Glioblastoma (GB) is a grade IV astrocytoma that maintains a poor prognosis with respect to current treatment options. Despite major advancements in the fields of surgery and chemoradiotherapy over the last few decades, the life expectancy for someone with glioblastoma remains virtually unchanged and warrants a new approach for treatment. Poly(amidoamine) (PAMAM) dendrimers are a type of nanomolecule that ranges in size (between 1 and 100 nm) and shape and can offer a new viable solution for the treatment of intracranial tumors, including glioblastoma. Their ability to deliver a variety of therapeutic cargo and penetrate the blood-brain barrier (BBB), while preserving low cytotoxicity, make them a favorable candidate for further investigation into the treatment of glioblastoma. Here, we present a systematic review of the current advancements in PAMAM dendrimer technology, including the wide spectrum of dendrimer generations formulated, surface modifications, core modifications, and conjugations developed thus far to enhance tumor specificity and tumor penetration for treatment of glioblastoma. Furthermore, we highlight the extensive variety of therapeutics capable of delivery by PAMAM dendrimers for the treatment of glioblastoma, including cytokines, peptides, drugs, siRNAs, miRNAs, and organic polyphenols. While there have been prolific results stemming from aggressive research into the field of dendrimer technology, there remains a nearly inexhaustible amount of questions that remain unanswered. Nevertheless, this technology is rapidly developing and is nearing the cusp of use for aggressive tumor treatment. To that end, we further highlight future prospects in focus as researchers continue developing more optimal vehicles for the delivery of therapeutic cargo.
IJV and IVC collapsibility correlated during spontaneous breathing but there was no statistically significant correlation during increased thoracic or intra-abdominal pressure. Increased intra-abdominal pressure was associated with a significant smaller maximal IVC diameter and cautions the reliability of IVC diameter in clinical settings that are associated with intra-abdominal hypertension or abdominal compartment syndrome.
Objectives: Resuscitation with IV fluids is a critical component in the management of sepsis. Although the optimal volume of IV fluid is unknown, there is evidence that excessive administration can be deleterious. Static measures of volume status have not proven to be meaningful resuscitative endpoints. Determination of volume responsiveness has putative benefits over static measures, but its effect on outcomes is unknown. The goal of this systematic review and meta-analysis was to determine if resuscitation with a volume responsiveness-guided approach leads to improved outcomes in septic patients. Data Sources: We searched PubMed, EMBASE, CINAHL, Web of Science, Cochrane Library, and Google Scholar from inception until April 2018. Study Selection: Prospective studies of patients with sepsis, severe sepsis, or septic shock that compared volume responsiveness-guided fluid resuscitation to standard techniques and reported mortality data. Data Extraction: We extracted study details, patient characteristics, volume responsiveness assessment method, and mortality data. Data Synthesis: Of the 1,224 abstracts and 31 full-texts evaluated, four studies (total 365 patients) met inclusion criteria. Using random effects modeling, the pooled odds ratio for mortality at time of longest follow-up with a volume responsiveness-guided strategy was 0.87 (95% CI, 0.49–1.54). Pooling of clinical data was not possibly owing to heterogeneity of reporting in individual studies. Conclusions: We found no significant difference in mortality between septic patients resuscitated with a volume responsiveness-guided approach compared with standard resuscitative strategies. It remains unclear whether the findings are due to the small sample size or a true lack of efficacy of a volume responsiveness-guided approach.
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