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1.
Jpn J Ophthalmol ; 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38990388

ABSTRACT

PURPOSE: To assess the effectiveness of switching from the concomitant use of brinzolamide 1% (BZM) and brimonidine 0.1% (BMD) to a BZM/BMD fixed-dose combination (BBFC) for the reduction of corneal epithelial damage. STUDY DESIGN: Retrospective cohort study. METHODS: This study involved 52 eyes of 52 glaucoma patients (26 women, 26 men; mean age: 67.0 ± 14.0 years) followed for more than 3 months after being switched from concomitant BZM and BMD to BBFC. Superficial punctate keratitis (SPK) was assessed by fluorescein staining according to the National Eye Institute classification, with the cornea divided into 5 areas: center, superior, nasal, temporal, and inferior. SPK density was graded as 0 (no SPK), 1 (separate SPK), 2 (moderately dense SPK), and 3 (high SPK with overlapping lesions). SPK scores and intraocular pressure (IOP) at pre switching to BBFC (pre-BBFC) and at 3-months post switching to BBFC (post-BBFC) were then compared using the Wilcoxon signed-rank test. RESULTS: At pre-BBFC and post-BBFC, respectively, mean IOP was 12.4 ± 2.5 and 12.4 ± 2.7 mmHg, thus illustrating no significant difference in IOP between pre and post switch (p = 0.924), and the mean SPK score for center, superior, nasal, temporal, and inferior was 0.06 ± 0.24, 0.04 ± 0.19, 0.52 ± 0.67, 0.15 ± 0.36, and 0.92 ± 0.74, and 0.04 ± 0.19, 0.02 ± 0.14, 0.37 ± 0.56, 0.04 ± 0.19, and 0.75 ± 0.62, thus clearly showing a significant reduction in SPK scores for the nasal, temporal, and inferior areas at post-BBFC compared to those at pre-BBFC (p < 0.05). CONCLUSION: Our findings reveal that compared with the concomitant use of BZM and BMD, BBFC is effective in reducing corneal epithelial damage.

2.
Front Med (Lausanne) ; 11: 1319980, 2024.
Article in English | MEDLINE | ID: mdl-38476443

ABSTRACT

In this study, we analyzed a relatively large subset of proteins, including 109 kinds of blood-circulating cytokines, and precisely described a cytokine storm in the expression level and the range of fluctuations during hospitalization for COVID-19. Of the proteins analyzed in COVID-19, approximately 70% were detected with Bonferroni-corrected significant differences in comparison with disease severity, clinical outcome, long-term hospitalization, and disease progression and recovery. Specifically, IP-10, sTNF-R1, sTNF-R2, sCD30, sCD163, HGF, SCYB16, IL-16, MIG, SDF-1, and fractalkine were found to be major components of the COVID-19 cytokine storm. Moreover, the 11 cytokines (i.e., SDF-1, SCYB16, sCD30, IL-11, IL-18, IL-8, IFN-γ, TNF-α, sTNF-R2, M-CSF, and I-309) were associated with the infection, mortality, disease progression and recovery, and long-term hospitalization. Increased expression of these cytokines could be explained in sequential pathways from hematopoietic progenitor cell differentiation to Th1-derived hyperinflammation in COVID-19, which might also develop a novel strategy for COVID-19 therapy with recombinant interleukins and anti-chemokine drugs.

3.
Front Oncol ; 14: 1365305, 2024.
Article in English | MEDLINE | ID: mdl-38515576

ABSTRACT

Background: Photodynamic therapy (PDT) involves the administration of a photosensitizing agent and irradiation of light at an excitation wavelength that damages tumor cells without causing significant damage to normal tissue. We developed indocyanine green (ICG)-modified liposomes in which paclitaxel (PTX) was encapsulated (ICG-Lipo-PTX). ICG-Lipo-PTX accumulates specifically in tumors due to the characteristics of the liposomes. The thermal and photodynamic effects of ICG and the local release of PTX by irradiation are expected to induce not only antitumor effects but also cancer immunity. In this study, we investigated the antitumor effects of ICG-Lipo-PTX in breast cancer. Methods: The antitumor effects of ICG-Lipo-PTX were examined in xenograft model mice subcutaneously implanted with KPL-1 human breast cancer cells. ICG-Lipo-PTX, ICG-Lipo, or saline was administered intraperitoneally, and the fluorescence intensity was measured with a fluorescence imaging system (IVIS). Intratumor temperature, tumor volume, and necrotic area of tumor tissue were also compared. Next, we investigated the induction of cancer immunity in an allogeneic transplantation model in which BALB-MC mouse breast cancer cells were transplanted subcutaneously in the bilateral inguinal region. ICG-Lipo-PTX was administered intraperitoneally, and PDT was performed on only one side. The fluorescence intensity measured by IVIS and the bilateral tumor volumes were compared. Cytokine secretory capacity was also evaluated by ELISPOT assay using splenocytes. Results: In the xenograft model, the fluorescence intensity and temperature during PDT were significantly higher with ICG-Lipo-PTX and ICG-Lipo in tumor areas than in nontumor areas. The fluorescence intensity in the tumor area was reduced to the same level as that in the nonirradiated area after two times of irradiation. Tumor growth was significantly reduced and the percentage of necrotic area in the tumor was higher after PDT in the ICG-Lipo-PTX group than in the other groups. In the allograft model, tumor growth on day 14 in the ICG-Lipo-PTX group was significantly suppressed not only on the PDT side but also on the non-PDT side. In addition, the secretion of interferon-γ and interleukin-2 was enhanced, whereas that of interleukin-10 was suppressed, in the ICG-Lipo-PTX group. Conclusion: The PDT therapy with ICG-Lipo-PTX may be an effective treatment for breast cancer.

4.
J Orthop Surg Res ; 18(1): 700, 2023 Sep 19.
Article in English | MEDLINE | ID: mdl-37723461

ABSTRACT

BACKGROUND: Postoperative surgical site infections (SSIs) are an important complication to prevent in surgical treatment. Patients with diabetes mellitus (DM) have a higher risk of SSIs. Preoperative glycemic control is required. For patients with orthopedic trauma, the duration of preoperative glycemic control is limited because delaying operative treatment is difficult. However, whether preoperative glycemic control would decrease the risk of SSIs in diabetic patients with lower extremity fractures is unclear. The first aim of this study was to investigate the rate of SSIs among patients with DM who had undergone preoperative glycemic control, compared with that of patients without DM. As the secondary aim, we sought to demonstrate among patients with DM whether preoperative glycemic control would affect the development of SSIs between patients with controlled DM and patients with poorly controlled DM. METHODS: In this retrospective cohort study, 1510 patients treated surgically for lower extremity fractures were enrolled. Data collected were patient age, sex, body mass index, history of DM, development of SSIs, tobacco use, the presence of an open fracture, the period between the day of injury and the operation, the length of surgery, and blood glucose levels on admission and on the day before surgery. RESULTS: The rate of total SSIs was 6.0% among patients with DM and 4.4% among patients without DM (p = 0.31). Multivariate logistic regression revealed a significant association between the development of SSIs and the presence of DM (odds ratio, 1.79; 95% confidence interval 1.01-3.19; p = 0.047). The results of the secondary study revealed that the rate of early SSIs was significantly higher in the poorly controlled DM group than in the controlled DM group (5.9% vs. 1.5%; p = 0.032). However, multivariate logistic regression revealed that control levels of DM were not significantly associated with the development of SSIs. CONCLUSIONS: Even though patients with DM had undergone preoperative glycemic control, SSIs were significantly associated with DM, especially when the patients had poorly controlled DM. This finding suggested that continuous glycemic control is important preoperatively and postoperatively to prevent SSIs.


Subject(s)
Fractures, Open , Glycemic Control , Humans , Retrospective Studies , Surgical Wound Infection/epidemiology , Surgical Wound Infection/etiology , Surgical Wound Infection/prevention & control , Lower Extremity/surgery
5.
Geriatr Gerontol Int ; 23(11): 830-835, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37751877

ABSTRACT

AIM: Patients with hip fractures have a high rate of mortality or decreased mobility, despite early operative treatment and rehabilitation. The first aim of this study was to investigate the factors of decreased walking ability after hip fracture based on whether walking ability was or was not maintained postoperatively. The second aim was to examine the usefulness of the Comprehensive Geriatric Assessment 7 (CGA7), modified from the conventional Comprehensive Geriatric Assessment, for predicting postoperative walking ability. METHODS: This study included patients who were treated surgically for hip fractures. We divided patients by whether they did or did not maintain their walking ability postoperatively. We registered the following demographic data: walking ability preadmission and at discharge, CGA7 score, cognitive impairment, the patient's prefracture status, fracture type, surgical waiting time, hospital stay duration, limitation of weight-bearing, postoperative complications, transfer to rehabilitation hospital, final living place, and follow-up period. The characteristics of the two groups were compared using Wilcoxon's rank-sum test, the chi-squared test, or Fisher's exact test. RESULTS: Among 855 patients, 616 (73.0%) patients maintained walking ability and 239 (27.0%) patients did not. Multivariate logistic regression revealed that the factors of age, sex, preoperative walking ability, and postoperative complications were significantly associated with maintaining postoperative walking ability. Furthermore, the higher the CGA7 score, the more likely were patients to maintain their walking ability (odds ratio, 0.72; 95% confidence interval, 0.61-0.85; P < 0.001). CONCLUSIONS: Patients who had a low CGA7 score had the potential risk of decreased walking ability. Geriatr Gerontol Int 2023; 23: 830-835.


Subject(s)
Geriatric Assessment , Hip Fractures , Humans , Aged , Hip Fractures/rehabilitation , Walking , Postoperative Complications/epidemiology
6.
Cancers (Basel) ; 15(11)2023 May 25.
Article in English | MEDLINE | ID: mdl-37296868

ABSTRACT

BACKGROUND/PURPOSE: The effect of the ABO blood group on the survival of patients with hepatocellular carcinoma (HCC) is unclear. The aim of the present study is to determine the prognostic impact of ABO blood types on the survival of a Japanese population of patients with HCC who underwent surgical resection. METHODS: Patients with HCC (n = 480) who underwent an R0 resection between 2010 and 2020 were retrospectively analyzed. Survival outcomes were investigated according to ABO blood type (A, B, O, or AB). Outcomes for type A (n = 173) and non-type A (n = 173) groups after surgery were compared using 1-to-1 propensity score matching to control for variables. RESULTS: In the study cohort, 173 (36.0%), 133 (27.7%), 131 (27.3%), and 43 (9.0%) of participants had Type A, O, B, and AB, respectively. Type A and non-type A patients were successfully matched based on liver function and tumor characteristics. Recurrence-free survival (RFS; hazard ratio [HR] 0.75, 95% confidence interval [Cl] 0.58-0.98, p = 0.038) and overall survival (OS; HR: 0.67, 95% Cl: 0.48-0.95, p = 0.023) for patients with blood type A were both significantly decreased relative to non-type A patients. Cox proportional hazard analysis demonstrated that patients with HCC who have blood type A had a worse prognosis than those with non-type A blood. CONCLUSION: ABO blood type may have a prognostic impact on patients with HCC after hepatectomy. Blood type A is an independent unfavorable prognostic factor for recurrence-free and overall survival (RFS and OS) after hepatectomy.

7.
Ophthalmol Sci ; 3(3): 100299, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37125267

ABSTRACT

Purpose: The purpose of the study was to clarify the interplay between metabolites and microRNAs (miRs) in the aqueous humor (AqH) of bullous keratopathy (BK) patients to retain human corneal endothelium (HCE) integrity. Design: Prospective, comparative, observational study. Participants: A total of 55 patients with BK and 31 patients with cataract (Cat) as control. Methods: A biostatic analysis of miRs and metabolites in the AqH, hierarchical clustering, and a least absolute shrinkage and selection operator (Lasso) analysis were employed. The miR levels in AqH of BK (n = 18) and Cat (n = 8) patients were determined using 3D-Gene human miR chips. Hierarchical clusters of metabolites detected by liquid chromatography-mass spectrometry or gas chromatography-mass spectrometry in AqH specimens from 2 disease groups, BK (total n = 55) and Cat (total n = 31), were analyzed twice to confirm the reproducibility. The analytical procedure applied for investigating the association between metabolites and miRs in AqH was the exploratory data analysis of biostatistics to avoid any kind of prejudice. This research procedure includes a heat-map, cluster analysis, feature extraction techniques by principal component analysis, and a regression analysis method by Lasso. The cellular and released miR levels were validated using reverse transcription polymerase chain reaction and mitochondria membrane potential was assessed to determine the functional features of the released miRs. Main Outcome Measures: Identification of interacting metabolites and miRs in AqH attenuating HCE degeneration. Results: The metabolites that decreased in the AqH of BK patients revealed that 3-hydroxyisobutyric acid (HIB), 2-aminobutyric acid (AB) and branched-chain amino acids, and serine were categorized into the same cluster by hierarchical clustering of metabolites. The positive association of HIB with miR-34a-5p was confirmed (P = 0.018), and the Lasso analysis identified the interplay between miR-34a-5p and HIB, between miR-24-3p and AB, and between miR-34c-5p and serine (P = 0.041, 0.027, and 0.009, respectively). 3-hydroxyisobutyric acid upregulated the cellular miR-34a expression, mitochondrial membrane potential, and release of miR-184 in dedifferentiated cultured HCE cells. Conclusions: Metabolites and miRs in AqH may synchronize in ensuring the integrity of the HCE to maintain efficient dehydration from the stroma. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

8.
Liver Cancer ; 12(1): 32-43, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36872920

ABSTRACT

Introduction: This study aimed to compare the prognostic impact of laparoscopic left hepatectomy (LLH) with that of open left hepatectomy (OLH) on patient survival after resection of left hepatocellular carcinoma (HCC). Methods: Among the 953 patients who received initial treatment for primary HCC that was resectable by either LLH or OLH from 2013 to 2017 in Japan and Korea, 146 patients underwent LLH and 807 underwent OLH. The inverse probability of treatment weighting approach based on propensity scoring was used to address the potential selection bias inherent in the recurrence and survival outcomes between the LLH and OLH groups. Results: The occurrence rate of postoperative complications and hepatic decompensation was significantly lower in the LLH group than in the OLH group. Recurrence-free survival (RFS) was better in the LLH group than in the OLH group (hazard ratio, 1.33; 95% confidence interval, 1.03-1.71; p = 0.029), whereas overall survival (OS) was not significantly different. Subgroup analyses of RFS and OS revealed an almost consistent trend in favor of LLH over OLH. In patients with tumor sizes of ≥4.0 cm or those with single tumors, both RFS and OS were significantly better in the LLH group than in the OLH group. Conclusions: LLH decreases the risk of tumor recurrence and improves OS in patients with primary HCC located in the left liver.

9.
Int J Clin Oncol ; 28(3): 468-481, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36607476

ABSTRACT

PURPOSE: Here, we investigated expression modules reflecting the reciprocal expression of the cancer microenvironment and immune response-related genes associated with poor prognosis in primary central nervous system lymphoma (PCNSL). METHODS: Weighted gene coexpression network analysis revealed representative modules, including neurogenesis, immune response, anti-virus, microenvironment, gene expression and translation, extracellular matrix, morphogenesis, and cell adhesion in the transcriptome data of 31 PCNSL samples. RESULTS : Gene expression networks were also reflected by protein-protein interaction networks. In particular, some of the hub genes were highly expressed in patients with PCNSL with prognoses as follows: AQP4, SLC1A3, GFAP, CXCL9, CXCL10, GBP2, IFI6, OAS2, IFIT3, DCN, LRP1, and LUM with good prognosis; and STAT1, IFITM3, GZMB, ISG15, LY6E, TGFB1, PLAUR, MMP4, FTH1, PLAU, CSF3R, FGR, POSTN, CCR7, TAS1R3, small ribosomal subunit genes, and collagen type 1/3/4/6 genes with poor prognosis. Furthermore, prognosis prediction formulae were constructed using the Cox proportional-hazards regression model, which demonstrated that the IP-10 receptor gene CXCR3 and type I interferon-induced protein gene IFI44L could predict patient survival in PCNSL. CONCLUSION: These results indicate that the differential expression and balance of immune response and microenvironment genes may be required for PCNSL tumor growth or prognosis prediction, which would help understanding the mechanism of tumorigenesis and potential therapeutic targets in PCNSL.


Subject(s)
Central Nervous System Neoplasms , Lymphoma , Humans , Central Nervous System Neoplasms/genetics , Central Nervous System Neoplasms/pathology , Proportional Hazards Models , Lymphoma/genetics , Immunity , Central Nervous System/metabolism , Central Nervous System/pathology , Prognosis , Tumor Microenvironment/genetics , Membrane Proteins/metabolism , RNA-Binding Proteins , Receptors, CXCR3/metabolism
10.
J Glaucoma ; 32(2): 127-132, 2023 02 01.
Article in English | MEDLINE | ID: mdl-36001508

ABSTRACT

PRCIS: We propose a new classification model to serve as a control for future genomic studies of glaucoma by distinguishing normal subjects maintaining non-glaucoma status for 10 years using the vertical cup-to-disc ratio (VCDR). PURPOSE: This study aimed to develop a classification for distinguishing subjects maintaining non-glaucoma status for 10 years using the VCDR. PARTICIPANTS AND METHODS: Among 842 volunteers 40 years and older, 421 volunteers participated in the second ophthalmic examination 10 years after their first examination. Each volunteer was diagnosed either as healthy normal or glaucoma suspect (GS) in the first glaucoma screening examinations. The former was further classified into the 3 grades of N1, N2, and N3. Specifically, N1 represented (1) VCDR <0.3; (2) no notching or nerve fiber layer defect; and (3) no undermining, N2 indicated 0.3≤VCDR<0.6 and conditions (2) and (3) of N1; and N3 represented 0.3≤VCDR<0.6 with undermining and condition (2), or 0.6≤VCDR<0.7 and condition (2) of N1. Glaucoma transition rates (GTRs) were evaluated in 421 volunteers who returned to participate after a 10-year period. RESULTS: GTRs were calculated as 1.3% in both N1 and N2, 3.9% in N3, and 18.2% in GS. The ratio of volunteers in the same category maintenance rate increased from N1 to N3. CONCLUSION: GTRs were lower in N1 and N2 than in N3 or GS during the 10-year study period. This novel classification of healthy non-glaucoma subjects may help identify those, especially Japanese males, who maintain a non-glaucoma status for an extended period of 10 years.


Subject(s)
Glaucoma , Ocular Hypertension , Optic Disk , Male , Humans , Longitudinal Studies , Intraocular Pressure , Glaucoma/diagnosis , Ocular Hypertension/diagnosis
11.
Eur J Neurosci ; 57(1): 5-16, 2023 01.
Article in English | MEDLINE | ID: mdl-36370145

ABSTRACT

In the present study, we examined neural circuit formation in the forebrain of the Olig2 knockout (Olig2-KO) mouse model and found disruption of the anterior commissure at the late foetal stage. Axon bundles of the anterior commissure encountered the wall of the third ventricle and ceased axonal extension. L1-CAM immunohistochemistry showed that Olig2-KO mice lose decussation formation in the basal forebrain. DiI tracing revealed that the thin bundles of the anterior commissure axons crossed the midline but ceased further extension into the deep part of the contralateral side. Furthermore, some fractions of DiI-labelled axons were oriented dorsolaterally, which was not observed in the control mouse forebrain. The rostral part of the third ventricle was much wider in the Olig2-KO mice than in wild-type mice, which likely resulted in the delay of midline fusion and subsequent delay and malformation of the anterior commissure. We analysed gene expression alterations in the Olig2-KO mice using a public database and found multiple genes, which are related to axon guidance and epithelial-mesenchymal transition, showing subtle expression changes. These results suggest that Olig2 is essential for anterior commissure formation, likely by regulating multiple biological processes.


Subject(s)
Axons , Prosencephalon , Animals , Mice , Prosencephalon/metabolism , Axons/physiology , Mice, Knockout , Oligodendrocyte Transcription Factor 2/genetics , Oligodendrocyte Transcription Factor 2/metabolism
12.
Cancers (Basel) ; 14(21)2022 Oct 27.
Article in English | MEDLINE | ID: mdl-36358711

ABSTRACT

We developed and evaluated a modified albumin-bilirubin grade and α-fetoprotein (mALF) score, a nutritional and oncological assessment tool for patients with hepatocellular carcinoma (HCC) after surgical resection. Patients (n = 480) who underwent R0 resection between 2010 and 2020 were analyzed retrospectively. The mALF score assigned one point for a modified albumin-bilirubin (mALBI) grade 2b or 3 and one point for an α-fetoprotein (AFP) level ≥ 100 ng/mL. Patients were classified by mALF scores of 0 (mALBI grade 1/2a, AFP < 100 ng/mL), 1 (mALBI grade 2b/3 or AFP ≥ 100 ng/mL), or 2 (mALBI grade 2b/3, AFP ≥ 100 ng/mL) points. Liver reserve deteriorated and cancer progressed with increasing score. Postoperative complications (Clavien−Dindo classification ≥ 3) differed significantly among groups. The 5-year recurrence-free survival (RFS) rates were 34.8%, 11.2%, and 0.0% for 0, 1, and 2 points, respectively (1 or 2 versus 0 points, p < 0.001). The 5-year overall survival (OS) rates were 66.0%, 29.7%, and 17.8% for 0, 1, and 2 points, respectively (1 or 2 versus 0 points, p < 0.001). The mALF score was an independent prognostic predictor of RFS and OS. In HCC, the mALF score was effective for predicting postoperative complications and long-term survival.

13.
Cancers (Basel) ; 14(21)2022 Nov 07.
Article in English | MEDLINE | ID: mdl-36358877

ABSTRACT

Accurate risk stratification selects patients who are expected to benefit most from surgery. This retrospective study enrolled 225 Japanese patients with intrahepatic cholangiocellular carcinoma (ICC) who underwent hepatectomy between January 2009 and December 2020 and identified preoperative blood test biomarkers to formulate a classification system that predicted prognosis. The optimal cut-off values of blood test parameters were determined by ROC curve analysis, with Cox univariate and multivariate analyses identifying prognostic factors. Risk classifications were established using classification and regression tree (CART) analysis. CART analysis revealed decision trees for recurrence-free survival (RFS) and overall survival (OS) and created three risk classifications based on machine learning of preoperative serum markers. Five-year rates differed significantly (p < 0.001) between groups: 60.4% (low-risk), 22.8% (moderate-risk), and 4.1% (high-risk) for RFS and 69.2% (low-risk), 32.3% (moderate-risk), and 9.2% (high-risk) for OS. No difference in OS was observed between patients in the low-risk group with or without postoperative adjuvant chemotherapy, although OS improved in the moderate group and was prolonged significantly in the high-risk group receiving chemotherapy. Stratification of patients with ICC who underwent hepatectomy into three risk groups for RFS and OS identified preoperative prognostic factors that predicted prognosis and were easy to understand and apply clinically.

14.
Mol Ther Oncolytics ; 25: 225-235, 2022 Jun 16.
Article in English | MEDLINE | ID: mdl-35615265

ABSTRACT

Malignant soft tissue tumors, particularly highly malignant leiomyosarcomas, are resistant to chemotherapy and associated with a poor prognosis. T-01, a third-generation genetically modified herpes simplex virus type 1, replicates in tumor cells alone and exerts a cell-killing effect. The current study aimed to investigate the antitumor effect of T-01, which is a novel treatment for leiomyosarcoma. In vitro, six human cell lines and one mouse sarcoma cell line were assessed for T-01 cytotoxicity. In vivo, the efficacy of T-01 was examined in subcutaneously transplanted leiomyosarcoma (SK-LMS-1) cells and subcutaneously or intraperitoneally transplanted mouse sarcoma (CCRF S-180II) cells. Cytokines were assessed using ELISpot assay with splenocytes from the allogeneic models for immunological evaluation. T-01 showed cytotoxicity in all seven cell lines (p < 0.001). In the SK-LMS-1 xenotransplantation model, tumor growth was suppressed by T-01 administration (p = 0.02). In the CCRF S-180II subcutaneous tumor model, bilateral tumor growth was significantly suppressed in the T-01-treated group compared with the control group (p < 0.001). In the peritoneal dissemination model, T-01 treatment caused significant survival prolongation compared with the control (p < 0.01). In conclusion, third-generation genetically modified herpes simplex virus type 1 may be an effective novel therapy against refractory sarcomas.

15.
Nanomaterials (Basel) ; 12(8)2022 Apr 15.
Article in English | MEDLINE | ID: mdl-35458072

ABSTRACT

Lenvatinib has a high response rate in unresectable advanced hepatocellular carcinoma (HCC). In this study, we investigated whether lenvatinib-incorporating poly(ε-caprolactone) sheets (lenvatinib sheets) as a drug delivery system (DDS) exerted antitumor effects in a murine HCC model. The lenvatinib sheets were designed for sustained release of approximately 1 mg lenvatinib for 14 days. For 14 days, 1 mg lenvatinib was orally administered to mice. Then, we compared the antitumor effects of lenvatinib sheets with those of oral lenvatinib. The tumor volume, body weight, and serum lenvatinib level were measured for 14 days. A peritoneal dissemination model was established to examine the survival prolongation effect of the lenvatinib sheets. Tumor growth was significantly inhibited in the lenvatinib sheet group compared with that in the no treatment and oral groups. The antitumor effect was significantly higher in the lenvatinib sheet group. Regardless of the insertion site, the serum lenvatinib levels were maintained and showed similar antitumor effects. The mitotic index was significantly inhibited in the lenvatinib sheet group compared with that in the control group. Furthermore, lenvatinib sheets improved the 30-day survival. Lenvatinib sheets showed sufficient antitumor effects and may serve as an effective novel DDS for advanced HCC.

16.
Jpn J Ophthalmol ; 66(4): 373-378, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35430642

ABSTRACT

PURPOSE: To assess the risk factors for intraocular pressure (IOP) elevation during the early period post cataract surgery. STUDY DESIGN: Retrospective study. METHODS: This study involved 1587 eyes that underwent cataract surgery at the Baptist Eye Institute, Kyoto, Japan between April 2020 and May 2021. In all subjects, risk factors for early postoperative IOP elevation (i.e., an increase of IOP of 10 mmHg or more at 1-day postoperative compared with that at baseline, or a postoperative IOP of 28 mmHg or more) were analyzed by multivariate logistic regression analysis. RESULTS: Of the 1587 treated eyes in this study, 100 (6.3%) experienced early-postoperative IOP elevation. Of those 100 eyes, 78.0% were men, 27.0% had an axial length (AL) of ≥ 26.5 mm, 23.0% had a history of glaucoma treatment, 11.0% had poor mydriasis and 10.0% had intraoperative floppy iris syndrome (IFIS). Multivariate analysis findings revealed that male [odds ratio (OR) 4.36; 95% confidence interval (CI) 2.63-7.23; P < 0.001], AL of ≥ 26.5 mm (3.11; 1.83-5.30; P < 0.001), a history of glaucoma treatment (2.83; 1.63-4.91; P < 0.001), poorly mydriasis (2.63; 1.16-6.01; P = 0.02), IFIS (4.37; 1.78-10.74; P = 0.001) and baseline high IOP (1.09; 1.01-1.18; P = 0.03) were associated with increased IOP during the early period post cataract surgery. CONCLUSIONS: The findings in this study reveal that male sex, high myopia, a history of glaucoma treatment, poor mydriasis, IFIS and baseline high IOP are risk factors for IOP elevation during the early period post cataract surgery.


Subject(s)
Cataract , Glaucoma , Mydriasis , Phacoemulsification , Cataract/complications , Female , Glaucoma/surgery , Humans , Intraocular Pressure , Male , Mydriasis/complications , Mydriasis/surgery , Retrospective Studies , Risk Factors
18.
Facial Plast Surg Aesthet Med ; 24(5): 385-390, 2022.
Article in English | MEDLINE | ID: mdl-34861113

ABSTRACT

Background: Brow-lift-induced eyelid closure impairment is commonly discussed in patients with facial paralysis but has not been well quantified. Objective: To measure the limitation of eyelid closure in patients with facial paralysis using simulated brow-lift with tape. Design, Setting, and Participants: For 50 facial paralysis patients with brow ptosis who visited our institution from October 2017 to December 2020, brow-lift was simulated by elevating the paralyzed-side brow using surgical tape, and closed palpebral fissure heights in spontaneous blinking were measured using high-speed videography. The effect of several factors on the change in closed palpebral fissure height was evaluated by multiple linear regression analysis. Results: Greater patient age (p = 0.021), single eyelids (p = 0.003), higher value of closed palpebral fissure height before simulation (p = 0.004), and higher value of brow elevation (p = 0.013) were significant for the increase of closed palpebral fissure height. Conclusions: Brow elevation to the degree that achieves symmetrical brow height could be detrimental to eyelid closure in patients with facial paralysis, especially who are elderly, have single eyelids, or present with preoperative decreased lid-closure function. UMIN Clinical Trials (UMIN Registry No. 000042974).


Subject(s)
Blepharoplasty , Facial Paralysis , Rhytidoplasty , Aged , Eyebrows , Eyelids/surgery , Facial Paralysis/surgery , Humans
19.
Cornea ; 41(2): 171-176, 2022 Feb 01.
Article in English | MEDLINE | ID: mdl-34369393

ABSTRACT

PURPOSE: The purpose of this article was to study the clinical, optical, and morphological correlates of visual function in patients with Fuchs endothelial corneal dystrophy (FECD). METHODS: The case records were analyzed for patients diagnosed with FECD between September 2019 and March 2020. The best-corrected visual acuity (BCVA) was recorded as decimal visual acuity and converted to the logarithm of the minimum angle of resolution units. Contrast sensitivity was measured with the Pelli-Robson contrast sensitivity test. Corneal alterations, including central corneal thickness, depression of the posterior cornea, and corneal densitometry values, were evaluated using Scheimpflug images. Corneal epithelial thickness was measured by spectral-domain optical coherence tomography. RESULTS: A total of 107 eyes of 61 patients (18 male and 43 female) with FECD were retrospectively investigated. The Spearman rank correlation coefficient showed moderate correlation between BCVA and contrast sensitivity (ρ = -0.66, P < 0.001), with some patients maintaining relatively good BCVA but having reduced contrast sensitivity. Logistic regression analysis demonstrated that age, central corneal thickness, depression of the posterior cornea, and epithelial thickening were negatively associated with contrast sensitivity but not with BCVA. CONCLUSIONS: Contrast sensitivity is a useful tool for assessing visual dysfunction and should be incorporated into the assessment protocol of patients with FECD. Alterations in the cornea, including central corneal thickness, depression of the posterior cornea, and epithelial thickening, might be objective parameters that can help the clinician in grading the severity of the disease and tracking its progression.


Subject(s)
Contrast Sensitivity/physiology , Cornea/diagnostic imaging , Corneal Pachymetry/methods , Fuchs' Endothelial Dystrophy/diagnosis , Tomography, Optical Coherence/methods , Visual Acuity , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Fuchs' Endothelial Dystrophy/physiopathology , Humans , Male , Middle Aged , Retrospective Studies , Young Adult
20.
Am J Ophthalmol ; 234: 235-240, 2022 02.
Article in English | MEDLINE | ID: mdl-34648775

ABSTRACT

PURPOSE: To investigate the trend of seasonal variation of intraocular pressure (IOP) in patients with normal-tension glaucoma over a 20-year period by retrospectively analyzing the Kyoto Prefectural University of Medicine Glaucoma Registry database as real-world data. DESIGN: Retrospective cohort study. METHODS: Data points (n = 49,007) were extracted retrospectively from the medical records of 1774 patients with normal-tension glaucoma (665 male patients and 1109 female patients; mean ± SD age was 59.8 ± 14.4 years; and mean ± SD observation period was 5.6 ± 4.4 years) seen over the 20-year period. We first calculated the mean IOP from all available data of each month from January 1997 through December 2016. The data were then categorized into 5 groups of 4 consecutive years each (1997-2000, 2001-2004, 2005-2008, 2009-2012, and 2013-2016) and the mean IOP of each month within the group was calculated. Seasonal variations of IOP over the 20-year study period and in the 5 consecutive groups were then investigated via nonlinear multiple regression analysis. RESULTS: A continuous decrease of IOP was detected throughout the 20-year period (P < .001), with distinct seasonal variation. The annual mean ± SD IOP was highest (13.9 ± 2.7 mm Hg) in the oldest group (1997-2000), with a gradual decrease in each subsequent group, finally becoming lowest (12.3 ± 2.7 mm Hg) in the most recent group (2013-2016) (P < .001), and all of them were accompanied by distinct seasonal variation (P < .001). CONCLUSIONS: Based on the Kyoto Prefectural University of Medicine Glaucoma Registry real-world longitudinal data, our findings revealed a continuous decrease and distinct seasonal variation of IOP in patients with normal-tension glaucoma throughout the 20-year study period.


Subject(s)
Glaucoma , Intraocular Pressure , Aged , Female , Humans , Male , Middle Aged , Retrospective Studies , Seasons , Tonometry, Ocular
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