Systematic review and meta-analysis of the use of high-energy devices for thyroid surgery.

BACKGROUND: We conducted a systematic review and meta-analysis to evaluate the role of High Energy Devices (HEDs) versus conventional clamp and tie technique in thyroidectomy. This work is endorsed by the Italian Society of Surgical Endoscopy (Italian Society of Endoscopic Surgery and new technologies-SICE) in the broader project on the evaluation of the role of HEDs in different surgical settings with the full health technology assessment report. MEHODS: Inclusion criteria were adult patients (≥ 18 years old) undergoing Thyroidectomy/Parathyroidectomy conducted with High Energy Devices (as ultrasonic (US), radiofrequency (RF), and hybrid energy (H-US/RF)) in the setting of thyroid surgery (both partial and total) for benign and malign diseases. However, some variability was found in included studies and described in the text. This systematic review and meta-analysis were performed according to the Cochrane handbook for systematic reviews, and the recommendations of the 2020 updated Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) guidelines were pursuit. Selection of abstracts was performed in Ryyan system by 2 independent reviewers, and doubts were solved by another independent reviewer. At the end of literature research, Randomized controlled trials and observational studies were included. Risk of Bias was assessed with ROB2 for RCTs, and New Castle Ottawa Scale for Observational studies. RESULTS: The literature search yielded 47 studies, including 29 RCTs and 18 observational studies. Meta-analysis was performed for 29 randomized clinical trials. Outcomes included in the comparison between High Energy Devise and conventional technique groups were operative time, operative blood loss, overall post-operative drainage volume, length of stay, complications, and costs. HED significantly reduced operative time (28 studies, 3097patients; MD -128.8; 95% CI -34.4 to -23.20; I2 = 96%, p < 0.00001, Random-effect), intra-operative blood loss (13 studies, 642 vs 519 patients; SMD -0.82; 95% CI -1.33 to -0.32; I2 = 93%, p < 0.00001, Random-effect), LOS (22 studies, 2808 vs 2789 patients; MD -0.38, 95% CI -0.59 to -0.17; I2 = 98%, p < 0.00001 Random-effect), and healthcare costs (8 studies, 1138 vs 1129 patients, SMD 1.05; 95% CI -0.06 to 2.16; I2 = 99%, p < 0.00001 Random-effect). The rate of overall intraoperative complications was significantly different between both groups (25 studies, 2804 vs 2775 patients; RR 0.88, 95% CI 0.80 to 0.97; I2 = 38%, p = 0.03 Random-effect), but the sensitivity analysis did not find a statistically significant difference (6 studies, 605 vs 594 patients, RR; 95% CI to; I2 = 0%, p = 0.50, Random-effect). There was no difference in the subgroup analysis for the occurrence of transient and permanent RLN palsy, nor hematoma formation and hypocalcaemia. DISCUSSION: Though findings of our systematic review and metanalysis are limited by heterogeneous data, surgeons, hospital managers, and policymakers should note that the use of High Energy Devices compared to conventional clamp and tie technique have reduced operative times, intra-operative blood loss, length of stay, and hospital costs in patients underwent to tyroid surgery. Future work must explore issues of equity to mitigate barriers to patient access to safe thyroid surgical care and define better this initial results.

Use of High Energy Devices (HEDs) versus electrocautery for laparoscopic cholecystectomy: a systematic review and meta-analysis of randomised controlled trials.

INTRODUCTION: According to the literature, there is no clear definition of a High Energy Devices (HEDs), and their proper indications for use are also unclear. Nevertheless, the flourishing market of HEDs could make their choice in daily clinical practice arduous, possibly increasing the risk of improper use for a lack of specific training. At the same time, the diffusion of HEDs impacts the economic asset of the healthcare systems. This study aims to assess the efficacy and safety of HEDs compared to electrocautery devices while performing laparoscopic cholecystectomy (LC). MATERIALS AND METHODS: On behalf of the Italian Society of Endoscopic Surgery and New Technologies, experts performed a systematic review and meta-analysis and synthesised the evidence assessing the efficacy and safety of HEDs compared to electrocautery devices while performing laparoscopic cholecystectomy (LC). Only randomised controlled trials (RCTs) and comparative observational studies were included. Outcomes were: operating time, bleeding, intra-operative and post-operative complications, length of hospital stay, costs, and exposition to surgical smoke. The review was registered on PROSPERO (CRD42021250447). RESULTS: Twenty-six studies were included: 21 RCTs, one prospective parallel arm comparative non-RCT, and one retrospective cohort study, while three were prospective comparative studies. Most of the studies included laparoscopic cholecystectomy performed in an elective setting. All the studies but three analysed the outcomes deriving from the utilisation of US sources of energy compared to electrocautery. Operative time was significantly shorter in the HED group compared to the electrocautery group (15 studies, 1938 patients; SMD - 1.33; 95% CI - 1.89 to 0.78; I2 = 97%, Random-effect). No other statistically significant differences were found in the other examined variables. CONCLUSIONS: HEDs seem to have a superiority over Electrocautery while performing LC in terms of operative time, while no difference was observed in terms of length of hospitalisation and blood loss. No concerns about safety were raised.

High-energy devices in different surgical settings: lessons learnt from a full health technology assessment report developed by SICE (Società Italiana di Chirurgia Endoscopica).

BACKGROUND: The present paper aims at evaluating the potential benefits of high-energy devices (HEDs) in the Italian surgical practice, defining the comparative efficacy and safety profiles, as well as the potential economic and organizational advantages for hospitals and patients, with respect to standard monopolar or bipolar devices. METHODS: A Health Technology Assessment was conducted in 2021 assuming the hospital perspective, comparing HEDs and standard monopolar/bipolar devices, within eleven surgical settings: appendectomy, hepatic resections, colorectal resections, cholecystectomy, splenectomy, hemorrhoidectomy, thyroidectomy, esophago-gastrectomy, breast surgery, adrenalectomy, and pancreatectomy. The nine EUnetHTA Core Model dimensions were deployed considering a multi-methods approach. Both qualitative and quantitative methods were used: (1) a systematic literature review for the definition of the comparative efficacy and safety data; (2) administration of qualitative questionnaires, completed by 23 healthcare professionals (according to 7-item Likert scale, ranging from - 3 to + 3); and (3) health-economics tools, useful for the economic evaluation of the clinical pathway and budget impact analysis, and for the definition of the organizational and accessibility advantages, in terms of time or procedures' savings. RESULTS: The literature declared a decrease in operating time and length of stay in using HEDs in most surgical settings. While HEDs would lead to a marginal investment for the conduction of 178,619 surgeries on annual basis, their routinely implementation would generate significant organizational savings. A decrease equal to - 5.25/-9.02% of operating room time and to - 5.03/-30.73% of length of stay emerged. An advantage in accessibility to surgery could be hypothesized in a 9% of increase, due to the gaining in operatory slots. Professionals' perceptions crystallized and confirmed literature evidence, declaring a better safety and effectiveness profile. An improvement in both patients and caregivers' quality-of-life emerged. CONCLUSIONS: The results have demonstrated the strategic relevance related to HEDs introduction, their economic sustainability, and feasibility, as well as the potentialities in process improvement.

Effectiveness of preconceptional and prenatal cystic fibrosis carrier screening: a systematic review

BACKGROUND: genetic testing for cystic fibrosis (CF) has been offered to people with higher risk of being carrier. OBJECTIVES: to assess the effectiveness of population-based CF carrier screening for adults of reproductive age and its optimal organizational features. DESIGN: systematic review. SETTING AND PARTICIPANTS: MedLine, Embase, Cochrane Library, CINAHL and LILACS (1990-2022) were searched to retrieve primary and secondary studies on adults (16 years and older), with no clinical indication or genetic risk, eligible for genetic testing for CF carrier status. MAIN OUTCOMES MEASURES: attitude to screening, uptake of screening offered, informed reproductive choices. RESULTS: a total of 3,326 records were screened and 292 potentially eligible full-text publications assessed. The review included 71 publications, corresponding to 3 reviews, 40 cohort studies (11 comparative, 29 single-arm), and 6 model studies, published between 1992 and 2021 (median 1998). Only one study compared screening or no screening. This study suggested an association between carrier screening and a lower incidence of CF. Comparative studies examined different approaches for invitation and testing, i.e., settings, target population (individuals/couples, prenatal/preconceptional), how invitations are organized (primary care/maternal hospitals), and format and content of the pre-test information. However, no firm conclusions can be drawn on the impact of these features on informed reproductive choices, uptake, and attitude, because of the limitations of the evidence collected. CONCLUSIONS: the broad heterogeneity of the studies, methodological weaknesses, and the limited transferability of the results mean there is still uncertainty about the effectiveness of preconceptional and prenatal CF carrier screening in the general population.

Clinical evidence supporting the marketing authorization of biosimilars in Europe.

PURPOSE: To review the marketing authorization of biosimilars and provide a critical analysis of the pivotal trials supporting their approval by the European Medicines Agency (EMA). METHODS: EMA website to identify the biosimilars approved up to July 2019 and the European Public Assessment Report for information on pivotal trial design, duration, intervention and control, primary outcome, data on immunogenicity, and comparability margins. RESULTS: The EMA has approved 55 biosimilars (62% in 2017-2019) of 16 biologic products, used in several clinical indications. Some biosimilars were licensed as multiple products, with different commercial names, by the same or different companies. The comparability exercise and subsequent approval of 49/55 (89%) biosimilars were based on one or more pivotal phase III trials testing their clinical efficacy. In all, biosimilars were approved on the basis of 55 trials, mostly phase III (42/55, 76%) assessing clinical efficacy; these were mainly equivalence trials (31/55, 56%). The pivotal phase III trials assessed surrogate measures of clinical effect, and 71% reported immunogenicity data. CONCLUSION: Analysis of the approval of biosimilars in Europe depicts a complex and heterogeneous scenario. The requirement for showing similarity in terms of clinical efficacy and safety provides a robust demonstration of comparable clinical outcomes but lays a burden on biosimilar manufacturers and may delay the introduction of the drugs. The development, licensing, and monitoring of biosimilars would benefit from new strategies to accelerate access to these drugs while reducing uncertainties about their use in practice.

[Cystic fibrosis carrier screening: a Health technology assessment.] / Lo screening del portatore di fibrosi cistica: una valutazione di Health technology assessment.

This project of Health technology assessment was aimed at defining the impacts of offering a cystic fibrosis (CF) carrier screening to the general population, compared to the current situation, where the test is offered to individuals at high-risk to give birth to a child with CF. Results revealed: i) a lack of robust and updated data; ii) a return on investment up to six years from the screening's introduction, despite important economic and organizational efforts; iii) a general positive attitude of healthcare professionals, people with CF, families and general population; iv) possible issues related to the social impact.

Corrigendum to "Utilisation Trend of Long-Acting Insulin Analogues including Biosimilars across Europe: Findings and Implications".

[This corrects the article DOI: 10.1155/2021/9996193.].

A Surface Plasmon Resonance-Based Assay for Simultaneous Measurement of Serum Concentrations of Therapeutic Antibodies and Anti-Drug Antibodies.

The monitoring of the blood levels of therapeutic antibodies and their immune responses is proposed to guide and optimize therapy with these expensive drugs. We describe a novel Surface Plasmon Resonance (SPR)-based assay suitable for the simultaneous determination of serum concentrations of infliximab and anti-infliximab antibodies. The real-time detection by SPR avoids the incubation/washing steps of commonly used methods, thus allowing faster and more reliable measurements, in particular for low-affinity anti-drug antibodies. This method proved to be highly reproducible and may be well applied to other biotherapeutics.

Switching Among Biosimilars: A Review of Clinical Evidence.

Biological medicines have improved patients' outcomes, but their high costs may limit access. Biosimilars, alternatives that have demonstrated high similarity in terms of quality, safety, and efficacy to an already licensed originator biological product, could increase competition and decrease prices. Given the expanding number of biosimilars, patients may switch from originator to biosimilar or among biosimilars. Randomized trials and observational studies conducted with multiple biosimilars over many disease areas confirmed the safety and efficacy of switching from originator to biosimilar. This study summarizes evidence on switching between biosimilars for which there are concerns to provide future guidance. A systematic search (MEDLINE, Embase, and Cochrane Library) for studies on anti-TNF agents, assessing clinical efficacy and safety of biosimilar-to-biosimilar switch in chronic inflammatory diseases, was performed. We retrieved 320 records and included 19 clinical studies. One study with historical control compared switching between biosimilars to maintenance of the same biosimilar. Ten were controlled cohort studies comparing switching between two biosimilars vs. switching from originator to a biosimilar or vs. multiple switches. Eight were single-arm cohort studies, where participants switched from one biosimilar to another, and the outcomes were compared before and after the switch. Overall, these studies did not highlight significant concerns in switching between biosimilars. Therefore, switching studies seem difficult to perform and unnecessary with the body of evidence suggesting no real problems in practice coupled with stringent regulatory requirements. Monitoring the use of biosimilars in clinical practice could support clinical decision-making, rational use of biological medicines, and help to further realize possible savings.

Second Cancers in Classical Hodgkin Lymphoma and Diffuse Large B-Cell Lymphoma: A Systematic Review by the Fondazione Italiana Linfomi.

BACKGROUND: The increase of lymphoma patient survival led to a modification of the incidence of long-term sequelae, including second malignancies (SM). Several groups have dealt with the incidence of SM, according to the primary treatment; however, a standardized approach for the early detection and screening of SM in the population of lymphoma survivors should be implemented. METHODS: A systematic review was conducted by Fondazione Italiana Linfomi (FIL), in order to define the incidence of SM, the impact of modern radiotherapy on SM risk, and the usefulness of tailored follow-up and screening strategies for early diagnosis of SM. Classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL) survivors were investigated. The MEDLINE, Embase, and Cochrane Library databases were checked for relevant reports published up to January 2020. The selection process was reported according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. RESULTS: A total of 27 full-text manuscripts resulted as eligible for the analysis. The incidence of SM in cHL patients treated with ABVD was higher compared to the general population and was even higher in patients treated with intensified regimens. The risk increased over time, as well as after 10-15 years from therapy, and was augmented by radiotherapy exposure. In DLBCL, more intensive regimens (i.e., R-CHOEP or R-MegaCHOEP) vs. R-CHOP were associated with a higher SM incidence. Salvage chemotherapy and autologous stem cell transplants increased the risk of SM in both cHL and DLBCL cohorts. A lower incidence of SM, particularly of breast cancer (BC), was shown in cohorts of cHL survivors treated with reduced radiation volumes and doses (involved fields vs. extended fields), but robust trials are still lacking. Considering the advantage of a structured screening for early detection of SM, all the included studies regarded cHL survivors and screening strategy for early BC detection. Moreover, the authors discuss additional papers, to guide the early diagnosis of lung, colorectal, skin, and thyroid cancer in patients at risk due to family history, drug or RT exposure, or unhealthy lifestyles. These screening strategies all passed through patient awareness. CONCLUSION: A modern approach to chemotherapy and radiotherapy led to a lower risk of SM, which should be confirmed over time. Early detection of secondary cancers could be achieved through a tailored screening program, according to the individual risk profile.

Late Endocrine and Metabolic Sequelae and Long-Term Monitoring of Classical Hodgkin Lymphoma and Diffuse Large B-Cell Lymphoma Survivors: A Systematic Review by the Fondazione Italiana Linfomi.

BACKGROUND: Overall survival after lymphoma has improved in recent years, but the high prevalence of late treatment-related sequelae has been observed as a counterpart. METHOD: In this systematic review, FIL researchers aimed to: (i) estimate the incidence or prevalence of late endocrine-metabolic sequelae, (ii) evaluate the effects of modern therapeutic approaches on incidence or prevalence of late endocrine-metabolic sequelae, and (iii) determine whether there is evidence of follow-up schemes for their screening/early diagnosis in the subset of long-term classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL) survivors treated at adult age. The MEDLINE, Embase and the Cochrane Library databases were searched for relevant articles published up to October, 2020. The study selection process was conducted by three independent reviewers and was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A risk of bias assessment was performed using the Cochrane tool for randomized trials and the Newcastle-Ottawa Scale for observational studies. RESULTS: In the final analysis, eight studies were included, four of which focused on thyroid disease, two on gonadal dysfunction, one on bone disease and one on metabolic syndrome. Hypothyroidism was reported in up to 60% of adult cHL survivors and was frequently recorded even with modern radiotherapy approaches. Menopause occurred in 52-72% of women after chemotherapy. An 86% reduction in vertebral density was reported following R-CHOP-like chemotherapy. Sarcopenia and metabolic syndrome were reported in 37.9% and 60% of patients, respectively. No validated screening protocols were found for the early diagnosis of long-term treatment-related endocrine and metabolic sequelae, thus the authors finally suggest the execution of screening exams according to the risk category which were identified in the epidemiologic studies.

Clinical Management of Long-Term Survivors after Classical Hodgkin Lymphoma and Diffuse Large B-Cell Lymphoma.

Compared to other patients suffering from hematological malignancies, classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL) patients have a long life expectancy when in complete remission at the end of first, or sometimes second, line treatments [...].

Availability and accessibility of monoclonal antibodies in Bosnia and Herzegovina: Findings and implications.

Background: Monoclonal antibodies (mAbs) represent the most numerous and significant group of biotherapeutics. While mAbs have undoubtedly improved treatment for many chronic diseases, including inflammatory diseases, they are typically expensive for health care systems and patients. Consequently, access to mAbs has been a problem for many patients especially among Central and Eastern European (CEE) countries. However, biosimilars can potentially help with costs, although there are concerns with their effectiveness and safety. This includes biosimilars for long-acting insulin analogues. Aim: Assess the availability and use of biological medicines, including biosimilars within Bosnia and Herzegovina (B&H). Methods: Assess the availability of mAbs via the current lists of approved and accessed mAbs versus those licenced in Europe and the United States and their utilisation, as well as specifically insulin glargine and its biosimilars, within B&H. Results: The availability of the mAbs in B&H appears satisfactory, which is encouraging. However, current usage is limited to a few mAbs which is a concern for subsequent patient care especially with limited use of biosimilars to address issues of affordability. We also see limited use of biosimilar insulin glargine. Conclusion: The limited use of mAbs including biosimilars needs to be addressed in B&H to improve the future care of patients within finite resources. We will monitor these developments.

Long-Term Follow-Up of Classical Hodgkin Lymphoma and Diffuse Large B-Cell Lymphoma Survivors: Aims and Methodological Approach for Fondazione Italiana Linfomi Systematic Reviews.

Advances in diagnosis and treatment of hematological malignancies has boosted attention on optimal follow-up care of survivors after cancer. To collect evidence that could inform the development of an optimal model for Italian hematology centers and the scientific community, Fondazione Italiana Linfomi (FIL) commissioned an analysis of the international follow-up approaches for long-term survivors after classical Hodgkin lymphoma (cHL) or diffuse large B-cell lymphoma (DLBCL). FIL set up multidisciplinary teams, representing all different skills relevant for cancer survivors. They conducted a series of systematic reviews focused on three main aspects: incidence of long-term toxicity; comparison of old or standard therapies and more recent ones; and evidence on specific follow-up approaches. The teams applied this framework to cardiological, endocrine-metabolic, neurological/cognitive, and psychological disorders, secondary cancers, fertility preservation, and lifestyles. Each team conducted comprehensive literature searches on PubMed, Embase and Cochrane Library databases up to 2020. Screening followed the PRISMA statement for reporting systematic reviews. The reviews report the results of this wide project covering the main areas of late toxicity and conditions in the long-term survival of cHL and DLBCL patients and their follow-up. From a clinical point of view, the series confirmed that the evidence on follow-up tended to focus on solid tumors with scant evidence on hematological malignancies.

The Impact of Healthy Lifestyles on Late Sequelae in Classical Hodgkin Lymphoma and Diffuse Large B-Cell Lymphoma Survivors. A Systematic Review by the Fondazione Italiana Linfomi.

BACKGROUND: In recent years, the scientific community has been paying ever more attention to the promotion of lifestyles aimed at the prevention of late toxicities related to anti-cancer treatments. METHODS: Fondazione Italiana Linfomi (FIL) researchers conducted a systematic review in order to evaluate the evidence in favor of the promotion of lifestyles aimed at the prevention of the main sequelae of long-term classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL) in survivors treated at adulthood with first-line or second-line therapy, including autologous stem cell transplants (ASCTs). Pubmed, Embase and Cochrane Library were searched up to December 2020. RESULTS: Seven studies were ultimately included in this systematic review; some of them were eligible for multiple PICOS. The majority of the studies emerged from data extraction regarding cHL; less evidence resulted for DLBCL survivors. Five studies in favor of physical activity provided consistent data for a reduction of the cardiovascular risk in cHL and also in survivors who underwent ASCT. A beneficial effect of physical activity in reducing chronic fatigue was found. Being overweight was associated with a higher risk of coronary heart disease in cHL survivors in one of the two eligible studies. Studies aiming to evaluate the impact of the Mediterranean diet on late toxicities and secondary cancers were lacking. Tailored survivorship care plans (SCP) seemed to represent an optimal tool to guide the follow-up and promote healthier lifestyles in the one eligible study. Thus, promotion of healthy lifestyles and empowering of lymphoma survivors should be implemented through structured models. The study also brought to light numerous areas of future clinical research.

Late Neurological and Cognitive Sequelae and Long-Term Monitoring of Classical Hodgkin Lymphoma and Diffuse Large B-Cell Lymphoma Survivors: A Systematic Review by the Fondazione Italiana Linfomi.

BACKGROUND: The continuously improving treatment outcome for classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL) over the last 25 years has led to a high number of long-term survivors. The impact of treatment, however, can sometimes be dramatic and long-lasting. Focusing on peripheral neuropathy (PN), cognitive impairment, fatigue, anxiety, and depression, researchers of the Fondazione Italiana Linfomi conducted a systematic review of the literature to collect the available data on sequelae incidence as well as evidence of follow-up strategies for long-term cHL and DLBCL survivors. METHODS: The review was carried out under the methodological supervision of the Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy. The literature search was conducted on three databases (MEDLINE, Embase, and the Cochrane Library) updated to November 2019. The selection process and data extraction were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: A total of 2236 abstracts were screened, 247 full texts were analyzed, and 35 papers were included in the final analysis. Fatigue was the most extensively studied among neuropsychological sequelae, with a mean prevalence among cHL survivors of 10-43%. Although many of the papers showed an increased incidence of PN, cognitive impairment, and anxiety and depression in long-term cHL and DLBCL survivors, no definite conclusions can be drawn because of the methodological limitations of the analyzed studies. No data on monitoring and follow-up strategies of PN and other neuropsychological sequelae were highlighted. CONCLUSIONS: Based on our findings, future studies in this setting should include well-defined study populations and have a longitudinal trial design to assess the outcomes of interest over time, thus as to structure follow-up programs that can be translated into daily practice.

Male and Female Fertility: Prevention and Monitoring Hodgkin' Lymphoma and Diffuse Large B-Cell Lymphoma Adult Survivors. A Systematic Review by the Fondazione Italiana Linfomi.

BACKGROUND: Adult patients with Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma (DLBCL) have prolonged survival but face the risk of treatment-induced impaired fertility. This systematic review, conducted by Fondazione Italiana Linfomi (FIL) researchers, aims to evaluate the incidence of treatment-related infertility, fertility preservation options, fertility assessment measures, and the optimal interval between the end of treatment and conception. METHODS: MEDLINE, the Cochrane Library, and EMBASE were systematically searched up to September 2020 for published cohort, case-control, and cross-sectional studies on fertility issues. RESULTS: Forty-five eligible studies were identified. Gonadotoxicity was related to sex, type and dosage of treatment, and, in females, to age. After receiving alkylating-agent-containing regimens, less than 30% of males recovered spermatogenesis, and 45% of females ≥30 years in age retained regular menstrual cycles. Sperm cryopreservation was offered to the majority of patients; sperm utilization resulted in a 33-61% pregnancy rate. After ovarian tissue transplantation, the spontaneous pregnancy and live birth rates were 38% and 23%; after IVF, the live birth rate was 38.4%. No data could be extracted on the utilization rate of cryopreserved mature oocytes. The results of studies on GnRH analogs are controversial; therefore, their use should not be considered an alternative to established cryopreservation techniques. Sperm count, FSH, and inhibin-B levels were appropriate measures to investigate male fertility; serum AMH levels and antral follicle count were the most appropriate markers for ovarian reserve. No data could be found regarding the optimal interval between the end of treatment and conception. CONCLUSIONS: The risk of infertility should be discussed with adult lymphoma patients at the time of diagnosis, and fertility preservation options should be proposed before first-line treatment with alkylating-agent-containing regimens.

Surface plasmon resonance unveils important pitfalls of enzyme-linked immunoassay for the detection of anti-infliximab antibodies in patients' sera.

Measurements of serum concentrations of therapeutic antibodies and anti-drug antibodies (ADA) can support clinical decisions for the management of non-responders, optimizing the therapy. In the present study we compared the results obtained by classical ELISA and a recently proposed surface plasmon resonance (SPR)-based immunoassay, in 76 patients receiving infliximab for inflammatory bowel diseases. The two methods indicated very similar serum concentrations of the drug, but there were striking differences as regards ADA. All the sera showing ADA by ELISA (14) also showed ADA by SPR, but the absolute amounts were different, being 7-490 times higher with SPR, with no correlation. Eight patients showed ADA only with SPR, and these ADA had significantly faster dissociation rate constants than those detectable by both SPR and ELISA. The underestimation, or the lack of detection, of ADA by ELISA is likely to reflect the long incubation steps which favor dissociation of the patient's low-affinity ADA, while the commercial, high-affinity anti-infliximab antibodies used for the calibration curve do not dissociate. This problem is less important with SPR, which monitors binding in real time. The possibility offered by SPR to detect ADA in patients otherwise considered ADA-negative by ELISA could have important implications for clinicians.

Late Cardiological Sequelae and Long-Term Monitoring in Classical Hodgkin Lymphoma and Diffuse Large B-Cell Lymphoma Survivors: A Systematic Review by the Fondazione Italiana Linfomi.

Cardiotoxicity represents the most frequent cause with higher morbidity and mortality among long-term sequelae affecting classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL) patients. The multidisciplinary team of Fondazione Italiana Linfomi (FIL) researchers, with the methodological guide of Istituto di Ricerche Farmacologiche "Mario Negri", conducted a systematic review of the literature (PubMed, EMBASE, Cochrane database) according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, in order to analyze the following aspects of cHL and DLBCL survivorship: (i) incidence of cardiovascular disease (CVD); (ii) risk of long-term CVD with the use of less cardiotoxic therapies (reduced-field radiotherapy and liposomal doxorubicin); and (iii) preferable cardiovascular monitoring for left ventricular (LV) dysfunction, coronary heart disease (CHD) and valvular disease (VHD). After the screening of 659 abstracts and related 113 full-text papers, 23 publications were eligible for data extraction and included in the final sample. There was an increased risk for CVD in cHL survivors of 3.6 for myocardial infarction and 4.9 for congestive heart failure (CHF) in comparison to the general population; the risk increased over the years of follow-up. In addition, DLBCL patients presented a 29% increased risk for CHF. New radiotherapy techniques suggested reduced risk of late CVD, but only dosimetric studies were available. The optimal monitoring of LV function by 2D-STE echocardiography should be structured according to individual CV risk, mainly considering as risk factors a cumulative doxorubicine dose >250 mg per square meter (m2) and mediastinal radiotherapy >30 Gy, age at treatment <25 years and age at evaluation >60 years, evaluating LV ejection fraction, global longitudinal strain, and global circumferential strain. The evaluation for asymptomatic CHD should be offered starting from the 10th year after mediastinal RT, considering ECG, stress echo, or coronary artery calcium (CAC) score. Given the suggested increased risks of cardiovascular outcomes in lymphoma survivors compared to the general population, tailored screening and prevention programs may be warranted to offset the future burden of disease.

Evidence-based public policy making for medicines across countries: findings and implications for the future.

Aim: Global expenditure on medicines is rising up to 6% per year driven by increasing prevalence of non-communicable diseases (NCDs) and new premium priced medicines for cancer, orphan diseases and other complex areas. This is difficult to sustain without reforms. Methods: Extensive narrative review of published papers and contextualizing the findings to provide future guidance. Results: New models are being introduced to improve the managed entry of new medicines including managed entry agreements, fair pricing approaches and monitoring prescribing against agreed guidance. Multiple measures have also successfully been introduced to improve the prescribing of established medicines. This includes encouraging greater prescribing of generics and biosimilars versus originators and patented medicines in a class to conserve resources without compromising care. In addition, reducing inappropriate antibiotic utilization. Typically, multiple measures are the most effective. Conclusion: Multiple measures will be needed to attain and retain universal healthcare.