Risk Stratification According to Baseline and Early Change in Neutrophil-to-Lymphocyte Ratio in Advanced Non-Small Cell Lung Cancer Treated with Chemoimmunotherapy: A Multicenter Real-World Study.

BACKGROUND: Chemoimmunotherapy is a standard treatment for advanced non-small-cell lung cancer (NSCLC). However, data on clinical predictive factors remain scarce. OBJECTIVE: We aim to identify clinical biomarkers in patients undergoing chemoimmunotherapy. METHODS: This multicenter, real-world cohort study included chemonaive patients who underwent chemoimmunotherapy between December 2018 and May 2022. Multivariate analysis was used to determine associations between survival outcomes and patient background, including baseline neutrophil-to-lymphocyte ratio (NLR) and its dynamic change (ΔNLR). To further investigate the clinical significance of NLR, patients were classified based on their peripheral immune status, defined by a combination of NLR and ΔNLR. RESULTS: The study included 280 patients with 30.1 months of median follow-up. Multivariate analysis revealed that older individuals, poor performance status, tumor proportion score < 1%, liver metastasis, baseline NLR ≥ 5, and ΔNLR ≥ 0 independently correlated significantly with shorter progression-free and overall survival (OS). Patients with high peripheral immune status (defined as NLR <5 and ΔNLR < 0) significantly improved long-term survival (2-year OS rate of 58.3%), whereas those with low peripheral immune status (defined as NLR ≥ 5 and ΔNLR ≥ 0) had extremely poor outcomes (2-year OS rate of 5.6%). Safety profiles did not differ significantly in terms of severe adverse events and treatment-related death rates despite the patients' peripheral immune status (P = 0.46 and 0.63, respectively). CONCLUSIONS: Our study provides real-world evidence regarding clinical prognostic factors for the efficacy of chemoimmunotherapy. The combined assessment of baseline NLR and ΔNLR could facilitate the identification of patients who are likely to achieve a durable response from chemoimmunotherapy.

[A Case of Stage â £ Gastric Cancer with Multiple Liver Metastases, Resected Primary Tumor after Chemotherapy, and Alive for 3.5 Years without Recurrence].

A 67-year-old man visited our hospital for epigastric pain. Esophagogastroduodenoscopy(EGD)revealed type 2 gastric cancer from the cardia to the gastric angle, and histopathological examination revealed papillary adenocarcinoma(pap), HER2-positive. Contrast-enhanced CT showed wall thickening mainly in the posterior wall of the gastric body, enlarged lymph nodes that were lumped together with the main lesion, and 8 low-absorption areas with ring shaped contrast effects in both lobes of the liver. The patient was diagnosed as gastric cancer cT4aN(+)M1[HEP], clinical Stage ⅣB. Six courses of capecitabine plus cisplatin plus trastuzumab(XP plus Tmab)therapy and 17 courses of capecitabine plus trastuzumab(X plus Tmab)therapy were performed. After chemotherapy, liver and lymph node metastases disappeared on CT and MRI. EGD showed residual gastric cancer, and the policy was to resect the primary tumor. Laparoscopic total gastrectomy with D2 lymph node dissection was performed. Pathological results showed T1b(SM)depth, no lymph node metastasis, and histologic response was Grade 2a. Six courses of X plus Tmab were administered as postoperative adjuvant chemotherapy, but were discontinued at the patient's request. Currently, 5 years have passed since the first chemotherapy and 3.5 years have passed since the surgery, and the patient is alive without recurrence, suggesting that the conversion surgery may have contributed to the prolonged survival.

Ten-Gram-Scale Total Synthesis of the Anticancer Drug Candidate E7130 to Supply Clinical Trials.

E7130 is a novel drug candidate with an exceedingly complex chemical structure of the halichondrin class, discovered by a total synthesis approach through joint research between the Kishi group at Harvard University and Eisai. Only 18 months after completion of the initial milligram-scale synthesis, ten-gram-scale synthesis of E7130 was achieved, providing the first good manufacturing practice (GMP) batch to supply clinical trials. This paper highlights the challenges in developing ten-gram-scale synthesis from the milligram-scale synthesis.

Cross-sectional association of skeletal muscle mass and strength with dietary habits and physical activity among first-year university students in Japan: Results from the KEIJI-U study.

OBJECTIVE: Recently, the high prevalence of young Japanese individuals who are underweight has received attention because of the potential risk for sarcopenia. The aim of this study was to examine the prevalence and characteristics of sarcopenia in Japanese youth. METHODS: In this cross-sectional study, we measured skeletal muscle mass using a multifrequency bioelectrical impedance analysis device and handgrip strength (HGS) and administered questionnaires on dietary habits and physical activity in 1264 first-year university students ages 18 to 20 y (838 men and 426 women). Sarcopenia was confirmed based on the presence of both low skeletal muscle mass and weak muscle strength. RESULTS: In all, 145 men (17%) and 69 women (16%) were diagnosed as underweight. Sarcopenia was diagnosed in 8 men (1%) and 5 women (1%). There was a significantly higher prevalence of low skeletal muscle mass index (SMI) and/or weak HGS in underweight individuals than in those in other body mass index (BMI) ranges. The multivariate analyses indicated that SMI and HGS were significantly associated with BMI in both sexes. Furthermore, after adjusting for BMI, both SMI and HGS were significantly associated with physical activity in men, and SMI was significantly associated with energy intake in women. CONCLUSIONS: First-year university students showed a high incidence of being underweight with low SMI and/or weak HGS, but the prevalence of sarcopenia was low in both sexes. There may be sex differences in factors related to muscle mass and strength, but further research is needed to clarify this.

Hepatoid adenocarcinoma of the stomach effectively treated with capecitabine with oxaliplatin as adjuvant chemotherapy: A case report and literature review.

INTRODUCTION: Hepatoid adenocarcinoma of the stomach (HAS) is an alpha-fetoprotein (AFP)-producing gastric carcinoma (GC) with a hepatocellular carcinoma-like histology. HAS is a relatively rare type of GC, with liver metastases being more common than peritoneal dissemination in the recurrent form, and the poor prognosis. PRESENTATION OF CASE: We present the case of a 70-year-old patient who underwent distal gastrectomy for GC and immunohistologically diagnosed as HAS. The patient had an intravenous tumor thrombus at the proximal margin of the resected stomach. Owing to the low possibility of radical resection and high probability of liver metastatic recurrence, capecitabine with oxaliplatin (CapeOX) was started as adjuvant chemotherapy (AC). After three courses of CapeOX, oxaliplatin was discontinued due to adverse events (peripheral neuropathy, grade3) and capecitabine alone was continued for 3 years postoperatively. Six years after surgery, no local recurrence or distant metastasis was detected on imaging studies. DISCUSSION: There is no established standard treatment for HAS. Recently, some studies have reported the efficacy of antimetabolites or platinum-based drugs as AC regimens. We thus decided to start a regimen consisting of a combination of antimetabolites and a platinum, i.e., CapeOX, which proved efficacious. CONCLUSION: CapeOX or capecitabine may be effective as AC for treating HAS.

Efficacy of Coagulofibrinolytic Markers for Postoperative Prediction of Venous Thromboembolism in Colorectal Surgery Patients: A Retrospective Observational Study.

Objectives: A low rate of the incidence of venous thromboembolism (VTE) after surgeries that are preoperatively classified as having high risk of VTE has been reported in recent years. We seek to identify the optimal cases to receive perioperative pharmacologic thromboprophylaxis. In this study, we evaluated the incidence rate of VTE among patients undergoing colorectal surgery who did not receive perioperative pharmacologic thromboprophylaxis, and the ability of coagulofibrinolytic markers to predict the postoperative development of VTE. Methods: We retrospectively analyzed the rate of postoperative development of VTE in 70 patients undergoing elective colorectal surgery without perioperative pharmacologic thromboprophylaxis and the ability of coagulofibrinolytic markers to predict the development of VTE. Results: The incidence of VTE was observed in 11 patients (15.7%); all cases were asymptomatic and distal-type deep vein thrombosis (DVT). Comparisons of time course changes in perioperative coagulofibrinolytic markers between patients with and without DVT revealed significant differences in soluble fibrin (SF), thrombin-antithrombin complex (TAT), fibrin/fibrinogen degradation product (FDP) and D-dimer. Dynamic postoperative physiological coagulofibrinolytic responses were shown, but all four markers at each postoperative point demonstrated moderate accuracy (median area under the curve [AUC]: 0.788, median sensitivity: 0.865, median specificity: 0.644) for predicting the development of DVT. Conclusions: The incidence of postoperative VTE was low in patients with colorectal surgery even in those who did not receive perioperative pharmacologic thromboprophylaxis. SF, TAT, FDP and D-dimer were useful for predicting the development of DVT when we set cut-off values taking the physiological perioperative coagulofibrinolytic responses into consideration.

Chrysin 7-O-ß-d-glucopyranoside increases hepatic low-density lipoprotein receptor expression through AMP-activated protein kinase activation.

Elevated plasma low-density lipoprotein (LDL) cholesterol level is a risk factor for developing atherosclerosis. Increased LDL receptor (LDLR) expression is expected to reduce the risk of atherosclerotic disease since hepatic LDLR is essential for clearing plasma LDL cholesterol. Here, we screened human LDLR promoter effectors and observed that extracts from peduncles of sweet cherry (Prunus avium) 'Sato-Nishiki' induce LDLR gene promoter activity. We used several analytical and chemical methods to show that chrysin 7-O-ß-d-glucopyranoside (chrysin-7G) is one of the compounds that stimulate LDLR gene promoter activity in cherry peduncle extracts. Furthermore, synthetic chrysin-7G increased the expression and activity of LDLR. The chrysin-7G-mediated increase in LDLR expression and activity was completely abolished by treatment with an AMP-activated protein kinase (AMPK) inhibitor, compound C. These results indicate that chrysin-7G increases LDLR expression through AMPK activation and may be a useful compound that can be recycled from waste parts of agricultural products.

Leydig cell tumor of the testis with characteristic contrast patterns of tumor and non-tumorous testicular parenchyma on MRI: a case report.

PURPOSE: Testicular Leydig cell tumor (LCT) is a rare subtype of testicular neoplasms that occurs in the interstitial tissue of testes, accounting for 1-3% of total testicular masses removed annually. We report a case of 70-year-old man diagnosed as testicular LCT. This report demonstrates a testicular LCT with intratumoral and non-tumorous testicular parenchymal enhancement in the affected testis, which should be considered characteristic findings of LCT. METHODS: Ultrasonography showed a hypoechoic mass. On magnetic resonance imaging, the tumor showed low signal intensity comparable to the surrounding testicular tissue on T1-weighted images (T1WI) and low signal intensity on T2-weighted images (T2WI). On gadolinium contrast-enhanced T1WI (CE-T1WI), the tumor showed a rapid and marked wash-in and subsequent prolonged washout. The spared, non-tumorous testicular parenchyma showed slow and progressive enhancement in the early phase, which was as strong as or stronger than that of the mass in the delayed phase. The patient underwent right orchiectomy. RESULTS: Pathologically, the tumor was diagnosed as a testicular Leydig cell tumor (LCT). Leydig cell proliferation was observed with well-developed microvessels, atrophy of the seminiferous tubules, and stromal edema in the non-tumorous testicular parenchyma. Leydig cells in the non-tumorous parenchyma were positive for estrogen receptors. CONCLUSION: Since the contrast findings in the non-tumorous testicular parenchymal region on CE-T1WI likely match the histopathological features of LCT, our case suggests that the presence of non-tumorous testicular parenchymal enhancement on imaging might indicate a diagnosis of LCT.

Association between bone marrow lesions and bone mineral density of the proximal tibia in end-stage osteoarthritic knees.

This retrospective cross-sectional study investigated the association between bone marrow lesions (BMLs) and bone mineral density (BMD) in the proximal tibia of end-stage osteoarthritic knees from a large patient sample. Overall, 1308 end-stage osteoarthritic knees were enrolled before total knee arthroplasty. The preoperative range of motion was recorded. Bone mineral density in the medial tibial plateau (MTP), lateral tibial plateau (LTP), and metaphysis were measured using dual-energy X-ray absorptiometry. The MTP/LTP, MTP/metaphysis, and LTP/metaphysis ratios were calculated. BMLs were scored using a whole-organ magnetic resonance imaging scoring system. The relationship between BMD and BML scores was investigated using linear regression analysis. The highest BMD was 0.787 ± 0.176 g/cm2 at the MTP, followed by 0.676 ± 0.180 g/cm2 and 0.572 ± 0.145 g/cm2 at the metaphysis and LTP, respectively. The prevalence of BMLs was 90.4% and 24.2% in the MTP and LTP, respectively. In women, higher BML scores at the MTP were positively correlated with the BMD of the MTP (p < 0.001, r = 0.278), MTP/LTP (p < 0.001, r = 0.267), and MTP/metaphysis ratios (p < 0.001, r = 0.243). Regression analysis showed that higher BML scores in the MTP were correlated with higher BMD in the MTP (p < 0.001) and lower BMD in the LTP (p < 0.001). High BML scores in the MTP were positively associated with high BMD in the MTP, which also induced the medial to lateral imbalance of BMD in the proximal tibia.

Spectroscopic Quantitative Measurement of the Cartilage Surface using Arthroscopy Correlates with a Conventional Macroscopic Grading System.

Purpose: To quantify the cartilage surface profile visualized during arthroscopic surgery and examine its clinical utility by comparing the results of quantitative measurements with a conventional grading system. Methods: Fifty consecutive patients diagnosed with knee osteoarthritis and who underwent arthroscopic surgery were included in this study. A 4 K camera system was used, and the cartilage surface profile was visualized using the augmented reality imaging program. The highlighted image was displayed in 2 colors: black (the worn cartilage area) and green (the part where the cartilage thickness was maintained). The percentage of the green area was calculated using ImageJ and used as an index of cartilage degeneration. The quantitative value was statistically compared with the International Cartilage Repair Society (ICRS) grade as a conventional macroscopic evaluation. Results: In the quantitative measurement, the median percentage of the green area was 60.7 at ICRS grades 0 and 1 (interquartile range [IQR], 67.3-51.0), 47.2 at grade 2 (IQR, 54.1-39.2), 36.5 at grade 3 (IQR, 43.2-30.4), and 34.0 at grade 4 (IQR, 38.5-29.3). There was a significant difference between the macroscopic grades, except for Grades 3 and 4. There was a significant negative correlation between macroscopic evaluation and quantitative measurement (r = -0.672, P < .001). Conclusions: The quantitative measurement of the cartilage surface profile using the spectroscopic absorption technique was significantly correlated with the conventional macroscopic grading system and demonstrated fair to good inter-rater and intra-rater reliabilities. Level of Evidence: Level II, diagnostic (prospective cohort study).

Protocadherin B9 Is Associated with Human Esophageal Squamous Cell Carcinoma Progression.

INTRODUCTION: Esophageal cancer is the sixth leading cause of cancer-related death worldwide. However, molecular targeted therapy and novel therapeutic targets are needed for esophageal squamous cell cancer (ESCC). In a previous study, we reported that protocadherin (PCDH) B9 plays an important role in several cancers. Therefore, in this study, we examined the clinical significance of PCDHB9 expression in ESCC. METHODS: PCDHB9 expression was examined using immunohistochemistry in 128 cases and using quantitative reverse transcription-polymerase chain reaction in 16 cases of ESCC. PCDHB9 function in ESCC cells was examined using RNA interference. RESULTS: High PCDHB9 expression was identified in 5 of 16 (31.3%). In total, 51 (40%) ESCC cases showed strong PCDHB9 expression, whereas nonneoplastic mucosa rarely showed its expression. High PCDHB9 expression was significantly associated with T classification, N grade, and stage in ESCC. In ESCC cell lines, PCDHB9 knockdown affected cell growth, migration, and adhesion. Further, the expression of integrin (ITG) A3, ITGA4, ITGA5, ITGB1, ITGB6, vimentin, snail family transcriptional repressor 1, and cadherin 2 (NCAD) was significantly reduced and cadherin 1 was significantly increased in PCDHB9 knockdown ESCC cells. CONCLUSION: These results suggest that PCDHB9 plays a tumor-promoting role and is a potential biomarker and therapeutic target in ESCC.

Concomitant Lateral Meniscus Tear is Associated with Residual Rotatory Knee Instability 1 Year after Anterior Cruciate Ligament Reconstruction: Case-cohort Study.

Lateral meniscus tear (LMT) accompanied by anterior cruciate ligament (ACL) injuries has been reported to provoke rotatory instability of the affected knee joint. Unfortunately, these previous papers did not determine whether LMT-derived rotatory knee instability is residual because only preoperative or time zero data exists. This study aimed to longitudinally investigate how the prevalence of comorbid LMT is associated with residual rotatory knee instability (RKI) 1 year after ACL reconstruction (ACLR). A total of 327 patients who underwent double-bundle ACLR (average age: 23.4 years, body mass index: 23.5 kg/m2, 215 females). The patients were divided into three groups based on arthroscopy: 1) intact lateral meniscus (LM); 2) unrepaired LMT; 3) repaired LMT. At the 1-year follow-up, the pivot-shift test was performed. The prevalence of RKI, determined according to IKDC grades (grade ≥1 denoted RKI), was compared with chi-square or Fisher's exact tests. Thirty-eight patients (11.6%) had RKI; 203 subjects (62.1%) showed LMT, and 124 patients were diagnosed with an intact LM. Out of the 203 patients, 79 (38.9%) underwent LM repair. RKI was more prevalent in the LMT group than in the intact group (13.8% versus 8.1%, p = 0.117; Odds ratio: 1.499 [95%CI: 0.864 - 2.600]). In addition, the prevalence of RKI was significantly higher in the LM-repair group than in the intact-LM group (17.7% versus 8.1%, p = 0.038; Odds Ratio: 2.455 [95%CI: 1.032 - 5.842]). Medial meniscus tear (MMT) was detected in 113 patients (34.6%); RKI prevalence was not statistically different between the intact-MM group and the MMT group (12.2% versus 10.6%, p = 0.681). The current cohort study clarified that LMT comorbid with ACL injury was longitudinally associated with increased RKI prevalence 1 year after ACLR. Therefore, patients who underwent both ACLR and LM repair demonstrated a significantly higher prevalence of residual RKI.

Feasibility and applicability of locomotive syndrome risk test in elderly patients who underwent total knee arthroplasty.

OBJECTIVES: The concept of locomotive syndrome (LS) and its evaluation method, the LS risk test, have been applied in an integrated manner to capture the decline in mobility resulting from musculoskeletal disorders. The purpose of this study was to evaluate the impact of total knee arthroplasty (TKA) in the elderly with knee osteoarthritis, a common disorder found in LS. METHODS: A total of 111 patients were registered prior to TKA and postoperatively followed up for 1 year. Three components of the LS risk test (the two-step test, stand-up test, and Geriatric Locomotive Function Scale-25) were assessed pre- and postoperatively. RESULTS: After surgery, all three components of the test showed significant improvements from the baseline. The ratio of Stage 3 LS patients (progressed stage of decrease in mobility) reduced from 82.3% to 33.9% postoperatively. There was no significant difference in the degree of change in the scores between the younger (60-74 years) and older (≥75 years) age groups. CONCLUSIONS: We found that TKA has a major impact in preventing the progression of LS in patients with knee osteoarthritis. The LS risk test is a feasible tool for the longitudinal evaluation of patients with musculoskeletal diseases of varying severity and with multiple symptoms.

[A Case of Postoperative Peritoneal Dissemination Recurrence of CY1 Gastric Cancer with cCR after Nab-PTX Therapy].

A 72-year-old man visited his local doctor for gastric discomfort. Esophagogastroduodenoscopy revealed a type 3 tumor on the gastric antrum, and histopathological examination revealed a moderately differentiated adenocarcinoma(tub2). The patient was referred to our hospital and CT scan revealed wall thickening with contrast effect in the gastric angle but no enlarged lymph nodes in the region. The patient was diagnosed as cT3N0M0, Stage ⅡB gastric cancer and underwent open distal gastrectomy and D2 lymph node dissection. No peritoneal dissemination was observed, but intraoperative laparoscopic cytology showed Class Ⅴ. The patient was diagnosed as CY1 Stage Ⅳ gastric cancer, and treated with S-1 plus Tmab therapy starting 1 month after surgery. One year postoperative follow-up CT revealed recurrence of peritoneal disseminations, and the patient was treated with nab-PTX as a second-line therapy. Tumor shrinkage was achieved steadily, and the peritoneal disseminations disappeared at the CT after 12 courses, resulting in cCR. Thereafter, cCR continued and treatment was terminated at the 17th course. Seven years have passed since the end of chemotherapy, and the patient is still alive without recurrence.

[A Case of Postoperative Recurrence of Liver Metastasis after Gastrectomy for Gastric Cancer-No Recurrence for Five Years after Twice Liver Resections].

The patient was an 89-year-old man. He underwent laparoscopic distal gastrectomy for gastric cancer and was diagnosed as T1bN1M0, Stage ⅠB. Eight months after surgery, a CT scan showed an 18 mm-sized hypodense mass in S6 of the liver, and the patient was diagnosed with recurrent liver metastasis. He was treated with 3 courses of CapeOX therapy, and the response was judged as partial response(PR). Laparoscopic partial hepatic S6 resection was performed for the single liver metastasis. The pathological results showed liver metastasis of gastric cancer. Capecitabine was started as adjuvant chemotherapy. Nine months after surgery for liver metastasis, CT scan showed a 12 mm-sized single tumor in S5 and the patient was diagnosed with recurrent liver metastasis. The patient underwent laparoscopic partial hepatectomy after 3 courses of weekly paclitaxel plus ramucirumab therapy. The pathological result showed liver metastasis of gastric cancer. After the surgery, adjuvant chemotherapy was not administered according to the patient's request. Seven years have passed since the resection of the gastric cancer, and 5 years have passed since the resection of the second liver metastasis, and the patient has not had any recurrence.

Ca2+/Calmodulin induces translocation of membrane-associated TSC2 to the nucleus where it suppresses CYP24A1 expression.

Tuberous sclerosis complex 2 (TSC2) is a tumor-suppressor protein. A loss of TSC2 function induces hyperactivation of mechanistic target of rapamycin (mTOR). The C-terminal region of TSC2 contains a calmodulin (CaM) binding region and the CaM-TSC2 interaction contributes to proper mTOR activity. However, other downstream signaling pathways/effectors activated by the CaM-TSC2 complex have not been fully elucidated. In this study, we found that activation of Ca2+/CaM signaling resulted in the translocation of membrane-associated TSC2 to the nucleus and suppressed the transcriptional activity of the vitamin D receptor (VDR). TSC2 was released from the membrane in an activated CaM-dependent state in rat brain and HeLa cells. It subsequently formed a transcriptional complex to partially suppress the transcription of CYP24A1, a well-known VDR target gene. These data suggest, in part, that TSC2 attenuates VDR-associated transcriptional regulation via Ca2+/CaM signaling.

Impact of treatment line on risks and benefits of immune checkpoint inhibitor in patients with advanced non-small cell lung cancer and interstitial lung disease: a systematic review and meta-analysis of cohort studies.

Background: There is no clear consensus regarding the safety and efficacy of immune checkpoint inhibitors (ICIs) in patients with advanced non-small cell lung cancer (NSCLC) and pre-existing interstitial lung disease (ILD). We aimed to elucidate the impact of ICIs on pre-existing ILD. Methods: We systematically queried PubMed-MEDLINE, Embase-Scopus, and ISI Web of Science databases up to January 10, 2022. The pooled any-grade and grade 3-5 ICI-associated pneumonitis (ICIP) rate and objective response rate (ORR) in patients with pre-existing ILD were mainly evaluated. The relative risk (RR) was also evaluated for pre-existing ILD and usual interstitial pneumonia (UIP) patterns. Sensitivity and subgroup analyses were performed to assess the heterogeneity. Results: In total, 17 studies involving 5,529 patients were included in the meta-analysis. The pooled ICIP rate was 30% [95% confidence interval (CI): 24-36%]; it was found to be significantly higher in patients with pre-existing ILD relative to those without (RR =3.05, 95% CI: 2.53-3.69; I2=0.0%). The pooled grade 3-5 ICIP rate was 12% (95% CI: 9-15%); this was also significantly higher in patients with pre-existing ILD (RR =3.19, 95% CI: 2.32-4.38; I2=0.0%). According to subgroup analysis, these ICIP rates were not significantly different among the treatment lines (first, ≥ second, and mixed) (P=0.33) whereas the pooled ORR was 36% (95% CI: 24-48%; I2=53.7%) with a significant difference among the treatment lines (P=0.027). The pooled ICIP rate was independent of the UIP pattern (RR =1.06, 95% CI: 0.86-1.32; I2=0.0%). Conclusions: Overall, ICIs should be administered cautiously in patients with pre-existing ILD, regardless of the treatment line. Moreover, the risks of ICIP may outweigh ICI benefits, especially in second-or later-line treatment. These results need to be further confirmed by meta-analyses including more observational cohort studies in clinical setting.

Effectiveness of photofunctionalized titanium alloy on osseointegration in rats with type 2 diabetes.

BACKGROUND: Ultraviolet (UV) light-mediated photofunctionalization improves the osseointegration of pure titanium and titanium alloy (Ti6Al4V). However, little is known about the effect of UV irradiation on Ti6Al4V, used frequently in orthopedic surgery, in diabetic patients. We examined the effect of UV irradiation on Ti6Al4V in rats with type 2 diabetes. METHODS: Cylinder Ti6Al4V implants were used. Half the animals were Sprague Dawley rats (the control group), and the other half were Spontaneously Diabetic Torii fatty rats (the diabetes mellitus model). For radiological analysis, bone density was observed and calculated using 3D microcomputed tomography. Histological analysis was performed to calculate the bone-implant contact (BIC) ratio. We used Pearson correlation to analyze the correlation between average blood glucose level and BIC ratio, and between average blood glucose level and bone volume (BV) ratio. RESULTS: In the UV light-treated group, the BIC ratios of the normal and diabetic rats increased significantly compared with those in the untreated group at 2 weeks; at 4 weeks, the BIC ratio of the diabetic rats increased significantly, but there was no significant increase in the control animals. In both the control and diabetic groups, there was no significant difference in the BV ratios between the UV-treated and untreated implants at 2 or 4 weeks. The average blood glucose level in the 4-week group negatively correlated with the BIC and BV ratios. The average blood glucose level in the UV-treated group negatively correlated with the BIC ratio. CONCLUSION: Photofunctionalization of Ti6Al4V implants may promote osseointegration in the early stages in rats with type 2 diabetes.

Bilateral ballism as limb-shaking transient ischemic attacks treated with unilateral carotid artery stent placement.

Bilateral limb-shaking transient ischemic attack (LS-TIA) is a rare disease involving carotid artery stenosis, characterized by ballism-like involuntary movements of the arms and legs. We describe the case report of a male patient in his 80s presented with continuous bilateral ballism in the arms and legs and tongue dyskinesia. Magnetic resonance imaging showed no ischemic lesions, while cerebral angiography revealed right internal carotid artery (ICA) occlusion and 80% stenosis of the left ICA. 99mTc-ethyl cysteinate dimer single-photon emission computed tomography demonstrated hypoperfusion in the right cerebral cortex but hyperperfusion in both basal ganglia. Left ICA stenting was performed, and involuntary limb shaking disappeared. This case report highlights the importance of accurate diagnosis and treatment of bilateral ballism as LS-TIA.