Collagen abnormalities in the spinal cord from patients with amyotrophic lateral sclerosis

During the last 10 years, we have demonstrated morphological and biochemical abnormalities of skin extracellular matrices in amyotrophic lateral sclerosis (ALS). However, currently little is known concerning collagen of the spinal cord in ALS. We measured the amount of collagen and characterized collagen at light and electron microscopic levels in posterior funiculus, posterior half of lateral funiculus and anterior horn of cervical enlargement of the spinal cord obtained from ten patients with ALS, 11 patients with other neurologic diseases (control group A), and ten patients without neurologic ones (control group B). In posterior half of lateral funiculus and anterior horn, (1) by light microscopy, there was no significant difference in vessel wall area between ALS patients and control groups A and B; (2) ultrastructurally, collagen bundles were more fragmented and widely separated, and the fibrils were randomly oriented in the perivascular space of capillaries in ALS patients, which were not observed in any areas of control groups or in posterior funiculus of ALS patients; and (3) the collagen contents in ALS were significantly lower (P<0.001 and P<0.001, respectively) than those in control groups A and B. Fragmented and widely separated collagen bundles in the interstitial tissue surrounding capillaries and markedly decreased amount of collagen in posterior half of lateral funiculus and in anterior horn of ALS could be related to the degeneration of the upper and lower motor neurons in the spinal cord in ALS, that is, selective neuronal vulnerability in ALS.     

iPhone charger-induced chemical burn from overnight contact with sweat: Two cases

Smartphones have become essential devices in modern society. The coverage rate of smartphones in 2017 in Japan was 75% according to the Ministry of Internal Affairs and Communications. The iPhone is one of the most well-known smartphone brands. According to the manufacturer of iPhones (Apple), more than 200 million iPhones had been sold worldwide by 2017. These devices are often charged at night-time, especially while being used in bed. There are only three reports of smartphone charger-induced skin damage. We present two new cases of skin ulcers induced by an iPhone charger. The iPhone’s “lightning cable” has electrodes outside, and we found that this can present a higher risk of causing a skin injury compared with other types of phone chargers. We also investigated the mechanism of the skin ulcers caused by the iPhone charger. The results indicated that these ulcers were chemical burns rather than an electrical injury or heat-induced burn.     

High calcium enhances the expression of double‐stranded RNA sensors and antiviral activity in epidermal keratinocytes

Double‐stranded RNA (dsRNA) sensors including TLR3, MDA5 and RIG‐I are expressed in epidermal keratinocytes and play an important immunological role by enhancing various innate and adaptive immune responses. Although the role of elevated extracellular calcium concentration in keratinocyte differentiation is well understood, the effect of high calcium on dsRNA sensors is not well studied. We investigated alterations in dsRNA sensor expression and antiviral activity induced by a high extracellular concentration of calcium in epidermal keratinocytes. Normal human epidermal keratinocytes (NHEKs) were stimulated with high calcium and/or synthetic dsRNA, poly (I:C). TLR3, IFIH1 (MDA5) and DDX58 (RIG‐I) expression were measured via qPCR, and IFN‐β and human beta‐defensin 2 (HBD2) levels were measured using ELISA. TLR3 localization was evaluated with immunocytofluorescence. Antiviral activity was quantified with virus plaque assays using herpes simplex virus type 1 (HSV‐1). High calcium significantly upregulated mRNA expression of TLR3, IFIH1 and DDX58 in NHEKs. In addition, high calcium significantly enhanced poly (I:C)‐induced anti‐HSV‐1 activity in NHEKs. The antiviral molecule HBD2 but not IFN‐β induction by poly (I:C) was enhanced by high calcium. Our findings indicate that high levels of extracellular calcium enhance the expression of dsRNA sensors and augment antiviral activity in epidermal keratinocytes.     

Subretinal injection of recombinant tissue plasminogen activator for submacular hemorrhage associated with ruptured retinal arterial macroaneurysm

Purpose

To evaluate the surgical outcomes of small-gauge vitrectomy with subretinal injection of recombinant tissue plasminogen activator (rt-PA) for a submacular hemorrhage caused by a ruptured retinal arterial macroaneurysm (RAM).

Methods

Non-comparative, consecutive case-series performed at two ophthalmological institutions. We examined 22 eyes of 22 patients with a submacular hemorrhage associated with a RAM but without a preretinal or sub-internal limiting membrane hemorrhage at the fovea. During 25-gauge vitrectomy, approximately 4000–8000 IU of rt-PA was injected subretinally, followed by the injection of air or 10 % sulfur hexafluoride as a tamponade. The patients maintained an upright position for 1 hour, then turned to a facedown position for 1 to 3 days. The best-corrected visual acuity (BCVA) and postoperative complications were evaluated.

Results

The average interval from the onset of symptoms to surgery was 8.4?±?7.6 days, and the average size of the subretinal hemorrhage was 3.4?±?1.0 disc diameters. The submacular hemorrhage was displaced from the foveal area in all eyes after 1 week. The mean baseline BCVA was 1.41?±?0.41 logMAR units, and it improved to 0.91?±?0.43 at 1 month and to 0.64?±?0.45 at the final visit (P?=?0.0001, P?<?0.0001 respectively). A macular hole was detected intraoperatively in two eyes and postoperatively in two eyes, and both were closed by internal limiting membrane peeling or a second vitrectomy.

Conclusions

Small-gauge vitrectomy with subretinal rt-PA injection and gas tamponade were effective in displacing a submacular hemorrhage associated with a RAM.

     

Simple echocardiographic scoring in screening aortic stenosis with focused cardiac ultrasonography in the emergency department

BackgroundNo established methodology exists for diagnosis of aortic stenosis (AS) using focused cardiac ultrasound (FOCUS). We evaluated the diagnostic accuracy of our developed visual AS score for screening AS in an emergency department.MethodsSeventy-two emergency outpatients with suspected cardiovascular disease were studied. Emergency physicians assessed the visual AS score in addition to conducting the standard FOCUS, and then the aortic valve area index (AVAI) was measured by expert sonographers in the echocardiography laboratory. AVAI values >0.85 cm²/m², 0.6–0.85 cm²/m², and <0.6 cm²/m² were defined as no or mild AS, moderate AS, and severe AS, respectively.ResultsSeventeen (24%) patients had moderate or severe AS. Visual AS scores assessed by emergency physicians and by expert sonographers showed excellent agreement (κ = 0.93), and a strong association was noted between the visual AS score assessed by emergency physicians and the AVAI assessed by expert sonographers (R = –0.71, p < 0.0001). A visual AS score ≥3 assessed by emergency physicians had a sensitivity of 82%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 95% for diagnosing moderate or severe AS. The prevalence of new-onset AS-related events during hospitalization was higher in patients with visual AS score ≥3 assessed by emergency physicians than in the remaining patients [7 (50%) vs. 2 (3%), p < 0.0001].ConclusionThe visual AS score is a useful AS screening tool for emergency physicians who are not expert cardiologists.     

Weight-based high- and low-dose ribavirin in combination with peginterferon α-2b therapy for genotype 2 chronic hepatitis C: A randomized trial

Aim: The optimal ribavirin dose in the treatment of patients infected with hepatitis C virus (HCV) genotype 2 remains to be elucidated. We aimed to seek the optimal ribavirin dose required for this genotype in a randomized trial. Methods: We compared the efficacy and tolerability of the 24‐week peginterferon α‐2b (1.5 µg/kg/week) therapy in combination with a weight‐based higher dose (600–1000 mg) and lower dose (400–800 mg) of ribavirin for genotype 2 patients. Noninferior margin was set at 10%. Results: A total of 120 patients were randomized to a higher‐dose or a lower‐dose group. Sustained virological response (SVR) by intention‐to‐treat analysis was achieved in 47/58 (81.0%, 90% confidential interval [CI]: 72.6–89.5) patients in the higher‐dose group and 41/60 (68.3%, 90% CI: 58.5–78.2) patients in the lower‐dose group (difference, ?12.7%; 90% CI, ?25.7 to 0.3). Relapse rates were 10% and 21.6% in the higher‐dose and the lower‐dose groups, respectively. Multiple logistic regression analysis showed that ribavirin dose/kg body weight was the only significant predictor of SVR (≥9.5 mg/kg per day vs <9.5 mg/kg per day; odds ratio = 3.34; 95% CI, 1.41–7.92; P = 0.006). Twenty‐one (36.2%) in the higher‐dose group required ribavirin dose reduction because of anemia, whereas seven patients (11.7%) did in the lower‐dose group (P < 0.01). Three of the higher‐dose group and two of the lower‐dose group required premature termination of therapy. Conclusions: Weight‐based lower‐dose ribavirin regimen was not equivalent to the higher‐dose counterpart in the treatment of HCV genotype 2. We discourage treating these patients with low‐dose ribavirin regimens. The peginterferon therapy in combination with ribavirin at a weight‐based higher dose (600–1000 mg) remains the standard‐of‐care treatment for this genotype.