Noninvasive Analysis of Peptidoglycan from Living Animals.

The role of the intestinal microbiota in host health is increasingly revealed in its contributions to disease states. The host-microbiome interaction is multifactorial and dynamic. One of the factors that has recently been strongly associated with host physiological responses is peptidoglycan from bacterial cell walls. Peptidoglycan from gut commensal bacteria activates peptidoglycan sensors in human cells, including the nucleotide-binding oligomerization domain-containing protein 2. When present in the gastrointestinal tract, both the polymeric form (sacculi) and depolymerized fragments can modulate host physiology, including checkpoint anticancer therapy efficacy, body temperature and appetite, and postnatal growth. To utilize this growing area of biology toward therapeutic prescriptions, it will be critical to directly analyze a key feature of the host-microbiome interaction from living hosts in a reproducible and noninvasive way. Here we show that metabolically labeled peptidoglycan/sacculi can be readily isolated from fecal samples collected from both mice and humans. Analysis of fecal samples provided a noninvasive route to probe the gut commensal community including the metabolic synchronicity with the host circadian clock. Together, these results pave the way for noninvasive diagnostic tools to interrogate the causal nature of peptidoglycan in host health and disease.

Gut Microbiota to Microglia: Microbiome Influences Neurodevelopment in the CNS.

The brain is traditionally viewed as an immunologically privileged site; however, there are known to be multiple resident immune cells that influence the CNS environment and are reactive to extra-CNS signaling. Microglia are an important component of this system, which influences early neurodevelopment in addition to modulating inflammation and regenerative responses to injury and infection. Microglia are influenced by gut microbiome-derived metabolites, both as part of their normal function and potentially in pathological patterns that may induce neurodevelopmental disabilities or behavioral changes. This review aims to summarize the mounting evidence indicating that, not only is the Gut-Brain axis mediated by metabolites and microglia throughout an organism's lifetime, but it is also influenced prenatally by maternal microbiome and diet, which holds implications for both early neuropathology and neurodevelopment.

Non-invasive Analysis of Peptidoglycan from Living Animals.

The role of the intestinal microbiota in host health is increasingly revealed in its contributions to disease states. The host-microbiome interaction is multifactorial and dynamic. One of the factors that has recently been strongly associated with host physiological responses is peptidoglycan from bacterial cell walls. Peptidoglycan from gut commensal bacteria activate peptidoglycan sensors in human cells, including the Nucleotide-binding oligomerization domain containing protein 2 (NOD2). When present in the gastrointestinal tract, both the polymeric form (sacculi) and de-polymerized fragments can modulate host physiology, including checkpoint anticancer therapy efficacy, body temperature and appetite, and postnatal growth. To leverage this growing area of biology towards therapeutic prescriptions, it will be critical to directly analyze a key feature of the host-microbiome interaction from living hosts in a reproducible and non-invasive way. Here we show that metabolically labeled peptidoglycan/sacculi can be readily isolated from fecal samples collected from both mice and humans. Analysis of fecal samples provided a non-invasive route to probe the gut commensal community including the metabolic synchronicity with the host circadian clock. Together, these results pave the way for non-invasive diagnostic tools to interrogate the causal nature of peptidoglycan in host health and disease.

Role of Effective Policy and Screening in Managing Pediatric Nutritional Insecurity as the Most Important Social Determinant of Health Influencing Health Outcomes.

Social Determinants of Health (SDOH) impact nearly half of health outcomes, surpassing the influence of human behavior, clinical care, and the physical environment. SDOH has five domains: Economic Stability, Education Access and Quality, Health Care Access and Quality, Neighborhood and Built Environment, and Social and Community Context. Any adversity arising out of these interlinked domains predominantly affects children due to their greater susceptibility, and the adverse outcomes may span generations. Unfavorable SDOH may cause food insecurity, malnutrition, unbalanced gut microbiome, acute and chronic illnesses, inadequate education, unemployment, and lower life expectancy. Systematic screening by health care workers and physicians utilizing currently available tools and questionnaires can identify children susceptible to adverse childhood experiences, but there is a deficiency with respect to streamlined approach and institutional support. Additionally, current ameliorating supplemental food programs fall short of pediatric nutritional requirements. We propose a nutrition-based Surveillance, Screening, Referral, and Reevaluation (SSRR) plan encompassing a holistic approach to SDOH with a core emphasis on food insecurity, coupled with standardizing outcome-based interventions. We also propose more inclusive use of Food Prescription Programs, tailored to individual children's needs, with emphasis on education and access to healthy food.

Real-time non-invasive fluorescence imaging of gut commensal bacteria to detect dynamic changes in the microbiome of live mice.

In mammals, gut commensal microbiota interact extensively with the host, and the same interactions can be dysregulated in diseased states. Animal imaging is a powerful technique that is widely used to diagnose, measure, and track biological changes in model organisms such as laboratory mice. Several imaging techniques have been discovered and adopted by the research community that provide dynamic, non-invasive assessment of live animals, but these gains have not been universal across all fields of biology. Herein, we describe a method to non-invasively image commensal bacteria based on the specific metabolic labeling of bacterial cell walls to illuminate the gut bacteria of live mice. This tagging strategy may additionally provide unprecedented insight into cell wall turnover of gut commensals, which has implications for bacterial cellular growth and division, in a live animal.

Reciprocal Interactions Between the Gut Microbiome and Mammary Tissue Mast Cells Promote Metastatic Dissemination of HR+ Breast Tumors.

Establishing commensal dysbiosis, defined as an inflammatory gut microbiome with low biodiversity, before breast tumor initiation, enhances early dissemination of hormone receptor-positive (HR+) mammary tumor cells. Here, we sought to determine whether cellular changes occurring in normal mammary tissues, before tumor initiation and in response to dysbiosis, enhanced dissemination of HR+ tumors. Commensal dysbiosis increased both the frequency and profibrogenicity of mast cells in normal, non-tumor-bearing mammary tissues, a phenotypic change that persisted after tumor implantation. Pharmacological and adoptive transfer approaches demonstrated that profibrogenic mammary tissue mast cells from dysbiotic animals were sufficient to enhance dissemination of HR+ tumor cells. Using archival HR+ patient samples, we determined that enhanced collagen levels in tumor-adjacent mammary tissue positively correlated with mast cell abundance and HR+ breast cancer recurrence. Together, these data demonstrate that mast cells programmed by commensal dysbiosis activate mammary tissue fibroblasts and orchestrate early dissemination of HR+ breast tumors.

A Comparison of Alternative Medicine Users and Non-Users in Patients With Hidradenitis Suppurativa.

BACKGROUND: Hidradenitis suppurativa patients often seek non-prescription therapies. OBJECTIVE: To determine the prevalence of alternative medicine use and characterize the differences between patients who report using alternative medications versus those who do not. METHODS: We surveyed 67 patients with hidradenitis suppurativa regarding demographics, alternative medicine use, disease severity, and quality of life. RESULTS: 25 (37.2%) of the HS subjects reported alternative medicine use. Alternative medicine users tended to be younger (36.7 vs 40.8 years), have a shorter time since diagnosis (12.6 vs14.6 years), and reported worse quality of life (14.1 vs 11.0) than non-users. These differences were not statistically significant. LIMITATIONS: Limitations included a small sample size. CONCLUSION: Alternative medicine use among patients with hidradenitis is common regardless of disease severity; even mild disease may drive patients to seek alternative treatment. J Drugs Dermatol. 2021;20(10):1072-1074. doi:10.36849/JDD.6046.

Adherence to levetiracetam for management of epilepsy: Assessment with electronic monitors.

INTRODUCTION: Anti-seizure medications are used to manage epilepsy and require long-term adherence to maintain therapeutic drug levels. We assessed adherence to levetiracetam and the use of a digital intervention to improve adherence in patients with epilepsy. METHODS: 30 participants with epilepsy were randomized 1:1 either to a digital email adherence intervention or control group. All patients were provided levetiracetam equipped with electronic monitoring caps to assess patient adherence to medication. Patients were followed for 6 months, with return visits at 1 month, 3 months, and 6 months. RESULTS: Subjects randomized to the control arm (n = 15) took 66% of the prescribed doses compared to the intervention group, who took 65% of prescribed doses (n = 15). Nine participants did not complete the study. Of the twenty-one participants that completed the study, the overall rate of adherence was 72% of prescribed doses taken. Two subjects in the control group and three subjects in the intervention group were adherent every month of the study-taking at least 80% of prescribed doses. Those randomized to the control group took the correct number of doses 44% of days in the study, and those in the intervention group took the correct number of doses 37% of days. DISCUSSION: Poor adherence to levetiracetam is common. An internet-based email survey intervention did not improve adherence to levetiracetam in epilepsy patients. Further advances in adherence are needed to help patients receive the maximum benefit of their medical treatments.

The External Oblique Intercostal Block: Anatomic Evaluation and Case Series.

STUDY OBJECTIVE: We report a modified block technique aimed at obtaining upper midline and lateral abdominal wall analgesia: the external oblique intercostal (EOI) block. DESIGN: A cadaveric study and retrospective cohort study assessing the potential analgesic effect of the EOI block. SETTING: Cadaver lab and operating room. PATIENTS: Two unembalmed cadavers and 22 patients. INTERVENTIONS: Bilateral ultrasound-guided EOI blocks on cadavers with 29 mL of bupivacaine 0.25% with 1 mL of India ink; single-injection or continuous EOI blocks in patients. MEASUREMENTS: Dye spread in cadavers and loss of cutaneous sensation in patients. MAIN RESULTS: In the cadaveric specimens, we identified consistent staining of both lateral and anterior branches of intercostal nerves from T7 to T10. We also found consistent dermatomal sensory blockade of T6-T10 at the anterior axillary line and T6-T9 at the midline in patients receiving the EOI block. CONCLUSIONS: We demonstrate the potential mechanism of this technique with a cadaveric study that shows consistent staining of both lateral and anterior branches of intercostal nerves T7-T10. Patients who received this block exhibited consistent dermatomal sensory blockade of T6-T10 at the anterior axillary line and T6-T9 at the midline. This block can be used in multiple clinical settings for upper abdominal wall analgesia.

The effects of diabetes mellitus on gastric emptying: A prospective observational cohort study.

STUDY OBJECTIVE: Our goal was to evaluate the effect of diabetic severity and duration on preoperative residual gastric volume. Secondarily we compared ultrasonic estimates of residual gastric volume with actual volume determined by aspiration during endoscopy. DESIGN: This was a prospective, observational cohort study that included adults with a history of diabetes mellitus and/or opioid use scheduled for gastrointestinal endoscopic procedures. SETTING: Endoscopy unit at Cleveland Clinic Main Campus from 2017 to 2019. PARTICIPANT: Adults scheduled for upper endoscopy with or without colonoscopy. INTERVENTION AND MEASUREMENTS: Residual gastric volumes were primarily determined by aspiration during endoscopy, and secondarily estimated with ultrasound. We evaluated the relationship between gastric residual volume and preoperative HBA1C concentration and duration of diabetes. Secondarily, we conducted an agreement analysis between the two gastric volume measurement techniques. MAIN RESULTS: Among 145 enrolled patients, 131 were diabetic and 17 were chronic opioid users. Among 131 diabetic patients, the mean ± SD HbA1c was 7.2 ± 1.5% and the median (Q1, Q3) duration of diabetes was 8.5 (3, 15) years. Neither HbA1c nor duration of diabetes was associated with residual gastric volume. The adjusted mean ratio of residual gastric volume was 1.07 (98.3% CI: 0.89, 1.28; P = 0.38) for 1% increase in HbA1c concentration, and 0.84 (98.3% CI: 0.63, 1.14; P = 0.17) for each 10-year increase induration of diabetes. The median [Q1-Q3] absolute difference between gastric ultrasound measurement and endoscopic measurement was 25 [15, 65] ml. CONCLUSIONS: In this prospective observational cohort study, neither the duration nor severity of diabetes influenced preoperative residual gastric volume. Gastric ultrasound can help identify patients who have excessive residual volumes despite overnight fasting.

The dermatology residency application process.

The dermatology application process is grueling, that is tough to navigate without the proper guidance. This commentary is meant to shed light on the factors that can help applicants stand out in order to be successful in the match. It includes observations from successful applicants from the most recent match process.

Patients' Perspectives of Diagnostic Error: A Qualitative Study.

OBJECTIVES: The Institute of Medicine (IOM) defines diagnostic error as the failure to establish an accurate or timely explanation for the patient's health problem(s) or effectively communicate the explanation to the patient. Using this definition, we sought to characterize diagnostic errors experienced by patients and describe patient perspectives on causes, impacts, and prevention strategies. METHODS: We conducted interviews of adults hospitalized at an academic medical center. We used the framework of the IOM definition of diagnostic error to perform thematic analysis of qualitative data. Descriptive statistics were used to summarize quantitative data. RESULTS: Based on the IOM's definition of diagnostic error, 27 of the 69 included patients reported at least one diagnostic error in the past 5 years. The errors were distributed evenly across the following three dimensions of the IOM definition: accuracy, communication, and timeliness. Limited time with doctors, communication, clinical assessment, and clinical management emerged as major themes for causes of diagnostic error and for strategies to reduce diagnostic error. Impacts of errors included emotional distress, adverse health outcomes, and impaired activities of daily living. CONCLUSIONS: This study uses the recent IOM definition of diagnostic error to provide insights into diagnostic error from the patient perspective. We found that diagnostic errors were commonly reported by hospitalized adults and have a profound impact on patients' well-being. Patients' insights regarding potential causes and prevention strategies may help identify opportunities to reduce diagnostic errors.

A Retrospective Case Series of Pericapsular Nerve Group (PENG) Block for Primary Versus Revision Total Hip Arthroplasty Analgesia.

The innervation of the hip joint is complex and it is challenging to provide effective analgesia after hip surgery utilizing any single regional anesthesia technique. The pericapsular nerve group (PENG) block is an interfascial plane block aiming to block articular branches supplied by femoral, obturator, and accessory obturator nerves. In this case series, we compare the efficacy of the PENG block to provide analgesia in primary and revision total hip arthroplasty (THA). The ultrasound-guided PENG block technique is described and post-operative pain scores and opioid requirements are reported. The PENG block was successfully used in primary THA as a solo block, and it may be used in combination with other regional blocks for any hip surgery. The PENG block is an easy regional technique to perform in the supine position with motor-sparing benefits.

Emotional Well-Being Is Impaired in Hidradenitis Suppurativa Patients.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory condition. OBJECTIVE: To measure emotional well-being in HS patients and compare to other populations, assess if there is an effect of disease severity on emotional well-being, and determine if emotional well-being is correlated with quality of life and depression. METHODS: A total of 153 HS subjects were recruited, and 66 Positive and Negative Affect Schedule (PANAS) surveys assessing emotional well-being were completed. Norms for comparison populations (disease-free undergraduates and adults) were used. A validated self-assessment tool was used to determine disease severity. Subjects completed the Patient Health Questionnaire-9 (PHQ-9) and Dermatology Life Quality Index (DLQI) to examine depression and quality of life, respectively. RESULTS: HS subjects had lower positive affect than undergraduates and higher negative affect than adults. There were no differences in PANAS scores by Hurley stage (p > 0.05). PANAS scores for HS subjects correlated with worse quality of life (r = 0.66, p < 0.00001) and depression (r = 0.74, p < 0.00001). CONCLUSION: HS patients have poor emotional well-being. PANAS scores correlated with worse quality of life and depression. Providing appropriate resources and treatments may be beneficial for HS patients.