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Antibiotics are a mainstay of modern medicine, but as they kill their target pathogen(s), they often affect the commensal microbiota. Antibiotic-induced microbiome dysbiosis is a growing research focus and health concern, often assessed via analysis of fecal samples. However, such analysis does not inform how antibiotics influence the microbiome across the whole host or how such changes subsequently alter host chemistry. In this study, we investigated the acute (1 day postadministration) and delayed (6 days postadministration) effects of a single parenteral dose of two common antibiotics, ampicillin or vancomycin, on the global metabolome and microbiome of mice across 77 different body sites from 25 different organs. The broader-spectrum agent ampicillin had the greatest impact on the microbiota in the lower gastrointestinal tract (cecum and colon), where microbial diversity is highest. In the metabolome, the greatest effects were seen 1 day posttreatment, and changes in metabolite abundances were not confined to the gut. The local abundance of ampicillin and its metabolites correlated with increased metabolome effect size and a loss of alpha diversity versus control mice. Additionally, small peptides were elevated in the lower gastrointestinal tract of mice 1 day after antibiotic treatment. While a single parenteral dose of antibiotic did not drastically alter the microbiome, nevertheless, changes in the metabolome were observed both within and outside the gut. This study provides a framework for how whole-organism -omics approaches can be employed to understand the impact of antibiotics on the entire host.IMPORTANCE We are just beginning to understand the unintended effects of antibiotics on our microbiomes and health. In this study, we aimed to define an approach by which one could obtain a comprehensive picture of (i) how antibiotics spatiotemporally impact commensal microbes throughout the gut and (ii) how these changes influence host chemistry throughout the body. We found that just a single dose of antibiotic altered host chemistry in a variety of organs and that microbiome alterations were not uniform throughout the gut. As technological advances increase the feasibility of whole-organism studies, we argue that using these approaches can provide further insight on both the wide-ranging effects of antibiotics on health and how to restore microbial communities to mitigate these effects.

Group B Streptococcus (GBS) causes frequent urinary tract infection (UTI) in susceptible populations, including individuals with type 2 diabetes and pregnant women; however, specific host factors responsible for increased GBS susceptibility in these populations are not well characterized. Here, we investigate cathelicidin, a cationic antimicrobial peptide, known to be critical for defense during UTI with uropathogenic Escherichia coli (UPEC). We observed a loss of antimicrobial activity of human and mouse cathelicidins against GBS and UPEC in synthetic urine and no evidence for increased cathelicidin resistance in GBS urinary isolates. Furthermore, we found that GBS degrades cathelicidin in a protease-dependent manner. Surprisingly, in a UTI model, cathelicidin-deficient (Camp-/-) mice showed decreased GBS burdens and mast cell recruitment in the bladder compared to levels in wild-type (WT) mice. Pharmacologic inhibition of mast cells reduced GBS burdens and histamine release in WT but not Camp-/- mice. Streptozotocin-induced diabetic mice had increased bladder cathelicidin production and mast cell recruitment at 24 h postinfection with GBS compared to levels in nondiabetic controls. We propose that cathelicidin is an important immune regulator but ineffective antimicrobial peptide against GBS in urine. Combined, our findings may in part explain the increased frequency of GBS UTI in diabetic and pregnant individuals.IMPORTANCE Certain populations such as diabetic individuals are at increased risk for developing urinary tract infections (UTI), although the underlying reasons for this susceptibility are not fully known. Additionally, diabetics are more likely to become infected with certain types of bacteria, such as group B Streptococcus (GBS). In this study, we find that an antimicrobial peptide called cathelicidin, which is thought to protect the bladder from infection, is ineffective in controlling GBS and alters the type of immune cells that migrate to the bladder during infection. Using a mouse model of diabetes, we observe that diabetic mice are more susceptible to GBS infection even though they also have more infiltrating immune cells and increased production of cathelicidin. Taken together, our findings identify this antimicrobial peptide as a potential contributor to increased susceptibility of diabetic individuals to GBS UTI.

Objectives: Tumors involving the vagus nerve are often clinically silent. We offer a case series with different clinical presentations and distinctive post-surgical sequelae that highlight some of the challenges associated with managing cervical vagal nerve tumors. Methods: Single-institution, retrospective review of patients with tumors involving the vagus nerve. We describe clinical presentations and postoperative sequelae of five patients who underwent surgical management of vagal nerve pathology with atypical presentation or subsequent clinical course. Results: Here, we present five patients treated at our institution for vagal tumors. In four of the five patients, the presenting symptoms resolved after surgery. Two patients presented with intractable neurogenic cough, and another two presented with autonomic symptoms, one with syncope/palpitations and the other with intractable sweating. The final patient presented with a rapidly enlarging vagal paraganglioma and developed intractable cough after resection. We present two patients with novel approach to vagal paragangliomas that underwent ligation of feeding blood supply without removing the tumor, resulting in resolution of an intractable cough in one patient and resolution of severe nighttime sweating in the other. Conclusion: Management of tumors associated with the cervical vagus nerve that present with symptoms or rapid growth poses a clinical dilemma. Consideration of the tumor origin with either enucleation of schwannomas or ligation of feeding vessels may preserve function while addressing the presenting symptoms. [ABSTRACT FROM AUTHOR]

This article examines the risk factors for spontaneous cerebrospinal fluid leaks (sCSF leaks) in patients with idiopathic intracranial hypertension (IIH). The study, which is based on a large multinational database, compares the demographic and treatment characteristics of patients with IIH who have sCSF leaks of the anterior or lateral skull base (IIHwL) to those without sCSF leaks (IIHwoL). The results show that IIHwL patients tend to be older, have a higher body mass index (BMI), and have more comorbidities compared to IIHwoL patients. They also experience a higher prevalence of symptoms such as headaches, tinnitus, and visual disturbance. The findings contribute to a better understanding of this unique subpopulation of IIH patients and may aid in their management. [Extracted from the article]

This article explores the differences in neuroimaging findings between patients with medically refractory idiopathic intracranial hypertension (IIH) and spontaneous cerebrospinal fluid (CSF) leak (IIHwL) and patients with IIH without spontaneous CSF leak (IIHwoL). The study conducted a retrospective review of medical records and compared demographic information, clinical presentations, venous sinus manometry data, lumbar puncture opening pressure, and neuroimaging findings between the two patient groups. The results showed that patients with IIHwL had different neuroimaging findings compared to those with IIHwoL, highlighting the importance of recognizing these differences for the timely identification and management of CSF leak patients with IIH. [Extracted from the article]

This article discusses the impact of venous sinus stenting (VSS) on symptoms and quality of life in patients with idiopathic intracranial hypertension (IIH) and a spontaneous cerebrospinal fluid (CSF) leak. The study included nine female patients who underwent VSS for IIH complicated by a CSF leak. The results showed that VSS effectively alleviated symptoms such as tinnitus and headaches, and allowed for discontinuation of medication in some patients. Complications were minimal, and there was no recurrence of CSF leak in the early postoperative period. [Extracted from the article]

Background: Regression is an immunological phenomenon described in cutaneous melanoma whereby tumor is replaced with tumor-infiltrating lymphocytes, granulation tissue, and mature fibroblasts often accompanied by pigment incontinence (accumulation of melanin in the upper dermis). Pigment incontinence results in grossly pigmented lesions that may be mistaken for viable tumor and has not been described in sinonasal mucosal melanoma (SNMM). This study investigates the presence of regression and pigment incontinence in patients with SNMM., Methods: A retrospective chart review was conducted on SNMM patients from 2007 to 2023. Pathology slides from surgical resection were examined by two pathologists blinded to treatment information for the presence and extent of pigment-laden macrophages and other histopathologic features of regression., Results: Seventeen patients with SNMM were included in this study who underwent surgical resection. Three patients received neoadjuvant therapy followed by surgical resection. Regression was present in 94% of patients and pigment incontinence was present in 65% of patients and occurred in both neoadjuvant treated patients and treatment naïve patients. All three patients with neoadjuvant treatment had evidence of pigment incontinence., Discussion: This study highlights that SNMM often displays characteristics of regression. This study is one of the first to describe the presence of pigment incontinence in patients with SNMM. Pigment incontinence can be a part of the natural tumor life cycle and grossly pigmented lesions could easily be confused for melanoma especially after neoadjuvant therapy. Developing an understanding of regression and pigment incontinence within SNMM is important for diagnosis and clinical management., Level of Evidence: IV Laryngoscope, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)