Endocrine, metabolic & immune disorders drug targets最新文献

Aim: The study aimed to compare the predictive capabilities of the traditional anthropometric indices with the novel anthropometric indices for incident hypertension.

Background: Some novel anthropometric indices, e.g., the Body Roundness Index (BRI) and A Body Shape Index (ABSI) have been associated with prevalent hypertension. There are a few cohort studies that have examined the association of the novel anthropometric indices with newonset hypertension in young adults.

Methods: This study included 2,448 military male and female young adults, aged 18-39 years, free of hypertension at baseline in Taiwan; they were followed for incidence of hypertension from 2014 till the end of 2020. Blood Pressure (BP) in mmHg was measured twice and averaged to verify hypertension, which was defined as systolic BP ≥130 and/or diastolic BP ≥80 or on antihypertensive medication therapy in each annual health examination. Anthropometric indices included the Body Mass Index (BMI) defined as the weight (kg)/height squared (m2), Waist Girth (WC) in cm, the Waist-to-height Ratio (WHtR), the BRI defined as 364.2 - 365.5 × {1 - [(WC/2π)/(0.5 × height)]2}0.5, as well as ABSI defined as WC/(BMI2/3 × height1/2). Multiple Cox regression analysis and Area Under the Curve (AUC) of the Receiver of Operating Characteristics (ROC) were utilized with adjustments for the baseline potential covariates to determine the association and compare the performance of various indices for incident hypertension.

Results: During a median follow-up period of 6.0 years, 920 new-onset hypertension cases (37.6%) developed. Higher BMI, WC, BRI (per each 1-unit increase) and WHtR (per each 0.1- unit increase) were associated with a greater risk of new-onset hypertension [Hazard Ratios (HRs) and 95% confidence intervals: 1.060 (1.035-1.085), 1.021 (1.011-1.030), and 1.178 (1.077-1.288), respectively], whereas there was no association between ABSI and new-onset hypertension. For the ROC, WC was observed with the greatest AUC for incident new-onset hypertension [0.661 (0.638-0.683)], followed by BMI [0.650 (0.628-0.673)], while the ABSI was found with the lowest AUC [0.544 (0.521-0.568)].

Conclusion: Most of the anthropometric indices were associated with a higher risk of new-onset hypertension among young adults, except for ABSI. In addition, this study has suggested the traditional indices, such as WC and BMI, to be superior to the latest ones, e.g., BRI and ABSI, for the prediction of new-onset hypertension.

Background: Autolοgous Hematopoietic Stem Cell Transplantation (AHSCT) is a treatment οption fοr patients with hematological malignancies that improves prοgnοsis and survival. Thus, it is necessary tο deal with its long-term cοmplications, such as sexual dysfunction and trauma that significantly affect survivors' quality οf life.

Objective: The aim οf this study was to evaluate the Sexual Function (SF) and the Pοst-traumatic Stress Disorder (PTSD) οf survivοrs οf hematolοgical malignancy and AHSCT.

Methods: A multicenter, quantitative, crοss-sectional, descriptive, and cοrrelational study was cοnducted from December 2019 to March 2022. Thrοugh cοnvenience sampling, 127 adults and sexually active survivors οf hematolοgic malignancy whο underwent AHSCT frοm 6 mοnths tο 5 years were recruited frοm 5 hοspitals in Athens. The survivοrs cοmpleted questionnaires on demοgraphic and clinical data, a male or female SF assessment tοοl [Internatiοnal Index Erectile Functiοn (IIEF) and Female Sexual Functiοn Index (FSFI), respectively], and the Impact of Event Scale-Revised (IES-R).

Results: Patients' mean age was 45.6 (±12.8) years. The median time frοm transplant was 3 years and the majοrity οf the survivοrs had Hodgkin's lymphοma. Accοrding tο the FSFI, wοmen had a mοderate level of SF, with a better functional area the "pain" and wοrse the "οrgasm". Accοrding tο the IIEF, men had a high level of SF, with a better functional area the "erection" and wοrse the "οverall satisfaction". Survivοrs had lοw levels οf PTSD based οn the IES-R, with nο differences between men and women. The subscale οf "hyperarοusal" had the lοwest values and the subscale οf "avοidance" had the highest values fοr bοth men and wοmen survivοrs. There was a lοw tο mοderate negative statistically significant cοrrelation between the IES-R and bοth FSFI and IIEF, suggesting a high level οf PTSD to be correlated with wοrse sexual function.

Conclusion: Survivοrs οf AHSCT had impaired SF tο varying degrees and areas of functionality depending οn their gender, but lοw levels of PTSD and lοw correlations between these twο variables. This matter is impοrtant in survivοrship care and needs further investigatiοn.

Background: Cushing's syndrome due to ectopic ACTH secretion is a rare clinical condition resulting from a dysregulatedACTH secretion by neuroendocrine tumors. The overall incidence of endogenous Cushing's syndrome is 0.7-2.4 per million peopleannually, with children accounting for only 10% of new cases each year.

Case report: When the patient first presented clinically, she was a 17-year-old girl who displayed psychiatric symptoms. Blood testsshowed diabetes mellitus and hypokalemia. She had hypertension and vertebral collapses. The hormone assay showed hypercortisolism,and because of this, she began taking metyrapone. The results of the 68Ga-PET/DOTATOC and 18FDG-PET scans were negative.The clinical course was intermittent. After one year, a 68Ga-PET/DOTATOC showed a nodule in the thymic lodge. Despite thethymectomy, the hypercortisolism persisted. A subsequent 68Ga-PET/DOTATOC repeated three months after surgery revealed anuptake corresponding to the thymic lodge. She underwent another surgery, which is finally being resolved. ACTH levels were monitoredbefore, during, and post-surgery. The laboratory provided the ACTH results promptly, and thoracic surgeons waited for hormonalresults before concluding the procedure. The adopted strategy permitted us to monitor the surgery outcome.

Conclusion: The heterogeneity of ectopic Cushing's syndrome makes diagnosis difficult. 68Ga-PET/DOTATOC proves to be a tracerwith good sensitivity and specificity for the identification of ACTH-secreting neuroendocrine lesions. The short half-life of ACTH isfound to be a strategy to monitor the complete surgical resection of the neuroendocrine lesion.

Introduction: We present an unusual case of a 28-year-old rheumatologic male patient who developed eosinophilia while he was on etanercept therapy first and then on golimumab.

Case representation: Although eosinophilia is rarely reported in the literature as a side-effect of various Tumor Necrosis Factor-alpha [TNF-alpha] antagonists, it represents a riddle about the future treatments of these patients since the persistence of therapy might lead to the onset of dermatologic or visceral eosinophilic complications in such patients.

Conclusion: Furthermore, the pathogenesis of eosinophilia is still unknown, and all the proposed hypotheses do not explain the eosinophilic proliferation in certain subjects.

Aim: This study aimed to describe characteristics and treatment choices among AMABs (Assigned Male At Birth) and AFABs (Assigned Female At Birth) transgenders enrolled from March 2021 to July 2023 at the PTA S. Giorgio of the ASP3-Catania.

Case history: A total of 145 patients were studied, and there was no prevalence of AMAB/AFAB. At first observation for AMABs, the age was 26 years and 25 years for AFABs, with 11 AMAB/AFAB declared as "non-binary" (average age 17 years).

Results: In AMAB/AFAB, we evaluated hormonal treatment, efficacy, and dosage/hormonal levels. In AMABs, oral estradiol valerate (4 mg/day) or transdermal estradiol in gel (2 mg/day) + oral cyproterone acetate (25 mg/day) for both estrogenic formulations were used. Testosterone (TE), LH, FSH, and PRL at baseline and during chronic treatment were measured. In AFABs, we used injectable TE (250 mg/3-4 weeks or 1 g/12-16 weeks) or transdermal TE (60- 80 mg/day). In these patients, we analyzed blood count, LH, FSH, and TE. Hematocrit, hemoglobin, and red blood cell count showed a modest elevation after 4-6 months of treatment. About 32% of AFABs complained of transient uterine bleeding, but no hypertension or ovarian pathology was detected.

Conclusion: In AMABs, despite the short observation period, no patient showed an increased risk of myocardial infarction and ischemic stroke. Among AFABs, no increased risk of cardiovascular or cerebrovascular disease was observed. Furthermore, given the complexity of the phenomenon, the integration between the different professional figures who require specific and qualified skills is fundamental.

Introduction: Postprandial hypoglycemia induced by Dumping Syndrome (DS) represents a side effect of bariatric surgery linked to glucose-dependent hyperinsulinemia, which can cause serious symptoms 2-3 hours after the meal hypoglycemia. This clinical case shows the effectiveness of semaglutide, a long-acting GLP1 receptor agonist, in one patient previously subjected to gastric bypass (GBP), with persistent late postprandial hypoglycaemic symptoms occurring after surgery.

Case report: A female patient, 31 years old, subjected to GBP 10 years earlier, with the diagnosis of diabetes, was admitted to our unit for persistent post-prandial reactive hypoglycemia, confirmed by Flash Glucose Monitoring (FGM) FreeStyle. The patient was intolerant to metformin, had been treated with acarbose with poor results. HbA1c 7.9%. Acarbose was suspended, and semaglutide was started sc at increasing doses, 0.25 mg/week for 1 month and subsequently 0.5 mg/week. After the first few weeks, symptoms of DS were significantly reduced with improvement of the daily glycemic profile and disappearance of hypoglycemic events. The time-below range, time spent with blood glucose <70 mg/dl, decreased by 12% to 4% during treatment with semaglutide 0.25 mg/week, up to 1% with a dose of 0.5 mg/week. The effect of the drug on reducing hypoglycemic episodes was persistent for up to 8 months.

Conclusion: Treatment of post-bariatric reactive hypoglycemia includes nutritional therapy, the use of glucosidase inhibitors, and somatostatin analogues. The use of short-acting GLP-1RA analogues has also recently been reported. In our patient, therapy with semaglutide s.c. significantly reduced episodes of reactive hypoglycemia with an improvement in the quality of life.

Background: There is a lack of solid long-term evidence with respect to the management over time of adrenal incidentalomas that miss clearly benign radiological features. We present the case of a 75-year-old man with a non-secreting adrenal mass, apparently stable in size (14 mm) and unchanged in features for 2 years, but subsequently diagnosed as adrenal carcinoma.

Case report: The patient was referred to Grande Ospedale Metropolitano Niguarda in August 2022 due to the presence of a large lesion in the left adrenal site. In 2017, a 14 mm, 20 HU, round, regular-edged lesion was detected at a CT scan without contrast medium. Over the next two years, the patient was re-evaluated every 6 months with follow-up CT scans with no apparent densitometric or dimensional changes in the known lesion. In September 2022, 3 years after the last CT scan, the patient was hospitalised for pneumonia. An abdominal CT scan acquired during the hospitalisation showed an increase of the lesion to 14.5x10x12 cm. The patient subsequently underwent open nephrosurrenectomy, and histological examination confirmed the presence of an adrenal carcinoma (proliferation index 5%, Weiss score 7). No adjuvant therapy was administered, and the last CT scan in December 2022 was negative for the recurrence of the disease.

Conclusion: Adrenal carcinoma usually presents as a clearly malignant lesion with rapid growth and a marked tendency to metastasise. This case highlights how an adrenal adenoma with indeterminate features is worthy of follow-up over time despite its apparent dimensional and radiological stability [1].

Background: Schmidt's syndrome (SS) is a subtype of polyglandular autoimmune syndrome type-2 combining autoimmune thyroiditis (AIT) and autoimmune Addison's disease (aAD). It occurs most frequently in young adult females, and aAD is the most common initial manifestation [1]. We present a rare case of SS with late-onset aAD and severe hyponatremia as the first sign.

Case report: A 73-year-old woman presented to the emergency department (ED) with a 10-day history of vomiting, diarrhea, and altered mental status. Her past medical history was remarkable for AIT and hypokinetic cardiomyopathy. Moreover, she had recently undergone a 2-week course of corticosteroid therapy for vertiginous symptoms, reporting subjective well-being. In ED, she appeared confused and hypotensive. Blood tests revealed a sodium level of 99 mEq/l with normal potassium. Initial treatment with saline infusions were started, followed by ex juvantibus intravenous hydrocortisone awaiting hormone results, which proved consistent with primary adrenal insufficiency (ACTH 1314 pg/ml, cortisol 4.72 ug/dL). Replacement therapy with both hydrocortisone and fludrocortisone was then implemented, with substantial clinical improvement and normalization of sodium levels. However, the patient later developed right heart failure and hypokalemia, which were likely caused by overreplacement and resolved after adjusting the treatment regimen. The final diagnosis of aAD was confirmed by positive adrenal autoantibodies.

Conclusions: aAD should be suspected in each case of severe hyponatremia [2], especially in patients with AIT independent of age. Furthermore, caution is needed in managing high-dose glucocorticoids along with fludrocortisone in elderly patients with cardiac disease to limit the risk of excessive mineralocorticoid activity and heart failure [3].

Aims: This study aimed to confirm the regulatory role and mechanism of circular RNA (circRNA) hsa_circ_0131922 in Papillary Thyroid Carcinoma (PTC) progression.

Background: Accumulating evidence suggests that N6-methyladenosine (m6A)-modified circular RNAs (circRNAs) perform pivotal functions in various malignancies. However, the specific role of the m6A modification of circRNA mediated by METTL3 in Papillary Thyroid Carcinoma (PTC) remains undocumented.

Objective: In this work, we aimed to examine the molecular mechanisms of a novel m6Amodified circRNA, hsa_circ_0131922, in PTC progression.

Methods: Potential circRNA was identified from GEO datasets. The RNA or protein levels of hsa_circ_0131922, METTL3, p53, and p21 were evaluated by qRT-PCR or western blot assays. The various cellular functions were checked by CCK8, wound healing, transwell, and xenograft tumor assays. MeRIP-qPCR was performed to observe the METTL3-mediated m6A modification of hsa_circ_0131922. Furthermore, the interactions between hsa_circ_0131922 and METTL3 in PTC were analyzed by bioinformatics analysis and various rescue experiments.

Results: The levels of hsa_circ_0131922 were markedly downregulated in PTC tissues and cell lines. In addition, the lower hsa_circ_0131922 levels correlated with poor prognosis in PTC patients. The hsa_circ_0131922 overexpression reduced the malignant phenotypes of PTC cells and activated the p53/p21 pathway. Bioinformatic analysis showed the m6A-modified sites of hsa_circ_0131922, and a positive correlation between hsa_circ_0131922 and METTL3. Moreover, overexpression of METTL3 increased the levels of m6A modification of hsa_circ_0131922. Mechanistically, the anti-tumor effects of hsa_circ_0131922 overexpression have been found to be partially reversed by silencing METTL3 in vivo and in vitro.

Conclusion: The results have demonstrated m6A-modified hsa_circ_0131922 by METTL3 to attenuate the progression of PTC by regulating the p53 pathway. Therefore, hsa_circ_0131922 could be a predictive prognostic biomarker and therapeutic target for PTC.

One important phytochemical is naringenin, which belongs to the flavanone class of polyphenols. It is found in citrus fruits, such as grapefruits, but it can also be found in tomatoes, cherries, and other food-grade medicinal plants. Naringenin has a significant chemotherapeutic promise, as several investigations have conclusively shown. Therefore, the goal of this review is to synthesize the literature that has been done on naringenin as a possible anti-cancer agent and clarify the mechanisms of action that have been described in treatment plans for different kinds of cancer. In a variety of cancer cells, naringenin works by affecting several pathways associated with cell cycle arrest, anti-metastasis, apoptosis, anti-angiogenesis, and DNA repair. It has been shown to alter several molecular targets linked to the development of cancer, such as drug transporters, transcription factors, reactive nitrogen species, reactive oxygen species, cellular kinases, and inflammatory cytokines and regulators of the cell cycle. In summary, this research provides significant insights into the potential of naringenin as a strong and prospective candidate for use in medicines, nutraceuticals, functional foods, and dietary supplements to improve the management of carcinoma.