Toxicity and Tolerability of 177Lu-DOTA-TATE PRRT with a Modified Administered Activity Protocol in NETs of Variable Origin – A Phase 2 Registry Study

Background: Peptide receptor radionuclide therapy (PRRT) has been recently approved for advanced, metastatic, or progressive neuroendocrine tumors (NETs). Objectives: This study reports the adverse events (AEs) observed with patient-tailored administered activity. Methods: Fifty-two PRRT naive patients were treated with 177Lu-DOTATATE. The administered activity ranges between 2.78 and 5.55 GBq/cycle using the patient's unique characteristics (age, symptoms, blood work, and biomarkers). Results: The protocol was well tolerated with the overwhelming majority of participants being forty-six (88%), completing all 4 induction therapy cycles. The median cumulative administered activity was 19.6 GBq (ranged 3.8-22.3 GBq). A total of 42/52 (81%) reported at least one symptom, and 43/52 (83%) had evidence of biochemical abnormality at enrollment that would meet grade 1 or 2 criteria for AEs. These symptoms only slightly increase with treatment to 50/52 (96%) and 51/52 (98%), respectively. The most common symptoms were mild fatigue (62%), shortness of breath (50%), nausea (44%), abdominal pain (38%), and musculoskeletal pain (37%). The most common biomarker abnormalities were mild anemia (81%), reduced estimated glomerular filtration rate (eGFR) (58%), increased alkaline phosphatase (ALP) (50%), and leukopenia (37%). Of critical importance, no 177Lu-DOTATATE related grade 3 or 4 AEs were observed. Conclusion: Tailoring the administered activity of 177Lu-DOTATATE to the individual patient with a variety of NETs is both safe and well-tolerated. No patient developed severe grade 3 or 4 AEs. Most patients exhibit symptoms or biochemical abnormality before treatment and this only slightly worsens following induction therapy.

Isolated hypophosphataemia as an early marker of primary hyperparathyroidism

Summary Primary hyperparathyroidism (PHPT) is a disease caused by overactive parathyroid glands with consequent hypercalcaemia. The main cause in 85–90% of the cases is the presence of a solitary parathyroid adenoma. The most common presentation is with asymptomatic hypercalcaemia diagnosed on routine biochemical testing. Although low serum phosphate levels are an associated finding in primary hyperparathyroidism, the diagnostic criteria for PHPT remain to be hypercalcaemia, high or inappropriately normal PTH and hypercalciuria. This case report presents a patient who presented with low phosphate levels without any other biochemical evidence of PHPT, who returned several years later with overt primary hyperparathyroidism. This report intends to raise interest among the medical fraternity whether there is a need to consider hypophosphataemia as an early sign of PHPT. Learning points Primary hyperparathyroidism is a relatively common condition with varying clinical and biochemical presentation. The most common presentations still remain as an asymptomatic biochemical abnormality closely related to calcium, PTH and bone metabolism. Not much attention is usually given to associated biochemical abnormalities, and hence they are usually less investigated. Further research is needed to establish if patients need long-term monitoring when no obvious cause for isolated hypophosphataemia has been found.

Main Role Of Morphogenetic Between Fgf-23 And Sklotho In The Development Of Herdic And Vasicular Models In Chronic Key Disease Patients

Diabetes is a major cause of chronic kidney disease (CKD). Poor blood sugar control accelerates the progression of CKD to terminal renal failure. Chronic kidney disease is also an important co-morbidity of diabetes. Impaired renal function further increases the risk of cardiovascular events in diabetic patients and ultimately carries a severe social and economic burden. Altered fibroblast growth factor 23 (FGF-23) and Klotho levels are considered the earliest biochemical abnormality of chronic kidney disease, the mineral and bone disease syndrome.

New Insights into the Role of FGF-23 and Klotho in Cardiovascular Disease in Chronic Kidney Disease Patients

Alterations of fibroblast growth factor 23 (FGF-23) and Klotho levels are considered to be the earliest biochemical abnormality of chronic kidney disease – mineral and bone disease (CKDMBD) syndrome. Moreover, emerging data suggests that the dysregulated FGF-23 and Klotho axis has many effects on the cardiovascular (CV) system and contributes significantly to the increased CV morbidity and mortality rates of CKD patients. This review examines recent evidence on the role of FGF-23 and Klotho in the development and progression of CV complications of uremia namely cardiac hypertrophy, uremic cardiomyopathy, and atherosclerotic and arteriosclerotic vascular lesions. Moreover, the available evidence on their associations with adverse clinical outcomes are summarized. Undoubtedly, more studies are needed to further elucidate the effects of FGF-23 and Klotho on the heart and vessels and to gain insights into their prognostic value as CV risk factors. Finally, large prospective studies are required to test the hypothesis that modification of their levels would have a favourable impact on the unacceptably high mortality rates of these patient populations.

Clinico-epidemiological study of neonatal seizures from a tertiary care hospital of Western Rajasthan, India

Background: Neonatal Seizures are frequent may be either symptoms of an underlying disorder and malfunction of the developing CNS or due to a primary epileptic condition. Their varied clinical presentations, delay in recognition and treatment results in poor neurological outcome. This study attempts to find out the clinical and etiologic profile of neonatal seizures and associated biochemical abnormalities in this geographical part of India.Methods: A hospital based prospective observational study undertaken in a tertiary care pediatric hospital of Medical College Jodhpur India, on 202 consecutive neonates who presented with seizures during period of one year. A detailed antenatal history and baseline characteristics of convulsing neonate at admission and clinical details of each seizure episode reported by the mother and subsequently observed by doctors on duty were recorded. Venous blood sample was analyzed as soon as possible for blood glucose, total serum calcium levels and electrolytes, before instituting any treatment. Data were managed on Microsoft Excel spreadsheet, and analysis was performed using SPSS version.Results: The overall frequency of neonatal seizures in our set up was recorded as 4.08%. Perinatal asphyxia with subsequent HIE was the most common (40.09%) cause of neonatal seizures while hypoglycemia was the most common metabolic cause (11.38%) observed specially in VLBW babies. Subtle seizures were the most common type (34.65%) and tonic seizures were the second most common (33.66%) type of seizures encountered. Hypocalcemia was the second commonest biochemical abnormality found in primary metabolic seizures. HIE, ICH and Hypoglycemia were the common seizure etiology in preterm neonates.Conclusions: Perinatal asphyxia and subsequent HIE was the commonest etiology with subtle, tonic and multifocal seizures being the commonest clinical types encountered. Hypoglycemia and hypocalcemia were the most frequent biochemical abnormality found.

A study of biochemical abnormalities and manifestations of neonatal seizures

Background: Neonatal seizure is a common neurological problem in the neonatal period with a frequency of 1.5 to 14/1000 neonates1. Neonatal seizures have always been a topic of particular interest because of their universal occurrence. A varied number of conditions are capable of causing seizures in the neonatal period. The presence of a seizure does not constitute a diagnosis but is a symptom of an underlying central nervous system disorder due to systemic or biochemical disturbances. This study aims to study the various clinical types of seizures and the biochemical abnormalities associated with them.Methods: This prospective study was conducted in the neonatology unit, department of pediatrics, C.S.I. Holdsworth Memorial Hospital, Mysore. Details of history, examination and investigations were recorded on predesigned proforma.Results: Out of total 54 cases, 47(87%) cases had seizures during first 3 days of life and hypoxic ischemic – encephalopathy (HIE) remains the main etiological factor in 20 (37.04%) cases. More than one metabolic abnormality was present in 6 cases. Hypoglycemia & hypomagnesemia were the commonest abnormality in neonates having seizures.Conclusions: A biochemical work up is necessary for all cases of neonatal seizures. The type of seizure does not give much information as to whether the seizures are purely metabolic or organic or about the type of biochemical abnormality.

Bowel Preparation for Colonoscopy in Children: 1 Day PEG-3350 with Bisacodyl versus 3 Day Sennosides

Background and Objectives: Bowel preparation (BP) for colonoscopy is a challenging procedure in children and different regimens have been used for this purpose. Polyethylene glycol (PEG) is the most preferred agent in recent years. The primary aim of this study was to evaluate the efficacy of 1-day PEG-3350 with bisacodyl (PEG-B) and comparing it with 3-day sennosides A+B. Method: In this prospective, randomized, and single-blinded study, children aged 2–18 years were included in the PEG-B group for 1 day or in Senna group for 3 days. The effectiveness of BP was assessed according to the Ottawa and Boston BP scales, compliance and adverse effects were also recorded. Pre- and post-preparation biochemistry were obtained for investigation of safety of both regimens. Results: Successful BP was observed in 88.3% (n = 53/60) of PEG-B and 86% (n = 55/64) of Senna groups according to Boston scale, and it was 85% (n = 51/60) and 84.4% (n = 54/64), respectively, according to Ottawa scale. The cecal intubation rate was 96.7% (n = 58/60) in the PEG-B group and 93.8% (n = 60/64) in the Senna group. Ease of administration and disturbance in regular daily activities was better in the PEG-B group (p < 0.05). There was no major adverse event and biochemical abnormality in both groups. The correlation between Ottawa and Boston scales was found to be excellent (r2 = –0.954, p < 0.01). Conclusions: The efficacy, safety, and adverse effect profile of 1-day BP with PEG-B regimen was found to be similar to 3-day sennosides regimen, however, the PEG-B regimen had advantages such as short duration, ease of administration, and better patient comfort. Also, high correlation rate between the Boston and Ottawa scales in pediatric patients was remarkable.