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Cureus Mar 2024Thyroidectomy technique and extent are related to parathyroid injury and hypoparathyroidism. Total thyroidectomy is one of the most commonly performed endocrine...
INTRODUCTION
Thyroidectomy technique and extent are related to parathyroid injury and hypoparathyroidism. Total thyroidectomy is one of the most commonly performed endocrine surgeries, and the majority of patients recover completely without any complications. However, persistent hypoparathyroidism is the most prevalent long-term consequence following total thyroidectomy. While it is seldom deadly, it can cause severe morbidity for the patient and raise healthcare expenses.
METHODS
This retrospective cohort study was conducted at King Abdulaziz Medical City, Jeddah, Saudi Arabia. We included all confirmed thyroid cancer cases that underwent thyroidectomy with or without neck dissection between July 2016 and August 2022. The data was collected from a chart review of the electronic medical record system (BEST-care), and a data collection sheet was utilized. SPSS version 26 was used to analyze the data.
RESULTS
A total of 192 patients undergoing thyroid surgery were enrolled. One hundred forty-three (74.5%) were females and the mean age of participants was 45.29 ± 16.88 years. Most patients, 170 (88.5%), had a papillary histological type, and total thyroidectomy was performed in 150 (78.1%). A significant association was found between the type of surgery and postoperative hypoparathyroidism (p=<0.05*). In addition, hypocalcemia was seen in 147 (76.6%) of the patients. Postoperative hypoparathyroidism was significantly higher among patients who had asymptomatic postoperative hypocalcemia and those who received IV calcium gluconate (p=<0.05*). Moreover, postoperative hypocalcemia, hypomagnesemia, and hyperphosphatemia were significantly associated with postoperative hypoparathyroidism (p=<0.05*).
CONCLUSION
The incidence of postoperative hypoparathyroidism is significantly higher among patients who underwent total thyroidectomy and had a normal level of preoperative parathyroid hormone (PTH) and magnesium (Mg) levels. Identifying these factors is a crucial step to minimize the occurrence of such complications.
PubMed: 38646308
DOI: 10.7759/cureus.56585 -
Medicine Apr 2024To construct an early clinical prediction model for AVF dysfunction in patients undergoing Maintenance Hemodialysis (MHD) and perform internal and external...
To construct an early clinical prediction model for AVF dysfunction in patients undergoing Maintenance Hemodialysis (MHD) and perform internal and external verifications. We retrospectively examined clinical data from 150 patients diagnosed with MHD at Hefei Third People's Hospital from January 2014 to June 2023. Depending on arteriovenous fistula (AVF) functionality, patients were categorized into dysfunctional (n = 62) and functional (n = 88) cohorts. Using the least absolute shrinkage and selection operator(LASSO) regression model, variables potentially influencing AVF functionality were filtered using selected variables that underwent multifactorial logistic regression analysis. The Nomogram model was constructed using the R software, and the Area Under Curve(AUC) value was calculated. The model's accuracy was appraised through the calibration curve and Hosmer-Lemeshow test, with the model undergoing internal validation using the bootstrap method. There were 11 factors exhibiting differences between the group of patients with AVF dysfunction and the group with normal AVF function, including age, sex, course of renal failure, diabetes, hyperlipidemia, Platelet count (PLT), Calcium (Ca), Phosphorus, D-dimer (D-D), Fibrinogen (Fib), and Anastomotic width. These identified factors are included as candidate predictive variables in the LASSO regression analysis. LASSO regression identified age, sex, diabetes, hyperlipidemia, anastomotic diameter, blood phosphorus, and serum D-D levels as 7 predictive factors. Unconditional binary logistic regression analysis revealed that advanced age (OR = 4.358, 95% CI: 1.454-13.062), diabetes (OR = 4.158, 95% CI: 1.243-13.907), hyperlipidemia (OR = 3.651, 95% CI: 1.066-12.499), D-D (OR = 1.311, 95% CI: 1.063-1.616), and hyperphosphatemia (OR = 4.986, 95% CI: 2.513-9.892) emerged as independent risk factors for AVF dysfunction in MHD patients. The AUC of the predictive model was 0.934 (95% CI: 0.897-0.971). The Hosmer-Lemeshow test showed high consistency between the model's predictive results and actual clinical observations (χ2 = 1.553, P = .092). Internal validation revealed an AUC of 0.911 (95% CI: 0.866-0.956), with the Calibration calibration curve nearing the ideal curve. Advanced age, coexisting diabetes, hyperlipidemia, blood D-D levels, and hyperphosphatemia are independent risk factors for AVF dysfunction in patients undergoing MHD.
Topics: Humans; Hyperphosphatemia; Models, Statistical; Prognosis; Retrospective Studies; Arteriovenous Fistula; Nomograms; Phosphorus; Diabetes Mellitus; Hyperlipidemias
PubMed: 38640314
DOI: 10.1097/MD.0000000000037737 -
TheScientificWorldJournal 2024Acute kidney injury (AKI) is a major medical problem affecting patients' quality of life and healthcare costs.
BACKGROUND
Acute kidney injury (AKI) is a major medical problem affecting patients' quality of life and healthcare costs.
OBJECTIVES
This study evaluated the severity, risk factors, and outcomes of patients diagnosed with acute kidney injury (AKI), including community-acquired AKI (CA-AKI) and hospital-acquired AKI (HA-AKI), who were admitted to tertiary institutions in Palestine.
METHODS
This retrospective cross-sectional study was conducted at multiple tertiary care hospitals in Palestine by reviewing patient charts from January 2020 to March 2023. The study included all patients aged ≥18 years who were admitted to the hospital and diagnosed with AKI at admission (CA-AKI) or who developed AKI 48 hours after admission (HA-AKI). Patients with incomplete medical records and those with no reported creatinine levels during their stay, pregnant women, kidney transplant patients, and end-stage renal disease patients were excluded. Data were analyzed using SPSS v22.0. The incidence of AKI in each group was compared using the chi-squared test.
RESULTS
This study included 259 participants. HA-AKI was present in 27.3% of the patients, while CA-AKI was 72.7%. The most common stage among patients was stage 3 (55.7%, HA-AKI) (42.9%, CA-AKI), and the most common comorbidity contributing to AKI was CKD. NSAIDs, ACE-I/ARBs, and DIURETICs were the most nephrotoxic drugs contributing to AKI. Patients with hyperphosphatemia, hyperkalemia, severe metabolic acidosis, or stage 3 AKI require renal replacement therapy. In addition, our findings revealed a significant association among AKI mortality, age, and heart disease.
CONCLUSION
CA-AKI was more prevalent than HA-AKI in Palestinian patients admitted for AKI. Risk factors for AKI included diabetes, CKD, and medications (antibiotics, NSAID, diuretics, and ACE-I/ARB). Preventive measures, medication management, and disease state management are necessary to minimize AKI during hospital admission or in the community.
Topics: Pregnancy; Humans; Female; Adolescent; Adult; Cross-Sectional Studies; Angiotensin Receptor Antagonists; Retrospective Studies; Arabs; Quality of Life; Angiotensin-Converting Enzyme Inhibitors; Acute Kidney Injury; Risk Factors; Kidney Failure, Chronic; Diuretics
PubMed: 38623388
DOI: 10.1155/2024/8897932 -
Cancer Research Communications Apr 2024Despite efficacy of approved FGFR inhibitors, emergence of polyclonal secondary mutations in the FGFR kinase domain leads to acquired resistance. KIN-3248 is a...
PURPOSE
Despite efficacy of approved FGFR inhibitors, emergence of polyclonal secondary mutations in the FGFR kinase domain leads to acquired resistance. KIN-3248 is a selective, irreversible, orally bioavailable, small-molecule inhibitor of FGFR1-4 that blocks both primary oncogenic and secondary kinase domain resistance FGFR alterations.
EXPERIMENTAL DESIGN
A first-in-human, phase I study of KIN-3248 was conducted in patients with advanced solid tumors harboring FGFR2 and/or FGFR3 gene alterations (NCT05242822). The primary objective was determination of MTD/recommended phase II dose (RP2D). Secondary and exploratory objectives included antitumor activity, pharmacokinetics, pharmacodynamics, and molecular response by circulating tumor DNA (ctDNA) clearance.
RESULTS
Fifty-four patients received doses ranging from 5 to 50 mg orally daily across six cohorts. Intrahepatic cholangiocarcinoma (48.1%), gastric (9.3%), and urothelial (7.4%) were the most common tumors. Tumors harbored FGFR2 (68.5%) or FGFR3 (31.5%) alterations-23 (42.6%) received prior FGFR inhibitors. One dose-limiting toxicity (hypersensitivity) occurred in cohort 1 (5 mg). Treatment-related, adverse events included hyperphosphatemia, diarrhea, and stomatitis. The MTD/RP2D was not established. Exposure was dose proportional and concordant with hyperphosphatemia. Five partial responses were observed; 4 in FGFR inhibitor naïve and 1 in FGFR pretreated patients. Pretreatment ctDNA profiling confirmed FGFR2/3 alterations in 63.3% of cases and clearance at cycle 2 associated with radiographic response.
CONCLUSION
The trial was terminated early for commercial considerations; therefore, RP2D was not established. Preliminary clinical data suggest that KIN-3248 is a safe, oral FGFR1-4 inhibitor with favorable pharmacokinetic parameters, though further dose escalation was required to nominate the MTD/RP2D.
SIGNIFICANCE
KIN-3248 was a rationally designed, next generation selective FGFR inhibitor, that was effective in interfering with both FGFR wild-type and mutant signaling. Clinical data indicate that KIN-3248 is safe with a signal of antitumor activity. Translational science support the mechanism of action in that serum phosphate was proportional with exposure, paired biopsies suggested phospho-ERK inhibition (a downstream target of FGFR2/3), and ctDNA clearance may act as a RECIST response surrogate.
Topics: Humans; Female; Male; Middle Aged; Receptor, Fibroblast Growth Factor, Type 3; Neoplasms; Aged; Receptor, Fibroblast Growth Factor, Type 2; Adult; Protein Kinase Inhibitors; Maximum Tolerated Dose; Mutation; Aged, 80 and over; Antineoplastic Agents; Circulating Tumor DNA
PubMed: 38602417
DOI: 10.1158/2767-9764.CRC-24-0137 -
Cureus Mar 2024Spurious hyperphosphatemia, also known as pseudo-hyperphosphatemia, refers to artifactually elevated serum phosphate values that do not correspond to their actual...
Spurious hyperphosphatemia, also known as pseudo-hyperphosphatemia, refers to artifactually elevated serum phosphate values that do not correspond to their actual systemic levels. Vascular access poses a significant challenge for individuals undergoing hemodialysis (HD) due to chronic kidney disease, primarily attributed to the elevated incidence of complications, such as infections or thrombosis associated with catheter use. To mitigate clotting risk during the inter-dialysis intervals, in recent years, a strategy involving the application of concentrated heparin (recombinant tissue plasminogen activator (rt-PA) e.g. alteplase) has been used. These infusions have a very high content of phosphorus, and if it is not removed sufficiently before collecting blood samples through the central venous catheter, it can cause erroneously high phosphate levels. Here we report two cases of pseudo-hyperphosphatemia caused by contaminated blood samples obtained from an HD catheter from the pediatric nephrology department. Absurd values found in routine samples led us to investigate the reason for these results. Further investigations carried out by the laboratory biochemistry department showed that all the analytical checks and proficiency testing performance were within acceptable limits. We hypothesized that there was a pre-analytical error such as possible contamination with the high phosphate content of heparin and alteplase solution in the catheter, contributing to the increased phosphate levels in these samples.
PubMed: 38590456
DOI: 10.7759/cureus.55818 -
Frontiers in Medicine 2024The purpose of this study was to examine associations of serum phosphate levels with mortality, target organ damage and length of hospital stay in adults with infectious...
OBJECTIVE
The purpose of this study was to examine associations of serum phosphate levels with mortality, target organ damage and length of hospital stay in adults with infectious diseases hospitalized outside of the intensive care unit.
METHODS
This nationwide retrospective cohort study comprised patients admitted with infections, to medical and surgical departments in eight tertiary hospitals during 2001-2020. The main exposure variable was the first serum phosphate levels at admission (up to 1 week). The analysis included multivariable logistic regression models and quantile regression.
RESULTS
Of 126,088 patients (49% males, mean age: 69.3 years), 24,809 (19.7%) had decreased phosphate levels, 92,730 (73.5%) normal phosphate levels, and 8,549 (6.8%) elevated phosphate levels on admission. Overall- and in-hospital mortality rates were highest among those with hyperphosphatemia (74.5 and 16.4%, respectively), followed by those with normophosphatemia (57.0 and 6.6%), and lastly the hypophosphatemia group (48.7 and 5.6%); < 0.001 for all. After adjusting for confounders, the lowest predicted mortality rate was observed in the normophosphatemia group. In the multivariable model, hyperphosphatemia conferred a higher probability of target organ damage (OR [95% CI]: 2.43 [2.06-2.86]), while moderate hypophosphatemia conferred a lower probability (OR [95% CI]: 0.73 [0.65-0.82]), compared to normal phosphate levels and extreme hypophosphatemia showed a non-significant association (OR [95% CI]: 0.87 [0.57-1.28]). The associations were independent of renal failure. In a multivariable model, hyperphosphatemia was associated with a slight increase of 0.33 days in length of stay compared to normal phosphate levels.
CONCLUSION
A J-shaped relation was found between phosphate levels and prognosis in patients hospitalized with infectious diseases, regardless of their renal function.
PubMed: 38590318
DOI: 10.3389/fmed.2024.1362106 -
American Journal of Translational... 2024Serum phosphate levels remain insufficiently controlled in chronic kidney disease (CKD) patients, and novel therapeutic strategies are needed. Blocking intestinal...
BACKGROUND
Serum phosphate levels remain insufficiently controlled in chronic kidney disease (CKD) patients, and novel therapeutic strategies are needed. Blocking intestinal phosphate absorption mediated by sodium-dependent phosphate cotransporter type 2b (NPT2b) holds promise as one such strategy.
METHODS
The in vitro cellular potency of DZ1462 was evaluated using a radioactive Pi uptake assay on stable Chinese hamster ovary (CHO) cell clones transfected with human NPT2b (hNPT2b) or rat NPT2b (rNPT2b). The ability of DZ1462 to inhibit phosphate absorption was studied in vivo in an acute model after oral bolus challenge with PO and in an adenine-induced chronic hyperphosphatemia rat model. PK and minitox was also evaluated.
RESULTS
The cellular assays with the hNPT2b-CHO and rNPT2b-CHO clones showed that DZ1462 significantly and potently inhibited phosphate uptake. In vivo, in a chronic Pi-fed rat model, DZ1462 effectively inhibited intestinal Pi uptake. In a hyperphosphatemia rat model, DZ1462 significantly inhibited Pi uptake, and DZ1462 in combination with sevelamer had a synergistic effect. The pharmacokinetics (PK) study confirmed that DZ1462 is a gastrointestinal (GI)-restricted compound that can remain in the intestine for a sufficient duration. In addition, DZ1462 also reduced cardiovascular events and ameliorated osteoporosis in a CKD animal model.
CONCLUSIONS
This study revealed that a GI-restricted NPT2b inhibitor DZ1462 potently inhibits NPT2b in vitro and blocks intestinal phosphate uptake in multiple animal models with potential to reduce various cardiovascular events in CKD models. Therefore, DZ1462 may be useful to treat renal disease patients who have shown an unsatisfactory response to phosphate binders.
PubMed: 38586086
DOI: 10.62347/UGTW5471 -
Frontiers in Medicine 2024We aimed to investigate the association between serum phosphate levels and the risk for developing sepsis associated acute kidney injury (SAKI).
OBJECTIVE
We aimed to investigate the association between serum phosphate levels and the risk for developing sepsis associated acute kidney injury (SAKI).
METHODS
Septic patients from the Medical Information Mart for Intensive Care IV (MIMIC IV) and the eICU Collaborative Research Database (eICU-CRD) were enrolled. Restricted cubic spline (RCS) was used to visualize the relationship between phosphate levels and the risk of SAKI. Patients were divided into four categories based on their serum phosphate levels. Logistic regression analysis, receiver operating characteristic (ROC) curve and subgroup analysis were performed to evaluate the predictive value of serum phosphate for SAKI.
RESULTS
A total of 9,244 and 2,124 patients from the MIMIC IV and eICU-CRD database were included in the final analysis. RCS curve revealed a non-linear correlation between phosphate levels and the risk of SAKI ( for non-linearity <0.05). Each 1 mg/dL increase in phosphate levels was associated with a 1.51 to 1.64-fold increased risk of SAKI (OR 2.51-2.64, < 0.001) in the MIMIC IV cohort and a 0.29 to 0.38-fold increased risk (OR 1.29-1.38, < 0.001) in the eICU-CRD cohort. Compared to the normal-low category, hyperphosphatemia and normal-high category were independently associated with an increased risk of SAKI, while hypophosphatemia was independently associated with a decreased risk in the MIMIC IV cohort. A similar trend was observed in the eICU-CRD cohort, but statistical significance disappeared in the hypophosphatemia category and the adjusted model of normal high category. These finding was consistent in subgroup analysis.
CONCLUSION
Elevated serum phosphate, even within the normal range, is an independent risk factor for developing SAKI in septic patients. Abnormal change in serum phosphate levels may be a novel biomarker for early prediction of SAKI occurrence.
PubMed: 38585149
DOI: 10.3389/fmed.2024.1367064 -
Cureus Mar 2024Hyperphosphatemia familial tumoral calcinosis (HFTC) and hyperphosphatemia hyperostosis syndrome (HHS) are rare autosomal recessive disorders caused by mutations in the...
Hyperphosphatemia familial tumoral calcinosis (HFTC) and hyperphosphatemia hyperostosis syndrome (HHS) are rare autosomal recessive disorders caused by mutations in the polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3), fibroblast growth factor 23 (FGF23), or klotho (KL) genes. They are characterized by hyperphosphatemia and recurrent episodes of bone lesions with hyperostosis and/or soft tissue calcinosis. Management options include phosphate-lowering therapies, anti-inflammatory medications, and surgical excision of the calcified masses in significantly disabled cases. We describe three cases from a consanguineous family who were found to have the same genetic mutation caused by a homozygous mutation in intron eight of GALNT3 c.1524+1 G>A (IVS8+1). The first case had a presentation similar to chronic osteomyelitis, while the second one presented with a calcified mass in her gluteal area. The third case presented with left leg pain. Being a rare disease, the findings of tumoral calcinosis/ bony abnormalities, along with elevated phosphate levels, should raise the possibility of this entity. Family history and biochemical findings can help reach the diagnosis.
PubMed: 38576700
DOI: 10.7759/cureus.55575 -
Cureus Feb 2024Albright's hereditary osteodystrophy is a rare hereditary disease due to a mutation of the complex guanine nucleotide-binding protein, alpha-stimulating activity...
Albright's hereditary osteodystrophy is a rare hereditary disease due to a mutation of the complex guanine nucleotide-binding protein, alpha-stimulating activity polypeptide. This condition is commonly associated with type 1A and 1C pseudohypoparathyroidism and pseudo-pseudohypoparathyroidism due to resistance of parathyroid hormone. Patients present with specific characteristics such as brachydactyly, short stature, round facies, subcutaneous ossifications, developmental delay, and obesity, associated with hypocalcemia and hyperphosphatemia. This case presents a 55-year-old woman with short stature and neurocognitive impairment, who was admitted to the emergency department with acute decompensated heart and respiratory failure. On admission, hypocalcemia and hyperphosphatemia were noted, which in combination with the patient's clinical history led to an etiological investigation. This case stresses the importance of not only treating the acute disease but also looking at the patient and their clinical and analytical features to diagnose this disease and prevent its complications.
PubMed: 38558694
DOI: 10.7759/cureus.55200