Impact of Energy Malnutrition on Exacerbation Hospitalization in Patients with Chronic Obstructive Pulmonary Disease: Retrospective Observational Study.

Nutritional disorders in patients with chronic obstructive pulmonary disease (COPD) are associated with cachexia, sarcopenia, and weight loss. In particular, weight loss is a prognostic factor in COPD independent of pulmonary function, and energy malnutrition is a contributing factor. Frequent exacerbation hospitalization is also a prognostic factor for COPD patients. The impact of energy malnutrition on adverse events such as exacerbation hospitalization is unknown, and this study aimed to investigate that. We included 163 male subjects with COPD. Respiratory quotient (RQ), an index of energy malnutrition, was calculated by expiratory gas analysis using an indirect calorimeter. RQ <0.85 was categorized as the energy malnutrition group. Kaplan-Meier analysis was used to compare the hospitalization avoidance rate between the with and without energy malnutrition groups. Independent factors associated with exacerbation hospitalization were evaluated by Cox regression analysis. We finally analyzed data from 56 selected subjects (median age: 74 y). The exacerbation hospitalization rate was significantly higher in the energy malnutrition group. Fifty percent of the energy malnutrition group was hospitalized for an exacerbation, and the median hospitalization avoidance time was 701 d. In Cox regression analysis (adjusted for age, BMI, mMRC dyspnea scale score, %FEV1, and 6-min walk test), energy malnutrition was an independent factor associated with exacerbation hospitalization (HR 4.14, 95% CI 1.13-15.1, p=0.03). Energy malnutrition may be the risk factor for exacerbation hospitalization. Energy malnutrition may be an early nutritional disorder and early detection and intervention may reduce exacerbation hospitalizations.

Resistance exercise in combination with aerobic exercise reduces the incidence of serious events in patients with liver cirrhosis: a meta-analysis of randomized controlled trials.

BACKGROUND: Exercise, particularly resistance exercise, is beneficial for sarcopenia in patients with liver cirrhosis. However, the effects of exercise on events remain unclear. We aimed to examine the effects of exercise on serious events in patients with liver cirrhosis using a meta-analysis of randomized controlled trials (RCTs). METHODS: A literature search was conducted in 2022. Eleven RCTs were selected for the meta-analysis (exercise group, n = 232; control group, n = 193). Serious events were defined as death or serious complications according to the original articles. A meta-analysis was performed using a random-effects model. The primary outcome was the incidence of serious events. RESULTS: In the 11 RCTs, the incidence of serious events was 5.6% (13/232) and 12.3% (24/193) in the exercise and control groups, respectively. However, a meta-analysis demonstrated no significant difference in the incidence of serious events between the two groups (risk difference [RD] - 0.03, 95% confidence intervals (CI) - 0.07 to 0.02). In a stratification analysis based on a combination of aerobic and resistance exercise, five RCTs (n = 185) were enrolled. The incidence of serious events was 6.25% (7/112) and 24.7% (18/73) in the combination exercise and control groups, respectively. A meta-analysis demonstrated a significant reduction in the incidence of serious events in the combination exercise group compared with the control group (RD - 0.12; 95% CI - 0.21 to - 0.03). CONCLUSIONS: Resistance exercise in combination with aerobic exercise reduces serious events in patients with liver cirrhosis. A combination of aerobic and resistance exercise may be beneficial to improve the prognosis of patients with liver cirrhosis.

The Relationship of Energy Malnutrition, Skeletal Muscle and Physical Functional Performance in Patients with Stable Chronic Obstructive Pulmonary Disease.

Weight loss is a factor that affects prognosis in patients with chronic obstructive pulmonary disease (COPD) independent of lung function. One of the major factors for weight loss is energy malnutrition. There have been no reports on the factors related to energy malnutrition in COPD patients. This retrospective observational study aimed to investigate these factors. We included 163 male subjects with COPD. Respiratory quotient (RQ), an index of energy malnutrition, was calculated by expiratory gas analysis using an indirect calorimeter. RQ < 0.85 was defined as the energy-malnutrition group and RQ ≥ 0.85 as the no energy-malnutrition group. Factors related to energy malnutrition were examined by multivariate and decision-tree analysis. We finally analyzed data from 56 selected subjects (median age: 74 years, BMI: 22.5 kg/m2). Energy malnutrition was observed in 43%. The independent factors associated with energy malnutrition were tidal volume (VT) (OR 0.99; 95% CI 0.985−0.998; p = 0.015) and Th12 erector spinae muscle cross-sectional area SMI (Th12ESMSMI) (OR 0.71; 95% CI 0.535−0.946; p = 0.019). In decision-tree profiling of energy malnutrition, VT was extracted as the first distinguishable factor, and Th12ESMSMI as the second. In ROC analysis, VT < 647 mL (AUC, 0.72) or Th12ESMSMI < 10.1 (AUC, 0.70) was the cutoff value for energy malnutrition. Energy malnutrition may be an early warning sign of nutritional disorders.

Effects of In-Hospital Exercise on Frailty in Patients with Hepatocellular Carcinoma.

Frailty including physical inactivity is associated with the survival of patients with hepatocellular carcinoma (HCC). We aimed to investigate the effects of in-hospital exercise on frailty in patients with HCC. This was a multi-center observational study. Patients with HCC were classified into exercise (n = 114) and non-exercise (n = 67) groups. The exercise group was treated with a mixture of aerobic and resistance exercises (20-40 min/day, median four days). Frailty was assessed using the liver frailty index (LFI). Factors for changes in LFI were examined by multivariate and decision-tree analyses. The factors were also examined after propensity score matching. During hospitalization, LFI was significantly improved in the exercise group compared to the non-exercise group (ΔLFI -0.17 vs. -0.02, p = 0.0119). In multivariate analysis, exercise (odds ratio (OR) 2.38, 95% confidence interval (CI) 1.240-4.570, p = 0.0091) and females (OR 2.09; 95%CI, 1.062-4.109; p = 0.0328) were identified as independent factors for the improvement of LFI. In the decision-tree analysis, exercise was identified as an initial classifier associated with the improvement of LFI. Similar findings were also seen in the propensity score matching analyses. We demonstrated that in-hospital exercise improved frailty in patients with HCC. Thus, in-hospital exercise may be beneficial for improving physical function in patients with HCC.

Effects of In-Hospital Physical Therapy on Activities of Daily Living in Patients with Hepatocellular Carcinoma.

Activities of daily living (ADL) are frequently impaired in patients with hepatocellular carcinoma (HCC). In this retrospective study, we aimed to investigate the effects of physical therapy on ADLs in patients with HCC during hospitalization for cancer treatment. Nineteen patients with HCC were enrolled. During hospitalization, patients performed a combination of resistance training, stretching, and aerobic exercise (20-60 min/day). ADLs were assessed using the functional independence measure (FIM). Changes in FIM were evaluated by before-after analysis. No significant difference was seen in Child-Pugh class before and after physical therapy. The bilateral knee extension strength and chair stand test were significantly increased after physical therapy compared with before physical therapy (p = 0.001 and p = 0.008, respectively). The total FIM score was significantly increased after physical therapy compared with that before physical therapy (p = 0.0156). Among the 18 indexes of FIM, the stairs index was significantly improved after physical therapy compared with that before physical therapy (5.9 vs. 6.4 points, p = 0.0241). We demonstrated that physical therapy improved muscle strength without worsening liver function. Furthermore, physical therapy improved FIM, especially in the stairs index, in patients with HCC. Thus, physical therapy may be beneficial in patients with HCC during cancer treatment.

Clinical utility of the Liver Frailty Index for predicting muscle atrophy in chronic liver disease patients with hepatocellular carcinoma.

AIM: Muscle atrophy is a prognostic factor for patients with chronic liver disease (CLD) and hepatocellular carcinoma (HCC). The Liver Frailty Index (LFI) is a simple physical function test; however, an association between LFI and muscle mass remains unclear. We aimed to investigate the utility of LFI for predicting muscle atrophy in CLD patients with HCC. METHODS: We enrolled 138 CLD patients with HCC (aged 77 years, female/male 34.8%/65.2%). Muscle mass was assessed by skeletal muscle index, and patients were classified into the muscle atrophy group (n = 109) or the non-muscle atrophy group (n = 29). Physical frailty was assessed by LFI. The optimal cut-off value of LFI for predicting muscle atrophy was identified by receiver operating characteristic analysis. RESULTS: In the muscle atrophy group, the prevalence of pre-frail/frail was significantly higher than the non-muscle atrophy group (87.2% vs. 58.6%, P = 0.0005). In the logistic regression analysis, being female and pre-frail/frail were identified as independent factors associated with muscle atrophy (pre-frail/frail; OR 3.601, 95% CI 1.381-9.400, P = 0.0088). In patients with normal grip strength, 71.1% of patients were pre-frail/frail, in which 82.8% of patients showed muscle atrophy. Receiver operating characteristic statistics provided an area under the curve of 0.74, and an LFI cut-off value of 2.94 for predicting muscle atrophy (sensitivity 88.06%, specificity 52.17%, accuracy 77.91%). CONCLUSIONS: We showed that pre-frail/frail was an independent factor for muscle atrophy in CLD patients with HCC. Furthermore, LFI predicted muscle atrophy with high sensitivity, even in patients with normal grip strength. Thus, LFI might be a useful screening tool for muscle atrophy in CLD patients with HCC.

Slow walking speed overlapped with low handgrip strength in chronic liver disease patients with hepatocellular carcinoma.

AIM: Walking speed and grip strength are parameters of muscle function; however, evaluating walking speed is not always available in clinical practice. We aimed to investigate the impact of walking speed on the evaluation of muscle dysfunction in chronic liver disease (CLD) patients with hepatocellular carcinoma (HCC). METHODS: We enrolled 107 consecutive CLD patients with HCC in this study (age 76 years [range 60-92 years]; female/male 39/68; body mass index 22.9 [range 20.0-25.3]; chronic hepatitis/liver cirrhosis 25/82). Muscle dysfunction was evaluated using the Asian Working Group for Sarcopenia criteria (grip strength or walking speed) and the Japan Society of Hepatology criteria (grip strength). A correlation between walking speed and skeletal muscle index was evaluated. Independent factors for slow walking speed were evaluated using a logistic regression analysis. RESULTS: There was no significant correlation between walking speed and skeletal muscle index (r = 0.14, P = 0.16). For both the Asian Working Group for Sarcopenia and Japan Society of Hepatology criteria, 33.6% of all patients were classified as having muscle dysfunction. All patients with slow walking speed (4.7% of all patients) also showed low handgrip strength. The logistic regression analysis identified grip strength as an independent factor for slow walking speed (OR 0.65; 95% CI 0.432-0.838; P = 0.008). CONCLUSIONS: No difference was seen in the prevalence of muscle dysfunction between the Asian Working Group for Sarcopenia and Japan Society of Hepatology criteria in CLD patients with HCC. Furthermore, all patients with slow walking speed also showed low handgrip strength. Thus, for the evaluation of muscle dysfunction, grip strength might be a suitable proxy for walking speed in CLD patients with HCC.

[Autoimmune pancreatitis with bowel obstruction caused by proximal jejunal stricture:a case report].

We herein report a rare case of autoimmune pancreatitis with small intestinal obstruction. A 72-year-old male was admitted to our hospital with abdominal fullness and vomiting and diagnosed with autoimmune pancreatitis by imaging and laboratory tests. Imaging studies also revealed narrowing of the proximal jejunum with dilated bowels and intramural cystic lesion adjacent to the pancreatic body. Small bowel resection was performed to alleviate stenosis. Pathological evaluation demonstrated invasion of IgG4-positive cells and fibrosis.

Serum levels of anti-Fcγ receptor IIB/C antibodies are increased in patients with systemic sclerosis.

Systemic sclerosis (SSc) is a systemic autoimmune disorder that results in fibrosis of the skin and multiple internal organs. Although the precise mechanism is unknown, it appears to result from the overproduction of extracellular matrix proteins and aberrant immune activations. Receptors for the Fc region of immunoglobulin (Ig)G (FcγR) are members of the Ig superfamily that modulate both activation and inhibition of immune responses. FcγRIIB is the sole inhibitory member, which has an intrinsic cytoplasmic immunoreceptor tyrosine-based inhibitory motif. The present study was undertaken to investigate the circulating concentrations of anti-FcγRIIB/C antibodies (Ab) in patients with SSc. Serum levels of anti-FcγRIIB/C Ab were significantly increased in patients with SSc compared to those in controls and in patients with localized scleroderma. Serum levels of anti-FcγRIIB/C Ab in patients with limited cutaneous SSc were similar to those in patients with diffuse cutaneous SSc. Among SSc patients, serum levels of anti-FcγRIIB/C Ab were increased in those with nail-fold bleeding and decreased in those with diffuse pigmentation and calcinosis. These findings support the notion that increased serum anti-FcγRIIB/C Ab levels are involved in aberrant immune responses in SSc.

Serum levels of soluble CD21 in patients with systemic sclerosis.

Systemic sclerosis (SSc) is a systemic disorder that typically results in fibrosis of the skin and multiple internal organ systems. Although the precise mechanism is unknown, overproduction of extracellular matrix proteins, including collagens and fibronectins, and aberrant immune activation might be involved in the pathogenesis. The soluble cluster of differentiation 21 (sCD21) represents the extracellular portion of the CD21 glycoprotein that is released by shedding from the cell surfaces into plasma. sCD21 binds complement fragments and activates monocytes through binding to membrane CD23. The present study was undertaken to investigate the serum levels of sCD21 in patients with SSc. Serum sCD21 levels were reduced with age both in patients with SSc and normal controls. Serum sCD21 levels in patients with SSc were significantly decreased compared to those in control subjects. When we divided patients with SSc into limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc), patients with lcSSc had lower levels of serum sCD21 than those with dcSSc. Moreover, the prevalence of pulmonary fibrosis in the patients with dcSSc inversely correlated with serum sCD21 levels. Our finding may support the notion that B-cell activation is involved in the mechanism for pulmonary fibrosis and skin sclerosis.

Efficacy of low-dose imatinib mesylate for cutaneous involvement in systemic sclerosis: a preliminary report of three cases.

In this pilot study, the effect of low-dose imatinib mesylate (100 mg/day) on cutaneous involvement in patients with systemic sclerosis (SSc) was analyzed. Three patients with SSc were treated with 100 mg/day of imatinib mesylate for 6 months because of pulmonary arterial hypertension refractory to conventional treatments, including beraprost, bosentan, sildenafil, and epoprostenol. Changes in cutaneous involvement were evaluated at 1, 3, and 6 months. During the treatment, the total skin score gradually improved in all of the patients. Contracture of phalanges was attenuated in two patients, one of whom also experienced the partial restoration of large-joint mobility. Nailfold bleeding, initially seen in two patients, was gradually attenuated and had completely disappeared at 6 months. In all patients, Raynaud's phenomenon was attenuated at around 3 months and had completely disappeared at 6 months. Although transient renal dysfunction was observed in one patient, none of the patients experienced common adverse effects of imatinib, such as edema, nausea, rash, and musculoskeletal pain. These clinical data indicate the tolerability and efficacy of low-dose imatinib in SSc, especially against cutaneous vascular involvement, including Raynaud's phenomenon and nailfold bleeding.

Significant attenuation of macrovascular involvement by bosentan in a patient with diffuse cutaneous systemic sclerosis with multiple digital ulcers and gangrene.

Systemic sclerosis (SSc) is characterized by vascular injuries, and bosentan has recently been proved to be efficacious for the prevention of new digital ulcers in SSc. We herein report a case of SSc in a patient with refractory digital ulcers and gangrene treated with bosentan. Stenosis of the ulnar artery, evaluated by magnetic resonance angiography, was attenuated by the bosentan treatment, suggesting that bosentan exerts a reverse remodeling effect against the pathological organic changes of arteries in SSc.

CCR10 and CCL27 are overexpressed in cutaneous squamous cell carcinoma.

C-C chemokine receptor (CCR)10 is a specific receptor for chemokine ligand (CCL)27, a selective chemoattractant for skin-associated memory T cells to cutaneous sites. In melanoma, CCR10 increases the ability of neoplastic cells to grow, invade tissues, disseminate to lymph nodes, and escape the host immune responses. In this study, we investigated the expression of CCR10 and its ligand CCL27 in squamous cell carcinoma (SCC). CCR10 and CCL27 were expressed in SCC, actinic keratosis (AK), Bowen's disease, and seborrheic keratosis (predominantly prickle cell type), but not in seborrheic keratosis (predominantly basal cell type) and basal cell carcinoma. Furthermore, CCR10 and CCL27 were overexpressed in SCC relative to Bowen's disease, an early stage of SCC. Consistently, a human SCC cell line, A253 cells, and HaCaT cells exhibited CCL27 production that was strongly induced by tumor necrosis factor-α and interleukin-1ß. Finally, A253 cells expressed stronger intracellular CCR10 compared to HaCaT cells by flow cytometry. These results suggest that CCR10 and CCL27 overexpression in SCC is related to the progression of SCC and is useful for the diagnosis of SCC.

α4ß7 Integrin is essential for contact hypersensitivity by regulating migration of T cells to skin.

BACKGROUND: ß7 Integrin, a cell adhesion molecule, is present in the form of α4ß7 integrin or αEß7 integrin. α4ß7 Integrin is expressed on most leucocytes and is essential for their migration to gut-associated lymphoid tissues by interacting with its primary ligand, mucosal addressin cell adhesion molecule-1, which is preferentially expressed in gut-associated lymphoid tissues. Although the importance of α4ß7 integrin in intestinal inflammation has been established, its role in cutaneous inflammation remains to be elucidated. OBJECTIVE: We sought to investigate the role of ß7 integrin in cutaneous inflammation. METHODS: We used a murine contact hypersensitivity model and examined the role of ß7 integrin by using ß7 integrin-deficient and αE integrin-deficient mice. RESULTS: ß7 Integrin-deficient mice, not αE integrin-deficient mice, are defective in contact hypersensitivity responses. ß7 Integrin deficiency does not affect irritant contact dermatitis. The distribution, migration, and function of antigen presenting cells from ß7 integrin-deficient mice are comparable to those from wild-type mice. Moreover, sensitized ß7 integrin-deficient T cells are able to respond to antigen stimuli in vitro and elicit contact hypersensitivity responses when directly injected into the skin. However, they are defective in reaching the skin under inflammatory conditions, resulting in reduced contact hypersensitivity responses when intravenously injected. Furthermore, intraperitoneal injection of anti-α4ß7 integrin neutralizing antibody elicit impaired contact hypersensitivity responses. CONCLUSION: α4ß7 Integrin contributes to contact hypersensitivity responses by regulating T-cell migration to inflammatory skin.

Health-related quality of life of outpatients with systolic and isolated diastolic dysfunction: Sado Heart Failure Study.

BACKGROUND: The impact of isolated diastolic dysfunction (IDD) and systolic dysfunction (SD) on health-related quality of life (HRQOL) is unknown. METHODS AND RESULTS: To evaluate HRQOL in patients with IDD and SD under treatment, information on outpatients aged 60-84 years was extracted from the records of 4,500 consecutive individuals who underwent echocardiographic examination at Sado General Hospital. The medical records of these patients were reviewed and a questionnaire, including the Medical Outcome Study Short Form 36, was mailed to 71 IDD and 99 SD patients; answers were obtained from 66 and 91 patients, respectively. The HRQOL of patients with cardiac dysfunction was impaired even when echocardiographic parameters improved with treatment. Patients with IDD showed an impairment of HRQOL similar to those with SD. Compared with males, female patients had a larger and more significant reduction in the physical and mental components of the HRQOL score. These scores correlated positively with exercise capacity in patients with IDD or SD. CONCLUSIONS: Impaired HRQOL, in both its mental and physical components, is a serious problem for IDD and SD patients under treatment. Because exercise intolerance may underlie the reduced HRQOL, improving exercise capacity could be an important target for managing outpatients with heart failure.