Rare case of exostosin 1/exostosin 2-related membranous lupus nephritis concomitant with dual ANCA- and anti-GBM antibody-associated crescentic glomerulonephritis effectively diagnosed by mass spectrometry: a case report.

BACKGROUND: Recent developments in mass spectrometry (MS) have revealed target antigens for membranous nephropathy (MN), including phospholipase A2 receptor and exostosin 1/exostosin 2 (EXT1/2). EXT1/2 are known antigens of autoimmune disease-related MN, especially membranous lupus nephritis. We describe the case of an elderly man who developed nephrotic syndrome followed by progressive renal dysfunction. CASE PRESENTATION: A 78-year-old man presented with rapidly progressive renal dysfunction with proteinuria and hematuria. Three years previously, he had developed leg edema but did not receive any treatment. Laboratory tests showed elevated anti-nuclear antibody (Ab), anti-dsDNA Ab titer, and hypocomplementemia, indicating systemic lupus erythematous. Myeloperoxidase anti-neutrophil cytoplasmic Ab (ANCA) and anti-glomerular basement membrane (GBM) Ab were also detected. The renal pathologic findings were compatible with crescentic glomerulonephritis (GN), whereas non-crescentic glomeruli exhibited MN without remarkable endocapillary or mesangial proliferative change. Immunofluorescence microscopy revealed glomerular IgG, C3, and C1q deposition. All IgG subclasses were positive in glomeruli. Anti-PLA2R Ab in serum was negative. MS analysis was performed to detect the antigens of MN, and EXT1/2 was detected in glomeruli. Therefore, we reached a diagnosis of membranous lupus nephritis concurrent with both ANCA-associated vasculitis and anti-GBM-GN. The simultaneous occurrence of these three diseases is extremely rare. CONCLUSIONS: This is the first report of EXT1/2-related membranous lupus nephritis concurrent with ANCA-associated vasculitis and anti-GBM-GN. This case demonstrates the usefulness of MS in diagnosing complicated cases of MN.

Income and Employment of Patients at the Start of and During Follow-up After Palliative Radiation Therapy for Bone Metastasis.

Purpose: The aim of this study was to understand the income and employment status of patients at the start of and during follow-up after palliative radiation therapy for bone metastasis. Methods and Materials: From December 2020 to March 2021, a prospective multi-institutional observational study was conducted to investigate income and employment of patients at the start of administration of radiation therapy for bone metastasis and at 2 and 6 months after treatment. Of 333 patients referred to radiation therapy for bone metastasis, 101 were not registered, mainly because of their poor general condition, and another 8 were excluded from the follow-up analysis owing to ineligibility. Results: In 224 patients analyzed, 108 had retired for reasons unrelated to cancer, 43 had retired for reasons related to cancer, 31 were taking leave, and 2 had lost their jobs at the time of registration. The number of patients who were in the working group was 40 (30 with no change in income and 10 with decreased income) at registration, 35 at 2 months, and 24 at 6 months. Younger patients (P = 0), patients with better performance status (P = 0), patients who were ambulatory (P = .008), and patients with lower scores on a numerical rating scale of pain (P = 0) were significantly more likely to be in the working group at registration. There were 9 patients who experienced improvements in their working status or income at least once in the follow-up after radiation therapy. Conclusions: The majority of patients with bone metastasis were not working at the start of or after radiation therapy, but the number of patients who were working was not negligible. Radiation oncologists should be aware of the working status of patients and provide appropriate support for each patient. The benefit of radiation therapy to support patients continuing their work and returning to work should be investigated further in prospective studies.

Clinical Outcomes of Definitive Chemoradiotherapy for Cervical Esophageal Cancer.

BACKGROUND/AIM: To investigate the clinical outcomes of concurrent chemoradiotherapy (CCRT) in patients with cervical esophageal carcinoma and analyze the prognostic factors. PATIENTS AND METHODS: Thirty-nine patients with cervical esophageal carcinoma were retrospectively identified among consecutive patients who received CCRT between November 2009 and September 2019 at our institution. The patients were treated by intensity-modulated radiation therapy (N=13) or three-dimensional conformal radiotherapy (N=26). RESULTS: The median follow-up period was 35 months (range=2-158 months). There were 32 men and 7 women with a median age of 66 years (range=50-83 years). Clinical stages were I in 6 patients, II in 4, III in 19, and IV in 10. Hypopharyngeal invasion was noted in 8 patients. The initial treatment responses were evaluated 3-6 weeks after the final session of CCRT: a complete response (CR) in 24 patients, a partial response (PR) in 13, and stable disease (SD) in 2. Two- and 5-year overall survival (OS) rates were 73.8 and 59.4%, respectively. Two- and 5-year progression-free survival (PFS) rates were 57.8 and 48.0%, respectively. A univariate analysis identified the initial treatment response (CR or non-CR) as a significant factor for OS (p=0.0002) and PFS (p=0.0026). The CR rate was 81.0% in patients with T1-3 and 33.3% in those with T4 (p=0.0038). CONCLUSION: Patients with cervical esophageal carcinoma in Nagasaki University Hospital in Japan achieved superior outcomes compared with previous studies. CR rate was higher in patients with T1-3 and correlated with better OS.

Long-term Outcomes and Prognostic Factors of Stereotactic Body Radiotherapy for Hepatocellular Carcinoma.

BACKGROUND/AIM: This study was conducted to determine the prognosis and risk factors for survival in patients treated with stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC). PATIENTS AND METHODS: This retrospective study analyzed 73 patients who underwent SBRT for HCC at Nagasaki University Hospital from December 2012 to July 2019 and examined the relationship between baseline information and prognosis. The Kaplan-Meier analysis and log-rank test were used to estimate the survival rate. Cox regression analysis was performed to determine the factors associated with overall survival (OS) after SBRT. RESULTS: The 1- and 2-year local control rates were 98.6% and 89.9%, respectively. Survival rates at 1, 3, and 5 years were 94.5%, 63.9%, and 45.5%, respectively. In the univariate analysis, baseline modified albumin-bilirubin grade (mALBI grade) [2b/3, hazard ratio (HR)=2.762, p=0.001], tumor size (≥2 cm, HR=2.479, p=0.003), and Barcelona Clinic Liver Cancer stage (BCLC) (B/C, HR=3.284, p<0.001) were significantly associated with poor prognosis. In multivariate analysis, baseline mALBI grade (2b/3, HR=2.283, p=0.009) and BCLC stage (B/C, HR=2.330, p=0.013) were significantly associated with poor prognosis. Only three patients (4.1%) developed grade 3 adverse events related to SBRT. CONCLUSION: SBRT is effective and safe in patients with HCC. The baseline mALBI grade is useful for predicting patient prognosis after SBRT. Patients with an mALBI grade of 1/2a are expected to have a better prognosis than patients with an mALBI grade of 2b/3.

Phase I study of amrubicin plus cisplatin and concurrent accelerated hyperfractionated thoracic radiotherapy for limited-disease small cell lung cancer: protocol of ACIST study.

BACKGROUND: Etoposide plus cisplatin (EP) combined with concurrent accelerated hyperfractionated thoracic radiotherapy (AHTRT) is the standard treatment strategy for unresectable limited-disease (LD) small cell lung cancer (SCLC), which has remained unchanged for over two decades. Based on a previous study that confirmed the non-inferiority of amrubicin (AMR) plus cisplatin (AP) when compared with EP for extensive-disease (ED) SCLC, we have previously conducted a phase I study assessing AP with concurrent TRT (2 Gy/time, once daily, 50 Gy in total) for LD-SCLC therapy. Our findings revealed that AP with concurrent TRT could prolong overall survival to 39.5 months with manageable toxicities. Therefore, we plan to conduct a phase I study to investigate and determine the effect of AP combined with AHTRT, recommended dose (RD), maximum tolerated dose (MTD), and dose-limiting toxicity (DLT) of AP in patients with LD-SCLC. METHODS: Treatment-naive patients with LD-SCLC, age between 20 and 75 years, who had a performance status of 0 or 1 and adequate organ functions will be enrolled. For chemotherapy, cisplatin 60 mg/m2 /day (day 1) and AMR (day 1 to 3) will be administered with AHTRT (1.5 Gy/time, twice daily, 45 Gy in total). The initial AMR dose is set to 25 mg/m2 /day. RD and MTD will be determined by evaluating toxicities. DISCUSSION: Based on our previous study, the initial dose of AMR 25 mg/m2 is expected to be tolerated and acceptable. Here, we aim to determine whether treatment with AP and concurrent AHTRT would be an optimal choice with manageable toxicities for LD-SCLC.

Phase II study of S-1 plus cisplatin with concurrent radiotherapy for locally advanced thymic carcinoma: Results of the LOGIK1605/JART-1501 study.

BACKGROUND: Combination chemotherapy is used to treat advanced thymic carcinoma; however, the effects are insufficient. METHODS: Previously untreated patients with unresectable locally advanced thymic carcinoma received two cycles of 80 mg/m2 /day S-1 orally on days 1-14 plus 60 mg/m2 /day cisplatin intravenously on day 1, and concurrent radiotherapy (60 Gy). RESULTS: Three patients were enrolled into the study. Toxicity and survival were assessable in all patients, but the treatment response was only assessable in one patient. The study was terminated because of poor case recruitment. The patients' characteristics were as follows: male/female = 2/1; PS 0/1 = 2/1; median age (range) = 59 (55-72); and stage III/IV = 2/1. The patient in which the treatment response was assessed exhibited SD (response rate: 0%). In both nonevaluable cases, the second course of chemotherapy was judged to be post-protocol treatment because it was delayed by ≥14 days, but a CR and PR were achieved after the end of the study, respectively. G4 leukopenia/neutropenia and G3 febrile neutropenia occurred in one patient each (33%). The median time to tumor progression was 17.6 months, and the 1-, 2-, 3-, and 4-year survival rates were 67, 33, 33, and 33%, respectively. The median overall survival time was not reached, and the 1-, 2-, 3-, and 4-year survival rates were 100, 67, 67, and 67%, respectively. CONCLUSIONS: Although it was difficult to recruit patients, there was a long-term survivor >4 years who appeared to have achieved a CR, indicating that such chemoradiotherapy may be effective against locally advanced thymic carcinoma.

Long-term clinical course of immunotactoid glomerulopathy complicated with diffuse large B-cell lymphoma.

We report a case of immunotactoid glomerulopathy (ITG) complicated with diffuse large B-cell lymphoma (DLBCL). A 68-year-old woman presented with leg edema and was diagnosed with nephrotic syndrome (NS). Renal biopsy revealed ITG. We treated the patient with prednisolone (20 mg/day) and she achieved complete remission of NS. Steroids were gradually reduced. After 1 year, the patient presented with a breast mass determined on biopsy to be DLBCL. She underwent six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) therapy. Follow-up revealed complete remission of both DLBCL and ITG. NS recurred after 5 years and she was simultaneously diagnosed with recurrence of DLBCL in bone marrow. She underwent four cycles of R-EPOCH (rituximab, etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin) therapy and entered remission for DLBCL. NS improved, but the treatment did not lead to remission. After 2 additional years, NS and DLBCL recurred again. She was administered rituximab and NS improved, although proteinuria tended to increase thereafter. One year later, we started prednisolone (10 mg/day), and proteinuria tended to decrease. She is currently undergoing outpatient follow-up. This case suggests that ITG with MGUS should be treated with the possibility of developing malignant hematological disease during the course.

Initiation of peritoneal dialysis in a patient with chronic renal failure associated with tetralogy of Fallot: a case report.

BACKGROUND: Tetralogy of Fallot is the most common cyanotic congenital heart disease. Patients with the condition have a high risk of developing chronic kidney disease. Treatment of kidney disease in patients with complex hemodynamics presents unique challenges. However, there are very few reports on the treatment of end-stage renal failure in patients with tetralogy of Fallot. CASE PRESENTATION: We present a rare case of peritoneal dialysis in a 47-year-old man with tetralogy of Fallot who had not undergone intracardiac repair. Peritoneal dialysis successfully removed fluids and solutes without adversely affecting the patient's hemodynamics. Our patient was managed with peritoneal dialysis for 5 years before he succumbed to sepsis secondary to digestive tract perforation. CONCLUSIONS: In this paper, we discuss the importance of monitoring acid-base balance, changes in cyanosis, and hyperviscosity syndrome during peritoneal dialysis in patients with tetralogy of Fallot. Lower leg edema and B-type natriuretic peptide level were useful monitoring parameters in this case. This case illustrates that with attention to the patient's unique requirements, peritoneal dialysis can provide successful renal replacement therapy without compromising hemodynamics in patients with tetralogy of Fallot.

Surgery or stereotactic body radiotherapy for metachronous primary lung cancer? A propensity score matching analysis.

OBJECTIVE: We compared outcomes after surgery or stereotactic body radiotherapy (SBRT) among patients with metachronous primary lung cancer (MPLC). METHODS: Patients with MPLC were treated with either surgery (2008-2018) or SBRT (2010-2018). We used propensity score matching (PSM) to reduce bias from various clinicopathological factors. MPLC was defined by the Martini and Melamed criteria. RESULTS: Of 77 patients, 51 underwent surgery and 26 received SBRT. Most median clinicopathological characteristics did not significantly differ between the surgery and SBRT groups (male sex: 67% vs 65%; age: 73 vs 77 years; time after first surgery: 6.2 vs 4.7 years; lobectomy as first procedure: 82% vs 85%; second tumor size: 11 vs 12 mm; clinical stage I: 96% vs 100%; CEA: 2.9 vs 3.0 ng/ml). However, the surgery group had significantly more ipsilateral second tumors (n = 71, 58%, P = 0.003), better performance status (P = 0.03), and preserved lung function (P = 0.02). Surgery, thus, tended to be selected for patients with good physical function and for the MPLC in the contralateral side. Five-year overall survival did not significantly differ between the surgery and SBRT groups, either before PSM (86.5% vs 65.8%, P = 0.24, log-rank) or after PSM (100% vs 84.4%, P = 0.73). CONCLUSIONS: Surgery and SBRT for MPLC patients are safe and feasible treatments with similar outcomes. However, this finding should be verified by a random controlled trial with a larger study cohort.

S-1 plus cisplatin with concurrent radiotherapy for locally advanced thymic carcinoma: Study protocol of LOGIK1605/JART-1501.

Thymic carcinoma is a rare epithelial tumor of the thymus with a poor prognosis, and multimodal approaches are important for its treatment. Recently, a number of studies have indicated that S-1 treatment is effective against thymic carcinoma. S-1 plus cisplatin with concurrent radiotherapy is a commonly used treatment for other malignancies, including non-small cell lung cancer (NSCLC). In addition, its safety has been confirmed, and it has been reported to have a marked effect against thymic carcinoma. Therefore, we conducted a phase II study of S-1 plus cisplatin with concurrent thoracic radiotherapy for locally advanced thymic carcinoma, in which the overall response rate was employed as the primary endpoint. The secondary endpoints were overall survival, progression-free survival, and safety.

Dose escalation study of amrubicin and cisplatin with concurrent thoracic radiotherapy for limited-disease small cell lung cancer.

BACKGROUND: Amrubicin and cisplatin is one of the active regimens used to treat patients with extensive-disease (ED)-small cell lung cancer (SCLC), whereas combined therapy involving chemotherapy and concurrent thoracic radiotherapy is the standard treatment for limited-disease (LD)-SCLC. PURPOSE: This study aimed to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of amrubicin and cisplatin with concurrent thoracic radiotherapy (TRT) for LD-SCLC. PATIENTS AND METHODS: Patients that fulfilled the following eligibility criteria were enrolled: being aged ≤ 75 years and chemotherapy-naïve and having a performance status (PS) of 0-1, LD-SCLC, and adequate organ function. The patients received escalating doses of amrubicin on days 1, 2, and 3, and a fixed 60-mg/m2 dose of cisplatin on day 1. Four cycles of chemotherapy were administered, with each cycle lasting 4 weeks. TRT involving 2 Gy/day, once daily, commenced on day 2 of the first cycle of chemotherapy. The initial dose of amrubicin was 20 mg/m2 (level 1), and the dose was escalated to 25 mg/m2 (level 2) and then 30 mg/m2 (level 3). RESULTS: Eight patients from three institutions were enrolled at three dose levels. The patients' characteristics were as follows: male/female: 3/5; median age (range): 68.5 (60-73); PS 0/1: 4/4; stage IIIA/IIIB disease: 3/5. Both level 3 patients experienced DLT (grade 4 neutropenia and/or leukopenia lasting > 4 days). Level 3 was defined as the MTD, and level 2 was recommended as the dose for this regimen. Seven patients exhibited partial responses, and 1 displayed progressive disease (response rate: 88%). The median progression-free survival and overall survival periods were 11.1 and 39.5 months, respectively. No treatment-related deaths occurred. CONCLUSIONS: When this regimen was combined with TRT for LD-SCLC, the MTD was 30 mg/m2 for amrubicin and 60 mg/m2 for cisplatin. In addition, neutropenia and leukopenia were DLT, and doses of 25 mg/m2 for amrubicin and 60 mg/m2 for cisplatin are recommended for this regimen.

Concurrent chemoradiotherapy using cisplatin and S-1, followed by surgery for stage II/IIIA non-small cell lung cancer.

OBJECTIVES: Because chemoradiotherapy using cisplatin and S-1, an oral fluoropyrimidine, is effective for unresectable non-small cell lung cancer (NSCLC), an induction setting was used in a multicenter phase II study (Clinical trial number: UMIN000008205). The correlations of relapse and clinicopathological factors were analyzed. METHODS: We defined locally advanced NSCLC as pathologically proven chest wall invasion or hilar and/or mediastinal lymph node metastases by endobronchial ultrasound-guided transbronchial needle aspiration. The patients received two courses of S-1 administration for 14 days and intravenous cisplatin injection on day 8. A total dose of 40 Gy radiotherapy was concurrently received. Surgical resection was performed after completion of the treatment. RESULTS: Of the 23 eligible patients, 18 had stage IIIA and 5 had stage IIB NSCLC. Twenty of the eligible patients (87.0%) completed the regimen. Six (26.1%) complete responses were identified and 12 cases (52.2%) were histopathologically downstaged by induction chemoradiotherapy (ICRT). The 3-year overall survival rate was 58.1% and relapse-free survival (RFS) rate was 52.0%, respectively. Among several clinicopathological parameters, univariate RFS analysis identified that only downstaging was significantly associated with longer RFS times (p = 0.003). The radiological response did not reflect pathological response. When the variables of preoperative pathologically proven N2 metastasis, pathological ICRT effectiveness, and downstaging were included in the Cox proportional hazard modes, only the parameter of downstaging displayed significant hazard ratio (hazard ratio 0.13, p = 0.010). CONCLUSION: This protocol is considered an option among preoperative therapies and has obvious benefits for pathologically downstaged cases. CLINICAL TRIAL NUMBER: UMIN000008205. TRIAL REGISTRATION DATE: June 19, 2012.

Retrospective analysis of definitive radiotherapy for neck node metastasis from unknown primary tumor: Japanese Radiation Oncology Study Group study.

OBJECTIVE: To investigate the optimal treatment method and risk factor of neck node metastasis from unknown primary tumors (NUP) treated by radiotherapy. METHODS: Retrospective case study based on a multi-institutional survey was conducted by the Japanese Radiation Oncology Study Group. Patients pathologically diagnosed as having NUP from 1998 to 2007 were identified. Univariate and multivariate analyses of overall survival (OS), progression free survival (PFS), neck progression free survival (NPFS) and mucosal progression free survival (MPFS) were evaluated. RESULTS: In total, 130 patients with median age of 65 years were included. Nodal stages N1, N2a, N2b and N2c were observed for 10, 26, 43, 12 and 39 patients, respectively. All the patients received radiotherapy (RT) with neck dissection in 60 and with chemotherapy in 67 cases. The median doses to the metastatic nodes, prophylactic neck and prophylactic mucosal sites were 60.0, 50.4 and 50.4 Gy, respectively. The median follow-up period for surviving patients was 42 months. Among 12 patients, occult primary tumors in the neck region developed after radiotherapy. The 5-year OS, PFS, NPFS and MPFS were 58.1%, 42.4%, 47.3% and 54.9%, respectively. Univariate analysis showed that lower N stage (N1-2b), non-bulky node (<6 cm) and negative extracapsular extension (ECE) status were the factors associated with favorable OS, PFS, NPFS and MPFS. Radical surgery proved to be a favorable factor of OS, NPFS and MPFS. On multivariate analysis, lower N stage and negative ECE status were correlated with improved survival. CONCLUSIONS: Lower nodal stage and negative ECE status showed a favorable impact on survival and disease control in patients with NUP treated by radiotherapy.

A Case of Urachal Carcinoma of the Abdominal Wall in a Kidney Transplant Recipient.

Urachal carcinoma is an extremely rare malignant tumor arising from the urachus in the fetus. We report a patient who developed urachal carcinoma 18 years after kidney transplantation. A 59-year-old man was admitted because of abdominal pain and massive ascites. He had undergone kidney transplantation 18 years earlier and had end-stage renal disease requiring dialysis. Abdominal CT showed massive ascites and an abdominal wall cystic mass separated from the peritoneal cavity. Hemodialysis was started, and paralytic ileus was diagnosed and treated. His ileus symptoms improved temporarily, but he died of myocardial infarction. An autopsy was performed, which revealed cystadenocarcinoma in the abdominal wall mass, leading to a diagnosis of urachal carcinoma.

Surgery or stereotactic body radiotherapy for elderly stage I lung cancer? A propensity score matching analysis.

PURPOSE: The aim of this study was to compare the outcomes of surgery and stereotactic body radiotherapy (SBRT) for elderly clinical stage I non-small cell lung cancer (NSCLC) patients. METHODS: Patients ≥80 years of age with clinical stage I NSCLC between August 2008 and December 2014 were treated either surgery or SBRT. Propensity score matching was performed to reduce bias in various clinicopathological factors. RESULTS: Surgery was performed in 57 cases and SBRT in 41 cases. In the surgery group, the operations included 34 lobectomies and 23 sublobar resections. In the SBRT group, 27 cases were given 48 Gy in 4 fractions, and 14 were given 60 Gy in 10 fractions. Similar characteristics were identified in age (82 years), gender (male:female ratio 2:1), tumor size (2.2 cm), carcinoembryonic antigen (3.6 ng/ml), Charlson comorbidity index (1), Glasgow prognostic scale (0), and forced expiratory volume in 1 s (1.7 L) after matching. Before matching, the 5-year overall survival (OS) in surgery (68.3%) was significantly better than that in SBRT (47.4%, p = 0.02), and the 5-year disease-specific survival (DSS) (94.1%, 78.2%, p = 0.17) was not significantly different between the groups. The difference in the 5-year OS became non-significant between the matched pairs (57.0%, 49.1%, p = 0.56). CONCLUSIONS: The outcomes of surgery and SBRT for elderly patients with the early stage NSCLC were roughly the same.

Clinical significance of awake oscillatory ventilation in patients with heart failure and effects of open-heart surgery.

BACKGROUND: Although sleep apnea has recently become a concern in patients with congestive heart failure (CHF), some patients with CHF exhibit characteristic oscillatory ventilation (OV) even when they are awake. We investigated the clinical significance of OV in patients with CHF, and effects of open-heart surgery on the OV. HYPOTHESIS: OV is an indicator of the severity of CHF, and this abnormal respiratory pattern improves with hemodynamic changes after open-heart surgery. METHODS: According to respiratory pattern in the cardiopulmonary exercise testing (CPX) before cardiac surgery, 50 patients with CHF were divided into 14 patients of OV-positive (OV+) and 36 patients of OV-negative (OV-). Then, the several indices of CPX before surgery, 1 week and 6 months after surgery were compared between the 2 groups. RESULTS: The peak VO2 before surgery was lower in OV+ patients than those in OV- patients (15.3 vs 18.8 m1/min/kg, p < 0.05). One week after surgery, anaerobic threshold (AT) and end-tidal C02 (ETC02) were lower in OV+ patients than those in OV- patients (AT: 9.5 vs 10,7 ml/min/kg, p < 0.05, ETCO2: 5.3 vs 5.6%, p < 0.05). However, 6 months after surgery, the statistical differences of these CPX parameters between the 2 groups were not found, and OV disappeared in 79% of OV+ patients. CONCLUSIONS: These data suggest that OV is an indicator of the severity of CHF, and gradually improved with the open-heart surgery.

Species-dependence of the redox potential of the primary quinone electron acceptor QA in photosystem II verified by spectroelectrochemistry.

The redox potentials E(m)(Q(A)/Q(A)(-)) of the primary quinone electron acceptor Q(A) in oxygen-evolving photosystem II complexes of three species were determined by spectroelectrochemistry. The E(m)(Q(A)/Q(A)(-)) values were experimentally found to be -162+/-3 mV for a higher plant spinach, -171+/-3 mV for a green alga Chlamydomonas reinhardtii and -104+/-4 mV vs. SHE for a red alga Cyanidioschyzon merolae. On the basis of possible deviations for the experimental values, as estimated to differ by 9-29 mV from each true value, plausible causes for such remarkable species-dependence of E(m)(Q(A)/Q(A)(-)) are discussed, mainly by invoking the effects of extrinsic subunits on the delicate structural environment around Q(A).

Prognostic value of myocardial perfusion SPECT images in combination with the maximal heart rate at exercise testing in Japanese patients with suspected ischemic heart disease: a sub-analysis of J-ACCESS.

OBJECTIVES: We assessed whether a combination of summed stress scores (SSS) using exercise myocardial perfusion SPECT (Ex-SPECT) and maximal heart rate accurately predicts cardiac events through a sub-analysis of J-ACCESS (Japanese Assessment of Cardiac Events and Survival Study by Quantitative Gated SPECT) which was conducted to evaluate the prognosis of Japanese patients with suspected ischemic heart disease. METHODS: In J-ACCESS, 2,373 patients with suspected coronary artery disease not receiving beta-blocker treatment underwent Ex-SPECT. These patients were categorized into the following four groups: Group A [achieved target heart rate (THR) and SSS < 4: n = 631], B (did not achieve THR and SSS < 4: n = 612), C (achieved THR and SSS >or= 4: n = 570), and D (did not achieve THR and SSS >or= 4: n = 560). We evaluated the incidence rate of cardiac events including cardiac death, myocardial infarction, and heart failure requiring hospital admission during a 3-year period. RESULTS: In Group A, B, C, and D, 9 of 631 (1.4%), 15 of 612 (2.4%), 23 of 570 (4.0%) and 30 of 560 (5.4%) patients experienced cardiac events, respectively. Although the hazard ratio of the SSS >or= 4 was 2.45 (p < 0.001) and that of the attained THR was 0.69 (p = 0.10) in the multiple Cox regression analysis, Kaplan-Meier curves showed that the cardiac events rate was lower in the order of A, B, C, and D (p < 0.001). CONCLUSION: The combination of SSS using Ex-SPECT and the maximal heart rate is a useful predictor of cardiac events in patients with suspected coronary artery disease.

Prognostic significance of PVCs and resting heart rate.

BACKGROUND: We sought to evaluate the prognostic significance of premature ventricular contractions (PVCs) on a routine electrocardiogram (ECG) and to evaluate the relationship between heart rate and PVCs. METHODS: Computerized 12-lead ECGs of 45,402 veterans were analyzed. Vital status was available through the California Health Department Service. RESULTS: There were 1731 patients with PVCs (3.8%). Compared to patients without PVCs, those with PVCs had significantly higher all-cause (39% vs 22%, P < 0.001) and cardiovascular mortality (20% vs 8%, P < 0.001). PVCs remain a significant predictor even after adjustment for age and other ECG abnormalities. The presence of multiple PVCs or complex morphologies did not add significant additional prognostic information. Those patients with PVCs had a significantly higher heart rate than those without PVCs (mean +/- SD: 78.6 +/- 15 vs 73.5 +/- 16 bpm, P < 0.001). When patients were divided into groups by heart rate (<60, 60-79, 80-99 and >100 bpm) and by the presence or absence of PVCs, mortality increased progressively with heart rate and doubled with the presence of PVCs. Using regression analysis, heart rate was demonstrated to be an independent and significant predictor of PVCs. CONCLUSIONS: PVCs on a resting ECG are a significant and independent predictor of all-cause and cardiovascular mortality. Increased heart rate predicts mortality in patients with and without PVCs and the combination dramatically increases mortality. These findings together with the demonstrated independent association of heart rate with PVCs suggest that a hyperadrenergic state is present in patients with PVCs and that it likely contributes to their adverse prognosis.

Prognostic Significance of Quantitative QRS Duration.

BACKGROUND: Although QRS duration is known to be a predictor of mortality in patients with left ventricular dysfunction, our purpose was to evaluate the prognostic power of computer-measured QRS duration in a general medical population. METHODS: Analyses were performed on the first electrocardiogram digitally recorded on 46,933 consecutive patients at the Palo Alto Veterans Affairs Medical Center between 1987 and 2000. Patients with electrocardiograms exhibiting Wolff-Parkinson-White were excluded (n = 44), and those with bundle branch block or electronic pacing were considered separately, leaving 44,280 patients for analysis (mean age 56 +/- 15 years; 90% were males). There were 3659 (8.3%) cardiovascular deaths (mean follow-up of 6.0 +/- 3.8 years). RESULTS: A survival plot showed significant separation according to a QRS duration score. After adjustment in the Cox model for age, gender, and heart rate, the QRS duration score was a strong independent predictor of cardiovascular mortality. For every 10-ms increase in QRS duration, there was an 18% increase in cardiovascular risk. The results were similar in patients with an abnormal electrocardiogram, a bundle branch block, and a paced rhythm. CONCLUSION: Quantitative QRS duration was a significant and independent predictor of cardiovascular mortality in a general medical population.