Relationships among Grip Strength Measurement, Response Time, and Frailty Criteria.

BACKGROUND: Muscle response in older adults is believed to decrease with maximal muscle strength, although it has not been adequately assessed; further, the relationship between frailty and muscle response remains unexamined. OBJECTIVES: This study aimed to develop a practical method for measuring muscle response using grip strength in older adults and to clarify the relationship between frailty and grip strength response. DESIGN, SETTING, AND PARTICIPANTS: We performed a cross-sectional, clinical, observational study. A total of 248 patients (94 men and 154 women, mean age: 78.2 years) who visited the outpatient unit in the Integrated Healthy Aging Clinic of our Hospital for the first time were enrolled. MEASUREMENTS: Using a grip strength measuring device originally developed by us, we measured grip strength response indices, such as reaction time, time constant, rate of force development (response speed), and maximum grip strength. Grip strength response indices were compared among three groups (robust, pre-frail, and frail) according to the Fried and Kihon checklist assessments for frailty. RESULTS: Based on Fried's assessment, marked differences were found between groups not only in maximal grip strength but also in response time and response speed. Based on the Kihon checklist assessment, there was no significant difference in response time; however, a considerable difference in response speed for the left hand was observed. Moreover, according to the Kihon checklist assessment, some cases showed differences in muscle response although not in maximal muscle strength. CONCLUSIONS: The response speed of grip strength was suggested to decrease with frailty. The results suggest that measurement of grip strength response in both hands is useful to examine the relationship between frailty and grip strength response.

The Mexican consensus on the detection and treatment of early gastric cancer. / Consenso mexicano sobre detección y tratamiento del cáncer gástrico incipiente.

Gastric cancer is one of the most frequent neoplasias in the digestive tract and is the result of premalignant lesion progression in the majority of cases. Opportune detection of those lesions is relevant, given that timely treatment offers the possibility of cure. There is no consensus in Mexico on the early detection of gastric cancer, and therefore, the Asociación Mexicana de Gastroenterología brought together a group of experts and produced the "Mexican consensus on the detection and treatment of early gastric cancer" to establish useful recommendations for the medical community. The Delphi methodology was employed, and 38 recommendations related to early gastric cancer were formulated. The consensus defines early gastric cancer as that which at diagnosis is limited to the mucosa and submucosa, irrespective of lymph node metástasis. In Mexico, as in other parts of the world, factors associated with early gastric cancer include Helicobacter pylori infection, a family history of the disease, smoking, and diet. Chromoendoscopy, magnification endoscopy, and equipment-based image-enhanced endoscopy are recommended for making the diagnosis, and accurate histopathologic diagnosis is invaluable for making therapeutic decisions. The endoscopic treatment of early gastric cancer, whether dissection or resection of the mucosa, should be preferred to surgical management, when similar oncologic cure results can be obtained. Endoscopic surveillance should be individualized.

Preliminary Study on Prevalence and Associated Factors with Sarcopenia in a Geriatric Hospitalized Rehabilitation Setting.

The reported prevalence of sarcopenia has shown a wide range, crucially based on the diagnostic criteria and setting. This cross-sectional study evaluated the prevalence of sarcopenia and sought to identify factors associated with sarcopenia on admission in a specialized geriatric rehabilitation setting based on the newly developed the Asian Working Group for Sarcopenia algorithm. Among 87 participants (mean age, 76.05 ± 7.57 years), 35 (40.2%) were classified as showing sarcopenia on admission. Prevalence was high, particularly among participants ≥80 years old, with tendencies toward lower body mass index, smoking habit, lower cognitive function, and greater functional impairment compared with the non-sarcopenic group. Identification of sarcopenia in elderly patients before rehabilitation and consideration of risk factors may prove helpful in achieving rehabilitation outcomes.

Morning vs evening dosing of the cathepsin K inhibitor ONO-5334: effects on bone resorption in postmenopausal women in a randomized, phase 1 trial.

UNLABELLED: The cathepsin K inhibitor, ONO-5334, improves bone mineral density in postmenopausal women with osteoporosis. The effects of morning versus evening administration of ONO-5334 were investigated by measuring bone turnover marker levels in healthy postmenopausal women. Morning administration of ONO-5334 showed a more consistent suppressive effect on bone resorption than evening administration. INTRODUCTION: Bone turnover is thought to be subject to circadian variation, and the efficacy of osteoporosis treatments may be optimized by regulating the time of dosing. This study assessed whether evening administration of the cathepsin K inhibitor, ONO-5334, had a differential effect on the bone turnover marker, C-terminal telopeptide of type I collagen (CTX-I), compared with morning administration. METHODS: This was a single-center, single blind crossover study. Fourteen healthy postmenopausal women were assigned to receive ONO-5334 150 mg once daily for 5 days in each period; they were randomized to receive either evening doses in the first period and morning doses in the second or vice versa. Serum and urinary levels of CTX-I were measured throughout the study. RESULTS: Both regimens showed similar patterns of reduction in serum and urinary CTX-I; however, CTX-I suppression was more consistently >60% over 24 h following morning administration. Morning administration led to 6% greater suppression of 24-h serum CTX-I area under the effect curve (AUE; 69 vs 63%; P < .05) and 7% greater suppression of urinary CTX-I/creatinine AUE (93 vs 86%; P < .01) than evening administration. Higher plasma ONO-5334 concentrations were observed between 12 and 24 h postdose following morning administration, with mean trough concentrations for the morning and evening regimens at 9.4 and 4.0 ng/mL, respectively. There were no safety findings of concern. CONCLUSION: Morning dosing of ONO-5334 is more efficacious at reducing markers of bone turnover in healthy postmenopausal women than evening dosing. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01384188 , registered on June 27, 2011 EudraCT: 2008-006284-37.

PBSC collection from family donors in Japan: a prospective survey.

Severe adverse events (SAE) and late hematological malignancies have been reported after PBSC donation. No prospective data on incidence and risk factors have been available for family donors so far. The Japan Society for Hematopoietic Cell Transplantation (JSHCT) introduced therefore in 2000 a mandatory registration system. It defined standards for donor eligibility and asked harvest centers to report any SAE immediately. All donors were examined at day 30 and were to be contacted once each year for a period of 5 years. Acute SAEs within day 30 were reported from 47/3264 donations (1.44%) with 14 events considered as unexpected and severe (0.58%). No donor died within 30 days. Late SAEs were reported from 39/1708 donors (2.3%). The incidence of acute SAEs was significantly higher among donors not matching the JSHCT standards (P=0.0023). Late hematological malignancies in PBSC donors were not different compared with a retrospective cohort of BM donors (N:1/1708 vs N:2/5921; P=0.53). In conclusion, acute and late SAEs do occur in PBSC donors at relatively low frequency but risk factors can be defined.

Efficacy of pleurodesis for malignant pleural effusions in breast cancer patients.

This study retrospectively compared long-term outcomes between two groups of breast cancer patients with malignant pleural effusion (MPE): those receiving only systemic therapy (ST) and those receiving ST following initial pleurodesis (P-ST). We identified 180 breast cancer patients from the National Cancer Center Hospital (Tokyo, Japan) database who had received ST and P-ST as an initial treatment for MPE between 1997 and 2008 for study inclusion. Pleural progression-free survival (PPFS) was defined as the time from ST in the ST group and from pleurodesis in the P-ST group to the first observation of pleural progression or death from any cause. Of the 180 patients, 78 received ST and 102 received P-ST after MPE diagnosis. Median duration of follow-up was 12.7 months (range 0.9-80.1 months). Median PPFS for the ST group and the P-ST group was 4.1 and 8.5 months, respectively. The difference in PPFS between the two groups was statistically significant (p < 0.001) and the hazard ratio after adjusting for prognostic factors in the P-ST group relative to the ST group was 0.24. Our results suggest that the efficacy of P-ST may be superior to that of ST alone with respect to local control of pleural effusions in breast cancer patients.

Time trend in treatment-related deaths of patients with advanced non-small-cell lung cancer enrolled into phase III trials of systemic treatment.

PURPOSE: Despite recent improvements in supportive care, treatment-related death (TRD) remains a serious problem for lung cancer patients undergoing systemic chemotherapy. However, few studies have formally assessed possible changes in the TRD rate over the past two decades. PATIENTS AND METHODS: We searched phase III trials to address the role of systemic treatment of advanced non-small-cell lung cancer (NSCLC). Time trend was assessed using linear regression analysis. RESULTS: The overall incidence of TRD was calculated from 119 trials including 263 chemotherapy arms (46 477 patients), with information about the causes of deaths available for 197 arms (75%, 30 147 patients). Cisplatin-based regimens were the most frequently investigated. The crude TRD rate in the overall cohort of 119 trials was 1.26% and has been notably consistent over the investigated time (P = 0.762). The most common cause of death was febrile neutropenia, with no significant change in its incidence over the years (P = 0.139). In contrast, deaths due to renal toxicity decreased significantly (P = 0.042), whereas deaths due to pulmonary disorder increased significantly (P = 0.007). Among the pharmacological agents investigated, docetaxel (Taxotere) and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) were associated with relatively high rates of deaths from pulmonary disorders, but EGFR-TKIs were not associated with death from any other cause. CONCLUSIONS: Despite of potential confounders in our results, the overall TRD rate has remained low, but not negligible, in phase III trials for advanced NSCLC, over the past two decades. Notably, the incidence and pattern of TRD stratified by cause have changed considerably.

[Submucosal endoscopic dissection]. / Disección endoscópica de la submucosa.

BACKGROUND: Endoscopic submucosal dissection (ESD) is a novel technique that increases the therapeutic spectrum for early-stage malignant lesions (T1mN0) of gastrointestinal tract. AIM: To review the current training requirements, indications and devices for ESD. METHODS: A PubMed search and selection for manuscripts between 2005 and 2009 was performed. Kew words used were of "endoscopic submucosal dissection", "indications", "training" and "devices". RESULTS: Indications for ESD in early gastrointestinal cancer are: I) Well differentiated and limited to mucosa: a) Non ulcerated: no matters size and shape or, b) Ulcerated: less than 3 cm; II) Poorly-differentiated limited to mucosa: non ulcerated and less than 2 cm; III) Invading submucosa: well differentiated, less than 3 cm with a maximum depth of 500 µm. The most frequently used technique to elevate submucosa is injection of isotonic saline solution with epinephrine and indigo. Technology is evolving with new devices for increasing safety. Training should include at least 30 animal models before attempting to perform the procedure in patients. CONCLUSIONS: ESD is an endoscopic procedure with well established indications that require a special training. Its use in well selected cases is safe and can replace a surgical procedure or other therapeutic modalities.

A cross-sectional study of sarcopenia in Japanese men and women: reference values and association with cardiovascular risk factors.

In this study of Japanese men and women, we determine reference values for sarcopenia and test the hypothesis that sarcopenia is associated with risk factors for cardiovascular disease, independent of waist circumference. A total of 1,488 Japanese men and women aged 18-85 years participated in this study. Appendicular muscle mass (AMM) was measured by dual-energy X-ray absorptiometry. Reference values for classes 1 and 2 sarcopenia (skeletal muscle index: AMM/height2, kg m-2) in each sex were defined as values one and two standard deviations below the sex-specific means of reference values obtained in this study from young adults aged 18-40 years. The reference values for class 1 and class 2 sarcopenia were 7.77 and 6.87 kg m-2 in men and 6.12 and 5.46 kg m-2 in women. In subjects both with class 1 and class 2 sarcopenia, body mass index and % body fat were significantly lower than in normal subjects. Despite whole-blood glycohaemoglobin A1c in men with class 1 sarcopenia was significantly higher than in normal subjects, and brachial-ankle pulse wave velocity in women both with class 1 and class 2 sarcopenia were significantly higher than in normal subjects, using one-way ANCOVA with adjustment for the covariate of waist circumference. Although sarcopenia is associated with thin body mass, it is associated with more glycation of serum proteins in men and with greater arterial stiffness in women, independent of waist circumference.

Age and cardiorespiratory fitness are associated with arterial stiffening and left ventricular remodelling.

Arterial stiffening, hypertension and left ventricular (LV) remodelling are associated with increased risk of cardiovascular disease. Cardiorespiratory fitness is associated with cardiovascular function and reduced risk of cardiovascular disease. This cross-sectional study was carried out to determine the relationships between cardiorespiratory fitness, arterial stiffness, blood pressure (BP) and LV remodelling in women. On the basis of peak oxygen uptake, a total of 159 premenopausal (young) and postmenopausal (older) women were categorized into either low (unfit) or high (fit) cardiorespiratory fitness groups. The arterial stiffness and LV remodelling were measured by brachial-ankle pulse wave velocity (baPWV) and carotid augmentation index (AI) and LV relative wall thickness (RWT). Two-way analysis of variance indicated a significant interaction between age and cardiorespiratory fitness in baPWV, carotid AI, BP and RWT. In the older group, arterial stiffness (baPWV; 1401+/-231 vs 1250+/-125 cm s(-1), P<0.01, AI; 32.9+/-9.9 vs 24.8+/-10.1%, P<0.01), systolic blood pressure (SBP) (130+/-22 vs 117+/-15 mm Hg, P<0.01) and RWT (0.47+/-0.08 vs 0.42+/-0.04, P<0.05) in fit women were lower than in unfit women. In older women, RWT was significantly related to baPWV (r=0.46, P<0.01), carotid AI (r=0.29, P<0.05), SBP (r=0.57, P<0.01) \[V(2peak) (r=-0.32, P<0.05). In young women, they were not significant correlations, except for a weak correlation between RWT and SBP (r=0.21, P<0.05). These results suggest that higher cardiorespiratory fitness is associated with lower arterial stiffness, BP and RWT in older women.

Statin-independent prognosis of patients with diffuse large B-cell lymphoma receiving rituximab plus CHOP therapy.

BACKGROUND: A recent laboratory study indicated that statins impaired the antitumor effects of rituximab by inducing conformational changes in CD20. Although these findings raised significant concerns about statin use during rituximab treatment, their clinical significance is unclear. PATIENTS AND METHODS: We conducted a retrospective study investigating the effects of statins on the prognosis of diffuse large B-cell lymphoma (DLBCL) treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP). Newly diagnosed DLBCL patients were analyzed (n = 256), including 35 patients taking statins. RESULTS: The 3-year progression-free survival rates were 84% and 73% (P = 0.38), while the overall survival rates were 89% and 78% (P = 0.28) for those patients treated with and without statins, respectively. After adjusting for the International Prognostic Index and serum cholesterol level, statin use was not associated with prognosis. CONCLUSIONS: These results indicate that statins do not influence the clinical prognosis of DLBCL treated with RCHOP. Further studies with larger numbers of patients are warranted to confirm the prognostic significance of statins for patients with DLBCL receiving rituximab-containing chemotherapy.

Association between incremental gains in the objective response rate and survival improvement in phase III trials of first-line chemotherapy for extensive disease small-cell lung cancer.

BACKGROUND: The duration of, resources required for and cost of clinical trials could be reduced if a surrogate end point was to be used in place of survival. We assessed the extent to which the objective response rate (ORR) is predictive of mortality, how much difference in the ORR is needed to predict an obvious survival difference and what factors could affect the association between the two parameters during the first-line treatment of extensive disease (ED)-small-cell lung cancer (SCLC). METHODS: We used the ORRs and median survival times (MSTs) from 48 phase III trials of first-line chemotherapy involving 8779 randomised patients with ED-SCLC in a linear regression analysis. The MST difference was calculated as the difference in MST between the investigational and reference arms; the ORR difference was similarly defined. RESULTS: ORR difference between the treatment arms was modestly associated with the MST difference in the overall trials (R(2) = 0.3314). In contrast, the relationship was stronger among only trials in which prophylactic cranial irradiation was given to those having an objective response to the initial chemotherapy (R(2) = 0.6279). In this trial setting, large differences in ORR were needed to predict a survival advantage (1.2-day survival advantage per 2% increase in ORR). CONCLUSIONS: In the first-line treatment of ED-SCLC, a favourable relationship was detected between the two parameters in the selected trial setting. Large ORR differences were needed to predict a survival benefit, clearly suggesting the need for new chemotherapeutic agents.

Muscle mass and bone mineral indices: does the normalized bone mineral content differ with age?

OBJECTIVE: To investigate the relationships between regional skeletal muscle mass (SM mass) and bone mineral indices and to examine whether bone mineral content (BMC) normalized to SM mass shows a similar decrease with age in young through old age. SUBJECTS/METHODS: One hundred and thirty-eight young and postmenopausal women aged 20-76 years participated in this study and were divided into three groups: 61 young women, 49 middle-aged postmenopausal women and 28 older postmenopausal women. Muscle thickness (MTH) was determined by ultrasound, and regional SM mass (arm, trunk and leg) was estimated based on nine sites of MTH. Whole-body and regional lean soft tissue mass (LSTM), bone mineral density (BMD) and BMC (whole body, arms, legs and lumbar spine) were measured using dual-energy X-ray absorptiometry. RESULTS: Ultrasound spectroscopy indicated that SM mass is significantly correlated with site-matched regional bone mineral indices and these relationships correspond to LSTM. The BMC and BMD in older women were significantly lower than those in middle-aged women. When BMC was normalized to site-matched regional SM mass, BMC normalized to SM mass in arm and trunk region were significantly different with age; however, whole-body and leg BMC normalized to SM mass showed no significant difference between middle-aged and older postmenopausal women. CONCLUSIONS: The age-related differences in BMC were found to be independent of the ageing of SM mass in the arm and trunk region. However, differences in BMC measures of the leg and whole body were found to correspond to age-related decline of SM mass in postmenopausal women.

Soluble interleukin-2 receptor retains prognostic value in patients with diffuse large B-cell lymphoma receiving rituximab plus CHOP (RCHOP) therapy.

BACKGROUND: Soluble interleukin-2 receptor (SIL-2R) is known to be a prognostic parameter in patients with diffuse large B-cell lymphoma (DLBCL) receiving cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) therapy. However, its prognostic value has not been well known since the introduction of rituximab. PATIENTS AND METHODS: We retrospectively evaluated the prognostic impact of SIL-2R in 228 DLBCL patients, comparing 141 rituximab-combined CHOP (RCHOP)-treated patients with 87 CHOP-treated patients as a historical control. RESULTS: Patients with high serum SIL-2R showed significantly poorer event-free survival (EFS) and overall survival (OS) than patients with low SIL-2R in both the RCHOP group (2-year EFS, 66% versus 92%, P<0.001; OS, 82% versus 95%, P=0.005) and the CHOP group (2-year EFS, 40% versus 82%; OS, 61% versus 90%, both P<0.001). Multivariate analysis including the five parameters of International Prognostic Index (IPI) and two-categorized IPI revealed that SIL-2R was an independent prognostic factor for EFS and OS in the RCHOP group as well as in the CHOP group. CONCLUSIONS: Our results demonstrate that SIL-2R retains its prognostic value in the rituximab era. The prognostic value of SIL-2R in DLBCL patients receiving rituximab-combined chemotherapy should be reassessed on a larger scale and by long-term follow-up.

Quantitative analysis of propionibacterial DNA in bronchoalveolar lavage cells from patients with sarcoidosis.

BACKGROUND AND AIM OF THE WORK: The causes of sarcoidosis are still unknown. Propionibacterial subspieces are thought to be one of the most likely sources of antigens. Here we attempted to measure the amount of propionibacterial DNA in bronchoalveolar lavage (BAL) cell samples from patients with sarcoidosis and other pulmonary diseases. METHODS: We examined BAL cells from 42 patients with sarcoidosis and 30 controls. Using quantitative polymerase chain reaction (PCR) for 16S rRNA of Propionibacterium acnes (P. acnes) and Propionibacterium granulosum (P. granulosum), we measured the amount of propionibacterial DNA in 500 ng of total DNA extracted from BAL cells from patients with sarcoidosis or other lung diseases. The correlation between clinical findings and the results of quantitative PCR were analyzed. RESULTS: The mean level of P. acnes DNA from patients with sarcoidosis was 59.9 genomes per 500 ng of total DNA, which was significantly higher than that in controls (20.7 genomes, p<0.000l). The mean level of P. granulosum DNA from patients with sarcoidosis was 1.2 genomes, which was similar to that in controls (1.0 +/-1.6 genomes, p=0.52). The number of genomes of P. acnes in BAL cells was correlated with the serum angiotensin-converting enzyme (ACE) level and the percentage of macrophages in BAL fluid from patients with sarcoidosis. CONCLUSIONS: The amount of P. acnes DNA in BAL cells from patients with sarcoidosis was significantly higher than that in BAL cells from patients with other pulmonary diseases. P. acnes may be involved in the pathogenesis of sarcoidosis.

Acute renal failure in a patient with severe malaria and dengue shock syndrome.

Malaria is an infectious disease caused by plasmodium, which lives and breeds in human blood cells, and is transmitted through the bites of Anopheles mosquitoes. Renal impairment, often caused by malaria, is acute renal failure (ARF) due to acute tubular necrosis (ATN). Dengue virus is transmitted from human to human through Aedes aegypti mosquito bites. Dengue hemorrhagic fever (DHF), the most severe stage of infection, is characterized by bleeding and shock tendencies (dengue shock syndrome, DSS). ARF is a less common complication in patients with DHF, with an incidence of less than 10%. Mixed infections of two infectious agents may cause overlapping symptoms and have been reported in Africa and India. We report here a patient with ARF due to mixed infection of severe malaria and DSS. The patient presented with fever and had a history of repeated malaria infection. Physical examination revealed stable vital signs and hepatosplenomegaly. Laboratory data showed hemoconcentration, thrombocytopenia and increased serum aminotransferase. Chest X-ray showed pleural effusion. A malarial antigen and thick smear examination showed the trophozoite stage of P. falciparum. On Day 3, blood pressure dropped to 80/60 mmHg, pulse was 120 beats/minute, weak, and body temperature 36.8 C, with icterus. Other tests revealed an increase of serum urea nitrogen and creatinine levels, and serologically anti-dengue IgG antibody (+) and anti-dengue IgM antibody (-). Based on these findings, we diagnosed the patient as having both malaria and DDS. We treated the patient with the parenteral anti-malarial agent, artemisinin. Supportive treatment and treatment of complications were also performed simultaneously for DSS. The patient experienced an oliguria episode but responded well to a diuretic. The patient was discharged after clinical and laboratory examinations showed positive progress.