The UPHILL study: A nutrition and lifestyle intervention to improve quality of life for patients with pulmonary arterial hypertension.

The aim of the UPHILL study (a nutrition and lifestyle intervention in patients with pulmonary arterial hypertension [PAH]: effect on quality of life [QoL]), was to determine the effect of innovative nutritional interventions on adjustments in nutritional intake and QoL. In this study a group of prevalent PAH patients at a single center in Amsterdam (the Netherlands) was informed about healthy nutrition using a newly designed video e-learning. They were subsequently instructed to follow a healthy diet during dietary intervention. Nutritional intake was assessed using a food frequency questionnaire (HELIUS) and QoL by the short-form (SF)-36 questionnaire. Nutritional parameters were determined in blood samples. Seventeen patients stable under treatment, who had been diagnosed with PAH 7.0 [3.0-14.0] years before, started and completed the intervention (2 males, 15 females; 45.35 ± 13.57 years). Since all patients in the intervention group made behavioral changes in nutritional intake, during study and follow-up, nutritional and lifestyle adaptations persisted. Despite the fact that patients had already high mean scores at baseline for both mental (74.10 [60.51-84.25]) and physical QoL (66.46 [50.21-73.84]), scores improved further during e-learning. Furthermore, patients who realized most nutritional adaptations, had the best improvement in QoL. This pilot study showed that e-learning modules on nutrition provide an unique opportunity to change nutritional intake in PAH patients and by that improve QoL.

Nutritional status in pulmonary arterial hypertension.

Nutritional deficiencies have been described in patients with pulmonary arterial hypertension (PAH), such as in iron and vitamin D. However, an extensive description of vitamin and mineral status is lacking and until now there is no data on dietary intake in PAH patients. We analyzed blood samples and determined nutritional intake using a food frequency questionnaire (HELIUS) in a cohort of prevalent PAH patients at a single center in Amsterdam, the Netherlands. Quality of life (QoL) was assessed by the SF-36 questionnaire. In total, 37 patients were included (6 males, 31 females; 48 ± 16 years). The dietary intake of sugar was above 25 g in 87% of the patients and fluid intake was above 1500 ml in 78% of the patients. Sodium intake was below 1800 mg in the majority (56%) of the patients. Sugar and fluid intake were linear related. We confirm previously observed deficiencies of iron and vitamin D in our study population. In addition, we observed a functional vitamin B12 deficiency in 29% of patients, which coincided with an increased expression of methylmalonic acid. 60% of patients had a low vitamin K1 status (<0.8 nmol/L). Finally, 40% of patients had selenium levels below <100 µg/L and low selenium levels associated with reduced vitality in these patients. Besides the known deficiencies in iron and vitamin D levels, we observed in a subset of patients signs of vitamin B12, vitamin K1 and selenium deficiencies. There is room for improving dietary intake. Future research aims to demonstrate the clinical importance and reveal the effect of nutritional interventions.

Measuring vitamin C in critically ill patients: clinical importance and practical difficulties-Is it time for a surrogate marker?

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2021. Other selected articles can be found online at  https://www.biomedcentral.com/collections/annualupdate2021 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from  https://link.springer.com/bookseries/8901 .

Short-term effect of low-dose colchicine on inflammatory biomarkers, lipids, blood count and renal function in chronic coronary artery disease and elevated high-sensitivity C-reactive protein.

AIMS: Inflammation plays a pivotal role in atherothrombosis. Colchicine is an anti-inflammatory drug that may attenuate this process. Cardiovascular protective effects of anti-inflammatory drugs, however, seem to be limited to patients with a biochemical response. We therefore investigated whether short-term exposure to colchicine reduced inflammatory markers and whether additional laboratory changes occur in patients with chronic coronary artery disease. METHODS & RESULTS: In 138 consecutive patients with chronic coronary artery disease and a high sensitivity C-reactive Protein (hs-CRP) ≥ 2 mg/L, inflammatory markers, lipids, haematologic parameters and renal function were measured at baseline and after 30 days exposure to colchicine 0.5mg once daily. Hs-CRP decreased from baseline 4.40 mg/L (interquartile range [IQR] 2.83-6.99 mg/L) to 2.33 mg/L (IQR 1.41-4.17, median of the differences -1.66 mg/L, 95% confidence interval [CI] -2.17 - -1.22 mg/L, p-value <0.01), corresponding to a median change from baseline of -40%. Interleukin-6 decreased from 2.51 ng/L (IQR 1.59-4.32 ng/L) to 2.22 ng/L (median of the differences -0.36 ng/L, 95%CI -0.70 - -0.01 ng/L, p-value 0.04), corresponding to a median change from baseline of -16%. No clinically relevant changes in lipid fractions were observed. Both leukocyte and thrombocyte count decreased (median change from baseline -7% and -4% respectively). Estimated glomerular filtration rate decreased with a mean change from baseline of -2%. CONCLUSION: In patients with chronic coronary artery disease and elevated hs-CRP, one-month exposure to colchicine 0.5 mg once daily was associated with a reduction of inflammatory markers. A small effect was seen on white blood cell count and platelet count, as well as a small decrease in estimated glomerular filtration rate.

Postoperative parathyroid hormone levels as a predictor for persistent hypoparathyroidism.

OBJECTIVE: Hypoparathyroidism is a common complication after thyroidectomy. It is not yet possible to predict in which patients hypoparathyroidism will persist. We aim to determine whether a decrease in PTH levels, measured at the first postoperative day, can identify patients with a high risk for persistent hypoparathyroidism one year after thyroidectomy. DESIGN: Prospective multi-center cohort study. METHODS: Patients undergoing total or completion thyroidectomy were included. We measured PTH levels preoperatively and on the first postoperative day. Primary outcome is the proportion of patients with persistent hypoparathyroidism, defined as the need for calcium supplementation one year after surgery. RESULTS: We included 110 patients of which 81 were used for analysis of the primary outcome. At discharge 72.8% of patients were treated with calcium supplementation. Persistent hypoparathyroidism was present in 14 patients (17.3%) at one-year follow-up, all of them had a decrease in PTH >70% at the first postoperative day. These 14 were 43.8% of the 32 patients who had such a decrease. In the group of 49 patients (59.8%) without a PTH >70% decrease, none had persistent hypoparathyroidism one year after surgery (P-value <0.001). A decrease of >70% in PTH levels had a sensitivity of 100.0% (95% CI: 85.8-100.0%), a specificity of 73.1% (95% CI: 62.5-83.7%) and an area under the curve of 0.87 (95% CI: 0.79-0.94) to predict the risk for persistent hypoparathyroidism. CONCLUSION: In our study a decrease in PTH levels of >70% after total or completion thyroidectomy is a reliable predictor for persistent hypoparathyroidism, and this should be confirmed in larger cohorts.

Predictive value of sperm morphology and progressively motile sperm count for pregnancy outcomes in intrauterine insemination.

OBJECTIVE: To investigate the value of sperm parameters to predict an ongoing pregnancy outcome in couples treated with intrauterine insemination (IUI), during a methodologically stable period of time. DESIGN: Retrospective, observational study with logistic regression analyses. SETTING: University hospital. PATIENT(S): A total of 1,166 couples visiting the fertility laboratory for their first IUI episode, including 4,251 IUI cycles. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Sperm morphology, total progressively motile sperm count (TPMSC), and number of inseminated progressively motile spermatozoa (NIPMS); odds ratios (ORs) of the sperm parameters after the first IUI cycle and the first finished IUI episode; discriminatory accuracy of the multivariable model. RESULT(S): None of the sperm parameters was of predictive value for pregnancy after the first IUI cycle. In the first finished IUI episode, a positive relationship was found for ≤4% of morphologically normal spermatozoa (OR 1.39) and a moderate NIPMS (5-10 million; OR 1.73). Low NIPMS showed a negative relation (≤1 million; OR 0.42). The TPMSC had no predictive value. The multivariable model (i.e., sperm morphology, NIPMS, female age, male age, and the number of cycles in the episode) had a moderate discriminatory accuracy (area under the curve 0.73). CONCLUSION(S): Intrauterine insemination is especially relevant for couples with moderate male factor infertility (sperm morphology ≤4%, NIPMS 5-10 million). In the multivariable model, however, the predictive power of these sperm parameters is rather low.

Reducing Inter-Laboratory Differences between Semen Analyses Using Z Score and Regression Transformations.

BACKGROUND: Standardization of the semen analysis may improve reproducibility. We assessed variability between laboratories in semen analyses and evaluated whether a transformation using Z scores and regression statistics was able to reduce this variability. MATERIALS AND METHODS: We performed a retrospective cohort study. We calculated between-laboratory coefficients of variation (CVB) for sperm concentration and for morphology. Subsequently, we standardized the semen analysis results by calculating laboratory specific Z scores, and by using regression. We used analysis of variance for four semen parameters to assess systematic differences between laboratories before and after the transformations, both in the circulation samples and in the samples obtained in the prospective cohort study in the Netherlands between January 2002 and February 2004. RESULTS: The mean CVBwas 7% for sperm concentration (range 3 to 13%) and 32% for sperm morphology (range 18 to 51%). The differences between the laboratories were statistically significant for all semen parameters (all P<0.001). Standardization using Z scores did not reduce the differences in semen analysis results between the laboratories (all P<0.001). CONCLUSION: There exists large between-laboratory variability for sperm morphology and small, but statistically significant, between-laboratory variation for sperm concentration. Standardization using Z scores does not eliminate between-laboratory variability.

Imprecision and limit of quantification of the new architect 25-hydroxyvitamin D assay.

We examined imprecision and limit of quantification (LOQ) of the new Architect 25-hydroxyvitamin D immunoassay in a multicenter setting. Mean intracenter interlot imprecision varied from 22.0 to 5.0%CV in the concentration range of 16 - 92 nmol/L. LOQs were locally determined as 10.8, 11.2, and 13.5 nmol/L. We conclude that the Architect 25(OH)D assay provides a precise and analytically sensitive method for routine measurement of 25(OH)D.

Multicenter comparison study of current methods to measure 25-hydroxyvitamin D in serum.

OBJECTIVES: Measurement of serum 25-hydroxyvitamin D [25(OH)D] is generally considered to be a reliable indicator of vitamin D status. The recent increase in diversity of 25(OH)D assays prompted us to evaluate the performance of chromatographic methods (two in-house ID-LC-MS/MS and HPLC (ClinRep, Recipe)), a protein binding method (Cobas-25(OH)D-total, Roche) and immunochemical methods (Liaison and RIA (Diasorin), iSYS (IDS), ADVIA Centaur (Siemens), and Architect i1000 and i2000 (Abbott)). METHODS: Blood was drawn from randomly selected outpatients (N=60) at one site after informed consent. DEQAS and SRM 972 samples were obtained from the scheme organizer and NIST, respectively. Serum aliquots were prepared, frozen and transported to participating centers. Method comparison was performed according to CLSI-EP9 specifications. RESULTS: With these patient samples, and in comparison with ID-LC-MS/MS, Deming regression parameters slope, intercept and R were found to be within the ranges [0.57-1.07], [-1.7 to 6.9 nmol/L] and [0.88-0.98], respectively. 25(OH)D2 in DEQAS and SRM samples was fully recognized by chromatographic methods, but only partially by protein binding and immunochemical methods. Chromatographic methods, and to a lesser extent the protein binding assay, showed cross-reactivity with 3-epi-25(OH)D3. Agreement of 25(OH)D assays to ID-LC-MS/MS in sorting patients into distinct 25(OH)D categories varied between 53% and 88%. CONCLUSIONS: Significant bias exists between ID-LC-MS/MS and many, but not all, other 25(OH)D assays. The variable response among different assays for 25(OH)D metabolites impedes the use of uniform cut-off values for defining vitamin D status. Our results indicate the need towards further standardizing assays for 25(OH)D measurement.