A short-term preemptive treatment for cytomegalovirus infection in seropositive patients after liver transplantation

Background/purpose

Cytomegalovirus (CMV) infection remains a challenge following liver transplantation. Preemptive treatment is an effective strategy for CMV infection. However, how long preemptive treatment should be applied is not defined.

Methods

Clinical records of preemptive treatment for CMV infection in patients who underwent liver transplantation were collected. CMV antigenemia (pp65) was monitored weekly during hospital stay and subsequently on follow up whenever indicated clinically. Antiviral treatment was administered based on positive antigenemia (>1 positive cell per 500,000 leukocytes) and discontinued when antigenemia became negative.

Results

CMV infection was diagnosed in 58 (43.9%) of 132 liver transplantation patients. All 58 patients were seropositive for CMV before transplantation. CMV infection was first diagnosed at a median time of 20?days (interquartile range [IQR] 15.3?C26) after transplantation. Twelve (20.7%) patients developed repeated infections. Only one of 58 patients (1.7%) was suspected to have invasive disease. The median (IQR) duration of antiviral treatment was 7 (7?C12) days. Of these patients with CMV infection, 14 (24.1%) patients developed acute rejection peri-anti-CMV treatment and 36 (62.1%) developed other infectious complications.

Conclusion

Preemptive treatment is an effective way to halt the progression of asymptomatic CMV infection. A brief course of antiviral treatment is enough for seropositive patients with CMV infection after liver transplantation.     

Zytomegalievirus nach Nierentransplantation

Background

Despite widespread use of antiviral cytomegalovirus (CMV) prophylaxis, active CMV infections with progression to CMV disease remain of paramount importance after renal transplantation, which can lead to severe complications particularly in CMV seronegative recipients of a CMV seropositive donor kidney.

Objective

Risk stratification of active CMV infections and CMV disease, immune reactivity, clinical challenges, and development of approaches to disease management.

Methods

Discussion of recent developments and expert recommendations.

Results

There is a particularly high risk for the development of active CMV infections and CMV disease in CMV seronegative recipients of a CMV seropositive donor kidney. In this case CMV prophylaxis followed by preemptive therapy is recommended. The focus of this combined strategy is to prevent severe tissue-invasive CMV disease and to reduce the indirect effects of active CMV infections with inferior patient and transplant survival. Patients at increased risk who do not generate adequate CMV-specific cellular immunity after transplantation, nevertheless develop severe and occasionally recurrent active CMV infections after termination of prophylactic measures. In the case of life-threatening therapy-resistant CMV disease, adoptive transfer of CMV-specific T?cells has been proven to be a safe and effective therapy option.

Conclusion

Clinically problematic courses of active CMV infections are limited to those patients with severely impaired CMV-specific immunity. The quantification of CMV-specific cellular immunity represents an appropriate instrument to achieve a better stratification of the risk of active CMV infections in patients at increased risk and is the subject of current research studies.

     

Usefulness of real time PCR for the differentiation and quantification of 652 and JP2 Actinobacillus actinomycetemcomitans genotypes in dental plaque and saliva

Background

Low levels of Cytomegalovirus (CMV) viral load are frequently detected following allogeneic stem cell transplantation (SCT) and CMV disease may still develop in some allogeneic SCT patients who have negative pp65-antigenemia (pp65-Ag) or undetectable DNA. Pp65Ag is a sensitive method to diagnose CMV infection. Quantitative CMV-DNA PCR assay in plasma has been proposed to monitor CMV infection in SCT patients. We evaluated the clinical utility of pp65Ag and PCR assay in plasma of SCT recipients.

Methods

In a prospective longitudinal study, 38 consecutive patients at risk of CMV infection (donor and/or recipient CMV seropositive) were weekly monitored for CMV infection by both quantitative CMV-PCR in plasma (COBAS AMPLICOR CMV MONITOR) and pp65 Ag, during the first 100 days after SCT.

Results

A total of 534 blood samples were simultaneously analysed for pp65Ag and PCR. Overall, 28/38 patients (74%) had active CMV infection within 100 days from SCT. In 16 patients, CMV was first detected by pp65 Ag alone; in 5 patients by both methods and in 6 by PCR assay alone; one patient had CMV biopsy-proven intestinal disease without pp65Ag and PCR assays positivity before CMV disease. Overall, three patients developed intestinal CMV disease (7.9%): one had negative both pp65Ag and PCR assays before CMV disease, one had disease and concomitant positivity of both methods, while in the remaining patient, only pp65Ag was positive before CMV disease.

Conclusion

Plasma PCR(COBAS AMPLICOR CMV MONITOR) and pp65Ag assays were effective in detecting CMV infection, however, discordance between both methods were frequently observed. Plasma PCR and pp65Ag assays may be complementary for diagnosis and management of CMV infection.     

Risk factors associated with elevated blood cytomegalovirus pp65 antigen levels in patients with autoimmune diseases

Objectives

To further assess the relationship between elevated levels of cytomegalovirus (CMV) pp65 antigen in blood, as indicative of viral load, during treatment-free follow-up and CMV diseases in patients with autoimmune diseases and to identify any risk factors associated with elevated viral loads.

Methods

This was a retrospective review of the electronic medical charts of 148 patients with autoimmune diseases who tested positive for CMV pp65 antigen in the blood.

Results

A total of 106 patients were analyzed. During follow-up, elevated viral loads were detected in 35 patients who were not on antiviral therapy, of whom five developed CMV diseases. Elevated viral load was significantly associated with CMV diseases [5/35 vs. 0/71 (no elevated viral load); P = 0.001). Multivariate analysis revealed that lymphopenia [lymphocyte numbers <700/mm³, odds ratio (OR) 34.44, 95 % confidence interval (CI), 7.82–151.66; P < 0.001], systemic lupus erythematosus (SLE) (OR 6.71, 95 % CI, 1.23–36.49; P = 0.028), and polymyositis/dermatomyositis (PM/DM) (OR 10.62, 95 % CI 1.41–79.77; P = 0.022) were significantly associated with elevated viral load.

Conclusions

Elevated viral load was significantly associated with CMV diseases. Patients with SLE or PM/DM and lymphopenia would therefore benefit from a detailed viral load follow-up and careful physical examination.     

Guideline-Based Antibiotics and Mortality in Healthcare-Associated Pneumonia

Background

Guidelines recommend administration of antibiotics with activity against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa for treatment of healthcare-associated pneumonia (HCAP). It is unclear if this therapy improves outcomes for patients with HCAP.

Objective

To determine if administration of guideline-similar therapy (GST) was associated with a reduction in 30-day mortality for HCAP.

Design

Multi-center retrospective study.

Participants

Thirteen hundred and eleven admissions for HCAP in six Veterans Affairs Medical Centers.

Interventions

Each admission was classified as receiving GST, anti-MRSA or anti-pseudomonal components of GST, or other non-HCAP therapy initiated within 48 hours of hospitalization. Association between 30-day mortality and GST was estimated with a logistic regression model that included GST, propensity to receive GST, probability of recovering an organism from culture resistant to antibiotics traditionally used to treat community-acquired pneumonia (CAP-resistance), and a GST by CAP-resistance probability interaction.

Main Measures

Odds ratios and 95% confidence intervals [OR (95% CI)] of 30-day mortality for patients treated with GST and predicted probability of recovering a CAP-resistant organism, and ratio of odds ratios [ROR (95% CI)] for treatment by CAP-resistance probability interaction.

Key Results

Receipt of GST was associated with increased odds of 30-day mortality [OR?=?2.11 (1.11, 4.04), P?=?0.02)] as was the predicted probability of recovering a CAP-resistant organism [OR?=?1.67 (1.26, 2.20), P?P?=?0.05].

Conclusions

For HCAP patients with high probability of CAP-resistant organisms, GST was associated with lower mortality. Consideration of the magnitude of patient-specific risk for CAP-resistant organisms should be considered when selecting HCAP therapy.     

Who Needs Inpatient Detox? Development and Implementation of a Hospitalist Protocol for the Evaluation of Patients for Alcohol Detoxification

BACKGROUND

Clinicians caring for patients seeking alcohol detoxification face many challenges, including lack of evidence-based guidelines for treatment and high recidivism rates.

OBJECTIVES

To develop a standardized protocol for determining which alcohol dependent patients seeking detoxification need inpatient versus outpatient treatment, and to study the protocol’s implementation.

DESIGN

Review of best evidence by ad hoc task force and subsequent creation of standardized protocol. Prospective observational evaluation of initial protocol implementation.

PARTICIPANTS

Patients presenting for alcohol detoxification.

INTERVENTION

Development and implementation of a protocol for evaluation and treatment of patients requesting alcohol detoxification.

MAIN MEASURES

Number of admissions per month with primary alcohol related diagnosis (DRG), 30-day readmission rate, and length of stay, all measured before and after protocol implementation.

RESULTS

We identified one randomized clinical trial and three cohort studies to inform the choice of inpatient versus outpatient detoxification, along with one prior protocol in this population, and combined that data with clinical experience to create an institutional protocol. After implementation, the average number of alcohol related admissions was 15.9 per month, compared with 18.9 per month before implementation (p?=?0.037). There was no difference in readmission rate or length of stay.

CONCLUSIONS

Creation and utilization of a protocol led to standardization of care for patients requesting detoxification from alcohol. Initial evaluation of protocol implementation showed a decrease in number of admissions.     

CMV reactivation caused by methylprednisolone therapy for ARDS after esophagectomy

Background

Cytomegalovirus (CMV) infection is endemic worldwide. Although CMV reactivation often becomes a serious problem in immunocompromised patients, the prevalence of CMV reactivation caused by methylprednisolone therapy for ARDS after esophagectomy has yet to be determined.

Method

Among 175 consecutive patients with thoracic squamous cell esophageal cancer who underwent esophagectomy with extensive lymph node dissection at Akita University Hospital between 2007 and 2010, 11 patients (6.3?%) diagnosed with ARDS during the acute phase of esophagectomy were enrolled and treated with steroid pulse therapy, high-dose (15?C20?mg/kg/day) administration and tapering in this retrospective study.

Results

Seven of the 11 patients (63.6?%) were diagnosed with CMV reactivation based on CMV antigenemia assayed 19.1?days after the start of methylprednisolone administration and were treated with ganciclovir for 39.6?days. Six of the 7 patients (85.7?%) diagnosed with CMV reactivation were administered a total methylprednisolone dose of more than 4,000?mg. Though there was no significant difference between patients with and without CMV reactivation, there was a tendency that patients with CMV reactivation showed a lower minimum number of lymphocytes during the acute phase of esophagectomy (p = 0.051, Student??s t test, average 223.3 and 298.0/??l, respectively).

Conclusion

Though the number of study patients is small, the prevalence of CMV reactivation caused by high-dose methylprednisolone therapy for ARDS after esophagectomy is remarkably high. This result strikes a note of warning concerning the management of these patients and suggests the importance of screenings for CMV reactivation so as to make an accurate diagnosis and initiate treatment in a timely manner.     

Natural course of Fabry disease and the effectiveness of enzyme replacement therapy: a systematic review and meta-analysis

Objective

Current available evidence on long-term effectiveness of enzyme replacement therapy (ERT) for Fabry disease is limited. More insight is needed whether ERT effectiveness differs in patients with and without baseline end-organ damage.

Design

Through a systematic review, untreated and ERT treated males and females with Fabry disease were compared for main clinical outcomes: renal function, left ventricular mass (LVmass), cerebral white matter lesions (WMLs) and end-organ complications. Through a meta-analysis ERT effectiveness was estimated in different disease stages.

Data extraction

Two reviewers assessed quality of the included studies according to guidelines for prognosis research. Data were synthesized using a random effects meta-analysis.

Results

Thirty-one studies were systematically reviewed while six studies were included in the meta-analysis. In patients with a GFR?>?60 ml/min/1.73 m², decline of renal function was similar for treated and untreated patients. Only ERT treated males with a GFR?<?60 ml/min/1.73 m² had a slower rate of decline in renal function, possibly attributable to anti-proteinuric therapy. Regardless of left ventricular hypertrophy (LVH) at baseline, LVmass remained stable or increased in males despite ERT, however at a slower rate compared to untreated male patients. In ERT treated females with LVH LVmass decreased, and remained stable in females without LVH. WMLs can not be prevented by ERT. Stroke, cardiac and end-stage renal complications develop, though the incidence of new complications seems to be reduced during ERT.

Conclusion

ERT is effective in reducing LVH, but has a limited effect on renal function. Improved treatment options are needed for Fabry disease.     

Cytomegalovirus,inflammatory bowel disease,and anti-TNFα

Background and purpose

Anti-TNFα agents emerged in inflammatory bowel disease (IBD) as an effective option in situations that, otherwise, would be refractory to medical therapy. Cytomegalovirus infection may present with a high spectrum of manifestations and lead to high morbidity and mortality. However, its clinical significance in IBD course remains unknown and data on its association with anti-TNFα are limited.

Aims

This study aims to evaluate cytomegalovirus (CMV) infection/disease in patients with IBD treated with anti-TNFα; if possible, possible risk factors associated with CMV infection/disease in IBD patients under anti-TNFα as well as the influence of CMV infection/disease in IBD course would be determined.

Methods

During three consecutive years, all IBD patients starting infliximab in our department were included. Cytomegalovirus status before anti-TNFα was evaluated. Data regarding IBD, therapeutic and IBD course after infliximab, were recorded. CMV analysis was performed with polymerase chain reaction (PCR)-cytomegalovirus in peripheral blood and colonoscopy with biopsies (histopathology/immunohistochemistry).

Results

We included 29 patients: female—83%; Crohn’s disease–51.8%, ulcerative colitis—44.8%, non-classified colitis—3.4%; 23 cytomegalovirus seropositive. Median follow-up: 19 months (3–36). During follow-up, 14 patients were under combination therapy with azathioprine and 5 did at least 1 cycle of corticosteroids. Twenty-one patients responded to infliximab. We registered 8 exacerbations of IBD. Four patients discontinued infliximab: none had CMV infection. We documented 1 case of intestinal cytomegalovirus infection—detected in biopsies performed per protocol in an asymptomatic UC patient, who responded to valganciclovir without infliximab discontinuation.

Conclusions

Infliximab, with/without immunosuppression, does not confer an increased risk of (re)activation of cytomegalovirus. Cytomegalovirus was not responsible neither for significant morbidity nor mortality in IBD.

     

Reexamination of the assessment criteria for rheumatoid arthritis disease activity based on comparison of the Disease Activity Score 28 with other simpler assessment methods

Objective

To explore simpler and possibly more appropriate tools than the conventional Disease Activity Score 28 (DAS28) for assessing rheumatoid arthritis (RA) and to derive more reliable DAS28-based criteria.

Methods

The capabilities of assessing disease activities in 250 RA patients were compared between DAS28 and other methods, including the Simplified DA Index (SDAI), Clinical DA Index (CDAI), and Routine Assessment of Patient Index Data-3 (RAPID-3).

Results

SDAI and CDAI showed a good correlation and consistency with DAS28, whereas RAPID-3 yielded inferior results. In terms of remission criteria, DAS28 was less stringent than SDAI or CDAI; when RA remission was reexamined based on more stringent SDAI or CDAI criteria, cut-off values for DAS28-C-reactive protein of <1.72 were considered to be appropriate. The conventional DAS28 was considered to be appropriate for assessing low, middle and high disease activities because it provides criteria similar to or more stringent than those of other methods, while SDAI and CDAI were considered to be simpler and more appropriate criteria for assessing remission.

Conclusion

For assessing remission, DAS28-CRP provides the most appropriate criterion of the methods compared when the currently used cut-off value of 2.3 is lowered to a new value of 1.72.     

Prodromal Irritable Bowel Syndrome May Be Responsible for Delays in Diagnosis in Patients Presenting with Unrecognized Crohn��s Disease and Celiac Disease, but Not Ulcerative Colitis

Introduction

We aimed to determine the prevalence and duration of prodromal periods in patients with celiac disease and inflammatory bowel disease (Crohn??s disease and ulcerative colitis). Furthermore, we explored to what extent vague abdominal symptoms consistent with both disorders were attributed to irritable bowel syndrome (IBS) and if the presence of prodromal IBS (P-IBS) had an impact on prodrome duration.

Methods

In the study, 683 biopsy-proven patients (celiac n = 225, ulcerative colitis n = 228, Crohn??s disease n = 230) completed a postal survey including an assessment of prodromal periods and IBS symptoms during both the prodrome and at present (achieved by completion of the ROME II criteria). Results were compared to age/sex-matched controls (n = 348).

Results

Crohn??s disease patients had the highest prevalence of prodromes (94%) in comparison to ulcerative colitis (48%) and celiac disease (44%). However, Crohn??s disease patients have the lowest prevalence of P-IBS (29%) in comparison to ulcerative colitis (38%) and celiac disease (67%). Prodrome duration in patients with P-IBS Crohn??s disease was 4 years in comparison to 2 years without (p = 0.018). Prodrome duration in P-IBS celiac disease was 10 years in comparison to 7 years without (p = 0.046). Prodrome duration in patients with ulcerative colitis was not affected by P-IBS (p ?? 0.05). Age and sex were not confounding factors.

Conclusions

This is the first study to make direct comparisons of prodrome periods between celiac disease and IBD. Prodrome duration in celiac disease is significantly longer and more often characterized by P-IBS than IBD. In celiac disease and CD, P-IBS increases prodrome duration. This may represent a failure to understand the overlap between IBS and celiac disease/IBD.     

Enhanced recovery after elective colorectal resection outside a strict fast-track protocol. A single centre experience

Introduction

Optimising the management of hospitalised patients is a major concern. In colorectal surgery, the concept of enhanced recovery has been popularised by means of “fast-track” protocols, aiming at patient's discharge on the second postoperative day. Nevertheless, a strict fast-track protocol has several limitations. It is very demanding for the patient and therefore applicable only to a limited number of patients.

Aim

In order to optimise, in every aspect, the postoperative recovery of each patient undergoing an elective colorectal resection inside our institution, we set up a “soft” enhanced recovery programme.

Material-methods

A retrospective analysis was conducted in 92 patients evaluating the respective impact of protocol application throughout the duration of the hospital stay.

Results

When all the required measures of our protocol were correctly implemented, the median discharge day was postoperative day 3 (range 3–5 days). On the contrary, when deviations occurred, they resulted in longer hospital stay (p?<?0.001). Patients operated by laparoscopy were discharged earlier than patients operated by laparotomy (p?<?0.001). The use of nasogastric tube and postoperative drainage prolonged significantly the length of stay (p?=?0.001 and p?<?0.001 respectively). When the urinary catheter was not removed or oral feeding not resumed on postoperative day 1, the patients were discharged later (p?<?0.001).

Conclusions

There are substantial possibilities of optimising the recovery process after an elective colorectal resection, outside a strict fast-track protocol.     

Increased Fracture Risk Assessed by Fracture Risk Assessment Tool in Greek Patients with Crohn’s Disease

Background

The World Health Organization has recently developed the Fracture Risk Assessment Tool (FRAX) based on clinical risk factors and bone mineral density (BMD) for evaluation of the 10-year probability of a hip or a major osteoporotic fracture. The aim of this study was to evaluate the use of the FRAX tool in Greek patients with inflammatory bowel disease (IBD).

Methods

FRAX scores were applied to 134 IBD patients [68 Crohn’s disease (CD); 66 ulcerative colitis (UC)] who underwent dual-energy X-ray absorptiometry scans at the femoral neck and lumbar spine during the period 2007–2012. Calculation of the FRAX scores, with or without BMD, was made through a web-based probability model used to compute individual fracture probabilities according to specific clinical risk factors.

Results

The median 10-year probability of a major osteoporotic fracture for IBD patients based on clinical data was 7.1 %, and including the BMD was 6.2 %. A significant overestimation with the first method was found (P = 0.01). Both scores with and without BMD were significantly higher in CD patients compared with UC patients (P = 0.02 and P = 0.005, respectively). The median 10-year probability of hip fracture based on clinical data was 0.8 %, and including the BMD was 0.9 %. The score with use of BMD was significantly higher in CD compared with UC patients (P = 0.04).

Conclusions

CD patients have significantly higher FRAX scores and possibly fracture risk compared with UC patients. The clinical FRAX score alone seems to overestimate the risk of osteoporotic fracture in Greek IBD patients.     

Effect of a 14-day course of foscarnet on cytomegalovirus (CMV) blood markers in a randomized study of human immunodeficiency virus-infected patients with persistent CMV viremia. Agence National de Recherche du SIDA 023 Study Group.

A randomized open-label phase 2 trial compared the virological and clinical effects on cytomegalovirus (CMV) infection of a 14-day course of intravenous foscarnet (100 mg/[kg x 12 h]) or no treatment in 42 HIV-infected patients with < 100 CD4 cells/mm3 and persistent asymptomatic CMV viremia. All CMV markers (blood culture, pp65 antigenemia, plasma and leukocyte DNA) either became negative or decreased significantly at day 14 in the foscarnet group. CMV blood culture results at day 14 were positive in 14% of those receiving foscarnet versus 60% of control patients (P = .004). However, after the end of treatment, all markers reappeared or the virus load rapidly increased. The probability of CMV disease at 6 months was 43% in both groups. Patients who had or who achieved a negative blood culture at any time had a reduced risk of CMV disease (RR = 2.64; 95% CI = 1.24-5.62; P = .02). This study suggests that sequential courses of intravenous foscarnet might not be a good strategy for preemptive therapy in this population and that in patients with a positive blood marker, treatment able to induce and maintain negative CMV blood cultures could constitute an effective intervention.     

Use of multiple methods for genotyping Fusarium during an outbreak of contact lens associated fungal keratitis in Singapore

Background

Since African-Americans have twice the prevalence of cytomegalovirus (CMV) infections as age-matched Caucasians we sought to determine the ages and possible sources of infection of African-American children.

Methods

Subjects were 157 African-American healthy children and adolescents and their 113 household adults in Richmond VA. Families completed a questionnaire, provided saliva for antibody testing, and adolescents were interviewed regarding sexual activity.

Results

Regardless of age CMV seropositivity was not associated with gender, breast feeding, health insurance, sexual activity, or household income, education, or size. In the final regression model, prior CMV infection in adults was over two-fold higher than in children (chi-square = 18.8, p < 0.0001). At one year of age the CMV seropositivity rate was 11% (95%CI = 4% – 24%) and increased 1.8% each year until age 13 years. Between ages 13 and 20 years the CMV seropositivity rate remained between 22% and 33%. For adults, the CMV seropositivity rate was 84% in 21 year olds (95%CI = 69%–.92%). There was no association between CMV infections of the children and their mothers but CMV infections among siblings were associated.

Conclusion

We observed that African-American children had CMV seroprevalence rates by age 20 years at less than one-half of that of their adult mothers and caregivers. Sibling-to-sibling transmission was a likely source of CMV infections for the children. The next generation of African-American women may be highly susceptible to a primary CMV infection during pregnancy and may benefit from a CMV vaccine.     

Hepatitis C viremia interferes with serum hepatitis B virus surface antigen and DNA levels in hepatitis B uremics

Purpose

Hepatitis B virus (HBV) and HCV might cause reciprocal interference. We aimed to elucidate the influence of HCV and interleukin-28B (IL-28B) genetic variants in the HBV DNA and HBsAg levels in uremic HBV carriers.

Methods

Assessment of HCV and HBV viral loads, HBsAg levels and IL-28B genotype were performed in 229 HBsAg-positive patients from a cohort of 1,681 uremics.

Results

Patients with HCV viremia had significantly lower HBV DNA (2.58 ± 0.80 vs. 3.16 ± 1.48 log IU/mL, p = 0.005) and HBsAg levels (1.33 ± 1.35 vs. 2.23 ± 1.31 log IU/mL, p = 0.002) compared with those without. IL-28B rs8099917 genotype had no impact on HBsAg and HBV DNA levels. In multivariate regression analysis, HCV RNA levels had a more significant negative correlation with HBsAg levels [β ?0.905; 95 % confidence interval (CI) ?1.477, ?0.334; p = 0.002] than with HBV DNA levels (β ?0.586; 95 % CI ?1.206, 0.034; p = 0.06). The serum HBV DNA and HBsAg levels had a positive correlation (r = 0.43, p < 0.001) among the 215 HBeAg-negative patients. However, the correlation was not observed in patients with HCV viremia (r = 0.23, p = 0.29). Linear regression analysis revealed that age (β ?0.286; 95 % CI ?0.043, ?0.014; p < 0.001) and the HBV DNA level (β 0.373; 95 % CI 0.239, 0.549; p < 0.001) correlated independently with the HBsAg level among HBeAg-negative patients without HCV viremia, but not among those with concomitant HCV viremia.

Conclusions

HCV viremia suppressed both HBsAg and HBV DNA levels. The HBsAg levels correlated with the HBV DNA levels only in patients without concomitant HCV viremia.     

Is transarterial chemoembolization beneficial for patients with diffuse infiltrative hepatocellular carcinoma?

Purpose

Diffuse infiltrative hepatocellular carcinoma (D-HCC) is an incurable disease with short survival time. Transarterial chemoembolization (TACE) was often used to alleviate patient’s symptoms and reduce tumor burden. However, it remains unknown if the TACE benefits the survival of D-HCC patients.

Methods

A hospital-based retrospective study was conducted at a large referral hospital in Taiwan for a 9-year period (2000–2008).

Results

Of the 150 D-HCC patients, 106 patients were related to hepatitis B virus (HBV), 17 to hepatitis C virus (HCV), 3 to both HBV and HCV, and 24 not to HBV or HCV. Multivariate Cox regression analysis showed treatment strategy, serum alpha-fetoprotein level, model for end-stage liver disease (MELD) score, serum gamma glutamyl transferase, and serum lactic acid dehydrogenase were associated with survival time. Compared to supportive treatment, the adjusted hazard ratios of transarterial chemoembolization (TACE) and chemotherapy including oral or systemic chemotherapy were 0.383 (p < 0.001) and 0.711 (p = 0.289), respectively.

Conclusion

TACE is a preferred therapy for D-HCC patients.     

Transforming Growth Factor beta1 Gene Variation Leu10Pro Affects Secretion and Function in Hepatic Cells

Background

Our previous work revealed transforming growth factor beta1 (TGFβ1) gene polymorphisms are associated with susceptibility to hepatocellular carcinoma and liver cirrhosis. However, no further study of functional substitution in hepatic cells has yet been reported.

Aims

This study was designed to uncover the functional mechanisms of TGFβ1 gene polymorphisms in the pathogenesis of liver diseases.

Methods

Two recombinant TGFβ1 expression plasmids containing TGFβ1 codon 10 Leu/Pro variation were constructed with CMV promoter and transfected into human hepatoma cell lines (HepG2 and SMMU 7721), hepatic stellate cells (LX-2), and immortalized hepatocytes (L02). The secretion capacities of TGFβ1 protein in the transfected cells were determined by ELISA. Apoptosis, proliferative activity, and expression of CD 105, CD83, and CD80 were also measured by use of flow cytometry.

Results

The ELISA results showed that cells transfected with CMV-Pro10 were more capable of TGFβ1 secretion than those transfected with CMV-Leu10. Functionally, CMV-Pro10 was more apoptosis-protective and induced more proliferation than CMV-Leu10 in transfected hepatic cells. Pro10 up-regulated expression of CD105 and down-regulated expression of CD83.

Conclusions

TGFβ1 gene Leu10Pro variation in signal peptide has significant effects on TGFβ1 secretion and functions in hepatic cells.     

Active CMV disease does not always correlate with viral load detection

The use of quantitative cytomegalovirus (CMV) real-time polymerase chain reaction (RT-PCR) and preemptive ganciclovir therapy is replacing prophylaxis as the management of choice in high-risk patients undergoing stem cell transplantation (SCT). However, there are limited data defining its role in this setting. In the current retrospective single-centre study, quantitative RT-PCR was used to determine CMV in 577 consecutive patients undergoing SCT (172 allogeneic and 405 autologous) over a 5-year period. CMV RT-PCR was performed weekly until cessation of immunosuppression (allogeneic) or for 30 days post-SCT (autologous). Treatment was commenced after two consecutive positive results or a high copy on the first occasion (> 1000 copies/ml, > 3 log). The overall CMV reactivation rate in patients undergoing allogeneic SCT was 30%, with reactivation observed in 72% of high-risk patients (recipient positive patients). CMV end-organ disease was observed in eight patients (1%); of these, four were CMV RT-PCR negative at the time of diagnosis of end-organ CMV disease, with three remaining negative throughout the course of the disease. CMV-related mortality was recorded in three patients. The current data support a preemptive treatment strategy-based CMV RT-PCR, but indicate that in symptomatic patients, a negative CMV PCR result does not exclude CMV end-organ disease.     

Efficacy and safety of sequential therapy versus standard triple therapy in Helicobacter pylori eradication in Kashmir India: a randomized comparative trial

Background

Increasing resistance against Helicobacter pylori has resulted in reduced eradication rates.

Objective

This study aims to determine whether eradication rates for H. pylori infection with sequential therapy is better than standard triple therapy.

Patients

Patients with endoscopy documented peptic ulcer and H. pylori infection confirmed by histology and rapid urease test.

Intervention

Patients were randomized into two groups; 134 received standard triple therapy (pantoprazole 40 mg, clarithromycin 500 mg and amoxicillin 1 g each administered twice daily) for 10 days and 138 received sequential regimen (pantoprazole 40 mg plus amoxicillin 1 g twice daily for 5 days followed by 40 mg pantoprazole, 500 mg clarithromycin, and 500 mg tinidazole each administered twice daily for 5 days). Eradication was confirmed by histology and rapid urease test. Compliance and adverse effects were determined by the recovery of empty medicine strips and questioning.

Results

The eradication rates with sequential therapy were significantly greater than with standard therapy on both intention-to-treat analysis (76.0 % vs. 61.9 %, p?=?0.005; difference, 14.1 % [95 % CI, 6.5–19 %] and per protocol analysis (84.6 % vs. 67.4 %, p?=?0.002; difference, 17.2 % [95 % CI, 8.5–23.5 %]). The incidence of side effects did not differ between the two therapy groups. One patient in standard therapy discontinued treatment due to side effects.

Limitation

Cultures were not performed. Loss to follow up was 5.2 % in standard therapy and 6.5 % in sequential therapy.

Conclusion

Sequential therapy was significantly more effective than standard therapy for eradicating H. pylori infection in peptic ulcer disease in Asian patients. Side effects were similar.