The patient-based outcome of upper-extremity surgeries using the DASH questionnaire and the effect of disease activity of the patients with rheumatoid arthritis

The Disabilities of the Arm, Shoulder and Hand (DASH) is a standardized patient-based outcome measure, which assesses integrated upper-extremity disorders. The objectives of this study were to investigate subjective outcome after upper-extremity surgeries for the patients with rheumatoid arthritis (RA) using the DASH questionnaire (Japanese version) and to investigate the influence of disease activity on the surgical outcome using the Disease Activity Score (DAS) 28-CRP(4). Approximately 127 surgical procedures for the upper extremities in 127 patients with RA were recruited in this study. Surgeries were performed in 4 shoulders, 35 elbows, 60 wrists and 28 hands. The DASH score (disability/symptom score) was investigated just before surgery and at follow-up. The mean follow-up period after the surgery was 15 months on average (range, 6 to 24 months). The preoperative DASH score (disability/symptom score) 50 +/- 23 (mean +/- SD) decreased significantly to 38 +/- 23 at the follow-up (n = 127, p < 0.01). Standardized response mean and effect size revealed a medium effect of -0.6 and -0.5. Patients with various degrees of disease activity improved and the improvements per se were comparable of preoperative disease activity and postoperative response to medical treatment. A favorable subjective outcome of rheumatoid upper-extremity surgeries can be anticipated under the good control of disease activity.     

Histopathologically-diagnosed splenic metastasis in a hepatocellular carcinoma case with adrenal metastasis

We encountered a patient with hepatocellular carcinoma (HCC), with adrenal gland metastasis, in whom splenic metastasis was diagnosed histopathologically. A 59-year-old man visited our hospital in May 2001 with chief complaints of abdominal distension and pretibial pitting edema. Multiple HCCs associated with HCV-positive liver cirrhosis were detected. Transarterial embolization (TAE) was performed a total of 4 times for HCCs. A left adrenal gland metastatic lesion was detected and it was found to increase in diameter from 3 cm to 6 cm over a four-month period; left adrenalectomy was performed in June 2002. Because of marked splenomegaly and findings of hypersplenism, the spleen was also resected. Although no metastatic lesions were evident on macroscopic examination of the spleen, a small metastatic lesion from moderately differentiated HCC, approximately 0.5 mm in diameter, was detected histopathologically. Splenic metastasis from HCC is rare, usually occurring with metastases involving other organs. Our patient also had adrenal gland metastasis. Therefore, hematogenous metastasis to the congested spleen via the systemic circulation was suspected.     

Effectiveness of fosfomycin combined with other antimicrobial agents against multidrug-resistant <Emphasis Type="Italic">Pseudomonas aeruginosa</Emphasis> isolates using the efficacy time index assay

We investigated the effectiveness of fosfomycin combined with other antibiotics, such as piperacillin, cefepime, ceftazidime, imipenem, meropenem, aztreonam, gentamicin, or levofloxacin, against 30 Pseudomonas aeruginosa strains, including multidrug-resistant strains, isolated from clinical specimens, using the efficacy time index (ETI) assay. The assay refers to the result of pharmacokinetics obtained from adult men volunteers, and yields an ETI to evaluate the effect of a combination of antimicrobial agents. With the ETI, based on serum concentration 3 h after the administration of two antimicrobial agents, the effectiveness of antimicrobial combinations was evaluated as follows: poor, ETI < 0.5; fair, 0.5 ≤ ETI < 1; good, 1 ≤ ETI < 8; and excellent, ETI ≥ 8. The combination of fosfomycin and cefepime (efficacy rate [excellent plus good], 76.7%) and fosfomycin/aztreonam (efficacy rate, 76.7%) appeared to be the most effective, followed by fosfomycin/meropenem (efficacy rate, 76.6%), fosfomycin/imipenem (efficacy rate, 73.3%), fosfomycin/ceftazidime (efficacy rate, 70%), fosfomycin/gentamicin (efficacy rate, 70%), fosfomycin/piperacillin (efficacy rate, 66.7%), and fosfomycin/levofloxacin (efficacy rate, 66.7%). Fosfomycin/cefepime, fosfomycin/aztreonam, and fosfomycin/meropenem may be clinically useful in selected patients, particularly for P. aeruginosa. The ETI assay provided information on the minimum inhibitory concentration (MIC) of many pairs of combined antimicrobial agents simultaneously. The ETI assay may be a useful technique with which to investigate the effect of combinations of antimicrobial agents against P. aeruginosa, including multidrug-resistant strains. Received: July 5, 2001 / Accepted: October 29, 2001     

Genetic Association Between Alcohol Withdrawal Symptoms and Polymorphism of CCK Gene Promoter

In the central nervous system, cholecystokinin (CCK) is an important neurotransmitter that gives the influences on firings, anxiety, notiception, and dopamine-related behavior. CCK co-exists in the dopaminergic neurons, interacting with dopamine. In this study, we examined the genetic variant −45 C to T substitution of the CCK gene promoter region among 195 healthy Japanese and 174 patients with alcohol withdrawal syndrome (52 delirium tremens, 39 hallucinosis, 20 seizures, and 92 lack of these symptoms) by using polymerase chain reaction-based single-strand conformational polymorphism analysis. Patients with delirium tremens showed a significantly higher frequency of the variant, compared with the controls (X²= 4.91, p < 0.03), but patients with other symptoms showed no difference. These data suggested that the individuals possessing allelic mutation (−45T) in the promoter region of the CCK gene might be susceptible to delirium tremens caused by alcohol abuse.     

Feasibility of postoperative adjuvant chemotherapy of cisplatin plus vinorelbine for completely resected non-small-cell lung cancer: A retrospective study in Japan

BackgroundThe efficacy of postoperative adjuvant cisplatin (CDDP)-based chemotherapy, such as the combination of CDDP and vinorelbine (VNR), has been established for surgically resected non-small-cell lung cancer (NSCLC). However, the optimal treatment schedule and dosage for CDDP and VNR are unknown. We evaluated patient compliance with and the safety of adjuvant chemotherapy of CDDP at 80 mg/m² administered on day 1 plus VNR at 25 mg/m² administered on days 1 and 8, every 3 weeks.MethodsMedical records of 100 surgically resected NSCLC patients, treated with a combination of CDDP and VNR at the Shizuoka Cancer Center between February 2006 and October 2011, were retrospectively reviewed.ResultsEighty-three (83%) patients completed the planned 4 cycles of CDDP plus VNR and 59 (59%) received the planned doses. Sixty-eight percent of the patients experienced a decreased neutrophil count (grade 3/4 toxicity); 1%, a decreased platelet count; and 4%, febrile neutropenia. No treatment-related deaths were noted in this study. Univariate analysis of the factors influencing patient compliance with this adjuvant chemotherapy showed that neither patient characteristics nor surgical procedure was significantly associated.ConclusionsOur results indicated that adjuvant chemotherapy with CDDP at 80 mg/m² administered on day 1 plus VNR at 25 mg/m² administered on days 1 and 8, every 3 weeks, was feasible for surgically resected NSCLC cases.     

Hydration with magnesium and mannitol without furosemide prevents the nephrotoxicity induced by cisplatin and pemetrexed in patients with advanced non-small cell lung cancer

Background

The aim of this study was to examine the effect of hydration with magnesium and mannitol without furosemide on the nephrotoxocity accompanying combination chemotherapy using cisplatin and pemetrexed in patients with advanced non-small cell lung cancer (NSCLC).

Methods

Fifty patients with NSCLC who received cisplatin plus pemetrexed, using either old hydration protocol including normal saline with mannitol and furosemide, or a new one including normal saline with magnesium and mannitol without furosemide were retrospectively analyzed. Nephrotoxicity was compared between patients treated using the old protocol and those treated with the new protocol. Univariate and multivariate analyses were performed to identify the independent factors associated with protection against nephrotoxicity in patients with NSCLC who received cisplatin plus pemetrexed.

Results

Thirty patients received the old hydration protocol, while 20 patients were treated using the new hydration protocol. The patients treated using the new hydration protocol showed a significantly greater increase in creatinine clearance (P=0.0004) and a decrease in the serum creatinine level (P=0.0148) after one course of chemotherapy compared with those treated using the old hydration protocol. There were no differences in the chemotherapeutic response or overall survival between the groups (P=0.572). The new hydration protocol with supplemented magnesium with mannitol without furosemide was an independent factor for the protection against nephrotoxicity induced by cisplatin and pemetrexed in patients with advanced NSCLC [HR 0.232 (95% CI: 0.055-0.986), P=0.039].

Conclusions

These results demonstrate that the new hydration protocol comprising supplementation with magnesium without furosemide could prevent the nephrotoxicity induced by cisplatin and pemetrexed without affecting the treatment outcome.KEY WORDS : Lung cancer, cisplatin, magnesium, nephrotoxicity, pemetrexed     

Neurological Manifestations and Long-term Sequelae in Hospitalized Patients with COVID-19

Objective Various neurological manifestations have been increasingly reported in coronavirus disease 2019 (COVID-19). We determined the neurological features and long-term sequelae in hospitalized COVID-19 patients. Methods We retrospectively studied 95 consecutive hospitalized patients with COVID-19 between March 1 and May 13, 2020. Acute neurological presentations (within two weeks of the symptom onset of COVID-19) were compared between 60 non-severe and 35 severely infected patients who required high-flow oxygen. In the 12 ventilated patients (the most severe group), we evaluated neurological complications during admission, subacute neurological presentations, and neurological sequelae (51 and 137 days from the onset [median], respectively). Results Of the 95 patients (mean age 53 years old; 40% women), 63% had acute neurological presentations, with an increased prevalence in cases of severe infections (83% vs. 52%, p＜0.001). Impaired consciousness and limb weakness were more frequent in severe patients than in non-severe ones (0% vs. 49%; p＜0.001, and 0% vs. 54%; p＜0.001, respectively). In the most severe group (mean age 72 years old; 42% women), 83% of patients had neurological complications [cerebrovascular disease (17%), encephalopathy (82%), and neuropathy (55%)], and 92% had subacute neurological presentations [impaired consciousness (17%), higher brain dysfunction (82%), limb weakness (75%), and tremor (58%)]. Neurological sequelae were found in 83% of cases, including higher brain dysfunction (73%), limb weakness (50%), and tremor (58%). Conclusions Neurological manifestations are common in COVID-19, with the possibility of long-lasting sequelae.     

gamma-Glutamyltransferase predicts cardiovascular death among Japanese women

The clinical importance of gamma-glutamyltransferase (GGT) has recently been debated. Although some studies have suggested that the relationship between GGT and cardiovascular disease (CVD) mortality is independent of alcohol consumption, to our knowledge no studies have reported the relationship between GGT and CVD mortality in never-drinker subgroups. Since Japanese women are known to have a lower prevalence of alcohol consumption, we examined whether GGT predicts CVD mortality in never-drinkers. We followed 2724 Japanese men and 4122 Japanese women without prior CVD or liver dysfunction for 9.6 years and observed 83 and 82 CVD deaths, respectively. Current alcohol drinkers comprised 59% of men and 7% of women. Among women, the multiple adjusted hazard ratio (HR) for CVD mortality compared with the reference group (GGT: 1-12 U/L) was 2.88 (95% confidence interval (CI), 1.14-7.28) for the elevated group (GGT>or=50 U/L). This positive relationship was unchanged in the never-drinkers subgroup (HR for log-transformed continuous GGT, 1.62 (95% CI, 1.11-2.37)). No significant relationships were observed in men. GGT displays a strong positive association with CVD mortality among Japanese women, for whom the prevalence of ever-drinkers is very low. Exploring the significance and biological mechanisms of GGT might provide useful insights into CVD prevention.     

Overcoming graft rejection in heavily transfused and allo-immunised patients with bone marrow failure syndromes using fludarabine-based haematopoietic cell transplantation

Allogeneic haematopoietic cell transplantation (HCT) can cure a variety of non-malignant haematological disorders. Although transplant outcomes for selected patients with severe aplastic anaemia (SAA) and paroxysmal nocturnal haemoglobinuria (PNH) have improved, older age, allo-immunisation from transfusions, prior immunosuppressive therapy and a prolonged time from diagnosis to transplantation are associated with worse outcome. Because of its potent immunosuppressive effects, we investigated a fludarabine-based non-myeloablative conditioning regimen in patients with transfusion-dependent non-malignant haematological disorders at increased risk for graft rejection with conventional transplant conditioning. Twenty-six patients with transfusion dependent/anti-thymocyte globulin (ATG)-refractory SAA, PNH or pure red cell aplasia underwent HCT from a human leucocyte antigen (HLA)-compatible relative. Transplant conditioning consisted of cyclophosphamide (120 mg/kg) and fludarabine (125 mg/m2) with or without ATG. Ciclosporine, alone or combined with mycophenolate mofetil or methotrexate, was used as graft-versus-host disease (GVHD) prophylaxis. All patients achieved durable engraftment and transfusion-independence. Twenty-four of 26 patients are alive at a median of 21 months following transplantation. Although a high cumulative incidence of acute (65% grades II-IV, 54% grades III-IV) and chronic GVHD (56%) was observed, only one patient died from transplant-related causes (cumulative incidence 7%). These data show that HCT following fludarabine-based non-myeloablative conditioning results in durable engraftment and excellent survival in SAA and PNH patients at high risk for graft rejection.     

Prognostic value of the Tei index combining systolic and diastolic myocardial performance in patients with acute myocardial infarction treated by successful primary angioplasty

Cardiac systolic (left ventricular ejection fraction) and diastolic (mitral inflow velocity pattern and/or mitral deceleration time) function were reported as predictors of clinical outcome or left ventricular remodeling in patients with acute myocardial infarction (AMI). Recently, a new index (Doppler-derived index combining systolic and diastolic myocardial performance; Tei index) for combined systolic and diastolic ventricular function has been reported to be a useful and convenient method for evaluation of global ventricular function. We therefore investigated the usefulness of the Tei index by echocardiography for evaluation of infarct size and clinical outcome in patients with AMI treated by successful primary angioplasty. We analyzed 10 age-matched control subjects and 43 consecutive patients with first AMI treated by successful primary angioplasty. The Tei index of the AMI patients was significantly greater than that of the control subjects (0.630 ± 0.106 vs 0.375 ± 0.036, P 0.0001). Also, the Tei index showed a significant positive correlation with peak creatine kinase values and ^99mTc-tetrofosmin scores. Moreover, multiple logistic regression analysis showed that the Tei index 0.70 (P = 0.0313, odds ratio = 14.14) was the only significant explanatory factor for cardiac death or developed congestive heart failure. The Tei index combining systolic and diastolic myocardial performance reflects infarct size and might be a predictor of clinical outcome in patients with AMI treated by successful primary angioplasty.