Systematic Review of Lung Cancer Screening: Advancements and Strategies for Implementation.

Lung cancer is the leading cause of cancer-related deaths in Europe, with low survival rates primarily due to late-stage diagnosis. Early detection can significantly improve survival rates, but lung cancer screening is not currently implemented in Italy. Many countries have implemented lung cancer screening programs for high-risk populations, with studies showing a reduction in mortality. This review aimed to identify key areas for establishing a lung cancer screening program in Italy. A literature search was conducted in October 2022, using the PubMed and Scopus databases. Items of interest included updated evidence, approaches used in other countries, enrollment and eligibility criteria, models, cost-effectiveness studies, and smoking cessation programs. A literature search yielded 61 scientific papers, highlighting the effectiveness of low-dose computed tomography (LDCT) screening in reducing mortality among high-risk populations. The National Lung Screening Trial (NLST) in the United States demonstrated a 20% reduction in lung cancer mortality with LDCT, and other trials confirmed its potential to reduce mortality by up to 39% and detect early-stage cancers. However, false-positive results and associated harm were concerns. Economic evaluations generally supported the cost-effectiveness of LDCT screening, especially when combined with smoking cessation interventions for individuals aged 55 to 75 with a significant smoking history. Implementing a screening program in Italy requires the careful consideration of optimal strategies, population selection, result management, and the integration of smoking cessation. Resource limitations and tailored interventions for subpopulations with low-risk perception and non-adherence rates should be addressed with multidisciplinary expertise.

The Impact of the Introduction of the Breast Unit Model in a Northwestern Italian Region.

Breast cancer is the most common tumor in middle-aged and older women. In 2003, the European Parliament recommended to Member States that all women with breast cancer should be treated by a multidisciplinary team and that a network of certified breast centers be organized (the centers have been called Breast Units (BUs)). With the present study, we aim to explore the impact of the introduction of the BU organizational model in the Liguria region, Italy, through different outcome indicators. An explorative retrospective analysis was conducted through the period from 2013 to 2019 to assess the impact of the introduction of the BU model in our region. We identified two periods: before (2014-2015) and after (2017-2018) the introduction of this organizational model to assess its value impact through the definition of six measurable outcome indicators. Length of hospitalization, repeated specialist outpatient diagnostic procedures and the rate of subjects who started radiotherapy treatment within 60 days improved after the introduction of BUs. The passive health migration rate only improved significantly for one local health unit (LHU), while reintervention and diagnosis-surgery time did not show any enhancement after the introduction of the BU model. The BU model seems to provide an increase in several aspects of the healthcare offered to breast cancer patients in Liguria, specifically in those areas where a shared guideline could assist healthcare workers. Future research, such as pilot studies, are needed to assess the impact of the introduction of the BU model in our reality.

Weight of risk factors for mortality and short-term mortality displacement during the COVID-19 pandemic.

Background: We conducted a population-based cohort study to estimate mortality before, during and after the COVID-19 peak and to compare mortality in 2020 with rates reported in previous years, with a view to helping decision makers to apply containment measures for high-risk groups. Methods: All deaths were collected between 2015 and 2020 from municipal registry database. In 2020, weeks 1-26 were stratified in three periods: before, during and after the COVID mortality peak. The Poisson Generalized Linear regression Model showed the "harvesting effect". Three logistic regressions for 8 dependent variables (age and comorbidities) and a t-test of differences described all-cause mortality risk factors in 2019 and 2020 and differences between COVID and non-COVID patients. Results: A total of 47,876 deaths were collected. All-cause deaths increased by 38.5% during the COVID peak and decreased by 18% during the post-peak period in comparison with the average registered during the control period (2015-19), with significant mortality displacement in 2020. Except for chronic renal injuries in subjects aged 45-64 years, diabetes and chronic cardiovascular diseases in those aged 65-84 years, and neuropathies in those aged > 84 years, the weight of comorbidities in deaths was similar or lower in COVID subjects than in non-COVID subjects. Discussions: Surprisingly, the weight of comorbidities in death, compared to weight in non-COVID subjects allows you to highlight some surprising results such as COPD, IBD and Cancer. The excess mortality that we observed in the entire period were modest in comparison with initial estimates during the peak, owing to the mild influenza season and the harvesting effect starting from the second half of May.

Italian Health Care Workers' Knowledge, Attitudes, and Practices Regarding Human Papillomavirus Infection and Prevention.

Objective: To assess healthcare workers' knowledge and attitudes about human papillomavirus (HPV) infection, related diseases, and prevention. Methods: A cross-sectional multicenter survey about HPV and its prevention, targeted to healthcare workers involved in HPV vaccine counseling, was performed from May 2017 to December 2018. Results: The overall median knowledge and attitude scores were 69.2% (25-75, p = 61.5-84.6) and 5 (25-75, p = 4-5), respectively. Both knowledge and attitudes statistically significantly differ between physicians and healthcare professions. The median propensity score before and after the educational intervention was stable and high, at 10 (25-75, p = 9-10). The predictors of statistically significantly high knowledge scores are to be a physician, general practitioner, or pediatrician, attending courses/congresses, and consulting technical product characteristics and scientific literature to obtain information about the HPV vaccine. Being a physician and consulting scientific literature to obtain information about the HPV vaccine were found also as predictors of statistically significantly different attitude scores among study participants. Conclusions: Although healthcare workers showed overall positive attitudes towards the relevance of HPV burden and prevention tools, demonstrated knowledge was largely suboptimal, particularly that shown by healthcare professions. Obtained results allow highlighting knowledge gaps, and thus improving counselling to HPV vaccine targets.

Assessment of Knowledge, Attitudes, and Propensity towards HPV Vaccine of Young Adult Students in Italy.

BACKGROUND: Human Papillomavirus (HPV) is a common sexually transmitted infection (STI), representing the main cause of genital warts and cervical cancer. This cross-sectional study evaluated knowledge and attitudes about HPV infection, related diseases, and prevention and propensity towards HPV vaccine among undergraduate students. METHODS: An online and written survey about HPV and its prevention, targeted to young adults of both genders, was addressed to students attending health sciences and other schools at Universities of Genoa and Bari. RESULTS: The overall median knowledge and attitude scores were 56.3% (25-75 p = 40-68.8%) and four out of five (25-75 p = 4-5), respectively. In the multivariate analysis, attending a health sciences university, using social networks ≤2 h a day, a history of STI, having heard about HPV and HPV vaccine previously resulted as predictors of higher knowledge scores. Having heard about HPV previously also predicted a high attitude score, together with a perceived economic status as good. Having Italian and healthcare worker parents, being employed, and following a specific diet, instead, predicted lower attitude score. CONCLUSIONS: Poor knowledge and good attitudes were found among undergraduates about HPV. In order to increase HPV vaccine compliance and the counselling skills of future healthcare workers, the improvement of training on HPV is needed.

Burden and Prevention of HPV. Knowledge, Practices and Attitude Assessment Among Pre-Adolescents and their Parents in Italy.

Despite infections due to HPV nowadays represent the most common sexually transmitted diseases worldwide with recognized effective and safe preventive strategies, knowledge, attitudes; however, awareness on HPV is considerably low. The present study has two main objectives: 1. To conduct a literature review to analyze the evolution of preventive tools, the complexity of the vaccine choice process, and the challenges posed by HPV vaccine hesitancy and refusal among pre-adolescents and their parents; 2. To assess knowledge, practices and attitudes toward HPV infection and vaccination in a sample of Italian pre-adolescents and their parents. The observational study was carried out through the use of two anonymous and self-administered pre- and postintervention questionnaires dedicated to the target populations. Between the administrations of the pre- and postintervention questionnaires, an educational intervention on HPV infection and related diseases, and prevention strategies was conducted. All participants demonstrated suboptimal knowledge and positive attitudes in the preintervention questionnaire. Higher levels of knowledge and attitudes were observed among pre-adolescents thatused social networks and had heard of sexually transmitted diseases at home/school/physician and from parents and also who had heard of HPV from General Practitioners, Gynecologists, family members and newspapers. A significant increase in HPV vaccination awareness was observed among pre-adolescents after the educational sessions. Health education programs aimed at increasing knowledge, attitudes and awareness on HPV are needed to implement the outcomes of HPV immunization programs, especially if supported by the physicians involved in counselling and recommendation processes.

Hospital and economic burden of influenza-like illness and lower respiratory tract infection in adults ≥50 years-old.

BACKGROUND: Influenza-like illnesses (ILIs) and lower respiratory tract infections (LRTIs) cause substantial morbidity and mortality worldwide. The study assessed the health and economic burden of ILI and LRTI according to age and comorbidities, since available evidence is limited and heterogeneous. METHOD: The prevalence of comorbidities, the seasonal incidence rates and the mean and per capita direct costs of ED accesses for ILI/LRTI, whether followed by hospitalization or not, recorded in adults aged ≥50 years over the last 6 years, in the referral hospitals located in the Genoese metropolitan area (Liguria, Italy) where the syndromic surveillance system is active, were evaluated through a retrospective observational study. Comorbidities were estimated through the Chronic Condition Data Warehouse that integrates multiple Medicare data sources. A comparison with the administrative healthcare International Classification of Diseases-9th revision-Clinical Modification (ICD-9-CM)-based data was also conducted. RESULTS: The prevalence of subjects with ≥1 comorbidity ranged from 23.49 to 59.92%. The most prevalent all-age comorbidities were cardiovascular diseases and cancer. The overall ILI/LRTI incidence rate was 6.73/1000 person-years, almost double the value derived from routine data, and increased with age. The highest rates were observed in patients with renal failure and bronchopneumopathies. The mean cost of ED accesses/hospitalization for ILI/LRTI was €3353 and was almost twice as high in the ≥85 years as in the youngest age-group. The highest mean costs were observed in patients with renal failure and cancer. The per capita costs increased from €4 to €71 with age, and were highest in patients with renal failure and bronchopneumopathy. CONCLUSION: The burden of ILIs/LRTIs in terms of ED accesses and hospitalizations in adults aged ≥50 years is heavy, and is related to increasing age and, especially, to specific comorbidities. These results could contribute to revising age- and risk-based anti-influenza and -pneumococcus immunization strategies.

Immunization Campaigns and Strategies against Human Papillomavirus in Italy: The Results of a Survey to Regional and Local Health Units Representatives.

Objective. The study aimed to assess the impact of HPV immunization campaigns organizational aspects, the characteristics of immunization program (vaccination targets and type of offer), and communicative strategies adopted by four Italian administrative regions on vaccination coverage observed. Methods. From November 2017 to March 2018, regional and Local Health Units (LHUs) representatives were invited to complete an online survey including 54 questions evaluating vaccination invite systems, access systems to vaccination centres, reminder and recall systems, and adverse events surveillance. An overall descriptive analysis was conducted. Since observed vaccine coverage (VC) obtained in females (2002-2004 birth cohorts) was lower than objectives fixed by the Italian Ministry of Health, variables were assessed using the national VC mean obtained in the 2003 girls birth cohort as outcome. Results. Twenty-six LHUs belonging to 4 Northern and Southern Italian regions participated in the study. Organizational aspects significantly related to VC lower than the national mean were access to vaccine centres without appointment and parents' reservation as appointment planning system. Recall systems for both the first and the second dose, including the appointment in the invitation letter, the availability of regional immunization registry, and education of healthcare workers on universal HPV immunization strategies, instead, were related to higher VC. As regards preadolescent immunization strategies, both VC obtained in girls and boys were far from the Ministerial goals. Only 20% of LHUs introduced multicohort female strategies while all LHUs adopted copayment targeting both men and women. Immunizations strategies targeting subjects at risk were implemented only in half of participating LHUs. Conclusions. VC observed in participating LHUs are largely lower than the national objectives in all anti-HPV vaccine targets. Both organizational and educational strategies have to be implemented to improve the VC goals.

Universal influenza virus vaccines: what needs to happen next?

INTRODUCTION: Influenza occurs worldwide and causes significant disease burden in terms of morbidity, associated complications, hospitalizations, and deaths. Vaccination constitutes the primary approach for controlling influenza. Current influenza vaccines elicit a strain-specific response yet occasionally exhibit suboptimal effectiveness. This review describes the limits of available immunization tools and the future prospects and potentiality of universal influenza vaccines. AREAS COVERED: New 'universal' vaccines, which are presently under development, are expected to overcome the problems related to the high variability of influenza viruses, such as the need for seasonal vaccine updates and re-vaccination. Here, we explore vaccines based on the highly conserved epitopes of the HA, NA, or extracellular domain of the influenza M2 protein, along with those based on the internal proteins such as NP and M1. EXPERT OPINION: The development of a universal influenza vaccine that confers protection against homologous, drifted, and shifted influenza virus strains could obviate the need for annual reformulation and mitigate disease burden. The scientific community has long been awaiting the advent of universal influenza vaccines; these are currently under development in laboratories worldwide. If such vaccines are immunogenic, efficacious, and able to confer long-lasting immunity, they might be integrated with or supplant traditional influenza vaccines.

Nosocomial candidemia in patients admitted to medicine wards compared to other wards: a multicentre study.

PURPOSE: Risk factors for nosocomial candidemia, severity of sepsis, treatment, and outcome were compared between patients admitted to medicine wards and those to surgical and intensive care units (ICUs). METHODS: Data were retrospectively collected from patients belonging to six referral hospitals in Italy between January 2011 and December 2013. Risk factors for 30-day mortality were evaluated in the whole patient population. RESULTS: A total of 686 patients (mean age 70 ± 15 years) with candidemia were included. 367 (53.5 %) patients were in medicine wards, and 319 in surgery and ICUs. Host-related risk factors for candidemia were more common in medicine patients whereas healthcare-related factors in surgery/ICU patients. These patients showed severe sepsis and septic shock more commonly (71.7 %) than medicine patients (59.9 %) (p 0.003). The latter underwent central venous catheter (CVC) removal and adequate antifungal therapy less frequently than surgery/ICU patients. 149 (40.6 %) patients died with candidemia in medicine wards and 69 (21.6 %) in other wards (p < 0.001). Overall, the 30-day mortality was 36.3 %. At multivariate analysis, independent risk factors for death were aging, higher Charlson score, severe sepsis and septic shock, and no antifungal therapy, while major surgery and CVC removal were associated with higher probability of survival. CONCLUSIONS: The burden of risk factors for candidemia was different between medicine patients and those in other wards. Despite the lower severity of candidemia in medicine patients, their mortality turned out to be higher than in surgery or ICU patients. Awareness of the best management of candidemia should be pursued, especially in medicine wards.

Clinical and therapeutic aspects of candidemia: a five year single centre study.

BACKGROUND: Candida is an important cause of bloodstream infections (BSI) in nosocomial settings causing significant mortality and morbidity. This study was performed to evaluate contemporary epidemiology, species distribution, antifungal susceptibility and outcome of candida BSI in an Italian hospital. METHODS: All consecutive patients who developed candidemia at Santa Maria della Misericordia University Hospital (Italy) between January 2009 and June 2014 were enrolled in the study. RESULTS: A total of 204 episodes of candidemia were identified during the study period with an incidence of 0.79 episodes/1000 admissions. C. albicans was isolated in 60.3% of cases, followed by C. parapsilosis (16.7%), C. glabrata (11.8%) and C. tropicalis (6.4%). Of all Candida BSI, 124 (60.8 %) occurred in patients admitted to IMW, 31/204 (15.2 %) in ICUs, 33/204 (16.2%) in surgical units and 16/204 (7.8%) in Hematology/Oncology wards. Overall, 47% of patients died within 30 days from the onset of candidemia. C. parapsilosis and C. glabrata candidemia were associated with the lowest mortality rate (36%), while patients with C. tropicalis BSI had the highest mortality rate (58.3%). Lower mortality rates were detected in patients receiving therapy within 48 hours from the time of execution of the blood cultures (57,1% vs 38,9%, P < 0.05). At multivariate analysis, steroids treatment (OR = 0.27, p = 0.005) and CVC removal (OR = 3.77, p = 0.014) were independently associated with lower and higher survival probability, respectively. Candidemia in patients with peripherally inserted central catheters (PICC) showed to be associated with higher mortality in comparison with central venous catheters (CVC, Short catheters and Portacath) and no CVC use. For each point increase of APACHE III score, survival probability decreased of 2%. Caspofungin (OR = 3.45, p = 0.015) and Amphothericin B lipid formulation (OR = 15.26, p = 0.033) were independently associated with higher survival probability compared with no treatment.

Immunomodulation due to plasma or plasma-platelet apheresis donation: Events occurring during donation procedures.

BACKGROUND: It has been recently shown that during therapeutic apheresis procedure, a large amount of soluble HLA class I molecules settles onto plastic apheresis circuits, inducing sustained TGFß1 pre/post-transcriptional modulation in activated patients' leukocytes. Reportedly, donors' leukocytes may be exposed to similar immunosuppressing activities during donor apheresis procedures. On this basis, it could be hypothesized that such events can cause immune modulation. It is uncertain which blood cell population is most impacted by these events. This study is focused on the effects on the T lymphocytes. STUDY DESIGN AND METHODS: To assess if such events occur, lymphocytes from 20 apheresis donors collected before and after three closely timed plasma and platelet donation procedures were analyzed for sHLA-I mediated immunomodulation. RESULTS: The results confirmed that sHLA-I molecules bind to the apheresis circuit surfaces. Circuits can also transiently activate donors' CD8(+) T lymphocytes, to which sHLA-I molecules can bind, thus modulating short-lasting immune effects, such as transcriptional and post-transcriptional TGFß1 modulation and soluble Fas ligand release. However, no significant change in relative proportions, absolute number and cell viability of lymphocyte subpopulations was found and no ex vivo immune effect was detectable longer than 14 days after procedure in any cell type in all donors. CONCLUSION: Short-lived sHLA-I mediated immunomodulation was demonstrable in lymphocytes from every donor as a consequence of apheresis procedures, but no enrolled subject experienced any adverse reaction or showed any sign of immunosuppression during 24 months of follow-up after the donations.

Epidemiology of viral respiratory tract infections in an outpatient haematology facility.

Viral respiratory tract infections (VRTI) are an important cause of morbidity and mortality in haematology patients, particularly after haematopoietic stem cell transplantation (HSCT). The incidence, clinical presentation and outcome of symptomatic and asymptomatic VRTI in HSCT outpatient unit were prospectively evaluated during a single influenza season (January-March 2011). Pharyngeal swabs were performed at the first visit and if new symptoms were present. Molecular multiplex assay for 12 respiratory viruses was performed by the regional reference laboratory. Among 264 swabs from 193 outpatients, 58 (22 %) resulted positive for 61 viruses (influenza, n = 20; respiratory syncytial virus [RSV], n = 21; rhinovirus, n = 12; coronavirus, n = 4; adenovirus, n = 3; parainfluenza, n = 1). VRTI were detected more frequently in the presence of symptoms than in asymptomatic patients: 49 out of 162 (30 %) vs. 9 out of 102 (9 %), p < 0.001. Influenza-like illness syndrome (ILI) was significantly associated with a VRTI if compared to other presentations (42 %), while the European Centre for Disease Prevention and Control definition was not (30 %). Positive predictive value (PPV) of ILI for influenza was 17 %. Influenza and RSV peak periods were contemporary. Influenza prophylaxis was given to 25 patients following exposure. Low rate of progression from upper to lower respiratory tract infection (approximately 5 % for influenza and RSV), no nosocomial epidemics and no VRTI-related deaths were observed. VRTI are very frequent in high-risk haematology outpatients, but symptoms are aspecific and PPV of ILI is low. Symptoms of influenza and RSV overlap. Thus, microbiological diagnosis and contact preventive measures are crucial. Rather than universal influenza prophylaxis, prompt diagnosis and treatment of only documented infections could be pursued.

Adherence to international and national recommendations for the prevention of surgical site infections in Italy: results from an observational prospective study in elective surgery.

BACKGROUND: An observational prospective study of the perioperative procedures for prevention of surgical site infections (SSIs) was carried out in a tertiary referral teaching hospital in Liguria, Italy, to evaluate their adherence to international and national standards. METHODS: A 1-month survey was performed in all surgical departments, monitored by turns by trained survey teams. Data regarding presurgical patient preparation and intraoperative infection control practices were collected. RESULTS: A total of 717 elective interventions were actively monitored in 703 patients who underwent surgery. Hair-shaving was performed mainly using a razor (92%) by the nurses (72.8%) on the day before the operation (83.5%). All of the patients showered, either with a common detergent (87%) or with an antiseptic solution (13%). Antimicrobial prophylaxis was administered properly in 75.7% of the patients at induction of anaesthesia; however, according to current Italian guidelines, inappropriate prophylaxis was provided in 55.2% patients. Appropriate antisepsis of the incision area was done in 97.4% of the operations, and nearly 90% of the interventions lasted less than the respective 75th percentile. The doors of the operating theatres were mostly open during the duration of the operation in 36.3% of the cases. CONCLUSIONS: This review of infection control policies identified significant opportunities for improving the safety and the quality of routine surgical practice.

Synergistic interactions between HDAC and sirtuin inhibitors in human leukemia cells.

Aberrant histone deacetylase (HDAC) activity is frequent in human leukemias. However, while classical, NAD(+)-independent HDACs are an established therapeutic target, the relevance of NAD(+)-dependent HDACs (sirtuins) in leukemia treatment remains unclear. Here, we assessed the antileukemic activity of sirtuin inhibitors and of the NAD(+)-lowering drug FK866, alone and in combination with traditional HDAC inhibitors. Primary leukemia cells, leukemia cell lines, healthy leukocytes and hematopoietic progenitors were treated with sirtuin inhibitors (sirtinol, cambinol, EX527) and with FK866, with or without addition of the HDAC inhibitors valproic acid, sodium butyrate, and vorinostat. Cell death was quantified by propidium iodide cell staining and subsequent flow-cytometry. Apoptosis induction was monitored by cell staining with FITC-Annexin-V/propidium iodide or with TMRE followed by flow-cytometric analysis, and by measuring caspase3/7 activity. Intracellular Bax was detected by flow-cytometry and western blotting. Cellular NAD(+) levels were measured by enzymatic cycling assays. Bax was overexpressed by retroviral transduction. Bax and SIRT1 were silenced by RNA-interference. Sirtuin inhibitors and FK866 synergistically enhanced HDAC inhibitor activity in leukemia cells, but not in healthy leukocytes and hematopoietic progenitors. In leukemia cells, HDAC inhibitors were found to induce upregulation of Bax, a pro-apoptotic Bcl2 family-member whose translocation to mitochondria is normally prevented by SIRT1. As a result, leukemia cells become sensitized to sirtuin inhibitor-induced apoptosis. In conclusion, NAD(+)-independent HDACs and sirtuins cooperate in leukemia cells to avoid apoptosis. Combining sirtuin with HDAC inhibitors results in synergistic antileukemic activity that could be therapeutically exploited.

Treatment of recurrent hepatitis C (genotype 1) with pegylated interferon alfa-2b and ribavirin combination and maintenance therapy.

BACKGROUND/AIMS: This study aims at evaluating the efficacy of treatment with pegylated interferon (PEG-IFN) alfa-2b and ribavirin in patients with recurrent hepatitis C (genotype 1) after orthotopic liver transplantation (OLT) and the impact of this therapy on hepatic fibrosis at the end of conventional therapy and at the end of a period of maintenance treatment in non-responder patients. METHODOLOGY: Thirty-two consecutive patients diagnosed with recurrent HCV were considered candidates for antiviral therapy. RESULTS: Ten patients (31.2%) interrupted therapy due to side effects; sustained virological response (SVR) was observed in 27.2%, sustained biochemical response (SBR) in 31.8% and NR in 40.9% of cases. Eighteen patients underwent a biopsy at the end of conventional treatment: improved fibrosis score in all patients with SVR, improved score in 1 patient with SBR and stable score in 6 patients with SBR, worse score in 1 NR patient and stable in 6 NR patients. Six NR patients with stable score submitted to a maintenance therapy: improved score in 1 patient and stable score in 5 patients. CONCLUSIONS: In recurrent hepatitis C, in spite of the type of response, treatment slows down hepatic fibrotic evolution.

Impaired response to influenza vaccine associated with persistent memory B cell depletion in non-Hodgkin's lymphoma patients treated with rituximab-containing regimens.

Influenza vaccination is generally recommended for non-Hodgkin's lymphoma (NHL) patients, but no data are available about the activity of this vaccine after treatment with rituximab-containing regimens. We evaluated the humoral response to the trivalent seasonal influenza vaccine in a group of NHL patients in complete remission for ≥6 mo (median, 29 mo) after treatment with rituximab-containing regimens (n = 31) compared with age-matched healthy subjects (n = 34). B cell populations and incidence of influenza-like illness were also evaluated. For each viral strain, the response was significantly lower in patients compared with controls and was particularly poor in patients treated with fludarabine-based regimens. In the patient group, the response to vaccination did not fulfill the immunogenic criteria based on the European Committee for Medicinal Products for Human Use requirements. Among the patients, CD27(+) memory B cells were significantly reduced, and their reduction correlated with serum IgM levels and vaccine response. Episodes of influenza-like illness were recorded only in patients. These results showed that NHL patients treated with rituximab-containing regimens have persisting perturbations of B cell compartments and Ig synthesis and may be at particular risk for infection, even in long-standing complete remission.