IntroductionDespite its increasing use, first-line palliative systemic therapy alternated with electrostatic pressurised intraperitoneal aerosol chemotherapy with oxaliplatin (ePIPAC-OX), hereinafter ...referred to as first-line bidirectional therapy, has never been prospectively investigated in patients with colorectal peritoneal metastases (CPM). As a first step to address this evidence gap, the present study aims to assess the safety, feasibility, antitumour activity, patient-reported outcomes, costs and systemic pharmacokinetics of first-line bidirectional therapy in patients with isolated unresectable CPM.Methods and analysisIn this single-arm, phase II study in two Dutch tertiary referral centres, 20 patients are enrolled. Key eligibility criteria are a good performance status, pathologically proven isolated unresectable CPM, no previous palliative systemic therapy for colorectal cancer, no (neo)adjuvant systemic therapy ≤6 months prior to enrolment and no previous pressurised intraperitoneal aerosol chemotherapy (PIPAC). Patients receive three cycles of bidirectional therapy. Each cycle consists of 6 weeks first-line palliative systemic therapy at the medical oncologists’ decision (CAPOX-bevacizumab, FOLFOX-bevacizumab, FOLFIRI-bevacizumab or FOLFOXIRI-bevacizumab) followed by ePIPAC-OX (92 mg/m2) with an intraoperative bolus of intravenous leucovorin (20 mg/m2) and 5-fluorouracil (400 mg/m2). Study treatment ends after the third ePIPAC-OX. The primary outcome is the number of patients with—and procedures leading to—grade ≥3 adverse events (Common Terminology Criteria for Adverse Events V.5.0) up to 4 weeks after the last procedure. Key secondary outcomes include the number of bidirectional cycles in each patient, treatment-related characteristics, grade ≤2 adverse events, tumour response (histopathological, cytological, radiological, biochemical, macroscopic and ascites), patient-reported outcomes, systemic pharmacokinetics of oxaliplatin, costs, progression-free survival and overall survival.Ethics and disseminationThis study is approved by the Dutch competent authority, a medical ethics committee and the institutional review boards of both study centres. Results will be submitted for publication in peer-reviewed medical journals and presented to patients and healthcare professionals.Trial registration numberNL8303.
Abstract Background Serum levels of 25-OH vitamin D3 (vitamin D) have been shown to be prognostic for disease-free survival in patients with breast cancer. We investigated the predictive value of ...these levels for pathological response after neoadjuvant chemotherapy in patients with breast cancer taking part in the NEOZOTAC phase-III trial. Additionally, the effect of chemotherapy on vitamin D levels was studied. Materials and methods Serum vitamin D was measured at baseline and before the last cycle of chemotherapy. The relationship between these measurements and clinical outcome, as defined by pathological complete response in breast and lymph nodes (pCR) was examined. Results Baseline and end of treatment vitamin D data were available in 169 and 91 patients, respectively. Median baseline vitamin D values were 58.0 nmol/L. In patients treated with chemotherapy only, serum vitamin D levels decreased during neoadjuvant chemotherapy (median decrease of 16 nmol/L, P = 0.003). The prevalence of vitamin D levels < 50 nmol/L increased from 38.3% at baseline to 55.9% after chemotherapy. In the total population, baseline and end of therapy vitamin D levels were not related to pathological response. No associations were found between pCR and vitamin D level changes. Conclusion The significant decrease in vitamin D post-neoadjuvant chemotherapy suggests that vitamin D levels should be monitored and in case of decrease of vitamin D levels, correction may be beneficial for skeletal health and possibly breast cancer outcome.
Highlights • The optimal duration for adjuvant endocrine treatment of breast cancer has not yet been established. • Current evidence for extended adjuvant endocrine therapy is based on an outdated ...regime of 5 years of tamoxifen. • Multiple clinical trials are being conducted using modern AI-containing regimes. • Prognostic markers used for decisions on chemotherapy, could also be valuable to decide on extended endocrine treatment.
Prebiopsy magnetic resonance imaging (MRI) increases the detection rate of clinically significant prostate cancer (csPCa). Prostate-specific membrane antigen-positron emission tomography/computed ...tomography (PSMA PET/CT) maximum standardized uptake value (SUVmax) of the prostate may offer additional value in predicting the likelihood of csPCa in biopsy.
A single-center cohort study involving patients with biopsy-proven PCa who underwent both MRI and PSMA PET/CT between 2020 and 2021. Logistic regression models were developed for International Society of Urological Pathology (ISUP) Grade Group (GG) ≥ 2 and GG ≥ 3 using noninvasive prebiopsy parameters: age, (log-)prostate-specific antigen (PSA) density, PI-RADS 5 lesion presence, extraprostatic extension (EPE) on MRI, and SUVmax of the prostate. Models with and without SUVmax were compared using Likelihood ratio tests and area under the curve (AUC). DeLong's test was used to compare the AUCs.
The study included 386 patients, with 262 (68%) having ISUP GG ≥ 2 and 180 (47%) having ISUP GG ≥ 3. Including SUVmax significantly improved both models' goodness of fit (p < 0.001). The GG ≥ 2 model had a higher AUC with SUVmax 89.16% (95% confidence interval CI: 86.06%-92.26%) than without 87.34% (95% CI: 83.93%-90.76%) (p = 0.026). Similarly, the GG ≥ 3 model had a higher AUC with SUVmax 82.51% (95% CI: 78.41%-86.6%) than without 79.33% (95% CI: 74.84%-83.83%) (p = 0.003). The SUVmax inclusion improved the GG ≥ 3 model's calibration at higher probabilities.
SUVmax of the prostate on PSMA PET/CT potentially improves diagnostic accuracy in predicting the likelihood of csPCa in prostate biopsy.
Some studies investigating the prognostic value of lymph vascular space invasion (LVSI) have shown an association between LVSI and disease-free survival. Definitive criteria and optimal determination ...of this parameter remain unclear, however, especially regarding the clinical relevance of LVSI quantification.
A subset of node-negative breast carcinomas from premenopausal patients from the European Organization for the Research and Treatment of Cancer trial 10854 (assessing efficacy of perioperative chemotherapy patients with T1–T3, N0–2, and M0 breast cancer (BC) was selected and scored for LVSI. In 358 evaluable breast carcinomas, the number of LVSI foci and tumor cells was determined in the largest tumor embolus within the lymph vessels. These two parameters were multiplied to calculate the LVSI tumor burden (LVSI TB). The optimal cutoff for this parameter was calculated in a test set (N = 120), tested in a validation set (N = 238), and compared with simple quantitation of the number of LVSI foci.
Tumors with a single LVSI focus are not associated with increased risk for relapse hazard ratio (HR) 1.423, 95% confidence interval (CI) 0.762–2.656. The LVSI TB had higher sensitivity and specificity compared with simple determination of the number of LVSI foci. LVSI TB was independently associated with disease-free survival in the validation set (HR 2.366, 95% CI 1.369–4.090, P = 0.002) in multivariate analysis and provided prognostic information in both the low- and high-risk node-negative BC groups (P < 0.001 and P = 0.007, respectively).
The determination of the number of LVSI foci multiplied by the number of tumor cells gives the most reliable quantitative assessment of this parameter, which can provide prognostic information in node-negative BC.
Infection is a major cause of death in the intensive care unit (ICU). Strategies to reduce rates of infection in ICUs include selective digestive tract decontamination (SDD), in which cefotaxime and ...topical antimicrobial agents are administered for 4 days, and selective oropharyngeal decontamination (SOD), in which only topical antimicrobial agents are administered. In this cluster-randomization study involving 13 ICUs in the Netherlands, SOD and SDD did not affect crude mortality but did appear to reduce mortality slightly at day 28, with adjustment for covariates.
Strategies to reduce rates of infection in ICUs include selective digestive tract decontamination (SDD) and selective oropharyngeal decontamination (SOD). In this study involving 13 ICUs in the Netherlands, SOD and SDD did not affect crude mortality but did appear to reduce mortality slightly at day 28.
Infections acquired in the intensive care unit (ICU) are important complications of the treatment of critically ill patients, increasing morbidity, mortality, and health care costs.
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Reductions in the incidence of respiratory tract infections have been achieved with the use of prophylactic antibiotic regimens, such as selective decontamination of the digestive tract (SDD)
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,
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and selective oropharyngeal decontamination (SOD).
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,
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The SDD approach
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,
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consists of prevention of secondary colonization with gram-negative bacteria,
Staphylococcus aureus,
and yeasts through application of nonabsorbable antimicrobial agents in the oropharynx and gastrointestinal tract, preemptive treatment of possible infections with commensal respiratory tract bacteria through systemic . . .
BACKGROUND
Chromosome segregation errors during human oocyte meiosis are associated with low fertility in humans and the incidence of these errors increases with advancing maternal age. Studies of ...mitosis and meiosis suggest that defective remodeling of chromatin plays a causative role in aneuploidy. We analyzed the histone deacetylation pattern during the final stages of human oocyte maturation to investigate whether defective epigenetic regulation of chromatin remodeling in human oocytes is related to maternal age and leads to segregation errors.
METHODS
Human surplus oocytes of different meiotic maturation stages germinal vesicle (GV), metaphase (M)I and MII were collected from standard IVF/ICSI treatments. Oocytes were analyzed for acetylation of different lysines of histone 4 (H4K5, H4K8, H4K12 and H4K16) and for α-tubulin.
RESULTS
Human GV oocytes had an intense staining of the chromatin for all four histone 4 lysine acetylations. MI and MII stage oocytes showed either normal deacetylation or various amounts of defective histone deacetylation. Residual H4K12 acetylation was more frequently found in oocytes obtained from older women, with a significant correlation between defective deacetylation and maternal age (r = 0.185, P = 0.007). Eighty-eight percent of the oocytes with residual acetylation had misaligned chromosomes, whereas only 33% of the oocytes that showed correct deacetylated chromatin had misaligned chromosomes (P < 0.001).
CONCLUSIONS
We conclude that defective deacetylation during human female meiosis increases with maternal age and is correlated with misaligned chromosomes. As chromosome misalignment predisposes to segregation errors, our data imply that defective regulation of histone deacetylation could be an important factor in age-related aneuploidy.
The influence of the neonatal intensive care unit (NICU) design on the acquisition of multidrug-resistant organisms (MDROs) has not been well-documented.
To examine the effect of single room unit ...(SRU) versus open bay unit (OBU) design on the incidence of colonization with MDROs and third-generation cephalosporin-resistant bacteria (3G-CRB) in infants admitted to the NICU.
Retrospective cohort study, including all infants admitted to the NICU of a tertiary care academic hospital two years prior to and two years following the transition from OBU to SRU in May 2017. Weekly cultures of throat and rectum were collected to screen for MDRO carriership. Incidence of colonization (percentage of all infants and incidence density per 1000 patient-days) with MDROs and 3G-CRB were compared between OBU and SRU periods.
Incidence analysis of 1293 NICU infants, identified 3.2% MDRO carriers (2.5% OBU, 4.0% SRU, not significant), including 2.3% extended-spectrum β-lactamase-producing Enterobacterales carriers, and 18.6% 3G-CRB carriers (17% OBU, 20% SRU, not significant). No differences were found in MDRO incidence density per 1000 patient-days between infants admitted to OBU (1.56) compared to SRU infants (2.63).
Transition in NICU design from open bay to SRUs was not associated with a reduction in colonization rates with MDROs or 3G-CRB in our hospital. Further research on preventing the acquisition and spread of resistant bacteria at high-risk departments such as the NICU, as well as optimal ward design, are needed.
To analyze the diagnostic accuracy of abdominal computed tomography (CT) in diagnosing internal herniation (IH) following Rouxen-Y gastric bypass (RYGB) surgery.
IH is one of the most important and ...challenging complications following RYGB. Therefore, early and adequate diagnosis of IH is necessary. Currently, exploratory surgery is considered the gold standard in diagnosing IH. Although CT scans are frequently being used, the true diagnostic accuracy in diagnosing IH remains unclear.
PubMed, Embase, and Cochrane databases were systematically searched for relevant articles describing the diagnostic accuracy of abdominal CT in diagnosing IH after RYGB. Data were extracted, recalculated, and pooled to report on the overall diagnostic accuracy of CT in diagnosing IH, and the diagnostic accuracy of specific radiological signs.
A total of 20 studies describing 1637 patients were included. seventeen studies provided data regarding the overall diagnostic accuracy: pooled sensitivity of 82.0%, specificity of 84.8%, positive predictive value of 82.7%, and negative predictive value of 85.8% were calculated. Eleven studies reported on specific CT signs and their diagnostic accuracy. The radiological signs with the highest sensitivity were the signs of venous congestion, swirl, and mesenteric oedema (sensitivity of 78.7%, 77.8%, and 67.2%, respectively).
This meta-analysis demonstrates that CT is a reliable imaging modality for the detection of IH. Therefore, abdominal CT imaging should be added to the diagnostic work-up for RYGB patients who present themselves with abdominal pain suggestive of IH to improve patient selection for explorative surgery.
Gallium-68 prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) and additional targeted biopsies can be used to detect more aggressive prostate cancer ...previously missed in patients recently started with active surveillance. Thereby PSMA PET/CT has the potential to further improve risk stratification and patient selection for active surveillance.
The use of clinical parameters, including prebiopsy magnetic resonance imaging (MRI), to decide between active surveillance (AS) and active therapy for prostate cancer (PCa) leads to imperfect selection. Additional prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) imaging may improve risk stratification.
To study risk stratification and patient selection for AS with the addition of PSMA PET/CT to standard practice.
A single-centre prospective cohort study (NL69880.100.19) enrolled patients recently diagnosed with PCa who started AS. At diagnosis, all participants had undergone prebiopsy MRI and targeted biopsy for visualised lesions. Patients underwent an additional 68Ga-PSMA PET/CT and targeted biopsy of all PSMA lesions with a maximum standardised uptake value (SUVmax) of ≥4 not covered by previous biopsies.
The primary outcome was the number needed to scan (NNS) to detect one patient with upgrading. The study was powered to detect an NNS of 10. Regarding secondary outcomes, univariate logistic regressions analyses were performed on all patients and on the patients who received additional PSMA targeted biopsies on the likelihood of upgrading.
A total of 141 patients were included. Additional PSMA targeted biopsies were performed in 45 (32%) patients. In 13 (9%) patients, upgrading was detected: nine grade group (GG) 2, two GG 3, one GG 4, and one GG 5. The NNS was 11 (95% confidence interval 6–18). Of all participants, PSMA PET/CT and targeted biopsies yielded upgrading most frequently in patients with negative MRI (Prostate Imaging Reporting and Data System PI-RADS 1–2). Of patients who received additional PSMA targeted biopsies, upgrading was most frequently found in those with higher prostate-specific antigen density and negative MRI. Limitations included the lack of comparison with standard repeat biopsy, no central review of MRI, and possibility of biopsy sampling error.
PSMA PET/CT can further improve PCa risk stratification and selection for AS patients diagnosed after MRI and targeted biopsies.
Prostate-specific membrane antigen positron emission tomography/computed tomography and additional targeted prostate biopsies can identify more aggressive prostate cancer cases previously missed in patients recently started with expectant management for favourable-risk prostate cancer.
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