Normal Rate Research Articles

Establishing Benchmarks for Airway Replacement: Long-Term Outcomes of Tracheal Autografts in a Large Animal Model.

Airway replacement is a challenging surgical intervention and remains an unmet clinical need. Due to the risk of airway stenosis, anastomotic separation, poor vascularization, and necrosis, it is necessary to establish the gold-standard outcomes of tracheal replacement. In this study, we use a large animal autograft model to assess long-term outcomes following tracheal replacement. Four New Zealand White rabbits underwent tracheal autograft surgery and were observed for 6 months. Clinical and radiographic surveillance were recorded, and grafts were analyzed histologically and radiographically at endpoint. All animals survived to the endpoint with minimal respiratory symptoms and normal growth rates. No complications were observed. Computed tomography scans of the post-surgical airway demonstrated graft patency at all time points. Histological sections showed no sign of stenosis or necrosis with preservation of the native structure of the trachea. We established benchmarks for airway replacement. Our findings suggest that a rabbit model of tracheal autograft with direct reimplantation is feasible and does not result in graft stenosis or airway collapse.

Resting heart rate and outcomes in patients with heart failure: impact of AF from the Thai-Heat Failure Registry (THFR - HRAF study)

Abstract Introduction Heart rate (HR) is a significant prognosis factor and target of the treatment in patients with heart failure (HF) but this relationship in heart failure patients with atrial fibrillation (AF) is uncertain. Methods A total of 2,996 patients with HF were enroll in the Thai-Heart Failure registry between 2023 to 2024, from 37 heart failure clinics in Thailand. Patients were classified by resting HR and whether having AF or not. The primary outcomes are all-cause death and/or HF. The continuous prognostic relationship and interaction were determined by Cubic-spline model. Results Total of 2,932 patients with available resting heart rate and AF status were analyzed (mean age 59.3±14.5 years, 67.9% male, mean LVEF 31.9%, 12.4% having AF). There were 273, 1,497, 895 and 267 patients have HR <60, 60-80, 80-100 and >100 bpm, respectively. From the lowest HR to the highest group, the all-cause death and/or HF were 16.5%, 10.4% 13.7% and 14.0%. Interestingly, the patients in the lowest, high and highest HR group were associated with poorer outcomes when compared to patients with normal HR (60-80 bpm). (p <0.001, 0.004 and 0.033, respectively). There were no statistic significances in patient with LVEF >40% (p= 0.37, 0.48 and 0.41, respectively). The hazard ratio is lowest between 64 to 91 bpm. The relationship is the same in patient with AF (p for interaction 0.071) but higher hazard ratio at any giving heart rate. Conclusion The normal heart rate (between 60-80 bpm) is associated with the best outcomes, not lower is better. HR is a significant prognosis factor whether having AF or not. The relationship is mainly in patient with HFrEF.Figure

Experimental Investigation of the Lubricant Effect of Thixotropic Slurry on Pipe–Soil Interfacial Friction Characteristics

Based on the technical issues encountered during underground pipe jacking construction in the Jining area, a series of ring shear tests were conducted on silty clay below the groundwater level to investigate the interfacial friction characteristics under the lubrication of thixotropic slurry during construction. Seven different slurry formulations were prepared, and ring shear tests were conducted under varying normal stresses, shear rates, and shear displacements. The friction characteristics during the shearing process were analyzed, and the corresponding friction coefficients were determined. The experimental results indicate that shear stress increases with increasing normal stress, but it is not affected by shear rate and shear displacement. As normal stress increases, the friction coefficient also exhibits a slight rise, which may be due to the uneven distribution of the slurry under pressure. Among the seven formulations, Slurry 1 exhibited the best lubricating effect, which reduced the friction coefficient by 64.5%, while Slurry 0 had the poorest effect with a reduction of 42.6% in friction coefficient. Additionally, the excessive addition of bentonite in the slurry reduces its lubricating effect, and the content of fiber has a significant effect on the friction reduction degree by thixotropic slurry.

Global and Local Shear Behavior of the Frozen Soil–Concrete Interface: Effects of Temperature, Water Content, Normal Stress, and Shear Rate

The interface between soil and concrete in cold climates has a significant effect on the structural integrity of embedded structures, including piles, liners, and others. In this study, a novel temperature control system was employed to conduct direct shear tests on this interface. The test conditions included normal stress (25 to 100 kPa), temperature (ranging from 20 to −6 °C), water content (from 10 to 19%), and shear rates (0.1 to 1.2 mm/min). Simultaneously, the deformation process of the interface was continuously photographed using a modified visual shear box, and the non-uniform deformation mechanism of the interface was analyzed by combining digital image correlation (DIC) technology with the photographic data. The findings revealed that the shear stress–shear displacement curves did not exhibit a discernible peak strength at elevated temperatures, indicating deformation behavior characterized by strain hardening. In the frozen state, however, the deformation softened, and the interfacial ice bonding strength exhibited a positive correlation with decreasing temperature. When the initial water content was 16% and the normal stress was 100 kPa, the peak shear strength increased significantly from 99.9 kPa to 182.9 kPa as the test temperature dropped from 20 °C to −6 °C. Both shear rate and temperature were found to have a marked effect on the peak shear strength, with interface cohesion being the principal factor contributing to this phenomenon. At a shear rate of 0.1 mm/min, the curve showed hardening characteristics, but at other shear rates, the curves exhibited strain-softening behavior, with the softening becoming more pronounced as shear rates increased and temperatures decreased. Due to the refreezing of interfacial ice, the residual shear strength increased in proportion to the reduction in shear rate. On a mesoscopic level, it was evident that the displacement of soil particles near the interface exhibited more pronounced changes. At lower shear rates, the phenomenon of interfacial refreezing became apparent, as evidenced by the periodic changes in interfacial granular displacement at the interface.

Shear creep deformation of rock fracture distrubed by dynamic loading

The long-term stability of jointed rock masses is usually dominated by fault activation, which may be triggered by the dynamic disturbance generated by blasting during mining activities, leading to the occurrence of disasters such as landslides in open-pit and rockbursts in deep mining. The initial stress and dynamic disturbance are key factors that strongly affect the shear creep behavior of rock fractures. In this work, the shear failure instability of rock fractures of sandstone under creep-impact loading was experimentally investigated by using a creep-impact test machine, which allows for applying creep loading and an additional dynamic disturbance on rock fractures. Three stages of shear creep deformation, creep strain rate, and time-to-failure are examined under different creep stress levels and impact energies. Experimental results show that the tangential and normal creep rates increase with the increase of creep stress and impact energy, but the increment of tangential creep rate is higher than that of the normal creep rate. The time-to-failure of the creeping specimen is shortened under high creep stress and large impact energy, while the time-to-failure after the last dynamic disturbance of the specimen is determined by the total impact energy and creep stress level. By using high-speed photography, it is found that the failure types of rock depend on the magnitude of impact energy and creep stress level; that is, rock mainly slides with low stress levels and shears off with high stress levels. In addition, under different impact energy and creep stress levels, the variation of height is between 0.38 and 0.52, while the defined fracture factor, which describes the degree of failure of serrations, is between 0.30 and 0.54. The findings can provide deep insight into the fault sliding mechanism caused by mining activities, which provides theoretical support for the safe mining of ore in fault fracture zones.

Determining Rock Joint Peak Shear Strength Based on GA-BP Neural Network Method

The peak shear strength of a rock joint is an important indicator in rock engineering, such as mining and sloping. Therefore, direct shear tests were conducted using an RDS-200 rock direct shear apparatus, and the related data such as normal stress, roughness, size, normal loading rate, basic friction angle, and JCS were collected. A peak shear strength prediction model for rock joints was established, by which a predicted rock joint peak shear strength can be obtained by inputting the influencing factors. Firstly, the study used the correlation analysis method to find out the correlation coefficient between the above factors and rock joint peak shear strength to provide a reference for factor selection of the peak shear strength prediction model. Then, the JRC-JCS model and four established GA-BP neural network models were studied to identify the most valuable rock joint peak shear strength prediction method. The GA-BP neural network models used a genetic algorithm to optimize the BP neural network with different input factors to predict rock joint peak shear strength, after dividing the selected data into 80% training set and 20% test set. The results show that the error of the JRC-JCS model is a little bigger, with a value of 11.2%, while the errors of the established GA-BP neural network models are smaller than 6%, which indicates that the four established GA-BP neural network models can well fit the relationship between the peak shear strength and selected input factors. Additionally, increasing the factor number of the input layer can effectively improve the prediction accuracy of the GA-BP neural network models, and the prediction accuracy of the GA-BP neural network models will be higher if factors that have higher correlation with the output results are used as input factors.

A comparison of the therapeutic efficacy of Tenofovir Disoproxil Fumarate and Entecavir in patients with chronic Hepatitis-B

Objective: To compare the therapeutic efficacy of tenofovir disoproxil fumarate (TDF) and entecavir (ETV) in patients with chronic Hepatitis-B (CHB). Methods: This retrospective study included 110 patients with CHB who received treatment at The First People’s Hospital of Linping District, Hangzhou from January 2021 to January 2023. Clinical data of the patients were reviewed and the patients were classified according to the treatment received: TDF group (n=53, patients received TDF treatment) and ETV group (n=57, patients received ETV treatment). Hepatitis-B virus deoxyribonucleic acid (HBV DNA) levels, liver function indicators, hepatitis-B e antigen (HBeAg) seroconversion rate, alanine transaminase (ALT) normalization rate, HBV DNA negative conversion rate, overall efficacy, and incidence of adverse reactions were compared. Results: The total efficacy of the treatment in the TDF group was 94.33%, significantly higher than that in the ETV group (78.95%; P<0.05). After the treatment, the HBV DNA levels in both groups decreased compared to pretreatment levels, and were significantly lower in the TDF group compared to the ETV group (P<0.05). Both groups showed significant post-treatment improvement in liver function that was markedly better in the TDF group compared to the ETV group (P<0.05). The HBeAg seroconversion rate, ALT normalization rate, and HBV DNA conversion rate in the TDF group were significantly higher compared to the ETV group (P<0.05). There was no difference in the incidence of adverse reactions between the two groups. Conclusions: Compared with ETV, TDF has comparable adverse reaction profile but has more significant clinical effects in patients with CHB, improving HBeAg seroconversion rate, ALT normalization rate, and HBV DNA negative conversion rate. TDF is associated with lower HBV DNA levels after treatment and better improvements in liver function of patients. doi: https://doi.org/10.12669/pjms.40.10.10307 How to cite this: Wang H, Wu L. A comparison of the therapeutic efficacy of Tenofovir Disoproxil Fumarate and Entecavir in patients with chronic Hepatitis-B. Pak J Med Sci. 2024;40(10):2390-2394. doi: https://doi.org/10.12669/pjms.40.10.10307 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

The maternity dashboard is an effective tool for the improvement of maternal and neonatal care outcomes: a prospective observational study from Iraq

Background: The implementation of maternal dashboards in hospitals is both feasible and effective in improving healthcare quality. The dashboards provide rapid feedback on local outcomes in an accessible format and enable early detection of potential problems. They serve as a simple computerized tool that graphically presents the health facility’s clinical data, utilizing a traffic-light coding system so as to alert front-line staff about changes in the frequency of clinical outcomes. Aim: The aim of this study was to assess the effectiveness of the maternity dashboard in improving maternal health, reducing Neonatal Intensive Care Unit (NICU) admissions, as well as enhancing maternal and neonatal outcomes in an Iraqi hospital. Methodology: Data were collected over one year, from January 1st to December 30th, 2023. A prospective observational study (hospital-based record review) was conducted at the Obstetrics and Gynaecology Teaching Hospital in Kerbala, Iraq. Data were obtained from the medical records of all patients admitted to the obstetrical ward for labor, delivery, and the postpartum period during 2023. The maternal dashboard, a traffic light program (green, amber, red), was used in order to monitor outcomes. Data were collected manually from the outpatient department, the labor ward, the NICU registers, and the electronic records by using Excel. Results: A total of 136,519 women (who were either pregnant, in labor, or postpartum for up to 42 days) were admitted to the Obstetrics and Gynaecology Teaching Hospital in Kerbala during the study period, with 18,791 of them delivering. The implementation of the maternity dashboard resulted in significant changes: the normal vaginal delivery rate increased from 66% to 68% (p=0.0024), the caesarean section rate decreased from 33% to 31% (p=0.0001), the stillbirth monthly cases declined from 16±5 to 12±3 (p<0.05), the NICU admission monthly instances decreased from 96±14 to 71±17 (p<0.05), and early neonatal death monthly cases were reduced from 12±5 to 9±3 (p<0.05). Conclusion: The study results show that maternity dashboards are vital instruments for monitoring and improving the quality of maternity care. They effectively enhance maternal and neonatal care quality indicators when comparing results before and after their implementation.

Sparrowhawk imitation or convergent alarm signal? A new hypothesis for bubbling call of cuckoos with empirical testing

Abstract Alarm calls in bird vocalizations serve as acoustic signals announcing danger. Owing to the convergent evolution of alarm calls, some bird species can benefit from eavesdropping on certain parameters of alarm calls of other species. Vocal mimicry, displayed by many bird species, aids defense against predators and may help brood parasites during parasitism. In the coevolutionary dynamics between brood parasites, such as the common cuckoo (Cuculus canorus), and their hosts, female cuckoo vocalizations can induce hosts to leave the nest, increasing the probability of successful parasitism and reducing the risk of host attacks. Such cuckoo calls were thought to mimic those of the sparrowhawk. However, owing to their similarity to alarm calls, we propose a new hypothesis: female cuckoos cheat their hosts by mimicking the parameters of the host alarm call. In this study, we tested this new hypothesis and the sparrowhawk mimicry hypothesis simultaneously by manipulating the syllable rate in male and female common cuckoo vocalizations and playing them in front of the host Oriental reed warbler (Acrocephalus orientalis) for examination. The results indicate that similar to a normal female cuckoo call, a female call with a reduced syllable rate prompted the hosts to leave their nests more frequently and rapidly than male cuckoo calls. Additionally, the male cuckoo calls with increased syllable rate did not prompt the host to leave their nests more frequently or quickly compared with the male cuckoo calls with a normal syllable rate. Our results further confirm that female common cuckoos mimic the vocalizations of Eurasian sparrowhawks, reveal the function mechanisms underlying such mimicry, and support the theory of imperfect mimicry.

The Dependence of Growth on the Profitability of Capital in the Kaleckian Literature: A Critical Evaluation

ABSTRACT Kaleckian models can be considered as the most relevant set of theoretical works which study growth as a demand-led phenomenon. In these models, the pace of accumulation depends on demand expansion and on different measures of capital profitability. The relevance of the latter is generally assumed without any in-depth scrutiny of theoretical principles. This article identifies the theoretical underpinnings of this alleged dependence and reconsiders and develops the criticisms of them which can be found in the literature. This analysis leads to argue that this fundamental assumption of the Kaleckian models is not sufficiently argued as much as its cruciality would require. In particular, we will critically review the following assumptions: (i) the identification between the expected rate of profit and the realized rate of profit, (ii) the role of the normal (and therefore expected) rate of profit as a quantitative regulator of the amount of investment, (iii) the automatic identification between the possibilities for financing investments, due to realized profits, and the realization of a corresponding level of actual investments.

Comparison of Recombinant Cumulase with Bovine Derived Hyaluronidase for Oocyte Denudation before ICSI in Sibling Oocytes

Assisted Reproductive Technology (ART) with Intra-cytoplasmic Sperm Injection (ICSI) commonly utilizes Bovine-Derived Hyaluronidase for oocyte denudation. The emergence of Recombinant Cumulase as an alternative merit an examination of its impact upon ICSI outcomes. We compared the effects of Recombinant Cumulase and Bovine-Derived Hyaluronidase on oocyte denudation during ICSI, investigating impact upon fertilization rates, blastulation rates, and euploidy rates, aiming to improve clinical practice and optimize ART for patient outcomes. This was a retrospective observational study involving 59 patients undergoing ICSI conducted at First IVF Fertility Centre, Abu Dhabi, United Arab Emirates. Oocytes from each patient were divided one group which employed Recombinant Cumulase, and the other group utilised Bovine-Derived hyaluronidase. Parameters such as age, number of oocytes retrieved, denudation outcomes, and euploidy rates were assessed to determine enzyme impact. Comparative analysis revealed no substantial difference in fertilisation rates or embryo development (blastocyst rate) between recombinant Cumulase and bovine-derived Hyaluronidase. However, the recombinant Cumulase group exhibited significantly higher (p<0.05) rates of normal euploid embryos (Recombinant Cumulase-48.5%; Bovine Derived Hyaluronidase- 38.0%), indicating a potential advantage. However, the results are from small cohort and need to be validated with large sample size. Selecting enzymes for ART procedures is challenging. Although no significant differences were observed in fertilisation rates, the Recombinant Cumulase group treated oocytes exhibited yielding higher normal euploid embryo rates. Not many studies have looked at the Euploidy rates with use of different enzymes for oocyte denudation. Further investigations are essential to refine best practices and advance patient outcomes in assisted reproduction.

Acute toxicity of trypsin inhibitor from tamarind seeds in embryo and adult zebrafish (Danio rerio)

The trypsin inhibitor isolated from tamarind seeds (TTI) is being investigated for potential applications in the treatment of noncommunicable diseases (NCD), such as hypertension, obesity, and diabetes. This study aimed to assess TTI embryotoxicity and acute toxicity in adult zebrafish (Danio rerio). TTI was extracted and isolated from tamarind seeds. Embryonic and adult zebrafish were exposed for 96 hours to three concentrations of TTI (12.5, 25, and 50 mg/L). Zebrafish embryos (n=60 per group) were evaluated for survival, hatching, malformations, and potential developmental marker alterations, in addition to cardiotoxicity and neurotoxicity tests. For acute toxicity assessment in adults (n=20 per group), survival and locomotor and anxiety-like behaviors were assessed, along with genotoxicity (micronucleus) evaluation. Embryos exposed to TTI showed no significant adverse effects, presented normal heart rates and positive reflex response in the neurotoxicity tests. In adult fish, TTI did not cause mortality or significant behavioral changes, suggesting no neurotoxicity and no genotoxicity. Histopathological analyses of the whole body showed only changes in the liver and spinal cord, similar to those observed in the control group not exposed to TTI. These findings indicate TTI's biosafety and therapeutic potential in complex organisms. Further research is required to evaluate its long-term effects and efficacy in treating non-communicable diseases.

Spatially correlated stellar accretion in the Lupus star-forming region. Evidence for ongoing infall from the interstellar medium

Growing evidence suggests that protoplanetary discs may be influenced by late stage infall from the interstellar medium (ISM). It remains unclear the degree to which infall shapes disc populations at ages $ 1$ Myr. We explored possible spatial correlations between stellar accretion rates in the Lupus star-forming region, which would support the hypothesis that infall can regulate stellar accretion. We considered both the `clustered' stars towards the centre of Lupus 3, and the `distributed' stars that are more sparsely distributed across the Lupus complex. We took the observed accretion rates in the literature and explore spatial correlations. In particular, we tested whether the clustered stars exhibit a radial gradient in normalised accretion rates, and whether the distributed stars have spatially correlated accretion rates. We found statistically significant correlations for both the clustered and distributed samples. The clustered sample exhibits higher accretion rates in the central region, consistent with the expected Bondi-Hoyle-Lyttleton accretion rate. Stars that are spatially closer among the distributed population also exhibit more similar accretion rates. These results cannot be explained by the stellar mass distribution for either sample. Age gradients are disfavoured, though not discounted because normalised disc dust masses are not spatially correlated across the region. Spatially correlated stellar accretion rates within the Lupus star-forming region argue in favour of an environmental influence on stellar accretion, possibly combined with internal processes in the inner disc. Refined age measurements and searches for evidence of infalling material are potential ways to further test this finding.

A new approach for neural decoding by inspiring of hyperdimensional computing for implantable intra-cortical BMIs

In the field of Brain Machine Interface (BMI), the process of translating motor intention into a machine command is denoted as decoding. However, despite recent advancements, decoding remains a formidable challenge within BMI. The utilization of current decoding algorithms in the field of BMI often involves computational complexity and requires the use of computers. This is primarily due to the reliance on mathematical models to address the decoding issue and perform subsequent output calculations. Unfortunately, computers are not feasible for implantable BMI systems due to their size and power consumption. To address this predicament, this study proposes a pioneering approach inspired by hyperdimensional computing. This approach first involves identifying the pattern of each stimulus by considering the normal firing rate distribution of each neuron. Subsequently, the newly observed firing pattern for each input is compared with the patterns detected at each moment for each neuron. The algorithm, which shares similarities with hyperdimensional computing, identifies the most similar pattern as the final output. This approach reduces the dependence on mathematical models. The efficacy of this method is assessed through the utilization of an authentic dataset acquired from the Frontal Eye Field (FEF) of two male rhesus monkeys. The output space encompasses eight possible angles. The results demonstrate an accuracy rate of 51.5% while exhibiting significantly low computational complexity, involving a mere 2050 adder operators. Furthermore, the proposed algorithm is implemented on a field-programmable gate array (FPGA) and as an ASIC designe in a standard CMOS 180 nm technology, underscoring its suitability for real-time implantable BMI applications. The implementation required only 2.3 Kbytes of RAM, occupied an area of 2.2 mm2, and consumed 9.32 µW at a 1.8 V power supply. Consequently, the proposed solution represents an accurate, low computational complexity, hardware-friendly, and real-time approach.

8278 Myxedema Coma With COVID-19 Infection

Abstract Disclosure: R. Kalas: None. V. Manohar: None. N.S. Bapat: None. Y. Kim: None. Myxedema coma is a rare medical emergency that occurs in severe hypothyroidism with a mortality rate reaching 60%. The hallmarks include depressed mental status and hypothermia, but hypotension, hyponatremia, bradycardia, and hypoventilation can also occur. This complication can occur in patients with a longstanding history of severe hypothyroidism especially when precipitated by an acute event such as infection, myocardial infarction, or surgery. Prompt recognition and treatment of the condition is important to prevent fatal outcomes. We present a case of myxedema coma in the setting of COVID-19 infection and nonadherence to medication. A 91-year-old woman with history of hypothyroidism, hypertension, coronary artery disease, cardiomyopathy, and chronic obstructive pulmonary disease presented with dyspnea. Her home medications included levothyroxine 75 mcg daily, which she reported not taking for at least 3 weeks. Vital signs revealed a normal heart rate and blood pressure of 84 beats/min and 137/78 mmHg, but the patient was hypothermic to 35.7 °C. On exam, she was somnolent. Labs were notable for markedly elevated TSH level of 111 (0.380 - 4.700 uIU/mL), low free T4 level of 0.57 (0.93 - 1.70 ng/dL), random cortisol level of 25.5 (6.2-18.4 ug/dL), and positive SARS-COV-2 PCR test. Chest x-ray revealed bilateral lower lung parenchymal consolidations and arterial blood gas revealed a pH of 7.29 and pCO2 of 52.5 (35-45 mm Hg), indicating hypercapnia. She was treated for COVID pneumonia and given concern for COVID induced myxedema coma she was given IV levothyroxine 100 mcg for 2 days, after which the patient’s hypothermia and somnolence improved, with an improved repeat free T4 level 0.87 ng/dL. She was subsequently transitioned to oral levothyroxine 112 mcg daily and discharged after improvement of her COVID symptoms. Myxedema coma is a rare complication of decompensated hypothyroidism, frequently triggered by an infection. Thyroid hormone plays an important role in regulating both the innate and adaptive immune systems. As a result, individuals with hypothyroidism are at increased risk of acquiring infections, which can further lead to myxedema coma. COVID-19 infection has been associated with thyrotoxicosis, thyroiditis and hypothyroidism. Given the associated high mortality rate, regardless of the underlying precipitant, prompt diagnosis and early administration of thyroid hormone replacement therapy is crucial to improve outcomes. Presentation: 6/3/2024

12342 Retrospective Multicenter Study Of Prolactinomas In Men

Abstract Disclosure: M.A. Guitelman: None. G. Cardenas: None. A. Rogozinski: None. C. Ballarino: None. M.F. Battistone: None. K. Danilowicz: None. S. Diez: None. P. Fainstein-Day: None. A. Furioso: None. V. Garcia Roel: None. M.S. Gonzalez Pernas: None. D.A. Katz: None. M.G. Loto: None. S. Mallea Gil: None. M.P. Manavela: None. M.S. Martinez: None. K.A. Miragaya: None. P. Slavinsky: None. S. Sosa: None. J. Tkatch: None. G. Tubert: None. M. Vitale: None. M. Glerean: None. Prolactinomas in men: a retrospective multicenter study Introduction and Objectives: prolactinomas in men have recently been included by the World Health Organization as a more aggressive tumor category due to their size, invasiveness and response to treatment. Our objective was to evaluate clinical, biochemical, and imaging characteristics, therapeutic response, and long-term evolution (outcome) of a cohort of men with prolactinoma. Patients and Methods: multicenter retrospective study including 311 men with prolactinoma. Initial clinical parameters, therapeutic modalities, PRL normalization rate and gonadal recovery, as well as tumor reduction were analyzed. The results were expressed as median (min-max range). Results: 35 micro (Mi) and 276 macroadenomas (Ma) were found (199 invasive, 71 Giant ≥4 cm). The median age at diagnosis was 41 (13-84) and 40 y-old (15-73) for micro and macro respectively. The most frequent reasons for consultation were symptoms of hypogonadism in patients with Mi, while visual disturbances, headache, and incidental findings were seen in patients with Ma. Apoplexy as presentation was observed in two patients with Ma. Hypogonadotrophic hypogonadism was present in 90 % of patients in whole cohort. Median basal PRL was 144 in Mi and 1633 ng/ml in Ma. Treatment with cabergoline (CAB) was indicated in all but one patient with Ma who remitted after surgery. Normalization of PRL was achieved in 85.7% and 65.7% of Mi and Ma respectively. The median follow-up time was 48 months (6-240). Sixty-three Ma and only one Mi were submitted to surgery, 2 patients achieved remission criteria (Mi/Ma); a patient with micro experienced recurrence after 3 years, the remaining patients continued or started CAB after surgery. Ki-67 ≥3% was reported in 17/46 available pathologies. The maximum dose of CAB was 4.5 and 12 mg/wk , with a median of 0.5 and 1.5 mg/wk for Mi and Ma, respectively. Resistance to CAB (dose ≥3mg/week) occurred in 5.7% Mi and 35.4% Ma. Gonadal function recovery without testosterone requirement was achieved in 80% of Mi and 63% of Ma. Tumor remnant was observed in 34% and 49% of Mi and Ma respectively Ten patients with Ma received radiotherapy. Five patients presented CSF fistula during treatment with CAB, and another 3 impulse control disorder. One patient with carcinomatous transformation was treated with temozolomide. Conclusions: In our series of 311 men with prolactinomas, majority Ma consulted for neuro-ophthalmological symptoms, while hypogonadism was the most frequent initial symptom in Mi, despite the fact that 90% of the total population showed it at presentation. Giant, invasive and proliferative tumor were highly prevalent in Ma. Pharmacological treatment continues to be the first line of choice, with a high rate of normalization of PRL and recovery of gonadal function, but a low rate of long-term remission. Presentation: 6/2/2024

Assessment of Biventricular Systolic and Diastolic Function Using Conventional and Strain Echocardiography in Children with Sickle Cell Disease Surviving 1-year After Hematopoietic Stem Cell Transplant.

Hematopoietic stem cell transplant (HSCT) is a potentially curative therapy for children with sickle cell disease (SCD). The effects of HSCT on ventricular function are not well characterized in children with SCD. Echocardiograms from children with SCD who underwent HSCT between 2007 and 2017 were retrospectively analyzed before and 1-year after HSCT. Left ventricular (LV) volumes, mass, and ejection fraction were calculated by the 5/6 area*length method. LV end-diastolic and systolic dimensions, septal, and posterior wall thickness, and fractional shortening were measured by M-mode. Mitral and tricuspid inflow Dopplers (E and A waves) as well as mitral, tricuspid, and septal tissue Dopplers (E', A') were assessed. E/A, E'/A' and E/E' ratios were calculated. Biventricular strain imaging was performed using speckle-tracking echocardiography. Peak global systolic longitudinal and circumferential LV strain, and global longitudinal right ventricular strain, as well as early and late diastolic strain rate, were measured on LV apical 4-chamber, LV short-axis mid-papillary, and RV apical views, respectively. Forty-seven children (9.7 ± 5.5years, 60% male) met inclusion criteria. Pre-HSCT, subjects had mild LV dilation with normal LV systolic function by conventional measure of ejection fraction and fractional shortening. There was a significant reduction in LV volume, mass, and ejection fraction after HSCT, but measurements remained within normal range. LV longitudinal and circumferential strain were normal pre-HSCT and showed no significant change post-HSCT. RV strain decreased after HSCT, but the absolute change was small, and mean values were normal both pre- and post-HSCT. Conventional measures of diastolic function were all normal pre-HSCT. Post-HSCT there was a reduction in select parameters, but all parameters remained within normal range. Early and late diastolic strain rate parameters showed no significant change from pre- to post-HSCT. At one-year after HSCT in children with SCD conventional measures of systolic and diastolic function are within normal limits. Except for a small decrease in RV systolic strain with values remaining within normal limits, systolic strain and diastolic strain rate values did not significantly change 1-year after HSCT.

Pathogenic variants in CFAP46, CFAP54, CFAP74, and CFAP221 cause Primary Ciliary Dyskinesia with a defective C1d projection of the central apparatus.

Primary ciliary dyskinesia (PCD) is a rare genetic disorder caused by insufficient mucociliary clearance leading to chronic airway infections. The diagnostic guideline of the European Respiratory Society (ERS) primarily recommends the evaluation of the clinical history (e. g. by the PICADAR prediction tool), nasal nitric oxide (nNO) production rate measurements, high-speed videomicroscopy analysis (HSVMA) of ciliary beating, and the assessment of ciliary axonemes via transmission electron microscopy (TEM). Genetic testing can be implemented as a last step. In this study, we aimed to characterise PCD with a defective C1d projection of the ciliary central apparatus (CA) and evaluated the applicability of the ERS diagnostic guideline to this PCD type. Using a high-throughput sequencing approach of genes encoding C1d components, we identified pathogenic variants in the novel PCD genes CFAP46 and CFAP54, and the known PCD gene CFAP221. To fully assess this PCD type, we also analysed individuals with pathogenic variants in CFAP74. Careful evaluation revealed that C1d-defective PCD is associated with normal situs composition, normal nNO-production rates, normal ciliary ultrastructure by TEM, and normal ciliary beating by HSVMA. Despite chronic respiratory disease, PICADAR does not reliably detect this PCD type. However, we could show by in-vitro ciliary transport assays that affected individuals exhibit insufficient ciliary clearance. Overall, this study extends the spectrum of PCD genes and highlights that C1d-defective PCD individuals elude diagnosis in the current diagnostic algorithm. To enable diagnosis, genetic testing should be prioritised in future diagnostic guidelines.

Effects of ovarian stimulation on embryo euploidy: an analysis of 12874 oocytes and 3106 blastocysts in cycles with preimplantation genetic testing for monogenic disorders.

Does ovarian stimulation and the ovarian response affect embryo euploidy? Ovarian stimulation and the ovarian response in women undergoing preimplantation genetic testing for monogenic disorders (PGT-M) cycles did not affect the rates of blastocyst euploidy. Whether or not ovarian stimulation in IVF-embryo transfer has potential effects on embryo euploidy is controversial among studies for several reasons: (i) heterogeneity of the study populations, (ii) biopsies being performed at different stages of embryo development and (iii) evolution of the platforms utilized for ploidy assessment. Patients who undergo PGT-M cycles typically have no additional risks of aneuploidy, providing an ideal study population for exploring this issue. A retrospective cohort study including embryos undergoing PGT-M was conducted at a single academically affiliated fertility clinic between June 2014 and July 2021. A total of 617 women with 867 PGT-M cycles involving 12874 retrieved oocytes and 3106 trophectoderm biopsies of blastocysts were included. The primary outcome of the study was median euploidy rate, which was calculated by dividing the number of euploid blastocysts by the total number of biopsied blastocysts for each cycle. Secondary outcomes included the median normal fertilization rate (two-pronuclear (2PN) embryos/metaphase II oocytes) and median blastulation rate (blastocyst numbers/2PN embryos). Comparable euploidy rates and fertilization rates were observed across all age groups, regardless of variations in ovarian stimulation protocols, gonadotropin dosages (both the starting and total dosages), stimulation durations, the inclusion of human menopausal gonadotrophin supplementation, or the number of oocytes retrieved (all P > 0.05). Blastulation rates declined with increasing starting doses of gonadotropins in women aged 31-34 years old (P = 0.005) but increased with increasing gonadotrophin starting doses in women aged 35-37 years old (P = 0.017). In women aged 31-34, 35-37, and 38-40 years old, blastulation rates were significantly reduced with increases in the number of oocytes retrieved (P = 0.001, <0.001, and 0.012, respectively). Limitations include the study's retrospective nature and the relatively small number of patients of advanced age, especially patients older than 40 years old, leading to quite low statistical power. Second, as we considered euploidy rates as outcome measures, we did not analyze the effects of ovarian stimulation on uniform aneuploidy and mosaicism, respectively. Finally, we did not consider the effects of paternal characteristics on embryo euploidy status due to the fact that blastocyst aneuploidy primarily originates from maternal meiosis. However, sperm factors might have an effect on embryo development and the blastulation rate, and therefore also the number of blastocysts analyzed. The exclusion of patients with severe teratozoospermia and the fact that only ICSI was used as the insemination technique for women undergoing PGT-M contributed to minimize the effect of paternal factors. Ovarian stimulation and response to stimulation did not affect blastocyst euploidy rates in women undergoing PGT-M cycles. However, in women aged 31-40 years old, there was a significant decline in blastulation rates as the number of retrieved oocytes increased. This study was supported by the National Natural Science Foundation of China (Grant No. 81701407, 82301826); the National Key Research and Development Program of China (2022YFC2702901, 2022YFC2703004); China Postdoctoral Science Foundation (2022M710261), and China Postdoctoral Innovation Talent Support Program (BX20220020). There is no conflict of interest. N/A.

A-063 Correlation of 1,5-anhydroglucitol (AG) with A1c: understanding this relationship in terms of an established physiological model for AG mass balance as a function of [glucose

Abstract Background Diet-derived 1,5-anhydroglucitol (AG) is an unmetabolizable glucose analogue present in plasma (reference interval: 7.4-32.5 µg/mL). In diabetes, hyperglycemia can accelerate AG excretion, producing an inverse relationship between A1c and AG. There are no established guidelines regarding use or interpretation of AG in diabetes, but it is often described as being useful for detection of short-term variation in [glucose]. We examined AG usage at our institution, and, additionally, analyzed the information content of AG as derived from an established model for the relationship between AG and [glucose]. Methods Medical records were scanned for all combined orders for AG and A1c between September 2020 and August 2023. Estimated average glucose (eAG) was calculated from A1c [PMID: 18540046]. AG vs. A1c data were compared to calculations for AG vs. eAG using an established physiological model for AG mass balance [PMID: 9357814]. Results Among 104 AG measurements, there were 93 AG/A1c measurement pairs (see Figure). 70% had elevated A1c (n=65). 43% had decreased AG (n=40), all with elevated A1c. Among all AG/A1c pairs, 66% (closed points; n=61) were within the boundaries of model calculations for AG when assuming a simple steady-state [glucose] equal to eAG, a normal glomerular filtration rate, and a normal AG ingestion rate. AG outside of these boundaries (34%; open points, n=32) were almost entirely above the upper boundary (32%; n=30), where results are consistent either with increased AG ingestion rate, decreased glomerular filtration rate, or a discrepancy between eAG and A1c. Only two points (2.2%) were compatible with interpretation of variation in prevailing glucose from eAG. Conclusions For our data, paired AG/A1c measurements were in majority well characterized by a physiological model based simply on steady-state (invariant) [glucose] equal to eAG as derived from A1c alone. Only a small fraction of AG results suggested possible variation in [glucose].