Capecitabine-associated enterocolitis: Narrative literature review of a rare adverse event and a case presentation.

Capecitabine is an oral 5-fluorouracil prodrug with antimetabolite activity commonly used in advanced colorectal and breast cancer. It presents with a generally good toxicity profile and most of the adverse events can be managed effectively. Enterocolitis is a rare, under-reported, but potentially fatal adverse event associated with capecitabine use. To the best of our knowledge, there are 21 cases of capecitabine-related enterocolitis reported in the literature. We herein present a narrative literature review of enteritis/colitis cases associated with capecitabine use, with highlight to the most common clinical presentation, common imaging and microscopic findings and management approach. We furthermore present a case of severe capecitabine-related enteritis.

The Role of Decoy Receptor DcR3 in Gastrointestinal Malignancy.

Malignancies are among the leading causes of mortality worldwide. Early detection and treatment are the primary targets of clinical and translational research, and may be facilitated by the recognition of novel diagnostic and prognostic biomarkers. Decoy receptor 3 (DcR3) is a soluble receptor of the tumor necrosis factor receptor superfamily of proteins (TNFRSF), which associates with its respective TNF-like ligands, Fas-L, LIGHT, and TL1A. DcR3 has been recognised as a significant anti-apoptotic factor with prominent involvement in various inflammatory and neoplastic conditions. Increased intratumor expression of DcR3 and elevated soluble DcR3 protein content in the sera of patients has been reported for various malignancies. Recent published work has suggested that monitoring of local and systemic DcR3 may provide an attractive biomarker, mainly for defining subgroups of patients with aggressive tumor behaviour and poor prognosis. The aim of the present review is to summarize and critically present existing evidence regarding the potential clinical importance of monitoring DcR3 expression in patients with malignancies of the gastrointestinal tract, as well as liver and pancreatic cancer. We also present a detailed description of the pathophysiological basis that may underlie the involvement of DcR3 in gastrointestinal carcinogenesis. Based on these data, we comment on the potential applicability of DcR3 monitoring in the diagnosis and, most importantly, the prognostic stratification of patients.

Venous thromboembolism in COVID-19: A systematic review and meta-analysis.

Severe coronavirus disease 2019 (COVID-19) is associated with increased risk of venous thromboembolism events (VTE). This study performed a systematic review in PubMed/EMBASE of studies reporting the prevalence of VTE in patients with COVID-19 who were totally screened/assessed for deep vein thrombosis (DVT) and/or for pulmonary embolism (PE). Among 47 candidate studies (n = 6459; 33 in Europe), 17 studies (n = 3973; weighted age 63.0 years, males 60%, intensive care unit (ICU) 16%) reported the prevalence of PE with a pooled estimate of 32% (95% CI: 25, 40%), and 32 studies (n = 2552; weighted age 62.6 years, males 57%, ICU 49%) reported the prevalence of DVT with a pooled estimate of 27% (95% CI: 21, 34%). A total of 36 studies reported the use of at least prophylactic antithrombotic treatment in the majority of their patients. Meta-regression analysis showed that the prevalence of VTE was higher across studies with a higher percentage of ICU patients and higher study population mean D-dimer values, and lower in studies with mixed dosing of anticoagulation in ⩾ 50% of the population compared to studies with standard prophylactic dosing of anticoagulation in < 50% of the population. The pooled odds ratio for death in patients with COVID-19 and VTE versus those without VTE (17 studies, n = 2882) was 2.1 (95% CI: 1.2, 3.6). Hospitalized patients with severe COVID-19 are at high VTE risk despite prophylactic anticoagulation. Further research should investigate the individualized VTE risk of patients with COVID-19 and the optimal preventive antithrombotic therapy. PROSPERO Registration No.: CRD42020185543.

Procalcitonin to Reduce Long-Term Infection-associated Adverse Events in Sepsis. A Randomized Trial.

Rationale: Although early antimicrobial discontinuation guided by procalcitonin (PCT) has shown decreased antibiotic consumption in lower respiratory tract infections, the outcomes in long-term sepsis sequelae remain unclear.Objectives: To investigate if PCT guidance may reduce the incidence of long-term infection-associated adverse events in sepsis.Methods: In this multicenter trial, 266 patients with sepsis (by Sepsis-3 definitions) with lower respiratory tract infections, acute pyelonephritis, or primary bloodstream infection were randomized (1:1) to receive either PCT-guided discontinuation of antimicrobials or standard of care. The discontinuation criterion was ≥80% reduction in PCT levels or any PCT ≤0.5 µg/L at Day 5 or later. The primary outcome was the rate of infection-associated adverse events at Day 180, a composite of the incidence of any new infection by Clostridioides difficile or multidrug-resistant organisms, or any death attributed to baseline C. difficile or multidrug-resistant organism infection. Secondary outcomes included 28-day mortality, length of antibiotic therapy, and cost of hospitalization.Measurements and Main Results: The rate of infection-associated adverse events was 7.2% (95% confidence interval [CI], 3.8-13.1%; 9/125) versus 15.3% (95% CI, 10.1-22.4%; 20/131) (hazard ratio, 0.45; 95% CI, 0.20-0.98; P = 0.045); 28-day mortality 15.2% (95% CI, 10-22.5%; 19/125) versus 28.2% (95% CI, 21.2-36.5%; 37/131) (hazard ratio, 0.51; 95% CI, 0.29-0.89; P = 0.02); and median length of antibiotic therapy 5 (range, 5-7) versus 10 (range, 7-15) days (P < 0.001) in the PCT and standard-of-care arms, respectively. The cost of hospitalization was also reduced in the PCT arm.Conclusions: In sepsis, PCT guidance was effective in reducing infection-associated adverse events, 28-day mortality, and cost of hospitalization.Clinical trial registered with www.clinicaltrials.gov (NCT03333304).

The Greek Response to COVID-19: A True Success Story from an IBD Perspective.

BACKGROUND: After the first case of infection with the novel coronavirus, SARS-CoV-2, in China, an outbreak rapidly spread, finally evolving into a global pandemic. The new disease was named coronavirus disease 2019 (COVID-19) and by May 10, 2020, it has affected more than 4 million people worldwide and caused more than 270,000 deaths. METHODS: We describe the Greek experience regarding the response to COVID-19, with particular focus on 2 COVID-19 reference hospitals in the metropolitan area of Athens, the capital of Greece. RESULTS: The first case of SARS-CoV-2 infection in Greece was reported on February 26, 2020, and prompted a decisive response from the Greek government. The primary focus was containment of virus spread, considering shortage of ICU beds. A general lockdown was implemented early on, and the national Health Care System underwent massive re-structuring. Our 2 gastrointestinal (GI) centers, which provide care for more than 1500 inflammatory bowel disease (IBD) patients, are located in hospitals that were transformed to COVID-19 reference centers. To maintain sufficient care for our patients, while also contributing to the fight against COVID-19, we undertook specific measures. These included provision of telemedicine services, electronic prescriptions and home delivery of medications, isolation of infusion units and IBD clinics in COVID-free zones of the hospitals, in addition to limiting endoscopies to emergencies only. Such practices allowed us to avoid interruption of appropriate therapies for IBD patients. In fact, within the SECURE-IBD database, there have been only 4 Greek IBD patients, to date, who have been reported as positive for SARS-CoV-2. CONCLUSION: Timely application of preventive measures and strict compliance to guidelines limited the spread of COVID-19 in Greece and minimally impacted our IBD community, without interfering with therapeutic management.

The "Old" and the "New" Antibiotics for MDR Gram-Negative Pathogens: For Whom, When, and How.

The recent expansion of multidrug resistant and pan-drug-resistant pathogens poses significant challenges in the treatment of healthcare associated infections. An important advancement, is a handful of recently launched new antibiotics targeting some of the current most problematic Gram-negative pathogens, namely carbapenem-producing Enterobacteriaceae (CRE) and carbapenem-resistant P. aeruginosa (CRPA). Less options are available against carbapenem-resistant Acinetobacter baumannii (CRAB) and strains producing metallo-beta lactamases (MBL). Ceftazidime-avibactam signaled a turning point in the treatment of KPC and partly OXA- type carbapenemases, whereas meropenem-vaborbactam was added as a potent combination against KPC-producers. Ceftolozane-tazobactam could be seen as an ideal beta-lactam backbone for the treatment of CRPA. Plazomicin, an aminoglycoside with better pharmacokinetics and less toxicity compared to other class members, will cover important proportions of multi-drug resistant pathogens. Eravacycline holds promise in the treatment of infections by CRAB, with a broad spectrum of activity similar to tigecycline, and improved pharmacokinetics. Novel drugs and combinations are not to be considered "panacea" for the ongoing crisis in the therapy of XDR Gram-negative bacteria and colistin will continue to be considered as a fundamental companion drug for the treatment of carbapenem-resistant Enterobacteriaceae (particularly in areas where MBL predominate), for the treatment of CRPA (in many cases being the only in vitro active drug) as well as CRAB. Aminoglycosides are still important companion antibiotics. Finally, fosfomycin as part of combination treatment for CRE infections and P. aeruginosa, deserves a greater attention. Optimal conditions for monotherapy and the "when and how" of combination treatments integrating the novel agents will be discussed.

What's new in the epidemiology of skin and soft tissue infections in 2018?

PURPOSE OF REVIEW: Skin and soft tissue infections (SSTIs) are among the most common infections in outpatients and the most frequent infectious cause of referrals to emergency departments in developed world, contributing to significant morbidity and healthcare expenditures. We sought to review recent literature covering epidemiology of SSTIs. RECENT FINDINGS: Staphylococcus aureus and streptococci predominate and methicillin-resistant S. aureus (MRSA) poses additional challenges; community-acquired-MRSA in some areas is superseding methicillin-susceptible S. aureus and multidrug resistance is evolving. Incidence data of SSTIs from United States show a decreasing trend, whereas trends of hospitalization rates were increasing. Despite low mortality associated with SSTIs, high rates of treatment failure and relapses are of concern. Diagnosis and management decisions in the emergency department (ED) lack validated tools for prediction of clinical response particularly among elderly, immunocompromised, obese, and patients with comorbidities. A variety of modifiable and nonmodifiable risk factors of the host and data from local epidemiology should be considered to prevent recurrence and treatment failure. SUMMARY: An evolving epidemiology of SSTIs make microbiologic documentation and surveillance of local data imperative. New assessment algorithms with potential use in the ED are a priority. The universal applicability of international guidelines is questioned in this setting.

New treatments of multidrug-resistant Gram-negative ventilator-associated pneumonia.

Ventilator-associated pneumonia (VAP) remains an important clinical problem globally, being associated with significant morbidity and mortality. As management of VAP requires adequate and timely antibiotic administration, global emergence of antimicrobial resistance poses serious challenges over our ability to maintain this axiom. Development of antimicrobials against MDR Gram-negative pathogens has therefore emerged as a priority and some new antibiotics have been marketed or approach late stage of development. The aim of this review is to analyse new therapeutic options from the point view of potential treatment of VAP. Among recently developed antimicrobials presented herein, it is obvious that we will have promising therapeutic options against VAP caused by Enterobacteriaceae excluding those producing metallo-ß-lactamases, against which only cefiderocol and aztreonam/avibactam are expected to be active. Against infections caused by carbapenem non-susceptible Pseudomonas aeruginosa, ceftolozane/tazobactam and to a lesser extend ceftazidime/avibactam may cover a proportion of current medical needs, but there still remain a considerable proportion of strains which harbor other resistance mechanisms. Murepavadin and cefiderocol hold promise against this particularly notorious pathogen. Finally, Acinetobacter baummannii remains a treatment-challenge. Eravacycline, cefiderocol and probably plazomicin seem to be the most promising agents against this difficult-to treat pathogen, but we have still a long road ahead, to see their position in clinical practice and particularly in VAP. In summary, despite persisting and increasing unmet medical needs, several newly approved and forthcoming agents hold promise for the treatment of VAP and hopefully will enrich our antimicrobial arsenal in the next few years. Targeted pharmacokinetic and clinical studies in real-life scenario of VAP are important to position these new agents in clinical practice, whereas vigilant use will ensure their longevity in our armamentarium.

Crazy paving pattern as a rare radiological manifestation of peripheral T-cell lymphoma (PTCL) with lung involvement: A case report.

We report on a 70-year old woman with dyspnea, systemic lymphadenopathy and abnormal chest computed tomography (CT) findings. A complete laboratory testing as well as mediastinal tissue sampling via Endobronchial Ultrasound (EBUS)-guided Transbronchial Needle Biopsy (TBNB) did not reveal a definite diagnosis. After experiencing acute respiratory failure which led to intensive care unit, the patient underwent a cervical lymph node biopsy which revealed peripheral T-cell lymphoma not otherwise specified (PTCL-NOS). A CT-guided trans-thoracic lung biopsy was performed that showed involvement of the lung parenchyma in the context of PTCL-NOS. Lung involvement is a rare extra-nodal manifestation of PTCL. The imaging patterns of this lymphoma have not been well described. We conclude that the finding of crazy paving pattern is a rare manifestation of this disease. In patients with pre-existing lymphoma, lung involvement should be included in the differential due to high pre-test probability.

Validation of the professional device for blood pressure measurement Microlife WatchBP Office in adults and children according to the American National Standards Institute/Association for the Advancement of Medical Instrumentation/International Organization for Standardization standard.

OBJECTIVE: To assess the accuracy of the professional oscillometric blood pressure (BP) monitor Microlife WatchBP Office in adults and children according to the American National Standards Institute/Association for the Advancement of Medical Instrumentation/International Organization for Standardization (ANSI/AAMI/ISO) 81060-2:2013 standard. METHODS: Adults and children (aged 3-12 years) were recruited to fulfil the age, sex, BP and cuff distribution criteria of the ANSI/AAMI/ISO standard using the same-arm sequential BP measurement method. Three cuffs of the test device were used for arm circumferences of 14-22, 22-32 and 32-42 cm. RESULTS: A total of 115 participants were recruited and 88 were included in the analysis (51 adults and 37 children). For criterion 1, the mean±SD of the differences between the test device and reference BP was -1.0±7.0/-4.7±5.4 mmHg (systolic/diastolic). For criterion 2, the SD of the averaged BP differences between the test device and reference per participant was 5.15/4.77 mmHg (systolic/diastolic). CONCLUSION: The professional Microlife WatchBP Office BP monitor fulfilled the requirements of the ANSI/AAMI/ISO validation standard for adults and children and can be recommended for clinical use.

Association of Central Versus Brachial Blood Pressure With Target-Organ Damage: Systematic Review and Meta-Analysis.

Accumulating evidence suggests that central blood pressure (BP) may reflect the hemodynamic stress on target organs more accurately than brachial BP. A systematic review assessing the relationship of central versus brachial BP with preclinical target-organ damage was performed. Meta-analysis of cross-sectional data showed that central compared with brachial systolic BP was more closely associated with (1) left ventricular mass index (12 studies, n=6431; weighted age [SD], 49.9 [13.1] years; 51% hypertensives): pooled correlation coefficients r=0.30; 95% confidence interval (CI), 0.23-0.37 versus r=0.26; 95% CI, 0.19-0.33, respectively; P<0.01 for difference; (2) carotid intima-media thickness (7 studies, n=6136; weighted age, 55.6 [13.2] years; 48% hypertensives): r=0.27; 95% CI, 0.19-0.34 versus r=0.23; 95% CI, 0.16-0.30, respectively; P<0.01 for difference; (3) pulse-wave velocity (14 studies, n=3699; weighted age, 53.9 [13.3] years; 53% hypertensives): r=0.42; 95% CI, 0.37-0.47 versus r=0.39; 95% CI, 0.33-0.45, respectively; P<0.01 for difference. Four studies assessing urine albumin excretion (n=3718; weighted age, 56.4 [5] years; 69% hypertensives) reported similar correlations (P=not significant) with central (r=0.22; 95% CI, 0.14-0.29) and brachial systolic BP (r=0.22; 95% CI, 0.12-0.32). Similar findings were observed for central compared with brachial pulse pressure in terms of relationship with target-organ damage. Metaregression analyses did not reveal any significant effect of age. In conclusion, central compared with brachial BP seems to be more strongly associated with most of the investigated indices of preclinical organ damage.