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For decades, we have known from autopsy observations that the proximate cause of the majority of acute coronary syndromes ( ACS) is occlusive thrombosis generated by plaque rupture or, less frequently, superficial erosion. Patients with ACS caused by plaque erosion seem to have a better long-term prognosis compared to those with plaque rupture, and may be stabilized by dual antiplatelet therapy without the need for stenting in a non-trivial proportion of cases, limiting the expenses and potential complications of invasive procedures. The accurate prediction of plaque erosion and the identification of specific biomarkers that could be used at the point-of-care without the need of invasive imaging would take us a step closer to the holy grail of precision medicine in patients with ACS.

The aim of this study was to quantify the incidence of short-term postoperative complications and functional disorders at 1 year from transanal endoscopic microsurgery (TEM) for rectal neoplasms, to compare patients treated with TEM alone and with TEM after preoperative chemoradiotherapy (CRT) and to analyse factors influencing postoperative morbidity and functional outcomes. A retrospective study was conducted on all patients treated with TEM for rectal neoplasms at our institution in January 2000–December 2017. Data from a prospectively maintained database were retrospectively analysed. Patients were divided into two groups: adenoma or early rectal cancer (no CRT group) and locally advanced extraperitoneal rectal cancer with major or complete clinical response after preoperative CRT (CRT group). Short-term postoperative mortality and morbidity and the functional results at 1 year were recorded. The two groups were compared, and a statistical analysis of factors influencing postoperative morbidity and functional outcomes was performed. Functional outcome was also evaluated with the low anterior resection syndrome (LARS) score (0–20 no LARS, 21–29 minor LARS and 30–42 major LARS). One hundred and thirteen patients (71 males, 42 females, median age 64 years [range 41–80 years]) were included in the study (46 in the CRT group). The overall postoperative complication rate was 23.0%, lower in the noCRT group (p

Spatiotemporal parameters of walking are used to identify gait impairments and provide a tailored therapy program. Baropodometric platforms are not often used for measuring spatiotemporal parameters and walking speed and it is required to determine accuracy. The aim of this study was to compare FreeMed® Platform gait outcomes with a validated inertial measurement unit. There were 40 healthy adults without walking impairments enrolled. Each subject walked along a 15-m walkway at self and slow self-selected speed wearing an inertial measurement unit on the FreeMed® Platform. Stride length and time, right and left stance, swing time, and walking speed were recorded. Walking speed, stride length, and step time showed a very high level of agreement at slow walking speed and a high and moderate level of agreement at normal walking speed. FreeMed® Platform is useful to assess gait outcomes and could improve the exercise prescription.

In contrast to other tumour entities such as lung carcinoma, melanoma or gynaecological and gastrointestinal tumours, the routine application of mutation analyses using high-throughput sequencing via next-generation sequencing (NGS) has not yet been widely established in haematopathology, especially not in lymphomas.Here we describe our experience with the use and routine implementation of a lymphoma NGS panel primarily developed for research purposes.In addition to a discussion of the steps necessary for transferring such a panel into the routine framework of an accredited institute, we show by the comprehensive workup of 80 investigations and the presentation of several case studies how the panel was able to guide us to the correct diagnosis and how it also provided clinicians with indications for possible tailored therapy options.Even if NGS does not (yet) have to be routinely applied in lymphoma diagnostics for every case, a respectively dedicated NGS panel offers the advantage of having an additional option in the case of difficult differential diagnostic considerations or uncertainties as well as at the request of the treating oncologist to identify potential targets for tailored treatment of the patients.

Canine atopic dermatitis is a model of human atopic dermatitis. This review provides an outline and discussion of clinical and other phenotypes of atopic dermatitis in dogs to better understand this disease in both dogs and humans. Although phenotypes of canine atopic dermatitis can vary widely, there is little research in dogs that has identified reliable phenotypic markers to be able to predict disease progression or response to therapy. Currently, canine atopic dermatitis patients need individually tailored therapy without the practitioner understanding why a certain treatment works well for one patient and not another. Perhaps by categorizing phenotypes, genetic or immunologic mechanisms will be discovered to result in better prevention and management of this common and often frustrating condition in both dogs and humans.

Background Few studies have compared the efficacy and safety profile of a tailored eradication (TR) strategy based on the presence of a 23S ribosomal RNA point mutation with those of empirical bismuth-based quadruple therapy (EBQT) for first-line eradication of Helicobacter pylori (H. pylori) in Korean patients. Aim To compare the efficacy and safety of a TR strategy and those of EBQT regimen as first-line eradication therapy for H. pylori. Methods This is an open-label, comparative study in which we prospectively enrolled patients over 18 years of age with H. pylori infection and retrospectively reviewed their data. H. pylori-positive patients diagnosed by rapid urease test, Giemsa staining, or dual priming oligonucleotide polymerase chain reaction (DPO-PCR) were enrolled from May 2016 to September 2018 at Gil Medical Center. Patients with H. pylori infection received either a TR regimen or the EBQT regimen. In the tailored therapy group that underwent DPO-PCR testing, patients with A2142G and/or A2143G point mutations were treated with a bismuth-containing quadruple regimen. The eradication rate, patient-reported side effect rate, and H. pylori eradication success rate were evaluated and compared between the groups. Results A total of 150 patients were assigned to the TR (n = 50) or EBQT group (n = 100). The first-line eradication rate of H. pylori did not differ between the groups (96.0% vs 95.7%, P = 0.9). The rate of eradication-related side effects for TR was 12.0%, which differed significantly from that of EBQT (43.0%) for first-line treatment (P Conclusion DPO-PCR-based TR for H. pylori eradication may be equally efficacious, with less treatment-related complications, compared to EBQT in Korea, where clarithromycin resistance is high.

As high clarithromycin resistance (&gt, 20%) in the Split-Dalmatia region of Croatia hinders the treatment of H. pylori infection, the primary objective of this study was to compare concomitant quadruple with the tailored, personalized therapy as first-line eradication treatment of H. pylori. In an open-label, randomized clinical trial, 80 patients with H. pylori infection were randomly assigned to either concomitant (esomeprazole 40 mg, amoxicillin 1 gr, metronidazole 500 mg, clarithromycin 500 mg, twice daily for 14 days) or tailored therapy in accordance with the results of the antimicrobial susceptibility testing. Eradication status was assessed 4 weeks after treatment. Eradication rates were significantly higher in tailored group than in concomitant group both in intention-to-treat (70 vs. 92.5%, p = 0.010) and per-protocol (87.5 vs. 100%, p = 0.030) analysis in the setting of increasing antibiotic resistance (clarithromycin 37.5%, metronidazole 17.5%, dual resistance 10%). Adverse effects were more frequent in the concomitant group (32.5 vs. 7.5%, p = 0.006). Tailored therapy achieves higher eradication with a lower adverse events rate. With the increasing resistance of H. pylori strains to antibiotic treatment, eradication regimes with such characteristics should be strongly considered as a reasonable choice for first-line treatment.

Myxopapillary ependymomas are low grade neoplasms, which originate mostly from the medullary conus, cauda equina and the filum terminale. To date the principal treatment is surgical, total- or subtotal removal (GTR or STR), which can be associated with adjuvant radiotherapy. We report a patient with two tumor locations, one larger tumor at the L3 to S1 level and a smaller S2-S3 localized lesion. The patient was treated successfully with a combined approach of GTR of L3-S1 lesion and radiosurgical treatment of S2-S3 lesion.

Our aim was to investigate the efficacy and safety of initial neoadjuvant endocrine therapy with exemestane alone followed by tailored treatment, either continued exemestane monotherapy or exemestane plus docetaxel–cyclophosphamide (TC) combination therapy, in postmenopausal patients with primary invasive estrogen receptor–positive, human epidermal growth factor receptor 2–negative, stage I‐IIIA breast cancer and Ki67 labeling index ≤30%. In this open‐label phase II study, patients initially received exemestane 25 mg/d for 12 weeks. Responders were defined as patients who achieved complete response (CR), partial response (PR) with Ki67 labeling index ≤5% after treatment, or stable disease with Ki67 labeling index ≤5% both before and after treatment. For the subsequent 12 weeks, exemestane monotherapy was continued for responders (group A), whereas nonresponders received exemestane plus four cycles of TC (docetaxel 75 mg/m2 and cyclophosphamide 600 mg/m2 every 3 weeks) (group B). Clinical response rate (ie the proportion of patients with CR or PR) at 24 weeks was the primary endpoint. Of 64 patients provisionally enrolled between December 2010 and May 2016, 58 (median age 60 years) started the study treatment. Five patients discontinued treatment in the initial exemestane monotherapy period, and 39 completed the study treatment. Clinical response rates at 8‐12 and 24 weeks were 71% (10/14, 95% confidence interval [CI] 41.9%‐91.6%) and 57% (8/14, 95% CI 28.9%‐82.3%), respectively, in group A, and 16% (4/25, 95% CI 4.5%‐36.1%) and 56% (14/25, 95% CI 34.9%‐75.6%), respectively, in group B. Grade ≥3 adverse events were reported in 8% (1/15) and 53% (20/38) in group A and group B, respectively. The tailored treatment maintained the favorable clinical response to exemestane alone in responders and improved clinical response in nonresponders. Trial number UMIN000004752 (UMIN Clinical Trials Registry)., Change in Ki67 labeling index over the course of the study in patients receiving continued exemestane monotherapy (A) and those receiving exemestane plus docetaxel–cyclophosphamide) (B).

Hepatitis C virus (HCV) infects around 71 million people worldwide and in 2018 it is still a major health problem. Since 2011, anti-HCV therapy with availability of direct-acting antiviral drugs has revolutionized the clinical response and paved the way to eradication strategies. However, despite the high rate of sustained virological response, treatment failure may occur in a limited percentage of patients, possibly due to resistance-associated substitutions (RASs), either emergent or pre-existent even in minority viral populations. Clearly this problem may impair success of eradication strategies. With this background, several questions marks still exist around HCV treatment, including whether pan-genotypic treatments with complete effectiveness in any clinical conditions really exist outside clinical trials, the actual cost-effectiveness of genotyping testing, and utility of RAS detection in viral quasispecies by next generation sequencing approach. In this review, we describe these critical points by discussing recent literature data and our research experience.

Purpose The purposes of this study are to introduce the concept of vocal priorities based on acoustic correlates, to develop an instrument to determine these vocal priorities, and to analyze the pattern of vocal priorities in patients with voice disorders. Method Questions probing the importance of 5 vocal attributes (vocal clarity, loudness, mean speaking pitch, pitch range, vocal endurance) were generated from consensus conference involving speech-language pathologists, laryngologists, and voice scientists, as well as patient feedback. The responses to the preliminary items from 213 subjects were subjected to exploratory factor analysis, which confirmed 4 of the predefined domains. The final instrument consisted of a 16-item Vocal Priority Questionnaire probing the relative importance of clarity, loudness, mean speaking pitch, and pitch range. Results The Vocal Priority Questionnaire had high reliability (Cronbach's α = .824) and good construct validity. A majority of the cohort (61%) ranked vocal clarity as their highest vocal priority, and 20%, 12%, and 7% ranked loudness, mean speaking pitch, and pitch range, respectively, as their highest priority. The frequencies of the highest ranked priorities did not differ by voice diagnosis or by sex. Considerable individual variation in vocal priorities existed within these large trends. Conclusions A patient's vocal priorities can be identified and taken into consideration in planning behavioral or surgical intervention for a voice disorder. Inclusion of vocal priorities in treatment planning empowers the patient in shared decision making, helps the clinician tailor treatment, and may also improve therapy compliance.

The earliest marketed insulins were crude acidic formulations with concentrations of ≤10 units/mL. Since the early 1920s, insulins have improved continually, via bioengineering, process, and chemical modifications. Today, most insulin formulations have a concentration of 100 units/mL (U100). However, more concentrated insulin formulations (200, 300, and 500 units/mL; U200, U300, and U500, respectively) are also available. There is a tendency to assume that concentrated insulins are similar, both to each other and to their U100 counterparts, but this is not always the case: two concentrated insulins, namely insulin degludec U200 and insulin lispro U200, are bioequivalent to their U100 counterparts, whereas regular human insulin U500 and insulin glargine U300 are not. The advent of these concentrated insulins offers greater opportunities to provide tailored therapy for patients; it also introduces potential confusion, and highlights the need for prescriber and patient education. Precise and accurate dedicated insulin delivery devices are also necessary for the safe use of these concentrated insulins. Although some clinicians only use concentrated insulin with obese and severely insulin-resistant patients, other patients would also benefit from the reduced injection volume associated with concentrated insulins, or the modified time-action profile of some concentrated insulins. The aim of this review is to enhance understanding of the historic development and the safe and effective use of concentrated insulins in clinical practice.

Recently in Korea, where triple therapy is accepted as the first-line Helicobacter pylori (H. pylori) eradication treatment, antibiotic resistance to clarithromycin has increased considerably, resulting in eradication rates of less than 80%. We investigated the efficacy of tailored therapy after a clarithromycin resistance test compared with empirical therapy for H. pylori eradication. The cost-effectiveness of H. pylori eradication success was evaluated according to the average medical cost per patient. A total of 364 patients were enrolled in the study. The first-line H. pylori eradication rate was significantly higher in patients who received tailored therapy than in those who received empirical therapy. The total medical costs for the tailored and empirical groups were 46,374 Won and 53,528 Won. The total treatment period for each ultimately successful eradication in the tailored group was 79.8 ± 2.8 days, which is shorter than that of the empirical group (99.2 ± 7.4 days). The rate of eradication-related adverse events for the tailored group and empirical group was 12.9% and 14.8%, respectively. Tailored therapy could be a useful option to achieve a higher successful eradication rate, shorter treatment periods, and lower medical costs than empirical therapy in the era of increasing antibiotic resistance.

Increased morbidity and mortality from SARS‐CoV‐2 coronavirus disease (COVID‐19) in people with obesity has illuminated the intersection of obesity with impaired responses to infections. While data is being rapidly generated on mechanisms by which COVID‐19 impacts health, there is a critical need to better understand the pulmonary, vascular, metabolic, and immunologic aspects that drive the increased risk for complications from COVID‐19 in people with obesity. In this review, we provide a broad overview of the intersection between COVID‐19 and physiology of obesity to highlight potential mechanisms by which COVID‐19 disease severity is increased by obesity, and to identify areas for future investigation towards developing tailored therapy for people with obesity who develop COVID‐19.

Inflammation is the main pathophysiological process involved in atherosclerotic plaque formation, progression, instability, and healing during the evolution of coronary artery disease (CAD). The use of colchicine, a drug used for decades in non-ischemic cardiovascular (CV) diseases and/or systemic inflammatory conditions, stimulated new perspectives on its potential application in patients with CAD. Previous mechanistic and preclinical studies revealed anti-inflammatory and immunomodulatory effects of colchicine exerted through its principal mechanism of microtubule polymerization inhibition, however, other pleiotropic effects beneficial to the CV system were observed such as inhibition of platelet aggregation and suppression of endothelial proliferation. In randomized double-blinded clinical trials informing our clinical practice, low doses of colchicine were associated with the significant reduction of cardiovascular events in patients with stable CAD and chronic coronary syndrome (CCS) while in patients with a recent acute coronary syndrome (ACS), early initiation of colchicine treatment significantly reduced major adverse CV events (MACE). On the other hand, the safety profile of colchicine and its potential causal relationship to the observed increase in non-CV deaths warrants further investigation. For these reasons, postulates of precision medicine and patient-tailored approach with regards to benefits and harms of colchicine treatment should be employed at all times due to potential toxicity of colchicine as well as the currently unresolved signal of harm concerning non-CV mortality. The main goal of this review is to provide a balanced, critical, and comprehensive evaluation of currently available evidence with respect to colchicine use in the setting of CAD.

Management of endometrial cancer, an adenocarcinoma of the endometrium which occupies most uterine corpus neoplasms, including uterine sarcomas, has been more relevant due to its increasing incidence. Extensive research on tumorigenesis molecular mechanisms and molecular characterization across cancers has brought paradigm shifts in the treatment of various malignant tumors. Endometrial cancer treatment has been traditionally guided according to the disease extent or histology types, while recent studies on molecular features have led to the introduction of targeted agents into clinical use, along with conventional chemotherapeutic agents in patients with recurrent or metastatic disease. Considering the proven efficacy and relatively tolerable toxicities of targeted therapies across malignant tumors, improvement of treatment outcomes is also expected in endometrial cancer by adopting an individualized therapy depending on the specific molecular features. Efficacy assessment of new biological agents is still ongoing based on previous preclinical data on endometrial cancer molecular features. Here, endometrial cancer molecular characterization will be reviewed, and then, we will introduce preclinical data, directing the adoption of new biological agents.

Introduction: Monitoring of cerebral autoregulation (CA) in patients with a traumatic brain injury (TBI) can provide an individual ‘optimal’ cerebral perfusion pressure (CPP) target (CPPopt) at which CA is best preserved. This potentially offers an individualized precision medicine approach. Retrospective data suggest that deviation of CPP from CPPopt is associated with poor outcomes. We are prospectively assessing the feasibility and safety of this approach in the COGiTATE [CPPopt Guided Therapy: Assessment of Target Effectiveness] study. Its primary objective is to demonstrate the feasibility of individualizing CPP at CPPopt in TBI patients. The secondary objectives are to investigate the safety and physiological effects of this strategy.

Over the past 3 decades, significant advancements in the understanding of the pathophysiology of ANCA-associated vasculitis has led to the development of a multitude of potential candidate biomarkers. Accompanied by the advent of increasingly effective therapeutic strategies, the need for a dependable biomarker to help determine the extent of disease activity and risk of relapse is ever present. Implementation of such a biomarker would enable tailored therapy, optimizing disease control while helping to mitigate unnecessary exposure to therapy and potential treatment-related damage. Although far from perfect, ANCA serology and B-cell population are the two main staple biomarker tools widely used in practice to help supplement clinical assessment. Over recent years, the application and progress of more novel biomarker tools have arisen in both organ-limited and multisystem disease, including genomics, urinary proteins, degradation products of the alternative complement system, cytokines, metabolomics, and biospectroscopy. Validation studies and clinical translation of these tools are required, with serial assessment of disease activity and determination of therapy according to biomarker status correlated with patient outcomes.

BackgroundThere is limited understanding of heterogeneity in outcomes across hospitalized patients with coronavirus disease 2019 (COVID-19). Identification of distinct clinical phenotypes may facilitate tailored therapy and improve outcomes.ObjectiveIdentify specific clinical phenotypes across COVID-19 patients and compare admission characteristics and outcomes.Design, Settings, and ParticipantsRetrospective analysis of 1,022 COVID-19 patient admissions from 14 Midwest U.S. hospitals between March 7, 2020 and August 25, 2020.MethodsEnsemble clustering was performed on a set of 33 vitals and labs variables collected within 72 hours of admission. K-means based consensus clustering was used to identify three clinical phenotypes. Principal component analysis was performed on the average covariance matrix of all imputed datasets to visualize clustering and variable relationships. Multinomial regression models were fit to further compare patient comorbidities across phenotype classification. Multivariable models were fit to estimate the association between phenotype and in-hospital complications and clinical outcomes.Main outcomes and measuresPhenotype classification (I, II, III), patient characteristics associated with phenotype assignment, in-hospital complications, and clinical outcomes including ICU admission, need for mechanical ventilation, hospital length of stay, and mortality.ResultsThe database included 1,022 patients requiring hospital admission with COVID-19 (median age, 62.1 [IQR: 45.9-75.8] years; 481 [48.6%] male, 412 [40.3%] required ICU admission, 437 [46.7%] were white). Three clinical phenotypes were identified (I, II, III); 236 [23.1%] patients had phenotype I, 613 [60%] patients had phenotype II, and 173 [16.9%] patients had phenotype III.When grouping comorbidities by organ system, patients with respiratory comorbidities were most commonly characterized by phenotype III (p=0.002), while patients with hematologic (pConclusionIn this retrospective analysis of patients with COVID-19, three clinical phenotypes were identified. Future research is urgently needed to determine the utility of these phenotypes in clinical practice and trial design.

Vascular malformations include various disorders characterized by morphological, structural and/or functional alterations of blood and lymph vessels. Most are sporadic, due to somatic mutations. Here, we report a cohort of patients with sporadic and/or unifocal vascular malformations, in whom we carried out next generation sequencing analysis of a panel of genes associated with vascular malformations. The 115 patients analyzed were from different clinical centres. In 37 patients (32%), we found pathogenic mutations: most of these were gain&ndash, of&ndash, function mutations in PIK3CA (18%, 21/115) and TEK (13/115, 11%). We also found mutations in GNAQ, CCM2 and PTEN. Identifying pathogenic variants in patients with vascular malformations can help improve management, particularly in cases with activating mutations that cause an increase in cell proliferation. Personalized pharmacological treatment, if possible, is now considered preferable to surgery and can help prevent recurrences, i.e., long&ndash, term complications of residual malformation or regrowth of tumors. For instance, rapamycin is currently being investigated for the treatment of various vascular malformations associated with hyperactivation of the phosphoinositide 3&ndash, kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway.

Introduction Resistance to clarithromycin and fluoroquinolones is increasing in many countries. We aimed to assess the efficacy of a tailored PCR-guided triple therapy versus an empirical triple therapy in the treatment of H. pylori infection. Patients and methods French multicenter prospective open-label randomized study to assess H. pylori and resistance to clarithromycin and levofloxacin with GenoType HelicoDR® test. Patients of the control group were treated with empirical therapy of proton pump inhibitor (PPI), amoxicillin, and clarithromycin for 7 days. Patients of the experimental group with clarithromycin-susceptible strains, clarithromycin-resistant/levofloxacin-susceptible strains, and with clarithromycin-resistant/levofloxacin-resistant strains received tailored therapy of PPI, amoxicillin, and clarithromycin for 7 days, PPI, amoxicillin, and levofloxacin for 10 days, and PPI, amoxicillin, and metronidazole for 14 days, respectively. H. pylori eradication was assessed by 13C urea breath test at least 28 days after the end of treatment. Results We included 526 patients: 260 (49.4%) were randomly assigned to empirical triple therapy and 266 (50.6%) to tailored therapy. Clarithromycin and levofloxacin resistances were 23.3% and 12.8%, respectively. Follow-up urea breath test was available for 415 (78.9%) patients. Tailored therapy was superior to empirical therapy in terms of eradication (85.5% vs. 73.1%, RR = 1.85, 95%CI [1.25–2.78], p = 0.003). Findings were consistent in the susceptibility analysis using multiple imputation (RR = 1.61, 95%CI [1.14–2.27], P = 0.003) and per-protocol analysis (RR = 1.89, 95%CI [0.25–2.78], p = 0.003). Conclusion In a country with a high level of clarithromycin resistance, tailored PCR-guided therapy was superior to empirical triple therapy for H. pylori eradication ( https://www.ClinicalTrials.gov : NCT01168063 ).

Transdermal drug delivery is a key technology for administering drugs. However, most devices are “one-size-fits-all”, even though drug diffusion through the skin varies significantly from person-to-person. For next-generation devices, personalization for optimal drug release would benefit from an augmented insight into the drug release and percutaneous uptake kinetics. Our objective was to quantify the changes in transdermal fentanyl uptake with regards to the patient’s age and the anatomical location where the patch was placed. We also explored to which extent the drug flux from the patch could be altered by miniaturizing the contact surface area of the patch reservoir with the skin. To this end, we used validated mechanistic modeling of fentanyl diffusion, storage, and partitioning in the epidermis to quantify drug release from the patch and the uptake within the skin. A superior spatiotemporal resolution compared to experimental methods enabled in-silico identification of peak concentrations and fluxes, and the amount of stored drug and bioavailability. The patients’ drug uptake showed a 36% difference between different anatomical locations after 72 h, but there was a strong interpatient variability. With aging, the drug uptake from the transdermal patch became slower and less potent. A 70-year-old patient received 26% less drug over the 72-h application period, compared to an 18-year-old patient. Additionally, a novel concept of using micron-sized drug reservoirs was explored in silico. These reservoirs induced a much higher local flux (µg cm-2 h-1) than conventional patches. Up to a 200-fold increase in the drug flux was obtained from these small reservoirs. This effect was mainly caused by transverse diffusion in the stratum corneum, which is not relevant for much larger conventional patches. These micron-sized drug reservoirs open new ways to individualize reservoir design and thus transdermal therapy. Such computer-aided engineering tools also have great potential for in-silico design and precise control of drug delivery systems. Here, the validated mechanistic models can serve as a key building block for developing digital twins for transdermal drug delivery systems.

Background After the failure of clarithromycin- and bismuth-based quadruple therapy (CBQT), levofloxacin- and bismuth-based quadruple therapy (LBQT) is recommended for Helicobacter pylori eradication. We compared the efficacies of second-line tailored bismuth-based quadruple therapy (TBQT) and empirical LBQT. Methods Patients with CBQT failure were randomly assigned to receive TBQT or LBQT for 14 days. All patients underwent endoscopy for culture-based antibiotic susceptibility testing. Patients in the TBQT group exhibiting levofloxacin susceptibility were randomized to receive amoxicillin, levofloxacin, esomeprazole, and colloidal bismuth pectin (ALEB) or amoxicillin, furazolidone, esomeprazole, and colloidal bismuth pectin (AFEB) for 14 days; patients with levofloxacin resistance received AFEB. Results From May 2016 to June 2019, 364 subjects were enrolled. Eradication rates were significantly higher in the TBQT group (n = 182) than in the LBQT group (n = 182) according to both intention-to-treat (ITT) analysis (89.6% vs. 64.8%, P Conclusions TBQT was more effective than LBQT as a second-line strategy after CBQT failure. In the absence of antibiotic susceptibility testing, AFEB therapy might be used as a rescue therapy to eradicate H. pylori and avoid levofloxacin resistance. Trial registration: Chinese Clinical Trial Registry (www.chictr.org.cn): ChiCTR1900027743.

Inhibition of platelet function by means of dual antiplatelet therapy (DAPT) is the cornerstone of treatment of acute coronary syndrome (ACS). While preventing ischemic recurrences, inhibition of platelet function is clearly associated with an increased bleeding risk, a feared complication that may lead to significant morbidity and mortality. Since bleeding risk management is intrinsically associated with therapeutic adjustments undertaken during the whole clinical history of patients with acute coronary syndrome, single decisions taken from the very first day to years of follow-up might be decisive. This review aims at providing a clinically oriented, patient-tailored approach in reducing the risk and manage bleeding complications in ACS patients treated with DAPT. The steps in clinical decision making from the day of ACS to follow-up are analyzed. New treatment strategies to enhance the safety of DAPT are also described.

The central paradigm of novel therapeutic approaches in cancer therapy is identifying and targeting molecular biomarkers. One such target is the nuclear DNA repair enzyme Poly-(ADP ribose) polymerase 1 (PARP1). Sensitivity to PARP inhibition in certain cancers such as gBRCAmut breast and ovarian cancers has led to its exploitation as a target. The overexpression of PARP1 in several types of cancer further evoked interest in its use as an imaging target. While PARP1-targeted inhibitors have fast developed and approved in this past decade, determination of PARP1 expression might help to predict the response to PARP inhibitor treatment. This has the potential of improving prognosis and moving towards tailored therapy options and/or dosages. This review summarizes the recent pre-clinical advancements in imaging and theranostic PARP1 targeted tracers. To assess PARP1 levels, several imaging probes with fluorescent or beta/gamma emitting radionuclides have been proposed and three have advanced to ongoing clinical evaluation. Apart from its diagnostic value in detection of primary tumors as well as metastases, this shall also help in delivering therapeutic radionuclides to PARP1 overexpressing tumors. Henceforth nuclear medicine has now advanced towards conjugating theranostic radionuclides to PARP1 inhibitors. This paves the way for a future of PARP1-targeted theranostics and personalized therapy.

Dual antiplatelet therapy (DAPT) after percutaneous coronary intervention has become the standard of care, particularly in patients with acute coronary syndrome (ACS). Current clinical guidelines recommend novel P2Y12 inhibitors (e.g., prasugrel or ticagrelor) in addition to aspirin based on the results of representative randomized controlled trials conducted predominantly in Western countries. These agents were superior to clopidogrel in reducing the composite ischemic events, with a trade-off of the increased bleeding events. However, multiple differences exist between East Asian and Western patients, especially with respect to their physique, thrombogenicity, hemorrhagic diathesis, and on-treatment platelet reactivity. Recent studies from East Asian countries (e.g., Japan or South Korea) have consistently demonstrated that use of novel P2Y12 inhibitors is associated with a higher risk of bleeding events than use of clopidogrel, despite borderline statistical difference in the incidence of composite ischemic events. Additionally, multiple studies have shown that the optimal duration of DAPT may be shorter in East Asian than Western patients. This review summarizes clinical studies of antithrombotic strategies in East Asian patients with ACS. Understanding these differences in antithrombotic strategies including DAPT and their impacts on clinical outcomes will aid in selection of the optimal tailored antithrombotic therapy for patients with ACS.

Introduction: Colorectal cancer (CRC) is one of the leading cancers in terms of incidence and mortality, rate requiring a multidisciplinary approach. The discovery of specific CRC biomarkers has caused a paradigm shift in its clinical management. Areas covered: The aim is to illustrate the possible clinical applications of CRC biomarkers through an updated literature review (from 2015 to 2020) based on the PubMed database. A relationship between cancer localization and genetic profile has been identified. Nowadays, the tumor markers are largely used to select patients that could really benefit from a specific type of adjuvant therapy, in order to optimize treatment programs, especially in metastatic patients. This review highlights both CRC biomarkers’ advantages and critical issues. Expert opinion: New biomarker discoveries allow to set noninvasive tests that could increase patient’s compliance with therapy. They also permit a cost-effective early diagnosis, as well as patient-tailored treatments, improving the overall survival. The CRC biomarkers could also have a prognostic value, and usually, they are included in follow-up programs. However, despite the continuous progression of new technologies, their clinical validation is still debated. In this context, additional clinical studies are still necessary to identify, among potential markers, the most effective ones.

The combination of atrial fibrillation (AF) and acute coronary syndrome (ACS) is a complex situation in which a three-dimensional risk—cardioembolic, coronary, and hemorrhagic—has to be carefully managed. Triple antithrombotic therapy (TAT) is burdened with a high risk of serious bleeding, while dual antithrombotic therapy with an anticoagulant (DAT) likely provides only suboptimal coronary protection early after stent implantation. Moreover, TAT precludes the advantages provided by the use of the latest and more potent P2Y12 inhibitors in ACS patients. Here, we aimed to simulate and compare the expected coronary, cardioembolic, and hemorrhagic outcomes offered by DAT, TAT, or modern dual antiplatelet therapy (DAPT) with aspirin plus one of the latest P2Y12 inhibitors in AF patients early after an ACS. The comparison of numbers needed to treat to prevent major adverse events with the various antithrombotic regimens suggests that AF–ACS patients at high ischemic and hemorrhagic risk and at moderately low embolic risk (CHA2DS2VASc score 2–4) might safely withhold anticoagulation after revascularization for one month taking advantage of a modern DAPT, with a favorable risk-to-benefit ratio. In conclusion, this strategy, not sufficiently addressed in recent European and North American guidelines or consensus documents, adds to the spectrum of treatment options in these difficult patients; it might be the best choice in a substantial number of patients; and should be prospectively tested in a randomized controlled trial.

In detection, treatment, and follow-up, male breast cancer has historically lagged behind female breast cancer. On the whole, breast cancer is less common among men than among women, limiting utility of screening, yet the incidence of male breast cancer is rising, and there are men at high risk for breast cancer. While women at high risk for breast cancer are well characterized, with clearly established guidelines for screening, supplemental screening, risk prevention, counseling, and advocacy, men at high risk for breast cancer are poorly identified and represent a blind spot in public health. Today, more standardized genetic counseling and wider availability of genetic testing are allowing identification of high-risk male relatives of women with breast cancer, as well as men with genetic mutations predisposing to breast cancer. This could provide a new opportunity to update our approach to male breast cancer. This article reviews male breast cancer demographics, risk factors, tumor biology, and oncogenetics; recognizes how male breast cancer differs from its female counterpart; highlights its diagnostic challenges; discusses the implications of the widening clinical use of multigene panel testing; outlines current National Comprehensive Cancer Network guidelines (version 1, 2018) for high-risk men; and explores the possible utility of targeted screening and surveillance. Understanding the current state of male breast cancer management and its challenges is important to shape future considerations for care. Shifting the paradigm of male breast cancer detection toward targeted precision medicine may be the answer to improving clinical outcomes of this uncommon disease.

Aim: We develop a subgroup selection procedure using both prognostic and predictive biomarkers to identify four patient subpopulations: low- and high-risk responders, and low- and high-risk nonresponders. Methods: We utilize three regression models to identify three sets of biomarkers: S, prognostic biomarkers; T, predictive biomarkers; and U, prognostic and predictive biomarkers. The prognostic signature C(S) combines with a predictive signature, either C(T) or C(U), to develop two procedures C(S,T) and C(S,U) for identification of four subgroups. Results: Simulation experiment showed that proposed models for identifying the biomarker sets S and U performed well, as did the procedure C(S,U) for subgroup identification. Conclusion: The proposed model provides more comprehensive characterization of patient subpopulations, and better accuracy in patient treatment assignment.

Patients with estrogen receptor (ER)‐positive breast cancer are less likely to achieve a pathological complete response (pCR) with neoadjuvant chemotherapy. Neoadjuvant endocrine therapy may be more appropriate than neoadjuvant chemotherapy in these hormone‐sensitive patients. Most patients with ER‐positive breast cancer are postmenopausal, and therefore, generally older and less able to tolerate chemotherapy. We aimed to investigate the efficacy and safety of tailored neoadjuvant endocrine and chemoendocrine therapy for postmenopausal breast cancer patients. Untreated patients with primary invasive ER‐positive, HER2‐negative, stage I‐IIIA breast cancer, and Ki67 index ≤30% were enrolled. Patients received exemestane 25 mg/d for 12 weeks. Based on clinical response and change in Ki67 index, assessed at 8‐12 weeks, patients with complete response (CR), partial response (PR) with Ki67 index ≤5% after treatment, or stable disease (SD) with Ki67 index ≤5% before and after treatment were defined as responders. For the subsequent 24 weeks, responders continued exemestane monotherapy (group A), and nonresponders received exemestane 25 mg/d plus cyclophosphamide 50 mg/d (group B). The primary endpoint was clinical response at weeks 24 and 36. A total of 59 patients (median age, 69 years) started initial exemestane monotherapy. After exclusion of three patients who discontinued during this period, 56 remained enrolled to receive subsequent treatment. Clinical response rates (CR and PR) and 95% CI at weeks 24 and 36 were 85% (12/14; 57.2%‐98.2%) and 71% (10/14; 41.9%‐91.6%), respectively, in group A; and 54% (23/42; 38.7%‐70.2%) and 71% (30/42; 55.4%‐84.3%), respectively, in group B. At week 36, no significant difference was found in median Ki67 index between the groups (3.5% and 4.0%). There were no treatment‐related deaths. We found that clinical response comparable to that of responders was achieved in nonresponders after addition of cyclophosphamide to the initial endocrine therapy.

Background The incidence of post-surgical chronic pain ranges between 20% and 40% in Europe. Osteoarthritis pain after prosthesis implantation is one of the most severe secondary syndromes, depending not only on surgery but also on organic changes before and after joints replacement. No data are available about risk factors. An excessive inflammatory response plays a central role but a best therapy is not defined yet. It is not clear whether opioid administration could influence post-surgical pain and lead to tolerance or addiction. Interestingly, the immune system, together with the nervous and peptidergic ones, is involved in hypersensibility. The connection across the three biological systems lies in the presence of opioid receptors on immune cells surface. Here, we show a method to analyze whether opioids could modulate lymphocytes, by proposing opioid receptors as biological markers to prevent chronic pain and opioid tolerance or addiction after hip surgery. Methods/design After institutional independent ethics committee approval, 60 patients, in pain and undergoing hip surgery, will be enrolled in a single-blind, randomized, phase IV, pilot study. Pain treatment will be selected inside a class of non-steroidal anti-inflammatory drugs (NAISDs) or paracetamol or a class of opioids, into three medication arms: 25 mg tapentadol twice daily; 75 mg tapentadol twice daily; NSAIDs or paracetamol in accordance with surgeon’s custom. For each group, we will collect blood samples before, during and after surgery, to apply molecular analysis. We will perform lymphocyte opioid receptors genes and proteins expression and functional analysis. Data will be statistically analyzed. Discussion This project has the potential to obtain a personalized diagnostic kit, by considering lymphocyte opioid receptors as biological markers. Starting from a simple blood sample, it will be possible to decide the best therapy for a single patient. Using a noninvasive approach, we expect to fix a daily standard dose and timing, before and after surgery, to bypass hip chronic pain and the insurgence of tolerance or addiction. The analysis of opioid receptors sensitivity will help to identify the best drug administration in each specific case (tailored therapy). Trial registration ISRCTN, ISRCTN12559751. Retrospectively registered on 23 May 2017. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2363-z) contains supplementary material, which is available to authorized users.

Acute lymphoblastic leukaemia (ALL) is the most common paediatric malignancy. Despite the fact that the outcome of treatment of ALL in children has improved in the last decades, still as many as 20% of children will undergo treatment failure. Over the last years, there have been great efforts to characterize the genetic alterations of leukaemic cells, which could affect the clinical course of the disease and become new markers that may be targeted with novel therapies. Genomic profiling and sequencing studies have not only identified new subtypes of ALL (e.g. Philadelphia chromosome-like ALL, early T-cell precursor ALL) but also helped to understand the genetic basis of leukaemogenesis and predict treatment failure. Those efforts contributed not only to better risk stratification of children with ALL, but also to development of new tailored therapeutic strategies. So far, improvements in survival of children with Ph + ALL (Philadelphia positive ALL) have been demonstrated due to combination of intensive chemotherapy with tyrosine kinase (TK) inhibitor (imatinib). There are also some pre- and clinical testing of other inhibitors (TK, FLT3, PI3K/mTOR, MEK) and specific antibodies (CD19 and CD22). Widespread use of modern diagnostic techniques at the early stage of the disease would enable rapid identification of children with a high-risk leukaemia and use of more intensive and tailored therapy.

The main problem of Helicobacter pylori (H. pylori) infection management is linked to antibiotic resistances. This phenomenon has grown in the last decade, inducing a dramatic decline in conventional regimen effectiveness. The causes of resistance are point mutations in bacterial DNA, which interfere with antibiotic mechanism of action, especially clarithromycin and levofloxacin. Therefore, international guidelines have recently discouraged their use in areas with a relevant resistance percentage, suggesting first-line schedules with expected high eradication rates, i.e., bismuth containing or non-bismuth quadruple therapies. These regimens require the daily assumption of a large number of tablets. Consequently, a complete adherence is expected only in subjects who may be motivated by the presence of major disorders. However, an incomplete adherence to antibiotic therapies may lead to resistance onset, since sub-inhibitory concentrations could stimulate the selection of resistant mutants. Of note, a recent meta-analysis suggests that susceptibility tests may be more useful for the choice of first than second-line or rescue treatment. Additionally, susceptibility guided therapy has been demonstrated to be highly effective and superior to empiric treatments by both meta-analyses and recent clinical studies. Conventional susceptibility test is represented by culture and antibiogram. However, the method is not available everywhere mainly for methodology-related factors and fails to detect hetero-resistances. Polymerase chain reaction (PCR)-based, culture-free techniques on gastric biopsy samples are accurate in finding even minimal traces of genotypic resistant strains and hetero-resistant status by the identification of specific point mutations. The need for an invasive endoscopic procedure has been the most important limit to their spread. A further step has, moreover, been the detection of point mutations in bacterial DNA fecal samples. Few studies on clarithromycin susceptibility have shown an overall high sensitivity and specificity when compared with culture or PCR on gastric biopsies. On these bases, two commercial tests are now available although they have shown some controversial findings. A novel PCR method showed a full concordance between tissue and stool results in a preliminary experience. In conclusion, despite poor validation, there is increasing evidence of a potential availability of noninvasive investigations able to detect H. pylori resistances to antibiotics. These kinds of analysis are currently at a very early phase of development and caution should be paid about their clinical application. Only further studies aimed to evaluate their sensitivity and specificity will afford novel data for solid considerations. Nevertheless, noninvasive molecular tests may improve patient compliance, time/cost of infection management and therapeutic outcome. Moreover, the potential risk of a future increase of resistance to quadruple regimens as a consequence of their use on large scale and incomplete patient adherence could be avoided.

Functional mitral regurgitation is a debilitating condition, related to worsening of functional capacity and heart failure symptomatology. Cardioband (Valtech Cardio, Or Yehuda, Israel) is a novel technology designed for transcatheter repair of the mitral valve in the treatment of functional MR. Areas covered: A brief summary to direct the reader to important further reading, relevant websites; www.valtechcardio.com . An article about this device, relevant websites; www.ncbi.nlm.nih.gov/pubmed using search word 'Cardioband'. Expert commentary: This device has been designed to be completely implantable percutaneously in a closed beating heart fashion. The adjustability features under the beating heart and guided by echocardiography allow to provide a tailored therapy to each particular mitral valve and regurgitation condition.

The improved knowledge of pathogenetic mechanisms underlying lymphomagenesis and the discovery of the critical role of tumor microenvironments have enabled the design of new drugs against cell targets and pathways. The Food and Drug Administration (FDA) has approved several monoclonal antibodies (mAbs) and small molecule inhibitors (SMIs) for targeted therapy in hematology. This review focuses on the efficacy results of the currently available targeted agents and recaps the main ongoing trials in the setting of mature B-Cell non-Hodgkin lymphomas. The objective is to summarize the different classes of novel agents approved for mature B-cell lymphomas, to describe in synoptic tables the results they achieved and, finally, to draw future scenarios as we glimpse through the ongoing clinical trials. Characteristics and therapeutic efficacy are summarized for the currently approved mAbs [i.e., anti-Cluster of differentiation (CD) mAbs, immune checkpoint inhibitors, chimeric antigen receptor (CAR) T-cell therapy, and bispecific antibodies] as well as for SMIs i.e., inhibitors of B-cell receptor signaling, proteasome, mTOR BCL-2 HDAC pathways. The biological disease profiling of B-cell lymphoma subtypes may foster the discovery of innovative drug strategies for improving survival outcome in lymphoid neoplasms, as well as the trade-offs between efficacy and toxicity. The hope for clinical advantages should carefully be coupled with mindful awareness of the potential pitfalls and the occurrence of uneven, sometimes severe, toxicities.

Background Current recommendations on the treatment of Rheumatoid Arthritis (RA) are based on a treat to target approach, nevertheless which biologic drug should be used in an unresponsive patient is not clarified (1). Such a strategy is essentially justified by the fact that no biotechnological drug has proved to be superior to any other (2). Recent studies have reported some disease or patient features that are associated with a greater or lesser likelihood of response (3). Nevertheless, an adapted therapy to the single patient and based on physiopathological mechanisms has not been acquired yet. Objectives Aim of this study was to evaluate if the choice of a tailored therapy, based on patient and disease features, would be an effective strategy. Methods From April 1st 2017, at our Department of Rheumatology of the University of Campania, each patient with RA has been characterized, at enrolment, for demographic and disease features, and started a biological Disease-modifying antirheumatic drug based on an established algorithm (Figure 1). Attainment of the targeted end point i.e. remission (R) as assessed by Simplified Disease Activity Index (SDAI) Results Forty-nine patients were admitted to our centre from April 1st2017 to December 31st2018. Out of them, 36 patients have been followed up at least for 3 months and were included in the study (algorithm+ patients). Out of them, 26 (72.2%) reached 6 months of treatment, while 16 (44.4%) 12 months of treatment. Among the 26 patients evaluated at 6 months, 23(88.5%) achieved the targeted end point. At 12 months, 16/16 patients (100%) preserved a status of remission or at least low disease activity. We compared our results to those registered, from January 2015 to September 2016, in a RA cohort of 79 patients (RA general cohort). We found a significant difference in regard to attainment of the target at 6 months (23/26 patients, 88.5% algorithm+ vs 45/67 patients, 67.2% RA general cohort; p=0.04) and at 12 months (16/16 patients, 100% algorithm+ vs 40/57 patients, 70.2% RA general cohort; p=0.01) (Table 1). Notably, 32 out of the 79 patients had undergone a biological drug which didn’t follow the predefined algorithm. These patients (algorithm- patients) presented a further lower incidence of response with regard to those enrolled according to the algorithm: 22/32 patients (68.7%) at 3 months; p=0.4; 17/29 (58.6%) at 6 months; p=0.001; 17/24 (70.8%) at 12 months; p=0.03). Conclusion The choice of a personalized approach toward treatment of RA might be an effective strategy to achieve the targeted end point of remission or at least low disease activity in every patient. References [1] Smolen JS et al. Ann Rheum Dis 2017;76:960–77 [2] Pierreisnard A et al. Joint Bone Spine. 2013;80:386-92. [3] Daien CI et al. Mediators of Inflammation 2014;2014:386148 Disclosure of Interests DANIELA IACONO Speakers bureau: PFIZER company, Ilenia Pantano: None declared, SERENA FASANO: None declared, GIUSEPPE SCALISE: None declared, Francesco Ciccia Grant/research support from: CELGENE, PFIZER, Consultant for: UCB, NOVARTIS, CELGENE, PFIZER, LILLY, Paid instructor for: UCB, NOVARTIS, CELGENE, PFIZER, LILLY, JANSSEN, Speakers bureau: UCB, NOVARTIS, CELGENE, PFIZER, LILLY, JANSSEN, MSD, ROCHE, AMGEN

In the acute myeloid leukemia (AML) setting, research has extensively investigated the existence and relevance of molecular biomarkers, in order to better tailor therapy with newly developed agents and hence improve outcomes and/or save the patient from poorly effective therapies. In particular, in patients with AML, residual disease after therapy does reflect the sum of the contributions of all factors associated with diagnosis and post-diagnosis resistance. The evaluation of minimal/measurable residual disease (MRD) can be considered as a key tool to guide patient’s management and a promising endpoint for clinical trials. In this narrative review, we discuss MRD evaluation as biomarker for tailored therapy in AML patients; we briefly report current evidence on the use of MRD in clinical practice, and comment on the potential ability of MRD in the assessment of the efficacy of new molecules.

Obstructive Sleep Apnoea (OSA) is a common sleep disorder that is associated with daytime symptoms and a range of comorbidity and mortality. Continuous Positive Airway Pressure (CPAP) therapy is highly efficacious at preventing OSA when in use and has long been the standard treatment for newly diagnosed patients. However, CPAP therapy has well recognised limitations in real world effectiveness due to issues with patient acceptance and suboptimal usage. There is a clear need to enhance OSA treatment strategies and options. Although there are a range of alternative treatments (e.g. weight loss, oral appliances, positional devices, surgery, and emerging therapies such as sedatives and oxygen), generally there are individual differences in efficacy and often OSA will not be completely eliminated. There is increasing recognition that OSA is a heterogeneous disorder in terms of risk factors, clinical presentation, pathophysiology and comorbidity. Better characterisation of OSA heterogeneity will enable tailored approaches to therapy to ensure treatment effectiveness. Tools to elucidate individual anatomical and pathophysiological phenotypes in clinical practice are receiving attention. Additionally, recognising patient preferences, treatment enhancement strategies and broader assessment of treatment effectiveness are part of tailoring therapy at the individual level. This review provides a narrative of current treatment approaches and limitations and the future potential for individual tailoring to enhance treatment effectiveness.

Note Benign vascular lesions of bone are relatively common and occur most frequent as an asymptomatic incidental finding in the skull or spine. Primary malignant vascular tumors of bone are rare. They represent less than 1% of primary malignant bone tumors reported by the Netherlands Committee on Bone Tumors and 0,5% of those registered at the Mayo Clinic. Clinically they are extremely aggressive and have a very poor prognosis. Survival rates are unknown, but in those cases reported patients die very soon after diagnosis due to wide spread metastasis and lack of tailored therapy.

Bismuth-containing quadruple treatment (BQT) and concomitant treatment (CT) were recommended as alternative first-line treatments of Helicobacter pylori (H. Pylori). A meta-analysis was performed to evaluate the cure rates and compare efficacy and safety of BQT and CT for H. Pylori eradication. PubMed, Cochrane Library, and Embase databases were searched on June 16, 2020. Meta-analysis, sensitivity analysis, and subgroup analysis were conducted by Review Manager 5.3 and Stata 11.0. Ten studies were collected. We found no difference of cure rate between BQT and CT in intention-to-treat (ITT) analysis (84.6% vs. 82.9%, OR = 1.14, 95% CI: 0.94–1.38; P = 0.19) and marginally statistical difference in per-protocol (PP) analysis (92.4% vs 90.1%, OR = 1.32, 95% CI: 1.00–1.73; P = 0.05). Based on the results of subgroup analyses, we found statistical difference of eradication rate between BQT and CT (amoxicillin + clarithromycin + metronidazole + PPI treatment) according to PP analysis (94.3% vs. 91.5%, OR = 1.49, 95% CI:1.03–2.15; P = 0.03) and marginally statistical difference according to ITT analysis (87.5% vs. 84.6%, OR = 1.28, 95% CI:1.00–1.65; P = 0.05). BQT and CT may be both good treatment options for H. pylori infection. However, BQT was superior to current scheme of CT (amoxicillin + clarithromycin + metronidazole + PPI treatment) in subgroup analysis. It is very necessary to choose tailored therapy as an outstanding way to reduce the impact of antibiotic.

Pretreatment characteristics are suggested as predictive and/or prognostic factors for nasopharyngeal carcinoma (NPC); however, individual tumor radiosensitivities have previously not been considered. As boost planning is recommended for NPC, we performed interim assessments of magnetic resonance (MR) images for boost planning and retrospectively evaluated their predictive value for the survival of NPC patients. Radiation therapy via elective nodal irradiation (median dose: 39.6 Gy) with/without chemotherapy was used to treat 63 NPC patients. Boost irradiation (median total dose: 70 Gy) was performed based on the interim assessment. The largest lymph node (LN) was measured on MR images acquired at the time of interim assessment. The site of first failure was local in 8 (12.7%), regional in 7 (11.1%), and distant in 12 patients (19.0%). All 7 patients with regional failure harbored LNs ≥15 mm at interim assessment. We divided the 63 patients into two groups based on LN size [large (≥15 mm), n = 10 and small (

Valvular heart disease may be a pre-existing complication of pregnancy or it may be diagnosed for the first time during pregnancy. Accurate diagnosis, tailored therapy and an understanding of the physiology and pathophysiology of pregnancy are necessary components of management, best achieved through the use of multidisciplinary clinics. This review outlines the management of specific lesions, with particular reference to post-rheumatic valvular heart disease.

Remarkable progress has been made in the last decade in understanding the biology and oncogenesis of this relatively rare childhood brain tumor-the ependymoma. Surgery and irradiation are the mainstays of therapeutic options; chemotherapy is yet to predictably affect outcome, and its role is currently being explored in several clinical trials. While WHO scores this tumor into three grades, grading of ependymoma into grade II and grade III is controversial because of its elusive histological criteria where no cut-offs have been defined for mitoses or percentage of tumor depicting increased cellularity. Grading remains unreliable in predicting outcome in several instances. There is a compelling need to integrate the molecular biomarkers highlighted in several studies over the past decade into patient risk stratification to help in better predicting the clinical outcome and to design effective tailored therapy. Genomic and transcriptomic studies lately have defined distinct molecular subgroups within ependymoma arising at three anatomic compartments-supratentorial, posterior fossa, and spinal cord. Review of pertinent literature on several seminal studies that have established a paradigm shift in understanding the oncogenesis of ependymoma has been carried out. The outcome, impact, and clinical relevance of these studies are also discussed. The review provides an update on progress and recent advances in understanding the biology and oncogenesis of ependymoma. The establishment of robust subgroups which are demographically, clinically, and molecularly distinct will provide new avenues for further refinement of therapeutic strategies.

There is significant intertumoral heterogeneity within the four molecular subgroups of medulloblastoma. In this issue of Cancer Cell, Cavalli et al. apply similarity network fusion to gene expression and DNA methylation data to identify 12 medulloblastoma subtypes with distinct molecular and clinical profiles, making an important step toward molecularly tailored therapy.

Treatment for medulloblastoma carries significant risks, particularly in resource-constrained settings. We report a case of a Mexican infant with desmoplastic/nodular medulloblastoma. Given the nature of her tumor, we developed a tailored regimen following subtotal resection to avoid both radiation therapy and the high-dose cisplatin therapy offered at most centers in the United States. The patient is in remission 4 years after the initial diagnosis. This case suggests an alternative treatment plan for this particular tumor variant that accommodates the limited resources of many centers around the world and avoids the risks associated with radiation therapy at a young age.

Brain tumors constitute the largest source of oncologic mortality in children and low-grade gliomas are among most common pediatric central nervous system tumors. Pediatric low-grade gliomas differ from their counterparts in the adult population in their histopathology, genetics, and standard of care. Over the past decade, an increasingly detailed understanding of the molecular and genetic characteristics of pediatric brain tumors led to tailored therapy directed by integrated phenotypic and genotypic parameters and the availability of an increasing array of molecular-directed therapies. Advances in neuroimaging, conformal radiation therapy, and conventional chemotherapy further improved treatment outcomes. This article reviews the current classification of pediatric low-grade gliomas, their histopathologic and radiographic features, state-of-the-art surgical and adjuvant therapies, and emerging therapies currently under study in clinical trials.

Background Over the last decade, the intra-coronary imaging (ICI) has emerged to guide percutaneous coronary intervention (PCI), thus overcoming the limitations of "luminology" offered by angiography. Methods In this review, we aim at purely focusing on the clinical implications of the employment of ICI in the routine practice, thus providing suggestions for future applications. In particular, we will describe the principal contributions and implications of ICI in the following different clinical settings: 1) assessment of clinical and imaging outcomes of PCI; 2) guiding PCI before and after stent implantation; 3) identification of mechanisms of stent failure. Results Several studies showed the capability of ICI in assessing the clinical and imaging outcomes of PCI. In particular, they have compared the ICI-guided PCI with the angiography-guided procedures, emphasizing the advantages of using imaging. Indeed, ICI can characterize the coronary plaque, provide a precise estimation of the coronary stenosis, select the appropriate method of intervention, and optimize stent deployment and lesion coverage. Finally, ICI has been shown to be useful to point out the mechanisms of stent failure. Conclusions. ICI can facilitate decision-making in patients with unclear angiographic findings, guide-selected interventions and optimize the final PCI results in complex lesions or. in high-risk patients. Finally, by the identification of specific mechanisms of stent failure, the ICI can allow to adopt a tailored therapy for the singles cases.

The mortality associated with invasive candidiasis remains unacceptably high. The T2 magnetic resonance (T2MR) assay is a novel US FDA-approved molecular diagnostic assay for the diagnosis of candidemia that can rapidly detect the five most commonly isolated Candida spp. In clinical trials, T2MR has exhibited good clinical sensitivity and specificity. Potential benefits from the adoption of T2MR technology in the diagnostic and therapeutic algorithms for invasive candidiasis can arise from timely diagnosis of disease, increased case detection, tailored therapy and decrease in empiric antifungal treatment. As everyday clinical experience with the assay is evolving, we discuss the utility of T2MR in invasive candidiasis with and without candidemia based on the currently available evidence regarding its performance.

Background: The World Health Organization (WHO) and the American Joint Cancer Committee (AJCC) modified the grading of pancreatic neuroendocrine neoplasms from a three-tier (WHO-AJCC 2010) to a four-tier system by introducing the novel category of NET G3 (WHO-AJCC 2017). Objectives: This study aims at validating the WHO-AJCC 2017 and identifying the most effective grading system. Method: A total of 2,102 patients were enrolled; entry criteria were: (i) patient underwent surgery; (ii) at least 2 years of follow-up; (iii) observation time up to 2015. Data from 34 variables were collected; grading was assessed and compared for efficacy by statistical means including Kaplan-Meier method, Cox regression analysis, Harrell’s C statistics, and Royston’s explained variation in univariable and multivariable analyses. Results: In descriptive analysis, the two grading systems demonstrated statistically significant differences for the major category sex but not for age groups. In Cox regression analysis, both grading systems showed statistically significant differences between grades for OS and EFS; however, no statistically significant difference was observed between the two G3 classes of WHO-AJCC 2017. In multivariable analysis for the two models fitted to compare efficacy, the two grading systems performed equally well with substantially similar optimal discrimination and well-explained variation for both OS and EFS. The WHO-AJCC 2017 grading system retained statistically significant difference between the two G3 classes for OS but not for EFS. Conclusions: The WHO-AJCC 2017 grading system is at least equally performing as the WHO-AJCC 2010 but allows the successful identification of the most aggressive PanNET subgroup. Grading is confirmed as probably the most powerful tool for predicting patient survival.