Objective. To determine if increasing variability of blood pressure influences determination of cerebral autoregulation. Methods. A prospective observational study was performed at the ICU of a ...university hospital in the Netherlands. 13 comatose patients after cardiac arrest underwent baseline and intervention (tilting of bed) measurements. Mean flow velocity (MFV) in the middle cerebral artery and mean arterial pressure (MAP) were measured. Coefficient of variation (CV) was used as a standardized measure of dispersion in the time domain. In the frequency domain, coherence, gain, and phase were calculated in the very low and low frequency bands. Results. The CV of MAP was significantly higher during intervention compared to baseline. On individual level, coherence in the VLF band changed in 5 of 21 measurements from unreliable to reliable and in 6 of 21 measurements from reliable to unreliable. In the LF band 1 of 21 measurements changed from unreliable to reliable and 3 of 21 measurements from reliable to unreliable. Gain in the VLF and LF band was lower during intervention compared to baseline. Conclusions. For the ICU setting, more attention should be paid to the exact experimental protocol, since changes in experimental settings strongly influence results of estimation of cerebral autoregulation.
An increased level of interleukin-6 (IL-6) in epithelial ovarian cancer (EOC) is correlated with a worse prognosis. IL-6 stimulates tumor-growth and inflammation. We investigated the intricate ...interaction between the IL-6 signaling pathway and tumor-infiltrating myeloid cells (TIMs) to determine their prognostic impact in EOC. 160 EOC samples were analyzed for the expression of IL-6, its receptor (IL-6R) and downstream signaling via pSTAT3 by immunohistochemistry. Triple color immunofluorescence confocal microscopy was used to identify myeloid cell populations by CD14, CD33, and CD163. The relationship between these markers, tumor-infiltrating immune cells, clinical-pathological characteristics and survival was investigated. EOC displayed a dense infiltration with myeloid cells, in particular of the CD163
+
type. The distribution pattern of all myeloid subtypes was comparable among the different histological subtypes. Analysis of the tumor cells revealed a high expression of IL-6R in 15% and of IL-6 in 23% of patients. Interestingly, tumors expressing IL-6 or IL-6R formed two different groups. Tumors with a high expression of IL-6R displayed low mature myeloid cell infiltration and a longer disease-specific survival (DSS), especially in late stage tumors. High expression of IL-6R was an independent prognostic factor for survival by multivariate analyses (hazard ratio = 0.474, p = 0.011). In contrast, tumors with high epithelial IL-6 expression displayed a dense infiltration of mature myeloid cells and were correlated with a shorter DSS. Furthermore, in densely CD8
+
T-cell infiltrated tumors, the ratio between these lymphoid cells and CD163
+
myeloid cells was predictive for survival. Thus, IL-6 and IL-6R are opposite markers for myeloid cell infiltration and survival.
Based on excellent outcomes from high-volume centres, laparoscopic liver resection is increasingly being adopted into nationwide practice which typically includes low-medium volume centres. It is ...unknown how the use and outcome of laparoscopic liver resection compare between high-volume centres and low-medium volume centres. This study aimed to compare use and outcome of laparoscopic liver resection in three leading European high-volume centres and nationwide practice in the Netherlands.
An international, retrospective multicentre cohort study including data from three European high-volume centres (Oslo, Southampton and Milan) and all 20 centres in the Netherlands performing laparoscopic liver resection (low-medium volume practice) from January 2011 to December 2016. A high-volume centre is defined as a centre performing >50 laparoscopic liver resections per year. Patients were retrospectively stratified into low, moderate- and high-risk Southampton difficulty score groups.
A total of 2425 patients were included (1540 high-volume; 885 low-medium volume). The median annual proportion of laparoscopic liver resection was 42.9 per cent in high-volume centres and 7.2 per cent in low-medium volume centres. Patients in the high-volume centres had a lower conversion rate (7.4 versus 13.1 per cent; P < 0.001) with less intraoperative incidents (9.3 versus 14.6 per cent; P = 0.002) as compared to low-medium volume centres. Whereas postoperative morbidity and mortality rates were similar in the two groups, a lower reintervention rate (5.1 versus 7.2 per cent; P = 0.034) and a shorter postoperative hospital stay (3 versus 5 days; P < 0.001) were observed in the high-volume centres as compared to the low-medium volume centres. In each Southampton difficulty score group, the conversion rate was lower and hospital stay shorter in high-volume centres. The rate of intraoperative incidents did not differ in the low-risk group, whilst in the moderate-risk and high-risk groups this rate was lower in high-volume centres (absolute difference 6.7 and 14.2 per cent; all P < 0.004).
High-volume expert centres had a sixfold higher use of laparoscopic liver resection, less conversions, and shorter hospital stay, as compared to a nationwide low-medium volume practice. Stratification into Southampton difficulty score risk groups identified some differences but largely outcomes appeared better for high-volume centres in each risk group.
Short-term fasting protects tumor-bearing mice against the toxic effects of chemotherapy while enhancing therapeutic efficacy. We randomized 131 patients with HER2-negative stage II/III breast ...cancer, without diabetes and a BMI over 18 kg m
, to receive either a fasting mimicking diet (FMD) or their regular diet for 3 days prior to and during neoadjuvant chemotherapy. Here we show that there was no difference in toxicity between both groups, despite the fact that dexamethasone was omitted in the FMD group. A radiologically complete or partial response occurs more often in patients using the FMD (OR 3.168, P = 0.039). Moreover, per-protocol analysis reveals that the Miller&Payne 4/5 pathological response, indicating 90-100% tumor-cell loss, is more likely to occur in patients using the FMD (OR 4.109, P = 0.016). Also, the FMD significantly curtails chemotherapy-induced DNA damage in T-lymphocytes. These positive findings encourage further exploration of the benefits of fasting/FMD in cancer therapy. Trial number: NCT02126449.
The patient-ventilator breath contribution (PVBC) index estimates the relative contribution of the patient to total tidal volume (Vt
) during mechanical ventilation in neurally adjusted ventilator ...assist mode and has been used to titrate ventilator support. The reliability of this index in ventilated patients is unknown and was investigated in this study. PVBC was calculated by comparing tidal volume (Vt
) and diaphragm electrical activity (EAdi) during assisted breaths (Vt
/EAdi)
and during unassisted breaths (Vt
/EAdi)
. Vt
was normalized to peak EAdi (EAdi
) using
) one assisted breath,
) five consecutive assisted breaths, or
) five assisted breaths with matching EAdi preceding the unassisted breath (
PVBC
,
PVBC
, and
, respectively). In addition, PVBC was calculated by comparing only Vt
for breaths with matching EAdi (PVBCβ
). Test-retest reliability of the different PVBC calculation methods was evaluated with the intraclass correlation coefficient (ICC) using five repeated PVBC maneuvers performed with a 1-min interval. In total, 125 PVBC maneuvers were analyzed in 25 patients. ICC 95% confidence interval values were 0.46 0.23-0.66, 0.51 0.33-0.70, and 0.42 0.14-0.69 for
PVBC
,
PVBC
,
, respectively. Complex waveform analyses showed that insufficient EAdi filtering by the ventilator software affects reliability of PVBC calculation. With our new EAdi-matching techniques reliability improved (PVBCβ
ICC: 0.78 0.60-0.90). We conclude that current techniques to calculate PVBC exhibit low reliability and that our newly developed criteria and estimation of PVBC-using Vt
of assisted breaths and unassisted breaths with matching EAdi-improves reliability. This may help implementation of PVBC in clinical practice.
The patient-ventilator breath contribution (PVBC) index estimates the relative contribution of the patient to tidal volume generated by the patient and the mechanical ventilator during mechanical ventilation in neurally adjusted ventilator assist mode. It could be used to titrate ventilator support and thus to limit development of diaphragm dysfunction in intensive care unit patients. Currently available methods for bedside assessment of PVBC are unreliable. Our newly developed criteria and estimation of PVBC largely improve reliability and help to quantify patient contribution to total inspiratory effort.
Human immunodeficiency virus (HIV) type 1 load in breast milk and mastitis were examined as risk factors for vertical transmission of HIV-1. Six weeks after delivery, HIV-1 load and sodium (an ...indicator of mastitis) were measured in breast milk from 334 HIV-1—infected women in Malawi. Median breast milk HIV-1 load was 700 copies/mL among women with HIV-1—infected infants versus undetectable (<200 copies/mL) among those with uninfected infants, respectively (P < .0001). Elevated breast milk sodium levels consistent with mastitis occurred in 16.4% of HIV-1—infected women and were associated with increased vertical transmission of HIV-1 (P < .0001). Median breast milk HIV-1 load was 920 copies/mL among women with versus undetectable among those without elevated breast milk sodium levels, respectively (P < .0001). Mastitis and breast milk HIV-1 load may increase the risk of vertical transmission of HIV-1 through breast-feeding.
For optimal oncological care, it is recommended to discuss every patient with cancer in a multidisciplinary team meeting (MDTM). This is a time consuming and expensive practice, leading to a growing ...demand to change the current workflow. We aimed to investigate the number of patients discussed in MDTMs and to identify characteristics associated with not being discussed.
Data of patients with a newly diagnosed solid malignant tumour in 2015 and 2016 were analysed through the nationwide population-based Netherlands Cancer Registry (NCR). We clustered tumour types in groups that were frequently discussed within a tumour-specific MDTM. Tumour types without information about MDTMs in the NCR were excluded. Multivariable logistic regression analyses were used to analyse factors associated with not being discussed.
Out of 105.305 patients with cancer, 91% were discussed in a MDTM, varying from 74% to 99% between the different tumour groups. Significantly less frequently discussed were patients aged ≥75 years (odds ratio OR = 0.7, 95% confidence interval CI = 0.6–0.7), patients diagnosed with disease stage I (OR = 0.5, 95% CI = 0.5–0.6), IV (OR = 0.4, 95% CI = 0.4–0.4) or unknown (OR = 0.2, 95% CI = 0.2–0.2) and patients who received no treatment (OR = 0.3, 95% CI = 0.3–0.3). Patients who received a multidisciplinary treatment were more likely to be discussed in contrary to a monodisciplinary treatment (OR = 4.6, 95% CI = 4.2–5.1).
In general, most patients with cancer were actually discussed in a MDTM, although differences were observed between tumour groups. Factors associated with not being discussed may, at least partially, reflect the absence of a multidisciplinary question. These results form a starting point for debate on a more durable and efficient new MDTM strategy.
•Of 105.305 patients with cancer, 91% is discussed in a multidisciplinary team meeting.•Lower discussion rates were found for higher age and disease stages I, IV or unknown.•A multidisciplinary question seems an important reason to discuss a patient.
Recently, excellent results are reported on laparoscopic lavage in patients with purulent perforated diverticulitis as an alternative for sigmoidectomy and ostomy.The objective of this study is to ...determine whether LaparOscopic LAvage and drainage is a safe and effective treatment for patients with purulent peritonitis (LOLA-arm) and to determine the optimal resectional strategy in patients with a purulent or faecal peritonitis (DIVA-arm: perforated DIVerticulitis: sigmoidresection with or without Anastomosis).
In this multicentre randomised trial all patients with perforated diverticulitis are included. Upon laparoscopy, patients with purulent peritonitis are treated with laparoscopic lavage and drainage, Hartmann's procedure or sigmoidectomy with primary anastomosis in a ratio of 2:1:1 (LOLA-arm). Patients with faecal peritonitis will be randomised 1:1 between Hartmann's procedure and resection with primary anastomosis (DIVA-arm). The primary combined endpoint of the LOLA-arm is major morbidity and mortality. A sample size of 132:66:66 patients will be able to detect a difference in the primary endpoint from 25% in resectional groups compared to 10% in the laparoscopic lavage group (two sided alpha = 5%, power = 90%). Endpoint of the DIVA-arm is stoma free survival one year after initial surgery. In this arm 212 patients are needed to significantly demonstrate a difference of 30% (log rank test two sided alpha = 5% and power = 90%) in favour of the patients with resection with primary anastomosis. Secondary endpoints for both arms are the number of days alive and outside the hospital, health related quality of life, health care utilisation and associated costs.
The Ladies trial is a nationwide multicentre randomised trial on perforated diverticulitis that will provide evidence on the merits of laparoscopic lavage and drainage for purulent generalised peritonitis and on the optimal resectional strategy for both purulent and faecal generalised peritonitis.
Nederlands Trial Register NTR2037.
'Precision oncology' can ensure the best suitable treatment at the right time by tailoring treatment towards individual patient and comprehensive tumour characteristics. In current molecular ...pathology, diagnostic tests which are part of the standard of care (SOC) only cover a limited part of the spectrum of genomic changes, and often are performed in an iterative way. This occurs at the expense of valuable patient time, available tissue sample, and interferes with 'first time right' treatment decisions. Whole Genome Sequencing (WGS) captures a near complete view of genomic characteristics of a tumour in a single test. Moreover, WGS facilitates faster implementation of new treatment relevant biomarkers. At present, WGS mainly has been applied in study settings, but its performance in a routine diagnostic setting remains to be evaluated. The WIDE study aims to investigate the feasibility and validity of WGS-based diagnostics in clinical practice.
1200 consecutive patients in a single comprehensive cancer centre with (suspicion of) a metastasized solid tumour will be enrolled with the intention to analyse tumour tissue with WGS, in parallel to SOC diagnostics. Primary endpoints are (1) feasibility of implementation of WGS-based diagnostics into routine clinical care and (2) clinical validation of WGS by comparing identification of treatment-relevant variants between WGS and SOC molecular diagnostics. Secondary endpoints entail (1) added clinical value in terms of additional treatment options and (2) cost-effectiveness of WGS compared to SOC diagnostics through a Health Technology Assessment (HTA) analysis. Furthermore, the (3) perceived impact of WGS-based diagnostics on clinical decision making will be evaluated through questionnaires. The number of patients included in (experimental) therapies initiated based on SOC or WGS diagnostics will be reported with at least 3 months follow-up. The clinical efficacy is beyond the scope of WIDE. Key performance indicators will be evaluated after every 200 patients enrolled, and procedures optimized accordingly, to continuously improve the diagnostic performance of WGS in a routine clinical setting.
WIDE will yield the optimal conditions under which WGS can be implemented in a routine molecular diagnostics setting and establish the position of WGS compared to SOC diagnostics in routine clinical care.
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