Effect of Neuromuscular Electrical Stimulation in Patients With Critical Illness: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: Neuromuscular electrical stimulation (NMES) is used in the rehabilitation of patients with critical illness. However, it is unclear whether NMES prevents ICU-acquired weakness (ICU-AW). For this purpose, we conducted an updated systematic review and meta-analysis. DATA SOURCES: We searched the MEDLINE, Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi databases from April 2019 to November 2022 to identify new randomized controlled trials to the previous meta-analysis. STUDY SELECTION: We systematically searched the literature for all randomized controlled trials on the effect of NMES in patients with critical illness. DATA EXTRACTION: Two authors independently selected the studies and extracted data. They calculated the pooled effect estimates associated with the occurrence of ICU-AW and adverse events as primary outcomes and muscle mass change, muscle strength, length of ICU stay, mortality, and quality of life as secondary outcomes. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. DATA SYNTHESIS: Overall, eight studies were added to the previous 10 studies. Evidence suggests that the use of NMES reduces the occurrence of ICU-AW (six trials; risk ratio [RR], 0.48; 95% CI, 0.32-0.72); however, NMES may have little to no effect on pricking sensation in patients (eight trials; RR, 6.87; 95% CI, 0.84-56.50). NMES is likely to reduce the change in muscle mass (four trials; mean difference, -10.01; 95% CI, -15.54 to -4.48) and may increase muscle strength (six trials; standardized mean difference, 0.43; 95% CI, 0.19-0.68). Further, NMES may result in little to no difference in the length of ICU stay, and the evidence is uncertain about the effect on mortality and quality of life. CONCLUSIONS: This updated meta-analysis revealed that the use of NMES may result in a lower occurrence of ICU-AW in patients with critical illness, but its use may have little to no effect on pricking sensation in patients.

Ultrasound Elastography can Detect Placental Tissue Abnormalities.

BACKGROUND: In this prospective cohort study, we examined the utility of elastography to evaluate the fetus and placenta. PATIENTS AND METHODS: Pregnant women in their third trimester of pregnancy, by which time the placenta has formed, were included in this study. A total of 111 women underwent ultrasound examinations, including elastography. Elastographic evaluation was performed using two protocols. First, the placental index (PI) was measured, which quantitatively assesses the hardness of tissue. Second, regions of interest (ROI) were categorized into 3-step scores according to the frequency of the blue area (hardness of placental tissue score [HT score]), which is a qualitative method. After delivery, 40 of the 111 placentas were pathologically examined. RESULTS: The average PI was 44.3 (± 29.4) in the in utero SGA group, which was significantly higher than that in the normal group (8.8 (± 10.0); p < 0.01) during pregnancy. There was a significant correlation between the PI and z score for estimated fetal weight (EFW) (r = -0.55; p < 0.01). Moreover, a significant positive correlation was observed between the PI and the z score of birth weight (r = -0.39; p < 0.01). Pathological ischemia findings of the placenta were identified in 67% of the HT score 3 group, representing 6 of the 9 patients, and in 20% of the HT score 1 group, representing only 3 of the 15 patients. CONCLUSIONS: Placental hardness, as determined by elastography, correlates with both lower estimated fetal body weight and birth weight. These results suggest that ultrasound elastography in the placenta may be an additional marker of intrauterine fetal well-being.

Bauhinia purprea agglutinin-modified liposomes for human prostate cancer treatment.

Bauhinia purprea agglutinin (BPA) is a well-known lectin that recognizes galactosyl glycoproteins and glycolipids. In the present study, we firstly found that BPA bound to human prostate cancer specimens but not to normal prostate ones. Therefore, we sought to develop BPA-PEG-modified liposomes (BPA-PEG-LP) encapsulating anticancer drugs for the treatment of prostate cancer. We examined the tumor targetability of BPA-PEG-LP with human prostate cancer DU145 cells, and observed that fluorescently labeled BPA-PEG-LP dominantly associated with the cells via the interaction between liposome-surface BPA and cell-surface galactosyl molecules. We also observed that BPA-PEG-LP accumulated in the prostate cancer tissue after the i.v. injection to DU145 solid cancer-bearing mice, and strongly bound to the cancer cells. In a therapeutic study, DU145 solid cancer-bearing mice were i.v. injected thrice with BPA-PEG-LP encapsulating doxorubicin (BPA-PEG-LPDOX, 2 mg/kg/day as the DOX dosage) or PEG-modified liposomes encapsulating DOX (PEG-LPDOX). As a result, BPA-PEG-LPDOX significantly suppressed the growth of the DU145 cancer cells, whereas PEG-LPDOX at the same dosage as DOX showed little anti-cancer effect. The present study suggested that BPA-PEG-LP could be a useful drug carrier for the treatment of human prostate cancers.

Association of IL28B rs8099917 genotype and female sex with spontaneous clearance of hepatitis C virus infection: a Japanese cross-sectional study.

Hepatitis C virus (HCV) infection is a serious global health problem. Previous studies have suggested that the interleukin 28B (IL28B) rs8099917 genotype is related to spontaneous clearance of HCV in Caucasian populations. Our objective was to investigate the association of the IL28B rs8099917 genotype with spontaneous clearance of HCV by community-dwelling Japanese. A cross-sectional community-based population study of 993 Japanese residents was conducted. Based on anti-HCV antibody and HCV RNA levels, 50 subjects were assigned to the spontaneous-clearance group, 155 to the chronic-infection group, and 788 to the control group. Logistic regression analysis was done to examine the roles of the IL28B rs8099917 genotype and sex. To analyze the interactions between these factors, an "IL28B rs809991 genotype × sex" interaction term was included in the multivariate analysis. Significantly more subjects in the spontaneous-clearance group than in the chronic-infection group had the favorable IL28B rs8099917 genotype and were female. Multivariate logistic regression analysis extracted the favorable IL28B rs8099917 TT genotype (odds ratio [OR] 9.39; 95% confidence interval [CI], 2.16-40.83, P = 0.003) and female sex (OR, 2.27; 95% CI, 1.16-4.45, P = 0.017) as factors contributing to the spontaneous clearance of HCV. No significant interaction was found between the IL28B rs8099917 genotype and sex (P for interaction = 0.428). Both the favorable IL28B rs8099917 genotype and female sex were associated with the spontaneous clearance of HCV in this Japanese population.

The kinetics of the hepatitis B surface antigen level after the initiation of antiretroviral therapy for hepatitis B virus and human immunodeficiency virus coinfected patients.

BACKGROUND: Hepatic flares (HF), which reflect hepatitis B virus (HBV)-related immune reconstitution inflammatory syndrome (IRIS), frequently occur in patients with HBV and human immunodeficiency virus (HIV) coinfection after the start of antiretoroviral therapy (ART). The rate of hepatitis B envelope antigen (HBeAg) and hepatitis B surface antigen (HBsAg) loss is higher for patients with HF after the initiation of ART. METHODS: We retrospectively examined the kinetics of the HBsAg and HBeAg levels of six HBV/HIV coinfected patients after the commencement of ART that included tenofovir. All were male and HBeAg positive. RESULTS: Three patients developed HF after the initiation of ART. All subsequently lost HBeAg and one of them lost HBsAg after HF. None who did not experience HF lost HBeAg. The HBsAg and HBeAg levels remarkably decreased when HF occurred, but the decline of HBsAg was very slow in the periods before and after HF. The median decline of the HBsAg level at 48 weeks was 2.20 Log IU/mL for patients with HF, but only 1.00 Log IU/ml for patients without HF. Little decline was seen for either group in the median decline of the HBsAg level from 48 weeks to 96 weeks, 0.28 Log IU/mL in the HF group and 0.06 Log IU/mL in the non-HF group. CONCLUSION: The immune reconstitution of a HBV/HIV coinfected patient plays an important role in the clearance of HBV. If HBsAg and HBeAg levels decrease rapidly when HF occurs, the hepatic flare would be due to HBV-related IRIS.

[Hepatitis B Virus Infection: Current Trends and Issues].

Hepatitis B virus (HBV) infection is a global public health problem. HBV has been classified into eight genotypes (A to H) based on complete nucleotide sequencing. The prevalence of specific genotype varies geographically. The rationale for treatment in patients with chronic hepatitis B is to reduce the risk of progressive chronic liver disease, such as cirrhosis and hepatocellular carcinoma. Treatment strategies for chronic HBV infection include interferon and nucleotide analogues (lamivudine, adefovir dipivoxil, entecavir, and tenofovir disoproxil). HBV persists in the body even after serological recovery from acute hepatitis B. Thus, individuals who have been exposed to HBV are at risk of the reactivation of infection, which may result in an increase in serum aminotransferases or a flare when the immune response is suppressed. Patients requiring immunosuppressive therapy should undergo serologic testing for markers of HBV infection. This topic review summarizes these issues related to the management of hepatitis B.

Therapeutic drug monitoring of telaprevir in chronic hepatitis C patients receiving telaprevir-based triple therapy is useful for predicting virological response.

OBJECTIVES: This prospective, pharmacokinetic study was done to investigate the impact of telaprevir plasma trough concentration (Ctrough) in the early stage of treatment on the response to telaprevir-based triple therapy for chronic hepatitis C patients. METHODS: Participants were 70 chronic hepatitis C patients infected with genotype 1. All patients received 12 week triple therapy that included telaprevir (2250 mg/day), pegylated interferon-α2b (pegylated-IFNα2b) (60-150 µg/week) and ribavirin (600-1000 mg/day) followed by a 12 week dual therapy that included pegylated-IFNα2b and ribavirin. Plasma telaprevir Ctrough was determined by a validated assay using HPLC at days 3, 7 and 14. The study was registered as a clinical trial on the University Hospital Medical Information Network (ID 000009656). RESULTS: The rates of undetectable hepatitis C virus RNA at week 4 [rapid virological response (RVR)] and at 24 weeks after therapy [sustained virological response (SVR)] were 71.4% and 82.9%, respectively. Of the patients with RVR, 90% achieved SVR. The mean telaprevir Ctrough levels at days 3, 7 and 14 of SVR patients (2.748, 2.733 and 2.999 µg/mL, respectively) were significantly higher than those of non-SVR patients (1.616, 1.788 and 2.314 µg/mL, respectively) (all P < 0.05). Multiple logistic regression analysis of possible predictors of SVR extracted higher telaprevir Ctrough at day 3 (OR 1.012 by 0.001 µg/mL, P < 0.0001) and interleukin 28B (rs8099917) TT allele (OR 6.16 versus non-TT alleles, P < 0.0001). CONCLUSIONS: Therapeutic drug monitoring of telaprevir in the early stage of treatment is useful in clinical practice for predicting the virological response of patients receiving telaprevir-based triple therapy.

A case of successful treatment with telaprevir-based triple therapy for hepatitis C infection after treatment failure with vaniprevir-based triple therapy.

Recently direct-acting antiviral agents, such as hepatitis C virus (HCV) non-structural 3/4A (NS3/4A) protease inhibitors (PI), have been introduced, and triple therapy regimens that include PI with conventional pegylated interferon α and ribavirin have significantly improved the sustained virological response (SVR) rate, up to 80% for both treatment-naïve and treatment-experienced patients with HCV genotype 1. We here report for the first time a case of the successful treatment of HCV genotype 1 infection with a first generation PI drug (telaprevir) based triple therapy after treatment failure with a second generation PI drug (vaniprevir) based triple therapy. A 67-year-old treatment-naïve Japanese man with HCV genotype 1b infection took part in a phase III clinical trial of vaniprevir-based triple therapy. His serum HCV RNA had become undetectable at week 2 and SVR was highly expected, but HCV RNA reappeared at week 4 after vaniprevir treatment. Polymerase chain reaction direct sequence of the HCV NS3/4A gene at week 8 after vaniprevir treatment showed the emergence of a vaniprevir-resistance mutation (D168V), the probable reason for the treatment failure. Six months later, retreatment with telaprevir-based triple therapy was started. Although the dosages of telaprevir and ribavirin had to be reduced due to severe anemia, the patient achieved an SVR. This case shows the value of repeating PI-based triple therapy with a different drug, a process that would reduce the chance of drug resistant mutation.

A case of successful hepatitis C virus eradication by 24 weeks of telaprevir-based triple therapy for a hemophilia patient with hepatitis C virus/human immunodeficiency virus co-infection who previously failed pegylated interferon-α and ribavirin therapy.

In Japan, the human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection of some patients with hemophilia was caused by the transfusion of imported blood products, such as unheated coagulation factor. With the development of antiretroviral therapy (ART) for HIV, chronic HCV infection has become a major cause of liver disease and mortality for hemophiliac patients coinfected with HCV/HIV. Data is limited regarding the efficacy and safety of antiviral therapy with the HCV protease inhibitor telaprevir (TVR) in combination with pegylated interferon-α (PegIFN-α) and ribavirin (RBV) for hemophilia patients coinfected with HCV/HIV. We report a case of a Japanese patient with hemophilia and HCV/HIV coinfection who had partial response to prior to PegIFN-α and RBV therapy. This is the first published report of 24-week TVR-based triple therapy for a hemophilia patient coinfected with HCV/HIV. The patient had HCV genotype 1a infection with a high viral load. His single-nucleotide polymorphism of the interleukin 28B (rs8099917) gene was the TT major allele. He presented with undetectable HIV RNA and a high CD4(+) T cell counts by taking ART including tenofovir, emtricitabine and raltegravir. He was again treated for HCV with TVR plus PegIFN-α2b and RBV for the first 12 weeks, followed by the continuation of PegIFN-α2b and RBV for 12 additional weeks while continuing ART. He had rapid virological response and achieved sustained virological response with the 24-week treatment. No serious adverse events such as skin rash, severe anemia or exacerbated bleeding tendency were observed, only a mild headache. No dose adjustment was necessary when tenofovir and raltegravir were used in combined with TVR, and no HIV breakthrough was observed. TVR-based triple therapy with ART could can an effective treatment for hemophilia patients coinfected with HCV (genotype 1)/HIV regardless of prior response. TVR can be used in combination with tenofovir, emtricitabine and raltegravir for patients with hemophilia. Furthermore, patients with undetectable HCV RNA at week 4 could be successfully treated with a 24-week regimen.

The Usefulness of Magnetic Resonance Imaging in the Management of Acute Phlegmonous Esophagitis.

Acute phlegmonous esophagitis is a rare life-threatening disease that often requires surgical intervention in case of complications, including esophageal abscess, perforation, or mediastinitis. We present a case of acute phlegmonous esophagitis, in which magnetic resonance imaging (MRI) proved useful in planning the treatment strategy. An 89-year-old woman was admitted to the emergency department with painful swallowing and respiratory distress. She was diagnosed with acute phlegmonous esophagitis and a hypopharyngeal abscess based on computed tomography (CT) findings. However, there was a discrepancy between the clinical course and CT findings. Given the improvement of the patient's condition with conservative treatment with ampicillin/sulbactam, the CT findings suggested an apparent abscess due to increased esophageal wall thickness. However, MR diffusion-weighted images showed a slightly high-intensity signal, suggesting that the enlargement was due to edema rather than an abscess. The patient recovered successfully following conservative treatment. Thus, our findings demonstrate the utility of MRI in the treatment planning of acute phlegmonous esophagitis, especially in cases with unreliable contrast-enhanced CT findings. However, future studies are warranted to explore the utility of MRI in the management of such cases.

Effects of Mobilization within 72 h of ICU Admission in Critically Ill Patients: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Previous systematic review and meta-analysis indicates that rehabilitation within a week of intensive care unit (ICU) admission benefits physical function in critically ill patients. This updated systematic review and meta-analysis aim to clarify effects of initiating rehabilitation within 72 h of ICU admission on long-term physical, cognitive, and mental health. We systematically searched the MEDLINE, Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi for randomized controlled trials (RCTs) between April 2019 and November 2022 to add to the previous review. Two investigators independently selected and extracted data. Pooled effect estimates for muscle strength, cognitive function, mental health after discharge, and adverse events were calculated. Evidence certainty was assessed via Grading of Recommendations, Assessment, Development, and Evaluations. Eleven RCTs were included in the meta-analysis. Early rehabilitation may improve muscle strength (three trials; standard mean difference [SMD], 0.16; 95% confidence interval [CI], -0.04-0.36) and cognitive function (two trials; SMD, 0.54; 95% CI, -0.13-1.20). Contrastingly, early mobilization showed limited impact on mental health or adverse events. In summary, initiating rehabilitation for critically ill patients within 72 h may improve physical and cognitive function to prevent post-intensive care syndrome without increasing adverse events. The effect on mental function remains uncertain.

A bedtime dose of ARB was better than a morning dose in improving baroreflex sensitivity and urinary albumin excretion--the J-TOP study.

The hypothesis that the bedtime dosing of angiotensin receptor blocker (ARB) is superior to morning dose in improving baroreflex sensitivity (BRS) and urinary albumin/creatinine ratio (UACR) was tested in this study. Baroreflex sensitivity was measured at baseline and at 6th month (N = 109) and was found to increase in the bedtime-dose group (P = .004), but not in the morning-dose group. The correlations between the change in BRS and the change in UACR were insignificant in the morning-dose group (r = 0.17, P = .26), but were significant in the bedtime-dose group (r = -0.29, P = .04). In conclusion, the improvement of BRS could be one of the mechanisms by which bedtime dosing of ARB confers renal protection.

Single nedaplatin treatment as salvage chemotherapy for platinum/taxane-resistant/refractory epithelial ovarian, tubal and peritoneal cancers.

AIM: To evaluate toxicity, response and progression-free survival of single nedaplatin chemotherapy in women with platinum/taxane-resistant/refractory epithelial ovarian, tubal and peritoneal cancer. METHODS: Seventeen patients with platinum/taxane-resistant/refractory epithelial ovarian, fallopian tube or primary peritoneal cancer who were treated with a single nedaplatin regimen at 90 mg/m(2) administration on day 1 of a 28-day cycle in our institution between 2005 and 2007 were retrospectively investigated. RESULTS: Ten of 17 patients (59%) had measurable disease. Seven patients were evaluated according to cancer antigen (CA) 125 levels. The overall response was 24% (complete response, 2 patients; partial response, 2 patients). Two of these 4 patients had measurable disease. Stable disease and progressive disease was noted in 6 (35%) and 7 (41%) patients. Median progression-free survival was 8 months (range 3-11) in patients who responded to therapy and 4 months (range 2-6) in patients with stable disease. Mean platinum-free interval due to treatment without using platinum analogues after developing platinum-resistant/refractory disease was 11 months (range 8-12) in patients who responded to nedaplatin regimen and 3 months (range 1-11) in patients who did not (P < 0.01), whereas mean treatment-free interval was 3 months (range 1-5) in responders and 1 month (range 1-3) in non-responders, which did not show a significant difference. Grade 4 hematological toxicity was observed in 2 of 17 patients (12%). No grade 3 or 4 non-hematological toxicity occurred. All toxicities were managed on an outpatient basis. CONCLUSIONS: Single nedaplatin treatment for platinum/taxane-resistant/refractory ovarian, tubal and peritoneal cancer patients is the candidate of salvage chemotherapy with comparable effectiveness and less toxicity to other approved regimens.

Cardiovascular risks of dipping status and chronic kidney disease in elderly Japanese hypertensive patients.

Chronic kidney disease (CKD) increases the risk of cardiovascular events and is often associated with the nondipping pattern of blood pressure (BP). We evaluated ambulatory BP, CKD, and the incidence of cardiovascular events in 811 older hypertensive patients. CKD and the dipping pattern increased the risk of cardiovascular events independent of the 24-hour systolic BP level (CKD: hazard ratio [HR], 2.37; 95% confidence interval [CI], 1.24-4.54; nondippers: HR, 2.16; 95% CI, 1.19-3.91; extreme dippers: HR, 2.38; 95% CI, 1.17-4.83). However, after adjustment for covariates that included CKD, the risk in nondippers was insignificant (HR, 1.83; 95% CI, 0.998-3.34; P=.051), while the risk in extreme dippers remained (HR, 2.59; 95% CI, 1.26-5.32; P=.009) (CKD: HR, 1.81; 95% CI, 0.93-3.54; P=.081). Patients with CKD have an increased risk of cardiovascular events. CKD and other cardiovascular risk factors may account for some of the increased risk in nondippers, but it does not explain the higher risk in extreme dippers.

[Hemodynamic factors associated with the development of hypertension].

Recent studies have focused on the prevention of hypertension among high-risk, nonhypertensive individuals. In this review, we present that the deficiency of renal sodium excretion, small artery remodeling, and arterial stiffening might be potent mechanisms underlying the development of hypertension. The changes of these hemodynamic factors cause to increase blood pressure, and increasing blood pressure would accelerate those changes again. To break the vicious circle, not only the management of risk factors such as diabetes, obesity, or smoking, but also the intervention with antihypertensive agents is considered as a useful and effective procedure.

Higher dietary cholesterol and ω-3 fatty acid intakes are associated with a lower success rate of Helicobacter pylori eradication therapy in Japan.

Background:Helicobacter pylori infection is a known risk factor for duodenal ulcers, gastritis, and gastric cancer. The eradication of H. pylori is successful in treating these disorders; however, the success rate of eradication therapy is declining. There may be an interaction with nutrient intake to account for this decline.Objective: We investigated the influence of food and nutrient intake on H. pylori eradication therapy.Design: In this study, 4014 subjects underwent endoscopy, were tested for serum antibodies to H. pylori (2046 positive; 51.0%), and had their food intake assessed with the use of a food-frequency questionnaire (FFQ). Of the positive subjects, endoscopies showed that 389 (19.0%) had gastritis and/or duodenal ulcers and were also positive for a 13C-urea breath test (UBT). These 389 subjects received 1-wk H. pylori eradication therapy with lansoprazole, amoxicillin, and clarithromycin and a second UBT 8 wk after treatment. Complete demographic characteristics, serum lipid, insulin, glycated hemoglobin, C-reactive protein (CRP), and creatinine concentrations as well as complete FFQs were available for 352 subjects. Multivariate logistic regression analyses were performed to determine factors that were associated with successful H. pylori eradication therapy.Results: The success rate of eradication therapy was 60.4% (235 of 389). Factors associated with the failure of eradication therapy included increased age (P = 0.02), higher CRP concentrations (P < 0.01), higher dietary cholesterol (P < 0.01) or egg intake (P < 0.01), higher ω-3 (n-3) fatty acid (P = 0.02) or fish intake (P = 0.01), and higher vitamin D intake (P = 0.02). Moreover, the higher vitamin D intake was strongly linked to higher fish intake. A limitation of the study is that we did not assess the antibiotic resistance of H. pyloriConclusions: Our results indicate that higher egg and fish intake may be negatively correlated with successful H. pylori eradication therapy in H. pylori-positive subjects with gastritis and/or duodenal ulcers.

Comparison of the Abbott RealTime HCV and Roche COBAS Ampliprep/COBAS TaqMan HCV assays for the monitoring of sofosbuvir-based therapy.

BACKGROUND: On-treatment HCV kinetics play an invaluable role in evaluating the efficacy of interferon-based therapies. However, the importance of HCV RNA monitoring has not been well discussed concerning treatment with sofosbuvir (SOF)-based regimens, especially for the utility of the Abbott RealTime HCV (ART) assay. METHODS: This study consisted of 151 patients infected with HCV genotype-1 or -2, including patients with prior treatment-experience or cirrhosis. HCV genotype-1 patients were treated with SOF/ledipasvir and genotype-2 patients with SOF/ribavirin, both for 12 weeks. Serial measurements of HCV RNA were performed with both the ART and COBAS AmpliPrep/COBAS TaqMan v2.0 (CAP/CTM) assays simultaneously at weeks 0, 1, 2, 4, 6, 8, 10 and 12 of treatment. RESULTS: The rates of HCV RNA target not detected (TND) by ART were significantly lower than those by CAP/CTM between weeks 2 and 12 (end of treatment [EOT]), irrespective of prior treatment-experience or cirrhosis. 11 (11.6%) genotype-1 and 8 (14.3%) genotype-2 patients did not achieve HCV RNA TND by ART at EOT, in contrast to all having HCV RNA TND by CAP/CTM; however, all achieved sustained virological response. The time at which HCV RNA became TND or unquantifiable was not associated with treatment outcome by either the ART or CAP/CTM assay. CONCLUSIONS: Over 10% of the patients continued to have detectable HCV RNA by ART at EOT, irrespective of HCV genotype, prior treatment-experience and/or cirrhosis. However, prolonged residual HCV RNA was not associated with treatment failure.

The Expression Level of Neutrophil CD64 Is a Useful Marker of Systemic Inflammation Associated with HIV Infection.

CD64 is an Fc-gamma-receptor type 1. The expression level of neutrophil CD64 (nCD64) is a known bacterial infection marker, and it also increases in viral infections. We examined the absolute nCD64 before and after the initiation of antiretroviral therapy (ART) to determine its role as an infection and inflammation marker of human immunodeficiency virus (HIV) infection. In this prospective observational study, 94 HIV-infected patients were enrolled and classified into ART (n = 62), ART naive (n = 24), and acute/early phase groups (n = 8). The median nCD64 was 1,430 molecules/cell in the ART group, 2,994 in the ART naive group, 4,625 in the acute/early phase group, and 1,196 in the healthy control group. The nCD64 in the ART group was significantly higher compared with the healthy controls (p = .041), and the nCD64 in the ART naive and acute/early phase groups was significantly higher compared with the ART group (both p < .001). In the ART naive group, nCD64 was significantly higher in patients with than without concomitant infections (3,942 ± 1,519 vs. 2,300 ± 784, p = .004). However, this was influenced by the fact that nCD64 elevated as the stage of HIV infection progressed. nCD64 decreased significantly during the 24 weeks after starting ART (p = .004), although an upward trend in nCD64 was observed at weeks 2 and 4, without symptoms. When immune reconstitution inflammatory syndrome occurred, nCD64 elevated with a wider range than did C-reactive protein. This preliminary study suggests that nCD64 would be useful as a marker of the systemic inflammation of HIV-infected patients.

Successful surgical intervention for rectal perforation due to polyarteritis nodosa: report of a case.

BACKGROUND: Polyarteritis nodosa (PAN) is a primary systemic necrotizing vasculitis with diffuse organ involvements, resulting in a high mortality rate due to multiple organ failure. Although the small bowel is the frequently targeted organ of PAN-associated vasculitis, rectal involvement is very rare, and only one case of rectal bleeding has been previously reported. The mortality rate of PAN with gastrointestinal (GI) perforation is reportedly much higher than that of without severe GI involvement. We herein report the first case of rectal perforation due to PAN, successfully managed with an adequate surgical intervention. CASE PRESENTATION: A 66-year-old woman with PAN had abdominal pain and melena with guarding. Computed tomography scan showed abdominal free air and bubbles in the rectal hematoma. We diagnosed it acute peritonitis, and emergency surgery was performed. After removing rectal hematoma and necrotic tissue, a huge lack of rectal wall spreading to the pelvirectal space was observed. In order to totally remove the necrotic tissue, abdominoperineal resection was needed. Together with histopathological examinations which showed neutrophils and fibrinous necrosis, we finally diagnosed rectal perforation due to PAN. At 19-month follow-up after surgery, she was still healthy with a stable disease of PAN. CONCLUSIONS: We herein reported the first case of successfully managed rectal perforation due to PAN. Early adequate surgical resection may be important for the case with rectal perforation.

Impact of HCV kinetics on treatment outcome differs by the type of real-time HCV assay in NS3/4A protease inhibitor-based triple therapy.

Repeated measurement of the HCV RNA level is essential for properly monitoring treatment efficacy. The aim of this study was to determine the utility of two HCV real-time assays in the evaluation of the impact of hepatitis C virus (HCV) kinetics on the outcome of triple therapy with NS3/4A protease inhibitors (PIs), telaprevir or simeprevir. This study consisted of 171 Japanese patients infected with HCV genotype 1. All 3266 serum samples taken during and post treatment were tested with both the COBAS AmpliPrep/COBAS TaqMan (CAP/CTM) HCV Test v2.0 and the Abbott RealTime (ART) HCV Test. Of the 2597 samples undetectable (lower limit of detection [