Normal Reference Range Research Articles

Association between hypothyroidism and metabolic syndrome in Qinghai, China

ObjectiveTo investigate the epidemiological characteristics of hypothyroidism in Qinghai Province, analyze its related influencing factors, establish the normal reference range of thyroid function, and explore the relationship between thyroid hormone (THs), thyroid stimulating hormone (TSH) and metabolic syndrome (MS) in Qinghai population within the normal range, so as to provide some scientific basis for the prevention and treatment of hypothyroidism in Qinghai Province.MethodsA total of 2790 residents aged 18 and over from Qinghai were selected through stratified cluster random sampling. Data were collected via questionnaires, physical examinations, and laboratory tests.Results1. A total of 2628 eligible residents in Qinghai were included in this study, and the total prevalence of hypothyroidism was 30.25%, among which the prevalence of subclinical hypothyroidism was 29.22%, and the prevalence of clinical hypothyroidism was 1.03%. 2. The prevalence of hypothyroidism in women was significantly higher than that in men (36.69% vs 24.30%); smoking and drinking were risk factors for hypothyroidism. 3. In the excluded subjects, 1544 were abnormal thyroid ultrasound, abnormal thyroid function and/or positive thyroid autoantibodies, and the remaining 1084 were reference populations. According to the reference population data, the 95% reference ranges of TSH, FT4, FT3 were 0.43-5.51 mIU/L, 11.0-20.4 pmol/L, 3.63-5.73 pmol/L, respectively. 4. In the normal thyroid function population in Qinghai, MS and its related components were positively correlated with FT3 and FT4 levels, but not significantly correlated with TSH levels.Conclusion1. The prevalence of hypothyroidism in adults in Qinghai is relatively high, accounting for about one-thirtieth of the total population. Smoking and drinking have a certain impact on the incidence of hypothyroidism. 2. It provides a reference range for the diagnosis of thyroid diseases in Qinghai province, which is different from that of reagent suppliers, and has certain promotion significance in the western region. 3. MS and its related components are positively correlated with FT3 and FT4 levels, but not with TSH levels in people with normal thyroid function in Qinghai. Early thyroid function screening is of great significance for the prevention of MS.

Reference Range of Quantitative MRI Metrics Corrected T1 and Liver Fat Content in Children and Young Adults: Pooled Participant Analysis.

Multiparametric MRI markers of liver health corrected T1 (cT1) and proton density fat fraction (PDFF) have shown utility in the management of various chronic liver diseases. We assessed the normal population reference range of both cT1 and PDFF in healthy child and adult volunteers without any known liver disease. A retrospective multi-centre pooled analysis of 102 child and young adult (9.1 years (6-18)) volunteers from three centres: Children's Memorial Health Institute (N = 21), University Hospital Southampton (N = 28) and Hospital Infantil de Mexico (N = 53). Sex and ethnic differences were investigated for both cT1 and PDFF. Age effects were investigated with comparison to a pooled adult cohort from the UK Biobank (N = 500) and CoverScan (N = 71), covering an age range of 21 to 81 years. cT1 values were normally distributed with a median of 748 ms (IQR: 725-768 ms; 2.5-97.5 percentiles: 683-820 ms). PDFF values followed a normal distribution with a median of 1.7% (IQR: 1.3-1.9%; 2.5-97.5 percentiles: 1-4.4%). There were no significant age and sex differences in cT1 and PDFF between children and young adults. No differences in cT1 and PDFF were found between ethnicities. Age comparisons showed statistically significant, but clinically negligible, cT1 (748 ms vs. 732 ms) and PDFF (2.4% vs. 1.9%) differences between paediatric and adult groups, respectively. Median healthy cT1 and PDFF reference ranges in children and young adults fall within the reported limits for normal of 800 ms and 5%, respectively.

8169 Bilateral Inferior Petrosal Sinus Sampling Using Metyrapone as a Reliable Alternative to Differentiate Between Cushing Disease and Ectopic ACTH Syndrome- A Single Center Experience

Abstract Disclosure: M. Azmath: None. S. Faisal: None. C. Caetano: None. T. Vedere: None. H. Aftab: None. B. Tendler: None. C. Malchoff: None. Introduction: Bilateral IPSS is a crucial test in accurately diagnosing Cushing disease (CD) and differentiating it from ectopic ACTH syndrome (EAS). [1] CRH stimulated IPSS is the gold standard technique but cannot be performed due to current shortage of CRH. Metyrapone is a safe and reliable alternative to CRH that can stimulate corticotrophs to secrete ACTH and hence used for IPSS. [2] We would like to share a single center experience using a novel low dose metyrapone protocol for IPSS that successfully helped differentiate CD and EAS. Methods: This was a retrospective analysis of patients presenting with Cushing syndrome. Initial diagnosis was confirmed based on standard testing including 24-hour urinary free cortisol (UFC), late night saliva concentrations (LNSC) and MRI. Metyrapone 500 mg every 4 hours for 3 doses was administered orally starting midnight prior to IPSS performed in the morning. ACTH levels drawn during initial evaluation for Cushing syndrome was compared to ACTH values post metyrapone from the peripheral vein sample to calculate a gradient. Ultimately, pituitary CD or EAS was confirmed based on cure following surgery and /or positive ACTH of tumor staining on pathology and/or concordant results with CRH stimulated IPSS. Results: There were 9 patients, out of which 5 had pituitary CD, and 4 had EAS. Pre ACTH levels for patients ranged between 14.5 and1164 pg/ml (normal reference range 6-50). Following metyrapone, ACTH level rose to 40-4705 pg/ml (normal reference range 6-50). The increase in ACTH levels ranged from 81-547% pre and post metyrapone. An average of 5-6 ACTH samples were drawn during IPSS. Catheterization was successful in all patients and was confirmed by IR. The mean central to peripheral (C/P) ACTH ratio for patients with confirmed CD was 20.53 in comparison with a ratio of 1.34 in patients with EAS. IPSS was confirmed to be diagnostic for pituitary CD if the peak ratio after metyrapone administration was more than 3. No adverse effects were observed during or after the procedure and no hospitalization was required pre-procedure. Discussion: We present single center experience with a novel low dose metyrapone protocol for IPSS. Our protocol was successful in increasing ACTH/cortisol secretion by tumorous cells as evidenced by increase in ACTH levels post metyrapone. It is an easy oral protocol which proved to be safe without the risk for adrenal insufficiency that can occur with higher doses. It also mitigates the small thromboembolic risk that can occur with DDAVP administration. A clear distinction in C/P ACTH ratios was observed in patients with CD versus EAS as early as the 3rd sample. In conclusion, our low dose metyrapone protocol was safe and reliable in accurately differentiating between CD and EAS in small sample of patients at our institution. Presentation: 6/1/2024

7410 Bevacizumab Induced Hypothyroidism

Abstract Disclosure: A.L. McKenna: None. S. Thota-Kammili: None. K. Grennan: None. S. Rao: None. It is known that thyroid dysfunction is an adverse effect of tyrosine kinase inhibitors (TKIs) via inhibition of the vascular endothelial growth factor receptor (VEGFR). The VEGF signaling pathway is important in regulating angiogenesis in tumors and normal tissue. As a highly vascularized gland, it is expected the thyroid may be compromised because of VEGFR inhibitors. Proposed mechanisms of thyroid dysfunction include capillary regression and constriction leading to reduced vascular perfusion to the gland. Bevacizumab is a monoclonal antibody that targets VEGF and inhibits activation of VEGFR, reducing angiogenesis; interestingly, this is not commonly reported in the literature. Here we present a case where bevacizumab altered thyroid function in a patient with pre-existing primary hypothyroidism. A 60-year-old woman presented with worsening hypothyroidism. She reported a history of nonautoimmune primary hypothyroidism diagnosed in her early 20s; she still had an intact thyroid with no history of head/neck radiation. In the months leading to the presentation, she had been receiving maintenance chemotherapy with 5 fluorouracil and bevacizumab every 2 weeks for metastatic duodenal carcinoma. Prior to starting chemotherapy, she had been on a steady dose of 112 mcg of levothyroxine (LT4) daily. After 6 months on chemotherapy, she reported symptoms of fatigue and hair loss. Workup revealed an elevated TSH of 41 mIU/L (reference 0.3-4.2 mIU/L). She denied any significant changes in weight or malabsorption issues. Aside from the chemotherapy, no other new medications were introduced. Her LT4 dose was increased to 137 mcg daily, and 3 months later, there was improvement in TSH to 6.5 mIU/L as well as her symptoms. At this point, bevacizumab was briefly on hold for 2 months due to an upcoming procedure, hence there was no change to LT4 to avoid over correction. Her TSH normalized and was trending lower while bevacizumab was on hold. Once bevacizumab resumed, LT4 was preemptively increased to 150 mcg daily. Four months after resuming bevacizumab, her TSH remains within the normal reference range on 150 mcg LT4. It is hypothesized that this VEGF blocker led to worsening of her underlying hypothyroidism.Given the shared down regulation in the VEGF signaling pathway, it would be expected that TKIs and monoclonal antibodies against VEGF would share similar adverse reactions to the thyroid. However, to our knowledge, there have been limited reports of bevacizumab induced thyroid dysfunction in the literature. Explanations to this may include the more targeted VEGF inhibition with bevacizumab versus the inhibition of multiple kinase receptors from the TKIs. Further research into this will be needed. This case demonstrates that bevacizumab can impact thyroid function and thyroid labs may need to be monitored at the onset and during VEGF inhibitor therapies. Presentation: 6/3/2024

6797 Pituitary Apoplexy as initial Presentation of IgG4-Related hypophysitis

Abstract Disclosure: M. Alameri: None. A. Alnuaimi: None. Introduction: IgG4-related hypophysitis is a rare disease due to IgG4 lymphoplasmacytic infiltration of the pituitary gland. It can either be isolated or part of a multisystemic disease. We report a rare case of pituitary apoplexy as first manifestation of IgG4-RD. Case report: A 27-year-old previously healthy male presented to emergency department with severe headache, nausea, vomiting and visual impairment. CT brain showed a large sellar suprasellar mass of 3cm with thick rim enhancement. Blood test showed evidence of central adrenal insufficiency, central hypothyroidism and secondary hypogonadism. Patient was started on hormone replacement therapy for central adrenal insufficiency and central hypothyroidism. Pituitary magnetic resonance imaging (MRI) demonstrated a 3.1 x 2.4 x 2.4 cm well-defined large sellar suprasellar mass with thick rim enhancement with intrinsic heterogeneous T2 signal with hypointense T1 signal on fat-suppressed post contrast imaging consistent with necrotic haemorrhagic suggestive of pituitary apoplexy and background of hypophysitis. Upward displacement of optic chiasm was noted without involvement of cavernous sinus. The patient was initially treated with high-dose steroids aiming for reduction of the pituitary mass. However, eventually, he underwent transsphenoidal surgery due to alternated level of consciousness. Pituitary histopathology showed that vast majority of the tissue is necrotic. A small fragment of viable anterior pituitary tissue is present, which measures up to 5.5 mm in greatest dimension which exhibited marked chronic inflammation, predominantly comprised of small lymphocytes. Plasma cells were present and staining with IgG/IgG4 revealed two high-power fields with clusters of approximately 25 and 50 IgG4 positive plasma cells, respectively. Blood test showed elevated blood IgG4 levels of >2.60 g/L (normal reference range 0.03-2.01 g/L). Case was discussed at Endocrine MDT meeting which agreed that blood tests result along with histopathology findings were in keeping with IgG4-Related hypophysitis as per the Mayo Clinic, Leporati and Japan-Korea proposed criteria. Because blood IgG4 levels were elevated, a systemic evaluation was performed. No evidence of other systemic disease found. High dose steroid therapy was initiated, which reduced remnant inflammatory sellar changes. Discussion and conclusion: IgG4-related pituitary disease should be considered as differential diagnosis in unusual presentations of pituitary apoplexy in the context of sellar suprasellar hypophysitis. Presentation: 6/2/2024

12526 Acromegaly Secondary to Sparsely Granulated Adenoma

Abstract Disclosure: D. John: None. M. Kinaan: None. J. Titus: None. K. Lamar: None. The most common pathological finding in acromegaly is a densely granulated adenoma which is composed of large round eosinophilic cells with prominent nucleoli and spherical nuclei that closely resemble a somatotroph cell. Less common finding is a sparsely granulated adenoma that is composed of sheets of poorly cohesive, pleiomorphic nuclei, chromophobic cells. We present a case of a 58-year-old gentleman presenting to our endocrine clinic for evaluation of a pituitary macroadenoma. The patient was hospitalized for nausea, vertigo, headaches, and blurring of vision. CT brain at that time showed a pituitary mass measuring 2.4 x 1.6 x 1.7 cm centered in the right cavernous sinus and inseparable from the pituitary gland. Hormonal work-up in the hospital was remarkable for high GH level. IGF-1 level was not done. Patient was advised to follow-up with neurosurgery as outpatient and no emergent surgery was planned. In the clinic, patient denied symptoms of DI, adrenal insufficiency or hypothyroidism. He has history of hypogonadotropic hypogonadism and was on testosterone therapy, but he stopped it since his hospitalization. On physical examination, he was noted to have macroglossia, deep voice, prominent jawbone, and soft tissue swelling in the hands and feet. Patient did not have any visible joint swelling. He stated he did not notice these changes personally and that he’s always been a “big guy” and always had a deep voice since he was a teenager. Repeat hormonal workup (done at 8 AM) showed: normal CMP, ACTH, cortisol, prolactin, TSH, T4, and T3. Testosterone was low with LH and FSH inappropriately within the normal reference range consistent withhypogonadotropic hypogonadism. IGF-I was elevated at 628ng/mL with a Z score of 3.9. These findings were consistent with acromegaly. He underwent surgery for tumor resection and pathology report showed that about 40% of the cells demonstrated weak immunoreactivity for GH, and rare (less than 1%) prolactin-positive cells were present within the tumor. The specimen was negative for TSH, ACTH, FH, and LH immunostains. Immunostain for CAM5.2 showed predominantly perinuclear dot-like immunoreactivity. The *MIB1 proliferation index is about 1%. The findings were consistent with a sparsely granulated gonadotrophic adenoma, which may demonstrate aggressive behavior. Postoperative MRI showed postoperative changes with residual pituitary tissue (normal gland vs. residual tumor). Postoperative cortisol >16. Postoperative GH dropped from 4.39 to 2.69 after 1 month. After 3 months, patient was doing well with no symptoms. However, IGF1 level (>400) showing that surgery was not curative. Currently he is awaiting gamma knife radiation therapy with possible medical therapy afterwards. Our case will provide an overview of the specific management considerations for these tumor and how they differ from densely-granulated tumors. Presentation: 6/3/2024

Stretched Penile Length for Syrian Children Aged 0-5 Years: Cross-Sectional Study

BackgroundThe early detection of the anatomical anomalies (e.g. micropenis) of the male external genital organs is crucial for both medical and psychological reasons. During routine pediatric visits, careful inspection using standards of penis size is beneficial for the diagnosis of micropenis and macropenis. Stretched penile length (SPL) has been shown to be more dependable than the flaccid penis length. Consequently, the SPL must be measured and compared to age-appropriate normal values. ObjectiveThis cross-sectional study aimed to determine the normal range of stretched penile length in newborns and children aged 1 month to 5 years in Syria and explore the correlation between SPL, height, and weight. Study DesignData was collected from 300 Syrian males aged 0 to 5 years. SPL measurements were taken using a standardized procedure. Participants were divided into eight age groups. Statistical analysis determined the mean SPL, standard deviation, range, and rate of increase in SPL for each group. The distribution of SPL data was assessed using the Shapiro-Wilk test. Pearson correlation analysis examined the relationship between SPL and height, weight, and BMI. ResultsMean SPL increased with age, ranging from 2.36 cm in newborns to 4.29 cm in children aged 48-60 months. The 48-60 months group exhibited the largest range of SPL. The rate of SPL increase was highest in children aged 1-2.9 months. SPL values followed a normal distribution. Significant positive correlations were found between SPL and weight in the 36-47.99 months group and between SPL and height in the 6-11.9 months and 36-47.99 months groups. ConclusionThis study establishes the normal reference range of SPL in Syrian newborns and children aged 1 month to 5 years. The findings indicate that SPL is influenced significantly by height and weight in certain age groups. These results contribute to understanding penile development and can assist in the diagnosis and treatment of conditions affecting penile size.

Sudden death due to aortic rupture in New Zealand sheep

ABSTRACT Case history Over a period of 2 months in the spring and early summer of 2021, 13 cases of sudden death in cull ewes due to aortic rupture were diagnosed at a small number of New Zealand abattoirs. Clinical findings In 12/13 (92%) cases, a large blood clot was present in the thorax, and in one case the blood clot was seen in the tissues dorsal to the heart. There were no obvious signs of external trauma. The pluck (heart and lungs) or fixed aorta was submitted for histological examination in seven cases and in all of these, a tear in the aorta was found. Comparing the microscopic appearance of the proximal aorta in these seven cases to three clinically normal ewes from unaffected farms, the aortic wall thickness appeared thinner in the case ewes than the unaffected ewes. Subjectively, there was increased collagen in the tunica media in 3/7 and decreased elastin fibres in 5/7 case ewes compared to the control ewes. Further investigations on the index farm (where the first cases originated), found that the mean liver and serum Cu concentrations in 10 similarly aged, clinically normal ewes were within the normal reference range for New Zealand sheep. Similarly, the liver Cu concentrations of the seven case ewes were within the normal reference range. Diagnosis Aortic rupture due to an unknown aetiology. Clinical relevance Clinicians should be aware of this condition as a differential diagnosis for sudden death in older sheep and to assist the Ministry for Primary Industries in establishing the extent of this problem in New Zealand.

Comparative clinical study of Mist Amen Fevermix and Edhec Malacure: two polyherbal products used for the treatment of uncomplicated malaria in Ghana against Artemether/Lumefantrine

The use of herbal products for the treatment of malaria, has increased globally. However, inadequate scientific studies about the safety and effectiveness of such herbal products have been raised. Also, the reduced sensitivity of the malaria parasites to artemisinin-based combination therapies is of concern. There is therefore the need for new antimalarial medications including those from alternative sources such as herbal medicinal products. In this study, a prospective, comparative parallel group randomized, clinical study was done to assess the safety and effectiveness of Mist Amen Fevermix and Mist Edhec Malacure with Artemether/Lumefantrine as control at the Tafo Government Hospital, Kumasi between July and November 2019, after Committee on Human Research, Publication and Ethics approval (CHRPE/AP/424/19). The study was conducted in accordance with Good Clinical and Laboratory Practice (GCLP) and registered with the Pan African Clinical Trials Registry with trial number PACTR202109664146698. Participant completed an informed consent form. Randomization was based on a single sequence to allocate participants to a group. SPSS version 19. One-way ANOVA test and exploratory statistics was used for data analysis. Total sample size was 150 participants with 50 on each arm of the group. Male and female patients aged 15–45 years and meet inclusion criteria with clinically established malaria were treated with Mist Amen Fevermix and Mist Edhec Malacure, at the specified doses of 45 mls (0.1063 g) and 30 mls (0.0521 g) three times daily after meals for three days. Artemether/Lumefantrine was administered at a dose of 80/480 mg/kg twice daily after meals for three days. Baseline data was taken on day 0. Patients were then followed up on Day 3, 7 and 28 to establish treatment outcomes and any side effect using a checklist for signs and symptoms and Karnofsky’s scale to assess the quality of life. Mist Amen Fevermix was effective with a cure rate of 95.89%. Mist Edhec Malacure was also effective with a cure rate of 91.87%. The cure rate of Artemether/Lumefantrine was 97.25%. Kidney and liver panels were within normal reference range at the end of the 28-day study. This study supports the use of Mist Amen Fevermix and Mist Edhec Malacure, two multi-component products as safe and effective for the treatment of uncomplicated malaria. Both products achieved a comparable clinical treatment outcome with Artemether/Lumefantrine.

Osteodystrophy Fibrosa in a Goat Kid: Clinical Assessment and Management

Fibrous osteodystrophy is a mineral based caprine metabolic disease in which bones are resorbed as a result of prolonged hypersecretion of parathyroid hormone. High phosphorus or low calcium in the diet frequently contributes to fibrous osteodystrophy. This was a case of 8 months old kid presented to the Referral Veterinary Polyclinic of ICAR-IVRI with the history of anorexia and prominent bilateral facial swelling. History-taking revealed that owner was regularly feeding wheat bran and barley to the kid in the diet. On clinical examination, goat kid was found to be dull and depressed with rectal temperature lying within the normal reference range. Haematobiochemical analysis exhibited decreased level of serum calcium (7 mg/dl) and increased level of serum phosphorus (8.2 mg/dl). In dorsovental cephalometric radiography, facial bones appeared radiolucent. Treatment of osteodystrophy began with the administration of injection AD3E at the dose of 1 ml I/M for 5 days, injection pheniramine maleate (AvilTM) at 1 ml I/M for 5 days, syrup CalcimustTM at 5 ml PO for 5 days and injection Calcium sandozTM at 10 ml mixed with 200 ml NSS I/V SD and anabolic steroid Nandrolone at 50 mg SD. Concurrently, the owner was advised to immediately stop feeding wheat bran and barley to the kid. After 5 days of the treatment, kid’s condition started to improve and uneventful recovery was achieved 14 days post-therapy.

Normative values of oxygen saturation by pulse oximetry (SpO2) in apparently healthy children from Eastern India - A cross-sectional study.

The primary objective was to determine normative values of oxygen saturation (SpO2) by pulse oximetry in apparently healthy children, aged 1 month to 14 years. The secondary objective was to explore any variation in oxygen saturation levels by age and gender. It was a cross-sectional study conducted at a tertiary care centre and schools in Bhubaneswar, Odisha, India, from January 2021 to December 2022. Apparently healthy children were enrolled. Using a standardized pulse oximeter and appropriately sized probes, SpO2 was recorded after stabilization of plethysmograph waves. Three consecutive readings were taken, and an average was noted. The 2.5th centile SpO2 value was taken as the lower limit of normal. The median (IQR) saturation of the sample population was 99.7% (99-100). The 2.5th, 5th, 25th, and 75th percentiles were 97.7%, 98%, 99%, and 100%, respectively. Median SpO2 and its percentiles were estimated for each age group. The 2.5th centile SpO2 for infantile age group was 96.4%. No significant age and gender-wise variations of SpO2 were noted. The present study established normal reference range oxygen SpO2 levels in apparently healthy children from an eastern India region that is situated at 62 m (204 ft) above the sea level.

Normal Value of Thrombocytes Indices in Indonesian Adults: Focus on Gender and Ages

BACKGROUND: Monitoring platelet count and related indices is crucial for managing hematological disorders. No studies are reporting normal platelet indices in the adult Indonesian population. Therefore, this study was conducted to establish normal reference values for platelet count and indices in a healthy population in Indonesia and investigate their association with platelet count and each parameter.METHODS: This cross-sectional study included healthy adults from both sexes who underwent hematological testing in our laboratory. Two mL of venous blood was drawn and analyzed using an automated machine ADVIA 2120 to identify platelet count, mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (PCT), mean platelet component (MPC), platelet component distribution width (PCDW), mean platelet mass (MPM), platelet mass distribution width (PMDW), and large platelet count.RESULTS: This study included 1037 subjects with median of 27 (18–58) years old. Normal reference range values for platelet indices in adult Indonesians was established, which was significantly different between males and females (p<0.05) in following parameters: platelet count (191.77–400.37 vs. 203.00–433.00 ×109/L), MPV (7.30–9.91 vs. 7.20–10.00 fL), PDW (38.09–59.83 vs. 37.10–58.50%), PCT (0.17–0.33 vs. 0.17–0.35%), PMDW (0.68–1.06 vs. 0.67–1.04 pg) for males vs. females, respectively. However, other parameters such as MPC, PCDW, MPM, and large platelet, did not show any significant differences.CONCLUSION: The reference intervals of platelet indices in the adult Indonesian population were different from previously established reference values, indicating the importance of dedicated reference interval determination with gender consideration.KEYWORDS: thrombocyte indices, platelet count, hematology reference values, blood platelet analysis

Determining the normal range of the calcaneus-metatarsal angles in the second-trimester fetal ultrasound examination using the novel measurement technique "Melek's angles": A cross-sectional study.

The aim of this study is to establish the normal calcaneus-metatarsal angles in order to facilitate the recognition of fetal foot deformities. Therefore, a novel measurement technique was determined using ultrasound and applied to nonanomalous fetuses in the 18th to 23rd gestational weeks. This cross-sectional study included 100 low-risk, nonanomalous fetuses in the 18th to 23rd weeks of gestation. Measurements were obtained using the novel measurement technique in fetal ultrasound examination. Fetal biometry, foot sole length, first and fifth metatarsal diaphyseal length measurements were taken. The acute angle measurement of the line segment passing between the calcaneus outer lateral and proximal fifth metatarsal with the long axis of the first metatarsal diaphysis (CA-mtt1) and long axis of the fifth metatarsal diaphysis (CA-mtt5) was taken. Interobserver and intraobserver reliabilities were assessed by intraclass correlations (ICC). A strong positive correlation was detected between bi-parietal diameter (BPD) and foot sole length, first metatarsal diaphyseal length and fifth metatarsal diaphyseal length (p < 0.0001). No significant correlation of these CA-mtt1 and CA-mtt5 angles with BPD was detected (p = 0.35, p = 0.82, respectively). The data suggest that the CA-mtt1 and CA-mtt5 angles remained consistently within a narrow range and were determined to be 20.0° ± 8.7° and 7.8° ± 7.5°, respectively. Intraobserver and interobserver agreement for CA-mtt1 angle was moderate (ICC, 0.655) and moderate (ICC, 0.615), for CA-mtt5 angle was moderate (ICC, 0.631) and moderate (ICC, 0.605), respectively. A normal reference range was established for fetal sole length, first metatarsal diaphysis length, fifth metatarsal diaphysis length, CA-mtt1 angle, and CA-mtt5 angle in the 18th to 23rd weeks of gestation. It was determined that the CA-mtt1 and CA-mtt5 angles remained relatively constant within a narrow range throughout the assessed gestational weeks.

The association between taurine concentrations and dog characteristics, clinical variables, and diet in English cocker spaniels: The Canine taURinE (CURE) project.

Occurrence of low blood taurine concentrations (B-TauC) and predisposing factors to taurine deficiency in English Cocker Spaniels (ECS) are incompletely understood. Investigate the occurrence of low B-TauC in a Swedish population of ECS and evaluate the association between B-TauC and dog characteristics, clinical variables, and diet composition. One-hundred eighty privately owned ECS. Dogs were prospectively recruited and underwent physical examination, blood analyses, and echocardiographic and ophthalmic examinations. Dogs with clinical signs of congestive heart failure (CHF) also underwent thoracic radiography. Taurine concentrations were analyzed in plasma (EDTA and heparin) and whole blood. Diets consumed by the dogs at the time of the examination were analyzed for dietary taurine- (D-TauC), cysteine- (D-CysC), and methionine concentrations (D-MetC). Fifty-three of 180 dogs (29%) had low B-TauC, of which 13 (25%) dogs had clinical and radiographic signs of CHF, increased echocardiographic left ventricular (LV) dimensions and volumes, and impaired LV systolic function. Five (9%) dogs with low B-TauC had retinal abnormalities. Dietary MetC, dietary animal protein source (red/white meat), and age were associated with B-TauC in the final multivariable regression model (P < .001, R2 adj = .39). Low B-TauC suggests that taurine deficiency may play a role in the development of myocardial failure and CHF in ECS. Low D-MetC and diets with red meat as the animal protein source were associated with low B-TauC. Dogs with B-TauC below the normal reference range were older than dogs with normal concentrations.

The value of dehydroepiandrosterone sulfate in the differential diagnosis of primary bilateral adrenal macronodular hyperplasia

Objective: To investigate the value of serum dehydroepiandrosterone sulfate (DHEAS) in the differential diagnosis of primary bilateral macronodular adrenal hyperplasia (PBMAH) from nonfunctional adenoma tumors (NFA), adrenocortical adenoma (ADA) and Cushing's disease (CD). Methods: A cross-sectional study. The clinical data of 302 patients with PBMAH, NFA, ADA and CD diagnosed and treated in the First Medical Center of PLA General Hospital from January 2010 to June 2021 were retrospectively analyzed. Among them, 97 were males and 205 were females, aged (45.7±7.2) years. The area under receiver operating characteristic (ROC) curve was used to evaluate the DHEAS ratio (serum DHEAS value divided by the lower limit of normal reference range for the corresponding age and sex) and the 8∶00 adrenocorticotropic hormone (ACTH) level in the differential diagnosis of PBMAH from NFA, ADA and CD. The maximum value of Youden index was cut-off value. Results: Among the 302 patients, 33 were in PBMAH group, 125 were in NFA group, 67 were in ADA group, and 77 were in CD group. The DHEAS ratio in CD group, NFA group, PBMAH group and ADA group decreased successively, with values of 6.34(4.44, 9.93), 3.37(2.24, 4.79), 1.14(1.04, 2.40) and 0.58(0.27, 1.05), respectively. There was statistical significance among all groups (all P<0.01). The area under the ROC curve for distinguishing PBMAH from NFA, ADA and CD were 0.803, 0.741 and 0.930, and the cut-off value were 2.59, 0.99 and 2.92, respectively. The sensitivity was 66.1%, 64.2% and 87.9%, respectively. The specificity was 81.8%, 81.2% and 85.7%. According to the level of 8∶00 ACTH, PBMAH was divided into ACTH-inhibited group (ACTH<2.2 pmol/L,n=18) and ACTH-non-inhibited group (ACTH≥2.2 pmol/L, n=15).The DHEAS ratio in ACTH-non-inhibited PBMAH group was higher than that in ACTH-inhibited PBMAH group(P<0.01).The area under ROC curve of DHEAS ratio for identifying ACTH-non-inhibited PBMAH and CD was 0.877, the cut-off value was 4.55, the sensitivity was 93.3%, and the specificity was 75.3%. If the DHEAS ratio combined with 8∶00 ACTH was used as a differential diagnostic indicator, the area under the ROC curve for distinguishing ACTH-non-inhibitory PBMAH from CD can reach 0.967, with the sensitivity of 100.0% and the specificity of 81.8%. Conclusions: DHEAS ratios is different in PBMAH, NFA, ADA and CD patients, which can assist in the differential diagnosis of PBMAH from NFA、ADA and CD patients, especially in the differential diagnosis of ACTH-non-inhibited PBMAH patients and CD patients.

Cross-Sectional Study of Thiamine Deficiency and Its Associated Risks in Emergency Care.

Growing data indicates that thiamine deficiency occurs during acute illness in the absence of alcohol use disorder. Our primary objective was to measure clinical factors associated with thiamine deficiency in patients with sepsis, diabetic ketoacidosis, and oncologic emergencies. This was an analysis of pooled data from cross-sectional studies that enrolled adult emergency department (ED) patients at a single academic center with suspected sepsis, diabetic ketoacidosis, and oncologic emergencies. We excluded patients who had known alcohol use disorder or who had received ED thiamine treatment prior to enrollment. Investigators collected whole blood thiamine levels in addition to demographics, clinical characteristics, and available biomarkers. We defined thiamine deficiency as a whole blood thiamine level below the normal reference range and modeled the adjusted association between this outcome and age. There were 269 patients, of whom the average age was 57years; 46% were female, and 80% were Black. Fifty-five (20.5%) patients had thiamine deficiency. In univariate analysis, age >60years (odds ratio [OR] 2.5, 95% confidence interval [CI], 1.3-4.5), female gender (OR 1.9, 95% CI 1.0-3.4), leukopenia (OR 4.9, 95% CI 2.3-10.3), moderate anemia (OR 2.8, 95% CI 1.5-5.3), and hypoalbuminemia (OR 2.2, 95% CI 1.2-4.1) were associated with thiamine deficiency. In adjusted analysis, thiamine deficiency was significantly higher in females (OR 2.1, 95% CI 1.1-4.1), patients >60years (OR 2.0, 95% CI 1.0-3.8), and patients with leukopenia (OR 5.1, 95% CI 2.3-11.3). In this analysis, thiamine deficiency was common and was associated with advanced age, female gender, and leukopenia.

Correlation between Morphological Typing and Monoclonality of Bone Marrow Plasma Cells and Its Diagnostic Value for High-Risk Smoldering Multiple Myeloma

To investigate the correlation between morphological typing and monoclonality of bone marrow plasma cells, and explore the diagnostic value of plasma cell morphological typing for high-risk smoldering multiple myeloma(HR-SMM). The correlation between the morphological characteristics and the monoclonality of bone marrow plasma cells was analyzed in 84 patients with HR-SMM who treated in our hospital. The consistency of morphologically abnormal bone marrow plasma cells with serum free light chain (sFLC) ratio, next-generation sequencing (NGS) detection results, and its correlation with monoclonal plasma cells detected by flow cytometry (FCM) were further verified. The immunoglobulin types and levels of non-involved immunoglobulins in serum of the patients were detected, and the distribution of plasma cell clusters in patients with different disease was observed. The mean percentage of mature plasma cells were decreased successively in the order of reactive plasmacytosis (RP) group, monoclonal gammopathy of undetermined significance (MGUS) group, smoldering multiple myeloma (SMM) group, HR-SMM group and multiple myeloma (MM) group; while the mean percentage of immature, primitive, reticular and flaming plasma cells were increased successively in the order of RP group, MGUS group, SMM group, and HR-SMM group, and the difference between any two groups was statistically significant (P < 0.05).The average proportion of abnormal plasma cells in the bone marrow of HR-SMM patients was 96.2% of the total plasma cells. The proportion of abnormal plasma cells were in good agreement with the sFLC ratio and the results of NGS detection in HR-SMM patients (kappa=0.879 and kappa=0.891, both >0.75)，and showed good correlation with the monoclonal plasma cells with immunophenotype of CD45-/CD38+/CD138+/CD56+/CD19-( γ=0.825). The levels of non-involved immunoglobulin in IgG, IgA and IgM type HR-SMM patients were all decreased by more than 25% compared with the normal reference range, and the differences were statistically significant (P < 0.05). There was no significant difference in the distribution ratio of plasma cell clusters among different disease groups (P >0.05). In HR-SMM patients, the immature, primitive, reticular and flaming plasma cells in bone marrow are considered as abnormal plasma cells, and they are correlated with monoclonal plasma cells. The proportion of abnormal plasma cells in total plasma cells of bone marrow and the reduction extent of non-involved immunoglobulin level in patients have certain reference value for the diagnosis of HR-SMM.

TEG® 6s coagulation testing with a novel heparin neutralization cartridge: Technical validation and determination of normal reference ranges.

We sought to establish normal reference ranges (NRRs) for a novel TEG 6s cartridge (TEG 6s Citrated: K, KH, RTH, FFH [Global Hemostasis]) (Haemonetics Corporation, Boston, MA, US). Healthy volunteers (≥18 years of age) included in this single-arm study provided single samples of whole blood. Primary end points included TEG parameters in the citrated kaolin (CK), CK with heparinase (CKH), RapidTEG with heparinase (CRTH), and functional fibrinogen with heparinase (CFFH) assays. Evaluable data were contributed by 164 volunteers (48.8% female; 62% White/Caucasian). The following NRRs were established: CK maximum amplitude (MA), 51.0 to 67.6mm; CKH-MA, 51.8 to 67.9mm; CRTH-MA, 53.0 to 68.9mm; CFFH-MA, 15.3 to 34.4mm; CK reaction time, 5.0 to 9.1 minutes; CKH reaction time, 4.9 to 9.4 minutes; CKH lysis 30 minutes after MA, 0% to 3.2%. Duplicate measurements demonstrated high reproducibility. CFFH-MA correlated with Clauss fibrinogen concentration (Pearson correlation coefficient, 0.74). Laboratory-based studies demonstrated maintenance of the relationship between CFFH-MA and fibrinogen up to 1344mg/dL (hyperfibrinogenemic samples) and acceptability of heparin neutralization up to concentrations of low molecular weight and unfractionated heparin of 1.3 IU/mL and 5 IU/mL, respectively. This study established NRRs for the Global Hemostasis cartridge and serves as a proof of concept for the validity of results obtained using this cartridge.

The evaluation of kidney function estimation during lifestyle intervention in children with overweight and obesity

BackgroundChildren with overweight and obesity are at risk for developing chronic kidney disease (CKD). During lifestyle adjustment, the first step in the treatment of childhood obesity, body proportions are likely to change. The aim of this study was to examine how lifestyle intervention affects creatinine-based kidney function estimation in children with overweight and obesity.MethodsThis longitudinal lifestyle intervention study included 614 children with overweight and obesity (mean age 12.17 ± 3.28 years, 53.6% female, mean BMI z-score 3.32 ± 0.75). Loss to follow-up was present: 305, 146, 70, 26, and 10 children were included after 1, 2, 3, 4, and 5 (about yearly) follow-up visits, respectively. Serum creatinine (SCr) was rescaled using Q-age and Q-height polynomials.ResultsAt baseline, 95–97% of the children had a SCr/Q-height and SCr/Q-age in the normal reference range [0.67–1.33]. SCr/Q significantly increased each (about yearly) follow-up visit, and linear mixed regression analyses demonstrated slopes between 0.01 and 0.04 (corresponding with eGFR FAS reduction of 1.1–4.1 mL/min/1.73 m2) per visit. BMI z-score reduced in both sexes and this reduction was significantly higher in males. No correlation between change in rescaled SCr and BMI z-score reduction could be demonstrated.ConclusionsRescaled serum creatinine (SCr/Q) slightly increases during multidiscipline lifestyle intervention in this cohort of children with overweight and obesity. This effect seems to be independent from change in BMI z-score. Whether this minor decrease in estimated kidney function has clinical consequences in the long term remains to be seen in trials with a longer follow-up period.Clinical Trial registrationClinicalTrial.gov; Registration Number: NCT02091544.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information

271 Effects of Bariatric Surgery on Metabolic and Hormonal Balance: A 10-Year Retrospective Study

Abstract Background The increasing demand on Gastric bypass and other weight-loss surgeries known collectively as bariatric surgery is well documented but the long-term effects on some parameters have not been satisfactorily analysed over the years. Surgeons are dealing with a level of uncertainty regarding the most likely reason behind this metabolic derangement following such procedures in the follow up clinics. Aim To study the long-term effects of bariatric surgery and weight reduction procedures on Parathyroid function, calcium levels, Vitamin D and determinants of bone health. Method 10-year retrospective study looking at patients underwent bariatric surgery between the years 2006 – 2008 within the Yorkshire area and their follow up data. Results We found that the median calcium levels have decreased significantly compared to its level prior to the operation, even though the absolute value of calcium remained within the normal reference range, it was lower than that of the baseline for each individual, resulting in an increased PTH and ALP levels to a low statistical significance and important clinical significance. Conclusions Calcium levels being lower than the baseline but still within the normal reference range is affecting both PTH and ALP leaving the patient at increased risk of bone weakness complications and other hormonal disturbances. Recommendation During the post-operative follow up plan, calcium levels should be adjusted to mimic the levels of the individuals’ pre-operative values, and the baseline should be the reference range rather than the actual lab reference assuming Calcium levels preoperatively were within the normal range.