Browsing by Author "Jenks, Jeffrey D"

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    A challenging case of invasive pulmonary aspergillosis after near-drowning: a case report and literature review.
    (Infectious diseases in clinical practice (Baltimore, Md.), 2015-09) Jenks, Jeffrey D; Preziosi, Michael
    Near-drowning, a relatively common event, is often complicated by subsequent pneumonia. While endogenous and exogenous bacteria are typical pathogens, rarely fungi are as well. We report a complicated case of invasive pulmonary aspergillosis in a 30-year-old man after a near-drowning event. We also review the medical literature for similar cases. All cases of invasive pulmonary aspergillosis after near-drowning reported in the literature involve Aspergillus fumigatus. The majority of cases involved submersion in stagnant water after a motor vehicle accident (MVA). Treatment varied considerably, with amphotericin B used in the majority of cases. Morbidity was considerable with prolonged hospitalization occurring in every case, and mortality occurring in fifty percent of the reported cases. Although a rare complication of near-drowning, invasive pulmonary aspergillosis can occur and lead to significant morbidity and mortality. After near-drowning A. fumigatus isolated from the respiratory tract should be assumed to be a true pathogen and treated accordingly.
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    An update on current and novel molecular diagnostics for the diagnosis of invasive fungal infections
    (Expert Review of Molecular Diagnostics) Jenks, Jeffrey D; White, P Lewis; Kidd, Sarah E; Goshia, Tyler; Fraley, Stephanie I; Hoenigl, Martin; Thompson, George R
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    Antimicrobial-Resistant Shigella spp. in San Diego, California, USA, 2017-2020.
    (Emerging infectious diseases, 2022-06) Gaufin, Thaidra; Blumenthal, Jill; Ramirez-Sanchez, Claudia; Mehta, Sanjay; Pride, David T; Fierer, Joshua; Jenks, Jeffrey D
    Annually, Shigella spp. cause ≈188 million cases of diarrheal disease globally, including 500,000 cases in the United States; rates of antimicrobial resistance are increasing. To determine antimicrobial resistance and risk factors in San Diego, California, USA, we retrospectively reviewed cases of diarrheal disease caused by Shigella flexneri and S. sonnei diagnosed during 2017-2020. Of 128 evaluable cases, S. flexneri was slightly more common than S. sonnei; most cases were in persons who were gay or bisexual cisgender men, were living with HIV, were unhoused, or used methamphetamines. Overall, rates of resistance to azithromycin, fluoroquinolones, ampicillin, and trimethoprim/sulfamethoxazole (TMP/SMX) were comparable to the most recent national data reported from the Centers for Disease Control and Prevention; 55% of isolates were resistant to azithromycin, 23% to fluoroquinolones, 70% to ampicillin, and 83% to TMP/SMX. The rates that we found for TMP/SMX were slightly higher than those in national data.
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    Blood Aspergillus PCR: The Good, the Bad, and the Ugly.
    (Journal of fungi (Basel, Switzerland), 2020-01) Egger, Matthias; Jenks, Jeffrey D; Hoenigl, Martin; Prattes, Juergen
    Invasive Aspergillosis (IA) is one of the most common invasive fungal diseases and is accompanied by high morbidity and mortality. In order to maximize patient outcomes and survival, early and rapid diagnosis has been shown to be pivotal. Hence, diagnostic tools aiding and improving the diagnostic process are ambitiously searched for. In this context, polymerase chain reaction (PCR) may represent a potential candidate. Its additional value and benefits in diagnosis have been demonstrated and are scientifically established. Nevertheless, standardized and widespread usage is sparse because several factors influence diagnostic quality and need to be considered in order to optimize diagnostic performance and outcome. In the following review, the current role of PCR in the diagnosis of IA is explored, with special focus on the strengths and limitations of PCR in different settings.
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    Breakthrough invasive fungal infections: Who is at risk?
    (Mycoses, 2020-10) Jenks, Jeffrey D; Cornely, Oliver A; Chen, Sharon C-A; Thompson, George R; Hoenigl, Martin
    The epidemiology of invasive fungal infections (IFIs) in immunocompromised individuals has changed over the last few decades, partially due to the increased use of antifungal agents to prevent IFIs. Although this strategy has resulted in an overall reduction in IFIs, a subset of patients develop breakthrough IFIs with substantial morbidity and mortality in this population. Here, we review the most significant risk factors for breakthrough IFIs in haematology patients, solid organ transplant recipients, and patients in the intensive care unit, focusing particularly on host factors, and highlight areas that require future investigation.
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    Broad spectrum triazoles for invasive mould infections in adults: Which drug and when?
    (Medical mycology, 2019-04) Jenks, Jeffrey D; Mehta, Sanjay R; Hoenigl, Martin
    Invasive mould infections are an increasing cause of morbidity and mortality globally, mainly due to increasing numbers of immunocompromised individuals at risk for fungal infections. The introduction of broad spectrum triazoles, which are much better tolerated compared to conventional amphotericin B formulations, has increased survival, particularly in invasive mould infection. However, early initiation of appropriate antifungal treatment remains a major predictor of outcome in invasive mould infection, but despite significant advances in diagnosis of these diseases, early diagnosis remains a challenge. As a result, prophylaxis with mould-active triazoles is widely used for those patients at highest risk for invasive mould infection, including patients with prolonged neutropenia after induction chemotherapy for acute myeloid leukemia and patients with graft-versus-host-disease. Posaconazole is the recommended drug of choice for antimould prophylaxis in these high-risk patients. Voriconazole has its primary role in treatment of invasive aspergillosis but not in prophylaxis. Recently, isavuconazole has been introduced as an excellent alternative to voriconazole for primary treatment of invasive aspergillosis in patients with hematological malignancies. Compared to voriconazole, isavuconazole and posaconazole have broader activity against moulds and are therefore also an option for treatment of mucormycosis in the presence of intolerance or contraindications against liposomal amphotericin B.
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    Clinical characteristics and outcomes of invasive Lomentospora prolificans infections: Analysis of patients in the FungiScope® registry.
    (Mycoses, 2020-05) Jenks, Jeffrey D; Seidel, Danila; Cornely, Oliver A; Chen, Sharon; van Hal, Sebastiaan; Kauffman, Carol; Miceli, Marisa H; Heinemann, Melina; Christner, Martin; Jover Sáenz, Alfredo; Burchardt, Alexander; Kemmerling, Björn; Herbrecht, Raoul; Steinmann, Joerg; Shoham, Shmuel; Gräber, Sandra; Pagano, Livio; Deeren, Dries; Slavin, Monica A; Hoenigl, Martin
    OBJECTIVES:Invasive fungal infections caused by Lomentospora prolificans are associated with very high mortality rates and can be challenging to treat given pan-drug resistance to available antifungal agents. The objective of this study was to describe the clinical presentation and outcomes in a cohort of patients with invasive L prolificans infections. METHODS:We performed a retrospective review of medical records of patients with invasive L prolificans infection in the FungiScope® registry of rare invasive fungal infections. Patients diagnosed between 01 January 2008 and 09 September 2019 were included in for analysis. RESULTS:The analysis included 41 patients with invasive L prolificans infection from eight different countries. Haematological/oncological malignancies were the most frequent underlying disease (66%), disseminated infection was frequent (61%), and the lung was the most commonly involved organ (44%). Most infections (59%) were breakthrough infections. Progression/deterioration/treatment failure was observed in 23/40 (58%) of patients receiving antifungal therapy. In total, 21/41 (51%) patients, and 77% of patients with underlying haematological/oncological malignancy, had a fatal outcome attributed to invasive fungal infection. Combination antifungal therapy was frequent (24/40) and associated with improved survival. In particular, treatment regimens including terbinafine were significantly associated with higher treatment success at final assessment (P = .012), with a positive trend observed for treatment regimens that included voriconazole (P = .054). CONCLUSIONS:Lomentospora prolificans infections were associated with mortality rates of 77% and above in patients with underlying haematological/oncological malignancies and those with disseminated infections. While combination therapy is the preferred option for now, the hope lies with novel antifungals currently under development.
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    Combating COVID-19 Vaccine Inequity During the Early Stages of the COVID-19 Pandemic.
    (Journal of racial and ethnic health disparities, 2023-03) Mortiboy, Marissa; Zitta, John-Paul; Carrico, Savannah; Stevens, Elizabeth; Smith, Alecia; Morris, Corey; Jenkins, Rodney; Jenks, Jeffrey D
    Throughout the COVID-19 pandemic, populations of color have been disproportionately impacted, with higher rates of infection, hospitalization, and mortality, compared to non-Hispanic whites. These disparities in health outcomes are likely related to a combination of factors including underlying socioeconomic inequities, unequal access to healthcare, higher rates of employment in essential or public-facing occupations, language barriers, and COVID-19 vaccine inequities. In this manuscript the authors discuss strategies of how one local health department responded to vaccine inequities to better serve historically excluded communities throughout the early stages of the COVID-19 pandemic in 2021. These efforts helped increase vaccination rates in marginalized communities, primarily in the Black or African American population in Durham County, North Carolina.
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    COVID-19 Associated Pulmonary Aspergillosis (CAPA)-From Immunology to Treatment.
    (Journal of fungi (Basel, Switzerland), 2020-06) Arastehfar, Amir; Carvalho, Agostinho; van de Veerdonk, Frank L; Jenks, Jeffrey D; Koehler, Philipp; Krause, Robert; Cornely, Oliver A; S Perlin, David; Lass-Flörl, Cornelia; Hoenigl, Martin
    Like severe influenza, coronavirus disease-19 (COVID-19) resulting in acute respiratory distress syndrome (ARDS) has emerged as an important disease that predisposes patients to secondary pulmonary aspergillosis, with 35 cases of COVID-19 associated pulmonary aspergillosis (CAPA) published until June 2020. The release of danger-associated molecular patterns during severe COVID-19 results in both pulmonary epithelial damage and inflammatory disease, which are predisposing risk factors for pulmonary aspergillosis. Moreover, collateral effects of host recognition pathways required for the activation of antiviral immunity may, paradoxically, contribute to a highly permissive inflammatory environment that favors fungal pathogenesis. Diagnosis of CAPA remains challenging, mainly because bronchoalveolar lavage fluid galactomannan testing and culture, which represent the most sensitive diagnostic tests for aspergillosis in the ICU, are hindered by the fact that bronchoscopies are rarely performed in COVID-19 patients due to the risk of disease transmission. Similarly, autopsies are rarely performed, which may result in an underestimation of the prevalence of CAPA. Finally, the treatment of CAPA is complicated by drug-drug interactions associated with broad spectrum azoles, renal tropism and damage caused by SARS-CoV-2, which may challenge the use of liposomal amphotericin B, as well as the emergence of azole-resistance. This clinical reality creates an urgency for new antifungal drugs currently in advanced clinical development with more promising pharmacokinetic and pharmacodynamic profiles.
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    Cystic Mediastinal Thymic Lymphangioma Mimicking Echinococcal Cyst.
    (Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2015-10) Jenks, Jeffrey D; Katsivas, Theodoros F
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    Diagnosis of Breakthrough Fungal Infections in the Clinical Mycology Laboratory: An ECMM Consensus Statement.
    (Journal of fungi (Basel, Switzerland), 2020-10) Jenks, Jeffrey D; Gangneux, Jean-Pierre; Schwartz, Ilan S; Alastruey-Izquierdo, Ana; Lagrou, Katrien; Thompson Iii, George R; Lass-Flörl, Cornelia; Hoenigl, Martin; European Confederation of Medical Mycology (ECMM) Council Investigators
    Breakthrough invasive fungal infections (bIFI) cause significant morbidity and mortality. Their diagnosis can be challenging due to reduced sensitivity to conventional culture techniques, serologic tests, and PCR-based assays in patients undergoing antifungal therapy, and their diagnosis can be delayed contributing to poor patient outcomes. In this review, we provide consensus recommendations on behalf of the European Confederation for Medical Mycology (ECMM) for the diagnosis of bIFI caused by invasive yeasts, molds, and endemic mycoses, to guide diagnostic efforts in patients receiving antifungals and support the design of future clinical trials in the field of clinical mycology. The cornerstone of lab-based diagnosis of breakthrough infections for yeast and endemic mycoses remain conventional culture, to accurately identify the causative pathogen and allow for antifungal susceptibility testing. The impact of non-culture-based methods are not well-studied for the definite diagnosis of breakthrough invasive yeast infections. Non-culture-based methods have an important role for the diagnosis of breakthrough invasive mold infections, in particular invasive aspergillosis, and a combination of testing involving conventional culture, antigen-based assays, and PCR-based assays should be considered. Multiple diagnostic modalities, including histopathology, culture, antibody, and/or antigen tests and occasionally PCR-based assays may be required to diagnose breakthrough endemic mycoses. A need exists for diagnostic tests that are effective, simple, cheap, and rapid to enable the diagnosis of bIFI in patients taking antifungals.
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    Drug-Resistant Fungi: An Emerging Challenge Threatening Our Limited Antifungal Armamentarium.
    (Antibiotics (Basel, Switzerland), 2020-12) Arastehfar, Amir; Gabaldón, Toni; Garcia-Rubio, Rocio; Jenks, Jeffrey D; Hoenigl, Martin; Salzer, Helmut JF; Ilkit, Macit; Lass-Flörl, Cornelia; Perlin, David S
    The high clinical mortality and economic burden posed by invasive fungal infections (IFIs), along with significant agricultural crop loss caused by various fungal species, has resulted in the widespread use of antifungal agents. Selective drug pressure, fungal attributes, and host- and drug-related factors have counteracted the efficacy of the limited systemic antifungal drugs and changed the epidemiological landscape of IFIs. Species belonging to Candida, Aspergillus, Cryptococcus, and Pneumocystis are among the fungal pathogens showing notable rates of antifungal resistance. Drug-resistant fungi from the environment are increasingly identified in clinical settings. Furthermore, we have a limited understanding of drug class-specific resistance mechanisms in emerging Candida species. The establishment of antifungal stewardship programs in both clinical and agricultural fields and the inclusion of species identification, antifungal susceptibility testing, and therapeutic drug monitoring practices in the clinic can minimize the emergence of drug-resistant fungi. New antifungal drugs featuring promising therapeutic profiles have great promise to treat drug-resistant fungi in the clinical setting. Mitigating antifungal tolerance, a prelude to the emergence of resistance, also requires the development of effective and fungal-specific adjuvants to be used in combination with systemic antifungals.
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    Early cerebritis resulting in a first-time seizure in an otherwise healthy young man.
    (Infectious diseases in clinical practice (Baltimore, Md.), 2016-11) Jenks, Jeffrey D; Benson, Constance A
    We report the case of an otherwise healthy 28-year-old-man who presented with a first-time seizure. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a circumscribed left frontal lobe heterogeneous mass most consistent with a neoplasm. He underwent left supraorbital craniotomy with mass resection of the lesion, with histopathology of the brain tissue revealing heightened cellularity with perivascular neutrophilic predominance and neutrophils percolating through the brain parenchyma and surrounding cortical neurons, most consistent with a diagnosis of early cerebritis. He completed six weeks of empiric antimicrobial therapy with resolution of his seizures. Early cerebritis, which was elegantly demonstrated on histopathology in this case, is an uncommon diagnosis as patients typically present later with progressive disease and signs and symptoms reflective of an underlying brain abscess.
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    Early Monoclonal Antibody Administration Can Reduce Both Hospitalizations and Mortality in High-Risk Outpatients With Coronavirus Disease 2019 (COVID-19).
    (Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2022-03) Jenks, Jeffrey D; Aslam, Saima; Horton, Lucy E; Law, Nancy; Bharti, Ajay; Logan, Cathy; Taremi, Mahnaz; Vaida, Florin; Ritter, Michele; COVID-19 Clinic Team
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    Fungal Endocarditis: Pathophysiology, Epidemiology, Clinical Presentation, Diagnosis, and Management.
    (Clinical microbiology reviews, 2023-07) Thompson, George R; Jenks, Jeffrey D; Baddley, John W; Lewis, James S; Egger, Matthias; Schwartz, Ilan S; Boyer, Johannes; Patterson, Thomas F; Chen, Sharon C-A; Pappas, Peter G; Hoenigl, Martin
    Fungal endocarditis accounts for 1% to 3% of all infective endocarditis cases, is associated with high morbidity and mortality (>70%), and presents numerous challenges during clinical care. Candida spp. are the most common causes of fungal endocarditis, implicated in over 50% of cases, followed by Aspergillus and Histoplasma spp. Important risk factors for fungal endocarditis include prosthetic valves, prior heart surgery, and injection drug use. The signs and symptoms of fungal endocarditis are nonspecific, and a high degree of clinical suspicion coupled with the judicious use of diagnostic tests is required for diagnosis. In addition to microbiological diagnostics (e.g., blood culture for Candida spp. or galactomannan testing and PCR for Aspergillus spp.), echocardiography remains critical for evaluation of potential infective endocarditis, although radionuclide imaging modalities such as 18F-fluorodeoxyglucose positron emission tomography/computed tomography are increasingly being used. A multimodal treatment approach is necessary: surgery is usually required and should be accompanied by long-term systemic antifungal therapy, such as echinocandin therapy for Candida endocarditis or voriconazole therapy for Aspergillus endocarditis.
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    Global guideline for the diagnosis and management of rare mould infections: an initiative of the European Confederation of Medical Mycology in cooperation with the International Society for Human and Animal Mycology and the American Society for Microbiology.
    (The Lancet. Infectious diseases, 2021-08) Hoenigl, Martin; Salmanton-García, Jon; Walsh, Thomas J; Nucci, Marcio; Neoh, Chin Fen; Jenks, Jeffrey D; Lackner, Michaela; Sprute, Rosanne; Al-Hatmi, Abdullah MS; Bassetti, Matteo; Carlesse, Fabianne; Freiberger, Tomas; Koehler, Philipp; Lehrnbecher, Thomas; Kumar, Anil; Prattes, Juergen; Richardson, Malcolm; Revankar, Sanjay; Slavin, Monica A; Stemler, Jannik; Spiess, Birgit; Taj-Aldeen, Saad J; Warris, Adilia; Woo, Patrick CY; Young, Jo-Anne H; Albus, Kerstin; Arenz, Dorothee; Arsic-Arsenijevic, Valentina; Bouchara, Jean-Philippe; Chinniah, Terrence Rohan; Chowdhary, Anuradha; de Hoog, G Sybren; Dimopoulos, George; Duarte, Rafael F; Hamal, Petr; Meis, Jacques F; Mfinanga, Sayoki; Queiroz-Telles, Flavio; Patterson, Thomas F; Rahav, Galia; Rogers, Thomas R; Rotstein, Coleman; Wahyuningsih, Retno; Seidel, Danila; Cornely, Oliver A
    With increasing numbers of patients needing intensive care or who are immunosuppressed, infections caused by moulds other than Aspergillus spp or Mucorales are increasing. Although antifungal prophylaxis has shown effectiveness in preventing many invasive fungal infections, selective pressure has caused an increase of breakthrough infections caused by Fusarium, Lomentospora, and Scedosporium species, as well as by dematiaceous moulds, Rasamsonia, Schizophyllum, Scopulariopsis, Paecilomyces, Penicillium, Talaromyces and Purpureocillium species. Guidance on the complex multidisciplinary management of infections caused by these pathogens has the potential to improve prognosis. Management routes depend on the availability of diagnostic and therapeutic options. The present recommendations are part of the One World-One Guideline initiative to incorporate regional differences in the epidemiology and management of rare mould infections. Experts from 24 countries contributed their knowledge and analysed published evidence on the diagnosis and treatment of rare mould infections. This consensus document intends to provide practical guidance in clinical decision making by engaging physicians and scientists involved in various aspects of clinical management. Moreover, we identify areas of uncertainty and constraints in optimising this management.
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    Immune Parameters for Diagnosis and Treatment Monitoring in Invasive Mold Infection.
    (Journal of fungi (Basel, Switzerland), 2019-12) Jenks, Jeffrey D; Rawlings, Stephen A; Garcia-Vidal, Carol; Koehler, Philipp; Mercier, Toine; Prattes, Juergen; Lass-Flörl, Cornelia; Martin-Gomez, M Teresa; Buchheidt, Dieter; Pagano, Livio; Gangneux, Jean-Pierre; van de Veerdonk, Frank L; Netea, Mihai G; Carvalho, Agostinho; Hoenigl, Martin
    Infections caused by invasive molds, including Aspergillus spp., can be difficult to diagnose and remain associated with high morbidity and mortality. Thus, early diagnosis and targeted systemic antifungal treatment remains the most important predictive factor for a successful outcome in immunocompromised individuals with invasive mold infections. Diagnosis remains difficult due to low sensitivities of diagnostic tests including culture and other mycological tests for mold pathogens, particularly in patients on mold-active antifungal prophylaxis. As a result, antifungal treatment is rarely targeted and reliable markers for treatment monitoring and outcome prediction are missing. Thus, there is a need for improved markers to diagnose invasive mold infections, monitor response to treatment, and assist in determining when antifungal therapy should be escalated, switched, or can be stopped. This review focuses on the role of immunologic markers and specifically cytokines in diagnosis and treatment monitoring of invasive mold infections.
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    Impact of climate change and natural disasters on fungal infections
    (The Lancet Microbe, 2024-03) Seidel, Danila; Wurster, Sebastian; Jenks, Jeffrey D; Sati, Hatim; Gangneux, Jean-Pierre; Egger, Matthias; Alastruey-Izquierdo, Ana; Ford, Nathan P; Chowdhary, Anuradha; Sprute, Rosanne; Cornely, Oliver; Thompson, George R; Hoenigl, Martin; Kontoyiannis, Dimitrios P
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    Improving the rates of Aspergillus detection: an update on current diagnostic strategies.
    (Expert review of anti-infective therapy, 2019-01) Jenks, Jeffrey D; Salzer, Helmut JF; Hoenigl, Martin

    Introduction

    The spectrum of disease caused by Aspergillus spp. is dependent on the immune system of the host, and ranges from invasive aspergillosis (IA) to chronic pulmonary aspergillosis (CPA). Early and reliable diagnosis of Aspergillus disease is important to decrease associated morbidity and mortality. Areas covered: The following review will give an update on current diagnostic strategies for the diagnosis of IA and CPA. Expert commentary: Several new diagnostics for IA (including point-of-care tests) are now available to complement galactomannan testing. In particular, immunoPET/MRI imaging may be a promising approach for diagnosing IA in the near future. Notably, nearly all new biomarkers and tests for IA have been evaluated in the hematology setting only. Validation of biomarkers and tests is therefore needed for the increasing proportion of patients who develop IA outside the hematology setting. As an important first step, reliable definitions of IA are needed for non-hematology settings as clinical presentation and radiologic findings differ in these settings. CPA diagnosis is based on a combination of radiological findings in chest CT, mycological evidence (e.g. by the Aspergillus-specific IgG assay), exclusion of alternative diagnosis and chronicity. ([18F]FDG) PET/CT and immuno PET/MRI imaging are promising new imaging approaches.