Local delivery of pamidronate with collagen matrix mitigates buccal bone resorption following immediate implant placement - An experimental in vivo study.

AIMS: The aim of this experimental in vivo pilot study was to evaluate the effect of the local delivery of pamidronate within a collagen membrane on the changes in the buccal soft and hard tissue dimensions at the time of immediate implant placement and whether this effect was influenced by the placement of bone substitutes. METHODS: In six beagle dogs, the distal roots of the third and fourth premolars were extracted, and immediate implants were placed. Treatment groups were randomly allocated to each socket: (i) covering the buccal bone with pamidronate-soaked collagen membrane (BP group), (ii) filling the gap defect with synthetic bone substitute (BS group), (iii) filling the gap defect with synthetic bone substitute and covering the buccal bone with pamidronate soaked collagen membrane (BP/BS group), (iv) no treatment (control group). Intraoral scanning was performed immediately after the surgery and at 20 weeks. Histomorphometric and micro-computed tomography (CT) outcomes were evaluated at 20 weeks. RESULTS: The micro CT analysis demonstrated that the BP group showed no apparent difference in vertical bone level with residual mesial root area, while control group showed significant buccal bone resorption at the implant site. The histomorphometric analysis demonstrated that the vertical bone level of buccal plate was significantly differed between the BP and control group (0.34 ± 0.93 and 1.27 ± 0.56 mm, respectively; p = .041). There was no statistically significant difference in the horizontal ridge width (HRW 1, 2, 3) among the groups. Also, the thickness, height and buccal contours of the soft tissue did not reveal significant changes among the groups. CONCLUSION: The local delivery of pamidronate to the outer surface of the buccal wall at the time of immediate implant placement effectively limits buccal bone resorption. The results from the present investigation should be interpreted with caution, as well as its clinical translatability. Further investigation is needed to understand the pamidronate binding and releasing kinetic, as well as the ideal carrier of this drug for its topical application.

Is transmucosal healing of an implant as effective as submerged healing when simultaneous guided bone regeneration is performed? A preclinical study.

AIM: To investigate whether transmucosal healing is as effective as submerged healing in terms of buccal bone regeneration when guided bone regeneration (GBR) is performed simultaneously with implant placement. MATERIALS AND METHODS: In six dogs, buccal dehiscence defects were created in the edentulous mandibular ridge, sized 5 × 5 × 3 mm (length × height × depth). In each defect, a bone-level implant was placed, and four experimental groups were randomly assigned as follows: (i) transmucosal healing with GBR (T-GBR), (ii) transmucosal healing without GBR (T-control), (iii) submerged healing with GBR (S-GBR) and (iv) submerged healing without GBR (S-control). Data analyses were based on histological slides 5 months after implant placement. RESULTS: The T-GBR group showed significant differences compared to the control groups regarding defect height resolution, buccal bone thickness and mineralized tissue area (p < .05), but showed no significant differences when compared with the S-GBR group (p > .05). CONCLUSIONS: The mode of healing (transmucosal vs. submerged) does not influence bone regeneration at implant sites. The clinician may therefore choose the approach based on further clinical and patient-specific parameters.

Flapless early implant placement into the uncalcified provisional matrix-Does it lead to osseointegration of the implant? A preclinical study.

AIM: To test whether early implant placement into the extraction socket containing an uncalcified provisional matrix leads to successful osseointegration and stable marginal bone levels. MATERIALS AND METHODS: In six mongrel dogs, the mandibular molars were extracted. Three weeks later, early implant placement was performed according to three experimental protocols: (i) flapless implant placement with preservation of the provisional matrix; (ii) flap elevation, socket debridement and implant placement; and (iii) flap elevation, socket debridement, implant placement and guided bone regeneration (GBR). One untreated extraction socket served as a control group. Data analyses were based on histologic slides 3 months after implant placement. RESULTS: There were no differences in bone-to-implant contact between the three experimental groups (66.97%, 58.89% and 60.89%, respectively) (inter-group comparison p = .42). Marginal bone levels, first bone-to-implant contact as well as the thickness of the connective tissue did not reveal any significant differences between the groups (p = .85, .60 and .65, respectively). CONCLUSIONS: Flapless early implant placement into posterior extraction sockets was as effective as an open flap approach in conjunction with GBR. Mineralization of the socket seems to occur irrespective of the presence of dental implants or biomaterials.

Does an untreated peri-implant dehiscence defect affect the progression of peri-implantitis?: A preclinical in vivo experimental study.

OBJECTIVE: To investigate the early impact of plaque accumulation in a buccal dehiscence defect on peri-implant marginal bone resorption. MATERIALS AND METHODS: In six male Mongrel dogs, four dental implants were placed in the posterior maxilla on both sides (two implants per side). Based on the group allocation, each implant was randomly assigned to one of the following four groups to decide whether buccal dehiscence defect was prepared and whether silk ligation was applied at 8 weeks post-implant placement for peri-implantitis induction: UC (no defect without ligation); UD (defect without ligation); LC (no defect with ligation); and LD (defect with ligation) groups. Eight weeks after disease induction, the outcomes from radiographic and histologic analyses were statistically analyzed (p < .05). RESULTS: Based on radiographs, the exposed area of implant threads was smallest in group UC (p < .0083). Based on histology, both the distances from the implant platform to the first bone-to-implant contact point and to the bone crest were significantly longer in the LD group (p < .0083). In the UD group, some spontaneous bone fill occurred from the base of the defect at 8 weeks after implant placement. The apical extension of inflammatory cell infiltrate was significantly more prominent in the LD and LC groups compared to the UC group (p < .0083). CONCLUSION: Plaque accumulated on the exposed implant surface had a negative impact on maintaining the peri-implant marginal bone level, especially when there was a dehiscence defect around the implant.

Ridge preservation using a self-retaining block type bone substitute for extraction sockets with buccal dehiscence defects - A preclinical study.

OBJECTIVE: To evaluate the effect of a self-retaining block-type bone substitute (srBB) on the dimensional stability of the horizontal ridge width at the coronal level in a buccal dehiscence model. MATERIALS AND METHODS: Four box-shaped bone defects with a buccal dehiscence were surgically prepared in the partially edentulous mandible (n = 6). Experimental biomaterials were randomly assigned to each site: (1) Control group: no treatment, (2) particle-type bone substitute (PBS) group, (3) collagenated soft block bone substitute (csBB) group, and (4) self-retaining synthetic block bone (srBB) group. In all grafted groups, a collagen membrane covered the biomaterials. At 16 weeks, clinical, histological, and radiographic analyses were performed. RESULTS: Three of the six blocks in the srBB group became exposed and fell out during the first week after surgery. Therefore, the remaining three specimens were renamed RsrBB group. The RsrBB group showed an increase horizontal ridge compared to the pristine bone width at 2-4 mm below the CEJ, while the other groups showed resorption (augmented width at 2 mm below: 4.2, 42.4, 36.2, and 110.1% in the control, PBS, csBB, and RsrBB groups, respectively). The mineralized bone area was largest in the RsrBB group (4.74, 3.44, 5.67, and 7.77 mm2 in the control, PBS, csBB, and RsrBB groups, respectively.). CONCLUSIONS: The srBB group demonstrated the highest volume stability at the coronal level. These findings would potentially suggest that self-retaining block bone substitute might be a good candidate for alveolar ridge preservation.

Multicenter exploration of tenecteplase transition factors: A quantitative analysis.

BACKGROUND: Tenecteplase (TNK) is gaining recognition as a novel therapy for acute ischemic stroke (AIS). Despite TNK offering a longer half-life, time and cost saving benefits and comparable treatment and safety profiles to Alteplase (ALT), the adoption of TNK as a treatment for AIS presents challenges for hospital systems. OBJECTIVE: Identify barriers and facilitators of TNK implementation at acute care hospitals in Texas. METHODS: This prospective survey used open-ended questions and Likert statements generated from content experts and informed by qualitative research. Stroke clinicians and nurses working at 40 different hospitals in Texas were surveyed using a virtual platform. RESULTS: The 40 hospitals had a median of 34 (IQR 24.5-49) emergency department beds and 42.5 (IQR 23.5-64.5) inpatient stroke beds with 506.5 (IQR 350-797.5) annual stroke admissions. Fifty percent of the hospitals were Comprehensive Stroke Centers, and 18 (45 %) were solely using ALT for treatment of eligible AIS patients. Primary facilitators to TNK transition were team buy-in and a willingness of stroke physicians, nurses, and pharmacists to adopt TNK. Leading barriers were lack of clinical evidence supporting TNK safety profile inadequate evidence supporting TNK use and a lack of American Heart Association guidelines support for TNK administration in all AIS cases. CONCLUSION: Understanding common barriers and facilitators to TNK adoption can assist acute care hospitals deciding to implement TNK as a treatment for AIS. These findings will be used to design a TNK adoption Toolkit, utilizing implementation science techniques, to address identified obstacles and to leverage facilitators.

Door to needle time trends after transition to tenecteplase: A Multicenter Texas stroke registry.

BACKGROUND: Tenecteplase (TNK) is considered a promising option for the treatment of acute ischemic stroke (AIS) with the potential to decrease door-to-needle times (DTN). This study investigates DTN metrics and trends after transition to tenecteplase. METHODS: The Lone Star Stroke (LSS) Research Consortium TNK registry incorporated data from three Texas hospitals that transitioned to TNK. Subject data mapped to Get-With-the-Guidelines stroke variables from October 1, 2019 to March 31, 2023 were limited to patients who received either alteplase (ALT) or TNK within the 90 min DTN times. The dataset was stratified into ALT and TNK cohorts with univariate tables for each measured variable and further analyzed using descriptive statistics. Logistic regression models were constructed for both ALT and TNK to investigate trends in DTN times. RESULTS: In the overall cohort, the TNK cohort (n = 151) and ALT cohort (n = 161) exhibited comparable population demographics, differing only in a higher prevalence of White individuals in the TNK cohort. Both cohorts demonstrated similar clinical parameters, including mean NIHSS, blood glucose levels, and systolic blood pressure at admission. In the univariate analysis, no difference was observed in median DTN time within the 90 min time window compared to the ALT cohort [40 min (30-53) vs 45 min (35-55); P = .057]. In multivariable models, DTN times by thrombolytic did not significantly differ when adjusting for NIHSS, age (P = .133), or race and ethnicity (P = .092). Regression models for the overall cohort indicate no significant DTN temporal trends for TNK (P = .84) after transition; nonetheless, when stratified by hospital, a single subgroup demonstrated a significant DTN upward trend (P = 0.002). CONCLUSION: In the overall cohort, TNK and ALT exhibited comparable temporal trends and at least stable DTN times. This indicates that the shift to TNK did not have an adverse impact on the DTN stroke metrics. This seamless transition is likely attributed to the similarity of inclusion and exclusion criteria, as well as the administration processes for both medications. When stratified by hospital, the three subgroups demonstrated variable DTN time trends which highlight the potential for either fatigue or unpreparedness when switching to TNK. Because our study included a multi-ethnic cohort from multiple large Texas cities, the stable DTN times after transition to TNK is likely applicable to other healthcare systems.

Carbohydrate antigen 19-9 plus carcinoembryonic antigen for prognosis in colorectal cancer: An observational study.

AIM: Carcinoembryonic antigen (CEA) is a primary prognostic marker and can detect colorectal cancer (CRC) recurrence; however, it has low sensitivity. Carbohydrate antigen 19-9 (CA 19-9) can be used as a supplemental tumour marker along with CEA. The purpose of this study was to determine whether preoperative CA 19-9 added to CEA helped predict long-term prognosis and whether follow-up CA 19-9 added to CEA had additional benefits in diagnosing the recurrence of CRC. METHOD: We retrospectively assessed patients who underwent surgery for primary CRC between January 2004 and December 2015 at Seoul National University Hospital. Data on demographics, preoperative and follow-up CEA and CA 19-9 levels, recurrence and survival were obtained and analysed with respect to tumour marker levels to ascertain their prognostic and diagnostic values. RESULTS: A total of 4972 and 1530 patients were included to analyse preoperative and follow-up tumour marker levels, respectively. The 5-year relapse-free survival rates were 72.2% ± 0.8%, 52.5% ± 2.2%, 55.5% ± 3.2% and 32.1% ± 2.3% in the normal CEA and CA 19-9, high CEA, high CA 19-9, and high CEA and high CA 19-9 groups, respectively (all P < 0.001). Patients whose elevated CEA or CA 19-9 levels reduced to normal levels had better survival outcomes than those with postoperatively elevated levels. Elevated follow-up CA 19-9 and CEA levels were related to higher incidences of distant metastasis (CA 19-9, 14.0% vs. 23.1%, P = 0.004; CEA, 12.6% vs. 30.1%, P < 0.001) but not to local recurrence. Combined follow-up CEA and CA 19-9 increased the sensitivity for recurrence to 31.4%, with a 5% difference from the sensitivity of CEA alone. In the subgroup with high preoperative CA 19-9 levels, sensitivity increased by 18.2% overall. CONCLUSION: CA 19-9 is a valuable prognostic and diagnostic marker for CRC when used adjunctively with CEA and can be a supplementary marker with CEA to improve sensitivity, especially with elevated preoperative CA 19-9.

Machilin D Promotes Apoptosis and Autophagy, and Inhibits Necroptosis in Human Oral Squamous Cell Carcinoma Cells.

Oral squamous cell carcinoma (OSCC) accounts for about 90% of all head and neck cancers, the prognosis is very poor, and there are no effective targeted therapies. Herein, we isolated Machilin D (Mach), a lignin, from the roots of Saururus chinensis (S. chinensis) and assessed its inhibitory effects on OSCC. Herein, Mach had significant cytotoxicity against human OSCC cells and showed inhibitory effects against cell adhesion, migration, and invasion by inhibiting adhesion molecules, including the FAK/Src pathway. Mach suppressed the PI3K/AKT/mTOR/p70S6K pathway and MAPKs, leading to apoptotic cell death. We investigated other modes of programmed cell death in these cells and found that Mach increased LC3I/II and Beclin1 and decreased p62, leading to autophagosomes, and suppressed the necroptosis-regulatory proteins RIP1 and MLKL. Our findings provide evidence that the inhibitory effects of Mach against human YD-10B OSCC cells are related to the promotion of apoptosis and autophagy and inhibition of necroptosis and are mediated via focal adhesion molecules.

Prostaglandin E2 receptor PTGER4-expressing macrophages promote intestinal epithelial barrier regeneration upon inflammation.

OBJECTIVE: Dysfunctional resolution of intestinal inflammation and altered mucosal healing are essential features in the pathogenesis of inflammatory bowel disease (IBD). Intestinal macrophages are vital in the process of inflammation resolution, but the mechanisms underlying their mucosal healing capacity remain elusive. DESIGN: We investigated the role of the prostaglandin E2 (PGE2) receptor PTGER4 on the differentiation of intestinal macrophages in patients with IBD and mouse models of intestinal inflammation. We studied mucosal healing and intestinal epithelial barrier regeneration in Csf1r-iCre Ptger4fl/fl mice during dextran sulfate sodium (DSS)-induced colitis. The effect of PTGER4+ macrophage secreted molecules was investigated on epithelial organoid differentiation. RESULTS: Here, we describe a subset of PTGER4-expressing intestinal macrophages with mucosal healing properties both in humans and mice. Csf1r-iCre Ptger4fl/fl mice showed defective mucosal healing and epithelial barrier regeneration in a model of DSS colitis. Mechanistically, an increased mucosal level of PGE2 triggers chemokine (C-X-C motif) ligand 1 (CXCL1) secretion in monocyte-derived PTGER4+ macrophages via mitogen-activated protein kinases (MAPKs). CXCL1 drives epithelial cell differentiation and proliferation from regenerating crypts during colitis. Specific therapeutic targeting of macrophages with liposomes loaded with an MAPK agonist augmented the production of CXCL1 in vivo in conditional macrophage PTGER4-deficient mice, restoring their defective epithelial regeneration and favouring mucosal healing. CONCLUSION: PTGER4+ intestinal macrophages are essential for supporting the intestinal stem cell niche and regeneration of the injured epithelium. Our results pave the way for the development of a new class of therapeutic targets to promote macrophage healing functions and favour remission in patients with IBD.

Evaluation of Selective COX-2 Inhibition and In Silico Study of Kuwanon Derivatives Isolated from Morus alba.

Six kuwanon derivatives (A/B/C/E/H/J) extracted from the roots of Morus alba L. were evaluated to determine their cyclooxygenase (COX)-1 and 2 inhibitory effects. Cyclooxygenase (COX) is known as the target enzyme of nonsteroidal anti-inflammatory drugs (NSAIDs), which are the most widely used therapeutic agents for pain and inflammation. Among six kuwanon derivatives, kuwanon A showed selective COX-2 inhibitory activity, almost equivalent to that of celecoxib, a known COX inhibitor. Kuwanon A showed high COX-2 inhibitory activity (IC50 = 14 µM) and a selectivity index (SI) range of >7.1, comparable to celecoxib (SI > 6.3). To understand the mechanisms underlying this effect, we performed docking simulations, fragment molecular orbital (FMO) calculations, and pair interaction energy decomposition analysis (PIEDA) at the quantum-mechanical level. As a result, kuwanon A had the strongest interaction with Arg120 and Tyr355 at the gate of the COX active site (-7.044 kcal/mol) and with Val89 in the membrane-binding domain (-6.599 kcal/mol). In addition, kuwanon A closely bound to Val89, His90, and Ser119, which are residues at the entrance and exit routes of the COX active site (4.329 Å). FMO calculations and PIEDA well supported the COX-2 selective inhibitory action of kuwanon A. It showed that the simulation and modeling results and experimental evidence were consistent.

Impacts of anemia and transfusion on oncologic outcomes in patients undergoing surgery for colorectal cancer.

PURPOSE: This study aimed to evaluate the prevalence of preoperative anemia and impacts of anemia and transfusion on survival in patients undergoing surgery for colorectal cancer. METHODS: This study included patients who underwent surgery for primary colorectal cancer between 2011 and 2012. The influence of preoperative anemia and postoperative transfusion on recurrence-free survival and overall survival were retrospectively investigated. Anemia was defined as hemoglobin level < 13 g/dL in males and < 12 g/dL in females. The primary outcome was the prevalence of preoperative anemia in patients with colorectal cancer. Secondary outcomes included preoperative anemia management, postoperative 30-day mortality and morbidity, tumor recurrence, and overall survival. RESULTS: Among a total of 1899 patients, 823 patients (43.3%) were anemic preoperatively, and 264 patients (13.9%) received postoperative transfusions. Postoperative transfusion was associated with 30-day postoperative complications (OR = 1.514, 95% CI = 1.020 ~ 2.247) but not preoperative anemia (OR = 1.143, 95% CI, 0.811 ~ 1.611). Preoperative anemia (HR = 1.459, 95% CI = 1.104 ~ 1.929) and postoperative transfusion (HR = 1.566, 95% CI = 1.089 ~ 2.252) were significantly associated with worse recurrence-free survival in multivariable analysis. Preoperative anemia (HR = 1.572, 95% CI = 1.274 ~ 1.940) and postoperative transfusion (HR = 1.381, 95% CI = 1.076 ~ 1.773) were significant independent risk factors for worse overall survival. CONCLUSIONS: Preoperative anemia and postoperative transfusion were associated with worse survival in patients undergoing surgery for colorectal cancer. An alternative therapy to treat anemia and reduce transfusions should be introduced to improve oncologic outcomes.

7-HYB, a Phenolic Compound Isolated from Myristica fragrans Houtt Increases Cell Migration, Osteoblast Differentiation, and Mineralization through BMP2 and ß-catenin Signaling.

The seeds (nutmegs) of Myristica fragrans Houtt have been used as popular spices and traditional medicine to treat a variety of diseases. A phenolic compound, ((7S)-8'-(benzo[3',4']dioxol-1'-yl)-7-hydroxypropyl)benzene-2,4-diol (7-HYB) was isolated from the seeds of M. fragrans. This study aimed to investigate the anabolic effects of 7-HYB in osteogenesis and bone mineralization. In the present study, 7-HYB promotes the early and late differentiation of MC3T3-E1 preosteoblasts. 7-HYB also elevated cell migration rate during differentiation of the preosteoblasts with the increased phosphorylation of mitogen-activated protein kinases (MAPKs) including ERK1/2, p38, and JNK. In addition, 7-HYB induced the protein level of BMP2, the phosphorylation of Smad1/5/8, and the expression of RUNX2. 7-HYB also inhibited GSK3ß and subsequently increased the level of ß-catenin. However, in bone marrow macrophages (BMMs), 7-HYB has no biological effects in cell viability, TRAP-positive multinuclear osteoclasts, and gene expression (c-Fos and NF-ATc1) in receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis. Our findings suggest that 7-HYB plays an important role in osteoblast differentiation through the BMP2 and ß-catenin signaling pathway. It also indicates that 7-HYB might have a therapeutic effect for the treatment of bone diseases such as osteoporosis and periodontitis.

Oncologic outcomes after adjuvant chemotherapy with capecitabine compared to 5-fluorouracil/leucovorin for geriatric stage II colon cancer: a retrospective cohort study.

PURPOSE: After curative resection of stage II colon cancer, adjuvant chemotherapy with 5-fluorouracil/leucovorin (FL) or capecitabine is selectively recommended. However, there is little evidence of the effect of capecitabine on oncologic outcome in geriatric patients with stage II colon cancer compared to that of FL. The aim of this study was to determine the difference in recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) in patients older than 70 years of age with stage II colon cancer receiving capecitabine and FL. METHODS: Patients over 70 years of age diagnosed with primary pathologic stage II colon cancer at the Seoul National University Hospital from January 2005 to December 2015 were included. A prospectively collected database was analyzed retrospectively. Patients were separated into an FL group and a capecitabine group. The primary outcomes were RFS, CSS, and OS. RESULTS: Of the 154 included patients, 96 patients received FL and 58 patients received capecitabine. There was no difference between the two groups in RFS, CSS, or OS (p = 0.763, p = 0.221, and p = 0.470, respectively) as measured by Kaplan-Meier analysis with log-rank test. Administration of capecitabine as compared to FL was not a factor affecting RFS (hazard ratio [HR] 0.503, 95% confidence interval [CI] 0.145-1.745), CSS (HR 1.519, 95% CI 0.348-6.629), or OS (HR 0.941, 95% CI 0.290-3.053) on multivariable analysis. CONCLUSIONS: Capecitabine is a safe regimen in terms of oncologic outcomes compared with FL in older patients with stage II colon cancer.

The impact of visceral adipose tissue amount on the adequacy of lymph node retrieval in colorectal cancer surgery.

BACKGROUND: Obesity is increasing worldwide, potentially influencing surgical outcomes in colorectal cancer (CRC) patients. We analyzed the effects of obesity indexes on lymph node (LN) retrieval in CRC patients. METHOD: We applied obesity indexes of body mass index (BMI) and visceral (VAT) and subcutaneous (SAT) adipose tissue volumes to stage I-III CRC patients. The primary outcome was the effect of these indexes on the number of retrieved LNs (12 > LNs ≥ 12). RESULTS: Among 519 patients, 35.6% had a BMI ≥ 25 kg/m2 . After adjusting for gender, age, tumor location, resected colon length, and local invasion and LN statuses, patients in the highest VAT quartile showed a 5.848 decrease in the number of retrieved LNs, with an odds ratio of 0.483 (95% confidence interval [CI] 0.260-0.8979) for adequate LN retrieval (≥12), compared with those in the lowest quartile (P < 0.001 for both). Analysis of the model predicting LN retrieval revealed VAT as the only obesity index (area under the curve [AUC] = 0.721) providing significant additional predictive power (P = 0.037) to the model including age, gender, staging, tumor location, and resected colon length (AUC = 0.707). CONCLUSION: Increased VAT may cause inadequate LN retrieval in CRC patients. In viscerally obese patients, VAT volumes should be considered when clinically interpreting LN status.

Prognostic significance of sealed-off perforation in colon cancer: a prospective cohort study.

BACKGROUND: Perforated colon cancer is a rare complication, but has a high risk of recurrence. However, most studies have not distinguished sealed-off perforation from free perforation, and the prognosis is unclear. The aim of this study was to evaluate the oncologic outcome of colon cancer with sealed-off perforation. METHODS: Eighty-six consecutive patients who underwent resection for colon cancer with sealed-off or free perforation were included. We defined sealed-off perforation as a colon perforation with localized abscess identified on operative, computed tomography, or pathologic findings, with no evidence of free perforation, including fecal contamination and dirty fluid collection in the peritoneal cavity. Oncologic outcomes were compared between patients with colon cancer with sealed-off perforation and free perforation using a log-rank test and Cox regression analysis. RESULTS: The sealed-off perforation group included 62 patients, and 24 patients were in the free perforation group. TNM stage and lymphatic, venous, and perineural invasion were similar between the groups. The median follow-up period was 28.9 months (range 0-159). The sealed-off perforation group had better prognosis compared with the free perforation group in terms of progression-free survival (PFS) and overall survival (OS), although there were no statistically significant differences in PFS (5-year PFS 53.7% vs. 40.5%, p = 0.148; 5-year OS 53.6% vs. 22.9%, p = 0.001). However, in multivariable analysis using the Cox progression test, sealed-off perforation did not show a significant effect on cancer progression (p = 0.138) and OS (p = 0.727). CONCLUSIONS: Colon cancer with sealed-off perforation showed no difference in prognosis compared with free perforation.

Immunoglobulin G4 (IgG4)-Positive Ocular Adnexal Mucosa-Associated Lymphoid Tissue Lymphoma and Idiopathic Orbital Inflammation.

PURPOSE: To report clinical and pathological characteristics of idiopathic orbital inflammation and ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma with immunoglobulin G4 (IgG4)-positive plasma cells. METHODS: A retrospective histopathological review and clinical case series. A total of 51 biopsy samples from January 2005 to December 2015 were used in this study, including 21 cases of biopsy-confirmed idiopathic orbital inflammation and 30 cases of biopsy-confirmed ocular adnexal MALT lymphoma. Most cases of ocular adnexal lymphoma were conjunctival tissue. Retrospective immunohistochemical studies were performed to estimate the IgG4 and IgG4/IgG ratios. Histopathologic features, demographic and clinical data, radiologic findings, treatment, and follow-up information for each patient were analyzed. RESULTS: Among idiopathic orbital inflammation, 6 (28.6%) of the 21 patients were diagnosed as "probable" ocular adnexal IgG4-related diseases and 13 (43.3%) of the 30 patients were diagnosed as MALT lymphoma with IgG4-positive plasma cells. Six cases of 13 IgG4-positive MALT lymphoma group had contralateral chronic inflammatory lesions infiltrated by IgG4-positive plasma cells, which was significantly (p = 0.007) higher than that in the IgG4-negative group. Conjunctival involvement was 69% of the IgG4-positive MALT lymphoma cases. Bilateral involvement of the ocular adnexa was significantly (p = 0.02) more frequent among IgG4-positive MALT lymphoma patients than that in IgG4-positive idiopathic orbital inflammation patients. Recurrence rate in the IgG4-positive group was higher (p = 0.05) than that in the IgG4-negative group but not significantly. CONCLUSIONS: This study presented an unusual framework of ocular adnexal IgG4-related inflammation, in conjunctiva. It is important to understand contralateral chronic inflammatory lesions and their relationship with IgG4-positive MALT lymphoma. Tissue biopsy and IgG4 immunostaining are required for all cases because IgG4-positive MALT lymphoma can arise from a pre-existing IgG4-positive chronic inflammatory lesions. This is the first study that performs IgG4 immunostaining for tissue from a relatively large number of conjunctival MALT lymphomas in a single center. Therefore, it will help to diagnose conjunctival lymphoproliferative disease.

Cinnamomum loureirii Extract Inhibits Acetylcholinesterase Activity and Ameliorates Trimethyltin-Induced Cognitive Dysfunction in Mice.

The pathogenesis of Alzheimer's disease (AD) has been linked to the deficiency of neurotransmitter acetylcholine (ACh) in the brain, and the main treatment strategy for improving AD symptoms is the inhibition of acetylcholinesterase (AChE) activity. In the present study, we aimed to identify potent AChE inhibitors from Cinnamomum loureirii extract via bioassay-guided fractionation. We demonstrated that the most potent AChE inhibitor present in the C. loureirii extract was 2,4-bis(1,1-dimethylethyl)phenol. To confirm the antiamnesic effects of the ethanol extract of C. loureirii, mice were intraperitoneally injected with the neurotoxin trimethyltin (2.5 mg/kg) to induce cognitive dysfunction, and performance in the Y-maze and passive avoidance tests was assessed. Treatment with C. loureirii extract significantly improved performance in both behavioral tests, suggesting that this extract may be neuroprotective and therefore beneficial in preventing or ameliorating the degenerative processes of AD, potentially by restoring cholinergic function.

Effect of a topical nonsteroidal anti-inflammatory agent (0.1 % pranoprofen) on acute central serous chorioretinopathy.

PURPOSE: To investigate the effects of topical pranoprofen 0.1 % on acute central serous chorioretinopathy (CSC). METHODS: The medical records of 52 cases (52 patients) of CSC were retrospectively reviewed. Twenty-six patients were treated with topical pranoprofen 0.1 % (treatment group) and 26 patients did not receive treatment (control group). Baseline and follow-up values for visual acuity, subfoveal choroidal thickness (SCT), subretinal fluid (SRF) maximum height, and central macular thickness (CMT) were examined and compared between groups. RESULTS: In the treatment group, mean SCT decreased from 365.5 ± 52.9 µm at baseline to 288.9 ± 36.1 µm at 6 months after initiation of treatment (p = 0.005). Both SRF maximum height and CMT were also decreased from baseline at 1 month (SRF maximum height, baseline: 221.5 ± 108.4, 1 month: 97.7 ± 54.3 µm, p = 0.002; CMT, baseline: 403.9 ± 114.6, 1 month: 270.1 ± 37.9 µm, p = 0.003). In the control group, SCT decreased throughout the follow-up period, but the change was not significant. Subretinal fluid maximum height and CMT were significantly decreased after 3 months in the control group (SRF, baseline: 265.4 ± 112.4 µm, 6 months: 64.8 ± 116.9 µm, p = 0.005; CMT, baseline: 459.1 ± 104.9 µm, 6 months: 304.6 ± 92.8 µm, p < 0.001). Visual acuity was improved from baseline in both groups after 6 months, but the improvement was only significant in the treatment group (p = 0.002). The rate of disease recurrence was lower in the treatment group (23 %) than in the control group (38 %), but this difference between groups was not statistically significant (p = 0.229, chi-square test). CONCLUSIONS: Topical pranoprofen 0.1 % was effective in treating acute CSC, as demonstrated by an increase in visual acuity and a decrease in SRF, SCT, and CMT after treatment. These results suggest that topical pranoprofen 0.1 % may be useful in treating patients with acute CSC.

Effect of Chaenomeles sinensis Extract on Choline Acetyltransferase Activity and Trimethyltin-Induced Learning and Memory Impairment in Mice.

The aim of this study was to search for a novel choline acetyltransferase (ChAT) activator from plants traditionally grown in Korea. An ethanol extract from Chaenomeles sinensis Koehne showed the highest ChAT-activating effect in vitro in an assay that used human neuroblastoma cells and [(14)C]acetyl-CoA. The active compound was speculated to be stearic acid methyl ester (SAME). In an in vivo experiment, C. sinensis extract and SAME improved trimethyltin (TMT)-induced deficits in learning and memory in mice as assessed by a Y-maze behavioral test and a passive avoidance test. The C. sinensis extract might attenuate the TMT-induced brain disorder. This study suggests that SAME from C. sinensis might be useful in the treatment of Alzheimer's disease.