Neoadjuvant personalized cancer vaccines: the final frontier?

INTRODUCTION: Clinical trials of personalized cancer vaccines have shown that on-demand therapies that are manufactured for each patient, result in activated T cell responses against individual tumor neoantigens. However, their use has been traditionally restricted to adjuvant settings and late-stage cancer therapy. There is growing support for the implementation of PCV earlier in the cancer therapy timeline, for reasons that will be discussed in this review. AREAS COVERED: The efficacy of cancer vaccines may be to some extent dependent on treatment(s) given prior to vaccine administration. Tumors can undergo radical immunoediting following treatment with immunotherapies, such as checkpoint inhibitors, which may affect the presence of the very mutations targeted by cancer vaccines. This review will cover the topics of neoantigen cancer vaccines, tumor immunoediting, and therapy timing. EXPERT OPINION: Therapy timing remains a critical topic to address in optimizing the efficacy of personalized cancer vaccines. Most personalized cancer vaccines are being evaluated in late-stage cancer patients and after treatment with checkpoint inhibitors, but they may offer a greater benefit to the patient if administered in earlier clinical settings, such as the neoadjuvant setting, where patients are not facing T cell exhaustion and/or a further compromised immune system.

[Optimal timing of endovascular treatment for uncomplicated Stanford type B aortic dissection].

Stanford type B aortic dissection (TBAD) is an acute and life-threatening disease. The treatment of TBAD used to be depended on whether it is complicated. The therapeutic guidelines recommend thoracic endovascular aortic repair (TEVAR) as first-line treatment for patients with acute complicated TBAD, while recommend best medical therapy for patients with acute uncomplicated TBAD (UTBAD). However, the latest studies suggest that patients with UTBAD also should be treated with pre-emptive TEVAR, which can significantly improve aortic remodeling and clinical outcome. Considering improvement of aortic remodeling and prevention of severe complications, the best timing of pre-emptive TEVAR may be 14-90 days after the onset of TBAD (subacute phase). The other main issue is identifying which patients with UTBAD should undergo pre-emptive TEVAR. Several risk factors including imaging, clinical and laboratory parameters have been shown to be associated with aortic-related events in patients with UTBAD. Among imaging finding, the diameters of aortic or false lumen, the status of true or false lumen, the size or number of entry tears have identified to be as predictors of adverse aortic events in patients with UTBAD.

Effect of timing of renal replacement therapy on outcomes of critically ill patients in the intensive care unit.

AIM: Currently, indications for renal replacement therapy (RRT) remain controversial. Whether early RRT can improve the prognosis of critically ill patients in the ICU is unclear. This study aimed to assess the relationship between timing of RRT initiation and short-term prognosis of patients in the ICU. METHODS: This was a retrospective study of data obtained from 28 hospitals in Beijing. The subjects received RRT treatment in the ICU from March 2012 to August 2012. RESULTS: A total of 9049 cases were reviewed, and 281 patients who underwent RRT were enrolled and divided into the non-survival (n = 144) and survival (n = 137) groups, according to their outcome at 28 days from ICU admission. Median RRT initiation times were 1 (0-25) and 1 (0-21) days in the non-survival and survival groups, respectively (P = 0.001) and oliguria/anuria frequency at RRT initiation were 76.6% and 65.3% (P = 0.036), respectively. The mortality of patients administered RRT within 24 h of ICU admission was lower than that of those treated after 24 h (P = 0.014). In patients with oliguria/anuria at RRT initiation, the 28-day mortality rate was 52.8%, which was higher than 39.0% obtained for those with no oliguria/anuria at RRT initiation (P = 0.036). Multivariate logistic analysis showed that late initiation of RRT was an independent risk factor for 28-day mortality (HR = 1.139, 95%CI 1.046-1.242, P = 0.003). CONCLUSION: Timing of RRT is associated with 28-day mortality of ICU treated patients. Early RRT might improve patient survival.

Optimal timing of endovascular treatment for uncomplicated Stanford type B aortic dissection / 中华外科杂志

Stanford type B aortic dissection (TBAD) is an acute and life-threatening disease. The treatment of TBAD used to be depended on whether it is complicated. The therapeutic guidelines recommend thoracic endovascular aortic repair (TEVAR) as first-line treatment for patients with acute complicated TBAD, while recommend best medical therapy for patients with acute uncomplicated TBAD (UTBAD). However, the latest studies suggest that patients with UTBAD also should be treated with pre-emptive TEVAR, which can significantly improve aortic remodeling and clinical outcome. Considering improvement of aortic remodeling and prevention of severe complications, the best timing of pre-emptive TEVAR may be 14-90 days after the onset of TBAD (subacute phase). The other main issue is identifying which patients with UTBAD should undergo pre-emptive TEVAR. Several risk factors including imaging, clinical and laboratory parameters have been shown to be associated with aortic-related events in patients with UTBAD. Among imaging finding, the diameters of aortic or false lumen, the status of true or false lumen, the size or number of entry tears have identified to be as predictors of adverse aortic events in patients with UTBAD.

Updates in timing of initiation of renal replacement therapy in patients with acute kidney injury / 解放军医学杂志

Acute kidney injury (AKI) is one of the most common serious complications in Intensive Care Unit (ICU),and also an independent risk factor for death.It is associated with a substantial increase in morbidity and mortality.AKI occurs in about 13 million people per year,and the mortality of AKI was 13.1％.A meta analysis showed that the incidence of AK1 was 0.99％-11.6％ in China.Renal replacement therapy (RRT) has become one of the conventional treatments for AKI patients,however the timing of RRT initiation in patients with AKI has not yet been defined.In this article,based on the two recent large randomized controlled trials (RCT),the timing to start or terminate the treatment are reviewed.

Does timing of antiretroviral treatment influence treatment outcomes of visceral leishmaniasis in Northwest Ethiopia?

Background: Visceral leishmaniasis (VL) patients with HIV co-infection should receive antiretroviral treatment (ART). However, the best timing for initiation of ART is not known. Among such individuals, we assessed the influence of ART timing on VL outcomes. Methods: A retrospective cohort study was conducted in Northwest Ethiopia among VL patients starting ART between 2008 and 2015. VL outcomes were assessed by the twelfth month of starting ART, within 4 weeks of VL diagnosis or thereafter. Results: Of 213 VL-HIV co-infected patients with ART initiation, 96 (45.1%) had moderate to severe malnutrition, 53 (24.9%) had active TB and 128 (60.1%) had hemoglobin levels under 9 g/dL. Eighty-nine (41.8%) were already on ART before VL diagnosis, 46 (21.6%) started ART within 4 weeks, and 78 (36.6%) thereafter. Definitive cure in those starting ART within 4 weeks 59% (95% CI 43-75%) and those starting thereafter 56% (95% CI 44-68%) was not significantly different. Those starting ART before primary VL had higher 12-months mortality compared to those starting later (RR 0.6; 95% CI 0.4-0.9; p=0.012). Conclusions: VL-HIV patients are severely ill and with serious additional comorbidities. Outcomes of HIV-VL management are unsatisfactory and early ART initiation was associated with higher mortality. Further research on the optimal timing of ART initiation, and ensuring earlier diagnosis of VL patients, with improved management of comorbidities are needed.

Research advance of the timing of renal replacement therapy among people with acute kidney injury / 中华危重病急救医学

Acute kidney injury (AKI) is one of the most common serious complications in critically ill patients, and it is an independent risk factor for death. In recent years, renal replacement therapy (RRT) has become one of the routine treatments for AKI patients, however there is no accepted consensus on the optimal timing of RRT over the world. This paper reviewed the clinical studies carried out by researchers in the field of critical care and nephrology, thereby summarized and analyzed the related parameters of the optimal time to carry out, with the exception of previously acknowledged classic RRT indications such as hyperkalemia, severe metabolic acidosis, volume overload and so on. The feasible parameters such as serum creatinine (SCr), blood urea nitrogen (BUN), urine volume, the time admitted in the intensive care unit (ICU) and several standards distinguished AKI stages are discussed in order to find out the cutoff points of those parameters which were best for the patients' outcome, and to provide guidance of decision making for the optimal timing of RRT for AKI patients.