Prevalence and predictors for postpartum sleep disorders: a nationwide analysis.

OBJECTIVE: To describe the prevalence and predictors of postpartum sleep disorders. DESIGN: A retrospective cohort study. SETTING: Postpartum. POPULATION: Commercially insured women delivering in California (USA) between 2011 and 2014. METHODS: Using the Optum Clinformatics Datamart Database. MAIN OUTCOME MEASURES: Prevalence of a postpartum sleep disorder diagnosis with and without a depression diagnosis up to 12 months following hospital discharge for inpatient delivery. We also identified predictors of a postpartum sleep disorder diagnosis using multivariable logistic regression. RESULTS: We identified 3535 (1.9%) women with a postpartum sleep disorder diagnosis. The prevalence of sleep disorder diagnoses was insomnia (1.3%), sleep apnea (0.25%), and other sleep disorder (0.25%). The odds of a postpartum sleep disorder were highest among women with a history of drug abuse (adjusted odds ratio (aOR): 2.70, 95% confidence interval (CI): 1.79-4.09); a stillbirth delivery (aOR: 2.15, 95% CI: 1.53-3.01); and chronic hypertension (aOR: 1.82; 95% CI: 1.57-2.11). A comorbid diagnosis of a postpartum sleep disorder and depression occurred in 1182 women (0.6%). These women accounted for 33.4% of all women with a postpartum sleep disorder. The strongest predictors of a comorbid diagnosis were a history of drug abuse (aOR: 4.13; 95% CI: 2.37-7.21) and a stillbirth delivery (aOR: 2.93; 95% CI: 1.74-4.92). CONCLUSIONS: Postpartum sleep disorders are underdiagnosed conditions, with only 2% of postpartum women in this cohort receiving a sleep diagnosis using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes. Insomnia was the most common disorder and one-third of women diagnosed with a postpartum sleep disorder had a co-morbid diagnosis of depression. Future studies are needed to improve the screening and diagnostic accuracy of postpartum sleep disorders.

Artificial intelligence for the automated single-shot assessment of psoriasis severity.

BACKGROUND: PASI score is globally used to assess disease activity of psoriasis. However, it is relatively complicated and time-consuming, and the score will vary due to the inconsistent subjectivity between dermatologists. Therefore, an AI system capable of assessing psoriasis severity will be useful. OBJECTIVES: To propose a simplified PASI system (Single-Shot PASI) and associated AI models capable of assessing psoriasis severity. METHODS: Overall, 705 psoriasis images of the trunk's front and back were used in our research. Considering the relatively small number of images, we used data augmentation techniques to expand the data. A psoriasis expert's scores were used as teacher data. Various convolutional neural network models and hyperparameters were adjusted using a fivefold cross-validation. From these adjustments, we discovered that fine-tuning Imagenet2012-pretrained InceptionV3 whose last linear layer was replaced by a two-layer perceptron (30 hidden units and five output units) exhibited the best performance. RESULTS: To validate our deep learning system, 10 images were selected as test sets and were excluded from the training sets. The AI assessment of Single-Shot PASI was almost consistent with the clinical severity. We examined whether AI assistance would affect human scoring. In this study, 13 dermatologists and 9 medical students were invited as evaluators. Mean absolute differences from AI scores and standard deviation among evaluators reduced with AI assistance. In addition, the evaluator's scores got close to the teacher's score with AI's assistance. CONCLUSIONS: We proposed a Single-Shot PASI system and developed an associated AI system capable of assessing psoriasis severity simply by uploading a single clinical image. An easy-to-use scoring system and our freely available AI software would help dermatologists and patients with psoriasis.

A systematic review of patient-reported outcome measures used to assess sleep in postpartum women using Consensus Based Standards for the Selection of Health Measurement Instruments (COSMIN) guidelines.

STUDY OBJECTIVES: We performed a systematic review to identify the best patient-reported outcome measure (PROM) of postpartum sleep in women. METHODS: We searched four databases for validated PROMs used to assess postpartum sleep. Studies were considered if they evaluated at least one psychometric measurement property of a PROM. An overall performance rating was assigned for each psychometric measurement property of each PROM based upon COSMIN criteria. A modified GRADE approach was used to assess the level of evidence and recommendations were then made for each PROM. RESULTS: We identified 15 validation studies of eight PROMs, in 9,070 postpartum women. An adequate number of sleep domains was assessed by five PROMs: Bergen Insomnia Scale (BIS), Pittsburgh Sleep Quality Index (PSQI), General Sleep Disturbance Scale (GSDS), Athens Insomnia Scale (AIS), and the Sleep Symptom Checklist (SSC). BIS and GSDS were the only PROMs to demonstrate adequate content validity and at least a low level of evidence of sufficient internal consistency, resulting in Class A recommendations. The BIS was the only PROM, which is easily accessible and free to use for noncommercial research, that achieved a Class A recommendation. CONCLUSION: The BIS is the best currently available PROM of postpartum sleep. However, this PROM fails to assess several important domains such as sleep duration (and efficiency), chronotype, sleep-disordered breathing and medication usage. Future studies should focus on evaluating the psychometric measurement properties of BIS in the North American setting and in different cultural groups, or to develop a more specific PROM of postpartum sleep.

The development of the hypothalamus-pituitary-adrenal axis during infancy may be affected by antenatal glucocorticoid therapy.

BACKGROUND: Developmental changes in the hypothalamus-pituitary-adrenal (HPA) axis during infancy have been reported in term infants, but those in preterm infants have yet to be elucidated. If developmental changes in the HPA axis of preterm infants are modulated by any factors, it may affect their future health. Few studies have examined the lasting consequences of antenatal glucocorticoids on the development of the HPA axis. METHODS: We measured pre- and post-palivizumab vaccination salivary cortisol values in two conforming periods of three-months intervals during infancy, and compared cortisol values and the response of cortisol secretion between groups with and without antenatal glucocorticoid (AG) therapy. RESULTS: Although the strength of the response of cortisol secretion to palivizumab fell age-dependently (until late infancy) in the Non-AG group, the opposite pattern was exhibited in the AG group. The changes of the delta cortisol values between the 2 groups were significant. CONCLUSIONS: This study suggests that the HPA axis of preterm infants whose mothers receive AG therapy may be upregulated during infancy, possibly leading to long lasting health problems.

Growth activation of influenza virus by trypsin and effect of T-705 (favipiravir) on trypsin-optimized growth condition.

Influenza virus is activated by proteolytic cleavage of hemagglutinin by trypsin. After determining the optimal trypsin concentration, intracellular and extracellular influenza A/PR/8/34 (H1N1) and A/Victoria/361/2011 (H3N2) virus productions were compared in cultures treated with T-705 (favipiravir) and GS 4071 (an active form of oseltamivir). Although both drugs efficiently inhibited extracellular viral RNA release in a dose-dependent manner, T-705 inhibited it to the level of the inoculum without trypsin treatment, while GS 4071 inhibited it to a final level 10 times higher than that without trypsin. T-705 inhibited intracellular viral RNA production to the level of input virus in both trypsin-treated and untreated cells. In contrast, GS 4071 dose-dependently inhibited intracellular viral RNA production in cells treated with trypsin but allowed viral RNA synthesis. The level of maximum inhibition by GS 4071was 10 times higher than that of cells without trypsin and 1,000 times greater than the inoculum titer in cells without trypsin. T-705 inhibited both intracellular and extracellular virus production 1,000 and 10 times more strongly, respectively, than GS 4071. T-705 has powerful anti-influenza activity in the absence of trypsin and even in the trypsin-optimized growth condition, suggesting the therapeutic advantage in treatment of influenza complicated with bacterial pneumonia. Keywords: influenza; T-705; Tamiflu; trypsin; bacterial trypsin-like protease.

Visualization and quantification of anastomotic perfusion in colorectal surgery using near-infrared fluorescence.

BACKGROUND: Anastomotic leakage (AL) is one of the most troublesome complications in colorectal surgery. Recently, near-infrared fluorescence (NIRF) imaging has been used intraoperatively to detect sentinel lymph nodes and visualize the blood supply at the region of interest (ROI). The aim of this study was to evaluate the role of visualization and quantification of bowel perfusion around the anastomosis using NIRF system in predicting AL. METHODS: A prospective study was conducted on patients who had laparoscopic surgery for colorectal cancer at our institution. Perfusion of the anastomosis was evaluated with NIRF imaging after intravenous injection of indocyanine green (ICG). The time course of fluorescence intensity was recorded by an imaging analyzer We measured the time from ICG injection to the beginning of fluorescence (T0), maximum intensity (Imax), time to reach Imax (Tmax), time to reach Imax 50% ([Formula: see text]) and slope (S) after the anastomosis. RESULTS: Tumor locations were as follows; cecum: 2, ascending colon: 2, transverse colon: 7, descending colon: 1, sigmoid colon: 2, rectosigmoid colon: 3 and rectum: 6 (one case with synchronous cancer). All operations were performed laparoscopically. Four patients were diagnosed with or suspected to have AL (2 patients with grade B anastomotic leakage after low anterior resection, 1 patient with minor leakage in transverse colon resection and 1 patient needing re-anastomosis intraoperatively in transverse colon resection). T0 was significantly longer in the AL group than in patients without AL (64.3 ± 27.6 and 18.2 ± 6.6 s, p = 2.2 × 10-3). CONCLUSIONS: Perfusion of the anastomosis could be successfully visualized and quantified using NIRF imaging with ICG. T0 might be a useful parameter for prediction of AL.

Analysis of the Beaufort Gyre Freshwater Content in 2003-2018.

Hydrographic data collected from research cruises, bottom-anchored moorings, drifting Ice-Tethered Profilers, and satellite altimetry in the Beaufort Gyre region of the Arctic Ocean document an increase of more than 6,400 km3 of liquid freshwater content from 2003 to 2018: a 40% growth relative to the climatology of the 1970s. This fresh water accumulation is shown to result from persistent anticyclonic atmospheric wind forcing (1997-2018) accompanied by sea ice melt, a wind-forced redirection of Mackenzie River discharge from predominantly eastward to westward flow, and a contribution of low salinity waters of Pacific Ocean origin via Bering Strait. Despite significant uncertainties in the different observations, this study has demonstrated the synergistic value of having multiple diverse datasets to obtain a more comprehensive understanding of Beaufort Gyre freshwater content variability. For example, Beaufort Gyre Observational System (BGOS) surveys clearly show the interannual increase in freshwater content, but without satellite or Ice-Tethered Profiler measurements, it is not possible to resolve the seasonal cycle of freshwater content, which in fact is larger than the year-to-year variability, or the more subtle interannual variations.

Changes in surface tension of saliva in Down syndrome.

OBJECTIVE: Surface tension in saliva might contribute to the maintenance of upper airway patency. The present study aimed to determine whether salivary surface tension is altered in patients with Down syndrome who are predisposed to upper airway collapse. PATIENTS AND METHODS: We used the pull-off force technique to measure surface tension in samples (100 µL) of saliva collected from twenty-three male patients with Down syndrome and twenty-three healthy males (controls). p < 0.05 was considered to indicate significance. RESULTS: Salivary surface tension was significantly lower in the patients than in the controls (57.3 ± 4.9 vs. 60.3 ± 4.7 mN/m; p = 0.039). Age and surface tension positively correlated in the patients (p = 0.001). CONCLUSIONS: The lower surface tension of saliva in patients with Down syndrome might compensate for an anatomical predisposition towards upper airway collapsibility and other risk factors. The function of surface tension in saliva might be altered due to aging in such patients.

Genome-wide association mapping and examination of possible maternal effect for the pace trait of horses.

Previously, a single nucleotide polymorphism (SNP) related to gait type was identified at position 22 999 655 of chromosome 23 in the coding region of DMRT3 (DMRT3:Ser301Ter) by showing that a cytosine (C) to adenine (A) mutation of this SNP induced pace in the Icelandic horse. We investigated the effect of DMRT3:Ser301Ter on the gait of Hokkaido Native Horses, a Japanese native breed, and examined genetic factors other than DMRT3 by exploring genome-wide SNPs related to gait determination. All animals exhibiting pace were AA for DMRT3:Ser301Ter, confirming the association of DMRT3:Ser301Ter with gait determination; however, 14.3% of the animals exhibiting trot also had AA for DMRT3:Ser301Ter, suggesting the presence of another factor(s) cooperatively working with DMRT3:Ser301Ter for gait determination. SNPs on chromosomes 13 and 23 were detected by genome-wide association analysis (false discovery rate <0.05), although SNPs on chromosome 23 were all located in the vicinity of DMRT3:Ser301Ter, confirming the association with DMRT3. A genome-wide association study targeting only animals with AA for DMRT3:Ser301Ter to examine genetic factors cooperatively working with DMRT3:Ser301Ter for gait determination suggested associations of 23 SNPs on six chromosomes. In a series of analyses of the effect of a maternal factor (dam's gait) on gait determination, the effect was suggested in comparison of the frequencies of exhibiting pace in gait checks in only two animal groups having dams with different DMRT3:Ser301Ter genotypes (P < 0.05), suggesting that the gait of the dam does not have a major effect on whether progeny homozygous for the DMRT3:Ser301Ter mutation will preferentially pace or trot.

Silent KEL alleles identified from Japanese individuals with the Ko phenotype.

BACKGROUND AND OBJECTIVE: The rare Ko phenotype lacks all 36 antigens in the Kell blood system. The molecular basis of the Ko phenotype has been investigated, and more than 40 silent KEL alleles are reported by many investigators. The majority of silent alleles are the KEL*02 background. Here, we report molecular genetic analysis of the KEL gene in Japanese individuals with the Ko phenotype. MATERIALS AND METHODS: The Ko phenotype was screened from Japanese blood donors for several years using monoclonal anti-Ku or anti-K14 by an automated blood grouping system PK7300. Kell-related antigens were typed by standard tube tests. Genomic DNA was extracted from the blood samples, and KEL gene was analysed by polymerase chain reaction (PCR) and Sanger sequencing. RESULTS: We collected 35 Ko blood samples with K-k-, Kp(a-b-), Js(a-b-) and K14-. PCR and sequence analysis revealed that 11 individuals were homozygous for a mutant KEL allele with a c.299G>C (p.Cys100Ser) mutation (rs. 200268316). Three individuals were homozygous for the KEL*02N.24 allele that is c.715G>T (p.Glu239*), and one individual was homozygous for the KEL*02N.40 allele that is c.1474C>T (p.Arg492*). Five individuals were homozygous for novel KEL alleles with single-nucleotide mutations, four individuals had a c.2175delC (p.Pro725 fs*43), and one individual had a c.328delA (p.Arg110 fs*79). The remaining 15 individuals were compound heterozygous, and eight new alleles were identified from them. CONCLUSIONS: We identified three known and ten new silent KEL alleles from Japanese individuals with the Ko phenotype. The KEL allele with the c.299G>C (p.Cys100Ser) mutation was the most frequent.

Single-molecule quantum dot as a Kondo simulator.

Structural flexibility of molecule-based systems is key to realizing the novel functionalities. Tuning the structure in the atomic scale enables us to manipulate the quantum state in the molecule-based system. Here we present the reversible Hamiltonian manipulation in a single-molecule quantum dot consisting of an iron phthalocyanine molecule attached to an Au electrode and a scanning tunnelling microscope tip. We precisely controlled the position of Fe2+ ion in the molecular cage by using the tip, and tuned the Kondo coupling between the molecular spins and the Au electrode. Then, we realized the crossover between the strong-coupling Kondo regime and the weak-coupling regime governed by spin-orbit interaction in the molecule. The results open an avenue to simulate low-energy quantum many-body physics and quantum phase transition through the molecular flexibility.

Evaluation of skin perfusion pressure to assess refractory foot ulcers.

OBJECTIVE: The number of patients with foot gangrene caused by critical ischaemia and severe infection is increasing significantly in developed countries. The measurement of perilesional skin blood flow by skin perfusion pressure (SPP) is useful to select the appropriate treatment of gangrenous lesions, in that it is not affected by calcifications of blood vessels. However, the prognosis of a foot ulcer may also be affected by the level of blood sugar and infections. This study aimed to validate the use of SPP in cases of foot gangrene and ulcers in patients with and without diabetes mellitus (DM) and infection. METHOD: Clinical symptoms, ankle-brachial pressure index (ABPI) and SPP were assessed to evaluate the condition of each foot ulcer. Every foot ulcer was treated as independent, even if a participant had multiple ulcers. All ulcers for which we measured SPP were subject to the analysis. All ulcers were purely ischaemic in nature and were exclusively located on the foot or toes. RESULTS: Data were collected from 117 foot ulcers on 91 toes and feet from 65 patients. Almost all SPP values in healed cases were > 27 mmHg. There were three patients whose ulcers failed to heal by conservative treatments were complicated with severe infection. However, no effect of DM on the relationship between SPP values and prognosis was observed. Logistic regression analysis of all ulcers except for the 5 cases complicated with infection revealed that those with 30 mmHg or lower SPP values are likely to heal by conservative treatment with 23% or lower probability, whereas any ulcer with more than 50 mmHg SPP value and without severe infection may heal without the need for further operations with 80% or higher probability. CONCLUSION: The combination of SPP and careful evaluation of infection may be a good parameter to decide the appropriate treatment for ischaemic skin ulcers, regardless of the complication of DM.

Gonadotropin levels in urine during early postnatal period in small for gestational age preterm male infants with fetal growth restriction.

OBJECTIVE: The objective of this study was to estimate gonadotropin concentrations in small for gestational age (SGA) male infants with the reactivation of the hypothalamic-pituitary-gonadal axis during the first few months of life that is important for genital development. STUDY DESIGN: We prospectively examined 15 SGA and 15 appropriate for gestational age (AGA) preterm male infants between 2013 and 2014 at Kyoto University Hospital. Gonadotropin concentrations (luteinizing hormone (LH) and follicle-stimulating hormone (FSH)) were measured in serial urine samples from the postnatal days 7 to 168 and compared between SGA and AGA infants using the Mann-Whitney test. RESULTS: A longitudinal analysis showed that SGA infants had higher LH and lower FSH concentrations (P=0.004 and P=0.006, respectively) than AGA infants. CONCLUSION: Male infants who are SGA at birth because of fetal growth restriction have gonadotropin secretion abnormalities in the first few months of life.

Beneficial effects of Lactobacillus casei strain Shirota on academic stress-induced sleep disturbance in healthy adults: a double-blind, randomised, placebo-controlled trial.

The present study examined whether Lactobacillus casei strain Shirota (LcS) improves sleep quality under psychological stress. A double-blind, placebo-controlled trial was conducted in healthy 4th year medical students exposed to academic examination stress. The trial was repeated over two consecutive years in different groups of students, and the data were pooled. For 8 weeks prior to and 3 weeks after a national standardised examination, a total of 48 and 46 subjects received a daily dose of 100 ml of LcS-fermented milk or non-fermented placebo milk, respectively. Study measures included subjective anxiety, overnight single-channel electroencephalography (EEG) recordings, and the Oguri-Shirakawa-Azumi (OSA) sleep inventory scores of subjective sleep quality. Total OSA scores were significantly lower than baseline on the day before the exam and recovered after the exam, indicating a stress-induced decline in sleep quality. There was a significant positive effect of LcS treatment on OSA factors for sleepiness on rising and sleep length. Sleep latency measured by EEG lengthened as the exam approached in the placebo group but was significantly suppressed in the LcS group. The percentage of stage 3 non-REM (N3) sleep decreased in the placebo group as the exam approached, whereas it was maintained in the LcS group throughout the trial. Delta power during the first sleep cycle, measured as an index of sleep intensity, increased as the exam approached in the LcS group and was significantly higher than in the placebo group. These findings suggest that daily consumption of LcS may help to maintain sleep quality during a period of increasing stress. The observed retention of N3 sleep and increased delta power in the LcS group may have contributed to higher perceived sleep satisfaction.

The FGF23/KLOTHO Regulatory Network and Its Roles in Human Disorders.

The functions of Klotho (KL) are multifaceted and include the regulation of aging and mineral metabolism. It was originally identified as the gene responsible for premature aging-like symptoms in mice and was subsequently shown to function as a coreceptor in the fibroblast growth factor (FGF) 23 signaling pathway. The discovery of KL as a partner for FGF23 led to significant advances in understanding of the molecular mechanisms underlying phosphate and vitamin D metabolism, and simultaneously clarified the pathogenic roles of the FGF23 signaling pathway in human diseases. These novel insights led to the development of new strategies to combat disorders associated with the dysregulated metabolism of phosphate and vitamin D, and clinical trials on the blockade of FGF23 signaling in X-linked hypophosphatemic rickets are ongoing. Molecular and functional insights on KL and FGF23 have been discussed in this review and were extended to how dysregulation of the FGF23/KL axis causes human disorders associated with abnormal mineral metabolism.

The Leuven Immunomodulatory Protocol Promotes T-Regulatory Cells and Substantially Prolongs Survival After First Intestinal Transplantation.

Intestinal transplantation (ITx) remains challenged by frequent/severe rejections and immunosuppression-related complications (infections/malignancies/drug toxicity). We developed the Leuven Immunomodulatory Protocol (LIP) in the lab and translated it to the clinics. LIP consists of experimentally proven maneuvers, destined to promote T-regulatory (Tregs)-dependent graft-protective mechanisms: donor-specific blood transfusion (DSBT); avoiding high-dose steroids/calcineurin-inhibitors; and minimizing reperfusion injury and endotoxin translocation. LIP was tested in 13 consecutive ITx from deceased donors (2000-2014) (observational cohort study). Recipient age was 37 years (2.8-57 years). Five-year graft/patient survival was 92%. One patient died at 9 months due to aspergillosis, another at 12 years due to nonsteroidal anti-inflammatory drug-induced enteropathy. Early acute rejection (AR) developed in two (15%); late AR in three (23%); all were reversible. No chronic rejection (CR) occurred. No malignancies developed and estimated glomerular filtration rate remained stable post-Tx. At last follow-up (3.5 years [0.5-12.5 years]), no donor-specific antibodies were detected and 11 survivors were total parenteral nutrition free with a Karnofsky score >90% in 8 recipients (follow-up >1 years). A high frequency of circulating CD4+ CD45RA- Foxp3hi memory Tregs was found (1.8% [1.39-2.21]), comparable to tolerant kidney transplant (KTx) recipients and superior to stable immunosuppression (IS)-KTx, KTx with CR, and healthy volunteers. In this ITx cohort we show that DSBT in a low-inflammatory/pro-regulatory environment activates Tregs at levels similar to tolerant-KTx, without causing sensitization. LIP limits rejection under reduced IS and thereby prolongs long-term survival to an extent not previously attained after ITx.

Probiotic Lactobacillus casei strain Shirota relieves stress-associated symptoms by modulating the gut-brain interaction in human and animal models.

BACKGROUND: This study aimed to examine the effects of Lactobacillus casei strain Shirota (LcS) on gut-brain interactions under stressful conditions. METHODS: Three double-blind, placebo-controlled trials were conducted to examine the effects of LcS on psychological and physiological stress responses in healthy medical students under academic examination stress. Subjects received LcS-fermented milk or placebo daily for 8 weeks prior to taking a national standardized examination. Subjective anxiety scores, salivary cortisol levels, and the presence of physical symptoms during the intervention were pooled and analyzed. In the animal study, rats were given feed with or without LcS for 2 weeks, then submitted to water avoidance stress (WAS). Plasma corticosterone concentration and the expression of cFos and corticotropin releasing factor (CRF) in the paraventricular nucleus (PVN) were measured immediately after WAS. In an electrophysiological study, gastric vagal afferent nerve activity was monitored after intragastric administration of LcS to urethane-anesthetized rats. KEY RESULTS: Academic stress-induced increases in salivary cortisol levels and the incidence rate of physical symptoms were significantly suppressed in the LcS group compared with the placebo group. In rats pretreated with LcS, WAS-induced increases in plasma corticosterone were significantly suppressed, and the number of CRF-expressing cells in the PVN was reduced. Intragastric administration of LcS stimulated gastric vagal afferent activity in a dose-dependent manner. CONCLUSIONS & INFERENCES: These findings suggest that LcS may prevent hypersecretion of cortisol and physical symptoms under stressful conditions, possibly through vagal afferent signaling to the brain and reduced stress reactivity in the PVN.

Changes in tumor expression of HER2 and hormone receptors status after neoadjuvant chemotherapy in 21,755 patients from the Japanese breast cancer registry.

BACKGROUND: We investigate rates of pathologic complete response (pCR) and tumor expression of ER, PgR, HER2 discordance after neoadjuvant chemotherapy using Japanese breast cancer registry data. PATIENTS AND METHODS: Records of more than 300,000 breast cancer cases treated at 800 hospitals from 2004 to 2013 were retrieved from the breast cancer registry. After data cleanup, we included 21,755 patients who received neoadjuvant chemotherapy and had no distant metastases. pCR was defined as no invasive tumor in the breast detected during surgery after neoadjuvant chemotherapy. HER2 overexpression was determined immunohistochemically and/or using fluorescence in situ hybridization. RESULTS: pCR was achieved in 5.7% of luminal tumors (n = 8730), 24.6% of HER2-positive tumors (n = 4403), and 18.9% of triple-negative tumors (n = 3660). Among HER2-positive tumors, pCR was achieved in 31.6% of ER-negative tumors (n = 2252), 17.0% of ER-positive ones (n = 2132), 31.4% of patients who received trastuzumab as neoadjuvant chemotherapy (n = 2437), and 16.2% of patients who did not receive trastuzumab (n = 1966). Of the 2811 patients who were HER2-positive before treatment, 601 (21.4%) had HER2-negative tumors after neoadjuvant chemotherapy, whereas 340 (3.4%) of the 9947 patients with HER2-negative tumors before treatment had HER2-positive tumors afterward. Of the 10,973 patients with ER-positive tumors before treatment, 499 (4.6%) had ER-negative tumors after neoadjuvant chemotherapy, whereas 519 (9.3%) of the 5607 patients who were ER-negative before treatment had ER-positive tumors afterward. CONCLUSION: We confirmed that loss of HER2-positive status can occur after neoadjuvant treatment in patients with primary HER2-positive breast cancer. We also confirmed that in practice, differences in pCR rates between breast cancer subtypes are the same as in clinical trials. Our data strongly support the need for retest ER, PgR, HER2 of surgical sample after neoadjuvant therapy in order to accurately determine appropriate use of targeted therapy.