A Rare Case of Streptococcus agalactiae Ventriculitis and Endocarditis.

Streptococcus agalactiae infection is typically seen in specific populations, including neonates, pregnant women, and the elderly. These patients have immature, lower, and waning immune systems, which makes them more susceptible to infections. Typical S. agalactiae infections manifest as cellulitis, bacteremia, endocarditis, meningitis, ventriculitis (a rare complication of meningitis), and osteomyelitis. In rare cases, a patient can present with two or more of these typical infection manifestations. The authors present a case of a 48-year-old female with a past medical history of hypothyroidism and chronic back pain who presented to the emergency department with altered mental status. The patient developed nausea and vomiting two days prior to presentation after a family gathering, followed by occipital headache and agitation. On arrival at the emergency department, the patient did not follow commands and was drowsy. The initial examination showed positive for Brudzinski and Kernig signs. The patient was tachycardic, tachypneic, and hypertensive. Initial computed tomography (CT) head without contrast was negative for any acute pathology. Neurology was consulted, and a bedside lumbar puncture was performed, which was significant for elevated opening pressure of 32 cm H2O. The patient was initially started on ceftriaxone, ampicillin, vancomycin, acyclovir, and dexamethasone. Magnetic resonance imaging (MRI) of the brain with and without contrast showed acute ventriculitis, mild leptomeningeal enhancement, and a right posterior corona radiata acute lacunar infarct. Meningitis panel, BioFire (BioFire Diagnostics, Salt Lake City, UT), was positive for S. agalactiae, and the patient was de-escalated to ceftriaxone. Cerebrospinal fluid and blood cultures returned positive for S. agalactiae. A transthoracic echocardiogram was negative for endocarditis, but a transesophageal echocardiogram was significant for a 0.7 × 0.4 cm mobile echodensity attached to the posterior leaflet of the mitral valve (P1/P2 scallop). Repeat blood cultures, additional cerebrospinal fluid analysis, and infectious workup remained negative. Cardiology was consulted and recommended medical treatment. The patient improved clinically, continued ceftriaxone, and was discharged to complete a total of six weeks of treatment with outpatient follow-up evaluations. This case depicts a rare presentation of endocarditis, meningitis, and ventriculitis S. agalactiae infection and the need for a definite treatment algorithm in the management of complicated conditions such as the one presented.

Sending a Message: Use of mRNA Vaccines to Target the Tumor Immune Microenvironment.

While cancer immunotherapies have become central to treatment, challenges associated with the ability of tumors to evade the immune system remain significant obstacles. At the heart of this issue is the tumor immune microenvironment, the complex interplay of the tumor microenvironment and the immune response. Recent advances in mRNA cancer vaccines represent major progress towards overcoming some of the challenges posed by deleterious components of the tumor immune microenvironment. Indeed, major breakthroughs in mRNA vaccine technology, such as the use of replacement nucleotides and lipid nanoparticle delivery, led to the vital success of mRNA vaccine technology in fighting COVID-19. This has in turn generated massive additional interest and investment in the platform. In this review, we detail recent research in the nature of the tumor immune microenvironment and in mRNA cancer vaccines and discuss applications by which mRNA cancer vaccines, often in combination with various adjuvants, represent major areas of potential in overcoming tumor immune microenvironment-imposed obstacles. To this end, we also review current mRNA cancer vaccine clinical trials.

Construct validity of the electronic Veterans Affairs Frailty Index against clinician frailty assessment.

BACKGROUND: Electronic frailty indices (eFIs) can expand measurement of frailty in research and practice and have demonstrated predictive validity in associations with clinical outcomes. However, their construct validity is less well studied. We aimed to assess the construct validity of the VA-FI, an eFI developed for use in the U.S. Veterans Affairs Healthcare System. METHODS: Veterans who underwent comprehensive geriatric assessments between January 31, 2019 and June 6, 2022 at VA Boston and had sufficient data documented for a comprehensive geriatric assessment-frailty index (CGA-FI) were included. The VA-FI, based on diagnostic and procedural codes, and the CGA-FI, based on geriatrician-measured deficits, were calculated for each patient. Geriatricians also assessed the Clinical Frailty Scale (CFS), functional status (ADLs and IADLs), and 4-meter gait speed (4MGS). RESULTS: A total of 132 veterans were included, with median age 81.4 years (IQR 75.8-88.7). Across increasing levels of VA-FI (<0.2; 0.2-0.4; >0.4), mean CGA-FI increased (0.24; 0.30; 0.40). The VA-FI was moderately correlated with the CGA-FI (r 0.45, p < 0.001). Every 0.1-unit increase in the VA-FI was associated with an increase in the CGA-FI (linear regression beta 0.05; 95% confidence interval [CI] 0.03-0.06), higher CFS category (ordinal regression OR 1.69; 95% CI 1.24-2.30), higher odds of ADL dependency (logistic regression OR 1.59; 95% CI 1.20-2.11), IADL dependency (logistic regression OR 1.68; 95% CI 1.23-2.30), and a decrease in 4MGS (linear regression beta -0.07, 95% CI -0.12 to -0.02). All models were adjusted for age and race, and associations held after further adjustment for the Charlson Comorbidity Index. CONCLUSION: Our results demonstrate the construct validity of the VA-FI through its associations with clinical measures of frailty, including summary frailty measures, functional status, and objective physical performance. Our findings complement others' in showing that eFIs can capture functional and mobility domains of frailty beyond just comorbidity and may be useful to measure frailty among populations and individuals.

Antitumor Activity of 1,18-Octadecanedioic Acid-Paclitaxel Complexed with Human Serum Albumin.

We describe the design, synthesis, and antitumor activity of an 18 carbon α,ω-dicarboxylic acid monoconjugated via an ester linkage to paclitaxel (PTX). This 1,18-octadecanedioic acid-PTX (ODDA-PTX) prodrug readily forms a noncovalent complex with human serum albumin (HSA). Preservation of the terminal carboxylic acid moiety on ODDA-PTX enables binding to HSA in the same manner as native long-chain fatty acids (LCFAs), within hydrophobic pockets, maintaining favorable electrostatic contacts between the ω-carboxylate of ODDA-PTX and positively charged amino acid residues of the protein. This carrier strategy for small molecule drugs is based on naturally evolved interactions between LCFAs and HSA, demonstrated here for PTX. ODDA-PTX shows differentiated pharmacokinetics, higher maximum tolerated doses and increased efficacy in vivo in multiple subcutaneous murine xenograft models of human cancer, as compared to two FDA-approved clinical formulations, Cremophor EL-formulated paclitaxel (crPTX) and Abraxane (nanoparticle albumin-bound (nab)-paclitaxel).