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Background: Lung ultrasound (LUS) has been recently proposed as a convenient and radiation-free imaging modality for the evaluation of systemic sclerosis–related interstitial lung disease. Objectives: The current study evaluates the relation between LUS and both high-resolution computed tomography (HRCT) and capillaroscopy findings in patients with systemic sclerosis. Design: This cross-sectional study included 32 patients with systemic sclerosis. Methods: Besides clinical evaluation, all participants underwent LUS, HRCT, pulmonary function tests (PFT), and nailfold video-capillaroscopy (NVC). All participants' data were compared and correlated. Results: There is an excellent agreement between number of B-lines and HRCT score (interclass correlation = 0.864, P -value <.001). A significant positive correlation exists between number of B-lines and disease duration (r = 0.459, P -value =.008). Conversely, the number of B-lines is negatively correlated with capillary density (r = −0.687, P -value <.001), forced expiratory volume in the first second (FEV1) (r = −0.886, P -value <.001), and forced vital capacity (FVC) (r = −0.898, P -value <.001). Patients with either neoangiogenesis or previous/current digital ulcers had significantly higher number of B-lines than those without (P -value <.001,.016, respectively). Conclusion: The number of B-lines parallels the HRCT score and the extent of digital vascular damage as indicated by NVC and clinical digital ulcers. Lung ultrasound has proven to be a reliable radiation-free modality for screening of systemic sclerosis–related interstitial lung disease and detecting its extent. [ABSTRACT FROM AUTHOR]

Background and Objectives: Familial Mediterranean fever (FMF) is a lifelong autoinflammatory disease characterized by episodes of fever and aseptic polyserositis. Commonly associated with vasculitis, FMF's impact on microcirculation was investigated by examining nailfold capillaries using capillaroscopy. Materials and Methods: This study included 32 female and 28 male FMF patients diagnosed according to the Tel Hashomer and Yalçınkaya criteria and a control group of 20 female and 10 male age-matched cases. Demographic characteristics, medical history (abdominal pain, fever, chest pain, and joint pain), and physical examination findings of the cases were assessed. FMF gene mutations, acute-phase reactants, urine analysis, and spot urine protein/creatinine ratios were evaluated. Nailfold capillaries were examined via capillaroscopy by the same dermatology specialist. Results: There was no significant age or gender difference between groups. The most common symptoms in the case group were abdominal pain (81.7%) and joint pain (65%). Pathological findings in capillaroscopy, such as microhemorrhages and avascular areas, were significantly more frequent in the FMF case group (p < 0.001; p < 0.001). Physiological findings, including hairpin-shaped capillaries and shortened loops, were significantly more common in the control group (p = 0.001; p = 0.034). No significant relationships were found between kidney involvement, subclinical inflammation, presence of microhemorrhages and avascular areas in capillaroscopy, and disease duration. Additionally, no significant differences were observed in capillaroscopic findings between those with exon-10 mutations in the MEFV gene and those with non-exon-10 mutations. Conclusions: In conclusion, our study demonstrated secondary microvascular findings due to inflammation in FMF patients using capillaroscopy, a cost-effective and safe tool. [ABSTRACT FROM AUTHOR]

This pilot study investigates distinctive features within the nail-enthesis complex among Psoriatic arthritis (PsA), Psoriasis (PSO), Rheumatoid Arthrit is (RA), and Healthy Control (HC) groups, utilizing a combined approach of ultrasound (US) and nailfold videocapillaroscopy (NVC). Clinical assessments and comprehensive US and NVC evaluations of the nail-enthesis complex were conducted on 72 subjects (18 PsA, 16 PSO, 19 RA, 19 HC). Unsupervised clustering models and factor analysis were employed to identify patterns and interrelationships between US and NVC parameters. Significant structural differences were detected, emphasizing the discriminatory power of semiquantitative US scores (GS BUNES, Wortsman type). Trends in vascularization aligned with literature, showcasing dysregulated angiogenesis in PsA and PSO. The clustering model effectively distinguished HC from PsA subjects, revealing a potential continuum between PSO and PsA. RA subjects exhibited subsets with features akin to both HC and PsA/PSO, underscoring the complexity of its manifestations. This study provides insights into nail-enthesis complex alterations, highlighting distinctions among PsA, PSO, RA, and HC subjects. The clustering model emphasizes potential overlap between PSO and PsA. Factor analysis elucidates collinearity in US-detected characteristics, while suggesting limited discriminative power of some quantitative parameters. These findings advocate for further exploration in prospective trials, potentially predicting the evolution of undifferentiated early arthritis and arthritis onset in PSO patients. [ABSTRACT FROM AUTHOR]

Introduction: Psoriasis is a chronic inflammatory skin disorder affecting millions worldwide. Dermoscopy and proximal nailfold capillaroscopy have emerged as valuable tools for understanding the pathophysiology and treatment response of psoriasis lesions. Objectives: This study aimed to contribute to the limited literature on using dermoscopic findings to detect treatment effectiveness in patients with psoriasis vulgaris. Methods: This prospective, single-blinded, observational cohort study included 101 patients aged 18–71 years diagnosed with psoriasis vulgaris who initiated or altered systemic treatment. Monthly dermoscopic and capillaroscopic evaluations were performed alongside assessments of Psoriasis Area Severity Index (PASI), Body Surface Area (BSA), and Dermatology Life Quality Index (DLQI) scores. Results: A significant relationship was found between first-month dermoscopic findings and third-month severity scores (PASI, BSA, DLQI). Patients with positive treatment responses exhibited changes from baseline regular capillary dilations to hemorrhagic spots or the absence of vascular findings during the first month. The correlations between dermoscopic changes and severity scores evolved over time, becoming stronger in the second and third months. Nailfold capillaroscopy findings at the third month of treatment showed significant differences from baseline. Conclusions: Dermoscopy is a fast, practical, and inexpensive tool for early prediction of treatment effectiveness in psoriasis vulgaris. The disappearance of regular capillary dilations or their change to hemorrhagic spots suggests treatment efficacy, while their persistence indicates poor treatment response. Early detection of treatment effectiveness using dermoscopic findings can facilitate timely adjustments, improving patient outcomes and reducing unnecessary treatment exposure. [ABSTRACT FROM AUTHOR]

Background: Microvascular alteration in scleroderma patients is well documented. Microcirculatory changes can be visualized by nailfold capillary microscopy (NFC) examination which is a safe and noninvasive technique. This study aims to identify possible association between neutrophil-to-lymphocyte ratio (NLR) and microvascular changes detected by nailfold capillaroscopic examination in scleroderma patients. Results: The study was conducted on 25 patients with systemic sclerosis. On studying the correlation of NLR with laboratory parameters, we found significant positive correlations with erythrocyte sedimentation rate "ESR" and C-reactive protein "CRP" values (p = 0.000). Regarding the clinical manifestations, higher NLR was significantly related to the presence of digital ulcer (p = 0.023) and Raynaud's phenomenon (p = 0.015). There was significantly negative relation between NLR with cyclophosphamide treatment. Regarding NFC examination's results, there was significant negative correlation of NLR with capillary number/mm (p = 0.000) and significant positive correlation of NLR with capillary width (p = 0.005), and a significant relation of NLR with the presence of capillary hemorrhage and presence of active scleroderma pattern (p = 0.010) was also reported. Conclusion: High N/L ratio as a marker of inflammation was found to reflect severity of systemic sclerosis and is associated with larger capillary diameter and lower capillary number in nailfold capillaroscopy. Active scleroderma pattern was associated with high N/L ratio. Further longitudinal studies are needed to determine the frequency of nailfold videocapillaroscopy and N/L ratio. [ABSTRACT FROM AUTHOR]

Dermatomyositis (DM) is an immune mediated inflammatory disease classically associated with muscular and cutaneous involvement. Existing studies have suggested characteristic nailfold findings may be observed in DM, indicating a potential role for nailfold microscopic examination in the diagnosis of DM. To that end, we performed a systematic review of literature pertaining to nailfold microscopic, capillaroscopic, and dermoscopic findings observed in patients with DM, with a secondary review of the association of nailfold microscopic findings with myositis-specific antibody (MSA) and myositis-associated antibody (MAA) status. Thirty-seven papers, representing 346 patients, met inclusion criteria. The most prevalent nailfold findings were evidence of increased vascular diameter (64.5%, n = 223) and decreased vascularity (57.5%, n = 199). Scleroderma-spectrum pattern and microhemorrhage or hemorrhage were both observed in 156 (45.1%) patients. Fifty-one patients had nailfold capillaroscopic findings reported in direct association with antibody positivity and demonstrated a range of nailfold findings, preliminarily suggesting associations between antibody-status and capillaroscopic findings. The results of our study align with existing data indicating the scleroderma-spectrum pattern and the pattern’s composite features are prevalent in patients with DM. Our review further demonstrates a variety of nailfold capillaroscopic findings are found in patients positive for MSAs and MAAs. [ABSTRACT FROM AUTHOR]

Nail diseases are often associated with significant physical and psychosocial burden, but diagnosis is challenging due to nonspecific clinical and histological findings. Nailfold capillaroscopy has been studied for the diagnosis of systemic diseases, but studies on nail diseases are lacking. The objectives of our study were to characterize and compare capillary changes in a set of nail conditions versus controls, between nail groups, and based on demographic/clinical criteria. This was a prospective cross-sectional study of patients with nail psoriasis, onychomycosis, idiopathic onycholysis, brittle nail syndrome, nail lichen planus, retronychia, other nail conditions, and no nail findings (controls) undergoing capillaroscopy imaging/analysis. Nail psoriasis versus control patients demonstrated decreased capillary length/density and increased abnormal capillaries, with higher frequency in older, male patients. Onychomycosis was associated with increased meandering capillaries compared with controls, nail psoriasis, and nail lichen planus. Retronychia is associated with increased disorganized polymorphic capillaries compared with controls and onychomycosis. Limitations include a small sample size for certain nail conditions and small numbers of nail psoriasis patients with psoriatic arthritis. Our findings highlight nailfold capillaroscopy as a potentially quick, cost-effective, and noninvasive imaging modality, as an adjunct for diagnosis and treatment initiation for patients with onychodystrophies. [ABSTRACT FROM AUTHOR]

Abstract Background Microvascular alteration in scleroderma patients is well documented. Microcirculatory changes can be visualized by nailfold capillary microscopy (NFC) examination which is a safe and noninvasive technique. This study aims to identify possible association between neutrophil-to-lymphocyte ratio (NLR) and microvascular changes detected by nailfold capillaroscopic examination in scleroderma patients. Results The study was conducted on 25 patients with systemic sclerosis. On studying the correlation of NLR with laboratory parameters, we found significant positive correlations with erythrocyte sedimentation rate “ESR” and C-reactive protein “CRP” values (p = 0.000). Regarding the clinical manifestations, higher NLR was significantly related to the presence of digital ulcer (p = 0.023) and Raynaud’s phenomenon (p = 0.015). There was significantly negative relation between NLR with cyclophosphamide treatment. Regarding NFC examination’s results, there was significant negative correlation of NLR with capillary number/mm (p = 0.000) and significant positive correlation of NLR with capillary width (p = 0.005), and a significant relation of NLR with the presence of capillary hemorrhage and presence of active scleroderma pattern (p = 0.010) was also reported. Conclusion High N/L ratio as a marker of inflammation was found to reflect severity of systemic sclerosis and is associated with larger capillary diameter and lower capillary number in nailfold capillaroscopy. Active scleroderma pattern was associated with high N/L ratio. Further longitudinal studies are needed to determine the frequency of nailfold videocapillaroscopy and N/L ratio.

The analysis of nail-fold anatomy can effectively evaluate microcirculation and diagnose vascular-related diseases. Early detection of these conditions is crucial due to the risk of severe complications if intervention is delayed. Extensive research supports the notion that nail-fold capillary morphology serves as a critical biomarker for various disease processes, with the degree of capillary structural damage potentially reflecting the involvement of internal organs. This study proposes a non-invasive methodology for detecting nail-fold capillary morphology by integrating an object detection model for improvement within a deep learning framework. We conducted an ablation study to enhance YOLOv8’s performance in detecting nail-fold capillaries and classifying their morphology. Our enhancements included adding a detection layer to improve the detection of various-sized objects, implementing Efficient Channel Attention (ECA) mechanisms, and incorporating data augmentation techniques and hyper-parameter tuning. These modifications yielded a notable improvement in mean Average Precision at IoU 0.50 (mAP@50), with increases of 3.7% in mAP, 3.6% in precision, and 2.5% in recall compared to the baseline YOLOv8 model. This culminated in a mAP@50 score of 79.9%. We also utilized Slicing-Aided Hyperinference (SAHI) to enhance inference performance on untrained multi-scale images and smaller capillaries, demonstrating significant effectiveness in real-time testing scenarios. The results from this research are promising for advancing early-stage diabetes detection using nail-fold image analysis and could potentially enable real-time applications in clinical environments.

Introduction Capillaroscopy is a simple method of nailfold capillary imaging, used to diagnose diseases from the systemic sclerosis spectrum. However, the assessment of the capillary image is time-consuming and subjective. This makes it difficult to use for a detailed comparison of studies assessed by various physicians. This pilot study aimed to validate software used for automatic capil­lary counting and image classification as normal or pathological. Material and methods The study was based on the assessment of 200 capillaroscopic images obtained from patients suffering from systemic sclerosis or scleroderma spectrum diseases and healthy people. Dinolite MEDL4N Pro was used to perform capillaroscopy. Each image was analysed manually and described using working software. The neural network was trained using the fast.ai library (based on PyTorch). The ResNet-34 deep residual neural network was chosen; 10-fold cross-validation with the validation and test set was performed, using the Darknet-YoloV3 state of the art neural network in a GPU-optimized (P5000 GPU) environment. For the calculation of 1 mm capillaries, an additional detection mechanism was designed. Results The results obtained under neural network training were compared to the results obtained in manual analysis. The sensitivity of the automatic tool relative to manual assessment in classification of correct vs. pathological images was 89.0%, specificity 89.4% for the training group, in validation 89.0% and 86.9% respectively. For the average number of capillaries in 1 mm the precision of real images detected within the region of interest was 96.48%. Conclusions The pilot software for fully automatic capillaroscopic image assessment can be a useful tool for the rapid classification of a normal and altered capillaroscopy pattern. In addition, it allows one to quickly calculate the number of capillaries. In the future, the tool will be developed and will make it possible to obtain full imaging characteristics independent of the experience of the examiner.

This study aimed to analyze the relationship between cutaneous microcirculation reactivity, retinal circulation, macrocirculation function, and specific adhesion molecules in young patients with uncomplicated type 1 diabetes. Fifty-five patients with type 1 diabetes mellitus (T1DM), aged 8 to 18 years, were divided into subgroups based on skin microcirculation reactivity. The cutaneous microcirculatory vessels were considered reactive if post-test PORH coverage increased compared to pre-test coverage. Optical coherence tomography (OCT) was conducted to detect early retinopathic changes. Macrocirculation was described using pulsatility indices (PIs) determined for common carotid (CCA) and peripheral arteries of the upper and lower limbs. The ankle–brachial index was also assessed. There were no significant differences in retinal circulation and macrocirculation between the studied subgroups. However, there were significant differences between the various subgroups concerning the age at onset of diabetes and the sP-selectin levels but not ICAM-1 and sVCAM-1. The sP-selectin differences remained true after adjusting for age at onset. The sP-selectin level was significantly higher in the subgroup of patients with non-reactive cutaneous microcirculation. The results of our study indicate that sP-selectin may be considered as an immunological marker for cutaneous abnormalities, which serve as an early indicator of endothelial dysfunction in young patients with type 1 diabetes in the absence of classical complication. [ABSTRACT FROM AUTHOR]

Simple Summary: This article aims to provide a first-of-its-kind summary of the literature on oral capillaroscopy—a non-invasive technique used to study the structure of tiny blood vessels beneath the mouth's surface in different conditions and lesions. This research has shown that oral capillaroscopy can provide both qualitative and quantitative insights into the health of these microvessels and highlight differences and peculiarities in specific diseases and conditions. This technology has promising applications in oral pathology and oncology, where it can be used to study cancer-related blood vessel growth in real time and monitor chronic inflammatory diseases. Future research may focus on using capillaroscopy to image oral potentially malignant disorders and better understand their microvascular components for diagnostic and prognostic purposes. The oral cavity may suffer from diseases and lesions of different natures that can result in changes to the underlying microvasculature. These changes are typically observed during the examination of biopsy samples, but there is still a need to investigate methods for characterizing them in live tissues. Capillaroscopy, a medical imaging technique using polarized light and magnification, has shown promise in providing enhanced imaging of the oral mucosa microvasculature in preliminary studies. The present work proposed to review the literature on what capillaroscopy is, its applications in the imaging of oral mucosa microvasculature, and its diagnostic and prognostic significance in various diseases and conditions. While there is the limited literature available, further research in oral capillaroscopy, particularly in the field of oral oncology, is needed to determine its potential benefits in diagnosing and predicting outcomes for potentially malignant oral disorders and cancers. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the structural and microvascular changes in the retina and choroid after strabismus surgery. Methods: The study included 44 eyes from 44 patients who underwent strabismus surgery between August 2020 and December 2021. Among these patients, 9 (20%) underwent horizontal one-muscle surgery, 27 (61%) underwent horizontal two-muscle surgery, and 8 (18%) underwent inferior oblique muscle anteriorization surgery. Optical coherence tomography angiography scans were conducted preoperatively and at 1 day, 1 week, 1 month, and 3 months postoperatively. Results: The outer retinal blood flow showed a significant increase at 1 day postoperatively in horizontal two-muscle and inferior oblique muscle anteriorization surgery, whereas no significant difference was observed between periods in horizontal one-muscle surgery (P =.007). Choriocapillaris blood flow exhibited a significant increase at 1 day and 1 month postoperatively compared to the preoperative period (P <.001). Whole image superficial capillary plexus vascular density was significantly lower at 1 day postoperatively than preoperatively and 1 and 3 months postoperatively (P <.001). Whole image deep capillary plexus vascular density was significantly lower at 1 day than at 1 month postoperatively (P =.002). Conclusions: Following strabismus surgery, temporary changes in the hemodynamic microcirculation in the retina and choroid are observed. A transient decrease in retinal artery blood supply may be noticed, possibly attributed to the reduced anterior segment blood supply. [J Pediatr Ophthalmol Strabismus. 2024;61(6):397–403.] [ABSTRACT FROM AUTHOR]

Background: Nailfold capillaroscopy is recommended to diagnose primary or secondary Raynaud's phenomenon (RP). Capillaroscopy is normal in primary RP, which is the most frequent. Screening for RP capillary anomalies with nailfold dermoscopy has been promising. Objective: To determine whether normal nailfold dermoscopy—based on the absence of five criteria that define a sclerodermic pattern—is able to predict normal capillaroscopy with good positive‐predictive value (PPV). Methods: Prospective, 2‐phase (monocentre and multicentre) study on patients at first consultation for RP undergoing nailfold video capillaroscopy (NVC) and nailfold dermoscopy by two different 'blinded' trained observers, respectively, a vascular specialist and a dermatologist, not familiar with capillaroscopy. The five criteria noted were as follows: disorganization, megacapillaries, low capillary density, avascular areas and haemorrhages. Results: Based on 105 patients, the dermoscopy PPV for a normal NVC was 100% (p = 0.015), with 37.9% sensitivity, when no criterion was observed. Excluding haemorrhages, the PPV remained 100% (p < 0.0001), with sensitivity rising to 73.7% and 100% specificity. Conclusions: Normal nailfold dermoscopy with the absence of four easy‐to‐observe criteria predicts normal NVC with an excellent PPV. [ABSTRACT FROM AUTHOR]

Introduction: Endothelial damage is associated with acute and long-term Coronavirus disease 2019 (COVID-19) complications. Proximal nailfold capillaries are windows for monitoring important microvascular changes associated with endothelial dysfunction. Objective: We aimed to use dermoscopy to examine the proximal nailfold capillaries of COVID-19 patients and identify microvascular changes. Methods: A prospective study was designed to evaluate the dermoscopic features of proximal nail fold capillaries in mild to moderate COVID-19 patients and healthy controls between June 2022 and December 2023. The patients underwent their initial dermoscopic examination 2 weeks after the onset of symptoms, followed by a follow-up evaluation 10-14 months later. Results: The study included 46 patients with mild-to-moderate COVID-19 and 62 healthy controls. The presence of avascular areas (P

This pilot study investigates distinctive features within the nail-enthesis complex among Psoriatic arthritis (PsA), Psoriasis (PSO), Rheumatoid Arthrit is (RA), and Healthy Control (HC) groups, utilizing a combined approach of ultrasound (US) and nailfold videocapillaroscopy (NVC). Clinical assessments and comprehensive US and NVC evaluations of the nail-enthesis complex were conducted on 72 subjects (18 PsA, 16 PSO, 19 RA, 19 HC). Unsupervised clustering models and factor analysis were employed to identify patterns and interrelationships between US and NVC parameters. Significant structural differences were detected, emphasizing the discriminatory power of semiquantitative US scores (GS BUNES, Wortsman type). Trends in vascularization aligned with literature, showcasing dysregulated angiogenesis in PsA and PSO. The clustering model effectively distinguished HC from PsA subjects, revealing a potential continuum between PSO and PsA. RA subjects exhibited subsets with features akin to both HC and PsA/PSO, underscoring the complexity of its manifestations. This study provides insights into nail-enthesis complex alterations, highlighting distinctions among PsA, PSO, RA, and HC subjects. The clustering model emphasizes potential overlap between PSO and PsA. Factor analysis elucidates collinearity in US-detected characteristics, while suggesting limited discriminative power of some quantitative parameters. These findings advocate for further exploration in prospective trials, potentially predicting the evolution of undifferentiated early arthritis and arthritis onset in PSO patients.

Purpose: To analyze radial peripapillary capillaris (RPC) and intra-papillary capillaris (IPC) using optical coherence tomography angiography (OCTA) in acute retinal necrosis (ARN) with good outcome. Methods: RPC and IPC were analyzed by OCTA in patients diagnosed with ARN and treated with pharmacotherapy alone without surgery at the Tokyo Medical University Hospital. Results: A total of 13 patients were studied. Ophthalmoscopic examination showed no abnormality in the optic disc in 12 of the 13 patients. However, OCTA findings of the affected eye compared with the unaffected fellow eye revealed morphological abnormalities in RPC in nine cases (69%) and decrease in capillary network in RPC or IPC in eight cases (62%). Conclusion: In ARN, RPC and IPC were impaired even in eyes that were healed with medical treatment only without requiring surgical intervention and had no abnormal findings on ophthalmoscopic examination. This result suggests the presence of some degrees of optic neuropathy even in mild cases with good visual prognosis. [ABSTRACT FROM AUTHOR]

Background: The cachexia index (CXI), which consists of skeletal muscle, inflammation, and nutritional status, has been associated with prognosis in patients with hepatocellular carcinoma (HCC). We hypothesized that dynamic changes in CXI might be associated with long‐term outcomes in HCC. Methods: This study comprised 131 patients who had undergone primary hepatic resection for HCC between 2008 and 2019. Preoperative CXI (pre‐CXI) and postoperative CXI (post‐CXI) were calculated by the following formula: skeletal muscle index x serum albumin level / neutrophil‐to‐lymphocyte ratio. Pre‐ and post‐CXI were classified into two groups (high vs. low). We retrospectively investigated the association of perioperative dynamic changes in CXI with disease‐free and overall survival. Results: In multivariate analyses, negative HBs‐antigen (p = 0.02), high serum PIVKA‐II level (p < 0.01), poor tumor differentiation (p = 0.02), multiple tumors (p < 0.01), microvascular invasion (p < 0.01), partial resection (p < 0.01), postoperative complications (p < 0.01), and low‐pre‐CXI (p < 0.01) were significant predictors of disease‐free survival, while high ICGR15 (p = 0.01), poor tumor differentiation (p < 0.01), multiple tumors (p = 0.01), postoperative complications (p < 0.01), low‐pre‐CXI (p < 0.01), and low‐post‐CXI (p < 0.01) were significant predictors of overall survival. Low‐post‐CXI was associated with older age (p = 0.045), larger tumor (p < 0.01), longer operation time (p = 0.047), greater intraoperative bleeding (p < 0.01), and intraoperative blood transfusion (p < 0.01). Moreover, dynamic changes in CXI were associated with overall survival in each subgroup of patients with low‐pre‐CXI (p = 0.02) or high‐pre‐CXI (p = 0.03). Conclusions: Not only post‐CXI but also dynamic changes in CXI from pre‐ to post‐hepatectomy can be a prognostic indicator of HCC, providing a compelling rationale for aggressive perioperative nutritional and physical interventions to improve long‐term outcomes. [ABSTRACT FROM AUTHOR]

The article discusses the use of sublingual microcirculatory function as an indicator of overall microvascular health, specifically through the application of handheld incident darkfield (IDF) imaging. Topics discussed include the methodology of IDF imaging, the interpretation of microcirculatory metrics such as total vessel density and perfused vessel density, and the current limitations and potential future applications of this technology in clinical settings.

BACKGROUND: Long-COVID refers to a variety of symptoms that continue for at least 4 weeks following the onset of acute COVID-19 infection. "Microclots/microvasculopathy" is a potential cutting-edge theory. Nailfold capillaroscopy is a non-invasive method used to assess microvascularity. In this study, we aimed to compare baseline characteristics and capillaroscopic findings of patients with and without long-COVID syndrome. METHODS: Baseline clinical characteristics of 53 patients who tested positive for SARS-CoV-2 were recorded. At the time of COVID-19 diagnosis, patients underwent nailfold capillaroscopy. One year later, patients were rescreened for long-COVID symptoms. Comparisons were made between patients with and without long-COVID syndrome in terms of their baseline characteristics and capillaroscopic findings. RESULTS: There were 35 individuals (66%) with long-COVID syndrome. The most common symptoms related to long-COVID were fatigue (43.4%), myalgia (34%), arthralgia (20.8%), dyspnea (20.8%). In total, 22 patients (41.5%) had abnormal capillaroscopy findings. Like other baseline characteristics, the proportion of patients with abnormal capillaroscopic findings (40% vs 44%, p=0.76) was similar between patients with and without long-COVID syndrome. CONCLUSION: Microvasculopathy and microthrombotic vascular damage are among the strongest hypotheses discussed in this regard. Our results may suggest that factors, rather than baseline microvasculopathy, may drive pathophysiological mechanism underlying the poorly understood long-COVID syndrome [ABSTRACT FROM AUTHOR]

Objectives: Connective tissue-associated interstitial lung diseases (CTD-ILD) are believed to be caused by microvascular damage. The objective of this study was to assess the nailfold capillaroscopy (NFC) pattern in patients diagnosed with both CTD-ILD and non-CTD-ILD to identify microvascular changes and determine the relation between capillaroscopic parameters, clinical variables, and disease-related measurements. Patients and methods: This cross-sectional study included 95 patients with interstitial lung disease who applied to our Rheumatology and Chest Clinics between September 2021 and July 2023. The patients were divided into two groups based on their diagnosis: non-CTD-ILD (group 1) and CTD-ILD (group 2). Nailfold capillaroscopy was performed. Results: Ninety-five patients, 49 (51% female, mean age 62.31 ± 11.027 years) in group 1 and 46 (69.6% female, mean age 62.09 ± 10.887 years) in group 2, were included in the study. Abnormal capillary morphologies were both detected in the CTD-ILD group and the non-CTD-ILD groups. In patients with a usual interstitial pneumonia (UIP) pattern on chest computed tomography (CT), tortuosity was higher than in patients with non-specific interstitial pneumonia (NSIP) (P = 0.041), and the proportion of tortuosity increased significantly as the duration of the disease increased (P = 0.016). Conclusion: Our study highlights capillaroscopic abnormalities alone may not be sufficient to differentiate CTD-ILD (other than systemic sclerosis) from non-CTD-ILD. The presence of NFC abnormalities in non-CTD-ILD may suggest that fibrotic lung disease could potentially play a role in the deterioration of the microvascular structure or abnormal angiogenesis. Our study demonstrated that a multidisciplinary approach, incorporating clinical, morphological, pathological, and serological evaluations, is necessary for interpreting ILD. Key Points • Capillaroscopic abnormalities can also be seen in non-CTD-ILD. • Capillaroscopy findings do not distinguish the non-Ssc etiology of ILD. • Nailfold capillaroscopy may have the potential to serve as a useful tool in predicting prognosis and monitoring the disease progression in patients with idiopathic pulmonary fibrosis (IPF). [ABSTRACT FROM AUTHOR]

The peripheral microangiopathy may be well evaluated and studied by nailfold capillaroscopy (NFC) which is a safe and non-invasive technique. NFC has been reported to have both diagnostic and prognostic values in patients presenting with Raynaud's phenomenon. The overarching objective of this work was to make a consensus on what domains should be included in a capillaroscopy report and that it can be used in daily clinical practice and clinical research in the area of rheumatology. A Delphi questionnaire was developed regarding capillaroscopy report from a literature review and expert consensus. The first Delphi round included 14 core areas, its 18 domains with 50 subdomains, derived from a systematic literature review. The level of evidence was determined for each core set using the Oxford Centre for Evidence-based Medicine (CEBM) system. Nine response categories have been set per each item ranging between 1 and 9. Round 2, aimed to reach preliminary consensus "in" or "out" for domains. It included all items that were rated "critical" by at least 80% of the participants as well as any new domains proposed in round 1. The participants to the first, and second round were 11 experts. Fourteen domains were discussed in the two rounds. At the end of the survey, the final report template of NFC in rheumatology reached a consensus. A nailfold capillaroscopy report template has been developed by this study, based on outcomes of a Delphi process, by international participants panel. All domains met the 80% voting threshold set in this work. The reporting template can be used for both clinical research as well as day to day practice to provide guidance and standardize the NFC reporting. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Little is known about the extent to which microvascular disease is associated with cardiorespiratory fitness (CRF) among individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 4,766 participants with type 2 diabetes underwent maximal exercise testing in the Look AHEAD (Action for Health in Diabetes) study at baseline. Low CRF was defined based on the Aerobics Center Longitudinal Study reference standards. Microvascular disease was defined as having one or more of diabetes-related kidney disease (DKD), retinopathy, and neuropathy. The burden of microvascular disease was defined as the number of microvascular beds affected. RESULTS: Of the 4,766 participants (mean age 58.9 ± 6.7 years, 58.5% women, 66.1% White individuals), 1,761 (37%) had microvascular disease. Participants with microvascular complications in three vascular territories had a lower CFR than those without any microvascular disease (mean adjusted metabolic equivalent of task [MET] 6.58 vs. 7.26, P = 0.001). Participants with any microvascular disease had higher odds of low CRF than those without microvascular disease (adjusted odds ratio [OR] 1.45, 95% CI 1.24–1.71). An increasing burden of microvascular disease was associated with higher odds of low CRF (for microvascular disease in three vascular territories, adjusted OR 2.82, 95% CI 1.36–5.85). Adjusted ORs for low CRF were 1.24 (95% CI 0.99–1.55), 1.34 (95% CI 1.02–1.76), and 1.44 (95% CI 1.20–1.73) for neuropathy, retinopathy, and DKD associations, respectively. CONCLUSIONS: In a large cohort of adults with type 2 diabetes, the presence of microvascular disease and its burden were independently associated with lower CRF. [ABSTRACT FROM AUTHOR]

Anderson–Fabry disease (AFD) is a genetic lysosomal storage disorder caused by mutations in the α-galactosidase A gene, leading to impaired lysosomal function and resulting in both macrovascular and microvascular alterations. AFD patients often exhibit increased intima-media thickness (IMT) and reduced flow-mediated dilation (FMD), indicating non-atherosclerotic arterial thickening and the potential for cardiovascular events. Nailfold capillaroscopy, a non-invasive diagnostic tool, has shown potential in diagnosing and monitoring microcirculatory disorders in AFD, despite limited research. This study evaluates nailfold capillaroscopy findings in AFD patients, exploring correlations with GLA gene variant subgroups (associated with classical or late-onset phenotypes and variants of uncertain significance (VUSs)), and assessing morpho-functional differences between sexes. It aims to determine whether capillaroscopy can assist in the early identification of individuals with multiorgan vascular involvement. A retrospective observational study was conducted with 25 AFD patients from AOUP "G. Rodolico-San Marco" in Catania (2020–2023). Patients underwent genetic testing, enzyme activity evaluation, and nailfold capillaroscopy using Horus basic HS 200 videodermatoscopy. Parameters like angiotectonic disorder, vascular areas, capillary density, and intimal thickening were assessed. The study identified significant differences in capillaroscopy findings among patients with different GLA gene variant subgroups. Classic AFD variant patients showed reduced capillary length and signs of erythrocyte aggregation and dilated subpapillary plexus. No correlation was found between enzymatic activity and capillaroscopy parameters. However, Lyso-Gb3 levels were positively correlated with average capillary length (ῤ = 0.453; p = 0.059). Sex-specific differences in capillaroscopy findings were observed in neoangiogenesis and average capillary length, with distinct implications for men and women. This study highlights the potential of nailfold capillaroscopy in the diagnostic process and clinical management of AFD, particularly in relation to specific GLA gene mutations, as a valuable tool for the early diagnosis and monitoring of AFD. [ABSTRACT FROM AUTHOR]

Objective: Managing hand symptoms in patients with systemic sclerosis is difficult, and the current treatments often provide only limited relief of. In 2014 a new treatment for theses patients was proposed for improving hand function, namely the digital injection of adipose tissue derived stem cells. Methods: From 2015 to 2017 seven systemic sclerosis patients with an impaired hand function were treated with the aforesaid injections. A medical chart review was performed to collect pre- and postoperative patient specific data. Results: Our findings indicated no significant improvement in nailfold capillaroscopic measurements or in the healing of preexisting digital ulcers. Additionally, patients reported a slight worsening in hand function after the treatment. However, we observed a decrease in the modified Rodnan skin score, which measures skin thickness Although previous research has verified the safety and feasibility of this treatment, we found no definitive evidence of its effectiveness. Conclusion: Our results suggest that the specific conditions under which this treatment could be beneficial need to be identified through randomized controlled trials involving larger groups of patients. Level of Evidence: Level IV, therapeuticstudy. [ABSTRACT FROM AUTHOR]

Reduced peripheral microvascular reactivity is associated with an increased risk for major adverse cardiac events (MACEs). Tools for noninvasive assessment of peripheral microvascular function are limited, and existing technology is poorly validated in both healthy populations and patients with cardiovascular disease (CVD). Here, we used a handheld incident dark-field imaging tool (CytoCam) to test the hypothesis that, compared with healthy individuals (no risk factors for CVD), subjects formally diagnosed with coronary artery disease (CAD) or those with ≥2 risk factors for CAD (at risk) would exhibit impaired peripheral microvascular reactivity. A total of 17 participants (11 healthy, 6 at risk) were included in this pilot study. CytoCam was used to measure sublingual microvascular total vessel density (TVD), perfused vessel density (PVD), and microvascular flow index (MFI) in response to the topical application of acetylcholine (ACh) and sublingual administration of nitroglycerin (NTG). Baseline MFI and PVD were significantly reduced in the at-risk cohort compared with healthy individuals. Surprisingly, following the application of acetylcholine and nitroglycerin, both groups showed a significant improvement in all three microvascular perfusion parameters. These results suggest that, despite baseline reductions in both microvascular density and perfusion, human in vivo peripheral microvascular reactivity to both endothelial-dependent and -independent vasoactive agents remains intact in individuals with CAD or multiple risk factors for disease. NEW & NOTEWORTHY: To our knowledge, this is the first study to comprehensively characterize in vivo sublingual microvascular structure and function (endothelium-dependent and -independent) in healthy patients and those with CVD. Importantly, we used an easy-to-use handheld device that can be easily translated to clinical settings. Our results indicate that baseline microvascular impairments in structure and function can be detected using the CytoCam technology, although reactivity to acetylcholine may be maintained even during disease in the peripheral microcirculation. [ABSTRACT FROM AUTHOR]

Gender, through genetic, epigenetic and hormonal regulation, is an important modifier of the physiological mechanisms and clinical course of diseases. In diabetes mellitus, there are gender differences in incidence, prevalence, morbidity, and mortality. This disease also has an impact on the microvascular function. Therefore, this cross-sectional study was designed to investigate how gender affects the cutaneous microcirculation. We hypothesized that gender should be an important factor in the interpretation of capillaroscopy and transcutaneous oxygen saturation results. The study group consisted of 42 boys and 55 girls, uncomplicated diabetic pediatric patients. Females (F) and males (M) did not differ in terms of age, age at onset of diabetes, or diabetes duration. Furthermore, they did not differ in metabolic parameters. The comparison showed that group F had lower BP, higher pulse, and higher HR than group M. Group F had significantly lower creatinine and hemoglobin levels than group M. In children and adolescents with type 1 diabetes without complications, there was a gender difference in microcirculatory parameters. The resting transcutaneous partial pressure of oxygen was significantly higher in females than in males. However, there were no gender-related differences in basal capillaroscopic parameters or vascular reactivity during the PORH test. Our results indicate that studies investigating the structure and function of the microcirculation should consider the role of gender in addition to known cofactors such as puberty, body mass index, physical activity, and cigarette smoking. [ABSTRACT FROM AUTHOR]

A 58‐year‐old female smoker diagnosed with myelodysplastic syndrome (MDS) presented with Raynaud's phenomenon and a "scleroderma‐like" pattern on nailfold capillaroscopy. The capillaroscopic abnormalities were observed across all fingers, including those without clinical manifestations of onychomycosis. Over a two‐year follow‐up, there was no evidence of clinical or serological progression toward a connective tissue disease, particularly systemic sclerosis. This case underscores the potential contributory role of MDS and smoking in the development of microvascular dysfunction, presenting as capillaroscopic abnormalities in the absence of an underlying autoimmune disorder. [ABSTRACT FROM AUTHOR]

Background and Objectives: Familial Mediterranean fever (FMF) is a lifelong autoinflammatory disease characterized by episodes of fever and aseptic polyserositis. Commonly associated with vasculitis, FMF’s impact on microcirculation was investigated by examining nailfold capillaries using capillaroscopy. Materials and Methods: This study included 32 female and 28 male FMF patients diagnosed according to the Tel Hashomer and Yalçınkaya criteria and a control group of 20 female and 10 male age-matched cases. Demographic characteristics, medical history (abdominal pain, fever, chest pain, and joint pain), and physical examination findings of the cases were assessed. FMF gene mutations, acute-phase reactants, urine analysis, and spot urine protein/creatinine ratios were evaluated. Nailfold capillaries were examined via capillaroscopy by the same dermatology specialist. Results: There was no significant age or gender difference between groups. The most common symptoms in the case group were abdominal pain (81.7%) and joint pain (65%). Pathological findings in capillaroscopy, such as microhemorrhages and avascular areas, were significantly more frequent in the FMF case group (p < 0.001; p < 0.001). Physiological findings, including hairpin-shaped capillaries and shortened loops, were significantly more common in the control group (p = 0.001; p = 0.034). No significant relationships were found between kidney involvement, subclinical inflammation, presence of microhemorrhages and avascular areas in capillaroscopy, and disease duration. Additionally, no significant differences were observed in capillaroscopic findings between those with exon-10 mutations in the MEFV gene and those with non-exon-10 mutations. Conclusions: In conclusion, our study demonstrated secondary microvascular findings due to inflammation in FMF patients using capillaroscopy, a cost-effective and safe tool.

It is necessary to verify whether nail fold capillaroscopy can be utilized for the early detection of breast cancer. To establish this technology, an animal model was developed, utilizing mice for nail fold observations. Nail fold capillaroscopy revealed a human-like anatomical pattern and facilitated the observation of cellular movement within blood vessels. Injection of MCF-7 or mammary fibroblasts in mice allowed the observation of cellular vibrations using motion microscopy from nail fold. We have named this technology 'capillary cell motion microscopy.' Intriguingly, we were able to identify distinct cellular vibrations in the MCF-7 group. Moreover, evaluating its effectiveness in mice with chemically induced cancer revealed higher sensitivity (81%-85%) compared to conventional methods (45%-68%). Capillary cell motion microscopy, operating at 0.5–1.5 Hz, provided clear distinction of tumor cells and demonstrated potential applicability in human subjects. While condition adjustments may be necessary, this method holds promise for noninvasive breast cancer detection through nail fold observations. [ABSTRACT FROM AUTHOR]

Background: Diabetes control is poor globally and leads to burdensome microvascular and macrovascular complications. We aimed to assess post hoc between-group differences in sustained risk factor control and macrovascular and microvascular endpoints at 6.5 years in the Center for cArdiovascular Risk Reduction in South Asia (CARRS) randomized trial. Methods and findings: This parallel group individual randomized clinical trial was performed at 10 outpatient diabetes clinics in India and Pakistan from January 2011 through September 2019. A total of 1,146 patients with poorly controlled type 2 diabetes (HbA1c ≥8% and systolic BP ≥140 mm Hg and/or LDL-cholesterol ≥130 mg/dl) were randomized to a multicomponent quality improvement (QI) strategy (trained nonphysician care coordinator to facilitate care for patients and clinical decision support system for physicians) or usual care. At 2.5 years, compared to usual care, those receiving the QI strategy were significantly more likely to achieve multiple risk factor control. Six clinics continued, while 4 clinics discontinued implementing the QI strategy for an additional 4-year follow-up (overall median 6.5 years follow-up). In this post hoc analysis, using intention-to-treat, we examined between-group differences in multiple risk factor control (HbA1c <7% plus systolic BP <130 mm Hg and/or LDL-cholesterol <100 mg/dl) and first macrovascular endpoints (nonfatal myocardial infarction, nonfatal stroke, death, revascularization [angioplasty or coronary artery bypass graft]), which were coprimary outcomes. We also examined secondary outcomes, namely, single risk factor control, first microvascular endpoints (retinopathy, nephropathy, neuropathy), and composite first macrovascular plus microvascular events (which also included amputation and all-cause mortality) by treatment group and whether QI strategy implementation was continued over 6.5 years. At 6.5 years, assessment data were available for 854 participants (74.5%; n = 417 [intervention]; n = 437 [usual care]). In terms of sociodemographic and clinical characteristics, participants in the intervention and usual care groups were similar and participants at sites that continued were no different to participants at sites that discontinued intervention implementation. Patients in the intervention arm were more likely to exhibit sustained multiple risk factor control than usual care (relative risk: 1.79; 95% confidence interval [CI], 1.45, 2.20), p < 0.001. Cumulatively, there were 233 (40.5%) first microvascular and macrovascular events in intervention and 274 (48.0%) in usual care patients (absolute risk reduction: 7.5% [95% CI: −13.2, −1.7], p = 0.01; hazard ratio [HR] = 0.72 [95% CI: 0.61, 0.86]), p < 0.001. Patients in the intervention arm experienced lower incidence of first microvascular endpoints (HR = 0.68 [95% CI: 0.56, 0.83), p < 0.001, but there was no evidence of between-group differences in first macrovascular events. Beneficial effects on microvascular and composite vascular outcomes were observed in sites that continued, but not sites that discontinued the intervention. Conclusions: In urban South Asian clinics, a multicomponent QI strategy led to sustained multiple risk factor control and between-group differences in microvascular, but not macrovascular, endpoints. Between-group reductions in vascular outcomes at 6.5 years were observed only at sites that continued the QI intervention, suggesting that practice change needs to be maintained for better population health of people with diabetes. Trial registration: ClinicalTrials.govNCT01212328. Nikhil Tandon and colleagues explore the impact of a quality improvement strategy for patients with type 2 diabetes 6.5 years after its implementation for the CARRS randomised trial. Author summary: Why was this study done?: Data on whether improvements in diabetes care goal achievement can be sustained (>5 years) with quality improvement (QI) strategies are lacking from low- and middle-income countries (LMICs). Prior studies of QI strategies to improve care goal achievement among people with diabetes from high-income countries reported modest benefits in blood glucose, blood pressure, and lipids, but the effects of these improvements on reducing vascular complications and deaths related to diabetes are unknown. What did the researchers do and find?: In the Center for cArdiovascular Risk Reduction in South Asia (CARRS) randomised trial of 1,146 patients with type 2 diabetes attending 10 diverse diabetes clinics in India and Pakistan, the QI strategy was associated with benefits on diabetes care goals (HbA1c <7% plus systolic BP <130 mm Hg and/or LDL-cholesterol <100 mg/dl) at 2.5 years after randomization. Four clinics discontinued implementation, while 6 clinics continued to implement the QI strategy for an additional 4 years. This report assesses whether benefits were sustained and reduced vascular complications and deaths associated with diabetes at 6.5 years. Patients receiving the QI strategy, compared to those receiving usual care, experienced sustained benefits on diabetes care goals and less microvascular endpoints (eye, kidney, and nerve diseases) at 6.5 years after randomization. Total macrovascular and microvascular events were also lower in those receiving the QI strategy, and this was only observed at sites that continued implementation of the QI strategy for 6.5 years. What do these findings mean?: These findings add to our knowledge of the long-term effects of multicomponent QI strategies in sustaining multiple risk factor control and reducing combined vascular events compared to usual care in resource-limited settings. In view of these findings, clinical decision support and trained nonphysician health workers may be important QI strategies to consider integrating into India's healthcare system to improve diabetes care quality and reduce morbidity and mortality. One limitation of the study is that the tertiary care facilities included in the CARRS trial may not be generalizable across LMICs. [ABSTRACT FROM AUTHOR]

Introduction: Nail-fold capillaroscopy is a non-invasive method for assessment of the microcirculation in nail folds. This examination is particularly useful for diagnosis, assessment of activity, evaluation of the response to treatment, and assessment of the correlation of changes in microvessels with changes in organs in systemic sclerosis and in scleroderma-spectrum diseases, i.e. dermatomyositis, polymyositis, mixed connective tissue disease, and undifferentiated connective tissue disease. Aim: To perform capillaroscopic analyses of lesions in patients with scleroderma-spectrum diseases and determine the correlation of the capillaroscopic image with organ manifestations and the serological profile. Material and methods: The study involved 15 patients with scleroderma-spectrum disorders. Results: Mixed systemic connective tissue disease was diagnosed in 8 patients, and dermatomyositis was detected in 7 patients. The study assessed the frequency of clinical symptoms, e.g. interstitial lung disease or arthritis, and the presence of ANA antibodies. Scleroderma-like microangiopathy was diagnosed in 47% of patients with scleroderma-spectrum disorders. The early pattern was found in patients with mixed systemic connective tissue disease, whereas dermatomyositis was characterized by the late pattern. Non-specific changes were found in 27% of the patients, and a normal image was observed in 27% of the patients. Conclusions: The analysis also revealed that the reduced number of vessels correlated with the occurrence of interstitial lung disease, and the incidence of Raynaud's phenomenon and arthritis was statistically significantly higher in patients with systemic connective tissue disease than in those with dermatomyositis. [ABSTRACT FROM AUTHOR]

Primary Raynaud's phenomenon (pRP) is difficult to distinguish from secondary (sRP). Although nailfold capillaroscopy (NFC) may detect early alterations, no universal criteria yet discriminate between pRP from sRP. To create and validate two NFC scores that could distinguish pRP from sRP and that could predict systemic sclerosis (SSc), respectively. We performed NFC on two separate cohorts with isolated RP, and recorded number of capillaries per field, enlarged/giant capillaries, crossed/bizarre patterns, microhemorrhages, neoangiogenesis, rarefaction, edema, blood flow velocity, stasis. By multivariate regression analysis, we evaluated the adjusted prognostic role of these features in a derivation cohort of 656 patients. Results were used to construct algorithm-based prognostic scores (A and B). These scores were then tested on a confirmation cohort of 219 patients. Score A was unable to discriminate sRP from pRP (low negative predictive values with high positive predictive values for any cut-point); score B was unable to discriminate progression to SSc or a SSc-spectrum disorder (low positive predictive values with high negative predictive values for lower cut-points). NFC patterns, believed as specific, showed low discriminatory power and on their own are unable to reliably discriminate sRP from pRP or predict evolution to SSc. [ABSTRACT FROM AUTHOR]

Background: Serum trace elements and oxidative stress factors are related to diabetic microvascular complications. The study was to investigate the complex relationship between trace elements, oxidative stress factors, and the severity of microvascular complications of diabetes in older adults. Methods: The present study included patients with or without type 2 diabetes, and blood glucose, blood lipids, trace elements (iron, magnesium, zinc), oxidative stress factors (malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC)) were evaluated. Risk factors for the severity of diabetic microvascular complications in older adults with diabetes were also estimated. Results: There were statistically significant differences in fasting blood glucose (FBG), triglycerides (TG), low density lipoprotein (LDL), glycated hemoglobin (HbAlc), MDA, NO, SOD, T-AOC, magnesium, and zinc between the two groups (P< 0.05). Iron (rZinc = 0.147, rSOD = 0.180, rT-AOC = 0.193, P < 0.05) was positively correlated with zinc, SOD and T-AOC. Iron was negatively correlated with MDA (rMDA = − 0.146, P < 0.05). Magnesium was positively correlated with SOD (rMagnesium = 0.147, P < 0.05). Zinc (rSOD = 0.616, rT-AOC = 0.575, P < 0.01) was positively correlated with SOD and T-AOC. Zinc (rMDA =− 0.636, rNO=− 0.616, P< 0.01) was positively correlated with MDA and negatively correlated with NO. The course of disease (18.653, [5.726; 60.764], P < 0.01), FBG (1.265, [1.059; 1.511], P < 0.05), HbAlc (1.545, [1.431; 1.680], P < 0.01), MDA (2.989, [1.900; 4.702], P < 0.01) were risk factor for the severity of diabetic microvascular complications. Zinc (0.680, [0.503; 0.919], P < 0.05) and SOD (0.820, [0.698; 0.964], P < 0.05) were protective factors for the severity of diabetic microvascular complications. Conclusion: Serum trace elements are related to oxidative stress levels in older adults with type 2 diabetes. The more stable trace element in older adults with diabetes, the lower the oxidative stress and the fewer microvascular complications of diabetes. [ABSTRACT FROM AUTHOR]

Introduction: The identification of new, easily measurable biomarkers might assist clinicians in diagnosing and managing systemic sclerosis (SSc). Although the full blood count is routinely assessed in the evaluation of SSc, the diagnostic utility of specific cell-derived inflammatory indices, i.e., neutrophil-tolymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-tolymphocyte ratio (MLR), has not been critically appraised in this patient group. Methods: We conducted a systematic review and meta-analysis of studies investigating the NLR, PLR, and MLR, in SSc patients and healthy controls and in SSc patients with and without relevant complications. PubMed, Scopus, and Web of Science were searched from inception to 23 February 2024. Risk of bias and certainty of evidence were assessed using validated tools. Results: In 10 eligible studies, compared to controls, patients with SSc had significantly higher NLR (standard mean difference, SMD=0.68, 95% CI 0.46 to 0.91, p<0.001; I² = 74.5%, p<0.001), and PLR values (SMD=0.52, 95% CI 0.21 to 0.83, p=0.001; I² = 77.0%, p=0.005), and a trend towards higher MLR values (SMD=0.60, 95% CI -0.04 to 1.23, p=0.066; I² = 94.1%, p<0.001). When compared to SSc patients without complications, the NLR was significantly higher in SSc with interstitial lung disease (ILD, SMD=0.31, 95% CI 0.15 to 0.46, p<0.001; I² = 43.9%, p=0.11), pulmonary arterial hypertension (PAH, SMD=1.59, 95% CI 0.04 to 3.1, p=0.045; I² = 87.6%, p<0.001), and digital ulcers (DU, SMD=0.43, 95% CI 0.13 to 0.74, p=0.006; I² = 0.0%, p=0.49). The PLR was significantly higher in SSc patients with ILD (SMD=0.42, 95% CI 0.25 to 0.59, p<0.001; I² = 24.8%, p=0.26). The MLR was significantly higher in SSc patients with PAH (SMD=0.63, 95% CI 0.17 to 1.08, p=0.007; I² = 66.0%, p=0.086), and there was a trend towards a higher MLR in SSc patients with ILD (SMD=0.60, 95% CI -0.04 to 1.23, p=0.066; I² = 94.1%, p<0.001). Discussion: Pending the results of appropriately designed prospective studies, the results of this systematic review and meta-analysis suggest that blood cellderived indices of inflammation, particularly the NLR and PLR, may be useful in the diagnosis of SSc and specific complications. [ABSTRACT FROM AUTHOR]

Objective: To analyze the performance of custom semi-automated software for quantitative analysis of retinal capillaries in eyes with macula-off rhegmatogenous retinal detachment (RRD) and the role of these microvascular measures as potential biomarkers of postoperative visual outcomes. Methods: A prospective, observational, and single-center study was conducted on consecutive patients who underwent 25G pars-plana vitrectomy for primary uncomplicated macula-off RRD. Optical coherence tomography angiography (OCTA) was performed in the fellow and RRD eyes before surgery and in months 1, 3, and 6 after surgery. The preoperative values of the fellow eyes were used as surrogates of macula-off ones. The primary endpoints were the mean vessel diameter index (VDI); vessel area density (VAD); and vessel skeleton density (VSD) at month 6. Results: Forty-four eyes (44 patients) were included in the study. Considering the fellow eyes as a surrogate of preoperative values of macula-off eyes, VDI in superficial (SCP) and deep (DCP) capillary plexuses was significantly reduced at month 6 (p = 0.0087 and p = 0.0402, respectively); whereas VSD in SCP increased significantly from preoperative values (p = 0.0278). OCTA built-in software parameters were significantly reduced from month 1 to month 6 in both SCP and DCP (p values ranged between 0.0235 and <0.0001). At month 6, 25 (56.8%) eyes achieved a best-corrected visual acuity BCVA ≥ 0.3 (LogMAR). The greater the preoperative BCVA, the greater the probability of achieving good visual outcomes (Odds ratio: 11.06; p = 0.0037). However, none of the OCTA parameters were associated with the probability of achieving a BCVA improvement ≥ 0.3. Conclusions: Quantitative evaluation of capillary density and morphology through OCTA and semi-automated software represents a valuable tool for clinical assessment and managing the disease comprehensively. [ABSTRACT FROM AUTHOR]

Primary graft dysfunction (PGD) remains a challenge for lung transplantation (LTx) recipients as a leading cause of poor early outcomes. New methods are needed for more detailed monitoring and understanding of the pathophysiology of PGD. The measurement of particle flow rate (PFR) in exhaled breath is a novel tool to monitor and understand the disease at the proteomic level. In total, 22 recipient pigs underwent orthotopic left LTx and were evaluated for PGD on postoperative day 3. Exhaled breath particles (EBPs) were evaluated by mass spectrometry and the proteome was compared to tissue biopsies and bronchoalveolar lavage fluid (BALF). Findings were confirmed in EBPs from 11 human transplant recipients. Recipients with PGD had significantly higher PFR [686.4 (449.7–8,824.0) particles per minute (ppm)] compared to recipients without PGD [116.6 (79.7–307.4) ppm, p = 0.0005]. Porcine and human EBP proteins recapitulated proteins found in the BAL, demonstrating its utility instead of more invasive techniques. Furthermore, adherens and tight junction proteins were underexpressed in PGD tissue. Histological and proteomic analysis found significant changes to the alveolar-capillary barrier explaining the high PFR in PGD. Exhaled breath measurement is proposed as a rapid and non-invasive bedside measurement of PGD. [ABSTRACT FROM AUTHOR]

Background: Nailfold capillaroscopy (NFC) is useful in the diagnosis and assessment of various connective tissue diseases. In this study, NFC findings were studied in patients of systemic sclerosis (SS), systemic lupus erythematosus (SLE) and dermatomyositis. Aims: To study the nailfold capillaroscopic findings in patients with connective tissue disorders, their correlation with disease severity, and changes in findings following treatment or disease progression. Methods: This observational prospective time-bound clinico-epidemiological study was conducted in 43 patients over 20 months at Topiwala National Medical College and BYL Nair Ch. Hospital, Mumbai. NFC was performed using the polarising mode of a USB 2.0 video-dermatoscope in all 10 fingernails at 50X and 200X. It was repeated at three follow-up visits to look for changes in findings. Results: Among SLE patients, eleven (52.4%) had non-specific NFC patterns and eight (38.1%) had SLE patterns. Among systemic sclerosis patients, eight (42.1%) cases had active and late SS patterns respectively, while one (5.3%) each had SLE, non-specific and early SS patterns. After three follow-ups, 10 out of 11 (90.9%) cases with improvement in NFC also showed clinical improvement; this figure was significantly more than 11 out of 23 (47.8%) cases who had no change in NFC but showed clinical improvement. Two of the three dermatomyositis patients showed a non-specific pattern while one showed a late SS pattern at baseline. Limitations: A larger sample size would have yielded results with more validity. Standardisation of the interval between baseline and last follow-up to equal to or more than six months would have yielded results with more accuracy. Conclusion: Capillary findings change significantly over time and reflect changes in the clinical status of patients of both SLE and systemic sclerosis, and hence are an important prognostic marker. Rather than an overt change in NFC pattern, reduction or increase in abnormal capillaries is a better predictor of change in disease activity. [ABSTRACT FROM AUTHOR]

Hemifacial spasm (HFS) is a syndrome characterized by involuntary contractions of the facial muscles innervated by the ipsilateral facial nerve. Currently, microvascular decompression (MVD) is an effective treatment for HFS. Diffusion weighted imaging (DWI) is a non-invasive advanced magnetic resonance technique that allows us to reconstruct white matter (WM) virtually based on water diffusion direction. This enables us to model the human brain as a complex network using graph theory. In our study, we recruited 32 patients with HFS and 32 healthy controls to analyze and compare the topological organization of whole-brain white matter networks between the groups. We also explored the potential relationships between altered topological properties and clinical outcomes. Compared to the HC group, the white matter network was disrupted in both preoperative and postoperative groups of HFS patients, mainly located in the somatomotor network, limbic network, and default network (All P < 0.05, FDR corrected). There was no significant difference between the preoperative and postoperative groups (P > 0.05, FDR corrected). There was a correlation between the altered topological properties and clinical outcomes in the postoperative group of patients (All P < 0.05, FDR corrected). Our findings indicate that in HFS, the white matter structural network was disrupted before and after MVD, and that these alterations in the postoperative group were correlated with the clinical outcomes. White matter alteration here described may subserve as potential biomarkers for HFS and may help us identify patients with HFS who can benefit from MVD and thus can help us make a proper surgical patient selection. [ABSTRACT FROM AUTHOR]

Objective: Raynaud’s phenomenon (RP) is a condition characterized by vasoconstrictive attacks, and it can be diagnosed using nail-fold dermoscopy or videocapilloscopy. This study aimed to investigate the differences in nail-fold dermoscopy between patients with RP and a control group. Material and Methods: The study included 42 patients with RP and 33 individuals in the control group. Dermoscopic and clinical photographs of each finger nailfold were taken, resulting in 750 images that were categorized into 4 groups based on modified Maricq criteria: normal, suspect-capillary dilatation, abnormal-giant capillaries-hemorrhages, and unclassified. To assess the consistency of the staging, 40 random photographs were shown to 69 dermatologists who were asked to provide a rating. Results: The patient group had an underlying disease in 27 patients and the RF in these patients were evaluated as secondary RP. The nail-fold dermoscopy stages were categorized as follows: 31% stage 2, 28.6% stage 3, 28.6% stage 1, and 11.9% stage 4. The inter-observer reliability analysis was 69.56%, and the intra-observer reliability was 75.36%, with Cohen kappa >41. The study found that nail-fold dermoscopy has both inter-observer and intraobserver reliability, and it can be used for the detection of capillary abnormalities, even with minimal training. Therefore, it can be a useful technique in the early diagnosis of concomitant diseases in patients with RP. Conclusion: One notable aspect of this study was the use of a descriptive, simple ordinal score of severity to grade the overall capillaroscopic appearance. Overall, the widespread use of nail-fold dermoscopy in the diagnosis of Raynaud’s phenomenon can be a useful tool for early detection of concomitant diseases. [ABSTRACT FROM AUTHOR]

Objective: Proton pump inhibitors (PPIs) are widely prescribed to treat gastroesophageal reflux disease (GERD) in Systemic Sclerosis (SSc). However, not all patients adequately respond to the treatment, and there are frequent concerns about the safety of long‐term use of PPIs. Our aim was to identify the main problems/complaints of SSc patients on PPIs, as well as understand their unmet needs. Methods: SSc patients treated with PPIs were invited through international patient associations and social media to participate in an online survey. Results: We gathered 301 valid responses from 14 countries (United Kingdom 19.3% and United States 70.4%). Multiple PPIs use (two: 30% and three: 21% in series) was common. The majority (89%) reported improvement in gastrointestinal symptoms from receiving PPIs. Side effects attributed to receiving PPIs were uncommon (19%); however, most (79%) were potentially concerned. Around half (58%) had received lifestyle information, and most (85%) had searched online for information about PPIs. Only in the minority (12%) had a surgical approach been discussed; however, half (46%) indicated that they would be willing to undergo surgery to resolve their GERD symptoms but had important concerns. Conclusion: Despite the frequent use of PPIs in patients with SSc, there is significant heterogeneity in prescription, and combination therapy (PPIs plus other medication for acid reflux) is not uncommon (approximately 40%). Patients have significant concerns about PPIs side effects. Education about PPIs is often neglected, and patients very frequently use online sources to obtain information on drug treatment. A surgical approach is infrequently discussed, and patients fear this potential therapeutic approach. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the earliest changes in the structure and function of the peripheral microcirculation using capillaroscopy and transcutaneous oxygen pressure measurement in children and adolescents with type 1 diabetes mellitus at baseline and during post-occlusive reactive hyperemia (PORH) in the function of diabetes duration. Sixty-seven patients with type 1 diabetes mellitus (T1D), aged 8 to 18 years, and twenty-eight age- and sex-matched healthy subjects were included in the analysis. Diabetic patients were divided into subgroups based on median disease duration. The subgroups differed in chronological age, lipid levels, and thyroid hormones. Capillaroscopy was performed twice: at baseline and then again after the PORH test. Transcutaneous oxygen pressure also was recorded under baseline conditions during and after the PORH test. Comparison of capillaroscopy and transcutaneous oxygen pressure parameters at rest and after the PORH showed no statistically significant difference between the subgroups. This remained true after adjusting for variables that differentiated the two subgroups. However, in the group of patients with long-standing diabetes, significant negative correlations were observed between the Coverage value after the PORH test and capillary reactivity with TcPO2_zero (biological zero). Significant positive correlations were also found between distance after the PORH test and TcPO2_zero. The results of our study indicate that in patients with a shorter duration of diabetes, the use of multiple tests provides a better characterization of the structure and function of microcirculation because the onset of dysfunction does not occur at the same time in all the tests. [ABSTRACT FROM AUTHOR]

Primary graft dysfunction (PGD) remains a challenge for lung transplantation (LTx) recipients as a leading cause of poor early outcomes. New methods are needed for more detailed monitoring and understanding of the pathophysiology of PGD. The measurement of particle flow rate (PFR) in exhaled breath is a novel tool to monitor and understand the disease at the proteomic level. In total, 22 recipient pigs underwent orthotopic left LTx and were evaluated for PGD on postoperative day 3. Exhaled breath particles (EBPs) were evaluated by mass spectrometry and the proteome was compared to tissue biopsies and bronchoalveolar lavage fluid (BALF). Findings were confirmed in EBPs from 11 human transplant recipients. Recipients with PGD had significantly higher PFR [686.4 (449.7-8,824.0) particles per minute (ppm)] compared to recipients without PGD [116.6 (79.7-307.4) ppm, p = 0.0005]. Porcine and human EBP proteins recapitulated proteins found in the BAL, demonstrating its utility instead of more invasive techniques. Furthermore, adherens and tight junction proteins were underexpressed in PGD tissue. Histological and proteomic analysis found significant changes to the alveolar-capillary barrier explaining the high PFR in PGD. Exhaled breath measurement is proposed as a rapid and non-invasive bedside measurement of PGD. [ABSTRACT FROM AUTHOR]

Introduction: The foot sole endures high magnitudes of pressure for sustained periods which results in transient but habitual cutaneous ischemia. Upon unloading, microvascular reactivity in cutaneous capillaries generates an influx of blood flow (PORH: post-occlusive reactive hyperemia). Whether pressure induced cutaneous ischemia from loading the foot sole impacts mechanoreceptor sensitivity remains unknown. Methods: Pressure induced ischemia was attained using a custom-built-loading device that applied load to the whole right foot sole at 2 magnitudes (15 or 50% body weight), for 2 durations (2 or 10 minutes) in thirteen seated participants. Mechanoreceptor sensitivity was assessed using Semmes-Weinstein monofilaments over the third metatarsal (3MT), medial arch (MA), and heel. Perceptual thresholds (PT) were determined for each site prior to loading and then applied repeatedly to a metronome to establish the time course to return to PT upon unload, defined as PT recovery time. Microvascular flux was recorded from an in-line laser speckle contrast imager (FLPI-2, Moor Instruments Inc.) to establish PORH peak and recovery rates at each site. Results: PT recovery and PORH recovery rate were most influenced at the heel and by load duration rather than load magnitude. PT recovery time at the heel was significantly longer with 10 minutes of loading, regardless of magnitude. Heel PORH recovery rate was significantly slower with 10minutes of loading. The 3MT PT recovery time was only longer after 10 minutes of loading at 50% body weight. Microvascular reactivity or sensitivity was not influenced with loading at the MA. A simple linear regression found that PORH recovery rate could predict PT recovery time at the heel (R2=0.184, p<0.001). Conclusion: In populations with degraded sensory feedback, such as diabetic neuropathy, the risk for ulcer development is heightened. Our work demonstrated that prolonged loading in healthy individuals can impair skin sensitivity, which highlights the risks of prolonged loading and is likely exacerbated in diabetes. Understanding the direct association between sensory function and microvascular reactivity in age and diabetes related nerve damage, could help detect early progressions of neuropathy and mitigate ulcer development. [ABSTRACT FROM AUTHOR]