Background Hypophosphatemia, defined as a serum phosphate level less than 2.5 mg/dL, is a frequent finding in patients with chronic obstructive pulmonary disease (COPD) and has been speculated to negatively affect weaning outcomes. This study aimed to determine the incidence of hypophosphatemia in COPD patients requiring mechanical ventilation and evaluate the predictive role of hypophosphatemia as an indicator of successful weaning from mechanical ventilation in such patients admitted to the intensive care unit (ICU) in a tertiary care hospital in eastern India. Methodology This prospective observational study included 60 adult patients aged 18 to 75 years with acute exacerbations of COPD on mechanical ventilation in the ICU who were planned to undergo a weaning trial. Serum phosphate levels were assessed at the time of admission and before each weaning attempt. Weaning outcomes at each attempt, length of ventilator and ICU stay, and mortality were recorded. Data collection was initiated after approval of the Institutional Ethics Committee. Receiver operating curve (ROC) analysis was done to identify the cut-off value of serum phosphate which predicted successful weaning. Results Of 60 participants, hypophosphatemia on admission was present in 15 (25%) patients. Despite the correction, 13 (21.7%) patients had hypophosphatemia before the first weaning attempt. Only 22 patients out of 60 were successfully weaned off from mechanical ventilation in the first trial, accounting for a success rate of 36.7%, of whom 20 were normophosphatemic (90.9%). In the second and third weaning trials, hypophosphatemia was significantly associated with weaning failure. Overall differences in mean serum phosphate levels among those who failed to wean in each weaning trial and the successful attempt were statistically significant (p < 0.001). On ROC analysis of serum phosphate level before the first weaning trial, a cut-off value of ≥3.0 mg/dL was identified to have 86.4% sensitivity, 55.3% specificity, 52.8% positive predictive value, 87.5% negative predictive value, and 66.7% diagnostic accuracy in predicting weaning success. Five patients died, accounting for a mortality rate of 8.3%. Lower mean serum phosphate levels before the first weaning trial, higher mean age, and longer ventilator and ICU days were significantly associated with mortality among our study participants (p < 0.05). Conclusions Our findings suggest that maintaining normal serum phosphate levels is critical to successfully weaning off patients with COPD from ventilator support.

UNASSIGNED: This study explores tumor-induced osteomalacia (TIO) through a case series and literature review, assessing the diagnostic potential of 18F-AlF-NOTA-octreotide (18F-OC) positron emission tomography/computed tomography (PET/CT).
UNASSIGNED: We analyzed TIO patients who underwent 18F-OC PET/CT. Parameters such as tumor dimension, the maximum standardized uptake value (SUVmax), the mean standardized uptake value (SUVmean) and metabolic tumor volume (MTV) were meticulously assessed. Clinical features and imaging characteristics pertinent to TIO were reviewed.
UNASSIGNED: 6 patients with clinical suspicion of TIO exhibited hypophosphatemia (0.25 to 0.64 mmol/L), elevated alkaline phosphatase (ALP) levels (142 to 506 U/L), and increased parathyroid hormone (PTH) levels (92.9 to 281.7 pg/mL). Of these patients, two underwent FGF-23 testing, with results of 3185.00 pg/ml and 17.56 pg/ml, respectively. Conventional imaging modalities depicted widespread osteoporosis, with several cases demonstrating fractures indicative of osteomalacic and associated pathological fractures. Subsequent 18F-OC PET/CT facilitated the accurate localization of causative tumors, with histopathological examination confirming the diagnosis of phosphaturic mesenchymal tumor (PMT). The interval from initial clinical presentation to definitive TIO diagnosis spanned approximately 2.5 years (range: 1 - 4 years), with tumors varying in size (maximum diameter: 7.8 to 40.0 mm), SUVmax (5.47 to 25.69), SUVmean (3.43 to 7.26), and MTV (1.27 to 18.59 cm3).
UNASSIGNED: The implementation of whole-body 18F-OC PET/CT imaging emerges as a critical tool in the identification of occult tumors causing TIO. Future investigations incorporating a broader cohort are imperative to further delineate the diagnostic and therapeutic implications of 18F-OC PET/CT in managing TIO.

Ventricular septal defects (VSDs) are recognized as one of the commonest congenital heart diseases (CHD), accounting for up to 40% of all cardiac malformations, and occur as isolated CHDs as well as together with other cardiac and extracardiac congenital malformations in individual patients and families. The genetic etiology of VSD is complex and extraordinarily heterogeneous. Chromosomal abnormalities such as aneuploidy and structural variations as well as rare point mutations in various genes have been reported to be associated with this cardiac defect. This includes both well-defined syndromes with known genetic cause (e.g., DiGeorge syndrome and Holt-Oram syndrome) and so far undefined syndromic forms characterized by unspecific symptoms. Mutations in genes encoding cardiac transcription factors (e.g., NKX2-5 and GATA4) and signaling molecules (e.g., CFC1) have been most frequently found in VSD cases. Moreover, new high-resolution methods such as comparative genomic hybridization enabled the discovery of a high number of different copy number variations, leading to gain or loss of chromosomal regions often containing multiple genes, in patients with VSD. In this chapter, we will describe the broad genetic heterogeneity observed in VSD patients considering recent advances in this field.

BACKGROUND: Phosphorus is a vital mineral crucial for various physiological functions. Critically ill trauma patients frequently experience hypophosphatemia during the immediate post-traumatic phase, potentially impacting outcomes. This study aims to investigate the incidence of early hypophosphatemia in critically major trauma patients.
METHODS: In this prospective observational study, trauma patients admitted to the intensive care unit (ICU) within one day were enrolled. These patients were categorized into Hypo-P groups and Non-hypo groups based on the development of new-onset hypophosphatemia within 72 h after feeding. The primary outcome assessed was the incidence of new-onset hypophosphatemia. The secondary outcomes included ICU and hospital stay, ventilation duration, and mortality.
RESULTS: 76.1% of patients developed a new onset of hypophosphatemia within 72 h after feeding. The Hypo-P group had significantly longer ICU stays (8.1 days ± 5.5 vs. 4.4 days ± 3.1; p = 0.0251) and trends towards extended hospital stay, ventilation duration, and higher mortality. Additionally, they demonstrated significantly higher urine fractional excretion of phosphate (FEPO4) on the first ICU day (29.2% ± 14.23 vs. 19.5% ± 8.39; p = 0.0242).
CONCLUSIONS: Critically ill trauma patients exhibited a significantly higher incidence of early hypophosphatemia than typical ICU rates, indicating their heightened vulnerability. The significantly high urine FEPO4 underscores the crucial role of renal loss in disrupting phosphate metabolism in this early acute phase after trauma. A significant correlation was observed between hypophosphatemia and longer ICU stays. Monitoring and managing phosphate levels may influence outcomes, warranting further investigation.

Phosphate is essential for numerous biological processes, and serum levels are tightly regulated to accomplish these functions. The regulation of serum phosphate in a narrow physiological range is a well-orchestrated process and involves the gastrointestinal (GI) tract, bone, kidneys, and several hormones, namely, parathyroid hormone, fibroblast growth factor 23 (FGF23), and 1,25-dihydroxyvitamin D (1,25 Vitamin D). Although primarily synthesized in the bone, FGF23, an endocrine FGF, acts on the kidney to regulate phosphate and Vitamin D homeostasis by causing phosphaturia and reduced levels of 1,25 Vitamin D. Recent studies have highlighted the complex regulation of FGF23 including transcriptional and post-translational modification and kidney-bone cross talk. Understanding FGF23 biology has led to the identification of novel therapeutic agents to treat diseases that disrupt phosphate metabolism secondary to FGF23. The focus of this review is to provide an overview of phosphate homeostasis, FGF23 biology, and the role of FGF23 in phosphate balance.

BACKGROUND: Refeeding syndrome (RFS) is a life-threatening metabolic derangement occurring when nutrition is reintroduced after prolonged starvation. Limited data exist regarding RFS prevalence, risk factors, and outcome, particularly in critically ill patients.
METHODS: A retrospective cohort study was conducted in a medical intensive care unit from June 2018 to August 2020. RFS diagnostic criteria from the National Institute for Health and Care Excellence (NICE) and the American Society for Parenteral and Enteral Nutrition (ASPEN) were used. The primary outcome was 30-day mortality.
RESULTS: Among 216 patients, RFS was diagnosed in 22.7% and 27.3% of patients per the NICE and ASPEN criteria, respectively. There was no significant difference in 30-day mortality between patients with and without RFS (22/59 [37.3%] vs 53/157 [33.8%]; P = 0.627). Independent predictors of RFS were malignancy (odds ratio [OR] = 2.09; 95% CI = 1.06-4.15; P = 0.035), septic shock (OR = 2.26; 95% CI = 1.17-4.39; P = 0.016), and high NICE RFS risk classification (OR = 2.52; 95% CI = 1.20-5.31; P = 0.015). Factors associated with reduced RFS risk were Sequential Organ Failure Assessment (SOFA) scores >12 (OR = 0.45; 95% CI = 0.23-0.88; P = 0.020) and high-dose vasopressor treatment (OR = 0.34; 95% CI = 0.14-0.79; P = 0.012).
CONCLUSIONS: RFS affected one-fourth of the critically ill patients but did not significantly impact 30-day mortality. Malignancy, septic shock, and high NICE RFS risk classification were positively associated with RFS, whereas high SOFA scores and extensive vasopressor use were linked to decreased risk.

The increasing prevalence of cannabis worldwide requires awareness of a potential, less recognized, paradoxical entity, the cannabinoid hyperemesis syndrome (CHS). This includes cyclic episodes of nausea, vomiting, and compulsive hot water bathing for alleviation in individuals with chronic cannabis use. An 18-year-old male with daily and prolonged cannabis use has excessive nausea and vomiting, is diagnosed with CHS, and is further complicated by severe and rapidly fluctuating hypophosphatemia. He was successfully managed with intravenous (IV) antiemetic (metoclopramide) and IV normal saline in the emergency department. Hypophosphatemia was treated with IV phosphorous. Although hypophosphatemia in CHS is a rare encounter, the authors share their experience to promote broader recognition and insight into successful management.

BACKGROUND: X-linked hypophosphatemia (XLH) represents the most prevalent cause of hereditary hypophosphatemia. X-linked hypophosphatemia causes an elevation of fibroblast growth factor 23 (FGF23), a hormone responsible for inducing hyperphosphaturia, and reduced active vitamin D synthesis. Challenges in diagnosis and the absence of well-defined clinical guidelines have resulted in higher rates of late diagnoses. While numerous reports focus on pediatric X-linked hypophosphatemia patients, studies in adults are limited.
METHODS: Multicenter, cross-sectional, observational study of a cohort of adult patients diagnosed with X-linked hypophosphatemia. The study identified demographic, clinical, genetic, laboratory variables, treatments used, comorbidities, and complications.
RESULTS: Twenty patients diagnosed with X-linked hypophosphatemia were collected. The median age at diagnosis was 11 (1-56) years and at data collection was 44 (21-68) years. Fifty percent of cases were diagnosed in adulthood. Main clinical manifestation was osteoarticular pain, in 75% of cases, and no relation to age at diagnosis, height, phosphorus, or parathyroid hormone (PTH) levels was observed (p > 0.05). Lower limb deformities were associated with reduced stature and earlier diagnosis (p < 0.05). Sixty percent of patients reported pain requiring chronic medication and no significant correlation was found with other variables. Anxiety and depression were found in an important number of patients. FGF23 levels were not related to any of the clinical variables studied (p > 0.05).
CONCLUSIONS: This is the largest study on adult patients with X-linked hypophosphatemia in southern Europe. It may offer valuable insights into the natural progression and course of the condition in adults, which can aid in better clinical management.

Tumor-induced osteomalacia (TIO) is an exceedingly rare paraneoplastic condition characterized by hypophosphatemia, osteomalacia, fragility fractures, and fatigue. A 39-year-old man was assessed for hemoptysis, pathological rib fractures, and fatigue, and was found to have a chest mass with lung metastasis. Biopsy of the mass suggested high-grade epithelioid and spindle cell neoplasm. He was initially treated for soft tissue sarcoma with an ifosfamide-based regimen and developed Fanconi syndrome that resolved on cessation of ifosfamide. Serum phosphate remained low. A low tubular maximum reabsorption of phosphate to glomerular filtration rate ratio (TmP/GFR) indicated disproportionate phosphaturia, while a severely elevated fibroblast growth factor-23 (FGF23) level enabled a diagnosis of TIO. He was started on phosphate and calcitriol supplementation. Subsequent next-generation sequencing demonstrated a RET-fusion mutation, leading to reclassification of his malignancy to a sarcomatoid non-small cell lung carcinoma. He was switched to selpercatinib, a targeted RET-kinase inhibitor approved for locally advanced or metastatic RET-fusion-positive solid tumors. This induced tumor remission with subsequent normalization of his FGF23 levels and hypophosphatemia. Despite the presence of a confounding etiology like drug-induced Fanconi syndrome, persistence of hypophosphatemia should prompt a workup of TIO, especially in the presence of a tumor.

Diabetic ketoacidosis (DKA) is one of the most serious complications of type 1 diabetes mellitus. Its treatment requires fluid and electrolyte replacement and insulin. Hypophosphatemia as a complication of treatment has been scarcely evaluated.
OBJECTIVE: To estimate the incidence of hypophosphatemia in children with DKA, treated with subcutaneous regular insulin (IRS), and to explore factors associated with this complication.
METHODS: Prospective, observational study. Patients diagnosed with DKA hospitalized in the general care ward were included. Data on phosphatemia, glycemia, acid-base status, and IRS amount (U/kg) received were recorded at baseline and after 24 h of treatment. Hypophosphatemia was defined as values below 2.5 mg/dl. The correlation between initial phosphate and at 24 h of treatment was evaluated; the incidence of hypophosphatemia at 24 h was expressed as a percentage of the total number of patients.
RESULTS: 30 patients were included, 15 were female, mean age 11.4 ± 3.2 years. At 24 h of treatment with IRS, 36.7% (95%CI 22-55%) presented hypophosphatemia, mean value 1.9 ± 1.5 mg/dl. Initial bicarbonate < 10 mmol/L acted as a predictor of hypophosphatemia (OR 7.5; 95%CI 1.4-39.8%; p = 0.01). No patient required intravenous phosphate correction, and no associated clinical complications were observed.
CONCLUSIONS: In the group studied, the incidence of hypophosphatemia reached 36.7% at 24 hours of treatment. Initial bicarbonate lower than 10 mmol/L was significantly associated with hypophosphatemia. No complications associated with hypophosphatemia were observed.