Partial Substitution of Glucose with Xylitol Prolongs Survival and Suppresses Cell Proliferation and Glycolysis of Mice Bearing Orthotopic Xenograft of Oral Cancer

Many types of cancer have metabolic alterations with increased glycolysis. Identification of alternative sweeteners that do not fuel cancer is a novel approach to cancer control. The present study aimed to investigate the effects of xylitol on tumor growth and survival of mice bearing orthotopic xenograft of tongue cancers. The results showed that partial substitution of glucose with xylitol (glucose 0.35 g plus xylitol 2.06 g/kg body weight) non-significantly reduced tumor volume, and significantly prolonged the median survival time from 19 days in the control to 30.5 days in the xylitol group. Immunohistochemical data of the tongue tissue shows significantly lower intense-to-mild staining ratios of the proliferation marker Ki-67 in the xylitol than those of the control group (p = 0.04). Furthermore, the xylitol substitution significantly reduced the expression of the rate-limiting glycolytic enzyme, phosphofructokinase-1 (PFK-1) (p = 0.03), and showed a non-significant inhibition of PFK activity. In summary, partial substitution of glucose with xylitol at the equivalent dose to human household use of 10 g/day slows down tumor proliferation and prolongs survival of mice bearing an orthotopic oral cancer xenograft, possibly through glycolytic inhibition, with minimal adverse events. The insight warrants clinical studies to confirm xylitol as a candidate sweetener in food products for cancer survivors.     

Pembrolizumab-related Immune Thrombocytopenia in a Patient with Lung Adenocarcinoma Treated by Radiotherapy: Potential Immune-related Adverse Event Elicited by Radiation Therapy

The effect of radiotherapy during immunotherapy on immune-related adverse events (irAEs) is not fully understood. We herein report a 74-year-old woman diagnosed with lung adenocarcinoma with programmed death ligand 1 expression ≥50% and treated with pembrolizumab. She developed fatal immune thrombocytopenia associated with pembrolizumab immediately following radiotherapy. A flow cytometry analysis of peripheral blood detected an increased expression of programmed death-1 (PD-1) and Ki-67 in CD4^＋ and CD8^＋ T cells after radiotherapy, compared with pre-irradiation measurements. This case suggests that radiotherapy may evoke irAEs during treatment with anti-PD-1 antibodies, which physicians should consider when using radiotherapy in patients treated with these drugs.     

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.     

Cytoskeletal organization in the supporting cell of the guinea pig organ of Corti

The rapid-freeze, deep-etch method was used to visualize the three-dimensional organization of cytoskeletons in the supporting cells of the guinea pig organ of Corti. Deep-etched replicas showed that both the head and basal portions of the pillar cell were composed of a filamentous network consisting of several kinds of fibrous elements, into which numerous microtubules and actin filaments were tightly inserted. Myosin S1-decoration showed that the main constituent element in such filamentous networks in the basal portion of the pillar cell was the actin and tiny cross-bridges interconnected the randomly oriented adjacent actin filaments.     

Two cases of intratemporal facial nerve neurilemmomas

The patients with neurilemmomas of the facial nerve within the temporal bone were treated. Although most of cases of the facial nerve neurilemmoma in the temporal bone present with a facial palsy, a few cases have normal facial nerve function and are especially difficult to diagnose preoperatively because of few symptoms. Case 1, a 31-year-old man, developed progressive left facial palsy with protrusion of the posterior wall of the external auditory meatus over a five-month period. Case 2, a 64-year-old man, complained of only fullness and tinnitus of the right ear without any facial nerve symptoms. Polytomography of the temporal bone demonstrated no abnormal findings in both cases. However, computed tomography revealed a soft-tissue density area in the left mastoid cavity with destruction of the posterior wall of the external auditory meatus in case 1. A similar soft-tissue density mass was found in the right tympanic cavity in case 2, suggesting the presence of the tumor in the temporal bone. At operation, the tumors were found to originate from the vertical portion of the facial nerve in both cases. It was assumed that normally existing dehiscences of fallopian canal might account for why some patients have normal facial nerve function.     

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     

A surgical treatment for frank rupture of acute type a small intramural hematoma

A 71‐year‐old woman was admitted to the hospital due to cardiac tamponade. Computed tomography revealed that the diameter and wall thickness of the ascending aorta were 36 and 9 mm, respectively. An emergent ascending aortic replacement was performed uneventfully. The pathological findings indicated frank rupture of intramural hematoma.