A nomogram to predict the pathological complete response in patients with breast cancer based on the TILs-US score.

BACKGROUND: The tumor-infiltrating lymphocytes-ultrasonography score is a calculation system for predicting lymphocyte-predominant breast cancers in surgical specimens. A nomogram based on the tumor-infiltrating lymphocytes-ultrasonography score was developed to predict the pathological complete response in breast cancer treated with neoadjuvant chemotherapy. METHODS: A retrospective evaluation was conducted on 118 patients with breast cancer treated with neoadjuvant chemotherapy at Hiroshima University Hospital. Tumor-infiltrating lymphocytes-ultrasonography scores ≥4 were classified as high. A nomogram was developed using a stepwise logistic regression model for pathological complete response (ypT0 ypN0), based on the smallest Akaike information criterion. The predictive ability and clinical usefulness of the nomogram were also evaluated. RESULTS: Among 118 patients, 34 (28.8%) achieved a pathological complete response, and 52 (44.1%) exhibited high tumor-infiltrating lymphocytes-ultrasonography. In multivariate logistic regression analysis, high tumor-infiltrating lymphocytes-ultrasonography (odds ratio, 6.01; P < 0.001), clinical complete response (odds ratio, 4.83; P = 0.004) and hormone receptor (odds ratio, 3.48; P = 0.038) were independent predictors of pathological complete response. A nomogram based on tumor-infiltrating lymphocytes-ultrasonography score, clinical complete response, hormone receptor and clinical N status was developed. The nomogram showed an area under the curve of 0.831 and a bias-corrected area under the curve of 0.809. The calibration plot showed a good fit between the expected and actual pathological complete response values. Decision curve analysis also showed the clinical utility of the nomogram for predicting pathological complete responses. CONCLUSIONS: A nomogram based on the tumor-infiltrating lymphocytes-ultrasonography score exhibited a favorable predictive ability for pathological complete response in patients with breast cancer, which can be useful in predicting the residual disease status after neoadjuvant chemotherapy.

[A Case of Lynch Syndrome with Repeated Asynchronous Colorectal Cancer in a Short Period].

This case was a 73-year-old woman who previously underwent a partial colectomy for ascending colon cancer at the age of 70. She had a history of cancer of the uterus, descending colon, bladder, and left ureter. She had a family history of colorectal cancer and met the Amsterdam Ⅱ criteria for Lynch syndrome. She was diagnosed as Lynch syndrome with a MSH2 germline mutation by genetic analysis. One year later, a partial colectomy was performed for sigmoid colon cancer. Six months later, colonofiberscopy revealed early-stage cancer in the rectum, and EMR was performed. Despite adequate surveillance, she had frequent recurrences of advanced colorectal cancer within a short period of time. We report here risk factors of colorectal cancer in Lynch syndrome and indications for prophylactic total colectomy.

[A Case of Laparoscopic Surgery for Colon Metastasis of Renal Cancer].

A 67-year-old man underwent laparoscopic partial left nephrectomy for renal cell carcinoma 2.5 years ago. CT showed a well-defined 3 cm mass with contrast effect bordering on the descending colon, and PET-CT showed an accumulation of SUVmax 6.01 in the same area. Colonoscopy revealed a submucosal tumor-like mass in the descending colon. The patient was diagnosed with a local recurrence of renal cell carcinoma and invasion of the descending colon, and laparoscopic colectomy was performed. The excised specimen was a pale yellowish submucosal tumor measuring 4.5×3.8 cm, which was histologically diagnosed as metastasis of clear cell renal cell carcinoma. Surgical resections for metastases of renal carcinoma have been reported and expected prolong survival. We report a case of laparoscopic colon resection for recurrence of descending colon metastasis of renal cell carcinoma.

Instability of turing patterns in reaction-diffusion-ODE systems.

The aim of this paper is to contribute to the understanding of the pattern formation phenomenon in reaction-diffusion equations coupled with ordinary differential equations. Such systems of equations arise, for example, from modeling of interactions between cellular processes such as cell growth, differentiation or transformation and diffusing signaling factors. We focus on stability analysis of solutions of a prototype model consisting of a single reaction-diffusion equation coupled to an ordinary differential equation. We show that such systems are very different from classical reaction-diffusion models. They exhibit diffusion-driven instability (turing instability) under a condition of autocatalysis of non-diffusing component. However, the same mechanism which destabilizes constant solutions of such models, destabilizes also all continuous spatially heterogeneous stationary solutions, and consequently, there exist no stable Turing patterns in such reaction-diffusion-ODE systems. We provide a rigorous result on the nonlinear instability, which involves the analysis of a continuous spectrum of a linear operator induced by the lack of diffusion in the destabilizing equation. These results are extended to discontinuous patterns for a class of nonlinearities.

The Development and Evaluation of the Interprofessional Education Facilitation Program for Health Professionals Using the Attention, Relevance, Confidence, and Satisfaction (ARCS) Model of Instructional Design.

Background It is important to learn interprofessional education (IPE) facilitation skills to promote interprofessional collaboration in healthcare. Nonetheless, to date, only a handful of IPE facilitation programs have been developed through research. Objective The objective of this study was to create an IPE facilitation program for healthcare professionals who wanted to promote interprofessional collaboration in their organizations based on the tenets of instructional design and evaluate its effectiveness. Methods This study's methodology was a mixed method based on relative subjectivism. We developed a two-day IPE facilitation program to learn IPE facilitation skills and promote interprofessional collaboration in the participants' own organizations. The program was developed based on the instructional design principles of the attention, relevance, confidence, and satisfaction (ARCS) model, measuring the participants' Interprofessional Facilitation Scale (IPFS) scores at three time points: before the first day, after the second day, and approximately one year after the course was completed. A one-way analysis of variance test was used to compare IPFS means at the three time points, and open-ended statements were qualitatively analyzed using thematic analysis. Results Twelve healthcare providers (four physicians, two pharmacists, one nurse, one rehabilitation worker, one medical social worker, one clinical psychologist, one medical secretary, and one other) participated in the completed IPE facilitation program. Their IPFS scores increased significantly from 17.4 ± 16.1 before the program to 38.1 ± 9.4 after the program and remained at 35.1 ± 11.7 for one year (p = 0.008). In addition, qualitative analysis suggested that the knowledge and skills learned in the program could be applied in the participants' workplaces, which helped them maintain their IPE facilitation skills. Conclusion We developed a two-day IPE facilitation program based on the ARCS instructional design model, and the participants' IPE facilitation skills scores increased and were maintained one year later.

Impact of oral hygiene on febrile neutropenia during breast cancer chemotherapy.

PURPOSE: Oral hygiene is crucial in the management of oral and febrile complications during chemotherapy for cancer. This study aimed to investigate the impact of oral hygiene on the incidence of febrile neutropenia (FN) throughout the course of chemotherapy for breast cancer. METHODS: A total of 137 patients with breast cancer who underwent four cycles of adjuvant chemotherapy with docetaxel and cyclophosphamide (TC) combination therapy or docetaxel alone were assessed for oral hygiene by quantifying the number of oral bacteria they harbored. These patients received professional oral health care (POHC). Eighteen patients underwent primary prophylaxis with granulocyte colony-stimulating factors. The relationship between oral bacteria count and FN incidence was retrospectively assessed. RESULTS: The FN incidence rate was 47.4% throughout all treatment cycles (32.8%, 13.5%, 14.3%, and 14.4% in cycles 1, 2, 3, and 4, respectively). The oral bacteria count decreased with each treatment cycle (cycle 1: 9.10 × 106 colony-forming units (CFU)/mL, cycle 2: 5.89 × 106 CFU/mL, cycle 3: 4.61 × 106 CFU/mL, cycle 4: 5.85 × 106 CFU/mL, P = 0.004). Among 281 treatment cycles, FN occurred in 63 (22.4%). In the treatment cycle-based analysis, high oral bacteria count was an independent risk factor for FN. CONCLUSION: FN incidence decreased with each treatment cycle and was associated with changes in oral bacteria counts. The oral bacterial count was one of risk factors for FN development in breast cancer.

An incidentally discovered paraganglioma that caused sinus arrest after resection.

Paragangliomas are neural-crest-derived nonepithelial neuroendocrine tumors distributed along the parasympathetic and sympathetic nerves. To our knowledge, no studies were reported regarding sinus arrest on day 4 after paraganglioma resection. A 66-year-old female patient with a history of pulmonary vein isolation visited our department for sigmoid colon cancer treatment. Enhanced computed tomography revealed an enhanced small nodule-like lymph node near the root of the inferior mesenteric artery. The patient underwent laparoscopic colectomy with regional lymph node dissection. Postoperatively, paroxysmal atrial fibrillation attacks developed, and the patient resumed oral medication. Additionally, sinus arrest after tachycardia developed. Changing the oral medication could maintain her circulatory dynamics. Pathological examination revealed that differentiated tubular adenocarcinoma infiltrated the submucosa. Immunohistochemically, the excised nodule as a lymph node was considered a functional paraganglioma. Our case indicates that paraganglioma resection and oral medication resumption may contribute to sinus arrest. When arrhythmias affecting the circulation occur perioperatively, the presence of a catecholamine-producing tumor should be considered in addition to cardiac disease. J. Med. Invest. 70 : 503-507, August, 2023.

An oligonucleotide/oligosaccharide-binding-fold protein enhances the alternative splicing event producing thylakoid membrane-bound ascorbate peroxidase in Nicotiana tabacum.

The stromal and thylakoid membrane-bound ascorbate peroxidase isoforms are produced by the alternative splicing event of the 3'-terminal region of the APXII gene in spinach (Spinacia oleracea) and tobacco (Nicotiana tabacum), but not in Arabidopsis (Arabidopsis thaliana). However, all alternative splicing variants were detected in APXII gene-transformed Arabidopsis, indicating the occurrence of its regulatory mechanisms in Arabidopsis. The efficiency of this alternative splicing event in producing thylakoid membrane-bound ascorbate peroxidase mRNA is regulated by a splicing regulatory cis element, but trans splicing regulatory factor(s) for alternative splicing remain unclear. To identify this factor, we conducted a forward genetic screen using Arabidopsis in combination with a luciferase reporter system to evaluate the alternative splicing efficiency of thylakoid membrane-bound ascorbate peroxidase mRNA production. We isolated 9 mutant lines that showed low efficiency of the AS in producing thylakoid membrane-bound ascorbate peroxidase mRNA compared with that in the control plants. From one mutant [APXII alternative splicing inhibition (apsi1)], the causal gene responsible for the phenotype, AT5G38890 (oligonucleotide/oligosaccharide-binding-fold protein, APSI1), was identified. The levels of thylakoid membrane-bound ascorbate peroxidase mRNA from the transformed APXII gene decreased and increased in APSI1 knockout and APSI1-overexpressing plants, respectively. APSI1 was localized to the nucleus and specifically bound to the splicing regulatory cis element sequence. Tobacco plants that disrupted the closest homologs of APSI1 showed low levels of endogenous thylakoid membrane-bound ascorbate peroxidase mRNA. These results indicate that APSI1 is an enhancing component of the alternative splicing event of APXII.

Effect of Secondary Prophylactic G-CSF on the Occurrence of Febrile Neutropenia in Breast Cancer.

BACKGROUND/AIM: Docetaxel and cyclophosphamide (TC) combination therapy is widely used as adjuvant chemotherapy for early-stage breast cancer and is associated with a high incidence of febrile neutropenia (FN). Granulocyte colony-stimulating factor (G-CSF) is recommended in the primary prevention of febrile neutropenia (FN). This study aimed to evaluate the FN-suppressing effect of G-CSF in patients with breast cancer receiving TC. PATIENTS AND METHODS: We performed 272 treatment cycles after FN onset in 106 patients with breast cancer receiving TC. We retrospectively evaluated the effect of G-CSF as secondary prophylaxis. The frequency of FN was calculated based on the treatment cycles to adjust for differences in the number of cycles per case and FN occurrence. RESULTS: FN occurred in 58 cycles (21.3%). The incidence of FN with and without secondary prophylactic G-CSF was 10.1% and 25.9%, respectively (p=0.003). Multivariate analysis showed secondary prophylactic G-CSF administration to be an independent predictor of FN incidence [odds ratio (OR)=0.33, 95% confidence interval (CI)=0.14-0.74, p=0.007]. CONCLUSION: Secondary prophylaxis with G-CSF is recommended for patients with breast cancer undergoing TC chemotherapy to reduce the incidence of FN.

Falciform ligament abscess with disseminated intrahepatic foci: a case report.

BACKGROUND: Falciform ligament abscess (FLA) is a rare disease, and its diagnosis can be challenging without typical image findings of an abscess. We report a patient with FLA that presented as a mass, with an indistinct border between it and the liver, in addition to disseminated foci within the liver. This made it difficult to determine whether it was FLA or a malignancy. CASE PRESENTATION: A 69-year-old man presented with epigastric pain. Contrast-enhanced computed tomography revealed a 25-mm mass below the middle of the diaphragm. Based on an initial diagnosis of infection of the falciform ligament, we administered conservative antibiotic treatment and there was initial improvement in the patient's clinical condition and laboratory data. However, he continued to experience mild epigastric pain. A month later, imaging studies revealed enlargement of the falciform ligament mass and the emergence of a new nodule in the liver, whereas laboratory findings showed re-elevated C-reactive protein levels. Since conservative treatment had failed, we decided to perform surgery. Considering the imaging study findings, malignant disease could not be ruled out. Based on the operative findings, we performed combined resection of the falciform ligament, left liver, and gallbladder. Histopathological examination of the resected specimens revealed extensive neutrophil infiltration and the presence of giant cells and foam cells within the lesions. These findings were indicative of abscess. Pseudomonas aeruginosa was cultured from the pus in the falciform ligament mass and bile in the gallbladder. Although multiple abscesses postoperatively developed in the residual portion of the liver, they could be treated through antibiotic therapy. CONCLUSIONS: FLA can spread to both adjacent and distant organs via its rich vascular and lymphatic networks. When FLA displays atypical image findings and/or an atypical clinical course, it can be difficult to distinguish it from malignant disease. In such cases, surgical treatment, with intraoperative pathological diagnosis, should be attempted.

Efficacy of chemotherapy and palliative hypofractionated radiotherapy for cats with nasal lymphoma.

Nasal lymphoma (NL) is the most common nasal tumor in cats, and radiotherapy, chemotherapy, or a combination of these treatments have been described as the treatment for this disease. However, the previous studies included various machines and protocols of radiotherapy. Therefore, we aimed to retrospectively compare the prognosis among cases treated with palliative hypofractionated radiotherapy, chemotherapy, and a combination of them with united machine and protocol of radiotherapy. When compared overall survival and progression free survival, there was no significant difference among these three groups. The data of this study suggested that similar efficacy could be achieved by palliative hypofractionated radiotherapy, chemotherapy, or a combination of them.

Downregulation of sphingosine-1-phosphate receptors in bronchial smooth muscle of mouse experimental asthma.

To determine whether or not sphingosine-1-phosphate (S1P) is involved in the augmented bronchial smooth muscle (BSM) contractility, one of the causes of airway hyperresponsiveness in asthmatics, the effects of S1P on BSM tone were investigated in control and repeatedly antigen-challenged mice. Both in the control and antigen-challenged animals, S1P had no effect on basal tone of the isolated BSM tissues. However, in the BSMs pre-depolarized by 60mM K(+), S1P caused a significant increase in tension in the control mice. The S1P-mediated contraction was abolished by JTE-013, a selective S1P receptor 2 (S1PR2) antagonist, but not by W123, a selective S1PR1 antagonist, and BML-241, a selective S1PR3 antagonist. The S1P-mediated contraction observed in BSMs of the control mice was also inhibited by Y-27632, a Rho-kinase inhibitor, suggesting that the contraction is mediated via activations of S1PR2 and probably its downstream Rho-kinase. On the other hand, interestingly, the S1P-mediated contraction was not observed at all in BSMs of the repeatedly antigen-challenged mice. A marked and significant downregulation of mRNA for S1PR2 was also observed in BSM tissues of the diseased animals. In conclusion, S1P could augment the BSM contraction via activations of its JTE-013-sensitive receptor, probably S1PR2, and the RhoA/Rho-kinase signaling in normal mice. In BSMs of the repeatedly antigen-challenged mice, the expression level of S1PR2 was much decreased, resulting in a loss of the S1P-mediated contraction.

Histamine stimulates interleukin-6 production through histamine H1 receptors in human amnion cells.

BACKGROUND/AIMS: Previous studies have stated that maternal allergic diseases are associated with increased risk of preterm labor/delivery, but the underlying mechanisms remain unclear. This study tested the hypothesis that histamine induces interleukin (IL)-6 production in amnion cells. METHODS: Using cultured human amnion cells, we examined expression of histamine receptors and effects of histamine on IL-6 production. RESULTS: Reverse transcription-polymerase chain reaction and Western blotting revealed expression of histamine H1 receptor (H1R) and H2 receptor (H2R) in human amnion. Histamine stimulation significantly increased concentrations of IL-6 in conditioned medium, as did tumor necrosis factor-alpha and IL-1beta in positive controls. In addition, the H1R antagonist olopatadine significantly blocked histamine-induced production of IL-6, whereas the H2R antagonist ranitidine did not. CONCLUSION: Histamine appears to induce IL-6 production through H1R in human amnion cells.

Assessment of objective ocular cyclodeviation under monocular condition and binocular condition using fundus photography.

OBJECTIVE: The relationship between retinal structure and function of glaucomatous eyes has attracted a great deal of research attention. However, visual field tests are conducted under monocular condition, and ophthalmic imaging was performed in patients without occlusion. We aimed to assess the objective ocular cyclodeviation between monocular occlusion and binocular conditions using fundus photography. METHODS AND ANALYSIS: This study included 76 healthy participants. We obtained six photos of the right eye of each patient using fundus photography. Three of the photographs were taken under monocular conditions, and the other three, under binocular conditions. We measured the optic disc margin-fovea angle (MFA) of the line connecting one point of the disc limbus and the fovea. One-way repeated analysis of variance was used to compare the angles under both conditions. We also examined the direction of ocular rotation under the binocular condition regarding the monocular condition. RESULTS: The MFAs were 12.12°±3.83° and 12.19°±3.95° under the monocular and binocular conditions, respectively. There was no significant difference in both MFAs (F=1.19, p=0.28). The mean cyclodeviation was 0.07°±0.80° (range: -2.40° to +2.75°). A total of 38 eyes showed excycloduction, while another 38 showed incycloduction. CONCLUSION: Significant cyclodeviation did not occur regardless of the existence of an occlusion. When examining the relationship between retinal structure and function, the difference in rotation angle under both conditions need not be taken into consideration if the other disease did not cause pathological cyclodeviation.

Concurrent onset of acute lupus myocarditis, pulmonary arterial hypertension and digital gangrene in a lupus patient: a possible role of vasculitis to the rare disorders.

Acute lupus myocarditis and pulmonary arterial hypertension (PAH) are rare complications associated with systemic lupus erythematosus (SLE). No previous reports have shown the coexistence of these disorders. Here we present a 41-year-old patient with SLE who concurrently developed severe acute lupus myocarditis and PAH with digital gangrene as an initial manifestation. Acute lupus myocarditis and PAH were successfully treated with prednisolone and intravenous cyclophosphamide pulse therapy (600-700 mg × 6) along with anticoagulant therapy. Catheter-directed thrombolysis was required for digital gangrene caused by vasculitis. Concurrent development of these rare disorders may represent a common mechanism such vasculitis as an underlining cause of SLE.

Polar recruitment of RLD by LAZY1-like protein during gravity signaling in root branch angle control.

In many plant species, roots maintain specific growth angles relative to the direction of gravity, known as gravitropic set point angles (GSAs). These contribute to the efficient acquisition of water and nutrients. AtLAZY1/LAZY1-LIKE (LZY) genes are involved in GSA control by regulating auxin flow toward the direction of gravity in Arabidopsis. Here, we demonstrate that RCC1-like domain (RLD) proteins, identified as LZY interactors, are essential regulators of polar auxin transport. We show that interaction of the CCL domain of LZY with the BRX domain of RLD is important for the recruitment of RLD from the cytoplasm to the plasma membrane by LZY. A structural analysis reveals the mode of the interaction as an intermolecular ß-sheet in addition to the structure of the BRX domain. Our results offer a molecular framework in which gravity signal first emerges as polarized LZY3 localization in gravity-sensing cells, followed by polar RLD1 localization and PIN3 relocalization to modulate auxin flow.

Anti-IL-10 antibody in systemic lupus erythematosus.

PURPOSE: IL-10 is a cytokine known to inhibit inflammatory cytokines. To determine its role in the pathogenesis of systemic lupus erythematosus (SLE), the presence of anti-IL-10 antibody is required to be examined. Although antibodies against cytokines are known to be present in SLE, no studies have determined the role of IL-10, particularly in Japanese patients. We assayed anti-IL-10 antibody in SLE and examined the clinical significance. PATIENTS AND METHODS: We performed a retrospective study of 80 Japanese patients with SLE. Sixteen scleroderma patients, 19 rheumatoid arthritis (RA) patients, 23 Behcet's disease patients, and 23 healthy subjects were selected as control groups. Clinical information was abstracted from medical records. Anti-IL-10 antibody level was determined with an ELISA. RESULTS: With the cutoff established as serum absorbance +2 SDs (OD 0.729) in healthy subjects, we defined any sample above this cutoff as anti-IL-10 antibody-positive. Fourteen patients with SLE (17.5%) were found to be anti-IL-10 antibody positive. Absorbance was significantly higher in serum from patients with SLE and RA than in healthy individuals. In SLE, patients with low complement values were significantly more common in the antibody-positive group. Serum IgG levels were significantly higher in the antibody-positive group. In multivariable analysis, high level of serum IgG is associated with anti-IL-10 antibody positive. CONCLUSION: The present study found that anti-IL-10 antibody is present in SLE and related to clinical parameters. These results suggest that the presence of anti-IL-10 antibody was associated with high level of serum IgG, but is not associated with disease activity in patients with SLE.

Application of gas chromatography-surface ionization organic mass spectrometry to forensic toxicology.

Surface ionization (SI), which consists in the formation of positive and negative ions along the course of thermal desorption of particles from a solid surface, was first applied as a detector for gas chromatography (GC), GC-surface ionization detection (SID); we developed many new sensitive methods for the determination of abused and other drugs by GC-SID. Recently, Fujii has devised a combination of SI and a quadrupole mass spectrometer and named this system a surface ionization organic mass spectrometer (SIOMS), which is highly selective and sensitive for organic compounds containing tertiary amino groups. We have tried to apply this mass spectrometer to forensic toxicological study; so far we have succeeded in determining important drugs-of-abuse and toxic compounds, such as phencyclidine (PCP), pethidine, pentazocine, MPTP and its derivatives from human body fluids with high sensitivity and selectivity. In this review, we describe our recent studies on the application of GC-SIOMS to forensic toxicology.

Sensitive determination of pethidine in body fluids by gas chromatography-tandem mass spectrometry.

We have presented a simple and sensitive method for determining pethidine, a narcotic analgesic drug in body fluids by gas chromatography-tandem mass spectrometry (GC-MS/MS). Pethidine and 4'-piperidinoacetophenone (internal standard) were extracted from body fluids with Bond Elut C(18) columns; the recoveries were above 85% for both compounds. The calibration curves for blood and urine showed good linearities in the range of 1.25-40 ng/ml. Its detection limits (signal-to-noise ratio=3) were estimated to be approximately 0.5 ng/ml of whole blood and urine.

The restriction of all minerals in the diet enhancing paraquat toxicity is regarded primarily as the shortage of Mg.

This study compares the effect of the restriction of Mg with that of all-minerals in the diet on the toxicity of paraquat. To compare the severity of the toxicity, several biological values were examined; kininogen in plasma, thiobarbituric acid reactive substances in liver, Ca level in kidney, and Mg levels in liver and kidney. Osteogenic disorder Shionogi rats that cannot synthesize vitamin C like humans did not display paraquat symptoms after receiving minute amounts of paraquat dichloride, i.e. 125 ppm in the diet for 8 days, and those biological values remained the same as those of the control. Rats fed with Mg at half of the recommended amounts also did not show any changes in those levels. The dosage of 125 ppm paraquat under the restriction of Mg, however, induced paraquat intoxication and increased those levels greatly. This result arises a question whether the intoxication is due to the imbalance of Ca and Mg or due to the shortage of Mg itself, because imbalance of Ca and Mg sometimes induces more serious effects than the shortage of Mg itself. Therefore, we fed rats an all-mineral restricted diet where the balance of Ca and Mg was maintained. The dosage of paraquat under all-mineral restriction, however, induced much more serious intoxication than that under Mg restriction. In conclusion, the shortage of Mg itself seems to be responsible for the induction of paraquat intoxication.