The ketogenic diet does not improve cardiac function and blunts glucose oxidation in ischemic heart failure.

AIMS: Cardiac energy metabolism is perturbed in ischemic heart failure and is characterized by a shift from mitochondrial oxidative metabolism to glycolysis. Notably, the failing heart relies more on ketones for energy than a healthy heart, an adaptive mechanism that improves the energy-starved status of the failing heart. However, whether this can be implemented therapeutically remains unknown. Therefore, our aim was to determine if increasing ketone delivery to the heart via a ketogenic diet can improve the outcomes of heart failure. METHODS: C57BL/6J male mice underwent either a sham surgery or permanent left anterior descending (LAD) coronary artery ligation surgery to induce heart failure. After 2 weeks, mice were then treated with either a control diet or a ketogenic diet for 3 weeks. Transthoracic echocardiography was then carried out to assess in vivo cardiac function and structure. Finally, isolated working hearts from these mice were perfused with appropriately 3H or 14C labelled glucose (5 mM), palmitate (0.8 mM), and ß-hydroxybutyrate (0.6 mM) to assess mitochondrial oxidative metabolism and glycolysis. RESULTS: Mice with heart failure exhibited a 56% drop in ejection fraction which was not improved with a ketogenic diet feeding. Interestingly, mice fed a ketogenic diet had marked decreases in cardiac glucose oxidation rates. Despite increasing blood ketone levels, cardiac ketone oxidation rates did not increase, probably due to a decreased expression of key ketone oxidation enzymes. Furthermore, in mice on the ketogenic diet no increase in overall cardiac energy production was observed, and instead there was a shift to an increased reliance on fatty acid oxidation as a source of cardiac energy production. This resulted in a decrease in cardiac efficiency in heart failure mice fed a ketogenic diet. CONCLUSIONS: We conclude that the ketogenic diet does not improve heart function in failing hearts, due to ketogenic diet-induced excessive fatty acid oxidation in the ischemic heart and a decrease in insulin-stimulated glucose oxidation.

Ketones provide an extra source of fuel for the failing heart without impairing glucose oxidation.

BACKGROUND: Cardiac glucose oxidation is decreased in heart failure with reduced ejection fraction (HFrEF), contributing to a decrease in myocardial ATP production. In contrast, circulating ketones and cardiac ketone oxidation are increased in HFrEF. Since ketones compete with glucose as a fuel source, we aimed to determine whether increasing ketone concentration both chronically with the SGLT2 inhibitor, dapagliflozin, or acutely in the perfusate has detrimental effects on cardiac glucose oxidation in HFrEF, and what effect this has on cardiac ATP production. METHODS: 8-week-old male C57BL6/N mice underwent sham or transverse aortic constriction (TAC) surgery to induce HFrEF over 3 weeks, after which TAC mice were randomized to treatment with either vehicle or the SGLT2 inhibitor, dapagliflozin (DAPA), for 4 weeks (raises blood ketones). Cardiac function was assessed by echocardiography. Cardiac energy metabolism was measured in isolated working hearts perfused with 5 mM glucose, 0.8 mM palmitate, and either 0.2 mM or 0.6 mM ß-hydroxybutyrate (ßOHB). RESULTS: TAC hearts had significantly decreased %EF compared to sham hearts, with no effect of DAPA. Glucose oxidation was significantly decreased in TAC hearts compared to sham hearts and did not decrease further in TAC hearts treated with high ßOHB or in TAC DAPA hearts, despite ßOHB oxidation rates increasing in both TAC vehicle and TAC DAPA hearts at high ßOHB concentrations. Rather, increasing ßOHB supply to the heart selectively decreased fatty acid oxidation rates. DAPA significantly increased ATP production at both ßOHB concentrations by increasing the contribution of glucose oxidation to ATP production. CONCLUSION: Therefore, increasing ketone concentration increases energy supply and ATP production in HFrEF without further impairing glucose oxidation.

Functional Protein Dynamics in a Crystal.

Proteins are molecular machines and to understand how they work, we need to understand how they move. New pump-probe time-resolved X-ray diffraction methods open up ways to initiate and observe protein motions with atomistic detail in crystals on biologically relevant timescales. However, practical limitations of these experiments demands parallel development of effective molecular dynamics approaches to accelerate progress and extract meaning. Here, we establish robust and accurate methods for simulating dynamics in protein crystals, a nontrivial process requiring careful attention to equilibration, environmental composition, and choice of force fields. With more than seven milliseconds of sampling of a single chain, we identify critical factors controlling agreement between simulation and experiments and show that simulated motions recapitulate ligand-induced conformational changes. This work enables a virtuous cycle between simulation and experiments for visualizing and understanding the basic functional motions of proteins.

Report on hematopoietic cell transplantations performed in 2018/2019 focusing on the trends of selection of stem cell sources in the Asia-Pacific region: APBMT Activity Survey.

The number of hematopoietic stem cell transplantations (HCTs) is increasing annually worldwide, and the Asia-Pacific (AP) region is no exception. We report on the absolute number of HCTs in 2018 and 2019 and the trends in graft selection and disease indication in the past few decades. In 2018, 24,292 HCTs were performed in the AP region, of which 8,754 (36.0%) were autologous and 15,538 (64.0%) were allogeneic. Among the allogeneic HCTs, 10,552 (67.9%) of the recipients were related to their donors, whereas 4,986 (32.1%) were unrelated. In 2019, 27,583 HCTs were reported, of which 17,613 (63.9%) were allogeneic and 9,970 (36.1%) were autologous. Although, in 2010, there was a nearly equal number of related and unrelated HCTs, the difference has shown an annual increase, with more than double (2.05) the number of related than unrelated HCTs in 2019. Recent trends in the AP region show that peripheral blood has overwhelmingly surpassed the bone marrow as a graft source for both related and unrelated HCTs, with the haploidentical donor type being preferred; however, their trends in each country/region were quite different among countries/regions. In 2019, the main conditions requiring HCT were acute myelogenous leukemia (n=6,629 [24.0%]), plasma cell disorders (PCD) (n=4,935 [17.9%]), malignant lymphoma (ML) (n=4,106 [14.9%]), acute lymphoblastic leukemia (AML) (n=3,777 [13.7%]), myelodysplastic syndrome or myelodysplastic/myeloproliferative neoplasm (n=1,913 [6.9%]), severe aplastic anemia (n=1,671 [6.1%]), and hemoglobinopathy (n=910 [3.3%]). PCD and ML were the main indications for autologous HCT, and the number of PCD cases has grown more prominent than the corresponding of ML. The increased number of allogeneic transplants for hemoglobinopathy remains prominent, as well as that of AML and acute lymphocytic leukemia for the past 5 years. There was a significant regional variation in the number of facilities performing HCTs, ranging from one in Mongolia and Nepal to 313 in Japan, and differing regional densities varying from 0.1 in Indonesia and Pakistan to 24.7 in Japan. The total transplant density per 10 million population in each country/region also differed (0.2 in Indonesia and 627 in New Zealand). This annual Activity Survey aims to help all participating countries/regions understand the changes in HCT, serve as an asset in promoting HCT activities in the AP region, and be used as a reference for comparison with other registries from Europe and the United States.

Electroacupuncture for abdominal pain relief in patients with acute pancreatitis: A three-arm randomized controlled trial.

BACKGROUND: Electroacupuncture (EA) may reduce the severity of acute pancreatitis (AP) and provide additional pain relief in patients with chronic pancreatitis. However, the ability of EA to relieve pain in patients with AP has not been well documented. OBJECTIVE: This study was undertaken to compare the pain-relieving effects of EA and conventional treatment in patients with AP. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This study was conducted using a randomized, controlled, three-arm, parallel-group and multi-center design. Patients diagnosed with AP were randomly and equally assigned to EA1, EA2 or control groups. All participants received conventional standard-of-care therapy for AP. Local EA alone was administered in EA1, and local plus distal EA was given in EA2. Local EA included two abdominal acupoints, while distal EA included twelve peripheral acupoints. EA groups underwent one session of EA daily for 4 days (days 1-4), or until pain was resolved or discharged. MAIN OUTCOME MEASURES: The primary outcome measure was the change in the visual analogue scale (VAS; 0-100) pain score between baseline and day 5. RESULTS: Eighty-nine participants were randomized into EA1, EA2 and control groups, and 88 (EA1, 30; EA2, 29; control, 29) were included in the full-analysis set. VAS score change (median [interquartile range]) on day 5 was (12.3 ± 22.5) in the EA1 group, (10.3 ± 21.5) in the EA2 group, and (8.9 ± 15.2) in the control group. There were not significant differences in the change in VAS score among treatments (P = 0.983). However, time to food intake was significantly shorter in the EA group (EA1 + EA2) than in the control group (median 2.0 days vs 3.0 days), with a hazard ratio of 0.581 (P = 0.022; 95% CI, 0.366-0.924). No significant adverse events occurred. CONCLUSION: EA treatment did not significantly reduce pain after 4 days of treatment in patients with AP-associated abdominal pain but significantly reduced time to first food intake. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03173222. Please cite this article as: Jang DK, Lee JK, Jung CY, Kim KH, Kang HR, Lee YS, Yoon JH, Joo KR, Chae MK, Baek YH, Seo BK, Lee SH, Lim C. Electroacupuncture for abdominal pain relief in patients with acute pancreatitis: A three-arm randomized controlled trial. J Integr Med. 2023; 21(6): 537-542.

The effect of MnCO3 on the gain coefficient for the 4I13/2 → 4I15/2 transition of Er3+ ions and near-infrared emission bandwidth flatness of Er3+/Tm3+/Yb3+ co-doped barium zinc silicate glasses.

The roles of Mn2+ ions in the MnCO3 compound, leading to the formation of an Mn2+-Yb3+ dimer and affecting the gain coefficient for the 4I13/2 → 4I15/2 transition of Er3+ ions and near-infrared (NIR) emission bandwidth flatness of Er3+/Tm3+/Yb3+ co-doped in SiO2-ZnO-BaO (SZB) barium zinc silicate glasses, were investigated in this work. The composition of all elements from the original raw materials that exist in the host glasses was determined using energy-dispersive X-ray spectroscopy (EDS). Under the excitation of a 980 nm laser diode (LD), the NIR emission of Er3+/Tm3+/Yb3+-co-doped SZB glasses produced a bandwidth of about 430 nm covering the O, E, and C bands. The effects of Mn2+ ions and the Mn2+-Yb3+ dimer on the gain coefficient for the 4I13/2 → 4I15/2 transition of Er3+ ions and bandwidth flatness of NIR emission of Er3+/Tm3+-co-doped and Er3+/Tm3+/Yb3+-co-doped SZB glasses were also assigned. The optimal molar concentration of Mn2+ ions was determined such that the NIR bandwidth flatness of Er3+/Tm3+/Yb3+-co-doped SZB glasses was the flattest. In addition, the role of Mn2+ ions in reducing the gain coefficient for the 4I13/2 → 4I15/2 transition of Er3+ ions was also calculated and discussed.

Choroid plexuses carry nodal-like cilia that undergo axoneme regression from early adult stage.

Choroid plexuses (ChPs) produce cerebrospinal fluid and sense non-cell-autonomous stimuli to control the homeostasis of the central nervous system. They are mainly composed of epithelial multiciliated cells, whose development and function are still controversial. We have thus characterized the stepwise order of mammalian ChP epithelia cilia formation using a combination of super-resolution-microscopy approaches and mouse genetics. We show that ChP ciliated cells are built embryonically on a treadmill of spatiotemporally regulated events, starting with atypical centriole amplification and ending with the construction of nodal-like 9+0 cilia, characterized by both primary and motile features. ChP cilia undergo axoneme resorption at early postnatal stages through a microtubule destabilization process controlled by the microtubule-severing enzyme spastin and mitigated by polyglutamylation levels. Notably, this phenotype is preserved in humans, suggesting a conserved ciliary resorption mechanism in mammals.

Optical band gaps and spectroscopy properties of Bi m+/Eu n+/Yb3+ co-doped (m = 0, 2, 3; and n = 2, 3) zinc calcium silicate glasses.

In this study, the indirect/direct optical band gaps and spectroscopy properties of Bi m+/Eu n+/Yb3+ co-doped (m = 0, 2, 3; and n = 2, 3) zinc calcium silicate glasses under different excitation wavelengths were investigated. Zinc calcium silicate glasses with the main compositions of SiO2-ZnO-CaF2-LaF3-TiO2 were prepared by the conventional melting method. EDS analysis was performed to determine the elemental composition existing in the zinc calcium silicate glasses. Visible (VIS)-, upconversion (UC)-, and near-infrared (NIR)-emission spectra of Bi m+/Eu n+/Yb3+ co-doped glasses were also investigated. Indirect optical band gaps and direct optical band gaps of Bi m+-, Eu n+- single-doped, and Bi m+-Eu n+ co-doped SiO2-ZnO-CaF2-LaF3-TiO2-Bi2O3-EuF3-YbF3 zinc calcium silicate glasses were calculated and analyzed. CIE 1931(x, y) color coordinates for VIS and UC emission spectra of Bi m+/Eu n+/Yb3+ co-doped glasses were determined. Besides, the mechanism of VIS-, UC-, NIR-emissions, and energy transfer (ET) processes between Bi m+ and Eu n+ ions were also proposed and discussed.

KIR genotype and haplotype frequencies in the multi-ethnic population of Malaysia.

Killer cell immunoglobulin-like receptors (KIR) genotype and haplotype frequencies have been reported to vary distinctly between populations, which in turn contributes to variation in the alloreactivity of natural killer (NK) cells. Utilizing the diverse KIR genes to identify suitable transplant donors would prove challenging in multi-ethnic countries, even more in resource-limited countries where KIR genotyping has not been established. In this study, we determined the KIR genotypes from 124 unrelated Malaysians consisting of the Malays, Chinese, Indians, and aboriginal people through polymerase chain reaction sequence-specific primer (PCR-SSP) genotyping and employing an expectation-maximization (EM) algorithm to assign haplotypes based on pre-established reference haplotypes. A total of 27 distinct KIR haplotypes were discerned with higher frequencies of haplotype A (55.2%) than haplotype B (44.8%). The most frequent haplotypes were cA01:tA01 (55.2%), cB01:tB01 (18.1%), and cB02:tA01 (13.3%), while the least frequent haplotypes were cB03:tB01 (1.2%), cB04:tB03 (0.4%), and cB03:tA01 (0.4%). Several haplotypes were identified to be unique to a specific ethnic group. The genotype with the highest frequency was genotype AB (71.8%), followed by AA (19.4%), and BB (8.9%). The Indians exhibited the lowest genotype AA but the highest genotype BB, whereas genotype BB was absent in the aboriginal people. Despite the limitations, the genotype and haplotypes in the Malaysian population were successfully highlighted. The identification of ethnic-specific KIR genotypes and haplotypes provides the first step to utilizing KIR in identifying suitable transplant donors to further improve the transplant outcome in the Malaysian population.

Unfermented ß-fructan Fibers Fuel Inflammation in Select Inflammatory Bowel Disease Patients.

BACKGROUND & AIMS: Inflammatory bowel diseases (IBD) are affected by dietary factors, including nondigestible carbohydrates (fibers), which are fermented by colonic microbes. Fibers are overall beneficial, but not all fibers are alike, and some patients with IBD report intolerance to fiber consumption. Given reproducible evidence of reduced fiber-fermenting microbes in patients with IBD, we hypothesized that fibers remain intact in select patients with reduced fiber-fermenting microbes and can then bind host cell receptors, subsequently promoting gut inflammation. METHODS: Colonic biopsies cultured ex vivo and cell lines in vitro were incubated with oligofructose (5 g/L), or fermentation supernatants (24-hour anaerobic fermentation) and immune responses (cytokine secretion [enzyme-linked immunosorbent assay/meso scale discovery] and expression [quantitative polymerase chain reaction]) were assessed. Influence of microbiota in mediating host response was examined and taxonomic classification of microbiota was conducted with Kraken2 and metabolic profiling by HUMAnN2, using R software. RESULTS: Unfermented dietary ß-fructan fibers induced proinflammatory cytokines in a subset of IBD intestinal biopsies cultured ex vivo, and immune cells (including peripheral blood mononuclear cells). Results were validated in an adult IBD randomized controlled trial examining ß-fructan supplementation. The proinflammatory response to intact ß-fructan required activation of the NLRP3 and TLR2 pathways. Fermentation of ß-fructans by human gut whole microbiota cultures reduced the proinflammatory response, but only when microbes were collected from patients without IBD or patients with inactive IBD. Fiber-induced immune responses correlated with microbe functions, luminal metabolites, and dietary fiber avoidance. CONCLUSION: Although fibers are typically beneficial in individuals with normal microbial fermentative potential, some dietary fibers have detrimental effects in select patients with active IBD who lack fermentative microbe activities. The study is publicly accessible at the U.S. National Institutes of Health database (clinicaltrials.gov identification number NCT02865707).

Fabrication of 3D-Printed Implant for Two-Stage Ear Reconstruction Surgery and Its Clinical Application

Purpose@#Ear reconstruction is one of the most difficult areas in the field of reconstructive surgery. Due to limitations of the current practice, a novel method of auricular reconstruction is needed. Major advancements in three-dimensional (3D) printing technique have rendered the process of ear reconstruction more favorable. Herein, we present our experience in designing and clinically using 3D implants in both 1st and 2nd stage ear reconstruction surgery. @*Materials and Methods@#After obtaining 3D CT data from each patient, a 3D geometric ear model was created using mirroring and segmentation processes. The 3D-printed implant design resembles but does not exactly match the normal ear shape, and can be inserted in harmony with the currently used surgical technique. The 2nd stage implant was designed to minimize dead space and support the posterior ear helix. The 3D implants were finally fabricated with a 3D printing system and used in ear reconstruction surgery in our institute. @*Results@#The 3D implants were manufactured for application to the currently used two-stage technique while maintaining the shape of the patient’s normal ear. The implants were successfully used for ear reconstruction surgery in microtia patients. A few months later, the 2nd stage implant was used in the 2nd stage operation. @*Conclusion@#The authors were able to design, fabricate, and apply patient-specific 3D-printed ear implants for 1st and 2nd stage ear reconstruction surgeries. This design, combined with 3D bioprinting technique, may be a future alternative for ear reconstruction.

Comparison of Corneal Epithelial Wound Healing between Topical RCI001, Solcoseryl, and Polydeoxyribonucleotide in the Murine Ocular Alkali Burn Model

Purpose@#To compare the corneal epithelial wound healing effects of RCI001, Solcoseryl, and polydeoxyribonucleotide (PDRN) in a rat alkali burn model. @*Methods@#In 40 male Sprague-Dawley rats, we induced alkali burn using filter paper soaked in 0.2N sodium hydroxide. The rats were then treated with topical 0.5% RCI001, 1.0% RCI001, Solcoseryl, or PDRN twice a day for 2 weeks. Corneal epithelial integrity and epithelial healing rate were measured at day 0, 3, 5, 7, 10, and 14. Histologic and immunohistochemistry findings were also assessed. @*Results@#Both the 0.5% and 1.0% RCI001 groups showed significantly more epithelial healing compared to the control group at day 5, 7, 10, and 14 (each p < 0.05). No statistical difference was found between the 0.5% and 1.0% RCI001 groups. Neither the Solcoseryl nor the PDRN groups showed a significant difference from the control. RCI001 treatment resulted in significantly reduced stromal edema, and a trend towards less inflammatory cell infiltration. @*Conclusions@#Topical application of RCI001 showed enhanced corneal epithelial wound healing in the murine corneal alkali burn model, presumably by suppressing inflammation. Meanwhile, Solcoseryl and PDRN did not show sufficient therapeutic effects compared to RCI001.

Impact of Pulmonary Arterial Elastance on Right Ventricular Mechanics and Exercise Capacity in Repaired Tetralogy of Fallot

Background and Objectives@#Pathophysiological changes of right ventricle (RV) after repair of tetralogy of Fallot (TOF) are coupled with a highly compliant low-pressure pulmonary artery (PA) system. This study aimed to determine whether pulmonary vascular function was associated with RV parameters and exercise capacity, and its impact on RV remodeling after pulmonary valve replacement. @*Methods@#In a total of 48 patients over 18 years of age with repaired TOF, pulmonary arterial elastance (Ea), RV volume data, and RV-PA coupling ratio were calculated and analyzed in relation to exercise capacity. @*Results@#Patients with a low Ea showed a more severe pulmonary regurgitation volume index, greater RV end-diastolic volume index, and greater effective RV stroke volume (p=0.039, p=0.013, and p=0.011, respectively). Patients with a high Ea had lower exercise capacity than those with a low Ea (peak oxygen consumption [peak VO2 ] rate: 25.8±7.7 vs. 34.3±5.5 mL/kg/min, respectively, p=0.003), while peak VO2 was inversely correlated with Ea and mean PA pressure (p=0.004 and p=0.004, respectively). In the univariate analysis, a higher preoperative RV end-diastolic volume index and RV end-systolic volume index, left ventricular end-systolic volume index, and higher RV-PA coupling ratio were risk factors for suboptimal outcomes. Preoperative RV volume and RV-PA coupling ratio reflecting the adaptive PA system response are important factors in optimal postoperative results. @*Conclusions@#We found that PA vascular dysfunction, presenting as elevated Ea in TOF, may contribute to exercise intolerance. However, Ea was inversely correlated with pulmonary regurgitation (PR) severity, which may prevent PR, RV dilatation, and left ventricular dilatation in the absence of significant pulmonary stenosis.

Reliability of the Non-contact TONO-i Tonometer Compared with the Goldmann Applanation Tonometer

Purpose@#The accuracy and agreement of intraocular pressure (IOP) measurements using a noncontact self-measuring tonometer, TONO-i, compared with the Goldmann applanation tonometer (GAT). @*Methods@#A total of 35 healthy participants and 42 primary open angle or normal tension glaucoma patients were enrolled in this study. TONO-i and GAT measurements were obtained and the mean difference in IOPs was analyzed using a paired t-test. IOP agreement was calculated using the two-way random effects model. Bland-Altman analysis and simple linear regression were used to estimate the disagreement between IOP measurements. @*Results@#The mean IOPs measured using the TONO-i and GAT were 15.9 ± 3.3 mmHg and 16.4 ± 5.1 mmHg, respectively. In glaucoma patients, the mean values measured using the TONO-i (16.7 ± 4.1 mmHg) were lower than those measured using the GAT (17.9 ± 6.1 mmHg; p < 0.001). However, there was no significant difference among the healthy participants (p = 0.273). The intraclass coefficients (95% confidence interval) for all participants, normal participants, and glaucoma patients were 0.847 (0.702-0.920), 0.882 (0.804-0.941), and 0.828 (0.742-0.887), respectively, indicating good agreement between the IOP measurements. The mean difference and limits of agreement were not statistically significant. As IOP increased, the absolute difference between the GAT and TONO-i measurements also increased. @*Conclusions@#The TONO-i, a novel tonometer, may be used reliably for IOP self-measurement and detecting IOP elevations. However, caution must be exercised because of the possibility of underestimating high IOPs.

Psychological and Physiological Effects of a Smart Garden Program Using Mindfulness Meditation on Psychiatric Inpatients / 신경정신의학

Objectives@#This study investigates the psychological and physiological effects of a smart garden on psychiatric patients attending a day ward in a mental hospital. @*Methods@#A one-group pretest-posttest design was applied for this study. Twenty-four patients admitted to a mental hospital in ChunCheon City were included in the study and participated in a mindfulness meditation program in a cute-type indoor garden. The smart garden program was provided to the participants twice a week for 4 weeks, 10 minutes per session. A Self-Report Scale (SRS) and heart rate variability (HRV) of the patient were collected before and after experiencing the entire smart garden program. The SRS included three segments: Beck’s Depression Inventory (BDI), Beck’s Anxiety Inventory (BAI), and the World Health Organization Quality of Life Brief Version (WHOQOL-BREF). Furthermore, the patients’ HRV was assessed based on six parameters: standard deviation of the N-N intervals, square root of mean squared difference of successive N-N intervals (RMSSD), total power (TP), high-frequency, low-frequency, and low-frequency/high-frequency ratio. @*Results@#After attending the smart garden program, a significant difference emerged in three test areas in the SRS (BDI, BAI, and in the physical health domain of the WHOQOL-BREF; p<0.01), and in two HRV parameters (RMSSD and TP; p<0.05). @*Conclusion@#Results of the subjective and objective evaluation tools revealed that exposure to a smart garden program provides relaxing psychological and physiological effects to psychiatric patients.

Impact of Postmastectomy Radiation Therapy on Breast Cancer Patients According to Pathologic Nodal Status after Modern Neoadjuvant Chemotherapy / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The utility of postmastectomy radiation therapy (PMRT) for breast cancer patients after neoadjuvant chemotherapy (NAC) is highly controversial. This study evaluated the impact of PMRT according to pathologic nodal status after modern NAC. @*Materials and Methods@#We retrospectively reviewed 682 patients with clinical stage II-III breast cancer who underwent NAC and mastectomy from 2013 to 2017. In total, 596 patients (87.4%) received PMRT, and 86 (12.6%) did not. We investigated the relationships among locoregional recurrence-free survival (LRRFS), disease-free survival (DFS), overall survival (OS), and various prognostic factors. Subgroup analyses were also performed to identify patients who may benefit from PMRT. @*Results@#The median follow-up duration was 67 months. In ypN+ patients (n=368, 51.2%), PMRT showed significant benefits in terms of LRRFS, DFS, and OS (all p < 0.001). In multivariate analyses, histologic grade (HG) III (p=0.002), lymphovascular invasion (LVI) (p=0.045), and ypN2-3 (p=0.02) were significant risk factors for poor LRRFS. In ypN1 patients with more than two prognostic factors among luminal/human epidermal growth factor receptor-2–negative subtype, HG I-II, and absence of LVI, PMRT had no significant effect on LRRFS (p=0.18). In ypN0 patients (n=351, 48.8%), PMRT was not significantly associated with LRRFS, DFS, or OS. However, PMRT showed better LRRFS in triple-negative breast cancer (TNBC) patients (p=0.03). @*Conclusion@#PMRT had a major impact on treatment outcomes in patients with residual lymph nodes following NAC and mastectomy. Among ypN0 patients, PMRT may be beneficial only for those with TNBC.

A Case of Pirfenidone-Induced Photosensitive Drug Eruption

A 75-year-old male was diagnosed with idiopathic pulmonary fibrosis and treated with pirfenidone. He presented with an erythematous thick scaly patch on his face, neck, and both hands and arms. He had a history of significant exposure to sunlight without using sunscreen. All lesions were restricted to sun-exposed areas and appeared one month ago.Histopathological examination revealed necrotic keratinocytes, epidermal spongiosis, liquefaction degeneration of the basal layer, interface dermatitis, solar elastosis, and upper dermal perivascular lympho-histiocytic infiltration. Based on clinical and histopathological findings, the skin lesion could be diagnosed as photosensitive drug eruption induced by pirfenidone. Pirfenidone was discontinued for a month, and the patient was treated with oral and topical corticosteroids. Consequently, the skin lesion almost fully cleared, leaving mild postinflammatory hyperpigmentation. Although there are many reports of photosensitivity reactions to pirfenidone, dermatologists are still not familiar with this drug. Through this case presentation, clinicians should be aware of the potential phototoxic effects of pirfenidone and provide the necessary precautionary information to patients who take pirfenidone.

Refractory Bullous Pemphigoid Successfully Treated with Reslizumab: A Possible Novel Therapeutic Modality

Bullous pemphigoid (BP) is a chronic, autoimmune blistering disease that has concerning morbidity and mortality rates. Recently, several studies have focused on eosinophils due to their significant role in the pathogenesis of BP, considering that they are ubiquitous in the serum, tissue, and blister fluids of patients with BP. With this context, precision therapy that targets mediators of eosinophil activity could be a possible novel therapeutic strategy.Interleukin (IL)-5 is crucial for B-cell maturation, which consequently results in immunoglobulin production, and promotes eosinophil differentiation, proliferation, and activation. To our best knowledge, reslizumab has not yet been reported to treat BP. Herein, we report a case of steroid- and omalizumab-resistant BP treated successfully using reslizumab. Our data suggest that IL-5 could be a novel specific biologic target within the entire immunopathogenesis of BP, and reslizumab would be a novel therapeutic modality.

Unusual Complex Apocrine Tumor Consisting of Syringocystadenoma Papilliferum and Apocrine Hidrocystoma within a Single Lesion: A Case Report

Syringocystadenoma papilliferum (SCAP) and apocrine hidrocystoma (AH) are benign apocrine neoplasms that usually occur separately. SCAP arises predominantly in head and neck, while AH typically develop in periorbital area. We report a case of a 68-year-old male with an asymptomatic erythematous papulonodule that occurred on his back 3 years ago. Histologic examination showed cystic invagination extending from the epidermis into the dermis with some papillary projections. The invaginated portion was lined by epithelial bilayer composed of cuboidal and columnar cells, and decapitation secretion was observed in the inner epithelial layer. In the deep dermis, multiple cystic spaces with variable sizes were observed, and these cysts also presented double layers of the epithelium and decapitation secretion.According to such histologic features, the coexistence of SCAP and AH within a single lesion was demonstrated. The patient was recommended to completely remove the remaining lesion after punch biopsy, but he refused further surgical management. Herein, we report an unusual case of complex apocrine tumor with a rare composition in an atypical site.