Association between preoperative phase angle and all-cause mortality after cardiovascular surgery: A retrospective cohort study.

BACKGROUND: The importance of preoperative physical function assessment for post-operative intervention has been reported in older patients undergoing cardiovascular surgery. Phase angle (PhA), measured using bioelectrical impedance analysis, is an indicator of cellular health and integrity and is reported as a prognostic factor in several chronic diseases; however, its association with the long-term prognosis of cardiovascular surgery remains unclear. This study aimed to investigate the prognostic value of PhA for long-term mortality in patients undergoing cardiovascular surgery. METHODS: This retrospective cohort study included consecutive patients who underwent elective cardiovascular surgery between October 2016 and March 2021 at Nagoya Heart Center, Japan. PhA was assessed using bioelectrical impedance analysis before surgery, and physical function measures (gait speed, grip strength and short physical performance battery [SPPB]) were measured synchronously. The association between PhA and all-cause mortality after discharge was assessed using Kaplan-Meier and multivariate Cox regression analyses. The incremental prognostic value of PhA was compared with other physical function measures using net reclassification improvement (NRI) and integrated discrimination improvement (IDI). RESULTS: A total of 858 patients were included in the present analysis (mean age = 68.4 ± 11.9 years, 67.6% male). PhA positively correlated with body mass index (ρ = 0.38, P < 0.001), skeletal muscle mass index (ρ = 0.58, P < 0.001), usual gait speed (ρ = 0.44, P < 0.001), grip strength (ρ = 0.73, P < 0.001) and SPPB (ρ = 0.51, P < 0.001). The mean follow-up period, within which 44 (4.7%) died, was 908.9 ± 499.9 days for the entire cohort. Kaplan-Meier survival curves based on the PhA tertiles showed that higher PhA was associated with better survival (log-rank test, P < 0.001). The Cox regression analysis showed the independent association of PhA with mortality risk (hazard ratio: 0.91 per 0.1° increment; 95% confidence interval [CI]: 0.87-0.95; P < 0.001). The NRI and IDI showed significant improvements in predicting mortality after adding PhA to the clinical model consisting of age, sex and cardiac and renal function (NRI: 0.426, 95% CI: 0.124-0.729, P = 0.006; IDI: 0.037, 95% CI: 0.012-0.062, P = 0.003). The predictive model consisting of the clinical model and PhA was superior to the model consisting of the clinical model and each of the other physical function indicators (P < 0.05). CONCLUSIONS: PhA correlated with physical function and independently predicted long-term mortality after cardiovascular surgery. The additive prognostic value of PhA compared with the other physical function measures suggests the clinical usefulness of preoperative PhA for risk stratification in planning post-operative treatment and rehabilitation.

The Japanese Breast Cancer Society clinical practice guidelines for epidemiology and prevention of breast cancer, 2022 edition.

The Japanese Breast Cancer Society Clinical Practice Guidelines for Epidemiology and Prevention of Breast Cancer, 2022 Edition.

Association between outpatient cardiac rehabilitation and all-cause mortality after cardiovascular surgery: A propensity score-matched analysis.

Objectives: Cardiac rehabilitation (CR) is a class I recommendation in the treatment guidelines for cardiovascular disease; however, its postoperative prognostic effects after surgery are not fully understood. Therefore, this study aimed to examine the effect of multidisciplinary outpatient CR on postdischarge all-cause mortality in patients who underwent cardiovascular surgery. Methods: This retrospective cohort study included consecutive patients who underwent elective cardiovascular surgery between April 2015 and March 2021. Patients were categorized into CR and non-CR groups. The primary outcome measure was all-cause mortality. Propensity score-matching analysis was performed to minimize selection bias and differences in clinical characteristics. The propensity score for each patient was produced using logistic regression analysis, with the CR group and the subsequent 27 variables as the dependent and independent variables, respectively. Results: In our cohort (n = 1095), 51 patients (4.7%) died during the follow-up period (mean, 1042 days). The CR group had a significantly lower mortality rate than the non-CR group (hazard ratio, 0.45; 95% CI, 0.21-0.95; P = .036). After propensity score matching adjusted for confounders, the association between CR and reduced risk of all-cause mortality remained (hazard ratio, 0.35; 95% CI, 0.14-0.85; P = .02). Conclusions: Postdischarge multidisciplinary outpatient CR in patients who underwent cardiovascular surgery was associated with a substantial survival benefit, which persisted after adjusting for variables, including age, operative factors, physical and cognitive functions, and nutritional status.

Metabolic Oscillations and Glycolytic Phenotypes of Cancer Cells.

Cancer cells show several metabolic phenotypes depending on the cancer types and the microenvironments in tumor tissues. The glycolytic phenotype is one of the hallmarks of cancer cells and is considered to be one of the crucial features of malignant cancers. Here, we show glycolytic oscillations in the concentrations of metabolites in the glycolytic pathway in two types of cancer cells, HeLa cervical cancer cells and DU145 prostate cancer cells, and in two types of cellular morphologies, spheroids and monolayers. Autofluorescence from nicotinamide adenine dinucleotide (NADH) in cells was used for monitoring the glycolytic oscillations at the single-cell level. The frequencies of NADH oscillations were different among the cellular types and morphologies, indicating that more glycolytic cancer cells tended to exhibit oscillations with higher frequencies than less glycolytic cells. A mathematical model for glycolytic oscillations in cancer cells reproduced the experimental results quantitatively, confirming that the higher frequencies of oscillations were due to the higher activities of glycolytic enzymes. Thus, glycolytic oscillations are expected as a medical indicator to evaluate the malignancy of cancer cells with glycolytic phenotypes.

Glycolytic oscillations in HeLa cervical cancer cell spheroids.

Previous studies have unravelled glycolytic oscillations in cancer cells, such as HeLa cervical and DU145 prostate cancer cells, using a monolayer culture system. Here, we demonstrate glycolytic oscillations in HeLa cervical cancer cell spheroids. Experiments revealed that a small number of HeLa cells in spheroids exhibited heterogeneous oscillations with a higher frequency than those in monolayers. Model analyses and our previous experiments indicated that the higher frequencies of oscillations in spheroids were mostly due to the increase in glycolytic enzyme activity in the cells, and to the decrease in glucose concentration by diffusional transport of glucose from the surface to inside the spheroids, as well as the increase in cell density through spheroid formation. These results and our previous studies imply that more malignant cancer cells tend to exhibit glycolytic oscillations with higher frequencies than less malignant cells. Adjacent cells in spheroids oscillated within a 10% difference in frequency, but did not synchronize with each other. This suggests that weak cell-to-cell interactions might exist among HeLa cells connected with cadherins in the spheroid microenvironment; however, the interactions were not strong enough to induce synchronization of glycolytic oscillations.

Methotrexate-induced Transient Encephalopathy in an Adolescent and Young Adult Patient with Acute Lymphoblastic Leukemia.

A 17-year-old girl was diagnosed with acute lymphoblastic leukemia (ALL). After the administration of high-dose methotrexate (MTX) or intrathecal MTX, the patient experienced transient hemiparesis and motor aphasia. Diffusion-weighted magnetic resonance imaging showed a high-intensity lesion in the bilateral centrum semiovale, and a vasospasm was detected in the proximal segment of bilateral A1 on magnetic resonance angiography. Edaravone was administered, and leucovorin rescue treatment was continued; eventually, the patient's neurological symptoms completely resolved. This finding suggested that vasospasm might be a mechanism underlying MTX-induced transient encephalopathy in adolescent and young adult patients with ALL.

Smoking status and unruptured intracranial aneurysm among brain health check-up examinees: a cross-sectional study in Japan.

Objective: Although it is well known that smoking is a risk factor for subarachnoid hemorrhage, the association between smoking and unruptured intracranial aneurysms remains unclear. The aim of the present study was to investigate whether smoking status was associated with unruptured intracranial aneurysms among Japanese brain health check-up examinees. Materials and Methods: We conducted a cross-sectional study of 1,496 adults (aged 26-90 years) undergoing brain health check-ups at a single community medical support hospital in Akita, Japan between 2009 and 2013. In Japan, people can discretionarily undergo a brain health check-up for early detection of unruptured intracranial aneurysms or subarachnoid hemorrhages. Participants responded to a questionnaire on lifestyle, such as smoking status, and were classified into three groups: never, former, and current smoker. The evaluation of unruptured intracranial aneurysms detected by magnetic resonance angiography was performed by an expert physician. Multiple logistic regression models were used to estimate the odds ratio for unruptured intracranial aneurysms. We performed statistical analyses by age, sex, and family history of stroke. Results: The number of participants with unruptured intracranial aneurysms was 43 (2.9%). The mean age (standard deviation) and proportion of males was 55.8 (9.5) years and 53.3%, respectively. The adjusted odds ratios (95% confidence intervals) for unruptured intracranial aneurysms of 1.21 (0.48-3.08) among former smokers and 2.88 (1.10-7.50) among current smokers were compared to those of never smokers (p-trend = 0.041). After stratifying by age, sex, and family history of stroke, no interactions were found. Conclusion: This cross-sectional study conducted in Japan showed that smoking was positively associated with unruptured intracranial aneurysms among brain health check-up examinees.

Diagnostic utility of CD205 in breast cancer: Simultaneous detection of myoepithelial cells and dendritic cells in breast tissue by CD205.

BACKGROUND: CD205 can be used to detect myoepithelial cells (MECs) and dendritic cells (DCs) in breast tissue. However, the usefulness of CD205 immunostaining in the pathological diagnosis of breast tumors is not fully understood. The objective of this study was to re-evaluate CD205 co-expression with other MEC markers, such as p63 and CD10, in nonneoplastic and neoplastic breast tissue and to evaluate its pathological diagnostic utility in these types of breast cancer. MATERIAL AND METHODS: Nonneoplastic breast tissue samples with a terminal duct lobular unit and duct were obtained from fibroadenoma and mastopathy patients. Neoplastic breast tissue samples included ductal carcinoma in situ (DCIS) (n=43) and invasive ductal carcinoma (IDC) (n=60), including the tubule-forming type (n=20). These specimens were investigated by CD205, p63, and CD10 immunostaining. RESULTS: In addition to p63 and CD10, CD205 was expressed on MECs in nonneoplastic breast and DCIS tissue samples; CD205 was simultaneously detected on DCs that had infiltrated DCIS and IDC tumor nests. CD205 was expressed on cancer cells themselves in only 7.3% of the breast cancer samples. The number of intratumoral CD205⁺ DCs in tubular IDC was significantly higher than that in DCIS (P<0.01). CONCLUSION: Because CD205 was simultaneously detected on MECs and DCs in the same breast tissue sections, it may be useful for distinguishing tubular IDC from DCIS.

Endovascular Stenting Following Stereotactic Radiosurgery for Meningioma Involving the Superior Sagittal Sinus.

Objective: Surgical removal of meningiomas that have partially invaded the superior sagittal sinus (SSS) is difficult because it requires reconstruction of the SSS, which can lead to SSS occlusion and venous infarction. The present report details the case of an SSS-involved meningioma treated by stereotactic radiosurgery (SRS) and stenting. Case Presentation: A 60-year-old woman was admitted to the hospital with blurred vision and papilledema. Lumbar puncture showed markedly increased intracranial pressure (ICP; 340 mm H2O). Gadolinium-enhanced T1-weighted imaging revealed a 1-cm meningioma located mainly in the SSS. Digital subtraction angiography revealed severe stenosis, at the posterior part of the SSS, and no collateral flow. The ICP was considered a result of the stenosis caused by the meningioma. A combined therapy comprising transarterial embolization (for tumor growth suppression), endovascular stenting of the SSS (for intracranial hypertension improvement), and SRS (for tumor control) was planned. SRS was performed first to avoid interference by the metal artifacts caused by the stent. After placement of a self-expanding stent, partial recanalization was achieved. Two months after stenting, SSS stenosis improved and MRI results showed shrinkage of the meningioma. Thirty months after the treatment, no tumor recurrence was observed. Conclusion: The treatment strategy of SRS followed by stenting was successful for a SSS-involved meningioma. ICP and a pressure gradient between the pre- and post-stenotic segments should be considered indications for stenting.

[A case of possible elderly onset rheumatoid meningitis without arthritis].

A 93-year-old man was admitted to our hospital with disturbance of consciousness. Brain magnetic resonance imaging (MRI) showed hyperintensity of the subarachnoid space in the left frontal and parietal lobes on diffusion weighted imaging (DWI) and fluid attenuated inversion recovery (FLAIR). Gadolinium-enhancement of the pia mater was also observed. We did not perform biopsy because of a high risk of perioperative complication. Although physical examination found no evidence of the rheumatoid arthritis, rheumatoid factors and anti-cyclic citrullinated peptides antibodies were elevated. He was suspected to have rheumatoid meningitis. We treated him with intravenous methylprednisolone (0.5 g/day) for 3 days. Rheumatoid meningitis often shows hyperintensity of the subarachnoid space on the DWI and FLAIR, and steroid therapy is effective.

Modeling studies of heterogeneities in glycolytic oscillations in HeLa cervical cancer cells.

Previous experiments demonstrated that a population of HeLa cells starved of glucose or both glucose and serum exhibited a strong heterogeneity in the glycolytic oscillations in terms of the number of oscillatory cells, periods of oscillations, and duration of oscillations. Here, we report numerical simulations of this heterogeneous oscillatory behavior in HeLa cells by using a newly developed mathematical model. It is simple enough that we can apply a mathematical analysis, but capture the core of the glycolytic pathway and the activity of the glucose transporter (GLUT). Lognormal distributions of the values of the four rate constants in the model were obtained from the experimental distributions in the periods of oscillations. Thus, the heterogeneity in the periods of oscillations can be attributed to the difference in the rate constants of the enzymatic reactions. The activity of GLUT is found to determine whether the HeLa cells were oscillatory or non-oscillatory under the same experimental conditions. Simulation with the log-normal distribution of the maximum uptake velocity of glucose and the four randomized rate constants based on the log-normal distributions successfully reproduced the time-dependent number of oscillatory cells (oscillatory ratios) under the two starving conditions. The difference in the initial values of the metabolites has little effect on the simulated results.

Differential expression of estrogen receptor-α on follicular dendritic cells from patients with grade 1-2 and grade 3 follicular lymphoma.

Hormone therapy has been used for patients with estrogen receptor alpha (ERα)-positive breast cancers. Recently, some studies reported the expression of ERα on neoplastic cells from B-cell lymphomas. However, there has been only one report of ERα expression on the follicular dendritic cells (FDCs) that structurally and functionally support the microenvironment of follicular lymphomas (FLs). The objective of this study was to investigate the frequency of ERα expression on FDCs in nonneoplastic reactive lymphoid tissues and to compare the frequency of ERα expression on FDCs in the axillary lymph nodes between patients with and without antiestrogen therapy and among patients with grades 1-3 of FL. Reverse transcription-polymerase chain reaction was performed to detect ERα mRNA in FL. In nonneoplastic germinal centers (GCs) from patients with tonsillitis or reactive lymphadenitis, ERα was expressed in the light zone. ERα-positive cells strongly correlated with the width of GCs (rs  = 0.81, P < 0.01) and the CD21-positive (rs  = 0.69, P < 0.01) and CD23-positive (rs  = 0.83, P < 0.01) FDC meshwork. The axillary lymph nodes had fewer ERα-positive cells, smaller GCs, and a looser CD21- and CD23-positive FDC meshwork with hormone therapy than without hormone therapy (P < 0.01). Neoplastic follicles of G1-2 FL had more ERα-positive cells and a larger CD23+ FDC meshwork than those of G3 FL (P < 0.01). ERα mRNA was detected in both G1-2 FL and G3 FL by reverse transcription-polymerase chain reaction. In conclusion, these results suggested that antiestrogen hormone therapy may decrease the number of ERα-positive FDCs and that the responses mediated by the estrogen-ERα interaction on FDCs may differ between G1-2 FL and G3 FL.

Effect of Perioperative Neuromuscular Electrical Stimulation in Patients Undergoing Cardiovascular Surgery: A Pilot Randomized Controlled Trial.

A randomized, controlled trial was conducted to examine the effects of perioperative neuromuscular electrical stimulation on muscle proteolysis and physical function using blinded assessment of physical function. Consecutive patients undergoing cardiovascular surgery were screened for eligibility as study subjects. Participants were randomly assigned to receive either neuromuscular electrical stimulation or the usual postoperative mobilization program. The intervention group received neuromuscular electrical stimulation on bilateral legs 8 times before and after surgery. The primary outcomes were the mean 3-methylhistidine concentration corrected for urinary creatinine content from baseline to postoperative day 6, and knee extensor isometric muscle strength on postoperative day 7. Secondary outcomes were usual walking speed and grip strength. Physical therapists blinded to patient allocation performed measurements of physical function. Of 498 consecutive patients screened for eligibility, 119 participants (intervention group, n = 60; control group, n = 59) were enrolled. In the overall subjects, there were no differences in any outcomes between the intervention and control groups. The results demonstrated no significant effects of neuromuscular electrical stimulation on muscle proteolysis and physical function after cardiovascular surgery, suggesting the need to explore indications for neuromuscular electrical stimulation and to clarify the effects in terms of the dose-response relationship.

Gigantic mammary Paget's disease of a very elderly woman.

BACKGROUND: Recently, surgical stress due to breast cancer has been reduced, more so for elderly patients. However, an expanded resection is still required in some situations. CASE PRESENTATION: We present a case of a 90-year-old woman with a 15 × 15 cm2 erythema and localized skin ulceration with hemorrhage in her right breast. A punch biopsy indicated mammary Paget's disease. Computed tomography showed that the tumor was only located on the surface of the breast with no metastasis, including of the axillar lymph nodes. We decided to perform surgery with sufficient informed consent. We performed muscle-sparing mastectomy with sampling of an axillar lymph node, adding two stress-relaxation sutures to avoid diastasis. The patient's postoperative course was good. A histological examination revealed mammary Paget's disease without invasion and no evidence of a residual tumor of the entire stumps. Her quality of life was improved after surgery. CONCLUSION: Mammary Paget's disease has a relatively good prognosis. However, advanced mammary Paget's disease leads to a decrease of quality of life with symptoms such as skin ulcer and bleeding. Surgery should be performed in such cases, considering the risks and benefits, even in older patients with comorbidities.

Primordial oscillations in life: Direct observation of glycolytic oscillations in individual HeLa cervical cancer cells.

We report the first direct observation of glycolytic oscillations in HeLa cervical cancer cells, which we regard as primordial oscillations preserved in living cells. HeLa cells starved of glucose or both glucose and serum exhibited glycolytic oscillations in nicotinamide adenine dinucleotide (NADH), exhibiting asynchronous intercellular behaviors. Also found were spatially homogeneous and inhomogeneous intracellular NADH oscillations in the individual cells. Our results demonstrate that starved HeLa cells may be induced to exhibit glycolytic oscillations by either high-uptake of glucose or the enhancement of a glycolytic pathway (Crabtree effect or the Warburg effect), or both. Their asynchronous collective behaviors in the oscillations were probably due to a weak intercellular coupling. Elucidation of the relationship between the mechanism of glycolytic dynamics in cancer cells and their pathophysiological characteristics remains a challenge in future.

[A patient with advanced breast cancer who developed bacterial meningitis after chemotherapy].

A 76-year-old woman was admitted to our hospital because of a right breast tumor and a skin ulcer. The patient was diagnosed as having advanced breast cancer T4bN2M1(lung), Stage IV. A regimen of 5-fluorouracil(500mg/m2)with epirubicin(100mg/m / 2)and cyclophosphamide(500mg/m2)(FEC100)was administered. However, the patient was hospitalized 12 days later because of febrile neutropenia. The patient experienced a stiff neck the next day, and bacterial meningitis was diagnosed on the basis of cerebrospinal fluid examination. Antibacterial agents were administered according to the clinical practice guidelines of bacterial meningitis. The patient recovered and was discharged from our hospital 24 days after admission. Bacterial meningitis after chemotherapy is rare, but this could be progress to a serious condition. Early diagnosis and treatment are paramount in such cases.

[Successful treatment of a case of steroid-dependent neuro-Sweet disease with dapsone].

A 35-year-old Japanese man was admitted to our hospital with recurrent meningoencephalitis of unknown etiology. He presented with fever, convulsions and loss of consciousness, which started at age 33. We diagnosed him with neuro-Sweet disease (NSD) based on human leukocyte antigen (HLA) B-54/Cwl positivity and neutrophilic infiltration into the dermis in a biopsied skin plaque. Intravenous methylprednisolone and oral prednisolone markedly improved his fever and CSF pleocytosis. Five years later he was again admitted to our hospital with high fever, oral aphthae and dull-red edematous plaques on the face and body. He was conscious, but he had neck stiffness, mild hyperreflexia in all limbs and an extensor plantar response. Laboratory tests revealed increased white blood cell, erythrocyte sedimentation rate (ESR) and C-reactive protein level. CSF analysis indicated mild pleocytosis. A skin biopsy from an edematous plaque revealed neurotrophils infiltrating the upper dermis. We treated him with intravenous methylprednisolone (1 g/day) for 3 days, followed by oral prednisolone (50 mg/day). His symptoms improved remarkably; however, he had recurrence of symptoms, such as fever, meningial irritation and oral aphtae, with attempted taper of prednisolone. We started treatment with dapsone (75 mg/day) in addition to prednisolone, and could taper oral prednisolone, without a relapse. However, because some mildly recurred with the tapering of dapson, we maintained dapsone treatment at 75 mg daily, added colchicine (1 mg/ day) and tapered only prednisolone. His symptoms were improved and no relapse has been observed. NSD is characterized by neurotrophic hyperactivation and infiltration of tissues. It is highly responsive to systemic corticosteroid therapy; however, some cases show frequent recurrences on tapering of corticosteroids. Dapsone is considered to prevent neurotrophic overactivity. In this case, dapsone was supposed to be effective to prevent reccurence of NSD upon tappering corticosteroids. Dapsone should be a therapeutic options for steroid-dependent NSD showing frequent recurrence.

[Advanced gastric cancer showing complete response to neoadjuvant chemotherapy with CPT-11 and S-1-a case report].

We report a case of advanced gastric cancer that showed a complete histological response to neoadjuvant chemotherapy. The patient, a 56-year-old man, was diagnosed as having advanced gastric cancer with lymph node metastases( cT3 cN1 cH0 cP0 cM0, cStageIIIA). He was initially treated with combined neoadjuvant chemotherapy comprising CPT-11+S-1. S-1(120 mg/day)was administered orally for 21 days, followed by CPT-11(130 mg/body)divon days 1 and 15. The primary lesion and lymph node metastases were diminished by 2 courses of chemotherapy, and no serious toxicities were observed. Distal gastrectomy and lymph node dissection(D2)were performed. Only a small ulcer was observed on the resected stomach. Histological examination of the resected stomach and lymph nodes revealed no remaining viable cancer cells. The patient has been doing well without any recurrence for 1 year since the start of treatment.