Systemic Metabolomic Profiles in Adult Patients with Bacterial Sepsis: Characterization of Patient Heterogeneity at the Time of Diagnosis.

Sepsis is a dysregulated host response to infection that causes potentially life-threatening organ dysfunction. We investigated the serum metabolomic profile at hospital admission for patients with bacterial sepsis. The study included 60 patients; 35 patients fulfilled the most recent 2016 Sepsis-3 criteria whereas the remaining 25 patients only fulfilled the previous Sepsis-2 criteria and could therefore be classified as having systemic inflammatory response syndrome (SIRS). A total of 1011 identified metabolites were detected in our serum samples. Ninety-seven metabolites differed significantly when comparing Sepsis-3 and Sepsis-2/SIRS patients; 40 of these metabolites constituted a heterogeneous group of amino acid metabolites/peptides. When comparing patients with and without bacteremia, we identified 51 metabolites that differed significantly, including 16 lipid metabolites and 11 amino acid metabolites. Furthermore, 42 metabolites showed a highly significant association with the maximal total Sequential Organ Failure Assessment (SOFA )score during the course of the disease (i.e., Pearson's correlation test, p-value < 0.005, and correlation factor > 0.6); these top-ranked metabolites included 23 amino acid metabolites and a subset of pregnenolone/progestin metabolites. Unsupervised hierarchical clustering analyses based on all 42 top-ranked SOFA correlated metabolites or the subset of 23 top-ranked amino acid metabolites showed that most Sepsis-3 patients differed from Sepsis-2/SIRS patients in their systemic metabolic profile at the time of hospital admission. However, a minority of Sepsis-3 patients showed similarities with the Sepsis-2/SIRS metabolic profile even though several of them showed a high total SOFA score. To conclude, Sepsis-3 patients are heterogeneous with regard to their metabolic profile at the time of hospitalization.

Patients with Bacterial Sepsis Are Heterogeneous with Regard to Their Systemic Lipidomic Profiles.

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. In the present study, we investigated the systemic/serum lipidomic profile at the time of hospital admission for patients with bacterial sepsis. The study included 60 patients; 35 patients fulfilled the most recent 2016 Sepsis-3 criteria (referred to as Sepsis-3) whereas the remaining 25 patients had sepsis only according to the previous Sepsis-2 definition and could be classified as having Systemic Inflammatory Response Syndrome (SIRS). A total of 966 lipid metabolites were identified. Patients fulfilling the Sepsis-3 criteria differed from the Sepsis-2 patients with regard to only 15 lipid metabolites, and especially sphingolipids metabolism differed between these patient subsets. A total of only 43 metabolites differed between patients with and without bacteremia, including 12 lysophosphatidylcholines and 18 triacylglycerols (15 C18/C20 fatty acid metabolites decreased and three C14 myristate acid metabolites that were increased in bacteremia). Unsupervised hierarchical clustering analyses based on the identified sphingolipids, phosphatidylcholine and triacylglycerols showed that (i) the majority of Sepsis-3 patients differed from SIRS patients especially with regard to lysophosphatidylcholine levels; (ii) the minority of Sepsis-3 patients that clustered together with the majority of SIRS patients showed lower Sequential Organ Failure Assessment (SOFA) scores than the other Sepsis-3 patients; and (iii) the variation between the patients in the identified/altered sphingolipid and triacylglycerol metabolites further increased the heterogeneity of Sepsis-3 patients with regard to their systemic lipidomic profile at the time of diagnosis. To conclude, patients fulfilling the Sepsis-3 criteria differ with regard to their metabolic profile, and this variation depends on disease severity.

Long COVID in a prospective cohort of home-isolated patients.

Long-term complications after coronavirus disease 2019 (COVID-19) are common in hospitalized patients, but the spectrum of symptoms in milder cases needs further investigation. We conducted a long-term follow-up in a prospective cohort study of 312 patients-247 home-isolated and 65 hospitalized-comprising 82% of total cases in Bergen during the first pandemic wave in Norway. At 6 months, 61% (189/312) of all patients had persistent symptoms, which were independently associated with severity of initial illness, increased convalescent antibody titers and pre-existing chronic lung disease. We found that 52% (32/61) of home-isolated young adults, aged 16-30 years, had symptoms at 6 months, including loss of taste and/or smell (28%, 17/61), fatigue (21%, 13/61), dyspnea (13%, 8/61), impaired concentration (13%, 8/61) and memory problems (11%, 7/61). Our findings that young, home-isolated adults with mild COVID-19 are at risk of long-lasting dyspnea and cognitive symptoms highlight the importance of infection control measures, such as vaccination.

Carbapenem-Resistant Enterobacteriaceae-Implications for Treating Acute Leukemias, a Subgroup of Hematological Malignancies.

Acute leukemias (AL) are a group of aggressive malignant diseases associated with a high degree of morbidity and mortality. Patients with AL are highly susceptible to infectious diseases due to the disease itself, factors attributed to treatment, and specific individual risk factors. Enterobacteriaceae presence (e.g., Klebsiella pneumonia and Escherichia coli) is a frequent cause of bloodstream infections in AL patients. Carbapenem-resistant Enterobacteriaceae (CRE) is an emerging health problem worldwide; however, the incidence of CRE varies greatly between different regions. Carbapenem resistance in Enterobacteriaceae is caused by different mechanisms, and CRE may display various resistance profiles. Bacterial co-expression of genes conferring resistance to both broad-spectrum ß-lactam antibiotics (including carbapenems) and other classes of antibiotics may give rise to multidrug-resistant organisms (MDROs). The spread of CRE represents a major treatment challenge for clinicians due to lack of randomized clinical trials (RCTs), a limited number of antibiotics available, and the side-effects associated with them. Most research concerning CRE infections in AL patients are limited to case reports and retrospective reviews. Current research recommends treatment with older antibiotics, such as polymyxins, fosfomycin, older aminoglycosides, and in some cases carbapenems. To prevent the spread of resistant microbes, it is of pivotal interest to implement antibiotic stewardship to reduce broad-spectrum antibiotic treatment, but without giving too narrow a treatment to neutropenic infected patients.

Febrile Neutropenia in Acute Leukemia. Epidemiology, Etiology, Pathophysiology and Treatment.

Acute leukemias are a group of aggressive malignant diseases associated with a high degree of morbidity and mortality. An important cause of both the latter is infectious complications. Patients with acute leukemia are highly susceptible to infectious diseases due to factors related to the disease itself, factors attributed to treatment, and specific individual risk factors in each patient. Patients with chemotherapy-induced neutropenia are at particularly high risk, and microbiological agents include viral, bacterial, and fungal agents. The etiology is often unknown in infectious complications, although adequate patient evaluation and sampling have diagnostic, prognostic and treatment-related consequences. Bacterial infections include a wide range of potential microbes, both Gram-negative and Gram-positive species, while fungal infections include both mold and yeast. A recurring problem is increasing resistance to antimicrobial agents, and in particular, this applies to extended-spectrum beta-lactamase resistance (ESBL), Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE) and even carbapenemase-producing Enterobacteriaceae (CPE). International guidelines for the treatment of sepsis in leukemia patients include the use of broad-spectrum Pseudomonas-acting antibiotics. However, one should implant the knowledge of local microbiological epidemiology and resistance conditions in treatment decisions. In this review, we discuss infectious diseases in acute leukemia with a major focus on febrile neutropenia and sepsis, and we problematize the diagnostic, prognostic, and therapeutic aspects of infectious complications in this patient group. Meticulously and thorough clinical and radiological examination combined with adequate microbiology samples are cornerstones of the examination. Diagnostic and prognostic evaluation includes patient review according to the multinational association for supportive care in cancer (MASCC) and sequential organ failure assessment (SOFA) scoring system. Antimicrobial treatments for important etiological agents are presented. The main challenge for reducing the spread of resistant microbes is to avoid unnecessary antibiotic treatment, but without giving to narrow treatment to the febrile neutropenic patient that reduce the prognosis.

Francisella tularensis bacteraemia causing multi-organ failure.

Tularemia is a zoonosis caused by the gram-negative coccobacillus Francisella tularensis. The bacterium can be transmitted in several ways including direct contact with animal reservoirs, ingestion, inhalation and bites, and typical clinical symptoms are headache, fever, diarrhea and dyspnea. Francisella tularensis has two predominant subspecies (ssp), namely ssp. tularensis and ssp. holarctica. Ssp. holarctica is less virulent and does usually not cause fatal disease. We here present a 51-year-old male with sepsis and multi-organ failure caused by F. tularensis ssp. holarctica infection suggesting that atypical agents including F. tularensis should be considered in patients presenting symptoms of infections without response to standard treatments.

Successful eradication of leptomeningeal plasma cell disease.

Plasma cell leukaemia (PCL) is a rare and aggressive form of malignant monoclonal gammopathy characterized by the presence of high levels of plasma cells in peripheral blood. Central nervous system involvement of PCL has no established treatment and an extremely poor prognosis. We here present a 59-year-old male patient diagnosed with PCL, initially treated with induction chemotherapy followed by autologous peripheral blood hematopoietic stem cell transplantation. After achieving a partial response, he relapsed and presented with leptomeningeal disease. He was then successfully treated with dexamethasone, pomalidomide, and an intrathecal combination of methotrexate, methylprednisolone and cytarabine. This cleared his cerebrospinal fluid from plasma cells achieving a durable partial response.

Autonomous dysfunction in Lyme neuroborreliosis. A case report.

The diagnosis of Lyme neuroborreliosis should be considered whenever a patient presents with neurological symptoms and comes from an endemic area. However, atypical clinical presentation occurs including gastrointestinal manifestations because of autonomous dysfunction.

Hypomagnesemia in critically ill patients.

BACKGROUND: Magnesium (Mg) is essential for life and plays a crucial role in several biochemical and physiological processes in the human body. Hypomagnesemia is common in all hospitalized patients, especially in critically ill patients with coexisting electrolyte abnormalities. Hypomagnesemia may cause severe and potential fatal complications if not timely diagnosed and properly treated, and associate with increased mortality. MAIN BODY: Mg deficiency in critically ill patients is mainly caused by gastrointestinal and/or renal disorders and may lead to secondary hypokalemia and hypocalcemia, and severe neuromuscular and cardiovascular clinical manifestations. Because of the physical distribution of Mg, there are no readily or easy methods to assess Mg status. However, serum Mg and the Mg tolerance test are most widely used. There are limited studies to guide intermittent therapy of Mg deficiency in critically ill patients, but some empirical guidelines exist. Further clinical trials and critical evaluation of empiric Mg replacement strategies is needed. CONCLUSION: Patients at risk of Mg deficiency, with typical biochemical findings or clinical symptoms of hypomagnesemia, should be considered for treatment even with serum Mg within the normal range.

Non-curative surgery for aortoenteric fistula.

Graft infection with secondary aortic fistula is a rare complication following implantation of aortic prostheses, frequently occurring after emergency procedures and reoperations. The condition is associated with considerable morbidity and mortality. Curative treatment consists of explantation of the infected graft followed by fistula revision and implantation of a new graft in combination with antimicrobial therapy. Non-curative treatment with aortic stentgraft and long-term substitution treatment with antibiotics may be an option in cases where graft explantation is deemed too risky. We present an elderly patient with aortoenteric fistula following surgery for ruptured abdominal aortic aneurysm. Implantation of an aortic stentgraft and fistula revision was performed but the original aortic prosthesis was not explanted. The aortoenteric fistula recurred twice, but the patient has survived more than 12 years following non-curative surgery with good quality of life.

Hypomagnesemia as a potentially life-threatening adverse effect of omeprazole.

Hypomagnesemia can be caused by a wide range of diseases (e.g. gastrointestinal disorders, kidney diseases or endocrine disorders), but it can also be a side effect of several drugs. It can be asymptomatic or cause many different clinical symptoms, and the clinical manifestations mainly depend on the rate of development rather than the actual serum magnesium concentration. We here present a 40-year-old female patient with Torsade de pointes ventricular tachycardia and cardiac arrest caused by severe hypomagnesemia as an adverse effect of the proton pump inhibitor omeprazole.

[Changes in smoking habits among medical students in Bergen 2004-2006]. / Endring i røykevaner hos medisinstudenter i Bergen 2004-06.

BACKGROUND: Smoking and snuff habits among medical students are of interest because they may reflect the attitude to smoking and snuff among future doctors, but few longitudinal studies have been performed. MATERIAL AND METHOD: A standard questionnaire, developed by Statistics Norway, was handed out to all medical students at the University of Bergen during plenum lectures in the spring 2004 and 2006. The questionnaires were marked by personal codes to enable follow-up of smoking and snuff habits for each individual student during the study period. New questionnaires were sent by post to all students who did not respond after the initial handout. RESULTS: 799 medical students (89 %) responded in the spring 2004 and 789 students (84 %) in the spring 2006. The study revealed that 3 % of the students smoked regularly in 2004 and 1 % in 2006 and that 20 % were occasional smokers in 2004 and 18 in 2006. 15 % of the students were snuff users in 2004 and this had increased to 24 % in 2006. INTERPRETATION: A decrease was observed in both daily and occasional smokers among medical students in Bergen during the two-year study period. However, the frequency of snuff users increased. The frequency of regular smokers is low, but the number of occasional smokers is higher than in the general population of the same age.