Are Deep Odontogenic Infections Associated With an Increased Risk for Sepsis?

BACKGROUND: Quick Sequential Organ Failure Assessment (qSOFA) is recommended to identify sepsis. Odontogenic infection (OI) can progress to sepsis, causing systematic inflammatory complications or organ failure. PURPOSE: The purpose of the study was to measure the association between OI location and risk for sepsis at admission. STUDY DESIGN, SETTING, AND SAMPLE: This retrospective cohort study included subjects treated for OI at Baylor University Medical Center in Dallas, TX, from January 9, 2019 to July 30, 2022. Subjects > 18 years old who were treated under general anesthesia were included. OI limited to periapical, vestibular, buccal, and/or canine spaces were excluded from the sample. PREDICTOR VARIABLE: The primary predictor variable was OI anatomic location (superficial or deep). Superficial OI infection includes submental, submandibular, sublingual, submasseteric, and/or superficial temporal spaces. Deep OI includes pterygomandibular, deep temporal, lateral pharyngeal, retropharyngeal, pretracheal, and/or prevertebral. MAIN OUTCOME VARIABLES: The primary outcome variable was risk for sepsis measured using a qSOFA score (0 to 3). A higher score (>0) indicates the patient has a high risk for sepsis. COVARIATES: Covariates were demographics, clinical, laboratory, and radiological findings, antibiotic route, postoperative endotracheal intubation, tracheostomy, intensive care unit, admission, and length of stay. ANALYSES: Descriptive and bivariate analyses were performed. A χ2 test was used for categorical variables. The Mann-Whitney U test was used for continuous variables. Statistical significance was P < .05. RESULTS: The sample was composed of 168 subjects with a mean age of 42.8 ± 21.5 and 69 (48.6%) subjects were male. There were 11 (6.5%) subjects with a qSOFA score > 0. The relative risk of a qSOFA > 0 for a deep OI is 5.4 times greater than for a superficial OI (136 (95.8) versus 21 (80.8%): RR (95% confidence interval): 5.4 (1.51 to 19.27), P = .004). After adjusting for age, sex, American Society of Anesthesiologists score, and involved anatomical spaces, there was a significant correlation between laterality and the number of involved anatomical spaces and qSOFA score (odd ratio = 9.13, 95% confidence interval: 2.48 to 33.55, adjusted P = <.001). CONCLUSION AND RELEVANCE: The study findings suggest that the OI location is associated with the qSOFA score >0.

A stagewise response to mitochondrial dysfunction in mitochondrial DNA maintenance disorders.

Mitochondrial DNA (mtDNA) deletions which clonally expand in skeletal muscle of patients with mtDNA maintenance disorders, impair mitochondrial oxidative phosphorylation dysfunction. Previously we have shown that these mtDNA deletions arise and accumulate in perinuclear mitochondria causing localised mitochondrial dysfunction before spreading through the muscle fibre. We believe that mito-nuclear signalling is a key contributor in the accumulation and spread of mtDNA deletions, and that knowledge of how muscle fibres respond to mitochondrial dysfunction is key to our understanding of disease mechanisms. To understand the contribution of mito-nuclear signalling to the spread of mitochondrial dysfunction, we use imaging mass cytometry. We characterise the levels of mitochondrial Oxidative Phosphorylation proteins alongside a mitochondrial mass marker, in a cohort of patients with mtDNA maintenance disorders. Our expanded panel included protein markers of key signalling pathways, allowing us to investigate cellular responses to different combinations of oxidative phosphorylation dysfunction and ragged red fibres. We find combined Complex I and IV deficiency to be most common. Interestingly, in fibres deficient for one or more complexes, the remaining complexes are often upregulated beyond the increase of mitochondrial mass typically observed in ragged red fibres. We further find that oxidative phosphorylation deficient fibres exhibit an increase in the abundance of proteins involved in proteostasis, e.g. HSP60 and LONP1, and regulation of mitochondrial metabolism (including oxidative phosphorylation and proteolysis, e.g. PHB1). Our analysis suggests that the cellular response to mitochondrial dysfunction changes depending on the combination of deficient oxidative phosphorylation complexes in each fibre.

Corrigendum to "RPN (Radius, Position of tumour, iNvasion of renal sinus) Classification and Nephrometry Scoring System: An Internationally Developed Clinical Classification To Describe the Surgical Difficulty for Renal Masses for Which Robotic Partial Nephrectomy Is Planned" [Eur. Urol. Open Sci. 54 (2023) 33-42].

[This corrects the article DOI: 10.1016/j.euros.2023.05.007.].

Systematic review of the ophthalmic complications of robotic-assisted laparoscopic prostatectomy.

This study aims to review ophthalmic injuries sustained during of robotic-assisted laparoscopic prostatectomy (RALP). A search of Medline, Embase, Cochrane and grey literature was performed using methods registered a priori. Eligible studies were published 01/01/2010-01/05/2023 in English and reported ophthalmic complications in cohorts of > 100 men undergoing RALP. The primary outcome was injury incidence. Secondary outcomes were type and permanency of ophthalmic complications, treatments, risk factors and preventative measures. Nine eligible studies were identified, representing 100,872 men. Six studies reported rates of corneal abrasion and were adequately homogenous for meta-analysis, with a weighted pooled rate of 5 injuries per 1000 procedures (95% confidence interval 3-7). Three studies each reported different outcomes of xerophthalmia, retinal vascular occlusion, and ophthalmic complications unspecified in 8, 5 and 2 men per 1000 procedures respectively. Amongst identified studies, there were no reports of permanent ophthalmic complications. Injury management was poorly reported. No significant risk factors were reported, while one study found African-American ethnicity protective against corneal abrasion (0.4 vs. 3.9 per 1000). Variables proposed (but not proven) to increase risk for corneal abrasion included steep Trendelenburg position, high pneumoperitoneum pressure, prolonged operative time and surgical inexperience. Compared with standard of care, occlusive eyelid dressings (23 vs. 0 per 1000) and foam goggles (20 vs. 1.3 per 1000) were found to reduce rates of corneal abrasion. RALP carries low rates of ophthalmic injury. Urologists should counsel the patient regarding this potential complication and pro-actively implement preventative strategies.

OPTIMAL: An OPTimized Imaging Mass cytometry AnaLysis framework for benchmarking segmentation and data exploration.

Analysis of imaging mass cytometry (IMC) data and other low-resolution multiplexed tissue imaging technologies is often confounded by poor single-cell segmentation and suboptimal approaches for data visualization and exploration. This can lead to inaccurate identification of cell phenotypes, states, or spatial relationships compared to reference data from single-cell suspension technologies. To this end we have developed the "OPTimized Imaging Mass cytometry AnaLysis (OPTIMAL)" framework to benchmark any approaches for cell segmentation, parameter transformation, batch effect correction, data visualization/clustering, and spatial neighborhood analysis. Using a panel of 27 metal-tagged antibodies recognizing well-characterized phenotypic and functional markers to stain the same Formalin-Fixed Paraffin Embedded (FFPE) human tonsil sample tissue microarray over 12 temporally distinct batches we tested several cell segmentation models, a range of different arcsinh cofactor parameter transformation values, 5 different dimensionality reduction algorithms, and 2 clustering methods. Finally, we assessed the optimal approach for performing neighborhood analysis. We found that single-cell segmentation was improved by the use of an Ilastik-derived probability map but that issues with poor segmentation were only really evident after clustering and cell type/state identification and not always evident when using "classical" bivariate data display techniques. The optimal arcsinh cofactor for parameter transformation was 1 as it maximized the statistical separation between negative and positive signal distributions and a simple Z-score normalization step after arcsinh transformation eliminated batch effects. Of the five different dimensionality reduction approaches tested, PacMap gave the best data structure with FLOWSOM clustering out-performing phenograph in terms of cell type identification. We also found that neighborhood analysis was influenced by the method used for finding neighboring cells with a "disc" pixel expansion outperforming a "bounding box" approach combined with the need for filtering objects based on size and image-edge location. Importantly, OPTIMAL can be used to assess and integrate with any existing approach to IMC data analysis and, as it creates .FCS files from the segmentation output and allows for single-cell exploration to be conducted using a wide variety of accessible software and algorithms familiar to conventional flow cytometrists.

The anti-cancer efficacy of a novel phenothiazine derivative is independent of dopamine and serotonin receptor inhibition.

Introduction: An attractive, yet unrealized, goal in cancer therapy is repurposing psychiatric drugs that can readily penetrate the blood-brain barrier for the treatment of primary brain tumors and brain metastases. Phenothiazines (PTZs) have demonstrated anti-cancer properties through a variety of mechanisms. However, it remains unclear whether these effects are entirely separate from their activity as dopamine and serotonin receptor (DR/5-HTR) antagonists. Methods: In this study, we evaluated the anti-cancer efficacy of a novel PTZ analog, CWHM-974, that was shown to be 100-1000-fold less potent against DR/5-HTR than its analog fluphenazine (FLU). Results: CWHM-974 was more potent than FLU against a panel of cancer cell lines, thus clearly demonstrating that its anti-cancer effects were independent of DR/5-HTR signaling. Our results further suggested that calmodulin (CaM) binding may be necessary, but not sufficient, to explain the anti-cancer effects of CWHM-974. While both FLU and CWHM-974 induced apoptosis, they induced distinct effects on the cell cycle (G0/G1 and mitotic arrest respectively) suggesting that they may have differential effects on CaM-binding proteins involved in cell cycle regulation. Discussion: Altogether, our findings indicated that the anti-cancer efficacy of the CWHM-974 is separable from DR/5-HTR antagonism. Thus, reducing the toxicity associated with phenothiazines related to DR/5-HTR antagonism may improve the potential to repurpose this class of drugs to treat brain tumors and/or brain metastasis.

High Proportions of Newly Detected Visible Lesions and Pathology Grade Change Among Patients with Barrett's Esophagus Referred to Expert Centers.

BACKGROUND AND AIMS: Endoscopic eradication therapy for Barrett's esophagus (BE)-related neoplasia is increasingly being performed at tertiary and community centers. While it has been suggested that these patients should be evaluated at expert centers, the impact of this practice has not been evaluated. We aimed to assess the impact of referral of BE-related neoplasia patients to expert centers by assessing the proportion of patients with change in pathological diagnosis and visible lesions detected. METHODS: Multiple databases were searched until December 2021 for studies of patients with BE referred from the community to expert center. The proportions of pathology grade change and newly detected visible lesions at expert centers were pooled using a random-effects model. Subgroup analyses were performed based on baseline histology and other relevant factors. RESULTS: Twelve studies were included (1630 patients). The pooled proportion of pathology grade change after expert pathologist review was 47% (95% CI 34-59%) overall and 46% (95% CI 31-62%) among patients with baseline low-grade dysplasia. When upper endoscopy was repeated at an expert center, the pooled proportion of pathology grade change was still high 47% (95% 26-69%) overall and 40% (95% CI 34-45%) among patients with baseline LGD. The pooled proportion of newly detected visible lesions was 45% (95% CI 28-63%) and among patients referred with LGD was 27% (95% CI 22-32%). CONCLUSION: An alarmingly high proportion of newly detected visible lesions and pathology grade change were found when patients were referred to expert centers supporting the need for centralized care for BE-related neoplasia patients.

Tissue factor expression in monocyte subsets during human immunothrombosis, endotoxemia and sepsis.

INTRODUCTION: Tissue factor expression on monocytes is implicated in the pathophysiology of sepsis-induced coagulopathy. How tissue factor is expressed by monocyte subsets (classical, intermediate and non-classical) is unknown. METHODS: Monocytic tissue factor surface expression was investigated during three conditions. Primary human monocytes and microvascular endothelial cell co-cultures were used for in vitro studies. Volunteers received a bolus of lipopolysaccharide (2 ng/kg) to induce endotoxemia. Patients with sepsis, or controls with critical illness unrelated to sepsis, were recruited from four intensive care units. RESULTS: Contact with endothelium and stimulation with lipopolysaccharide reduced the proportion of intermediate monocytes. Lipopolysaccharide increased tissue factor surface expression on classical and non-classical monocytes. Endotoxemia induced profound, transient monocytopenia, along with activation of coagulation pathways. In the remaining circulating monocytes, tissue factor was up-regulated in intermediate monocytes, though approximately 60 % of individuals (responders) up-regulated tissue factor across all monocyte subsets. In critically ill patients, tissue factor expression on intermediate and non-classical monocytes was significantly higher in patients with established sepsis than among non-septic patients. Upon recovery of sepsis, expression of tissue factor increased significantly in classical monocytes. CONCLUSION: Tissue factor expression in monocyte subsets varies significantly during health, endotoxemia and sepsis.

The Clinical Observership Program: A Valuable Experience for Oral & Maxillofacial Surgery Residents.

PURPOSE: Training during oral and maxillofacial surgery residency must include exposure to the scope of the specialty, but success in practice often requires particular experience and knowledge of complex oral regenerative procedures such as bone grafting and implant surgery, as well as practice management. Osteo Science Foundation created the Clinical Observership Program (COP) in 2017 to provide residents the opportunity to spend several weeks in an established oral and maxillofacial surgery practice to increase experience in these areas. The purpose of this study is to report the results of a survey of all resident participants in the COP from 2017 to 2021 in which participants were asked to rate their experience numerically. MATERIALS AND METHODS: This is an institutional retrospective case series completed via an electronic survey sent to all participants in the COP from 2017 to 2021. The primary outcome is the subjective assessment of the COP based on six questions in which the respondent was asked to rate the program on a scale of 1 to 10 (10 being best). Categories included: 1) Did the program achieve expectations? 2) Was adequate time spent with the mentor? 3) Did you observe/participate in a variety of procedures? 4) Did the mentor provide additional didactic education? 5) Did you learn about practice management? and 6) How would you rate the overall experience? Descriptive statistics including mean score and standard deviation of each question were calculated, and no other covariates were analyzed. RESULTS: All 55 participants in the COP from 2017 to 2021 were contacted and 55 complete responses were received. The overall mean score for all categories rated by the residents was 9.63, the mean rating for questions 1 to 6 were 9.55, 9.89, 9.21, 9.60, 9.69, and 9.86 respectively, and the range of scores was 7 to 10. CONCLUSION: Overall, residents rated the COP experience highly. This survey indicates that the COP is a valuable supplemental experience in oral and maxillofacial surgery resident education.

Calcium isotopes as a biomarker for vascular calcification in chronic kidney disease.

Calcium balance is abnormal in adults with chronic kidney disease (CKD) and is associated with the development of vascular calcification. It is currently not routine to screen for vascular calcification in CKD patients. In this cross-sectional study, we investigate whether the ratio of naturally occurring calcium (Ca) isotopes, 44Ca and 42Ca, in serum could be used as a noninvasive marker of vascular calcification in CKD. We recruited 78 participants from a tertiary hospital renal center: 28 controls, 9 subjects with mild-moderate CKD, 22 undertaking dialysis and 19 who received a kidney transplant. For each participant, systolic blood pressure, ankle brachial index, pulse wave velocity, and estimated glomerular filtration rate were measured, along with serum markers. Calcium concentrations and isotope ratios were measured in urine and serum. While we found no significant association between urine Ca isotope composition (noted δ44/42Ca) between the different groups, δ44/42Ca values in serum were significantly different between healthy controls, subjects with mild-moderate CKD and those undertaking dialysis (P < 0.01). Receiver operative characteristic curve analysis shows that the diagnostic utility of serum δ44/42Ca for detecting medial artery calcification is very good (AUC = 0.818, sensitivity 81.8% and specificity 77.3%, P < 0.01), and performs better than existing biomarkers. Although our results will need to be verified in prospective studies across different institutions, serum δ44/42Ca has the potential to be used as an early screening test for vascular calcification.

Evaluation of Medication Incidents in a Long-term Care Facility Using Electronic Medication Administration Records and Barcode Technology.

Objective To describe the frequency, type, and severity of reported medication incidents that occurred at a long-term care facility (LTCF) despite electronic medication administration record and barcode-assisted medication administration (eMAR-BCMA) use. The study also contains analysis for the contribution of staff workarounds to reported medication administration errors (MAEs) using an established typology for BCMA workarounds, characterize if the eMAR-BCMA technology contributed to MAEs, and explore characteristics influencing incident severity. Design Retrospective incident report review. Setting A 239-bed LTCF in Alberta, Canada, that implemented eMAR-BCMA in 2013. Participants 270 paper-based, medication incident reports submitted voluntarily between June 2015 and October 2017. Interventions None. Results Most of the 264 resident-specific medication incidents occurred during the administration (71.9%, 190/264) or dispensing (28.4%, 75/264) phases, and 2.3% (6/264) resulted in temporary harm. Medication omission (43.7%, 83/190) and incorrect time (22.6%, 43/190) were the most common type of MAE. Workarounds occurred in 41.1% (78/190) of MAEs, most commonly documenting administration before the medication was administered (44.9%, 35/78). Of the non-workaround MAEs, 52.7% (59/112) were notassociated with the eMAR-BCMA technology, while 26.8% (30/112) involved system design shortcomings, most notably lack of a requirement to scan each medication pouch during administration. MAEs involving workarounds were less likely to reach the resident (74.4 vs 88.8%; relative risk = 0.84, 95% CI 0.72-0.97). Conclusion Administration and dispensing errors were the most reported medication incidents. eMAR-BCMA workarounds, and design shortcomings were involved in a large proportion of reported MAEs. Attention to optimal eMAR-BCMA use and design are required to facilitate medication safety in LTCFs.

Modulating drift dynamics of circle swimmers by periodic potentials.

We propose a method to modulate the drifting motion of overdamped circle swimmers in steady fluid flows by means of static sinusoidal potentials. Using Langevin formalism, we study drift velocity as a function of potential strength and wavelength with and without diffusional motion. Drift velocity is essentially quantized without diffusion, but in the presence of noise, the displacement per cycle has a continuous range. As a function of dimensionless potential wave number, domains of damped oscillatory and plateau regimes are observed in the drift velocity diagram. At weak potential and fluid velocity less than powered velocity, there is also a regime where drift velocity exceeds the fluid velocity. Methods based on these results can be used to separate biological and artificial circle swimmers based on their dynamical properties.

CXCR2 inhibition enables NASH-HCC immunotherapy.

OBJECTIVE: Hepatocellular carcinoma (HCC) is increasingly associated with non-alcoholic steatohepatitis (NASH). HCC immunotherapy offers great promise; however, recent data suggests NASH-HCC may be less sensitive to conventional immune checkpoint inhibition (ICI). We hypothesised that targeting neutrophils using a CXCR2 small molecule inhibitor may sensitise NASH-HCC to ICI therapy. DESIGN: Neutrophil infiltration was characterised in human HCC and mouse models of HCC. Late-stage intervention with anti-PD1 and/or a CXCR2 inhibitor was performed in murine models of NASH-HCC. The tumour immune microenvironment was characterised by imaging mass cytometry, RNA-seq and flow cytometry. RESULTS: Neutrophils expressing CXCR2, a receptor crucial to neutrophil recruitment in acute-injury, are highly represented in human NASH-HCC. In models of NASH-HCC lacking response to ICI, the combination of a CXCR2 antagonist with anti-PD1 suppressed tumour burden and extended survival. Combination therapy increased intratumoural XCR1+ dendritic cell activation and CD8+ T cell numbers which are associated with anti-tumoural immunity, this was confirmed by loss of therapeutic effect on genetic impairment of myeloid cell recruitment, neutralisation of the XCR1-ligand XCL1 or depletion of CD8+ T cells. Therapeutic benefit was accompanied by an unexpected increase in tumour-associated neutrophils (TANs) which switched from a protumour to anti-tumour progenitor-like neutrophil phenotype. Reprogrammed TANs were found in direct contact with CD8+ T cells in clusters that were enriched for the cytotoxic anti-tumoural protease granzyme B. Neutrophil reprogramming was not observed in the circulation indicative of the combination therapy selectively influencing TANs. CONCLUSION: CXCR2-inhibition induces reprogramming of the tumour immune microenvironment that promotes ICI in NASH-HCC.

Detecting respiratory chain defects in osteoblasts from osteoarthritic patients using imaging mass cytometry.

Osteoporosis is a skeletal disease which is characterised by reduced bone mass and microarchitecture, with a subsequent loss of strength that predisposes to fragility and risk of fractures. The pathogenesis of falling bone mineral density, ultimately leading to a diagnosis of osteoporosis is incompletely understood but the disease is currently thought to be multifactorial. Humans are known to accumulate mitochondrial mutations and respiratory chain deficiency with age and mounting evidence suggests that this may indeed be the overarching cause intrinsic to the changing phenotype in advancing age and age-related disease. Mitochondrial mutations are detectable from the age of about 30 years onwards. Mitochondria contain their own genome which encodes 13 essential mitochondrial proteins and accumulates somatic variants at up to 10 times the rate of the nuclear genome. Once the concentration of any pathogenic mitochondrial genome variant exceeds a threshold, respiratory chain deficiency and cellular dysfunction occur. The PolgD257A/D257A mouse model is a knock-in mutant that expresses a proof-reading-deficient version of PolgA, a nuclear encoded subunit of mtDNA polymerase. These mice are a useful model of age-related accumulation of mtDNA mutations in humans since their defective proof-reading mechanism leads to a mitochondrial DNA mutation rate 3-5 times higher than in wild-type mice. These mice showed enhanced levels of age-related osteoporosis along with respiratory chain deficiency in osteoblasts. To explore whether respiratory chain deficiency is also seen in human osteoblasts, we developed a protocol and analysis framework for imaging mass cytometry in bone tissue sections to analyse osteoblasts in situ. By comparing bone tissue sampled at one timepoint from femoral neck of 10 older healthy volunteers aged 40-85 with samples from young patients aged 1-19, we have identified complex I defect in osteoblasts from 6 out of 10 older volunteers, complex II defect in 2 out of 10 older volunteers, complex IV defect in 1 out of 10 older volunteers and complex V defect in 4 out of 10 older volunteers. These observations are consistent with findings from the PolgD257A/D257A mouse model and suggest that respiratory chain deficiency, as a consequence of the accumulation of age-related pathogenic mitochondrial DNA mutations, may play a significant role in the pathogenesis of human age-related osteoporosis.

Orthognathic Surgery of the Mandible.

Orthognathic surgery performed in conjunction with orthodontic treatment is commonly performed to correct skeletal irregularities and realign the maxillomandibular relationship to improve occlusal function and facial esthetics. A thorough understanding of soft tissue esthetics, skeletal and occlusal relationships, and surgical techniques is required to obtain successful results. Surgical techniques have evolved greatly throughout history, as technological advances such as virtual surgical planning have become available and widely used to obtain predictable movements with minimized complications. The aim of this article is to review the orthognathic surgical procedures of the mandible, with particular attention to the indications, contraindications, preoperative assessment, surgical technique, and possible complications encountered.

Lip Augmentation.

A heightened cultural emphasis on youth and beauty has resulted in an increase in cosmetic surgery in the Western world. Lip augmentation is one of the most popular cosmetic procedures done because full lips are considered youthful and voluptuous. With reliable and improved techniques, it is possible to change the appearance of the lips utilizing injectable materials and surgical techniques. This article focuses on popular materials and techniques utilized to augment the size and volume of the lips-the most common are dermal fillers. Lip augmentation requires a thorough understanding of anatomy and managing patient expectations, available materials, and techniques.

Bittersweet: infective complications of drug-induced glycosuria in patients with diabetes mellitus on SGLT2-inhibitors: two case reports.

BACKGROUND: Sodium-glucose co-transporter 2 (SGLT2) inhibitors are novel hypoglycemic agents which reduce reabsorption of glucose at the renal proximal tubule, resulting in significant glycosuria and increased risk of genital mycotic infections (GMI). These infections are typically not severe as reported in large systematic reviews and meta-analyses of the medications. These reviews have also demonstrated significant cardiovascular benefits through other mechanisms of action, making them attractive options for the management of Type 2 diabetes mellitus (T2DM). We present two cases with underlying abnormalities of the urogenital tract in which the GMI were complicated and necessitated cessation of the SGLT2 inhibitor. CASE PRESENTATIONS: Both cases are patients with T2DM on empagliflozin, an SGLT2 inhibitor. The first case is a 64 year old man with Candida albicans balanitis and candidemia who was found to have an obstructing renal calculus and prostatic abscess requiring operative management. The second case describes a 72 year old man with Candida glabrata candidemia who was found to have prostatomegaly, balanitis xerotica obliterans with significant urethral stricture and bladder diverticulae. His treatment was more complex due to fluconazole resistance and concerns about urinary tract penetration of other antifungals. Both patients recovered following prolonged courses of antifungal therapy and in both cases the SGLT2 inhibitor was ceased. CONCLUSIONS: Despite their cardiovascular benefits, SGLT2 inhibitors can be associated with complicated fungal infections including candidemia and patients with anatomical abnormalities of the urogenital tract may be more susceptible to these infections as demonstrated in these cases. Clinicians should be aware of their mechanism of action and associated risk of infection and prior to prescription, assessment of urogenital anatomical abnormalities should be performed to identify patients who may be at risk of complicated infection.

Multiple Immunostainings with Different Epitope Retrievals-The FOLGAS Protocol.

We describe a sequential multistaining protocol for immunohistochemistry, immunofluorescence and CyTOF imaging for formalin-fixed, paraffin-embedded specimens (FFPE) in the formalin gas-phase (FOLGAS), enabling sequential multistaining, independent from the primary and secondary antibodies and retrieval. Histomorphologic details are preserved, and crossreactivity and loss of signal intensity are not detectable. Combined with a DAB-based hydrophobic masking of metal-labeled primary antibodies, FOLGAS allows the extended use of CyTOF imaging in FFPE sections.

Associations Among Plant-Based Diet Quality, Uremic Toxins, and Gut Microbiota Profile in Adults Undergoing Hemodialysis Therapy.

OBJECTIVE: The objective of the study was to evaluate associations among diet quality, serum uremic toxin concentrations, and the gut microbiota profile in adults undergoing hemodialysis therapy. DESIGN AND METHODS: This is a cross-sectional analysis of baseline data from a clinical trial involving adults receiving hemodialysis therapy. Usual dietary intake was determined using a diet history method administered by Accredited Practising Dietitians. Two approaches were used for diet quality assessment: (1) using three a priori defined plant-based diet indices-an overall plant-based diet index (PDI), a healthy PDI, and an unhealthy PDI and (2) classification of food group intake. Serum uremic toxins (p-cresyl sulfate and indoxyl sulfate (IS); free and total) were determined by ultra-performance liquid chromatography. Gut microbiota composition was established through sequencing the 16S rRNA gene in stool samples. RESULTS: Twenty-two adults (median age 70.5 [interquartile range: 59-76], 64% male) were included in the final analysis. Higher adherence to the PDI was associated with lower total IS levels (P = .028), independent of dialysis adequacy, urinary output, and blood albumin levels. In contrast, higher adherence to the unhealthy PDI was associated with increases in both free and total IS. Several other direct and inverse associations between diet quality with uremic toxins, microbial relative abundances, and diversity metrics were also highlighted. Diet-associated taxa showed significantly different trends of association with serum uremic toxin concentrations (P < .05). Higher adherence to the PDI was negatively associated with relative abundances of Haemophilus and Haemophilus parainfluenzae that were related to elevated total IS levels. In contrast, increased intake of food items considered unhealthy, such as animal fats, sweets and desserts, were associated with bacteria linked to higher IS and p-cresyl sulfate (total and free) concentrations. CONCLUSIONS: The quality of diet and food selections may influence uremic toxin production by the gut microbiota in adults receiving hemodialysis. Well-designed dietary intervention trials that adopt multi-omic technologies appropriate for the functional annotation of the gut microbiome are needed to validate our findings and establish causality.

Mandibular metastasis from lung adenocarcinoma as the first sign of occult malignancy.

Metastatic disease to the oral and maxillofacial region is rare, with only about 1% of oral malignancy attributed to metastases. In approximately 20% of these patients, oral metastases are discovered before the detection of the primary tumor. Here we present a case of a 66-year-old man who presented with vague left mandibular pain and new-onset lip numbness as the first sign of occult malignancy from lung adenocarcinoma with multiple metastases.