Biochemical Evaluation Research Articles

8385 Coexistence of Parathyroid Adenoma & Papillary Thyroid Cancer: A Rare Case Report

Abstract Disclosure: K. Dash: None. S. Verma: None. U. Ayyagari: None. M. Roy: None. S. Rathore: None. Prevalence of primary hyperparathyroidism (pHPT) ranges from 0.1- 0.4% in general population. Nodular thyroid disease is an increasingly common incidental diagnosis due to widespread use of ultrasound. Papillary thyroid cancer (PTC) is the most common cancer of thyroid gland. Here we report a 53 year old post-menopausal woman presented with weight loss, generalised body aches, arthralgia, myalgia, and proximal muscle weakness. She was hypertensive and clinically euthyroid. Physical examination revealed generalized tenderness all over the body but no thyroid or parathyroid nodules on palpation. Biochemical evaluation showed hypercalcemia 12.1mg/dl (8.4-10.2mg/dl), PTH>2000pg/ml (14-72pg/ml), ALP-1855 U/L (40–125 U/L), decreased phosphorous of 2.4mg/dl (25-4.6 mg/dl), and vitamin-D of 46 nmol/L ( 75-250 nmol/L). USG neck revealed a heterogeneous lesion at the lower pole of right lobe of thyroid gland & two small hypoechoic nodules seen in the right lobe of thyroid gland. FNAC from nodules was inconclusive. USG abdomen revealed nephrocalcinosis. DEXA scan showed severe osteoporosis. Tc99mSestamibi SPECT-CT showed uptake at lower pole of right lobe of thyroid. On exploration, two nodules were palpated in the right lobe of the thyroid and simultaneous right hemi-thyroidectomy was performed. Histopathologic report confirmed parathyroid adenoma (figure 1) as well as presence of carcinoma in the two nodules: one was a papillary thyroid cancer (Classic variant) and the other a follicular variant of papillary thyroid carcinoma (figure 2). Margins were negative for malignancy. She was treated with levothyroxine to maintain TSH <0.1U/L and followed up with annual ultrasound screening. At 2 year follow up, patient was symptom free with improved T score on DEXA scan and no nodule over residual thyroid gland. Discussion: Co-existence of pHPT and PTC ranges from 2.3-4.3%. The use of ultrasound neck as a routine imaging modality for localisation of parathyroid adenoma allows detection of thyroid nodules. Benign and/or malignant thyroid nodules are commonly seen in patients with pHPT and this can range from 2-15%. Women have higher risk for co-existence. The relationship between the two diseases is thought to be incidental. Some authors have suggested possible role of shared genes, embryological factors, transcription factors, vitamin-D deficiency and hyperparathyroidism that could lead to activation of angiogenic factors and carcinogenesis. Fig. 1. Parathyroid adenoma. (a)Tc99m sestamibi scan showing right inferior parathyroid adenoma (b) Parathyroid adenoma (400x high power) comprising predominantly of Chief cells with mild pleomorphism. Fig. 2. Histopathology of PTC. (a)Papillary Carcinoma thyroid. 10xPhotomicrograph showing areas of calcification. (b) Papillary Carcinoma thyroid. Photomicrograph showing thyroid with papillary pattern with areas of infiltration. Presentation: 6/1/2024

8365 Bilateral Adrenal Hemorrhage Unveiling Adrenal Metastases In A Patient With Retroperitoneal Sarcoma

Abstract Disclosure: R.J. Shah: None. A.C. Goldberg: None. S. Jasim: None. Introduction: Metastatic disease to the adrenal gland is the most commonly occurring malignancy of the adrenal glands. Adrenal hemorrhage (AH) however is a rare but potentially fatal manifestation of malignancy. This case report highlights the unusual presentation of retroperitoneal sarcoma, manifesting as bilateral adrenal hemorrhage in the context of underlying metastases. Case Presentation: A 53-year-old man presented with a 4-week history of fatigue, intermittent abdominal pain radiating to the back, and vomiting. CT revealed bilateral adrenal masses measuring up to 8.5cm on the left side, with Hounsfield units (HU) 27, and 5.9cm on the right, HU 27, consistent with large areas of bilateral adrenal hemorrhage later confirmed on MRI. Biochemical evaluation included ACTH-stimulated cortisol, which was borderline at 17.4mcg/dl (recommended above 18-20mcg/dl), with a significantly elevated ACTH level of 103.8pg/nl (reference range 7.0-63.0pg/ml). Plasma metanephrines, electrolytes, aldosterone, and DHEA-S were normal. Although hemodynamically stable, he was started on prednisone 5mg daily as he was at high risk for primary adrenal insufficiency (AI). He was referred to endocrine surgery and further workup with PET/CT demonstrated a new FDG-avid periaortic retroperitoneal mass, with an interval increase in the size of the adrenal masses and development of hypoattenuating lesions in the kidneys and pancreas favoring aggressive metastatic disease. He underwent biopsy of the retroperitoneal mass, and pathology was consistent with high-grade sarcoma. Oncology started treatment with dexrazoxane and doxorubicin. His adrenal masses remained unchanged in size, and the patient died related to rapid progression of disease. Discussion: Spontaneous bilateral adrenal hemorrhage is rare with a reported incidence of 0.14 to 1.8%. Although most cases have been associated with sepsis, anticoagulation, hematologic disorders and trauma, it is important to maintain a high level of suspicion for underlying adrenal tumors and metastatic disease. AH can be a diagnostic challenge because of its non-specific presentation, and imaging is vital for timely recognition. Patients with bilateral AH should be managed with corticosteroids to avert AI-related fatalities. Presentation: 6/1/2024

8162 A Unique Presentation of Ovarian Steroid Cell Tumor Causing Hyperandrogenism in a Postmenopausal Woman

Abstract Disclosure: A. Rehan: None. M. Pandey: None. I. Goyal: None. E. Punni: None. N. Shakir: None. Background:­­­ Steroid cell tumors of the ovary are a rare entity, constituting less than 0.1% of all ovarian tumors. These tumors can present with diverse endocrine and paraneoplastic effects, including androgen excess and polycythemia. Hyperandrogenism in females can lead to hirsutism, virilization, alopecia, menstrual irregularities, acne, and emotional changes, with complications including hyperlipidemia and insulin resistance. There are various causes of androgen excess in a female including polycystic ovary syndrome (PCOS), androgen-secreting tumors, Cushing’s syndrome, and congenital adrenal hyperplasia. In a postmenopausal woman displaying signs of androgen excess, one must consider androgen-secreting tumors, and even the rare ovarian steroid cell tumor as a possible cause. Clinical Case: A 62-year-old female with type 2 diabetes mellites, obstructive sleep apnea, anxiety and depression initially presented to her primary care provider with fatigue, light-headedness, and weight loss. Initial blood work done revealed a hemoglobin greater than 20 g/dL (NR 12-16) and hematocrit greater than 60% (NR 36-48), requiring several sessions of phlebotomy. Symptoms persisted and she was finally referred to a hematologist who noted physical exam findings of hirsutism and virilization, including temporal hair loss and excess facial/body hair growth. Other concerning signs included clitoromegaly, decrease in chest size, and deepening voice. Menopause had occurred at age 50, and the patient did not have any issues with fertility during her reproductive years. Biochemical evaluation revealed testosterone level of greater than 1500 ng/dL (NR 19-82) with normal sex hormone binding globulin level, DHEA-S 652 ug/dL (NR 29-220), appropriately suppressed FSH/ LH, and normal salivary cortisol levels. Tumor markers showed normal CEA, and alpha fetoprotein but elevated CA 125 to 80.5 U/ml (NR < 38.1). Pelvic ultrasound demonstrated a 12 cm heterogeneously echoic, vascular right adnexal mass concerning for ovarian malignancy. Pelvic MRI showed a 9.8 cm right sided cystic and solid adnexal mass. The patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy, peritoneal biopsies, and omentectomy. Pathology revealed a stage IA steroid cell tumor measuring 11.4 cm. After resection, the patient reported improvement in facial hair and fatigue. Labs showed normalization of hemoglobin, hematocrit, and testosterone levels. Conclusion: This rare case highlights the importance of considering steroid cell tumor as a cause of polycythemia with hyperandrogenism. Timely diagnosis and intervention play a critical role in preventing irreversible virilization, mitigating malignant risks, and, in certain instances, preserving fertility. Generally, the prognosis is favorable, and symptom and lab normalization is often achieved through surgical resection. Presentation: 6/2/2024

7745 Hirsutism in young girls, Beyond PCOS

Abstract Disclosure: I. Mishra: None. A. Baliarsinha: None. Hirsutism is excessive terminal hair that appears in a male pattern in women.Though obesity,insulin resistance and PCOS are common cause of hirsutism in young girls,suspicion of other etiologies must be made on a background of overlapping features.We describe 3 cases of young females presenting with hirsutism with varied etiologies. Case 1.16 year 11months old female presented with oligomenorrhea -3years,excessive hair growth over face -2 years.On examination,BMI was 25.2 kg/m2,Grade 2 acanthosis,A3P5B5,modified FG- 16/36,clitoral length-1.3cm and clitoral index - 70 mm2.Biochemical evaluation revealed normal thyroid function tests,s.prolactin- 23.65 ng/ml,ONDST- 1.2 mcg/dl,LH - 1.49 IU/ml,FSH- 7.44IU/ml,serum testosterone- 70ng/dl,17OHP- 7.03 ng/ml,DHEAS- 553mcg/dl and post synacthen 17OHP- 36.89 ng/ml respectively. USG abdomen & pelvis was normal.HOMA-IR was 4.1. Diagnosis was LOCAH Case 2.19 year old female presented with hair growth in androgen dependent areas-5years, regular predictable menstrual cycles and was treated as a case of PCOS for 5 years with no changes in hair growth pattern.She was off therapy since 1 year prior presenting to us.On examination,BMI was 24 kg/m2,acanthosis absent,A3P5B5,modified FG- 18/36, clitoral length- 6 mm,clitoral index - 25mm2.Biochemical evaluation revealed normal thyroid function tests,s.prolactin- 22.9 ng/ml,ONDST- 0.508 mcg/dl,LH - 5.98 IU/ml,FSH- 5.29 IU/ml, serum testosterone- 23.4 ng/dl,17OHP- 1.01 ng/ml and DHEAS- 298 mcg/dl respectivelyUSG Abdomen & pelvis;RO - 5.7cc,LO - 5.6 cc with B/L PCOM.Review TVS was normal.In view of discordant results DHT and luteal phase serum progesterone were done which were 80.5 pg/ml and 2.1ng/ml respectively.HOMA IR was 1.9.Diagnosis was IDIOPATHIC HIRSUTISM. Case 3.12 year old female child presented with excessive hair growth over face,chest,back and abdomen- 1yr,hoarseness of voice - 1 yr,onset of breast enlargement apprx 8 to 9yrs with non-attainment of menarche.On examination BMI was 30 kg/m2,Grade 3 acanthosis, A3P5B3,modified FG- 15/36,clitoral length- 2.8 cm & clitoral index - 120 mm2. Biochemical evaluation revealed normal thyroid function tests,LH - 15.3 IU/ml,FSH- 6 IU/ml,s.prolactin- 11.2 ng/ml,ONDST- 0.38 mcg/dl,DHEAS- 161 mcg/dl,serum testosterone- 140 ng/dl,17OHP- 3.9 ng/ml and post synacthen 17OHP- 4.10 ng/ml respectively.USG abdomen-s/o PCOS with normal adrenals. In view of discordant results short DAST was done which was Testosterone(ng/dl)baseline-125;4hr-91.1, DHEAS (mcg/dl) baseline-180;4hr-188 cortisol (mcg/dl) baseline-7.04;4hr-0.95.HOMA-IR was 5.4. Diagnosis was PCOS(OVARIAN THECOSIS).Varied presentations of hyperandrogenic disorders occurs in young females.A need to revise the diagnosis must be made if no response is obtained with initial drug regimes. Presentation: 6/3/2024

7242 Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia (DIPNECH) In A Patient With Recurrent Carcinoid

Abstract Disclosure: F. Woron: None. T.L. Anderson: None. P. Madhavan: None. Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare generalized proliferation of pulmonary neuroendocrine cells. It is considered to be a pre-invasive lesion for pulmonary carcinoid, a rare neuroendocrine tumor (NET). DIPNECH is thought to be underdiagnosed, as patients can be asymptomatic or present with nonspecific cough and dyspnea, though it is also associated with fibrotic lung changes. Long-term annual surveillance imaging is recommended for due to the potential for development and metastasis of carcinoid tumors. We present a patient with recurrent pulmonary carcinoid later diagnosed with probable DIPNECH based on CT findings. The patient is a 72-year-old female with a prior 15 pack-year smoking history, who initially had a left lower lobe typical carcinoid tumor diagnosed and resected in 2018, with no evidence of lymph node metastasis. The patient’s medical history also includes pulmonary sarcoidosis, adrenal adenoma, thyroid nodule, hiatal hernia, and prediabetes. She has no family history of neuroendocrine tumors. Physical exam showed stable vitals with blood pressure of 112/70 mmHg in the right upper arm, heart rate of 84 bpm, and a body mass index of 39. Physical exam was unremarkable except for thyroid nodularity and obesity. Extensive biochemical evaluation for markers including chromogranin A and 24-hour urine 5-HIAA levels were within normal limits. In 2022, surveillance CT imaging showed a new 9 mm nodule in the right lobe within the bronchus, which was shown to be carcinoid on FNA. She complained of dyspnea and wheezing at this time, which has been managed with an albuterol inhaler. In 2023, PET/CT copper 64 dotatate scan showed a focal area of activity related to the nodule in the superior segment, also identified on recent CT scan, with the nodule measuring approximately 2.05 cm x 1.8 cm with a maximal SUV of 4.2. Interestingly, somatostatin receptor scintigraphy did not show any pick-up in the lung in 2018 or 2022. In 2023, the patient underwent right lower lobe superior segmentectomy after the nodule was found to have increased in size. Pathology showed G1, well-differentiated 1.1 cm typical carcinoid tumor with margins negative for invasive carcinoma. All 18 regional lymph nodes were negative for tumor. Immunohistochemical tests show that the tumor cells were positive for INSM1 and chromogranin with a low Ki-67 proliferation index (<2%), supporting the diagnosis. The patient is currently being monitored by yearly CT imaging and followed by both endocrinology and pulmonology. Given this case, we propose that DIPNECH should be considered as a differential in cases of pulmonary carcinoid, especially recurrent ones. Given that DIPNECH is thought to be underdiagnosed and a precursor for carcinoid associated with fibrotic lung changes, it is essential for this disease to be identified in order for patients to receive appropriate long-term monitoring. Presentation: 6/1/2024

8571 Co existence of aldosterone excess in adrenal myelolipomas

Abstract Disclosure: I. Mishra: None. A. Baliarsinha: None. Co existence of aldosterone excess in adrenal myelolipomas Abstract: Adrenal myelolipomas are benign, lipomatous tumours, most of which present as adrenal incidentalomas.Co existence of cortisol excess states and aldosterone producing carcinomas is reported with adrenal myelolipomas,however isolated aldosterone excess without imaging features of adrenal malignancy is rare.We describe 3 cases presenting for evaluation of hyperaldosteronism but with imaging features consistent with myelolipomas. Case 1;58 year female presented with hypertension and spontaneous hypokalemia.On evaluation BMI was 25.3kg/m2,Gr 2 hypertensive retinopathy with systemic examination within normal limits.Biochemical evaluation revealed; Pl.Aldo(ng/dl)32.5; PRA(ng/ml/hr)0.54; ARR 60.5; SIT Pl.Aldo(ng/ml)27.8; AVS- not done; IMAGING(CT) Left adrenal fat attenuating 16×13mm lesion baseline HU < - 20 ?adrenal myelolipoma; Mx Left adrenalectomy H/P Adrenocortical hyperplasia;post op-resolution of hypokalemia with persistence of hypertension controlled with decreased number of drugs. Case 2;38 year male presented with resistant hypertension ,cerebro vascular accident,right hemiparesis and diuretic induced hypokalemia.On evaluation BMI was 31 kg/m2,Gr 1 hypertensive retinopathy with right hemiparesis.Biochemical evaluation revealed; Pl.Aldo(ng/dl)12.3; PRA(ng/ml/hr) 0.82; ARR 15; SIT Pl.Aldo(ng/ml)7.79; AVS- not done; IMAGING(CT) Left adrenal fat attenuating 28×30mmlesion baseline HU < -20? adrenal myelolipoma; Mx Left adrenalectomy H/P adrenal myelolipoma;post op-resolution of hypokalemia ,recovery of weakness and normalization of hypertension without drugs. Case 3;49 year male presented with hypertension ,incidental detection of adrenal lesion on ultrasound for pain abdomen and normokalemia.On evaluation BMI was 27 kg/m2,no significant findings on general examination with systemic examination within normal limits. Biochemical evaluation revealed; Pl.Aldo(ng/dl)12.2; PRA(ng/ml/hr) 0.58; ARR 20.2; SIT Pl.Aldo(ng/ml)11; AVS- not done; IMAGING(CT) Left adrenal fat attenuating 22x 26 mm lesion baseline HU < -20? adrenal myelolipoma; Mx drug therapy for hypertension due to refusal for surgical therapy with monitoring of blood pressure. In surgically treated adrenal myelolipomas, adrenal hormone excess is reported in 5-6% of cases, with autonomous cortisol secretion being most common .Even on the background of CT findings consistent with myelolipomas, patients fulfilling the screening and confirmatory criterias of primary hyperaldosteronism must be subjected to apt therapeutic modality.The presence of aldosterone clusters with excessive aldosterone synthase activity in these lesions could be reason for occurrence of primary hyperaldosteronism in myelolipomas. Presentation: 6/3/2024

7735 A Rare Case of Paraganglioma in Pregnancy

Abstract Disclosure: H. Kreit: None. J. Patel: None. N.L. Shah: None. K.B. Guttenberg: None. Introduction: Paragangliomas are rare neuroendocrine tumors that consist of an abnormal growth of chromaffin cells. Exceptionally rare is a paraganglioma in pregnancy. Case Report: A 30-year-old woman presented at 21 weeks gestation with a syncopal episode while ambulatory at work. She reported dizziness, palpitations, sweating, and dyspnea prior to this episode. In the Emergency Department, she was found to have supraventricular tachycardia (SVT) with a heart rate (HR) of 170 beats per minute that resolved after vagal maneuvers. Initial evaluation, including thyroid function tests and echocardiogram, was unremarkable. Symptoms were thought to be due pregnancy, and she was discharged home. She continued to report intermittent palpitations, sweating, and dizziness that resolved spontaneously. Due to her tachycardia and persistent symptoms, biochemical evaluation for pheochromocytoma was obtained at 30 weeks gestation. This was notable for elevated 24 hour urine normetanephrine (4462 mcg, normal 40-412 mcg), normal 24 hour urine metanephrine (85 mcg, normal 25-222 mcg), elevated plasma normetanephrine (1334.7 pg/mL, normal < 148 pg/mL), and normal plasma metanephrine (42.8 pg/mL, normal < 57 pg/mL). MRI abdomen and pelvis without contrast was unremarkable. She was readmitted to the hospital and started on doxazosin. This was followed by initiation of metoprolol and a high sodium diet. C-section was planned for 37 weeks gestation. One day prior to her scheduled C-section, she presented to the hospital with contractions. She was diagnosed with hypertensive emergency complicated by pulmonary edema. Emergent C-section was performed. MRI abdomen and pelvis with contrast subsequently revealed bilateral enhancing retroperitoneal masses, measuring 4.4 cm on the right and 3.7 cm on the left. Retroperitoneal masses were resected 3 months after delivery without complication. Pathology showed a left-sided paraganglioma and a right-sided paraganglioma of undetermined malignant potential. Genetic testing was recommended. Conclusion: Paraganglioma in pregnancy is very rare. If left unrecognized and untreated, it carries increased risk of mortality to both the fetus and mother. A multidisciplinary approach with close monitoring is crucial for management. Presentation: 6/1/2024

Quercetin as a Modulator of PTPN22 Phosphomonoesterase Activity: A Biochemical and Computational Evaluation.

Cancer, a group of diseases characterized by uncontrollable cell proliferation and metastasis, remains a global health challenge. This study investigates quercetin, a natural compound found in many fruits and vegetables, for its potential to inhibit the phosphomonoesterase activity of protein tyrosine phosphatase nonreceptor type 22 (PTPN22), a key immune response regulator implicated in cancer and autoimmune diseases. We started by screening seven (7) natural compounds against the activities of PTPN22 in vitro. The initial screening identified quercetin with the highest percentage inhibition (81%) among the screened compounds when compared with ursolic acid that has 84%. After the identification of quercetin, we proceeded by investigating the effect of increasing concentrations of the compound on the activity of PTPN22. In vitro studies showed that quercetin inhibited PTPN22 with an IC50 of 29.59 μM, outperforming the reference standard ursolic acid, which had an IC50 of 37.19 μM. Kinetic studies indicated a non-competitive inhibition by quercetin with a Ki of 550 μM. In silico analysis supported these findings, showing quercetin's better binding affinity (ΔGbind -24.56 kcal/mol) compared to ursolic acid, attributed to its higher reactivity and electron interaction capabilities at PTPN22's binding pocket. Both quercetin and ursolic acid improved the structural stability of PTPN22 during simulations. These results suggest quercetin's potential as an anticancer agent, meriting further research. However, in vivo studies and clinical trials are necessary to fully assess its efficacy and safety, and to better understand its mechanisms of action.

The possible connection between neutrophil-to-high-density lipoprotein ratio and cerebral perfusion in clinically established corticobasal syndrome: a pilot study.

Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) are tauopathic atypical parkinsonisms. Given their overlap in terms of clinical manifestation, there is growing interest in the mechanisms leading to these entities. In total, 71 patients were included in the study, 19 of whom were clinically diagnosed with CBS, 37 with PSP, and 15 with Parkinson's disease (PD). The mean ages of the participants were 72.8, 72.9, and 64.0 years, respectively, and the disease duration varied from 3 to 6 years. Each individual underwent blood collection. Morphological and biochemical evaluation of blood samples was performed to analyze the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-high-density lipoprotein ratio (NHR). A single-photon emission computed tomography (SPECT) with technetium-99m hexamethylpropyleneamine oxime (99Tc-HMPAO) tracer was used to assess perfusion in two regions of interest (ROI): the thalamus and insula. Using Pearson correlation to assess the linear relationship between NHR and perfusion in the insula and thalamus for CBS, PSP, and PD patients, the authors intended to verify possible correlations between NLR, PLR, and NHR and perfusion in the indicated ROIs. The study revealed a negative linear correlation between NHR and perfusion of both the left (Insula L; R = -0.59) and right (Insula R; R = -0.58) insula regions. Similar to the insula, a linear correlation between NHR and activity in both the left (Thalamus L) and right (Thalamus R) thalamus regions in CBS subjects with a relatively stronger correlation in the right thalamus (R = -0.64 vs. R = -0.58) was found. These observations were not confirmed in PSP and PD patients. Simultaneously using non-specific parameters for peripheral inflammation (NLR, PLR, and NHR) and perfusion, SPECT may be an interesting beginning point for further analysis of inflammatory disease mechanisms. To the best of our knowledge, this is the first study to address the potential correlation between the peripheral neuroinflammatory markers NLR, PLR, and NHR and perfusion disturbances in particular ROIs.

B-301 Deciphering Neuropathy features in the Context of Nitrous Oxide abuse: An Integrated Analysis of Electrophysiology and Metabolism

Abstract Background Nitrous oxide (N2O), used medically for its analgesic and anxiolytic properties, has emerged as a common recreational substance, leading to a rise in chronic toxicity cases. N2O abuse induces peripheral neurological damage with a spectrum of clinical presentations, ranging from mild sensory disturbances to severe motor deficits. Neurological complications from N2O include axonal and demyelinating neuropathies, leading to diagnostic and prognostic challenges. The pathophysiology of N2O toxicity is linked to functional inactivation of vitamin B12, resulting in biochemical and electrophysiological alterations. This study aims to enhance understanding of N2O pathophysiology by examining metabolic changes in consumers with axonal and demyelinating patterns. Methods This study included 35 patients with recent N2O abuse (last declarative consumption within the past week) who were treated at Lille University Hospital between March 2020 and April 2023 and underwent electromyography. The collected clinical features encompassed sensory symptoms, motor weakness, gait abnormalities and deep tendon reflexes. Patients were classified based on clinical phenotypes, distinguishing between length-dependent and non-length dependent, sensory or sensory-motor involvement and their peripheral neuropathy disability (PND) score (ranging from I to IV). Neurophysiological data analysis followed the criteria of Hadden et al. to identify patients with demyelinating criteria, while those lacking demyelinating criteria were categorized as “axonal” in the neuropathy group. Simultaneously, biochemical evaluations of serum vitamin B12 and B9 by CLIA methods (Roche), along with plasma homocysteine by LC/MS/MS and CLIA methods (Snibe), methylmalonic acid (MMA), and methionine by LC/MS/MS, were systematically performed for all patients. Results 40% of the selected patients exhibited demyelination criteria. The demyelinated group showed a significantly higher disability PND score compared to the axonal group (3.0 and 2.2, respectively; p-value = 0.028). Elevated levels of homocysteine and methylmalonic acid were found in all patients. Interestingly, plasma concentrations of homocysteine were significantly higher in the group of patient with axonal outcomes compared to the demyelinating group (90 µM and 114 µM; p-value = 0.04), suggesting an involvement of homocysteine in the type of lesion related to N2O abuse. Conclusions This study highlights the diverse electrophysiological manifestations of N2O-induced neuropathy and highlight the potential role of metabolic parameters as biomarkers to understand the pathophysiology. Indeed, lower hyperhomocysteinemia levels were observed in demyelinating patterns, highlighting a potentially biochemical difference between the groups: plasma homocysteine could also be used as a marker of neurological severity. The homocysteine assay used in these conditions must enable the patient to be managed rapidly: it would therefore be preferable to use rapid methods such as immunoanalysis. On the other hand, plasma methylmalonic acid did not differ between groups, which also suggests that other mechanisms have yet to be identified in the pathophysiology of N2O abuse.

Protocolo diagnóstico endocrinológico de la infertilidad

Infertility affects approximately 15% to 20% of couples. Factors can include both females and males as well as mixed factors and its causes may be idiopathic or unknown. The main causes of female infertility include ovulatory dysfunctions; uterine or cervical abnormalities; fallopian tube problems; and endocrinological causes such as polycystic ovary syndrome, hyperprolactinemia, hypothyroidism, hyperthyroidism, and obesity. The evaluation begins with a complete medical history and physical examination followed by tests to assess ovulatory function as well as a biochemical and hormonal analysis. Male infertility, which affects a significant proportion of couples, may be caused by testicular dysfunction, endocrinopathies, lifestyle factors, congenital anatomical anomalies, exposure to gonadotoxic drugs, and aging. The evaluation includes a detailed medical history and complete physical examination followed by semen analysis to assess sperm concentration, motility, and morphology. Imaging tests and molecular and chromosomal studies are also performed in specific cases.In both sexes, a biochemical and hormonal evaluation is crucial to identify possible endocrinological causes of infertility. Levels of hormones such as FSH, LH, testosterone, and prolactin must be measured to determine gonadal function and detect possible underlying hormonal disorders. The interpretation of these results helps guide the diagnosis and treatment of infertility.

Phytochemical and Toxicity Evaluation of Methanol Extracts of Leaves and Fruits of Zanthoxylum rhetsa (Rutaceae)

Zanthoxylum rhetsa is extensively utilized in the realm of gastronomy and therapeutics. However, existing literature lacks any documentation concerning the systematic assessment of the toxicity characteristics of the foliage and produce of Z.rhetsa. Consequently, the present inquiry was executed to appraise the immediate toxicity examinations of the methanol extract derived from the leaves and fruits in mice, in accordance with the regulations delineated by the Organization for Economic Cooperation and Development (OECD 420, 2001). In this investigation, a solitary dosage of 5000 mg/kg body mass of the specimen was administered to female mice, as stipulated by the OECD guidelines. Daily surveillance ensued for a total of fourteen days, with the objective of detecting any indications of toxicity or fatality. Upon the culmination of this two-week period, a comprehensive analysis involving hematological, biochemical, and histopathological evaluations was conducted. The outcomes of the immediate toxicity investigations evinced that neither the leaves nor the fruits extract exhibited any morbidity, conspicuous alterations in corporeal mass, nor any discernible impairment in behavioral or motor neural activities in the mice. The haematological and serum biochemical parameters did not exhibit significant disparities from the control groups. These findings were corroborated by histopathological investigations, wherein no abnormalities or pathological alterations were detected in the vital organs. The LD 50 (oral lethal dose) of the samples was determined to exceed 5000 mg/kg body weight. Consequently, the methanol extract of leaf and fruit extract of Z.rhetsa can be regarded as non-toxic and demonstrated a broad margin of safety for its therapeutic application.

Clinical, radiographic and biochemical assessment of proximal cavities restored with composite resin using incremental vs. bulk packing techniques: One-year randomized clinical trial

BackgroundBulk-fill resin composites may suffer from recurrent caries around compound proximal restorations in posterior teeth, especially at the proximo-gingival interface.Over 12 months, will the bulk fill technique affect the caries recurrence rate at gingival margins when compared to the conventional incremental packing technique? How early will the first clinical, radiographical, and biochemical evidence of caries recurrence occur?MethodsAfter randomization, in 30 patients with two compound (OM or OD) supragingival lesions, one tooth was restored using the bulk fill technique on one side (group 1) (n = 15). In contrast, the other tooth on the other side was restored utilizing the incremental layering technique (group 2) (n = 15). Both teeth received restorative material (X-tra fil, Voco, Cuxhaven, Germany). The FDI criteria were used to evaluate restorations. As for the periodontal assessment, the gingival index, plaque index, papillary bleeding scoring index and periodontal pocket depth were evaluated. The gingival crevicular fluid (GCF) specimens were gathered, and MMP-9 was extracted and quantitated by ELISA. A customized radiographic template was designed, and 3D printed digital bitewing radiographs were taken. Assessments were done clinically, radiographically and biochemically at baseline (1 week) and after 3, 6 and 12 months. Data was statistically analyzed.ResultsThe null hypothesis was accepted clinically; no statistically significant differences appeared between bulk and incrementally filled posterior restorations. As for the radiographic assessment, the null hypothesis was accepted except for increased periodontal ligament width at 3 months. The null hypothesis for the biochemical evaluation was rejected as there were significant changes in levels of MMP-9 at different testing times.Conclusions1. With similar results but less sensitivity and significant time saving, the bulk fill technique can be considered an efficient alternative to the incremental fill technique in restoring proximal cavities. 2. Early evidence of caries recurrence can be correlated to an increase in the MMP-9 level in gingival crevicular fluid, followed by an increase in radiographic periodontal ligament width measurement.Trial registrationAn ethical approval from the Research Ethics Committee at the Faculty of Dentistry, October 6 University, (Approval No. RECO6U/5-2022). The study was registered at the Pan African Clinical Trials Registry on 24/07/2023 with an identification number (PACTR202307573531455).

The chronic heart failure evolutions: Different fates and routes.

Individual prognostic assessment and disease evolution pathways are undefined in chronic heart failure (HF). The application of unsupervised learning methodologies could help to identify patient phenotypes and the progression in each phenotype as well as to assess adverse event risk. From a bulk of 7948 HF patients included in the MECKI registry, we selected patients with a minimum 2-year follow-up. We implemented a topological data analysis (TDA), based on 43 variables derived from clinical, biochemical, cardiac ultrasound, and exercise evaluations, to identify several patients' clusters. Thereafter, we used the trajectory analysis to describe the evolution of HF states, which is able to identify bifurcation points, characterized by different follow-up paths, as well as specific end-stages conditions of the disease. Finally, we conducted a 5-year survival analysis (composite of cardiovascular death, left ventricular assist device, or urgent heart transplant). Findings were validated on internal (n=527) and external (n=777) populations. We analyzed 4876 patients (age=63 [53-71], male gender n=3973 (81.5%), NYHA class I-II n=3576 (73.3%), III-IV n=1300 (26.7%), LVEF=33 [25.5-39.9], atrial fibrillation n=791 (16.2%), peak VO2% pred=54.8 [43.8-67.2]), with a minimum 2-year follow-up. Nineteen patient clusters were identified by TDA. Trajectory analysis revealed a path characterized by 3 bifurcation and 4 end-stage points. Clusters survival rate varied from 44% to 100% at 2years and from 20% to 100% at 5years, respectively. The event frequency at 5-year follow-up for each study cohort cluster was successfully compared with those in the validation cohorts (R=0.94 and R=0.84, P<0.001, for internal and external cohort, respectively). Finally, we conducted a 5-year survival analysis (composite of cardiovascular death, left ventricular assist device, or urgent heart transplant observed in 22% of cases). Each HF phenotype has a specific disease progression and prognosis. These findings allow to individualize HF patient evolutions and to tailor assessment.

Motor deficits and brain pathology in the Parkinson's disease mouse model hA53Ttg.

Parkinson's disease (PD) is a debilitating neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons and the accumulation of α-synuclein (α-syn) aggregates. The A53T missense point mutation occurs in autosomal dominant familial PD and has been found to promote the aggregation of α-syn. To investigate the role of the A53T mutation in PD, researchers have developed various mouse models with this mutation. We therefore conducted a comprehensive characterization of the tg(THY1-SNCA*A53T)M53Sud mouse model (hA53Ttg mice) for its motor and pathological features. hA53Ttg mice were tested for motor impairments in a series of motor tests at 2, 4 or 6 months of age. Human α-syn and α-syn pSer129, as well as GFAP and Iba1 signal were labeled and quantified in the cortex, hippocampus, and brainstem. Neurofilament light chain (NF-L) levels were measured in the cerebrospinal fluid (CSF) and plasma. Ex vivo analyses were performed at the age of 2, 4, 6, and 10 months. Behavioral tests revealed early muscle weakness and motor impairments that progressed with age. Immunohistochemical analyses demonstrated elevated levels of human α-syn and α-syn pSer129 in all evaluated brain regions. α-syn pSer129 labeling further revealed fiber-like structures in the cortex of older animals. Neuroinflammation was observed in an age-dependent manner. Biochemical evaluation revealed elevated NF-L levels in the plasma and CSF. Overall, our findings highlight the value of hA53Ttg mice in modeling PD-associated pathologies that closely resemble those observed in PD patients. Our results thus suggest that hA53Ttg mice are a useful tool for studying the underlying mechanisms of PD.

PRIMARY DATA ON REDUCTION OF CONSEQUENCES OF COVID-19 THROUGH THE USE OF PROPOLIS IN ALBANIAN PATIENTS

During 2020- 2021 Albania faced COVID-19 pandemics. According to the data gathered by World Health Organization, Albania is classified as a high mortality state as a result of the pandemics. However, several infected patients applied the use of Propolis and its mixtures accompanied by oregano oil as a means to treat COVID-19. In this study realized from March 2020 to August 2021, almost 3500 infected patients, part of which beekeepers were treated with Propolis and oregano oil to fight COVID-19. This study observed their health improvements by surveys conducted via telephone calls and consults in alternative medicine clinic “Merja” health. According to the results from this sample of patients, only 3% had average health issues caused by the pandemics, whereas the other 97% treated with Propolis and Oregano, had no complications regarding COVID-19 and did experience its symptoms without issues. What makes the study quite interesting is the fact that none of the treated patients did die. Overall, the study combines the application of Propolis and oregano products with biochemical evaluation as a methodology to raise body immunity and reduce COVID-19 effects in humans.

Biochemical Evaluation and Stability Assessment of Eye Drops Manufactured at Mengo Hospital: A Quality Control Study

This comprehensive study undertook a thorough evaluation of the biochemical composition and stability of eye drops manufactured at Mengo Hospital. A range of analytical tests were conducted to assess the eye drops' pH, osmolarity, viscosity, protein content, and susceptibility to microbial contamination. Additionally, stability testing was performed under various storage conditions to simulate real-world scenarios. The results of the study revealed that the eye drops manufactured at Mengo Hospital largely conformed to regulatory standards for pH and osmolarity. However, significant variations were observed in viscosity and protein content, indicating inconsistencies in the manufacturing process. Furthermore, stability testing under accelerated conditions demonstrated degradation of the eye drops, highlighting concerns regarding their shelf life and potency. Notably, microbial contamination was detected in some samples, raising concerns about the risk of eye infections and the need for improved sterilization protocols. A comparative analysis with commercial eye drops revealed similarities in biochemical composition but distinct differences in stability profiles. This suggests that while the Mengo Hospital eye drops may possess similar characteristics to commercial products, their stability and longevity may be compromised. The findings of this study have significant implications for quality improvement initiatives at Mengo Hospital. Recommendations include optimizing the manufacturing process to minimize variations in viscosity and protein content, implementing enhanced sterilization protocols to prevent microbial contamination, and conducting regular stability testing to ensure the eye drops' potency and shelf life. By addressing these areas, Mengo Hospital can enhance the quality and safety of its eye drops, ultimately benefiting patients and maintaining trust in its products.

A natural language processing-informed adrenal gland incidentaloma clinic improves guideline-based care.

Adrenal gland incidentalomas (AGIs) are found in up to 5% of cross-sectional images. However, rates of guideline-based workup for AGIs are notoriously low. We sought to determine if a natural language processing (NLP)-informed AGI clinic could improve the rates of indicated biochemical evaluation and adrenal-specific imaging. An NLP algorithm was created to detect clinically significant adrenal nodules from radiology reports of cross-sectional images at an academic institution. The NLP algorithm was applied to scans occurring between June 2020 and July 2021 to form a baseline cohort. The NLP algorithm was re-applied to scans from August 2021 to February 2023 and identified patients were invited to join an outpatient clinic dedicated to AGIs. Patients evaluated in the clinic from March 2022 to February 2023 were included in the intervention cohort. Statistical analysis utilized chi-square, t-test, and a multivariable logistic regression. The baseline and intervention cohorts included 1784 and 322 unique patients, respectively. Patients in the intervention cohort were more likely to be female (59% vs. 51%, p=0.01), be younger (60±13.1 vs. 64±13.2years, p<0.001), have smaller nodules (1.7cm, IQR 1.4-2.1 vs. 1.8cm, IQR 1.4-2.5cm, p=0.017), have had biochemical workup (99% vs. 13%, p<0.001), and have had adrenal-specific imaging (40% vs. 11%, p<0.001). In a multivariable analysis, intervention cohort patients were significantly more likely to have had biochemical workup (odds ratio ,OR 1209, confidence interval ,CI 434-5117, p<0.001) and adrenal-specific imaging (OR 8.89, CI 6.42-12.4, p<0.001). The implementation of an NLP-informed AGI clinic was associated with a seven-fold increase in biochemical workup and a three-fold increase in adrenal-specific imaging in participating patients.

Therapeutic potential of Cordyceps sinensis targeting oxidative stress and inflammatory response in the treatment of COPD rats: insights from metabolomics analysis

This study aimed to investigate the effects of wild Cordyceps sinensis on chronic obstructive pulmonary disease (COPD) rats through metabolomics approach, combined with biochemical parameters evaluations. Consequently, C. sinensis exhibited regulatory effects on the lung’s metabolic profiles in COPD rats. Treatment with C. sinensis potentially modulated glycerophospholipid metabolism, glutathione metabolism, and tryptophan metabolism, thereby alleviating oxidative stress (by decreasing MDA and GSSG, while increasing SOD and GSH) and inflammatory response (by inhibiting TNF-α, IL-8, and MMP-9) in COPD rats while improving lung tissue damage.

Abstract C028: Challenging PDAC adaptability: Uncovering therapeutic vulnerabilities in APE1 DNA repair mechanisms

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a therapeutically challenging malignancy notorious for its resilience to therapeutic strategies and ability to thrive under extreme conditions. The cancer's inherent ability to adaptively resist treatments underscores the need for novel and combinatorial therapeutic approaches. Our research focuses on elucidating the role of Apurinic-apyrimidinic endonuclease/Redox effector factor 1 (APE1/Ref-1), a critical multifunctional protein in PDAC pathobiology. APE1 serves two essential functions: as the principal endonuclease in the base excision repair (BER) pathway for DNA repair and as a redox regulator of transcription factors essential for cancer cell proliferation. While the therapeutic targeting of APE1’s redox function has been effective and continues to yield significant advances, the development of treatments aimed at its DNA repair function has proven more challenging with comparatively limited progress. Since standard PDAC treatment regimens involve DNA damaging agents potentially repaired via BER and APE1, we engineered three mutant cell lines with knock-in mutations resulting in a reduction of APE1’s BER activity while maintaining full redox activity. Biochemical evaluations confirmed the effects of the mutation, revealing a 30-fold reduction in DNA repair capacity. Surprisingly, with respect to growth and proliferation, the mutant and wild-type cell lines behaved similarly. Analyses of cytotoxic vulnerabilities revealed similar findings with the mutant lines exhibiting minimal phenotypic differences in sensitivity when challenged with cytotoxic and DNA damaging agents in proliferation-based assays. These findings led us to posit that the mutant cell lines were relying on compensatory DNA repair pathways which were providing sufficient compensation for the decrease in APE1 activity. We further hypothesized that the cell lines may still have hidden, long-term deficiencies in DNA damage processing which are not apparent during the initial stress response. Subsequent colony formation assays revealed that the mutant cell lines do exhibit poor long-term survival even after only short-term exposure to DNA damage. In vivo orthotopic mouse model experiments further corroborated these findings, showing a significant reduction in tumor size and decreased metastasis to the lungs and liver in mutant cell lines compared to wild-type controls. While APE1 is the primary endonuclease in the BER pathway, studies have demonstrated APE1-independent BER in rare, specific contexts. We are probing the hypothesis that these APE1-independent BER pathways function as the compensatory mechanism safeguarding these cells in short-term stress situations. Identifying and characterizing these backup pathways will not only offer a better understanding of APE1’s DNA repair capabilities within PDAC but will also provide a better understanding of how DNA repair mechanisms can be therapeutically targeted for novel therapeutic options or combinations. This opens the path to enhance standard of care treatments such as FOLFIRINOX. Citation Format: Eyram K Kpenu, Randall Wireman, Mahmut Mijiti, Silpa Gampala, Melissa L Fishel, Mark R Kelley. Challenging PDAC adaptability: Uncovering therapeutic vulnerabilities in APE1 DNA repair mechanisms [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr C028.