Predicting the Readmission and Mortality in Older Patients Hospitalized with Pneumonia with Preadmission Frailty.

BACKGROUND: In older people, frailty has been recognized as an important prognostic factor. However, only a few studies have focused on multidimensional frailty as a predictor of mortality and readmission among inpatients with pneumonia. OBJECTIVE: The present study aimed to assess the association between preadmission frailty and clinical outcomes after the hospitalization of older patients with pneumonia. DESIGN: Single-center, retrospective case-control study. SETTING: Acute phase hospital at Kobe, Japan. PARTICIPANTS: The present study included 654 consecutive older inpatients with pneumonia. MEASUREMENTS: Frailty status before admission was assessed using total Kihon Checklist (KCL) score, which has been used as a self-administered questionnaire to assess comprehensive frailty, including physical, social, and cognitive status. The primary outcome was a composited 6-month mortality and readmission after discharge. RESULTS: In total, 330 patients were analyzed (median age: 79 years, male: 70.4%, median total KCL score: 10 points), of which 68 were readmitted and 10 died within 6 months. After multivariate analysis, total KCL score was associated with a composited 6-month mortality and readmission (adjusted hazard ratio, 1.07; 95% confidence interval, 1.02-1.12; p = 0.006). The cutoff value for total KCL score determined by receiver operating characteristic curve analysis was 15 points (area under the curve = 0.610). The group with a total KCL score ≥ 15 points had significantly higher readmission or mortality rates than the groups with a total KCL score < 15 points (p < 0.001). CONCLUSIONS: Preadmission frailty status in older patients with pneumonia was an independent risk factor for readmission and survival after hospitalization.

Linear correlation between acetoacetate/beta-hydroxybutyrate in arterial blood and oxidized flavoprotein/reduced pyridine nucleotide in freeze-trapped human liver tissue.

A comparison of two methods of measuring liver mitochondrial redox state demonstrated that a linear correlation exists between acetoacetate/beta-hydroxybutyrate ratio in arterial blood (arterial ketone body ratio; AKBR) and oxidized flavoprotein/reduced pyridine nucleotide in human liver tissue (FP/PN) as measured by tissue fluorescence spectroscopy, such that [FP/PN] = 0.64 + 0.49 x [AKBR] (r = 0.84, P less than 0.001). This result supports the validity of AKBR as a method of measuring the hepatic mitochondrial redox state of pyridine nucleotide using arterial blood.

Quantitative analysis of redox gradient within the rat liver acini by fluorescence images: effects of glucagon perfusion.

The redox gradient along the sinusoid in the rat liver was studied using a redox scanner, a device based on tissue fluorescence scanning spectroscopy measuring the fluorescence signals of oxidized flavoprotein (FP) and reduced pyridine nucleotide (PN). The FP/(FP+PN) ratio reflects the mitochondrial redox state in the liver tissue. The distribution of mitochondrial redox state on the scanned area is expressed as two-dimensional gray-scale images with a 20 micron resolution. Using this instrument, we have scanned a 2.5 x 2.5 mm area of the frozen rat liver sample to investigate the redox gradient within acini and the effects of glucagon on the changes in the redox distribution. The redox images obtained in the perfused livers showed mosaic patterns implicating a regular heterogeneity of redox state in an acinus. The analysis of gradient curve, furthermore, clarified that the redox level in an acinus decreased sigmoidally from the periportal to the pericentral region. Glucagon, which has been reported to reduce the intracellular redox state, decreased the redox potential in whole acini, especially, in the periportal region, when compared with the perfusion without glucagon. These results strongly indicate an intraacinus heterogeneity of glucagon function, with glucagon selectively operating in the upstream of the sinusoid.

Delayed oxidation of intramitochondrial pyridine nucleotide oxidoreduction state as compared with tissue oxygenation in human liver transplantation.

Intra- and post-operative oxygenation of graft liver and subsequent oxidation of the intramitochondrial oxido-reduction state of pyridine nucleotide were studied in partial liver transplantation from living related donors with the ratio of acetoacetate to beta-hydroxybutyrate in arterial blood (AKBR), the ratio of oxidized flavoprotein to reduced pyridine nucleotide (FP/PN ratio) and oxygen saturation of hemoglobin in liver tissue (hepatic SO2). Decreased hepatic SO2 and its heterogenous distribution after reflow of portal vein and hepatic artery were normalized by the end of operation, while the intramitochondrial oxido-reduction state was still reduced at the end of operation and was normalized only at 24 h after the operation. The observed delay in oxidation of the intramitochondrial oxido-reduction state as compared with tissue oxygenation indicates the transition of the intramitochondrial oxido-reduction state associated with the initiation of metabolic activity from the cold preserved state, and suggests an important role for microcirculation in the normalization of the oxido-reduction state.

Changes in the distribution of the control of the mitochondrial oxidative phosphorylation in regenerating rabbit liver.

Applying the metabolic control theory, inhibitor titration studies were carried out on Complex I, III, IV, ATP synthase, ATP/ADP carrier and P(i) carrier of mitochondrial oxidative phosphorylation in normal and regenerating rabbit liver in order to examine the acceleration mechanism of mitochondrial oxidative phosphorylation. In regenerating rabbit liver the rate of state 3 respiration, respiratory control ratio and phosphorylation rate in the presence of mM glutamate, 250 microM ADP and 3 mM inorganic phosphate increased significantly as compared with the control by 73%, 48% and 76%, respectively. The control of the rate of state 3 respiration in normal liver was exerted by Complexes I, IV and steps other than the aforementioned six steps, whose flux control coefficients were 0.317, 0.214 and 0.469, respectively. By contrast, in regenerating liver, the control was more evenly distributed among these steps in oxidative phosphorylation and the possibility is suggested that Complexes I, IV and steps other than the six steps are activated during regeneration. The activation of Complexes I and IV was attributed to their increased activity, since it was not accompanied by an increase in the amount of the enzymes.

Optical determination of fatty change of the graft liver with near-infrared time-resolved spectroscopy.

A novel method for quantifying the fatty change of the graft liver by characterizing the optical property of the tissue was introduced. A wide range of lipid content in the rat liver was obtained by using different feeding regimens, with lipotropic chow (choline/methionine deficient or low chow). The liver was removed and flushed with Krebs-Ringer buffer solution with 3% albumin, and the optical properties of the liver, i.e., absorption and reduced scattering coefficients (mu(a) and mu(s)'), were measured by time-resolved spectroscopy. The fatty liver showed lower mu(a) and higher mu(s)' than the normal liver. Lower mu(a) and lower succinate dehydrogenase activity of the fatty liver suggested that the decrease in mu(a) might indicate a decrease in the mitochondrial content. The value of mu(s)' was positively correlated with the lipid content of the liver, which indicates that fat droplets inside the hepatocyte act as dominant scatterers. To subtract the contribution of the mitochondrial compartment to mu(s)', the ratio of mu(s)' to mu(a) (mu(s)':mu(a)) was useful for the assessment of the lipid content of the liver. These findings were also relevant with prediction of light scattering by the Mie theory. It was concluded that mu(a) and mu(s)' of the graft liver, measured by time-resolved spectroscopy, can be useful parameters for quantifying the fatty change of the graft liver.

Postoperative monitoring of the oxygenation state of the graft liver in cases with hepatopulmonary syndrome.

Postoperative changes in the oxygen saturation of hemoglobin in the graft liver (graft SO2) were monitored by near-infrared spectroscopy in four cases complicated by hepatopulmonary syndrome. A plastic cylinder was placed in the abdominal wall, and optical measurements of the graft liver were obtained through this window. Our findings were as follows; (1) graft SO2 decreased after abdominal wall closure, and decreased further 1 day after surgery. (2) Graft SO2 was maintained despite severe hypoxemia, with partial pressure of oxygen in arterial blood as low as 50 mmHg. High hematocrit was beneficial for oxygenating the graft. (3) Graft livers could tolerate hypoxia with a graft SO2 as low as 20%. (4) It may be useful to monitor graft SO2 during the critical period after transplantation for the assessment of graft function.

Backgrounds of early intragraft immune activation and rejection in liver transplant recipients. Impact of graft reperfusion quality.

In solid organ transplantation, acute rejections are most frequent during the first weeks. The aim of this study was to investigate the relationship between graft reperfusion injury and later immune responses against the graft. Intragraft immune activation was routinely monitored by transplant aspiration cytology in 47 recipients of hepatic allografts. As a parameter of reperfusion quality, oxygen saturation of hemoglobin (SO2) in hepatic tissue was determined intraoperatively by a near-infrared spectroscopy. Grafts that presented aspiration cytology scores of 2 or more (i.e., more than 10% of lymphocytes activated) at 1 week after operation (group I, n = 14) were associated with a higher heterogeneity of hepatic tissue SO2 at the end of operation (coefficient of variation in 12 points 18.3 +/- 18.3%, mean +/- SD) than grafts with no or very mild intragraft immune activation (group II, n = 33, 9.2 +/- 4.2%; P < 0.01). Group I was also accompanied by higher postoperative peak glutamic oxalacetic transaminase level (corrected by graft size, P < 0.05) and higher donor age (43.9 +/- 12.9 vs. 32.6 +/- 13.9 years, P < 0.02). Heterogenous reperfusion (P < 0.01), higher peak glutamic oxalacetic transaminase level (P < 0.01), and higher donor age (P < 0.05) were also associated with clinical rejection at 1 week (n = 10), but not with later-onset rejection (n = 11). These data suggest that intragraft immune activation and clinical rejection in the early phase after hepatic engraftment are strongly influenced by graft injury, which can be recognized early after reperfusion.

Living related liver transplantation across ABO blood groups.

We performed 13 pediatric liver transplants from ABO-incompatible living related maternal or paternal donors using a combination of preoperative removal of isohemagglutinin and postoperative immunosuppressive therapy with FK506 and prophylactic OKT3. Tissue near-infrared spectroscopy was applied to evaluate hemodynamics using the hemoglobin of red cells in the sinusoids as an index. The data obtained indicated that the preoperative removal of isohemagglutinin prevented hyperacute humoral rejection with hemorrhagic infiltration in the sinusoids in 10 successful cases. The incidence of acute rejection was not significantly different among ABO-identical, -compatible, and -incompatible groups. The estimated 1-year survival rate of the ABO-incompatible group was 77%.

Increased platelet aggregability in response to shear stress in acute myocardial infarction and its inhibition by combined therapy with aspirin and cilostazol after coronary intervention.

Although antiplatelet therapy with a specific inhibitor of phosphodiesterase-3 cilostazol improves stent patency compared with use of aspirin (ASA) alone, the specific role of cilostazol on platelet aggregation in patients with acute myocardial infarction (AMI) is less well understood. Thirty-six patients with AMI who were successfully treated with primary angioplasty were randomized to 3 antiplatelet regimens: ASA alone (n = 12), ASA + ticlopidine (n = 12), and ASA + cilostazol (n = 12). We measured shear stress-induced platelet aggregation (SIPA) using a modified cone-plate viscometer on admission and on day 7, and evaluated the inhibitory effects of combination therapy with ASA + cilostazol on SIPA. Compared with cases of stable coronary artery disease, significant increases in SIPA and plasma von Willebrand factor activity were observed in patients with AMI before they received antiplatelet therapy. On day 7 after primary angioplasty, ASA did not inhibit SIPA (65 +/- 15% vs 57 +/- 11%, p = 0.086), whereas both combination therapies of ASA + ticlopidine and ASA + cilostazol significantly inhibited SIPA in patients with AMI (ASA + ticlopidine: 61 +/- 15% vs 45 +/- 13%, p <0. 0001; ASA + cilostazol: 64 +/- 14% vs 43 +/- 9%, p <0.005). There was a significant correlation of SIPA with adenosine diphosphate (ADP)-induced platelet aggregation (r = 0.412, p = 0.003) and with plasma von Willebrand factor activity (r = 0.461, p = 0.0008). These data suggest that patients with AMI have increased platelet aggregability in response to high shear stress. Combined antiplatelet therapy with ASA + cilostazol appears to be as effective as therapy with ASA + ticlopidine for reducing SIPA in patients with AMI who are undergoing primary angioplasty.

Optical analysis of cirrhotic liver by near infrared time-resolved spectroscopy.

The severity of liver cirrhosis was related with the optical properties of liver tissue. Various grades of liver cirrhosis were produced in rats by intraperitoneal injection of thioacetamide (TAA) for different periods: 4 weeks, 8 weeks, 12 weeks, and 16 weeks. Optical properties of the liver, absorption coefficient (µa) and scattering coefficient (µs'), were measured by near-infrared time-resolved spectroscopy. Histological examination confirmed cirrhotic changes in the liver, which were more severe in rats with TAA administration for longer periods. The µa increased in 4- and 8-week rats, and then decreased in 12- and 16-week rats. The µa of blood-free liver decreased as liver cirrhosis progressed. The hemoglobin content in the liver calculated from the µa values increased in 4- and 8-week rats and decreased in 12- and 16-week rats. The µs' decreased in the cirrhotic liver, probably reflecting the decrease in the mitochondria content. It was shown that µa and µs' determination is useful to assess the severity of liver cirrhosis. © 1999 Society of Photo-Optical Instrumentation Engineers.

Energy metabolism of the liver in brain dead dogs assessed by 31P-NMR spectroscopy and arterial ketone body ratio.

The changes in hepatic energy state were assessed by 31P-nuclear magnetic resonance spectroscopy (31P-MRS) and arterial ketone body ratio (AKBR) in brain dead dogs. 31P-MRS and AKBR were measured before and at 3 hours after brain death. Wiggers' shock model was employed to compare the energy metabolism during hypotension. 1) The brain death model: Systemic blood pressure changed from 178.3/115.0 mmHg (mean) in the control period, to 259.5/162.5 mmHg during Cushing phenomenon (CU period) and to 63.3/51.7 mmHg after completion of brain death (BD period). beta-ATP/Pi increased from 1.27 +/- 0.14 (mean +/- SEM) to 1.46 +/- 0.16 in the early CU period, and then decreased to 1.11 +/- 0.15 at 60 minutes after BD, followed by a gradual increase to 1.33 +/- 0.13 at 3 hours after BD. Intracellular pH (pHi) increased alkaline to the control value. AKBR decreased from 1.10 +/- 0.26 to 0.46 +/- 0.15 in the CU period (p less than 0.05) and then increased to 1.48 +/- 0.25 after BD. 2) Wiggers' shock model: Systemic blood pressure was 190.0/112.5 mmHg in the control period, 83.8/51.3 mmHg during exsanguination (EX period) and 185.0/117.0 mmHg after retransfusion (RT period). beta-ATP/Pi decreased from 1.17 +/- 0.13 to 0.61 +/- 0.10 in the EX period (p less than 0.05) and increased to 1.37 +/- 0.08 in the RT period. The pHi deviated from 7.33 +/- 0.07 to 6.82 +/- 0.14 in the EX period (p less than 0.01) and to 7.51 +/- 0.21 in the RT period. AKBR decreased from 1.00 +/- 0.11 to 0.21 +/- 0.04 in the EX period and increased to 1.08 +/- 0.12 in the RT period. The energy metabolism of the liver was well maintained in the state of brain death in spite of remarkable hypotension, although that was not the case with Wiggers' shock model. It was suggested that the combination of 31P-MRS and AKBR was useful for the evaluation of graft liver viability.

Application of near-infrared time-resolved spectroscopy to rat liver--a preliminary report for surgical application.

The applicability of near-infrared time-resolved spectroscopy to rat liver surgery was investigated. First, the technical reliability in determining the absorption coefficient (mu(a)) and reduced scattering coefficient (mu'(s)) of the liver was checked. Next, boundary effects in determining mu(a) and mu'(s) of the rat liver were examined. Finally, changes in mu(a) and mu'(s) of rat liver with ischaemia were directly measured by TRS. Our TRS system showed that the mu(a) value held a linear correlation with the ink concentration in a lipid emulsion until mu(a) reached 1.2 cm(-1), while the mu'(s) was fairly independent. The mu(a) values of blood-free rat liver and blood-containing rat liver at 780 nm were observed to be 0.43 cm(-1) and 0.67 cm(-1) by using the matching method, indicating that TRS is reliable in determining mu(a) and mu'(s) of the liver. Possible errors in mu(a) and mu'(s) determination due to the boundary effects of the rat liver were as small as 7%, when the mu(a) value was as high as observed for the liver. The oxygen saturation of haemoglobin (SO2) was changed from 64.9% to 8.0%, and the haemoglobin content (THB) from 189.1 microM to 131.6 microM by ischaemia. Mu'(s) dynamically changed in the range 7.06 cm(-1) to 11.36 cm(-1). We conclude that time-resolved measurement is applicable in the high-mu(a) region observed in the liver, and can give quantitative estimations of SO2 and THB in the liver.

Oxygenation and blood volume changes in flaps according to near-infrared spectrophotometry.

OBJECTIVE: To test the ability of near-infrared spectrophotometry (NIRS) to predict vascular compromise in flaps postoperatively. DESIGN: Pilot study. SUBJECTS: Eleven denervated latissimus dorsi flaps were assessed in 8 pigs. INTERVENTIONS: Flaps were isolated on their vascular pedicle. We used NIRS to demonstrate tissue oxygen saturation and quantities of deoxygenated hemoglobin and oxygenated hemoglobin when flaps underwent venous or arterial occlusions. Oxygen saturation (percentage of oxygenated hemoglobin) was calculated as the difference between the 2 light intensities (860-750 nm) with the use of 2 time periods: preoperative (80%) oxygen saturation and during arterial occlusion (0%) oxygen saturation with NIRS. Blood volume changes within the flap were also measured. RESULTS: Arterial occlusion resulted in significant decreases in oxygen saturation and in blood volume with immediate recovery. Venous occlusion resulted in an initial rapid increase in blood volume with no appreciable early deoxygenation. CONCLUSIONS: Near-infrared spectrophotometry appears promising as a noninvasive, low-cost, portable bedside monitor that can demonstrate in real time changes in blood volume and oxygen saturation within a flap at a variety of tissue depths.

Giant malignant phyllodes tumor with(99m)Tc-Ses-tamibi accumulation: Report of a case.

We report a case of a giant malignant phyllodes tumor examined by(99m)Tc-ses-tamibi (MIBI) mammoscintigraphy. The patient was a 51 year-old woman who complained of bleeding from a large mass in her right breast. The tumor was well circumscribed, with an ulcerized surface. The accumulation of(99m)Tc-MIBI in the tumor was recognized on(99m)Tc-MIBI scintigraphy. A standard radical mastectomy was performed with a wide margin of skin. The resected specimen measured 20 X 17 X 13 cm, weighed 2100 g and was histologically diagnosed as a malignant phyllodes tumor. The skin defect was reconstructed by a rectus abdominis musculocutaneous flap, with good cosmetic results.(99m)Tc-MIBI scintigraphy may have the potential to distinguish a malignant from benign phyllodes tumors.

Extension of surgical indication for advanced hepatocellular carcinoma: is it possible to prolong life span or improve quality of life?

BACKGROUND/AIMS: We have tried to break through the limitations of treatment for advanced hepatocellular carcinoma (HCC), which has been regarded as a contraindication for surgical treatment. MATERIALS AND METHODS: In 640 cases of hepatic resection for Liver cancer, we analyzed 55 cases of HCC with tumor thrombi in the trunk or first branch of the portal vein (PV) which required additional PV thrombectomy, 5 cases with direct invasion or compression to the inferior vena cava (IVC) which required replacement of IVC with a polytetrafluoroethylene (PTFE) tube, 9 cases with involvement of the extrahepatic bile duct (BD) which required additional extirpation of tumor fragments in the BD, 6 cases with tumor thrombi in the IVC which required IVC thrombectomy, and 4 cases of huge main tumor with intrahepatic metastasis in the entire liver which required intraoperative ethanol injection. RESULTS: Mean survival times in these groups were 796, 717, 650, 220, and 147 days, respectively. All patients with IVC thrombi and large tumor with intrahepatic metastasis in the entire liver died of early recurrence in spite of surgical treatment. By contrast, half of the patients with PV thrombi, BD involvement and IVC invasion or compression survived approximately 500 days because of a combination of hepatic resection, additional intraoperative treatment and postoperative treatment, and some patients could enjoy a longer life. CONCLUSIONS: Multimodality treatment including hepatic resection should be encouraged for advanced HCC patients with PV thrombi, BD involvement or compression or invasion of the IVC, as long as the remnant liver can overcome postoperative liver failure.

Analysis of factors affecting the graft oxygenation state in living related liver transplantation.

BACKGROUND/AIMS: In liver transplantation, graft dysoxia after reperfusion may lead to graft failure. The aim of this study is to investigate the relationship between the factors, which were supposed to affect the oxygen supply to the graft, and the oxygenation state of the graft in order to determine which factor is important to prevent the graft from dysoxia. MATERIALS AND METHODS: The relationship between oxygen supply and oxygenation state of the graft was investigated in 56 successful cases of living related liver transplantation. Factors affecting the oxygen supply to the graft were considered as follows; portal venous flow (PVF), mean velocity of the hepatic artery (HA-Vm), hemoglobin concentration in the peripheral blood (Hb), size of the graft liver relative to the recipient body weight (G/R ratio), partial oxygen pressure in the arterial blood (PaO2), and rate-pressure product (BP*PR). Oxygenation state of the graft was estimated by oxygen saturation of hemoglobin in the graft tissue (graft SO2) as measured by tissue near infrared spectroscopy. RESULTS: 1) Graft SO2 was rather independent of PVF and HA-Vm probably due to compensatory interrelation between the portal venous flow and hepatic arterial flow. 2) Significant correlation between G/R ratio and graft SO2 was observed after portal reflow (p < 0.01), but the correlation diminished after hepatic arterial reflow. Positive correlation between G/R ratio and AKBR after portal reflow suggested that the graft with large G/R ratio is likely to suffer dysoxia early after reperfusion. 3) Graft SO2 was positively correlated with Hb (p < 0.05), while there was no significant correlation between graft SO2 and PaO2 or BP*PR. CONCLUSION: This study clarified the contribution of the factors which were supposed to affect the oxygen supply to the graft and the oxygenation state of the graft, and which factor is important to prevent the graft from dysoxia.

Three patients with bilateral breast tumors examined by technetium-99m-sestamibi scintimammography.

We presented three patients with bilateral breast tumors (one with breast cancers, one with breast cancer and fibroadenoma, and one with fibroadenomas) examined by 99mTc-hexakis 2-methoxy-isobutylisonitrile (MIBI) scintimammography. In all cases 99mTc-MIBI uptake was recognized only in the breast cancers. 99mTc-MIBI scintimammography was useful in evaluating bilateral breast tumors since preoperative diagnosis is valuable in determining correct surgical treatment.

Technetium-99m-sestamibi scintimammography of benign and malignant phyllodes tumors.

We presented two cases of phyllodes tumor of the breast examined by 99mTc-sestamibi (MIBI) two-phase scintimammography. In the case with malignant phyllodes tumor, 99mTc-MIBI accumulation was recognized on both early and delayed images. In the case with benign phyllodes tumor, however, 99mTc-MIBI accumulation was recognized on only the early image. 99mTc-MIBI delayed imaging may have the potential to distinguish between benign and malignant phyllodes tumors.