METHODS: This narrative review examines various septic markers to identify the appropriate tools for diagnosis and to distinguish between diabetic ketoacidosis with and without infection. Electronic databases were searched using the Google engine with the keywords "Diabetes Mellitus", "Diabetic Ketoacidosis", "Infection with Diabetic Ketoacidosis", "biomarkers for infection in Diabetic Ketoacidosis", "Procalcitonin", "Inflammatory cytokines in DKA", "Lactic acidosis in DKA", and "White blood cell in infection in DKA".
RESULTS: This narrative review article presents the options for diagnosis and also aims to create awareness regarding the gravity of diabetic ketoacidosis with infection and emphasizes the importance of early diagnosis for appropriate management. Diabetes mellitus is a clinical condition that may lead to several acute and chronic complications. Acute diabetic ketoacidosis is a life-threatening condition in which an excess production of ketone bodies results in acidosis and hypovolemia. Infection is one of the most common triggers of diabetic ketoacidosis. When bacterial infection is present along with diabetic ketoacidosis, the mortality rate is even higher than for patients with diabetic ketoacidosis without infection. The symptoms and biomarkers of diabetic ketoacidosis are similar to that of infection, like fever, C reactive protein, and white blood cell count, since both create an environment of systemic inflammation. It is also essential to distinguish between the presence and absence of bacterial infection to ensure the appropriate use of antibiotics and prevent antimicrobial resistance. A bacterial culture report is confirmatory for the existence of bacterial infection, but this may take up to 24 h. Diagnosis needs to be performed approximately in the emergency room upon admission since there is a need for immediate management. Therefore, researching the possible diagnostic tools for the presence of infection in diabetic ketoacidosis patients is of great importance. Several of such biomarkers have been discussed in this research work.
METHODS: STORM-C-1 is a two-stage, open-label, phase 2/3 single-arm clinical trial in six public academic and non-academic centres in Malaysia and four public academic and non-academic centres in Thailand. Patients with HCV with compensated cirrhosis (Metavir F4 and Child-Turcotte-Pugh class A) or without cirrhosis (Metavir F0-3) aged 18-69 years were eligible to participate, regardless of HCV genotype, HIV infection status, previous interferon-based HCV treatment, or source of HCV infection. Once daily ravidasvir (200 mg) and sofosbuvir (400 mg) were prescribed for 12 weeks for patients without cirrhosis and for 24 weeks for those with cirrhosis. The primary endpoint was sustained virological response at 12 weeks after treatment (SVR12; defined as HCV RNA <12 IU/mL in Thailand and HCV RNA <15 IU/mL in Malaysia at 12 weeks after the end of treatment). This trial is registered with ClinicalTrials.gov, number NCT02961426, and the National Medical Research Register of Malaysia, NMRR-16-747-29183.
FINDINGS: Between Sept 14, 2016, and June 5, 2017, 301 patients were enrolled in stage one of STORM-C-1. 98 (33%) patients had genotype 1a infection, 27 (9%) had genotype 1b infection, two (1%) had genotype 2 infection, 158 (52%) had genotype 3 infection, and 16 (5%) had genotype 6 infection. 81 (27%) patients had compensated cirrhosis, 90 (30%) had HIV co-infection, and 99 (33%) had received previous interferon-based treatment. The most common treatment-emergent adverse events were pyrexia (35 [12%]), cough (26 [9%]), upper respiratory tract infection (23 [8%]), and headache (20 [7%]). There were no deaths or treatment discontinuations due to serious adverse events related to study drugs. Of the 300 patients included in the full analysis set, 291 (97%; 95% CI 94-99) had SVR12. Of note, SVR12 was reported in 78 (96%) of 81 patients with cirrhosis and 153 (97%) of 158 patients with genotype 3 infection, including 51 (96%) of 53 patients with cirrhosis. There was no difference in SVR12 rates by HIV co-infection or previous interferon treatment.
INTERPRETATION: In this first stage, ravidasvir plus sofosbuvir was effective and well tolerated in this diverse adult population of patients with chronic HCV infection. Ravidasvir plus sofosbuvir has the potential to provide an additional affordable, simple, and efficacious public health tool for large-scale implementation to eliminate HCV as a cause of morbidity and mortality.
FUNDING: National Science and Technology Development Agency, Thailand; Department of Disease Control, Ministry of Public Health, Thailand; Ministry of Health, Malaysia; UK Aid; Médecins Sans Frontières (MSF); MSF Transformational Investment Capacity; FIND; Pharmaniaga; Starr International Foundation; Foundation for Art, Research, Partnership and Education; and the Swiss Agency for Development and Cooperation.