While many diseases of aging have been linked to the immunological system, immune metrics with which to identify the most at-risk individuals are lacking. We studied the blood immunome of 1001 individuals aged 8-96 and developed a deep learning method based on patterns of systemic age-related inflammation. The resulting inflammatory clock of aging (iAge) tracked with multiple morbidities, immunosenescence, frailty and cardiovascular aging. We demonstrate that iAge is associated with exceptional longevity in a separate cohort of centenarians. The strongest contributor to this metric was the chemokine CXCL9, which was involved in cardiac aging, adverse cardiac remodeling, and decreased vascular function.Furthermore, aging endothelial cells in human and mice show loss of function, indicators of early cellular senescence and hallmark phenotypes of arterial stiffness, all of which are reversed by silencing CXCL9. In conclusion, we identify a key role of CXCL9 in age-related systemic chronic inflammation and derive a novel metric for age-related multimorbidity that can also be used for early detection of age-related clinical phenotypes.

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Despite myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) affecting millions of people worldwide, many clinicians lack the knowledge to appropriately diagnose or manage ME/CFS. Unfortunately, clinical guidance has been scarce, obsolete, or potentially harmful. Consequently, up to 91% of patients in the United States remain undiagnosed, and those diagnosed often receive inappropriate treatment. These problems are of increasing importance because after acute COVID-19, a significant percentage of people remain ill for many months with an illness similar to ME/CFS. In 2015, the US National Academy of Medicine published new evidence-based clinical diagnostic criteria that have been adopted by the US Centers for Disease Control and Prevention. Furthermore, the United States and other governments as well as major health care organizations have recently withdrawn graded exercise and cognitive-behavioral therapy as the treatment of choice for patients with ME/CFS. Recently, 21 clinicians specializing in ME/CFS convened to discuss best clinical practices for adults affected by ME/CFS. This article summarizes their top recommendations for generalist and specialist health care providers based on recent scientific progress and decades of clinical experience. There are many steps that clinicians can take to improve the health, function, and quality of life of those with ME/CFS, including those in whom ME/CFS develops after COVID-19. Patients with a lingering illness that follows acute COVID-19 who do not fully meet criteria for ME/CFS may also benefit from these approaches.

Background Standard testing fails to identify a pathogen in most patients with febrile neutropenia (FN). We evaluated the ability of the Karius microbial cell-free DNA (mcfDNA) sequencing Test (KT) to identify infectious etiologies of FN and its impact on antimicrobial management. Methods This prospective study (ClinicalTrials.gov; NCT02912117) enrolled and analyzed 55 patients with FN. Up to 5 blood samples were collected per subject within 24h of fever onset (T1) and every 2-3 days. KT results were compared to blood culture (BC) and standard microbiological testing (SMT) results. Results Positive agreement was defined as KT identification of ≥1 isolate also detected by BC. At T1, positive and negative agreement were 90% (9/10) and 31% (14/45) respectively; 61% of KT detections were polymicrobial. Clinical adjudication by 3 independent infectious diseases specialists categorized Karius results as: unlikely to cause FN (N=0); Definite (N=12): KT identified ≥1 organism also found by SMT within 7 days; Probable (N=19): KT result was compatible with a clinical diagnosis; Possible (N=10): KT result was consistent with infection but not considered a common cause of FN. Definite, probable and possible cases were deemed true positives. Following adjudication, KT sensitivity and specificity were 85% (41/48) and 100% (14/14) respectively. Calculated time to diagnosis was generally shorter with KT (87%). Adjudicators determined real-time KT results could have allowed early optimization of antimicrobials in 47% of patients, by addition of antibacterials (20%) (mostly against anaerobes [12.7%]), antivirals (14.5%) and/or antifungals (3.6%); and antimicrobial narrowing in 27.3% of cases. Conclusion KT shows promise in the diagnosis and treatment optimization of FN.

Background Rising antimicrobial resistance rates may impact the efficacy of empirical antibiotic treatment for febrile neutropenia in high-risk cancer patients. Lacking contemporary data about the epidemiology, antibiotic resistance patterns, and clinical outcomes from bloodstream infections (BSI) in U.S. cancer patients, it is unclear if current guidelines remain relevant. Methods In a cross-sectional study, fourteen U.S. cancer centers prospectively identified BSIs in high-risk FN patients, including those receiving chemotherapy for hematologic malignancies or hematopoietic stem cell transplantation. Results Among 389 organsims causing BSI in 343 patients, there was an equal distribution of Gram-negative (GN) and Gram-positive (GP) bacteria, with variability across centers. Cefepime and piperacillin-tazobactam were the most commonly prescribed empirical antibiotics for FN, at 62% and 23% respectively; a GP-directed agent was empirically included in nearly half of all FN episodes within the first 24 hours. Susceptibility to fluoroquinolones, cefepime, piperacillin-tazobactam, and carbapenems was 49%, 84%, 88% and 96% respectively among GN isolates. Critical illness (CrI), defined as a new requirement for mechanical ventilation, vasopressor or death within 30 days, occurred in 15% and did not correlate with fluoroquinolone prophylaxis, organism type, initial antibiotics or adequacy of coverage. Only severity of illness at presentation, signified by a Pitt bacteremia score > 2, predicted for critical illness within 30 days. Mortality was 4% by day 7 and 10% overall. Conclusion In accordance with U.S. guidelines, cefepime or piperacillin-tazobactam remain effective agents or empirical treatment for high risk cancer patients with FN who are stable at presentation, maintaining high GN pathogen susceptibility and yielding excellent outcomes.

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Cancer treatment, especially hormonal therapy and therapy directed toward the pelvis, can contribute to sexual problems, as can depression and anxiety, which are common in cancer survivors. Thus, sexual dysfunction is common in survivors and can cause increased distress and have a significant negative impact on quality of life. This section of the NCCN Guidelines for Survivorship provides screening, evaluation, and treatment recommendations for female sexual problems, including those related to sexual desire, arousal, orgasm, and pain.

Myalgic encephalomyelitis, or chronic fatigue syndrome (ME/CFS) is a serious disease whose cause has yet to be identified. Objective markers of the disease are also not well understood and would serve as important tools in diagnosis and management. One potential biomarker or transmitter of immune signals in ME/CFS is the extracellular vesicle (EV) compartment. These small, membrane bound particles have been shown to play a key role in intercellular signaling. Our laboratory has focused on methods of detection of EVS in clinical samples. In this study we explored whether the prevalence of EVs in the plasma of participants with mild or severe ME/CFS differed from the plasma of healthy control participants. By staining for multiple cell surface molecules, plasma EVs could be fingerprinted as to their cell of origin. Our study revealed a significant correlation between severe ME/CSF and levels of EVs bearing the B cell marker CD19 and the platelet marker CD41a, though these changes were not significant after correction for multiple comparisons. These findings point to potential dysregulation of B cell and platelet activation or homeostasis in ME/CFS, which warrants validation in a replication cohort and further exploration of potential mechanisms underlying the association.