Effect of nociception level-directed analgesic management on opioid usage in robot-assisted laparoscopic radical prostatectomy: a single-center, single-blinded, randomized controlled trial.

PURPOSE: To assess the importance of appropriate opioid administration methods according to nociceptive monitoring. METHODS: We conducted a randomized controlled trial involving 54 patients who underwent robot-assisted laparoscopic radical prostatectomy at our hospital. Patients were randomly allocated to either receive nociception level (NOL)-directed intraoperative opioid management with a minimum flow of remifentanil (NOL group) or conventional intraoperative analgesic management (control group). The primary outcome was the mean intraoperative remifentanil infusion flow rate (intraoperative remifentanil usage [µg]/ideal body weight [kg]/operation time [min]). The main secondary outcomes were plasma concentrations of three perioperative inflammatory biomarkers (interleukin-6, C-reactive protein [CRP], and cortisol levels) and postoperative pain (Numeric Rating Scale [NRS]) scores 2 h postoperatively and on postoperative days 1, 2, 3, and 7. RESULTS: Compared with standard analgesia management, NOL-directed analgesic management reduced remifentanil consumption by 20% ( - 0.038; 95% confidence interval, - 0.059 to - 0.017; p = 0.0007). NOL-directed management did not lead to an increase in IL-6, CRP, or cortisol levels compared with conventional analgesic management. Furthermore, this protocol led to improvements in the NRS scores at rest 2 h postoperatively and upon movement up to postoperative day 3. CONCLUSION: NOL-directed analgesic management reduced remifentanil consumption by 20% and the NRS scores at rest 2 h postoperatively and upon movement up to postoperative day 3 without an increase in inflammatory marker levels. REGISTRY NUMBER: Japan Registry of Clinical Trials, JRCTs052220034.

Laryngeal herpes zoster with multiple symptoms in a child.

Herpes zoster caused by reactivation of latent varicella-zoster virus (VZV) usually develop in later adulthood. In the pediatric population, herpes zoster is unusual, and involvement of pharyngolaryngeal lesion and cranial nerves is rare. Here, we report a 14-year-old boy who was diagnosed with laryngeal herpes zoster (LHZ), and developed subsequent cranial nerve symptoms suspected of vagus neuropathy. This case provides additional evidence that children can develop LHZ and subsequent cranial nerve symptoms. LHZ should be considered if a pediatric patient with a history of varicella, has unilateral throat pain, with or without cranial nerve symptoms.

CTX-M group gene distribution of extended spectrum beta-lactamase-producing Enterobacteriaceae at a Japanese Children's hospital.

Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae have spread globally as one of the most common multidrug resistant organisms. Although a wide variety of ESBL genes were known in each geographical region, few reports existed on the distribution of ESBL genes in Japanese children. To clarify the distribution of ESBL genes, we investigated the CTX-M type of the ESBL-producing Enterobacteriaceae and patient characteristics among hospital-acquired and community-acquired cases. Total of 253 isolates of ESBL-producing Enterobacteriaceae were recovered from 238 pediatric patients. ESBL-producing Enterobacteriaceae were mostly recovered from children with underlying diseases (76.5%). Ratio of community-acquired and hospital-acquired cases was 58.8% and 41.2%, respectively. Compared to the hospital-acquired cases, community-acquired cases had younger age, fewer underlying diseases, and the dominant detection of Escherichia coli. The most common ESBL-producing Enterobacteriaceae was E. coli (79.8%), followed by Klebsiella pneumoniae (9.1%). CTX-M9 group was the most prevalent CTX-M group gene (63.2%), which was dominantly detected in E. coli (72.7%). This was the largest descriptive study to find CTX-M9 group as the most prevalent ESBL genotype among Enterobacteriaceae isolated from Japanese children in line with adult's epidemiology.

Parechovirus-A3 encephalitis presenting with focal seizure mimicking herpes simplex virus infection.

BACKGROUND: Febrile neonates and young infants presenting with seizure require immediate evaluation and treatment. Herein we experienced two young infants with parechovirus-A3 (PeV-A3) encephalitis, initially presented with focal seizure suspecting herpes simplex virus (HSV) encephalitis. CASES: We have experienced 2 infantile cases, initially presented with focal seizure. At presentation, HSV encephalitis was strongly suspected and empiric acyclovir therapy was started; however, serum and/or cerebrospinal fluid (CSF) PCR for HSV were negative. Instead, serum and/or CSF PCR for parechovirus-A was positive. PeV-A3 infection was confirmed by genetic sequence analyses. Both cases required multiple anticonvulsant therapy and intensive care for intractable seizure. Diffusion-weighted imaging of brain magnetic resonance imaging (MRI) showed distinct findings; high-intensity lesions in the gray matter of parietal and occipital lobes in Case 1, and bilateral decreased diffusion of the deep white matter and corpus callosum in Case 2. We have followed two cases more than four years; Case 1 developed epilepsy, has been on an anticonvulsant to control her seizure. Case 2 has significant neurodevelopmental delay, unable to stand or communicate with language. CONCLUSIONS: PeV-A3 encephalitis needs to be in differential diagnosis when neonates and young infants present with focal seizure, mimicking HSV encephalitis. Special attention may be necessary in patients with PeV-A3 encephalitis given it could present with intractable seizure with high morbidity in a long-term.

Manifestation of coronary subclavian steal phenomenon using reactive hyperemia in the ipsilateral forearm.

Coronary subclavian steal syndrome (CSSS) is a coronary steal phenomenon secondary to subclavian artery stenosis in patients who have undergone coronary bypass surgery with the internal thoracic artery. Most commonly, CSSS is diagnosed angiographically. Our case emphasizes that stress ultrasound assessment using reactive hyperemia in the ipsilateral arm elicits a functional diagnosis of CSSS.

Coding exons function as tissue-specific enhancers of nearby genes.

Enhancers are essential gene regulatory elements whose alteration can lead to morphological differences between species, developmental abnormalities, and human disease. Current strategies to identify enhancers focus primarily on noncoding sequences and tend to exclude protein coding sequences. Here, we analyzed 25 available ChIP-seq data sets that identify enhancers in an unbiased manner (H3K4me1, H3K27ac, and EP300) for peaks that overlap exons. We find that, on average, 7% of all ChIP-seq peaks overlap coding exons (after excluding for peaks that overlap with first exons). By using mouse and zebrafish enhancer assays, we demonstrate that several of these exonic enhancer (eExons) candidates can function as enhancers of their neighboring genes and that the exonic sequence is necessary for enhancer activity. Using ChIP, 3C, and DNA FISH, we further show that one of these exonic limb enhancers, Dync1i1 exon 15, has active enhancer marks and physically interacts with Dlx5/6 promoter regions 900 kb away. In addition, its removal by chromosomal abnormalities in humans could cause split hand and foot malformation 1 (SHFM1), a disorder associated with DLX5/6. These results demonstrate that DNA sequences can have a dual function, operating as coding exons in one tissue and enhancers of nearby gene(s) in another tissue, suggesting that phenotypes resulting from coding mutations could be caused not only by protein alteration but also by disrupting the regulation of another gene.

Novel approach for chirp and output power compensation applied to a 40-Gbit/s EADFB laser integrated with a short SOA.

We propose a novel approach for simultaneously controlling the chirp and increasing the output power of an EADFB laser by monolithically integrating a short-cavity SOA. We achieved a 40-Gbit/s 5-km SMF transmission at a wavelength of 1.55 µm by using an EADFB SOA with a lower power consumption than a stand-alone EADFB laser.

Laparoscopic Gastrectomy Using External Oblique Intercostal Block Versus Wound Infiltration: A Trial Protocol.

OBJECTIVE: A novel external oblique intercostal block (EOIB) might have analgesic effects on T6-10 and be indicated for laparoscopic gastrectomy. However, EOIB effects on postoperative pain are unknown. We aim to generate evidence to support such EOIB application. We will compare the efficacy of EOIB and wound infiltration (WI) in a single-center, single-blind, randomized controlled trial. METHODS: We will assess plasma concentrations of levobupivacaine after EOIB, its pharmacokinetics, and the pinprick test in patients randomly assigned to receive EOIB or WI before laparoscopic or robot-assisted gastric distal or total gastrectomy. The EOIB and WI will start after general anesthesia induction with 20 and 40 mL of 0.25% levobupivacaine per side, respectively, before skin closure. The outcomes will be numeric rating scale (NRS) scores at 12 h postoperatively (primary) and postoperative NRS scores at 2, 24, and 48 h; fentanyl application; QoR-15 scores on postoperative days 1, 2, and 7; and World Health Organization Disability Assessment Schedule 2.0 scores at 3 months (secondary). CONCLUSIONS: We hope that our study will provide evidence to support EOIB application in laparoscopic surgery. Plasma concentrations will help determine levobupivacaine pharmacokinetics, which if similar to conventional nerve blocks, will indicate EOIB's safety.

Comparison of Analgesic Method in Laparoscopic Gastrectomy Using External Oblique Intercostal Block Versus Wound Infiltration: A Randomized Controlled Trial.

Background: External oblique intercostal block (EOIB) is effective in relieving pain in the T6 to T10 dermatomes; however, there is limited evidence comparing EOIB with conventional regional anesthesia. In this randomized controlled trial, it was hypothesized that EOIB would provide more effective analgesia than wound infiltration (WI) in laparoscopic gastrectomy. Methods: Thirty-two patients (aged 20-85 years) with American Society of Anesthesiologists Performance Status of 1 to 2, scheduled for laparoscopic gastrectomy, were randomly divided into EOIB and WI groups. Both procedures were performed using 40 mL of 0.25% levobupivacaine. The primary outcome was the numerical rating scale (NRS) score 12 h postoperatively. Secondary outcomes were NRS at 2, 24, and 48 h postoperatively, variation in quality of recovery-15 score on postoperative days 1 and 2 from preoperative baseline, postoperative fentanyl consumption, and variation in World Health Organization Disability Assessment Scale 2.0 scores between baseline and 3 months postoperatively. Plasma concentrations of levobupivacaine and pinprick sensation in the T4-11 dermatomes post-EOIB were evaluated to determine the exploratory endpoints. Results: There were no differences in the NRS scores 12 h postoperatively at rest and during movement between the EOIB and WI groups (mean standard deviation 1.3 [1.1] vs. 1.5 [1.4] and 3.1 [1.6] vs. 3.8 [1.7], respectively). Secondary outcomes did not differ significantly between the groups. The time to peak plasma concentration of levobupivacaine following EOIB was 45 min. Conclusions: No significant differences in NRS scores were observed between the analgesic effects of EOIB and WI at 12 h postoperatively.

Ultracompact, 160-Gbit/s transmitter optical subassembly based on 40-Gbit/s × 4 monolithically integrated light source.

The first ultracompact transmitter optical subassembly for long-distance, beyond-100-Gbit/s data communication systems based on a monolithically integrated light source is developed. The light source consists of four InGaAlAs-based electroabsorption modulator integrated DFB lasers (EADFB lasers) and their optical multiplexer and these components are monolithically integrated on one chip, resulting in very small chip size of 2.4 × 3.3 mm2. This small chip makes it possible to reduce the size of the transmitter module. Very small transmitter optical subassemblies (TOSAs), using the chip and employing three-dimensional interconnection board, is fabricated, whose volume is only 1.82 cc. By using the TOSA, 40-Gbit/s × 4 operation with the clear eye openings up to 10-km single mode fibre transmission is demonstrated. Electrical crosstalk under the multi-lane operation is also evaluated, and the error-free transmission is achieved with the power penalty to the discrete operation of 1 dB.

Human Rhinovirus as a Cause of Fever in Neonates and Young Infants During the COVID-19 Pandemic, 2020-2022.

BACKGROUND: Human rhinovirus (HRV) was predominant and persistent during the coronavirus disease 2019 (COVID-19) pandemic despite nonpharmaceutical interventions. The data whether HRV persistence also occurred in neonates and young infants were very limited. METHODS: This prospective observational study was conducted in Niigata, Japan, between January 2020 and September 2022. The participants were hospitalized neonates and infants aged less than 4 months with fever. We excluded patients with evidence of bacterial infection or obvious sick contact with influenza or respiratory syncytial virus infection, as confirmed by rapid antigen detection tests. COVID-19 diagnosed by polymerase chain reaction (PCR) or rapid antigen detection tests were also excluded. Parechovirus and enterovirus were examined by PCR using serum and/or cerebrospinal fluid. FilmArray Respiratory Panel v1.7 was conducted on nasopharyngeal swabs. If HRV was positive, the genotype was identified. RESULTS: We included 72 patients (median age, 54 days; interquartile range, 28.5-79 days), and sepsis was diagnosed in 31 (43.1%) patients. In total, 27 (37.5%) patients had had positive multiplex PCR tests. These patients were more likely to have rhinorrhea (P = 0.004), cough (P = 0.01), and sick contact (P < 0.001) than those who with negative multiplex PCR. HRV was the most frequently detected virus (n = 23, 85.2%), and species A (n = 15, 71.4%) and C (n = 6, 28.6%) were genotyped. No seasonality or monthly predominance of the specific HRV types was observed. CONCLUSIONS: HRV was an important cause of fever in neonates and young infants during the COVID-19 pandemic, 2020 to 2022.

Comparison of Clinical Characteristics of Children Infected With Coronavirus Disease 2019 Between Omicron Variant BA.5 and BA.1/BA.2 in Japan.

BACKGROUND: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has dramatically altered the clinical profile of pediatric coronavirus disease 2019 (COVID-19). In Japan, we experienced a pandemic of omicron subvariant BA.1/BA.2 from January through June 2022. However, after the emergence of BA.5 in early July 2022, the number of children hospitalized with COVID-19 increased dramatically in Japan. METHODS: We collected data on monthly numbers of cases and clinical characteristics of hospitalized children with COVID-19 in 13 hospitals, the total number of pediatric COVID-19 cases, and COVID-19 vaccination rates in Niigata, Japan, for the period from January 2020 through August 2022. We compared clinical presentation during the periods of BA.1/BA.2 predominance (January-June 2022) and BA.5 predominance (July-August 2022) and estimated vaccine effectiveness (VE) against hospitalization during the BA.5-predominant period. RESULTS: Between January 1, 2020, and August 31, 2022, 49,387 children (19,085 children/100,000 population) were newly diagnosed as having COVID-19, and 393 were hospitalized for COVID-19. Hospitalization for febrile seizure, especially complex seizure, was significantly higher during BA.5 predominance than during BA.1/BA.2 predominance (27.9% vs. 7.0%, P < 0.01). VE against hospitalization during BA.5 predominance was estimated to be 75% (95% confidence interval, 48%-88%, P < 0.01). CONCLUSIONS: The emergence of BA.5 significantly affected children in Japan; the number with complex febrile seizure who required hospitalization was higher than during BA.1/BA.2 predominance. The COVID-19 vaccination rate in children must be increased to prevent hospitalization for COVID-19 and to prepare for current and future variant outbreaks.

Anterior Quadratus Lumborum Block and Quadriceps Strength: A Prospective Cohort Study.

The decrease in quadriceps strength after anterior quadratus lumborum block (AQLB) has not been quantified. This prospective cohort study investigated the incidence of quadriceps weakness after AQLB. We enrolled patients undergoing robot-assisted partial nephrectomy, and AQLB was performed at the L2 level with 30 mL of 0.375% ropivacaine. We evaluated each quadriceps' maximal voluntary isometric contraction using a handheld dynamometer preoperatively and postoperatively at 1 and 4 days. The incidence of muscle weakness was defined as a 25% reduction in muscle strength compared with the preoperative baseline, and "muscle weakness possibly caused by nerve block" was defined as a 25% reduction compared with the non-block side. We also assessed the numerical rating scale and quality of recovery-15 scores. Thirty participants were analyzed. The incidence of muscle weakness compared with preoperative baseline and the non-block side was 13.3% and 30.0%, respectively. Patients with a numerical rating scale ≥ 4 or quality of recovery-15 score < 122, which was classified as moderate or poor, had decreased muscle strength with relative risks of 1.75 and 2.33, respectively. All patients ambulated within 24 h after surgery. The incidence of quadriceps weakness possibly caused by nerve block was 13.3%; however, all patients could ambulate after 1 day.

Rhabdomyolysis associated with antimicrobial drug-resistant Mycoplasma pneumoniae.

We describe a case of rhabdomyolysis in a patient infected with antimicrobial drug-resistant Mycoplasma pneumoniae The patient's acute-phase serum levels of interleukin-18 and tumor necrosis factor-α were high, which suggests a pathogenic role for M. pneumoniae. In an era of increasing antimicrobial drug resistance, a system for rapidly identifying resistant M. pneumoniae would be beneficial.

Utility of Superb Microvascular Imaging in the Assessment of Foot Perfusion in Patients with Critical Limb Ischemia.

(1) Background: Although the ankle-brachial index (ABI) and skin perfusion pressure (SPP) are commonly used to evaluate the peripheral circulation in critical limb ischemia (CLI), they often cannot be performed on sore areas. We investigated the utility of superb microvascular imaging (SMI) for assessing foot perfusion in CLI patients. (2) Methods: We measured the SMI-based vascular index (SMI-VI) at six sites in the foot before and after endovascular treatment (EVT) in 50 patients with CLI who underwent EVT of the superficial femoral artery and compared the results with SPP values and the ABI. (3) Results: SMI visualized foot perfusion in all subjects in accordance with the angiosome, including the toe areas, while the ABI was unmeasurable in three patients on hemodialysis and SPP failed in four patients. SMI-VI values were significantly lower in the CLI group than in controls, and the plantar SMI-VI had the highest diagnostic performance for CLI (sensitivity 88.6%, specificity 95.6%). After EVT, the increase in the SMI-VI was positively correlated with the increase in SPP but not that in the ABI, implying that the SMI-VI reflects foot microcirculation. (4) Conclusions: SMI enables the visualization and quantification of foot microcirculation based on the angiosome. SMI has high utility as a tool for assessing foot perfusion in CLI.

Effect of NOciception Level-Directed analgesic management on Opioid usage in Robot-assisted laparoscopic radical prostatectomy (NOLDOR): study protocol for a single-centre single-blinded randomised controlled trial.

Background: The nociception level (NOL) index discriminates noxious stimuli during surgery with high sensitivity and specificity. Although some studies have reported that a NOL-directed opioid protocol reduces intraoperative opioid consumption, one study implied that it might cause an unintended increase in the stress response. Therefore, we designed a study to investigate the effects of the NOL-directed opioid protocol and measure inflammatory biomarkers. Methods: This single-centre RCT will enrol 54 patients undergoing robot-assisted laparoscopic radical prostatectomy. Eligible patients will be randomly allocated to receive (i) NOL-directed intraoperative opioid management (NOL group) or (ii) conventional intraoperative analgesic management (control group). The remifentanil infusion rate will be determined solely using the NOL index during surgery in the NOL group. The primary outcome will be the mean intraoperative remifentanil infusion rate. Secondary outcomes will include the plasma concentrations of three perioperative inflammatory biomarkers (interleukin-6, C-reactive protein, and cortisol) and the variation in the NOL index at the start of pneumoperitoneum and with postural changes. Conclusions: This study is expected to accumulate evidence on the effects of NOL-directed analgesic opioid protocol and provide additional evidence regarding the variability of stress responses and the character of the NOL index. Clinical trial registration: JRCTs052220034.

Sudden and severe cardiotoxicity induced with pembrolizumab, its clinical course, therapeutic intervention, and outcome.

Immune checkpoint inhibitors (ICIs), including cytotoxic T-lymphocyte associated antigen-4 inhibitors, and inhibitors of programmed cell death 1 and its ligand, are widely used in the treatment of several malignant tumors. Immune-related adverse events occur in two-thirds of recipients. Among them, cardiotoxicities are very rare (about 1%), albeit fatal. Pembrolizumab-induced cardiotoxicity in a patient was successfully treated with high-dose corticosteroids, and his cardiac function was maintained by adrenergic drugs and intra-aortic balloon pumping in the intensive care unit for 1 week. Cardiotoxicity with ICIs is an oncologic emergency, and should be managed in a pluridisciplinary setting involving cardiologists.

An advanced ultrasound application used to assess peripheral vascular diseases: superb microvascular imaging.

Over the past several years, a novel ultrasound imaging modality termed superb microvascular imaging (SMI) has enabled visualization of microvessels. SMI ultrasound studies of peripheral artery diseases have significantly extended our knowledge of tissue microcirculation and the arterial microenvironments of atherosclerotic lesions. We here present an overview of current knowledge on the utility of SMI assessment of vascular diseases and highlight certain peripheral microcirculation disorders for which SMI is particularly valuable. The evidence indicates that SMI can detect intraplaque neovascularization and usefully assess carotid plaque vulnerability; vascularization of the carotid arterial wall detected by SMI is a potential marker of disease activity in patients with Takayasu arteritis; SMI reveals the foot microcirculation and yields a quantitative vascular index (in line with the angiosome concept); and, SMI may serve as an auxiliary diagnostic modality for hereditary hemorrhagic telangiectasia and Raynaud syndrome. In general, microcirculatory evaluation by SMI is an attractive field for future research on therapeutic strategies for peripheral vascular diseases.