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This article covers the salient and updated themes of the Japanese Pediatric Guidelines for the Treatment and Management of Asthma (JPGL) 2020 published by the Japanese Society of Pediatric Allergy and Clinical Immunology. In the 2020 guidelines, five new clinical questions (CQs) have been added to address the 12 CQs regarding the treatment of childhood asthma. "Infant and preschool asthma" is diagnosed when young children (6 years of age) have three or more episodes of clear expiratory wheezing, which continue for more than 24 h, and symptom improvement can be observed after beta-2 agonist inhalation. In children without clear improvement, diagnostic therapeutic trial for the duration of 1 month with controller treatment can be used. Since long-term management is initiated, the treatment level is adjusted based on the current control status and the management of risk factors, with the provision for holistic care. This underscores the smooth transition of pediatric patients into adult services. There are several differences between the JPGL and the guidelines of other countries. Further evidence is obtained as the utility of the newly proposed management plans should be evaluated in the Japanese population.

Peritoneal lavage cytology is widely used to predict peritoneal recurrence after surgery, but cases of peritoneal recurrence are often recognized in patients with peritoneal lavage cytology negativity (CY0) who underwent no residual tumour (R0) surgery. We used peritoneal lavage fluid before and after gastric cancer surgery to detect cytokeratin 20 (KRT20) and carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) mRNA by RT-PCR.We collected peritoneal lavage fluid before and after surgery from 58 patients who underwent gastrectomy. RNA was extracted from these samples and RT-PCR was performed. RNA expression was defined as positive and negative in cases with values higher or lower than the median value. We investigated the relationship between mRNA expression and clinicopathological and surgical factors and prognosis.Tumour invasion to the sub-serosa (T3) or penetration of the serosa (T4a), lymph node metastasis, and more than 150 ml intraoperative bleeding were significantly correlated with KRT20 mRNA expression. Multivariate analysis of its relationship with peritoneal recurrence showed that the odds ratio of CEACAM6 mRNA for recurrence was high (odds ratio=24.753; 95%CI=0.883-694.06; p=0.0592). All cases with peritoneal recurrence were CEACAM6-positive at pre- or post-surgery. The prognosis of peritoneal recurrence for both KRT20- and CEACAM6-positive cases was significantly poorer than that of other cases. The recurrence-free survival of the CEACAM6-positive group was significantly poorer than that of the CEACAM6-negative group.Measurement of CEACAM6 mRNA in peritoneal lavage fluid at pre- and post-surgery may be useful as a predictor of peritoneal recurrence.

Long-acting muscarinic antagonists (LAMA) are used for long-term treatment of bronchial asthma in adults. Its use in the management of pediatric bronchial asthma, however, is currently not approved in Japan. Nonetheless, there have been a few reports of its use in children, particularly in cases of severe bronchial asthma or those without atopic disease that are refractory to existing treatment protocols. We report the progress of LAMA in infantile asthma patients.Three out of four patients had LAMA introduced at 3 to 5 years of age after being diagnosed with asthma at 1 to 3 years old. Three patients had non-IgE-related asthma and an underlying disease, such as Apert and Noonan syndrome, while one patient had severe IgE-related asthma without a pre-existing disease. In all cases, conventional long-term medications such as medium to high-dose inhaled corticosteroids and long-acting beta-agonists, were given. However, severe bronchial asthma persisted, with some patients having uncontrolled secretions. Since uncontrolled severe-persistent bronchial asthma results in repeated hospitalization and intensive care unit admission, we introduced LAMA, specifically 2.5μg/day of tiotropium (Tio). After the introducing Tio, none of the patients had an acute exacerbation that required hospitalization and the frequency of wheezing was reduced. LAMA was administered for up to 19 months, with no adverse events.The results of this series suggest that LAMA is an effective and safe option for uncontrolled infantile asthma.

Background Robotic gastrectomy (RG) is being increasingly performed globally; it is considered an evolved type of conventional laparoscopic surgery with excellent dexterity and precision, but higher costs and longer operation time. Thus, there is a need to identify the benefits from RG and its specific candidates. Methods This retrospective study analyzed data from a prospectively collected clinical database at our center. Data of patients with primary gastric cancer undergoing either robotic or laparoscopic radical gastrectomy from June 2014 to June 2020 were reviewed. Surgical outcomes were compared between the two groups, and multivariable analyses were performed to elucidate the relevant factors for postoperative complications in several subgroups. Results A total of 1172 patients were divided into those who underwent RG (n = 152) and those who underwent laparoscopic gastrectomy (LG) (n = 1020). Baseline characteristics were similar in the two groups, except the RG group included more patients undergoing total/proximal gastrectomy (TG/PG) and patients at clinical stage III. Compared with the LG group, the RG group had lower incidences of postoperative complications ≥ Clavien-Dindo grade III (2/152 (1.3%) versus 72/1020 (7.1%); P = 0.004), and intraabdominal complications ≥ grade II (6/152 (3.9%) versus 119/1020 (11.7%); P = 0.004). Multivariable analysis revealed that RG was a significant relevant factor for reducing overall postoperative complications (≥ grade III) (odds ratio (OR) 0.16, P = 0.013), and intraabdominal complications (≥ grade II) (OR 0.29, P = 0.002). Subgroup analyses demonstrated that this tendency was enhanced in patients undergoing TG/PG (OR 0.29, P = 0.021) or at clinical stage II/III (OR 0.10, P = 0.027). Conclusions RG reduces the incidence of postoperative complications compared with conventional LG and this tendency may be enhanced in technically complicated procedures with demanding anastomosis or D2 lymphadenectomy. Patients requiring such procedures would most benefit from RG.

Background Robotic distal gastrectomy (RDG) has been increasingly used for the treatment of gastric cancer (GC). However, whether RDG has a clinical advantage over laparoscopic distal gastrectomy (LDG) is yet to be determined. Thus, this study aimed to assess the feasibility and safety of RDG for the treatment of GC as compared with LDG. Methods In total, 157 patients were enrolled between February 2018 and August 2020 in this retrospective study. We then compared the surgical outcomes between RDG and LDG using propensity score-matching (PSM) analysis to reduce the confounding differences. Results After PSM, a clinicopathologically well-balanced cohort of 100 patients (50 in each group) was analyzed. The operation time for the RDG group (350.1 ± 58.1 min) was determined to be significantly longer than that for the LDG group (257.5 ± 63.7 min; P P = 0.092 and P = 0.061, respectively). In addition, postoperative hospital stay was statistically slightly shorter in the RDG group as compared with the LDG group (12.0 ± 5.6 vs. 13.0 ± 12.3 days; P = 0.038). Conclusions Our study confirmed that RDG is a feasible and safe procedure for GC in terms of short-term surgical outcomes. A surgical robot might reduce postoperative severe complications and length of hospital stay.

Fish allergy is generally thought to be persistent, and approximately 80% of patients with fish allergies do not develop tolerance even 10 years after diagnosis. There have been no reports of rapid tolerance development in patients with severe fish allergies. We report the development of tolerance 16 months after the diagnosis of fish allergies. A 13-month-old boy was diagnosed with rosefish allergy (Sebastes matsubarae) and Japanese jack mackerel allergy (Trachurus japonicus). To find out which species of fish he could consume safely, he under-went several oral food challenge (OFC) tests. It was determined that he could consume tuna, salmon, cod, sardine, chub mackerel (Scomber japonicus), and Japanese amberjack (Seriola quinqueradiata) without eliciting signs of allergy. He continued to eat the fish that did not produce allergic reactions three to four times a week. The titer of serum allergen-specific immunoglobulin E (IgE) to fish had decreased in a subsequent ImmunoCAP®-specific IgE blood test performed 16 months after the diagnosis of the rosefish allergy. Following this test result, he underwent OFCs with rosefish and Japanese jack mackerel, both of which turned out to be negative, and it was determined that he had developed tolerance to fish. In this case, the repeated OFCs were useful in identifying fish species that were safe for consumption. In addition, the decrease in allergen-specific IgE was useful in predicting the development of tol-erance. We hypothesize that proactive consumption of available fish species may lead to this rapid induction of tolerance to fish allergens.

A 13-year-old male patient suffered several episodes of anaphylaxis during exercise after consuming wheat. Provocation tests (consisting of exercise after wheat ingestion) were conducted twice at our hospital. Both tests were positive, resulting in a diagnosis of food-dependent exercise-induced anaphylaxis (FDEIA) due to wheat. The patient was instructed to avoid exercise after wheat ingestion. The patient had also been previously diagnosed with idiopathic chronic urticaria, which was treated with antihistamines and leukotriene receptor antagonists. Since the idiopathic chronic urticaria worsened despite the use of these medications, 300 mg per four weeks of omalizumab was initiated. The patient's symptoms improved, and a third provocation test came back negative. The patient was asymptomatic without exercise restriction when treated with omalizumab. Omalizumab is not typically prescribed for treating food allergies and EIA in Japan; however, there are some reports on their effectiveness in treating them, suggesting omalizumab may also be helpful in resolving FDEIA symptoms.

The Japanese Guideline for Childhood Asthma (JGCA) 2020 is a translation of the Japanese Pediatric Guideline for the Treatment and Management of Asthma (JPGL) 2017 into English, which was published by the Japanese Society of Pediatric Allergy and Clinical Immunology. It makes recommendations for best practices in the management of childhood asthma, including management of acute exacerbations and non-pharmacological and pharmacological management. These guidelines will be of interest to non-specialist physicians involved in the care of children with asthma. In JPGL, JPGL2017 is the first evidence-based guidelines updated according to the GRADE system and Minds approach, and it addresses eight clinical questions about the treatment of childhood asthma. In children aged ≤5 years, infant and preschool asthma is diagnosed according to the response to short acting beta2 agonists or the effect of a therapeutic trial during 1 month with controller treatment and worsening after treatment cessation. Long-term management both promotes pharmacological therapy and measures against risk factors that induce exacerbation, better patient education and a partnership with trinity. In addition, long-term management should not be carried out without review but rather be based on a cycle of evaluation, adjustment and treatment. In JPGL2017, the transdermal patch and oral beta2 agonists are positioned as drugs within the concept of "short-term additional treatment" to be used until the symptoms are stabilized when the control state transiently deteriorates.

Acquired factor X deficiency (AFXD) is a very rare coagulation disorder. A 40-year-old man with no comorbidities suffering from a fever, malaise, and severe hemorrhagic symptoms, including massive hematuria, was emergently admitted. His platelet count was normal, but his prothrombin time and activated partial thromboplastin time were markedly prolonged, which was thought to be due to autoantibody against a coagulation factor in the common pathway. Despite severe massive hematuria resulting in transient renal failure, he was successfully treated with urgent immunosuppressive therapy. Computed tomography revealed bronchopneumonia, which improved with antibiotic administration. AFXD without evidence of amyloidosis was subsequently diagnosed.

Although the indication for sublingual immunotherapy (SLIT) was expanded in pediatric patients with allergic rhinitis in recent years, some patients choose subcutaneous immunotherapy (SCIT).The objective of this study was to investigate the reason why they chose SCIT in spite of injection pain and high risk of systemic reaction.The subjects were 58 patients who diagnosed with allergic rhinitis and introduced SCIT at our hospital between June 2018 and January 2021. The reasons why they chose SCIT were collected from medical records.The median age at the start of treatment was 9 years 0 months. The most common reason why they chose SCIT was "difficult to maintain adherence of SLIT" in 28 cases (48%). Other reasons were as follows: "side effects of SLIT", "expectation for the effect of SCIT", "young age (under 5 years old)" and "motivation for allergic disease treatment".Two-thirds of the reasons why they chose SCIT were because it was difficult to continue SLIT for some reasons.

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated gastrointestinal food allergy. Some studies have reported that FPIES was associated with elevated C-reactive protein (CRP). However, the number of reports on the relationship between FPIES and procalcitonin (PCT) is limited. This case report highlights the fact that PCT levels can be markedly elevated in patients with acute FPIES. An 11-month-old girl previously diagnosed with FPIES underwent an oral food challenge test (OFC). Her serum PCT levels were measured after she developed severe symptoms including fever and shock following administration of 100mL of formula milk. The PCT levels were extremely elevated but improved without antibiotics the next day. The fact that serum PCT levels may be significantly elevated in FPIES means that differentiating severe FPIES from sepsis could be more challenging than was previously thought.

Interventions for gestational diabetes mellitus (GDM), diagnosed in early pregnancy, have been a topic of controversy. This study aimed to elucidate factors that predict patients with GDM diagnosed before 24 gestational weeks (early GDM: E-GDM) who require insulin therapy later during pregnancy. Furthermore, we identified patients whose impaired glucose tolerance should be strictly controlled from early gestation onward. Women diagnosed with GDM were categorized based on the gestational age at diagnosis into E-GDM (n = 388) or late GDM (L-GDM, diagnosed after 24 weeks, n = 340) groups. Clinical features were compared between the groups, and the predictors for insulin therapy was evaluated in the E-GDM group. There were no significant between-group differences in terms of perinatal outcomes (e.g., gestational weeks at delivery, fetal growth, hypertensive disorder of pregnancy), with the exception of the Apgar score at 5 min. Moreover, there was no significant difference in the frequency of insulin therapy during pregnancy between the two groups. Using multiple logistic regression analysis, pre-pregnancy body mass index (BMI) ≥25 kg/m2, a family history of diabetes, and higher fasting plasma glucose (FPG), 1 h-plasma glucose (PG), and 2 h-PG values increased insulin therapy risk during pregnancy in the E-GDM group. Furthermore, since E-GDM patients with abnormal levels of FPG, as well as 1 h-PG or 2 h-PG, and those with pre-pregnancy BMI ≥25 kg/m2 and a family history of diabetes had a higher risk of later insulin therapy during pregnancy, they may require more careful follow-up in the perinatal period.

Background Cow's milk, along with hen's egg, are common causes of food allergies in children worldwide. Accidental ingestion of milk is common and often induces severe allergic reactions. Oral food challenge test (OFC) is usually performed in patients with or suspected of having a food allergy. However, the evidence of whether cow's milk OFC is useful in IgE-dependent cow's milk allergy patients to avoid total elimination is not known. Methods After setting the clinical question and outcomes, we performed a systematic review for relevant articles published from January 1, 2000 to August 31, 2019 using PubMed® and Ichushi-Web databases. Each article was then evaluated for the level of evidence. All positive results of the OFC were defined as adverse events. Results Forty articles were selected in this study. Our review revealed that cow's milk OFC was able to avoid the complete elimination of cow's milk in 66% of the patients with cow's milk allergy. We also found that adverse events occurred frequently (50.5%). Conclusions This analysis supports the recommendation of conducting cow's milk OFC to avoid complete elimination of cow's milk, however the test should be conducted with careful consideration of the patient's safety. As the methods of OFC and subjects varied among the articles selected in this study, further studies are needed to obtain higher quality evidence.

Objective This study aimed to validate new staging of Japanese patients with human papillomavirus-mediated oropharyngeal cancer (HPV+-OPC) and the effectiveness of transoral surgery. Methods Fifty-three patients with HPV+-OPC were classified according to the seventh and eighth editions of the American Joint Committee on Cancer (AJCC) staging, along with assessment of prognosis, smoking and alcohol status, and treatment outcome. Transoral videolaryngoscopic surgery (TOVS) was performed as transoral surgery. Results The 5-year overall survival (OS) rate was 77.3% in all patients. Five-year OS rates of seventh edition staging were as follows: II, 100%; III, 100%; IVa, 75.9%; and IVb and IVc, 0%. Five-year OS rates of the eighth edition clinical staging were as follows: I, 89.3%; II, 88.9%; III, 46.3%; and IV, 0%. In non-smoking and smoking patients with HPV+-OPC, the 5-year OS rates were 90.9% and 70.7%, respectively. TOVS was used for treating 20 smokers with HPV+-OPC (5-year OS: 85.7%), while 12 were treated with chemoradiotherapy (5-year OS: 75.0%). Conclusions The eighth edition of the AJCC determines the prognosis of HPV+-OPC more accurately than the seventh edition in clinical staging. Smokers with HPV+-OPC have a poor prognosis, but TOVS might improve the prognosis.

Many neuropsychiatric risk genes contribute to epigenetic regulation but little is known about specific chromatin-associated mechanisms governing the formation of neuronal connectivity. Here we show that transcallosal connectivity is critically dependent on C11orf46, a nuclear protein encoded in the chromosome 11p13 WAGR risk locus. C11orf46 haploinsufficiency was associated with hypoplasia of the corpus callosum. C11orf46 knockdown disrupted transcallosal projections and was rescued by wild type C11orf46 but not the C11orf46R236H mutant associated with intellectual disability. Multiple genes encoding key regulators of axonal development, including Sema6a, were hyperexpressed in C11orf46-knockdown neurons. RNA-guided epigenetic editing of Sema6a gene promoters via a dCas9-SunTag system with C11orf46 binding normalized SEMA6A expression and rescued transcallosal dysconnectivity via repressive chromatin remodeling by the SETDB1 repressor complex. Our study demonstrates that interhemispheric communication is sensitive to locus-specific remodeling of neuronal chromatin, revealing the therapeutic potential for shaping the brain’s connectome via gene-targeted designer activators and repressor proteins., Although many neuropsychiatric risk genes are known to contribute to epigenetic regulation of gene expression, very little is known about specific chromatin-associated mechanisms that govern the formation and maintenance of neuronal connectivity. Here, the authors report that transcallosal connectivity is critically dependent on C11orf46/ARL14EP, a nuclear protein encoded in the chromosome 11p13 WAGR risk locus, and that RNA-guided epigenetic editing of hyperexpressed Sema6a gene promoters in C11orf46-knockdown neurons resulted in normalization of expression and rescue of transcallosal dysconnectivity via repressive chromatin remodeling.

Being in a prolonged depressed state increases the risk of developing depression. To investigate whether green tea intake is effective in improving depression-like moods, we used an experimental animal model of depression with lipopolysaccharide (LPS) and clarified the effects of green tea on the biological stress response and inflammation in the brain. Regarding the stress reduction effect of green tea, we found that the sum of caffeine (C) and epigallocatechin gallate (E) relative to the sum of theanine (T) and arginine (A), the major components of green tea, or the CE/TA ratio, is important. The results showed that depression-like behavior, adrenal hypertrophy as a typical stress response, and brain inflammation were suppressed in mice fed green tea components with CE/TA ratios of 2 to 8. In addition, the expression of Npas4, which is reduced in anxiety and depression, was maintained at the same level as controls in mice that consumed green tea with a CE/TA ratio of 4. In clinical human trials, the consumption of green tea with CE/TA ratios of 3.9 and 4.7 reduced susceptibility to subjective depression. These results suggest that the daily consumption of green tea with a CE/TA ratio of 4–5 is beneficial to improving depressed mood.

Introduction Women who have undergone radical trachelectomy as a fertility-sparing treatment for early-stage cervical cancer may be at higher risk for retained tissues after early-term miscarriage due to cervical cerclage or cervical necrosis. Dilatation and curettage or aspiration may present additional risks in these women. The aim of this study was to assess the efficacy of expectant management for early pregnancy miscarriage after radical trachelectomy. Material and methods Keio University Hospital records were reviewed for women who conceived after abdominal radical trachelectomy and received perinatal care between 1 April 2012 and 31 March 2020. A total of 62 women (76 pregnancies) were identified, and 13 of these women experienced miscarriage before 12 gestational weeks. The management and outcome of these cases were reviewed in detail. Results The median maternal age at miscarriage was 39 years (range 31-42 years) and the median duration from abdominal radical trachelectomy to conception was 2.60 years (range 0.49-7.30 years). Cervical necrosis before conception occurred in one case (8%). One patient requested treatment with aspiration and the remaining 12 cases were managed with observation for a median of 23 days (range 7-50 days). There were no cases of endometritis or cases requiring dilatation and curettage for residue tissue. Further, no cases developed laceration of the residual cervix and no loss of cerclage sutures after discharge was noted. Conclusions Expectant management seems to be safe and appropriate for first trimester miscarriage after abdominal radical trachelectomy.

It is not fully understood how enzymes are regulated in the tiny reaction field of a cell. Several enzymatic proteins form cytoophidia, a cellular macrostructure to titrate enzymatic activities. Here, we show that the epileptic encephalopathy-associated protein Tbc1d24 forms cytoophidia in neuronal cells both in vitro and in vivo. The Tbc1d24 cytoophidia are distinct from previously reported cytoophidia consisting of inosine monophosphate dehydrogenase (Impdh) or cytidine-5’-triphosphate synthase (Ctps). Tbc1d24 cytoophidia is induced by loss of cellular juvenescence caused by depletion of Gm14230, a juvenility-associated lncRNA (JALNC) and zeocin treatment. Cytoophidia formation is associated with impaired enzymatic activity of Tbc1d24. Thus, our findings reveal the property of Tbc1d24 to form cytoophidia to maintain neuronal cellular juvenescence.

Hepatitis C virus (HCV) infection has an adverse impact on outcomes after allogeneic hematopoietic stem cell transplantation (HSCT). It is recommended that HSCT candidates infected with HCV receive the treatment prior to transplantation. Although the recent approval of direct-acting antivirals (DAAs) has led to great advances in the treatment of HCV infection, little information is available on the efficacy and safety of DAA therapy in patients receiving allogeneic HSCT. Herein, we report the clinical course of an umbilical cord blood (UCB) recipient treated with DAAs for HCV infection. The patient achieved HCV RNA negativity with glecaprevir and pibrentasvir after consolidation therapy for acute myeloid leukemia (AML), and underwent transplantation before confirming sustained virological response (SVR) at 12 weeks. The HCV viral load became detectable on day +28 after transplantation and second HCV treatment with sofosbuvir, velpatasvir, and ribavirin was required. It is important to confirm SVR prior to transplantation, but it is often difficult. If early transplantation is required, close monitoring of HCV RNA after transplantation is needed. Further investigation is required to clarify the optimal management of HCV infection for allogeneic HSCT recipients in the DAA era.

Background The presence of acute coagulopathy and its effect on prognosis in burn patients are unclear. No studies are extant verifying early coagulopathy before fluid administration in burn patients. The current study focused on arrival coagulopathy before volume resuscitation was begun in earnest. Methods Data from 137 burn patients transported directly to the hospital without fluid administration from January 2006 to December 2019 were analyzed retrospectively. Results The non-survival group had significantly increased age, total burn surface area (TBSA) burned, various scoring systems, prothrombin time-international normalized ratio (PT-INR), activated partial thromboplastin time (APTT), the presence of coagulopathy, and lactate levels compared to the survival group. In the logistic regression analysis, the incidence of coagulopathy was independently associated with mortality. The coagulopathy group had significant increases in TBSA burned, various scoring systems, PT-INR, APTT, lactate levels, and the mortality than the noncoagulopathy group. The prognostic burn index (PBI) was significantly correlated with PT-INR and APTT. We also found a significant correlation between the serum lactate and the PT-INR, APTT, and PBI. Conclusions Acute coagulopathy of burn patients might be present on arrival to the hospital before fluid replacement which is an independent risk factor for in-hospital mortality.

Proteasomes are protease complexes essential for cellular homeostasis, and their activity is crucial for cancer cell growth. However, the mechanism of how proteasome activity is maintained in cancer cells has remained unclear. The CNC family transcription factor NFE2L1 induces the expression of almost all proteasome-related genes under proteasome inhibition. Both NFE2L1 and its phylogenetically closest homolog, NFE2L3, are highly expressed in several types of cancer, such as colorectal cancer. Here, we demonstrate that NFE2L1 and NFE2L3 complementarily maintain basal proteasome activity in cancer cells. Double knockdown of NFE2L1 and NFE2L3 impaired basal proteasome activity in cancer cells and cancer cell resistance to a proteasome inhibitor anticancer drug, bortezomib, by significantly reducing the basal expression of seven proteasome-related genes: PSMB3, PSMB7, PSMC2, PSMD3, PSMG2, PSMG3, and POMP. Interestingly, the molecular basis behind these cellular consequences was that NFE2L3 repressed NFE2L1 translation by the induction of the gene encoding the translational regulator CPEB3, which binds to the NFE2L1 3′ untranslated region and decreases polysome formation on NFE2L1 mRNA. Consistent results were obtained from clinical analysis, wherein patients with cancer having tumors expressing higher levels of CPEB3/NFE2L3 exhibit poor prognosis. These results provide the novel regulatory mechanism of basal proteasome activity in cancer cells through an NFE2L3-CPEB3-NFE2L1 translational repression axis.

Background and objectives: Massive postpartum hemorrhage (PPH) is the most common cause of maternal death worldwide. A massive transfusion protocol (MTP) may be used to provide significant benefits in the management of PPH, however, only a limited number of hospitals use MTP protocol to manage massive obstetric hemorrhages, especially in Japan. This study aimed to assess the clinical outcomes in patients in whom MTP was activated in our hospital. Materials and Methods: We retrospectively reviewed the etiology of PPH, transfusion outcomes, and laboratory findings among the patients treated with MTP after delivery in our hospital. Results: MTP was applied in 24 cases (0.7% of deliveries). Among them, MTP was activated within 2 h of delivery in 15 patients (62.5%). The median estimated blood loss was 5017 mL. Additional procedures to control bleeding were performed in 19 cases, including transarterial embolization (18 cases, 75%) and hysterectomy (1 case, 4.2%). The mean number of units of red blood cells, fresh frozen plasma, and platelets were 17.9, 20.2, and 20.4 units, respectively. The correlation coefficients of any two items among red blood cells, fresh frozen plasma, platelets, blood loss, and obstetrical disseminated intravascular coagulation score ranged from 0.757 to 0.892, indicating high levels of correlation coefficients. Although prothrombin time and activated partial thromboplastin time levels were significantly higher in the &lt, 150 mg/dL fibrinogen group than in the ≥150 mg/dL fibrinogen group at the onset of PPH, the amount of blood loss and blood transfusion were comparable between the two groups. Conclusions: Our MTP provides early access to blood products for patients experiencing severe PPH and could contribute to improving maternal outcomes after resuscitation in our hospital. Our study suggests the implementation of a hospital-specific MTP protocol to improve the supply and utilization of blood products to physicians managing major obstetric hemorrhage.

Purpose The aim of this study is to present an easy and quick technique for embolization of the inferior mesenteric artery (IMA) during endovascular aneurysm repair (EVAR). Technique We performed IMA embolization using a conventional EVAR device alone with the femoral artery approach during EVAR, which has not been reported previously. First, a 16F or 18F DrySeal Sheath is inserted from the femoral artery into the site around the IMA. Second, cannulation is performed in the IMA with an angiography catheter having a 0.038-inch inner lumen that is used for gate cannulation during EVAR. Third, IMA embolization is performed using the Amplatzer Vascular Plug 4 (AVP4). The use of the DrySeal Sheath facilitates cannulation of the IMA, and its combination with a stent-graft balloon allows the AVP4 to be placed at the root of the IMA without deviation of the catheter. The success rate of the procedure was 90.9% (30/33 cases). The median procedure time was 11.6 min. No complications due to IMA embolization were noted. Conclusion This procedure enables safe and quick placement of the AVP4 in the IMA using the catheter insertion approach from the femoral artery, which has been conventionally regarded as difficult.

The resection of the medial and lateral pyriform sinus was associated with post-operative voice impairment after TOVS. Scar contracture around the cricoarytenoid joint lead to arytenoid fixation toward lateral position, and this wound healing process caused insufficient glottis closure. Although oncological and functional outcomes of TOVS was satisfactory, surgeons should mention the risk of post-operative voice impairment in pre-operative counseling.Transoral surgery is a minimally invasive treatment option for hypopharyngeal and supraglottic cancer. Post-operative vocal function was satisfactory in most cases, but in some cases vocal cord was fixed and occasionally voice impairment persists.Vocal function of 55 patients who underwent transoral videolaryngoscopic surgery (TOVS) for hypopharyngeal and supraglottic cancers was evaluated by the GRBAS perceptive scale, aerodynamic tests and acoustic analyses, and the Voice Handicap Index questionnaire. The risk factors for voice impairment were identified.Voice impairment (G score ≧2) was found in 16 cases (29.1%). Univariate analysis revealed that the resection of medial and lateral pyriform sinus (p = .0018) and neck dissection (p = .0421) were associated with post-operative voice impairment. Multivariate analysis revealed that the resection of medial and lateral pyriform sinus (p = .0021) was associated with post-operative voice impairment.

Objective The aim of this study was to evaluate the efficacy and safety of local steroid injections to prevent scar contracture after transoral videolaryngoscopic surgery (TOVS) in hypopharyngeal cancer patients. Methods Patients were enrolled in this study if they had received a local steroid injection during TOVS and had attended an outpatient clinic after at least three months. All patients were being treated for hypopharyngeal cancer and received a single session of triamcinolone acetonide, injected using a 21-gage needle. Retrospective chart reviews were performed, and the degree of scar contracture, pharyngeal stenosis, vocal fold movements, and adverse events were evaluated. Scar contracture was assessed using a scoring system, which compared the endoscopic findings of treatment and matched pair control groups. Results A total of 20 patients received local steroid injections during TOVS and were enrolled in the treatment. Scar contracture was seen in 14 patients (70%); however, the degree of scar contracture was significantly decreased when compared to control cases. Vocal fold immobility was observed in five patients, but no pharyngeal stenosis was noted. Adverse effects, such as postoperative laryngeal chondritis or cervical spondylitis, were seen in three patients who had previously been treated with resection to the muscularis propria or definitive irradiation. Conclusion Local steroid injection during TOVS significantly reduced the degree of postoperative scar contracture. However, caution should be used when treating with local steroid injection during TOVS, as this may complicate wound healing in patients who have already received treatment.

We report a resected case of basaloid squamous cell carcinoma (BSC). BSC is a rare type of malignant lung tumor. A 79-year-old woman had a 13 mm tumor in the left upper lobe on chest computed tomography (CT). On fluorodeoxyglucose-position emission tomography (FDG-PET), the tumor showed the accumulation of FDG with an SUVmax of 14.7. A left upper lobectomy with lymph node dissection was performed by video-assisted thoracoscopic surgery. The pathological diagnosis was BSC (pT2aN0M0, stage IB). There was no recurrence following lung cancer resection for 12 months. BSC is generally poor prognosis.

Standardized allergen extracts are recommended for allergen immunotherapy. Since 2015, for patients with house dust mite allergies, we used a standardized house dust mite extract for subcutaneous immunotherapy, rather than non-standardized house dust extract. This study hypothesizes that standardized house dust mite extract (HDM group) was superior to non-standardized house dust extract (HD group) for subcutaneous immunotherapy.In this noninterventional, retrospective study, we enrolled patients with allergic rhinitis and sensitization to house dust mites. The HDM group (27 patients) received subcutaneous standardized extract immunotherapy since 2015, and the HD group (37 patients) received non-standardized extracts before 2015. We assessed the safety and efficacy between the two groups; the safety was assessed by the systemic reaction (SR) rate. The efficacy was assessed by reductions in the allergic rhinitis symptom-medication score, and the asthma treatment score, over a year.The SR rate of the HDM group (44%) was significantly higher than that (14%) of the HD group. The HDM group displayed a 57% reduction in the allergic rhinitis symptom-medication score, which was markedly higher than the 40% reduction observed in the HD group. In the standardized group, there was a 66% reduction occurred in the asthma medication score, markedly higher than the 36% reduction observed among patients in the HD group.Standardized house dust mite extract was more effective than non-standardized house dust extract for subcutaneous immunotherapy; however, the establishment of safer methods is warranted.

Backgroud Among various myocyte-derived bioactive molecules (myokines), β-aminoisobutyric acid (BAIBA) is a unique myokine that attenuates skeletal muscle insulin resistance and inflammation, increases browning of white adipose tissue, and enhances hepatic fatty acid oxidation, resulting in upregulated energy expenditure of the whole body. In the present study, we investigated the effects of BAIBA on the vascular endothelial cell function. Methods The mRNA levels of proinflammatory molecules, antioxidants, and their related transcription regulators were examined by quantitative RT-PCR in BAIBA-treated human aortic or umbilical vein endothelial cells (HAEC or HUVEC, respectively), with or without tumor necrosis factor (TNF)-α stimulation. The protein expression and phosphorylation of AMP-activated protein kinase (AMPK) and endothelial nitric oxide synthase (eNOS) were determined by Western blot analysis. Results BAIBA pretreatment significantly suppressed the mRNA levels of the adhesion molecules in the TNF-α-stimulated HAEC and HUVEC. BAIBA treatment significantly increased the mRNA levels of antioxidant molecules, catalase, superoxide dismutases, thioredoxin, and gamma-glutamylcysteine ligases, together with mitochondrial biogenesis-related molecules, nuclear respiratory factor 1, and mitochondrial transcription factor A. In addition, BAIBA treatment significantly increased the transcription factors that regulated these genes [i.e., peroxisome proliferator-activated receptor (PPAR)-δ, PPAR-γ, estrogen-related receptor α (ERRα), and peroxisome proliferator-activated receptor gamma coactivator (PGC)-1β]. Adenovirus-mediated PGC-1β overexpression significantly increased the mRNA levels of all antioxidant molecules. The phosphorylation levels of AMPK and eNOS were unaltered by BAIBA. Conclusions In vascular endothelial cells, BAIBA had antiatherogenic effects through the PGC-1β−ERRα/PPAR-δ and PPAR-γ pathway. This can explain the beneficial effects of exercise on vascular endothelial function.

Objective Transoral videolaryngoscopic surgery (TOVS) was developed as a non-robotic procedure for en bloc laryngo-hypopharyngeal cancer resection. Straight devices had been used for this procedure, however, some cases had difficulty to reach the lesions especially in hypopharyngeal area. To overcome this problem, technical updates to facilitate transoral manipulation were developed and long term oncological and functional results were analyzed. Methods Surgical indications were Tis, T1, T2 and selected T3 cases. In advanced T3 or T4 lesions, neoadjuvant chemotherapy was performed before surgery. Radiation failure cases (rT1 and rT2) were also indicated for TOVS. Resectable nodal involvement can be managed by combination of neck dissection. Ninety hypopharyngeal and 25 supraglottic cancer cases were retrospectively reviewed for survival analyses. In fresh hypopharyngeal cancer, 51 Stage 0–II disease and 32 Stage III-IV disease were included. In supraglottic cancer, 11 Stage I–II disease and 9 Stage III-IV disease were included. Twelve radiation failure cases were analyzed separately. As new devices, malleable forceps and malleable suction coagulator were introduced to reach the whole laryngo-hypopharynx. New curved blades for the FKWO retractor were developed and these were applied for difficult hypopharyngeal exposure cases by conventional blades. Swallowing functional outcome and risk factors for postoperative dysphagia were evaluated by univariate analysis. Results The 5-year overall survival, disease-specific survival and larynx preservation rate of fresh hypopharyngeal cancer cases were 83.2%, 94.3% and 94.6%, respectively. Those of supraglottic cancer cases were 80%, 95% and 94.7%, respectively. Those of salvage cases were 87.5%, 87.5% and 82.5%, respectively. Those of T3 and T4 hypopharyngeal cancer treated by neoadjuvant chemotherapy with TOVS were 75.0%, 82.5% and 100% respectively. Surgical complication included bleeding (2.6%) and emergency tracheostomy (3.4%). Oral intake was maintained in 94.8% cases. By univariate analysis, patient’s age (especially 80 years of age or older), larger resected area, arytenoid resection and tracheostomy were regarded as risk factors for postoperative dysphagia. Among 31 recent cases, 5 cases had difficulty in exposing hypopharyngeal lesions by conventional blades. These exposure problems were solved by curved blades. Conclusion Using malleable devices and new curved blades for the FKWO retractor, exposure problems in the hypopharynx could be solved and TOVS could be applied in more cases. Although oncological outcomes and functional outcomes were good, patients with risk factors for dysphagia should be carefully indicated.

In clinical N0 (cN0) cases with head and neck squamous cell carcinoma (HNSCC), a treatment selection is still controversial: elective neck dissection or watchful waiting. We focused on sentinel lymph node (SLN)–targeted therapy using the urokinase-type plasminogen activator (uPA)-dependent oncolytic Sendai virus “BioKnife.” The objectives of this study were to investigate BioKnife migration into SLNs and elucidate its antitumor effect on lymph node metastases (LNM). We established an orthotopic nude mouse model of HNSCC, with LNM being frequently induced. We inoculated HSC-3-M3, human highly metastatic tongue squamous cell carcinoma cells, in the tongue of the nude mice, and after 2 weeks, we injected BioKnife into the primary tumor. We tracked BioKnife migration into the SLNs by immunostaining, RT-PCR, and an in vivo imaging system. We also examined its antitumor effects and mechanisms through serial section analysis of lymph nodes. GFP reporter expression was clearly visible in the lymph nodes of virus groups, which corresponded to SLNs. Relative GFP mRNA was significantly increased in both the tongues and lymph nodes in the virus groups compared with that in the control group (P < 0.05). Serial section analysis showed that BioKnife infected cancer cells and exhibited significant antitumor effect against LNM compared with the control groups (P < 0.05). We detected apoptosis in LNM infected by BioKnife. BioKnife migrated into SLNs after its injection into the primary tumor and effectively suppressed LNM, suggesting that SLN-targeted therapy using BioKnife has great potential to provide a novel and promising alternative to elective neck dissection in cN0 patients with HNSCC.

Background Securing food for patients with food allergies may be more difficult during disasters, but reports on the status of household allergen-free food reserves in preparation for disasters are limited. This study investigated the household stock status of allergen-free foods in preparation for disasters in Kobe City after the Great Hanshin-Awaji Earthquake. Methods The survey targets were 172 parents of patients with a food allergy who underwent in-hospital oral food challenge test for allergies at four hospitals from October 2016 to March 2017. Of these, 158 patients with allergies to eggs, milk and wheat were included in the analysis. The first survey was performed to investigate patient characteristics and stockpiling status of allergen-free foods in parallel with oral food challenge tests. The second survey was performed on the follow-up visit to investigate any changes in behavior. Results Median patient age was 3 years, with boys comprising 68.4% of the patients. Eggs were the most eliminated food, and the median number of foods avoided was 2. A total of 82.3% of parents had experienced disasters. The proportion of households that stockpiled allergy-free meals was 42.4%, and the median amount was 3 days. The stockpiling situation did not differ according to the parents' disaster experience. In the second survey, 45.3% had modified their stockpiling practice. Conclusions Even in this area where the Great Hanshin-Awaji Earthquake occurred, household stockpiles of allergen-free foods are inadequate; therefore, all medical staff should educate families about the necessity of stocking allergen-free food for disasters.

This study aimed to determine the specific fluid distribution pattern in legs with lymphedema (LE) in comparison to normal legs and legs with venous edema (VE) using bioelectrical impedance analysis (BIA).BIA was performed in 47 patients with lymphedema (LE; 63 legs), 33 patients with venous edema (VE; 60 legs), and 33 normal subjects (N; 66 legs). The ratio of intracellular fluid (ICF) resistance (Ri) to extracellular fluid (ECF) resistance (Re) of a whole leg normalized to the right arm (Ri/Re leg), a surrogate parameter for ECF/ICF, and the Ri/Re of the thigh and calf without normalization (Ri/Re thigh, Ri/Re calf, respectively) were obtained. Increases in Ri/Re leg (N 2.5 ± 0.7, VE 3.9 ± 3.7, LE 3.7 ± 1.5), Ri/Re thigh (N 1.8 ± 0.5, VE 3.2 ± 3.8, LE 3.8 ± 1.9), and Ri/Re calf (N 2.6 ± 0.6, VE 4.6 ± 1.7, LE 4.4 ± 2.2) were confirmed in VE and LE compared to normal subjects. However, the ratios of Ri/Re calf to Ri/Re thigh in normal subjects and those with untreated VE/LE were all ∼1.5 (N 1.5 ± 0.3, VE 1.5 ± 0.7, LE 1.6 ± 0.7).Fluid content was increased in legs with VE and LE compared to normal subjects, while the mode of gravitational fluid distribution was similar among all legs. Thus, no specific finding for LE was confirmed.

Activator protein‐1 (AP‐1) is a transcriptional factor that regulates the expression of various genes associated with tumor invasion and migration. The purpose of our study was to assess the therapeutic effects of a novel selective AP‐1 inhibitor, T‐5224, in preventing lymph node metastasis in head and neck squamous cell carcinoma (HNSCC) in an orthotopic mouse model. We assessed the effect of T‐5224 on HNSCC cell invasion, migration, proliferation, and MMP activity by carrying out an in vitro study using an invasion assay, scratch assay, WST‐8 assay, and gelatin zymography. We also observed morphological changes in HNSCC cells by time‐lapse microscopy. Furthermore, cervical lymph node metastasis was assessed using an orthotopic tumor model of human oral squamous cell carcinoma cells (HSC‐3‐M3) injected in the tongue of a BALB/c nude mouse. T‐5224 (150 mg/kg) or vehicle was given orally every day for 4 weeks. Animals were killed and assessed for lymph node metastasis by H&E staining of resected lymph nodes. T‐5224 significantly inhibited the invasion, migration, and MMP activity of HNSCC cells in a dose‐dependent manner; there was no significant influence on cell proliferation. The antimetastatic effect of T‐5224 was also confirmed in our animal study. The rate of cervical lymph node metastasis in the model was 40.0% in the T‐5224‐treated group (n = 30) versus 74.1% in the vehicle‐treated group (n = 27; P < 0.05). In conclusion, T‐5224 inhibited the invasion and migration of HNSCC cells in vitro, and prevented lymph node metastasis in head and neck cancer in an animal model.

Although the serum 1,3-β-D-glucan test has been used as an early diagnostic marker of candidemia, there are few studies regarding the association of serum 1,3-β-D-glucan levels with candidemia in severe burn patients. The purpose of this study was to elucidate the clinical significance of 1,3-β-D-glucan for the diagnosis of candidemia in severe burn patients. Data from 51 severe burn patients whose serum levels of 1,3-β-D-glucan had been measured for the suspicion of invasive fungal infection were analyzed retrospectively. The primary outcome in this study was the detection of candidemia. The levels of 1,3-β-D-glucan (pg/ml) in candidemia and noncandidemia groups ranged from 41.1 to 600.0 with a median of 90.6 and from 5.0 to 41.3 with a median of 6.8, respectively. A significant difference in the levels of 1,3-β-D-glucan was observed between the two groups. The optimal cutoff value was 40 pg/ml, with a sensitivity of 100% and a specificity of 95%, whereas the conventional cutoff value (11 pg/ml) resulted in a sensitivity of 100% and a specificity of 68%. The 1,3-β-D-glucan test was found to be useful for detecting candidemia in severe burn patients, and the cutoff value might be set to 40 pg/ml to detect it more accurately.

Objective The fiber-guided carbon dioxide (CO2) laser is a useful device for laryngopharyngeal surgery. The flexible CO2 wave-guide laser has been developed and commercially available for several years. However, the transnasal use of CO2 flexible wave-guided laser surgery through the instrument channel of a flexible endoscope (CO2 TNFLS) is not permitted in Japan. This feasibility study aimed to assess the value and the safety of an in-office CO2 TNFLS procedure. Methods Patients with small laryngopharyngeal diseases were enrolled from June 2015. Eligible patients had indications with lesions generally localized superficial lesions such as the benign tumor, leukoplakia, and premalignant lesion-like carcinoma in situ (CIS). Patients were locally well anesthetized using xylocaine. After removing as much of the lesion(s) as possible with flexible forceps, the remainder of the lesions were evaporated using CO2 TNFLS through the instrument channel of a flexible endoscope under local anesthesia. Results Eighteen surgeries involving 13 patients, including 9 papilloma (7 recurrent respiratory papilloma [RRP]), 2 carcinoma in situ, 1 leukoplakia, and 1 large epiglottic cyst), were performed. Four patients with RRP required multiple surgeries. Except for 3 patients with RRP, all patients achieved disease control without additional intervention. All procedures were completed with no severe adverse events. Conclusion Office-based CO2 TNFLS is safe and feasible for patients with laryngopharyngeal pathologies. It is especially valuable for RRP patients with small lesions to avoid surgery under general anesthesia.

We report a resected case of fetal adenocarcinoma. Fetal adenocarcinoma is a rare type of malignant lung tumor. A 53-year-old man had a 25 mm tumor in the right upper lobe on chest computed tomography. On fluorodeoxyglucose-positron emission tomography( FDG-PET), the tumor showed the accumulation of FDG with a standardized uptake value( SUV) max of 5.63. He underwent bronchoscopic examination, but a diagnosis was not established. We suspected that the tumor was primary lung cancer or metastatic lung tumor of rectal cancer which was resected prior to the treatment for pulmonary lesion. A right upper lobectomy with lymph node dissection was performed and the pathological diagnosis was high-grade fetal adenocarcinoma, stage IB (pT2aN0M0). The patient was treated with postoperative adjuvant chemotherapy. There has been no recurrence after surgery resection for 9 months.

We compared skin and subcutaneous tissue strains in legs with lymphedema (LE) of varying severity and legs with lipodermatosclerosis (LDS) using real-time tissue elastography. Strain was assessed at the inner thigh and calf in 62 legs with LE (International Society of Lymphology [ISL] stage 0: 16, stage I: 5, stage II: 28, late stage II: 7, stage III: 6) and 15 legs with LDS. In thighs and calves with LE, skin strain and subcutaneous tissue strain did not significantly differ between ISL stage 0, that is, asymptomatic legs, and other stages. However, strain values in calves with LDS were lower than values in calves with stage 0, II and late II LE. These results indicate that skin and subcutaneous tissue strains were not lower in legs with symptomatic LE than in asymptomatic legs until an advanced stage.

Objectives To study the differences in impact on venous hemodynamics between larger size strong graduated elastic compression stockings (GECS) and appropriate size strong/moderate GECS. Method In healthy legs fitted for a small (Group S; n = 8) and large (Group L; n = 8) GECS, air plethysmography was performed without GECS, with an appropriate size strong GECS (GECS1), with a three-size too large strong GECS (GECS2), and with an appropriate size moderate GECS (GECS3) in this order. Results In Group S, interface pressure with GECS2 was equal to or higher than that with GECS3. Decreased venous volume, unchanged ejection volume, and decreased residual volume were achieved by GECS, but differences in these parameters among GECS were not observed. Although insignificant, a similar tendency was found in Group L. Conclusions A larger size strong GECS seemed to have equivalent interface pressure and impact on venous hemodynamics compared to an appropriate size moderate or strong GECS.

We report a case of torsion of the gallbladder displaced under the right subphrenic space in a patient with liver cirrhosis. An 82-year-old Japanese woman was admitted to our hospital for acute pain in the right upper quadrant. Clinical features suggested gallbladder torsion. She was under treatment for hepatitis C virus-related cirrhosis at our hospital. Abdominal CT showed the swollen fundus and body of the gallbladder under the right subphrenic space. Emergency laparoscopic cholecystectomy was performed. Intraoperative findings included a grossly necrotic gallbladder in the right subphrenic space with 360° clockwise torsion, together with liver cirrhosis and localized peritonitis. The clinical features and imaging findings in this rare case of misplaced gallbladder in right subphrenic space resembled those described in typical strangulated gallbladder. The displacement was probably related to right liver lobe atrophy associated with liver cirrhosis. Appropriate diagnosis and prompt surgical treatment are essential for a positive outcome.

Background Total aortic arch replacement is associated with considerable mortality and morbidity. Although operative death is the most extreme adverse clinical end point, postoperative morbidity can also be devastating for survivors. Methods We examined the short-term and long-term outcomes of 146 patients who underwent total aortic arch replacements between September 2003 and September 2011. Results The overall in-hospital mortality was 4.8%, and major postoperative morbidity during hospitalization occurred in 29 patients (19.9%). Multivariate analyses demonstrated that risk factors for hospital death were left thoracotomy (odds ratio [OR], 51.92; p = 0.01), high preoperative serum creatinine values (OR, 3.88; p = 0.02), and intraoperative blood loss (OR, 1.01; p = 0.04). Ruptured aorta (OR, 7.13; p = 0.02) and previous myocardial infarction (OR, 5.13; p = 0.04) were identified as independent risk factors for major postoperative morbidity. The postoperative survival of all patients at 5 years was 76.7% ± 5%. After hospital discharge, the standardized mortality ratios showed no significant difference between hospital survivors and a comparable Japanese population and were 1.09 ( p = 0.41) among patients without major morbidity and 1.82 ( p = 0.12) among those with major morbidity. The development of renal failure requiring hemodialysis increased the risk of long-term death (hazard ratio, 5.59; p = 0.03), even among hospital survivors. Conclusions Our approach for total arch replacement resulted in low in-hospital mortality and morbidity. Long-term outcomes are stable in hospital survivors, especially in the absence of a postoperative requirement for dialysis.

The purpose of this study was to confirm the therapeutic effects of mixed sheets consisting of peripheral blood mononuclear cells (PBMNCs) and fibroblasts on cutaneous skin ulcers. Vascular endothelial growth factor (VEGF) secretion in mixed cell sheets was much higher than in PBMNCs and fibroblasts. Concerning the mechanism, transforming growth factor beta 1 and platelet-derived growth factor BB secreted from PBMNCs enhanced VEGF production in fibroblasts. In wounds created on the backs of diabetic mice, the therapeutic effect of mixed cell sheets was similar to that of daily treatment with trafermin, a recombinant human basic fibroblast growth factor. Although abnormal granulation tissue and inflammatory cell infiltration were observed in trafermin-treated wounds, the transplantation of mixed cell sheets resulted in the natural anatomy of subcutaneous tissues. The expression patterns of identical wound-healing factors in wounds were different between mixed sheet-transfected and trafermin-treated animals. Because mixed cell sheets transplanted into full-thickness skin defects were eliminated in hosts by day 21 in syngeneic transplantation models, allogeneic transplantation was performed using mice with different genetic backgrounds. The wound-healing rates were similar between the mixed cell sheet and trafermin groups. Our data indicated that mixed cell sheets represent a promising therapeutic material for cutaneous ulcers.

It has been well established that patients with head and neck cancer (HNC) have an elevated risk of developing a second primary cancer (SPC), owing to the common carcinogenic risk factors, including tobacco and alcohol consumption, and inactive aldehyde dehydrogenase-2 genotype. Here we investigated the current state of SPC in Japanese HNC patients.We retrospectively investigated the incidence and treatment outcomes of synchronous and metachronous SPCs among 434 newly diagnosed HNC patients. Moreover, the associations between various carcinogenic risk factors and SPC were also assessed.Fifty-two (12.0%) and 104 patients (24.0%) had synchronous and metachronous SPCs, respectively. The cases with SPC were associated with high rates of smoking and alcohol histories (81.1% and 74.6%, respectively). Immunohistochemical analysis revealed that 47.5% of all oropharyngeal cancer cases showed positive p16 expression, and there was no significant difference between p16-positive and -negative cases in terms of the proportions of patients with SPC. The 3-year overall survival rates were 78.8%, 75.3% and 75.9% in patients without, with synchronous, and with metachronous SPC, respectively (P = 0.4048).Given the distinct features of the carcinogenic risk factors for HNC in Japan, care should be taken not to underestimate the frequency of SPC, even for human papillomavirus-related oropharyngeal cancer patients. Considering the high incidence of SPC associated with HNC, the appropriate diagnostic strategy to allow for early detection of SPC and a treatment strategy aimed at avoiding unnecessary radiotherapy for the index tumor would contribute to improving the prognosis for HNC.

Objective To use subcutaneous ultrasonography to differentiate legs with edema because of obesity-related functional venous insufficiency (FVI ob ), immobility-related FVI (FVI im ), secondary lymphedema (LE), LE complicated by obesity (LE ob ), and LE complicated by immobility (LE im ). Methods Ninety-nine legs with edema (16 FVI ob , 32 FVI im , 22 LE, 9 LE ob , and 20 LE im ), and 10 normal legs were examined. Subcutaneous tissue ultrasonography was performed at eight points (medial, lateral, upper, lower, thigh, and calf) in each leg. Subcutaneous echogenicity (SEG) and subcutaneous echo-free space (SEFS) were assessed, and each graded as 0, 1, and 2 according to their severity. Results In normal legs, SEG and SEFS were graded 0 in almost all parts of the leg. SEG was diffusely increased in FVI ob , whereas SEG was increased in accordance with gravity in FVI im (upper medial thigh, 0.6 ± 0.5 vs lower medial calf, 1.2 ± 0.4; P P ob : upper medial thigh, 0.2 ± 0.4 vs lower medial calf, 0.7 ± 0.8; P = .05; FVI im : upper medial thigh, 0.1 ± 0.2 vs lower medial calf, 1.3 ± 0.7; P P ob or LE im were diffuse and similar. As determined via stepwise logistic regression analyses, the increases in SEG in the upper medial thigh and SEFS in the lower medial thigh in LE cases, the increases in SEG in the upper lateral thigh and SEFS in the lower lateral thigh in cases with obesity-related leg edema (ie, FVI ob and LE ob ), and the increase in SEFS in the lower lateral calf in cases with immobility-related leg edema (ie, FVI im and LE im ) were determined to be significant factors to characterize each leg edema. Conclusions Differences in the extent and distribution of SEG and SEFS might help in differentiating LE from FVI ob and FVI im , although assessment of LE complicated by obesity vs immobility remains difficult.

Advanced age affects various tissue-specific stem cells and decreases their regenerative ability. We therefore examined whether aging affected the quantity and quality of cardiac stem cells using cells obtained from 26 patients of various ages (from 2 to 83 years old). We collected fresh right atria and cultured cardiosphere-derived cells (CDCs), which are a type of cardiac stem cell. Then we investigated growth rate, senescence, DNA damage and the growth factor production of CDCs. All samples yielded a sufficient number of CDCs for experiments and the cellular growth rate was not obviously associated with age. The expression of senescence-associated b-galactosidase and the DNA damage marker, gH2AX, showed a slightly higher trend in CDCs from older patients (≥65 years). The expression of VEGF, HGF, IGF-1, SDF-1, and TGF-b varied among samples and the expression of these beneficial factors did not decrease with age. An in vitro angiogenesis assay also showed that the angiogenic potency of CDCs was not impaired, even in those from older patients. Our data suggest that the impact of age on the quantity and quality of CDCs is quite limited. These findings have important clinical implications for autologous stem cell transplantation in elderly patients.

In recent years there have been few reports on the effects of immunotherapy on bronchial asthma (BA) and allergic rhinitis (AR) in Japanese children.To investigate the safety and efficacy of house dust extract immunotherapy for one year.Thirty-five children with AR and BA were subjected to rush immunotherapy with house dust extract. Systemic reactions were counted to evaluate safety. BA medication score and AR symptom-medication score were recorded.Three patients (8.3% of all patients) experienced 6 systemic reactions (0.15% of doses). BA medication score decreased from 567 to 325 (a reduction rate of 43%). AR symptom-medication score improved from 5.1 to 2.9 (a reduction rate of 43%).Rush immunotherapy with house dust extract is safe and effective for Japanese children.

Improved therapies for individuals with head and neck squamous cell carcinoma (HNSCC) may be developed by identification of appropriate biomarkers. The aim of this study was to evaluate the usefulness of serum midkine measurement as a biomarker for HNSCC. Pretreatment serum midkine concentrations were measured in 103 patients with HNSCC and 116 control individuals by enzyme‐linked immunosorbent assay. Midkine expression in tumor tissues from 33 patients with HNSCC who underwent definitive surgical resection without preoperative treatment was examined by immunohistochemistry. The cut‐off serum midkine concentrations for predicting the presence of head and neck malignancy and chemosensitivity to induction chemotherapy, as determined using receiver operating characteristic curves, were 482 and 626 pg/mL, respectively. Spearman bivariate correlations showed positive correlations between serum midkine levels and immunohistochemistry staining score (r = 0.612, P

Myositis ossificans (MO) is a rare benign cause of heterotopic bone formation in soft tissue that most commonly affects young adults, typically following trauma. We report the case of an 11-year-old girl who developed MO mimicking osteosarcoma in her right shoulder. Plain radiography and computed tomography showed poorly defined flocculated densities in the soft tissue and a periosteal reaction along the proximal humerus. On magnetic resonance imaging, the mass displayed an ill-defined margin and inhomogeneous signal change. Histologically, the mass had a pseudosarcomatous appearance. Based on these findings, the patient was initially misdiagnosed with osteosarcoma at another hospital. The diagnosis was difficult because the patient was 11 years old and had no trauma history, with atypical radiographic changes and a predilection for the site of origin for osteosarcomas. We finally made the correct diagnosis of MO by carefully reviewing and reflecting on the pathological differences between stages.

Total laryngectomy is a well established method for the treatment of laryngeal cancer. In some cases such as elderly patients or patients with severe complications, a shorter surgical time is preferred. Total laryngectomy using a linear stapler is reportedly advantageous for shortening of the surgical time and for lowering the rate of pharyngeal fistula formation. We applied this surgical technique in three laryngeal cancer cases. After skeletonization of the larynx, the linear stapler is inserted between the larynx and the pharyngeal mucosa. Excision of the larynx and suturing of the pharyngeal mucosa are performed simultaneously. Although the number of cases is small for statistical analysis, the surgical time was shortened by about 30 minutes compared to laryngectomy with manual suturing. Total laryngectomy by linear stapler cannot be applied in all cases of advanced laryngeal cancer. However, if the tumor is confined to the endolarynx, it is a useful tool for some cases that require a shorter surgical time.