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Periampullary cancer is a malignant tumor occurring around the ampullary region of the liver and pancreas, encompassing a variety of tissue types and sharing numerous biological characteristics, including interactions with the nervous system. The nervous system plays a crucial role in regulating organ development, maintaining physiological equilibrium, and ensuring life process plasticity, a role that is equally pivotal in oncology. Investigations into nerve-tumor interactions have unveiled their key part in controlling cancer progression, inhibiting anti-tumor immune responses, facilitating invasion and metastasis, and triggering neuropathic pain. Despite many mechanisms by which nerve fibers contribute to cancer advancement still being incompletely understood, the growing emphasis on the significance of nerves within the tumor microenvironment in recent years has set the stage for the development of groundbreaking therapies. This includes combining current neuroactive medications with established therapeutic protocols. This review centers on the mechanisms of Periampullary cancer's interactions with nerves, the influence of various types of nerve innervation on cancer evolution, and outlines the horizons for ongoing and forthcoming research.
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OBJECTIVES: This study aimed to provide a universal and reliable reference system quantifying temporomandibular joint (TMJ) morphological and positional changes. METHODS: Large field-of-view (FOV) cone-beam computed tomography (CBCT) images (20 TMJs) from 10 preorthognathic surgery patients and limited FOV CBCT images (40 TMJs) from 20 splint therapy-treated patients with temporomandibular disorders were collected. TMJ-specific reference system including a TMJ horizontal reference plane (TMJHP) and a local coordinate system (TMJCS) was constructed with landmarks on cranial base. Its application for TMJ measurements and its spatial relationship to common Frankfort horizontal plane (FHP) and maxillofacial coordinate system (MFCS) were evaluated. RESULTS: Five relevant landmarks were selected to optimally construct TMJ-specific reference system. General parallelism between TMJHP and FHP was demonstrated by minimal angular and constant distance deviation (1.714â ±â 0.811º; 2.925â ±â 0.817 mm). Additionally, tiny axial orientational deviations (0.181â ±â 6.805º) suggested TMJCS rivaled MFCS. Moreover, small deviations in orientations and distances (1.232â ±â 0.609º; 0.310â ±â 0.202 mm) indicated considerable reliability for TMJCS construction, with intraclass correlation coefficients (ICCs) ranging from 0.999 to 1.000. Lastly, slight discrepancies in translations and rotations revealed high reliability for condylar positional and morphological measurements (ICC, 0.918-0.999). LIMITATIONS: TMJ-specific reference system was merely tested in two representative FOVs. CONCLUSIONS: This study provides a universal and reliable reference system for TMJ assessment that is applicable to both limited and large FOV CBCT. It would improve comparability among diverse studies and enable comprehensive evaluations of TMJ positional and morphological changes during TMJ-related treatment follow-up such as splint therapy and disease progression.
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Cóndilo Mandibular , Trastornos de la Articulación Temporomandibular , Humanos , Cóndilo Mandibular/diagnóstico por imagen , Reproducibilidad de los Resultados , Articulación Temporomandibular/diagnóstico por imagen , Trastornos de la Articulación Temporomandibular/diagnóstico por imagen , Trastornos de la Articulación Temporomandibular/terapia , Tomografía Computarizada de Haz Cónico/métodosRESUMEN
AIMS: Patients undergoing insulin-based therapy for type 1 diabetes often experience poor glycemic control characterized by significant fluctuations. This study was undertaken to analyze the effect of sodium-glucose cotransporter 2 inhibitors (SGLT2Is), as an adjunct to insulin, on time in range (TIR) and glycemic variability in patients with type 1 diabetes, using continuous glucose monitoring (CGM). In addition, we examined which type of SGLT2I yielded a superior effect compared to others. METHODS: We conducted a comprehensive search of PubMed, EMBASE, the Cochrane Library, Web of Science, and clinical trial registry websites, retrieving all eligible randomized clinical trials (RCTs) published up until February 2023. We analyzed the mean TIR, mean amplitude of glucose excursions (MAGE), mean daily glucose (MDG), diabetic ketoacidosis (DKA), standard deviation (SD), total insulin dose, and severe hypoglycemia to evaluate the efficacy and safety of SGLT2Is. A random-effects model was also employed. RESULTS: This study encompassed 15 RCTs. The meta-analysis revealed that the use of SGLT2Is as an adjuvant therapy to insulin led to a significant increase in TIR (MD = 10.78, 95%CI = 9.33-12.23, I2 = 42 %, P < 0.00001) and a decrease in SD (MD = -0.38, 95%CI = -0.50 to -0.26, I2 = 0 %, P < 0.00001), MAGE (MD = -0.92, 95%CI = -1.17 to -0.67, I2 = 19 %, P < 0.00001), MDG(MD = -1.01, 95%CI = -1.32 to -0.70, I2 = 48 %, P < 0.00001), and total insulin dose (MD = -5.81, 95%CI = -7.81 to -3.82, I2 = 32 %, P < 0.00001). No significant increase was observed in the rate of severe hypoglycemia (RR = 1.04, 95 % CI = 0.76-1.43, P = 0.80). However, SGLT2I therapy was associated with increased DKA occurrence (RR = 2.79, 95 % CI = 1.42-5.48; P = 0.003, I2 = 16 %). In addition, the subgroup analyses based on the type of SGLT2Is revealed that dapagliflozin might exhibit greater efficacy compared to other SGLT2Is across most outcomes. CONCLUSIONS: SGLT2Is exhibited a positive effect on improving blood glucose level fluctuations. Subgroup analysis showed that dapagliflozin appeared to have more advantages. However, giving due consideration to preventing adverse effects, particularly DKA, is paramount. REGISTRATION: Prospero CRD42023408276.
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Diabetes Mellitus Tipo 1 , Cetoacidosis Diabética , Hipoglucemia , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Insulina/efectos adversos , Hipoglucemiantes/efectos adversos , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Insulina Regular Humana/uso terapéutico , Cetoacidosis Diabética/inducido químicamente , Cetoacidosis Diabética/epidemiología , Cetoacidosis Diabética/prevención & control , Hipoglucemia/inducido químicamente , Hipoglucemia/epidemiología , Hipoglucemia/prevención & control , Glucosa , Sodio , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Commonly used glucocorticoids replacement regimens in patients with hypopituitarism have difficulty mimicking physiological cortisol rhythms and are usually accompanied by risks of over-treatment, with adverse effects on glucose metabolism. Disorders associated with glucose metabolism are established risk factors of cardiovascular events, one of the life-threatening ramifications. AIM: To investigate the glycometabolism profile in patients with hypopituitarism receiving prednisone (Pred) replacement, and to clarify the impacts of different Pred doses on glycometabolism and consequent adverse cardiovascular outcomes. METHODS: Twenty patients with hypopituitarism receiving Pred replacement [patient group (PG)] and 20 normal controls (NCs) were recruited. A flash glucose monitoring system was used to record continuous glucose levels during the day, which provided information on glucose-target-rate, glucose variability (GV), period glucose level, and hypoglycemia occurrence at certain periods. Islet ß-cell function was also assessed. Based on the administered Pred dose per day, the PG was then regrouped into Pred > 5 mg/d and Pred ≤ 5 mg/d subgroups. Comparative analysis was carried out between the PG and NCs. RESULTS: Significantly altered glucose metabolism profiles were identified in the PG. This includes significant reductions in glucose-target-rate and nocturnal glucose level, along with elevations in GV, hypoglycemia occurrence and postprandial glucose level, when compared with those in NCs. Subgroup analysis indicated more significant glucose metabolism impairment in the Pred > 5 mg/d group, including significantly decreased glucose-target-rate and nocturnal glucose level, along with increased GV, hypoglycemia occurrence, and postprandial glucose level. With regard to islet ß-cell function, PG showed significant difference in homeostasis model assessment (HOMA)-ß compared with that of NCs; a notable difference in HOMA-ß was identified in Pred > 5 mg/d group when compared with those of NCs; as for Pred ≤ 5 mg/d group, significant differences were found in HOMA-ß, and fasting glucose/insulin ratio when compared with NCs. CONCLUSION: Our results demonstrated that Pred replacement disrupted glycometabolic homeostasis in patients with hypopituitarism. A Pred dose of > 5 mg/d seemed to cause more adverse effects on glycometabolism than a dose of ≤ 5 mg/d. Comprehensive and accurate evaluation is necessary to consider a suitable Pred replacement regimen, wherein, flash glucose monitoring system is a kind of promising and reliable assessment device. The present data allows us to thoroughly examine our modern treatment standards, especially in difficult cases such as hormonal replacement mimicking delicate natural cycles, in conditions such as diabetes mellitus that are rapidly growing in worldwide prevalence.
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PURPOSE: Liraglutide, a type of glucagon-like peptide-1 receptor agonist, has significant anti-hyperglycaemic activity without increasing the incidence of hypoglycaemia. In addition, it can improve ß-cell function and insulin resistance. The flash glucose monitoring system (FGMS) is a novel method to document consecutive and detailed interstitial glucose levels, further reflecting blood glucose levels. This study aimed to investigate the therapeutic effect of liraglutide on blood glucose management (glucose variability, hyperglycaemia, and the incidence of hypoglycaemia), ß-cell function, and insulin resistance in patients with diabetes. PATIENTS AND METHODS: Thirty-three patients with type 2 diabetes mellitus were recruited in this study. On the basis of metformin monotherapy, these patients received liraglutide add-on treatment for 3 months. The FGMS was used to document glucose levels before and after add-on treatment. Parameters of glucose variability, blood glucose levels at specific time periods, and the incidence of hypoglycaemia were assessed according to FGMS data and compared before and after liraglutide add-on treatment. Further, ß-cell function and insulin resistance were assessed and compared before and after liraglutide add-on treatment. RESULTS: According to FGMS monitoring data, liraglutide add-on treatment significantly improved general, within-day, and day-to-day glucose variability and the glucose-target-rate. Further, the specifically analysed blood glucose levels at different time periods showed that blood glucose levels significantly decreased at nocturnal, fasting, and postprandial periods after add-on treatment. The incidence of hypoglycaemia was comparable during the whole day, daytime, and night-time according to the prespecified cutoffs (3.9 mmol/L and 3.0 mmol/L) before and after add-on treatment. Analysis of other assessed parameters revealed significant differences in glycosylated hemoglobin A1c and fasting blood glucose levels as well as parameters of ß-cell function and insulin resistance before and after add-on treatment. CONCLUSION: In type 2 diabetes mellitus, liraglutide treatment can effectively decrease glucose variability and ameliorate hyperglycaemia without increasing the incidence of hypoglycaemia. In addition, liraglutide can significantly improve the ß-cell function and insulin resistance.
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Here, we report a case of a patient with symptoms of Cushing syndrome, who is diagnosed with primary generalized glucocorticoid hypersensitivity in the end. The patient's relevant laboratory tests and imaging examinations are described. Mifepristone, a glucocorticoid receptor antagonist, was prescribed and its therapeutic effect on the patient's electrolyte level, lipid metabolism, and bone metabolism was observed during the treatment. The endocrine assessment indicated normal pituitary-adrenal axis regulation function but reduced cortisol secretion. Quantitative reverse transcription-polymerase chain reaction indicated reduced mRNA level of mineralocorticoid receptor gene. Pituitary magnetic resonance imaging showed normal pituitary anatomy, while adrenal computed tomography scan showed bilateral adrenal atrophy and increased content of visceral and abdominal subcutaneous fat. Moreover, chromosome examination revealed a normal 46, XY chromosome. In this case, mifepristone was administered to treat primary generalized glucocorticoid hypersensitivity. To the best of our knowledge, there are a few reports on mifepristone-treated primary generalized glucocorticoid hypersensitivity. In the one-year follow-up visits, the evaluated results of electrolyte level, lipid metabolism, and bone metabolism indicated that the patient's symptoms resulting from cortisol hypersensitivity were relieved progressively.
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BACKGROUND: Multiple studies demonstrate that fluctuating blood glucose level produces greater damage compared with sustained hyperglycemia. Flash glucose monitoring system is an effective method in documenting blood glucose variability, contributing to better glucose management and reduced hypoglycemic event occurrence. AIM: To investigate the improvement in glycemic variability (GV), blood glucose level, and metabolic indexes of patients with type 2 diabetes mellitus after combined treatment of exenatide once weekly (EXQW) and metformin. METHODS: Twenty-five patients with type 2 diabetes mellitus suffering from poor blood glucose control under metformin treatment were recruited. The recruited patients were prescribed with oral metformin only (maintaining a dosage of metformin at ≥ 1500 mg/day) for 2 wk (screening period), and then given EXQW (2 mg, subcutaneous injection) for 12 wk (experimental period). The flash glucose monitoring system was used to document blood glucose values during the screening period and the last 2 wk of the experimental period. RESULTS: Four patients were excluded for various reasons, yielding a total of 21 patients, including 17 males and 4 females, with an average age of 48.8 years, who completed this study. The estimated glycated hemoglobin, mean blood glucose, fasting and postprandial blood glucose levels, and percentage of blood glucose above 7.8 mmol/L decreased compared to those at baseline (P = 0.003, 0.003, 0.008, 0.010, 0.014, 0.017, and 0.005, respectively), while the percentage of blood glucose between 3.9 and 7.8 mmol/L significantly increased (P = 0.005). Parameters of GV including standard deviation of blood glucose, mean amplitude of glycemic excursions, mean of daily difference, area under the curve difference between percentiles 25 and 75, and area under the curve difference between percentiles 10 and 90 were significantly lower compared to that of baseline (P = 0.017, 0.006, 0.000, 0.024, 0.036, respectively). The durations of blood glucose below 3.9 mmol/L during the day and nocturnal periods significantly increased after treatment (P = 0.041 and 0.028, respectively), but there was no significant increase in severe hypoglycemia (< 3.0 mmol/L) compared with that at baseline (P = 0.207). In addition, some metabolic indicators improved after EXQW treatment. CONCLUSION: EXQW combined with metformin can effectively improve blood glucose levels, reduce GV, and improve metabolic indicators. However, there is still a risk of nocturnal hypoglycemia, and careful attention should be paid to patients with EXQW treatment.