Insulin-like growth factor 1 predicts decompensation and long-term prognosis in patients with compensated cirrhosis

AimInsulin-like growth factor 1 (IGF-1), which is primarily produced in hepatocytes and is associated with liver functional reserve, plays a crucial role in the pathological condition of cirrhosis. This study aimed to investigate the usefulness of serum IGF-1 levels for predicting the long-term prognosis and decompensation development in patients with cirrhosis.MethodsWe retrospectively evaluated 148 patients with cirrhosis and divided them into three groups according to baseline IGF-1 levels: low (L)-, intermediate (I)-, and high (H)-IGF-1 groups. The cumulative survival rates were compared among these groups in compensated and decompensated cirrhosis, respectively. Significant and independent factors associated with mortality and decompensation development were identified using Cox proportional hazards regression analysis.ResultsThe median observation period was 57.1 (41.7–63.2) months. Thirty (20.3%) patients died of liver disease-related events and 21 (22.3%) patients with compensated cirrhosis developed decompensation. Multivariate analysis identified low serum IGF-1 levels as a significant and independent factor associated with mortality (all patients: hazard ratio [HR], 0.967; p = 0.004; patients with compensated cirrhosis: HR, 0.927; p = 0.002). The cumulative survival rates were significantly lower in the L-IGF-1 group than in the H-IGF-1 and I-IGF-1 groups (all patients: p < 0.001 and = 0.009; patients with compensated cirrhosis: p = 0.012 and 0.003, respectively). However, in decompensated cirrhosis, the cumulative survival rates demonstrated no significant differences among the three groups. The cumulative decompensation incidence rates were significantly higher in the L-IGF-1 group than in the H-IGF-1 and I-IGF-1 groups (p < 0.001 and = 0.009, respectively). Low serum IGF-1 levels were significantly and independently associated with decompensation development (HR, 0.939; p < 0.001).ConclusionLow serum IGF-1 levels were significantly and independently associated with decompensation development and poor long-term prognosis in patients with compensated cirrhosis. Therefore, IGF-1 may be useful for predicting decompensation-related events and should be regularly monitored in the management of compensated phase

Hemobilia Derived from Cystic Artery Pseudoaneurysm

Cystic artery pseudoaneurysm (CAP) is a rare disease, with small number of previous reports related to CAP. Besides, it is frequently prone to critical condition due to arterial bleeding. Here, we presented a case of ruptured CAP with acute calculus cholecystitis and its subsequent successful management with temporary endoscopic biliary drainage for obstructive jaundice and embolization for the culprit artery without cholecystectomy. Since CAP is at high risk of bleeding, intravascular treatment, which is only one currently available therapeutic option, is urgently required in the clinical sites

Autophagy promotes degradation of internalized collagen and regulates distribution of focal adhesions to suppress cell adhesion

Adhesion of cells to the extracellular matrix (ECM) via focal adhesions (FAs) is crucial for cell survival, migration, and differentiation. Although the regulation of FAs, including by integrins and the ECM, is important to cell behavior, how FAs are regulated is not well known. Autophagy is induced by both cell adhesion and cell detachment. Here, we showed that autophagosomes are located close to internalized collagen and paxillin, which is a well-known marker of FAs. Autophagy-deficient cells showed increased levels of internalized collagen compared with control cells. Moreover, paxillin exhibited a more peripheral distribution and the area of paxillin was increased, and adhesion-induced focal adhesion kinase signaling was impaired and adhesion was enhanced, in autophagy-deficient cells. These results suggest that autophagy suppressed cell adhesion by regulating internalized ECM and FAs

The Clinical Potential of Oligonucleotide Therapeutics against Pancreatic Cancer

Although many diagnostic and therapeutic modalities for pancreatic cancer have been proposed, an urgent need for improved therapeutic strategies remains. Oligonucleotide therapeutics, such as those based on antisense RNAs, small interfering RNA (siRNA), microRNA (miRNA), aptamers, and decoys, are promising agents against pancreatic cancer, because they can identify a specific mRNA fragment of a given sequence or protein, and interfere with gene expression as molecular-targeted agents. Within the past 25 years, the diversity and feasibility of these drugs as diagnostic or therapeutic tools have dramatically increased. Several clinical and preclinical studies of oligonucleotides have been conducted for patients with pancreatic cancer. To support the discovery of effective diagnostic or therapeutic options using oligonucleotide-based strategies, in the absence of satisfactory therapies for long-term survival and the increasing trend of diseases, we summarize the current clinical trials of oligonucleotide therapeutics for pancreatic cancer patients, with underlying preclinical and scientific data, and focus on the possibility of oligonucleotides for targeting pancreatic cancer in clinical implications

Low geriatric nutritional risk index predicts poor prognosis in patients with cirrhosis: a retrospective study

AimMalnutrition, which increases the risk of liver disease-related events and mortality, is a serious complication in cirrhosis. This study aimed to investigate whether the geriatric nutritional risk index (GNRI) could predict the long-term prognosis in patients with cirrhosis.MethodsWe retrospectively evaluated 266 patients with cirrhosis and classified them into two groups based on baseline GNRI scores: risk (≤98, n = 104) and no-risk groups (>98, n = 162). The cumulative survival rates were compared between the two groups in patients with compensated and decompensated cirrhosis, respectively. Cox proportional hazards regression analysis was used to identify significant and independent factors associated with mortality.ResultsThe median observation period was 54.9 (33.6–61.7) months and 65 (24.4%) liver disease-related deaths occurred during the follow-up period. The GNRI scores significantly and inversely correlated with Child-Pugh score (r = −0.579), model for end-stage liver disease score (r = −0.286), and Mac-2 binding protein glycosylation isomer (r = −0.494). Multivariate analysis identified low GNRI as a significant and independent factor associated with mortality [overall cohort: hazard ratio (HR), 0.926; p < 0.001; compensated cirrhosis: HR, 0.947; p = 0.003; decompensated cirrhosis: HR, 0.923; p < 0.001]. The risk group demonstrated significantly lower cumulative survival rates than the no-risk group in overall cohort, and patients with compensated and decompensated cirrhosis (p < 0.001, <0.001, and = 0.013, respectively).ConclusionLow GNRI was associated with poor long-term prognosis in both patients with compensated and decompensated cirrhosis. Therefore, the GNRI is a simple and useful tool for predicting prognosis and modifying the nutritional status in patients with cirrhosis

Serum Insulin-Like Growth Factor 1 Levels, Facture Risk Assessment Tool Scores and Bone Disorders in Patients with Primary Biliary Cholangitis

Insulin-like growth factor 1 (IGF-1) plays an important role in bone growth and maintenance, and its decreased levels are associated with bone disorders. This study aimed to evaluate the association of serum IGF-1 levels with osteoporosis, prevalent fractures and fracture risk based on the Fracture Risk Assessment Tool (FRAX) in patients with primary biliary cholangitis (PBC). This study included 127 consecutive patients with PBC. Based on the baseline serum IGF-1 levels, the participants were classified into the low (L)-, intermediate (I)- and high (H)-IGF-1 groups. According to the FRAX score, high fracture risk was defined as a 10-year major osteoporotic fracture probability (FRAX-MOF) ≥ 20% or a 10-year hip fracture probability (FRAX-HF) ≥ 3%. The serum IGF-1 levels were positively correlated with bone mineral density, and were negatively correlated with the FRAX-MOF/FRAX-HF. The L-IGF-1 group had the highest prevalence of osteoporosis (58.1%), prevalent fracture (48.4%) and high fracture risk (71.0%). Meanwhile, the H-IGF-1 group had the lowest prevalence of osteoporosis (9.7%), prevalent fracture (12.9%) and high fracture risk (9.7%). The prevalence of these events increased stepwise with decreasing serum IGF-1 levels. The cutoff values of IGF-1 for predicting osteoporosis, prevalent fracture and high fracture risk were 61.5 ng/mL (sensitivity/specificity, 0.545/0.894), 69.5 ng/mL (0.633/0.784) and 61.5 ng/mL (0.512/0.929), respectively. Serum IGF-1 levels were associated with bone disorders and the FRAX-derived fracture risk, and may be a useful indicator for initiating therapeutic intervention to prevent the incidence of fracture in patients with PBC

Pain sensitivity after low-level clenching is influenced by preloading eccentric exercise

PURPOSE: To examine the effect of preloading eccentric exercise on pain sensitivity in healthy volunteers. METHODS: In 20 healthy volunteers, pain-related sensations (6 items: pain, unpleasantness, fatigue, stiffness, tension, and soreness during maximum biting), and pain intensities induced by repeated electrical stimuli on the masseter and the hand palm were evaluated using a visual analog scale (VAS) of 0-100 mm. Eccentric exercise (6 min-test) or gum chewing (6 min-control) was used as preloading exercise to evaluate the effect on pain sensitivities before and after low-level clenching (15 min) performed 2 days after the preloading exercise. RESULTS: Eccentric exercise induced only low levels of pain-related sensations 2 days later. However, the time course of temporal summation induced by four repeated electrical stimuli on the masseter was influenced by the type of preloading exercise, i.e., temporal summation increased after the low-level clenching (P = 0.016) when preloading was done by the eccentric exercise, while no significant change was observed when preloading was done by the gum chewing. CONCLUSIONS: Eccentric exercise may facilitate pain sensitivity induced by subsequent low-level clenching via the central nervous system. In addition, it was demonstrated that pain sensitivity after the low-level clenching could be influenced by the type of preloading exercise. These experimental results may suggest that eccentric exercise could act as one of the triggering factors in the mechanism by which tooth clenching leads to a chronic pain condition in susceptible individuals.status: publishe

Clinical Usefulness of FRAX Score for Predicting Sarcopenia in Patients with Chronic Liver Disease

We investigated the usefulness of the Fracture Risk Assessment tool (FRAX) for predicting sarcopenia in chronic liver disease (CLD). In this cross-sectional study, we evaluated 321 patients with CLD. The FRAX with and without bone mineral density (BMD) was employed to calculate the 10-year risks of major osteoporotic and hip fractures. The FRAX score for high fracture risk was defined as a 10-year major osteoporotic fracture probability of ≥20% or a 10-year hip fracture probability of ≥3%. The diagnosis of sarcopenia was based on the Japan Society of Hepatology criteria. According to the FRAX, with and without BMD, 134 (41.7%) and 193 (60.1%) patients had a high fracture risk, respectively. The high fracture risk group had a significantly higher frequency of sarcopenia than the non-high fracture risk group. FRAX scores of major osteoporotic and hip fractures were negatively correlated with handgrip strength and muscle mass. Using the FRAX with BMD, the cutoff scores of major osteoporotic and hip fractures for predicting sarcopenia were 8.55% (sensitivity/specificity, 0.847/0.568) and 3.35% (0.729/0.746), respectively. Using the FRAX without BMD, they were 18.5% (0.635/0.725) and 7.65% (0.729/0.758), respectively. The FRAX is a simple and convenient screening tool for predicting sarcopenia in patients with CLD