Dyschromatosis symmetrica hereditaria: A clue to early diagnosis of Aicardi-Goutières syndrome.

A 6-year-old female with a history of Aicardi-Goutières syndrome (AGS) presented to dermatology clinic with hypopigmented and hyperpigmented macules and patches consistent with dyschromatosis symmetrica hereditaria (DSH). Previous genetic workup demonstrated a de novo, heterozygous mutation in the adenosine deaminase acting on RNA 1 (ADAR) gene. While the co-occurrence of AGS and DSH has previously been described in mutations of the ADAR gene, our case highlights the potential association between these disorders that may aid in earlier future diagnosis of AGS.

3D-Printed Conformal Meta-Lens with Multiple Beam-Shaping Functionalities for Mm-Wave Sensing Applications.

In this paper, a 3D conformal meta-lens designed for manipulating electromagnetic beams via height-to-phase control is proposed. The structure consists of a 40 × 20 array of tunable unit cells fabricated using 3D printing, enabling full 360° phase compensation. A novel automatic synthesizing method (ASM) with an integrated optimization process based on genetic algorithm (GA) is adopted here to create the meta-lens. Simulation using CST Microwave Studio and MATLAB reveals the antenna's beam deflection capability by adjusting phase compensations for each unit cell. Various beam scanning techniques are demonstrated, including single-beam, dual-beam generation, and orbital angular momentum (OAM) beam deflection at different angles of 0°, 10°, 15°, 25°, 30°, and 45°. A 3D-printed prototype of the dual-beam feature has been fabricated and measured for validation purposes, with good agreement between both simulation and measurement results, with small discrepancies due to 3D printing's low resolution and fabrication errors. This meta-lens shows promise for low-cost, high-gain beam deflection in mm-wave wireless communication systems, especially for sensing applications, with potential for wider 2D beam scanning and independent beam deflection enhancements.

Spatial characterization and quantification of CD40 expression across cancer types.

BACKGROUND: CD40, a TNF receptor family member, is expressed by a variety of immune cells and is involved in the activation of both adaptive and innate immune responses. Here, we used quantitative immunofluorescence (QIF) to evaluate CD40 expression on the tumor epithelium of solid tumors in large patient cohorts of lung, ovarian, and pancreatic cancers. METHODS: Tissue samples from nine different solid tumors (bladder, breast, colon, gastric, head and neck, non-small cell lung cancer (NSCLC), ovarian, pancreatic and renal cell carcinoma), constructed in tissue microarray format, were initially assessed for CD40 expression by QIF. CD40 expression was then evaluated on the large available patient cohorts for three of the tumor types demonstrating high CD40 positivity rate; NSCLC, ovarian and pancreatic cancer. The prognostic impact of CD40 expression on tumor cells was also investigated. RESULTS: CD40 expression on tumor cells was found to be common, with 80% of the NSCLC population, 40% of the ovarian cancer population, and 68% of the pancreatic adenocarcinoma population displaying some degree of CD40 expression on cancer cells. All of three of these cancer types displayed considerable intra-tumoral heterogeneity of CD40 expression, as well as partial correlation between expression of CD40 on tumor cells and on surrounding stromal cells. CD40 was not found to be prognostic for overall survival in NSCLC, ovarian cancer, or pancreatic adenocarcinoma. CONCLUSIONS: The high percentage of tumor cells expressing CD40 in each of these solid tumors should be considered in the development of therapeutic agents designed to target CD40.

National Wastewater Reconnaissance of Analgesic Consumption in Australia.

A wastewater-based epidemiology (WBE) method is presented to estimate analgesic consumption and assess the burden of treated pain in Australian communities. Wastewater influent samples from 60 communities, representing ∼52% of Australia's population, were analyzed to quantify the concentration of analgesics used to treat pain and converted to estimates of the amount of drug consumed per day per 1000 inhabitants using pharmacokinetics and WBE data. Consumption was standardized to the defined daily dose per day per 1000 people. The population burden of pain treatment was classified as mild to moderate pain (for non-opioid analgesics) and strong to severe pain (for opioid analgesics). The mean per capita weighted total DDD of non-opioid analgesics was 0.029 DDD/day/person, and that of opioid-based analgesics was 0.037 DDD/day/person across Australia. A greater burden of pain (mild to moderate or strong to severe pain index) was observed at regional and remote sites. The correlation analysis of pain indices with different socioeconomic descriptors revealed that pain affects populations from high to low socioeconomic groups. Australians spent an estimated US $3.5 (AU $5) per day on analgesics. Our findings suggest that WBE could be an effective surveillance tool for estimating the consumption of analgesics at a population scale and assessing the total treated pain burden in communities.

Managing Monkeypox Virus: Characterizing Common Cutaneous Manifestations and Antiviral Efficacy.

BACKGROUND: The Monkeypox virus (MPX) has been detected in multiple non-endemic countries since May 2022. The cutaneous manifestations of MPX can have multiple distinct presentations, including pustular and vesicular. Although there are no approved treatments, three antivirals (brincidofovir, cidofovir, tecovirimat) have been utilized. The objective of our study was to conduct a systematic review to evaluate antiviral efficacy (first aim) and cutaneous manifestations of MPX (second aim). METHODS: Utilizing PRISMA guidelines, we searched PubMed and SCOPUS databases to identify studies utilizing antiviral treatment in human subjects for MPX and studies reporting cutaneous characteristics of MPX lesions. RESULTS: For our first aim, six articles met inclusion criteria. For our second aim, 27 met inclusion criteria. Eighty-eight percent had complete resolution with tecovirimat (n=28) which was well tolerated, and decreased hospitalization time (10 days) compared to brincidofovir (29 days). Forty-four percent of patients had <10 cutaneous lesions and 36% had 10-100 lesions. The most common lesion type was pustular (32%, n=380). CONCLUSION: This limited sample of studies suggests that tecovirimat is well tolerated and may be an effective antiviral for MPX treatment. Further studies are required to better understand the role of antivirals for MPX treatment among human patients. J Drugs Dermatol. 2023;22(3): doi:10.36849/JDD.7263.

Differences in prescriptions for systemic medications and nonsteroidal topicals among children with atopic dermatitis.

Nonsteroidal topicals and systemic therapies are often utilized for atopic dermatitis (AD) in children with inadequate response to topical corticosteroids. We sought to characterize patient factors associated with prescriptions for nonsteroidal topical (tacrolimus, pimecrolimus, crisaborole), systemic immunosuppressant (methotrexate, mycophenolate, cyclosporine, azathioprine), and systemic corticosteroid therapy among children with AD. In a cross-sectional study of patients <18 years old with AD seen at a large children's hospital between 2009 and 2017, we found that nonsteroidal topical and systemic medication prescriptions were associated with older age of the patient, male sex, comorbid atopy, greater healthcare utilization, specialist care, and race/ethnicity. Compared to White patients, Black and Hispanic patients were less likely to be prescribed nonsteroidal topicals and non-White patients were less likely to be prescribed systemic medications, suggesting that further examination of potential disparities in pediatric AD treatment is needed.

Generation of Mixed-OAM-Carrying Waves Using Huygens' Metasurface for Mm-Wave Applications.

Antennas that generate orbital angular momentum (OAM) have the potential to significantly enhance the channel capacity of upcoming wireless systems. This is because different OAM modes that are excited from a shared aperture are orthogonal, which means that each mode can carry a distinct stream of data. As a result, it is possible to transmit multiple data streams at the same time and frequency using a single OAM antenna system. To achieve this, there is a need to develop antennas that can create several OAM modes. This study employs an ultrathin dual-polarized Huygens' metasurface to design a transmit array (TA) that can generate mixed-OAM modes. Two concentrically-embedded TAs are used to excite the desired modes by achieving the required phase difference according to the coordinate position of each unit cell. The prototype of the TA, which operates at 28 GHz and has a size of 11 × 11 cm 2, generates mixed OAM modes of -1 and -2 using dual-band Huygens' metasurfaces. To the best of the authors' knowledge, this is the first time that such a low-profile and dual-polarized OAM carrying mixed vortex beams has been designed using TAs. The maximum gain of the structure is 16 dBi.

Awareness of undergraduate dental students, interns, and freshly graduated dentists about oral manifestation associated with COVID-19.

OBJECTIVE: There is growing evidence supporting the presence of oral manifestations associated with COVID-19. The study investigates the knowledge of dental undergraduates and recently graduated dentists concerning oral presentations related to COVID-19. METHODS: A cross-sectional descriptive study in Saudi Arabia comprised 305 individuals, including undergraduate dental students, interns, and freshly graduated dentists. Data were collected using a questionnaire disseminated to approximately 500 subjects via WhatsApp groups and other applications. The questionnaire was tested in a pilot study for validity, edited, and validated by 2 supervisors at the College of Dentistry, Qassim University, Buraydah, Saudi Arabia. The questionnaire consisted of questions regarding sociodemographic attributes, the level of expertise of dental practitioners, and their knowledge and perspectives regarding COVID-19 and the implementation of oral lesions interrelated to it. The data was subjected to analysis through the utilization of descriptive statistics and chi-square tests, employing the statistical software SPSS (version 24). RESULTS: About 43.9% of subjects stated that COVID-19 causes oral symptoms. Respondents most frequently reported COVID-19-related dry mouth. Oral ulcers, Candida infection, Hyperpigmentation, tongue coating, atrophy, Petechiae, Herpes, white lesions, Gingivitis, and Periodontitis are further symptoms. COVID-19's oral manifestation was unknown to 41.0% of subjects, and 37.7% of respondents lacked knowledge regarding the most impacted locations of oral manifestations. Oral signs and COVID-19 symptoms are debated and significantly associated with higher educational levels. CONCLUSION: The dental students and freshly graduated dentists in this study have proper knowledge of COVID-19 and its symptoms. Also, most dental students and newly graduated dentists recognize the potential correlation between COVID-19 and oral manifestations with an average to excellent knowledge of the types and sites commonly affected. The level of awareness was associated with higher educational levels.

Deep learning trained on hematoxylin and eosin tumor region of Interest predicts HER2 status and trastuzumab treatment response in HER2+ breast cancer.

The current standard of care for many patients with HER2-positive breast cancer is neoadjuvant chemotherapy in combination with anti-HER2 agents, based on HER2 amplification as detected by in situ hybridization (ISH) or protein immunohistochemistry (IHC). However, hematoxylin & eosin (H&E) tumor stains are more commonly available, and accurate prediction of HER2 status and anti-HER2 treatment response from H&E would reduce costs and increase the speed of treatment selection. Computational algorithms for H&E have been effective in predicting a variety of cancer features and clinical outcomes, including moderate success in predicting HER2 status. In this work, we present a novel convolutional neural network (CNN) approach able to predict HER2 status with increased accuracy over prior methods. We trained a CNN classifier on 188 H&E whole slide images (WSIs) manually annotated for tumor Regions of interest (ROIs) by our pathology team. Our classifier achieved an area under the curve (AUC) of 0.90 in cross-validation of slide-level HER2 status and 0.81 on an independent TCGA test set. Within slides, we observed strong agreement between pathologist annotated ROIs and blinded computational predictions of tumor regions / HER2 status. Moreover, we trained our classifier on pre-treatment samples from 187 HER2+ patients that subsequently received trastuzumab therapy. Our classifier achieved an AUC of 0.80 in a five-fold cross validation. Our work provides an H&E-based algorithm that can predict HER2 status and trastuzumab response in breast cancer at an accuracy that may benefit clinical evaluations.

Junctional epidermolysis bullosa with extensive lung involvement in three patients with a LAMB3 Mutation.

Junctional epidermolysis bullosa (JEB) is characterized by skin and mucous membrane fragility leading to easy blistering. Blistering may be the result of multiple genetic mutations, including the LAMB3 gene encoding a subunit of laminin 332, an important protein in the basement membrane zone. The clinical presentation of JEB includes blistering and granulation tissue forming anywhere on the skin including around oral and nasal cavities, fingers, toes, and within mucous membranes such as the upper respiratory tract. Lung pathology associated with JEB is less commonly reported; we describe three children with LAMB3 pathogenic variants with extensive lung injury contributing to decline in clinical status and likely leading to their demise early in life.

First molecular description of Macracanthorhynchus hirudinaceus in wild boars from Italy with pathomorphological and epidemiological insights.

Macracanthorhynchus hirudinaceus is a zoonotic parasite affecting suids worldwide which are the definitive hosts for this helminth species. Macracanthorhynchus hirudinaceus is of significant economic and management concern due to its pathogenicity, causing intestinal obstruction and perforation in the definitive hosts. Current study is the preliminary investigation from Sardinia, Italy, reporting the pathomorphological findings and molecular characterization of M. hirudinaceus in the wild boars (Sus scrofa meridionalis). A total of 59 wild boars were examined showing acanthocephalan infection in 8 (13.6%) animals. In total, 49 parasites were collected with a mean intensity of 6.1. Comparatively higher infection levels were observed for males (16.7%) and young boars (14.3%); however, these epidemiological differences were statistically non-significant. Histopathological examination revealed the presence of a variable number of nodules (∼5 mm) in the intestine of M. hirudinaceus infested animals surrounded by a hyperemic-hemorrhagic halo. Several parasites were recovered from the intestinal lumen attached by the means of characteristic hooks showing necrosis in muscle layers. A moderate number of plump reactive fibroblasts and lesser numbers of fibrocytes were embedded with and at the borders of the inflammatory nodules in a moderate amount of homogeneous intensely eosinophilic fibrillary material rupturing the cell membrane. For molecular characterization, six isolated worms were amplified for the partial mitochondrial cox1 gene showing distinct interindividual variations. This first pathological and molecular description from southern Europe provided new knowledge about the diffusion of M. hirudinaceus in wild boars, furthering the research into the origin and transmission status of M. hirudinaceus in endemic localities.

Excreta quality and digestive function of singly versus couple caged Sardinian partridges (Alectoris barbara barbara Bonnaterre, 1790) as non-invasive indicators of birds' coping ability to forced pairing.

The Sardinian partridge is a monogamous wild bird species of least concern according to IUCN list at present, though formerly accounted among threatened species for decades. The creation of couples is crucial in captivity, because forced pairing in cages can lead to poor welfare of birds, specially of females. This study investigated the impact of single versus couple caging of Sardinian partridges during non-laying period based on the collection and interpretation of indirect and non-invasive parameters (feed intake; space availability; excreta quality; and nutrient utilization). A total of 24 couples of breeding partridges were enrolled for two consequent phases of a same investigation (lasting 15 days each). During phase 1, all couples were fed ad libitum with a pelleted complete diet (DM, 905 g kg-1 of diet; CP, 160 g kg-1 ; and EE, 25 g kg-1 ). In phase 2, each male from 12 out of 24 couples was moved to an identical cage close to that where the female remained alone, to keep visual contact. The rest of couples continued to be kept like in phase 1. During phases 1 and 2, feed intake and excreta outputs were recorded daily. Pooled excreta of the last 3 days from couples and single birds were assessed for pH and DM, CP and ash content. Nutrient digestibility was calculated. No significant differences were noted between single versus couple caging regarding body weight (438 vs. 422 g respectively) or nutrient digestibility. However, singly housed males reduced daily feed intakes and females increased daily feed intake per g-1 BW (0.041 vs. 0.052 g, respectively, p < 0.001). Our results suggest that singly caged partridges from permanent couples can improve the access to feed and reduce competition during the non-mating season.

Genetic diversity and transmission patterns of Echinococcus granulosus sensu stricto among domestic ungulates of Sardinia, Italy.

Cystic echinococcosis (CE), a parasitic zoonosis of public health and economic concern, is highly endemic in Sardinia, Italy. The study involved examining the intraspecific variability and demographic structure of Echinococcus granulosus sensu stricto (s.s.) in common hosts of this parasite. Molecular surveillance included the fragment amplification of a partial mitochondrial gene, cox1 (750 bp), for a total of 69 isolates derived from sheep (n = 52), cattle (n = 11), pigs (n = 4), and goats (n = 2). It was ascertained that E. granulosus s.s. was the primary agent of infection among these ungulates and G1 genotype was highly prevalent (79.71%). Considerable intraspecific variation was found, revealing the existence of 22 haplotypes with relatively high haplotype (0.8555 ± 0.033) and low nucleotide diversities (0.00281 ± 0.00030). Population demographics indicated an expanding parasitic population signifying negative deviation from neutrality indices. Little genetic differentiation was found between the subpopulations of E. granulosus s.s. in the island. Moreover, the geographic dispersal of genotypes G1 and G3 also indicated similarity between Sardinian and mainland Echinococcus granulosus s.s. populations reaffirming the sympatric occurrence and efficient transmission of G1 and G3 genotypes. Molecular survey of CE has the potential to yield baseline information on the infective genotypes among the intermediate hosts and helps in devising suitable control strategies for curtailing the disease.

Meta-Analysis of Randomized Controlled Trials Comparing the Efficacy of Radioactive Iodine Monotherapy versus Radioactive Iodine Therapy and Adjunctive Lithium for the Treatment of Hyperthyroidism.

Background: The objective of this article is to evaluate the outcomes in patients undergoing radioactive iodine (RAI) with adjunctive lithium (Li) therapy versus (vs.) RAI therapy alone for the treatment of hyperthyroidism.Methods: A systematic review of the literature was undertaken to analyze clinical trials comparing RAI with adjunctive Li therapy vs. RAI therapy alone for the treatment of hyperthyroidism.Results: Six randomized-controlled trials (RCT) involving 755 patients were analyzed. RAI with adjunctive Li was associated with a significantly higher cure rate for hyperthyroidism when compared to RAI alone. Furthermore, a significantly higher cure rate for hyperthyroidism at 12 months was achieved with RAI and adjunctive Li. Adjuvant Li with RAI for ≤ 7 days showed significantly higher cure rate compared to RAI alone, whereas > 7 days of adjuvant Li with RAI did not show any difference in cure rate compared to RAI alone. RAI with adjunctive Li was associated with a significantly higher cure rate for patients with Graves' disease compared to RAI alone. There was no significant difference between RAI with adjunctive Li and RAI alone for toxic nodular thyroid disorder (toxic nodule and toxic multinodular goiter) and thyroid volume >40 grams and ≤40 grams.Conclusions: RAI with adjunctive Li therapy demonstrated superiority over RAI therapy alone with regards to both curing hyperthyroidism and, reduced time till cure, with a limited side effect profile. A large multicenter RCT is required, and if this confirms the data from these smaller trials, then this could change current practice.

Pro-Inflammatory and Neurotrophic Factor Responses of Cells Derived from Degenerative Human Intervertebral Discs to the Opportunistic Pathogen Cutibacterium acnes.

Previously, we proposed the hypothesis that similarities in the inflammatory response observed in acne vulgaris and degenerative disc disease (DDD), especially the central role of interleukin (IL)-1ß, may be further evidence of the role of the anaerobic bacterium Cutibacterium (previously Propionibacterium) acnes in the underlying aetiology of disc degeneration. To investigate this, we examined the upregulation of IL-1ß, and other known IL-1ß-induced inflammatory markers and neurotrophic factors, from nucleus-pulposus-derived disc cells infected in vitro with C. acnes for up to 48 h. Upon infection, significant upregulation of IL-1ß, alongside IL-6, IL-8, chemokine (C-C motif) ligand 3 (CCL3), chemokine (C-C motif) ligand 4 (CCL4), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), was observed with cells isolated from the degenerative discs of eight patients versus non-infected controls. Expression levels did, however, depend on gene target, multiplicity and period of infection and, notably, donor response. Pre-treatment of cells with clindamycin prior to infection significantly reduced the production of pro-inflammatory mediators. This study confirms that C. acnes can stimulate the expression of IL-1ß and other host molecules previously associated with pathological changes in disc tissue, including neo-innervation. While still controversial, the role of C. acnes in DDD remains biologically credible, and its ability to cause disease likely reflects a combination of factors, particularly individualised response to infection.

Prospective multi-institutional evaluation of pathologist assessment of PD-L1 assays for patient selection in triple negative breast cancer.

The US Food and Drug Administration (FDA) approved the PD-L1 immunohistochemical assay, SP142, as a companion test to determine eligibility for atezolizumab therapy in patients with advanced triple negative breast cancer (TNBC) but data in lung cancer studies suggest the assay suffers from poor reproducibility. We sought to evaluate reproducibility and concordance in PD-L1 scoring across multiple pathologists. Full TNBC sections were stained with SP142 and SP263 assays and interpreted for percentage (%) immune cell (IC) staining by 19 pathologists from 14 academic institutions. Proportion of PD-L1 positive cases (defined as ≥1% IC) was determined for each assay as well as concordance across observers. We utilized a new method we call Observers Needed to Evaluate Subjective Tests (ONEST) to determine the minimum number of evaluators needed to estimate concordance between large numbers of readers, as occurs in the real-world setting. PD-L1 was interpreted as positive with the SP142 assay in an average 58% of cases compared with 78% with SP263 (p < 0.0001). IC positive continuous scores ranged from 1 to 95% (mean = 20%) and 1 to 90% (mean = 10%) for SP263 and SP142, respectively. With SP142, 26 cases (38%) showed complete two category (<1% vs. ≥1%) concordance; with SP263, 38 cases (50%) showed complete agreement. The intraclass correlation coefficient (ICC) for two category scoring of SP263 and SP142 was 0.513 and 0.560. ONEST plots showed decreasing overall percent agreement (OPA) as observer number increased, reaching a low plateau of 0.46 at ten observers for SP263 and 0.41 at eight observers for SP142. IC scoring with both assays showed poor reproducibility across multiple pathologists with ONEST analysis suggesting more than half of pathologists will disagree about IC scores. This could lead to many patients either receiving atezolizumab when they are unlikely to benefit, or not receiving atezolizumab when they may benefit.

Can wastewater analysis be used as a tool to assess the burden of pain treatment within a population?

Pain is a global health priority that is challenging to asses. Here we propose a new approach to estimating the burden of pain treatment in a population using wastewater-based epidemiology (WBE). WBE is able to quantify multiple pharmaceutical compounds in order to estimate consumption by a population. Wastewater samples collected from areas representing whole communities can be analysed to estimate the consumption of drugs used to treat pain, such as nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids. The collection and analysis of wastewater can be conducted systematically to estimate the total consumption of NSAIDs and/or opioids in the population of a catchment area and to compare changes over time within the catchment or between different catchment populations. Consumption estimates can be combined by standardising the mass consumed to Defined Daily Doses (DDD) or morphine equivalents in order to assess, the population burden of pain treatment from mild to moderate (for NSAIDs) and for strong and severe pain (for opioids). We propose this method could be used to evaluate the total pain treatment burden between locations and over time. While this concept shows promise, future studies should evaluate the applicability as a tool to measure the burden of pain receiving treatment in a community.

A review of microscopy-based evidence for the association of Propionibacterium acnes biofilms in degenerative disc disease and other diseased human tissue.

PURPOSE: Recent research shows an increasing recognition that organisms not traditionally considered infectious in nature contribute to disease processes. Propionibacterium acnes (P. acnes) is a gram-positive, aerotolerant anaerobe prevalent in the sebaceous gland-rich areas of the human skin. A ubiquitous slow-growing organism with the capacity to form biofilm, P. acnes, recognized for its role in acne vulgaris and medical device-related infections, is now also linked to a number of other human diseases. While bacterial culture and molecular techniques are used to investigate the involvement of P. acnes in such diseases, definitive demonstration of P. acnes infection requires a technique (or techniques) sensitive to the presence of biofilms and insensitive to the presence of potential contamination. Fortunately, there are imaging techniques meeting these criteria, in particular, fluorescence in situ hybridization and immunofluorescence coupled with confocal laser scanning microscopy, as well as immunohistochemistry. METHODS: Our literature review considers a range of microscopy-based studies that provides definitive evidence of P. acnes colonization within tissue from a number of human diseases (acne vulgaris, degenerative disc and prostate disease and atherosclerosis), some of which are currently not considered to have an infectious etiology. RESULTS/CONCLUSION: We conclude that P. acnes is an opportunistic pathogen with a likely underestimated role in the development of various human diseases associated with significant morbidity and, in some cases, mortality. As such, these findings offer the potential for new studies aimed at understanding the pathological mechanisms driving the observed disease associations, as well as novel diagnostic strategies and treatment strategies, particularly for degenerative disc disease. These slides can be retrieved under Electronic Supplementary Material.

Anti-Angiogenic miR-222, miR-195, and miR-21a Plasma Levels in T1DM Are Improved by Metformin Therapy, Thus Elucidating Its Cardioprotective Effect: The MERIT Study.

Type 1 diabetes (T1DM) is associated with increased cardiovascular disease (CVD) and reduced life expectancy. We thus hypothesized that anti-angiogenic miRs are increased in T1DM, and the cardioprotective effect of metformin is mediated via reducing those miRs. In an open label, case-controlled study, 23 T1DM patients without CVD were treated with metformin for eight weeks (TG), matched with nine T1DM patients on standard treatment (SG) and 23 controls (CG). Plasma miR-222, miR-195, miR-21a and miR-126 were assayed by real-time RT-qPCR. The results were correlated with: endothelial function (RHI), circulating endothelial progenitor cells (cEPCs) (vascular repair marker, CD45dimCD34⁺VEGFR2⁺ cells) and circulating endothelial cells (cECs) (vascular injury marker, CD45dimCD34⁺CD133⁻CD144⁺ cells). miR-222, miR-195 and miR-21a were higher in T1DM than CG; p = 0.009, p < 0.0001, p = 0.0001, respectively. There was an inverse correlation between logmiR-222 and logRHI (p < 0.05) and a direct correlation between logmiR-222 and logCD34⁺ (p < 0.05) in TG. Metformin reduced miR-222, miR-195 and miR-21a levels in TG; p = 0.007, p = 0.002 p = 0.0012, respectively. miRs remained unchanged in SG. miR-126 was similar in all groups. There was a positive association between changes in logmiR-222 and logcECs after metformin in TG (p < 0.05). Anti-angiogenic miRs are increased in T1DM. Metformin has cardioprotective effects through downregulating miR-222, miR-195 and miR-21a, beyond improving glycemic control.