Rapid Correction Research Articles

Rapid correction of hyperglycemia: A necessity but at what price? A brief report of a patient living with type 1 diabetes

The complication of diabetes, which is known as diabetic foot ulcer (DFU), is a significant concern due to its association with high rates of disability and mortality. It not only severely affects patients’ quality of life, but also imposes a substantial burden on the healthcare system. In spite of efforts made in clinical practice, treating DFU remains a challenging task. While mesenchymal stem cell (MSC) therapy has been extensively studied in treating DFU, the current efficacy of DFU healing using this method is still inadequate. However, in recent years, several MSCs-based drug delivery systems have emerged, which have shown to increase the efficacy of MSC therapy, especially in treating DFU. This review summarized the application of diverse MSCs-based drug delivery systems in treating DFU and suggested potential prospects for the future research.

Osmotic Demyelination Syndrome: A Rare Clinical Image.

The term "Osmotic Demyelination Syndrome" (ODS) is synonymous with central pontine myelinolysis (CPM), denoting a condition characterised by brain damage, particularly affecting the white matter tracts of the pontine region. This damage arises due to the rapid correction of metabolic imbalances, primarily cases of hyponatremia. Noteworthy triggers encompass severe burns, liver transplantations, anorexia nervosa, hyperemesis gravidarum, and hyperglycaemia, all linked to the development of CPM. Clinical manifestations encompass a spectrum of signs and symptoms, including dysphagia, dysarthria, spastic quadriparesis, pseudobulbar paralysis, ataxia, lethargy, tremors, disorientation, catatonia, and, in severe instances, locked-in syndrome and coma. A recent case involving a 45-year-old woman illustrates these complexities. Upon admission to the Medicine Intensive Care Unit, she presented with symptoms indicative of diminished responsiveness and bilateral weakness in the upper and lower limbs. Of significance, the patient had a pre-existing medical history of hyperthyroidism. Extensive diagnostic investigations were undertaken, revealing compelling evidence of profound hyponatremia through blood analyses. Furthermore, magnetic resonance imaging (MRI) was performed, unveiling conspicuous areas of abnormal hyperintensity located in the central pons, intriguingly accompanied by spared peripheral regions. These radiological findings align with the characteristic pattern associated with osmotic demyelination syndrome, illuminating the underlying pathology.

Treatment‐induced neuropathy of diabetes: an update

Abstract Background and aims: Treatment‐induced neuropathy of diabetes is an acute small‐fibre neuropathy associated with rapid glycaemia improvement.Methods: This study is a narrative review carried out based on a bibliographic review, using articles indexed in PubMed/Medline and Scielo.Results: This entity is more frequent in adult patients with poor previous glycaemic control. Its precise pathophysiology is unknown, but it is likely related to unrestored microcirculation changes that occurred during the hyperglycaemic period. It presents with intense, sudden neuropathic pain and autonomic dysfunction after a rapid glycaemic correction and a poorer analgesic response than in diabetic neuropathy.Conclusions: Since rapid glycaemia correction is the cause of this problem, clinical practice guidelines that can help physicians to prevent, diagnose and manage this entity should be developed. Copyright © 2023 John Wiley & Sons.

Intensive care in severe acute bowel obstruction (clinical lecture)

Most patients with severe acute small bowel obstruction in the early postoperative period require treatment in the intensive care unit. The main principles of intensive care are identifying major vital function disorders, their rapid correction, as well as supporting the functions of the affected organs and systems. The leading pathophysiological disorders that require intensive correction during small bowel obstruction are impaired intestinal barrier function (for bacteria and toxins), hypovolemia, hypotension and microcirculation disorders, primarily in the abdominal organs, fluid and electrolyte and acid-base disorders. Such disorders, in turn, could cause repeated development of intra-abdominal hypertension with impaired perfusion of the abdominal organs. Thus, the efficiency of intensive care for dynamic acute bowel obstruction primarily depends on the speed of correction of fluid and electrolyte disorders and restoration of intestinal blood flow, normalization of gut parietal digestion rather than on the quantity of the drugs that stimulate bowel movement. The primary method of gut microcirculation restoration is the ROSE approach to fluid resuscitation. The main criteria of the intensive care efficiency should be control of intra-abdominal pressure and timely treatment of intra-abdominal hypertension.

Diagnostic and Therapeutic Strategies to Severe Hyponatremia in the Intensive Care Unit.

Hyponatremia is the most common electrolyte abnormality encountered in critically ill patients and is linked to heightened morbidity, mortality, and healthcare resource utilization. However, its causal role in these poor outcomes and the impact of treatment remain unclear. Plasma sodium is the main determinant of plasma tonicity; consequently, hyponatremia commonly indicates hypotonicity but can also occur in conjunction with isotonicity and hypertonicity. Plasma sodium is a function of total body exchangeable sodium and potassium and total body water. Hypotonic hyponatremia arises when total body water is proportionally greater than the sum of total body exchangeable cations, that is, electrolyte-free water excess; the latter is the result of increased intake or decreased (kidney) excretion. Hypotonic hyponatremia leads to water movement into brain cells resulting in cerebral edema. Brain cells adapt by eliminating solutes, a process that is largely completed by 48 h. Clinical manifestations of hyponatremia depend on its biochemical severity and duration. Symptoms of hyponatremia are more pronounced with acute hyponatremia where brain adaptation is incomplete while they are less prominent in chronic hyponatremia. The authors recommend a physiological approach to determine if hyponatremia is hypotonic, if it is mediated by arginine vasopressin, and if arginine vasopressin secretion is physiologically appropriate. The treatment of hyponatremia depends on the presence and severity of symptoms. Brain herniation is a concern when severe symptoms are present, and current guidelines recommend immediate treatment with hypertonic saline. In the absence of significant symptoms, the concern is neurologic sequelae resulting from rapid correction of hyponatremia which is usually the result of a large water diuresis. Some studies have found desmopressin useful to effectively curtail the water diuresis responsible for rapid correction.

The management of severe traumatic brain injury in the initial postinjury hours - current evidence and controversies.

To provide an overview of recent studies discussing novel strategies, controversies, and challenges in the management of severe traumatic brain injury (sTBI) in the initial postinjury hours. Prehospital management of sTBI should adhere to Advanced Trauma Life Support (ATLS) principles. Maintaining oxygen saturation and blood pressure within target ranges on-scene by anesthetist, emergency physician or trained paramedics has resulted in improved outcomes. Emergency department (ED) management prioritizes airway control, stable blood pressure, spinal immobilization, and correction of impaired coagulation. Noninvasive techniques such as optic nerve sheath diameter measurement, pupillometry, and transcranial Doppler may aid in detecting intracranial hypertension. Osmotherapy and hyperventilation are effective as temporary measures to reduce intracranial pressure (ICP). Emergent computed tomography (CT) findings guide surgical interventions such as decompressive craniectomy, or evacuation of mass lesions. There are no neuroprotective drugs with proven clinical benefit, and steroids and hypothermia cannot be recommended due to adverse effects in randomized controlled trials. Advancement of the prehospital and ED care that include stabilization of physiological parameters, rapid correction of impaired coagulation, noninvasive techniques to identify raised ICP, emergent surgical evacuation of mass lesions and/or decompressive craniectomy, and temporary measures to counteract increased ICP play pivotal roles in the initial management of sTBI. Individualized approaches considering the underlying pathology are crucial for accurate outcome prediction.

THU473 Acute Hypercalcemia In The Setting Of Acute Fatty Liver Of Pregnancy, A Case Report

Abstract Disclosure: M. Ahmad: None. M. Mack: None. A. Arif: None. L.A. Tejada: None. U. Siddiqui: None. Introduction: Hypercalcemia in pregnancy is rare and often goes unrecognized due to the overlapping symptoms of hypercalcemia and pregnancy. The most common cause of hypercalcemia in pregnant patients is primary hyperparathyroidism, with malignancy, milk alkali syndrome and familial hypocalciuric hypercalcemia being less common. Additionally, endogenous PTHrP production by breast and placental tissue have also been described as rare causes of hypercalcemia in pregnancy. We describe an interesting case of severe hypercalcemia in a pregnant woman presenting with acute fatty liver of pregnancy (AFLP) which rapidly corrected after delivery. Case description: The patient was a 32-year-old female with a past medical history of hypothyroidism and type 2 diabetes mellitus who presented to the emergency department at 32 weeks gestation due to four days of nausea, vomiting and epigastric pain. The patient’s vital signs were as follows: blood pressure: elevated to 133/79 mmHg, heart rate: 75 beats per minute, temperature: 36.7 C, and respiratory rate: 12 breaths per minute. On physical exam, the patient had diffuse abdominal tenderness with no vaginal bleeding. The patient’s blood work was significant for: bicarbonate: 17 mmol/L, creatinine: 1.26 mg/dL (baseline 0.7 mg/dL), corrected calcium of 15.1 mg/dL, ALP: 438 IU/L, AST: 653 IU/L, ALT: 666IU/L, total bilirubin: 2.3 mg/dL, INR 1.3, and ammonia: 43 mcmol/L. She was taken to the operating room for emergent cesarian delivery for concerns of AFLP. Further workup of the patient’s hypercalcemia, revealed a low normal PTH level of 11 pg/dL (normal 11-65 mg/dL), PTHrP level of <5 mg/dL, TSH of 1.37 uIU/ml, 25-OH vitamin D 55 ng/ml, and 1,25-OH vitamin D: 20 pg/ml. After delivery, the patient had alleviation of her symptoms and was kept on dextrose 5% with lactated ringers at 100 cc/h for a total of two days and had complete resolution of her hypercalcemia (corrected calcium of 10.2 mg/dL on discharge). The patient follows with endocrinology as an outpatient and since has had normal calcium levels. Discussion: Hypercalcemia in pregnancy is rare, only affecting 0.03% of women in the reproductive age group, with primary hyperparathyroidism being the most common cause. Hypercalcemia in pregnancy can often be missed due to the hemodilution of serum calcium in pregnancy and also the nonspecific symptoms present in pregnant patients. Our case describes a patient presentation of severe hypercalcemia with AFLP, who had rapid correction of her calcium levels after delivery. The exact mechanism of her severe hypercalcemia developed remains unclear, however, given its rapid resolution with delivery of the placenta potential etiologies include the AFLP itself or possibly the placenta contributing to hypercalcemia. Through this case report, we hope to highlight a possible association between AFLP and hypercalcemia. Presentation: Thursday, June 15, 2023

THU350 Rapid Decrease Of Glycemic Levels In Three Patients With Severe Insulin Resistance Associated With Bell’s Palsy.

Abstract Disclosure: E. Chuki: None. M. Lightbourne: None. B. Abel: None. R.J. Brown: None. Bell’s palsy (BP) is associated with diabetic angiopathy and facial nerve ischemia and may be the first sign of diabetic mononeuropathy. Specific risk factors for diabetic mononeuropathy have not been well established. Rapid tightening of glycemic control has been associated with worsening diabetic retinopathy. However, this association has not been reported previously in the development of diabetic mononeuropathy or BP. We describe three patients with extreme insulin resistance, in whom rapid correction of hyperglycemia was temporally associated with development of BP. Case 1: A 63 year-old African American male with history of type 2 diabetes (T2D) and peripheral neuropathy was admitted with sudden onset severe insulin resistance and DKA, leading to a diagnosis of type B insulin resistance. Serum glucose was >600 mg/dl and A1c was 13.4%. He was treated with an insulin drip, then transitioned to subcutaneous insulin U-500 at a total daily dose of ∼3000 units, resulting in blood glucose between 140 and 180 mg/dl. On Day 5 after initiating U-500 and achieving tight control of glycemia, the patient developed bilateral Bell’s Palsy, which resolved after 4 years. Case 2: A 25 year-old African American female with history of T2D was admitted with sudden onset severe insulin resistance and DKA requiring an insulin drip of ∼3,000 units per day, leading to a diagnosis of type B insulin resistance. A1c on admission was 14%. After ∼5 days, she transitioned to U-500 that was titrated over 2 weeks to a total daily dose of 3,000 units with blood glucose between 98 and 177 mg/dL. She developed bilateral BP approximately 43 days from onset of DKA and 36 days after starting U-500 insulin with improved glycemic control. At last follow up 5 years later she still had residual facial weakness. Case 3: A 25 year-old Caucasian male with history of diabetes due to type A insulin resistance (Rabson-Mendenhall Syndrome) and recurrent ketosis on U500 insulin >1,000 units daily had poor adherence to insulin and diet with A1c of 14.3%. 3 weeks after A1c measurement he was started on a Continuous Glucose Monitor (CGM), leading to dramatic change in diet and medication adherence, with reduction in the estimated A1c based on glucose management indictor (GMI) to 7.7% within 3 weeks. 3 weeks after starting CGM use with improved compliance and glycemic control, he developed unilateral BP, which fully recovered after 1 month.We report 3 cases in which onset of BP was observed in rapid temporal correlation with massive increases in insulin dose and/or improvement in glycemia. Severe insulin resistance and rapid decrease of glycemic levels may lower intravascular volume and narrow vessels, leading to microvascular disruption of the vasa nervorum, ultimately causing mononeuropathy. A more gradual approach to glycemia management in patients with severe insulin resistance may be warranted to mitigate this risk. Presentation: Thursday, June 15, 2023

FRI497 Thyroid Storm And Recurrent Myopericarditis

Abstract Disclosure: D.J. Gomez D' Aza: None. T. Zahedi: None. F. Zhang: None. Introduction: Thyroid storm is an acute life-threatening complication of hyperthyroidism with high mortality rate. Plasmapheresis is often used in patients who are unresponsiveness to conventional treatment for thyroid storm. About 5% of thyroid storm patients present with heart failure while other cardiovascular dysfunctions include tachycardia, arrhythmias, hypertension, and pericardial disease. Myopericarditis is characterized by pericarditis associated with myocardial inflammation evident by elevated cardiac biomarkers. Thyrotoxicosis associated with pericarditis and myocarditis is rare. Here, we report a case of recurrent myopericarditis and thyroid storm in Grave’s disease treated with plasmapheresis. Case Report: A 47 years male with a history of Schizophrenia and Hyperthyroidism due to Grave’s disease was presented with poor oral intake, generalized weakness, and tachycardia with HR 180 bpm. Labs showed elevated troponin 0.505 ng/mL, Free T4 > 6.99 mg/dL, T3 > 651 ng/dL, and low TSH < 0.015 mg/dL. Burch-Warsofsky scale was 50 points which suggested thyroid storm. EKG revealed atrial fibrillation. Patient was managed with propranolol, propylthiouracil (PTU), iodine solution, hydrocortisone, and Diltiazem. However, his mental status deteriorated requiring intubation and patient developed cardiac shock with BP 77/53 mmHg. Troponin I trended up to 23.60 ng/mL and EKG showed ST-segment elevation in the anterior and inferior leads. Echocardiogram revealed severely reduced ejection fraction of 15 % and diffuse hypokinesis. Cardiac catheterization was unremarkable. PTU was discontinued due to liver dysfunction with AST and ALT levels above 1500 U/L and 2500 U/L. A session of plasmapheresis was initiated and the post labs showed an improvement of thyroid and liver function to Free T4 2.46 mg/dL, TSH 0.022 mg/dL, and ALT/AST 641/682 U/L. Patient was hemodynamically stable with normal sinus rhythm. Cardiac magnetic resonance images revealed left ventricular dilation with high T2 signal, late gadolinium enhancement in the pericardial region of basal inferolateral, inferior, and mid segments, consistent with pericarditis. Previous record showed patient had a similar admission 4 months ago with a diagnosis of myopericarditis. Discussion: The association of recurrent myopericarditis and hyperthyroidism may be related with the autoimmune dysfunction and underlying viral infection that precipitated inflammation of the thyroid gland, triggered thyroid storm, and caused cardiac event. Rapid correction of the hyperthyroid state is warranted in thyroid storm in addition to aggressive treatments for heart failure, arrhythmias, and myopericarditis. Our patient’s cardiac function improved rapidly after achieving euthyroidism by plasmapheresis. The treatment of hyperthyroidism is critical in preventing the recurrence of myopericarditis. Presentation: Friday, June 16, 2023

THU388 Insulin Edema Associated With Glargine: A Case Report And Brief Review Of Literature

Abstract Disclosure: J. Wood: None. V. Samji: None. F.S. Celi: None. P. Majety: None. Introduction: Insulin edema is an uncommon and poorly understood complication of insulin therapy in patients with diabetes. We report a patient with type 1 diabetes (T1DM) who developed edema within days of initiating insulin glargine that resolved with discontinuation of this medication. Case Report: A 20-year-old man with no past medical history presented with nausea, vomiting, polydipsia, and a 15-pound weight loss and was noted to have a hemoglobin A1c greater than 14.0%. Diabetic ketoacidosis (DKA) was ruled out and was started on weight-based insulin therapy with glargine and lispro three units with meals. Additional diabetes workup was notable for positive Anti-IA2 antibodies. Blood glucose levels improved prior to discharge. A week after discharge, he complained of swelling of limbs. Patient denied any shortness of breath, cough, chest pain, orthopnea, or nocturnal dyspnea. He was found to have extensive 2+ pitting edema in bilateral feet extending up to his calves. Dorsalis Pedis pulses were 2+ bilaterally. No warmth or erythema of legs was noted. His weight in clinic was 70.2 kg (154.4 lbs), up 11.6 kg (25.5 lbs) ten days post discharge. Evaluation for bilateral pedal edema was performed. Labs were notable for normal liver enzymes, creatinine, glomerular filtration rate and urine albumin levels, ruling out hepatic and renal causes of edema. Thyroid function tests were normal. His presentation was discussed with cardiology and brain natriuretic peptide level was drawn which was also normal. No further cardiac workup was recommended at that time given the patient’s history and lack of other clinical signs or symptoms of heart failure. After ruling out other systemic causes of edema in our patient, a diagnosis of insulin edema was made. Based on prior case reports of glargine associated insulin edema, he was switched from insulin glargine to insulin degludec. He noted significant improvement within 24 hours of switching insulin with a 6.4-pound weight loss in just one day and complete resolution of edema within 3 days. He had no recurrence of edema once glargine was discontinued despite increasing insulin dosing for glycemic control. Conclusion: The pathophysiology of insulin edema is unclear. Insulin’s role in renal sodium handling, vasodilation, and increased vascular permeability, have been postulated as possible mechanisms. Risk factors for developing insulin edema include T1DM, high A1C, high dose of insulin, rapid correction of hyperglycemia, DKA on presentation and poor nutritional status. Additional risk factors for developing insulin edema include thiamine deficiency and an underlying genetic predisposition related to a mitochondrial mutation, although this seems to be rare. Insulin edema is a diagnosis of exclusion. Clinicians should be aware of this rare complication, and its occurrence should be documented and differentiated from other causes of edema. Presentation: Thursday, June 15, 2023

SAT475 Levothyroxine and Liothyronine Treated Myxedema Coma with Irreversible Cardiopulmonary Failure: A Rare Phenomenon

Abstract Disclosure: T. Menon: None. Y. Xie: None. A. Wang: None. Introduction: We describe a case of myxedema coma associated with irreversible cardiogenic shock and the challenges in optimal management. Case Presentation: A previously healthy 23-year-old man with a history of untreated hypothyroidism (TSH 100 uIU/mL six months prior) presented to the hospital for abdominal pain, shortness of breath, and cough. He soon had two cardiac arrests with successful resuscitation and was stabilized via mechanical ventilation and vasopressors. Physical exam showed peripheral and facial edema with mild jaundice. Laboratory results showed elevated creatinine 1.73 (0.5-1.30 mg/dL), AST 440 (10-40 U/L), ALT 353 (10-45 U/L), and total bilirubin 3.6 (0.2-1.2 mg/dL). Thyroid function tests showed TSH 857 (0.27-4.20 uIU/mL), FT4 <0.1 (0.9-1.8 ng/dL), and TT3 < 20 (80-200 ng/dL), and negative thyroglobulin and TPO antibodies. A thyroid ultrasound showed a small thyroid gland. Echocardiogram revealed severe bi-ventricular failure, with an ejection fraction of 10-15%, dilated chambers, pulmonary hypertension, and moderate pericardial effusion. The patient was initiated on VA-ECMO and treated medically for cardiogenic shock. Myxedema coma treatment was started with IV levothyroxine (LT4) 400 mcg, IV Liothyronine (LT3) 10 mcg, and IV hydrocortisone 100 mg every eight hours. The patient subsequently received IV LT4 100 mcg daily and IV LT3 10-30 mcg daily based on levels of daily FT4 and TT3. Hydrocortisone was tapered down as free cortisol levels prior to steroid administration were elevated at 4.6 (0.2-1.8 ug/dL). Despite significant improvements in TSH values (from 857 to 67 uIU/L), FT4 (from <0.1 to 1.2 ng/dL), and TT3 (from < 20 to 60 ng/dL), the patient’s cardiac function did not improve and he underwent successful orthotopic heart transplantation two weeks after initial presentation. A cardiac biopsy demonstrated cardiomegaly with left ventricular hypertrophy, subendocardial fibrosis, and patent arteries, without other etiologies of heart failure. The patient recovered and was discharged on oral LT4 137 mcg daily, LT3 5 mcg twice daily, and prednisone per cardiac transplantation protocol. Discussion: Several cases describe myxedema coma with reversible heart failure in 4 to 5 days with appropriate hypothyroidism treatment. This case, however, describes irreversible cardiomyopathy despite optimal medical therapy, eventually requiring heart transplantation. Because the cardiac myocyte is dependent on plasma T3 due to lack of intracellular deiodinase, T3 administration may improve cardiac function in myxedema coma induced heart failure. Consensus regarding the use, optimal dose, and duration of LT3 in these situations requires further investigation. Conclusion: We report an unusual case of irreversible cardiomyopathy due to myxedema coma in a young, healthy patient, highlighting the need for rapid correction of hypothyroidism with both IV LT4 and LT3. Presentation Date: Saturday, June 17, 2023

Syndrome of Inappropriate Antidiuretic Hormone Release Secondary to Ectopic Olfactory Neuroblastoma: Case Report and Review of Literature.

Ectopic olfactory neuroblastoma (ONB) is a rare neuroendocrine sinonasal malignancy which arises from sinonasal regions where olfactory neuroepithelium does not exist. Presentation of syndrome of inappropriate antidiuretic hormone release (SIADH) in patients with ectopic ONB is extremely rare. We report a case of a 22-year-old patient with ectopic ONB and paraneoplastic SIADH that was managed at our center. The ONB was arising from the left lamina papyracea and extending into the maxillary and ethmoid sinuses and filling the nasal cavity. Correction of sodium levels occurred within 24 hours of endoscopic resection via a combined trans-nasal transorbital approach. To avoid negative sequela secondary to rapid sodium correction, the patient was managed by desmopressin to obtain gradual sodium correction, which was achieved on the fourth postoperative day. Ectopic presentation of ONB with paraneoplastic SIADH is extremely rare with only 7 cases reported in the literature to date. Management via surgical resection and/or radiotherapy for these patients requires the managing clinician to be vigilant of serum sodium levels. A multidisciplinary approach is essential for optimal outcomes.

Rate of Correction and All-Cause Mortality in Patients With Severe Hypernatremia

Hypernatremia is common among hospitalized patients and is associated with high mortality rates. Current guidelines suggest avoiding fast correction rates but are not supported by robust data. To investigate whether there is an association between hypernatremia correction rate and patient survival. This retrospective cohort study examined data from all patients admitted to the Tel Aviv Medical Center between 2007 and 2021 who were diagnosed with severe hypernatremia (serum sodium ≥155 mmol/L) at admission or during hospitalization. Statistical analysis was performed from April 2022 to August 2023. Patients were grouped as having fast correction rates (>0.5 mmol/L/h) and slow correction rates (≤0.5 mmol/L/h) in accordance with current guidelines. All-cause 30-day mortality. A total of 4265 patients were included in this cohort, of which 2621 (61.5%) were men and 343 (8.0%) had fast correction rates; the median (IQR) age at diagnosis was 78 (64-87) years. Slow correction was associated with higher 30-day mortality compared with fast correction (50.7% [1990 of 3922] vs 31.8% [109 of 343]; P < .001). These results remained significant after adjusting for demographics (age, gender), Charlson comorbidity index, initial sodium, potassium, and creatinine levels, hospitalization in an ICU, and severe hyperglycemia (adjusted odds ratio [aOR], 2.02 [95% CI, 1.55-2.62]), regardless of whether hypernatremia was hospital acquired (aOR, 2.19 [95% CI, 1.57-3.05]) or documented on admission (aOR, 1.64 [95% CI, 1.06-2.55]). There was a strong negative correlation between absolute sodium correction during the first 24 hours following the initial documentation of severe hypernatremia and 30-day mortality (Pearson correlation coefficient, -0.80 [95% CI, -0.93 to -0.50]; P < .001). Median (IQR) hospitalization length was shorter for fast correction vs slow correction rates (5.0 [2.1-14.9] days vs 7.2 [3.5-16.1] days; P < .001). Prevalence of neurological complications was comparable for both groups, and none were attributed to fast correction rates of hypernatremia. This cohort study of patients with severe hypernatremia found that rapid correction of hypernatremia was associated with shorter hospitalizations and significantly lower patient mortality without any signs of neurologic complications. These results suggest that physicians should consider the totality of evidence when considering the optimal rates of correction for patients with severe hypernatremia.

A rapid outliers detection and correction method for external ballistic velocity measurement data

Due to the influence of various sudden and abnormal factors during the tracking environment, equipment working conditions, and operation process, there are inevitable outliers in the tracking measurement process of aircraft such as carrier rockets, artificial satellites, and missiles. Therefore, the prerequisite for ensuring the reliability of processing results is to timely and accurately detect and correct outliers. In this paper, we proposed the sliding window-based variable degree B-spline function method (SWVD B-spline), which can handle isolated outliers and spotted outliers. SWVD B-spline uses variable degree B-spline function to model observed data in sliding windows, which can detect and correct outliers point by point along with window sliding. Then, we propose an initial window data selection method to remove outliers in initial windows to ensure the processing effect. In addition, because there are often inflection points in external ballistic velocity measurement data, differential evolution is used to optimize variable degree B-spline in windows that include inflection points to improve processing accuracy. The experimental results verify that SWVD B-spline can handle various outliers rapidly and efficiently.

Effects of PCSK9 inhibitors on coronary microcirculation, inflammation and cardiac function in patients with CHD after PCI: a protocol for systematic review and meta-analysis

IntroductionCoronary heart disease (CHD) is one of the common cardiovascular diseases that seriously jeopardise human health, and endothelial inflammation and dyslipidaemia are the initiating links leading to its occurrence. Percutaneous...

Understanding DNA Damage Response and DNA Repair in Multiple Myeloma.

Multiple myeloma (MM) is a plasma cell malignancy characterized by several genetic abnormalities, including chromosomal translocations, genomic deletions and gains, and point mutations. DNA damage response (DDR) and DNA repair mechanisms are altered in MM to allow for tumor development, progression, and resistance to therapies. Damaged DNA rarely induces an apoptotic response, given the presence of ataxia-telangiectasia mutated (ATM) loss-of-function or mutations, as well as deletions, mutations, or downregulation of tumor protein p53 (TP53) and tumor protein p73 (TP73). Moreover, DNA repair mechanisms are either hyperactive or defective to allow for rapid correction of the damage or permissive survival. Medications used to treat patients with MM can induce DNA damage, by either direct effects (mono-adducts induced by melphalan), or as a result of reactive oxygen species (ROS) production by proteasome inhibitors such as bortezomib. In this review, we will describe the mechanisms of DDR and DNA repair in normal tissues, the contribution of these pathways to MM disease progression and other phenotypes, and the potential therapeutic opportunities for patients with MM.

Intravenous iron and erythropoietin therapy for postoperative anemia among orthopedic surgery patients

BackgroundPostoperative anemia is a risk factor for adverse surgical outcomes. Our study aimed to assess the role of intravenous iron and erythropoietin therapy for the rapid correction of anemia following orthopedic surgery.MethodsPatients undergoing elective orthopedic surgery were prospectively enrolled and randomly divided into three groups: Control (placebo), Group 1 (IV iron monotherapy), and Group 2 [combined IV iron and recombinant human erythropoietin (rHuEPO) therapy]. Blood tests were performed preoperative (baseline) and on postoperative days (PODs) 1, 3, and 7.ResultsAll groups demonstrated significantly lower hemoglobin (Hb) concentrations compared to baseline, with no significant inter-group differences in postoperative Hb concentrations (p > 0.05). Serum erythropoietin, ferritin, and vitamin B12 levels, and reticulocyte count increased beyond normal ranges in all groups. Significantly lower serum iron levels were observed postoperatively in all groups (p < 0.05). No significant inter-group differences in hepcidin level were observed (p > 0.05).ConclusionPostoperative treatment with combined intravenous iron and rHuEPO was ineffective in correcting postoperative anemia among orthopedic surgery patients, besides achieving higher reticulocyte counts in the first week of surgery. No improvement in mobilization of storage iron was achieved with rHuEPO. We further suggest against vitamin B12 administration during the early postoperative period.

Severe hyponatremia with consciousness disturbance after receiving SARS-CoV-2 mRNA vaccination.

There are very few reports of syndrome of inappropriate antidiuresis hormone secretion (SIADH) after receiving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine. Herein, we present the case of an 84-year-old woman who developed severe hyponatremia following the second administration of the SARS-CoV-2 mRNA vaccine. The patient presented with nausea, vomiting, and headache. Laboratory tests showed a plasma sodium level of 119 mmol/L. After receiving 500 mL of intravenous saline over a 2-h period, her plasma sodium level raised to 121 mmol/L, but her symptoms persisted. Considering that rapid plasma sodium correction was necessary, we started 3% saline solution overnight. Her plasma sodium level raised to 132 mmol/L and her symptoms completely resolved. Clinical and laboratory findings were consistent with a diagnosis of SIADH. In the absence of any other triggering factors, we concluded that the condition was likely associated with the vaccination. Clinicians should be aware of the potential for hyponatremia, particularly SIADH, associated with SARS-CoV-2 mRNA vaccination. Reports of syndrome of inappropriate antidiuresis hormone secretion after receiving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination are limited. If nausea, headache, and confusion are observed immediately after SARS-CoV-2 vaccination, clinicians should consider the presence of hyponatremia. As similar case reports to date have presented with severe hyponatremia, prompt treatment may be required.

Portfolio management and performance of deposit money banks (Dmbs) in Nigeria (1990–2020)

There have been a renewed focus on portfolio management of deposit money banks since the global financial crisis of 2007–09. This renewed focus is based on the understanding that an efficient portfolio management reduces risks and loss associated with uncertainty of investment returns which may impact on the performance of banks. In this study, we investigated the connection between portfolio management and performance of deposit money banks in Nigeria. The study essentially sought to ascertain whether portfolio management has predictive value for the out-of-sample predictability of profitability of deposit money banks in Nigeria. The Markowitz portfolio theory underpin the study while time series data on deposit money banks’ liquidity, financial assets, foreign portfolio asset, deposit mix, and private sector concentration were utilized for the analysis. The time series spanned from 1990 to 2020 based on data availability. To increase the robustness of the result, the entire 24 DMBs were included in the study. The unit root test and bound cointegration test were employed to check times series behaviour of the variables. The Autoregressive Distributed Lag (ARDL) was used to estimate both the short-run and long-run dynamics and rapid correction to long-run equilibrium. Our findings reveal that portfolio management and its variants had significant effect on the profit after tax (PAT), return on investment (ROI), asset quality (ASQ), and capital adequacy (CA) of deposit money banks in Nigeria.

Impact of Intensive Glycemic Treatment on Diabetes Complications-A Systematic Review.

Diabetes complications can be related to the long duration of the disease or chronic hyperglycemia. The follow-up of diabetic patients is based on the control of chronic hyperglycemia, although this correction, if obtained rapidly in people living with severe chronic hyperglycemia, can paradoxically interfere with the disease or even induce complications. We reviewed the literature describing the impact of the rapid and intense treatment of hyperglycemia on diabetic complications. The literature review showed that worsening complications occurred significantly in diabetic microangiopathy with the onset of specific neuropathy induced by the correction of diabetes. The results for macroangiopathy were somewhat mixed with the intensive and rapid correction of chronic hyperglycemia having a neutral impact on stroke and myocardial infarction but a significant increase in cardiovascular mortality. The management of diabetes has now entered a new era with new therapeutic molecules, such as gliflozin for patients living with type 2 diabetes, or hybrid insulin delivery systems for patients with insulin-treated diabetes. Our manuscript provides evidence in support of these personalized and progressive algorithms for the control of chronic hyperglycemia.