Outcomes After Intensive Rehabilitation for Mechanically Ventilated Patients: A Nationwide Retrospective Cohort Study

ObjectiveTo examine the effects of intensive rehabilitation on mortality and liberation from mechanical ventilation among patients with mechanical ventilation in intensive care units.DesignRetrospective cohort study using the Diagnosis Procedure Combination inpatient database.SettingPatients discharged from acute care hospitals from April 2010 to March 2016.ParticipantsPatients (N=46,438) aged 20 years and older who were admitted to intensive care units and who started rehabilitation within 3 days of starting mechanical ventilation.InterventionIntensive rehabilitation in intensive care unit in the first 5 days after admission. Amount of rehabilitation was defined as the average number of units per day in the first 5 days after admission and was dichotomized as intensive (≥1.0 unit/d) or nonintensive (<1.0 unit/d) rehabilitation.Main Outcome MeasuresThe primary outcome was in-hospital mortality. The secondary outcome was liberation from mechanical ventilation.ResultsWe identified 29,982 eligible patients, including intensive (n=7745) and nonintensive (n=22,237) rehabilitation groups. In the propensity score-matched analysis, the intensive rehabilitation group had significantly lower in-hospital mortality (risk difference: ?3.4%; 95% CI, ?4.9% to ?1.9%) and a higher proportion of liberation from mechanical ventilation (subdistribution hazard ratio, 1.08; 95% CI, 1.03-1.13) compared with the nonintensive rehabilitation group.ConclusionsPatients receiving a higher amount of rehabilitation in intensive care units were less likely to die and more likely to be liberated from mechanical ventilation.     

A protective role of interleukin 11 on hepatic injury in acute endotoxemia

The liver is one of the major target organs affected in sepsis, and its failure always results in critical consequences. It has been reported that recombinant human interleukin 11 (rhIL-11), a pleiotropic cytokine, may be useful in the treatment of sepsis. However, the effect of IL-11 specifically on the hepatic failure in sepsis has not been evaluated. In the present study, we examined the effect of rhIL-11 on the hepatic injury in a rat endotoxemia model. Acute endotoxemia was induced in male Sprague-Dawley rats by intraperitoneal injection (i.p.) of bacterial lipopolysaccharide (LPS, 20 mg/kg). Immediately after injection of LPS, rats were treated with rhIL-11 (150 microg/kg, i.p.) or the vehicle. LPS treatment induced severe hepatic injury as revealed by marked increases in serum alanine transaminase (ALT) and aspartate transaminase (AST) activities, extensive hepatocyte necrosis, tumor necrosis factor-alpha (TNF-alpha) mRNA, inducible nitric oxide synthase (iNOS) mRNA, and DNA-binding activity of nuclear factor-kappaB (NF-kappaB). In contrast, rhIL-11 treatment significantly ameliorated the LPS-induced hepatic injury, as judged by marked improvement in all these indices. In addition, rhIL-11 treatment markedly decreased LPS-induced mortality. These results indicate that rhIL-11 plays a significant protective role in LPS-induced hepatic injury in acute endotoxemia.     

A case of renin-producing adrenocortical cancer

Here we report a case of a renin-producing adrenocortical carcinoma. A 57-year-old woman was referred to our hospital complaining of thirst and generalized muscle weakness. She was diagnosed as being hypertensive and diabetic with associated hypokalemia and she had a hard elastic mass with a diameter of 10 cm on the left side of her neck. An abdominal computed tomography scan revealed a suprarenal mass on the left side (8.5 x 8 x 6.5 cm). Endocrinological examination demonstrated a marked elevation in the patient's serum glucocorticoid and sex steroid hormones as well as plasma renin activity. Histological examination of a sample taken from the neck mass revealed a metastasis from an adrenal carcinoma, which was stained positively with antibodies against cytochrome P450 and renin, establishing the diagnosis of a renin-producing adrenocortical carcinoma. Trilostane was effective in reducing serum cortisol levels, but mitotane was ineffective.     

Current status of development of anticancer agents in Japan

To investigate the current status of the development of anticancer agents in Japan, we examined the number of these agents developed after 1999, their target diseases, and the association between the number of approved agents and the number of patients with the diseases. The data were obtained via the Internet. Of the 487 agents approved from 1999 to April 2007, 84 were anticancer drugs. Of these 84, 46 were approved based on clinical trials and 38 were approved through the new drug application for off-label usages without clinical trials. The target diseases of the 46 agents approved through clinical trials were nonhematologic tumors in 29, hematologic malignancies in 13, and others in 4. Of the 38 approved through the new drug application for off-label usages, 31 were for nonhematologic tumors and 7 for hematologic malignancies. The number of approved anticancer agents for hematologic malignancies per unit patient population was 6.5-times as many as that for nonhematologic tumors. This study demonstrated that the situation regarding the development of anticancer agents differs among tumor types. The majority of anticancer agents developed target hematologic malignancies, while the newly developed anticancer agents have affected treatment strategies for solid tumors.     

Natural history of minute hepatocellular carcinoma smaller than three centimeters complicating cirrhosis. A study in 22 patients

Twenty-two patients with cirrhosis and minute hepatocellular carcinoma less than 3 cm in diameter were followed for periods of 6-37 mo without specific treatment. The survival curve drawn by the Kaplan-Meier method showed a 1-yr survival of 90.7%, a 2-yr survival of 55.0%, and a 3-yr survival of 12.8%. The ultrasonic patterns of these masses in the liver were correlated with the size and showed a tendency to change from a low echo pattern to a low periphery and, finally, to a massive pattern. The growth speed calculated from the doubling time for tumor volume varied considerably from case to case with an average of 6.5 +/- 5.7 mo; it also changed in some cases during the observation period. Serum alpha-fetoprotein levels were generally low, rarely assisted in diagnosis, but tended to increase when the mass attained a diameter of greater than 3 cm; sudden acceleration in the rate of increase in alpha-fetoprotein level often coincided with a change of ultrasonic pattern to the massive one.     

Salvage esophagectomy after definitive chemoradiotherapy for esophageal cancer

Salvage esophagectomy is performed for esophageal cancer after definitive chemoradiotherapy. The clinical significance and safety of salvage surgery has not been well established. We reviewed 14 cases of salvage esophagectomy following definitive chemoradiotherapy from 1994 through 2005 and investigated complication rates and outcomes. Seven of 14 cases were completely resected with salvage surgery. Operation time and bleeding were greater in patients who experienced incomplete resection (R1/R2). Anastomosis leakage, pulmonary dysfunction and heart failure were recognized in four, two and one patients, respectively. The postoperative complications were more frequent (71.4%) in patients with incomplete resection (R1/R2) than in patients with complete resection (R0) (28.4%). Two patients with complete resection (R0) showed long-term survival. Salvage esophagectomy may be indicated when the tumor can be resected completely after definitive chemotherapy. However, all cases of T4 cancer cannot be resected completely, resulting in a high risk for complications and poor survival.     

Significance of the level of monocyte chemoattractant protein-1 in human atherosclerosis.

BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1), a potent chemoattractant for monocytes, plays an important role in the earliest events of atherogenesis. However, direct evidence of the effects of MCP-1 on atherosclerosis in chronic hemodialysis (HD) patients has not been reported. METHODS AND RESULTS: The serum MCP-1 concentrations and the intimal - medial thickness (IMT) in the carotid arteries were measured in 42 non-diabetic chronic HD patients and 20 age-matched controls. The expression of MCP-1 was examined immunohistochemically in radial arterial tissues obtained from the HD patients. IMT and the serum concentration of MCP-1 in the HD patients were both significantly greater than in controls. Multiple regression analysis revealed that the serum concentration of MCP-1 was an independent factor influencing IMT. Tissue immunostaining showed that MCP-1 is expressed in both endothelial and smooth muscle cells and that its level of expression correlates with the serum concentration of MCP-1. CONCLUSIONS: An increase in MCP-1 may be an important factor in the progression of atherosclerosis in non-diabetic HD patients.     

Safety and efficacy of long-term diflunisal administration in hereditary transthyretin (ATTR) amyloidosis

Background: A recent 2-year randomized controlled trial indicated that the transthyretin (TTR) tetramer stabilizer, diflunisal, inhibits polyneuropathy progression and preserves quality of life in hereditary ATTR amyloidosis. However, its long-term outcomes are unknown. Here, we report tolerance and efficacy of long-term diflunisal administration in hereditary ATTR amyloidosis.

Methods: Diflunisal was administered orally at 500?mg/day to 40 Japanese hereditary ATTR amyloidosis patents who were not candidates for liver transplantation. The observation period ranged from 2 to 116 months (mean?±?SD: 38.0?±?31.2 months).

Results: Diflunisal-related adverse events included deterioration of renal function and thrombocytopenia resulting in discontinuation of the drug in three patients. Orally administered diflunisal significantly increased serum TTR concentration (p?=?0.001) and stabilized TTR tetramer structure in each patient. Longitudinal analyses of data collected at baseline, 24 months, and after 24 months confirmed sustaining effects of diflunisal on both neurological and cardiac functions. Notably, ulnar compound muscle action potential amplitude, cardiac wall thickness, and ejection fraction were not deteriorated after 24 months of treatment.

Conclusions: Diflunisal was tolerated well by most hereditary ATTR amyloidosis patients, although renal function and blood cell counts must be carefully monitored. Clinical effects of diflunisal were sustained after 2 years of treatment.