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Frontiers in Endocrinology 2023Hypothalamic-pituitary axis dysfunction is a common complication in post-operative craniopharyngioma(CP) patients, and it greatly impacts the long-term quality of life...
OBJECTIVE
Hypothalamic-pituitary axis dysfunction is a common complication in post-operative craniopharyngioma(CP) patients, and it greatly impacts the long-term quality of life of such patients. To better understand the effects of postoperative hypothalamic-pituitary dysfunction and long-term hormone replacement therapy in patients with childhood CP, we assessed approximately 200 patients with childhood-onset CP postoperatively.
METHODS
Clinical details of patients with childhood-onset CP who underwent sellar tumor resection in Beijing Children's Hospital and Beijing Tiantan Hospital from 2018 to 2019 were retrieved retrospectively. The participants were followed up to assess the effects of post-operative long-term hormone replacement therapy and assess the tumor recurrence rate.
RESULTS
The median age of admission was 8.1 (1.8, 14.3) years. Headache (45.5%), visual impairment (39.5%), and nausea (33.0%) were the most common clinical manifestations. ACP accounted for 95% of all CP cases. The incidence of central adrenal insufficiency and central hypothyroidism within the first week after surgery was 56.2% and 70.3%, respectively. At the same time 85.5% of the patients required at least one dose of desmopressin to control urine output. Total survival and tumor recurrence rates were 98.6% and 26.1%, respectively, with a median follow-up time of 29.7 (19.0, 40.3) months. During the follow-up period, 28.1% patients met the diagnostic criteria for short stature, while 54.4% fit the criteria for obesity. In addition, 94.4% of the patients were taking at least one kind of hormone substitution, and 74.7% were taking three or more. The prevalence of levothyroxine, glucocorticoid, desmopressin, and growth hormone replacement therapy was 87.3%, 77.5%, 78.9% and 31.0%, respectively. The proportion of patients treated with the substitutive combination of levothyroxine, hydrocortisone, and desmopressin was 54.9%.
CONCLUSION
This study is a large-sample systematic postoperative endocrine function evaluation of patients with childhood-onset CP. Due to the high prevalence of post-operative hypothalamic-pituitary dysfunction, patients with CP usually require long-term multiple hormone substitution therapy. Individualized management and accurate hormone replacement dosage for postoperative childhood-onset CP patients are of great importance.
Topics: Humans; Child; Craniopharyngioma; Retrospective Studies; Thyroxine; Quality of Life; Deamino Arginine Vasopressin; Neoplasm Recurrence, Local; Pituitary Neoplasms; Hypothalamic Diseases; Pituitary Diseases; Hormone Replacement Therapy; Hydrocortisone
PubMed: 38027203
DOI: 10.3389/fendo.2023.1241145 -
World Journal of Oncology Dec 2023Colorectal cancer (CRC) is a leading cause of cancer-associated mortality worldwide. Despite being an essential component of systemic chemotherapy for advanced CRC,...
BACKGROUND
Colorectal cancer (CRC) is a leading cause of cancer-associated mortality worldwide. Despite being an essential component of systemic chemotherapy for advanced CRC, 5-fluorouracil (5-FU) clinical use has severe limitations, such as high toxicity, low selectivity and drug resistance. [VQ]dDAVP (1-deamino-4-valine-5-glutamine-8-D-arginine vasopressin) is a peptide vasopressin analog and a selective agonist of the arginine vasopressin type 2 membrane receptor (AVPR2), expressed in microvascular and tumor tissue. This synthetic compound has well-proven antitumor and antimetastatic activity in different tumor types, including metastatic CRC. The objective of this work was to assess the potential combinational benefits in preclinical CRC models after [VQ]dDAVP addition to 5-FU.
METHODS
Effects on cellular viability, cell cycle progression, apoptosis and molecular mechanisms associated to [VQ]dDAVP treatment in combination with 5-FU were evaluated in murine CT-26 and human COLO-205 cell lines. , impact of dual therapy was explored on CRC tumor growth and metastatic spread.
RESULTS
In CRC cells, [VQ]dDAVP (1 µM) addition to sub-IC 5-FU concentrations resulted in the enhancement of cytostatic effects induced by chemotherapy. Reduction of cell viability after combined treatment was associated with cell cycle arrest in the G/G phase, induction of apoptosis and increased gene expression of the cyclin-dependent kinase inhibitor p21 (CDKN1A) and the tumor suppressor p53 (TP53) in malignant cells, as assessed by flow cytometry, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL), and quantitative reverse transcription polymerase chain reaction (qRT-PCR), respectively. , intravenous administration of [VQ]dDAVP (0.3 µg/kg) in combination with safe low doses of 5-FU (50 or 80 mg/kg for CT-26 or COLO-205 tumor models, respectively) effectively abrogated CRC growth, reducing aggressiveness of primary lesions and increasing survival of tumor-bearing mice. In addition, concomitant administration of [VQ]dDAVP and 5-FU inhibited pulmonary metastasis formation by CT-26 cells in immunocompetent mice, especially reducing macrometastatic disease.
CONCLUSIONS
[VQ]dDAVP seems to enhance the efficacy of 5-FU-based chemotherapy in CRC by modulating tumor progression, as well as metastatic dissemination, suggesting its potential role as a safe and cost-effective co-adjuvant agent for the management of advanced CRC.
PubMed: 38022396
DOI: 10.14740/wjon1715 -
Cureus Oct 2023Anesthesia for awake neurosurgery requires meticulous planning. We report the case of a 44-year-old female with glioblastoma undergoing an awake craniotomy. Due to her...
Anesthesia for awake neurosurgery requires meticulous planning. We report the case of a 44-year-old female with glioblastoma undergoing an awake craniotomy. Due to her asthma and von Willebrand disease, an opioid-free approach was chosen. Conscious sedation was attained using propofol and dexmedetomidine. The operation was successful after nine hours with patient comfort maintained. The patient was discharged from the intensive care unit in two days without sequelae. However, the use of desmopressin caused hyponatremia and cerebral edema. The scalp block was effective for pain management. This case highlights the importance of individualized anesthetic strategies in awake neurosurgeries.
PubMed: 38022194
DOI: 10.7759/cureus.47103 -
International Journal of Molecular... Nov 2023A murine osmotic demyelinating syndrome (ODS) model was developed through chronic hyponatremia, induced by desmopressin subcutaneous implants, followed by precipitous...
Thalamic Neuron Resilience during Osmotic Demyelination Syndrome (ODS) Is Revealed by Primary Cilium Outgrowth and ADP-ribosylation factor-like protein 13B Labeling in Axon Initial Segment.
A murine osmotic demyelinating syndrome (ODS) model was developed through chronic hyponatremia, induced by desmopressin subcutaneous implants, followed by precipitous sodium restoration. The thalamic ventral posterolateral (VPL) and ventral posteromedial (VPM) relay nuclei were the most demyelinated regions where neuroglial damage could be evidenced without immune response. This report showed that following chronic hyponatremia, 12 h and 48 h time lapses after rebalancing osmolarity, amid the ODS-degraded outskirts, some resilient neuronal cell bodies built up primary cilium and axon hillock regions that extended into axon initial segments (AIS) where ADP-ribosylation factor-like protein 13B (ARL13B)-immunolabeled rod-like shape content was revealed. These AIS-labeled shaft lengths appeared proportional with the distance of neuronal cell bodies away from the ODS damaged epicenter and time lapses after correction of hyponatremia. Fine structure examination verified these neuron abundant transcriptions and translation regions marked by the ARL13B labeling associated with cell neurotubules and their complex cytoskeletal macromolecular architecture. This necessitated energetic transport to organize and restore those AIS away from the damaged ODS core demyelinated zone in the murine model. These labeled structures could substantiate how thalamic neuron resilience occurred as possible steps of a healing course out of ODS.
Topics: Animals; Mice; Hyponatremia; Axon Initial Segment; ADP-Ribosylation Factors; Cilia; Neurons; Demyelinating Diseases
PubMed: 38003639
DOI: 10.3390/ijms242216448 -
Medicine Nov 2023There is a relative wealth of experience in the initial treatment of IgG4-related disease (IgG4-RD), but little is known about therapeutic measures for recurrent cases... (Review)
Review
RATIONALE
There is a relative wealth of experience in the initial treatment of IgG4-related disease (IgG4-RD), but little is known about therapeutic measures for recurrent cases combined with multiple organ and tissue involvement.
PATIENT CONCERNS
A 43-year-old man with a previous diagnosis of IgG4-RD due to recurrent right lacrimal gland enlargement with eyelid erythema presented with diabetes insipidus.
DIAGNOSES
We performed a pituitary Magnetic Resonance Imaging which revealed posterior pituitary rim changes with inhomogeneous enhancement and nodular-like thickening of the pituitary stalk, and performed a water-deprivation-vasopressin test confirmed central diabetes insipidus, and in combination with the patient's elevated IgG4 levels and past medical conditions, we diagnosed central diabetes insipidus, IgG4-related hypophysitis, and IgG4-RD.
INTERVENTIONS
After the patient was admitted to the hospital we gave methylprednisolone 500 mg intravenously once daily for 4 days and again for 4 consecutive days after a 10-day interval. During this period combined with mycophenolate mofetil 250 mg twice daily and desmopressin acetate 0.1 mg 3 times daily.
OUTCOMES
The patient was followed up for a sustained period of 6 months and no side effects of glucocorticoid therapy were noted, there were no signs of recurrence, and the daily urine output stabilized in the normal range.
LESSONS
We recognized that IgG4 levels do not reflect relapse or long-term control, and that glucocorticoid shock therapy is an optional and reliable treatment strategy for relapsed patients.
Topics: Male; Humans; Adult; Glucocorticoids; Diabetes Insipidus, Neurogenic; Immunoglobulin G4-Related Disease; Diabetes Insipidus; Immunoglobulin G; Diabetes Mellitus
PubMed: 37986296
DOI: 10.1097/MD.0000000000036129 -
Journal of Pediatric Urology Apr 2024The voiding chart is part of the initial evaluation of enuresis, since the data gathered this way are assumed to carry predictive information. However, there is little...
BACKGROUND
The voiding chart is part of the initial evaluation of enuresis, since the data gathered this way are assumed to carry predictive information. However, there is little evidence that the voiding chart actually does predict therapy response. Lundmark & Nevéus performed a pilot investigation in 2020 and found that anamnestic and voiding chart data did not predict response to second-line therapies. This study aims at evaluating whether these findings could be replicated.
PATIENTS AND METHODS
This is an evaluation of clinical practice. All patients in a tertiary outpatient clinic with enuresis resistant to first-line therapy (i.e. the enuresis alarm and desmopressin medication) during the evaluation period were included in the study. Baseline anamnestic data focused on bladder and bowel habits, were gathered and the families were instructed to complete a voiding chart including measurements of nocturnal urine production. The children were then treated in accordance with international guidelines, which are anticholinergics and antidepressants as second- and third-line treatment, respectively. Desmopressin was added if needed.
RESULTS
In total, 70 patients were included. At the end of the study 37 of these patients were dry, 11 patients were still wetting their beds and 22 patients were lost to follow-up. Of the dry patients 21 became dry on anticholinergics (and/or mirabegron, with or without desmopressin), five on tricyclic antidepressants (with or without desmopressin), seven after a new attempt with the alarm and five became dry spontaneously. The only statistically significant differences between responders and non-responders to the various treatments were that children responsive to anticholinergics had harder and more infrequent stools (p = 0.04 and p = 0.03, respectively).
CONCLUSION
This study found that anamnestic and voiding chart data do not predict response to treatment in children with therapy-resistant enuresis. Because of this and the fact that we lose some children who need our help by demanding that they complete a voiding chart before initiating treatment, we question the use of this instrument in the evaluation of therapy-resistant enuresis.
Topics: Child; Humans; Deamino Arginine Vasopressin; Enuresis; Nocturnal Enuresis; Urinary Bladder; Cholinergic Antagonists
PubMed: 37977907
DOI: 10.1016/j.jpurol.2023.10.036 -
Blood Advances Dec 2023Innovation in therapies for patients with von Willebrand disease (VWD) has lagged far behind that for hemophilia, creating inequity in the bleeding disorder community....
Innovation in therapies for patients with von Willebrand disease (VWD) has lagged far behind that for hemophilia, creating inequity in the bleeding disorder community. Although currently existing treatments of antifibrinolytics, desmopressin, and plasma-derived von Willebrand factor replacement are considered effective, multiple studies report poor quality of life in patients with VWD, especially those with heavy menstrual bleeding (HMB). This disconnect underscores the need for novel therapies that are safe and effective and that consider a patient's specific contraceptive and reproductive needs. Recombinant von Willebrand factor is the most recent new therapy for VWD; the data specific to women are reviewed. We also present emerging data on emicizumab for the treatment of VWD, BT200 (rondoraptivon pegol), generalized hemostatic therapies (VGA039 and HMB-011), as well as treatments based on nanotechnology (platelet-inspired nanoparticles and KB-V13A12). We are optimistic as we move toward pivotal clinical trials for these elegant and innovative treatments.
Topics: Humans; Female; von Willebrand Diseases; von Willebrand Factor; Quality of Life; Menorrhagia; Antifibrinolytic Agents
PubMed: 37967378
DOI: 10.1182/bloodadvances.2023010716 -
Laboratory Animal Research Nov 2023Diarrhea is the increase of excretion of human water content and an imbalance in the physiologic processes of the small and large intestine while shikimic acid is an...
BACKGROUND
Diarrhea is the increase of excretion of human water content and an imbalance in the physiologic processes of the small and large intestine while shikimic acid is an important biochemical metabolite in plants. This study aims to study the anti-diarrheal activity of shikimic acid through restoring kidney function, antioxidant activity, inflammatory markers, sodium/potassium-ATPase activity, apoptosis genes, and histology of the kidney in SD rats fed lactose diet to induce diarrhea.
RESULTS
Thirty-six male SD rats (150 ± 10 g, 12 weeks old) were divided into 2 equal groups (18 rats/group) as follows: normal and diarrheal rats. Normal rats were divided into 3 equal groups of 6 rats each: the control, shikimic acid, and desmopressin drug groups. Diarrheal rats were also divided into 3 equal groups of 6 rats each: diarrheal, diarrheal rats + shikimic acid, and diarrheal rats + desmopressin drug groups. Shikimic acid restored serum urea and creatinine, urinary volume, kidney weight, sodium, potassium, and chloride balance in serum and urine. The acid returned the antioxidant (superoxide dismutase, glutathione peroxidase, catalase, malondialdehyde, NADPH oxidase activity, conjugated dienes, and oxidative index) activity and the inflammatory markers (tumor necrosis factor-α, interleukin-1β, interleukin-6, and interleukin-10) to values approaching the control values. Shikimic acid also restored the sodium/potassium-ATPase activity, the apoptosis genes p53 and bcl-2, and the histology of kidney tissue in diarrheal rats to be near the control group.
CONCLUSIONS
Shikimic acid rescues diarrhea and its complications through restoring kidney function, serum and urinary electrolytes, antioxidant activity, inflammatory markers, sodium/potassium-ATPase activity, the apoptosis genes, and the histology of the kidney in diarrheal rats to approach the control one.
PubMed: 37950334
DOI: 10.1186/s42826-023-00179-y -
Frontiers in Pediatrics 2023The desmopressin combined with anticholinergic agents for the treatment of nocturnal enuresis (NE) remains controversial. This meta-analysis assesses the efficacy and... (Review)
Review
BACKGROUND
The desmopressin combined with anticholinergic agents for the treatment of nocturnal enuresis (NE) remains controversial. This meta-analysis assesses the efficacy and safety of desmopressin compared with desmopressin plus anticholinergic agents for the treatment of NE.
METHODS
We searched MEDLINE, Embase, and Cochrane Controlled Trials Register databases for RCTs published for the treatment of NE. Systematic review was carried out using the Preferred Reporting Items for Systematic Reviews and Meta-analyses. This meta-analysis used RevMan v.5.1.0 to analyze data.
RESULTS
Eight studies involving 600 patients (293 in the combination group and 307 in the desmopressin group) contained meaningful data. The results were as follows: after one month of treatment, compared with the desmopressin monotherapy group, the combination group was significantly better in treating NE in FR (full responders, = 0.003), FR + PR (partial responders) ( < 0.0001), and the mean number of wet nights ( = 0.004); also, the combination group had a better effect in FR ( < 0.00001), FR + PR ( = 0.02) and the mean number of wet nights ( = 0.04) after 3 months' treatment. For side effects, combination therapy does not cause more adverse events in treating NE ( = 0.42).
CONCLUSIONS
This study elucidates that desmopressin combined with the anticholinergic agent was demonstrated to be more effective in treating NE than desmopressin monotherapy, and the anticholinergic agent does not increase the risk of adverse events (AEs).
PubMed: 37928358
DOI: 10.3389/fped.2023.1242777 -
JCEM Case Reports Mar 2023Lymphocytic infundibulo-neurohypophysitis (LINH) is a rare autoimmune inflammatory process that selectively affects the neurohypophysis and the pituitary stalk,...
Lymphocytic infundibulo-neurohypophysitis (LINH) is a rare autoimmune inflammatory process that selectively affects the neurohypophysis and the pituitary stalk, typically presenting with central diabetes insipidus (CDI). LINH is considered underdiagnosed because the definitive diagnosis requires invasive pituitary surgery with a high risk of complications. We present a case of CDI resulting from LINH, which was treated with conservative management, eschewing both glucocorticoid treatment and pituitary surgery. At presentation, the hormonal assessment indicated the presence of CDI without anterior pituitary dysfunction. Magnetic resonance imaging revealed stalk thickening without a posterior pituitary bright spot, and anti-rabphilin-3A antibodies were positive in serum. Collectively, we made a diagnosis of LINH. Considering that the patient did not exhibit any symptoms of mass effect, we chose conservative treatment with desmopressin acetate. One year later, the stalk thickening regressed spontaneously without surgical or glucocorticoid treatment, although the posterior pituitary bright spot remained absent, and CDI did not improve. The inflammatory process of LINH is mostly self-limited and recovers spontaneously, whereas life-long desmopressin treatment may be required because of pituitary stalk fibrosis and atrophy. Our case highlights the importance of noninvasive diagnosis and careful follow-up in preventing unnecessary interventions for patients with LINH.
PubMed: 37908468
DOI: 10.1210/jcemcr/luad020