Migration of Intraocular Silicone Oil from the Vitreous Cavity into the Upper Eyelid Causing Ptosis

Introduction

To report a case in which intraocular silicone oil migrated into the upper eyelid and caused ptosis.

Methods

A 65-year-old woman presented with proliferative vitreoretinopathy in the right eye. Vitrectomies, injection of silicone oil and encircling were performed. Two months after the last operation, swelling of her right eyelid occurred.

Result

Magnetic resonance imaging revealed moisture in the palpebral fat tissue. We incised the bulbar conjunctiva and confirmed silicone oil leakage from the vitreous cavity through the scleral button hole of the encircling suture. Postoperatively, the right upper eyelid swelling decreased. Histopathologically, dense macrophage infiltration was seen in the palpebral tissues.

Conclusions

We report a rare case with a postoperative complication caused by silicone oil. In cases with swelling of the eyelid and decreased silicon oil in the vitreous cavity postoperatively, clinicians should consider the possibility of silicone oil leakage.Key words: Migration of silicone oil, Upper eyelid, Vitrectomy, Scleral buckling, Postoperative complication, Ptosis     

Preclinical and first‐in‐human phase I studies of KW‐2450, an oral tyrosine kinase inhibitor with insulin‐like growth factor receptor‐1/insulin receptor selectivity

Numerous solid tumors overexpress or have excessively activated insulin‐like growth factor receptor‐1 (IGF‐1R). We summarize preclinical studies and the first‐in‐human study of KW‐2450, an oral tyrosine kinase inhibitor with IGF‐1R and insulin receptor (IR) inhibitory activity. Preclinical activity of KW‐2450 was evaluated in various in vitro and in vivo models. It was then evaluated in a phase I clinical trial in 13 patients with advanced solid tumors (NCT00921336). In vitro, KW‐2450 inhibited human IGF‐1R and IR kinases (IC₅₀ 7.39 and 5.64 nmol/L, respectively) and the growth of various human malignant cell lines. KW‐2450 40 mg/kg showed modest growth inhibitory activity and inhibited IGF‐1‐induced signal transduction in the murine HT‐29/GFP colon carcinoma xenograft model. The maximum tolerated dose of KW‐2450 was 37.5 mg once daily continuously; dose‐limiting toxicity occurred in two of six patients at 50 mg/day (both grade 3 hyperglycemia) and in one of seven patients at 37.5 mg/day (grade 3 rash). Four of 10 evaluable patients showed stable disease. Single‐agent KW‐2450 was associated with modest antitumor activity in heavily pretreated patients with solid tumors and is being further investigated in combination therapy with lapatinib/letrozole in patients with human epidermal growth factor receptor 2‐postive metastatic breast cancer.     

Pharmacodynamic evaluation of meropenem,cefepime, or aztreonam combined with a novel β-lactamase inhibitor,nacubactam, against carbapenem-resistant and/or carbapenemase-producing Klebsiella pneumoniae and Escherichia coli using a murine thigh-infection model

BackgroundCarbapenem-resistant Enterobacterales (CRE) and carbapenemase-producing Enterobacterales (CPE) are difficult to treat and are a serious public health threat. Nacubactam (NAC) is a novel non-β-lactam diazabicyclooctane β-lactamase inhibitor with in vitro activity against some Enterobacterales expressing classes of β-lactamases.MethodsThe antimicrobial efficacy of meropenem (MEM), cefepime (FEP), and aztreonam (ATM), each in combination with NAC, were assessed in vitro and in vivo against Klebsiella pneumoniae and Escherichia coli. Ten isolates, including CRE and/or CPE with β-lactamase genes, were used in this study. The relationship between phenotype and in vivo efficacy was assessed in a murine neutropenic thigh-infection model. Efficacy was determined by the change in bacterial quantity.ResultsThe results of the in vitro study showed the minimum inhibitory concentrations of the combination of NAC with either MEM, FEP, or ATM in a 1:1 ratio were 2 to >128-fold lower than those of MEM, FEP, or ATM alone against CRE+ isolates. In addition, combinations of β-lactams and NAC administered in the murine thigh-infection model showed greater efficacy against CRE+/CPE+, CRE+/CPE-, and CRE-/CPE+ isolates harboring various β-lactamase genes (IMP-1, IMP-6, KPC, DHA-1, or OXA-48) compared with MEM, FEP, ATM, and NAC alone.ConclusionMEM, FEP, or ATM in combination with NAC showed potent in vivo antimicrobial activity in a murine thigh-infection model caused by K. pneumoniae and E. coli, including CRE and/or CPE isolates. These findings indicate that these combinations of β-lactams and NAC are potential candidates for the treatment of CRE and/or CPE infections.     

Bowel Obstruction due to Shiitake Mushrooms: Diagnostic Features on Computed Tomography

Shiitake mushrooms are edible mushrooms popular in East Asian cuisine. We herein report a 69-year-old man with abdominal distension and vomiting after ingesting several pieces of sautéed Shiitake mushrooms. Abdominal computed tomography (CT) revealed ring-shaped and crescent-shaped low-density objects (-100 to -300 Hounsfield units) in the ileum. Based on the specific shapes and CT numbers of the foreign bodies, he was diagnosed with small bowel obstruction due to Shiitake mushrooms. After conservative treatment, he passed four pieces of Shiitake mushrooms. Despite the rarity, the condition can be diagnosed before exploratory surgery by careful and detailed interpretation of CT findings.     

Development of Acute Adult T-cell Leukemia Following PD-1 Blockade Therapy for Lung Cancer

Immune checkpoint inhibitors (ICIs) are widely used for the treatment of various cancers. However, paradoxical exacerbation of neoplasms, referred to as “hyperprogressive disease,” has been reported in a proportion of patients treated with anti-programmed cell death-1 (PD-1)/PD-1 ligand (PD-L1) blockade. We herein report a case of acute adult T-cell leukemia (ATL) that developed shortly after the administration of nivolumab, a PD-1 inhibitor, to treat non-small-cell lung cancer. There were no signs of ATL before the administration of nivolumab, and seropositivity for human T-cell leukemia virus type-1 (HTLV-1) was confirmed after the development of acute ATL. We speculate that nivolumab likely contributed to the development of acute ATL.     

Empagliflozin is associated with lower risk of cardiovascular events and all‐cause mortality in routine care in East Asia: Results from the EMPRISE study

Aims/IntroductionThe EMPA‐REG OUTCOME® trial demonstrated benefits of empagliflozin, a sodium‐glucose cotransporter‐2 inhibitor (SGLT2i), on cardiovascular, renal outcomes and all‐cause mortality in patients with type 2 diabetes and established cardiovascular disease. The EMPRISE study program evaluates how these effects translate in a broad population of patients with type 2 diabetes in routine clinical care across countries.Materials and MethodsThe study included patients ≥18 years with type 2 diabetes initiating empagliflozin or any dipeptidyl peptidase‐4 inhibitors (DPP‐4i) from large administrative databases in Japan, South Korea, and Taiwan. Propensity score‐matched (1:1) ‘as‐treated’ analyses comparing the risk of cardiovascular outcomes and all‐cause mortality between empagliflozin and DPP‐4i use were performed in each country. Pooled hazard ratios (pHR) with 95% confidence intervals (CI) were computed using random effects meta‐analysis models comparing both empagliflozin and SGLT2i with DPP‐4i use, respectively. Intention‐to‐treat and subgroup analyses in patients with/without cardiovascular disease and in patients receiving 10 mg empagliflozin were performed.ResultsThe study included 28,712 and 70,233 matched patient pairs for empagliflozin/DPP‐4i and SGLT2i/DPP‐4i analyses, respectively. The risk of composite outcomes including (i) hospitalization for heart failure (HHF) and all‐cause mortality was lower with empagliflozin (pHR 0.76, 95% CI 0.67–0.86) and SGLT2i (0.71, 0.65–0.77); (ii) combined myocardial infarction, stroke, and all‐cause mortality was also lower with empagliflozin (0.74, 0.61–0.88) and SGLT2i (0.69, 0.60–0.78) compared to DPP‐4i. The intention‐to‐treat and three subgroup analyses were consistent with results of the main analyses.ConclusionsThe results suggest that both empagliflozin and SGLT2i compared with DPP‐4i are associated with a lower risk of cardiovascular events and all‐cause mortality in routine clinical care in East Asia.     

Handgrip strength is correlated with activities of daily living,balance, and body composition in patients with thoracolumbar compression fracture

This study assessed the relationship between handgrip strength (HGS) and activities of daily living, balance, walking speed, calf circumference, body muscle, and body composition in elderly patients with thoracolumbar vertebral compression fracture (VCF). A cross-sectional study in a single hospital was performed with elderly patients diagnosed with VCF. After admission, we evaluated HGS, 10-meter walk test (speed), Barthel Index, Berg Balance Scale (BBS), numerical rating scale of body pain, and calf circumference. We examined skeletal muscle mass, skeletal muscle mass index, total body water (TBW), intracellular water, extracellular water (ECW), and phase angle (PhA) in patients with VCF using multi-frequency direct segmental bioelectrical impedance analysis after admission. A total of 112 patients admitted for VCF were enrolled (26 males, 86 females; mean age 83.3 years). The prevalence of sarcopenia according to the 2019 Asian Working Group for Sarcopenia guideline was 61.6%. HGS was significantly correlated with walking speed (P < .001, R = 0.485), Barthel Index (P < .001, R = 0.430), BBS (P < .001, R = 0.511), calf circumference (P < .001, R = 0.491), skeletal muscle mass index (P < .001, R = 0.629), ECW/TBW (P < .001, r = −0.498), and PhA (P < .001, R = 0.550). HGS was more strongly correlated with walking speed, Barthel Index, BBS, ECW/TBW ratio, and PhA in men than women. In patients with thoracolumbar VCF, HGS is associated with walking speed, muscle mass, activities of daily living measured using the Barthel Index, and balance measured using BBS. The findings suggest that HGS is an important indicator of activities of daily living, balance, and whole-body muscle strength. Furthermore, HGS is related to PhA and ECW/TBW.     

Different Clinical Courses of Nephronophthisis in Dizygotic Twins

Siblings with nephronophthisis occasionally show different clinical courses; however, the reasons for this remain unclear. We herein report cases of nephronophthisis in a pair of dizygotic twins with different clinical courses. The brother developed end-stage kidney disease at 17 years old; however, his sister did not show kidney insufficiency. Kidney biopsies revealed severe tubulointerstitial damage at 14 and 22 years old in the brother and sister, respectively. Both had a homozygous NPHP1 deletion with different heterozygous mutations related to hereditary cystic kidney disease. Since the dizygotic twins were exposed to similar environmental factors, genetic factors may have influenced their clinical course more strongly than environmental factors.