Small Anellovirus in Hepatitis C Patients and Healthy Controls

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A phase II study of cetuximab/irinotecan in patients with heavily pretreated metastatic colorectal cancer: Predictive value of early specific toxicities

Background: This study was designed to evaluate the predictive value of early specific toxicities on efficacy of weekly irinotecan/cetuximab administered as salvage therapy in patients with metastatic colorectal cancer (CRC) refractory to oxaliplatin and irinotecan. Patients and Methods: Seventy patients received a regimen composed of weekly irinotecan 125 mg/m(2) as a 1-hour intravenous infusion and cetuximab 400 mg/m(2) infused over 2 hours as the initial dose and 250 mg/m(2) infused over 1 hour for subsequent administrations. A single treatment cycle was composed of 4 weekly irinotecan infusions followed by 2 weeks of rest.The predictive value of adverse events (AEs) attributable to cetuximab (rash) and major toxicities attributable to irinotecan (gastrointestinal [GI] and hematologic) were observed after the first cycle of treatment and, therefore, correlated to activity and efficacy of cetuximab and weekly irinotecan. Results: Sixty-six of 70 patients received >= 1 cycle of chemotherapy and were therefore evaluable for response. Overall, toxicity observed was generally mild and manageable. According to an intent-to-treat analysis, a partial response was exhibited in 15.7% of patients, with a median progression-free survival (PFS) and median overall survival time of 4 months and 9 months, respectively. As expected, PFS (P =.01) and median survival (P =.04) correlated strongly with the presence and severity of the rash. Surprisingly, the presence of at least moderate hematologic and GI toxicity was associated with improved PFS (P =.03). Conclusion: Our data suggest that irinotecan-induced AEs might predict a better outcome in advanced CRC.This finding would identify a different subset of patients-those likely to benefit from a renewed sensitivity to irinotecan induced by cetuximab

Phase I/II trial of gemcitabine plus cisplatin and etoposide in patients with small-cell lung cancer

Objective: The objectives of this phase 1/11 study were to define the maximum tolerated dose (MTD), safety, and activity of cisplatin, etoposide, and gemcitabine (PEG) in the treatment of previously untreated patients with small-cell lung cancer (SCLC). Patients and Methods: Chemonaive patients received fixed doses of gemcitabine (1000 mg/m(2) on days I and 8) and cisplatin (70 mg/m(2) on day 2) and escalating doses of etoposide (starting dose of 50 mg/m(2) on days 3,4, and 5) every 3 weeks. No prophylactic granulocyte colony-stimulating factors were used. Results: From September 1998 to April 2000, 56 patients with limited- or extensive-stage SCLC were enrolled and received a total of 235 cycles. Two different etoposide doses were tested in eight patients. At the second level (75 mg/m(2)), two out of two patients experienced dose-limiting toxicities (neutropenia and thrombocytopenia) and no further dose-escalation was attempted, thus an etoposide dose of 50 mg/m 2 was defined as the MTD. In the subsequent phase 11 evaluation, 48 additional patients were enrolled, for a total of 54 patients treated at the MTD. Grade 3/4 neutropenia and thrombocytopenia occurred in 66.7 and 53.7%,, of patients, respectively. Non-hematologic toxicity was mild, with grade 3 diarrhea and fatigue as the main side effects. Two patients died of neutropenic sepsis (one at 75 mg/m(2) and the other at So I n g/In 2 etoposide). Ten complete and 29 partial responses were reported, for an overall response rate of 72.2% (95% confidence interval, 56.6-85.0%). The median duration of response and median survival were 8.0 and 10 months, respectively, with a 1-year survival probability of 37.5%. Conclusions: he combination of PEG is feasible and well tolerated as front-line chemotherapy in SCLC. A randomized comparison of this triplet is underway. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved

Imported arboviral infections in Italy, July 2014-October 2015: A National Reference Laboratory report

BACKGROUND: Imported cases of infections due to Dengue (DENV) and Chikungunya (CHIKV) viruses and, more recently, Zika virus (ZIKV) are commonly reported among travelers returning from endemic regions. In areas where potentially competent vectors are present, the risk of autochthonous transmission of these vector-borne pathogens is relatively high. Laboratory surveillance is crucial to rapidly detect imported cases in order to reduce the risk of transmission. This study describes the laboratory activity performed by the National Reference Laboratory for Arboviruses (NRLA) at the Italian National Institute of Health in the period from July 2014 to October 2015. METHODS: Samples from 180 patients visited/hospitalized with a suspected DENV/CHIKV/ZIKV infection were sent to the NRLA from several Italian Hospitals and from Regional Reference Laboratories for Arboviruses, in agreement with the National Plan on human surveillance of vector-borne diseases. Both serological (ELISA IgM test and Plaque Reduction Neutralization Test-PRNT) and molecular assays (Real Time PCR tests, RT-PCR plus nested PCR and sequencing of positive samples) were performed. RESULTS: DENV infection was the most frequently diagnosed (80 confirmed/probable cases), and all four genotypes were detected. However, an increase in imported CHIKV cases (41 confirmed/probable cases) was observed, along with the detection of the first ZIKV cases (4 confirmed cases), as a consequence of the recent spread of both CHIKV and ZIKV in the Americas. CONCLUSIONS: Main diagnostic issues highlighted in our study are sensitivity limitations of molecular tests, and the importance of PRNT to confirm serological results for differential diagnosis of Arboviruses. The continuous evaluation of diagnostic strategy, and the implementation of laboratories networks involved in surveillance activities is essential to ensure correct diagnosis, and to improve the preparedness for a rapid and proper identification of viral threats

Pathologic response and survival after neoadjuvant chemotherapy with or without pertuzumab in patients with HER2-positive breast cancer: the Neopearl nationwide collaborative study

PurposeClinical trials have shown a significant increase in pathologic complete response (pCR) with the addition of pertuzumab to neoadjuvant chemotherapy for patients with early-stage HER-2 positive breast cancer. To date, limited studies have examined comparative outcomes of neoadjuvant pertuzumab in real-world setting. The Neopearl study aimed to assess comparative real-life efficacy and safety of neoadjuvant pertuzumab for these patients.MethodsWe conducted a nationwide retrospective analysis involving 17 oncology facilities with a certified multidisciplinary breast cancer treatment committee. We identified patients with HER-2 positive stage II-III breast cancer treated with neoadjuvant chemotherapy based on trastuzumab and taxanes with or without pertuzumab. All patients underwent breast surgery and received a comprehensive cardiologic evaluation at baseline and after neoadjuvant treatment. Patients who received the combination of pertuzumab, trastuzumab, and chemotherapy constituted case cohort (PTCT), whereas those treated with trastuzumab and chemotherapy accounted for control cohort (TCT). The pCR rate and 5-year event free survival (EFS) were the primary outcomes. Secondary end-points were rates of conversion from planned modified radical mastectomy (MRM) to breast conservation surgery (BCS) and cardiotoxicities.ResultsFrom March 2014 to April 2021, we included 271 patients, 134 (49%) and 137 (51%) in TCT and PTCT cohort, respectively. Positive axillary lymph nodes and stage III were more frequent in PTCT cohort. The pCR rate was significantly increased in patients who received pertuzumab (49% vs 62%; OR 1.74, 95%CI 1.04-2.89) and with HER-2 enriched subtypes (16% vs 85%; OR 2.94, 95%CI 1.60-5.41). After a median follow-up of 5 years, the 5-year EFS was significantly prolonged only in patients treated with pertuzumab (81% vs 93%; HR 2.22, 95%CI 1.03-4.79). The same analysis performed on propensity score matched population showed concordant results. On univariate analysis, only patients with positive lymph nodes were found to benefit from pertuzumab for both pCR and 5-year EFS. The rates of conversion from MRM to BCS and cardiologic toxicities did not differ between the cohorts.ConclusionOur findings support previous data on improved outcomes with the addition of pertuzumab to trastuzumab-based neoadjuvant chemotherapy. This benefit seems to be more significant in patients with clinically positive lymph nodes

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Cell therapies for treatment of human immunodeficiency virus infection

After the serendipitous discovery of HIV eradication in the "Berlin patient", interest has grown in curing HIV infection by replacing the patient's replication-competent blood cells with infection-resistant ones. At the same time, induced pluripotent stem cell technologies and genetic engineering have boosted cell therapy transfer into the clinic. Currently available cell therapy approaches to attempt to cure HIV infection include the following: (1) Transplantation of autologous or allogeneic cells spontaneously resistant or edited to resist HIV infection; (2) Transplantation of autologous T-lymphocytes spontaneously targeting or redirected against HIV; and (3) Transplantation of autologous cells engineered to work as anti-HIV antibody factories. We review here the preliminary results and potential for future applications of these approaches

Short-term kinetics of torque teno virus viraemia after induction immunosuppression confirm T lymphocytes as the main replication-competent cells

Torque teno virus (TTV) is increasingly considered a universal marker of global immune function. The virus is supposed to replicate in lymphocytes, but poor information is available about fluctuations of viraemia after administration of anti-lymphocyte agents. We studied TTV kinetics in a cohort of 70 kidney\ub1pancreas recipients receiving one of two different anti-T-cell induction immunosuppressants. During the first 30 days after anti-T-cell antibody administration, we report kinetics of TTV viraemia compatible with replication in T lymphocytes, and highly dependent on the potency of the anti-T-cell drug administere

Lymphotropic Polyomavirus and Progressive Multifocal Leukoencephalopathy

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Lack of KIs virus DNA in plasma and cerebrospinal fluid in Italy

Dear Sirs, Satoh et al. recently screened 516 Japanese blood donors with PCR using primers constructed from the consensus domain of the helicase of positive-stranded RNA viruses. They reported a novel enveloped virus with a circular double-stranded DNA genome (tentatively named KIs virus, KIs-V) (Satoh et al., 2011) occurring in 36 out of the 100 hepatitis E (HEV) antibody-positive donors with elevated alanine aminotransferase (ALT) levels (>60 IU/L). More recently, Biagini et al. failed to find KIs-V in plasma from 576 French blood donors with unknown HEV serostatus and unknown ALT values (Biagini et al., 2012). Based on an HEV seroprevalence of 3-52% in France, the authors suggested an uncommon frequency of KIs-V infection in healthy persons in France. To date, no information has been available on the prevalence of KIs-V DNA in Italy. In the present paper, we analyzed KIs-V in 242 plasma samples of blood donors, transplant recipients, and patients with chronic viral infections, and in 52 cerebrospinal fluid (CSF) samples of patients with different neurological disorders. Informed consent was obtained from all patients and the study was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its amendments. Viral DNA extraction was carried out on 200 \u3bcl of plasma or 200 \u3bcl of CSF by using QIAamp DNA blood kit (Qiagen, Hilden, Germany) according to the manufacturer's instructions. Extracted nucleic acids were amplified for KIs-V DNA with the nested PCR protocol developed by Satoh et al. (2011) and used for screening Japanese blood donors. The first and second PCR rounds were designed on 458 and 304 nt-length fragments, respectively. To validate the amplification process, positive controls obtained from plasma dilutions of a synthetic template corresponding to the target sequence were run in each PCR. PCR sensitivity was less than 5 copies of target sequence. Fourteen liver and 16 kidney and/or pancreas transplant recipients were tested before transplantation and at the time after transplantation when viremia levels of TTV were highest, TTV having been validated by our group and others as a marker of functional immune deficiency (Focosi et al., 2014). None of the samples tested positive for KIs-V. At the same time, we also tested 79 healthy blood donors. Since determination of ALT is a mandatory part of on blood donation according to Italian law we could establish that only 2 donors had ALT values >60 IU/L but in any case <80 IU/L: all of them tested negative for KIs-V. No information on HEV status was available and HEV seroprevalence studies are limited in Italy (Arends et al., 2014). However regional studies show prevalences ranging from 2.9% to 8.8% (Masia et al., 2009). We also tested 50 HIV-positive patients, 41 HCV-positive patients, and 42 HBV-positive patients. None of the samples tested positive for KIs-V. Finally, cerebrospinal fluid from 52 patients with different neurological disorders was also tested. All these samples were negative for KIs-V DNA. Thus, although we cannot rule out the possibility that KIs-V circulates in Italy at a very low level and genetically different from the virus found in Japanese population, the results seem to demonstrate a very low prevalence of this novel virus in the Italian population. While the implication of KIs-V in human health remains under debate, extensive regional surveys will help to elucidate the geographical spread of KIs-V and to understand the natural history of the infection in human beings