Safety and feasibility of a novel total percutaneous post-closure technique after bedside Impella decannulation in patients with cardiogenic shock.

OBJECTIVES: The Impella (Abiomed) is a widely used percutaneous mechanical circulatory support device for high-risk percutaneous coronary intervention in patients with cardiogenic shock. This study aimed to determine the safety and feasibility of a non-angio-guided post-closure approach using the Perclose ProGlide (Abbott) to decannulate the Impella in the intensive care unit. METHODS: This retrospective study included consecutive patients who were successfully weaned from mechanical circulatory support using the Impella device between April 2019 and April 2022 at Hamamatsu University School of Medicine. Fifteen patients underwent complete post-closure of the femoral artery access sites at the bedside. Technical success of the post-closure hemostasis technique was defined as no evidence of bleeding or additional medical procedures after manual compression. The safety endpoints comprised the Valve Academic Research Consortium-3 and Bleeding Academic Research Consortium criteria. RESULTS: All patients achieved successful hemostasis with this novel technique without surgical conversion. There was no significant bleeding; however, procedure-related vessel occlusion was observed in 1 patient who was recanalized with balloon angioplasty. CONCLUSIONS: Bedside post-closure using the Perclose ProGlide device is a safe and feasible alternative to manual compression and surgical removal of the Impella device with low bleeding or vascular complications rates.

Clinical impact of proton pump inhibitor and potassium-competitive acid blocker for predicting the curability of endoscopic resection in ulcerative early gastric cancer.

BACKGROUND: Endoscopic diagnosis is essential for predicting the curability of early gastric cancer (EGC; R0 resection) before treatment, but the relationship between ulcerative lesions and clinical outcomes remains unclear. We aimed to investigate the effect of proton pump inhibitor (PPI) or potassium-competitive acid blocker (P-CAB) on the morphological changes of ulcerative EGCs and its relevance to the clinical outcomes. METHODS: Altogether, 143 patients with differentiated ulcerative EGC that were resected by endoscopic submucosal dissection were retrospectively identified and divided into the following two cohorts depending on their PPI/P-CAB administration status: PPI/P-CAB (n = 76) and non-PPI/P-CAB (n = 67) cohorts. Furthermore, in each cohort, the patients were further divided into the improved and unimproved subgroups based on the ulcerative changes. RESULTS: In the PPI/P-CAB cohort, the deep submucosal invasion and lymphovascular invasion rates were significantly higher in the unimproved subgroup than in the improved subgroup, resulting in a significantly lower R0 resection rate. Contrarily, no significant differences were found between the two subgroups in the non-PPI/P-CAB cohort. The significance of PPI/P-CAB administration was observed only in the ulcerative EGCs with open-type atrophy (R0 resection rate; improved vs. unimproved, 90.9% vs. 48.0%, p = 0.001). When the finding of improved ulcer with PPI/P-CAB administration was used as the indication of endoscopic resection in ulcerative EGCs with open-type atrophy, high sensitivity (78.9%) and accuracy (76.3%) rates for the curability were observed which were higher than those of conventional endoscopic diagnosis alone (p = 0.021). CONCLUSION: PPI or P-CAB administration might contribute to the potential selection of ulcerative EGCs, enabling endoscopic curative resection.

Role of protein kinase D1 in vasoconstriction and haemodynamics in rats.

AIMS: Protein kinase D (PKD), once considered an effector of protein kinase C (PKC), now plays many pathophysiological roles in various tissues. However, little is known about role of PKD in vascular function. We investigated the role of PKD in contraction of rat aorta and human aortic smooth muscle cells (HASMCs) and in haemodynamics in rats. METHODS AND RESULTS: Isometric tension of rat aortic was measured to examine norepinephrine-induced contraction in the presence of PKD, PKC and Rho-kinase inhibitors. Phosphorylation of PKD1, myosin targeting subunit-1 (MYPT1), myosin light chain (MLC), CPI-17 and heat-shock protein 27 (HSP27), and actin polymerization were measured in the aorta. Phosphorylation of MYPT1 and MLC was also measured in HASMCs knocked down with specific siRNAs of PKD 1, 2 and 3. Intracellular calcium concentrations and cell shortening were measured in HASMCs. Norepinephrine-induced aortic contraction was accompanied by increased phosphorylation of PKD1, MYPT1 and MLC and actin polymerization, all of which were attenuated with PKD inhibitor CRT0066101. PKD1 phosphorylation was not inhibited by PKC inhibitor, chelerythrine or Rho kinase inhibitor, fasudil. In HASMCs, the phosphorylation of MYPT1 and MLC was attenuated by PKD1, but not PKD2, 3 knockdown. In HASMCs, CRT0066101 inhibited norepinephrine-induced cell shortening without affecting calcium concentration. Administration of CRT0066101 decreased systemic vascular resistance and blood pressure without affecting cardiac output in rats. CONCLUSIONS: PKD1 may play roles in aorta contraction and haemodynamics via phosphorylation of MYPT1 and actin polymerization in a calcium-independent manner.

A prospective cohort study of a new electrosurgical unit for preventing colorectal post-endoscopic submucosal dissection coagulation syndrome.

BACKGROUND AND AIM: Post-endoscopic submucosal dissection coagulation syndrome (PECS) is a recognized complication of colorectal endoscopic submucosal dissection (ESD); however, there is a lack of interventions for preventing PECS. We therefore conducted a prospective study to evaluate the utility of maXium, a novel electrosurgical unit, for preventing PECS. METHODS: This single-center, prospective cohort study prospectively enrolled patients undergoing colorectal ESD. The voltage and power of the electrosurgical units were measured. PECS was defined as a visual analog scale (VAS) ≥ 30 mm, an increase of VAS ≥ 20 mm from baseline, body temperature ≥ 37.5°C, or white blood cell count ≥ 10 000/µL after ESD. PECS was classified into type I (without extra-luminal air) and type II (with peri-luminal air). The primary endpoint was the incidence of PECS. A sample size of 92 patients was required to ensure the upper limit of the 90% CI for the incidence of PECS was less than 15%. RESULTS: At resistances greater than 400 Ω, the maXium unit allowed submucosal dissection with lower power than with the VIO300D unit. Ninety-one patients meeting the inclusion criteria were included in the final study analysis. The incidence of PECS was 16% (90% CI, 10-23%), comprising type I (11%) and type II (5%) PECS. Simple extra-luminal air without PECS was observed in 7% of patients. CONCLUSION: Use of the maXium electrosurgical unit did not reduce the incidence of PECS after colorectal ESD; however, the maXium unit had equivalent performance to a conventional electrosurgical unit used for colorectal ESD.

Failure of Limb Salvage in a Patient with Chronic Limb-Threatening Ischemia due to Persistent Sciatic Artery Stenosis: Direct Therapeutic Intervention is Important.

A 79-year-old woman presented to our hospital with a complaint of feeling a cold sensation in her right foot. After performing a contrast-enhanced computed tomography angiography, severe stenosis in the right persistent sciatic artery (PSA) was identified. However, stenting was considered inadvisable due to compression issues when sitting. Following anticoagulant therapy, the patient's symptoms improved. However, after seventeen months, she experienced recurrent severe pain in her right foot. Catheter angiography revealed occlusions in both the anterior and posterior tibial arteries. To address the issue, we conducted endovascular therapy, followed by a femoro-popliteal artery bypass and ligation of the PSA. Unfortunately, despite these efforts, a below-knee amputation was eventually performed. Limited experience with the PSA and delayed intervention may have led to the need for amputation. Therefore, it is crucial to emphasize the importance of prompt therapeutic intervention following the onset of initial symptoms.

Synthesis and Characterization of Dibenzothieno[a,f]pentalenes Enabling Large Antiaromaticity and Moderate Open-Shell Character through a Small Energy Barrier for Bond-Shift Valence Tautomerization.

Experimental and theoretical rationalization of bond-shift valence tautomerization, characterized by double-well potential surfaces, is one of the most challenging topics of study among the rich electronic properties of antiaromatic molecules. Although the pseudo-Jahn-Teller effect (PJTE) is an essential effect to provide attractive characteristics of 4nπ systems, an understanding of the structure-property relationship derived from the PJTE for planar 4nπ electron systems is still in its infancy. Herein, we describe the synthesis and characterization of two regioisomers of the thiophene-fused diareno[a,f]pentalenes 6 and 7. The magnetic and optoelectronic properties characterize these sulfur-doped diareno[a,f]pentalenes as open-shell antiaromatic molecules, in sharp contrast to the closed-shell antiaromatic systems of 3 and 5, in which these main cores consist of the same number of π electrons as 6 and 7. Notably, thiophene-fused 6b and 7b showed pronounced antiaromaticity, the strongest among the previous systems, as well as moderate open-shell characteristics. Our experimental and theoretical investigations concluded that these properties of 6b and 7b are derived from the small energy barrier Ea‡ for the bond-shift valence tautomerization. The energy profile of the single crystal of 6b showed the temperature-dependent structural variations assigned to the dynamic mutual exchange between the two Cs-symmetric structures, which was also supported by changes in the chemical shifts of variable-temperature 1H NMR spectra in the solution phase. Both experimental and computational results revealed the importance of introducing heteroaromatic rings into 4nπ systems for controlling the PJTE and manifesting the antiaromatic and open-shell natures originating from the high-symmetric structure. The findings of this study advance the understanding of antiaromaticity characterized by the PJTE by controlling the energy barrier for bond-shift valence tautomerizations, potentially leading to the rational design of optoelectronic devices based on novel antiaromatic molecules possessing the strong contributions of their high-symmetric geometries.

Impact of rotational atherectomy on the incidence of side branch compromise in calcified bifurcation lesions undergoing elective percutaneous coronary intervention.

BACKGROUND: Percutaneous coronary intervention (PCI) to the calcified bifurcation lesion is still a challenging issue even for experienced interventional cardiologists. In such bifurcation lesions, side branch compromise caused by carina-shift or plaque shift just following stent implantation or balloon dilatation is one of the most important complications. It remains unclear whether rotational atherectomy (RA) to the main vessel reduces the incidence of side branch compromise in the calcified bifurcation lesions. The aim of this retrospective study was to compare the incidence of side branch compromise/occlusion between PCI with versus without RA. METHODS: This was a retrospective, single-center study. Side branch compromise/occlusion was defined as final Thrombolysis in Myocardial Infarction flow grade of side branch ≤2/≤1. We included 302 calcified bifurcation lesions, and divided those into the RA group (n = 140) and the non-RA group (n = 162) according to use of RA to the main vessel. RESULTS: The incidence of side branch compromise/occlusion was significantly less in the RA group than in the non-RA group (compromise: 6.4 % versus 14.2 %, p = 0.038; occlusion: 3.6 % versus 10.5 %, p = 0.017). RA was inversely associated with the incidence of side branch compromise [odds ratio (OR) 0.272, 95 % confidence interval (CI) 0.096-0.772, p = 0.014] and occlusion (OR 0.175, 95 % CI 0.049-0.628, p = 0.008). CONCLUSIONS: RA to the main vessel was associated with a lower incidence of side branch compromise/occlusion. RA to the main vessel only may be a reasonable approach to reduce the risk of side branch compromise/occlusion in calcified bifurcation lesions.

Comparison of the Incidence of Periprocedural Myocardial Infarction in Bifurcation Lesions Between Medina (1,1,1) and (0,1,1) in Elective Percutaneous Coronary Intervention.

Periprocedural myocardial infarction (PMI) following percutaneous coronary intervention (PCI) is more frequently observed in true bifurcation lesions such as Medina (1,1,1) and (0,1,1). The aim of this study is to compare the incidence of PMI in elective PCI between Medina (1,1,1) and (0,1,1) bifurcation lesions. This was a retrospective, single-center study. We included 162 true bifurcation lesions, which were divided into the (1,1,1) group (n = 85) and the (0,1,1) group (n = 77). We compared the incidence of PMI between the two groups and performed multivariate logistic regression analysis using PMI as a dependent variable. The incidence of PMI was similar in the (1,1,1) group and the (0,1,1) group (12.9% versus 15.6%, P = 0.658). The final TIMI flow grade of the side branches and that of the main branches were also similar in the two groups. In multivariate logistic regression analysis, Medina classification (1,1,1) was not associated with PMI (odds ratio (OR), 0.996; 95% confidence interval (CI), 0.379-2.621; P = 0.994), but the angle of the side branch < 45° (OR, 3.569; 95% CI, 1.320-9.654; P = 0.012), lesion length in a main vessel (per 10-mm increase) (OR, 1.508; 95% CI, 1.104-2.060; P = 0.010), and absence of side branch protection (OR, 3.034; 95% CI, 1.095-8.409; P = 0.033) were significantly associated with PMI. In conclusion, the Medina (1,1,1) bifurcation lesions did not increase the incidence of PMI as compared to Medina (0,1,1). However, the narrow side branch angle, diffuse long lesion, and absence of side branch protection were significantly associated with PMI. We should pay attention to these high-risk features in the treatment of true bifurcation lesions.

Asymptomatic Penetration of the Median Nerve by a Peripherally Inserted Central Catheter: A Case Report.

We report a rare case in which a peripherally inserted central catheter (PICC) asymptomatically penetrated the median nerve. The patient was a 71-year-old man who displayed no neurological symptoms until 4 days after PICC placement. An ultrasound scan revealed that the PICC had penetrated the median nerve. He underwent surgery to remove the catheter and had no sequelae. When placing a PICC, selecting the brachial vein as a puncture site is associated with a high risk of nerve injury. Furthermore, circumspect observation is needed until withdrawal as neurological symptoms may be absent even when the catheter has punctured a nerve.

Right ventricular overloading is attenuated in monocrotaline-induced pulmonary hypertension model rats with a disrupted Gpr143 gene, the gene that encodes the 3,4-l-dihydroxyphenyalanine (l-DOPA) receptor.

Pulmonary hypertension (PH) is a severe and progressive disease that causes elevated right ventricular systolic pressure, right ventricular hypertrophy and ultimately right heart failure. However, the underlying pathophysiologic mechanisms are poorly understood. We previously showed that 3,4-l-dihydroxylphenyalanine (DOPA) sensitizes vasomotor response to sympathetic tone via coupling between the adrenergic receptor alpha1 (ADRA1) and a G protein-coupled receptor 143 (GPR143), a DOPA receptor. We investigated whether DOPA similarly enhances ADRA1-mediated contraction in pulmonary arteries isolated from rats, and whether GPR143 is involved in the PH pathogenesis. Pretreating the isolated pulmonary arteries with DOPA 1 µM enhanced vasoconstriction in response to phenylephrine, an ADRA1 agonist, but not to U-46619, a thromboxane A2 agonist or endothelin-1. We generated Gpr143 gene-deficient (Gpr143-/y) rats, and confirmed that DOPA did not augment phenylephrine-induced contractile response in Gpr143-/y rat pulmonary arteries. We utilized a rat model of monocrotaline (MCT)-induced PH. In the MCT model, the right ventricular systolic pressure was attenuated in the Gpr143-/y rats than in WT rats. Phenylephrine-induced cell migration and proliferation were also suppressed in Gpr143-/y pulmonary artery smooth muscle cells than in WT cells. Our result suggests that GPR143 is involved in the PH pathogenesis in the rat models of PH.

Long-term outcomes of nasogastric tube with Gastrografin for adhesive small bowel obstruction.

BACKGROUND: We had previously reported that the administration of Gastrografin through a nasogastric tube (NGT-G) followed by long tube (LT) strategy could be a novel standard treatment for adhesive small bowel obstruction (ASBO); however, the long-term outcomes after initial improvement remain unknown. This study aimed to analyze the long-term outcomes of first-line NGT-G. METHODS: Enrolled patients with ASBO were randomly assigned to receive LT or NGT-G between July 2016 and November 2018. Thereafter, the cumulative surgery rate, cumulative recurrence rate, and overall survival (OS) rate were analyzed. In addition, subset analysis was conducted to determine the cumulative recurrence rate according to colonic contrast with Gastrografin at 24 h. RESULTS: A total of 223 patients (LT group, n = 111; NGT-G group, n = 112) were analyzed over a median follow-up duration of 550 days. The cumulative 1-year surgery rates, cumulative 1-year recurrence rates, and 1-year OS rates in the LT and NGT-G groups were 18.8% and 18.1%, 30.0% and 31.7%, and 99.1% and 96.6%, respectively; no significant differences were observed between both groups. In the NGT-G group, a negative colonic contrast at 24 h demonstrated a higher tendency for future recurrence compared with a positive colonic contrast at 24 h (1-year recurrence rate: negative contrast, 46.9% vs positive contrast, 27.6%). CONCLUSIONS: Gastrografin through a nasogastric tube followed by LT can be a promising treatment strategy for ASBO, with long-term efficacies equivalent to initial LT placement.

Comparison of the incidence of periprocedural myocardial infarction between percutaneous coronary intervention with versus without rotational atherectomy using propensity score-matching.

Complications such as slow flow are frequently observed in percutaneous coronary intervention (PCI) with rotational atherectomy (RA). However, it remains unclear whether the high incidence of slow flow results in the high incidence of periprocedural myocardial infarction (PMI), reflecting real myocardial damage. The aim of this study was to compare the incidence of PMI between PCI with versus without RA using propensity score-matching. We included 1350 elective PCI cases, which were divided into the RA group (n = 203) and the non-RA group (n = 1147). After propensity score matching, the matched RA group (n = 190) and the matched non-RA group (n = 190) were generated. The primary interest was to compare the incidence of PMI between the matched RA and non-RA groups. Before propensity score matching, the incidence of slow flow and PMI was greater in the RA group than in the non-RA group. After matching, the incidence of slow flow was still greater in the matched RA group than in the matched non-RA group (16.8% vs. 9.5%, p = 0.048). However, the incidence of PMI was similar between the matched RA and matched non-RA group (7.4% vs. 5.3%, p = 0.528, standardized difference: 0.086). In conclusion, although use of RA was associated with greater risk of slow flow, use of RA was not associated with PMI after a propensity score-matched analysis. The fact that RA did not increase the risk of myocardial damage in complex lesions would have an impact on revascularization strategy for severely calcified coronary lesions.

Optimal definition of coagulation syndrome after colorectal endoscopic submucosal dissection: a post hoc analysis of randomized controlled trial.

PURPOSE: Endoscopic clipping closure after colorectal endoscopic submucosal dissection (ESD) did not reduce the incidence of post-ESD coagulation syndrome (PECS) in our recent randomized controlled trial (RCT); however, the definition of PECS is still controversial. The aim of this study is to establish optimal definition of PECS with additional analysis of RCT based on another definition. METHODS: In this multicenter, single-blind RCT, individuals were randomly assigned to colorectal ESD followed by endoscopic clipping closure or non-closure. In this post hoc analysis, the definition of PECS was modified as both localized abdominal pain on visual analogue scale and inflammatory response (fever or leukocytosis), from either localized abdominal pain or inflammatory response in the original study. All participants underwent a computed tomography after ESD, and PECS was classified into type I, conventional PECS without extra-luminal air, and type II, PECS with peri-luminal air. RESULTS: A total of 155 patients (84 in the non-closure group and 71 in the closure group) were analyzed. As a result of criteria modification, 21 type I PECS and four type II PECS cases in the original study, which included patients with clear pain and inflammatory response, were downgraded to no adverse event and simple peri-luminal air, respectively. The frequency of PECS showed no significant difference between non-closure and closure groups. CONCLUSION: Clipping closure after colorectal ESD does not reduce the incidence of PECS regardless of the diagnostic criteria. Either localized abdominal pain or inflammatory response might be optimal criteria of PECS (UMIN000027031). TRIAL REGISTRATION NUMBER: UMIN000027031 DATE OF REGISTRATION: April 18, 2017.

Determinants of Periprocedural Myocardial Infarction in Current Elective Percutaneous Coronary Interventions.

Periprocedural myocardial infarction (PMI) is closely associated with long-term cardiovascular events. The factors associated with PMI are not fully understood. The purpose of this study was to investigate the determinants of PMI in contemporary elective percutaneous coronary intervention (PCI). Overall, 731 elective PCI was divided into the PMI (n = 27) and non-PMI (n = 704) groups. Univariate and multivariate logistic regression analysis was used to find factors associated with PMI. In the univariate analysis, PMI was associated with complex lesion characteristics, such as the lesion length, lesion angle, calcification, and Medina classification. In the multivariate logistic regression analysis, the lesion length (per 10-mm increase: odds ratio (OR), 1.477; 95% confidence interval (CI), 1.161‒1.879; P = 0.002), lesion angle ≥ 45° (versus lesion angle < 45°: OR, 4.244; 95% CI, 1.187‒15.171; P = 0.026), and Medina classification (0,1,1) / (1,1,1) (versus other lesions: OR, 14.843; 95% CI, 6.235‒35.334; P < 0.001) were significantly associated with PMI. Of the 24 lesions with lesion angle ≥ 45° in the PMI group, 14 had final TIMI flow grade ≤ 2 in side branches and 9 had transient slow flow in main branches/transient ST elevation during PCI. Of the 87 lesions with Medina classification (1,1,1) / (0,1,1), 19 had final TIMI grade ≤ 2 in side branches. In conclusion, the lesion length, lesion angle ≥ 45°, and Medina classification (0,1,1) / (1,1,1) were significantly associated with PMI in contemporary elective PCI. Preventing flow limitation in both side branches and main vessels in elective PCI for the diffuse long, angulated, or true bifurcation lesions is important.

The first management using intubation of a nasogastric tube with Gastrografin enterography or long tube for non-strangulated acute small bowel obstruction: a multicenter, randomized controlled trial.

BACKGROUND: Gastrointestinal decompression is generally applied to a non-strangulated acute small bowel obstruction (NSASBO). Although long tube (LT) placement and administration of Gastrografin through a nasogastric tube (NGT-G) have shown advantages over NGT alone in previous studies, no studies appear to have compared LT and NGT-G. METHODS: In this multicenter, randomized controlled trial, patients with NSASBO were randomly assigned to receive LT or NGT-G between July 2016 and November 2018 at 11 Japanese institutions. The primary endpoint was non-inferiority of NGT-G compared to LT for non-surgery rate, and the lower limit of the 95% confidence interval for the non-surgery rate (-15%) was set as the lower margin for inferiority of NGT-G compared to LT. RESULTS: In total, 223 patients (LT group, n = 111; NGT-G group, n = 112) were analyzed in the present trial. The non-surgery rate was 87.4% in the LT group and 91.1% in the NGT-G group, with a 3.7% difference between NGT-G and LT (95.3%CI - 5.55 to 12.91; non-inferiority P = 0.00002923). On the other hand, the non-surgery rate with pure NGT-G alone (76.8%) that represents non-cross-over NGT-G without subsequent LT was significantly lower than that with LT (P = 0.039). Median procedure time was significantly shorter with NGT-G (1 min) than with LT (25 min; P < 0.001), whereas no significant differences in mortality or hospital stay were noted between groups. CONCLUSION: NGT-G is an effective alternative to LT as a first-line treatment for NSASBO. A sequential strategy comprising NGT-G followed by LT might offer a new standard for NSASBO. CLINICAL TRIALS REGISTRATION: This trial was registered with the University Hospital Medical Information Network Clinical Trials Registry (umin.ac.jp/ctr Identifier: UMIN000022669) prior to the start of this trial.

The Molar Ratio of Total Branched-chain Amino Acids to Tyrosine Predicts a Digit Symbol Test Abnormality in Cirrhotic Patients.

Objective We aimed to investigate the association between the digit symbol test (DST) and clinical characteristics, including the nutritional status of liver cirrhosis patients. Methods Fifty-nine cirrhotic patients without a history of overt hepatic encephalopathy were retrospectively evaluated. We examined neuropsychological abnormalities (NPAs) using the DST. We also estimated the detailed nutritional status using the Food Frequency Questionnaire (FFQ). The patients were divided into two groups according to their DST status: patients with normal DST scores (DST-Nor group, n=45) and those with abnormal DST scores (DST-Abn group, n=14). The clinical and nutritional findings of the two groups were compared. Results Overall, 14 (23.7%) patients had a DST abnormality. There were significant differences between the two groups in serum albumin (Alb; p=0.0043), valine (Val; p=0.0016), leucine (Leu; p=0.0078), isoleucine (Ile; p=0.0022), the molar ratio of total branched-chain amino acids to tyrosine (BTR; p=0.00025), total-bilirubin (T-Bil; p=0.0071), prothrombin time (%) (PT; p=0.028), and serum sodium (Na; p=0.035). A multivariate analysis found the BTR to be the only independent predictor of a DST abnormality (hazard ratio, 9.24; p<0.031). An FFQ analysis, revealed that the nutritional findings of patients with and without a DST abnormality, were similar. Conclusion The BTR was useful for predicting the risk of NPAs, as defined by a DST abnormality. The risk of NPAs may be estimated by monitoring the BTR.

Efficacy and safety of glecaprevir/pibrentasvir in patients with hepatitis C virus infection aged ≥75 years.

AIM: Opportunities to treat older patients with hepatitis C virus infection have increased. We investigated the efficacy and safety of glecaprevir/pibrentasvir in patients with HCV infection aged ≥75 years. METHODS: We retrospectively evaluated 131 patients with hepatitis C virus infection treated with glecaprevir/pibrentasvir at nine institutions in Japan. The patients were divided into two groups according to their age: the elderly group (n = 43, aged ≥75 years) and younger group (n = 88, aged <75 years). We compared the clinical characteristics, virologic response and adverse events between the two groups. The predictive factors for adverse events were also assessed. RESULTS: The presence of cirrhosis (27.9%), a history of hepatocellular carcinoma (23.3%) and comorbidities (88.4%) were more frequently observed in the elderly group than in the younger group. Six (14.0%) patients in the elderly group and 19 (21.6%) in the younger group dropped out before the sustained virologic response 12 assessment. In the intention-to-treat population, 86.0% in the elderly group and 78.4% in the younger group achieved sustained virologic response 12 (P = 0.30). In the modified intention-to-treat population, all patients achieved sustained virologic response 12. A total of 27.5% of patients experienced adverse events. The most frequently observed adverse events was pruritus, and was significantly associated with female sex, the presence of hemodialysis and serum albumin at baseline <4.0 g/dL. CONCLUSION: Glecaprevir/pibrentasvir therapy was effective and well tolerated, even in elderly patients with hepatitis C virus infection aged ≥75 years. Geriatr Gerontol Int 2020; ••: ••-••.

Anterior quadratus lumborum block for postoperative recovery after total hip arthroplasty: a study protocol for a single-center, double-blind, randomized controlled trial.

BACKGROUND: Appropriate pain management is essential to improve the postoperative recovery after total hip arthroplasty (THA). Various case reports have indicated that anterior quadratus lumborum block (QLB) provides effective postoperative analgesia in lower limb surgeries. However, few randomized controlled trials have confirmed the efficacy of anterior QLB for lower limb surgeries. The aim of this single-center, double-blind, randomized controlled trial is to confirm the efficacy of anterior QLB for postoperative recovery after THA. METHODS: The participants will be randomly assigned to either the anterior QLB or placebo groups, using a set of random numbers for the allocation sequence. Only pharmacists will be aware of the allocations; other investigators will be blinded until study completion. After induction of general anesthesia, anterior QLB will be performed by using 0.25% levobupivacaine or normal saline. Fentanyl will be administered according to blood pressure change during the surgery. The primary outcome will be the quality of recovery 40 score (QoR-40). Secondary outcomes will include the visual analog scale score of pain intensity at rest and movement, intraoperative and postoperative doses of fentanyl, and incidence of postoperative nausea and vomiting. Statistical analysis will be performed by using the Student's t test, Mann-Whitney U test, and Fisher's exact test as appropriate. A P value of less than 0.05 will be considered statistically significant. DISCUSSION: The results of our study will reveal whether anterior QLB is effective for postoperative recovery after THA. TRIAL REGISTRATION: UMIN Clinical Trials Registry, UMIN000032255. Registered on 15 April 2018.

Role of NPR2 mutation in idiopathic short stature: Identification of two novel mutations.

BACKGROUND: C-type natriuretic peptide (CNP, NPPC) and its receptor, natriuretic peptide receptor-B (NPR-B, NPR2), are critical for endochondral ossification. A monoallelic NPR2 mutation has been suggested to mildly impair long bone growth. This study was performed to identify the NPR2 mutations in Korean patients with idiopathic short stature (ISS). METHODS: One hundred and sixteen subjects with nonsyndromic ISS were enrolled in this study, and the NPPC and NPR2 were sequenced. In silico prediction and in vitro functional analysis, using a cell-based assay, were performed to confirm their protein derangement. RESULTS: Mean age at diagnosis of ISS was 8.0 years, and the height z-score was -2.65. Three pathogenic variants (R921Q, R495C, and Y598N) and one benign variant (R787W) of the NPR2 were identified, while no novel sequence variant of the NPPC was found in all subjects. Two novel pathogenic mutants (R495C and Y598N) were predicted as highly pathogenic by several computational methods. In vitro study involving stimulation with CNP, R495C-, and Y598N-transfected cells showed decreased cGMP production compared to wild type-transfected cells. CONCLUSION: Heterozygous NPR2 mutations were found in 2.6% of ISS Korean subjects. This prevalence and the dominant-negative effect of mutant NPR-B on growth signals imply that it is one of genetic causes of ISS.