Mortality risk in patients with preserved ratio impaired spirometry: assessing the role of physical activity.

BACKGROUND: While all-cause mortality is reportedly increased in preserved ratio impaired spirometry (PRISm), no remedial efforts have been suggested. AIM: To study the ability of physical activity (PA) on reducing the morality increased in PRISm patients. DESIGN: We prospectively enrolled a cohort of Taiwanese adults from 1994 to 2018 in a health surveillance program. METHODS: Mortality risks of those who were inactive were compared against those meeting the current recommendation of 150 min/week of PA. Cox proportional hazards models were used for hazard ratios and life table method was for estimating loss of life expectancy. RESULTS: A total of 461 183 adults were enrolled. Among them, one-seventh of the cohort (65 832 or 14.3%) had PRISm, and 53.1% were inactive. Those who were inactive with PRISm had 28% increased mortality from all-cause, 45% from cardiovascular diseases (CVDs) and 67% from respiratory disease, with a 3-year reduction in life expectancy (males, 3.72 and females, 2.93). In PRISm patients who met the exercise recommendation, excess mortality was reduced by two-third, both all-cause (from 28% to 9%) and CVD (from 45% to 15%). CONCLUSION: PRISm involves a large portion of general population (14.3%) and shortens life expectancy by 3 years. More than half of the subjects were physically inactive, and adherence to 150 min/week of PA was associated with a two-third reduction of excess mortality from all cause and from CVD. Recommending PA among those with PRISm might be highly beneficial, although exercise alone may not eliminate all risks associated with PRISm.

Nutritional Status and Renal Function in Relation to Frailty among the Community-Dwelling Elderly Taiwanese Population.

OBJECTIVES: Frailty is a significant public health and clinical issue among the elder population. This study aimed to evaluate the nutritional status and renal function in relation to frailty among elderly Taiwanese. DESIGN: We administered community-based health surveys to the elder population in Chiayi County, Taiwan, from 2017 to 2019. MEASUREMENTS: We measured nutritional status (including serum albumin and total protein levels), renal function (including serum blood urea nitrogen, creatinine, urine protein, and urine creatinine levels), hand grip strength (GS) and calculated appendicular muscle mass (AMM). RESULTS: The study recruited 3739 participants (2139 women). Participants of both sexes with normal GS had higher serum albumin levels and lower urine protein/creatinine ratios (UPCRs). For the men with normal and weak GS, serum albumin levels were 4.15 ± 0.2 and 4.10 ± 0.2 g/dL (p < 0.01), and UPCRs were 123.1 ± 219.6 and 188.7 ± 366.2 (p < 0.001), respectively. GS was positively correlated with serum albumin and urine creatinine levels (r = 0.136 and 0.177, both p < 0.001). AMM was also positively correlated with serum albumin and urine creatinine levels (r = 0.078 and 0.091, both p < 0.001). In the multivariate regression model, for every 1 g/dL increase in serum albumin level, there was a 1.9 and 1.7-kg increase in GS for men and women (p < 0.05 and p < 0.01), respectively. The final model for predicting GS included age, albumin, BUN, and UPCR (urine creatinine for women) which presented a variance of 22.1% and 13.8%, respectively. CONCLUSION: Proper dietary nutritional intake and maintaining renal function are key elements for preventing frailty among elder population in Taiwan.

A user-friendly objective prediction model in predicting colorectal cancer based on 234 044 Asian adults in a prospective cohort.

BACKGROUND: Prediction models of colorectal cancer (CRC) had limited application for not being user-friendly. Whether fecal immunochemical tests (FITs) can help predict CRC has been overlooked. PATIENTS AND METHODS: With 1972 CRCs identified, 234 044 adults aged ≥40 years were successively enrolled between 1994 and 2008. Prediction models were developed by questionnaire/medical screening and quantitative FIT. NNS (number needed to scope to find one cancer) is time dependent, spanning entire study period. Significant 'risk factors' were family history, body mass index, smoking, drinking, inactivity, hypertension, diabetes, carcinoembryonic antigen, and C-reactive protein. RESULTS: Positive FIT (≥20 µg/g hemoglobin/feces) had cancer risk 10-fold larger than negative FIT, and within each age group, another 10-fold difference. The C statistic of FIT (0.81) with age and sex alone was superior to the 'common risk-factors' model (0.73). NNS, stratified by age and by FIT values, demonstrated a scorecard of cancer risks, like 1/15 or 1/25, in 5 years. When FIT was negative, cancer risk was small (1/750-1/3000 annually). The larger the FIT, the sooner the appearance of CRC. For every 80-µg/g increase of FIT, there were 1.5-year earlier development of CRC incidence and 1-year earlier development of CRC mortality, respectively. Given the same FIT value, CRC events appeared in the proximal colon sooner than the distal colon. CONCLUSIONS: A simple user-friendly model based on a single FIT value to predict CRC risk was developed. When positive, NNS offered a simple quantitative value, with a better precision than most risk factors, even combined. When FIT is negative, risk is very small, but requiring a repeat every other year to rule out false negative. FIT values correlated well with CRC prognosis, with worst for proximal CRC.

Heart rate and suicide: findings from two cohorts of 533 000 Taiwanese and 75 000 Norwegian adults.

OBJECTIVE: To investigate the association of resting heart rate with suicide in two large cohorts. METHOD: The MJ cohort (Taiwan) included 532 932 adults from a health check-up programme (1994-2008). The HUNT cohort (Norway) included 74 977 adults in the Nord-Trøndelag County study (1984-1986), followed up to 2004. In both cohorts heart rate was measured at baseline, and suicide was ascertained through linkage to cause-of-death registers. Risk of suicide was estimated using Cox proportional hazards models. RESULTS: There were 569 and 188 suicides (average follow-up period of 8.1 and 16.9 years) in the MJ and HUNT cohorts respectively. Sex- and age-adjusted hazard ratio for every 10 beat increase in heart rate per minute was 1.08 (95% Confidence Interval 1.00-1.16) and 1.24 (1.12-1.38) in the MJ and HUNT cohorts, respectively. In the MJ cohort this association was confined to individuals with a history of heart diseases vs. those without such a history (P for interaction = 0.008). In the HUNT cohort the association did not differ by history of heart diseases and was robust to adjustment for health-related life style, medication use, and symptoms of anxiety and depression. CONCLUSION: Elevated resting heart rate may be a marker of increased suicide risk.

Sjögren's syndrome associated with protein losing gastroenteropathy manifested by intestinal lymphangiectasia successfully treated with prednisolone and hydroxychloroquine.

Protein-losing gastroenteropathy (PLGE), a rare manifestation of primary Sjögren's syndrome (SS), is characterized by profound edema and severe hypoalbuminemia secondary to excessive serum protein loss from the gastrointestinal tract and is clinically indistinguishable from nephrotic syndrome. We report a case of a 30-year-old Taiwanese woman with PLGE-associated SS. In addition to a positive Schirmer's test, she had eye-dryness, thirst, and high levels of anti-SSA antibodies, fulfilling SS criteria. PLGE diagnosis was highly appropriate given the clinical profile of hypoalbuminemia, hypercholesterolemia, pleural effusion, and ascites, with absent cardiac, hepatic, or renal disease. We were unable to perform technetium-99 m-labeled human serum albumin scintigraphy ((99m)Tc-HAS). However, the patient's edema and albumin level improved dramatically in response to a 3-month regime of oral prednisolone followed by oral hydroxychloroquine.

Heart rate variability during hemodialysis and following renal transplantation.

Previous studies have shown awareness of uremic dysfunction in end-stage renal disease (ESRD) patients. Dysautonomia in ESRD patients may be reversible after renal transplantation. We used a power spectral analysis (PSA) of heart rate variability (HRV) to assess alterations of autonomic activity in 14 controls and 14 nondiabetic hemodialysis ESRD patients who had undergone renal transplantation. Compared with matched control subjects, the power frequency determinations of low frequency (LF; 3.42 ln(ms(2)) vs 6.38 ln(ms(2)); P < .05 high frequency (HF; 2.29 ln(ms(2)) vs 5.27 ln(ms(2)); P < .05)), and total power (TP; 5.39 ln(ms(2)) vs 7.53 ln(ms(2)); P < .05) were significantly suppressed in ESRD patients undergoing hemodialysis. ESRD patients showed significantly improved HRV after renal transplantation. After renal transplantation, there was no significant difference in the TP (6.82 ln(ms(2)) vs 7.53 ln(ms(2)); P = .15) component between measurements in both patient subgroups. We further divided the ESRD patients into 2 groups based on their pretransplantation HRV, observing alterations in HRV after renal transplantation. Patients with significantly improved HRV were those with more suppressed HRV before transplantation (HF <3 In(ms(2)). Autonomic dysfunction in ESRD patients was not irreversible even if severe, and recovery was observed as early as 6 months after transplantation.

Gene expression of P-glycoprotein and cytochrome P450 3A4 in peripheral blood mononuclear cells and correlation with expression in liver.

Long-term immunosuppression in renal transplant recipients generally includes calcineurin inhibitors (CNIs), which demonstrate marked interindividual diversity and a narrow therapeutic range. In the clinical setting, it is important to reach therapeutic drug concentrations to prevent allograft rejection. The same immunosuppressant dosage leads to different drug concentrations. Therefore, we investigated factors that influence the metabolism of immunosuppressant agents. The CNIs are substrates of cytochrome P450 (CYP450) and P-glycoprotein. The CYP450 3A genotype significantly influences CNI concentration. Differences in expression of these proteins may explain interindividual pharmacokinetic variations. However, it is risky and impractical to obtain specimens from the liver in renal transplant recipients. Therefore, we investigated the correlation of gene expression between peripheral blood mononuclear cells (PBMCs) and liver parenchyma. We observed that the correlation of relative P-glycoprotein gene expression between PBMCs and liver is not significant (r2=0.03; P=.65). In addition, the correlation of CYP450 3A4 gene expression between PBMCs and liver is not strong (r2=0.23; P=.42). The expression level of CYP450 3A5 is too low to be detected in the sample from PBMCs.

Combined sirolimus-calcineurin inhibitor immunosuppressive therapy in simultaneous heart and kidney transplantation: a retrospective analysis of a single hospital's experience.

Simultaneous heart and kidney transplantation (SHKT) has become an accepted therapeutic option for patients with end-stage heart failure associated with end-stage renal disease. The immunosuppressive therapy is usually based upon a heart transplantation protocol using a calcineurin inhibitor (CNI). Sirolimus (SRL) is a potent nonnephrotoxic immunosuppressant with antiproliferative activity in nonimmune cells. Its use has recently been reported to show less nephrotoxicity among both heart and kidney transplants. However, the data for the SHKT are limited. We retrospectively examined the causes of 5 patients who received combined SRL-CNI immunosuppressive therapy with reduced CNI doses from 2003 to 2009. There was no mortality during follow-up. Two of the 3 patients who received a conversion regimen recovered renal function. One who suffered severe proteinuria after transplantation proceeded to hemodialysis at 3 years after conversion. Both of the patients who received the combined regimen de novo remained stable regarding their renal function. Cardiac function was stable in these patients; there was neither allograft rejection nor allograft coronary vasculopathy. We observed that patients without dyslipidemia or hyperuricemia before SHKT were less likely to develop these disorders under the combined regimen. Early medical intervention after close follow-up of lipid and uric acid values by dose adjustments resulted in a stable status of our patients.

Simultaneous heart and kidney transplantation for combined cardiac and renal failure.

Simultaneous heart and kidney transplantation (SHKT) is feasible for combined cardiac and renal failure. Herein we reviewed our 10-year experience in SHKT. Six patients underwent SHKT from June 1995 to December 2004. Their ages ranged from 13 to 63 years old with a mean of 45.5 +/- 15.8 years. They were all men except one girl, who was the youngest (aged 13) who suffered from dilated cardiomyopathy with congestive heart failure and chronic renal failure due to systemic lupus erythematosus. Because of aggravating heart failure, she changed from hemodialysis to peritoneal dialysis. Because of intractable heart failure, she underwent SHKT from a 24-year-old female donor. All received hemodialysis before SHKT. The indications for heart transplantation included dilated cardiomyopathy (n = 3), ischemic cardiomyopathy (n = 1), cardiac allograft vasculopathy (n = 1), and cardiac allograft failure (n = 1). The immunosuppressive protocol and rejection surveillance were these employed for heart transplantation. No operative mortality was noted in this study. The 1-year and 5-year survival rates were the same, 83%. The 10-year survival rate was 55%. No cardiac or renal allograft rejection was noted. No renal allograft loss was noted. There were two late mortalities: the one, who underwent redo heart transplantation for coronary artery vasculopathy died of cardiac allograft failure 1 year after SHKT. The other patient died of massive ischemic necrosis of the intestine at 6 years after SHKT. Our experience showed that SHKT had good short- and long-term results without increasing immunosuppressive doses. End-stage failure of either the heart or the kidney did not preclude heart plus kidney transplantation.

Infrared photodissociation spectroscopy of Mg(+)(H2O)Ar(n) complexes: isomers in progressive microsolvation.

Ion-molecule complexes of the form Mg(H2O)Ar(n)+ (n = 1-8) are produced by laser vaporization in a pulsed-nozzle cluster source. These complexes are mass-selected and studied with infrared photodissociation spectroscopy in the O-H stretch region. The spectra are interpreted with the aid of ab initio calculations on the n = 1-5 complexes, including examination of various isomeric structures. The combined spectroscopic and theoretical studies reveal the presence of multiple isomeric structures at each cluster size, as the argon atoms assemble around the Mg(+)(H2O) unit. Distinct infrared resonances are measured for argon-on-metal, argon-on-OH and argon-on-two-OH isomers.

Effects of and predictors for tacrolimus rescue therapy among renal transplant patients under cyclosporine-based immunosuppression.

BACKGROUND: Though cyclosporine has dramatically decreased rejection rates and improved graft survival rates of renal allografts, there is still a remarkable rate of acute rejection and progressive deterioration of renal function after transplantation. Rescue therapy with tacrolimus has been used for allografts failing under cyclosporine-based treatment in order to get some renal functional recovery or stabilization. The aim was to evaluate tacrolimus rescue therapy for failing allografts under cyclosporine-based immunosuppression for possible prediction factors for success. PATIENTS AND METHODS: Thirty-five renal allograft recipients with failing transplants under cyclosporine-based immunosuppression were enrolled into this study. Renal function was evaluated by reciprocal serum creatinine level (1/Cr) and calculated CCr. The slope of changes in 1/Cr and CCr were calculated before and after tacrolimus therapy. The possible risk factors that affect the outcome of tacrolimus rescue therapy were analyzed. RESULTS: Nineteen patients showed improved renal function (group 1) and 16 patients, persistent deterioration (group 2) after rescue therapy. Group 1 showed positive slopes of changes of 1/Cr and CCr after rescue therapy. Group 2 patients showed persistent negative slopes although less negative than before rescue therapy. Only the posttransplant time was the significant predictive factor for successful tacrolimus therapy (P = .018). CONCLUSION: Tacrolimus rescue therapy improved or stabilized renal function in some patients with failing grafts under cyclosporine-based immunosuppression. To assure a successful rescue effect, it should be given early after transplantation, if there is a tendency toward deterioration of renal function.

Evaluation of cyclosporine C2 levels in long-term stable renal allograft recipients.

BACKGROUND: The use of cyclosporine was traditionally monitored by the trough level (C(0)). However, the immunosuppressive effects of cyclosporine correlate with its drug exposure, represented by the area under curve (AUC). It was also noted that cyclosporine C(0) level correlated with AUC poorly, while C(2) level (concentration at 2 hours after drug administration) satisfactorily correlated with AUC. Most recent studies concern the use of C(2) levels in de novo renal transplant patients; target levels of C(2) have been suggested. There is rare discussion about the C(2) target level for long-term cyclosporine-maintenance patients. Our objectives were to analyze the cyclosporine C(2) levels of patients more than 12 months after transplantation as well as changes in C(2) with time and the correlation between C(2) level and renal function. METHODS AND PATIENTS: This was a cross-sectional case-controlled study of 101 kidney recipients immunosuppressed with a cyclosporine-based regimen for at least 12 months. Both C(0) and C(2) levels were examined at various time points during outpatient clinic follow-up. The patients were stratified according to the time after transplant surgery, or to their renal function. RESULTS: The 101 patients were divided into three groups based on the time after renal transplant surgery. Groups 1, 2, and 3 represented patients transplanted for 1 to 3 years (n = 16), 4 to 6 years (n = 35), and more than 6 years (n = 50), respectively. The C(2) levels for each group were 657 +/- 232, 561 +/- 186, and 580 +/- 243 ng/mL, respectively, (P = NS). When stratified into low versus high C(2) groups, there were no significant differences in renal function both at the beginning and at the end of 1 year follow-up. Seven of 67 patients shifted to stronger immunosuppression in the low C(2) group, but only 2/34 in the high C(2) group, a difference that was not significant (P = .234 by Fisher Exact Test). Patients with creatinine levels greater than 1.5 mg/dL or lower than 1.5 mg/dL showed no difference in C(2) on C(0) levels. Patients with deterioration of renal function during this period had no different C(2) levels as those with no deterioration of renal function. CONCLUSION: The average C(2) levels among long-term cyclosporine-maintained patients were significantly lower than those previously suggested. C(2) levels did not correlate with the long-term outcome of renal function in patients at least 1 year after renal transplantation.

Use of simulect can reduce the incidence of acute rejection and demonstrates with superior 3-year patient and graft survival rates in renal transplantation.

BACKGROUND: Acute rejection is a major cause of graft loss in renal transplantation. Because the highest risk for acute rejection is in the first month posttransplantation, improved prophylaxis could be most beneficial in this period. Simulect administration provides 30 to 45 days of immunoprophylaxis against acute rejection during the critical period after transplantation. OBJECTIVES: We sought to assess the incidence of acute rejection episodes and the safety and tolerability of Simulect plus Neoral immunosuppression. Patient and graft survival rates up to 3 years posttransplantation were evaluated. METHOD: Forty-one transplant recipients received Simulect by intravenous infusion of an initial 20-mg dose on the day of renal transplantation and a second 20-mg dose on day 4 posttransplant. All renal recipients received immunosuppression with Neoral and steroid. RESULTS: There were eight cases (19.5%) of acute rejection within 1 year. The rejection episodes were easily reversed with steroid pulse therapy in seven patients except for graft loss. The 1-, 2-, and 3-year graft survival rates were 95%, 93%, and 88%, respectively. Overall, the 3-year patient survival rate was 100%. CONCLUSIONS: Simulect in combination with Neoral and steroid-reduced the incidence of acute rejection without an increase in adverse events. The low incidence and severity of acute rejection may have led to the superior 3-year patient and graft survival rates in renal transplantation.