Effect of comorbid heart failure assessed by plasma B-type natriuretic peptide level on the activities of daily living in patients with hospitalization-associated disability after aspiration pneumonia.

PURPOSE: We investigated the effects of comorbid heart failure on rehabilitation outcomes in patients with hospitalization-associated disability after aspiration pneumonia (AP). METHODS: This study included 134 patients with hospitalization-associated disability after AP. Patients were classified into heart failure (B-type natriuretic peptide (BNP) ≧100 pg/ml, n = 39) and non-heart failure (BNP < 100 pg/ml, n = 95) groups, and the rehabilitation outcomes of both groups were compared. RESULTS: Rehabilitation effectiveness was lower in heart failure group than in non-heart failure group (21.1 ± 22.6% vs 36.2 ± 30.8, p < 0.01). The rate of independent walking at discharge in heart failure group (28.2%) was significantly lower than in non-heart failure group (53.7%). Multiple linear regression analysis revealed that age, male, handgrip strength, quadriceps strength, functional oral intake scale, Mini Nutritional Assessment Short Form, and BNP were significantly associated with rehabilitation effectiveness. DISCUSSION: Results suggest that comorbid heart failure has a negative impact on rehabilitation outcomes in patients with hospital-associated disability after AP.

CNP, the Third Natriuretic Peptide: Its Biology and Significance to the Cardiovascular System.

The natriuretic peptide family consists of three biologically active peptides: ANP, BNP, and CNP. CNP is more widely expressed than the other two peptides, with significant levels in the central nervous system, osteochondral system, and vascular system. The receptor that is mainly targeted by CNP is GC-B, which differs from GC-A, the receptor targeted by ANP and BNP. Consequently, the actions of CNP differ somewhat from those of ANP and BNP. CNP knockout leads to severe dwarfism, and there has been important research into the role of CNP in the osteochondral system. As a result, a CNP analog is now available for clinical use in patients with achondroplasia. In the cardiovascular system, CNP and its downstream signaling are involved in the regulatory mechanisms underlying myocardial remodeling, cardiac function, vascular tone, angiogenesis, and fibrosis, among others. This review focuses on the roles of CNP in the cardiovascular system and considers its potential for clinical application in the treatment of cardiovascular diseases.

B-Type Natriuretic Peptide (BNP) Revisited-Is BNP Still a Biomarker for Heart Failure in the Angiotensin Receptor/Neprilysin Inhibitor Era?

Myocardial wall stress, cytokines, hormones, and ischemia all stimulate B-type (or brain) natriuretic peptide (BNP) gene expression. Within the myocardium, ProBNP-108, a BNP precursor, undergoes glycosylation, after which a portion is cleaved by furin into mature BNP-32 and N-terminal proBNP-76, depending on the glycosylation status. As a result, active BNP, less active proBNP, and inactive N-terminal proBNP all circulate in the blood. There are three major pathways for BNP clearance: (1) cellular internalization via natriuretic peptide receptor (NPR)-A and NPR-C; (2) degradation by proteases in the blood, including neprilysin, dipeptidyl-peptidase-IV, insulin degrading enzyme, etc.; and (3) excretion in the urine. Because neprilysin has lower substrate specificity for BNP than atrial natriuretic peptide (ANP), the increase in plasma BNP after angiotensin receptor neprilysin inhibitor (ARNI) administration is much smaller than the increase in plasma ANP. Currently available BNP immunoassays react with both mature BNP and proBNP. Therefore, BNP measured with an immunoassay is mature BNP + proBNP. ARNI administration increases mature BNP but not proBNP, as the latter is not degraded by neprilysin. Consequently, measured plasma BNP initially increases with ARNI administration by the amount of the increase in mature BNP. Later, ARNI reduces myocardial wall stress, and the resultant reduction in BNP production more than offsets the increase in mature BNP mediated by inhibiting degradation by neprilysin, which lowers plasma BNP levels. These results suggest that even in the ARNI era, BNP can be used for diagnosis and assessment of the pathophysiology and prognosis of heart failure, though the mild increases early during ARNI administration should be taken into consideration.

Effect of short-duration, limited rehabilitation on maintenance of the activities of daily living in patients with acute phase of COVID-19.

[Purpose] To determine whether short-duration, limited rehabilitation is effective in patients with COVID-19. [Participants and Methods] Single-center, retrospective, observational study. Thirty-six inpatients were classified into the three groups: a close contact (CC) group with a negative polymerase chain reaction (PCR) test (n=14); a PCR-positive (PP) group (n=15); and a PCR-positive and transfer (PT) group with severe COVID-19 patients who were transferred to an acute care hospital for treatment and then returned to our hospital (n=7). Short-duration, limited rehabilitation was provided to the CC and PP groups in isolated rooms by a therapist wearing full personal protective equipment, and we assessed the changes in their activities of daily living. [Results] The patients' clinical characteristics at baseline were similar among the three groups. Functional Independence Measure scores in the CC, PP, and PT groups were not different at baseline (69 ± 29, 53 ± 26, and 63 ± 32), but differed after control of COVID-19 (63 ± 25, 47 ± 24, and 32 ± 19). Multivariate regression analysis showed that the implementation of a customized self-exercise program and the Mini Nutritional Assessment Short-Form at baseline were independently associated with Functional Independence Measure score after control of COVID-19. [Conclusion] These results suggest that even short-duration, limited rehabilitation may be effective for preventing decreases in activities of daily living in patients with COVID-19.

Cardiac Peptides-Current Physiology, Pathophysiology, Biochemistry, Molecular Biology, and Clinical Application.

The heart has long been considered a pumping organ, consisting of muscles [...].

NRSF-GNAO1 Pathway Contributes to the Regulation of Cardiac Ca2+ Homeostasis.

BACKGROUND: During the development of heart failure, a fetal cardiac gene program is reactivated and accelerates pathological cardiac remodeling. We previously reported that a transcriptional repressor, NRSF (neuron restrictive silencer factor), suppresses the fetal cardiac gene program, thereby maintaining cardiac integrity. The underlying molecular mechanisms remain to be determined, however. METHODS: We aim to elucidate molecular mechanisms by which NRSF maintains normal cardiac function. We generated cardiac-specific NRSF knockout mice and analyzed cardiac gene expression profiles in those mice and mice cardiac-specifically expressing a dominant-negative NRSF mutant. RESULTS: We found that cardiac expression of Gαo, an inhibitory G protein encoded in humans by GNAO1, is transcriptionally regulated by NRSF and is increased in the ventricles of several mouse models of heart failure. Genetic knockdown of Gnao1 ameliorated the cardiac dysfunction and prolonged survival rates in these mouse heart failure models. Conversely, cardiac-specific overexpression of GNAO1 in mice was sufficient to induce cardiac dysfunction. Mechanistically, we observed that increasing Gαo expression increased surface sarcolemmal L-type Ca2+ channel activity, activated CaMKII (calcium/calmodulin-dependent kinase-II) signaling, and impaired Ca2+ handling in ventricular myocytes, which led to cardiac dysfunction. CONCLUSIONS: These findings shed light on a novel function of Gαo in the regulation of cardiac Ca2+ homeostasis and systolic function and suggest Gαo may be an effective therapeutic target for the treatment of heart failure.

Molecular ratio of mature B-type natriuretic peptide in acute heart failure: an indicator for ventricular contractile recovery.

AIMS: The methodology to distinguish between the heart failure (HF) with recovered ejection fraction (HFrecEF) and those with continuously reduced ejection fraction (EF) (HFcrEF) on admission has not been established. We recently demonstrated that the ratio of plasma levels of pro-B-type natriuretic peptide (proBNP) to total BNP (proBNP plus mature BNP) is decreased on admission in patients with mild acute HF, but not in severe acute HF as a compensatory mechanism for activating cyclic GMP via increases of bioactive mature BNP. We aimed to test the hypothesis that the ratio of bioactive mature BNP to total BNP is associated with reverse remodelling capacity in patients with HF with reduced EF. METHODS AND RESULTS: Plasma proBNP and total BNP were measured in patients with acute decompensated HF by using specific and sensitive enzyme immunochemiluminescent assay. Estimated percent mature BNP (%emBNP) was calculated as ([total BNP - proBNP]/total BNP) × 100. We retrospectively identified the patients with reduced EF (≤40%, on admission) who had echocardiographic data after discharge (n = 93). We defined patients with increased EF by >10% during the follow-up term (median, 545 days) after the admission as HFrecEF group. We compared patient characteristics, %emBNP, and other biomarkers between HFrecEF and HFcrEF. Of the enrolled patients with HFrecEF (n = 32) and HFcrEF (n = 61), on admission, %emBNP was significantly higher in HFrecEF than in HFcrEF (44.1% vs. 36.9%; P < 0.05). There were no significant differences in left ventricular EF on admission between the two groups. The univariate analysis revealed that %emBNP on admission was associated with HFrecEF occurrence rate (P < 0.05), in contrast both total BNP and high-sensitive cardiac troponin-T levels were not associated with HFrecEF occurrence rate. CONCLUSIONS: The ratio of mature BNP to total BNP in plasma at the time of hospital admission may be predictive of left ventricular contractile recovery. Preservation of the capacity to convert proBNP to mature BNP, but not myocardial injury itself, is associated with future ventricular contractile recovery.

Effect of heart failure and malnutrition, alone and in combination, on rehabilitation effectiveness in patients with hip fracture.

BACKGROUND & AIMS: Heart failure and malnutrition are known to each negatively affect a patient's ability to improve their activities of daily living (ADL) through rehabilitation. Here, we investigated whether the negative effects of malnutrition and heart failure on ADL are additive in patients after hip fracture. METHODS: This retrospective observational cohort study included 155 patients with hip fracture admitted to convalescent rehabilitation wards. Nutritional status was measured with the Geriatric Nutritional Risk Index (GNRI). Heart failure was assessed using plasma B-type natriuretic peptide (BNP) levels. Based on their GNRIs and BNP levels, patients were classified into four groups: a high GNRI (≥92)-low BNP (<100 pg/ml) group (n = 54); high GNRI-high BNP (≥100 pg/ml) group (n = 7); low GNRI (<92)-low BNP group (n = 67); and low GNRI-high BNP group (n = 27). The main outcome was rehabilitation effectiveness (REs). To confirm above hypothesis, heart failure was also assessed by American College of Cardiology/American Heart Association (ACC/AHA) stage classification, whereas nutrition was assessed by Mini Nutritional Assessment Short Form (MNA-SF), either. RESULTS: REs in the high GNRI-low BNP group, high GNRI-high BNP group, low GNRI-low BNP group, and low GNRI-high BNP group were 64.8 ± 22.6%, 36.0 ± 22.0%, 40.6 ± 23.6% and 28.5 ± 25.9%, respectively. REs was higher in the high GNRI-low BNP group than in other three groups, and REs in the low GNRI-low BNP group was higher than in the low GNRI-high BNP group. When we evaluated heart failure by ACC/AHA stage classification instead of BNP, or evaluated nutrition by MNA-SF instead of GNRI, the similar results were demonstrated. Multiple linear regression analyses revealed that age (p < 0.01), handgrip strength (p < 0.01), GNRI (p < 0.05), and BNP (p < 0.01) were significantly associated with REs. CONCLUSIONS: These results suggest that malnutrition and heart failure are independently associated with REs and that they have an additive negative effect on improvement of ADL in elderly patients with hip fractures.

Potential pitfalls when interpreting plasma BNP levels in heart failure practice.

B-type (or brain) natriuretic peptide (BNP) is synthesized in cardiac myocytes and released constitutively into the circulation. Pressure/volume overload, neurohumoral factors, cytokines, and ischemia enhance BNP gene expression, and then precursor proBNP is produced. It has been thought that proBNP is cleaved into active BNP molecule and inactive marker molecule NT-proBNP intracellularly by processing enzyme furin, and they are released into the circulation. However, recent studies have shown that considerable amount of uncleaved proBNP circulates in the blood. The commercially available BNP assay kits consist of two antibodies that sandwich the BNP molecule. Therefore, if proBNP is present, BNP assay kit cross-reacts to proBNP and measures it as BNP. Therefore, it should be noted that the current BNP value is proBNP plus BNP. BNP and NT-proBNP have been established as a biomarker for heart failure patients presenting dyspnea. But many pitfalls are present for interpreting the BNP value. For example, the presence of renal dysfunction, age, female sex, atrial fibrillation, inflammation, hyperthyroidism, use of sacubitril/valsartan, and macro-proBNPemia overestimate BNP value, whereas the presence of obesity, immediately after acute coronary syndrome onset, and pericardial effusion underestimate BNP value. In the management for heart failure patients, BNP plays an important role. Therefore, clinicians should note the pitfall of interpretation of BNP and we describe the mechanism involved.

Effects of Banafine® , a fermented green banana-derived acidic glycoconjugate, on influenza vaccine antibody titer in elderly patients receiving gastrostomy tube feeding.

Immunosenescence can negatively affect cytokine production in elderly and may impair poor antibody responses to influenza vaccination and infection. Herein, the effects of Banafine® administration on influenza vaccine antibody titer in elderly patients (average age ∼80 years) receiving gastrostomy tube feeding were examined. In the double-blind, single-center, randomized clinical studies, 30 elderly bedridden patients were administered Banafine® or placebo for 8 weeks. At week 4, all patients received influenza vaccination against H1N1, H3N2, B/Yamagata, or B/Victoria. Blood biochemical indices and serum antibody titers were assessed. Banafine® administration significantly increased hemagglutination inhibition titers in response to vaccination against H1N1, H3N2, and B/Yamagata in the elderly patients (P < 0.05). Moreover, the seroconversion rate against H1N1 (47.1%) and H3N2 (29.4%) and seroprotection rate against H1N1 (71.4%) and both B strains (31.3% and 12.5%, respectively) were increased for the Banafine® group. These results suggest that Banafine® administration can increase antibody responses to influenza vaccination in bedridden hospitalized patients, and potentially modulate immune function in the elderly. PRACTICAL APPLICATION: Literature review suggested that most of the synbiotics are based on innate immunity, strain specific (probiotics), and are not consistently observed. Herein, in clinical studies we demonstrate that administration of Banafine® , a plant-based glycoconjugate, can increase antibody levels in bedridden hospitalized elderly patients following influenza vaccination.

Heart failure assessed based on plasma B-type natriuretic peptide (BNP) levels negatively impacts activity of daily living in patients with hip fracture.

Several studies have shown that nutrition and muscle strength were associated with functional recovery in patients with hip fracture. However, the impact of heart failure on the improvement of activity of daily living (ADL) in patients with hip fracture have not been fully investigated. The purpose was investigating the effect of heart failure on the ADL improvement by rehabilitation in patients with hip fracture. A total of 116 patients with hip fracture discharged from our convalescent rehabilitation ward were studied. Heart failure was assessed based on plasma B-type natriuretic peptide (BNP) levels on admission. ADL was assessed based on rehabilitation effectiveness (REs), which was calculated using the FIM instrument. Clinical, demographic, and nutritional variables were measured. Multiple regression analysis was performed with REs as the dependent variable; variables showing significant correlation with REs in univariate analyses were selected as independent variables. Based on plasma BNP levels, we assigned 39 patients to a Low group: 22 (17-25) median (interquartile) pg/mL, 39 to a Middle group: 52 (42-65) pg/mL, and 38 to a High group: 138 (93-209) pg/mL. REs, handgrip strength, Hb, albumin, and GNRI were higher and age was younger in the Low group than High group (each p < 0.01, respectively). Multiple linear regression analysis revealed that age (p < 0.05), sex (p < 0.05), handgrip strength (p < 0.01), FOIS at admission (p < 0.01), rehabilitation time per day (p < 0.01), and BNP (p < 0.05) were significantly associated with REs. The effect of rehabilitation on ADL improvement was significantly blunted in the High group compared to the Low group. In conclusion, these results suggest that heart failure assessed based on plasma BNP levels negatively impacts improvements in ADL achieved through rehabilitation in patients with hip fracture.

Change in the NT-proBNP/Mature BNP Molar Ratio Precedes Worsening Renal Function in Patients With Acute Heart Failure: A Novel Predictor Candidate for Cardiorenal Syndrome.

Background Early detection for worsening renal function (WRF) is indispensable in patients with acute decompensated heart failure (HF). We tested the hypothesis that the difference in the circulating levels of each B-type or brain natriuretic peptide (BNP) molecular form is associated with the occurrence of WRF. Methods and Results Circulating levels of proBNP, the NT-proBNP (N-terminal proBNP), and total BNP (proBNP+mature BNP) were prospectively measured in patients with acute decompensated HF using specific and sensitive enzyme immunochemiluminescent assays. An estimated mature BNP (emBNP) concentration was calculated by subtracting proBNP levels from total BNP levels. WRF was defined as a >20% decrease in the estimated glomerular filtration rate during the hospitalization. One-way repeated-measures ANOVA was used to compare the changes of variables between the patients with and without WRF. In patients with acute decompensated HF (New York Heart Association class III-IV; 96%) hospitalized for HF, NT-proBNP levels did not differ during the hospitalization between patients with and without WRF (n=42 and 140, respectively). By contrast, emBNP levels were lower in patients with WRF than in those without WRF on day 3 after admission. NT-proBNP/emBNP molar ratios were elevated on day 3 after admission in the patients with WRF, before estimated glomerular filtration rate declined, but were unchanged in patients without WRF. On day 3 after hospital admission, NT-proBNP/emBNP ratios were strongly associated with percentage decreases in estimated glomerular filtration rate. Conclusions These findings suggest that elevation of NT-proBNP/emBNP ratio precedes WRF in patients with acute HF and can be a potentially useful biomarker for risk stratification of cardiorenal syndrome.

Superiority of proatrial natriuretic peptide in the prognostic power in patients with acute decompensated heart failure on hospital admission: comparison with B-type natriuretic peptide and other natriuretic peptide forms.

Aims: There are significant differences in how atrial (A-type) and B-type natriuretic peptide (ANP and BNP) are secreted and metabolised, but there is little information available about the relative clinical significance of the two peptides. The aim of the present study was to investigate: (1) the association between the circulating level of each ANP molecular form and patient clinical background and (2) their prognostic power for patients with acute decompensated heart failure (ADHF). Methods: We used specific chemiluminescence enzyme immunoassays to prospectively evaluate the levels of six bioactive molecular forms of ANP (pro-ANP, ß-ANP and total ANP) and BNP (pro-BNP, N-terminal pro-BNP (NT-pro-BNP) and total BNP) in plasma samples collected from 173 patients with ADHF on their hospital admission. Results: We found that pro-ANP levels were strongly associated with left ventricular (LV) size and ejection fraction (p<0.001), but were not associated with left atrial size. Percent pro-ANP ([pro-ANP/total ANP]x100) was also associated with LV size and function. During the follow-up term (median: 469 days), composite adverse events (all causes of death or rehospitalisation for HF) occurred in 67 patients (38.7 %). Pro-ANP was significantly associated with composite adverse events even after adjusting by estimated glomerular filtration rate (eGFR) (p<0.05). In contrast, NT-pro-BNP was not independent of eGFR in the multivariate analysis. Conclusion: Circulating levels of pro-ANP are strongly associated with LV function and clinical outcomes of patients with ADHF. These findings suggest that during the acute phases of HF, pro-ANP has a prognostic power comparable with NT-pro-BNP independently of renal function.

Atrial and brain natriuretic peptides: Hormones secreted from the heart.

The natriuretic peptide family consists of three biologically active peptides: atrial natriuretic peptide (ANP), brain (or B-type) natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). Among these, ANP and BNP are secreted by the heart and act as cardiac hormones. Both ANP and BNP preferentially bind to natriuretic peptide receptor-A (NPR-A or guanylyl cyslase-A) and exert similar effects through increases in intracellular cyclic guanosine monophosphate (cGMP) within target tissues. Expression and secretion of ANP and BNP are stimulated by various factors and are regulated via multiple signaling pathways. Human ANP has three molecular forms, α-ANP, ß-ANP, and proANP (or γ-ANP), with proANP predominating in healthy atrial tissue. During secretion proANP is proteolytically processed by corin, resulting in secretion of bioactive α-ANP into the peripheral circulation. ProANP and ß-ANP are minor forms in the circulation but are increased in patients with heart failure. The human BNP precursor proBNP is proteolytically processed to BNP1-32 and N-terminal proBNP (NT-proBNP) within ventricular myocytes. Uncleaved proBNP as well as mature BNP1-32 and NT-proBNP is secreted from the heart, and its secretion is increased in patients with heart failure. Mature BNP, its metabolites including BNP3-32, BNP4-32, and BNP5-32, and proBNP are all detected as immunoreactive-BNP by the current BNP assay system. We recently developed an assay system that specifically detects human proBNP. Using this assay system, we observed that miR30-GALNTs-dependent O-glycosylation in the N-terminal region of proBNP contributes to regulation of the processing and secretion of proBNP from the heart.

Cutting Edge of Brain Natriuretic Peptide (BNP) Research　- The Diversity of BNP Immunoreactivity and Its Clinical Relevance.

Brain (or B-type) natriuretic peptide (BNP) is a cardiac hormone produced in the heart and an established biochemical marker for heart failure (HF) because the level in plasma increases in proportion to disease severity. Recently, the diversity of BNP molecular forms in the peripheral circulation, which includes mature BNP (BNP1-32) and its metabolites (BNP3-32, BNP4-32, and BNP5-32), was demonstrated. Moreover, studies showed that unprocessed BNP prohormone (proBNP) is also secreted from the heart, and its secretion is increased in patients with HF. Interestingly, BNP1-32, its metabolites, and proBNP are all detected as immunoreactive BNP by the currently available BNP assay system. Current N-terminal proBNP (NT-proBNP) assay systems also can react to both NT-proBNP and proBNP. In addition, the N-terminal region of proBNP and NT-proBNP are often O-glycosylated, which may result in underestimation of total NT-proBNP level, which includes both glycosylated and non-glycosylated NT-proBNP, by the NT-proBNP assay system. More recently, we have shown that miR30-GALNT-dependent O-glycosylation in the N-terminal region of proBNP affects the processing of proBNP and contributes to its secretion from the heart. The level of proBNP relative to BNP (proBNP/BNP ratio) in the coronary sinus is higher in patients with more severe HF. The proBNP/BNP ratio and the deglycosylated NT-proBNP level may be new and clinically useful biomarkers of HF.

Ratio of pro-B-type natriuretic peptide (BNP) to total BNP is decreased in mild, but not severe, acute decompensated heart failure patients: A novel compensatory mechanism for acute heart failure.

BACKGROUND: A recent study showed that both glycosylation of pro-B-type natriuretic peptide (BNP) and the proBNP/total BNP ratio are decreased in acute decompensated heart failure (ADHF). However, the following points regarding the proBNP/total BNP ratio have not been determined in patients with ADHF: 1) the relationship with the severity of ADHF, 2) the changes in the ratio during treatment, and 3) the relationship with cyclic guanosine monophosphate (cGMP)-generating activity. METHODS: Plasma proBNP and total BNP (proBNP+mature BNP) were measured in patients with ADHF (n=154). Measurement was performed on admission, 3 and 7days after admission, and before discharge using recently developed sandwich chemiluminescence enzyme immunoassays. The percent proBNP was calculated as: (proBNP/total BNP)×100. RESULTS: On admission, %proBNP was higher in patients with severe ADHF than in patients with mild ADHF (median: 61.7% vs. 56.2%, respectively; p<0.01), while the plasma cGMP/total BNP ratio, an index of the biological activity of BNP, was lower (p<0.001). In patients with severe ADHF, the higher %proBNP and lower cGMP/total BNP ratio were unchanged during hospitalization, whereas %proBNP increased gradually in patients with mild ADHF and the cGMP/total BNP ratio also increased at 3days after admission. CONCLUSION: These findings suggest that in patients with mild ADHF, compensation for heart failure occurs via increased proBNP processing, leading to increase of mature BNP and activation of the BNP/cGMP cascade. In contrast, this compensatory mechanism may be impaired in patients with severe ADHF and a vicious cycle can potentially occur.

Glottal Closure Surgery for Dysphagia Associated with Cerebral Hemorrhage, Tongue Defect, and Sarcopenia: A Case Report.

BACKGROUND: Dysphagia occurs often after oral cancer surgery. However, no case of dysphagia in combination with cerebral hemorrhage, tongue defect, and sarcopenia has been reported. We describe the case of a 70-year-old man with dysphagia associated with a cerebral hemorrhage, tongue defect, and sarcopenia who received rehabilitation nutrition and underwent glottal closure. CASE: At age 48 years, the patient had the left part of his tongue removed because of cancer. Twenty-two years later, he developed dysphagia and right hemiplegia after a cerebral hemorrhage. The patient was diagnosed with sarcopenia based on a low left handgrip strength (10 kg) and reduced calf circumference (26.5 cm). The patient's Functional Oral Intake Scale (FOIS) score was 1, and his tongue muscle mass indicated atrophy, making the maximum tongue pressure difficult to measure. Palatal augmentation prostheses (PAP) were made to increase swallowing and tongue pressures, and nutritional intake was changed from nasal tube feeding to a gastric fistula. Nutritional intake was increased to 2400 kcal/day and protein intake to 96 g/day. Although rehabilitation nutrition using PAP improved the patient's nutritional status, the dysphagia did not improve, and therefore he underwent glottal closure. This resulted in a weight gain of 13.7 kg and increased tongue muscle strength and volume. The patient's FOIS score increased to 7 (i.e., total oral diet with no restrictions) at 5 months after discharge. DISCUSSION: Glottic closure surgery may be useful for improving oral ingestion, nutritional status, and activities of daily living. BACKGROUND: Dysphagia occurs often after oral cancer surgery. However, no case of dysphagia in combination with cerebral hemorrhage, tongue defect, and sarcopenia has been reported. We describe the case of a 70-year-old man with dysphagia associated with a cerebral hemorrhage, tongue defect, and sarcopenia who received rehabilitation nutrition and underwent glottal closure. CASE: At age 48 years, the patient had the left part of his tongue removed because of cancer. Twenty-two years later, he developed dysphagia and right hemiplegia after a cerebral hemorrhage. The patient was diagnosed with sarcopenia based on a low left handgrip strength (10 kg) and reduced calf circumference (26.5 cm). The patient's Functional Oral Intake Scale (FOIS) score was 1, and his tongue muscle mass indicated atrophy, making the maximum tongue pressure difficult to measure. Palatal augmentation prostheses (PAP) were made to increase swallowing and tongue pressures, and nutritional intake was changed from nasal tube feeding to a gastric fistula. Nutritional intake was increased to 2400 kcal/day and protein intake to 96 g/day. Although rehabilitation nutrition using PAP improved the patient's nutritional status, the dysphagia did not improve, and therefore he underwent glottal closure. This resulted in a weight gain of 13.7 kg and increased tongue muscle strength and volume. The patient's FOIS score increased to 7 (i.e., total oral diet with no restrictions) at 5 months after discharge. DISCUSSION: Glottic closure surgery may be useful for improving oral ingestion, nutritional status, and activities of daily living.

Macro-pro-B-type natriuretic peptide (proBNP) and hidden macro-N-terminal proBNP: Case report.

B-type natriuretic peptide (BNP) is a cardiac hormone widely used as a biomarker for heart failure. Here, we present the first report of extremely high levels of immunoreactive BNP caused by formation of macro-proBNP. A 70-year-old woman with left ventricular hypertrophy and normal systolic function presented with extremely high plasma levels of BNP (35,374pg/ml) and N-terminal proBNP (NT-proBNP; 30,600pg/ml). Our recently developed proBNP immunoassay showed that nearly 100% of her immunoreactive BNP was proBNP. Polyethylene glycol precipitation tests reported extremely low BNP recovery (1.3%), while protein G addition tests also reported a remarkably low BNP fraction (3.3%). Gel filtration chromatography with normal elution buffer combined with BNP immunoassays showed a BNP peak with a retention time slightly shorter than that of IgG. With acidic elution buffer (pH3.0), however this peak disappeared and a new BNP peak consistent with glycosylated human proBNP appeared. These results suggest that in this case most BNP immunoreactivity consisted of macro-proBNP, which is an immune complex composed of proBNP and an anti-proBNP autoantibody. Gel filtration chromatography combined with NT-proBNP immunoassays revealed that the NT-proBNP assay cross-reacts with both the proBNP-IgG complex and proBNP. In addition, with acidic buffer, a new large peak appeared with a retention time the same as that of glycosylated NT-proBNP. These results suggest spuriously high levels of BNP and NT-proBNP are caused by macro-proBNP. Macro-NT-proBNP is not detected by the currently available NT-proBNP assay system.

Adrenomedullin as a Biomarker of Heart Failure.

Adrenomedullin (AM) is a vasodilatory peptide originally discovered in human pheochromocytoma tissue. Although AM is highly expressed in the adrenal glands, heart, lungs, and kidneys, vascular endothelium and smooth muscle are thought to be the main source of plasma AM. The AM precursor is processed to AM-glycine, which is then converted to AM-mature through C-terminal amidation. In this process, mid-regional pro-adrenomedullin (MR-proAM) is also produced. Plasma AM, AM-mature, AM-glycine, and MR-proAM levels are all higher in patients with heart failure than healthy subjects in proportional to the disease severity. All molecular forms of AM are prognostic markers for heart failure.