Adjuvant gemcitabine plus cisplatin versus capecitabine in node-positive extrahepatic cholangiocarcinoma: the STAMP randomized trial.

BACKGROUND AND AIMS: The effectiveness of gemcitabine-based adjuvant chemotherapy is unclear in cholangiocarcinoma. We investigated the role of adjuvant gemcitabine plus cisplatin (GemCis) in a homogeneous group of high-risk patients with resected, lymph node-positive extrahepatic cholangiocarcinoma. APPROACH AND RESULTS: Adenocarcinoma of perihilar or distal bile duct with regional lymph node metastasis who underwent curative-intent surgery (R0/R1) was eligible. Patients were randomized to receive GemCis (gemcitabine 1000 mg/m2, cisplatin 25 mg/m2 on days 1 and 8) or capecitabine (1250 mg/m2 twice daily on days 1-14) every 3 weeks for 8 cycles. Primary endpoint was disease-free survival. Secondary endpoints were overall survival and safety. All p values are 1 sided and were considered significant if <0.1. Between July 2017 and November 2020, 101 patients (50 in the GemCis and 51 in the capecitabine group) were included in the intention-to-treat population. Perihilar and distal bile ducts were the primary sites in 45 (44.6%) and 56 (55.4%) patients, respectively, and 32 (31.7%) had R1 resections. Median (1-sided 90% CI) follow-up duration was 33.4 (30.5-35.8) months. In the GemCis and capecitabine group, 2-year disease-free survival rates were 38.5% (29.5%-47.4%) and 25.1% (17.4%-33.5%) [HR=0.96 (CI, 0.71-1.30), p=0.430], and median overall survival was 35.7 months (29.5-not estimated) and 35.7 months (30.9-not estimated) [HR=1.08 (CI, 0.71-1.64), 1-sided p=0.404], respectively. Grade 3-4 adverse events occurred in 42 (84.0%) and 8 patients (16.0%) in the GemCis and capecitabine groups, respectively. No treatment-related deaths were reported. CONCLUSIONS: In resected lymph node-positive extrahepatic cholangiocarcinoma, adjuvant GemCis did not improve survival outcomes compared with capecitabine.

Real-world efficacy and safety of capecitabine with oxaliplatin in patients with advanced adenocarcinoma of the ampulla of Vater.

BACKGROUND: Adenocarcinoma of the ampulla of Vater (AoV) is one of the rare periampullary cancers, and due to its anatomical location, it is categorized into various histologic subtypes. Its rarity and diversity pose challenges in treatment decision-making for patients with advanced AoV carcinoma. This study investigated the efficacy and safety of the combined regimen of capecitabine and oxaliplatin (CAPOX) in a real-world clinical setting. METHODS: This investigation encompassed patients with advanced AoV carcinoma who underwent CAPOX treatment. Histologic phenotypes were identified through a combination of histopathological analysis and protein expression markers, including MUC1, CDX2, CK20, and MUC2. The correlation between histopathological determinants and survival outcomes was explored, in addition to an evaluation of the safety profile of CAPOX therapy. RESULTS: From January 2010 to June 2023, 42 patients received CAPOX. Of these, 14 patients (33.3%) had not received any prior palliative chemotherapy, while 28 patients (66.7%) had undergone one prior line of chemotherapy. At a median follow up of 9.0 months, the median progression-free survival (PFS) was 4.38 months (95% CI, 2.78-5.69) and the median overall survival (OS) was 9.57 months (95% CI 7.56-11.6). The objective response and disease control rates were 38.1% and 61.9%, respectively. Patients who received CAPOX as a second-line treatment had poorer PFS (HR = 2.62; 95% CI, 1.49-4.90, p = 0.003) and OS (HR = 2.82, 95% CI, 1.47-5.38, p = 0.001) compared to those who received CAPOX as a first-line chemotherapy. There were no statistically significant differences in PFS (p = 0.185) and OS (p = 0.097) between groups based on histologic subtypes. Neutropenia (14.3%) emerged as the predominant grade 3-4 toxicity. Notably, treatment cessation occurred in select instances owing to grade 3 fatigue (9.5%) and peripheral neuropathy (9.5%). CONCLUSIONS: This study confirmed the therapeutic efficacy and safety of CAPOX in a real-world setting, consistent with prior phase II trial results. While CAPOX proved feasible for advanced AoV carcinoma regardless of histologic subtype, its reduced effectiveness in second-line settings necessitates further research to determine its optimal palliative use.

Latissimus dorsi myocutaneous free flap for post-sacrectomy reconstruction: Outcomes compared with gluteal muscle flap.

BACKGROUND: Excision of sacral tumor results in extensive defects and vital organ exposure, requiring soft tissue reconstruction for dead space obliteration. Diverse reconstruction options, mainly regional flaps, have been utilized but are limited by high postoperative morbidity. A reliable reconstructive method with low morbidity and facilitated recovery has yet been sought for. In this study, we aimed to evaluate the use of free latissimus dorsi (LD) flap for post-sacrectomy defect reconstruction by comparing its outcomes with local gluteus maximus (GM) flap. METHODS: A retrospective review was conducted of all patients with sacral malignancy who underwent partial or total sacrectomy and immediate reconstruction with LD or GM flap between 2013 and 2022. Nineteen patients were analyzed, including 10 GM flaps and nine LD flaps. Postoperative outcomes were compared between the two groups. RESULTS: The average size of LD flaps was 173.8 cm2 . Seven patients developed complication in the GM group and two patients in the LD group. Complication rate at sacrectomy site was lower in the LD group (p = .003) showing complication-free sacrectomy site and two donor site seromas. The LD group resulted in shorter hospital stay (p = .033) and earlier ambulation than the GM group (p = .001). Mean follow-up period was 63 months for GM group and 17 months for LD group. Three patients in the GM group underwent re-operation, while no delayed complication was observed in the LD group. CONCLUSION: Free LD flaps may provide reliable outcomes with early recovery and may be considered an effective option for sacrectomy defect reconstruction.

Clinical significance of serum-derived exosomal PD-L1 expression in patients with advanced pancreatic cancer.

BACKGROUND: Interactions between the programmed cell death receptor 1 (PD-1) and its ligand (PD-L1) lead to immune evasion in various tumors and are associated with poor prognosis in patients with pancreatic cancer; however, the roles of PD-L1-containing exosomes in pancreatic cancer is poorly understood. Here, we investigated the correlation between circulating exosomal PD-L1 (exoPD-L1) and PD-L1 expression in tumor tissue, and survival outcomes in patients with advanced PDAC. METHODS: Exosomes were derived from pre-treatment serum samples isolated using ExoQuick kit from 77 patients with advanced pancreatic cancer. Exosomal PD-L1 (exoPD-L1) was detected by enzyme-linked immunosorbent assay, and matched tumor tissues PD-L1 expression were evaluated by PD-L1 immunohistochemistry (22C3) assay, described with combined positive score. Cutoff value of exoPD-L1 for survival was assessed with receiver operating characteristic curve analysis. Kaplan-Meier analysis was performed to obtain median overall survival (OS), and hazard ratio was estimated using a stratified Cox regression model. RESULTS: The median exoPD-L1 serum concentration was 0.16 pg/mg, with undetected levels in seven patients. ExoPD-L1 levels were significantly higher in patients with systemic disease than in those with locally advanced disease (p = 0.023). There was a significantly higher proportion of elevated exoPD-L1 levels in patients with positive PD-L1 expression compared to patients with negative PD-L1 expression (p = 0.001). Patients were classified into groups with low and high exoPD-L1 levels using ROC curve-derived cutoffs (0.165 pg/mg; area under the curve, 0.617; p = 0.078). At a median follow-up of 8.39 months, the median OS was 13.2 (95% CI, 8.17-18.3) and 6.36 months (95% CI, 3.27-9.45) in the low and high exoPD-L1 groups, respectively (HR = 0.61; 95% CI, 0.35-1.04; p = 0.059). ExoPD-L1 levels did not affect the proportion of CD8+CD69+ effector cytotoxic T cells in either of the groups (p = 0.166). CONCLUSIONS: The serum-derived exoPD-L1 levels were higher in metastatic pancreatic cancer than locally advanced disease. Collectively, higher serum exoPD-L1 levels in patients with advanced pancreatic cancer suggested worse survival outcomes and may have clinical implications.

Long-term Radiographic and Clinical Outcomes After Selective Thoracic Fusion for Adolescent Idiopathic Scoliosis With Lenke 1C Curve.

BACKGROUND: Despite the promising results with selective thoracic fusion (STF) in patients with adolescent idiopathic scoliosis (AIS) of the Lenke 1C curve, postoperative coronal imbalance and progression of the unfused lumbar curve have been concerns in long-term follow-up. In this study, we aimed to investigate the radiographic and clinical outcomes after STF for AIS with Lenke 1C curve with long-term follow-up. METHODS: A total of 30 patients with AIS with Lenke 1C curves who underwent STF between 2005 and 2017 were included. Minimum follow-up duration was 5 years. Time-dependent changes in radiographic parameters were investigated preoperatively, immediately postoperatively, and at the last follow-up. In addition, radiographic adverse events such as coronal decompensation (CD), lumbar decompensation (LD), distal adding-on (DA) phenomenon, and trunk shift were evaluated at the last follow-up. The Scoliosis Research Society-22 score was used for clinical outcome evaluation. RESULTS: The mean age at the time of surgery was 13.8 years. The mean follow-up duration was 6.7 ± 0.8 years. The main thoracic curve significantly improved from 57 degrees to 23 degrees (60% correction), and the thoracolumbar/lumbar curve significantly improved from 47 degrees to 28 degrees (41% correction). Coronal balance was 15 mm after surgery but significantly improved to 10 mm at the last follow-up ( P = 0.033). At the final follow-up, 11 patients (37%) sustained at least one of the radiographic adverse events: CD in 5 patients (17%), LD in 3 (10%), DA in 4 (13%), and trunk shift in 3 (10.%). However, there were no cases requiring revision surgery. In addition, there were no significant differences in any items or total Scoliosis Research Society-22 score between the patients with and without radiographic adverse events. CONCLUSION: STF in Lenke 1C curves showed an acceptable risk of adverse radiographic events such as CD, LD, DA, and trunk shift in long-term follow-up. We suggest that STF without fusion to the thoracolumbar/lumbar curve would be sufficient in treating AIS with Lenke 1C curve. LEVEL OF EVIDENCE: Level III.

Comparison of the effects of triglyceride variability and exposure estimate on clinical prognosis in diabetic patients.

BACKGROUND: Hypertriglyceridemia is an important feature of dyslipidemia in type 1 and type 2 diabetic patients and associated with the development of atherosclerotic cardiovascular disease. Recently, variability of lipid profile has been suggested as a residual risk factor for cardiovascular disease. This study compared the clinical impact of serum triglyceride variability, and their cumulative exposure estimates on cardiovascular prognosis in diabetic patients. METHODS: A total of 25,933 diabetic patients who had serum triglyceride levels measured at least 3 times and did not have underlying malignancy, myocardial infarction (MI), and stroke during the initial 3 years (modeling phase) were selected from three tertiary hospitals. They were divided into a high/low group depending on their coefficient of variation (CV) and cumulative exposure estimate (CEE). Incidence of major adverse event (MAE), a composite of all-cause death, MI, and stroke during the following 5 years were compared between groups by multivariable analysis after propensity score matching. RESULTS: Although there was a slight difference, both the high CV group and the high CEE group had a higher cardiovascular risk profile including male-dominance, smoking, alcohol, dyslipidemia, and chronic kidney disease compared to the low groups. After the propensity score matching, the high CV group showed higher MAE incidence compared to the low CV group (9.1% vs 7.7%, p = 0.01). In contrast, there was no significant difference of MAE incidence between the high CEE group and the low CEE group (8.6% vs 9.1%, p = 0.44). After the multivariable analysis with further adjustment for potential residual confounding factors, the high CV was suggested as an independent risk predictor for MAE (HR 1.19 [95% CI 1.03-1.37]). CONCLUSION: Visit-to-visit variability of triglyceride rather than their cumulative exposure is more strongly related to the incidence of MAE in diabetic patients.

SAMM50 Regulates Thermogenesis of Beige Adipocytes Differentiated from Human Adipose-Derived Stem Cells by Balancing Mitochondrial Dynamics.

Brown/beige adipocyte thermogenesis is a process that is important for energy balance. The thermogenesis of brown/beige adipocytes occurs in the mitochondria, which is modulated by the dynamic balance between mitochondrial fusion and fission. Mitophagy is also involved in mitochondrial dynamics. The sorting and assembly machinery (SAM) complex protein, SAMM50, plays a key role in mitochondrial dynamics and quality control through regulating mitophagy. However, the roles of SAMM50 in the thermogenesis of beige adipocytes remain unknown. Thus, the objective of this study was to conduct functional analyses of SAMM50. The expression of mitochondrial fusion genes was repressed by SAMM50 knockdown but was not altered by SAMM50 overexpression. These results agreed with the distribution of the fluorescence-stained mitochondria and an mtDNA copy number. In contrast, the expression of mitochondrial fission genes showed an opposite outcome. As a result, suppression by the SAMM50 shRNA inhibited the expression of thermogenic genes (UCP1, PPARGC1A, DIO2, ELOVL3, CIDEA, and CIDEC) and mitochondrial-related genes (CYCS, COX7A1, TFAM, CPT1B, and CPT2). Conversely, SAMM50 overexpression promoted the expression of the thermogenic genes and mitochondrial genes. Thus, SAMM50 links the balance between the mitochondrial dynamics and thermogenesis of beige adipocytes.

Nanoliposomal irinotecan plus fluorouracil and folinic acid as a second-line treatment option in patients with metastatic pancreatic ductal adenocarcinoma: a retrospective cohort study.

BACKGROUND: According to the NAPOLI-1 trial, nanoliposomal irinotecan (nal-IRI) plus fluorouracil/folinic acid (5-FU/LV) showed improved overall survival compared to fluorouracil alone for patients with metastatic pancreatic cancer who were previously treated with gemcitabine-based therapy. In that trial, Asian patients had frequent dose modification due to haematological toxicity. There has been limited information on the clinical benefits and toxicity of this regimen in real-world settings. In this study, we assessed real-world experience of nal-IRI plus 5-FU/LV in patients with advanced pancreatic cancer after gemcitabine failure. METHODS: We conducted a single institution, retrospective analysis of response, survival and safety in patients who had been treated with nal-IRI with 5-FU/LV. Patients with metastatic pancreatic ductal adenocarcinoma previously treated with gemcitabine-based therapy received nal-IRI (80 mg/m2) with 5-FU/LV every 2 weeks. Kaplan-Meier analysis was performed to obtain median progression free survival and median overall survival. The hazard ratio and 95% confidence interval (CI) were estimated using a stratified Cox regression model. A multivariate Cox proportional hazards regression model was used to identify the effects of clinical factors. RESULTS: Fifty-one patients received nal-IRI plus 5-FU/LV between January 2015 and December 2020. The median age was 67 years, and males were 58.8%. A total of 40 (78.4%) and 11 (21.6%) patients had received one and two lines of prior chemotherapy before enrollment, respectively. Median progression-free survival was 2.8 months (95% CI 1.8-3.7) and median overall survival was 7.0 months (95% CI 6.0-7.9). Chemotherapy doses were reduced or delayed in 33 (64.7%) patients during the first 6 weeks and median relative dose intensity was 0.87. Thirty-six (70.6%) patients experienced grade 3 or 4 adverse events, most commonly neutropenia (58.8%). Most non-haematologic adverse events were under grade 2. Since the start of first-line chemotherapy, median overall survival was 16.3 months (95% CI 14.1-18.4). CONCLUSIONS: Nal-IRI plus 5-FU/LV seems to be effective, with manageable toxicities, following gemcitabine-based treatment in patients with metastatic pancreatic ductal adenocarcinoma. Nal-IRI plus 5-FU/LV following gemcitabine with nab-paclitaxel is a feasible sequential treatment option in patients with metastatic pancreatic cancer. TRIAL REGISTRATION: Retrospectively registered.

Body mass index and cardiovascular outcomes in patients with acute coronary syndrome by diabetes status: the obesity paradox in a Korean national cohort study.

BACKGROUND: The "obesity paradox" has not been elucidated in the long-term outcomes of acute coronary syndrome (ACS). We investigated the association between obesity and cardiovascular (CV) outcomes in ACS patients with and without diabetes. METHODS: We identified 6978 patients with ACS aged 40-79 years from the Korean National Health Insurance Service-Health Screening Cohort between 2002 and 2015. Baseline body mass index (BMI) was categorized as underweight (< 18.5 kg/m2), normal weight (18.5-22.9 kg/m2), overweight (23.0-24.9 kg/m2), obese class I (25.0-29.9 kg/m2), and obese class II (≥ 30.0 kg/m2). The primary outcome was major adverse CV events (MACE)-CV death, myocardial infarction (MI), and stroke. The secondary outcomes were the individual components of MACE, hospitalization for heart failure (HHF), and all-cause death. RESULTS: After adjustment for confounding variables, compared to normal-weight patients without diabetes (reference group), obese class I patients with and without diabetes had a lower risk of MACE, but only significant in patients without diabetes (with diabetes: hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.78-1.14; without diabetes: HR 0.78, 95% CI 0.62-0.97). Obese class II patient with diabetes had a higher risk of MACE with no statistical significance (HR 1.14, 95% CI 0.82-1.59). Underweight patients with and without diabetes had a higher risk of MACE, but only significant in patients with diabetes (with diabetes: HR 1.79, 95% CI 1.24-2.58; without diabetes: HR 1.23, 95% CI 0.77-1.97). CONCLUSION: In ACS patients, obesity had a protective effect on CV outcomes, especially in patients without diabetes.

Perception of the blue light effect on Korean women's faces using the blue pearl pigment.

BACKGROUND: Transparent-looking skin is an objective of facial makeup products. However, this effect of makeup products has not been investigated to Korean women's faces. MATERIALS AND METHODS: We investigated the perception of blue light on women's faces using the blue pearl pigment. We compared colors and/or spectra of naked skin, standard makeup powder foundation (standard foundation), and test makeup powder foundations containing the blue pearl pigment 10% (w/w) (pearl foundation) or (ultramarine blue) blue pigment 0.2% (w/w) (pigment foundation) on real women's faces (n = 6) using spectrophotometry and facial image analysis. A self-administered questionnaire showed facial images (n = 3) with applied makeup powder foundations on computer monitor (n = 35); evaluated items were blooming, transparency, smoothness, gloss, and vitality. RESULTS: In vivo, the pearl foundation showed significantly lower b* values (degree of yellowness) than did naked skin, and pigment foundation and the samples also showed significantly higher reflection of blue light (410-490 nm) than did naked skin, standard foundation, or pigment foundation. In image analysis, the image with the pearl foundation showed significantly lower quasi-b* value. On the self-administered questionnaire, the results showed that the pearl foundation had a significantly higher grade than did naked skin, standard foundation, or pigment foundation at all evaluation items: blooming, transparency, smoothness, gloss, and vitality. CONCLUSION: Blue pearl pigment creates the perception of blue light effect, including transparency and gloss in Korean women.

Efficacy of capecitabine and oxaliplatin versus S-1 as adjuvant chemotherapy in gastric cancer after D2 lymph node dissection according to lymph node ratio and N stage.

BACKGROUND: We sought to assess the prognostic significance of lymph node ratio (LNR) and N stage in patients undergoing D2 gastrectomy and adjuvant chemotherapy, S-1, and XELOX and to compare the efficacy of them according to LNRs and N stages to evaluate the clinical impact of using LNRs compared with using N staging. METHODS: Patients undergoing D2 gastrectomy with adequate lymph node dissection and adjuvant chemotherapy for stage II/III gastric cancer between Mar 2011 and Dec 2016 were analysed. Of the 477 patients enrolled, 331 received S-1 and 146 received XELOX. LNR groups were segregated as 0, 0-0.1, 0.1-0.25, and > 0.25 (LNR0, 1, 2, and 3, respectively). Propensity score matching (PSM) was used to minimise potential selection bias and compare DFS and OS stratified by LNRs and N stages in the two treatment groups. RESULTS: After PSM, the sample size of each group was 110 patients, and variables were well balanced. All patients had more than 15 examined lymph nodes (median 51, range 16~124). In multivariate analysis, LNR (> 0.25) and N stage (N3) showed independent prognostic value in OS and DFS, but LNR (> 0.25) showed better prognostic value. In subgroup analysis, the LNR3 group showed better 5-year DFS (20% vs 54%; HR 0.29; p = 0.004) and 5-year OS (26% vs 67%; HR 0.28; p = 0.020) in the XELOX group. The N3 group showed better 5-year DFS (38% vs 66%; HR 0.40; p = 0.004) and 5-year OS (47% vs 71%; HR 0.45; p = 0.019) in the XELOX group. Stage IIIC showed better 5-year DFS (22% vs 57%; HR 0.32; p = 0.004) and 5-year OS (27% vs 68%; HR 0.32; p = 0.009) in the XELOX group. The LNR3 group within N3 patients showed better 5-year DFS (21% vs 55%; HR 0.31; p = 0.004) and 5-year OS (27% vs 68%; HR 0.34; p = 0.018) in the XELOX group. CONCLUSIONS: LNR showed better prognostic value than N staging. LNR3, N3 and stage IIIC groups showed the superior efficacy of XELOX to that of S-1. And the LNR3 group within N3 patients showed more survival benefit from XELOX. LNR > 0.25, N3 stage and stage IIIC were the discriminant factors for selecting XELOX over S-1. TRIAL REGISTRATION: Not applicable (retrospective study).

Improved early development of porcine cloned embryos by treatment with quisinostat, a potent histone deacetylase inhibitor.

Recently, the modification of the epigenetic status of somatic cell nuclear transfer (SCNT) embryos by treatment with histone deacetylase inhibitors (HDACis) has made it possible to alter epigenetic traits and improve the developmental competence of these embryos. In the current study, we examined the effects of an HDACi, quisinostat (JNJ), on the in vitro development of porcine cloned embryos and their epigenetic nuclear reprogramming status. SCNT embryos were cultured under various conditions, and we found that treatment with 100 nM JNJ for 24 h post activation could improve blastocyst formation rates compared to the control (P < 0.05). Therefore, this was chosen as the optimal condition and used for further investigations. To explore the effects of JNJ on the nuclear reprogramming of early stage embryos and how it improved cloning efficiency, immunofluorescence staining and quantitative real-time PCR were performed. From the pseudo-pronuclear to 2-cell stages, the levels of acetylation of histone 3 at lysine 9 (AcH3K9) and acetylation of histone 4 at lysine 12 (AcH4K12) increased, and global DNA methylation levels revealed by anti-5-methylcytosine (5-mC) antibody staining were decreased in the JNJ-treated group compared to the control (P < 0.05). However, JNJ treatment failed to alter AcH3K9, AcH4K12, or 5-mC levels at the 4-cell embryo stage. Moreover, JNJ treatment significantly upregulated the expression of the development-related genes OCT4, SOX2, and NANOG, and reduced the expression of genes related to DNA methylation (DNMT1, DNMT3a, and DNMT3b) and histone acetylation (HDAC1, HDAC2, and HDAC3). Together, these results suggest that treatment of SCNT embryos with JNJ could promote their developmental competence by altering epigenetic nuclear reprogramming events.

Diabetic retinopathy is associated with diastolic dysfunction in type 2 diabetic patients with non-ischemic dilated cardiomyopathy.

BACKGROUND: To investigate the association between diabetic retinopathy (DR) and myocardial dysfunction in patients with type 2 diabetes and dilated cardiomyopathy (dCMP). METHODS: Data were collected retrospectively from 89 patients with dCMP (46 with type 2 diabetes and 43 without diabetes) and no evidence of coronary artery disease. Echocardiographic parameters and laboratory data, including lipid profiles and fundus findings, were obtained from medical records. A left ventricular ejection fraction (LVEF) less than 40% was considered impaired systolic function, while an E/E' ratio greater than 15 was considered elevated left ventricular (LV) filling pressure. RESULTS: Baseline characteristics show that LVEF was not significantly different between patients with and without diabetes or between diabetic patients with and without DR. Among the diastolic function parameters, patients with DR exhibited higher E/E' ratios (left ventricular filling pressures) than patients without DR (23.75 ± 13.37 vs 11.71 ± 3.50, P = 0.022). Logistic regression analysis revealed that statin use lowered the risk of impaired systolic dysfunction in all patients (odds ratio (OR) 0.33, 95% confidence interval (CI) 0.12-0.92, P = 0.034) and in patients with diabetes (OR 0.273, 95% CI 0.08-0.99, P = 0.049), while the presence of DR was associated with a higher risk of elevated LV filling filling pressure in patients with diabetes (OR 18.00, 95% CI 1.50-216.62, P = 0.023). CONCLUSIONS: In conclusion, DR was associated with elevated LV filling pressure in patients with dCMP. DR may not only represent microvascular long-term complications in patients with diabetes but may also be associated with more advanced form of diastolic dysfunction among diabetic patients with cardiomyopathy.

Acute kidney injury induced by thrombotic microangiopathy in a patient with hemophagocytic lymphohistiocytosis.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a fatal clinical syndrome characterized by excessive immune activation and inflammation. It is frequently complicated by acute kidney injury (AKI) that often develops as acute tubular necrosis (ATN). Meanwhile, renal thrombotic microangiopathy (TMA) is a rare pathologic finding that mostly occurs in hemolytic uremic syndrome or thrombotic thrombocytopenic purpura. There are only few reports on TMA developing in patients with HLH. We present here a rare case of TMA associated HLH. CASE PRESENTATION: A 60-year-old woman was admitted for a fever of unknown origin that had persisted for several weeks. She presented with AKI and pancytopenia. Clinical, laboratory and bone marrow biopsy findings met the criteria of HLH. Kidney biopsy showed TMA and minimal ATN, which suggested that the primary cause of AKI was TMA in this case. Because of sustained oliguria, we initiated hemodialysis (HD) and also decided to use chemotherapy composed of dexamethasone, etoposide and cyclosporine for treatment of HLH. Six months after the initiation of chemotherapy, pancytopenia was completely resolved, indicating the resolution of HLH. At the same time, serum creatinine decreased to a normal range without the need for HD, suggesting the resolution of TMA. CONCLUSION: We report a case of renal TMA associated HLH. This case suggests that renal TMA should be considered as a primary cause of AKI in patients with underlying HLH.

Simple prediction method of lumbar lordosis for planning of lumbar corrective surgery: radiological analysis in a Korean population.

PURPOSE: This study aimed at deriving a lordosis predictive equation using the pelvic incidence and to establish a simple prediction method of lumbar lordosis for planning lumbar corrective surgery in Asians. METHODS: Eighty-six asymptomatic volunteers were enrolled in the study. The maximal lumbar lordosis (MLL), lower lumbar lordosis (LLL), pelvic incidence (PI), and sacral slope (SS) were measured. The correlations between the parameters were analyzed using Pearson correlation analysis. Predictive equations of lumbar lordosis through simple regression analysis of the parameters and simple predictive values of lumbar lordosis using PI were derived. RESULTS: The PI strongly correlated with the SS (r = 0.78), and a strong correlation was found between the SS and LLL (r = 0.89), and between the SS and MLL (r = 0.83). Based on these correlations, the predictive equations of lumbar lordosis were found (SS = 0.80 + 0.74 PI (r = 0.78, R (2) = 0.61), LLL = 5.20 + 0.87 SS (r = 0.89, R (2) = 0.80), MLL = 17.41 + 0.96 SS (r = 0.83, R (2) = 0.68). When PI was between 30° to 35°, 40° to 50° and 55° to 60°, the equations predicted that MLL would be PI + 10°, PI + 5° and PI, and LLL would be PI - 5°, PI - 10° and PI - 15°, respectively. CONCLUSION: This simple calculation method can provide a more appropriate and simpler prediction of lumbar lordosis for Asian populations. The prediction of lumbar lordosis should be used as a reference for surgeons planning to restore the lumbar lordosis in lumbar corrective surgery.

Analysis of the predictive role and new proposal for surgical strategies based on the modified Tomita and Tokuhashi scoring systems for spinal metastasis.

BACKGROUND: We sought to identify preoperative factors significantly correlated with survival. We also aimed to evaluate the validity of the prognostic scores in the Tomita and Tokuhashi systems and discuss several aspects to improve the predictive accuracy of these systems. Moreover, we suggest modified criteria for selecting treatment strategies. METHODS: In total, the outcomes of 112 patients with spinal metastasis who underwent surgery between January 2006 and June 2011 were retrospectively reviewed. The validity of the prognostic scores was assessed on the basis of their correlation with survival. For various primary malignancies, new scoring criteria were applied in each system according to the survival results obtained in this study. Each revised scoring system was adjusted with a similar principle of scoring as described previously. Patient survival according to each preoperative factor was analyzed by the Kaplan-Meier method. The predictive value of each scoring system was evaluated by the log-rank test and Cox regression analysis. RESULTS: The interval from the diagnosis of the primary malignancy to that of spinal metastasis (p = 0.023) and the interval from the diagnosis of spinal metastasis to surgery (p = 0.039) were significantly correlated with survival. Regarding Tokuhashi scores, the correlation coefficient was 0.790 before adjustment (p = 0.001) and 0.853 after adjustment (p < 0.001). For Tomita scores, the correlation coefficient was -0.994 (p < 0.001) both before and after adjustment. CONCLUSIONS: Tomita scores more accurately predicted survival than Tokuhashi scores. It is helpful to evaluate both scoring systems with adjustment for primary malignancy depending on the clinical setting. Patients with Tomita scores less than or equal to 8 and Tokuhashi scores greater than or equal to 6 are recommended to undergo surgical management.

Ideal Lumbar Lordosis Correction in Patients with Adult Spinal Deformity Without Adversely Impacting Pelvic Tilt and Pelvic Incidence Minus Lumbar Lordosis: A Study of 426 Cases.

STUDY DESIGN: Retrospective study. OBJECTIVES: To determine the ideal pelvic incidence (PI) - lumbar lordosis (LL) range to prevent pelvic tilt (PT) undercorrection while avoiding PI-LL overcorrection following adult spinal deformity (ASD) surgery. SUMMARY OF BACKGROUND: PI-LL and PT are the important sagittal parameters to be restored to an adequate range by surgery. Ideal PI-LL target without causing PI-LL overcorrection and PT undercorrection has not been documented. METHODS: We included patients with ASD undergoing ≥5-level fusion including the sacrum. Receiver operating characteristic (ROC) curve analysis was performed to calculate the lower limit of the ideal PI-LL without causing PI-LL overcorrection and the upper limit of ideal PI-LL without causing PT undercorrection. The calculated ideal PI-LL was validated in terms of proximal junctional kyphosis and failure (PJK and PJF) rates and clinical outcomes. Analyses were performed according to age subgroups (<70 and ≥70 y). RESULTS: In total, 426 patients were included in the study. Female patients were predominant (85.4%), with a mean age of 69.8 years. The lower limits of PI-LL were calculated as 4.9° for all patients, 2.3° for patients aged <70 years, and 7.9° for patients aged ≥70 years. Meanwhile, the upper limits of PI-LL were calculated as 12.7° for all patients, 12.5° for patients aged <70 years, and 13.3° for patients aged ≥70 years. There were no significant differences in the PJK and PJF rates among the new three PI-LL groups. Clinical outcomes were significantly better in patients with the ideal PI-LL group than those in patients with overcorrection or undercorrection groups for all age groups. CONCLUSION: The ideal PI-LL correction target without adversely impacting PT and PI-LL was calculated at 2.3°-12.5° for patients aged <70 years and 7.9°-13.3° for patients aged ≥70 years. These guideline parameters may help ensure optimal clinical outcomes without increasing the risk of PJK/F.

Predictor of Postoperative Ambulatory Recovery in Metastatic Spinal Cord Compression with Delayed Surgical Timing and Progressive Paraplegia.

OBJECTIVE: To analyze preoperative predictors of ambulatory recovery after surgical treatment in metastatic spinal cord compression (MSCC) patients with delayed surgical timing and progressive paraplegia. METHODS: We reviewed patients with a preoperative lower-extremity motor grade of ≤3 and surgical timing ≥48 hours after the nonambulatory status. The recovery group (group R) and nonrecovery group (group NR) were classified according to ambulation assessment during follow-up. The data on patient demographics, origin of the primary tumor, pre and postoperative chemotherapy and radiation therapy, surgical procedures, Tokuhashi score, Karnofsky score, preoperative lower-extremity motor grade, and surgical timing were collected for analyzing predictors of postoperative ambulatory recovery. RESULTS: Of the 55 patients, 24 (43.6%) were group R and 31 patients were group NR. The preoperative motor grade of the lower extremities was the only predictive factor (P < 0.05). The mean hip flexor and knee extensor motor grades in group R were 2.0 ± 1.0 and 2.4 ± 1.1 respectively, while in group NR, they were 1.2 ± 1.0 and 1.3 ± 1.0. The odds ratios for failing to regain ambulatory ability were 12.6 in the knee extensor and 4.8 in the hip flexor when the motor grades 0-2 and 3 groups were compared. The rescue ratio of the preoperative hip flexor and knee extensor motor grade 0-2 group were 34.1% and 21.2%, grades 3 group were 71.4% and 77.3%, respectively. CONCLUSIONS: The significant predictive factor for ambulatory recovery was the preoperative lower-extremity motor grade. The preoperative knee extensor motor grade was identified as a more important factor than hip flexor motor grade in predicting ambulatory recovery.

The positive impact of smoking cessation on fracture risk in a nationwide cohort study.

Many studies sought to demonstrate the association between smoking and fracture risk. However, the correlation between smoking and fractures remains controversial. This study aimed to examine the impact of smoking and smoking cessation on the occurrence of fractures using prospective nationwide cohort data. We enrolled those who underwent a National Health Insurance Service (NHIS) health checkup in 2009-2010 who had a previous health checkup 4-year prior (2005-2006). The study population of 4,028,559 subjects was classified into three groups (non-smoker, smoking cessation, current smoker). The study population was also analyzed according to fracture type (all fractures, vertebral fracture, hip fracture). Lastly, the smoking cessation group and current smoker group were divided into four subgroups based on a lifetime smoking amount cut-off of 20 pack-years (PY). Multivariate-adjusted hazard ratios (HRs) of fracture were examined through a Cox proportional hazards model. After multivariable adjustment, non-smokers showed the lowest risk of fracture (HR = 0.818, CI 0.807-0.828, p < 0.0001) and smoking cessation significantly lowered the risk of fracture (HR 0.938, 95% CI 0.917-0.959, p < 0.0001) compared to current smokers. Regardless of 20PY, all smoking cessation subgroups showed significantly less risk of fractures than current smokers with ≥ 20PYs. Smoking increases the risk of fracture, and smoking cessation lowers the risk of fracture.