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Introduction: We report the full analysis of the COMMANDS trial assessing efficacy and safety of luspatercept versus epoetin alfa (EA) in ESA-naive patients with LR-MDS. Methods: 363 patients (aged ≥18 y, with transfusion-dependent LR-MDS, serum erythropoietin

BACKGROUND AND OBJECTIVE: Positive surgical margins (PSMs) following radical prostatectomy (RP) have been seen as inherently unfavorable. However, a large international multi-institutional study recently revealed that unifocal PSMs (UPSMs) had no impact on prostate cancer-specific mortality (PCSM), whereas multifocal PSMs (MPSMs) did. Our aim was to assess the relative impact of PSMs versus percentage tumor volume (PTV) on PCSM. METHODS: We analyzed data for 1552 patients who underwent robot-assisted RP performed by a single surgeon between 2002 and 2018 at a tertiary referral center with up to 15-yr follow-up. Patients were divided into negative surgical margin (NSM), UPSM, and MPSM groups, with PTV stratification using a cutoff of 40%. The primary outcome was stepwise multivariate regression analysis of predictors of PCSM (pT stage, pathological Gleason grade group, PTV, UPSM, and MPSM). The secondary outcome was the risk of 15-yr PCSM via Kaplan-Meier analysis. KEY FINDINGS AND LIMITATIONS: The group with 40-100% PTV was older and presented with more advanced grade and stage. High PTV was significantly associated with greater risk of PSM, biochemical recurrence, PCSM, and overall mortality at 15 yr (p

Coronary artery fistulas (CAF) are rare abnormalities involving a connection between a coronary artery and an adjacent vessel or heart chamber. Here we discuss the case of a 47-year-old male patient who had multiple gunshot wounds (GSWs) to the chest and abdomen, suffering a through and through bullet wound to the heart from the left ventricle (LV) through the left anterior descending (LAD) coronary artery and exiting from the right ventricle (RV). At the time of his hospitalization, he underwent a non-ECG gated trauma CT scan and subsequent cardiac catheterization that showed patient has a CAF between the LAD and RVOT. Roughly 3 years after his injury, the patient had an ECG-gated coronary CT scan showing the CAF is still present. The patient is now experiencing symptoms of heart failure with suspected worsening of shunt flow from the fistula. This case sheds light on CAFs, their presentation and potential complications to raise awareness for clinicians and radiologists.

The objective of this study was to study the effect of laser irradiation on maturation rate of dromedary she-camel oocytes. Although in vitro fertilization (IVF) technique in she-camel has been established, but maturation rate of camel oocytes is still low comparing with other animal species. Several studies performed to improve in-vitro maturation rate using different types of media with different incubation times. In order to establish high sensitive and low cost maturation improvement technique, laser irradiation has been suggested in the present work. Cumulus oocytes complexes (COCʼs) were collected from ovaries by aspiration method and grade (A) oocytes were chosen and divided into five different groups, 62 oocytes served as control group, an un-irradiated (group 1), 64 oocytes exposed to 2 minutes of laser irradiation (group 2), 57 oocytes exposed to 3 minutes of laser irradiation (group 3), 49 oocytes exposed to 4 minutes of laser irradiation (group 4) and 52 oocytes exposed to 5 minutes of laser irradiation (group 5) with a total output power of 3 mW for different exposure durations; 2, 3, 4 and 5 minutes. Afterwards, oocytes were matured in TCM-199 medium at 38.5oC and 5% CO2 in humidified air for 42 h. Maturation rate was calculated based on expulsion of the first polar body and statistically analyzed by one way ANOVA test. The obtained results showed that, the oocytes reached germinal vesicles (GV) which exposed to laser beam for 5 minutes at 488 nm wavelength represent significantly (P

Converging lines of preclinical and clinical research indicate that females, in stark contrast to males, display an increased prevalence of chronic pain. Females also demonstrate weaker analgesic efficacy in response to opioid therapies when compared with males. These sex-specific differences may be driven by dimorphic endogenous opioidergic responses. In rodent models, analgesia exhibited in males but not females was reversed by inhibiting endogenous opioidergic reception. In humans, the sex-specific endogenous system(s) supporting the direct attenuation of evoked pain has not been identified. To determine whether opioidergic blockade reverses self-regulated analgesia in males as compared to females, the present study combined two operationally analogous clinical trials (n = 98; 51 females and 47 males). In a double-blinded, counterbalanced study involving healthy (n = 39) and chronic low back pain (n = 59) populations, a high-dose naloxone (μ-, κ-, δ-opioid antagonist) vs. placebo-saline cross-over design (15 mg/kg bolus +0.1 mg/kg/h) tested the hypothesis that endogenous opioids mediate analgesia in males but not females. An 11-point visual analog scale (VAS) (0 = no pain; 10 = worst pain imaginable) evaluated pain ratings in response to noxious heat stimulation (49 °C; calf). After baseline pain testing, participants were randomized to a validated four-session mindfulness meditation or sham mindfulness meditation training intervention. Participants practiced their respective meditation during noxious heat, intravenous high-dose naloxone, and placebo saline, respectively. In males and females, meditation significantly lowered evoked pain during saline infusion. Intravenous naloxone inhibited analgesia in males, but pain relief was well preserved in females. The present findings indicate that endogenous opioids mediate self-regulated analgesia in males but not females and underscore the need to establish sex-specific pain therapeutics.

The present study aimed to justify the effects of restricted feeding periods during last month of pregnancy and initiation of lactation on growth rate of Maghrebi she-camel and their offsprings. Sixteen pregnant she- camels with an average body weight 512.74 kg were divided randomly into three groups. The first group (G1) was fed 100% of their daily requirements concentrates. The second group (G2) was offered 75% of their daily requirement of concentrates after delivery for one month, while the third group (G3) was fed on 75% of their daily of concentrate requirements for two months (one month pre and another one post-partum). New born calves were divided after one month of lactation to four groups as following; calves born G1 dams were divided randomly to two subgroups. The first one (G11) suckled their dams naturally, while the other (G12) was artificial reared on a milk mixture (50% natural camel milk and 50% cattle milk replacer). Calves born to G2 and G3 dams were artificial reared on a mixture 50% natural camel milk and 50% cattle milk replacer. Results obtained showed that she-camels of G1 gained insignificant more live body weight than that of G3 during the pre-calving period 49.09 vs. 42.05 kg, respectively. There were insignificant differences among the 3 groups in calves birth weight 30.44, 32.8 and 29.73 kg, respectively. During lactation period, she-camels of G1 produced insignificantly more daily milk in compare with the corresponding she-camels of G2 and G3 (3.78 liter vs. 3.32 and 3.4 liter/ animal), respectively. She-camel of G3 lost significantly (P˂0.05) more LBW from the beginning of the experiment to the end of the study in compare with both of G1 and G2 she-camels. Calves of one month of age and born to G1 dams indicate faster (P˂0.05) daily gain (0.326 kg / h/ day) than those to both of G2 and G3 dams. Three months old age calves of different groups, indicated nearly similar growth, regardless of their dams feed restriction and type of calves rearing (natural vs. artificial). Data obtained showed also that neither she-camels feed restriction practice nor type of calves rearing have any significant effect on either calves daily gain or dams final LBW after 3 months of treatments.

Concerns over health care in US Immigration and Customs Enforcement (ICE) facilities have grown over the past decade, including reports of medical mismanagement, inadequate mental health care, and inappropriate use of solitary confinement. Despite being a federally funded agency, reporting and accountability of health outcomes in ICE facilities is limited. This manuscript outlines current standards for health in ICE detention, how compliance is evaluated, why this process fails, and how current processes can be improved to achieve transparency and accountability. Ultimately, health metrics must be: 1) frequent; 2) timely; 3) granular; 4) collected by an independent body; and 5) publicly reported. Financial compensation for health service providers must be contingent on meeting these required metrics, with contract termination for persistent violations. Transparent and accountable monitoring systems, as are required in other federally funded healthcare facilities, are essential to accurately measure health outcomes and harms of individuals held in detention.

Clonal cytopenia of undetermined significance (CCUS) represents a distinct disease entity characterized by myeloid-related somatic mutations with a variant allele fraction of ≥2% in individuals with unexplained cytopenia(s) but without a myeloid neoplasm (MN). Notably, CCUS carries a risk of progressing to MN, particularly in cases featuring high-risk mutations. Understanding CCUS requires dedicated studies to elucidate its risk factors and natural history. Our analysis of 357 CCUS patients investigated the interplay between clonality, cytopenia, and prognosis. Multivariate analysis identified 3 key adverse prognostic factors: the presence of splicing mutation(s) (score = 2 points), platelet count

Background and objective: Positive surgical margins (PSMs) following radical prostatectomy (RP) have been seen as inherently unfavorable. However, a large international multi-institutional study recently revealed that unifocal PSMs (UPSMs) had no impact on prostate cancer–specific mortality (PCSM), whereas multifocal PSMs (MPSMs) did. Our aim was to assess the relative impact of PSMs versus percentage tumor volume (PTV) on PCSM. Methods: We analyzed data for 1552 patients who underwent robot-assisted RP performed by a single surgeon between 2002 and 2018 at a tertiary referral center with up to 15-yr follow-up. Patients were divided into negative surgical margin (NSM), UPSM, and MPSM groups, with PTV stratification using a cutoff of 40%. The primary outcome was stepwise multivariate regression analysis of predictors of PCSM (pT stage, pathological Gleason grade group, PTV, UPSM, and MPSM). The secondary outcome was the risk of 15-yr PCSM via Kaplan-Meier analysis. Key findings and limitations: The group with 40–100% PTV was older and presented with more advanced grade and stage. High PTV was significantly associated with greater risk of PSM, biochemical recurrence, PCSM, and overall mortality at 15 yr (p

Physics is an essential subject in most fields of Science and Engineering which cannot be mastered simply by watching lectures or solving problems at the end of each chapter: students must fully engage in solving these problems. This often requires problem visualisation, which presents quite a challenge for some, especially for students who are studying Physics in a second language because their understanding of the question can be influenced by the gaps in their understanding of the language used. The focus of this study is to investigate the role the language used in the wording of Physics problems plays in students' ability to understand the question and accurately visualise the scenario that would be needed to extract the required information. 220 undergraduate students and 80 preparatory students volunteered to participate in this study. Students were asked to read two sets of Physics problems and to draw the scenario or image described in the text. The first set used the more advanced English that is commonly found in Physics textbooks and which includes passive voice and homonyms, while the other uses active voice and more simplified English. The results of the study highlight the fact that ESL students' struggle with certain types of advanced English used in Physics such as the passive voice, showing that they are more capable of translating text into images when active voice is used.

Introduction: The application of structural competency and structural vulnerability to emergency medicine (EM) research has not been previously described despite EM researchers routinely engaging structurally vulnerable populations. The purpose of this study was to conduct a scoping review and consensus-building process to develop a structurally competent research approach and operational framework relevant to EM research.Methods: We conducted a scoping review focused on structural competency and structural vulnerability. Results of the review informed the development of a structural competency research framework that was presented throughout a multi-step consensus process culminating in the 2021 Society for Academic Emergency Medicine Consensus Conference. Feedback to the framework was incorporated throughout the conference.Results: The scoping review produced 291 articles with 123 articles relevant to EM research. All 123 articles underwent full-text review and data extraction following a standardized data extraction form. Most of the articles acknowledged or described structures that lead to inequities with a variety of methodological approaches used to operationalize structural competency and/or structural vulnerability. The framework developed aligned with components of the research process, drawing upon methodologies from studies included in the scoping review. Conclusion: The framework developed provides a starting point for EM researchers seeking to understand, acknowledge, and incorporate structural competency into EM research. By incorporating components of the framework, researchers may enhance their ability to address social, historical, political, and economic forces that lead to health inequities, reframing drivers of inequities away from individual factors and focusing on structural factors.

BACKGROUND: This study describes the deaths of individuals in Immigration and Customs Enforcement (ICE) detention between FY2021-2023, updating a report from FY2018-2020, which identified an increased death rate amidst the COVID-19 pandemic. METHODS: Data was extracted from death reports published online by ICE. Causes of deaths were recorded, and death rates per 100,000 admissions were calculated using population statistics reported by ICE. Reports of individuals released from ICE custody just prior to death were also identified and described. RESULTS: There were 12 deaths reported from FY2021-2023, compared to 38 deaths from FY2018-2020. The death rate per 100,000 admissions in ICE detention was 3.251 in FY2021, 0.939 in FY2022, and 1.457 in FY2023, compared with a pandemic-era high of 10.833 in FY2020. Suicide caused 1 of 12 (8.3%) deaths in FY2021-2023 compared with 9 of 38 (23.7%) deaths in FY2018-2020. COVID-19 was contributory in 3 of 11 (25%) medical deaths in FY2021-2023, compared with 8 of 11 (72.7%) in the COVID-era months of FY2020 (p = 0.030). Overall, 4 of 11 (36.3%) medical deaths in FY2021-2023 resulted from cardiac arrest in detention facilities, compared with 6 of 29 (20.3%) in FY2018-2020. Three deaths of hospitalized individuals released from ICE custody with grave prognoses were identified. CONCLUSIONS: The death rate among individuals in ICE custody decreased in FY2021-2023, which may be explained in part by the release of vulnerable individuals following recent federal legal determinations (e.g., Fraihat v. ICE). Identification of medically complex individuals released from ICE custody just prior to death and not reported by ICE indicates that reported deaths underestimate total deaths associated with ICE detention. Attentive monitoring of mortality outcomes following release from ICE custody is warranted.

Medications and drugs constitute a well-known etiology of pancreatitis. Rare signs and symptoms of the disease can occur. We present a case of pancreatitis caused by valproic acid and that was complicated by subcutaneous panniculitis.

Background: Infectious bovine rhinotracheitis (IBR) is a global contagious respiratory disease of ruminants caused by Bovine Herpes virus-1(BoHV-1). It causes substantial financial losses in the dairy industry worldwide and is considered one of the most important causative agents of abortion and reproductive problems in dairy cattle. Aim: This study aimed to estimate the seroprevalence of IBR and the related risk factors in the dairy population in Gharbia governorate, Egypt. Methods: A cross-sectional study was conducted to investigate the seroprevalence and associated risk factors of IBR in bovine dairy herds in Qutur district, Gharbia governorate, Egypt from March 2023 to February 2024. A total of 12 smallholder farms and six commercial dairy farms that didn't use vaccination protocol against BoHV-1 were randomly selected. Serum samples (n = 400) were collected from 360 cattle and 40 Italian buffaloes and were subjected to evaluation of the serological status of BoHV-1 using indirect ELISA. A multivariate logistic regression model was implemented to evaluate the strength of the risk factors associated with the infection. Results: The overall seroprevalence of IBR was 22.5% (95% CI: 18.5% - 26.9%). The prevalence of IBR in animals reared under traditional and commercial systems was 28.04% and 21.06%, respectively. The multivariate logistic regression revealed that the risk of infection with IBR in winter months was significantly higher than in autumn [OR = 5.9, CI 95%: 2.22-16.16]. The seroprevalence of IBR was higher in weaned and yearling calves than in adult cattle (P- value = 0.000). The risk of exposure to IBR infection was higher in free stall houses than in tie stall houses [OR = 3.7, CI 95%: 1.11-12.35]. The risk of seropositivity to IBR was significantly higher in animals with a history of recent respiratory manifestation than those without a history of recent respiratory problems (P- value = 0.000) Conclusion: This research study revealed that IBR is prevalent among dairy cattle reared under both production systems in the Gharbia governorate. Introducing an appropriate vaccination protocol becomes inevitable to protect our dairy industries from potential economic losses due to this disease. [Open Vet J 2024; 14(11.000): 2960-2969]

Chronic low back pain (cLBP) is the most prevalent chronic pain condition. There are no treatments that haven been found to directly assuage evoked cLBP. To this extent, mindfulness-meditation is a promising pain therapy. Yet, it is unclear if meditation can be utilized to directly attenuate evoked chronic pain through endogenous opioids. A double-blind, randomized, and placebo-controlled clinical trial with a drug crossover design examined if mindfulness-meditation, as compared to sham mindfulness-meditation, attenuated straight leg-raise test evoked chronic pain during intravenous (0.15 mg/kg bolus + 0.15 mg/kg/hour maintenance) naloxone (opioid antagonist) and placebo-saline infusion. Fifty-nine individuals with cLBP (mean age = 46 years; 30 females) completed all study procedures. After the pre-intervention pain testing session, patients were randomized to a four-session (20-min/session) mindfulness (n = 30) or sham mindfulness-meditation (n = 29) intervention. After the interventions, mindfulness and sham mindfulness-meditation were associated with significant reductions in back pain during saline and naloxone infusion when compared to rest (non-meditation) in response to the cLBP-evoking straight leg-raise test. These results indicate that meditation directly reduces evoked chronic pain through non-opioidergic processes. Importantly, after the interventions, the mindfulness group reported significantly lower straight leg-raise induced pain than the sham mindfulness-meditation group during rest (non-meditation) and meditation. Mindfulness and sham mindfulness-meditation training was also associated with significantly lower Brief Pain Inventory severity and interference scores. The pain-relieving effects of mindfulness meditation were more pronounced than a robust sham-mindfulness meditation intervention, suggesting that non-reactive appraisal processes may be uniquely associated with improvements in chronic low-back pain.Trial Registration: ClinicalTrials.gov identifier: NCT04034004.

Racial/ethnic minorities have demonstrated worse survival after allogeneic hematopoietic cell transplantation (HCT) compared to whites. Whether the racial disparity in HCT outcomes persists in long-term survivors and possibly may be even exacerbated in this population, which frequently transitions back from the transplant center to their local healthcare providers, is unknown. In the current study, we compared long-term outcomes among 1-year allogeneic HCT survivors by race/ethnicity and socioeconomic status (SES). The Center for International Blood and Marrow Transplant Research database was used to identify 5473 patients with acute myeloid leukemia, acute lymphocytic leukemia, chronic myeloid leukemia, or myelodysplastic syndromes who underwent their first allogeneic HCT between 2007 and 2017 and were alive and in remission for at least 1 year after transplantation. The study was restricted to patients who underwent HCT in the United States. SES was defined using patient neighborhood poverty level estimated from the recipients ZIP code of residence; a ZIP code with ≥20% of persons below the federal poverty level was considered a high poverty area. The primary outcome was to evaluate the associations of race/ethnicity and neighborhood poverty level with overall survival (OS), relapse, and nonrelapse mortality (NRM). Cox regression models were used to determine associations of ethnicity/race and SES with OS, relapse, and NRM. Standardized mortality ratios were calculated to compare mortality rates of the study patients and their general population peers matched on race/ethnicity, age, and sex. The study cohort was predominately non-Hispanic white (n = 4385) and also included non-Hispanic black (n = 338), Hispanic (n = 516), and Asian (n = 234) patients. Overall, 729 patients (13%) resided in high-poverty areas. Significantly larger proportions of non-Hispanic black (37%) and Hispanic (26%) patients lived in high-poverty areas compared to non-Hispanic whites (10%) and Asians (10%) (P < .01). Multivariable analysis revealed no significant associations between OS, PFS, relapse, or NRM and race/ethnicity or poverty level when adjusted for patient-, disease- and transplantation-related covariates. Our retrospective cohort registry study shows that among adult allogeneic HCT recipients who survived at least 1 year in remission, there were no associations between race/ethnicity, neighborhood poverty level, and long-term outcomes.

Summary: Background: People with diabetes are at increased risk of hospitalisation, morbidity, and mortality following SARS-CoV-2 infection. Long-term outcomes for people with diabetes previously hospitalised with COVID-19 are, however, unknown. This study aimed to determine the longer-term physical and mental health effects of COVID-19 in people with and without diabetes. Methods: The PHOSP-COVID study is a multicentre, long-term follow-up study of adults discharged from hospital between 1 February 2020 and 31 March 2021 in the UK following COVID-19, involving detailed assessment at 5 and 12 months after discharge. The association between diabetes status and outcomes were explored using multivariable linear and logistic regressions. Findings: People with diabetes who survived hospital admission with COVID-19 display worse physical outcomes compared to those without diabetes at 5- and 12-month follow-up. People with diabetes displayed higher fatigue (only at 5 months), frailty, lower physical performance, and health-related quality of life and poorer cognitive function. Differences in outcomes between diabetes status groups were largely consistent from 5 to 12-months. In regression models, differences at 5 and 12 months were attenuated after adjustment for BMI and presence of other long-term conditions. Interpretation: People with diabetes reported worse physical outcomes up to 12 months after hospital discharge with COVID-19 compared to those without diabetes. These data support the need to reduce inequalities in long-term physical and mental health effects of SARS-CoV-2 infection in people with diabetes. Funding: UK Research and Innovation and National Institute for Health Research. The study was approved by the Leeds West Research Ethics Committee (20/YH/0225) and is registered on the ISRCTN Registry (ISRCTN10980107).

Background Research and practice show an urgent need for health interventions to be adapted in culturally and linguistically responsive ways for limited English proficient (LEP) communities where cultural and language discordance exacerbate challenges in accessing healthcare. Stop the Bleed (STB), an evidence-based life-saving bleeding control intervention training for lay community members is available in English and Spanish and does not reach members of other culturally and linguistically diverse US communities.Aims Our aim was to culturally and linguistically adapt STB materials and training to serve six language communities (Arabic, Burmese, Dari, Pashto, Somali, Swahili) in a two-phase project by following health literacy (HL) guidelines and Culturally and Linguistically Appropriate Services (CLAS) standards in materials development and training implementation.Methods Using a convenience and snowball sample of community residents contacted through face-to-face conversations and a flyer, a semi-structured focus group of eight participants with interpreters and two interviews were held to understand emergency medical services, emergency healthcare in home countries, and interest in STB training. The focus groups and interviews were completed before materials adaptation. Materials were adapted using focus guide/interview data and HL guidelines and shared with members of the targeted language groups to ensure cultural and linguistic responsiveness and understanding of terminology. Community members were recruited for a STB training through face-to-face and in-language flyers. STB training was delivered by certified instructors with interpreters.Results A total of 144 community members were trained over a two-year period. In the first phase (n = 46) we assessed knowledge and self-efficacy pre- and post-training; results indicate that there was a statistically significant increase in knowledge about life saving techniques and a significant increase in self-efficacy to use STB. Qualitative survey results indicated that in-language training was critical for skills improvement and appreciated by attendees. In the second phase (n = 98), we trained community and business leaders of a local elementary school and resettlement agency who live among and serve the broad refugee community in Clarkston.Discussion Culturally and linguistically responsive adaptations of health-related materials and training that follow HL and CLAS guidelines must include community members’ perspectives, cultural knowledge, and linguistic expertise. Adapted STB is a low cost feasible way to disseminate life-saving bleeding intervention training to diverse LEP communities.

Guanidinoacetic acid (GAA, Cas no. 352-97-6) is a feed additive that positively influences the energy and protein metabolism of animals, so it has the potential to improve the productivity of animals without affecting their health. The objective of the present study was to evaluate the influence of dietary supplementation with GAA on growth performance and blood chemistry profile of growing steers for 60 d. Forty growing crossbred male steers (Bos taurus × Bos indicus; 146.0 ± 0.5 kg body weight (BW)) were randomly divided into two experimental groups (n = 20): the first, consisted of a total mixed ration (TMR) without; and the second, substituted the 0.1 % of the TMR with GAA. Dietary supplementation of GAA decreased (P

BackgroundThe insulin-like growth factor 1 receptor (IGF-1R) and the thyrotropin receptor (TSH-R) are expressed on orbital cells and thyrocytes. These receptors are targeted in autoimmune-induced thyroid eye disease (TED). Effective therapeutic treatment of TED inhibits activation of the IGF-1R/TSH-R complex.MethodsThe inhibitory effect on cell proliferation of a small molecule targeting IGF-1R phosphorylation (Linsitinib) was investigated in an IGF-1R expressing cell line and a Chinese Hamster Ovary (CHO) cell line overexpressing TSH-R. An IGF-1R monoclonal antibody antagonist, Teprotumumab served as control. Both cell lines were plated in a 96-well format and treated with both compounds for 24 hours. After addition of tetrazolium, absorbance was measured. The apoptosis marker caspase-3/7 activity was measured. The half-maximal inhibitory concentration (IC50) of TSH-R-Ab induced stimulation (stimulatory monoclonal antibody, mAb, M22) of the TSH-R cell line was evaluated with a cell-based bioassay for blocking TSH-R-Ab. Cells were treated with ten rising concentrations of either Linsitinib, Linsitinib + Metformin, Teprotumumab, or a blocking TSH-R mAb (K1-70).ResultsLinsitinib strongly inhibited the proliferation of both cell lines at several concentrations: 31,612.5 ng/mL (IGF-1R cell line -78%, P=0.0031, TSH-R cell line -75%, P=0.0059), and at 63,225 ng/mL (IGF-1R cell line -73%, P=0.0073, TSH-R cell line -73%, P=0.0108). Linsitinib induced apoptosis of both cell lines, both morphologically confirmed and with an increased caspase-3/7 activity at concentrations of 31,612.5 ng/mL (IGF-1R cell line P=0.0158, TSH-R cell line P=0.0048) and 63,225 ng/mL (IGF-1R cell line P=0.0005, TSH-R cell line P=0.0020). Linsitinib markedly inhibited proliferation of the IGF-1R cell line at all concentrations compared to Teprotumumab (P=0.0286). Teprotumumab inhibition was significant only at 15,806.25 ng/mL with the TSH-R cell line (-15%, P=0.0396). In addition, in the TSH-R-Ab blocking bioassay, Linsitinib and the tested compounds demonstrated strong inhibition across all ten dilutions (100%).ConclusionsLinsitinib effectively induces apoptosis and inhibits proliferation of both IGF-1R and TSH-R expressing target cells, therefore demonstrating its therapeutic potential to block the reported crosstalk of the two mediators in autoimmune TED.