic expanding hematoma (CEH) was diagnosed based on a comprehensive assessment. CEH should be diagnosed early because progressive osteolysis may generate an extensive hematoma. Thus, it should be considered when progressive osteolysis of an unknown cause is encountered after THA.

Two cases of parapharyngeal space tumor resected by a double split mandibular osteotomy technique.

Parapharyngeal space tumors have poor subjective symptoms and often grow until diagnosed; therefore, mandibular transection may be needed to obtain a wider field of view during surgery. However, if a median lower lip incision is performed for the mandibular transection, esthetic problems occur after surgery. Here, we report two cases of parapharyngeal space tumors that were removed with a mandibular lateral segment-osteotomy technique without median lower lip incision to avoid esthetic problems. Case 1 was a 49-year-old woman. She was aware of a right tonsillar swelling, and an imaging test revealed a tumor lesion 60 mm in size in the right parapharyngeal space. Case 2 was a 40-year-old woman with an abnormal position of the uvula, and an imaging test showed the left parapharyngeal space tumor lesion 45 mm in size. Both cases were diagnosed as a pleomorphic adenoma, and surgery under general anesthesia was performed jointly with otolaryngology and oral surgery. The incision was performed from the lower part of the right auricle to the anterior part of the submandibular area. After the tumor resection, the mandible was repositioned, fixed by plates, and the intermaxillary fixation was performed with a surgical stent. In both cases, slight paralysis of the mandibular branch of the facial nerve and the mental nerve was observed after the operation, but they were improved immediately. One year after the operation, the plates were removed. There have been no recurrences until now.

Endofemoral Shooting Technique for Removing Well-fixed Cementless Stems.

Background: The removal of a well-fixed cementless stem poses technical challenges. The aim of this study was to evaluate the outcomes of our endofemoral extraction technique established in 2001. Methods: Between January 2001 and December 2016, 118 consecutive revisions following bipolar or total hip arthroplasty, which required cementless femoral stem removal, were performed at our institution. This retrospective study evaluated 106 patients (108 hips) who were followed up for a mean of 9.2 years (range, 5-20 years). The patients included 15 men and 91 women with a mean age of 65 years (range, 33-87 years). Endofemoral extracted stem removal was performed as follows. Multiple Kirschner wires were sequentially inserted into the interface between the implant and cortical bone, after which the implant was detached using a thin chisel. After the cementless stem was removed, it was replaced with a cemented stem using an autograft, as needed. Radiological loosening of the femoral stem was defined as definite or probable loosening, based on the criteria of Harris et al. Prosthesis survival was analyzed using the Kaplan-Meier method, with the endpoint set as repeat revision surgery for stem loosening or femoral fracture. Results: Re-revision surgery was performed in 7 hips. Stem loosening was observed in 4 hips, and the mean subsidence was 0.3 mm (0-3 mm). The 10-year survival rate was 97.7% (95% confidence interval, 93.2-100). Conclusions: Our technique for removing well-fixed cementless stems yielded successful results.

Presenilin Deficiency Increases Susceptibility to Oxidative Damage in Fibroblasts.

Alzheimer's disease (AD) is a genetic and sporadic neurodegenerative disease characterized by extracellular amyloid-ß-protein (Aß) aggregates as amyloid plaques and neuronal loss in the brain parenchyma of patients. Familial AD (FAD) is found to be genetically linked to missense mutations either in presenilin (PS) or amyloid precursor protein (APP). Most of PS mutations increase Aß42/Aß40 ratio, which is thought to result in early amyloid deposition in brain. However, PS deficiency in the fore brain of adult mouse leads to neuronal loss in an Aß independent manner and the underlying mechanism is largely unknown. In this study, we found that reactive oxygen species (ROS) are increased in PS deficient fibroblasts and that H2O2 and ferrous sulfate treatment produced more ROS in PS deficient fibroblasts than in wild-type fibroblasts. PS deficient fibroblasts showed significantly decreased cellular ferritin levels compared with wild-type fibroblasts, suggesting reduced iron sequestrating capability in PS deficient cells. Blockade of γ-secretase activity by a γ-secretase inhibitor, DAPT, decreased ferritin levels, indicating that γ-secretase activity is important for maintaining its levels. Moreover, overexpression PS1 mutants in wild-type fibroblasts decreased ferritin light chain levels and enhanced intracellular ROS levels. Our results suggest that dysfunction of PS may reduce intracellular ferritin levels and is involved in AD pathogenesis through increasing susceptibility to oxidative damage.

Perioperative oral care can prevent surgical site infection after colorectal cancer surgery: A multicenter, retrospective study of 1,926 cases analyzed by propensity score matching.

BACKGROUND: Surgical site infection is a common postoperative complication of colorectal cancer surgery, and surgical site infection increases medical costs, prolongs hospitalization, and worsens long-term prognosis. Perioperative oral care has been reported to be effective in preventing postoperative pneumonia, although there are only a few reports on its effectiveness in preventing surgical site infection. This study aimed to determine the role of perioperative oral care in surgical site infection prevention after colorectal cancer surgery. METHODS: In this study, 1,926 patients with colorectal cancer from 8 institutions were enrolled; 808 patients (oral care group) received perioperative oral care at the hospital's dental clinic, and 1,118 (control group) did not receive perioperative oral care. The data were matched by propensity score to reduce bias. Ultimately, a total of 1,480 patients were included in the analysis. RESULTS: The incidence of surgical site infection was significantly lower in the oral care group than in the control group (8.4% vs 15.7%, P < .001). Multivariate logistic regression analysis revealed 4 independent risk factors for surgical site infection: low albumin level, rectal cancer, blood loss, and lack of perioperative oral care. Lack of perioperative oral care had an odds ratio of 2.100 (95% confidence interval 1.510-2.930, P < .001). CONCLUSION: These results suggest that perioperative oral care can reduce the incidence of surgical site infection after colorectal cancer resection. Perioperative oral care may have an important role in the future perioperative management of colorectal cancer as a safe and effective method of surgical site infection prevention, although further validation in prospective studies is needed.

Presenilin Is Essential for ApoE Secretion, a Novel Role of Presenilin Involved in Alzheimer's Disease Pathogenesis.

Alzheimer's disease (AD) is a debilitating dementia characterized by progressive memory loss and aggregation of amyloid-ß (Aß) protein into amyloid plaques in patient brains. Mutations in presenilin (PS) lead to abnormal generation of Aß, which is the major cause of familial AD (FAD), and apolipoprotein E4 (ApoE4) is the major genetic risk factor for sporadic AD (SAD) onset. However, whether dysfunction of PS is involved in the pathogenesis of SAD is largely unknown. We found that ApoE secretion was completely abolished in PS-deficient cells and markedly decreased by inhibition of γ-secretase activity. Blockade of γ-secretase activity by a γ-secretase inhibitor, DAPT, decreased ApoE secretion, suggesting an important role of γ-secretase activity in ApoE secretion. Reduced ApoE secretion is also observed in nicastrin-deficient cells with reduced γ-secretase activity. PS deficiency enhanced nuclear translocation of ApoE and binding of ApoE to importin α4, a nuclear transport receptor. Moreover, the expression of PS mutants in PS-deficient cells suppressed the restoration effects on ApoE secretion compared with the expression of wild-type PS. Plasma ApoE levels were lower in FAD patients carrying PS1 mutations compared with normal control subjects. Our findings suggest a novel role of PS contributing to the pathogenesis of SAD by regulating ApoE secretion.SIGNIFICANCE STATEMENT Familial AD (FAD) typically results from mutations in the genes encoding amyloid precursor protein, presenilin 1 (PS1), or PS2. Many PS mutants have been found to exert impaired γ-secretase activity and increased amyloid-ß 42 (Aß42)/Aß40 ratio, which induce early amyloid deposition and FAD. On the other hand, apolipoprotein E4 (ApoE4) is the major genetic risk factor for sporadic AD (SAD) and contributes to AD pathogenesis because it has reduced Aß clearance capability compared with ApoE3 and ApoE2. FAD and SAD have long been considered to be caused by these two independent mechanisms; however, for the first time, we demonstrated that PS is essential for ApoE secretion and PS mutants affected ApoE secretion in vitro and in human samples, suggesting a novel mechanism by which PS is also involved in SAD pathogenesis.