METHODS: For this retrospective study of patients with culture-confirmed melioidosis admitted to Kapit Hospital, Sarawak, Malaysia, between July 2016 and July 2019, epidemiological, clinical and microbiological data were obtained. Univariate and multivariate logistic regression analyses were used to determine predictors of mortality.
RESULTS: Seventy three patients met inclusion criteria. Diabetes mellitus (28.8%) and hypertension (27.4%) were primary co-morbidities. Clinical spectrum of melioidosis ranged from bacteraemia (64.4%), pneumonia (61.6%) and internal organ abscesses (49.3%) to localised soft tissue (21.9%) and joint abscesses (6.9%). Mortality rate was 12.3%. Bacteraemia and pneumonia were significantly associated with septic shock, whereas patients with soft tissue abscesses tended to present with a milder form of melioidosis without septic shock. Septic shock, mechanical ventilation, intensive care unit admission, serum urea, creatinine, bicarbonate, albumin and aspartate transaminase were all significantly associated with increased mortality on univariate analysis (all P
METHODS: Herein, we have engineered antibiotic-loaded (doxycycline or vancomycin) LPHNPs with cationic and zwitterionic lipids and examined the effects on their physicochemical characteristics (size and charge), antibiotic entrapment efficiency, and the in vitro intracellular bacterial killing efficiency against Mycobacterium smegmatis or Staphylococcus aureus infected macrophages.
RESULTS: The incorporation of cationic or zwitterionic lipids in the LPHNP formulation resulted in a size reduction in LPHNPs formulations and shifted the surface charge of bare NPs towards positive or neutral values. Also observed were influences on the drug incorporation efficiency and modulation of the drug release from the biodegradable polymeric core. The therapeutic efficacy of LPHNPs loaded with vancomycin was improved as its minimum inhibitory concentration (MIC) (2 µg/mL) versus free vancomycin (4 µg/mL). Importantly, our results show a direct relationship between the cationic surface nature of LPHNPs and its intracellular bacterial killing efficiency as the cationic doxycycline or vancomycin loaded LPHNPs reduced 4 or 3 log CFU respectively versus the untreated controls.
CONCLUSION: In our study, modulation of surface charge in the nanomaterial formulation increased macrophage uptake and intracellular bacterial killing efficiency of LPHNPs loaded with antibiotics, suggesting alternate way for optimizing their use in biomedical applications.
METHODS: The MEDLINE, EMBASE, and Cochrane database were systematically searched. The inclusion criteria were as follows: (1) English articles, (2) noncomparative study or relevant study reporting clinical and/or stability results, and (3) timing of the ACL reconstruction as a primary objective. Study type, level of evidence, randomization method, exclusion criteria, number of cases, age, sex, timing of ACL reconstruction, follow-up, clinical outcomes, stability outcomes, and other relevant findings were recorded. Statistical analysis of the Lysholm scores and KT-1000 arthrometer measurements after early and delayed ACL reconstruction was performed using R version 3.3.1.
RESULTS: Seven articles were included in the final analysis. There were 6 randomized controlled trials and 1 Level II study. Pooled analysis was performed using only Level I studies. All studies assessed the timing of ACL reconstruction as a primary objective. The definition of early ranged broadly from 9 days to 5 months and delayed ranged from 10 weeks to >24 months, and there was an overlap of the time intervals between some studies. The standard timing of the delayed reconstruction was around 10 weeks from injury in the pooled analysis. After pooling of data, clinical result was not statistically different between groups (I2: 47%, moderate level of heterogeneity). No statistically significant difference was observed in the KT-1000 arthrometer measurements between groups (I2: 76.2%, high level of heterogeneity) either.
CONCLUSION: This systematic review and meta-analysis performed using currently available high-quality literature provides relatively strong evidence that early ACL reconstruction results in good clinical and stability outcomes. Early ACL reconstruction results in comparable clinical and stability outcomes compared with delayed ACL reconstruction.
LEVEL OF EVIDENCE: Level II, a systematic review and meta-analysis of Level I and II studies.