NKX2-5 regulates vessel remodeling in scleroderma-associated pulmonary arterial hypertension.

NKX2-5 is a member of the homeobox-containing transcription factors critical in regulating tissue differentiation in development. Here, we report a role for NKX2-5 in vascular smooth muscle cell phenotypic modulation in vitro and in vascular remodeling in vivo. NKX2-5 is upregulated in scleroderma patients with pulmonary arterial hypertension. Suppression of NKX2-5 expression in smooth muscle cells halted vascular smooth muscle proliferation and migration, enhanced contractility, and blocked the expression of extracellular matrix genes. Conversely, overexpression of NKX2-5 suppressed the expression of contractile genes (ACTA2, TAGLN, CNN1) and enhanced the expression of matrix genes (COL1) in vascular smooth muscle cells. In vivo, conditional deletion of NKX2-5 attenuated blood vessel remodeling and halted the progression to hypertension in a mouse chronic hypoxia model. This study revealed that signals related to injury such as serum and low confluence, which induce NKX2-5 expression in cultured cells, is potentiated by TGF-ß and further enhanced by hypoxia. The effect of TGF-ß was sensitive to ERK5 and PI3K inhibition. Our data suggest a pivotal role for NKX2-5 in the phenotypic modulation of smooth muscle cells during pathological vascular remodeling and provide proof of concept for therapeutic targeting of NKX2-5 in vasculopathies.

Working with roubles and failures in conversation between humans and robots: workshop report.

This paper summarizes the structure and findings from the first Workshop on Troubles and Failures in Conversations between Humans and Robots. The workshop was organized to bring together a small, interdisciplinary group of researchers working on miscommunication from two complementary perspectives. One group of technology-oriented researchers was made up of roboticists, Human-Robot Interaction (HRI) researchers and dialogue system experts. The second group involved experts from conversation analysis, cognitive science, and linguistics. Uniting both groups of researchers is the belief that communication failures between humans and machines need to be taken seriously and that a systematic analysis of such failures may open fruitful avenues in research beyond current practices to improve such systems, including both speech-centric and multimodal interfaces. This workshop represents a starting point for this endeavour. The aim of the workshop was threefold: Firstly, to establish an interdisciplinary network of researchers that share a common interest in investigating communicative failures with a particular view towards robotic speech interfaces; secondly, to gain a partial overview of the "failure landscape" as experienced by roboticists and HRI researchers; and thirdly, to determine the potential for creating a robotic benchmark scenario for testing future speech interfaces with respect to the identified failures. The present article summarizes both the "failure landscape" surveyed during the workshop as well as the outcomes of the attempt to define a benchmark scenario.

Vitamin D Levels in Chronic Rhinosinusitis in Patients With or Without Nasal Polyposis: A Systematic Review.

Chronic rhinosinusitis (CRS) is a large group of heterogeneous diseases characterized by extensive inflammation of the nasal mucosa and sinuses. Vitamin D (VD), as an immunoregulatory hormone, may play an important role in the pathophysiology of CRS. The purpose of this study is to review the existing literature that correlates VD levels with CRS with or without nasal polyps. A systematic manual search was conducted in the PubMed and Google Scholar databases up to July 2023. Articles from PubMed and the first 100 articles from Google Scholar were recorded for our research. Keywords used were the following: vitamin D, chronic rhinosinusitis, and nasal polyps. Among the 134 articles retrieved, only 18 were eligible. The other 116 studies were excluded as they related VD levels with other conditions (e.g., allergic rhinitis) and for other reasons. However, we identified two more eligible records through the manual research of the above-mentioned 132 studies, and finally, 20 records were included in the current review. The review concerned case-control studies, prospective, retrospective, and cross-sectional studies. Based on our review, we concluded that CRS patients are correlated with the lowest VD levels, accompanied by increased severity of the disease, especially in those with nasal polyposis. Patients can benefit from appropriate VD supplementation, and serum VD levels should be included in the laboratory assessment of CRS. However, due to the heterogeneity of the individuals involved, more well-designed clinical trials as well as randomized clinical trials should be conducted for further validation of the above findings in the general population in the future.

Clinical applications of gene therapy for rare diseases: A review.

Rare diseases collectively exact a high toll on society due to their sheer number and overall prevalence. Their heterogeneity, diversity, and nature pose daunting clinical challenges for both management and treatment. In this review, we discuss recent advances in clinical applications of gene therapy for rare diseases, focusing on a variety of viral and non-viral strategies. The use of adeno-associated virus (AAV) vectors is discussed in the context of Luxturna, licenced for the treatment of RPE65 deficiency in the retinal epithelium. Imlygic, a herpes virus vector licenced for the treatment of refractory metastatic melanoma, will be an example of oncolytic vectors developed against rare cancers. Yescarta and Kymriah will showcase the use of retrovirus and lentivirus vectors in the autologous ex vivo production of chimeric antigen receptor T cells (CAR-T), licenced for the treatment of refractory leukaemias and lymphomas. Similar retroviral and lentiviral technology can be applied to autologous haematopoietic stem cells, exemplified by Strimvelis and Zynteglo, licenced treatments for adenosine deaminase-severe combined immunodeficiency (ADA-SCID) and ß-thalassaemia respectively. Antisense oligonucleotide technologies will be highlighted through Onpattro and Tegsedi, RNA interference drugs licenced for familial transthyretin (TTR) amyloidosis, and Spinraza, a splice-switching treatment for spinal muscular atrophy (SMA). An initial comparison of the effectiveness of AAV and oligonucleotide therapies in SMA is possible with Zolgensma, an AAV serotype 9 vector, and Spinraza. Through these examples of marketed gene therapies and gene cell therapies, we will discuss the expanding applications of such novel technologies to previously intractable rare diseases.

Proximal Tibiofibular Joint Ganglion Cyst: A Rare Cause of Calf Pain.

Intramuscular cysts are rare at the proximal calf. However, their etiology is varied, making accurate diagnosis and treatment really difficult. Ganglion cyst (GC) of the proximal tibiofibular (PTF) joint is a very rare entity with an estimated prevalence of 0.76%. Intramuscular extension of the GC arising from the PTF joint is an even rarer lesion, and only a few cases have been published in the literature. Hereby, we report an infrequent case of a GC arising from the PTF joint with a sizable pedicle and intramuscular (lateral head of gastrocnemius) extension to the posterolateral aspect of the right calf.

Scalable RT-LAMP-based SARS-CoV-2 testing for infection surveillance with applications in pandemic preparedness.

Throughout the SARS-CoV-2 pandemic, limited diagnostic capacities prevented sentinel testing, demonstrating the need for novel testing infrastructures. Here, we describe the setup of a cost-effective platform that can be employed in a high-throughput manner, which allows surveillance testing as an acute pandemic control and preparedness tool, exemplified by SARS-CoV-2 diagnostics in an academic environment. The strategy involves self-sampling based on gargling saline, pseudonymized sample handling, automated RNA extraction, and viral RNA detection using a semiquantitative multiplexed colorimetric reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay with an analytical sensitivity comparable with RT-qPCR. We provide standard operating procedures and an integrated software solution for all workflows, including sample logistics, analysis by colorimetry or sequencing, and communication of results. We evaluated factors affecting the viral load and the stability of gargling samples as well as the diagnostic sensitivity of the RT-LAMP assay. In parallel, we estimated the economic costs of setting up and running the test station. We performed > 35,000 tests, with an average turnover time of < 6 h from sample arrival to result announcement. Altogether, our work provides a blueprint for fast, sensitive, scalable, cost- and labor-efficient RT-LAMP diagnostics, which is independent of potentially limiting clinical diagnostics supply chains.

Evaluation of the lignocellulose degradation potential of Mediterranean forests soil microbial communities through diversity and targeted functional metagenomics.

The enzymatic arsenal of several soil microorganisms renders them particularly suitable for the degradation of lignocellulose, a process of distinct ecological significance with promising biotechnological implications. In this study, we investigated the spatiotemporal diversity and distribution of bacteria and fungi with 16S and Internally Trascribed Spacer (ITS) ribosomal RNA next-generation-sequencing (NGS), focusing on forest mainland Abies cephalonica and insular Quercus ilex habitats of Greece. We analyzed samples during winter and summer periods, from different soil depths, and we applied optimized and combined targeted meta-omics approaches aiming at the peroxidase-catalase family enzymes to gain insights into the lignocellulose degradation process at the soil microbial community level. The microbial communities recorded showed distinct patterns of response to season, soil depth and vegetation type. Overall, in both forests Proteobacteria, Actinobacteria, Acidobacteria were the most abundant bacteria phyla, while the other phyla and the super-kingdom of Archaea were detected in very low numbers. Members of the orders Agaricales, Russulales, Sebacinales, Gomphales, Geastrales, Hysterangiales, Thelephorales, and Trechisporales (Basidiomycota), and Pezizales, Sordariales, Eurotiales, Pleosporales, Helotiales, and Diaporthales (Ascomycota) were the most abundant for Fungi. By using optimized "universal" PCR primers that targeted the peroxidase-catalase enzyme family, we identified several known and novel sequences from various Basidiomycota, even from taxa appearing at low abundance. The majority of the sequences recovered were manganese peroxidases from several genera of Agaricales, Hysterangiales, Gomphales, Geastrales, Russulales, Hymenochaetales, and Trechisporales, while lignin -and versatile-peroxidases were limited to two to eight species, respectively. Comparisons of the obtained sequences with publicly available data allowed a detailed structural analysis of polymorphisms and functionally relevant amino-acid residues at phylogenetic level. The targeted metagenomics applied here revealed an important role in lignocellulose degradation of hitherto understudied orders of Basidiomycota, such as the Hysterangiales and Gomphales, while it also suggested the auxiliary activity of particular members of Proteobacteria, Actinobacteria, Acidobacteria, Verrucomicrobia, and Gemmatimonadetes. The application of NGS-based metagenomics approaches allows a better understanding of the complex process of lignocellulolysis at the microbial community level as well as the identification of candidate taxa and genes for targeted functional investigations and genetic modifications.

Components of TOR and MAP kinase signaling control chemotropism and pathogenicity in the fungal pathogen Verticillium dahliae.

Filamentous fungi can sense useful resources and hazards in their environment and direct growth of their hyphae accordingly. Chemotropism ensures access to nutrients, contact with other individuals (e.g., for mating), and interaction with hosts in the case of pathogens. Previous studies have revealed a complex chemotropic sensing landscape during host-pathogen interactions, but the underlying molecular machinery remains poorly characterized. Here we studied mechanisms controlling directed hyphal growth of the important plant-pathogenic fungus Verticillium dahliae towards different chemoattractants. We found that the homologs of the Rag GTPase Gtr1 and the GTPase-activating protein Tsc2, an activator and a repressor of the TOR kinase respectively, play important roles in hyphal chemotropism towards nutrients, plant-derived signals, and heterologous α-pheromone of Fusarium oxysporum. Furthermore, important roles of these regulators were identified in fungal development and pathogenicity. We also found that the mitogen-activated protein kinase (MAPK) Fus3 is required for chemotropism towards nutrients, while the G protein-coupled receptor (GPCR) Ste2 and the MAPK Slt2 control chemosensing of plant-derived signals and α-pheromone. Our study establishes V. dahliae as a suitable model system for the analysis of fungal chemotropism and discovers new components of chemotropic signaling during growth and host-pathogen interactions of V. dahliae.

An Intrathoracic Meningocele in a Neurofibromatosis Type I Patient Mimicking Severe COVID-19 Disease.

Intrathoracic meningoceles (IM) are quite rare; they are commonly associated with neurofibromatosis type 1 (NF-1). We report a case of a 55-year-old lady who was admitted to our emergency department with a sore throat, mild fever, cough, and right-sided chest pain, and tested positive for coronavirus disease 2019 (COVID-19). Ιmaging revealed a meningocele in the right upper pulmonary area, attributed to her NF-1. Clinicians should be aware that patients with NF-1 can develop IM, and they should be included in the differential diagnosis of patients with an intrathoracic mass.

An infected Andersson lesion presented with incomplete paraplegia in a patient with ankylosing spondylitis. A unique case report with literature review.

INTRODUCTION: A relatively rare and unknown entity in patients with ankylosing spondylitis is the Andersson lesion (AL). It was first described by Andersson in 1937 as destructive vertebral or disco-vertebral lesion of the spine without history of trauma. AL may result from inflammation or stress fracture of the rigid spine, while there is no evidence for an infectious origin. To our knowledge, only one case with an infected AL has been published many years ago; we hereby present the second case, but the first one with severe neurologic deterioration. CASE PRESENTATION: A 79-year-old male patient was presented to our emergency department and his neurological examination on admission revealed incomplete paraplegia below the Th10 level. Plain radiograms at the level of 10th thoracic vertebra revealed a lesion mimicking a severe vertebral fracture. The computed tomography confirmed the diagnosis of the AL and due to the significant local instability and the neurologic deficit, the patient underwent posterior decompression and stabilization. During decompression, we noticed purulence and extensive debridement was performed. The cultures of the Th10 pus revealed Enterococus sp, while the same pathogen was developed to urine cultures. The patient received intravenous antibiotics for 4 weeks, followed by per os antibiotic therapy. At the 18-month follow-up our patient had significant improvement of this functional status. DISCUSSION: Most studies support that inflammatory or traumatic/mechanical (pseudarthrosis) etiology are the most possible causes of Anderson lesions. Possible neurological deterioration should be investigated and demonstrates significant spinal instability. The integrity of the posterior column should be investigated, and exclusion of other concomitant lesions should be done. In cases with instability due to the fractured posterior elements, surgical intervention is mandatory. Spine surgeons should be competent to differentiate fracture from the Andersson lesion. In this rare case we highlight also that spine surgeons should obtain intraoperative cultures in cases with Andersson lesions, to exclude the minor possibility of the infectious origin of the entity and/or the possible secondary contamination of the affected area.

Late-Onset Hematoma Due to Bleeding of a Small Branch of the Lateral Circumflex Femoral Artery Following Proximal Femur Intramedullary Nailing.

Intramedullary nailing of proximal femur fracture is not deprived of complications, although vascular complications are very rare and a high index of suspicion is required for timely diagnosis. This case report describes how a late-onset hematoma formation and bleeding of a small branch of the lateral circumflex femoral artery can complicate intramedullary nailing after a pertrochanteric fracture. To the best of our knowledge, this complication has never been reported and should be considered among the possible vascular complications of intramedullary nailing. Orthopedic surgeons should be aware of the vascular complications that can occur even with late-onset presentation and even from small vessels, while administration of anticoagulants is an aggravating factor. Elderly patients with proximal femur fractures are more susceptible to vascular injury due to the structure of their vessels and the vicinity of the fracture to the arterial supply of the hip.

Tibia Tuberosity Fracture and Patellar Tendon Rupture Combination in a Pediatric Patient: Case Report and Narrative Review.

A combination of tibial tuberosity (TT) fracture (TTF) along with patellar tendon (PT) rupture (PTR) is rare. We report a 15-year-old male who presented to our ED with acute knee pain and an inability to actively extend the knee after jumping during a basketball game. Diagnosis of simultaneous PTR is crucial as it changes clinical management. It is, therefore, important to maintain a high index of suspicion for the combination of TTF and PT injury.

Predictive value of sagittal craniocervical roentgenographic parameters for HRQOL after craniocervical fusion.

PURPOSE: Loss of "physiological" sagittal alignment following craniocervical fusion (CCF) for degenerative disease may be associated with loss of horizontal gaze, dysphagia and poor HRQOL. This study reports on sagittal craniocervical roentgenographic predictors of HRQOL (SF-36) in patients following uncomplicated CCF for fresh upper cervical traumatic (UCT) injuries. METHODS: Twenty-two consecutive adult patients (group P) aged 50 ± 16 years, who had undergone CCF for fresh unstable C1 and C2AO/type UCT injuries, were evaluated 39 ± 12 months postoperatively with upright lateral cervical roentgenograms and SF-36as HRQOL measure. Physiological data for cervical sagittal alignment and SF-36 were taken from an age-matched control group (C) of 30 individuals aged 52 ± 12 years. Several commonly used sagittal cervical roentgenographic parameters were tested as potential predictors of the SF-36 domains in both groups. Roentgenographic predictors for each of the nine SF-domains were calculated using stepwise multilinear regression analysis (MLRA). RESULTS: The roentgenographic predictors in patients included (1) the angle created by McGregor's line and the inferior surface of the axis (OC2a) for physical function (PF, P = 0.049), role limitations due to physical health (RLPH, P = 0.004),role limitation due to emotional problems (RLEP, P = 0.004), emotional functioning (EF) (P = 0.012), social functioning (SF) (P = 0.028) and general health (GH, P = 0.041). (2) The angle formed between a horizontal line and the superior endplate of T1-vertebra (T1-slope) was predictor for SF (P = 0.017) and pain (P = 0.021), and (3) the angle between McGregor's line and the line that links the center of the C1 anterior arch and the apex of cervical sagittal curvature (PIA) was predictor for health change (HC, P = 0.002). CONCLUSIONS: This study showed that postoperative OC2a, PIA and T1-slope safely predict HRQOL outcomes (SF-36) following CCF for fresh trauma. It seems theoretically that the adequate restoration of the upper cervical alignment including C1-C2 upper cervical lordosis (OC2a) and PIA, in interaction with T1-slope, is important for postoperative HRQOL scores close to physiological values. The authors speculate that C0-C4 fusion restores horizontal gaze and allows for painful regain of pre-trauma quality of life. Spine surgeons should realign and stabilize the craniocervical junction taking in consideration these roentgenographic predictors.

Sex without crossing over in the yeast Saccharomycodes ludwigii.

BACKGROUND: Intermixing of genomes through meiotic reassortment and recombination of homologous chromosomes is a unifying theme of sexual reproduction in eukaryotic organisms and is considered crucial for their adaptive evolution. Previous studies of the budding yeast species Saccharomycodes ludwigii suggested that meiotic crossing over might be absent from its sexual life cycle, which is predominated by fertilization within the meiotic tetrad. RESULTS: We demonstrate that recombination is extremely suppressed during meiosis in Sd. ludwigii. DNA double-strand break formation by the conserved transesterase Spo11, processing and repair involving interhomolog interactions are required for normal meiosis but do not lead to crossing over. Although the species has retained an intact meiotic gene repertoire, genetic and population analyses suggest the exceptionally rare occurrence of meiotic crossovers in its genome. A strong AT bias of spontaneous mutations and the absence of recombination are likely responsible for its unusually low genomic GC level. CONCLUSIONS: Sd. ludwigii has followed a unique evolutionary trajectory that possibly derives fitness benefits from the combination of frequent mating between products of the same meiotic event with the extreme suppression of meiotic recombination. This life style ensures preservation of heterozygosity throughout its genome and may enable the species to adapt to its environment and survive with only minimal levels of rare meiotic recombination. We propose Sd. ludwigii as an excellent natural forum for the study of genome evolution and recombination rates.

The NADPH Oxidase A of Verticillium dahliae Is Essential for Pathogenicity, Normal Development, and Stress Tolerance, and It Interacts with Yap1 to Regulate Redox Homeostasis.

Maintenance of redox homeostasis is vital for aerobic organisms and particularly relevant to plant pathogens. A balance is required between their endogenous ROS production, which is important for their development and pathogenicity, and host-derived oxidative stress. Endogenous ROS in fungi are generated by membrane-bound NADPH oxidase (NOX) complexes and the mitochondrial respiratory chain, while transcription factor Yap1 is a major regulator of the antioxidant response. Here, we investigated the roles of NoxA and Yap1 in fundamental biological processes of the important plant pathogen Verticillium dahliae. Deletion of noxA impaired growth and morphogenesis, compromised formation of hyphopodia, diminished penetration ability and pathogenicity, increased sensitivity against antifungal agents, and dysregulated expression of antioxidant genes. On the other hand, deletion of yap1 resulted in defects in conidial and microsclerotia formation, increased sensitivity against oxidative stress, and down-regulated antioxidant genes. Localized accumulation of ROS was observed before conidial fusion and during the heterokaryon incompatibility reaction upon nonself fusion. The frequency of inviable fusions was not affected by the deletion of Yap1. Analysis of a double knockout mutant revealed an epistatic relationship between noxA and yap1. Our results collectively reveal instrumental roles of NoxA and ROS homeostasis in the biology of V. dahliae.

Horizontal (Transverse) Intraarticular Metacarpal Head Fracture in a Young Adult.

Metacarpal head fractures are rare injuries that usually occur during trauma. These fractures are classified into 10 groups, with horizontal (transverse) being the rarest type of fractures. To our knowledge, very few cases have been reported in the literature to date. Here, we present the case of a 21-year-old male who sustained multiple ipsilateral hand injuries accompanied by a horizontal (transverse) fracture of the fourth metacarpal. He underwent open reduction and fixation with Kirschner wires followed by intensive rehabilitation. He finally regained complete active range of motion and grip strength three months after the operation. However, at nine months postoperatively, he developed avascular necrosis, which was asymptomatic and did not need any intervention. Therefore, it is important to maintain a high index of suspicion for possible complications and follow patients regularly, probably even for as long as 12 months after the initial injury.

Starvation-induced cell fusion and heterokaryosis frequently escape imperfect allorecognition systems in an asexual fungal pathogen.

BACKGROUND: Asexual fungi include important pathogens of plants and other organisms, and their effective management requires understanding of their evolutionary dynamics. Genetic recombination is critical for adaptability and could be achieved via heterokaryosis - the co-existence of genetically different nuclei in a cell resulting from fusion of non-self spores or hyphae - and the parasexual cycle in the absence of sexual reproduction. Fusion between different strains and establishment of viable heterokaryons are believed to be rare due to non-self recognition systems. Here, we investigate the extent and mechanisms of cell fusion and heterokaryosis in the important asexual plant pathogen Verticillium dahliae. RESULTS: We used live-cell imaging and genetic complementation assays of tagged V. dahliae strains to analyze the extent of non-self vegetative fusion, heterokaryotic cell fate, and nuclear behavior. An efficient CRISPR/Cas9-mediated system was developed to investigate the involvement of autophagy in heterokaryosis. Under starvation, non-self fusion of germinating spores occurs frequently regardless of the previously assessed vegetative compatibility of the partners. Supposedly "incompatible" fusions often establish viable heterokaryotic cells and mosaic mycelia, where nuclei can engage in fusion or transfer of genetic material. The molecular machinery of autophagy has a protective function against the destruction of "incompatible" heterokaryons. CONCLUSIONS: We demonstrate an imperfect function of somatic incompatibility systems in V. dahliae. These systems frequently tolerate the establishment of heterokaryons and potentially the initiation of the parasexual cycle even between strains that were previously regarded as "incompatible."

A Smart Technique to Remove Ruptured Inflatable Bone Tamp From the Vertebral Body in Balloon Kyphoplasty.

Accidental rupture of the inflatable bone tamp is a rare but possible complication during balloon kyphoplasty. We describe an easy and minimal invasive technique to remove this foreign body from fractured vertebra. A 62-year-old female patient with severe osteoporosis had a low energy trauma and sustained burst fracture of the 12th thoracic (Th12) vertebra. The inflated bone tamp was not possible to be fully deflated and during the maneuvers to withdraw the balloon, it was disassembled and trapped under the distal end of working cannula, remaining within the bone cavity formed by balloon. Since no standard recommendation for this complication exists in current literature, we faced the dilemma of either leaving ruptured bone tamp in situ or removing it with a more extensive approach. We decided to use an alternative minimal invasive technique and managed to remove it through the right pedicle using a small size straight pituitary rongeur forceps under biplane continuous image intensifier and neuromonitoring. Subsequently, balloon kyphoplasty (BK) was performed through the left cannula accompanied with pedicle screw fixation of the adjacent vertebrae. The patient was followed up to our outpatient department for one year without complications. This extremely rare complication during BK consists of a challenge for spine surgeons and interventional radiologists. The described technique is relatively easy, safe, minimal invasive, time-saving and avoids further complications related with trapping of foreign bodies within the vertebral body.

Os Vesalianum Pedis in a Young Adult: A Case Report and Literature Review.

Os vesalianum pedis is a rare accessory foot ossicle. It is usually asymptomatic, however, it can be an infrequent cause of lateral foot pain. We present the case of a 19-year-old healthy male with lateral foot pain after an inversion-type injury. Initial X-rays were mistaken for fracture of the fifth metatarsal, however, a high index of suspicion for the presence of the os vesalianum led us to perform imaging of the contralateral foot; a mirror image with contralateral os vesalianum was revealed. The patient was treated conservatively and had an excellent outcome. In the context of trauma, os vesalianum must be differentiated from other causes of lateral foot pain, such as Iselin's disease, avulsion fracture of the fifth metatarsal, Jones fracture, and others. Os vesalianum pedis is characterized as a rounded ossicle, with smooth edges, surrounded by cortical bone. Prompt diagnosis is essential as it changes the management.

Systematic Review: Are the Elderly With Diabetes Mellitus Type 2 Prone to Fragility Fractures?

Diabetes mellitus type 2 (T2DM) is an emerging public health issue with high prevalence rates among older adults while fragility fractures constitute a significant public health burden with a great impact. Osteoporosis is the most important metabolic bone disease in patients with diabetes mellitus. Based on current evidence, individuals with T2DM are more vulnerable to fragility fractures than their non-diabetic counterparts, although until now, there aren't any systematic reviews or meta-analyses concerning the impact of T2DM on the risk of fragility fractures in elderly patients. The aim of this study is to fill this gap in the current literature concerning this specific patient group. Literature in PubMed and Google Scholar was searched for relevant articles published up to January 2021. The keywords used were: elderly, diabetes mellitus type 2, and fragility fractures. Among the 180 articles retrieved, only four full-text articles were eligible and, finally, two studies (one population-based cohort study and one cross-sectional study) met the inclusion criteria for the review. Although we identified 15 records through the manual research, finally 17 records were included in the current review. The records retrieved from the manual research were 11 prospective cohort studies, two population-based studies, one prospective observational study, and one retrospective cohort study. The author's name, year of publication, country, type of study, and number of patients were reported. According to this systematic review, there is almost consensus about the increased prevalence of all kinds of fragility fractures and especially low-energy hip fractures among elderly patients with T2DM compared with their counterparts without T2DM while there is relative controversy concerning non-vertebral fractures. Vertebral fractures in the elderly with T2DM require further evaluation because the results from cohort studies are more conflicting. Finally, insulin usage can increase the possibility of fragility fractures and can even double this risk. Bone fragility should be recognized as a new complication of T2DM, especially in elderly patients, due to several additional aggravating factors such as senile osteoporosis, severe vitamin D deficiency, presence of many comorbidities, increased possibility of insulin usage, and the presence of diabetes-related complications (mainly neuropathy and retinopathy). Clinicians who treat these patients should be aware of the special diagnostic and therapeutic approaches concerning these patients.