High-quality identification of volatile organic compounds (VOCs) originating from breath.

INTRODUCTION: Volatile organic compounds (VOCs) can arise from underlying metabolism and are detectable in exhaled breath, therefore offer a promising route to non-invasive diagnostics. Robust, precise, and repeatable breath measurement platforms able to identify VOCs in breath distinguishable from background contaminants are needed for the confident discovery of breath-based biomarkers. OBJECTIVES: To build a reliable breath collection and analysis method that can produce a comprehensive list of known VOCs in the breath of a heterogeneous human population. METHODS: The analysis cohort consisted of 90 pairs of breath and background samples collected from a heterogenous population. Owlstone Medical's Breath Biopsy® OMNI® platform, consisting of sample collection, TD-GC-MS analysis and feature extraction was utilized. VOCs were determined to be "on-breath" if they met at least one of three pre-defined metrics compared to paired background samples. On-breath VOCs were identified via comparison against purified chemical standards, using retention indexing and high-resolution accurate mass spectral matching. RESULTS: 1471 VOCs were present in > 80% of samples (breath and background), and 585 were on-breath by at least one metric. Of these, 148 have been identified covering a broad range of chemical classes. CONCLUSIONS: A robust breath collection and relative-quantitative analysis method has been developed, producing a list of 148 on-breath VOCs, identified using purified chemical standards in a heterogenous population. Providing confirmed VOC identities that are genuinely breath-borne will facilitate future biomarker discovery and subsequent biomarker validation in clinical studies. Additionally, this list of VOCs can be used to facilitate cross-study data comparisons for improved standardization.

Transoral Ultrasound-Guided Core Biopsy for Minimally Invasive Sampling of Hard-to-Access Oropharyngeal Cancers.

Pathological diagnosis plays a pivotal role in risk classification and personalized treatment planning for patients with oropharyngeal cancers. However, challenges arise in cases involving trismus and tumors with submucosal spread, hindering traditional endoscopic biopsies and open incisional biopsies. In this study, we examined the clinical and pathological data of patients with trismus who underwent transoral ultrasound-guided core biopsy (USCB) for their oropharyngeal tumors, comparing this method with existing diagnostic approaches. Seventeen patients presenting with oropharyngeal tumors and trismus underwent transoral USCB for diagnosis. Of these, 14 patients were diagnosed with squamous cell carcinoma, while the remaining 3 were diagnosed with lymphoma. The procedure resulted in minimal wound size and effective bleeding control through compression, without encountering any complications. In conclusion, transoral USCB emerges as a precise diagnostic tool for patients with oropharyngeal tumors and trismus, offering a valuable adjunct to conventional open and endoscopic biopsies.

Establishing breath as a biomarker platform-take home messages from the Breath Biopsy Conference 2023.

The annual Breath Biopsy Conference hosted by Owlstone Medical gathers together the leading experts, early career researchers, and physicians working with breath as a biomarker platform for clinical purposes. The current topics in breath research are discussed and presented, and an overarching topical theme is identified and discussed as part of an expert panel to close the conference. The profiling of normal breath composition and the establishment of standards for analyzing breath compared to background signal were two important topics that were major focuses of this conference, as well as important innovative progress that has been made since last year, including the development of a non-invasive breath test for lung cancer and liver disease. This meeting report offers an overview of the key take-home messages from the various presentations, posters, and discussions from the conference.

Metabolic insights at the finish line: deciphering physiological changes in ultramarathon runners through breath VOC analysis.

Exhaustive exercise can induce unique physiological responses in the lungs and other parts of the human body. The volatile organic compounds (VOCs) in exhaled breath are ideal for studying the effects of exhaustive exercise on the lungs due to the proximity of the breath matrix to the respiratory tract. As breath VOCs can originate from the bloodstream, changes in abundance should also indicate broader physiological effects of exhaustive exercise on the body. Currently, there is limited published data on the effects of exhaustive exercise on breath VOCs. Breath has great potential for biomarker analysis as it can be collected non-invasively, and capture real-time metabolic changes to better understand the effects of exhaustive exercise. In this study, we collected breath samples from a small group of elite runners participating in the 2019 Ultra-Trail du Mont Blanc ultra-marathon. The final analysis included matched paired samples collected before and after the race from 24 subjects. All 48 samples were analyzed using the Breath Biopsy Platform with GC-Orbitrap™ via thermal desorption gas chromatography-mass spectrometry. The Wilcoxon signed-rank test was used to determine whether VOC abundances differed between pre- and post-race breath samples (adjustedP-value < .05). We identified a total of 793 VOCs in the breath samples of elite runners. Of these, 63 showed significant differences between pre- and post-race samples after correction for multiple testing (12 decreased, 51 increased). The specific VOCs identified suggest the involvement of fatty acid oxidation, inflammation, and possible altered gut microbiome activity in response to exhaustive exercise. This study demonstrates significant changes in VOC abundance resulting from exhaustive exercise. Further investigation of VOC changes along with other physiological measurements can help improve our understanding of the effect of exhaustive exercise on the body and subsequent differences in VOCs in exhaled breath.

Clinical outcomes and patient-reported outcomes after oncoplastic breast surgery in breast cancer patients: A matched cohort study.

BACKGROUND: Surgery is the recommended treatment for breast cancer, the most common cancer in women in Taiwan and the leading cause of cancer-related deaths. Although breast-conserving surgery (BCS) has good prognosis, in some cases, BCS may cause more significant deformities and interfere with the patient's psychosocial well-being. Oncoplastic breast surgery (OBS) is the treatment option in these cases. This study aimed to determine the outcomes of OBS and BCS regardless of clinical and patient-reported esthetic outcomes. METHODS: Between 2015 and 2020, 50 patients who underwent OBS at our hospital after complete treatment were enrolled. With 1:2 matched ratios, 100 patients were enrolled in the BCS control group. Clinical outcomes were analyzed. The BREAST-Q questionnaire was then assessed 6 months after the completion of treatment for subjective patient-reported outcomes. RESULTS: Due to the matching process, no difference was noted between the two groups in terms of demographic data such as age, comorbidities, or tumor characteristics. There were no significant differences in the local recurrence rate, disease-free survival, overall survival, positive margin rate, rewide excision rate, conversion to mastectomy rate, or complication rate (major or minor) between both groups. However, the OBS group showed higher satisfaction with breasts in the BREAST-Q questionnaire ( p < 0.001). The mean follow-up time was 38.77 ± 14.70 months in the BCS group and 29.59 ± 14.06 months in the OBS group. CONCLUSION: OBS seems to be a safe and feasible surgery in breast cancer patients because clinical outcomes are compatible with BCS. Moreover, the OBS group had better patient-reported outcomes in terms of satisfaction.

A Novel Technique for Autograft Preparation Using Patient-Specific Instrumentation (PSI) Assistance in Total Hip Arthroplasty in Developmental Dysplasia of Hip (DDH).

Due to the change in the structure of the proximal femur and acetabulum in patients with developmental dysplasia of the hip, total hip arthroplasty (THA) was difficult to perform for surgeons. To elevate the acetabular coverage rate, we developed a technique in the use of a patient-specific instrumentation (PSI) graft in patients with developmental dysplasia of hip (DDH) undergoing surgery. This study aims to evaluate the peri-operative outcomes of THA with PSI graft in patients with DDH. This study recruited 6 patients suffering from Crowe I DDH with secondary Grade IV osteoarthritis. All the patients underwent THA with PSI graft performed by a well-experienced surgeon. Perioperative outcomes included surgical procedures, blood loss during operation, the volume of blood transfusion, length of hospitalization, complications, and the mean difference in hemoglobin levels before and after surgery. All the outcomes analyzed were assessed by mean and standard deviation. The average duration of the surgical procedure was found to be 221.17 min, with an SD of 19.65 min. The mean blood loss during the operation was 733.33 mL, with an SD of 355.90 mL. The mean length of hospital stay was calculated to be 6 days, with an SD of 0.89 days. Furthermore, the mean difference between the pre- and postoperative hemoglobin levels was 2.15, with an SD of 0.99. A total of three patients received 2 units of leukocyte-poor red blood cells (LPR) as an accepted blood transfusion. There were no reported complications observed during the admission and one month after the operation. This study reported the peri-operative outcomes in the patients with DDH who underwent THA with PSI graft. We found that THA with PSI graft would provide a safe procedure without significant complications. We assumed that the PSI graft in THA may increase the coverage rate of the acetabulum, which may increase the graft union rates. Further cohort studies and randomized controlled trials were needed to confirm our findings.

Analgesic efficacy of collagen peptide in knee osteoarthritis: a meta-analysis of randomized controlled trials.

BACKGROUND: The management of knee osteoarthritis involves various treatment strategies. It is important to explore alternative therapies that are both safe and effective. Collagen peptides have emerged as a potential intervention for knee osteoarthritis. This study aims to evaluate the analgesic effects and safety of collagen peptide in patients diagnosed with knee osteoarthritis. METHODS: We conducted a systematic literature search following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Multiple databases including PubMed, Scopus, EMBASE, Web of Science, Cochrane, and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) published up to 27 May 2023 that focused on the analgesic outcomes and adverse events associated with collagen peptides or hydrolyzed collagen in patients with osteoarthritis. We assessed the quality of the included studies and the strength of evidence using the Cochrane ROB 2.0 tool and Grading of Recommendations, Assessment, Development, and Evaluations. RESULTS: Four trials involving 507 patients with knee osteoarthritis were included and analyzed using the random-effects model. All these trials were considered to have a high risk of bias. Our results revealed a significant difference in pain relief between the collagen peptide group and the placebo group in patients with knee osteoarthritis (standardized mean difference: - 0.58; 95% CI - 0.98, - 0.18, p = 0.004; I2: 68%; quality of evidence: moderate). However, there was no significant difference in the risk of adverse events between collagen peptide and placebo (odds ratio: 1.66; 95% CI 0.99, 2.78, p = 0.05; I2: 0%; quality of evidence: very low). CONCLUSIONS: Our findings demonstrate significant pain relief in patients with knee osteoarthritis who received collagen peptides compared to those who received placebo. In addition, the risk of adverse events did not differ significantly between the collagen peptide group and the placebo group. However, due to potential biases and limitations, well-designed randomized controlled trials are needed to validate and confirm these findings.

Dietary fatty acids differentially affect secretion of pro-inflammatory cytokines in human THP-1 monocytes.

Monocytes are a major population of circulating immune cells that play a crucial role in producing pro-inflammatory cytokines in the body. The actions of monocytes are known to be influenced by the combinations and concentrations of certain fatty acids (FAs) in blood and dietary fats. However, systemic comparisons of the effects of FAs on cytokine secretion by monocytes have not be performed. In this study, we compared how six saturated FAs (SFAs), two monounsaturated FAs (MUFAs), and seven polyunsaturated FAs (PUFAs) modulate human THP-1 monocyte secretion of TNF, IL-1ß, and IL-6 in the absence or presence of lipopolysaccharide. SFAs generally stimulated resting THP-1 cells to secrete pro-inflammatory cytokines, with stearic acid being the most potent species. In contrast, MUFAs and PUFAs inhibited lipopolysaccharide-induced secretion of pro-inflammatory cytokines. Interestingly, the inhibitory potentials of MUFAs and PUFAs followed U-shaped (TNF and IL-1ß) or inverted U-shaped (IL-6) dose-response curves. Among the MUFAs and PUFAs that were analyzed, docosahexaenoic acid (C22:6 n-3) exhibited the largest number of double bonds and was found to be the most potent anti-inflammatory compound. Together, our findings reveal that the chemical compositions and concentrations of dietary FAs are key factors in the intricate regulation of monocyte-mediated inflammation.

Applications of Hyaluronic Acid in Ophthalmology and Contact Lenses.

Hyaluronic acid (HA) is a glycosaminoglycan that was first isolated and identified from the vitreous body of a bull's eye. HA is ubiquitous in the soft connective tissues of animals and therefore has high tissue compatibility for use in medication. Because of HA's biological safety and water retention properties, it has many ophthalmology-related applications, such as in intravitreal injection, dry eye treatment, and contact lenses. Due to its broad range of applications, the identification and quantification of HA is a critical topic. This review article discusses current methods for analyzing HA. Contact lenses have become a widely used medical device, with HA commonly used as an additive to their production material, surface coating, and multipurpose solution. HA molecules on contact lenses retain moisture and increase the wearer's comfort. HA absorbed by contact lenses can also gradually release to the anterior segment of the eyes to treat dry eye. This review discusses applications of HA in ophthalmology.

Hemerythrin E3 Ubiquitin Ligases as Negative Regulators of Iron Homeostasis in Plants.

Iron (Fe) is an essential nutrient for plants, but at the same time its redox properties can make it a dangerous toxin inside living cells. Homeostasis between uptake, use and storage of Fe must be maintained at all times. A small family of unique hemerythrin E3 ubiquitin ligases found in green algae and plants play an important role in avoiding toxic Fe overload, acting as negative regulators of Fe homeostasis. Protein interaction data showed that they target specific transcription factors for degradation by the 26S proteasome. It is thought that the activity of the E3 ubiquitin ligases is controlled by Fe binding to the N-terminal hemerythrin motifs. Here, we discuss what we have learned so far from studies on the HRZ (Hemerythrin RING Zinc finger) proteins in rice, the homologous BTS (BRUTUS) and root-specific BTSL (BRUTUS-LIKE) in Arabidopsis. A mechanistic model is proposed to help focus future research questions towards a full understanding of the regulatory role of these proteins in Fe homeostasis in plants.

Hyperglycemia and risk of adverse outcomes following microvascular reconstruction of oncologic head and neck defects.

INTRODUCTION: Our aim is to examine the correlation between perioperative hyperglycemia and post-operative outcomes following microvascular reconstruction of head and neck defects. PATIENTS AND METHODS: Retrospective review of a prospectively collected database of 350 consecutive patients who underwent microvascular reconstruction of malignant head and neck defects over a 2 year period. The relationship between perioperative hyperglycemia (≥ 180 mg/dL) and the incidence of the following complications was evaluated: flap loss, flap-related complications and surgical site infections (SSI). Sub-group analysis based on timing of hyperglycemia was also performed. RESULTS: We identified 313 patients (89.4%) in the normoglycemic group and 37 patients (10.6%) in the hyperglycemic group. Baseline demographics, tumor stage, operative variable were comparable. There were no significant differences in flap-related complications and overall mortality. SSI were significantly higher in the hyperglycemic cohort (48% vs. 28%, p = 0.01). On multivariate analysis, hyperglycemia [OR 2.07; 95% CI, 1.87-4.89], perioperative insulin administration [OR 4.805; 95% CI, 2.18-10.60], prolonged operative time [OR 1.003; 95% CI, 1.002-1.025] and higher Charlson co-morbidity indices [II: OR 2.286 & III: OR 2.284] were independent predictors of SSI. On sub-group analysis, only patients with early (POD 1) post-operative hyperglycemia had a significant OR for SSI (OR 1.88; 95% CI, 1.07-3.29). CONCLUSION: Our findings suggest that perioperative hyperglycemia, specifically during the first 24 h post-operatively, is associated with SSI in microvascular head and neck reconstruction. This association highlights the need for strict screening of head and neck patients for hyperglycemia especially in the immediate post-operative period.

Third Repeat Microvascular Reconstruction in Head and Neck Cancer Patients Aged 65 Years and Older: A Longitudinal and Sequential Analysis.

Performing a sequential third free flap for reconstruction of a head and neck defect after cancer resection can be challenging, and the problem is further compounded in elderly patients. The outcomes in this clinical scenario are currently unknown and this study aims to compare the results in elderly patients with younger patients in a high-volume microsurgical unit. A retrospective review of 126 consecutive patients who had undergone three sequential free flap reconstructions after head and neck cancer was performed. The patients were divided into two groups - older or younger than 65 years old (n = 105 and n = 21, respectively). Patient demographics, intraoperative and postoperative outcomes were noted and analyzed. The overall flap success in this patient cohort was 94.4% (7 flap losses in 126 patients). Cardiovascular complications were significantly more common in the older group (19% vs. 1.9%, p = 0.001). Delirium occurred more frequently in the older group compared with the younger group (23.8% vs. 6.7%, p = 0.023). There were no significant differences regarding surgical complications. With adequate planning, a sequential third free flap can be performed safely and successfully in patients who are more than 65 years of age. Particular attention to the perioperative morbidity in elderly patients is crucial for successful outcomes.

Gold nanoparticles as amyloid-like fibrillogenesis inhibitors.

Amyloid aggregates are one of the likely key factors leading to the development of Alzheimer's disease (AD) and other amyloidosis associated diseases. Several recent studies have shown that some anti-diabetic drugs have a positive therapeutic effect on AD patients by crossing the blood brain barrier (BBB) and preventing or reducing insulin resistance. Nanoparticles (NPs) or nanoscale objects (<600Da.), are able to cross the BBB at low concentrations, and can specifically target amyloidogenic structures. Thus, NPs are fast becoming indispensable tools for directed drug delivery, particularly when targeting structures or regions in the brain. Here, we have explored the inhibitory effect of gold nanoparticles (AuNPs) on the fibrillogenesis process of insulin fibrils. We found that when AuNPs were co-incubated with insulin, the structural transformation into amyloid-like fibrils was delayed by about a week. Further, the fibrils that formed, exhibited altered structure, shape, and dynamics, which further reduced fibril growth, and the stability of available amyloid-like fibrils with cross-ß structure for aggregation. Our results demonstrate that AuNPs disrupt insulin amyloid fibrillation resulting in fibrils that are shorter and more compact, and thus may serve a useful role in new therapeutic and diagnostic strategies for amyloid-related disorders.

Use of laxative-augmented contrast medium in the evaluation of colorectal foci at FDG PET.

PURPOSE: To compare the diagnostic accuracy of fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) in the detection of colon lesions with that of delayed PET/computed tomography (CT) performed after the administration of a laxative-augmented contrast medium. MATERIALS AND METHODS: All patients gave written informed consent according to the guidelines issued by the institutional review board. In a prospective study performed from November 2005 to December 2006, images obtained in 847 patients were reviewed by two physicians in consensus. Colorectal FDG uptake on initial PET images that exceeded background FDG accumulation was graded as minimal, equivocal, or positive. When the initial PET scan revealed a colorectal region of increased uptake, either oral or anal laxative-augmented contrast medium was administered on the basis of the site of colorectal FDG focus and delayed PET/CT was performed. Initial PET findings were reevaluated and revised when necessary. Comparison was performed on a per-patient basis. Findings at histopathologic analysis and clinical follow-up served as the reference standard. The accuracy of PET was compared with that of PET/CT by using the McNemar test. RESULTS: Colorectal FDG foci were seen on initial images in 137 patients. Uptake on the initial images was reported as minimal in 14 patients, equivocal in 68, and positive in 55. With use of a laxative-augmented contrast medium and delayed PET/CT, the proportions of equivocal and positive results decreased by 84% (57 of 68 patients) and 58% (18 of 31 patients), respectively. The accuracy of delayed PET/CT in the depiction of colorectal cancer was greater than that of initial PET (93.4% [128 of 137 patients] vs 71.5% [98 of 137 patients], respectively; P < .01). CONCLUSION: Delayed PET/CT with laxative-augmented contrast medium is more accurate than initial PET alone in the detection of colorectal cancer. This approach has promise as a tool for guiding decisions about how to treat patients with colorectal FDG foci. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11101193/-/DC1.