Herpes zoster in frail elderly patients: prevalence, impact, management, and preventive strategies.

Population aging is a worldwide phenomenon with significant and manifold impacts on society. Advanced age correlates with the onset of frailty. In this vulnerable state, the immune response is weakened and a higher susceptibility to infectious diseases is observed. The present narrative review aims to cover the topic of herpes zoster (HZ) and its complications in frail populations. The lifetime risk of developing HZ is estimated at about 20-30%, and the risk increases with age. In older people, HZ can lead to the inability to recover the lifestyle, the interests, and the level of activity that existed before its development. Severity of the disease at presentation and depression are the major correlates of pain burden in patients with acute HZ and postherpetic neuralgia (PHN). The frail elderly need careful assessment prior to treatment initiation and could be affected to a greater extent by treatment-related adverse events. In light of the significant burden caused by HZ and its complications in the frail elderly, the adoption of a preventive strategy appears to be promising, particularly using vaccination in appropriate age- and risk-groups. Although very few vaccine studies consider explicitly the frail elderly as their study population, there is evidence that the live, attenuated vaccine induces significant immunological responses. An adjuvanted recombinant subunit vaccine has recently been approved in Canada, in the United States, in the European Union, and in Japan, and will likely provide additional opportunities for prevention.

Clinical features and outcome of hospitalized patients with HSV-1 DNA in the lower respiratory tract.

The aim of this study was to define the clinical impact of Herpes simplex virus-1 (HSV-1) DNA detection in the low respiratory tract of hospitalized patients. Forty-nine patients admitted to the University Hospital Tor Vergata, Rome, Italy, from May 2013 to June 2014, were analysed. Inclusion criteria were the presence or absence of HSV-1 DNA in clinical routine bronchoalveolar lavage (BAL) fluid specimens. Nineteen individuals were positive (cases) and 30 negative (controls) for the presence of HSV-1 DNA. The two groups were matched for age, gender and month of BAL collection. Cases and controls differed significantly according to length of stay in hospital (p=0.027), ICU transfer (p=0.02), disease severity (p=0.003), death (p=0.009), haematological and blood chemistry tests. Among cases, survivors and deceased patients differed significantly regarding ICU transfer (p=0.0001), mechanical ventilation (p=0.0048), disease severity (p=0.028) and risk of death (p=0.013). A trend towards higher HSV-1 loads was observed in the cases who died. These results suggest that detection of HSV-1 DNA in BAL fluid specimens is a marker of disease severity and poor outcome. Further prospective studies are necessary to deepen the clinical significance of HSV-1 DNA detection in the lower respiratory tract of hospitalized patients.

A systematic analysis of host factors reveals a Med23-interferon-λ regulatory axis against herpes simplex virus type 1 replication.

Herpes simplex virus type 1 (HSV-1) is a neurotropic virus causing vesicular oral or genital skin lesions, meningitis and other diseases particularly harmful in immunocompromised individuals. To comprehensively investigate the complex interaction between HSV-1 and its host we combined two genome-scale screens for host factors (HFs) involved in virus replication. A yeast two-hybrid screen for protein interactions and a RNA interference (RNAi) screen with a druggable genome small interfering RNA (siRNA) library confirmed existing and identified novel HFs which functionally influence HSV-1 infection. Bioinformatic analyses found the 358 HFs were enriched for several pathways and multi-protein complexes. Of particular interest was the identification of Med23 as a strongly anti-viral component of the largely pro-viral Mediator complex, which links specific transcription factors to RNA polymerase II. The anti-viral effect of Med23 on HSV-1 replication was confirmed in gain-of-function gene overexpression experiments, and this inhibitory effect was specific to HSV-1, as a range of other viruses including Vaccinia virus and Semliki Forest virus were unaffected by Med23 depletion. We found Med23 significantly upregulated expression of the type III interferon family (IFN-λ) at the mRNA and protein level by directly interacting with the transcription factor IRF7. The synergistic effect of Med23 and IRF7 on IFN-λ induction suggests this is the major transcription factor for IFN-λ expression. Genotypic analysis of patients suffering recurrent orofacial HSV-1 outbreaks, previously shown to be deficient in IFN-λ secretion, found a significant correlation with a single nucleotide polymorphism in the IFN-λ3 (IL28b) promoter strongly linked to Hepatitis C disease and treatment outcome. This paper describes a link between Med23 and IFN-λ, provides evidence for the crucial role of IFN-λ in HSV-1 immune control, and highlights the power of integrative genome-scale approaches to identify HFs critical for disease progression and outcome.

Preventing and managing herpes zoster: key actions to foster healthy aging.

Population aging is the demographic phenomenon characterizing all countries in the world, and it is challenging the national infrastructures, in particular health systems. However, aging itself is not associated with increased medical spending, but disability and comorbidity that affect older individuals are the actual drivers for health expenditures. Therefore, if people age in better health, medical spending may be significantly reduced. Preventative interventions proved to be effective in reducing/preventing disease and disability and often found to be cost effective, include diet and exercise interventions, medications, routine disease screenings, and immunizations. Vaccination can protect older citizens against life-threatening diseases, such as influenza, pneumococcal infections, tetanus, and against diseases which adversely impact their quality of life, such as herpes zoster (HZ). Including HZ vaccination in its citizens' lifetime immunization calendar can reinforce Europe's commitment toward active, healthy aging. This paper outlines the consensus statement of a group of Italian experts on HZ.

[Ebola Virus Disease (EVD): proposed guideline for hospital triage of suspect and probable cases]. / Malattia da Virus Ebola (MVE): proposta di linea guida per il triage ospedaliero dei casi sospetti e probabili.

The magnitude of the present Ebola epidemic and the resonance in the media has led to the need to draw clear guidelines for the health personnel potentially involved, since the fears raised by the high lethality of the disease may create inefficiencies Here we present the guidelines for a medium-sized hospital, where, at present, the chance to confront a case of Ebola virus disease is rare, but not impossible. The role and activities of each professional involved and the procedures have been set out. We think that this exercise will be useful for all structureswith characteristics similar to ours.

One-year follow-up of patients with long-lasting post-herpetic neuralgia.

BACKGROUND: Recent information on epidemiology and management of post-herpetic neuralgia (PHN), a painful complication of zoster, is scarce. METHODS: This study was conducted at the Pain Clinic of the Policlinico Tor Vergata, Rome, Italy, on eighty-five immunocompetent patients with a clinical diagnosis of PHN. At enrollment (time 0, T0), the patients were interviewed by physicians to obtain demographic data and information about their zoster clinical history and underwent a blood test for VZV-DNA research. DN4 and SF-12 questionnaires were used to assess the neuropathic nature of pain and the overall health status, respectively. A one-year follow-up was planned for enrolled cases, who were visited at regular intervals of at least 3 months. RESULTS: At T0 all the patients were at least 6 months from the episode of acute zoster and still presented with intense pain (mean VAS =6.7; mean DN4 = 5.7). Using antivirals within 72 hours from the rash onset was associated to a significant reduction of pain at T0 (p = 0.006 vs untreated patients). Only 2.6% of patients treated with antivirals during acute zoster but 18.6% of the untreated ones presented with neuropathic pain at T12 (p =0.007), even though the two groups were similar at T0. VZV-DNA was found in 5 out of the 50 available blood samples. At the last follow-up visit, PCS and MCS scores of the PHN patients were found to be recovered over those of the historical age-matched healthy controls. Undesirable side effects of analgesic therapies were observed in 15.3 to 28.8% of the patients. CONCLUSIONS: Patients who six months after acute zoster still have significant neuropathic pain, have a high probability of suffering from chronic pain in the subsequent months/years. The initial antiviral treatment has a significant impact on the pain. Current strategies of analgesic therapy are effective to achieve relief of pain in PHN patients, but they are burdened with heavy and undesirable side effects.

Burden of herpes zoster-associated chronic pain in Italian patients aged 50 years and over (2009-2010): a GP-based prospective cohort study.

BACKGROUND: Post-herpetic neuralgia (PHN) is the most common complication in herpes zoster (HZ) patients. METHODS: We performed a longitudinal, prospective study in 108 general practices throughout Italy to assess how many immunocompetent patients aged ≥50 years with newly diagnosed HZ develop HZ-associated pain, its duration and management over 6-months. HZ-associated pain was assessed by a direct question to the patient and by self-assessment of the worst pain felt in the previous two weeks on a visual analogue scale (VAS), a score ≥3 was taken as pain. PHN was defined as pain reported during the study period persisting for ≥3 months. Quality of life (QoL) was measured using the SF-12 questionnaire. RESULTS: At enrolment, 370 of the 413 patients (89.6%) reported HZ-associated pain which was still present in 20.6% and 9.2% of patients after three and six months, respectively, despite many patients receiving recommended anti-viral therapy. The overall QoL scores were lower than those in healthy Italians of similar age; scores for patients with HZ-associated pain were lower. The presence of >50 vesicles and VAS score ≥3 at enrolment, and being male were significantly associated with PHN at three months. CONCLUSIONS: These results suggest that HZ and PHN represent an important burden of disease in the elderly. There is a need for interventions that can prevent and reduce the burden of HZ to help improve the quality of life of the elderly. These data may be useful as baseline epidemiology data for the assessment of the impact of the VZV vaccine in Italy, after its implementation.

[Healthcare-associated infections and antibiotic resistance: a global challenge for the 21st century]. / Le infezioni correlate all'assistenza e l'antibioticoresistenza: una sfida globale del XXI secolo.

Healthcare-associated infections (HAIs) are a significant cause of patient morbidity and mortality. They represent one of the biggest Public Health problems today as they prolong hospital stay, reduce quality of life and increase mortality. The frequency and severity of HAIs have increased due to increased severity of patients being admitted to hospitals, increased use of vascular catheterization and progressive spread of antibioticresistant strains. In Italy, there are wide regional variations in antibiotic consumption and in the incidence of infections by multiresistant germs. This suggests the need to not only limit consumption of antibiotics but also to improve their appropriate use. Unfortunately, not all HAIs are preventable: it is therefore advisable to selectively monitor those that are attributable to problems in the quality of care. Prevention of HAIs is obviously aimed at protecting the health of patients; however, occupational exposure of healthcare workers (HCW) has also been receiving increased attention. This has resulted in the dissemination of guidelines and operating instructions aimed at minimizing the risk of exposure to biological agents, through the implementation of general and specific infection control measures. The authors also highlight that litigation related to HAIs is a trend that should be kept in mind by every HCW, especially in light of the fact that the frequency of malpractice liability claims is increasing.

Public awareness and knowledge of herpes labialis.

Between 20% and 40% of the population is estimated to suffer from episodes of recurrent herpes labialis, although few reports in the literature have addressed the public awareness of this infection in the general population. The aims of this study were to determine the existing level of awareness and knowledge of this disease and to assess the source of this knowledge, the ability of the public to recognize the characteristics of the disease and the behavior of patients with clinical cases of disease manifestation. To this end, 2,000 individuals (961 male and 1,039 female) of 14 years of age and older were surveyed using the ECOcapi system [Eurisko Consumer Omnibus-CAPI (computer-assisted personal interviewing) version]. Eighty-nine percent of those surveyed had some knowledge of herpes labialis; 92% were able to refer to at least one symptom of herpes labialis, 91% were able to identify correctly his infection from pictures, and 45% had experienced personally at least one episode of herpes labialis infection. The majority of the individuals suffering from herpes labialis self-medicated using a topical therapy. Women were found to be affected more commonly by herpes labialis than men [OR 1.42 (1.18-1.70)], and women were also more likely to recognize the disease [OR 1.65 (1.30-2.08)] and to seek medical advice for the condition [OR 1.38 (1.12-1.70)]. In conclusion, herpes labialis is a common and well-known condition, and it is often self-diagnosed correctly, as the prodromal phase and the use of self-medication are very common.

Common fragile sites in colon cancer cell lines: role of mismatch repair, RAD51 and poly(ADP-ribose) polymerase-1.

Common fragile sites (CFS) are specific chromosomal areas prone to form gaps and breaks when cells are exposed to stresses that affect DNA synthesis, such as exposure to aphidicolin (APC), an inhibitor of DNA polymerases. The APC-induced DNA damage is repaired primarily by homologous recombination (HR), and RAD51, one of the key players in HR, participates to CFS stability. Since another DNA repair pathway, the mismatch repair (MMR), is known to control HR, we examined the influence of both the MMR and HR DNA repair pathways on the extent of chromosomal damage and distribution of CFS provoked by APC and/or by RAD51 silencing in MMR-deficient and -proficient colon cancer cell lines (i.e., HCT-15 and HCT-15 transfected with hMSH6, or HCT-116 and HCT-116/3+6, in which a part of a chromosome 3 containing the wild-type hMLH1 allele was inserted). Here, we show that MMR-deficient cells are more sensitive to APC-induced chromosomal damage particularly at the CFS as compared to MMR-proficient cells, indicating an involvement of MMR in the control of CFS stability. The most expressed CFS is FRA16D in 16q23, an area containing the tumour suppressor gene WWOX often mutated in colon cancer. We also show that silencing of RAD51 provokes a higher number of breaks in MMR-proficient cells with respect to their MMR-deficient counterparts, likely as a consequence of the combined inhibitory effects of RAD51 silencing on HR and MMR-mediated suppression of HR. The RAD51 silencing causes a broader distribution of breaks at CFS than that observed with APC. Treatment with APC of RAD51-silenced cells further increases DNA breaks in MMR-proficient cells. The RNAi-mediated silencing of PARP-1 does not cause chromosomal breaks or affect the expression/distribution of CFS induced by APC. Our results indicate that MMR modulates colon cancer sensitivity to chromosomal breaks and CFS induced by APC and RAD51 silencing.

Predictors of pain intensity and persistence in a prospective Italian cohort of patients with herpes zoster: relevance of smoking, trauma and antiviral therapy.

BACKGROUND: Herpes zoster (HZ) is a common disease, characterized by rash-associated localized pain. Its main complication, post-herpetic neuralgia (PHN), is difficult to treat and may last for months to years in the wake of rash resolution. Uncertainties remain as to the knowledge of predictors of HZ-related pain, including the role of antiviral therapy in preventing PHN in ordinary clinical practice. This prospective cohort study was aimed at investigating pain intensity at HZ presentation and its correlates, as well as the incidence of PHN and its predictors. METHODS: Patients diagnosed with HZ were consecutively enrolled by a network of Italian General Practitioners and Hospital Units in the health district of Pescara, Italy, over two years. Uncertain cases were referred for microbiological investigation. Data were collected through electronic case report form (e-CRFs) at enrollment and at 1, 3, 6 and 12 months after enrollment. Pain intensity was coded on a five-degree semi-quantitative scale at each time point. PHN was defined as pain of any intensity during follow-up and quantified using an area-under-the-curve (AUC) method. RESULTS: Four hundred and forty-one patients composed the final sample. Mean age was 58.1 years (SD = 20.4 years); 43.5% of patients were males; 7.9% did not receive prescription of antivirals. Intense/very intense pain at presentation was reported by 25.2% of patients and was significantly associated with female gender, older age, cigarette smoking, trauma and/or surgery at HZ site (logistic regression). PHN was diagnosed in 51.2% of patients at one month and in 30.0% of patients at three months. PHN was significantly associated with pain intensity at presentation, age, smoking, trauma and missed antiviral prescription (generalized estimating equations model). The same factors were also independent predictors of the overall pain burden as described by the AUC method (linear regression). CONCLUSIONS: Smoking, traumas and surgery at the HZ site emerged as new predictors of both HZ-related pain intensity and persistence, opening new perspectives in the prevention of HZ-related pain. An independent line of evidence was provided for the efficacy of antiviral therapy in preventing PHN and reducing total pain burden.

Epidemiology and economic burden of herpes zoster and post-herpetic neuralgia in Italy: a retrospective, population-based study.

BACKGROUND: Data on the epidemiology and cost of herpes zoster (HZ) and post-herpetic neuralgia (PHN) in Italy are limited. This retrospective, population-based study was designed to determine the incidence of HZ and the proportion developing PHN in Italy and the associated medical resource utilisation and costs. It focused primarily on immunocompetent patients aged > or = 50 years who would be eligible for preventive vaccination. METHOD: Data were extracted from a primary-care database and national hospital-discharge records covering four major regions in Italy for 2003-2005. Cases of HZ and PHN (1 and 3 months' duration; PHN1 and PHN3) were identified by ICD9-CM codes and, additionally for PHN, prescription of neuropathic pain medication. RESULTS: Over 3 years, 5675 incident cases of HZ were documented in adults, of which 3620 occurred in immunocompetent patients aged > or = 50 years (incidence of 6.31 per 1000 person-years [95% CI: 6.01-6.62]). Of the immunocompetent patients aged > or = 50 years with HZ, 9.4% (95% CI: 8.2-10.7) and 7.2% (95% CI: 6.2-8.2) developed PHN1 and PHN3, respectively. Increasing age, female sex, and being immunologically compromised conferred increased risk for both HZ and PHN. Overall, about 1.3% of HZ and almost 2% of PHN cases required inpatient care, with 16.9% of all HZ-related hospitalisations due specifically to PHN. In patients aged > or = 50 years, mean stay was 7.8 +/- 5.4 days for HZ and 10.2 +/- 8.6 days for PHN, and direct costs associated with inpatient care were more than 20 times outpatient costs per HZ case (mean +/- SD: euro2592 +/- euro1313 vs. euro122.68 +/- euro97.51) and over 5 times more per episode of PHN (mean +/- SD: euro2806 +/- euro2641 vs. euro446.10 +/- euro442.97). Total annual costs were euro41.2 million, of which euro28.2 million were direct costs and euro13.0 million indirect costs. CONCLUSIONS: This study, the largest to date on the epidemiology and economic impact of HZ and PHN in Italy, confirms the considerable disease and economic burden posed by HZ. As HZ and PHN disproportionately affect the elderly, without intervention this problem is likely to grow as the proportion of elderly in the Italian population continues to increase.

The potential public health impact of Herpes Zoster vaccination in the 65 years of age cohort in Italy.

Herpes Zoster (HZ) presents a considerable public health burden in Italy among people aged ≥50 years. This study aimed to assess the clinical and economic impact of HZ vaccination in the 65 years of age (YOA) cohort in Italy, by comparing the new Adjuvanted Recombinant Zoster Vaccine (RZV) with the currently available Zoster Vaccine Live (ZVL). A static Markov model was developed to follow all 65 YOA subjects from the year of vaccination over their lifetime by comparing three different HZ vaccination strategies: no vaccination, vaccination with ZVL and vaccination with RZV. In the base-case scenario, three 65 YOA cohorts were assumed to be vaccinated within three years, with a vaccine coverage rate of 20%, 35% and 50% at Year 1, 2 and 3 respectively, as recommended by the National Immunization Plan. The three 65 YOA Italian cohorts accounted altogether for 2,290,340 individuals. Of these, it was assumed that 564,178 subjects could be vaccinated with either RZV or ZVL in three years. The vaccination with RZV could prevent an additional total number of 35,834 HZ and 8,131 postherpetic neuralgia (PHN) cases over ZVL, leading to additional total savings of €12.4 million for the national healthcare and social systems. The introduction of RZV can be expected to have higher impact on the burden of HZ disease in the 65 YOA cohort in Italy. The avoided HZ and PHN cases can lead to an associated reduction in economic burden to the healthcare and social systems.

Inhibition of homologous recombination by treatment with BVDU (brivudin) or by RAD51 silencing increases chromosomal damage induced by bleomycin in mismatch repair-deficient tumour cells.

Mismatch repair (MMR) has been shown to control homologous recombination (HR) by aborting strand exchange between divergent sequences. We previously demonstrated that MMR-deficient tumour cells are more resistant to chromosomal damage induced by bleomycin (BLM) during the G(2) phase, likely due to the lack of the MMR inhibitory effect on HR. Aim of this study was to investigate whether inhibition of HR by the nucleoside analogue BVDU [(E)-5(2-bromovinyl)-2'-deoxyuridine, brivudin], or silencing of genes involved in HR function, might affect sensitivity of MMR-deficient tumour cells to DNA damage induced by BLM in G(2). The results indicated that BVDU increased chromatid damage and DNA double strand breaks induced by BLM only in MMR-deficient MT-1, HL-60R, HCT116 cells, which are more resistant to BLM with respect to MMR-proficient TK-6, HL-60S and HCT116/3-6 lines. Silencing of RAD51, a key component of HR, increased sensitivity of MMR-deficient HCT-15 cells to BLM clastogenicity; in this case combined treatment with BVDU had no additional effect. Similarly, treatment with BVDU did not affect BLM clastogenicity in CAPAN-1 cells, characterized by a defective HR due to BRCA2 mutations. Conversely, BVDU increased chromatid breaks induced by BLM in HCT-15 cells transiently silenced for DNA-PK catalytic subunit, which plays a key role in non-homologous end joining. The BVDU-mediated increase of chromatid breaks in MMR-deficient cells did not depend on its previously reported inhibitory effect on poly(ADP-ribose) polymerase (PARP). In fact, it was observed also in cells stably silenced for PARP-1, which is responsible for most of cellular PARP activity. These data support the suggestion that the higher sensitivity of MMR-proficient versus MMR-deficient cells to BLM-induced chromatid breaks in the G(2) phase is a consequence of the inhibition of HR by MMR. In MMR-deficient cells, BVDU attenuates the repair of BLM-induced DSBs and this is likely to occur via inhibition of HR.

Quality of Life Impact of an Adjuvanted Recombinant Zoster Vaccine in Adults Aged 50 Years and Older.

BACKGROUND: To determine the efficacy of an adjuvanted recombinant zoster vaccine in reducing the herpes zoster (HZ) burden of illness, HZ burden of interference with activities of daily living, and HZ impact on quality of life. METHODS: The assessments were integrated in two Phase III trials, ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229). HZ burden of illness and HZ burden of interference with activities of daily living were assessed by the Zoster Brief Pain Inventory (ZBPI) instrument and quality of life by the EuroQol-5 Dimension (EQ-5D) utility index and the SF-36 health survey. We report the ZOE-50 results and a pooled analysis of patients aged 70 years and older from the trials combined. RESULTS: The estimated vaccine efficacy in reducing HZ burden of illness and HZ burden of interference was greater than 90% in both the ZOE-50 and the pooled ZOE-70 analysis. In confirmed HZ cases, adjuvanted recombinant zoster vaccine reduced the maximal ZBPI worst-pain score in the pooled ZOE-70 analysis (p = .032) and the maximal ZBPI average-pain scores in both the ZOE-50 (p = .049) and the pooled ZOE-70 analysis (p = .043). In breakthrough HZ cases, trends for diminished loss of quality of life compared with placebo-recipient HZ cases were observed, with differences up to 0.14 on the EQ-5D index at time points during the 4 weeks following HZ onset. CONCLUSIONS: Adjuvanted recombinant zoster vaccine reduced the HZ burden of illness significantly, particularly due to its very high vaccine efficacy in preventing HZ. For breakthrough HZ cases, the results suggest that the adjuvanted recombinant zoster vaccine mitigated severity of HZ-related pain, burden of interference with activities of daily living, and recipients' utility loss.

Effect of the BH3 Mimetic Polyphenol (-)-Gossypol (AT-101) on the in vitro and in vivo Growth of Malignant Mesothelioma.

Malignant mesothelioma (MM) is a primary tumor arising from mesothelial cells. The survival of MM patients following traditional chemotherapy is poor, thus innovative treatments for MM are needed. (-)-gossypol (AT-101) is a BH3 mimetic compound which possesses anti-tumoral activity by targeting multiple signaling transduction pathways. Several clinical trials employing AT-101 have been performed and some of them are still ongoing. Accordingly, we investigated the in vitro effects of AT-101 on cell proliferation, cell cycle regulation, pro-survival signaling pathways, apoptosis and autophagy of human (MM-B1, H-Meso-1, and MM-F1) and mouse (#40a) MM cell lines. In addition, we explored the in vivo anti-tumor activities of AT-101 in a mouse model, in which the transplantation of MM cells induces ascites in the peritoneal space. AT-101 inhibited in vitro MM cells survival in a dose- and time-dependent manner and triggered autophagy, but the process was then blocked and was coincident with apoptosis activation. To confirm the effect of AT-101 in inducing the apoptosis of MM cells, MM cells were simultaneously treated with AT-101 and with the caspase inhibitor, Z-VAD-FMK. Z-VAD-FMK was able to significantly reduce the number of cells in the subG1 phase compared to the treatment with AT-101 alone. This result corroborates the induction of cell death by apoptosis following treatment with AT-101. Indeed, Western blotting results showed that AT-101 increases Bax/Bcl-2 ratio, modulates p53 expression, activates caspase 9 and the cleavage of PARP-1. In addition, the treatment with AT-101 was able to: (a) decrease the ErbB2 protein expression; (b) increase the EGFR protein expression; (c) affect the phosphorylation of ERK1/2, p38 and AKT; (d) stimulate JNK1/2 and c-jun phosphorylation. Our in vivo results showed that the intraperitoneal administration of AT-101 increased the median survival of C57BL/6 mice intraperitoneally transplanted with #40a cells and reduced the risk of developing tumors. Our findings may have important implications for the design of MM therapies by employing AT-101 as an anticancer agent in combination with standard therapies.

Complications of herpes zoster in immunocompetent older adults: Incidence in vaccine and placebo groups in two large phase 3 trials.

BACKGROUND: An adjuvanted herpes zoster (HZ) subunit vaccine, HZ/su, demonstrated high efficacy against HZ and postherpetic neuralgia (PHN) in two randomized, observer-blind, placebo-controlled trials in adults aged ≥50 and ≥70 years (ZOE-50 and ZOE-70, respectively). METHODS: Data from ZOE-50 and ZOE-70 trials were analyzed to evaluate the efficacy of HZ/su against mortality, hospitalizations, and non-PHN complications of HZ including HZ-associated vasculitis, stroke, and disseminated, ophthalmic, neurologic, and visceral diseases. RESULTS: In the pooled ZOE-50/ZOE-70 analysis, 1 of 32 HZ/su recipients (3.1%) and 16 of 477 placebo recipients (3.4%) with a confirmed HZ episode had complications other than PHN. Efficacy against HZ-related complications was 93.7% (95% confidence interval, 59.5-99.9%) in adults aged ≥50 years and 91.6% (43.3-99.8%) in adults ≥70 years. Five HZ-related hospitalizations, all in placebo recipients, and no HZ-related deaths were reported. CONCLUSIONS: HZ/su reduces the risk of HZ-associated complications in older adults (NCT01165177; NCT01165229).

Clinical and psychosocial correlates of acute pain in herpes zoster.

BACKGROUND: Acute and persistent pain are the most significant clinical manifestations of herpes zoster (HZ), but the characteristics of acute pain in HZ patients have been inadequately investigated. OBJECTIVES: To correlate the severity of acute pain with clinical, demographic and psychosocial characteristics of HZ patients. STUDY DESIGN: Five hundred thirty-three patients with acute HZ were recruited by 119 dermatologists who collected medical and demographic data at diagnosis, provided counselling and therapy where appropriate and asked the patients to complete the Short Italian Questionnaire designed for comprehensive evaluation of HZ patients. RESULTS: In a univariate analysis, greater acute pain severity was significantly associated with female gender, number of dermatomes affected, presence of prodromal pain, abnormal sensations (dysesthesia), education level, anxiety and depression. Quality of life, even if greatly reduced, did not correlate with the intensity of pain. In a multivariate model, the intensity of pain was independently associated with the extent of rash (p=0.042), presence of prodromal pain (p=0.005), dysesthesia, education level (p=0.040), and depression (p<0.001), but not with gender, anxiety or quality of life. CONCLUSIONS: This study suggests that in patients with acute HZ the severity of the disease and depression at presentation are the main correlates of pain intensity.

Impact of Underlying Conditions on Zoster-Related Pain and on Quality of Life Following Zoster.

BACKGROUND: Chronic conditions have been investigated as risk factors for developing zoster, but in patients suffering from zoster, the impact of underlying conditions in zoster-related pain and quality of life (QOL) remains unclear. METHODS: We performed a post hoc analysis of a prospective cohort study in immunocompetent zoster patients aged 50 years or older, conducted by general practitioners in Italy between 2009 and 2010. Zoster symptoms, pain intensity and characteristics, and physical and mental health scores were assessed at baseline (zoster diagnosis) and at 1, 3, and 6 months of follow-up. RESULTS: Among 413 patients enrolled in the study, 73% (303/413) suffered from underlying conditions of which 69% (209/303) were aged 65 or older. Cardiovascular diseases (75%), diabetes (24%), and respiratory diseases (17%) were most frequent. One to three months after onset, zoster patients with underlying conditions experienced more intense zoster-related pain than those without. QOL scores were significantly lower in patients with underlying conditions, and age-adjusted difference in QOL scores between the groups increased over time, demonstrating a slower recovery for patients with underlying conditions. CONCLUSIONS: In addition to age, the main risk factor of zoster occurrence and severity, the presence of underlying conditions results in more painful and impactful zoster episodes, creating a significant burden for these patients.

Prevention of Herpes Zoster and its complications: From clinical evidence to real life experience.

Herpes zoster (HZ) is an acute viral illness characterized by a vesicular rash with unilateral distribution, which can also result in severe complications such as post-herpetic neuralgia (PHN), ophthalmic zoster, stroke or other neurological complications. The estimate incidence in Europe ranges between 2.0 and 4.6 cases per 1,000 person-years, with a sharp increase in >50 year-old subjects. Currently, treatment options for HZ are only partially effective in limiting the acute phase, while the management of complications is complex and often unsatisfactory. The total burden of the disease and the high costs related to its diagnostic and therapeutic management led researchers to develop a new preventive approach through a live attenuated virus vaccine. The currently available vaccine, with a high antigen content, is safe, well tolerated and reduces the incidence of HZ, PHN and the burden of illness. Several countries have introduced this vaccination, albeit with different recommendations and methods of financing. Taking into account the barriers to this immunization registered in some areas (difficulty of vaccine distribution, lack of physician recommendations, the cost of vaccine for patients, etc.), this group of Italian experts advocate that a common strategy able to guarantee a good compliance with this vaccination should be implemented. The same group addresses some practical questions concerning the use of zoster vaccine.