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Among the heat shock proteins (HSP), HSP27, HSP70 and HSP90 are the most studied stress-inducible HSPs, and are induced in response to a wide variety of physiological and environmental insults, thus allowing cells to survive to lethal conditions based on their powerful cytoprotective functions. Different functions of HSPs have been described to explain their cytoprotective functions, including their most basic role as molecular chaperones, that is to regulate protein folding, transport, translocation and assembly, especially helping in the refolding of misfolded proteins, as well as their anti-apoptotic properties. In cancer cells, the expression and/or activity of the three HSPs is abnormally high, and is associated with increased tumorigenicity, metastatic potential of cancer cells and resistance to chemotherapy. Associating with key apoptotic factors, they are powerful anti-apoptotic proteins, having the capacity to block the cell death process at different levels. Altogether, the properties suggest that HSP27, HSP70 and HSP90 are appropriate targets for modulating cell death pathways. In this review, we summarize the role of HSP90, HSP70 and HSP27 in apoptosis and the emerging strategies that have been developed for cancer therapy based on the inhibition of the three HSPs.

Septic shock is characterized by a dysregulated host response to infection and is associated with a mortality of 45 to 50%. In this multicenter, randomized, double-blind, placebo-controlled trial in 1241 patients, hydrocortisone plus fludrocortisone reduced 90-day mortality.

The expanding number of members in the various human heat shock protein (HSP) families and the inconsistencies in their nomenclature have often led to confusion. Here, we propose new guidelines for the nomenclature of the human HSP families, HSPH (HSP110), HSPC (HSP90), HSPA (HSP70), DNAJ (HSP40), and HSPB (small HSP) as well as for the human chaperonin families HSPD/E (HSP60/HSP10) and CCT (TRiC). The nomenclature is based largely on the more consistent nomenclature assigned by the HUGO Gene Nomenclature Committee and used in the National Center of Biotechnology Information Entrez Gene database for the heat shock genes. In addition to this nomenclature, we provide a list of the human Entrez Gene IDs and the corresponding Entrez Gene IDs for the mouse orthologs.

Whether hydrocortisone reduces mortality among patients with septic shock is unclear. Patients with septic shock undergoing mechanical ventilation were assigned to receive an infusion of hydrocortisone or placebo. Hydrocortisone did not result in lower 90-day mortality.

A large Scandinavian randomized trial showed no important outcome differences between hemoglobin levels of 7 g per deciliter and 9 g per deciliter as transfusion thresholds in patients with septic shock. Blood transfusions are frequently given to patients with septic shock. 1 – 4 Some of these transfusions are given to patients who are bleeding, but many nonbleeding patients also undergo transfusion. 5 The recommendations of the Surviving Sepsis Campaign regarding blood transfusion in patients with septic shock are complex and include a recommendation for transfusion to maintain a hematocrit of more than 30% in the presence of hypoperfusion in the first 6 hours. 6 After that, the transfusion threshold should be a hemoglobin level of less than 7 g per deciliter, aiming at levels between 7 g and 9 g per deciliter in patients . . .

Various molecular and cellular processes are involved in renal fibrosis, such as oxidative stress, inflammation, endothelial cell injury, and apoptosis. Heat shock proteins (HSPs) are implicated in the progression of chronic kidney disease (CKD). Our aim was to evaluate changes in urine and serum HSP levels over time and their relationships with the clinical parameters of CKD in children. In total, 117 children with CKD and 56 healthy children were examined. The CKD group was followed up prospectively for 24 months. Serum and urine HSP27, HSP40, HSP47, HSP60, HSP70, HSP72, and HSP90 levels and serum anti-HSP60 and anti-HSP70 levels were measured by ELISA at baseline, 12 months, and 24 months. The urine levels of all HSPs and the serum levels of HSP40, HSP47, HSP60, HSP70, anti-HSP60, and anti-HSP70 were higher at baseline in the CKD group than in the control group. Over the months, serum HSP47 and HSP60 levels steadily decreased, whereas HSP90 and anti-HSP60 levels steadily increased. Urine HSP levels were elevated in children with CKD; however, with the exception of HSP90, they decreased over time. In conclusion, our study demonstrates that CKD progression is a complicated process that involves HSPs, but they do not predict CKD progression. The protective role of HSPs against CKD may weaken over time, and HSP90 may have a detrimental effect on the disease course.

The DanGer Shock trial test the hypothesis that left ventricular (LV) mechanical circulatory support with Impella CP transvalvular microaxial flow pump improves survival in patients with ST segment elevation acute myocardial infarction complicated by cardiogenic shock (AMICS) compared to conventional guideline-driven treatment. This paper describes the rationale and design of the randomized trial, in addition to the baseline characteristics of the population screened and enrolled so far. The DanGer Shock study is a prospective, multicenter, open-label trial in patients with AMICS randomized 1:1 to Impella CP or current guideline-driven therapy with planned enrollment of 360 patients. Patients comatose after out of hospital cardiac arrest are excluded. Eligible patients are randomized immediately following shock diagnosis. Among patients randomized to receive Impella CP, the device is placed prior to angioplasty. The primary endpoint is all-cause mortality at 180 days. Baseline characteristics of patients screened and randomized in the DanGer Shock as of June 2018 are compared with 2 contemporary AMICS studies. As of end of June 2018, 314 patients were screened and 100 patients were randomized. Patients had median arterial lactate of 5.5 mmol/L (interquartile range 3.7-8.8 mmol/L), median systolic blood pressure of 76 mmHg (interquartile range 70-88 mmHg), and median LV ejection fraction of 20% (interquartile range 10%-30%). The DanGer Shock trial will be the first adequately powered randomized trial to address whether mechanical circulatory LV support with Impella CP can improve survival in AMICS. Baseline characteristics of the first 100 randomized patients indicate a population in profound cardiogenic shock.

In a randomized trial involving patients with STEMI and cardiogenic shock, mortality at 6 months was lower with mechanical circulatory support with a microaxial flow pump than with standard care alone.

In septic shock, the first few hours of care are critical for survival. In this study, two protocols for the care of patients with septic shock were compared with usual care with respect to 60-day mortality and other outcomes. There were no significant differences in outcome. There are more than 750,000 cases of severe sepsis and septic shock in the United States each year. 1 Most patients who present with sepsis receive initial care in the emergency department, and the short-term mortality is 20% or more. 2 , 3 In 2001, Rivers et al. reported that among patients with severe sepsis or septic shock in a single urban emergency department, mortality was significantly lower among those who were treated according to a 6-hour protocol of early goal-directed therapy (EGDT) than among those who were given standard therapy (30.5% vs. 46.5%). 4 On the basis of the premise that usual care . . .

In this multicenter, open-label trial, patients with septic shock were treated to maintain a mean arterial pressure target of either 80 to 85 mm Hg or 65 to 70 mm Hg. There were no significant between-group differences in 28-day mortality or in 90-day mortality. Septic shock is characterized by arterial hypotension despite adequate fluid resuscitation. The guidelines of the Surviving Sepsis Campaign 1 recommended initial resuscitation with vasopressors to reverse hypotension, with a mean arterial pressure target of at least 65 mm Hg (grade 1C, indicating a strong recommendation with a low level of evidence). This recommendation is based on the findings of small studies, which showed no significant differences in lactate levels or regional blood flow when the mean arterial pressure was elevated to more than 65 mm Hg in patients with septic shock. 2 , 3 However, as emphasized by the Surviving Sepsis Campaign guidelines, . . .