Clinico-Etiological Spectrum and Outcome in Patients With Septic Acute Kidney Injury and Its Comparison With Non-septic Acute Kidney Injury: A Hospital-Based Prospective Study Conducted in a Tertiary Care Hospital in North India.

Background Acute kidney injury (AKI) is a heterogenous syndrome defined by the impairment of kidney filtration and excretory function over days to weeks, resulting in the retention of nitrogenous and other waste products normally cleared by the kidneys. In addition, AKI is frequently recognized to be associated with sepsis and contributes to an unfavorable outcome in sepsis. This study was undertaken to study and compare the etiology and clinical profile of patients with septic and non-septic AKI and to study and compare the outcome in both groups. Materials and methods This is a prospective, observational, and comparative study with a total sample size of 200 patients selected randomly having sustained an acute kidney injury. Data was collected, recorded, analyzed, and compared for two groups of patients with septic and non-septic AKI. Results A total of 200 cases of AKI were enrolled, out of which 120 (60%) were due to non-septic etiology and 80 (40%) were of septic etiology. Urosepsis (37.5%) due to various urinary tract infections including pyelonephritis and chest sepsis (18.75%) including community-acquired pneumonia (CAP) and aspiration pneumonia were the predominant causes of sepsis. AKI secondary to nephrotoxic agents (27.5%) was the commonest cause in the non-septic group, followed by glomerulonephritis (13.3%), vitamin D intoxication-related hypercalcemia (12.5%), acute gastroenteritis (10.8%), etc. Patients of septic AKI had a significantly higher mean of maximum urea and creatinine than their non-septic AKI counterparts. In addition to having an increased duration of hospital stay, mortality was significantly higher in patients with septic AKI (27.5%) than in patients with non-septic AKI (4.1%). However, sepsis had no effect on renal functions, measured by urea and creatinine, at discharge. In patients with AKI, certain factors were found to increase the risk of mortality. These factors include being over 65 years old, needing mechanical ventilation or vasopressors, requiring renal replacement therapy (RRT), and having multiorgan dysfunction syndrome (MODS), septic shock, or acute coronary syndrome (ACS). However, pre-existing conditions such as diabetes, hypertension, malignancy, previous stroke, chronic kidney disease (CKD), and chronic liver disease (CLD) did not affect the overall mortality risk. Conclusion In the septic AKI group, urosepsis was the most frequent etiology of AKI, while the most frequent etiology of AKI in the non-septic group was nephrotoxin exposure. Patients with septic AKI had considerably longer hospital stays and greater in-hospital mortality rates than patients with non-septic AKI. The renal functions as determined by urea and creatinine at discharge were unaffected by sepsis. Finally, death was significantly impacted by age of >65 years, the necessity for mechanical ventilation, the use of vasopressors and RRT, and the presence of MODS, septic shock, and ACS.

Correlation Between Serum Tumor Necrosis Factor-Alpha (TNF-α) and Clinical Severity of Tuberculosis: A Hospital-Based Study.

AIM: The main aim of this study was to assess the correlation between serum tumor necrosis factor-alpha (TNF-α) levels the and clinical severity of tuberculosis. METHODS: This was a hospital-based case-control prospective study and was conducted at the Sher-i-Kashmir Institute of Medical Sciences, a tertiary care hospital in the northern part of India, from May 2016 to May 2018. The subjects were recruited in the study considering inclusion and exclusion criteria. All patients with pulmonary tuberculosis as well as patients with extrapulmonary tuberculosis were included as subjects and a clinical severity score based on anemia, weight loss, presence of hypoxia, and radiological features was calculated and compared with TNF-α levels. Age- and sex-matched healthy individuals were recruited as controls. RESULTS: A total of 75 subjects comprising 50 cases and 25 controls were taken for the study. There were 34 (68.0%) patients with elevated TNF-α levels while only 16 (32.0%) patients had normal TNF-α levels. And, TNF-α levels were normal in 21 (84%) control subjects as compared to tuberculosis (TB) patients. Such difference in serum TNF-α levels between cases and controls was statistically significant (p<0.05). The mean serum TNF-α level in TB cases was 1265.63 pg/mL, while the mean serum TNF-α level in controls was 312.06 pg/mL. The difference in serum TNF-α levels between the two groups was statistically significant (p<0.01). We observed a significant increase in serum TNF-α levels with the increase in clinical severity score. CONCLUSION: Serum TNF-α levels were significantly associated with increased severity of TB.

Hetero-Multivalent Targeted Liposomal Drug Delivery to Treat Pseudomonas aeruginosa Infections.

Pseudomonas aeruginosa is the leading nosocomial and community-acquired pathogen causing a plethora of acute and chronic infections. The Centers for Disease Control and Prevention has designated multidrug-resistant isolates of P. aeruginosa as a serious threat. A novel delivery vehicle capable of specifically targeting  P. aeruginosa, and encapsulating antimicrobials, may address the challenges associated with these infections. We have developed hetero-multivalent targeted liposomes functionalized with host cell glycans to increase the delivery of antibiotics to the site of infection. Previously, we have demonstrated that compared with monovalent liposomes, these hetero-multivalent liposomes bind with higher affinity to P. aeruginosa. Here, compared with nontargeted liposomes, we have shown that greater numbers of targeted liposomes are found in the circulation, as well as at the site of P. aeruginosa (PAO1) infection in the thighs of CD-1 mice. No significant difference was found in the uptake of targeted, nontargeted, and PEGylated liposomes by J774.A1 macrophages. Ciprofloxacin-loaded liposomes were formulated and characterized for size, encapsulation, loading, and drug release. In vitro antimicrobial efficacy was assessed using CLSI broth microdilution assays and time-kill kinetics. Lastly, PAO1-inoculated mice treated with ciprofloxacin-loaded, hetero-multivalent targeted liposomes survived longer than mice treated with ciprofloxacin-loaded, monovalent targeted, or nontargeted liposomes and free ciprofloxacin. Thus, liposomes functionalized with host cell glycans target P. aeruginosa resulting in increased retention of the liposomes in the circulation, accumulation at the site of infection, and increased survival time in a mouse surgical site infection model. Consequently, this formulation strategy may improve outcomes in patients infected with P. aeruginosa.