Development of Older Adults' Perceptions on Community-based Connectedness with People Scale: Reliability and validity evaluation.

AIM: We developed a self-assessment scale-Older Adults' Perceptions of Community-based Connectedness with People-to assess older adults' comprehensive perceptions of their connectedness with others in the community. A specific aim of this study is to evaluate the reliability and validity of this scale. METHODS: Participants consisted of 1000 men and women aged 65 years or older, living in Sapporo, Hokkaido, Japan. Factorial validity was assessed using exploratory and confirmatory factor analysis, while concurrent validity was assessed using correlation analysis. Reliability was confirmed by Cronbach's α coefficient using the internal consistency method, and the stability coefficient was confirmed using the test-retest method. RESULTS: Responses were received from 380 participants, and 358 participants who responded to all items were included in the analysis. The developed scale comprised 22 items with three factors: "Perception of Inclusion" (α = .947), "Perception of Reciprocity through Reception" (α = .937), and "Perception of Reciprocity through Provision" (α = .910). Correlation analyses indicated that concurrent scales were positively correlated with Ikigai and negatively correlated with loneliness on the total scale. The model fit was comparative fit index = 0.933, goodness-of-fit index = 0.854, adjusted goodness-of-fit index = 0.818, and root mean square of approximation = 0.081. The stability coefficient of the total scale scores was 0.875 (95% CI: [0.830, 0.908]). CONCLUSIONS: The developed scale had adequate reliability and validity. The perceptions of connectedness measured using this scale can be used by public health and nursing care professionals to prevent loneliness and isolation among older adults living in the community.

Older people's connectedness with people in the community in contemporary contexts: A concept analysis.

AIM: This study aimed to clarify the concept of older people's connectedness with people in the community within the literature. METHODS: This study was based on Walker and Avant's concept analysis method. We used PubMed, MEDLINE, CINAHL, and Web of Science databases and included peer-reviewed articles that were published in English between January 2010 and April 2023. After assessing eligibility and applying exclusion criteria, 25 articles were analyzed. RESULTS: Attributes included sense of belonging to the community achieved through interactions and feeling of togetherness through interrelationships, which consequently led to the maintenance of healthy physical and mental states and independent living, the acquisition of the ability to overcome difficulties, and the creation of a sense of meaning in life through coexistence. CONCLUSION: We identified the concept of older people's connectedness with people in the community in a contemporary context. Connectedness is a useful concept to consider in nursing care because it seems to evolve into comprehensive health, including the physical and psychosocial health of older adults.

Effects of a 'social activity program that encourages interaction' on rural older people's psychosocial health: Mixed-methods research.

BACKGROUND: We developed a program that encourages interaction among older people living at home by combining face-to-face and online activities and examined its effects on older adults' psychosocial health. METHODS: In this mixed-methods study, we recruited 11 women and 6 men (Mage = 79.5 ± 6.4 years), who lived in a rural community and participated in a senior citizen club. The intervention was conducted for 13 months, comprising monthly face-to-face group and social media activities. For the program process evaluation, we collected focus-group interview data on participants' perceptions of their personal lives, club membership, and community post-intervention. For the outcome evaluation, we collected six outcome measures pre- and post-intervention: loneliness, subjective health, subjective well-being, self-esteem, social support and social activity satisfaction. Finally, through the integration of the process-outcome evaluation, we inferred what effects the program had on participants' psychosocial health. RESULTS: In the process evaluation, we identified four themes: 'Stimulation brought about by relationships with peers,' 'Realization as to where they feel they belong,' 'Rethinking of oneself in the community,' and 'Awareness of attachment to and coexistence with the community.' In the outcome evaluation, the outcome measures were maintained without significant decline post-intervention. CONCLUSION: Through the integration of the process-outcome evaluation, we deduced three effects of the program on psychosocial health: (1) fulfilment of subjective health, (2) maintenance and assurance of moderate distance connectedness and (3) orientation toward aging in place. IMPLICATIONS FOR PRACTICE: This study offers a promising opportunity for further development and research into community-based preventive nursing care intervention strategies to maintain the psychosocial health of homebound older people in communities with social activity groups.

Characteristics of Patients With Metastatic Breast Cancer Who Survived more than 10 Years.

BACKGROUND/AIM: Despite advances in the treatment of breast cancer, metastatic breast cancer (MBC) remains difficult to cure, and few MBC patients survive 10 years after receiving a breast cancer metastasis diagnosis. We collected the cases of patients with MBC who survived >10 years post-metastasis diagnosis and assessed the patients' characteristics. PATIENTS AND METHODS: We retrospectively analyzed the cases of 245 consecutive patients diagnosed with MBC between January 2005 and December 2012 at our institution. Among them, 167 patients with confirmed survival of >10 years (i.e., long-term survival) or confirmed death at ≤10 years post-metastasis diagnosis were enrolled. RESULTS: There were 22 patients with MBC who survived >10 years. Regarding the cancer subtypes, 11 patients (50%) with long-term survival were HER2-positive. Seven of the 11 patients with HER2-positive MBC have been without recurrence although anti-HER2 therapy was discontinued. Triple-negative breast cancer (TNBC) was most common in the patients who survived ≤5 years but was not present in the >10-year survival group. In the HER2-negative cases, more cases in the long-term survival group were treated with local therapy (34.4% in the <5-year survival group, 43.8% in the 5-10-year group, and 72.7% in the >10-year group). CONCLUSION: MBC patients who survive >10 years after being diagnosed with metastasis are more likely to be HER2-positive and treated with local therapy. This suggests the efficacy of anti-HER2 therapy, and, conversely, clarifies unmet needs in TNBC and luminal-type MBC. The usefulness of local therapy was also supported by our findings.

Older rural people's perception of connectedness through a communication application: A qualitative descriptive study.

Connectedness among older people is essential for healthy communities, especially among rural populations where limited social interaction and associated health effects may be cause for concern. In this qualitative descriptive study, we explored older rural people's perception of connectedness through a communication application. The study assessed 10 participants (mean age = 76.2 years) living in rural Japan who regularly participated in a senior citizens' club. From July 2019 to January 2020, the participants used a social media application developed by our research team to meet the needs of older people. Semi-structured interviews were conducted. Six themes representing older rural people's perception of connectedness were identified: (1) thoughtful consideration for members strengthened even without them meeting face-to-face, (2) encouragement received from familiar members, (3) joy in sharing daily routine with neighbors, (4) courage to advance through face-to-face interaction, (5) willingness to continue club membership, and (6) fear of disrupting club's harmony. Participants who used the application felt compensated for the lack of social interaction opportunities in rural settings and strengthened their existing relationships.

A novel system for teaching the in-plane vascular access technique: A simulation study.

ABSTRACT: The long-axis in-plane approach is amenable to ultrasound-guided central venous catheterization. However, the long-axis in-plane approach is considered difficult to learn because the needle should remain visible in the ultrasound beam during the procedure. We developed a novel competency-based modular system to acquire the skills for the long-axis in-plane approach. The purpose of this study is to evaluate the efficacy of this system.The study was approved by the local ethics committee. Participants performed ultrasound guided venous catheterization (pre-test), attended a 2-hour hands-on session with the teaching system and were then evaluated again (posttest). The teaching system is a simulator device consisting of an ultrasound probe, a simulated vessel, a needle, and an endoscope connected to a computer to visualize the image inside the simulated vessel. The success rate, visualization of the needle tip, and puncture accuracy were measured before and after training. The puncture accuracy was determined by evaluating the distance of the needle tip and needle shaft from the center of a simulated vessel. Primary outcomes were the success rate and the puncture accuracy. The secondary outcome was needle tip visualization. McNemar test was used to analyze success rate and needle tip visualization. Tukey test was used to analyze puncture accuracy. A P value <.05 was considered statistically significant.Forty-seven participants were enrolled in this study. The success rate was significantly increased (pre-test 79%, posttest 94%, P = .04). Ultrasound images from 42 participants were analyzed for puncture accuracy. Puncture accuracy significantly increased for needle tip distance (P = .03), but not shaft distance (P = .1). The needle tip visualization was significantly improved (P = .02).A novel competency-based teaching system was constructed in a step-by-step manner, which improved needle tip visualization and puncture accuracy, with a higher success rate.

Validity of self-reported diagnoses of gynaecological and breast cancers in a prospective cohort study: the Japan Nurses' Health Study.

OBJECTIVES: To validate the self-reported diagnoses of gynaecological and breast cancers in a nationwide prospective cohort study of nursing professionals: the Japan Nurses' Health Study (JNHS). DESIGN AND SETTING: Retrospective analysis of the JNHS. PARTICIPANTS AND MEASURES: Data were reviewed for 15 717 subjects. The mean age at baseline was 41.6±8.3 years (median: 41), and the mean follow-up period was 10.5±3.8 years (median: 12). Participants are regularly mailed a follow-up questionnaire once every 2 years. Respondents who self-reported a positive cancer diagnosis were sent an additional confirmation questionnaire and contacted the diagnosing facility to confirm the diagnosis based on medical records. A review panel of experts verified the disease status. Regular follow-up, confirmation questionnaires and expert review were validated for their positive predictive value (PPV) and negative predictive value (NPV). RESULTS: New incidences were verified in 37, 47, 26 and 300 cervical, endometrial, ovarian and breast cancer cases, respectively. The estimated incidence rates were 22.0, 25.4, 13.8 and 160.4 per 100 000 person-years. These were comparable with those of national data from regional cancer registries in Japan. For regular follow-up, the corresponding PPVs for cervical, endometrial, ovarian and breast cancer were 16.9%, 54.2%, 45.1% and 81.4%, and the NPVs were 100%, 99.9%, 99.9% and 99.9%, respectively. Adding the confirmation questionnaire improved the PPVs to 31.5%, 88.9%, 76.7% and 99.9%; the NPVs were uniformly 99.9%. Expert review yielded PPVs and NPVs that were all ~100%. CONCLUSIONS: Gynaecological cancer cannot be accurately assessed by self-reporting alone. Additionally, the external validity of cancer incidence in this cohort was confirmed.

Optical skill-assist device for ultrasound-guided vascular access: A preliminary simulation study.

Ultrasound-guided central venous catheterization may cause lethal mechanical complications intraoperatively. We developed a novel device to prevent such complications. It works as a needle guide to supplement the operator's skill. We evaluated the utility of this device in terms of the success rate and visualization of the needle tip while penetrating the target vessel using a simulator.This study was approved by the local ethics committee. The new device - an optical skill-assist device - has a slit and a mirror in the center. The operator can see the needle's reflection in the mirror through the slit and can thus ensure that the needle is directed in line with the ultrasound beam. Participants were recruited by placing an advertisement for a hands-on seminar on ultrasound-guided vascular access. They received hands-on training on the in-plane approach for 2 hours. Pre-test and post-test without the device and an additional test using the device were performed to evaluate the proficiency of ultrasound-guided vascular access. An endoscope inserted into the simulated vessel was used to detect the precise location of the needle tip in the vessel.The primary outcomes were the success rate of the procedure. The secondary outcome was visualization of the needle tip while penetrating the simulated vessel. The chi-squared test was used for comparing the success rate and needle tip visualization between the different tests. P < .05 was considered to indicate significant differences.Forty-two participants were enrolled in this study. The success rate did not increase after the simulation training (P = .1). Using the optical skill-assist device, the rate improved to 100%. There was a significant difference in success rate between the pre-test and additional test using the optical skill-assist device (P = .003). Needle tip visualization significantly improved with the use of the optical skill-assist device compared to the pre-test (P < .001) and post-test (P = .001).Simulation training improved participants' skill for ultrasound-guided vascular access, but the improvement depended on each participant. However, further, improvement was achieved with the use of the optical skill-assist device.The optical skill-assist device is useful for supplementing the operator's skill for ultrasound-guided central venous catheterization.

Review of the efficacy of AST-120 (KREMEZIN®) on renal function in chronic kidney disease patients.

AST-120 (KREMEZIN®) consists of oral, spherical carbon particles that adsorb uremic toxins and their precursors within the gastrointestinal tract, allowing them to be excreted in the feces. Uremic toxins such as indoxyl sulfate and p-cresyl sulfate are abundant in the blood of chronic kidney disease (CKD) patients and are related to the progression of both CKD and cardiovascular disease. AST-120 was approved in Japan in 1991 followed by Korea (2004), Taiwan (2007) and the Philippines (2010) for treating uremic symptoms and prolonging the time to initiation of dialysis in patients with progressive CKD. In this review, we provide an overview of the past clinical data on AST-120 from 1982 to 2013. The effect of AST-120 for renal events was not supported in the primary analysis of randomized clinical trials. However, post-hoc analyses revealed significant differences between the AST-120 and control groups in the second Japanese phase III trial and in the multinational Evaluating Prevention of Progression in CKD (EPPIC) trials. Furthermore, inhibitory effects on the progression of CKD, as represented by amelioration in the estimated glomerular filtration rate (eGFR) decline and serum creatinine (sCr) elevation were suggested. These results suggest that AST-120 delays the decline in renal function. In addition, AST-120 may prolong the time to the initiation of dialysis, especially in patients with progressive CKD. For further verification of the clinical efficacy of AST-120, future study inclusion criteria should be determined carefully, defining progressive CKD using markers such as declines in eGFR and sCr elevation.

Risk factors for progression of chronic kidney disease in the EPPIC trials and the effect of AST-120.

BACKGROUND: Two randomized, double-blind, placebo-controlled trials (EPPIC-1 and EPPIC-2) investigated the efficacy and safety of AST-120, an oral spherical carbon adsorbent, in adults with chronic kidney disease (CKD). While the benefit of adding AST-120 to standard therapy was not supported by these trials, we performed a post hoc analysis to focus on CKD progression and to determine the risk factors for the primary endpoint in the EPPIC trial population. METHODS: In the EPPIC trials, patients were randomly assigned 1:1 to treatment with AST-120 or placebo. The primary endpoint was a composite of dialysis initiation, kidney transplantation, or doubling of serum creatinine. The EPPIC trial pooled population was evaluated with the same statistical methods used for analysis of the primary and secondary efficacy endpoints. The trials were registered on ClinicalTrials.gov (NCT00500682 [EPPIC-1] and NCT00501046 [EPPIC-2]). RESULTS: An analysis of the placebo population suggested baseline urinary protein to urinary creatinine ratio (UP/UCr) ≥1.0 and hematuria were independent risk factors for event occurrence and eGFR lowering. Analysis of the high risk patients revealed a difference in the primary endpoint occurrence between treatment groups, if angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers were administered (hazard ratio 0.74, 95% confidence interval 0.56-0.96). Also, the eGFR changes from baseline in the AST-120 group were smaller than that in the placebo group (P = 0.035). CONCLUSIONS: CKD progression may have an association with baseline UP/UCr and hematuria. Treatment with AST-120 may delay the time to the primary endpoint in patients with progressive CKD receiving standard therapy, thus warranting further investigation.

Uremic Toxin-Producing Gut Microbiota in Rats with Chronic Kidney Disease.

BACKGROUND: In patients with chronic kidney disease (CKD), many metabolites of gut microbiota retain in the body as uremic toxins (UTs). However, the kinds of bacteria producing UTs are rarely discussed. METHODS: We analyzed UT production and the composition of gut microbiota in CKD rats and cecectomized rats. AST-120, a spherical carbon adsorbent, was administrated to evaluate how the precursors of UT affect gut microbiota. Serum and urine levels of UTs were quantified by liquid chromatography/electrospray ionization-tandem mass spectrometry. Gut microbiota were analyzed using 454-pyrosequencing of the 16S rRNA gene. Operational taxonomic unit (OTU) clustering and UniFrac analysis were performed to compare gut microbiota among the groups. RESULTS: Serum and urine levels of indoxyl sulfate and phenyl sulfate were higher in CKD versus control rats (p < 0.05). AST-120 administration decreased UT production (p < 0.01) and changed overall gut microbiota composition in CKD rats. UT urinary excretion and gut microbiota composition changed in cecectomized rats, with the relative abundance of Clostridia- and Bacteroidia-affiliated species being significantly reduced (p < 0.01). We identified candidate indole- and phenol-producing intestinal microbiota, 3 Clostridia, and 2 Bacteroidia. These OTUs have a tryptophanase/tyrosine phenol-lyase gene in the closest sequenced genome out of the OTUs declined following cecectomy. CONCLUSION: Our data suggest that UT production is correlated with a subset of indigenous gut microbiota. However, UT may be induced by other non-symbiotic microbiota that are influenced by factors other than microbiota populations. The relationship between specific microbiota and UTs in patients requires further clarification.

The effects of AST-120 on chronic kidney disease progression in the United States of America: a post hoc subgroup analysis of randomized controlled trials.

BACKGROUND: The orally administered spherical carbon adsorbent AST-120 is used on-label in Asian countries to slow renal disease progression in patients with progressive chronic kidney disease (CKD). Recently, two multinational, randomized, double-blind, placebo-controlled, phase 3 trials (Evaluating Prevention of Progression in Chronic Kidney Disease [EPPIC] trials) examined AST-120's efficacy in slowing CKD progression. This study assessed the efficacy of AST-120 in the subgroup of patients from the United States of America (USA) in the EPPIC trials. METHODS: In the EPPIC trials, 2035 patients with moderate to severe CKD were studied, of which 583 were from the USA. The patients were randomly assigned to two groups of equal size that were treated with AST-120 or placebo (9 g/day). The primary end point was a composite of dialysis initiation, kidney transplantation, or serum creatinine doubling. RESULTS: The Kaplan-Meier curve for the time to achieve the primary end point in the placebo-treated patients from the USA was similar to that projected before the study. The per protocol subgroup analysis of the population from the USA which included patients with compliance rates of ≥67 % revealed a significant difference between the treatment groups in the time to achieve the primary end point (Hazard Ratio, 0.74; 95 % Confidence Interval, 0.56-0.97). CONCLUSIONS: This post hoc subgroup analysis of EPPIC study data suggests that treatment with AST-120 might delay the time to primary end point in CKD patients from the USA. A further randomized controlled trial in progressive CKD patients in the USA is necessary to confirm the beneficial effect of adding AST-120 to standard therapy regimens. TRIAL REGISTRATION: ClinicalTrials.gov NCT00500682 ; NCT00501046 .

[Phase I study of sequential S-1 and cyclophosphamide therapy in patients with metastatic breast cancer].

S-1 is a novel oral anticancer agent consisting of tegafur, a prodrug of 5-fluorouracil, and 2 modulators. A phase I study of sequential S-1 and cyclophosphamide(CPA)therapy was conducted to determine the dose-limiting toxicities(DLTs)and recommended doses(RDs)in patients with metastatic or recurrent breast cancer(MBC). Patients with MBC received sequential S-1 and CPA. Chemotherapy consisted of administration of S-1 twice daily on days 1-14 at escalating doses of 40, 50, 65, and 80mg/m2/day and CPA at 100 mg/body/day on days 15-28. The schedule was repeated twice at a 4-week interval. The purposes of this study were to determine the RDs, safety, and efficacy of the regimen. A total of 12 patients were registered. No patients experienced DLTs, and the RDs of S-1 and CPA were 80mg/m2/day and 100 mg/body/day, respectively. The response rate was 50. 0%. In conclusion, sequential therapy with S-1 and CPA could be safely and effectively used for the treatment of MBC, and the RDs for this regimen were determined to be 80mg/m2/day for S-1 and 100 mg/m2/day for CPA.

Collagen gel droplet-embedded culture-drug sensitivity test and Ki67 expression in estrogen receptor-positive and HER2-negative breast cancer.

Anthracyclines and taxanes are standard anticancer drugs used in breast cancer chemotherapy. In general, the efficacy of chemotherapy is lower in patients with estrogen receptor (ER)-positive tumors compared to patients with ER-negative tumors. Although less chemosensitive, ER-positive disease includes a subset of patients who significantly benefit from adjuvant chemotherapy. The collagen gel droplet-embedded culture-drug sensitivity test (CD-DST) is an in vitro chemosensitivity test that has several advantages over conventional tests. The aim of the present study was to examine the correlation between CD-DST and the expression of Ki67, an indicator of tumor proliferation, to evaluate the efficacy of anthracyclines and taxanes in patients with ER-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. CD-DST was performed in 68 patients with ER-positive and HER2-negative breast cancer between August 2001 and November 2006. The specimens obtained during surgery were used for the CD-DST and immunohistological examination of Ki67 expression. Chemosensitivity to the anticancer drugs adriamycin (ADM), epirubicin (EPI), docetaxel (DOC) and paclitaxel (PTX) was estimated using CD-DST. Results obtained from the CD-DST showed the chemosensitivity to each anticancer drug to be ADM, 23.7%; EPI, 75.0%; DOC, 69.2% and PTX, 43.6%. Ki67 expression was significantly higher in the group that was sensitive to DOC compared to the group that was resistant to DOC (P=0.048) and PTX (P=0.036). In addition, a significant correlation was observed between a Ki67 labeling index (LI) of >30% and chemosensitivity to PTX. In conclusion, results obtained from CD-DST and Ki67 expression levels are able to identify a subset of patients with ER-positive and HER2-negative breast cancer who exhibit sensitivity to chemotherapy, particularly to taxane therapy.

Topoisomerase II alpha expression and the Ki-67 labeling index correlate with prognostic factors in estrogen receptor-positive and human epidermal growth factor type-2-negative breast cancer.

BACKGROUND: Topoisomerase II alpha (Topo IIa) is involved in DNA replication and is a molecular target for anthracycline-based chemotherapy. The Ki-67 labeling index (LI) is an evaluation of tumor cell proliferation. The objective of this study was to evaluate relationships among Topo IIa expression, the Ki-67 LI, and prognostic factors in estrogen receptor (ER)-positive, human epidermal growth factor type-2 (HER2)-negative breast cancer. MATERIALS AND METHODS: Seventy-one patients were diagnosed with ER-positive, HER2-negative breast cancer between July 2003 and December 2004. Formalin-fixed, paraffin-embedded tumor specimens were stained for Topo IIa expression and Ki-67 LI. We investigated the correlation of the level of Topo IIa expression and the Ki-67 LI with clinical factors such as age, tumor size, progesterone receptor status, nodal status, nuclear grade, and lymphovascular invasion (LVI). RESULTS: Statistically significant differences were observed between Topo IIa overexpression, nuclear grade (p = 0.036), and LVI (p = 0.029). Topo IIa overexpression was statistically correlated with the Ki-67 LI (p < 0.0001). A statistically significant difference was observed between the Ki-67 LI and nuclear grade (p = 0.01). Survival analysis revealed the significant prognostic value of Ki-67 LI in patients with ER-positive, HER2-negative breast cancer (p = 0.003). CONCLUSIONS: Ki-67 LI is a strong prognostic factor in ER-positive HER2-negative breast cancer. Topo IIa overexpression was significantly correlated with the Ki-67 LI, nuclear grade, and LVI. These findings suggest use of Topo IIa expression as a proliferation marker and a prognostic factor in ER-positive, HER2-negative breast cancer.

Pathological complete response and prognosis in patients receiving neoadjuvant paclitaxel and trastuzumab with and without anthracyclines for stage II and III, HER2-positive operable breast cancer: a single-institute experience.

BACKGROUND: Trastuzumab and various chemotherapy combinations have shown superior results in patients with primary and metastatic breast cancer. However, cardiotoxicity becomes a major adverse event when trastuzumab is used with anthracycline-containing regimens. The purpose of this study was to determine the clinical and pathological efficacy of neoadjuvant chemotherapy (NAC), using trastuzumab and chemotherapy, with or without anthracyclines, for patients with primary breast cancer and human epidermal growth factor receptor 2 (HER2-)-positive tumors. PATIENTS AND METHODS: A retrospective analysis of 41 patients with stage II and III primary breast cancer and HER2-positive tumors treated with NAC was performed. NAC consisted of weekly paclitaxel plus trastuzumab with (PTA group, n=21) or without anthracycline (PT group, n=20). Patients in the PTA group received four courses of 5-fluorouracil, epirubicin, and cyclophosphamide every 3 weeks followed by concomitant 80 mg/m² paclitaxel and trastuzumab weekly for 12 weeks, and those in the PT group received four courses of 80 mg/m² paclitaxel weekly (days 1, 8, and 15) followed by a 1-week break and trastuzumab weekly (days 1, 8, 15, and 29). RESULTS: The median age of the patients was 50 years. Of 41 patients, 21 (51%) had a pathological complete response (pCR). Patients with clinical stage II cancer had a higher pCR rate compared with those with clinical stage III. Patients with estrogen receptor (ER)-negative tumors showed a trend toward a higher pCR rate. No significant difference was observed according age, clinical stage, ER status, clinical response, or pathological response between the PTA and the PT groups. The pCR rate of the PTA and the PT groups was 47.6% and 55.0%, respectively. No significant difference in disease-free survival was observed between the two groups at a median follow-up of 32 months. CONCLUSION: Trastuzumab-containing NAC is effective irrespective of anthracycline use for treating patients with primary breast cancer and HER2-positive tumors.

Papillary lesions of the breast diagnosed using core needle biopsies.

Papillary lesions of the breast include a broad spectrum of lesions, from benign papillomas to papillary carcinomas. It is difficult to determine whether a lesion is benign or malignant based on the fragmented material of a core needle biopsy (CNB). This study evaluated patients with papillary lesions examined using CNB. We retrospectively reviewed 31 papillary lesions diagnosed using CNB between 2004 and 2007. The clinical findings of benign and malignant papillary lesions were compared. The average patient age was 48.9 years. Twelve patients presented with a discharge and 10 patients presented with a lump. Eight patients were asymptomatic. The initial diagnoses by CNB of the 31 lesions were 25 intraductal papillomas, 4 intracystic papillomas and 2 adenomas. After CNB, excisional biopsies were performed in 23 patients and biopsies with a Mammotome(®) in 2 patients. Seven patients underwent regular follow-up. Five (16%) of the 31 patients with papillary lesions were ultimately diagnosed with breast cancer. The average distance from the nipple to a tumor diagnosed as malignant was 2.46 cm, which was longer than for a tumor diagnosed as benign. Ultimately, 5 papillary lesions (16%) were diagnosed as breast cancer. To avoid overlooking a malignancy, surgical excision is advantageous for papillary lesions, particularly those located far from the nipple.

Microbial populations responsive to denitrification-inducing conditions in rice paddy soil, as revealed by comparative 16S rRNA gene analysis.

Rice paddy soil has been shown to have strong denitrifying activity. However, the microbial populations responsible for nitrate respiration and denitrification have not been well characterized. In this study, we performed a clone library analysis of >1,000 clones of the nearly full-length 16S rRNA gene to characterize bacterial community structure in rice paddy soil. We also identified potential key players in nitrate respiration and denitrification by comparing the community structures of soils with strong denitrifying activity to those of soils without denitrifying activity. Clone library analysis showed that bacteria belonging to the phylum Firmicutes, including a unique Symbiobacterium clade, dominated the clones obtained in this study. Using the template match method, several operational taxonomic units (OTUs), most belonging to the orders Burkholderiales and Rhodocyclales, were identified as OTUs that were specifically enriched in the sample with strong denitrifying activity. Almost one-half of these OTUs were classified in the genus Herbaspirillum and appeared >10-fold more frequently in the soils with strong denitrifying activity than in the soils without denitrifying activity. Therefore, OTUs related to Herbaspirillum are potential key players in nitrate respiration and denitrification under the conditions used.

Cd1d-dependent regulation of bacterial colonization in the intestine of mice.

The accumulation of certain species of bacteria in the intestine is involved in both tissue homeostasis and immune-mediated pathologies. The host mechanisms involved in controlling intestinal colonization with commensal bacteria are poorly understood. We observed that under specific pathogen-free or germ-free conditions, intragastric administration of Pseudomonas aeruginosa, E. coli, Staphylococcus aureus, or Lactobacillus gasseri resulted in increased colonization of the small intestine and bacterial translocation in mice lacking Cd1d, an MHC class I-like molecule, compared with WT mice. In contrast, activation of Cd1d-restricted T cells (NKT cells) with alpha-galactosylceramide caused diminished intestinal colonization with the same bacterial strains. We also found prominent differences in the composition of intestinal microbiota, including increased adherent bacteria, in Cd1d-/- mice in comparison to WT mice under specific pathogen-free conditions. Germ-free Cd1d-/- mice exhibited a defect in Paneth cell granule ultrastructure and ability to degranulate after bacterial colonization. In vitro, NKT cells were shown to induce the release of lysozyme from intestinal crypts. Together, these data support a role for Cd1d in regulating intestinal colonization through mechanisms that include the control of Paneth cell function.

Neoadjuvant weekly paclitaxel with and without trastuzumab in locally advanced or metastatic breast cancer.

A phase II clinical trial was conducted to examine the clinical and pathologic efficacy and safety of neoadjuvant paclitaxel with or without trastuzumab in women with advanced or metastatic breast cancer. A total of 49 patients with advanced or metastatic breast cancer (clinical stage IIB -IV) were included. Patients with HER2-negative tumors received weekly paclitaxel 80 mg/m2 (days 1, 8, 15) followed by a 1-week break for 4 cycles. Patients with HER2-positive tumors received weekly paclitaxel 80 mg/m2 (days 1, 8, 15) followed by a 1-week break and a trastuzumab 4 mg/kg loading dose, intravenously, followed by 2 mg/kg weekly for 4 cycles. The age of the patients was 51.6 +/- 1.6 years (mean +/- SE) and the size of their tumors was 5.8 +/- 0.4 cm (mean +/- SE). Thirty-two patients had HER2-negative tumors and 17 had HER2-positive tumors. Of 49 patients, 13 (26.5%) had a clinical complete response and 24 (49.0%) had a clinical partial response. Five (10.2%) patients had a pathological complete response (pCR) and three (6.1%) patients had a near pCR in the breast. A total of eight (16.3%) patients had a pCR or near pCR in the breast. The pCR or near pCR rate was 3.1% in the HER2-negative group and 41.2% in the HER2-positive group. With a median follow-up of 28 months (range, 1-45), the 3-year overall survival was 88%. Clinical responders showed a significantly better overall survival than non-responders (p < 0.01). Pathological responders showed a better overall survival than non-responders. There was no significant difference in overall survival between patients with HER2-positive and -negative tumors. In conclusion, combined neoadjuvant weekly paclitaxel and trastuzumab achieved high clinical and pathological response rates for HER2 -overexpressing breast cancers, despite the omission of an anthracycline.