Prognostic significance of pre- and post-treatment hematological biomarkers in patients with head and neck cancer treated with chemoradiotherapy.

This study aimed to investigate the prognostic value of hematological biomarkers measured before and after treatment in patients with head and neck cancer (HNC). This study reviewed 124 patients with HNC who received chemoradiotherapy. Hematological biomarkers assessed before and after treatment were investigated. The pretreatment C-reactive protein/albumin ratio (pre-CAR) and post-treatment prognostic nutritional index (post-PNI) showed the highest area under the curve with cutoff values of 0.0945 and 34.9, respectively. Patients in the high pre-CAR group showed significantly worse prognosis than those in the low pre-CAR group with respect to the progression-free survival (PFS) (3-year PFS: 44.8% vs. 76.8%, p < 0.001) and overall survival (OS) (3-year OS: 65.8% vs. 94.0%, p < 0.001). Patients in the low post-PNI group showed significantly worse prognosis than those in the high post-PNI group with respect to the PFS (3-year PFS: 58.6% vs. 77.4%, p = 0.013) and OS (3-year OS: 75.2% vs. 96.9%, p = 0.019). Multivariate analysis revealed that advanced N stage (p = 0.008), high pre-CAR (p = 0.024), and low post-PNI (p = 0.034) were significantly associated with poorer OS. We suggest that the evaluation of hematological markers before and after treatment is useful for predicting disease progression and survival.

The Stop and Press Technique; an Occlusion Free Stop-and-Chop Technique in Cataract Patients with Soft to Moderate Nuclei.

The stop-and-chop technique, which involves occlusion and chopping using vacuum to stabilize the nucleus, is an excellent combination of the divide-and-conquer and phaco-chop techniques. However, effectively chopping an un-solid (soft to moderate) nucleus is not easy, since the optimal vacuum to hold an un-solid nucleus is often associated with breaking of occlusion and aspiration of the nucleus. We modified the stop-and-chop technique such that occlusion and tight nucleus holding using ultrasound (US) power is not necessary. After completing the central groove and cracking the nucleus into two hemi-sections, the right nucleus half is chopped without nucleus rotation and occlusion. The right hemi-nucleus is stabilized by pressing against the right sac with the US tip without occlusion. Since this technique can reduce the risk of nucleus perforation and posterior capsular rupture, the surgeons can place the US tip firmly in a deep position, which provide safe and efficient nucleus division.

Venom ophthalmia (keratoconjunctivitis) caused by nuchal gland secretion of Rhabdophis tigrinus: case report.

Rhabdophis tigrinus (R. tigrinus) is a common colubrid snake that possesses a series of paired sac-like nuchal glands behind the head. When pressure is applied to the nuchal area, the thin skin over the nuchal glands can rupture and release secretions. In Japan, 19 cases of ophthalmia caused by the nuchal gland secretion of R. tigrinus have been reported. However, only one case has been documented in an English report. A 72-year old woman was sprayed by the nuchal gland fluid of R. tigrinus in her right eye. She presented with symptoms of eye pain and blurred vision. A slit-lamp examination revealed diffuse superficial keratitis, corneal stromal edema with Descemet membrane folds, and conjunctival injection. The best-corrected visual acuity (BCVA) of her right eye was 0.6. She was prescribed 0.5% moxifloxacin and 0.1% fluorometholone eye drops four times a day, and the symptoms resolved without sequelae within 5 days. The BCVA in the right eye improved to 1.0. In previous reports, ophthalmic examinations revealed conjunctivitis, keratitis, and corneal edema with Descemet membrane folds. Topical antibiotics and corticosteroid were prescribed in most cases, and eyes healed within 5-7 days without any sequelae. While corneal edema may resolve spontaneously in a few days when inhibition of the toxin has ceased, the use of topical steroids is recommended, as it can increase the activity of Na/K pumps that remained functional, thereby accelerating recovery. In fact, our patient used a topical steroid and recovered without sequelae.

How to Manage the Cortex After CTR Insertion.

Capsular tension ring (CTR) realizes safe cataract surgery. However, residual cortex removal becomes difficult with CTR. Originally, the flushing technique was developed for intracameral antibiotic administration. Using this technique with larger amounts of solution enables surgeons to 1) deliver antibiotics to the anterior chamber and area behind the intraocular lens, resulting in stable, scheduled antibiotic concentration and 2) entirely irrigate and displace the area, leading to the effective cleansing of residual substances and bacterial pollution. When performing the flushing technique, the residual cortex and debris that were not eliminated by ordinary irrigation and aspiration can be pushed out to the anterior chamber. Applying flushing technique to CTR cases, the residual cortex and debris trapped between the CTR loop and capsular equator is lifted into the anterior chamber and easily removed. If the capsular bag is polluted by bacteria, it may also be lifted to the anterior chamber.

Audiological Features in 63 Patients With Cochlear Nerve Deficiency.

OBJECTIVE: We aimed to investigate the clinical features of cochlear nerve deficiency (CND), and in particular, the long-term course of hearing disability and audiogram shapes. STUDY DESIGN: Retrospective observational nonrandomized group study. SETTING: Academic medical center. PATIENTS/INTERVENTIONS: The subjects were 63 children with congenital hearing loss who visited our hospital between 2009 and 2019 and underwent MRI, based on which they were diagnosed with CND. There were 61 cases of unilateral CND and two cases of bilateral CND. MAIN OUTCOME MEASURES: Imaging tests by MRI and CT and audiometric assessments by pure-tone audiometry and distortion product otoacoustic emission were performed. RESULTS: Among the cases of CND diagnosed by assessing the cochlear nerve on MRI, approximately 20% of the bony cochlear nerve canals that could be assessed on CT were normal. Of the 61 cases diagnosed with unilateral CND, 55 cases had cochlear nerve aplasia (90.2%), and six had cochlear nerve hypoplasia (9.8%), with a mean hearing ability of 92.2 and 94.6 dB HL, respectively. Thus, the majority of cases had severe-to-profound hearing loss. The overall audiometric patterns were 78.7% flat, 9.8% cookie-bite, and 9.8% high-frequency. Six of 61 cases (9.8%) had a distortion product otoacoustic emission (DPOAE) response based on the affected side, and none of the cases lost the response during follow-up. CONCLUSIONS: Herein, we report the largest study on CND and performed CND image and audiometric assessments. Accurately in diagnosing CND requires not only CT but also MRI assessment. Hearing loss is often severe to profound; however, various audiometric patterns have been observed. CND includes a small number of cases that respond to DPOAE, indicating that some CND cases are clinically diagnosed with auditory neuropathy spectrum disorder (ANSD). A sustained DPOAE response might help in differentiating CND from other ANSDs. Children with congenital deafness who have passed the newborn hearing screening by DPOAE should be examined by MRI to rule out CND.

Bilateral diffuse anterior scleritis after unilateral cataract surgery: A case report.

Surgically induced scleritis (SIS) is a rare complication after a variety of ocular surgeries. Majority of the patients had had two or more surgical procedures before the onset of SIS. We report a patient who developed bilateral diffuse scleritis after unilateral cataract surgery. A 64-year-old man presented with red eye and tenderness in the right eye. An uneventful cataract surgery had been conducted in the right eye 5 months earlier. He had lost vision in the left eye 25 years ago, and there had been no ocular symptoms in both the eyes for the previous 20 years. Scleritis of the right eye appeared 5 months after cataract surgery, and scleritis of the left eye developed three months later. No previous reports referred to the possibility that the right eye surgery could induce scleritis in the left eye. Our case implies that surgical trauma in one eye can induce scleritis in both the eyes with a history of severe inflammation.

Quantitative Investigation of Viral Load in Acute to Subacute Human Adenovirus Type 54 Conjunctivitis.

To understand the clinical course of human adenoviral (HAdV) conjunctivitis and establish a better treatment regimen, 38 eyes of 19 patients with HAdV-54 conjunctivitis for less than one week from onset were evaluated for clinical signs and symptoms and DNA copy numbers. A viral load of 104-105 is required to develop symptoms of HAdV conjunctivitis, as symptoms were present in eyes with viral loads of ≥104 at least once during the course. Next, it was observed that asymptomatic infections in the contralateral eyes are common, as the virus was detected in most eyes that did not develop conjunctivitis. Furthermore, there was no rapid decrease in the viral load in healed eyes; on the contrary, the viral load in the healed eyes on day 15 was significantly higher than that in the unhealed eyes. This was likely due to corticosteroid instillation, which rapidly alleviated symptoms but prolonged the duration of viral shedding. Recently, combination treatment with iodine and corticosteroids has been recommended for HAdV conjunctivitis. Assessing changes in the viral load and clinical symptoms would be helpful to better understand the clinical course of this disease.

Efficacy of compartmentalization in controlling an adenovirus type 54 keratoconjunctivitis outbreak on Oki Island, Japan.

PURPOSE: To analyze the epidemiologic characteristics of an outbreak of human adenovirus type 54 (HAdV-54) on Oki Island, Shimane Prefecture, Japan, in 2017 and to assess the effectiveness of a compartmentalization method in controlling the incidence and spread. STUDY DESIGN: Retrospective cohort study. METHODS: The infection was diagnosed in 136 individuals, and typing was confirmed by PCR and direct sequencing. The epidemiologic characteristics of the disease including the infection rate, incubation period, and basic reproductive number (R0), ie, number of cases directly infected by an infectious patient during the course of the disease, were investigated. The effectiveness of compartmentalization for infection control was determined by simulating the outbreak using the Susceptible-Exposed-Infectious-Recovered (SEIR) model. RESULTS: The majority of the HAdV-54-infected individuals were the children of 3 nursery schools (A, B, and C) and their parents on Oki Island. The infection rates in the 3 schools were 13.2%, 16.9%, and 17.2%, respectively. The one class of school B without the index case was initially compartmentalized, and the infection rate in this compartment was 0%. The incubation period was calculated to be 9.3 ± 3.5 days, and the disease duration, 13.0 ± 5.4 days. The R0 was 1.43. Using these parameters, a SEIR model was constructed. The SEIR model well predicted the daily incidence of infection and indicated that the compartmentalization method provides effective reduction in the incidence of the infection, with much earlier control. CONCLUSIONS: The compartmentalization method is effective to control HAdV-54 outbreaks.

Diffuse anterior and posterior scleritis with multiple iris granular deposits following pterygium excision.

Surgically induced necrotizing scleritis has been reported after several types of ophthalmic surgeries; however, not many cases are reported following pterygium surgery (PS). A 79-year-old woman underwent primary pterygium excision and conjunctival autograft transportation with mitomycin C in her left eye. 18 months postoperatively, diffuse anterior and posterior scleritis was noted; however, scleral necrosis was not apparent. Multiple granular deposits were observed on the surface of the iris. The deposits, aqueous humor, and vitreous were examined. Since there were no signs of infection or malignancy, the patient was diagnosed with scleritis with intraocular inflammation following PS. Necrosis was accompanying at the surgical site in most cases of scleritis following PS. However, the scleral necrosis of the surgical site was not significant in our case. Posterior scleritis associated with PS has never been reported. This is the first report of anterior diffuse scleritis accompanied by posterior scleritis following PS. Abbreviations: PS = pterygium surgery, SINS = surgically induced necrotizing scleritis, MMC = mitomycin C, ANCA = antineutrophil cytoplasmic antibody.

Comparative study of topical regimen for adenoviral kearoconjunctivitis by 0.1% fluorometholone with and without polyvinyl alcohol iodine.

PURPOSE: The aim of this study was to compare the efficacy of the topical regimens of iodine/steroids vs. antibiotics/steroids in acute to subacute adenoviral keratoconjunctivitis. STUDY DESIGN: A prospective open-label study. PATIENTS AND METHODS: Nineteen patients diagnosed with unilateral or bilateral adenoviral conjunctivitis at less than 1 week from onset were enrolled in this study. Patients were divided randomly into two groups; group 1 was treated with 1.5% levofloxacin with 0.1% fluorometholone administered four times a day and group 2 was treated with a sixfold dilution of polyvinyl alcohol iodine (PAI) solution with 0.1% fluorometholone four times a day. Conjunctival samples from all affected eyes were obtained for real-time PCR. The total scores of acute signs (i.e., eyelid edema, conjunctival injecton, conjunctival discharge, follicules, pseudomembranes, subconjunctival hemorrhage) and symptoms, HAdV DNA copy number, and the presence of multiple subepithelial corneal infiltrates (MSI) were evaluated every 5 visits up to Day 30 after diagnosis. RESULTS: Comparing the total scores of acute signs and symptoms and viral load, we observed no significant differences between the two groups. At day 15 after diagnosis the proportion of patients with MSI in group 2 (35.7%) was significantly lower than in group 1 (0%). CONCLUSIONS: The impact of topical iodine/steroid therapy on acute signs and symptoms associated with adenoviral conjunctivitis is limited and not substantially different in the responses to antibiotics/steroids. However, this regimen results in a significant decrease in the incidence of MSI during the subacute phase of infection.

Publisher Correction: Toxicities of and inflammatory responses to moxifloxacin, cefuroxime, and vancomycin on retinal vascular cells.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Conjunctival bacterial flora and antimicrobial susceptibility in bacterial pathogens isolated prior to cataract surgery.

PURPOSE: To optimize prophylactic antibiotic administration, antibiotic susceptibility before cataract surgery was investigated using ocular bacteria isolated preoperatively. DESIGN: Retrospective cross-sectional study. METHODS: In 204 eyes of 102 patients who underwent routine bilateral cataract surgery, conjunctival sac scrapings were collected 1-2 weeks before surgery. A total of 192 major pathogens among the 470 isolated bacteria were subjected to susceptibility testing. The major pathogens included Staphylococcus aureus, Staphylococcus epidermidis, coagulase-negative staphylococci (CNS) other than S. epidermidis, Enterococcus faecalis, and Streptococcus spp. The following antibiotics were tested: cefmenoxime (CMX), ceftazidime (CAZ), tobramycin (TOB), vancomycin (VAN), erythromycin (EM), moxifloxacin (MFLX), gatifloxacin (GFLX), levofloxacin (LVFX), chloramphenicol (CP), and imipenem (IP). RESULTS: The proportions of isolates with minimum inhibitory concentration (MIC) of S. epidermidis (N = 82), exceeding 4 µg/ml were high for CAZ (95.1%), EM (32.9%), LVFX (39.0%), and CP (82.9%). Susceptible (S) proportion was high for CMX (98.8%), VAN (100%), CP (93.9%), and IP (97.6%) but relatively low for MFLX (59.8%), GFLX (54.9%), and LVFX (54.9%). The MIC90 values were high for CMX (16 µg/ml), CAZ (64 µg/ml), TOB (32 µg/ml), EM (128 µg/ml), LVFX (16 µg/ml), and CP (8 µg/ml). The MIC of quinolonesof pathogenic bacteria other than S.epidermidis (N = 108), exceeded 4 µg/ml for 11 isolates, including two Methicillin-resistant Staphylococcus aureus. CONCLUSIONS: The increase in resistance of resident bacteria present in the conjunctival sac to antibiotics indicates that systemic and topical antibiotics are no longer effective, especially against external organisms affecting the eye.

Effectiveness of intraoperative iodine in cataract surgery: cleanliness of the surgical field without preoperative topical antibiotics.

PURPOSE: To verify the possibility that preoperative topical antibiotics are not essential as long as iodine disinfection is performed during surgery. STUDY DESIGN: Crossover equivalence trial. PATIENTS AND METHODS: In 204 eyes of 102 patients who underwent routine bilateral cataract surgery, 1 eye was treated with intraoperative iodine, and the other, with preoperative topical antibiotics. For the intraoperative iodine eyes, 5 mL of 0.25% povidone-iodine was applied at 2 stages: (1) just after the placement of the speculum and (2) before intraocular lens (IOL) insertion. For the contralateral eyes, preoperative topical antibiotics were administered 3 days before surgery without intraoperative iodine. Conjunctival samples for culture were obtained at 3 time points: (a) presurgery, (b) beginning of surgery, and (c) postsurgery. Real-time polymerase chain reaction (PCR) samples were obtained at the beginning of surgery and before IOL insertion. Intracameral moxifloxacin was applied in all the cases. RESULTS: The respective positive bacterial culture rates for intraoperative iodine eyes and preoperative topical antibiotics eyes were 95.1% and 98.0% at (a), 7.8% and 5.9% at (b), and 60.8% and 62.7% at (c). A significant difference in the positive bacterial culture rate was not found at any time point. For the intraoperative iodine eyes, the bacterial DNA copy number at (b) was significantly lower than that for the preoperative topical antibiotics eyes. CONCLUSIONS: The cleanliness of the operative field without using topical antibiotics was revealed to be equivalent to that of the conventional method (using preoperative antibiotics without intraoperative iodine) as long as intraoperative iodine was used.

Toxicities of and inflammatory responses to moxifloxacin, cefuroxime, and vancomycin on retinal vascular cells.

Prophylactic intracameral injection of antibiotics is commonly used to prevent endophthalmitis after cataract surgery. However, devastating visual complications have been reported including hemorrhagic occlusive retinal vasculitis (HORV).To determine the toxic and inflammatory effects of moxifloxacin, cefuroxime, and vancomycin on human retinal vascular cells, human retinal vascular endothelial cells (RVEC) and pericytes were exposed to three antibiotics, and the adverse effects were assessed by membrane damage, loss of intrinsic esterase activity, kinetic cell viability, and inflammatory cytokine secretion. Their retinal toxicity was examined by live/dead assays after an intravitreal injection of the three antibiotics into mice eyes. In vascular cells in culture, membrane damage and loss of esterase activity were induced after exposure to the three antibiotics. The toxic effects were most obvious after moxifloxacin (RVEC, ≥125 µg/mL; pericytes, ≥1000 µg/mL) at 24 h. Cefuroxime also reduced esterase activity and the membrane integrity of vascular cells but were less toxic than moxifloxacin. Kinetic cell viability testing showed that 500 µg/mL of moxifloxacin exposure induced significant decrease (29%) in the viability as early as 1 h. When the inflammatory effects of the antibiotics were examined, a significant induction of IL-8 was observed especially by RVECs after exposure to cefuroxime or vancomycin which was exacerbated by L-alanyl-γ-D-glutamyl-meso-diaminopimelic acid (Tri-DAP), a NOD1 ligand. Intravitreal injections in mice showed that cefuroxime and vancomycin caused retinal and vascular toxicity extending to the inner nuclear layers. Collectively, moxifloxacin causes immediate damage to retinal vascular cells in vitro, while cefuroxime and vancomycin induced significant inflammatory effects on vascular endothelial cells and caused retinal toxicity. Surgeons need to be cautious of the toxicity when antibiotics are used prophylactically especially by intravitreal administration.

Atypical Symptoms in Migraine-Related Alice in Wonderland Syndrome: Expansion of the Phenotype and Reflection on the Pathomechanism.

We report an 8-year-old girl who experienced daily episodes of visual and somesthetic distortion and was diagnosed with Alice in wonderland syndrome (AIWS). Ophthalmologic assessment revealed best-corrected visual acuity of 0.2 in both eyes, and bilateral constricted tubular or spiral visual fields. Augmented amplitude of visually evoked potentials was revealed, and treatment with lomerizine and valproate showed favorable effect on the visual/somesthetic distortion as well as the visual field and acuity. Psychogenic visual problems can co-exist with the typical sensory distortion in AIWS, similarly to the case of psychogenic pseudo-seizures in subjects with epilepsy. Otherwise, an ambiguous borderline between psychological and physical pathomechanisms in migraine may also be characteristic of the migraine-related AIWS.

Human adenoviral type 54 keratoconjunctivitis accompanied by stellate keratitis and keratic precipitates: two cases.

BACKGROUND: Of the 10 patients with adenoviral type 54 keratoconjunctivitis examined at Nojima Hospital, 2 developed stellate keratitis and mutton-fat keratic precipitates (KPs) following acute symptoms. CASE PRESENTATION: We encountered 10 cases of epidemic keratoconjunctivitis from August to October 2017. All patients were adults with a mean age of 60.9 ± 10.0 years. The species D human adenovirus (HAdV)-54 was detected in the conjunctival scrapings of these patients. Fluorometholone instillation was administered during the first week for acute symptomatic relief. Case 1: A 64-year-old female was prescribed with fluorometholone instillation, which was discontinued after 1 week when her symptoms alleviated. One week after discontinuation of the instillation, she presented with blurred vision in her left eye with KPs and multiple stellate keratitis. The anterior chamber had no apparent cells. Her symptoms disappeared after 1 week of betamethasone instillation. Case 2: A 66-year-old female was prescribed with 0.1% fluorometholone instillation, which was discontinued within10 days. Three months after the appearance of initial symptoms, multiple subepithelial corneal infiltrates (MSI) appeared in her eyes. Stellate keratitis and dark-brown pigmentation were observed in the centres of MSI, with several cells in the anterior chamber. Betamethasone was prescribed, and MSI and stellate keratitis improved within 1 week. However, KPs were observed in the left eye. The instillation was continued for 3 more weeks until symptoms improved. CONCLUSIONS: MSI is an immune reaction that occurs after the disappearance of acute symptoms. Here, corneal findings and KPs were observed after improvement in eye redness and discontinuation of steroids. These symptoms were presumed to be secondary inflammation due to immune response to the adenoviral antigen. The clinical features of HAdV-54 keratoconjunctivitis on the ocular surface are initially moderate, but become active in the subacute to chronic phases. This may develop atypical findings, including stellate keratitis with KPs. Although early steroid administration can relieve acute symptoms, it may facilitate chronic corneal immunological reaction.

MMP-7 cleaves amyloid ß fragment peptides and copper ion inhibits the degradation.

The extracellular deposition of amyloid ß (Aß) is known to be the fundamental cause of Alzheimer's disease (AD). Aß1-42, generated by ß-secretases from the amyloid precursor protein (APP), is the main component of neuritic plaque, and the aggregation of this protein is shown to be dependent to an extent on metal ions such as copper and zinc. However, the mechanism by which Cu2+ affects the physicochemical properties of Aß1-42 or the central nervous system is still under debate. A recent series of studies have demonstrated that both the soluble-type matrix metalloproteinases (MMP-2 and MMP-9) and the membrane-type matrix metalloproteinase (MT1-MMP) are capable of degrading Aß peptides. MMP-7, one of the soluble-type matrix metalloproteinases, is expressed in hippocampal tissue; however, less information is available concerning the pathophysiological roles of this enzyme in the process and/or progress of Alzheimer's disease. In this study, we examined the degradation activity of MMP-7 against various Aß1-42's fragment peptides and the effect of Cu2+. Although Aß22-40 was degraded by MMP-7 regardless of Cu2+, Cu2+ inhibited the degradation of Aß1-19, Aß11-20, and Aß11-29 by MMP-7. These results indicate that MMP-7 is capable of degrading Aß1-42, and that Aß1-42 acquired resistance against MMP-7 cleavage through Cu2+-binding and structure changes. Our results demonstrate that MMP-7 may play an important role in the defensive mechanism against the aggregation of Aß1-42, which gives rise to the pathology of AD.

Identification of ACA-28, a 1'-acetoxychavicol acetate analogue compound, as a novel modulator of ERK MAPK signaling, which preferentially kills human melanoma cells.

The extracellular signal-regulated kinase (ERK) signaling pathway is essential for cell proliferation and is frequently deregulated in human tumors such as melanoma. Melanoma remains incurable despite the use of conventional chemotherapy; consequently, development of new therapeutic agents for melanoma is highly desirable. Here, we carried out a chemical genetic screen using a fission yeast phenotypic assay and showed that ACA-28, a synthetic derivative of 1'-acetoxychavicol acetate (ACA), which is a natural ginger compound, effectively inhibited the growth of melanoma cancer cells wherein ERK MAPK signaling is hyperactivated due to mutations in the upstream activating regulators. ACA-28 more potently inhibited the growth of melanoma cells than did the parental compound ACA. Importantly, the growth of normal human epidermal melanocytes (NHEM) was less affected by ACA-28 at the same 50% inhibitory concentration. In addition, ACA-28 specifically induced apoptosis in NIH/3T3 cells which were oncogenically transformed with human epidermal growth factor receptor-2 (HER2/ErbB2), but not in the parental cells. Notably, the ACA-28-induced apoptosis in melanoma and HER2-transformed cells was abrogated when ERK activation was blocked with a specific MEK inhibitor U0126. Consistently, ACA-28 more strongly stimulated ERK phosphorylation in melanoma cells, as compared in NHEM. ACA-28 might serve as a promising seed compound for melanoma treatment.