A Survey on the Safety of and Patient Satisfaction After Nipple-Areola Tattooing.

BACKGROUND: Nipple-areolar tattooing is well accepted as part of breast reconstruction, but the clinical data on its safety and patient satisfaction after the procedure are insufficient. We aimed to evaluate the complications of and patient satisfaction after nipple-areola tattooing in Japanese post-mastectomy breast reconstruction patients. METHODS: Patients who visited our center after undergoing nipple-areola tattooing from January 2017 to March 2020 were given an unmarked questionnaire with questions about complications related to their nipple-areola tattoo. Patients' registered their subjective evaluation responses regarding nipple-areola appearance using visual analog scale and that regarding overall satisfaction using 5-point Likert scale and free-text responses. Patients who were followed up within 6 months after tattooing or those with incomplete data were excluded. RESULTS: Sixty-two patients (average age: 49.7 ± 9.8 years), with an average post-tattooing period of 21.2 ± 10.5 months, were included. No patient had infections or allergic reactions. The average VAS score for nipple-areola appearance was high (8.5), and 59 patients (95.3%) answered that they were satisfied. In the free-text patient responses, 25 patients answered that they now felt comfortable going to the hot spring or taking a bath with their children, and 19 patients reported improved mental health after the procedure. CONCLUSION: Post-breast reconstruction nipple-areola tattooing with sterilized inorganic pigments could achieve high esthetics and patient satisfaction, without serious complications. It is recommended for Japanese individuals with a culture of visiting hot springs and public baths. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each submission to which evidence-based medicine rankings are applicable. This excludes review articles, book reviews, and manuscripts that concern basic science, animal studies, cadaver studies, and experimental studies. For a full description of these evidence-based medicine ratings, please refer to the table of contents or the online instructions to authors www.springer.com/00266 .

Color Change After Paramedical Pigmentation of the Nipple-Areola Complex.

BACKGROUND: Reconstruction of the nipple-areola complex is the final process in breast reconstruction. Local flaps and paramedical pigmentation is one of the major procedures for this. However, fading after paramedical pigmentation leads to a color difference between the selected pigment and its color in the skin. The aim of this study is to make a proposition in color choice of paramedical pigmentation for nipple-areola complex. METHODS: Our research focused on investigating the color changes over time after unilateral nipple-areola complex reconstruction using paramedical pigmentation in 25 patients to propose suitable color selections. We measured the color by spectrometer and conducted comparisons using the hue, saturation, and value (HSV) color space and the color space defined by the Commission International de L'eclairage based on one channel for luminance (lightness) (L) and two color channels (a and b) (L*a*b*). RESULTS: A comparison of the hue, value, and saturation of the reconstructed areola compared to the normal areolae was conducted using HSV color space; the value and saturation were satisfactory after 3 months and beyond, but the reconstructed areola tended to have stronger red hues. The color difference (ΔE00) calculated in L*a*b* color space showed slow fading after the scab was peeled off. CONCLUSIONS: This result indicates that a color with less redness and more yellowness, particularly 4-5 degrees of yellowness on the color wheel, than the normal side is the most appropriate color selection for this technique. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Neutrophil gelatinase-associated lipocalin regulates gut microbiota of mice.

BACKGROUND AND AIM: Because neutrophil gelatinase-associated lipocalin (NGAL) is known to provide significant bacteriostatic effects during infectious conditions, we tested the hypothesis that this protein is up-regulated and secreted into the intraluminal cavity of the gut under critically ill conditions and is thus responsible for the regulation of bacterial overgrowth. METHODS: With our institutional approval, male C57BL/6J mouse (6-7 weeks) were enrolled and applied for lipopolysaccharide or peritonitis model compared with naïve control. We assessed NGAL protein concentrations in intestinal lumen and up-regulation of NGAL expression in intestinal tissues in in vivo as well as ex vivo settings. Simultaneously, we examined the effects of NGAL protein administration on the growth of Escherichia coli (E. coli) in in vivo and in vitro experimental settings. The localization of NGAL in intestinal tissues and lumen was also assessed by immunohistological approach using NGAL antibody. RESULTS: Both lipopolysaccharide and peritonitis insults evoked the marked up-regulation of NGAL mRNA and protein levels in gut tissues such as crypt cells. In addition, the administration of NGAL protein significantly inhibited the outgrowth of enteric E. coli under both in vitro and in vivo conditions, accompanied by histological evidence. CONCLUSION: Neutrophil gelatinase-associated lipocalin protein accompanied by apparent bacteriostatic action accumulated in the intestinal wall and streamed into the mucosal layer during critically ill state, thereby possibly shaping microbiota homeostasis in the gut.

The effects of epidural anesthesia on growth of Escherichia coli at pseudosurgical site: the roles of the lipocalin-2 pathway.

BACKGROUND: Neutrophil-derived lipocalin-2 exerts bacteriostatic effects through retardation of iron uptake by the Gram-negative organisms like Escherichia coli. We tested the hypothesis that the expression of lipocalin-2, a bacteriostatic protein, was upregulated by induction of surgical site infection (SSI) with E coli in healthy and diseased rats and that epidural anesthesia modulated its expression. METHODS: Male Wistar rats were randomized into a healthy or disease group, the latter of which was administered lipopolysaccharide. Both groups were further divided into 3 subgroups, the control, saline, and lidocaine groups: group healthy control (n = 10), healthy saline (n = 10), and healthy lidocaine (n = 10) versus group disease control (n = 15), disease saline (n = 18), and disease lidocaine (n = 19), respectively. While saline was epidurally administered to the control and saline groups, lidocaine was administered to the lidocaine groups. Except for the control groups, E coli was injected to the pseudosurgical site to mimic SSI after abdominal surgery. Plasma concentrations of inflammatory cytokine and lipocalin-2 were measured. At 72 hours, the surgical site tissues were obtained to evaluate mRNA expression of lipocalin-2 and E coli DNA expression. RESULTS: All disease subgroups showed markedly increased plasma inflammatory cytokines versus the healthy subgroups. Among the disease subgroups, plasma concentrations of lipocalin-2 and tissue mRNA expression of lipocalin-2 were significantly increased in group disease lidocaine versus the others. Concurrently, E coli DNA expression in the tissue specimens was also significantly lower in group disease lidocaine as compared with group disease saline. CONCLUSIONS: Epidural anesthesia was associated with an increase in the expression lipocalin-2 and a decrease in the expression of E coli DNA at pseudosurgical sites in sick but not healthy rats. These observations suggest a potential mechanism by which epidural anesthesia could reduce the risk of SSI.

An evaluation of the best practices and barriers for the Nagasaki acute myocardial infarction secondary prevention clinical pathway.

AIMS: The Nagasaki Acute Myocardial Infarction Secondary Prevention Clinical Pathway (NASP), a guideline-based regional clinical pathway, was developed to manage low-density lipoprotein cholesterol levels for patients with acute myocardial infarction (AMI) in the Nagasaki prefecture in Japan. This study aimed to summarize the perceived best practices and barriers for the dissemination and operation of the NASP. METHODS: This exploratory sequential mixed methods study was developed around the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework. Focus group interviews were conducted with 24 physicians with experience treating AMI in alignment with the NASP at foundation hospitals. The identified themes and insights were integrated into the development of the questionnaire. The web-based, self-administered questionnaire with a cross-sectional study design was given to 62 physicians in the Nagasaki prefecture. Mixed-method data integration of the results from both study phases was conducted through meta-inferences made from the qualitative and quantitative data. RESULTS: The best practices included the development of multi-disciplinary operation teams at medical facilities in preparation for the implementation of the NASP, the simplification of the document preparation process, and the establishment of an additional medical fees policy for the utilization of the NASP instead of patient referral documents. Practices tailored to the type of medical institute such as instructing patients on the NASP regimen during index hospitalization for acute-care hospitals, and the development of NASP instructions and manuals for primary care hospitals/outpatient clinics were also recommended. In addition, barriers to the implementation of the NASP such as missed eligible AMI patients for the NASP and the inconsistent implementation to eligible AMI patients were identified. CONCLUSIONS: This study identified the perceived best practices and barriers for the NASP. This knowledge should be considered when expanding the NASP to other institutions across Japan.

[Regional anesthesia and cancer immunology].

Regional anesthesia has been widely applied as an excellent method for perioperative analgesia. Recent studies suggested that regional anesthesia is a promising approach to minimize the risk of surgical site infection and postoperative cancer recurrence, subsequently providing the benefits to the long-term outcome. In particular, it is of great interest that regional anesthesia might be able to reduce cancer recurrence. In cancer patients, innate immunity against cancer could be depressed, resulting in the predisposition to evoke metastasis. Besides, during the perioperative periods, tumor immunity is significantly depressed due to surgical pain, activation of sympathetic nervous system, inflammatory responses, and others. In this review article, we discuss the tumor immunity during the perioperative period, with focus on the alterations of tumor immunity and regional anesthesia.

Complications of permanent makeup procedures for the eyebrow and eyeline.

ABSTRACT: Japan is one of the few countries that consider the application of permanent makeup a medical procedure, and only doctors and nurses are allowed to perform this procedure. Studies on the safety and esthetic outcomes of permanent makeup procedures are not available, although there are studies that report allergies and other complications associated with permanent makeup. Thus, we aimed to study the complications and esthetic outcomes of permanent makeup.We surveyed clients who underwent permanent eyebrow or eyeline makeup procedures at the Shibuya Mori Clinic between November 2016 and March 2020 using a paper-based questionnaire. The permanent makeup procedures involved inorganic pigments, such as iron oxide and titanium dioxide. The questionnaire consisted of 2 parts: the first part asked whether the clients had experienced persistent redness, itching, swelling, infection, or any other complications (multiple answers possible). The second part used a 5-point Likert scale to rate the clients' satisfaction with the color, shape, and overall appearance of their permanent makeup. We retrospectively studied the clients' responses to survey items.A total of 1352 clients participated in the survey. The median period between the procedure and survey response was 15 days. Overall, complications were reported in 12.1% of cases. The most common complication for each type of procedure was itching for eyebrow procedures (8.2%) and swelling for eyeline procedures (13.2%). Infections were reported in 3 cases (0.2%). None of the post-procedure symptoms persisted until the time of this study. The Likert scale measurements revealed that 89.6% of subjects were satisfied with the aesthetic outcome of their permanent makeup procedure(s).We believe that all symptoms observed in this study were due to needle insertion. No allergies were observed, and the infection rate was quite low (0.2%). Thus, our results suggest that permanent makeup procedures are safe and are associated with high client satisfaction. We must note that the appropriate environment, equipment, and techniques are important prerequisites.

Mapping the Kansas City Cardiomyopathy Questionnaire (KCCQ) Onto EQ-5D-3L in Heart Failure Patients: Results for the Japanese and UK Value Sets.

Background. Health technology assessment bodies in several countries, including Japan and the United Kingdom, recommend mapping techniques to obtain utility scores in clinical trials that do not have a preference-based measure of health. This study sought to develop mapping algorithms to predict EQ-5D-3L scores from the Kansas City Cardiomyopathy Questionnaire (KCCQ) in patients with heart failure (HF). Methods. Data from the randomized, double-blind PARADIGM-HF trial were analyzed, and EQ-5D-3L scores were calculated using the Japanese and UK value sets. Several different model specifications were explored to best fit EQ-5D data collected at baseline with KCCQ scores, including ordinary least square regression, two-part, Tobit, and three-part models. Generalized estimating equations models were also fitted to analyze longitudinal EQ-5D data. To validate model predictions, the data set was split into a derivation (n = 4,465) from which the models were developed and a separate sample (n = 1,892) for validation. Results. There were only small differences between the different model classes tested. Model performance and predictive power was better for the item-level models than for the models including KCCQ domain scores. R 2 statistics for the item-level models ranged from 0.45 to 0.52. Mean absolute error in the validation sample was 0.10 for the models using the Japanese value set and 0.114 for the UK models. All models showed some underprediction of utility above 0.75 and overprediction of utility below 0.5, but performed well for population-level estimates. Conclusions. Using data from a large clinical trial in HF, we found that EQ-5D-3L scores can be estimated from responses to the KCCQ and can facilitate cost-utility analysis from existing HF trials where only the KCCQ was administered. Future validation in other HF populations is warranted.

Persistent hyperglycemia modulates gut immune function and microbiota in rats.

BACKGROUND: Since hyperglycemia-induced cellular dysfunction could be associated with alterations of the immune system, we tested the hypothesis that hyperglycemia augments the aberrant immune responses such as inflammation and differentiation of CD4(+) T lymphocytes in the mesenteric lymph nodes (MLNs), and induces alterations of microbiota both under physiological and pathological conditions. METHODS: Male Wistar rats were randomly allocated into 4 groups: Control and Endotoxemia (lipopolysaccharide, LPS 1 mg/kg) with or without hyperglycemia. The hyperglycemia groups were administered glucose solution (10-40 %), while the normoglycemia groups were administered saline. Alterations of the mRNA expressions of inflammatory cytokines and CD4(+) T lymphocyte transcriptional factor expressions in the MLNs, and those of the intestinal microbiota were analyzed at 24 hr. RESULTS: Hyperglycemia was kept approximately 250-350 mg/dL during the 24 hr study period. At the end of 24 hr, hyperglycemia augmented the mRNA expressions of interleukin (IL)-1ß and IL-6 in the MLNs, while both the helper T (Th) 2 and regulatory-T (Treg) transcriptional factors were simultaneously up-regulated under non-endotoxemic condition. LPS injection significantly modulated the obligate anaerobe bacterial populations of the Bacteroidetes class, and altered the population sizes of the Clostridium perfringens and the Bacteroides fragilis subgroup. Hyperglycemia did not enhance these alterations of the microbiota evoked by LPS, although it did modify the bacterial populations of the L. reuteri subgroup and staphylococci in healthy condition without endotoxemia. CONCLUSIONS: The present study indicates that both gut immune function and microbiota are significantly modulated by persistent hyperglycemia.

Increased prothrombotic property as a risk factor of acute kidney injury after surgical repair of abdominal aortic aneurysm: a prospective observational study.

BACKGROUND: Acute kidney injury (AKI) is one of the major morbidities after surgical repair of abdominal aortic aneurysm (AAA); however, precise pathogenesis of this morbidity has not been well determined. Since prothrombotic coagulation abnormality may precede organ dysfunction in systemic inflammatory state, we examined the kinetics of von Willebrand factor (VWF) and a disintegrin-like metalloprotease with thrombospondin type 1 motif 13 (ADAMTS13), a cleaving enzyme of VWF, on the development of AKI after AAA surgery. METHODS: The kinetics of ADAMTS13 and VWF were examined in ten patients who underwent surgical repair of AAA. The changes in plasma neutrophil gelatinase-associated lipocalin (NGAL), a novel biomarker for AKI, and serum creatinine concentration were also examined at four points until seventh postoperative day (POD). Clinical diagnosis of AKI was based on the change in serum creatinine concentration and urine output according to Acute Kidney Injury Network (AKIN) criteria. RESULTS: ADAMTS13 activity was significantly lower than normal level before the surgery and showed a trend of decrease toward 3POD. The VWF/ADAMTS13 ratio showed a significant increase on 1POD, which persisted until 7POD. None of patents was diagnosed as AKI based on AKIN criteria, although two patients received furosemide and/or carperitide therapy because of decreased urine output less than 0.5 ml/kg/h for several hours in ICU. Plasma NGAL showed a trend to increase after the surgery, which was significant on 3POD. The change in plasma NGAL was significantly correlated with VWF/ADAMTS13 ratio (P < 0.01). CONCLUSIONS: This study has shown that patients undergoing AAA surgery were prothrombotic after the surgery because of high VWF/ADAMTS13 ratio. Correlation between VWF/ADAMTS13 ratio and NGAL might indicate contribution of thrombotic event to subclinical AKI in the patients undergoing AAA surgery.

Beta-1 blocker improves survival of septic rats through preservation of gut barrier function.

OBJECTIVE: Since recent study demonstrated beneficial effects of ß-adrenergic blocker in sepsis, we tested the hypothesis that infusion of selective ß1-blocker, esmolol, improves outcome in sepsis by modulating inflammatory responses and gut barrier function. DESIGN: Prospective randomized animal study. SETTING: University research laboratory. SUBJECTS: Male Wistar rats. INTERVENTIONS: To assess the effects of esmolol infusion on survival time, 19 animals that underwent cecal ligation and perforation were randomized into control (n = 9) or esmolol (n = 10) groups, the latter of which received esmolol infusion (15 mg/kg/h) throughout the study period. In an additional 20 animals, levels of tumor necrosis factor-α (TNF-α) in both plasma and intraperitoneal fluid were measured, and mesenteric lymph nodes (MLNs) and ileum were excised for evaluation of bacterial translocation and mucosal injury at the 18-h study period. MEASUREMENTS AND RESULTS: Mean survival time in the esmolol group was significantly longer compared with the control group (69.5 ± 26.8 versus 28.6 ± 11.0 h). Plasma TNF-α was not detectable in either group, while intraperitoneal fluid TNF-α level was elevated in the control group but significantly depressed in the esmolol group (16.8 ± 10.7 versus 5.4 ± 7.1 pg/ml, P < 0.05). Simultaneously, the Escherichia coli positive rate of MLNs was higher (100% versus 44%, P < 0.05) and the gut mucosal injury score was elevated (4.1 ± 0.6 versus 2.8 ± 0.6, P < 0.01) in the control compared with the esmolol group. CONCLUSIONS: Beta-1 blocker therapy improves outcome in sepsis possibly through modulation of gut mucosal integrity and local inflammatory response.

Peroxidase-like catalytic activity of aqueous- and immobilized-Mn(3+)-octabromo-porphyrins on ion-exchange resin supplied as mimetic of horseradish peroxidase.

In order to explore the capability of metal porphyrins as an alternative of horseradish peroxidase (HRP), HRP-like activity of three manganese-porphyrins (Mn-Ps) and three Mn-octabromo-porphyrins (Mn-OBPs) was examined in both aqueous and immobilized states. It was found that Mn(3+)-octabromotetrakis(1-methyl-pyridinium-4yl)porphine (Mn-OBTMPyP) has an activity of at least 90% of HRP in an aqueous solution. Mn-OBTMPyP exhibited a catalytic activity even in the presence of hydrogen peroxide without suicide reaction. In addition, Mn-OBTMPyP was revealed to function as an alternative to HRP in the quantitative determination of serum uric acid. These results are of great interest because they indicate that metal-octabromo-porphyrins possibly include promising candidates of artificial enzyme capable of substituting for HRP.