NRASQ61R-driven atypical melanocytic tumor with blue nevus-like morphology: A case report.

NRAS Q61 mutations are driver genetic alterations associated with common melanocytic nevi. Herein, we describe a case of NRAS-mutant melanocytic tumor with a blue nevus-like morphology. A 71-year-old Japanese man presented with a 4.6-mm nodule on his back. Histopathological examination revealed a dense distribution of spindle-shaped melanocytes in the upper dermis and a sparse distribution of dendritic melanocytes in the mid-dermis. The vertical periadnexal extension reached the deep dermis at the center of the tumor. A small junctional component, hyperpigmentation, sclerotic stroma, mild nuclear atypia, and a few mitotic figures were observed. Immunohistochemical examination revealed no PRAME expression and preserved p16 expression. Diffuse RASQ61R immunoreactivity was observed in these tumor cells. Nuclear ß-catenin expression was not observed. Targeted RNA sequencing revealed two mutations, NRAS c.182A>G (Q61R) and FGFR2 c.-157A>G, but no other pathogenic alterations such as BRAF, GNAQ, GNA11, CTNNB1, PRKAR1A, or IDH1 mutations or kinase gene fusions. The histopathology fits that of compound-type blue nevus, which is called "Kamino nevus"; however, this tumor was genetically considered to be on the spectrum of conventional acquired melanocytic nevi but not on that of blue nevi. Morphologically, NRAS-driven melanocytic nevi resemble blue nevi without IDH1R132C coexistence.

Computed tomography numbers obtained for varying iodine contrast concentrations by different-generation dual-energy computed tomography scanners.

We compared the computed tomography (CT) numbers from monochromatic images obtained using the first-generation (Discovery CT750 HD: GE Healthcare, Milwaukee, WI) and second-generation (Revolution CT: GE HealthCare) dual-energy CT (first and second DECT) scanners in phantom and clinical studies. In a polypropylene phantom, eight polypropylene tubes containing iodine at various concentrations (0.5, 1, 2, 5, 10, 12, 20, 30 mg I per ml) were arranged in an outer circle. The iodine densities and CT numbers obtained after imaging with different-generation DECT scanners were analyzed. The CT numbers from images obtained from 61 consecutive patients with aortic disease who underwent CT with different-generation DECT scanners were compared during the arterial and delayed phases. The iodine concentration obtained from second DECT was more accurate than that from the first DECT in the phantom study. A significantly higher contrast enhancement was observed with the second DECT compared with the first DECT during the arterial phase in the clinical study. Contrast enhancement was higher with the second DECT than with the first DECT, and the second DECT was effective in minimizing the use of contrast materials.

Fading and Color Reproducibility of Nipple-Areola Tattoos in Asian Patients.

Background The purpose of this study was to clarify fading, red, green, and blue values (RGB) change, and color reproducibility for nipple-areola complex (NAC) tattoos. Methods NAC tattooing was performed on 60 sites in 59 Japanese patients prospectively. The evaluation was assessed using digital photo, Casmatch standardization, and RGB and luminance values preoperatively, immediately after, 1 week, 1, 3, 6, and 12 months after tattooing. RGB and luminance values changes over time, time-adjusted fading rate, and the rate of luminance at 12 months were calculated. In color reproducibility study ( n = 34), RGB values after 12 months were compared with the color sample about dark/reddish and light/less reddish pigments. Results RGB varied widely from immediately after to 1 month after tattooing. For RGB and luminance, significant differences were seen between pre and immediate after, 1 and 3 months, 3 and 6 months, and 6 and 12 months. In G values, significant differences were seen between all neighboring points. The fading rate tended to decrease as time progresses, but was not significant, that is, fading continued even between 6 and 12 months. Luminance was 9% brighter than contralateral NAC at 12 months. Color reproducibility tended to be higher with dark/reddish pigments, despite no significant differences. Conclusion The fading rate of tattooed NACs tended to decrease as time progresses, but fading still occurs between 6 and 12 months. Luminance was 9% brighter than contralateral NAC at 12 months after.

Clinical impact of hyperbaric oxygen therapy combined with steroid treatment for sudden sensorineural hearing loss: A case-control study.

Objectives: The aim of present study was to evaluate the clinical efficacy of hyperbaric oxygen therapy (HBOT) as a primary therapy combined with standard systemic corticosteroid treatment for sudden sensorineural hearing loss (SSNHL) compared to treatment without the use of HBOT (non-HBOT) through clinical data and advanced analytical approaches. Study Design: Case-control study. Methods: Conducted across three Japanese medical centers involving 298 SSNHL patients diagnosed between 2020 and 2023. Inclusion criteria encompassed first onset and treatment, WHO grade 3 or 4 initial hearing impairment, receipt of systemic corticosteroid therapy within 14 days of symptom onset, and initiation of HBOT within the same timeframe for the case group. The primary outcome measure was the difference in hearing improvement (mean hearing level in decibels, dB) between the two groups, assessed by pure-tone audiometry at baseline and 3 months post-treatment, using the inverse probability of treatment weighting (IPTW) method adjusted for covariate differences. Results: The study included 67 patients in the HBOT group and 68 in the non-HBOT group. The HBOT group exhibited significantly greater hearing improvement (IPTW-adjusted difference: 7.6 dB, 95% CI 0.4-14.7; p = 0.038). Patients without vertigo in the HBOT group demonstrated substantial hearing improvement (11.5 dB, 95% CI 2.3-20.6; p = 0.014), whereas those with vertigo showed no significant improvement (-1.8 dB, 95% CI -11.8-8.3; p = 0.729). The HBOT group also had a significantly higher association with complete recovery (IPTW-adjusted odds ratio: 2.57, 95% CI 1.13-5.85; p = 0.025). Conclusion: In SSHNL, HBOT combination therapy yielded slightly but significantly improved hearing outcomes compared to non-HBOT treatment. Level of Evidence: 4.

A Dibenzo[g,p]chrysene-Based Organic Semiconductor with Small Exciton Binding Energy via Molecular Aggregation.

Exciton binding energy (Eb) is understood as the energy required to dissociate an exciton in free-charge carriers, and is known to be an important parameter in determining the performance of organic opto-electronic devices. However, the development of a molecular design to achieve a small level of Eb in the solid state continues to lag behind. Here, to investigate the relationship between aggregation and Eb, star-shaped π-conjugated compounds DBC-RD and TPE-RD were developed using dibenzo[g,p]chrysene (DBC) and tetraphenylethylene (TPE). Theoretical calculations and physical measurements in solution showed no apparent differences between DBC-RD and TPE-RD, indicating that these molecules possess similar properties on a single-molecule level.  By contrast, pristine films incorporating these molecules showed significantly different levels of electron affinity, ionization potential, and optical gap. Also, DBC-RD had a smaller Eb value of 0.24 eV compared with that of TPE-RD (0.42 eV). However, these molecules showed similar Eb values under dispersed conditions, which suggested that the decreased Eb of DBC-RD in pristine film is induced by molecular aggregation. By comparison with TPE-RD, DBC-RD showed superior performances in single-component organic solar cells and organic photocatalysts. These results indicate that a molecular design suitable for aggregation is important to decrease the Eb in films.

Engineering Escherichia coli for efficient glutathione production.

Glutathione is a tripeptide of excellent value in the pharmaceutical, food, and cosmetic industries that is currently produced during yeast fermentation. In this case, glutathione accumulates intracellularly, which hinders high production. Here, we engineered Escherichia coli for the efficient production of glutathione. A total of 4.3 g/L glutathione was produced by overexpressing gshA and gshB, which encode cysteine glutamate ligase and glutathione synthetase, respectively, and most of the glutathione was excreted into the culture medium. Further improvements were achieved by inhibiting degradation (Δggt and ΔpepT); deleting gor (Δgor), which encodes glutathione oxide reductase; attenuating glutathione uptake (ΔyliABCD); and enhancing cysteine production (PompF-cysE). The engineered strain KG06 produced 19.6 g/L glutathione after 48 h of fed-batch fermentation with continuous addition of ammonium sulfate as the sulfur source. We also found that continuous feeding of glycine had a crucial role for effective glutathione production. The results of metabolic flux and metabolomic analyses suggested that the conversion of O-acetylserine to cysteine is the rate-limiting step in glutathione production by KG06. The use of sodium thiosulfate largely overcame this limitation, increasing the glutathione titer to 22.0 g/L, which is, to our knowledge, the highest titer reported to date in the literature. This study is the first report of glutathione fermentation without adding cysteine in E. coli. Our findings provide a great potential of E. coli fermentation process for the industrial production of glutathione.

Prognosis of isolated locoregional recurrence after early breast cancer with immediate breast reconstruction surgery: a retrospective multi­institutional study.

BACKGROUND: The prognosis in patients with breast cancer with isolated locoregional recurrence (ILRR) without simultaneous distant metastases after immediate breast reconstruction (IBR) remains unknown. We aimed to investigate the prognosis in this patient population. METHODS: This multi-institutional retrospective observational study evaluated 3295 patients with primary breast cancer who underwent IBR at 12 Japanese medical facilities between January 1, 2008 and December 31, 2016. The outcome measures were the prognostic factors for ILRR after IBR, 5-year distant metastasis-free interval (DMFI), and 5-year overall survival (OS). RESULTS: Mastectomy or skin-sparing mastectomy was performed in 3295 patients. ILRR occurred in 70 patients, and the median observation period from ILRR diagnosis was 39.3 months. Of the 70 patients, 9 (12.9%) had axillary lymph node recurrence (ALNR) at the time of ILRR diagnosis. The 5-year DMFI and OS rates after ILRR were 92.4% and 91.2%, respectively. Pathological lymph node metastasis at primary surgery (P = 0.041) and ALNR (P = 0.022) at ILRR were significantly associated with DMFI in the univariate analysis. ALNR was the only independent prognostic factor in the multivariate analysis (P = 0.041). Post-mastectomy radiation therapy (PMRT; P = 0.022) and ALNR (P = 0.043) were significantly associated with OS in the univariate analysis, and both PMRT (P = 0.010) and ALNR (P = 0.028) were independent prognostic factors in the multivariate analysis for OS. CONCLUSIONS: Although patients with breast cancer who had ILRR after IBR have favorable prognosis, ALNR may lead to poor prognosis. To the best of our knowledge, this study is the first to report the prognosis of these patients.

Acute upper airway obstruction due to cervical hematoma after cervicofacial liposuction.

Liposuction is a surgical procedure performed worldwide. Although many fatal complications of liposuction have been reported, to our knowledge, no cases of fatal liposuction complications specifically related to the face region have been reported. Here, we present a case of a woman in her 30s who developed a cervical hematoma and upper airway obstruction following facial liposuction. We present this unique case to highlight the rare occurrence of fatal complications specific to facial liposuction. The patient underwent liposuction during surgery at a cosmetic surgical clinic and awoke from anesthesia after the procedure. Two hours later, she developed a neck swelling and dyspnea. While the anesthesiologist managed her airway, she went into cardiopulmonary arrest. She was then transferred to the emergency room but died on day 7 of hospitalization. The autopsy revealed swelling of the right cheek and mandible, a subcutaneous hematoma in the same area, and laryngeal edema. A damaged facial artery branch was identified, which was consistent with the computed tomography (CT) findings on admission. CT also showed that the hematoma compressed the right internal jugular vein, suggesting that venous outflow impairment caused by the hematoma may have exacerbated the airway obstruction. This case reveals that cervical hematoma caused by facial liposuction can cause fatal upper airway obstruction and the onset of the hematoma may be gradual.

Effect of distal metal species on lewis basicity of a µ3-oxo ligand in a doubly oxo-bridged (µ3-O)[Rh(cod)]3(µ4-O)M core.

The Lewis basicity of a µ3-oxo ligand for (µ3-O)[Rh(cod)]3(µ4-O)M (cod = 1,5-cyclooctadiene) complexes was controllable by metal species on the µ4-oxo ligand locating at the opposite site of the µ3-oxo ligand. Coordination of the µ3-oxo ligand of [(µ3-O){Rh(cod)}3(µ4-O){Au(PPh3)}][BF4] (1) to [Au(PPh3)]+ indicated sufficient Lewis basicity of the µ3-oxo ligand in 1 to form [{(Ph3P)Au}(µ3-O){Rh(cod)}3(µ4-O){Au(PPh3)}][BF4] (2). In contrast, the addition of Li+ to 1 induced elimination of the originally coordinated [Au(PPh3)]+ due to the weak Lewis basicity of the µ3-oxo ligand for (µ3-O){Rh(cod)}3(µ4-O)Li(THF)3, in which a pentanuclear species, [{(Ph3P)Au}(µ3-O){Rh(cod)}3(µ4-O){Li(THF)3}][BF4] (3), was assumed to be generated in situ before the dissociation of [Au(PPh3)]+.

Nipple-areolar complex malposition in breast reconstruction after nipple-sparing mastectomy: a multi-institutional retrospective observational study in Japan.

BACKGROUND: Position of the nipple-areolar complex (NAC) is an important factor in the esthetic impression of the breast, and NAC malposition is often an issue in breast reconstruction after nipple-sparing mastectomy (NSM). The purpose of this study was to evaluate the degree of NAC malposition depending on several factors using data quantified with the Mamma Balance application (Medic Engineering K.K., Kyoto, Japan). METHODS: Patients who underwent unilateral breast reconstruction after NSM at eight hospitals in Japan between 2007 and 2020 were retrospectively investigated. Using Mamma Balance, NAC malposition was quantified separately in horizontal and vertical directions using patient photographs from pre-operatively and 6-24 months post-operatively. The degree of malpositioning was then statistically compared using various factors. RESULTS: The NAC deviated more cranially and medially with implants than that with flaps. Cases with latissimus dorsi flap showed lateral malposition more often than cases with deep inferior epigastric artery perforator flap. With flaps, lateral incisions showed more lateral malposition, and peri-areolar incisions tended to show more medial NAC malposition. In cases with severe post-operative infection of the implant, the NAC tended to deviate cranially. In radiation cases, the NAC deviated cranially. No significant difference was observed according to the degree of breast ptosis or use of the pull-down operation. Only a very weak correlation was observed between a larger amount of mastectomy and more cranial NAC malposition with both flaps and implants. CONCLUSIONS: This study provides insights into the tendencies and characteristics of NAC malposition.

Impact of neoadjuvant chemotherapy on the safety and long-term outcomes of patients undergoing immediate breast reconstruction after mastectomy.

BACKGROUND: In breast cancer patients receiving neoadjuvant chemotherapy (NAC), immediate breast reconstruction (IBR) as a breast cancer treatment option remains controversial. We assessed the impact of NAC on surgical and oncological outcomes of patients undergoing IBR. METHODS: This was a retrospective multicenter study of 4726 breast cancer cases undergoing IBR. The rate of postoperative complications and survival data were compared between IBR patients who received NAC and those who did not receive NAC. Propensity score matching analysis was performed to mitigate selection bias for survival. RESULTS: Of the total 4726 cases, 473 (10.0%) received NAC. Out of the cases with NAC, 96 (20.3%) experienced postoperative complications, while 744 cases (17.5%) without NAC had postoperative complications. NAC did not significant increase the risk of complications after IBR (Odds ratio, 0.96; 95%CI 0.74-1.25). At the median follow-up time of 76.5 months, 36 patients in the NAC group and 147 patients in the control group developed local recurrences. The 5-year local recurrence-free survival rate was 93.1% in the NAC group and 97.1% in the control group. (P < 0.001). After matching, there was no significant difference between the two groups. CONCLUSION: IBR after NAC is a safe procedure with an acceptable postoperative complication profile.

[A framework for promoting and evaluating "Kayoi-no-ba" initiatives according to the Plan-Do-Check-Action cycle: The ACT-RECIPE framework].

Objective　In 2019, the Ministry of Health, Labour and Welfare emphasized the importance of promoting "Kayoi-no-ba" (or "places to go") initiatives according to the Plan-Do-Check-Action (PDCA) cycle. However, it proposed no specific promotion measures or standardized evaluation frameworks. This study is intended to propose a framework for local government officials to promote and evaluate "Kayoi-no-ba" initiatives according to the PDCA cycle.Methods　The working group (WG) conducted a narrative review of research and extracted evaluation models and indicators that could be used to create the framework. The co-researcher review committee discussed a draft framework prepared by the WG, and the WG revised it based on the discussion; this process was repeated four times. Using the completed framework, we calculated the score of the "Kayoi-no-ba" initiatives in 50 Tokyo municipalities and conducted regional correlation analyses on the relationship between the score of the "Kayoi-no-ba" initiatives in 50 Tokyo municipalities and the number of "Kayoi-no-ba" per 1,000 older persons.Results　The completed framework (named "ACT-RECIPE" by rearranging the underlined characters below) comprised the following six evaluation phases: (1) Comprehension: understanding the key lessons around disability and frailty prevention, and the necessity for "Kayoi-no-ba"; (2) Research and Planning: clarifying the current status of "Kayoi-no-ba," the strengths of the community, and the issues to be addressed through a community assessment, and developing a plan to resolve the issues; (3) Team Building and Collaboration: building a team by collaborating with organizations to solve problems; (4) Implementation: implementing the initiatives necessary to solve problems; (5) Evaluation: verifying changes in output and outcome indicators from the initiatives; and (6) Adjustment and Improvement: re-examining plans, teams, content, and goals based on the evaluation results. In these six phases, we designated 10 core items and accompanying subitems. The median score rate of the ACT-RECIPE framework in 50 municipalities was 75% for "Comprehension," 61% for "Research and Planning," 69% for "Team Building and Collaboration," 64% for "Implementation," 31% for "Evaluation," and 56% for "Adjustment and Improvement," and the mean ACT-RECIPE score rate was 57%. A significant positive correlation (rs=0.43, P=0.002) was observed between the ACT-RECIPE mean score rate and the number of "Kayoi-no-ba" per 1,000 older persons.Conclusion　We proposed the ACT-RECIPE as a framework for promoting and evaluating "Kayoi-no-ba" initiatives according to the PDCA cycle. We hope that this framework will lead to further progress in "Kayoi-no-ba" initiatives and facilitate evaluation of their effectiveness according to the PDCA cycle.

Impact of radiation therapy for breast cancer with involved surgical margin after immediate breast reconstruction: A multi-institutional observational study.

INTRODUCTION: Involved surgical margins are risk factors for local recurrence and re-excision is often difficult, particularly in patients with breast cancer undergoing immediate breast reconstruction (IBR). However, the magnitude of the effect of radiation therapy on preventing local recurrence for breast cancers with involved margins has not been sufficiently assessed. MATERIALS AND METHODS: We retrospectively assessed sites of involved surgical margins and local recurrence after mastectomy with IBR in patients with early breast cancer between 2008 and 2016. The effect of postoperative radiation therapy was evaluated in patients with involved margins, adjusted for nuclear grade, lymphatic invasion, surgical procedures, and primary systemic therapy. RESULTS: A total of 274 (5.8 %) out of 4726 patients who underwent mastectomy with IBR had involved surgical margins: 133, 68, 88, and 26 had involvement of the skin, deep margin, lateral margins, and nipple, respectively (including duplicates). Radiation therapy was administered to 54 patients with involved margins. In patients with involved margins, 7-year cumulative incidences of local recurrence were 1.9 % and 12.6 % with and without radiation therapy, respectively (adjusted hazard ratio, 0.17; 95 % CI, 0.04-0.80). Local recurrence occurred in 28 patients, and the sites were skin, subcutaneous tissue, muscle, and nipple-areola complex in 7, 17, 1, and 3 patients, respectively. Among them, 23 (82.1 %) were associated with involved margin sites. CONCLUSIONS: Radiation therapy meaningfully reduced the incidence of local recurrence in patients with breast cancer with margin involvement after mastectomy with IBR. Most local recurrences occurred at involved margin-related sites.

Anatomical features of a crossing vein connecting left and right internal mammary veins: A preliminary study with computerized tomography or magnetic resonance imaging.

BACKGROUND: In breast reconstruction with free flaps, retrograde venous anastomosis into the internal mammary vein (IMV) is often unavoidable. Utility of a crossing vein between the right and left IMV, one of the anatomical foundations which make retrograde flow possible, has been reported but only with a few detailed features. This study evaluated the presence, actual location, and diameter of the crossing veins using preoperative imaging such as contrast-enhanced computed tomography (CECT), or contrast-enhanced magnetic resonance imaging (CEMRI). Moreover, this is a preliminary non-invasive study to clarify these processes on a larger scale. METHODS: We included 29 cases of unilateral breast reconstruction performed between July 2018 and September 2023 at our institution using unipedicled or bipedicled free deep inferior epigastric artery perforator (DIEP) flaps with retrograde venous anastomosis to only one IMV at the level of anastomosis. No congestion or necrosis was observed. In the final 24 cases with sufficient imaging coverage of preoperative contrast-enhanced images (15 CECT and 9 CEMRI), the crossing veins of IMVs were detected and the number, localization, and diameter were measured. RESULTS: In 20 cases of 24 images, the crossing veins between IMVs were completely identified (83%). In 18 of the cases, only one crossing vein was established immediately ventral to the xiphoid process, averaging 19.3 ± 7.18 mm caudal to the fibrous junction between the sternal body and xiphoid process. The average diameter of the veins was 1.57 ± 0.42 mm. In two other cases, the second crossing vein originated on the dorsal surface of the sternum, but it was a very thin vein of about 0.4 mm. Three images indicated incomplete identification of the crossing vein at the xiphoid process, and in one case, no crossing vein was observed between bilateral IMVs. CONCLUSION: The contrast-enhanced imaging study revealed an anatomic feature that the crossing veins (about 1.5 mm in diameter) connecting the right and left IMVs are located just ventral to the xiphoid process. Furthermore, the crossing veins can be identified on contrast-enhanced images, and refinement of this method is expected to lead to future non-invasive anatomical investigations in an even larger number of cases.

Objective Assessment of the Repeated Botox Treatment to the Synkinesis of Facial Paralysis by the Integrated Electromyography.

BACKGROUND: The widely used botox type A (BTX-A) is effective against synkinesis in facial palsy sequelae. Repeated injections are necessary and permanent improvements have been reported. We objectively evaluated the changes in synkinesis at >6 months after BTX-A injection, including changes over time with the number of administrations. METHODS: In 48 patients who received multiple BTX-A injections, evaluation by the Sunnybrook Facial Grading System (FGS) and integrated electromyography (iEMG) was performed before treatment and at least 6 months after the first, second, and third BTX-A injection. The iEMG ratio on the affected and healthy sides was calculated for each mimetic muscle and mimic motion. RESULTS: There was no significant difference in the FGS synkinesis score before treatment and after the third injection, although an improvement was observed. The iEMG ratio was significantly improved in the orbicularis oculi with open-mouth smile and lip pucker after the third dose compared to before treatment. The orbicularis oris showed a significant improvement when the eyelids were closed, while the platysma showed a significant improvement when the eyelids were closed and when the lip was pursed. Multiple regression analysis revealed that the orbicularis oculi and platysma had a greater effect on the iEMG ratio for the number of treatments than other factors. CONCLUSIONS: Repeated BTX-A injections showed improvements in synkinesis for the orbicularis oculi, orbicularis oris, and platysma, even after >6 months, compared to before treatment.

Metastatic Lymph Node Detection on Ultrasound Images Using YOLOv7 in Patients with Head and Neck Squamous Cell Carcinoma.

Ultrasonography is the preferred modality for detailed evaluation of enlarged lymph nodes (LNs) identified on computed tomography and/or magnetic resonance imaging, owing to its high spatial resolution. However, the diagnostic performance of ultrasonography depends on the examiner's expertise. To support the ultrasonographic diagnosis, we developed YOLOv7-based deep learning models for metastatic LN detection on ultrasonography and compared their detection performance with that of highly experienced radiologists and less experienced residents. We enrolled 462 B- and D-mode ultrasound images of 261 metastatic and 279 non-metastatic histopathologically confirmed LNs from 126 patients with head and neck squamous cell carcinoma. The YOLOv7-based B- and D-mode models were optimized using B- and D-mode training and validation images and their detection performance for metastatic LNs was evaluated using B- and D-mode testing images, respectively. The D-mode model's performance was comparable to that of radiologists and superior to that of residents' reading of D-mode images, whereas the B-mode model's performance was higher than that of residents but lower than that of radiologists on B-mode images. Thus, YOLOv7-based B- and D-mode models can assist less experienced residents in ultrasonographic diagnoses. The D-mode model could raise the diagnostic performance of residents to the same level as experienced radiologists.