[Diabetic ketoacidosis secondary to immunotherapy]. / Cetoacidosis diabética secundaria a inmunoterapia.

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that are increasingly used in cancer treatments. As experience in the use of immunotherapy increases, more is known about its safety profile and immune-mediated adverse effects. Among them is diabetic ketoacidosis (DKA), a rare but serious fatal complication of treatment. In this paper we describe the cases of three patients who presented with episodes of DKA during treatment with ICIs, two of which manifested with fulminant forms, leading to an acute course with initially normal glycosylated hemoglobin values. In addition, we conducted a review of the literature on DKA associated with ICIs in order to highlight the importance of noticing these potentially fatal complications and promptly establishing appropriate therapy.

Los inhibidores de puntos de control inmune (ICIs) son anticuerpos monoclonales cada vez más utilizados en tratamientos oncológicos. A medida que aumenta la experiencia en el uso de inmunoterapia, se conoce cada vez más su perfil de seguridad y los efectos adversos inmunomediados. Entre ellos se encuentra la cetoacidosis diabética (CAD), complicación infrecuente, grave y potencialmente mortal. En este trabajo describimos los casos de tres pacientes que se presentaron con episodios de CAD durante el tratamiento con ICIs, dos de los cuales manifestaron con formas fulminantes, llevando un curso agudo con valores de hemoglobina glicosilada inicialmente normales. Asimismo, realizamos una revisión de la literatura sobre la CAD asociada a ICIs a fines de resaltar la importancia de advertir estas complicaciones potencialmente fatales e instaurar rápidamente la terapéutica apropiada.

Eu- or hypoglycemic ketosis and ketoacidosis in children: a review.

The last decade has been characterized by exciting findings on eu- or hypoglycemic ketosis and ketoacidosis. This review emphasizes the following five key points: 1. Since the traditional nitroprusside-glycine dipstick test for urinary ketones is often falsely negative, the blood determination of ß-hydroxybutyrate, the predominant ketone body, is currently advised for a comprehensive assessment of ketone body status; 2. Fasting and infections predispose to relevant ketosis and ketoacidosis especially in newborns, infants, children 7 years or less of age, and pregnant, parturient, or lactating women; 3. Several forms of carbohydrate restriction (typically less than 20% of the daily caloric intake) are employed to induce ketosis. These ketogenic diets have achieved great interest as antiepileptic treatment, in the management of excessive body weight, diabetes mellitus, and in sport training; 4. Intermittent fasting is more and more popular because it might benefit against cardiovascular diseases, cancers, neurologic disorders, and aging; 5. Gliflozins, a new group of oral antidiabetics inhibiting the renal sodium-glucose transporter 2, are an emerging cause of eu- or hypoglycemic ketosis and ketoacidosis. In conclusion, the role of ketone bodies is increasingly recognized in several clinical conditions. In the context of acid-base balance evaluation, it is advisable to routinely integrate both the assessment of lactic acid and ß-hydroxybutyrate.

Sirolimus-induced Hypertriglyceridemia Leads to Acute Pancreatitis and Diabetic Ketoacidosis Post Stem Cell Transplant for Sickle Cell Disease.

Sirolimus (mammalian target of rapamycin inhibitor) is a potent immunosuppressive agent, used in patients receiving hematopoietic stem cell transplant (HSCT) for Graft vs Host disease prophylaxis. Compared to calcineurin inhibitors, sirolimus has no neurotoxicity or nephrotoxicity, but sirolimus causes dose-dependent thrombocytopenia, leukopenia, delayed wound healing, hyperlipidemia, and hypertriglyceridemia. Here we report a case of acute pancreatitis and diabetic ketoacidosis in a patient with sickle cell disease post haploidentical family donor HSCT which was managed conservatively without plasmapheresis. Based on our review of the literature, this is the first reported case of developing acute pancreatitis as an adverse effect of sirolimus-induced hypertriglyceridemia leading to diabetic ketoacidosis in a recipient of HSCT.

Severe Ketoacidosis After One Anastomosis Gastric Bypass Surgery.

BACKGROUND Bariatric surgeries, such as one anastomosis gastric bypass (OAGB), has become a popular treatment option for managing obesity and associated comorbidities, including type-2 diabetes mellitus (T2DM). However, severe starvation ketoacidosis is a rare but potentially life-threatening complication that can occur postoperatively in patients with T2DM. Despite the increasing prevalence of these surgeries, the existing literature has limited information on severe starvation ketoacidosis as a postoperative complication. It is essential for healthcare professionals to be aware of this complication, its manifestations, and risk factors to ensure patient safety and improve outcomes. Therefore, this article aims to address the current gap in the literature and provide a comprehensive review of severe starvation ketoacidosis as a postoperative complication of bariatric surgeries, specifically OAGB, and its associated risk factors and manifestations. CASE REPORT A 38-year-old man with severe obesity and inadequately managed T2DM underwent OAGB surgery. On the second postoperative day, the patient experienced severe starvation ketoacidosis, exhibiting symptoms such as drowsiness, fatigue, weakness, and Kussmaul breathing. Blood gas analysis indicated significant metabolic acidosis. He was quickly transferred to the Intensive Care Unit (ICU) and given intravenous glucose and insulin therapy. Following this intervention, he showed rapid recovery and normalization of blood gases. He was discharged 6 days after surgery with normal clinical examination results and laboratory indices. CONCLUSIONS This case study emphasizes the significance of thorough preoperative glycemic control, comprehensive perioperative multidisciplinary management, and close postoperative monitoring for diabetic patients undergoing metabolic and bariatric surgeries. By implementing these strategies, healthcare professionals can reduce the risk of complications such as hypoglycemia or hyperglycemia/diabetic ketoacidosis (DKA) and enhance patient outcomes. The case also highlights the need for continuous education and training for healthcare providers to identify and manage such rare complications effectively.

Diagnosis and Acute Management of Hyperglycemic Hyperosmolar Syndrome in Children and Adolescents.

ABSTRACT: Hyperglycemic hyperosmolar syndrome (HHS) is an indolent process characterized by significantly increased levels of serum glucose, high osmolality, and electrolyte abnormalities. The incidence of HHS has steadily risen in the pediatric population over the past several years. Patients with HHS often present with profound dehydration, fatigue, and early mental status changes. Primary emergency management of HHS involves fluid replacement, hemodynamic support, correcting electrolyte derangements, and addressing complications and underlying illnesses. Insulin is not an initial therapy in HHS and should be considered only after the patient's fluids and electrolytes have been repleted. Unlike in diabetic ketoacidosis, HHS patients are not acidotic, although children may present with mixed HHS/diabetic ketoacidosis syndromes. Complications of HHS include thrombosis, rhabdomyolysis, and, rarely, malignant hyperthermia.

Intraoperative diagnosis of type 1 diabetes and diabetic ketoacidosis during scoliosis surgery.

Diabetic ketoacidosis is the leading cause of morbidity and mortality in children with type 1 diabetes. Management of diabetic ketoacidosis requires meticulous monitoring and treatment of severe dehydration and metabolic derangement. We present an adolescent patient who was diagnosed with diabetic ketoacidosis during spinal fusion for idiopathic scoliosis and discuss the management of this unexpected intraoperative emergency.

Pneumomediastinum complicating diabetic ketoacidosis.

Pneumomediastinum is an uncommon finding in patients with diabetic ketoacidosis (DKA) and may occur spontaneously or secondary to an effort rupture of the oesophagus. Excluding oesophageal rupture is important, as delaying treatment increases the risk of mortality. We discuss a case of DKA complicated by vomiting, pneumomediastinum, pneumopericardium and air in the epidural space. Instead of fluoroscopic oesophagography, chest CT was used to investigate oesophageal rupture. We present an overview of case reports and retrospective studies illustrating the utility of chest CT in the investigation of oesophageal rupture over fluoroscopic oesophagography.

A series of patients with hospital-acquired diabetic ketoacidosis (HADKA): a descriptive analysis.

BACKGROUND: Hospital-acquired diabetic ketoacidosis (HADKA) can complicate hospital admission in people with type 1 diabetes (T1D) and type 2 diabetes (T2D). We aimed to determine the characteristics of such patients and the reasons for HADKA. METHODS: A retrospective analysis of patients referred to diabetes services with HADKA at Morriston Hospital between January 2016 and January 2022 was undertaken. Patients that were included were admitted without diabetic ketoacidosis (DKA), were aged 18 years and over, and who subsequently developed DKA in hospital. RESULTS: Twenty-five patients were included with a mean age of 65.2 years; nine (32.0%) were men, 13 (52.0%) had T1D and 12 (48.0%) had T2D. Patients had a mean pre-admission glycated haemoglobin of 84.7 mmol/mol, and 17 (68.0%) were insulin-treated. Most were admitted under medicine (n=14; 56.0%) and the remainder under surgery (n=11; 44.0%). More common reasons for HADKA were erroneous insulin administration (n=9; 36.0%), infection (n=7; 28.0%) and surgery (n=5; 20.0%).Five (20.0%) patients required intensive care admission, and the mean length of hospital stay was 42.6 days (range 2-173). Three (12.0%) patients died during the hospital admission. CONCLUSION: HADKA was identified in a significant number of patients at our hospital and was associated with significant mortality. Earlier recognition of ketonaemia and associated medication use may prevent HADKA and improve outcomes.

Feline Comorbidities: Clinical perspective on diabetes mellitus and pancreatitis.

PRACTICAL RELEVANCE: Diabetes mellitus (DM) is one of the most common feline endocrine disorders. It has been shown by several studies that DM in cats frequently coexists with pancreatitis. CLINICAL CHALLENGES: It has not been definitively established what the exact pathogenetic association between DM and pancreatitis is in the cat. However, the association between these two conditions is most likely bidirectional, with DM predisposing cats to pancreatitis and vice versa. Diagnosis of pancreatitis in cats with DM is crucial because concurrent pancreatitis commonly leads to difficulties in the management of DM. When pancreatitis is associated with diabetic ketoacidosis (DKA), therapeutic management is even more challenging. AIMS: This review focuses on the concurrent presence of DM or DKA and pancreatitis in cats, mainly focusing on their clinical management. EVIDENCE BASE: Information provided in this review is based on feline-specific clinical research when available. In addition, comparative and human research, as well as clinical experience, has been used to enrich knowledge in areas where feline-specific research is not yet available.

Polyendocrine Autoimmunity and Diabetic Ketoacidosis Following Anti-PD-1 and Interferon α.

Immune checkpoint inhibitor (ICI) therapies are now first-line therapy for many advanced malignancies in adults, with emerging use in children. With increasing ICI use, prompt recognition and optimal management of ICI-associated immune-related adverse events (IRAEs) are critical. Nearly 60% of ICI-treated adults develop IRAEs, which commonly manifest as autoimmune skin, gastrointestinal, and endocrine disease and can be life-threatening. The incidence, presentation, and disease course of spontaneous autoimmune diseases differ between adults and children, but the pattern of pediatric IRAEs is currently unclear. We report a case of a pediatric patient presenting with new onset autoimmune diabetes mellitus and diabetic ketoacidosis during ICI treatment of fibrolamellar hepatocellular carcinoma (FLC). Distinct from spontaneous type 1 diabetes mellitus (T1DM), this patient progressed rapidly and was negative for known ß cell autoantibodies. Additionally, the patient was positive for 21-hydroxylase autoantibodies, suggesting development of concomitant adrenal autoimmunity. Current guidelines for the management of IRAEs in adults may not be appropriate for the management of pediatric patients, who may have different autoimmune risks in a developmental context.

Supraventricular tachycardia associated with severe diabetic ketoacidosis in a child with new-onset type 1 diabetes mellitus.

Diabetic ketoacidosis is one of the most serious and common complications of diabetes, with between 15 and 70% of new-onset type 1 diabetes mellitus worldwide presented with diabetic ketoacidosis. Supraventricular tachycardia, however, is an infrequent complication of diabetic ketoacidosis. We present the case of a child with a new-onset type 1 diabetes mellitus with supraventricular tachycardia as a complication of paediatric diabetic ketoacidosis. The patient received intravenous fluid resuscitation, insulin, and potassium supplementation and subsequently developed stable supraventricular tachycardia initially, confirmed on a 12-lead electrocardiogram despite a structurally normal heart and normal electrolytes. Vagal manoeuvers failed to achieve sinus rhythm. The patient went into respiratory distress and was intubated, for mechanical ventilation. She received one dose of adenosine with successful conversion to sinus rhythm and a heart rate decreased from 200 to 140 beats per minutes. We conclude that supraventricular tachycardia can occur as a complication of diabetic ketoacidosis, including in new-onset type 1 diabetes mellitus. Furthermore, a combination of acidosis, potassium derangement, falling magnesium, and phosphate levels may have precipitated the event. Here, we report a case of supraventricular tachycardia as a complication of paediatric diabetic ketoacidosis.

Effects of nutritional support combined with insulin therapy on serum proteins, inflammatory factors, pentraxin-3, and serum amylase levels in patients with diabetic ketoacidosis complicated with acute pancreatitis.

ABSTRACT: To explore the effects of nutritional support combined with insulin therapy on serum protein, procalcitonin (PCT), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), pentraxin-3 (PTX-3), and serum amylase (AMS) levels in patients with diabetic ketoacidosis complicated with acute pancreatitis.A total of 64 patients with diabetic ketoacidosis complicated with acute pancreatitis admitted to our hospital from January 2018 to February 2019 were enrolled in this prospective study. They were divided into the study group and the control group according to the random number table method, with 32 patients in each group. Patients in the study group were given nutritional support combined with insulin therapy, and patients in the control group were given insulin therapy.There were no significant differences in general data including age, gender, body mass index, course and type of diabetes, acute physiology and chronic health evaluation II, RANSON, CT grades between the 2 groups before treatment (all P > .05). After 7 days of treatment, the clinical efficacy of the study group was significantly higher than that of the control group (study group vs control group, 94.44% vs 75.00%, P < .05). After 7 days of treatment, the levels of prealbumin and albumin in the study group were significantly higher than those in the control group (P < .05). After 7 days of treatment, the levels of PCT, CRP, TNF-α, PTX-3, and AMS in the 2 groups were significantly lower than those before treatment (P < .05), and the levels of PCT, CRP, TNF-α, PTX-3, and AMS in the study group were significantly lower than those in the control group. After 7 days of treatment, the levels of IgG, IgM, and IgA in the 2 groups were significantly higher than those before treatment, and the levels of IgG, IgM, and IgA in the study group were significantly higher than those in the control group (P < .05).Nutritional support combined with insulin is obviously effective in the treatment of diabetic ketoacidosis complicated with acute pancreatitis, which can improve serum protein levels, reduce inflammatory response, improve immune function, and is worthy of clinical application.

Severe bradycardia caused by diabetic ketoacidosis.

Atrial standstill is an uncommon but serious clinical entity that is often unrecognised in the clinical setting. Its diagnosis and treatment should be swift as malignant arrhythmias and thromboembolic complications can arise. We present a 79-year-old man brought to our emergency department with acute confusion, heart failure and severe bradycardia in the context of diabetic ketoacidosis, and discuss the diagnosis and management of this arrhythmic condition.

Pediatric Emergency Medicine Didactics and Simulation (PEMDAS): Pediatric Diabetic Ketoacidosis.

Introduction: Diabetic ketoacidosis (DKA) is a life-threatening illness which classically presents with polyuria, polydipsia, and polyphagia that can rapidly progress to severe dehydration and altered mental status from cerebral edema. Younger patients may present with subtle or atypical symptoms that are critical to recognize and emergently act upon. Such patients are often cared for by teams in the emergency department (ED) requiring multidisciplinary collaboration. Methods: This simulation case was designed for pediatric emergency medicine fellows and residents. The case was a 14-month-old male who presented to the ED with respiratory distress and dehydration. The team was required to perform an assessment, manage airway, breathing and circulation, and recognize and initiate treatment for DKA including judicious fluid administration and an insulin infusion. The patient developed altered mental status with signs of cerebral edema requiring the initiation of cerebral protection strategies. We created a debriefing guide and a participant evaluation form. Results: Forty-two participants completed this simulation across seven institutions including attendings, residents, fellows, and nurses. The scenario was rated by participants on a 5-point Likert scale and was generally well received (M = 5.0). Participants rated the simulation case as effective in teaching how to recognize (M = 4.8) and manage (M = 4.5) DKA with cerebral edema in a pediatric patient. Discussion: This simulation represents a resource for learners in the pediatric ED in the recognition and management of a toddler with DKA and can be adapted to learners at all levels and tailored to various learning environments.

Neurological Complications of Endocrine Emergencies.

PURPOSE OF REVIEW: Endocrine disorders are the result of insufficient or excessive hormonal production. The clinical course is long, and the manifestations are nonspecific due to the systemic effect of hormones across many organs and systems including the nervous system. This is a narrative review of the recent evidence of the diagnosis and treatment approach of these medical and neurological emergencies. RECENT FINDINGS: With the possible exception of diabetic ketoacidosis, hyperosmolar hyperglycemic state, and hypoglycemia, endocrinological emergencies are complex, uncommon yet life-threatening conditions with protean and often nonspecific early clinical signs. They frequently are the first manifestation of the endocrine derangement. The systemic effects of hormones extend to the nervous system and as such, these conditions can present with neurological complications manifested, in most cases, by a diffuse dysfunction of the brain in the form of encephalopathy, delirium, seizures, and coma; or specific and peculiar syndromes such as hemichorea, hemiballism, and epilepsia partialis continua. The severity of these conditions often necessitates management in the intensive care unit requiring substantial supportive care in addition to specific targeted therapy to correct the hormonal metabolic abnormalities while at the same time blocking hormonal activity, in cases of excessive function, or supplementing hormonal deficiencies. Endocrine emergencies and their neurological complications are infrequent. The major challenge for most is early recognition. Their morbidity and mortality are high and their diagnosis requires high index of suspicion. The neurological complication most often improves with the correction of the metabolic derangement and their acuity and severity require admission to the intensive care unit.

Features and long-term outcomes of patients hospitalized for diabetic ketoacidosis.

BACKGROUND: Diabetic ketoacidosis (DKA) is an acute metabolic complication characterized by hyperglycaemia, ketones in blood or urine, and acidosis. OBJECTIVE: The aim of this study was to characterize features of patients hospitalized for DKA, to identify triggers for DKA and to evaluate the long-term effects of DKA on glycaemic control, complications of diabetes, re-hospitalizations, and mortality. METHODS: Historical prospectively collected data of patients hospitalized to medical wards for DKA between 2011 and 2017. Data regarding comorbidities, mortality, triggers, and re-hospitalizations for DKA were also collected. RESULTS: The cohort consisted of 160 patients (mean age 38 ± 18 years, 43% male). One fifth of the patients (34 patients, 21%) were newly diagnosed with diabetes, and DKA was their first presentation of the disease. Among the 126 patients with pre-existing diabetes, the common identified triggers for DKA were poor compliance to treatment (22%) and infectious diseases (18%). During over 7 years of follow-up, mortality rate was 9% (15 patients), and re-hospitalization for DKA rate was 31% (50 patients). Risk factors for re-hospitalization for DKA included young age (OR = 1.02, 95% CI, 1.00-1.04), pre-existing diabetes compared to DKA as the first presentation (OR = 5.4, 95% CI, 1.7-18), and poorer glycaemic control before initial hospitalization (10.5 ± 2.5% vs. 9.4 ± 2.2%; OR = 0.8, 95% CI [0.68-0.96]) and after discharge (10.3 ± 2.4% vs. 9.0 ± 1.9%; OR = 0.73, 95% CI [0.61-0.87]). Laboratory tests during the initial hospitalization, smoking, alcohol, or comorbidities did not increase the risk for re-hospitalization for DKA. CONCLUSIONS: The risk for readmission for DKA is higher for young patients with long duration of diabetes, poor compliance of insulin treatment and poorly controlled diabetes.

Kayexalate-induced colitis and rectal stricture.

A 57-year-old man underwent emergency laparoscopic loop colostomy for acute recto-sigmoid obstruction. He was hospitalised 2 months previously, at another facility for diabetic ketoacidosis (DKA) and hyperkalaemia. He had no gastrointestinal symptoms prior to the hospitalisation. Both surgical exploration and intraoperative sigmoidoscopy showed ulcerations of sigmoid colon and proximal rectum with a pinhole stricture in mid-rectum. After ruling out all aetiologies, and due to persistence of the colonic ulcerations on a follow-up colonoscopy, a diagnosis of Crohn's colitis was made, and the patient was started on infliximab and 6-mercaptopurine (6-MP). Six months later, on rereview of all the biopsies, it was noted that a key element of presence of crystals suggestive of Kayexalate on the initial colorectal biopsies was missed. It was later found out that the patient had received rectal Kayexalate for treatment of DKA at the other facility. Hence, infliximab and 6-MP were both discontinued. All the colonoscopies, following the discontinuation of the medications, showed complete resolution of colitis but persistence of the mid-rectum stricture. This was treated with a fully covered metal stent for 12 weeks with only partial improvement of the stricture. He was hence referred for ultra-low anterior resection of rectum and take down of colostomy.