Early Time Courses of Recurrent Venous Thromboembolism and Bleeding during Apixaban or Dalteparin Therapy for Patients with Cancer.

BACKGROUND: In patients with acute venous thromboembolism (VTE), the rates of recurrence and major bleeding are highest during the first weeks of anticoagulation. The CARAVAGGIO trial demonstrated noninferiority of apixaban to dalteparin for treatment of cancer-associated VTE without an increased risk of major bleeding. We compared the early time course of VTE recurrence and major bleeding events of apixaban compared with dalteparin at 7, 30, and 90 days of treatment in patients with cancer-associated VTE. METHODS: The study design of the CARAVAGGIO trial has been described. Eligible patients were randomly assigned to receive monotherapy with either apixaban or dalteparin for 6 months. The primary efficacy outcome was the incidence of objectively confirmed recurrent VTE. The primary safety outcome was major bleeding. RESULTS: In 1,155 patients, recurrent VTE after 7, 30, and 90 days occurred in 6 (1%), 15 (2.6%), and 27 (4.7%) patients in the apixaban arm versus 5 (0.9%), 20 (3.5%), and 36 (6.2%) patients respectively in the dalteparin arm. By day 7, 30, and 90, major bleeding events had occurred in 3 (0.5%), 9 (1.6%), and 16 (2.8%) patients in the apixaban group versus 5 (0.9%), 11 (1.9%), and 17 (2.9%) patients in the dalteparin group. CONCLUSION: The frequencies of recurrent VTE and major bleeding events at 7, 30, and 90 days of apixaban compared with dalteparin were similar in patients with cancer-associated VTE. This supports the use of apixaban for the initiation and early phase of anticoagulant therapy in cancer-associated VTE.

Subacute Thyroiditis Causing Fever of Unknown Origin: A Reminder of the Uncommon Cause.

Subacute thyroiditis (SAT) is a transient inflammation of the thyroid gland that often occurs following a viral infection. It is an infrequent cause of fever of unknown origin (FUO). We present a 46-year-old gentleman who presented with two weeks of fever and some non-specific left-sided neck pain. His initial investigations and microbiological workup were unremarkable. He did not report any hyperthyroid symptoms. A computed tomography of the neck, chest, abdomen, and pelvis showed a heterogeneous appearance of his thyroid gland. Thyroid function was then performed, and it showed primary hyperthyroidism. His thyroid autoantibodies were negative. Ultrasonography of his thyroid showed features consistent with thyroiditis. He was treated with a course of oral steroids. His fever lysed. His thyroid function turned from a primary hyperthyroid pattern to subclinical hypothyroidism. His anti-thyroglobulin antibody level remained elevated after the steroid treatment. Our case highlights that SAT is an uncommon cause of FUO in patients without specific localizing symptoms. It can present without overt hyperthyroid clinical features. Steroid treatment is useful. There may be value in monitoring the anti-thyroid antibodies in SAT's management.

Nitrous oxide misuse: a clue not to be missed in young patients with venous thromboembolism.

A 27-year-old man presented with altered mental status and unilateral right lower limb swelling. Brain imaging and cerebrospinal fluid analysis were unremarkable. He reported history of nitrous oxide misuse after he recovered from his delirium. The diagnosis of drug induced psychosis was made. The right lower limb swelling was found to be due to extensive deep vein thrombosis. In another case, a 21-year-old woman presented with headache, vomiting and dipoplia. Brain imaging showed extensive cerebral venous sinus thrombosis. She also misused nitrous oxide. Both cases had low-normal vitamin B12 and elevated methylmalonic acid, consistent with nitrous oxide misuse. The woman was found to have elevated homocysteine because of functional vitamin B12 deficiency. Homocysteine was not measured in the man. Raised homocysteine is associated with increased thrombosis risk. Fourteen cases of nitrous oxide misuse associated arterial and venous thrombosis have been reported. These two cases highlighted the importance of inquiring about recreational drug use in young patients who presented with apparently unprovoked venous thromboembolism.

"Lockdown-thrombosis"-an unexpected problem of the COVID-19 pandemic?

Seated immobility thromboembolism syndrome (SIT) is the association of prolonged seated immobility with increased risk of venous thromboembolism (VTE). The advent of COVID-19 resulted in implementation of lockdowns to curb its spread. This resulted in compulsory work from home and minimization of outdoor activities. Consequently, this would have likely led to increased prolonged sitting and reduced mobility. Few case reports and studies have observed an increase in VTE incidence during the lockdown period. We likewise performed a clinical audit of our weekly thrombosis clinic cases and revealed three cases of VTE associated with prolonged sitting during Singapore's COVID-19 lockdown. Notably, all had other minor VTE risk factors in addition to prolonged sitting. All cases had intermediate-high risk pulmonary embolism and were given extended anticoagulation. With the pandemic still ongoing, periodic lockdown and quarantine measures may continue to be imposed. While the overall VTE risk conferred by prolonged seated immobility associated with lockdown measures is likely to be small, this risk can be easily mitigated and possibly prevented by simply staying mobile.

Myocardial injury in non-cardiac surgery: complexities and challenges.

The term MINS (myocardial injury after non-cardiac surgery) was coined to broadly describe perioperative troponin elevation that is deemed to be due to a cardiac cause. However, this term is commonly used in literature to represent cases that do not fulfil the criteria for the diagnosis of myocardial infarction. Asymptomatic troponin elevation that does not fulfil the criteria for acute coronary syndrome in the perioperative setting has been shown to be associated with increased mortality. The discovery of MINS presents new opportunities to improve outcomes for surgical patients. Unfortunately, awareness of MINS among practitioners remains low and implementation of perioperative troponin monitoring is poor. Given its significance, the detection, management and prevention of MINS should not be overlooked.

Osteonecrosis of the Jaw and Concomitant Atypical Femoral Fractures with Bisphosphonates: A Comprehensive Literature Review.

Bisphosphonates are the first line of treatment for osteoporosis. Complications of bisphosphonates, such as osteonecrosis of the jaw (ONJ) and atypical femoral fractures (AFF), have been reported in the medical literature. Concomitant occurrence of both of these complications is very rare. In this review article, we will discuss the etiology, pathogenesis, and clinical studies, as well as case studies and their management per the latest clinical guidelines.

Bilateral Basal Ganglia Calcification: Fahr's Disease.

Fahr's disease/syndrome is a condition defined as bilateral striato-pallido-dentate calcinosis, a neurodegenerative disease with radiological findings of symmetrical and bilateral idiopathic calcifications of the cerebellum, periventricular white matter, and basal ganglia. Clinical correlation with radiological and a calcium metabolism panel is crucial in differentiating between Fahr's disease and Fahr's syndrome. We describe a case that presented with the clinical feature of a cerebrovascular accident and had an incidental radiological finding of Fahr syndrome. The clinical features, laboratory investigations, and clinical management of Fahr's disease/syndrome will be discussed in detail in the article.

A case of Lemierre-like Syndrome: internal jugular vein thrombosis secondary to Staphylococcus aureus sternoclavicular joint septic arthritis.

Lemierre syndrome is the internal jugular vein (IJV) suppurative thrombophlebitis, usually secondary to oropharyngeal infection. Staphylococcus aureus is an emerging responsible pathogen. We report a unique case of IJV thrombosis secondary to methicillin-susceptible S. aureus sternoclavicular joint septic arthritis. We review the existing literature on Lemierre syndrome: its various manifestations, causative pathogens, treatment and management.

A case of mesenteric panniculitis associated with metastatic poorly differentiated cancer of unknown primary site.

Mesenteric panniculitis is the inflammation of intestinal mesentery. It may be associated with malignancy. We present a case of mesenteric panniculitis that manifested as unresolved fever which subsequently was found to be due to poorly differentiated metastatic carcinoma.

An Unusual Presentation of Parvimonas micra Infective Endocarditis.

Parvimonas micra has been identified as a prominent oral pathogen. This organism has been implicated in periodontal, soft tissue and bone infections. It causes a subacute presentation with high morbidity. We present a case of severe infective endocarditis caused by Parvimonas micra requiring valvular surgery despite appropriate antibiotics. To our knowledge, this is the second case report of Parvimonas micra infective endocarditis since its reclassification in 2006.

Reset Osmostat: A Challenging Case of Hyponatremia.

Hyponatremia is the most common electrolyte abnormality seen in hospitalised patients with up to 15-20% of patients having a sodium level of less than 135 mmol/L (Reddy and Mooradian, 2009). Cases of hyponatremia were first described in the 1950s (George et al., 1955). As the differential diagnosis for hyponatremia is broad, a systematic and logical approach is needed to identify the cause. We describe a case of a 30-year-old gentleman who was found to have chronic hyponatremia. After a thorough workup, he was diagnosed to have reset osmostat. Reset osmostat is an uncommon and under recognised cause of hyponatremia which does not require any treatment. This diagnosis needs to be considered when the hyponatremia workup suggests SIADH, but the hyponatremia is not amenable to fluid restriction, salt or urea supplementation, and diuretic treatment.

Appendicitis in non-typhoidal salmonella bacteraemia.

Salmonella typhi and paratyphi infections can manifest as acute abdomen due to intestinal perforations, salpingitis and rarely appendicitis. Non-typhoidal salmonella infection that usually only causes self-limiting gastroenteritis, is rarely associated with appendicitis. We present the case of a 78-year-old gentleman with Salmonella bacteraemia complicated by acute appendicitis. He was treated conservatively due to multiple comorbidities. His condition improved after completion of 2 weeks of antibiotics guided by the blood and stool culture results. Appendicitis is a rare but important complication to consider in Salmonella bacteraemia. More research needs to be done with regards to the clinical course of Salmonella related appendicitis.

A Case of Parvovirus-Related Haemophagocytic Lymphohistiocytosis in a Patient with HbH Disease.

Hemophagocytic lymphohistiocytosis (HLH) is rare and life-threatening medical emergency. Parvovirus infection is rarely associated with HLH. We report a case of parvovirus-related HLH in a patient with alpha thalassaemia (HbH disease). The patient responded well to a course of dexamethasone without the need of etoposide. Based on our literature search, this is the first case of parvovirus related HLH in a patient with HbH disease in the medical literature.

Preliminary Investigations Showing Venous Thromboembolism Recurrence in Patients with Residual Venous Obstruction in Singaporean Population.

This study aims to determine the association of residual venous obstruction (RVO) with recurrent venous thromboembolism (VTE). A retrospective cohort study was conducted determining if RVO on ultrasonography is associated with recurrent VTE in a Singaporean population. The subjects were identified from the Vascular Diagnostic Laboratory patients' record of Tan Tock Seng Hospital (TTSH), Singapore between 2008 and 2013. All the patients included had RVO after 3 months of anticoagulation. Data such as age, gender, race, thrombus location, etiology, history of malignancy, thrombophilia screen, treatment duration, and follow-up were recorded for analysis. Statistical analysis was performed using Stata/SE 13.1 (StataCorp LLC). The study was approved by the National Healthcare Group Domain Specific Review Board (DSRB), Singapore. Out of the 34 patients who had RVO, 6 (17.6%) developed VTE recurrence. Patients were treated with anticoagulation for a mean time of 24.5 months. The mean follow-up time for VTE recurrence was 25.4 months. Out of the six patients who had VTE recurrence, one had common iliac vein involvement, four had superficial femoral vein and common femoral vein involvement, zero had popliteal vein involvement, and one had calf veins involvement. There was a significant association between thrombophilia ( p = 0.0195) and malignancy ( p = 0.020) at inclusion with the risk of recurrent VTE. The presence of RVO after 3 months of anticoagulation is likely to increase the risk of VTE recurrence. Larger studies with RVO are needed to evaluate if there is an increased risk of VTE recurrence in the Asian population.