Insertional Achilles tendinopathy: A radiographic cross-sectional comparison between symptomatic and asymptomatic heel of 71 patients.

Purpose: This retrospective study aimed to investigate whether the standard radiographic indicators for Haglund's syndrome are applicable to insertional Achilles tendinopathy. Methods: Patients who underwent surgery for insertional Achilles tendinopathy in one heel and experienced no pain in the other heel were enrolled in this study. Preoperative calibrated radiographs of the lateral view of the calcaneus were assessed using (1) calcaneal pitch angle, (2) Fowler-Phillip angle, (3) posterior calcaneal angle, (4) Chauveau-Liet angle, (5) X/Y ratio, (6) Haglund's deformity height, (7) Haglund's deformity peak angle, (8) calcification length, (9) calcification width, (10) parallel pitch test, and (11) presence of free body. The Wilcoxon signed rank test and McNemar's test were used for statistical analyses. Results: Seventy-one patients (52 males; mean age, 57.2; mean body mass index, 27.1) were included. Mean values for each index in the symptomatic and asymptomatic heels were as follows, respectively: (1) 23.5, 23.0 (p = 0.30); (2) 58.9, 57.8 (p < 0.05); (3) 7.6, 9.2 (p < 0.05); (4) 15.8, 13.9 (p < 0.05); (5) 2.8, 2.8 (p = 0.87); (6) 5.4, 5.0 (p < 0.05); (7) 99.6, 99.0 (p = 0.44); (8) 10.5, 7.6 (p < 0.001); and (9) 5.1, 4.4 (p < 0.05). The sensitivity, specificity, and area under curve of significant indicators were as follows, respectively: (2) 0.78, 0.37, 0.55; (3) 0.45, 0.72, 0.58; (4) 0.63, 0.54, 0.57; (6) 0.45, 0.69, 0.59; (8) 0.48, 0.80, 0.66; and (9) 0.63, 0.54, 0.59. The presence of free body also showed a significant difference between both heels (p < 0.05). Conclusion: Some radiographic indicators for Haglund's syndrome are applicable to the diagnosis of insertional Achilles tendinopathy. A comparison of the parameters of Haglund's syndrome with those of insertional Achilles tendinopathy may illuminate the etiology and pathology of insertional Achilles tendinopathy and lead to novel treatments.

Fluoroscopic and Endoscopic Calcaneal Exostosis Resection and Achilles Tendon Debridement for Insertional Achilles Tendinopathy: Surgical Techniques.

This Technical Note describes the minimally invasive surgical techniques for insertional Achilles tendinopathy: fluoroscopic and endoscopic calcaneal exostosis resection and Achilles tendon debridement. First, two portals are placed 1 cm proximal and distal to the exostosis on the lateral heel. Next, blunt dissection around the exostosis and exostosis resection is performed under fluoroscopic guidance. The remaining space after the exostosis resection is used as the working space for endoscopy. Finally, the degenerated Achilles tendon is debrided endoscopically.

Distal Metatarsal and Proximal Phalangeal Osteotomies without Soft Tissue Procedure for Hallux Valgus with 80° Hallux Valgus Angle: A Case Report.

Introduction: The commonly performed procedure for treating severe hallux valgus is proximal metatarsal osteotomy or first tarsometatarsal arthrodesis combined with a soft tissue procedure in which the severe intermetatarsal angle (IMA) is corrected using proximal metatarsal osteotomy or first tarsometatarsal arthrodesis; although a severe hallux valgus angle (HVA) can be corrected using the soft tissue procedure alone, the correction ability is low. Therefore, the more severe the hallux valgus is, the more difficult it is to correct. Case Report: A 52-year-old woman (height, 142 cm; weight, 47 kg) with severe hallux valgus with an HVA of 80° and an IMA of 22° was treated with a combination of the distal metatarsal and proximal phalangeal osteotomies fixated using K-wires, which was a modification of Kramer's and Akin's procedures, without a soft tissue procedure. The concept behind this technique is that distal metatarsal osteotomy primarily corrects the hallux valgus, and when the correction is insufficient, the proximal phalanx osteotomy complements it, which ensures that the first ray is approximately straight. After 4.1 years of follow-up, the HVA and IMA were 16° and 13°, respectively. Conclusion: Distal metatarsal and proximal phalangeal osteotomies without a soft tissue procedure were effective in treating a patient with severe hallux valgus with an HVA of 80°.

Minimally invasive surgeries for insertional Achilles tendinopathy: A commentary review.

Studies of minimally invasive surgery for insertional Achilles tendinopathy are limited. To establish this surgery, the following techniques must be minimally invasive: Exostosis resection at the Achilles tendon insertion, debridement of degenerated Achilles tendon, reattachment using anchors or augmentation using flexor hallucis longus (FHL) tendon transfer, and excision of the posterosuperior calcaneal prominence. Studies on these four perspectives were reviewed to establish minimally invasive surgery for insertional Achilles tendinopathy. Techniques for exostosis resection were demonstrated in one case study, where blunt dissection around the exostosis was performed, and the exostosis was resected using an abrasion burr under fluoroscopic guidance. Techniques for debridement of degenerated Achilles tendon were demonstrated in the same case study, where the space left after resection of the exostosis was used as an endoscopic working space, and the degenerated Achilles tendon and intra-tendinous calcification were debrided endoscopically. Achilles tendon reattachment techniques using suture anchors have been demonstrated in several studies. However, there are no studies on FHL tendon transfer techniques for Achilles tendon reattachment. In contrast, endoscopic posterosuperior calcaneal prominence resection is already established. Additionally, studies on ultrasound-guided surgeries and percutaneous dorsal wedge calcaneal osteotomy as minimally invasive surgery were reviewed.

Inhibition of high-fat diet-induced inflammatory responses in adipose tissue by SF1-expressing neurons of the ventromedial hypothalamus.

Inflammation and thermogenesis in white adipose tissue (WAT) at different sites influence the overall effects of obesity on metabolic health. In mice fed a high-fat diet (HFD), inflammatory responses are less pronounced in inguinal WAT (ingWAT) than in epididymal WAT (epiWAT). Here we show that ablation and activation of steroidogenic factor 1 (SF1)-expressing neurons in the ventromedial hypothalamus (VMH) oppositely affect the expression of inflammation-related genes and the formation of crown-like structures by infiltrating macrophages in ingWAT, but not in epiWAT, of HFD-fed mice, with these effects being mediated by sympathetic nerves innervating ingWAT. In contrast, SF1 neurons of the VMH preferentially regulated the expression of thermogenesis-related genes in interscapular brown adipose tissue (BAT) of HFD-fed mice. These results suggest that SF1 neurons of the VMH differentially regulate inflammatory responses and thermogenesis among various adipose tissue depots and restrain inflammation associated with diet-induced obesity specifically in ingWAT.

Serum periostin levels in adolescents.

BACKGROUND: The significance of periostin as a biomarker of Th2-induced airway inflammation has recently been highlighted in adult patients with allergic diseases. It may help identify drug-responsive inflammatory phenotypes, particularly in children. However, little is known about the usefulness of this parameter as a biomarker for allergic diseases in children. Furthermore, it is not known how much adolescent bone metabolism affects allergic inflammation. OBJECTIVE: To evaluate the relationship between serum periostin levels and allergic diseases in adolescents, we investigated periostin levels and the prevalence of allergic diseases. METHODS: We conducted a cross-sectional observational study of 100 males and females in two age groups: age 9-12 years (pre-early adolescence) and 13-15 years (post-early adolescence). Serum periostin levels were determined using Enzyme-Linked Immuno Sorbent Assay (ELISA). Presence of allergic diseases and allergy sensitization were obtained via a self-reported survey and the Multiple Antigen Simultaneous Test (MAST). The protocol was registered in a clinical trial registry as UMIN 000036051. RESULTS: There were no significant differences in serum periostin levels between pre-early and post-early adolescents. There were no differences by gender. Age and Body Mass Index were not significantly associated with serum periostin levels. Periostin levels were elevated in adolescents with allergic diseases overall compared to healthy adolescents [mean (95%CI): 41.6 (33.4, 49.7) vs. 28.6 (21.9, 35.3) ng/ml; P < 0.05]. CONCLUSIONS: The effects of bone metabolism on serum periostin levels may be limited at 9-15 years of age. Further studies are required to determine reference values in adolescents.

Sliding Oblique Metatarsal Osteotomy Fixated With K-Wires Without Cheilectomy for All Grades of Hallux Rigidus: A Case Series of 76 Patients.

Background: Studies on decompression metatarsal osteotomy without cheilectomy for hallux rigidus are limited. This study aimed to review the data of patients who underwent this surgery for all grades of hallux rigidus. Methods: The medical records of patients who underwent this surgery between August 2017 and January 2021 were retrospectively reviewed. The outcomes were assessed using the visual analog scale (VAS), the Japanese Society for Surgery of the Foot (JSSF) score, and the hallux dorsiflexion angle. Patients who were followed up for more than 2 years were included. The plantar shift of the first metatarsal head (PS) and the shortening of the first metatarsal (SH) were measured to supplementally investigate the associations with other measurements. Results: A total of 76 patients (female, 42; male, 34; mean age, 60.3 years; mean body mass index, 23.1) with 80 feet were enrolled. Six patients (7.5%) were grade 1, 20 (25.0%) were grade 2, 30 (37.5%) were grade 3, and 24 (30.0%) were grade 4. The mean follow-up duration was 3.5 years. Overall, the mean VAS score improved from 63.2 to 6.2, the mean JSSF score from 59.0 to 82.6, and the mean dorsiflexion angle from 37.3 to 56.3 degrees. These measures improved for all grades, but the dorsiflexion angles and JSSF scores decreased as the grade advanced. No clear associations were found between the postoperative VAS and the PS and SH. Eight patients (10.5%) had complications: 4 (5.2%) had occasional plantar discomfort under the metatarsal head, 2 (2.6%) required shoe modification, 1 (1.3%) had wound pain, and 1 (1.3%) experienced breakage of a K-wire. Conclusion: The VAS scores, dorsiflexion angles, and JSSF scores improved for all grades of hallux rigidus within a relatively short period of follow-up; however, the dorsiflexion angles and JSSF scores decreased as the grade advanced. Level of Evidence: Level IV, retrospective case series.

Arthroscopic Autologous Bone Grafting for Hallux Sesamoid Fracture Nonunion Results in a High Rate of Complete Resolution.

Purpose: To review the outcomes of patients with hallux sesamoid fracture nonunion who underwent arthroscopic autologous bone grafting. Methods: Medical records of patients who underwent surgery between July 2017 and April 2020 were reviewed. The inclusion criterion was 2 years or more of follow-up. The exclusion criterion was less than 2 years of follow-up. Outcomes were assessed using the visual analog scale (VAS) for pain and the Japanese Society for Surgery of the Foot (JSSF) score. Improvements after surgery were analyzed using the Wilcoxon signed-rank test. Results: Eleven patients (3 women and 8 men) were enrolled. The mean age was 18.6 years (standard deviation [SD] ± 10.3 years), and the mean body mass index was 21.9 kg/m2 (SD ± 2.5 kg/m2). The mean follow-up duration was 3.2 years (SD ± 0.8 years). One patient had fracture nonunion in the fibular sesamoid and a hypoplastic tibial sesamoid. Another patient had fracture nonunion in the distal part of the congenital bipartite sesamoid. The other patients had fracture nonunion in the normal tibial sesamoids. The mean duration until bone union was 2.9 months (SD ± 0.8 months). The mean duration until returning to sports was 5.3 months (SD ± 3.6 months). The VAS score improved from 72.1 (SD ± 15.2) preoperatively to 12.0 (SD ± 26.7) postoperatively. The JSSF score improved from 58.7 (SD ± 15.8) preoperatively to 95.0 (SD ± 11.0) postoperatively (P < 0.01, respectively). All patients except the two previously described achieved a VAS score of 0 and a JSSF score of 100 postoperatively. The remaining 2 patients with congenitally distinct sesamoids and fractures had poor outcomes. No complications were observed. Conclusions: Nine of the 11 patients reported complete resolution. The remaining two patients with congenitally distinct sesamoids and fractures had poor outcomes.

Endoscopic Plantar Fascia Release Combined With Calcaneal Spur Resection: A Case Series of 40 Patients.

PURPOSE: To review the cases of patients treated using endoscopic plantar fascia release (PFR) with calcaneal spur resection (CSR) and examine why the combined procedures cause complications. METHODS: The medical records of patients treated with endoscopic PFR with CSR from November 2017 to December 2019 with a follow-up of >2 years were reviewed. RESULTS: A total of 40 feet in 40 patients (22 females, 18 males) were enrolled. The mean age and body mass index were 51.1 years and 24.7 kg/m2, respectively. The mean follow-up duration was 5.7 years. The visual analog scale for pain improved from 80.7 to 8.8 mm, and the Japanese Society for Surgery of the Foot score improved from 44.7 to 95.6 points (Wilcoxon signed rank test, P < .001 for both). Complications occurred in 8 patients (20%): 3 had flatfoot, 3 had an injury to the first branch of the lateral plantar nerve, 1 had scar pain, and 1 had a wound infection. CONCLUSION: The 40 patients treated with endoscopic PFR with CSR for plantar fasciitis had good outcomes with a high complication rate; the invasiveness of creating the working space for the combined procedures was thought to be responsible. LEVELS OF EVIDENCE: Level IV: Case series.

Fluoroscopic and Endoscopic Calcaneal Exostosis Resection and Achilles Tendon Debridement for Insertional Achilles Tendinopathy Results in Good Outcomes, Early Return to Sports Activities, and Few Wound Complications.

Purpose: To review the outcomes of patients with insertional Achilles tendinopathy who underwent a minimally invasive surgery: fluoroscopic and endoscopic calcaneal exostosis resection and Achilles tendon debridement. Methods: The medical records of consecutive patients who underwent this surgery from February 2017 to July 2019 were reviewed. The inclusion criterion was ≥2-year follow-up. The exclusion criterion was another surgery performed on the ipsilateral or contralateral foot. Haglund deformity resection was not combined with this surgery. The outcomes were assessed using the visual analog scale (VAS) score and the Japanese Society for Surgery of the Foot (JSSF) scores for all patients and the Victorian Institute of Sport Assessment self-administered Achilles (VISA-A) scores for patients participating in sports activities. The Wilcoxon signed-rank test and the thresholds of minimal clinically important difference (MCID) and patient acceptable symptom state (PASS) were used for statistical analyses. Results: Forty-four patients with a mean age of 55.7 ± 11.0 years and mean body mass index of 26.0 ± 4.0 kg/m2 were included. The mean follow-up duration was 2.8 ± 0.7 years. Of all participants, 22 participated in sports activities. The overall median VAS and JSSF scores improved from 64.5 to 6.5 mm and from 67.0 to 100 points, respectively (P < .001). The percentages of patients who achieved the MCID for the VAS, JSSF, and VISA-A scores were 100%, 93.2%, and 100%, respectively, and the percentages of patients who achieved the PASS for the VAS, JSSF, and VISA-A scores were 77.3%, 86.4%, and 81.8%, respectively. The median VISA-A scores improved from 40.5 to 95.0 points (P < .001). The median time to return to sport was 4.5 months. Complications included five cases of reoperation and two cases of scar sensitivity. Conclusion: For patients with insertional Achilles tendinopathy, fluoroscopic and endoscopic calcaneal exostosis resection and Achilles tendon debridement resulted in good outcomes, early return to sports activities, and few wound complications. Level of Evidence: IV, therapeutic case series.

Neural insights into sweet taste transduction and hunger-induced taste modification in mice.

Feeding is one of the most fundamental activities in the survival and reproduction of animals. During feeding, the gustatory system functions as a gatekeeper to evaluate food quality. Accumulated evidence in the field of taste research has shown that 5 basic tastes (sweet, umami, sour, bitter, and salty) are sensed by the corresponding taste receptors expressed in taste receptor cells on the tongue. In contrast, brain mechanisms that transduce or modify taste information have been less studied. In this review, I introduce our recent findings on the sweet taste transduction in the brainstem of mice and explain the hypothalamic neuronal network regulating hunger-induced taste modification. Finally, future perspectives are discussed.

Fluoroscopic and Endoscopic Calcaneal Spur Resection Without Plantar Fascial Release for Recalcitrant Plantar Fasciitis.

Background: Studies on endoscopic calcaneal spur resection (CSR) without plantar fascial release (PFR) are limited. This study aimed to review the data of patients who underwent fluoroscopic and endoscopic CSR without PFR for plantar fasciitis with a calcaneal spur to assess the effectiveness of CSR. Methods: Medical records of consecutive patients with plantar fasciitis with ≥2 mm calcaneal spur who underwent endoscopic CSR without PFR from November 2017 to December 2019 were reviewed. Patients with ≥2 years of follow-up were included, whereas those who underwent another surgery on the operated foot were excluded. Age, body mass index (BMI), follow-up duration, calcaneal spur length, duration to full weightbearing postoperatively, Japanese Society for Surgery of the Foot (JSSF) score, visual analog scale (VAS) score for pain, and complications were assessed. Results: The mean follow-up duration was 2.7 years. A total of 47 patients (31 female, 16 male; mean age, 56.4 years; mean BMI, 25.5) were included. The mean calcaneal spur length was 5.7 mm. The VAS score improved from 79.6 ± 12.9 mm preoperatively to 5.3 ± 7.3 mm postoperatively. The JSSF score improved from 54.0 ± 19.1 points preoperatively to 97.5 ± 5.7 points postoperatively (Wilcoxon signed-rank test, P < .001, respectively). The mean duration to full weightbearing postoperatively was 4.4 ± 4.2 days. Two patients presented with tenderness, and one presented with hypesthesia at the portal site. Conclusion: Endoscopic CSR without PFR resulted in good outcomes, early return to full weightbearing, and few complications in patients with plantar fasciitis with ≥2 mm calcaneal spur. The results suggested that CSR was sufficient to relieve symtoms and improve function. PFR may not be necessary for treating plantar fasciitis with calcaneal spur. Level of Evidence: Level IV, retrospective case series.

Sliding Oblique Metatarsal Osteotomy Fixated With a K-Wire Without Cheilectomy for Hallux Rigidus.

The current study aimed to assess the outcomes of sliding oblique metatarsal osteotomy fixated with a K-wire without cheilectomy for hallux rigidus. Pre- and postoperative variables, including dorsiflexion angle, visual analog scale score, and Japanese Society for Surgery of the Foot scale score, were assessed using the Wilcoxon signed-rank test. In addition, the surgical effects among the four grades were compared using the Kruskal-Wallis test. In total, 43 patients, including 11, 11, 15, and 6 with grade 1, 2, 3, and 4 hallux rigidus, respectively, were enrolled in this analysis. The mean age of the participants was 56.2 years, and the mean follow-up period was 3.0 years. Mean pre- and postoperative dorsiflexion angles were as follows: overall, 53.0° to 66.5° (p < .001); grade 1, 66.8° to 79.1°; grade 2, 59.1° to 68.6°; grade 3, 43.3° to 61.0°; and grade 4, 40.8° to 53.3°. Mean pre- and postoperative visual analog scale scores were as follows: overall, 70.1 to 6.5 (p < .001); grade 1, 74.2 to 3.0; grade 2, 66.4 to 7.6; grade 3, 69.5 to 8.4; and grade 4, 71.2 to 6.0. Finally, mean pre- and postoperative Japanese Society for Surgery of the Foot scale scores were as follows: overall, 61.2 to 86.6 (p < .001); grade 1, 63.8 to 93.6; grade 2, 68.3 to 85.9; grade 3, 54.4 to 83.1; and grade 4, 60.5 to 83.5. There was no statistically significant difference in the surgical effects among the four grades. Decompressive metatarsal osteotomy without cheilectomy was found to be effective. Moreover, the procedure could be performed for all grades of hallux rigidus.

Arthroscopic Sesamoidectomy for Hallux Sesamoid Disorders.

In this retrospective case series, we aimed to study arthroscopic sesamoidectomy, including surgical methods, clinical outcomes, and complications. We retrospectively reviewed the medical records of patients with hallux sesamoid disorders who underwent arthroscopic sesamoidectomy from July 2015 to July 2017. The visual analog scale for rating pain, Japanese Society for Surgery of the Foot scale scores, number of days taken to return to normal daily living, number of months taken to return to playing sports, and complications were analyzed. The mean follow-up duration was 3.2 years. Among 14 patients, there were 8 females and 6 males (median age: 39 years). The mean visual analog scale score improved from 75.4 to 14.3 mm; the mean Japanese Society for Surgery of the Foot score improved from 55.2 to 88.0 points. The mean time to return to activities of daily living was 5.3 days. Among the 5 patients who played sports, 3 and 2 patients resumed playing sports at 3 and 12 postoperative months, respectively. Complications included wound pain (n = 4), discomfort in severe weather (n = 4), numbness (n = 3), pain in the sole other than in the ball of the foot (n = 2), pain during hallux dorsiflexion (n = 2), residual sesamoid discomfort (n = 1), swelling (n = 1), toe-in gait (n = 1), and metatarsal head bone marrow edema (n = 1). Despite good clinical outcomes of arthroscopic sesamoidectomy, patients should be made aware of the many potential complications of this procedure prior to surgery.

De novo transcriptome analysis and comparative expression profiling of genes associated with the taste-modifying protein neoculin in Curculigo latifolia and Curculigo capitulata fruits.

BACKGROUND: Curculigo latifolia is a perennial plant endogenous to Southeast Asia whose fruits contain the taste-modifying protein neoculin, which binds to sweet receptors and makes sour fruits taste sweet. Although similar to snowdrop (Galanthus nivalis) agglutinin (GNA), which contains mannose-binding sites in its sequence and 3D structure, neoculin lacks such sites and has no lectin activity. Whether the fruits of C. latifolia and other Curculigo plants contain neoculin and/or GNA family members was unclear. RESULTS: Through de novo RNA-seq assembly of the fruits of C. latifolia and the related C. capitulata and detailed analysis of the expression patterns of neoculin and neoculin-like genes in both species, we assembled 85,697 transcripts from C. latifolia and 76,775 from C. capitulata using Trinity and annotated them using public databases. We identified 70,371 unigenes in C. latifolia and 63,704 in C. capitulata. In total, 38.6% of unigenes from C. latifolia and 42.6% from C. capitulata shared high similarity between the two species. We identified ten neoculin-related transcripts in C. latifolia and 15 in C. capitulata, encoding both the basic and acidic subunits of neoculin in both plants. We aligned these 25 transcripts and generated a phylogenetic tree. Many orthologs in the two species shared high similarity, despite the low number of common genes, suggesting that these genes likely existed before the two species diverged. The relative expression levels of these genes differed considerably between the two species: the transcripts per million (TPM) values of neoculin genes were 60 times higher in C. latifolia than in C. capitulata, whereas those of GNA family members were 15,000 times lower in C. latifolia than in C. capitulata. CONCLUSIONS: The genetic diversity of neoculin-related genes strongly suggests that neoculin genes underwent duplication during evolution. The marked differences in their expression profiles between C. latifolia and C. capitulata may be due to mutations in regions involved in transcriptional regulation. Comprehensive analysis of the genes expressed in the fruits of these two Curculigo species helped elucidate the origin of neoculin at the molecular level.

Recent Advances in Neural Circuits for Taste Perception in Hunger.

Feeding is essential for survival and taste greatly influences our feeding behaviors. Palatable tastes such as sweet trigger feeding as a symbol of a calorie-rich diet containing sugar or proteins, while unpalatable tastes such as bitter terminate further consumption as a warning against ingestion of harmful substances. Therefore, taste is considered a criterion to distinguish whether food is edible. However, perception of taste is also modulated by physiological changes associated with internal states such as hunger or satiety. Empirically, during hunger state, humans find ordinary food more attractive and feel less aversion to food they usually dislike. Although functional magnetic resonance imaging studies performed in primates and in humans have indicated that some brain areas show state-dependent response to tastes, the mechanisms of how the brain senses tastes during different internal states are poorly understood. Recently, using newly developed molecular and genetic tools as well as in vivo imaging, researchers have identified many specific neuronal populations or neural circuits regulating feeding behaviors and taste perception process in the central nervous system. These studies could help us understand the interplay between homeostatic regulation of energy and taste perception to guide proper feeding behaviors.

A novel MRI-based predictive index can identify patients suitable for preservation of the nipple-areola complex in breast reconstructive surgery.

INTRODUCTION: Accurately predicting nipple-areola complex (NAC) involvement in breast cancer is necessary for identifying patients who may be candidates for a nipple-sparing mastectomy. Although multiple risk factors are indicated in the guidelines, it is difficult to predict NAC involvement (NAC-i) preoperatively even if these factors are evaluated individually. This study aimed to develop a more accurate and practical preoperative NAC-i prediction model using magnetic resonance imaging (MRI). MATERIALS AND METHODS: All tumors in 252 patients were evaluated using postcontrast T1-weighted subtraction on MRI. RESULTS: The receiver operating characteristic curves identified cut-off values for tumor size and tumor-to-nipple distance (TND) as 4 cm and 1.2 cm, respectively. Multivariate analysis demonstrated that TND (p < 0.001), ductal enhancement extending to the nipple (DEEN) (p < 0.001), and nipple enhancement (NE) (p = 0.005) were independent clinical risk factors for pathological NAC-i. A formula was constructed using odds ratios for these three independent preoperative risk factors in multivariate analysis: the MRI-based NAC-i predictive index (mNACPI) = TND × 4 + DEEN × 3 + NE × 1. A total score of ≤4 points was defined as low risk and ≥5 points as high risk. NAC-i rates were 2.4% in the low-risk group and 89.4% in the high-risk group; a significant correlation was observed between the risk group and permanent pathological NAC-i (p < 0.001). Assuming that the NAC was preserved in low-risk patients and resected in high-risk patients, NAC-i was verified using the mNACPI. CONCLUSION: mNACPI may contribute greatly to the improvement of selecting suitable patients for NAC preservation in breast reconstructive surgery while maintaining oncological safety.

Homeostatic versus hedonic control of carbohydrate selection.

Macronutrient intake is associated with cardiometabolic health, ageing and longevity, but the mechanisms underlying its regulation have remained unclear. Most rodents increase carbohydrate selection under certain physiological and pathological conditions such as fasting. When presented with a choice between a basally preferable high-fat diet (HFD) and a high-carbohydrate diet (HCD) such as a high-sucrose diet, fasted mice first eat the HFD and then switch to the HCD during the first few hours of refeeding and continue to eat the HCD up to 24 h in the two-diet choice approach. Such consumption of an HCD after fasting reverses the fasting-induced increase in the plasma concentration of ketone bodies more rapidly than does refeeding with an HFD alone. 5'-AMP-activated protein kinase (AMPK)-regulated neurons in the paraventricular nucleus of the hypothalamus (PVH) that express corticotropin-releasing hormone (CRH) are necessary and sufficient for the fasting-induced selection of carbohydrate over an HFD in mice. These neurons appear to contribute to a fasting-induced increase in the positive valence of carbohydrate without affecting the preference for more palatable and energy-dense diets such as an HFD. Identification of the neural circuits in which AMPK-regulated CRH neurons in the PVH of mice are embedded should shed new light on the physiological and molecular mechanisms responsible for macronutrient selection.

Efficacy and Safety of Palbociclib and Fulvestrant in Japanese Patients With ER+/HER2- Advanced/Metastatic Breast Cancer.

BACKGROUND/AIM: Published data have shown that palbociclib-fulvestrant can significantly improve the progression-free survival (PFS) of estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-) metastatic breast cancer patients, but not of Japanese patients. We conducted this retrospective study to verify the efficacy and safety of palbociclib-fulvestrant in Japanese patients. PATIENTS AND METHODS: ER+/HER2- metastatic breast cancer patients treated with fulvestrant (n=39) or palbociclib-fulvestrant (n=31) at the Saitama Medical Center from July 2012 to November 2018 were evaluated. RESULTS: Overall response rates (ORRs) were 2.6% (fulvestrant) and 41.9% (palbociclib-fulvestrant) (p<0.001), and clinical benefit rates (CBRs) were 23.1% and 61.3% (p=0.002), respectively. The palbociclib-fulvestrant group had significantly higher CBR and PFS (hazard ratio(HR):0.272, 95% confidence interval(95CI):0.128-0.574 for PFS). Grade 3/4 neutropenia occurred in 80.6% of the palbociclib-fulvestrant group, while febrile neutropenia was not detected. CONCLUSION: Japanese ER+/HER2- metastatic breast cancer patients tolerated palbociclib-fulvestrant, with significantly improved clinical outcomes.

Hypothalamic neuronal circuits regulating hunger-induced taste modification.

The gustatory system plays a critical role in sensing appetitive and aversive taste stimuli for evaluating food quality. Although taste preference is known to change depending on internal states such as hunger, a mechanistic insight remains unclear. Here, we examine the neuronal mechanisms regulating hunger-induced taste modification. Starved mice exhibit an increased preference for sweetness and tolerance for aversive taste. This hunger-induced taste modification is recapitulated by selective activation of orexigenic Agouti-related peptide (AgRP)-expressing neurons in the hypothalamus projecting to the lateral hypothalamus, but not to other regions. Glutamatergic, but not GABAergic, neurons in the lateral hypothalamus function as downstream neurons of AgRP neurons. Importantly, these neurons play a key role in modulating preferences for both appetitive and aversive tastes by using distinct pathways projecting to the lateral septum or the lateral habenula, respectively. Our results suggest that these hypothalamic circuits would be important for optimizing feeding behavior under fasting.