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The treatment of complex aortic pathologies requires specialized techniques and tailored approaches due to each patient's unique anatomical and clinical challenges. The European Association for Cardiothoracic Surgery (EACTS) and the Society of Thoracic Surgeons (STS) new guidelines identify the aorta as the body's 24th organ and reiterate that multidisciplinary aortic teams are recommended for shared decision-making to determine optimal treatment strategies. Patients treated for conditions such as aneurysms, dissections, intramural hematomas, or penetrating aortic ulcers may develop complex forms over time, necessitating careful follow-up and timely corrective actions. Endovascular solutions can be favorable for older patients with complex anatomies and multiple comorbidities. However, when endovascular treatment is not feasible, hybrid treatments or open surgery must be considered if the patient's condition allows it. The risk–benefit ratio of each procedure must be carefully evaluated; choosing the best intervention or deciding not to intervene becomes a critical and challenging decision. At our Cardiac Surgery Center in Verona, a multidisciplinary team with over 20 years of experience in treating complex aortic arch pathologies extensively discussed different cases of complex aortic pathologies treated with endovascular, hybrid, or surgical approaches, emphasizing the importance of considering both anatomical and patient-specific characteristics. The decisions and treatments were often challenging, and unanimity was not always achieved, reflecting the complexity of finding the best solutions. [ABSTRACT FROM AUTHOR]

Non-bacterial thrombotic endocarditis (NBTE) is a form of non-infective endocarditis characterized by the deposition of sterile fibrin and platelets on cardiac valves. Even though some studies have identified important pathophysiological features, many aspects remain poorly understood. Given its wide availability, transthoracic echocardiography is typically the initial diagnostic approach to the patient. Additionally, recent technological advancements in transesophageal echocardiography, such as three-dimensional and multiplanar reconstruction analysis, have significantly improved diagnostic accuracy over time. By presenting our case series and performing a literature review, we focused on the main pathophysiologic, diagnostic, and therapeutic aspects of this rare but potentially life-threatening disease. [ABSTRACT FROM AUTHOR]

Proliferative vitreoretinopathy (PVR) has traditionally been managed with vitreoretinal surgery. Although there have been several recent innovations in this surgery to make the retinal approach as uninvasive as possible, the outcomes remain unsatisfactory. Significant complications remain and the complexity of the surgical approach is challenging. The focus of this review was to investigate and discuss the effectiveness of nanomedicine, featuring a wide range of drugs and molecules, as a novel potential treatment for PVR. To date, ocular drug delivery remains a significant issue due to the physiological and anatomical barriers, dynamic or static, which prevent the entry of exogenous molecules. We tried to summarize the nanotechnology-based ophthalmic drugs and new nanoparticles currently under research, with the intention of tackling the onset and development of PVR. The purpose of this review was to thoroughly and analytically examine and assess the potential of nano-based techniques as innovative strategies to treat proliferative vitreoretinopathy (PVR). This study aimed to emphasize the breakthroughs in nanomedicine that provide promising therapeutic options to enhance the results of vitreoretinal surgery and halt disease progression, considering the complexity and difficulty of PVR treatment. The future directions of the nanoparticles and nanotherapies applied to PVR highlight the importance of investing in the development of better designs and novel ophthalmic formulations in order to accomplish a mini-invasive ocular approach, replacing the standard-of-care vitreoretinal surgery. [ABSTRACT FROM AUTHOR]

Transcatheter aortic valve implantation (TAVI) now represents the mainstay of treatment for severe aortic stenosis. Owing to its exceptional procedural efficacy and safety, TAVI has been extended to include patients at lower surgical risk, thus now encompassing a diverse patient population receiving this treatment. Yet, long-term outcomes also depend on optimal medical therapy for secondary vascular prevention, with antithrombotic therapy serving as the cornerstone. Leveraging data from multiple randomized controlled trials, the current guidelines generally recommend single antithrombotic therapy, with either single antiplatelet therapy (SAPT) or oral anticoagulation (OAC) alone in those patients without or with atrial fibrillation, respectively. Yet, individualization of this pattern, as well as specific case uses, may be needed based on individual patient characteristics and concurrent procedures. This review aims to discuss the evidence supporting antithrombotic treatments in patients treated with TAVI, indications for a standardized treatment, as well as specific considerations for an individualized approach to treatment. [ABSTRACT FROM AUTHOR]

Background: The optimal duration of regimens for tailored therapy based on genotypic resistance for clarithromycin has yet to be established. Aim: This study was a nationwide, multicenter, randomized trial comparing empirical therapy with tailored therapy based on genotypic resistance for first‐line eradication of Helicobacter pylori. We also compared the eradication rates of 7‐ and 14‐day regimens for each group. Patients and Methods: Patients with H. pylori infection were first randomized to receive empirical or tailored therapy. Patients in each group were further randomized into 7‐ or 14‐day regimens. Empirical therapy consisted of a triple therapy (TT) regimen (twice‐daily doses of pantoprazole 40 mg, amoxicillin 1 g, and clarithromycin 500 mg) for 7 or 14 days. Tailored therapy consisted of TT of 7 or 14 days in patients without genotypic resistance. Patients with genotypic resistance were treated with bismuth quadruple therapy (BQT) regimens (twice‐daily doses of pantoprazole 40 mg, three daily doses of metronidazole 500 mg, and four times daily doses of bismuth 300 mg and tetracycline 500 mg) for 7 or 14 days. A 13C‐urea breath test assessed eradication rates. The primary outcome was eradication rates of each group. Results: A total of 593 patients were included in the study. The eradication rates were 65.7% (201/306) in the empirical therapy group and 81.9% (235/287) in the tailored therapy group for intention‐to‐treat analysis (p < 0.001). In the per‐protocol analysis, the eradication rates of the empirical therapy and tailored groups were 70.3% (201/286) and 85.5% (235/274) (p < 0.001), respectively. There was no difference in compliance between the two groups. The rate of adverse events was higher in the tailored group compared to the empirical group (p < 0.001). Discussion: Our study confirmed that tailored therapy based on genotypic resistance was more effective than empirical therapy for H. pylori eradication in Korea. However, no significant difference was found between 7‐ and 14‐day regimens for each group. Future studies are needed to determine the optimal duration of therapy for empirical and tailored therapy regimens. [ABSTRACT FROM AUTHOR]

Background: The systematic use of susceptibility testing and tailored first‐line treatment for Helicobacter pylori eradication has yet to be established. Aim: To compare 14‐day tailored PCR‐guided triple therapy to 14‐day non‐Bismuth concomitant quadruple therapy for first‐line Helicobacter pylori eradication. Patients and Methods: We performed a multicenter, parallel‐group, randomized noninferiority controlled trial. Naive adult patients with Helicobacter pylori infection were treated with 14‐day tailored PCR‐guided triple therapy (esomeprazole 40 mg and amoxicillin 1000 mg b.d. plus clarithromycin 500 mg or levofloxacin 500 mg b.d. according to clarithromycin susceptibility) or 14‐day non‐Bismuth concomitant quadruple therapy (esomeprazole 40 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and metronidazole 500 mg b.d.). The primary endpoint was H. pylori eradication. Results: We screened 991 patients for eligibility and randomized 241 patients. The first‐line eradication rate was 99.2% in the tailored PCR‐guided group and 95.9% in the control group (ITT population; absolute difference of +3.30%, with a lower bound of CI at −0.68%). Both first‐line therapies were well tolerated, with a formally significant difference in favor of the tailored PCR‐guided group (61.4% vs. 41.2%, p = 0.003). Economic analyses revealed a lower cost of the tailored PCR‐guided arm, with a 92% chance of being jointly more effective and less expensive than the control arm in the ITT population. Conclusion: In a country with a high level of clarithromycin resistance, the results of our study demonstrated the noninferiority of 14‐day tailored PCR‐guided triple therapy as a first‐line H. pylori eradication therapy compared to 14‐day non‐Bismuth quadruple therapy (ClinicalTrials.gov NCT02576236). [ABSTRACT FROM AUTHOR]

Proliferative vitreoretinopathy (PVR) has traditionally been managed with vitreoretinal surgery. Although there have been several recent innovations in this surgery to make the retinal approach as uninvasive as possible, the outcomes remain unsatisfactory. Significant complications remain and the complexity of the surgical approach is challenging. The focus of this review was to investigate and discuss the effectiveness of nanomedicine, featuring a wide range of drugs and molecules, as a novel potential treatment for PVR. To date, ocular drug delivery remains a significant issue due to the physiological and anatomical barriers, dynamic or static, which prevent the entry of exogenous molecules. We tried to summarize the nanotechnology-based ophthalmic drugs and new nanoparticles currently under research, with the intention of tackling the onset and development of PVR. The purpose of this review was to thoroughly and analytically examine and assess the potential of nano-based techniques as innovative strategies to treat proliferative vitreoretinopathy (PVR). This study aimed to emphasize the breakthroughs in nanomedicine that provide promising therapeutic options to enhance the results of vitreoretinal surgery and halt disease progression, considering the complexity and difficulty of PVR treatment. The future directions of the nanoparticles and nanotherapies applied to PVR highlight the importance of investing in the development of better designs and novel ophthalmic formulations in order to accomplish a mini-invasive ocular approach, replacing the standard-of-care vitreoretinal surgery.

Objectives: We aimed to explore the efficacy and safety of tailored therapy guided by genotypic resistance in the first‐line treatment of Helicobacter pylori (H. pylori) infection in treatment‐naive patients. Methods: Gastric mucosal specimens were taken during gastroscopy, and main mutations of clarithromycin‐ and levofloxacin‐resistant genes were detected by polymerase chain reaction (PCR). Sensitive antibiotics were selected individually for treating H. pylori infection with tailored bismuth‐containing quadruple therapy (BQT) consisting of esomeprazole 20 mg twice daily, bismuth potassium citrate 220 mg twice daily, amoxicillin 1 g twice daily, and clarithromycin 500 mg twice daily, or levofloxacin 500 mg once daily, or metronidazole 400 mg four times daily. Safety and patient compliance were assessed 1–3 days after eradication. Treatment outcome was evaluated by urea breath test 4–8 weeks after eradication. Results: One hundred and thirty‐two treatment‐naive patients with H. pylori infection were included. PCR results suggested resistance rates of 47.7% and 34.9% for clarithromycin and levofloxacin, respectively, and a dual resistance rate of 18.2%. Eradication rates of tailored BQT were 87.1% and 95.8% by intention‐to‐treat (ITT) analysis and per‐protocol (PP) analysis, respectively. There was no statistically significant difference in the efficacy of 7‐day clarithromycin‐containing, 7‐day levofloxacin‐containing, and 14‐day full‐dose metronidazole‐containing BQT (ITT analysis: P = 0.488; PP analysis: P = 0.833). The incidence of adverse events was 19.7%, and patient compliance was 97.7%. Conclusion: Tailored BQT guided by genotypic resistance can achieve satisfactory efficacy, safety, and patient compliance in the first‐line treatment of H. pylori infection. [ABSTRACT FROM AUTHOR]

Background and Aim: The prevalence of antibiotic resistance for Helicobacter pylori (H. pylori) has been increasing over the year, making it more difficult for traditional empirical therapy to successfully eradicate H. pylori. Thus, tailored therapy (TT) guided by molecular‐based antibiotic susceptibility testing (AST) has been frequently recommended. We conducted a single‐arm meta‐analysis to determine the efficacy of tailored therapy guided by molecular‐based AST. Methods: A systematic literature review was performed on multiple databases, and studies on molecular‐based TT were included. The eradication rates of TT by intention‐to‐treat (ITT) and per‐protocol (PP) analyses were pooled respectively. Results: A total of 35 studies from 31 literature (4626 patients) were included in the single‐arm meta‐analysis. Overall, the pooled eradication rate of TT was 86.9% (95% CI:84.7%–89.1%) by the ITT analysis, and 91.5% (95% CI:89.8%–93.2%) by PP analysis. The pooled eradication rates of first‐line TT and rescue TT were 86.6% and 85.1% by ITT analysis and 92.0% and 87.9% by PP analysis, respectively. When tailored rescue therapy was based on the genotypic resistance to at least four antibiotics, the pooled eradication rates reached 89.4% by ITT analysis and 92.1% by PP analysis. For genotype‐susceptive strains, the pooled eradication rate of TT with targeted antibiotics was 93.1% (95% CI:91.3%–94.9%), among which the pooled eradication rate of tailored bismuth quadruple therapy was the highest (94.3%). Besides, the eradication rate of 7‐day TT or tailored triple therapy without bismuth for genotype‐susceptive strains could both reach more than 93.0%. Conclusion: Tailored therapy guided by molecular‐based AST can achieve somewhat ideal therapeutic outcomes. TT with a 7‐day duration or without bismuth for genotype‐susceptible strains can achieve good eradication efficacy. The effectiveness of TT can be improved to some extent by expanding the coverage of AST or by adding bismuth. [ABSTRACT FROM AUTHOR]

Dual antiplatelet therapy (DAPT), comprising aspirin and a P2Y12 receptor inhibitor, is the cornerstone of post-percutaneous coronary intervention treatment to prevent stent thrombosis and reduce the risk of adverse cardiovascular events. The selection of an optimal DAPT regimen, considering the interplay of various antiplatelet agents, patient profiles, and procedural characteristics, remains an evolving challenge. Traditionally, a standard duration of 12 months has been recommended for DAPT in most patients. While contemporary guidelines provide general frameworks, DAPT modulation with longer or shorter treatment courses followed by aspirin or P2Y12 inhibitor monotherapy are evolving towards an individualized strategy to optimize the balance between efficacy and safety. This review comprehensively examines the current landscape of DAPT strategies after coronary stenting, with a focus on emerging evidence for treatment individualization. [ABSTRACT FROM AUTHOR]

Background: The role of tailored immunosuppression (IS) in the development of the humoral response (HR) to SARS-CoV-2 mRNA-based vaccination in liver transplant (LT) recipients is unknown. Methods: This is a single-centre prospective study of patients who underwent LT between January 2015 and December 2021 and who have received three doses of mRNA-based SARS-CoV-2 vaccination. Patients undergoing Tacrolimus-based immunosuppression (TAC-IS) were compared with those undergoing Everolimus-based immunosuppression (EVR-IS). Patients receiving the TAC-EVR combination were divided into two groups based on trough TAC concentrations, i.e., above or below 5 ng/mL. HR (analysed with ECLIA) was assessed at 30 to 135 days after vaccination. The primary outcome was the presence of a positive antibody titre (≥ 0.8 U/mL). Secondary outcomes were the presence of a highly protective antibody titre (≥ 142 U/mL), median antibody titre, and incidence of COVID-19. Results: Sixty-one participants were included. Twenty-four (40%) were receiving TAC-IS and thirty-seven (60%) were receiving EVR-IS. At the median follow-up of 116 (range: 89–154) days, there were no significant differences in positive antibody titre (95.8% vs. 94.6%; p = 0.8269), highly-protective antibody titre (83.3% vs. 81.1%; p = 0.8231), median antibody titre (2410 [IQ range 350–2500] vs. 1670 [IQ range 380–2500]; p = 0.9450), and COVID-19 incidence (0% vs. 5.4%; p = 0.5148). High serum creatinine and low estimated glomerular filtration rate were risk factors for a weak or absent HR. Conclusions: Three doses of mRNA-based SARS-CoV-2 vaccination yielded a highly protective HR in LT recipients. The use of TAC or EVR-based IS does not appear to influence HR or antibody titre, while renal disease is a risk factor for a weak or null HR. [ABSTRACT FROM AUTHOR]

The growing spread of infections caused by multidrug-resistant pathogens makes the need of tailoring antimicrobial therapies by means of a 'patient-centered' approach fundamental. In this scenario, therapeutic drug monitoring (TDM) of emerging antimicrobial candidates may be a valuable approach, but expert interpretation of TDM results should be granted for making them more clinically useful. The MD Clinical Pharmacologist may take over this task since this specialist may couple PK/PD expertise on drugs with a medical background and may provide expert interpretation of TDM results of antimicrobials for tailoring therapy on real-time in each single patient based on specific both drug/pathogen issues and patient issues. This article aims to highlight the main key-points and organizational aspects for implementing a successful TDM-based expert clinical pharmacological advice (ECPA) program for tailoring antimicrobial therapies on real-time in different hospitalized patient special populations. TDM-based ECPA programs lead by the MD Clinical Pharmacologist may represent a way forward for maximizing clinical efficacy and for minimizing the risk of resistance developments and/or toxicity of antimicrobials. Stakeholders should be aware of the fact that this innovative approach may be cost-effective. [ABSTRACT FROM AUTHOR]

Background. Genodermatoses are rare heterogeneous genetic skin diseases with multiorgan involvement. They severely impair an individual's well-being and can also lead to early death. Methods. During the progress of this review, we have implemented a targeted research approach, diligently choosing the most relevant and exemplary articles within the subject matter. Our method entailed a systematic exploration of the scientific literature to ensure a comprehensive and accurate compilation of the available sources. Results. Among genodermatoses, X-linked ones are of particular importance and should always be considered when pediatric males are affected. Regardless of other syndromic forms without prevalence of skin symptoms, X-linked genodermatoses can be classified in three main groups: keratinization defects, pigmentation defects, and inflammatory skin diseases. Typical examples are dyskeratosis congenita, keratosis follicularis spinulosa decalvans, hypohidrotic ectodermal dysplasia, chondrodysplasia punctata, hypohidrotic ectodermal dysplasia, incontinentia pigmenti, chronic granulomatous disease, CHILD syndrome and ichthyosis. In this field, genetic diagnosis of the specific disease is important, also considering that numerous clinical trials of orphan drugs and genetic therapies are being proposed for these rare genetic diseases. Conclusions. Thus, this chapter starts from clinical to molecular testing and ends with a review of all clinical trials on orphan drugs and gene therapy for genodermatoses. [ABSTRACT FROM AUTHOR]

We report a case of Klippel Trenaunay Syndrome that was monitored both clinically and molecularly over a period of 9 years. A somatic mosaic mutation of PIK3CA (p(E545G)) was identified using both cfDNA NGS liquid biopsy and tissue biopsy. At the age of 56, due to intervening clonal mutations in PIK3CA background, she developed a squamous cell carcinoma in the right affected leg which was treated surgically. Nine years later, lung bilateral adenocarcinoma arose on PIK3CA mutated tissues supported by different clonal mutations. One year later, the patient died from metastases led by a new FGFR3 clone unresponsive to standard-of-care, immunotherapy-based. Our results highlight the presence of a molecular hallmark underlying neoplastic transformation that occurs upon an angiodysplastic process and support the view that PIK3CA mutated tissues must be treated as precancerous lesions. Importantly, they remark the effectiveness of combining cfDNA NGS liquid and tissue biopsies to monitor disease evolution as well as to identify aggressive clones targetable by tailored therapy, which is more efficient than conventional protocols. [ABSTRACT FROM AUTHOR]

Ischemia with no obstructive coronary artery disease (INOCA) is not an uncommon diagnosis in patients presenting with chest pain who undergo clinically indicated coronary angiography. However, the symptoms reported by patients with INOCA may be heterogeneous, leading to misdiagnosis and undertreatment. Herein we report 3 clinical cases of INOCA misdiagnosis and describe how the cases were reinvestigated following the appropriate diagnostic pathway. (Level of Difficulty: Advanced.)

We report a case of Klippel Trenaunay Syndrome that was monitored both clinically and molecularly over a period of 9 years. A somatic mosaic mutation of PIK3CA (p(E545G)) was identified using both cfDNA NGS liquid biopsy and tissue biopsy. At the age of 56, due to intervening clonal mutations in PIK3CA background, she developed a squamous cell carcinoma in the right affected leg which was treated surgically. Nine years later, lung bilateral adenocarcinoma arose on PIK3CA mutated tissues supported by different clonal mutations. One year later, the patient died from metastases led by a new FGFR3 clone unresponsive to standard-of-care, immunotherapy-based. Our results highlight the presence of a molecular hallmark underlying neoplastic transformation that occurs upon an angiodysplastic process and support the view that PIK3CA mutated tissues must be treated as precancerous lesions. Importantly, they remark the effectiveness of combining cfDNA NGS liquid and tissue biopsies to monitor disease evolution as well as to identify aggressive clones targetable by tailored therapy, which is more efficient than conventional protocols.

For this reason, the presence of severe right valve insufficiency represents a relative contraindication to CCM therapy; however, in carefully selected cases of functional tricuspid regurgitation, CCM therapy-induced right ventricular reverse remodeling could induce a reduction of the degree of tricuspid regurgitation. Therefore, in patients with HFrEF and HFmrEF, CCM therapy should be considered, as an add-on therapy, after 3 months of optimizing disease-modifier drug therapy [[14]]. In randomized controlled trials, CCM therapy improves functional capacity (i.e. VO2 peak at cardiopulmonary exercise test) [[6]]; also, in a real-world registry, CCM therapy is associated with a lower rate of HF-related hospitalizations [[7]]. Keywords: Cardiac contractility modulation; device therapy; tailored therapy; heart failure with reduced ejection fraction; heart failure with mildly reduced ejection fraction EN Cardiac contractility modulation device therapy tailored therapy heart failure with reduced ejection fraction heart failure with mildly reduced ejection fraction 525 528 4 06/20/23 20230701 NES 230701 1. [Extracted from the article]

There are no randomized controlled trials that demonstrate the role of tailored therapy based on past medication history in improving efficacy of H. pylori eradication compared to empiric therapies. The objective of this study was to determine whether tailored triple plus bismuth therapy (TBT) can achieve higher eradication rates based on previous antibiotic history than empiric TBTs. 800 treatment-naïve patients were randomly assigned to four groups receiving clarithromycin-, levofloxacin- or metronidazole-containing empiric TBT and tailored TBT (clarithromycin and levofloxacin chosen based on previous macrolides and quinolones medication history). Correlation analyses were performed between past medication history and resistance or eradication rate. The eradication rates of tailored TBT were significantly higher than clarithromycin-, levofloxacin- and metronidazole-containing empiric TBT in both intention-to-treat (89.5%, 80.8%, 81.5% and 81.5%) and per-protocol (95.1%, 86.7%, 86.5% and 87.8%) analyses (P <0.05). In patients with previous macrolides, quinolones or nitroimidazoles medication history, the resistance rates of corresponding clarithromycin, levofloxacin or metronidazole were significantly higher than patients without past medication history, and the eradication rates of corresponding clarithromycin- or levofloxacin-containing empiric TBT were significantly lower. Tailored TBT based on previous antibiotic history can achieve higher eradication rates than empiric TBT for first-line H. pylori eradication. [ABSTRACT FROM AUTHOR]

Transdermal fentanyl patches are an effective alternative to the sustained release of oral morphine for chronic pain management. Due to the narrow therapeutic range of fentanyl, the concentration of fentanyl in the blood needs to be carefully monitored. Only then can effective pain relief be achieved while avoiding adverse effects such as respiratory depression. This study developed a physics-based digital twin of a patient by implementing drug uptake, pharmacokinetics, and pharmacodynamics models. The twin was employed to predict the in-silico effect of conventional fentanyl transdermal in a 20–80-year-old virtual patient. The results show that, with increasing age, the maximum transdermal fentanyl flux and maximum concentration of fentanyl in the blood decreased by 11.4% and 7.0%, respectively. However, the results also show that as the patient's age increases, the pain relief increases by 45.2%. Furthermore, the digital twin was used to propose a tailored therapy based on the patient's age. This predesigned therapy customized the duration of applying the commercialized fentanyl patches. According to this therapy, a 20-year-old patient needs to change the patch 2.1 times more frequently than conventional therapy, which leads to 30% more pain relief and 315% more time without pain. In addition, the digital twin was updated by the patient's pain intensity feedback. Such therapy increased the patient's breathing rate while providing effective pain relief, so a safer treatment. We quantified the added value of a patient's physics-based digital twin and sketched the future roadmap for implementing such twin-assisted treatment into the clinics.

Although survival in pediatric acute myeloid leukemia (AML) has increased considerably over the past decades, refractory disease and relapse rates remain high. Refractory and relapsed disease are difficult to treat, with overall survival rates less than 40– 50%. Preventing relapse should, therefore, be one of the highest priorities. Current conventional chemotherapy regimens are hard to intensify due to associated toxic complications, hence more effective therapies that do not increase toxicity are needed. A promising targeted agent is the CD33-directed antibody–drug conjugate gemtuzumab ozogamicin (GO). Because CD33 is highly expressed on leukemic cells in the majority of AML patients, GO can be useful for a broad range of patients. Better relapse-free survival (RFS) after therapy including GO has been reported in several pediatric clinical trials; however, ambiguity about the clinical value of GO in newly diagnosed children remains. Treatment with GO in de novo AML patients aged ≥ 1 month, in combination with standard chemotherapy is approved in the United States, whereas in Europe, GO is only approved for newly diagnosed patients aged ≥ 15 years. In this review, we aimed to clarify the clinical value of GO for treatment of newly diagnosed pediatric AML patients. Based on current literature, GO seems to have additional value, in terms of RFS, and acceptable toxicity when used in addition to chemotherapy during initial treatment. Moreover, in KMT2A-rearranged patients, the clinical value of GO was even more evident. Also, we addressed predictors of response, being CD33 expression and SNPs, PgP-1 and Annexin A5. The near finalized intent-to-file clinical trial in the MyeChild consortium investigates whether fractionated dosing has additional value for pediatric AML, which may pave the way for a broader application of GO in pediatric AML. [ABSTRACT FROM AUTHOR]

Out-of-hospital cardiac arrest (OHCA) outcomes are unsatisfactory despite postcardiac arrest care. Early prediction of prognoses might help stratify patients and provide tailored therapy. In this study, we derived and validated a novel scoring system to predict hypoxic-ischemic brain injury (HIBI) and in-hospital death (IHD). We retrospectively analyzed Korean Hypothermia Network prospective registry data collected from in Korea between 2015 and 2018. Patients without neuroprognostication data were excluded, and the remaining patients were randomly divided into derivation and validation cohorts. HIBI was defined when at least one prognostication predicted a poor outcome. IHD meant all deaths regardless of cause. In the derivation cohort, stepwise multivariate logistic regression was conducted for the HIBI and IHD scores, and model performance was assessed. We then classified the patients into four categories and analyzed the associations between the categories and cerebral performance categories (CPCs) at hospital discharge. Finally, we validated our models in an internal validation cohort. Among 1373 patients, 240 were excluded, and 1133 were randomized into the derivation (n = 754) and validation cohorts (n = 379). In the derivation cohort, 7 and 8 predictors were selected for HIBI (0–8) and IHD scores (0−11), respectively, and the area under the curves (AUC) were 0.85 (95% CI 0.82–0.87) and 0.80 (95% CI 0.77–0.82), respectively. Applying optimum cutoff values of ≥6 points for HIBI and ≥7 points for IHD, the patients were classified as follows: HIBI (−)/IHD (−), Category 1 (n = 424); HIBI (−)/IHD (+), Category 2 (n = 100); HIBI (+)/IHD (−), Category 3 (n = 21); and HIBI (+)/IHD (+), Category 4 (n = 209). The CPCs at discharge were significantly different in each category (p < 0.001). In the validation cohort, the model showed moderate discrimination (AUC 0.83, 95% CI 0.79–0.87 for HIBI and AUC 0.77, 95% CI 0.72–0.81 for IHD) with good calibration. Each category of the validation cohort showed a significant difference in discharge outcomes (p < 0.001) and a similar trend to the derivation cohort. We presented a novel approach for assessing illness severity after OHCA. Although external prospective studies are warranted, risk stratification for HIBI and IHD could help provide OHCA patients with appropriate treatment. [ABSTRACT FROM AUTHOR]

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The increase in antibiotic resistance to Helicobacter pylori (H. pylori) is associated with a decrease in the effectiveness of eradication therapy. Although some success has been achieved by adjusting therapeutic regimens according to local data on resistance to certain antibiotics, a new approach is needed to ensure a better therapeutic response. Tailored therapy, based on sensitivity tests to antibiotics, is increasingly proving to be a superior therapeutic option, even as a first-line therapy. Moreover, the recently published Maastricht VI guidelines emphasize utilizing a susceptibility-guided strategy in respect to antibiotic stewardship as the first choice for eradication therapy. In addition, polymerase chain reaction (PCR) technology is becoming a standard tool in the diagnosis of H. pylori infections through non-invasive testing, which further optimizes the eradication process. We provide a review regarding the current position of the individualized approach in eradication therapy and its future prospects. Based on novel understandings, the personalized approach is an effective strategy to increase the successful eradication of H. pylori infections. [ABSTRACT FROM AUTHOR]

Diffuse large B-cell lymphoma (DLBCL) represents a curable disease with a 60– 70% chance of cure with current R-CHOP chemoimmunotherapy. However, 30– 40% of patients are refractory or relapsing. Many attempts failed to improve the outcome of DLBCL patients, including the intensification of R-CHOP regimen, consolidation, or maintenance therapy since the introduction of R-CHOP in 2000. Better understanding of both molecular biology of lymphoma cells and the tumor microenvironment raised the hope for future improvement of DLBCL patients' survival. Novel molecular findings have initiated clinical trials exploring targeted therapy based on driver genetic alterations with an intent to improve survival of high-risk subsets of patients. But the preliminary results remain ambiguous. The approach "agnostic" to specific molecular alterations of lymphoma cell includes antibody-drug conjugates (especially polatuzumab vedotin), immunotherapy comprising different antibodies with immunomodulatory effect (tafasitamab, lenalidomide), and T-cell engaging therapy (bispecific antibodies, early use of CAR T-cell). This approach could increase the cure rates and change the current therapeutic paradigm. However, better prognostic stratification, smarter designs of clinical trials, modification of endpoints including the use of ctDNA are needed. This review covers the complexity of DLBCL management. [ABSTRACT FROM AUTHOR]

Transdermal fentanyl patches are an effective alternative to the sustained release of oral morphine for chronic pain management. Due to the narrow therapeutic range of fentanyl, the concentration of fentanyl in the blood needs to be carefully monitored. Only then can effective pain relief be achieved while avoiding adverse effects such as respiratory depression. This study developed a physics-based digital twin of a patient by implementing drug uptake, pharmacokinetics, and pharmacodynamics models. The twin was employed to predict the in-silico effect of conventional fentanyl transdermal in a 20-80-year-old virtual patient. The results show that, with increasing age, the maximum transdermal fentanyl flux and maximum concentration of fentanyl in the blood decreased by 11.4% and 7.0%, respectively. However, the results also show that as the patient's age increases, the pain relief increases by 45.2%. Furthermore, the digital twin was used to propose a tailored therapy based on the patient's age. This predesigned therapy customized the duration of applying the commercialized fentanyl patches. According to this therapy, a 20-year-old patient needs to change the patch 2.1 times more frequently than conventional therapy, which leads to 30% more pain relief and 315% more time without pain. In addition, the digital twin was updated by the patient's pain intensity feedback. Such therapy increased the patient's breathing rate while providing effective pain relief, so a safer treatment. We quantified the added value of a patient's physics-based digital twin and sketched the future roadmap for implementing such twin-assisted treatment into the clinics. [ABSTRACT FROM AUTHOR]

Simple Summary: Systemic inflammation is associated with an increased aggressiveness of breast cancer and can contribute to a decreased activity of neoadjuvant treatments. Biomarkers of systemic inflammation are easily obtained from routine blood counts and are highly cost-effective, having great potential to steer cancer prognosis in clinical practice. In our study, we tested the hypothesis that high values of these biomarkers might have an effect on the clinical outcomes in a population of patients treated with neoadjuvant chemotherapy for breast cancer. The results of our study, together with data from the literature, hint at a possible role of inflammatory markers in the diagnostic and therapeutic algorithm of breast cancer, where specific pre-operative blood cell ratios could be used in combination with biological and clinical factors to tailor adjuvant therapy. Immune inflammatory biomarkers are easily obtained and inexpensive blood-based parameters that recently showed prognostic and predictive value in many solid tumors. In this study, we aimed to investigate the role of these biomarkers in predicting distant relapse in breast cancer patients treated with neoadjuvant chemotherapy (NACT). All breast cancer patients who referred to our Breast Unit and underwent NACT were retrospectively reviewed. The pre-treatment neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and pan-immune-inflammation value (PIV) were calculated from complete blood counts. The primary outcome was 5-year distant-metastasis-free survival (DMFS). In receiver operating characteristic analyses, the optimal cutoff values for the NLR, PLR, MLR, and PIV were determined at 2.25, 152.46, 0.25, and 438.68, respectively. High levels of the MLR, but not the NLR, PLR, or PIV, were associated with improved 5-year DMSF in the study population using both univariate (HR 0.52, p = 0.03) and multivariate analyses (HR, 0.44; p = 0.02). Our study showed that the MLR was a significant independent parameter affecting DMFS in breast cancer patients undergoing NACT. Prospective studies are required to confirm this finding and to define reliable cutoff values, thus leading the way for the clinical application of this biomarker. [ABSTRACT FROM AUTHOR]

Background: Due to an increase in drug resistance, the eradication rate of H. pylori with empirical therapy has declined. Tailored therapy has been proposed as an alternative to standard empirical treatments. The necessity of personalized eradication therapy remains unclear. The aim of this study was to determine whether tailored therapy is superior to empirical therapy for H. pylori infection. Methods: We searched for eligible randomized controlled trials in the PubMed, Embase (Ovid), Wanfang, and Cochrane Central Register of Controlled Trials databases up to 10 December 2021. A random effects model comparing pooled relative risks (RRs) with 95% confidence intervals (CIs) was applied in the metaanalysis. Results: Twenty-one studies were included in the meta-analysis. In the first-line treatment, tailored therapy was more effective than empirical therapy (RR, 1.14 [95% CI, 1.08-1.21], I2 = 72.2%). In the second-line therapy setting, the results did not reveal significant differences between the two treatments (RR, 1.05 [95% CI, 0.84-1.30], I2 = 80.6%). A similar result was observed in mixed second- and third-line treatments (RR, 1.03 [95% CI, 0.96-1.11], I² = 0.0%). Regarding adverse events, no significant differences were found between the two treatments (RR, 0.90 [95% CI, 0.80-1.01], I² = 35.7%). Most of the results were highly heterogeneous. Conclusion: A tailored approach might provide a better eradication rate than empirical methods in first-line treatment. There might be no obvious advantage in second-line or mixed second- and third-line treatments third-line treatment. Due to the high heterogeneity, the results should be interpreted with caution. Further clinical studies are needed and justified. [ABSTRACT FROM AUTHOR]

Lung cancer continues to be the largest cause of cancer-related mortality among men and women globally, accounting for around 27% of all cancer-related deaths. Recent advances in lung cancer medicines, particularly for non-small-cell lung cancer (NSCLC), have increased the need for multidisciplinary disease care, thereby enhancing patient outcomes and quality of life. Different studies in the European community have evaluated the impact of multidisciplinary care on outcomes for lung cancer patients, including its impact on survival, adherence to guideline treatment, utilization of all treatment modalities, timeliness of treatment, patient satisfaction, quality of life, and referral to palliative care. This publication will examine the roles and duties of all multidisciplinary members and the influence of multidisciplinary care on lung cancer outcomes in Europe. Multidisciplinary treatment is the foundation of lung cancer treatment. The optimal setting for interdisciplinary collaboration between specialists with complementary functions is multidisciplinary meetings. Multidisciplinary care in lung cancer facilitates the delivery of a high-quality service, which may improve lung cancer patients' survival, utilization of all treatment modalities, adherence to guideline management, and quality of life, despite the fact that only limited observational data have demonstrated these results. To confirm the relationship between multidisciplinary treatment and improved lung cancer patient outcomes, however, further research is required. [ABSTRACT FROM AUTHOR]

Several different nosological classifications have been used over time for vascular malformations (VMs) since clinical and pathological signs are largely overlapping. In a large proportion of cases, VMs are generated by somatic mosaicism in key genes, belonging to a few different molecular pathways. Therefore, molecular characterization may help in the understanding of the biological mechanisms related to the development of pathology. Tissue biopsy is not routinely included in the diagnostic path because of the need for fresh tissue specimens and the risk of bleeding. Bypassing the need for bioptic samples, we took advantage of the possibility of isolating cell-free DNA likely released by the affected tissues, to molecularly characterize 53 patients by cfDNA-NGS liquid biopsy. We found a good match between the identified variant and the clinical presentation. PIK3CA variants were found in 67% of Klippel Trenaunay Syndrome individuals; KRAS variants in 60% of arteriovenous malformations; MET was mutated in 75% of lymphovenous malformations. Our results demonstrate the power of cfDNA-NGS liquid biopsy in VMs clinical classification, diagnosis, and treatment. Indeed, tailored repurposing of pre-existing cancer drugs, such as PIK3CA, KRAS, and MET inhibitors, can be envisaged as adjuvant treatment, in addition to surgery and/or endovascular treatment, in the above-defined VMs categories, respectively. [ABSTRACT FROM AUTHOR]

Objective: Comorbidity scores are increasingly used to reduce potential confounding in oncologic research. This is of paramount importance in endometrial cancer (EC) since it is characterized by quite indolent behavior. Here, we aim to evaluate the impact of various comorbidities and concurrent medications used on survival outcomes, adopting the age-adjusted Charlson comorbidity index (A-CCI). Design: This is an observational study. Charts of 257 EC patients were retrieved. Methods: We retrospectively evaluated data of patients who underwent surgical treatment for EC. A-CCI was calculated by summing the weighted comorbidities and age of each patient. A binomial value was assigned to different comorbidities and different drugs. Oncologic outcomes were evaluated using Cox proportional hazard models adjusted for age. Results: A-CCI ≥3 correlated with more aggressive tumor features (47.6% vs. 26.8%, p = 0.001), higher risk of recurrence (29.7% vs. 11.6%, p = 0.001), death (20.7% vs. 7.1%, p = 0.002), and death due to disease (16.6% vs. 6.3%, p = 0.012). Considering comorbidities and drugs at parsimonious multivariable analysis model: cardiac disease, liver disease, and proton pump inhibitors (PPIs) use were independent predictors of disease-free survival. Cardiac disease, autoimmune disease, and PPIs use were independent predictors of overall survival. Diabetes was the only independent predictor for cause-specific survival. Limitations: The major limitation of the present study is its retrospective nature and the relatively small sample size that limit the possibility to have firm conclusions. Conclusion: Patients with EC are characterized by a high burden of comorbidities. Comorbidities are associated directly with survival outcomes. Further attention is needed to improve the active management of comorbidities soon after EC treatments. Interventional studies are needed to improve patients' outcomes. [ABSTRACT FROM AUTHOR]

Introduction With the application of virtual reality (VR), tailored interventions can be created that mirror the traumatic experiences of veterans with post-traumatic stress disorder (PTSD). Visual elements can be mimicked, and auditory and other senses stimulated. In doing so, the degree of immersion can be adjusted to optimize the therapeutic process. Objectively measuring the sensory immersion is key to keep subjects within their personal window of tolerance. Based on this information the therapist can decide manipulate the sensory stimulation embedded in the treatment. Objectives The objectives of this study are to explore the different immersive design aspects of VRET that can be modified to influence the experienced presence in veterans with PTSD, and to discuss possible methods of measuring the emotional response facilitated by immersive design aspects and experienced presence. Methods Four design aspects are discussed: system, sensory cues, narrative and challenge. We also report on a user experiment in three veterans that informed on quality and depth of immersion. Results Believability of the neutral virtual environment was important for maintaining the veterans’ presence within the VR experience. The immersive design aspects that were personalized and supportive in the narrative of the veteran such as music and self-selected images appeared to have a strong influence on recall and reliving of the traumatic events. Conclusions Finally, in order to increase the therapeutic effect in veterans with PTSD, the highlighted design aspects should be recognized and tailored to maximize immersion in virtual reality exposure therapy. Disclosure No significant relationships.

BackgroundClarithromycin resistance reduces the eradication rate of Helicobacter pylori (H. pylori). Cultures with susceptibility testing and molecular determination of genotypes are recommended to guide-tailored therapy.MethodsWe retrospectively enrolled patients aged 6 and 18 years with H. pylori infection, who underwent an endoscopy and agreed to undergo both culture and genetic testing for clarithromycin resistance. Patients receiving tailored therapy based on traditional culture results (phenotype-guided therapy) or genetic testing results (genotype-guided therapy) were included in the study. 13C-urea breath test was used to evaluate the success of eradication at least 4 weeks after the completion of treatment. We aimed to determine whether the eradication rate of phenotype- or genotype-guided therapy based on clarithromycin resistance is greater than 90% in children.ResultsBetween September 2017 and October 2020, 226 eligible patients were enrolled. There were 71 with clarithromycin-sensitive strains in the phenotype-guided therapy group and 87 without 23S rRNA point mutations (A2142G, A2142C, and A2143G) in the genotype-guided therapy group. Eradication rates were 70.4% (50/71, [95% CI: 58.4–80.7%] for phenotype-guided therapy and 92.0% (80/87, [95% CI: 84.1–96.7%]) for genotype-guided therapy (P < 0.01). The incidence of side effects was 4.2% (3/71) and 10.3% (9/87), with no major differences between these two groups (P = 0.15), respectively. The compliance rate was also similar (97.2 vs. 95.4%, P = 0.87).ConclusionTailored therapy according to genetic testing results achieved eradication rates of 92% and was superior to tailored therapy guided by traditional culture results.

Abstract 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

The increase in antibiotic resistance to Helicobacter pylori (H. pylori) is associated with a decrease in the effectiveness of eradication therapy. Although some success has been achieved by adjusting therapeutic regimens according to local data on resistance to certain antibiotics, a new approach is needed to ensure a better therapeutic response. Tailored therapy, based on sensitivity tests to antibiotics, is increasingly proving to be a superior therapeutic option, even as a first-line therapy. Moreover, the recently published Maastricht VI guidelines emphasize utilizing a susceptibility-guided strategy in respect to antibiotic stewardship as the first choice for eradication therapy. In addition, polymerase chain reaction (PCR) technology is becoming a standard tool in the diagnosis of H. pylori infections through non-invasive testing, which further optimizes the eradication process. We provide a review regarding the current position of the individualized approach in eradication therapy and its future prospects. Based on novel understandings, the personalized approach is an effective strategy to increase the successful eradication of H. pylori infections.

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. [ABSTRACT FROM AUTHOR]

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Fentanyl transdermal patches are widely implemented for cancer-induced pain treatment due to the high potency of fentanyl and gradual drug release. However, transdermal fentanyl up-titration for opioid-naïve patients is difficult, which is why opioid treatment is often started with oral/iv morphine. Based on the daily dose of morphine, the initial dose of the fentanyl patch is decided upon. After reaching a stable level of pain, the switch is made from oral/iv morphine to transdermal fentanyl. There are standard calculation tools for transferring from oral/iv morphine to transdermal fentanyl, which is the same for all patients. By considering the variations in the physiology of the patients, a unique switching strategy cannot meet the needs of different patients. This study explores the outcome in terms of pain relief and minute ventilation during opioid therapy. For this, we used physics-based simulations on a virtually-generated population of patients, and we applied the same therapy to all patients. We could show that patients' physiology, such as gender, age, and weight, greatly impact the outcome of the therapy; as such, the correlation coefficient between pain intensity and age is 0.89, and the correlation coefficient between patient's weight and maximum plasma concentration of morphine and fentanyl is -0.98 and -0.97. Additionally, a different combination of the duration of overlap between morphine and fentanyl therapy with different doses of fentanyl was considered for the virtual patients to find the best opioid-switching strategy for each patient. We explored the impact of combining physiological features to determine the best-suited strategy for virtual patients. Our findings suggest that tailoring morphine and fentanyl therapy only based on a limited number of features is insufficient, and increasing the number of impactful physiological features positively influences the outcome of the therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract 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).

Background: 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. Methods: 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). Results: 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 < 0.001), but only 2.7% were grade ≥ 3. The most frequent complication was suture dehiscence (17.6%), which occurred less frequently in the noCRT group (p < 0.001). At 1 year from TEM, the most frequent symptoms was urgency (11.9%, without significant differences between the CRT group and the noCRT group); the noCRT group experienced a lower rate of soiling than the CRT group (0% vs. 7.7%; p: 0.027). The incidence of LARS was evaluated in 47 patients from May 2012 on and was 21.3% occurring less frequently in the noCRT group (10% vs. 41.2%; p: 0.012). Only 6.4% of the patients evaluated experienced major LARS. In multivariate analysis, preoperative CRT significantly worsened postoperative morbidity and functional outcomes. Conclusions: TEM is a safe procedure associated with only low risk of severe postoperative complications and major LARS. Preoperative CRT seems to increase the rate of postoperative morbidity after TEM and led to worse functional outcomes at 1 year after surgery. [ABSTRACT FROM AUTHOR]

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. Image 1 • Plaque erosion is responsible for more than one third of acute coronary syndromes (ACS) cases. • Patients with plaque erosion have a better prognosis than those with plaque rupture. • Plaque erosion may be stabilized by medical therapy without stent implantation. • Clinical, angiographic, and laboratory findings may aid plaque erosion's prediction. • Prediction of plaque erosion may allow to avoid unnecessary invasive procedures. [ABSTRACT FROM AUTHOR]