Luca Valerio

Johannes Gutenberg-Universität Mainz, Center for thrombosis and hemostasis, Faculty Member

Academic Medical Centre/ Universiteit van Amsterdam, Public Health, Graduate Student

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My research focuses on the prognosis and long-term course of pulmonary embolism, mortality for conditions related to thrombosis and hemostasis as estimated by large-scale observational and country-level data, and rare thromboinflammatory diseases such as Lemierre syndrome and other forms of septic thrombophlebitis.

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Papers by Luca Valerio

Predisposing factors for admission to intensive care units of patients with COVID-19 infection—Results of the German nationwide inpatient sample

Frontiers in Public Health

BackgroundIntensive care units (ICU) capacities are one of the most critical determinants in heal... more BackgroundIntensive care units (ICU) capacities are one of the most critical determinants in health-care management of the COVID-19 pandemic. Therefore, we aimed to analyze the ICU-admission and case-fatality rate as well as characteristics and outcomes of patient admitted to ICU in order to identify predictors and associated conditions for worsening and case-fatality in this critical ill patient-group.MethodsWe used the German nationwide inpatient sample to analyze all hospitalized patients with confirmed COVID-19 diagnosis in Germany between January and December 2020. All hospitalized patients with confirmed COVID-19 infection during the year 2020 were included in the present study and were stratified according ICU-admission.ResultsOverall, 176,137 hospitalizations of patients with COVID-19-infection (52.3% males; 53.6% aged ≥70 years) were reported in Germany during 2020. Among them, 27,053 (15.4%) were treated in ICU. COVID-19-patients treated on ICU were younger [70.0 (interqua...

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Re: Internal Jugular Vein and Cerebral Venous Sinus Infective Thrombophlebitis Detected With 99mTc-HMPAO White Blood Cell Scintigraphy

Clinical Nuclear Medicine

Management of Lemierre Syndrome

Minerva Medica

Lemierre syndrome is a rare form of septic thrombophlebitis of the head and neck veins, most typi... more Lemierre syndrome is a rare form of septic thrombophlebitis of the head and neck veins, most typically the internal jugular vein, which affects otherwise healthy adolescents and young adults after an oropharyngitis or other local infection and is characterized by multiple septic embolization. Despite treatment, Lemierre syndrome displays a high rate of in-hospital complications that include thrombus progression and new peripheral septic embolization, and it can be fatal or cause disabling sequelae. The mainstay of treatment is antibiotic therapy; anticoagulation is often used, but its role is controversial. Surgical treatment is often necessary in case of peripheral septic lesions. In the absence of prospective studies, what little guidance exists on its management is based on case series or on analogy with similar conditions such as other forms of septic thrombophlebitis or non-septic venous thrombosis. Over the last few years, new observational evidence has improved our knowledge of the clinical epidemiology of this condition and highlighted a number of promising management strategies. We provide an overview of the treatment patterns observed in the contemporary era, summarise the arguments proposed so far against or in favour of alternative treatments as well as possible decision rules on the use of anticoagulation, and outline the priorities of ongoing and future observational and interventional research.

Age-sex specific pulmonary embolism-related mortality in the USA and Canada, 2000–18: an analysis of the WHO Mortality Database and of the CDC Multiple Cause of Death database

The Lancet Respiratory Medicine, 2021

Background Pulmonary embolism (PE)-related mortality is decreasing in Europe. However, time trend... more Background Pulmonary embolism (PE)-related mortality is decreasing in Europe. However, time trends in the USA and Canada remain uncertain because the most recent analyses of PE-related mortality were published in the early 2000s. Methods For this retrospective epidemiological study, we accessed medically certified vital registration data from the WHO Mortality Database (USA and Canada, 2000-17) and the Multiple Cause of Death database produced by the Division of Vital Statistics of the US Centers for Disease Control and Prevention (CDC; US, 2000-18). We investigated contemporary time trends in PE-related mortality in the USA and Canada and the prevalence of conditions contributing to PE-related mortality reported on the death certificates. We also estimated PE-related mortality by age group and sex. A subgroup analysis by race was performed for the USA. Findings In the USA, the age-standardised annual mortality rate (PE as the underlying cause) decreased from 6•0 deaths per 100 000 population (95% CI 5•9-6•1) in 2000 to 4•4 deaths per 100 000 population (4•3-4•5) in 2006. Thereafter, it continued to decrease to 4•1 deaths per 100 000 population (4•0-4•2) in women in 2017 and plateaued at 4•5 deaths per 100 000 population (4•4-4•7) in men in 2017. Among adults aged 25-64 years, it increased after 2006. The median age at death from PE decreased from 73 years to 68 years (2000-18). The prevalence of cancer, respiratory diseases, and infections as a contributing cause of PE-related death increased in all age categories from 2000 to 2018. The annual age-standardised PE-related mortality was consistently higher by up to 50% in Black individuals than in White individuals; these rates were approximately 50% higher in White individuals than in those of other races. In Canada, the annual age-standardised mortality rate from PE as the underlying cause of death decreased from 4•7 deaths per 100 000 population (4•4-5•0) in 2000 to 2•6 deaths per 100 000 population (2•4-2•8) in 2017; this decline slowed after 2006 across age groups and sexes. Interpretation After 2006, the initially decreasing PE-related mortality rates in North America progressively reached a plateau in Canada, while a rebound increase was observed among young and middle-aged adults in the USA. These findings parallel recent upward trends in mortality from other cardiovascular diseases and might reflect increasing inequalities in the exposure to risk factors and access to health care.

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Potential Drug Interactions between Recombinant Interleukin-2 and Direct Oral Anticoagulants: Indirect Evidence from In Vivo Animal Studies

Hämostaseologie, 2020

Recombinant interleukin-2 (rIL-2) is indicated for metastatic renal cell carcinoma and melanoma. ... more Recombinant interleukin-2 (rIL-2) is indicated for metastatic renal cell carcinoma and melanoma. Over recent years low-dose rIL-2 has been studied for the treatment of autoimmune diseases and acute coronary syndrome because of its ability to expand and activate T regulatory (Treg) cells. However, several medical conditions potentially benefiting from rIL-2 administrations are characterized by an intrinsic prothrombotic risk, thus requiring concurrent anticoagulation. In our systematic review of the literature, we investigated the potential for drug interactions between oral anticoagulants and rIL-2 by assessing the influence of rIL-2 administration on transporters and cytochromes determining the pharmacokinetics of (direct) oral anticoagulants. We extracted data from 12 studies, consisting of 11 animal studies and one study in humans. Eight studies investigated the pharmacokinetics of P-glycoprotein (P-gp) substrates and reported that the intraperitoneal rIL-2 administration may inh...

Telemedicine and decentralized models of care: from anticoagulant monitoring to an expanded concept of vascular medicine

Internal and Emergency Medicine, 2019

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Microscopic colitis

World Journal of Gastroenterology, 2012

Microscopic colitis may be defined as a clinical syndrome, of unknown etiology, consisting of chr... more Microscopic colitis may be defined as a clinical syndrome, of unknown etiology, consisting of chronic watery diarrhea, with no alterations in the large bowel at the endoscopic and radiologic evaluation. Therefore, a definitive diagnosis is only possible by histological analysis. The epidemiological impact of this disease has become increasingly clear in the last years, with most data coming from Western countries. Microscopic colitis includes two histological subtypes [collagenous colitis (CC) and lymphocytic colitis (LC)] with no differences in clinical presentation and management. Collagenous colitis is characterized by a thickening of the subepithelial collagen layer that is absent in LC. The main feature of LC is an increase of the density of intra-epithelial lymphocytes in the surface epithelium. A number of pathogenetic theories have been proposed over the years, involving the role of luminal agents, autoimmunity, eosinophils, genetics (human leukocyte antigen), biliary acids, infections, alterations of pericryptal fibroblasts, and drug intake; drugs like ticlopidine, carbamazepine or ranitidine are especially associated with the development of LC, while CC is more frequently linked to cimetidine, non-steroidal antiinflammatory drugs and lansoprazole. Microscopic colitis typically presents as chronic or intermittent watery diarrhea, that may be accompanied by symptoms such as abdominal pain, weight loss and incontinence. Recent evidence has added new pharmacological options for the treatment of microscopic colitis: the role of steroidal therapy, especially oral budesonide, has gained relevance, as well as immunosuppressive agents such as azathioprine and 6-mercaptopurine. The use of anti-tumor necrosis factor-α agents, infliximab and adalimumab, constitutes a new, interesting tool for the treatment of microscopic colitis, but larger, adequately designed studies are needed to confirm existing data.

Efficacy of antioxidant therapy in improving painful chronic pancreatitis: A systematic review

Pancreatology, 2013

Background/aim: Background: Pancreatic pseudocysts are a common complication of acute and chronic... more Background/aim: Background: Pancreatic pseudocysts are a common complication of acute and chronic pancreatitis. While surgery is associated with significant complications and mortality, percutaneous drainage is associated with prolonged hospitalization and often times the need for other adjunctive treatment measures. Endoscopic drainage of pancreatic pseudocysts by expert endoscopists has become an accepted and is becoming increasingly popular. Aim: To assess the safety and the efficacy of single-step EUS-guided pseudocyst drainage, and evaluate the technical Feasibility and long-term outcome of this therapeutic procedure. Methods: Sixty-nine consecutive patients who had undergone Singlestep EUS-guided drainage of pancreatic pseudocysts were included. Controlled radial expansion wire guided balloon dilation of the puncture tract was performed followed by insertion 10 Fr. double pigtail stents were inserted into the pseudocyst from either the stomach or the duodenum in adults and 7F stents in children. We evaluated technical success, clinical response, adverse event of procedure and long-term follow-up results. Results: The mean age of 39 years for adults. Median pseudocyst size was 12.5 cm (range, 9-20 cm) in diameter. 56 patients had infected and rest of the patients had non-infected pseudocysts. Stent placement was successful in all patients. The technical success rate of EUS-guided drainage was 100%, and the treatment success rate was 98.5%. 54 patients had cystogastrostomy and rest of the patients had cystoduodenostomy with cyst drainage. There was only one case with an adverse event, perforation (1.5%). The case required emergency operation. 68 patients (98.5%) had complete resolution of a pseudocyst; with symptom relief. The double pigtail stent was removed in all cases after median duration of 10 weeks. Regarding long-term outcomes, recurrence of a pseudocyst was not observed any of our patients over a median follow-up of 58 weeks. Conclusions: A single-step approach EUS-guided transmural drainage technique is safe and is associated with high success rate. It can be the first choice for therapy of pancreatic pseudocyst with good technical feasibility, efficacy, and safety with long-term results are acceptable.

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Neoplastic spread after trauma: natural death or manslaughter?

Medicine, Science and the Law, 2010

We report an unusual death of a seemingly healthy 26-year-old man due to diffuse metastasization ... more We report an unusual death of a seemingly healthy 26-year-old man due to diffuse metastasization of adrenal paraganglioma caused by rupture of the primitive tumour with subsequent massive haemorrhage after a relatively minor trauma. Our report describes the results of forensic investigation and discusses the possible mechanisms of metastasization.

Isolated eosinophilic coronary arteritis

Journal of Clinical Pathology, 2010

P.18.4 Efficacy of Antioxidant Therapy in Improving Painful Chronic Pancreatitis: A Systematic Review

Digestive and Liver Disease, 2014

Lipomatous hypertrophy vs. cardiac hibernoma. What criteria differentiate them?

Cardiovascular Pathology, 2009

Subarachnoid Hemorrhage During Sexual Activity After Sildenafil Intake

American Journal of Forensic Medicine & Pathology, 2011

We report and describe an autopsy case of a man dead for rupture of cerebral artery aneurysm with... more We report and describe an autopsy case of a man dead for rupture of cerebral artery aneurysm with subsequent subarachnoid hemorrhage after sexual intercourse. Toxicologic analysis demonstrated that he had consumed sildenafil (Viagra). Although subarachnoid hemorrhage has been reported to be associated with sexual intercourse, it is not among the known adverse effects of sildenafil. However, sildenafil has been found to interact with vascular physiology via multiple mechanisms and in most of the vascular districts of the human body. This case provides an example of a very rare association between this drug and a fatal pathologic event and deserves to be added to the existing clinical knowledge about sildenafil and the pathophysiology of the events involved. This knowledge may be helpful in orienting further investigation into the mechanisms of action of sildenafil and their clinical implications.

Social determinants of health in pulmonary embolism management and outcome in hospitals: Insights from the United States nationwide inpatient sample

Research and Practice in Thrombosis and Haemostasis

Septic Pulmonary Embolism. A Contemporary Profile

Seminars in Thrombosis and Hemostasis

Septic pulmonary embolism (SPE) is a rare clinical entity that is distinct from the classic and m... more Septic pulmonary embolism (SPE) is a rare clinical entity that is distinct from the classic and more common non-septic thrombotic pulmonary embolism. SPE should be suspected in patients with a systemic acute inflammatory reaction or sepsis who develop signs and symptoms of pulmonary involvement. The diagnosis of SPE depends on the specific radiologic finding of multiple, peripheral, nodular, possibly cavitated lesions. SPE should prompt an immediate search for the primary source of infection; typically, right-sided infective endocarditis, cardiac implantable electronic devices, and septic thrombophlebitis as a complication of bone, skin, and soft tissue infection including Lemierre's syndrome, indwelling catheters, or direct inoculation via injection drug use. Invasive treatment of the infection source may be necessary; in thrombophlebitis, the efficacy and safety of anticoagulation remain undefined. Blood cultures may be negative, particularly among patients with recent antibio...

Erratum: Septic Pulmonary Embolism. A Contemporary Profile

Seminars in Thrombosis and Hemostasis

Cost‐of‐Illness Analysis of Long‐Term Health Care Resource Use and Disease Burden in Patients With Pulmonary Embolism: Insights From the PREFER in VTE Registry

Journal of the American Heart Association

Background As mortality from pulmonary embolism (PE) decreases, the personal and societal costs a... more Background As mortality from pulmonary embolism (PE) decreases, the personal and societal costs among survivors are receiving increasing attention. Detailing this burden would support an efficient public health resource allocation. We aimed to provide estimates for the economic and disease burden of PE also accounting for long‐term health care use and both direct and indirect costs beyond the acute phase. Methods and Results This is a cost‐of‐illness analysis with a bottom‐up approach based on data from the PREFER in VTE registry (Prevention of Thromboembolic Events—European Registry in Venous Thromboembolism). We calculated direct (clinical events and anticoagulation) and indirect costs (loss of productivity) of an acute PE event and its 12‐month follow‐up in 2020 Euros. We estimated a disability weight for the 12‐month post‐PE status and corresponding disability adjusted life years presumably owing to PE. Disease‐specific costs in the first year of follow‐up after an incident PE c...