Predictive analysis of breast cancer response to neoadjuvant chemotherapy through plasma metabolomics.

PURPOSE: Preoperative chemotherapy is a critical component of breast cancer management, yet its effectiveness is not uniform. Moreover, the adverse effects associated with chemotherapy necessitate the identification of a patient subgroup that would derive the maximum benefit from this treatment. This study aimed to establish a method for predicting the response to neoadjuvant chemotherapy in breast cancer patients utilizing a metabolomic approach. METHODS: Plasma samples were obtained from 87 breast cancer patients undergoing neoadjuvant chemotherapy at our facility, collected both before the commencement of the treatment and before the second treatment cycle. Metabolite analysis was conducted using capillary electrophoresis-mass spectrometry (CE-MS) and liquid chromatography-mass spectrometry (LC-MS). We performed comparative profiling of metabolite concentrations by assessing the metabolite profiles of patients who achieved a pathological complete response (pCR) against those who did not, both in initial and subsequent treatment cycles. RESULTS: Significant variances were observed in the metabolite profiles between pCR and non-pCR cases, both at the onset of preoperative chemotherapy and before the second cycle. Noteworthy distinctions were also evident between the metabolite profiles from the initial and the second neoadjuvant chemotherapy courses. Furthermore, metabolite profiles exhibited variations associated with intrinsic subtypes at all assessed time points. CONCLUSION: The application of plasma metabolomics, utilizing CE-MS and LC-MS, may serve as a tool for predicting the efficacy of neoadjuvant chemotherapy in breast cancer in the future after all necessary validations have been completed.

What are the Characteristics of Oral Injuries Caused by Playground Equipment?

PURPOSE: Studies regarding oral injuries from playground equipment in children remain limited. This study aimed to clarify the characteristics of oral injury caused by playground equipment and identify associations with concomitant head injury. METHODS: Children treated between 2011 and 2021 at an oral surgery clinic for oral injuries from playground equipment were retrospectively investigated. The following factors were analyzed: demographic characteristics, mechanism of injury, type of equipment causing the injury, classification of oral injury, and whether the Department of Emergency and Critical Care Medicine was consulted regarding the head injury. The data collected were statistically analyzed using the Fisher-Freeman-Halton test with significance adopted at the 5% level. RESULTS: This study analyzed data from 82 children. Injuries were concentrated in age groups of 2 to 3 years (32.9%), 4 to 5 years (28.0%), and 6 to 7 years (25.6%). Regarding the mechanism of injury, falls were more common (89.0%) than impact/striking (11.0%). The type of equipment most frequently causing injury was slides (29.3%), followed by swings (23.2%) and iron bars (18.3%). Injuries were classified as soft tissue injury alone (56.1%) or tooth injury and/or jaw fracture (43.9%). Consultation with the Department of Emergency and Critical Care Medicine for head injury was uncommon (13.4%), and all consultations for brain injury diagnosed minor injuries. CONCLUSION: Oral injuries caused by playground equipment were frequent between 2 and 7 years old. The most common cause was falls, with most injuries caused by slides, swings, or iron bars. Approximately half of the oral injuries were soft tissue injuries only, while the other half were associated with tooth and/or jaw injuries. Department of Emergency and Critical Care Medicine consultations for head trauma were uncommon and consistently confirmed minor injuries.

Efficacy and safety of dose-dense neoadjuvant chemotherapy with nab-paclitaxel followed by epirubicin and cyclophosphamide for operable breast cancer.

OBJECTIVE: Dose-dense chemotherapy has shown a better prognosis than standard interval chemotherapy in adjuvant settings for high-risk breast cancer. This study aimed to evaluate the efficacy and safety of dose-dense nanoparticle albumin-bound paclitaxel followed by dose-dense epirubicin and cyclophosphamide as neoadjuvant chemotherapy for human epidermal growth factor 2 (HER2)-negative operable breast cancer. METHODS: Patients with histologically confirmed stage I-III HER2-negative breast cancer were enrolled in this study. Patients received nanoparticle albumin-bound paclitaxel (260 mg/m2) followed by epirubicin (90 mg/m2) and cyclophosphamide (600 mg/m2) every 2 weeks with pegfilgrastim. The primary endpoint was the pathological complete response rate. Patients also underwent prophylactic management for peripheral neuropathy, which involved a combination of cryotherapy, compression therapy using elastic stockings and medications including goshajinkigan. RESULTS: Among the 55 patients enrolled in this study, 13 (23.6%) achieved pathological complete response, of whom 10/26 (38.5%) patients had triple-negative disease and 3/29 (10.3%) had luminal disease. The objective response was observed in 46 (83.6%) patients. Of the 36 patients who were initially planned for mastectomy, 11 (30.6%) underwent breast-conserving surgery after neoadjuvant chemotherapy. The most common grade 3-4 adverse events were myalgia (14.5%), fatigue (12.7%) and elevated transaminase levels (9.1%). No patients experienced febrile neutropenia. Eight (14.5%) patients discontinued treatments due to adverse events. CONCLUSIONS: Neoadjuvant dose-dense biweekly nanoparticle albumin-bound paclitaxel followed by dose-dense epirubicin and cyclophosphamide was effective, especially in patients with triple-negative disease, and feasible with pegfilgrastim support.

Large Nipple Volume as a Risk Factor of Nipple-areola Complex Necrosis Following Nipple-sparing Mastectomy.

BACKGROUND: Nipple-areola complex (NAC) necrosis, which is caused by local ischemia, remains one of the complications associated with nipple-sparing mastectomy. Obesity, smoking, diabetes mellitus, and immediate breast reconstruction have been identified as risk factors of NAC necrosis. The current study examined the correlation between NAC necrosis and nipple volume. MATERIALS AND METHODS: A total of 83 patients who underwent NSM for primary breast cancer from January 2016 to December 2019 were retrospectively analyzed. Nipple volume was determined using the formula: volume (cc) = length × width × height (mm), with measurements determined using contrast-enhanced magnetic resonance imaging. Total and partial NAC necrosis was defined as full-thickness necrosis requiring surgical procedures and epidermal necrosis managing local wound care, respectively. RESULTS: NAC necrosis was observed in 30 patients (36%), with 3 and 27 patients having total and partial necrosis, respectively. Large nipple volume (56% vs. 24%, p = 0.006), as well as smoking and immediate breast reconstruction (57 vs. 28%, p = 0.017; 48% vs. 20%, p = 0.009, respectively), were significantly correlated with NAC necrosis. Multivariate analysis identified nipple volume as an independent risk factor for NAC necrosis (OR, 3.75; 95% CI, 1.23-11.44; p = 0.02). Smoking (OR, 4.68; 95% CI, 1.37-15.94; p = 0.014) and immediate breast reconstruction (OR, 3.43; 95% CI, 1.05-11.23; p = 0.042) were also independently associated with NAC necrosis. CONCLUSIONS: This study suggested that a large nipple volume could be one of the risk factors for NAC necrosis following NSM.

What Are Possible Contributors to Associated Dental Injury in Mandibular Fractures?

PURPOSE: Among previous reports on dental injuries associated with mandibular fractures, there are few investigating the conditions under which dental injuries commonly occur. The aim of this study was to determine specific characteristics of mandibular fractures accompanied by dental injuries. METHODS: This retrospective cohort study included dentate patients with mandibular fractures treated at a tertiary trauma center between 2011 and 2019. The data were analyzed according to 2 outcome variables: patients with additional dental injuries and patients without. The predictor variables were patient age, sex, accident mechanism, number and location of mandibular fractures, and presence of submental lacerations. Odds ratios for the risk factors for dental injury were calculated in conjunction with descriptive statistics. Binary logistic regression analysis was also performed to identify the factors associated with dental injuries as dependent variables. RESULTS: Of 252 patients who had only mandibular fractures, 95 (37.7%) had associated dental injuries. In the group with dental injuries, 55.8% of mandibular fractures were caused by a fall (P = .003). Condyle fractures (77.9%) with dislocation (67.6%) and bilateral involvement (41.9%) were more common than in the group without dental injuries (P < .001). In patients with dental injuries, the incidence of 3 or more fractures (29.5%) was significantly higher than in the group without dental injuries. Dental injuries were more likely to occur in patients with concomitant submental lacerations (confidence interval (CI) 1.135-4.983, P = .02), and the risk of dental injury was significantly lower in the presence of angle fractures (CI 0.113-0.999, P = .045). CONCLUSIONS: A frontal impact involving the anterior part of the mandible is often associated with condyle and multiple mandibular fractures. This seems to be the typical mechanism for concomitant dental injuries. Submental laceration can be considered a prime sign of associated dental injuries.

Accidental oral bleeding in a dementia patient taking anticoagulants: A case report.

INTRODUCTION: Identifying the causes of accidental oral bleeding can be difficult in patients with dementia. The aim of this study was to highlight the effectiveness of multidisciplinary consultation, which proved extremely useful in investigating the cause of bleeding in this case. CASE PRESENTATION: An 86-year-old woman on anticoagulants who had been admitted to a geriatric facility experienced repeated oral bleeding of unknown cause, initially attributed to periodontitis. CONCLUSION: Along with anticoagulant use, a multidisciplinary consultation attributed the bleeding to the use of a spoon at mealtimes and possible scratching at the wound by the patient with her fingers.

Arterial Stiffness Index and Exercise Tolerance in Patients Undergoing Cardiac Rehabilitation.

Arterial stiffness contributes to the development of cardiovascular disease (CVD). However, the relationship between the arterial stiffness and exercise tolerance in CVD patients with preserved ejection fraction (pEF) and those with reduced EF (rEF) is unclear. We enrolled 358 patients who participated in cardiac rehabilitation and underwent cardiopulmonary exercise testing at Juntendo University Hospital. After excluding 195 patients who had undergone open heart surgery and 20 patients with mid-range EF, the patients were divided into pEF (n = 99) and rEF (n = 44) groups. Arterial stiffness was assessed using arterial velocity pulse index (AVI) and arterial pressure volume index (API) at rest. The patients in the pEF group were significantly older and had a higher prevalence of coronary artery disease than the rEF group. The pEF group had significantly lower AVI levels and higher API levels than the rEF group. In the pEF group, the peak oxygen uptake (peak VO2) and the anaerobic threshold was significantly higher than those in the rEF group. The peak VO2 was significantly and negatively correlated with AVI and API in the pEF group (All, P < 0.05), but not in the rEF group. Multivariate linear regression analyses demonstrated that AVI was independently associated with peak VO2 (ß = -0.34, P < 0.05) in the pEF group. In conclusion, AVI may be a useful factor for assessing exercise tolerance, particularly in CVD patients with pEF.

Diverticulum in buccal mucosa: A rare sac-like oral pouch.

OBJECTIVE: This article describes a rare case of oral diverticulum. BACKGROUND: Diverticulum represents a sac-like protrusion of the gastrointestinal tract, commonly arising in the colon wall of elder individuals. Zenker's diverticulum can also occur in the pharyngeal mucosa. However, oral diverticulum appears rare. MATERIAL AND METHOD: The patient was an 88-year-old man with dementia living in a geriatric facility. A dental hygienist incidentally identified a small pouch containing stagnant food residue in the left buccal mucosa during oral hygiene procedures. RESULTS: The small pouch with stagnant food residue was identified as a diverticulum. CONCLUSION: Diverticula may be identified from the stagnation of food residue. Dental specialists who practice oral hygiene should be aware of diverticula as a differential diagnosis.

Association between the tissue accumulation of advanced glycation end products and exercise capacity in cardiac rehabilitation patients.

BACKGROUND: Advanced glycation end products (AGEs) are associated with aging, diabetes mellitus (DM), and other chronic diseases. Recently, the accumulation of AGEs can be evaluated by skin autofluorescence (SAF). However, the relationship between SAF levels and exercise capacity in patients with cardiovascular disease (CVD) remains unclear. This study aimed to investigate the association between the tissue accumulation of AGEs and clinical characteristics, including exercise capacity, in patients with CVD. METHODS: We enrolled 319 consecutive CVD patients aged ≥40 years who underwent early phase II cardiac rehabilitation (CR) at our university hospital between November 2015 and September 2017. Patient background, clinical data, and the accumulation of AGEs assessed by SAF were recorded at the beginning of CR. Characteristics were compared between two patient groups divided according to the median SAF level (High SAF and Low SAF). RESULTS: The High SAF group was significantly older and exhibited a higher prevalence of DM than the Low SAF group. The sex ratio did not differ between the two groups. AGE levels showed significant negative correlations with peak oxygen uptake and ventilator efficiency (both P <  0.0001). Exercise capacity was significantly lower in the high SAF group than in the low SAF group, regardless of the presence or absence of DM (P <  0.05). A multivariate logistic regression analysis showed that SAF level was an independent factor associated with reduced exercise capacity (odds ratio 2.10; 95% confidence interval 1.13-4.05; P = 0.02). CONCLUSION: High levels of tissue accumulated AGEs, as assessed by SAF, were significantly and independently associated with reduced exercise capacity. These data suggest that measuring the tissue accumulation of AGEs may be useful in patients who have undergone CR, irrespective of whether they have DM.

Irijimasides A-E, Macrolide Glycosides from an Okeania sp. Marine Cyanobacterium.

Irijimasides A-E (1-5), a series of new 14-membered macrolide glycosides, were isolated from a marine cyanobacterium collected in Okinawa. The gross structures of 1-5 were established by spectroscopic analysis, including 2D NMR, while absolute stereostructures were determined based on NOESY spectra, chemical derivatization, and ECD data. All five macrolides suppressed receptor activator of nuclear factor-κB ligand (RANKL)-induced tartrate-resistant acid phosphatase (TRAP) activity in mouse RAW264 macrophage cells, indicating that these compounds inhibit osteoclast formation.

Effects of loss of consciousness on maxillofacial fractures in simple falls.

BACKGROUND/AIMS: Loss of consciousness while falling is reported to increase the risk of more severe injury. However, few studies of maxillofacial injuries have been reported. The aim of this study was to investigate the effects of loss of consciousness on maxillofacial fractures in falls on a level surface (simple falls). MATERIAL AND METHODS: Patients with maxillofacial fractures caused by simple falls were subdivided into two categories: patients who fell without loss of consciousness and patients who fell with loss of consciousness, according to the Guidelines for the Diagnosis and Management of Syncope (version 2009). The severity of the injuries was compared between these two groups. RESULTS: In 413 patients with maxillofacial fractures, 58 cases were falls without loss of consciousness, and 44 cases were falls with loss of consciousness. In falls with loss of consciousness, 54.5% were reflex syncope, followed by syncope due to orthostatic hypotension (15.9%), epilepsy (15.9%), and cardiac syncope (9.1%). The average number of fracture lines in the mandible was significantly lower in falls without loss of consciousness (1.53 ± 0.7) than in falls with loss of consciousness (2.00 ± 1.00) (P = 0.045). The average Facial Injury Severity Scale score was lower in falls without loss of consciousness (2.24 ± 1.20) than in falls with loss of consciousness (2.68 ± 1.39). Fractures of other parts of the body were significantly more common in falls without loss of consciousness (22.2%) than in falls with loss of consciousness (9.1%) (P = 0.0135). CONCLUSIONS: Patients with loss of consciousness and maxillofacial fractures due to simple falls showed a tendency to sustain more severe maxillofacial injuries than those without loss of consciousness.

Impact of Physical Activity on Coronary Plaque Volume and Components in Acute Coronary Syndrome Patients After Early Phase II Cardiac Rehabilitation.

BACKGROUND: Cardiac rehabilitation (CR) is an established multidisciplinary secondary preventive program. We investigated the effects of CR involving intensive physical activity (PA) on coronary plaque volume and components in patients with acute coronary syndrome (ACS).Methods and Results:We enrolled 32 consecutive patients with ACS in early phase II CR and randomly assigned them to an intensive CR group (n=18; CR participation ≥twice/week, daily PA ≥9,000 steps) or a standard CR group (n=14; CR participation ≥once/2weeks, daily PA ≥6,000 steps). Serial integrated backscatter intravascular ultrasound was performed for non-culprit lesions at baseline and after 8 months. Baseline clinical data were identical between the 2 groups. Unexpectedly, CR participation and PA did not differ significantly between the 2 groups, and there was no significant difference in plaque volume (PV) or components between the 2 groups. Subsequently, we classified the patients into 2 groups according to median PA (7,000 steps). There were significant differences in percent change of PV and of lipid volume between these 2 groups. In addition, these changes were negatively and independently correlated with PA. CONCLUSIONS: No significant difference was observed in PV or components between the intensive CR and the standard CR groups. Intensive PA, however, may retard coronary PV and ameliorate lipid component in patients with ACS participating in late phase II CR.

An orally administered oral pathobiont and commensal have comparable and innocuous systemic effects in germ-free mice.

BACKGROUND AND OBJECTIVES: We recently proposed a novel mechanism linking periodontitis and systemic diseases, in which orally administered Porphyromonas gingivalis affects gut microbiota composition and subsequently leads to systemic inflammation. However, the mechanism by which P. gingivalis generates systemic effects from the gut is unknown. MATERIAL AND METHODS: Six-week-old germ-free mice were orally administered with either an oral pathobiont P. gingivalis or an oral commensal Lactobacillus salivarius twice a week for 5 weeks. Control mice were administered with vehicle only. Alveolar bone resorption was evaluated histologically. The expression profile of various genes was analyzed in gingival tissue, liver, small intestine and large intestine using real-time polymerase chain reaction. Sera were analyzed for antibody, endotoxin and interleukin (IL)-6 levels. Antibody levels were also analyzed for culture supernatant of cells from mesenteric lymph nodes and spleens. A proportion of T-helper 17 and Treg in the cells from mesenteric lymph nodes and spleens was analyzed by flow cytometry. The level of IL-6 and IL-17 in the cell culture supernatants was analyzed by enzyme-linked immunosorbent assay. RESULTS: P. gingivalis administration did not induce alveolar bone resorption. Although P. gingivalis elicited systemic antibody response in germ-free mice, unlike in specific pathogen-free mice, P. gingivalis did not induce an inflammatory response in gingiva, liver and intestinal tissue, or alter the proportion of T-helper 17 and Treg. However, IL-6 and IL-17 productions were significantly elevated and tended to be elevated, respectively, in the cells from mesenteric lymph nodes of P. gingivalis-administered mice. Interestingly, the expression of IL-10 and tight junction protein in the gingiva and intestine, respectively, was significantly upregulated in P. gingivalis-treated mice. Administration of L. salivarius elicited almost similar effects as P. gingivalis. CONCLUSION: The oral pathobiont P. gingivalis did not induce any detectable pathogenic changes or any major host responses when administered to germ-free mice. There may be indirect mechanisms for gut-mediated systemic effects by P. gingivalis.

Ypaoamides B and C, Linear Lipopeptides from an Okeania sp. Marine Cyanobacterium.

Two new pyrrolinone-containing lipopeptides, ypaoamides B (1) and C (2), were isolated from an Okeania sp. marine cyanobacterium collected in Okinawa. Their structures were determined by spectroscopic analysis and Marfey's analysis of acid hydrolysates. Ypaoamides B (1) and C (2) stimulated glucose uptake in cultured rat L6 myotubes. In particular, ypaoamide B (1) showed potent activity and activated AMP-activated protein kinase.

Family-Centered Care in Neonatal Intensive Care Units: Combining Intensive Care and Family Support.

Advances in treatment in neonatal intensive care units (NICU) for preterm and sick newborns have improved the mortality rate of patients, but admission to the NICU may disrupt parent-infant interaction, with adverse consequences for infants and their families because of physical, psychological, and emotional separation. The concept of family centered care (FCC), in which family members are part of the care team and infants are close to the family, is important and has become popular in NICU. In 2013, we created a team called "Kodomo-Kazoku Mannaka" to promote FCC in Japan, and visited the NICU at Uppsala University Hospital in Sweden, which is internationally famous for FCC. Since this fruitful visit, we have been promoting FCC in Japan by exhibitions and presentations of the FCC ideas at academic conferences and using internet services. A questionnaire survey conducted in 2015 revealed that the importance and the benefits of FCC in NICU are recognized, although there are some barriers to FCC in each facility. It is hard to change facilities and social systems right away, but it is easier and more important to change people's minds. Our role is to spread the concept of FCC and to help each facility find its own way to adopt it. We will continue to make efforts encourage to promote FCC in Japan.

Association of the chromodomain helicase DNA-binding protein 4 (CHD4) missense variation p.D140E with cancer: potential interaction with smoking.

Chromodomain helicase DNA-binding protein 4 (CHD4) plays a pivotal role in chromatin-remodeling and has been implicated in the development of cancer. The aim of this study is to determine the association of CHD4 gene variants with cancer. Nine missense single nucleotide variations (SNVs) in CHD4 were retrieved from genotyping, by an exome-chip, 2,343 consecutive autopsy cases, in which the presence or absence of cancer was pathologically reviewed. The association of CHD4 variants with the presence of cancer and with different types of cancer was determined. Interaction with smoking was also determined. There were 1,446 patients with cancer and 897 patients without cancer. Of the nine SNVs, eight SNVs were monomorphic, while two nonsynonymous SNVs; rs7479004 (p.D140E) and rs1639122 (p.E139D) were further verified by direct sequencing. The p.D140E was associated with the presence of cancer (adjusted odds ratio [OR], 2.17; 95% confidence interval [CI], 1.37-3.44, P = 0.001), but not p.E139D. The effect size was larger in the smokers (adjusted OR, 4.66; 95% CI, 1.82-11.9; P =0.001), suggesting that there may be a gene environment interaction. For individual cancer types, p.D140E was associated with lung cancer (adjusted OR, 3.99; 95% CI, 2.07-7.67; P < 0.001), malignant lymphoma (adjusted OR, 3.24; 95% CI, 1.43-7.33; P = 0.005), and rectum cancer (adjusted OR, 6.23; 95% CI, 2.31-16.8; P < 0.001). A nonsynonymous SNV of CHD4, p.D140E, confers a risk of cancer and may interact with smoking habit to increase the risk.

[Intraoperative body temperature changes and short-term outcomes of open and minimally invasive esophagectomy].

BACKGROUND: Esophagectomy is a highly invasive procedure, and recently the use of minimally invasive esophagectomy (MIE) via thoracoscopy and laparoscopy increased, since this technique possibly enhances the recovery and outcomes of the patient compared with open esophagectomy (OE). However there is little data about intraoperative changes in body temperature during OE and MIE. METHODS: We retrospectively investigated the intraoperative body temperature and the postoperative short-term outcomes of patients undergoing OE (n = 33) or MIE (n = 24). The rectal temperature was recorded at 5 time points (at the start of the surgery, 1, 3, and 5 h after the start of the surgery, and at the end of the surgery). RESULTS: The average body temperature at the start was similar between the OE and MIE groups (36.5 +/- 0.4 vs. 36.6 +/- 0.5 degrees C, P = 0.497). Throughout the surgery, the temperature of the OE group increased to 37.1 +/- 0.6 degrees C, but the temperature in the MIE group decreased to 36.1 +/- 0.8 degrees C. There was no significant difference in 30-day mortality and short-term complications between the two groups. CONCLUSIONS: Our study showed that the intraoperative temperature during MIE tended to decrease compared with OE, but the short-term outcomes were comparable.

Do maxillary dentures protect the skull base from penetration injury?

Key Clinical Message: Foreign bodies penetrating from the oral cavity can damage surrounding tissues. This case is considered an extremely rare and fortunate instance in which a maxillary denture appeared to weaken the external force and change the direction of the scissors, preventing damage to vital organs. Abstract: The patient was a 73-year-old man. While on a ladder pruning a plant, he accidentally fell. The gardening scissors passed through the maxillary sinus from the maxillary alveolus and penetrated below the zygomatic arch. At the time of injury, the patient was wearing a metal-frame denture on the maxilla, and contact between the cutting edge and the denture was speculated to have weakened the piercing force of the blade and changed the direction of the cutting edge. This extremely rare case demonstrates how a maxillary denture could reduce the severity of a penetrating injury caused by scissors.