miR-203 secreted in extracellular vesicles mediates the communication between neural crest and placode cells required for trigeminal ganglia formation.

While interactions between neural crest and placode cells are critical for the proper formation of the trigeminal ganglion, the mechanisms underlying this process remain largely uncharacterized. Here, by using chick embryos, we show that the microRNA (miR)-203, whose epigenetic repression is required for neural crest migration, is reactivated in coalescing and condensing trigeminal ganglion cells. Overexpression of miR-203 induces ectopic coalescence of neural crest cells and increases ganglion size. By employing cell-specific electroporations for either miR-203 sponging or genomic editing using CRISPR/Cas9, we elucidated that neural crest cells serve as the source, while placode cells serve as the site of action for miR-203 in trigeminal ganglion condensation. Demonstrating intercellular communication, overexpression of miR-203 in the neural crest in vitro or in vivo represses an miR-responsive sensor in placode cells. Moreover, neural crest-secreted extracellular vesicles (EVs), visualized using pHluorin-CD63 vector, become incorporated into the cytoplasm of placode cells. Finally, RT-PCR analysis shows that small EVs isolated from condensing trigeminal ganglia are selectively loaded with miR-203. Together, our findings reveal a critical role in vivo for neural crest-placode communication mediated by sEVs and their selective microRNA cargo for proper trigeminal ganglion formation.

Gamut of Extratesticular Scrotal Masses: Anatomic Approach to Sonographic Differential Diagnosis.

The commonly taught tenet that intratesticular lesions are always malignant and extratesticular scrotal lesions are always benign is a simplistic statement that erroneously minimizes the significance of extratesticular scrotal masses and their diagnosis. Yet, disease in the extratesticular space is commonly encountered by clinicians and radiologists and is often a source of uncertainty in diagnosis and management. Given the embryologically rooted complex anatomy of this region, a wide range of pathologic conditions is possible. Radiologists may not be familiar with some of these conditions; further, many of these lesions can have a specific sonographic appearance, allowing accurate diagnosis that can minimize surgical intervention. Lastly, malignancies can occur in the extratesticular space-although this is less common than in the testicles-and proper recognition of findings that warrant additional imaging or surgery is critical in optimizing outcomes. The authors present a compartmental anatomic framework for differential diagnosis of extratesticular scrotal masses and provide a comprehensive illustrative display of many of the pathologic conditions that can be encountered to familiarize radiologists with the sonographic appearances of these lesions. They also review management of these lesions and scenarios where US may not be definitive in diagnosis and selective use of scrotal MRI can be helpful. © RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Microscopic approach for repairing nasal septal perforations using bilateral advancement flaps.

BACKGROUND: Septal perforations consist in an anatomic defect of the mucosal, cartilaginous and/or bone tissues of the nasal septum. A huge variety of approaches and techniques for nasal perforation repair have been reported. METHODOLOGY/PRINCIPAL: Between January 2008 and January 2017, 38 patients were treated for nasal septal perforation in Department of Otorhinolaryngology Head and Neck Surgery, Fundación Jiménez Díaz University Hospital, Madrid, Spain. A novel approach is presented based on microscope. Septal perforation closure was performed with endonasal bilateral advancement flaps-established technique and autologous cartilage and muscle temporal fascia grafts. We performed a retrospective review of closure rates and complications. RESULTS: A postoperative follow-up of at least 12 months was performed in 37 patients. The mean size of perforation was 1.33 cm. After the withdrawal of the silicone splints, perforations were completely closed in all cases. However, during the follow-up, four patients resulted in a reperforation, so our closure rate was 89.19%. For all cases, symptoms related to septal defect were solved. Only one case was reported of local infections that was resolved with antibiotics in a few days. CONCLUSIONS: Microscopic approach of septal perforation closure using bilateral advancement flaps can be an affordable technique with a high percent of success and low rate of complications.

Bow and Lean Test for Rare Variants of Vertical Semicircular Canal BPPV.

OBJECTIVE: The objective of this study was to assess the clinical significance of the Bow and Lean Test (BLT) for the diagnosis of different variants of vertical canal Benign Paroxysmal Positional Vertigo (BPPV). BLT is commonly used for diagnoses of lateral semicircular canal (LSC) BPPV. However, vertical nystagmus in the BLT may indicate the presence of other variants such as PSC-BPPV. METHODS: 567 patients with vertical canal BPPV were recruited. Patients with anterior semicircular canal (ASC) or PSC-BPPV were weekly examined until the negativization of BPPV. Nystagmus characteristics during BLT were analyzed. RESULTS: Of 567 patients with vertical canal BPPV, 1.4% had ASC-BPPV. BLT was positive in 155 patients, showing patterns like down-beating nystagmus in bowing and no nystagmus in leaning (15.52% of patients), and down-beating in bowing and up-beating in leaning (6.17%), which was predominantly present in PSC-canalolithiasis. Statistically significant differences were observed in the direction of nystagmus provoked by BLT in PSC-BPPV subtypes. No significant differences were found in nystagmus latency or duration during BLT positions. Among BPPV subtypes, there was a significant difference in nystagmus duration and latency, especially between cupulolithiasis and other variants. BLT's sensitivity was 0.93 in bowing and 1 in a leaning position, while specificity was 0.93 and 0.82 respectively. CONCLUSION: Beyond the LSC, the BLT has expanded to other variants. However, study results differ likely due to variations in patient characteristics and test execution. Currently, no specific features for ASC have been found to differentiate it from PSC-BPPV limiting the test's use for this variant. LEVEL OF EVIDENCE: 3, according to Oxford Center for Evidence-Based Medicine Laryngoscope, 134:2405-2410, 2024.

Serotonin and dopamine in the hypothalamus of control and malnourished mother rats during pregnancy and lactation and body composition of their offspring.

OBJECTIVE: To determine concentrations of serotonin and dopamine in the hypothalamus of undernourished rats and controls during pregnancy and lactation and body composition of their offspring. METHODS: Malnourished rats along with control rats were used during pregnancy and lactation. At birth of their offspring, control mothers nursed their young and malnourished rats and the undernourished mothers nursed their offspring and control pups. On days 5, 10, 15, and 21 of lactation (at the beginning and end of a feeding), L-tryptophan (L-Trp)-free, bound and total, plasma prolactin (PRL) and milk composition were determined. Serotonin and dopamine were measured in the hypothalamus. Body composition of offspring was determined. RESULTS: Increase of free L-Trp was confirmed in undernourished mothers. Furthermore, hypothalamic serotonin was elevated at the start of suckling and decreased at termination. There was also a decrease in dopamine in the hypothalamus at the beginning and end of suckling followed by an increase of plasma PRL that was greater in control mothers who breastfed malnourished offspring. Interestingly, undernourished offspring consumed more milk and showed a clear recovery of body composition with accumulation of body fat. DISCUSSION: Changes observed in hypothalamic neurotransmitters appear to be closely related to nutritional status and to the response and control of PRL production, possibly to adapt the offspring to the metabolic changes. It was also confirmed that on-demand feeding of undernourished offspring is the main factor involved in nutritional recovery and a predisposition to overweight in the recovered undernourished animals.

[Encephalitis associated to immune checkpoint inhibitors]. / Encefalitis por inhibidores del punto de control inmunitario.

Immune checkpoint inhibitors have been shown to improve the prognosis of multiple oncological diseases. Recently, adverse events related to immunotherapy have been reported. Neurologic toxicity is infrequent. We present the case of a patient with encephalitis associated to immune checkpoint inhibitors.

Los inhibidores del punto de control inmunitario han demostrado mejorar el pronóstico de múltiples enfermedades oncológicas. Recientemente se han reportado eventos adversos relacionados a la inmunoterapia. La toxicidad neurológica es poco frecuente. Se presenta el caso de un paciente con encefalitis relacionada con inhibidores del punto de control inmunitario.

Primary Central Nervous System Vasculitis Following Alemtuzumab Treatment for Multiple Sclerosis: A Case Report and Literature Review.

INTRODUCTION: Cerebral vasculitides are often devastating conditions that require immediate diagnosis and treatment. CASE REPORT: We report a pathologically proven clinical case of primary central nervous system vasculitis in a 50-year-old man with a diagnosis of relapsing-remitting multiple sclerosis after alemtuzumab therapy, which required additional immunosuppression to control this life-threatening condition. CONCLUSION: In patients presenting subacute neurological deterioration after alemtuzumab therapy, primary central nervous system vasculitis should be considered as a differential diagnosis among other autoimmune conditions.

Design and biopharmaceutical preclinical characterisation of a new thermosensitive hydrogel for the removal of gastric polyps.

BACKGROUND AND AIMS: Submucosal injection agents are widely used solutions in gastric polyp resection techniques. Currently, many different solutions are used in clinical practice, but most are not authorised for this use or are not biopharmaceutical characterised. The objective of this multidisciplinary work is to test the efficacy of a novel thermosensitive hydrogel designed specifically for this indication. METHODS: A mixture design of various components (Pluronic®, hyaluronic acid and sodium alginate) was carried out to select the combination with optimal properties for this use. Three final thermosensitive hydrogels were selected on which biopharmaceutical characterisation was performed and stability and biocompatibility were analysed. Efficacy in maintaining elevation was tested ex vivo on pig mucosa and in vivo in pigs RESULTS: The mixture design allowed selection of the ideal combinations of agents for the characteristics sought. The thermosensitive hydrogels studied showed high values of hardness and viscosity at 37 °C, maintaining good syringeability. One of them demonstrated superiority in maintaining polyp elevation in the ex vivo assay and non-inferiority in the in vivo assay. CONCLUSION: The thermosensitive hydrogel specifically designed for this use is promising both for its biopharmaceutical characteristics and for its demonstrated efficacy. This study lays the foundation for evaluating the hydrogel in humans.

Transoral CO2 laser surgery for supraglottic cancer.

There are several therapeutic options for laryngeal cancer, including those that provide a functional preservation without worsening the oncological results, such as transoral laser microsurgery (TLM). The aim of this study was to analyze both oncological and functional results of TLM in supraglottic cancer. We studied 49 consecutive patients with a primary supraglottic carcinoma who underwent a TLM between the years 1999 and 2009. Nineteen patients were classified as stage I-II and 30 as stage III-IV disease. Forty-five patients underwent also neck dissection. Thirteen patients received postoperative radiotherapy. The minimum follow-up was 24 months. Three- and five-year disease-specific survival rate was 93.2 and 82.2 %, respectively. Of the patients, 36.7 % had some complication after surgery, aspiration being the most frequent (16.32 %). Of the 43 patients who were alive, 39 (91 %) without evidence of disease 3 years after diagnosis had a functional larynx. Our results suggest that TLM is a safe and effective treatment for supraglottic cancer, with a low morbidity rate and excellent functional results.

Association of metabolic syndrome with reduced central serotonergic activity.

The aim of this study was to determine the differences between two groups of adolescents with metabolic syndrome (MetS) and normal controls in relation to brain serotonergic activity through intensity-dependent auditory-evoked potentials (IDAEPs) and plasma free fraction of L-tryptophan. Eighteen adolescents with MetS and thirteen controls were studied. Free fraction, bound and total plasma L-tryptophan, glucose, cholesterol, triglycerides, HDL-cholesterol, albumin and IDAEPs were determined. Glycemia, triglycerides were significantly elevated, and HDL-cholesterol in plasma was significantly reduced. Free fraction and free fraction/total L-tryptophan ratio were decreased. The slope of the amplitude/stimulus intensity function of the N1/P2 component significantly increased in adolescents with MetS. Decrease of free fraction of L-tryptophan in plasma and increase of the slope of the N1/P2 component suggest a low brain serotonin tone. Cortex responses are regulated by serotonergic innervations and may show a different behavior in young patients with MetS. Therefore, the slope of the N1/P2 component along with the free fraction of L-tryptophan in plasma, indicate that in adolescents with MetS the state of serotonergic brain activity is depressed and possibly related to psychiatric disorders.

Unclear origin vertigo protocol. / Protocolo de vértigo de origen dudoso.

BACKGROUND AND OBJECTIVE: Differential diagnosis of vertigo is a diagnostic challenge in the emergency setting. In our centre we have created a vertigo protocol to distinguish the different pathologies and their management in the emergency department. Our goal is to determine the efficacy of our hospital protocol in the diagnostic and therapeutic approach to acute vestibular syndrome. PATIENTS AND METHODS: It is a retrospective descriptive observational study on patients with a diagnosis of acute vestibular syndrome in the emergency department using our unclear origin vertigo protocol. All patients underwent an examination that included the HINTS protocol and had a minimum follow-up of 6 months. The results of the clinical assessments by the specialists were compared, as well as the physical examination with the different final diagnoses classified as peripheral, central and other-origin. RESULTS: We obtained 97 patients, with a mean age of 61.46 years. The final diagnoses were 26 patients for the peripheral group (26.8%), 38 for the other-origin group (39.2%) and 33 for the central group (34%). Stroke was found in 18 of the latter group, clinical-exploratory disagreement being the most frequent reason for activation of the protocol. CONCLUSIONS: Our protocol has proven to be a useful tool to differentiate a possible acute vestibular syndrome of central origin from a peripheral one, avoiding unnecessary imaging tests. The most frequent cause of activation of the protocol was clinical-exploratory disagreement seen by the ENT doctor.

Vibration-induced nystagmus and head impulse test screening for vestibular schwannoma.

LEVEL OF EVIDENCE: II-2. BACKGROUND: Vestibular schwannomas are benign tumors of the eight cranial nerve that may cause asymmetric sensorineural hearing loss (ASHL) and vestibular dysfunction. OBJECTIVE: The aim of this study was to assess the role of the video head impulse test (vHIT) and vibration-induced nystagmus (VIN) test in diagnosing vestibular schwannoma in a population of patients with Asymmetric sensorineural hearing loss. MATERIAL AND METHODS: For this prospective case-control study, 23 consecutive patients with ASHL and normal magnetic resonance were enrolled in the control group, and 33 consecutive patients with ASHL and vestibular schwannoma were enrolled in the case group. Gold standard was magnetic resonance imaging. Audiometry, vHIT, and VIN tests were performed for each patient. Significance of VIN and vHIT testing was determined by evaluation of their sensitivity, specificity, and correlation with vestibular function tests. RESULTS: Regarding the vHIT, sensitivity and specificity were 45.5% and 82.6%, respectively, for horizontal canal gain, 60.6% and 87.6%, respectively, for posterior canal gain, and 45.5% and 78.3%, respectively, when analyzing superior canal gains. Regarding the VIN test, the sensitivity and specificity were 81.8% and 73.9%, respectively, when based on the presence of a VIN with any mastoid stimulation. CONCLUSIONS: Our results suggest that using the VIN test may be an efficient approach to screen for vestibular schwannoma in patients with asymmetric sensorineural hearing loss. SIGNIFICANCE: Our results suggest that using the VIN test may be an efficient approach to screen for vestibular schwannoma in patients with ASHL.

Encefalitis por inhibidores del punto de control inmunitario / Encephalitis associated to immune checkpoint inhibitors

Resumen Los inhibidores del punto de control inmunitario han demostrado mejorar el pronóstico de múltiples enfer medades oncológicas. Recientemente se han reportado eventos adversos relacionados a la inmunoterapia. La to xicidad neurológica es poco frecuente. Se presenta el caso de un paciente con encefalitis relacionada con inhibido res del punto de control inmunitario.

Abstract Immune checkpoint inhibitors have been shown to improve the prognosis of multiple oncological diseases. Recently, adverse events related to immunotherapy have been reported. Neurologic toxicity is infrequent. We pre sent the case of a patient with encephalitis associated to immune checkpoint inhibitors.

Lack of agreement between the revised criteria of impaired fasting glucose and impaired glucose tolerance in children with excess body weight.

OBJECTIVE: The aim of this study was to describe the agreement between impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) in children with excess body weight using the original and the revised definitions of IFG. RESEARCH DESIGN AND METHODS: Obese and overweight children aged 4-17 years were included (n = 533). Anthropometric parameters and biochemical tests (fasting and 2-h glucose tests after an oral glucose load [1.75 g/kg]) were performed. Case subjects with a fasting plasma glucose >/=126 mg/dl were excluded. The diagnostic parameters of the original and the revised definitions of IFG for detecting IGT were estimated. The analysis of agreement between these categories was made using the kappa test. RESULTS: The prevalence of IFG increased from 6.2 to 13.3% using the new criteria. The prevalence of IFG became closer to the prevalence of IGT (14.8%). The revised criteria increased the sensitivity from 26.6 to 36.7%. However, the new IFG definition was not useful for identifying IGT cases. Of the 71 case subjects with IFG, only 29 (40.8%) had IGT. In addition, 50 case subjects with IGT (9.4%) and 13 with diabetes (2.4%) had a fasting glycemia <100 mg/dl. A poor agreement was found between the 2003 IFG definition and abnormal 2-h postchallenge plasma glucose (kappa = 0.359). The proportion of false-positive cases increased (36.3-59.1%) under the new definition. CONCLUSIONS: The new definition modestly increases the sensitivity of IFG for detecting IGT in children with excess body weight. Despite this, more than one-half of these cases are not detected. In addition, the false-positive rate was increased by 61%.

Minimally invasive video-assisted parathyroidectomy without intraoperative parathyroid hormone monitoring.

INTRODUCTION AND OBJECTIVES: surgical treatment of primary hyperparathyroidism has evolved from the classical bilateral neck exploration to minimally invasive techniques due to recent advances in preoperative localisation methods. The additional value of intraoperative parathyroid hormone (PTH) monitoring is questioned. The aim of this study was to analyse the results of minimally invasive video-assisted parathyroidectomy (MIVAP) without intraoperative PTH monitoring. METHODS: the patients who underwent MIVAP without PTH monitoring for primary hyperparathyroidism between 2007 and 2013 were evaluated. In all cases the suspected enlarged gland was identified preoperatively by 99Tc-sestamibi scintigraphy, ultrasound or computed tomography. RESULTS: 71 patients were studied (56 females and 15 males), with a mean age of 60 years. In 3 cases (4%) the technique was converted to open parathyroidectomy. Calcium and PTH levels were normalised after first surgery in 69 cases (97%), and after a second surgery in the remaining 2 cases (a second contralateral and a second intrathyroid adenoma). One patient developed a postoperative wound infection, 1 postoperative hypocalcaemia, and 4 transient vocal fold paralysis. No permanent vocal fold paralysis or other complications were observed. CONCLUSIONS: MIVAP is a safe, effective surgical technique to cure primary hyperparathyroidism. Intraoperative PTH monitoring may not be routinely necessary in patients treated with this technique.

[Acoustic voice analysis using the Praat program: comparative study with the Dr. Speech program]. / Análisis acústico de la voz mediante el progama Praat: estudio comparativo con el programa Dr. Speech.

INTRODUCTION AND OBJECTIVES: The European Laryngological Society (ELS) basic protocol for functional assessment of voice pathology includes 5 different approaches: perception, videostroboscopy, acoustics, aerodynamics and subjective rating by the patient. In this study we focused on acoustic voice analysis. The purpose of the present study was to correlate the results obtained by the commercial software Dr. Speech and the free software Praat in 2 fields: 1. Narrow-band spectrogram (the presence of noise according to Yanagihara, and the presence of subharmonics) (semi-quantitative). 2. Voice acoustic parameters (jitter, shimmer, harmonics-to-noise ratio, fundamental frequency) (quantitative). MATERIAL AND METHODS: We studied a total of 99 voice samples from individuals with Reinke's oedema diagnosed using videostroboscopy. One independent observer used Dr. Speech 3.0 and a second one used the Praat program (Phonetic Sciences, University of Amsterdam). The spectrographic analysis consisted of obtaining a narrow-band spectrogram from the previous digitalised voice samples by the 2 independent observers. They then determined the presence of noise in the spectrogram, using the Yanagihara grades, as well as the presence of subharmonics. As a final result, the acoustic parameters of jitter, shimmer, harmonics-to-noise ratio and fundamental frequency were obtained from the 2 acoustic analysis programs. RESULTS: The results indicated that the sound spectrogram and the numerical values obtained for shimmer and jitter were similar for both computer programs, even though types 1, 2 and 3 voice samples were analysed. CONCLUSIONS: The Praat and Dr. Speech programs provide similar results in the acoustic analysis of pathological voices.

SOX2 expression in hypopharyngeal, laryngeal, and sinonasal squamous cell carcinoma.

Squamous cell carcinoma (SCC) of the head and neck display high frequencies of DNA copy number gains at chromosomal region 3q26-27. Recently SOX2 has been postulated as a driver oncogene for these amplifications; however, its role as a prognostic marker is still a matter of debate. The aim of this study was to evaluate the involvement of SOX2 protein expression in three different sublocalizations of head and neck SCC and its possible role as prognostic marker. SOX2 expression was analyzed by immunohistochemistry in 102 pharyngeal, 67 laryngeal, and 51 sinonasal SCCs, and the relation to clinicopathological and follow-up data was studied by χ(2) and Kaplan-Meier analysis. SOX2 expression was significantly (P = .002) more frequent in hypopharyngeal and laryngeal SCC (38%, 39/101) and (42%, 28/67), respectively, compared to sinonasal cancer SCC (14%, 7/51). SOX2 expression did not correlate to disease stage, T or N classification, lymph node metastasis, recurrence or clinical outcome in any of the three sublocalizations. These results indicate that SOX2 expression is a common event in hypopharynx and larynx, but not in sinonasal SCC. The absence of correlation to clinical outcome, may suggest a role for SOX2 in tumor initiation, but not in tumor progression.

DNA methylation signatures identify biologically distinct thyroid cancer subtypes.

OBJECTIVE: The purpose of this study was to determine the global patterns of aberrant DNA methylation in thyroid cancer. RESEARCH DESIGN AND METHODS: We have used DNA methylation arrays to determine, for the first time, the genome-wide promoter methylation status of papillary, follicular, medullary, and anaplastic thyroid tumors. RESULTS: We identified 262 and 352 hypermethylated and 13 and 21 hypomethylated genes in differentiated papillary and follicular tumors, respectively. Interestingly, the other tumor types analyzed displayed more hypomethylated genes (280 in anaplastic and 393 in medullary tumors) than aberrantly hypermethylated genes (86 in anaplastic and 131 in medullary tumors). Among the genes indentified, we show that 4 potential tumor suppressor genes (ADAMTS8, HOXB4, ZIC1, and KISS1R) and 4 potential oncogenes (INSL4, DPPA2, TCL1B, and NOTCH4) are frequently regulated by aberrant methylation in primary thyroid tumors. In addition, we show that aberrant promoter hypomethylation-associated overexpression of MAP17 might promote tumor growth in thyroid cancer. CONCLUSIONS: Thyroid cancer subtypes present differential promoter methylation signatures, and nondifferentiated subtypes are characterized by aberrant promoter hypomethylation rather than hypermethylation. Additional studies are needed to determine the potential clinical interest of the tumor subtype-specific DNA methylation signatures described herein and the role of aberrant promoter hypomethylation in nondifferentiated thyroid tumors.

Prognostic significance of postoperative wound infections after total laryngectomy.

BACKGROUND: In oncologic surgery, the relationship between postoperative wound infections and prognosis remains unclear. The purpose of this study was to establish the prognostic significance of surgical wound infections in laryngectomized patients. METHOD: We studied 129 consecutive patients with previously untreated laryngeal or hypopharyngeal squamous cell carcinoma who underwent a total laryngectomy. Minimum follow-up was 24 months. RESULTS: Fifty-seven patients (44%) developed a wound infection. Infections were more frequent in hypopharyngeal tumors (p < .001). Surgical wound infection was associated with a worse disease-specific survival (p = .046), but this association was due to the hypopharyngeal subgroup of cases (p = .024). In multivariate analysis, the only parameters significantly associated with a worse disease-specific survival in these cases were nodal extracapsular invasion (p < .001) and surgical wound infection (p = .02). CONCLUSION: Our results suggest that the development of a postoperative wound infection is a poor prognostic sign in patients with advanced hypopharyngeal cancers surgically treated.

The role of natural killer T (NKT) cells in the pathogenesis of type 1 diabetes.

In type 1 diabetes, a failure in the regulation of either innate or acquired immunity may be the cause of autoimmune response. A cell population that may have a regulatory role of the immune response are the Natural Killer T (NKT) cells, which are a population expressing T lymphocyte antigen receptor (TCR), and are a common marker for NK cells. A distinctive characteristic in NKT cells is their capacity to produce large amounts of immune-modulating cytokines. A decrease in the number and/or functional incapability of NKT cells is associated with progression of type 1 diabetes and with other self-immune diseases. However, the relevance of such findings is not completely understood. Limitations of the current studies include the existing methods to measure NKT activation and the lack of assessment of the expression of genes affected by NKT action. Nevertheless, the study of NKT cells may be a new clinical approach to detect individuals at risk for having type 1 diabetes. Additional studies are needed to evaluate the clinical value of this new predictive tool.