The effect of hormonal contraceptive therapy on clinical laboratory parameters: a literature review.

Hormonal contraceptives (HC) are widely used among women in reproductive ages. In this review, the effects of HCs on 91 routine chemistry tests, metabolic tests, and tests for liver function, hemostatic system, renal function, hormones, vitamins and minerals were evaluated. Test parameters were differently affected by the dosage, duration, composition of HCs and route of administration. Most studies concerned the effects of combined oral contraceptives (COC) on the metabolic, hemostatic and (sex) steroids test results. Although the majority of the effects were minor, a major increase was seen in angiotensinogen levels (90-375 %) and the concentrations of the binding proteins (SHBG [∼200 %], CBG [∼100 %], TBG [∼90 %], VDBP [∼30 %], and IGFBPs [∼40 %]). Also, there were significant changes in levels of their bound molecules (testosterone, T3, T4, cortisol, vitamin D, IGF1 and GH). Data about the effects of all kinds of HCs on all test results are limited and sometimes inconclusive due to the large variety in HC, administration routes and dosages. Still, it can be concluded that HC use in women mainly stimulates the liver production of binding proteins. All biochemical test results of women using HC should be assessed carefully and unexpected test results should be further evaluated for both methodological and pre-analytical reasons. As HCs change over time, future studies are needed to learn more about the effects of other types, routes and combinations of HCs on clinical chemistry tests.

A higher incidence of chondral injuries on the medial femoral condyle in concomitant ACL ruptures, no significant difference in treatment: A systematic review.

PURPOSE: The associated damage to articular cartilage in anterior cruciate ligament (ACL) injured patients is a well-recognized phenomenon; however, there is a relative paucity in the literature regarding the different treatment techniques and outcomes. The purpose of this systematic review was to identify patients treated for acute ACL rupture and associated cartilage injury, with interest in the surgical management of these chondral injuries and any difference in patient-reported outcome measures (PROMs) differing techniques. METHODS: A systematic review was performed looking for treatment or management of International Cartilage Repair Society grade 3 or 4 articular cartilage injury at the time of ACL reconstruction. RESULTS: Seventeen studies fit the criteria, a total of 892 patients were included, 64.6% were male with a mean age of 33.7 and the average time to follow-up was 41.7 months. 68.2% of the lesions were on the medial femoral condyle (MFC) with a mean lesion size of 3.9 cm2. Six different operative methods of dealing with chondral lesions were identified, there was no significant difference in PROMs between the techniques, although there was a significant difference between the preoperative and postoperative outcome measures. CONCLUSIONS: The systematic review found that chondral defects on the MFC are more common in concomitant ACL injuries, despite the pattern of bone bruising being more common on the lateral femoral condyle as reported in the literature. It also found no significant difference in the PROMs between the six different techniques identified for the concomitant management of ACL reconstruction and chondral defects. LEVEL OF EVIDENCE: Level II.

Faecal Volatile Organic Compound Analysis in De Novo Paediatric Inflammatory Bowel Disease by Gas Chromatography-Ion Mobility Spectrometry: A Case-Control Study.

The gut microbiota and its related metabolites differ between inflammatory bowel disease (IBD) patients and healthy controls. In this study, we compared faecal volatile organic compound (VOC) patterns of paediatric IBD patients and controls with gastrointestinal symptoms (CGIs). Additionally, we aimed to assess if baseline VOC profiles could predict treatment response in paediatric IBD patients. We collected faecal samples from a cohort of de novo therapy-naïve paediatric IBD patients and CGIs. VOCs were analysed using gas chromatography-ion mobility spectrometry (GC-IMS). Response was defined as a combination of clinical response based on disease activity scores, without requiring treatment escalation. We included 109 paediatric IBD patients and 75 CGIs, aged 4 to 17 years. Faecal VOC profiles of paediatric IBD patients were distinguishable from those of CGIs (AUC ± 95% CI, p-values: 0.71 (0.64-0.79), <0.001). This discrimination was observed in both Crohn's disease (CD) (0.75 (0.67-0.84), <0.001) and ulcerative colitis (UC) (0.67 (0.56-0.78), 0.01) patients. VOC profiles between CD and UC patients were not distinguishable (0.57 (0.45-0.69), 0.87). Baseline VOC profiles of responders did not differ from non-responders (0.70 (0.58-0.83), 0.1). In conclusion, faecal VOC profiles of paediatric IBD patients differ significantly from those of CGIs.

Nonoperative Treatment as an Option for Isolated Anterior Cruciate Ligament Injury: A Systematic Review and Meta-analysis.

Background: An anterior cruciate ligament (ACL) tear is a risk factor for early osteoarthritis (OA) onset. Generally, ACL reconstruction (ACLR) is associated with better outcomes. However, there is a lack of evidence regarding the effect of operative versus nonoperative treatment for preventing premature knee OA in isolated ACL tears while achieving good functional outcomes. Purpose/Hypothesis: The purpose of the study was to compare the outcomes of ACLR to primarily nonoperative management of isolated ACL tears. It was hypothesized that the outcomes between treatment types would be similar. Study Design: Systematic review; Level of evidence, 3. Methods: This systematic review was registered on the International Prospective Register of Systematic Reviews (PROSPERO) (registration No. CRD42021285901) and was conducted according to the Cochrane Handbook guidelines. We systematically searched for randomized and nonrandomized studies that compared ACLR with nonoperative treatments in isolated ACL tears in 3 databases until October 25, 2021. The risk of bias and quality of evidence of the included studies was assessed in accordance with the Cochrane guidelines. The primary outcome was radiologic signs of OA, and the secondary outcomes were functional parameters. Using the common effects model, we calculated pooled mean differences (MDs) and odds ratios (ORs) with 95% CIs. Results: Five studies-2 randomized controlled trials (RCTs) and 3 retrospective non-RCTs-were included. There was a moderate risk of bias in 2 studies and a serious risk of bias in 1 study. The quality of evidence was rated low because of the higher risk of bias and inconsistency. Nonoperatively treated knees showed a trend toward lower odds of developing radiological signs of OA (OR, 1.84 [95% CI, 0.90 to 3.75]); however, surgically reconstructed knees had significantly better stability (MD, -2.44 [95% CI, -3.21 to -1.66 ]) and a trend toward better but clinically not meaningful Lysholm scores (MD, 2.88 [95% CI, -1.09 to 6.85]). The qualitative synthesis showed that surgical reconstruction was protective against subsequent injuries but not superior when returning to previous activity levels or various functional tests. Conclusion: Findings indicated that there is no certain evidence that ACLR for an isolated ACL tear is superior to nonoperative treatment. Clinicians should consider nonoperative treatments with a well-designed rehabilitative program as a primary option. However, these findings must be interpreted with caution because of low study quality and high risk of bias.

Micronutrient Status of Critically Ill Patients with COVID-19 Pneumonia.

Micronutrient deficiencies can develop in critically ill patients, arising from factors such as decreased intake, increased losses, drug interactions, and hypermetabolism. These deficiencies may compromise important immune functions, with potential implications for patient outcomes. Alternatively, micronutrient blood levels may become low due to inflammation-driven redistribution rather than consumption. This explorative pilot study investigates blood micronutrient concentrations during the first three weeks of ICU stay in critically ill COVID-19 patients and evaluates the impact of additional micronutrient administration. Moreover, associations between inflammation, disease severity, and micronutrient status were explored. We measured weekly concentrations of vitamins A, B6, D, and E; iron; zinc; copper; selenium; and CRP as a marker of inflammation state and the SOFA score indicating disease severity in 20 critically ill COVID-19 patients during three weeks of ICU stay. Half of the patients received additional (intravenous) micronutrient administration. Data were analyzed with linear mixed models and Pearson's correlation coefficient. High deficiency rates of vitamins A, B6, and D; zinc; and selenium (50-100%) were found at ICU admission, along with low iron status. After three weeks, vitamins B6 and D deficiencies persisted, and iron status remained low. Plasma levels of vitamins A and E, zinc, and selenium improved. No significant differences in micronutrient levels were found between patient groups. Negative correlations were identified between the CRP level and levels of vitamins A and E, iron, transferrin, zinc, and selenium. SOFA scores negatively correlated with vitamin D and selenium levels. Our findings reveal high micronutrient deficiency rates at ICU admission. Additional micronutrient administration did not enhance levels or expedite their increase. Spontaneous increases in vitamins A and E, zinc, and selenium levels were associated with inflammation resolution, suggesting that observed low levels may be attributed, at least in part, to redistribution rather than true deficiencies.

Appropriate use of blood cultures in the emergency department through machine learning (ABC): study protocol for a randomised controlled non-inferiority trial.

INTRODUCTION: The liberal use of blood cultures in emergency departments (EDs) leads to low yields and high numbers of false-positive results. False-positive, contaminated cultures are associated with prolonged hospital stays, increased antibiotic usage and even higher hospital mortality rates. This trial aims to investigate whether a recently developed and validated machine learning model for predicting blood culture outcomes can safely and effectively guide clinicians in withholding unnecessary blood culture analysis. METHODS AND ANALYSIS: A randomised controlled, non-inferiority trial comparing current practice with a machine learning-guided approach. The primary objective is to determine whether the machine learning based approach is non-inferior to standard practice based on 30-day mortality. Secondary outcomes include hospital length-of stay and hospital admission rates. Other outcomes include model performance and antibiotic usage. Participants will be recruited in the EDs of multiple hospitals in the Netherlands. A total of 7584 participants will be included. ETHICS AND DISSEMINATION: Possible participants will receive verbal information and a paper information brochure regarding the trial. They will be given at least 1 hour consideration time before providing informed consent. Research results will be published in peer-reviewed journals. This study has been approved by the Amsterdam University Medical Centers' local medical ethics review committee (No 22.0567). The study will be conducted in concordance with the principles of the Declaration of Helsinki and in accordance with the Medical Research Involving Human Subjects Act, General Data Privacy Regulation and Medical Device Regulation. TRIAL REGISTRATION NUMBER: NCT06163781.

Methotrexate accumulation in target intestinal mucosa and white blood cells differs from non-target red blood cells of patients with Crohn's disease.

BACKGROUND: Intracellular methotrexate polyglutamates (MTX-PGs) concentrations are measurable in red blood cells (RBCs) during MTX treatment. MTX-PG3 concentrations correlate with efficacy in patients with Crohn's disease (CD). Since RBCs are not involved in pathogenesis of CD and lack extended MTX metabolism, we determined MTX-PGs accumulation in peripheral blood mononuclear cells (PBMCs: effector cells) and intestinal mucosa (target cells) and compared those with RBCs as a potential more precise biomarker. METHODS: In a multicentre prospective cohort study, blood samples of patients with CD were collected during the first year of MTX therapy. Mucosal biopsies were obtained from non-inflamed rectum and/or inflamed intestine. MTX-PGs concentrations in mucosa, PBMCs and RBCs were measured by liquid chromatography-tandem mass spectrometry. RESULTS: From 80 patients with CD, a total of 27 mucosal biopsies, 9 PBMC and 212 RBC samples were collected. From 12 weeks of MTX therapy onwards, MTX-PG3 was the most predominant species (33%) in RBCs. In PBMCs, the distribution was skewed towards MTX-PG1 (48%), which accounted for an 18 times higher concentration than in RBCs. Long-chain MTX-PGs were highly present in mucosa: 21% of MTX-PGtotal was MTX-PG5. MTX-PG6 was measurable in all biopsies. CONCLUSIONS: MTX-PG patterns differ between mucosa, PBMCs and RBCs of patients with CD.