Diabetic Ketoacidosis and SGLT-2 Inhibitors

Diabetic ketoacidosis is a condition that is becoming more common in patients with type 1 diabetes who are prescribed an SGLT-2 inhibitor. This is due to patients inappropriately reducing their insulin dose, which causes them to lose glucose into their urine and not have enough insulin to meet their glucose metabolism needs. In a randomized controlled trial, rates of ketoacidosis-related adverse events were as high as 9% in patients prescribed canagliflozin 300 mg. Therefore, insulin dose reduction in patients with type 1 diabetes taking an SGLT-2 inhibitor should only be carried out with specialist advice, and off-label use is not widely recommended.

Hyperosmolar non-ketotic state is an incorrect diagnosis for this condition, as there is evidence of elevated lactate and metabolic acidosis, and the rise in blood glucose is very modest. The acidosis is not related to SGLT-2 inhibition directly, but due to down titration of insulin dosing. The ketosis is not due to starvation, but glycosuria does create a relative calorie deficit. Acidosis is usually seen in the context of tissue hypoxia/hypoperfusion, but usually in the context of a profound hypotensive episode.

Stroke Assessment and Investigations

Whilst diagnosing a stroke may be straightforward in some cases, it can be challenging in others due to vague symptoms. The FAST screening tool, which stands for Face/Arms/Speech/Time, is a well-known tool used by the general public to identify stroke symptoms. However, medical professionals use a validated tool called the ROSIER score, recommended by the Royal College of Physicians. The ROSIER score assesses loss of consciousness or syncope, seizure activity, and new, acute onset of asymmetric facial, arm, or leg weakness, speech disturbance, or visual field defect. A score of more than zero indicates a likely stroke.

When investigating suspected stroke, a non-contrast CT head scan is the first line radiological investigation. The key question is whether the stroke is ischaemic or haemorrhagic, as this determines the appropriate treatment. Ischaemic strokes may show areas of low density in the grey and white matter of the territory, which may take time to develop. On the other hand, haemorrhagic strokes typically show areas of hyperdense material (blood) surrounded by low density (oedema). It is crucial to determine the type of stroke promptly, given the increasing role of thrombolysis and thrombectomy in acute stroke management. In rare cases, a third pathology such as a tumour may also be detected.

Vertebral Artery Dissection: A Common Cause of Stroke in Young Patients

Vertebral artery dissection is a well-known cause of stroke in patients under the age of 45. It has a mortality rate of 10% during the acute phase and can lead to death due to intracranial dissection, brainstem infarction, or subarachnoid hemorrhage. The causes of vertebral artery dissection include structural defects of the arterial wall, connective tissue disease, trauma, and chiropractic manipulation of the neck.

The typical clinical presentation of vertebral artery dissection is a severe occipital headache followed by focal neurological signs that can be attributed to brainstem or cerebellum ischemia. However, other less likely differential diagnoses of stroke in this age group include focal seizure, migraine with prolonged aura and migraine variants, multiple sclerosis, and conversion disorders.

It is important to recognize vertebral artery dissection as a common cause of stroke in young patients and to consider it in the differential diagnosis of stroke. Early diagnosis and treatment can improve outcomes and prevent mortality.

Acid maltase deficiency, also known as glycogen storage myopathy type 2, has three clinical forms. The adult form is characterized by a gradual weakening of the shoulder, pelvic girdle, and trunk muscles. In some cases, diaphragmatic weakness may be the primary issue, leading to a visit to the Accident and Emergency Department. The differential diagnosis for this condition includes motor neurone disease, myasthenia gravis, and nemaline rod myopathy. Diagnosis is confirmed through muscle biopsy, which reveals vacuolated sarcoplasm containing Periodic acid–Schiff (PAS)-positive diastase digestible material. The glycogen particles are found in aggregates, some of which occupy lysosomal vesicles, indicating that this is a lysosomal disease. Positive ischaemic forearm tests may occur in other forms of glycogen storage disorder, but a normal test result is expected in acid maltase deficiency. The adult form of acid maltase deficiency has a better prognosis than the infantile form, with patients surviving until their 6th or 7th decade.

Management of Malignant Hypercalcaemia

Standard management of malignant hypercalcaemia involves the administration of intravenous fluids followed by an infusion of a bisphosphonate. Pamidronate is the most commonly used bisphosphonate and can restore normocalcaemia in 70-75% of cases at five to seven days. However, its effect may last for only approximately 2 ½ weeks.

Retesting the patient’s calcium level two days after receiving the infusion may be too early to see a response. If the patient has already received the maximum dose of pamidronate, other treatment options must be considered. Steroids have been shown to inhibit osteoclastic activity, but their effect may take several days to manifest. Calcitonin is relatively non-toxic and can lower serum calcium levels within four hours, but it is rarely effective in cases where bisphosphonates have failed. Its frequent administration and short-lived effect make it an uncommon choice in the palliative care setting.

It is crucial to maintain adequate hydration to facilitate the correction of the calcium level. Bloods should be rechecked five to seven days post-infusion of pamidronate to assess the maximal effect of the drug. Bisphosphonates are generally poorly absorbed orally and have a much slower onset of action, making them unsuitable for the rapid correction of dangerously high calcium levels. Therefore, prompt and appropriate management of malignant hypercalcaemia is essential to prevent serious complications.

Understanding Renal Replacement Therapy

Chronic kidney disease affects a significant portion of the population, with around 10% of those with CKD developing renal failure. For patients with renal failure, the options are either renal replacement therapy (RRT) or conservative management. RRT involves taking over the physiology of the kidneys, and there are several types available, including haemodialysis, peritoneal dialysis, and renal transplant. The decision about which RRT option to choose should be made jointly by the patient and their healthcare team, taking into account various factors such as predicted quality of life, life expectancy, patient preference, and co-existing medical conditions.

Haemodialysis is the most common form of RRT, where the blood is filtered through a dialysis machine in the hospital. Peritoneal dialysis is another option where the filtration occurs within the patient’s abdomen. Renal transplantation involves receiving a kidney from either a live or deceased donor. Each option has its own set of complications, such as site infection, peritonitis, DVT/PE, and more.

Without adequate RRT, the symptoms of renal failure can be severe, including breathlessness, fatigue, insomnia, pruritus, poor appetite, swelling, weakness, weight gain/loss, abdominal cramps, nausea, muscle cramps, headaches, cognitive impairment, anxiety, depression, and sexual dysfunction. It is crucial for patients and their healthcare team to carefully consider the best RRT option for their individual needs and circumstances.

SVCO, a medical emergency commonly seen in lung cancer and lymphomas, requires immediate treatment with steroids and proton pump inhibitors for gastric protection. Other treatment options include stent insertion, radiotherapy, and chemotherapy.

However, in the case of this patient who cannot lie flat, radiotherapy may not be a suitable option as it can cause acute swelling before long-term shrinkage. As lymphomas are highly responsive to chemotherapy, second-line chemotherapy should be considered to shrink the mediastinal disease.

Stent insertion is the most effective immediate treatment for relieving SVCO, but it is important to check and optimize the patient’s haemoglobin, platelets, and clotting. It is also important to note that stents can still become blocked in patients with end-stage disease.

Understanding Superior Vena Cava Obstruction

Superior vena cava obstruction is a medical emergency that occurs when the superior vena cava, a large vein that carries blood from the upper body to the heart, is compressed. This condition is commonly associated with lung cancer, but it can also be caused by other malignancies, aortic aneurysm, mediastinal fibrosis, goitre, and SVC thrombosis. The most common symptom of SVC obstruction is dyspnoea, but patients may also experience swelling of the face, neck, and arms, headache, visual disturbance, and pulseless jugular venous distension.

The management of SVC obstruction depends on the underlying cause and the patient’s individual circumstances. Endovascular stenting is often the preferred treatment to relieve symptoms, but certain malignancies may require radical chemotherapy or chemo-radiotherapy instead. Glucocorticoids may also be given, although the evidence supporting their use is weak. It is important to seek advice from an oncology team to determine the best course of action for each patient.

Lutembacher Syndrome and Eisenmenger’s Syndrome: A Cardiac Explanation

Lutembacher syndrome is a rare cardiac condition characterized by both mitral stenosis and atrial septal defect (ASD). It can occur congenitally or as a result of rheumatic fever. Women are more likely to develop this syndrome due to the higher incidence of congenital ASD. Symptoms typically present in later life and include fatigue and atrial fibrillation. Early surgery is recommended to prevent the development of Eisenmenger syndrome, which leads to cyanotic heart disease.

Eisenmenger’s syndrome occurs when a long-standing left-to-right shunt reverses to a right-to-left cardiac shunt, resulting in cyanotic heart disease.

When evaluating a patient with a mid-diastolic tricuspid murmur, isolated mitral stenosis and isolated ASD can be ruled out due to the presence of the mitral murmur. Tricuspid regurgitation is also unlikely as there are no other associated symptoms. Lutembacher syndrome with increased tricuspid flow is the most likely diagnosis.

Differential Diagnosis for a Patient with Fevers and Malaise

When a patient presents with fevers and malaise, it can be difficult to determine the underlying cause. In the case of chikungunya, the most common symptoms include fevers and malaise, which can be easily confused with dengue in the early stages of the disease. However, two significant differences may help distinguish between them. Firstly, rashes appear on the torso and arms in chikungunya, while in dengue, they appear on the arms and face. Secondly, joint pain in chikungunya is experienced in the hands, wrists, feet, and legs, while in dengue, it is experienced in the shoulders and knees.

Dengue is an important differential diagnosis, as it is also a mosquito-borne tropical disease that can cause similar symptoms, including a high fever, headache, vomiting, joint pains, and a characteristic skin rash. It may be indistinguishable from chikungunya early in the disease.

Other potential diagnoses to consider include rheumatoid arthritis, which is unlikely given the acute presentation and lack of fever or rash, and malaria, which should be considered in any patient with fevers and non-specific symptoms travelling from an endemic area. Malaria may present with fevers, malaise, diaphoresis, headaches, cough, and arthralgia. However, in our patient’s case, chikungunya is more likely as it commonly presents with joint pains and rash.

Chikungunya: A Mosquito-Borne Alphavirus Disease

Chikungunya is a disease caused by infected mosquitoes that is prevalent in Africa, Asia, and the Indian subcontinent. Although it has been rare in Southern Europe, there have been a few reported cases in recent years. The first reported case was in Tanzania.

The disease is characterized by severe joint pain and a sudden onset of high fever. Other symptoms include muscle aches, headaches, and fatigue, which are similar to those of dengue fever. However, chikungunya tends to cause more joint pain, which can be debilitating. A rash may also develop, and joint swelling is common.

There is no specific treatment for chikungunya, and relief of symptoms is the only available option.

Understanding Anti-Phospholipid Syndrome

Anti-phospholipid syndrome, also known as Hughes syndrome, is a condition characterized by venous and arterial thromboembolism, recurrent first trimester miscarriages, livedo reticularis, chorea, and Libman–Sacks endocarditis. It is diagnosed when positive anti-cardiolipin antibodies or a lupus anticoagulant are detected on two separate occasions, separated by at least 6 weeks.

Lifelong anticoagulation with warfarin is the standard management for this condition, with a target international normalized ratio (INR) of 2-3. A normal activated partial thromboplastin time (APTT) does not rule out the presence of a lupus anticoagulant, and phospholipid-dependent measures of clotting, such as the dilute Russell viper venom time, should be assessed to rule this out.

Other skin conditions that may be confused with livedo reticularis include erythema ab igne, erythema chronicum migrans, erythroderma, and erythema multiforme. It is important to differentiate these conditions to ensure proper diagnosis and management.