Suboptimal Serum Research Articles

Intraperitoneally Administered Vancomycin Results in Suboptimal Serum and Peritoneal Effluent Drug Levels in Patients with PD-related Peritonitis

Background Intraperitoneal vancomycin is commonly used to treat peritoneal dialysis (PD)-related peritonitis. Therapeutic drug level monitoring helps optimize the use of vancomycin in CKD patients. We studied whether sufficient serum levels were achieved in patients with PD-related peritonitis treated with the commonly used dose of vancomycin in patients with end stage renal disease. Materials and Methods All consecutive patients with PD-related peritonitis during 19 months were studied. Patients received IP Vancomycin 15 mg/kg Q96H and amikacin 2 mg/kg while awaiting culture reports. Vancomycin concentration in serum and dialysate was determined by a validated liquid chromatography-tandem mass spectrometry assay at 1, 12, 24, and 96 h. The primary outcome was the drug levels in serum and peritoneal fluid, and the secondary outcome was peritonitis treatment failure. Results A total of 45 episodes of PD-related peritonitis were treated, of which 41 fulfilled the inclusion criteria and were included in the PK analysis. Recommended serum vancomycin trough level of >15 mg/L was achieved in only two cases. Twenty-one episodes required catheter removal. Conclusion In patients with PD-related peritonitis, intermittent intraperitoneal administration of 15 mg/kg of vancomycin every 96 h does not achieve the recommended serum and dialysate levels of vancomycin. There is an urgent need for pharmacokinetic studies on commonly used IP antibiotics in the PD population to facilitate correct dose recommendations.

P-662 Effect of rescue-dose progesterone in patients with low serum progesterone levels on the day of embryo transfer in frozen embryo transfer cycles

Abstract Study question What is the effect of rescue-dose progesterone in patients with low serum progesterone on the day of embryo transfer in frozen embryo transfer cycles? Summary answer In patients with low serum progesterone on the day of embryo transfer, rescue dose progesterone results in significantly higher clinical pregnancy rates. What is known already Frozen embryo transfer (FET) has become more common lately with many centers utilizing hormone replacement therapy (HRT) to electively plan embryo transfer with improved compliance rates. Serum progesterone level on the day of embryo transfer is a very simple, useful investigation which can be used as a predictor of clinical outcomes. Patients with lower progesterone levels (<5ng/ml) are associated with lower clinical pregnancy and ongoing pregnancy rates. Progesterone levels of > 10ng/ml are considered optimal by various studies. There is limited data on the efficacy of progesterone supplementation in patients with low progesterone levels. Study design, size, duration This study was conducted to assess the effect of rescue dose progesterone in patients with low serum progesterone levels on the day of embryo transfer in patients with HRT-FET cycles. This was a retrospective study and data was collected from prospectively maintained records of patients undergoing treatment at Miracles IVF and fertility center, Gurgaon, India between December, 2021 to November, 2023. Participants/materials, setting, methods All were HRT-FET cycles with vaginal progesterone supplementation of 800 mg/day. Serum progesterone levels were done on day of embryo transfer and if 5-10 ng/ml, rescue dose progesterone (100 mg intramuscular) was given. Single blastocyst embryo transfer was done. Inclusion criteria: 1.Age 25-35 years, 2.Endometrial thickness >7.5mm on day of start of progesterone. Exclusion criteria: 1.Transfer day progesterone <5ng/ml, 2. BMI > 30, 3. Previously failed embryo transfer The primary outcome was clinical pregnancy rate. Main results and the role of chance A total of 121 patients underwent 165 cycles during the study period with 93 patients included in the study after fulfilling the inclusion and exclusion criteria. 35 patients (37.6%) received rescue dose progesterone (RD group) and remaining 58 patients (62.4%) received no rescue dose (NRD group) as per their serum progesterone levels. All these patients were followed as per protocol and serum bhcg was done after 14 days of embryo transfer. Patients with positive values were monitored till positive clinical pregnancy. Biochemical pregnancy rates were 20 out of 35 (57.1%), 35 out of 58 ( 60.3%) and 55 out of 93 ( 59.1%) in RD group, NRD group and overall respectively. Clinical pregnancy rates were 18 out of 35 (51.4%), 34 out of 58 ( 58.6%) and 52 out of 93 ( 55.9%) in RD group, NRD group and overall respectively. RD group had significantly improved outcomes in terms of clinical pregnancy rates which were comparable to NRD group Limitations, reasons for caution Limitations, reasons for caution: Ours was a single center retrospective study with limited sample size. Though, our study revealed comparable outcome between the two groups but large volume multicenter studies are needed for making conclusive recommendations. Wider implications of the findings This study provides an insight into the role of serum progesterone levels on the day of embryo transfer. Rescue progesterone dosage for patients with sub-optimal serum progesterone levels may help in achieving similar clinical pregnancy rates and improving overall outcomes. Trial registration number not applicable

Clinical Effects and Functional State of the Endothelium in Patients with Arterial Hypertension with a Suboptimal Level of K+ in the Dynamics of Treatment with a Potassium-Magnesium Mineral Complex

Today, electrolyte dysbalance plays an important role in the formation and progression of cardiovascular diseases. The risk of development cardiovascular events also depends on potassium and magnesium deficiency. However, the issue of risks and clinical consequences of suboptimal serum potassium remains poorly understood. The objective: to analyze the influence of the mineral complex on the clinical status, serum levels of potassium and magnesium and the functional state of the endothelium, heart rhythm and parameters of the blood lipid spectrum in patients with arterial hypertension (AH) of the 2nd grade. Materials and methods. 60 patients from 43 to 65 years old with grade 2 AH, II stage took part in the study. Patients (36 men and 24 women) were divided into two groups of 30 persons each. Patients of the 1st group received antihypertensive therapy (perindopril 5–10 mg/day or valsartan 80–120 mg/day + hydrochlorothiazide 12.5 mg) and atorvastatin 20 mg/day. Patients of the 2nd group, in addition to the above-mentioned therapy, were prescribed a mineral complex of natural potassium and magnesium, 1 sachet per day for 3 months. Endothelial function was examined for all participants, the peak blood flow index was determined, arterial blood pressure (ABP) and electrocardiogram (ECG) were monitored daily. Results. In patients of the 2nd group, gradual increased levels of K+ and Mg+ in the blood plasma were determined: the median level of K+ increased by 25.9%, and the median Mg+ concentration – by 16.4% (р˂0.01). Endothelium-dependent vasodilatation after three months of potassium-magnesium citrate use became 2.17 times higher than the initial indicator and 1.94 times higher than in the 1st group (p<0.05). In the 2nd group of patients who additionally took the mineral complex, statistically significant positive dynamics of the blood pressure level were found: after 3 months, the median daily systolic blood pressure (SBP) decreased to 133.56 mm Hg. (LQ=131.64; HQ=135.29) (p<0.01). A significant decrease in the medians of both day and night SBP and diastolic blood pressure was also determined (p<0.01). At the same time, compared to the initial values, the number of ectopic arrhythmias decreased: supraventricular extrasystoles – by 47%, single and paired ventricular extrasystoles – by 37.5% and 47.1%, respectively (p<0.01). Positive dynamics of lipid indicators were found in the patients of the 2nd group. Conclusions. Prescribing a mineral complex to patients with AH and a suboptimal level of K+ who receive therapy including a thiazide diuretic has a complex positive effect: it increases the effectiveness of antihypertensive and hypolipidemic therapy, improves the functional state of the endothelium and vasodilatation, reduces the number of heart rhythm disorders and prevents the occurrence of hypokalemia and hypomagnesemia.

Expression of the cobalamin transporters cubam and MRP1 in the canine ileum-Upregulation in chronic inflammatory enteropathy.

Chronic inflammatory enteropathy (CIE) in dogs, a spontaneous model of human inflammatory bowel disease (IBD), is associated with a high rate of cobalamin deficiency. The etiology of hypocobalaminemia in human IBD and canine CIE remains unknown, and compromised intestinal uptake of cobalamin resulting from ileal cobalamin receptor deficiency has been proposed as a possible cause. Here, we evaluated the intestinal expression of the cobalamin receptor subunits, amnionless (AMN) and cubilin (CUBN), and the basolateral efflux transporter multi-drug resistance protein 1 (MRP1) in 22 dogs with CIE in comparison to healthy dogs. Epithelial CUBN and AMN levels were quantified by confocal laser scanning microscopy using immunohistochemistry in endoscopic ileal biopsies from dogs with (i) CIE and normocobalaminemia, (ii) CIE and suboptimal serum cobalamin status, (iii) CIE and severe hypocobalaminemia, and (iv) healthy controls. CUBN and MRP1 expression was quantified by RT-qPCR. Receptor expression was evaluated for correlation with clinical patient data. Ileal mucosal protein levels of AMN and CUBN as well as mRNA levels of CUBN and MRP1 were significantly increased in dogs with CIE compared to healthy controls. Ileal cobalamin receptor expression was positively correlated with age, clinical disease activity index (CCECAI) score, and lacteal dilation in the ileum, inversely correlated with serum folate concentrations, but was not associated with serum cobalamin concentrations. Cobalamin receptor downregulation does not appear to be the primary cause of hypocobalaminemia in canine CIE. In dogs of older age with severe clinical signs and/or microscopic intestinal lesions, intestinal cobalamin receptor upregulation is proposed as a mechanism to compensate for CIE-associated hypocobalaminemia. These results support oral supplementation strategies in hypocobalaminemic CIE patients.

Evaluation of the role of vitamin D in patients with psoriasis

Objectives: Investigate whether there is any association between the levels of vitamin D in the blood and the seriousness of psoriasis or its development. Methods: The study is characterized as observational, retrospective, composed of 40 patients with psoriasis who had serum vitamin D levels, who underwent clinical care at a dermatology outpatient clinic in Passo Fundo/RS, from August 2019 to June 2021. Results: Of the 40 interviewees, 60% were female and 40% male. Phototypes II and III prevailed. Regarding family health history, 50% had a history of the disease. Regarding the duration of psoriasis, the predominant group was between 1-10 years (57.5%). The most prevalent psoriasis subtype was vulgaris (62.5%). Regarding serum vitamin D results, the lowest index was 15.2 ng ̸ mL, the highest was 42.3 ng ̸ mL and the average was 25.99 ng ̸mL. In the predominant age group, between 20-40 years, the proportion of patients with vitamin D was less than 30 ng ̸mL is 83.33%. The lower the phototype, the greater the proportion of patients with suboptimal serum vitamin D. In the group of patients with disease duration > 10 years, vitamin D levels were lower. There is no extreme difference in the effectiveness of treatments when analyzing the average, minimum and maximum serum levels of vitamin D. Conclusion: There was no relationship between serum levels of 25-hydroxyvitamin D (25OHD) and the development of psoriasis or even control – worsening of the clinical picture of disease.

Selenium status and its determinants in very old adults: insights from the Newcastle 85+ Study.

There is a dearth of data on Se status in very old adults. The aims of this study were to assess Se status and its determinants in 85-year-olds living in the Northeast of England by measuring serum Se and selenoprotein P (SELENOP) concentrations and glutathione peroxidase 3 (GPx3) activity. A secondary aim was to examine the interrelationships between each of the biomarkers. In total, 757 participants (463 women, 293 men) from the Newcastle 85+ Study were included. Biomarker concentrations were compared with selected cut-offs (serum Se: suboptimal 70 µg/l and deficient 45 µg/l; SELENOP: suboptimal 4·5 mg/l and deficient 2·6 mg/l). Determinants were assessed using linear regressions, and interrelationships were assessed using restricted cubic splines. Median (inter-quartile range) concentrations of serum Se, SELENOP and of GPx3 activity were 53·6 (23·6) µg/l, 2·9 (1·9) mg/l and 142·1 (50·7) U/l, respectively. Eighty-two percentage and 83 % of participants had suboptimal serum Se (< 70 µg/l) and SELENOP (< 4·5 mg/l), and 31 % and 40 % of participants had deficient serum Se (< 45 µg/l) and SELENOP (< 2·6 mg/l), respectively. Protein intake was a significant determinant of Se status. Additional determinants of serum Se were sex, waist:hip ratio, self-rated health and disease, while sex, BMI and physical activity were determinants of GPx3 activity. There was a linear association between serum Se and SELENOP, and nonlinear associations between serum Se and GPx3 activity and between SELENOP and GPx3 activity. These findings indicate that most participants had suboptimal Se status to saturate circulating SELENOP.

Luteal phase support using micronized vaginal progesterone as pessaries or capsules in artificial cycles: is there any difference?

Research questionIs there a difference between the proportion of patients with serum progesterone <8.8 ng/ml on the day of embryo transfer when micronized vaginal progesterone (MVP) for luteal phase support (LPS) is given as pessaries versus capsules? DesignThis retrospective, matched-cohort, single-centre study compared pessaries (Cyclogest) versus capsules (Utrogestan, Progeffik) for LPS in hormone replacement treatment–embryo transfer (HRT-ET) cycles. Patients under 50 years old with a triple-layer endometrial thickness of ≥6.5 mm underwent transfer of one or two blastocysts. Serum progesterone concentrations were measured on the day of transfer; patients with concentrations <8.8 ng/ml received a single ‘rescue’ dose of additional progesterone by subcutaneous injection. ResultsIn total 2665 HRT-ET cycles were analysed; 663 (24.9%) used pessaries for LPS and 2002 (75.1%) used capsules. Mean serum progesterone concentrations with standard deviations on the day of embryo transfer were significantly higher in the group using MVP pessaries compared with those using capsules (14.5 ± 5.1 versus 13.0 ± 4.8 ng/ml; P = 0.000). The percentage of participants with suboptimal serum progesterone concentrations on the day of embryo transfer (<8.8 ng/ml) was significantly lower in the pessary group than the capsule group (10.3%, 95% confidence interval [CI] 7.9–12.6% versus 17.9%, 95% CI 16.2–19.6%; adjusted odds ratio 0.426, 95% CI 0.290–0.625; P = 0.000). No differences in pregnancy outcome were observed between the groups. ConclusionsUsing MVP pessaries rather than capsules for LPS resulted in significantly fewer patients having suboptimal serum progesterone concentrations on the day of embryo transfer. Consequently, almost 50% fewer patients in the pessary group needed rescue treatment.

Can vitamin D be an adjuvant therapy for juvenile rheumatic diseases?

Vitamin D, known for its essential role in calcium and bone homeostasis, has multiple effects beyond the skeleton, including regulation of immunity and modulation of autoimmune processes. Several reports have shown suboptimal serum 25 hydroxyvitamin D [25(OH)D] levels in people with different inflammatory and autoimmune rheumatic conditions, and an association between 25(OH)D levels, disease activity and outcomes. Although most available data pertain to adults, insights often are extended to children. Juvenile rheumatic diseases (JRDs) are a significant health problem during growth because of their complex pathogenesis, chronic nature, multisystemic involvement, and long-term consequences. So far, there is no definitive or clear evidence to confirm the preventive or therapeutic effect of vitamin D supplementation in JRDs, because results from randomized controlled trials (RCTs) have produced inconsistent outcomes. This review aims to explore and discuss the potential role of vitamin D in treating selected JRDs. Medline/PubMed, EMBASE, and Scopus were comprehensively searched in June 2023 for any study on vitamin D supplementary role in treating the most common JRDs. We used the following keywords: "vitamin D" combined with the terms "juvenile idiopathic arthritis", "juvenile systemic scleroderma", "juvenile systemic lupus erythematosus", "juvenile inflammatory myopathies", "Behcet disease", "periodic fever syndromes" and "juvenile rheumatic diseases". Observational studies have found that serum 25(OH)D concentrations are lower in juvenile idiopathic arthritis, juvenile systemic lupus erythematosus, juvenile systemic scleroderma, Behcet disease and proinflammatory cytokine concentrations are higher. This suggests that vitamin D supplementation might be beneficial, however, current data are insufficient to confirm definitively the complementary role of vitamin D in the treatment of JRDs. Considering the high prevalence of vitamin D deficiency worldwide, children and adolescents should be encouraged to supplement vitamin D according to current recommendations. More interventional studies, especially well-designed RCTs, assessing the dose-response effect and adjuvant effect in specific diseases, are needed to determine the potential significance of vitamin D in JRDs treatment.

Influence of Vitamin D on the Incidence of Metabolic Syndrome and Hormonal Balance in Patients with Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder that affects 8-13% of women of reproductive age. It is one of the most common causes of infertility and is associated with hyperandrogenism in the form of hirsutism and acne, non-ovulatory cycles, and characteristic ovarian morphology. The available research on serum vitamin D deficiency in patients with PCOS and the appropriateness of vitamin D supplementation in this group of women is inconclusive, so we decided to investigate the influence of vitamin D on the incidence of metabolic syndrome and hormonal balance in patients with polycystic ovary syndrome. The study comprised 120 women aged between 18 and 42 years, who were divided into two groups: a group with diagnosed polycystic ovary syndrome (PCOS) and a group of regularly menstruating women without features of androgenisation, in whom polycystic ovary syndrome was excluded. Each patient underwent a history and physical examination, including a gynecological examination, anthropometric measurements were taken, including height, weight, waist, and hip circumference, and blood pressure was measured using the Korotkow method. In the female patients, the following parameters were also determined from the blood: follicle-stimulating hormone (FSH), luteinizing hormone (LH), oestradiol, TSH, ft4, prolactin (PRL), total testosterone, DHEASO4, 17-hydroxyprogesterone (17-OHP), sex-hormone-binding globulin (SHBG), androstendione, 25(OH) vitamin D3 metabolite. The majority of the patients with polycystic ovary syndrome were found to have deficient or suboptimal serum vitamin D levels, and the effects of vitamin D on the SHBG levels and free-androgen indices in these patients was examined. The effects of vitamin D on the incidence of metabolic syndrome and BMI, waist-to-hip ratio, waist circumference, and blood pressure in patients with polycystic ovary syndrome were also found.

Is the Pharmacokinetics of First-Line Anti-TB Drugs a Cause of High Mortality Rates in TB Patients Admitted to the ICU? A Non-Compartmental Pharmacokinetic Analysis.

Patients with tuberculosis (TB) may develop multi-organ failure and require admission to intensive care. In these cases, the mortality rates are as high as 78% and may be caused by suboptimal serum concentrations of first-line TB drugs. This study aims to compare the pharmacokinetics of oral rifampin, isoniazid, pyrazinamide and ethambutol patients in intensive care units (ICU) to outpatients and to evaluate drug serum concentrations as a potential cause of mortality. A prospective pharmacokinetic (PK) study was performed in Amazonas State, Brazil. The primary PK parameters of outpatients who achieved clinical and microbiological cure were used as a comparative target in a non-compartmental analysis. Thirteen ICU and twenty outpatients were recruited. The clearance and volume of distribution were lower for rifampin, isoniazid, pyrazinamide and ethambutol. ICU thirty-day mortality was 77% versus a cure rate of 89% in outpatients. ICU patients had a lower clearance and volume of distribution for rifampin, isoniazid, pyrazinamide and ethambutol compared to the outpatient group. These may reflect changes to organ function, impeded absorption and distribution to the site of infection in ICU patients and have the potential to impact clinical outcomes.

Vitamin D deficiency during the COVID-19 pandemic and war in Ukraine

Background. Data from numerous studies indicate a significant prevalence of vitamin D deficiency in Ukraine and the world. In recent years, the Ukrainian medical community has faced two important challenges — the COVID-19 pandemic and the russian aggression, which significantly affected the organization and availability of medical care. Despite the previous epidemiological studies in Ukraine devoted to the vitamin D status, there are no data during the past 5 years that became the background for this research. The purpose was to analyze the vitamin D status in the adult population of Ukraine during the COVID-19 pandemic and russian aggression. Materials and methods. Data of the serum level of 25-hydroxyvitamin D (25(OH)D) in 5029 adults aged 20–99 years, who for various reasons applied for its measurement, were retrospectively analyzed. The analysis was performed depending on the year and month of observation, the age and gender of the subjects, and the 25(OH)D level. Results. The mean serum level of 25(OH)D in the total group was 33.2 [24.1–43.8] ng/ml. The assessment of the number of 25(OH)D tests for 2018–2022 did not reveal any significant differences in 2018 and 2019 but established a significant decrease during the russian aggression in Ukraine in 2022 (by 55.7%) compared to 2018, as well as indices during the COVID-19 pandemic (by 21.6 % compared to 2020, by 23.5 % in 2021). During the observation period, it was established a decrease in the vitamin D deficiency proportion from 20.6 % in 2018 to 9.3 % in 2022, and an increase in the proportion of subjects with suboptimal (from 6.6 to 11.4 %, respectively) and high serum concentrations of 25(OH)D (from 2.2 to 12.7 %). Conclusions. Our results indicate a grown serum 25(OH)D level during 2020–2022 in the adult population of Ukraine compared to the indices of previous years and a decreased share of vitamin D deficiency in the Ukrainian population. In addition, a decrease in the number of 25(OH)D level tests was established, especially during the period of the russian aggression, which should be taken into account during the planning measures to optimize the vitamin D status in the adult population of Ukraine.

Vitamin D deficiency in Ukraine: current evidence

BackgroundData from numerous studies demonstrate the high frequency of vitamin D deficiency (VDD) and insufficiency (VDI) in many countries worldwide that depend on age and sex, seasons, country, and concomitant pathology. This research aimed to study vitamin D status in the Ukrainian population during 2016–2022 years depending on age, sex, month, and year of the observation, and compare the results with the data of previous Ukrainian epidemiologic studies.MethodsIn a single-center cohort study, we analyzed the serum total 25-hydroxyvitamin D (25(OH)D) level in 7,418 subjects aged 20–99 years. The analysis was performed depending on age, sex, month, season, and year of the observation. Also, we compared the results with the data of previous Ukrainian studies. 25(OH)D level was measured using the electrochemiluminescence method.ResultsThe mean serum 25(OH)D level in the total group was 31.0 [22.3–41.1] ng/mL, the lowest level was in the age group 90–99 years old. No gender differences were found in 25(OH)D levels, except the one for the women aged 60–69 years old who had higher vitamin D levels compared to male parameters. 41.6% of the subjects had an optimal (> 30–50 ng/mL) 25(OH)D level, 27.3% had VDI, and 19.5% had a VDD. The suboptimal and high serum concentration of 25(OH)D (> 50–100 ng/mL) was found in 11.4% of the subjects. Also, we established the increase of serum 25(OH)D level from 2016 to 2022 with the highest values in 2020–2022. Seasonal variations of 25(OH)D concentration confirmed the highest index in autumn (33.0 [24.0–42.4] ng/mL) and the lowest one in the spring (28.5 [19.7–38.7] ng/mL) with the highest 25(OH)D level in September and the lowest one in March.ConclusionOur results confirmed a decrease in VDD and VDI in 2020–2022 in the Ukrainian population compared to the previous years (2016–2019) and previous Ukrainian studies with similar age and seasonal particularities. It may be the consequence of an improvement in public awareness of global vitamin D deficiency, its positive skeletal and extra-skeletal effects, as well as more intensive vitamin D supplementation due to the COVID-19 pandemic in the recent years.

Effect of Prolonged Serum Storage Time and Varied Temperatures on Biochemical Values in African Savanna Elephants (Loxodonta africana)

Blood samples are routinely collected from wild populations in remote locations with limited electricity, minimal diagnostic capabilities, and extreme environmental conditions. Under these conditions, serum samples may be stored for prolonged time under varied temperatures prior to processing, which could affect the ability to interpretation the results. This study’s objective was to evaluate the effects of delayed processing of serum samples and varied storage temperatures on biochemical values in African savanna elephants (Loxodonta africana). Blood samples were collected from six elephants managed by the North Carolina Zoo. For each elephant, seven red top tubes were collected. One serum sample for each elephant was analyzed on Day 0 (control group). The remaining samples were stored under different temperatures including room temperature (23 °C), refrigeration (2.2 °C), and incubation (32.2 °C), with samples from each temperature group being analyzed on Day 5 and Day 10. Many of analytes (10 out of 18) did not change significantly regardless of storage temperature or time. Refrigeration improved stability in an additional four analytes over prolonged storage. We conclude that if serum is properly separated shortly after collection, many serum biochemical analytes can be accurately measured even after suboptimal serum storage, but refrigeration and prompt evaluation are still required for some analytes.

Association of Serum Vitamin D level and COVID-19 infection: A Case-control Study.

Vitamin D is considered a potent modulator of the immune system, albeit its role in COVID-19 infection is a matter of debate. The present study aimed to estimate the association between serum vitamin D levels and COVID-19 among people in Qatar. This case-control study, approved by the Institutional Review Board of Primary Health Care Corporation (PHCC) Qatar, retrospectively evaluated the principal public healthcare sector population data repository retrieved from the cloud-based Electronic Health Record (EHR) software-Cerner, during April 2020-2021. The health records of all adult patients aged >18 years who had undergone the reverse transcription-polymerase chain reaction (RT-PCR) test and whose medical records had documented serum 25-hydroxyvitamin D [25 (OH)D] levels were analyzed. A total of 924,173 EHRs were extracted, of which 62,451 EHR comprised of 16,446 (26.3%) COVID-19 patients and 46,005 (73.7%) negative-control group patients met the inclusion criteria. The odds ratio (OR) among different categories of vitamin D deficiency (VDD) revealed that people with mild/moderate VDD were 1.18 times (95% CI 1.126-1.258) and those with severe VDD were 1.90 times (95% CI 1.116-1.251) more likely to have COVID-19 infection when compared to the people with optimal serum vitamin D level. On applying multiple logistic regression, the odds of having COVID-19 infection were found to be 1.27 times (95% CI 1.184-1.371) higher among those with mild/moderate VDD and 1.32 times (95% CI 1.206-1.405) higher among those with severe VDD when compared to people with optimal vitamin D level (p<0.001). Our findings demonstrated a significant association between the suboptimal serum vitamin D level and COVID-19 infection. Further studies are required to determine the effects of VDD on the severity and outcomes of COVID-19 infections.

Suboptimal Plasma Vitamin C Is Associated with Lower Bone Mineral Density in Young and Early Middle-Aged Men: A Retrospective Cross-Sectional Study.

Background: This study was conducted to evaluate associations between bone mineral density (BMD) and four selected circulating nutrients, particularly vitamin C, among adults aged 20–49 years. Methods: In this retrospective cross-sectional study, the lumbar spine BMD of 866 men and 589 women were measured by dual-energy X-ray absorptiometry and divided into tertiles, respectively. Logistic regressions were used to identify the predictors of low BMD by comparing subjects with the highest BMD to those with the lowest. Results: Multivariate logistic regressions identified suboptimal plasma vitamin C (adjusted odds ratio (AOR) 1.64, 95% confidence interval (CI) 1.16, 2.31), suboptimal serum vitamin B12 (AOR 2.05, 95% CI 1.02, 4.12), and low BMI (BMI < 23) (AOR 1.68, 95% CI 1.12, 2.53) as independent predictors for low BMD in men. In women, low BMI was the only independent predictor for low BMD. Plasma vitamin C, categorized as suboptimal (≤8.8 mg/L) and sufficient (>8.8 mg/L), was positively significantly correlated with the lumbar spine BMD in men, but there was no association in women. Conclusions: Plasma vitamin C, categorized as suboptimal and sufficient, was positively associated with the lumbar spine BMD in young and early middle-aged men. A well-designed cohort study is needed to confirm the findings.

P-374 Serum progesterone levels on the of embryo transfer in replacement cycles (HRT-ET): soft capsules vs suppositories may make a difference

Abstract Study question Are there differences in serum progesterone levels when vaginal progesterone is administered in soft capsules vs suppositories in HRT-ET? Summary answer Mean serum levels of progesterone in embryo replacement cycles are higher when progesterone suppositories are used instead of soft capsules. What is known already Serum levels of progesterone on the day of the embryo transfer has captured recent attention, as it may vary among patients and different vaginal progesterone formulations. Previous studies have suggested that natural micronized vaginal progesterone induces a comparable decidual transformation and clinical pregnancy rates to vaginal progesterone gel. However, no data exists comparing suppositories versus soft capsules. Study design, size, duration Prospective, observational, single center study to compare serum progesterone levels on the day of the embryo transfer in women undergoing HRT-ET and being treated with vaginal progesterone in capsules or suppositories. Also, a patient satisfaction questionnaire was given to women participating in the study to investigate patient experience. Sample size calculation estimated 50 patients per group needed for a = 0.05 and power 90%, considering standard deviation of 5.1. Participants/materials, setting, methods From April to October 2021, 100 patients undergoing HRT-ET were recruited. Only one type of progesterone was administered. 50 patients received soft capsules (Progeffik©, Utrogestan©) and the other half suppositories (Cyclogest©). After estradiol priming for 10-12 days and once confirmed that endometrial thickness was &amp;gt;7mm, 400 mg vaginal progesterone was started b.i.d. Blood was drawn on the day of embryo transfer by venipuncture and progesterone levels in blood were evaluated. Main results and the role of chance Mean serum levels of progesterone were significantly higher when suppositories were compared with soft capsules (16.2 ± 7 vs 12.5 ± 5.2 ng/ml, p = 0.0034). According to our previous studies we considered an adequate cut-off of progesterone of 8.8 ng/ml, and patients with a suboptimal serum level of progesterone were supplemented with subcutaneous progesterone. Of those patients receiving suppositories, only 6 out 50 (12%) required subcutaneous supplementation, whereas it was needed in 12 out of 50 (24%) women receiving soft capsules. No differences were observed in pregnancy rate (70% vs 50%) or ongoing pregnancy rate (48% vs 36%). Regarding patient satisfaction, no differences were observed in the frequency of itching, burning, leakage of medication or drowsiness between groups. Limitations, reasons for caution We should consider the limited sample size and the study design, not randomized, before generalizing the results observed. Wider implications of the findings In luteal support of frozen embryo replacement cycles, vaginal progesterone suppositories yields superior progesterone serum levels than soft capsules. Trial registration number Not applicable

Correlation of Gut Microbiota, Vitamin D Status, and Pulmonary Function Tests in Children With Cystic Fibrosis.

BackgroundChildren with cystic fibrosis (CF) are expected to have suboptimal serum vitamin D status and altered gut microbiota. The altered gut microbiota is hypothesized to have a pro-inflammatory effect that further complicates the existing respiratory inflammation. Emerging evidence suggests an association between vitamin D and gut microbiota. The aim of this study was to assess the relationships between 25-hydroxyvitamin D [25(OH)D] status, pulmonary function, and fecal bacteria in children with CF.MethodsIn this cross-sectional study, a total of 35 children with CF (8.7 ± 2.83 years) and 24 controls without CF (9 ± 2.7 years) were included in this study. Serum 25(OH)D status was measured using the Elecsys vitamin D total II assay. In the CF group, gut microbiota composition was assessed using real-time PCR analysis. Pulmonary function tests (PFTs) were measured using spirometry. Comparisons between the CF and non-CF controls were conducted using the independent sample t-test. In the CF group, one-way analysis of variance (ANOVA) was used to assess differences in PFTs and gut microbiota composition across the three vitamin D subgroups. The correlations between 25(OH)D status and PFTs, or gut microbiota composition, and PFTs with gut microbiota composition were analyzed using the Pearson's correlation coefficient test.ResultsChildren with CF had significantly lower serum 25(OH)D levels compared with children without CF (44.3 ± 22.4 vs. 59 ± 25.5, respectively, P = 0.026). Children with CF with optimal serum 25(OH)D level had significantly higher levels of Bacteroidetes, Firmicutes, and total bacteria (P = 0.007, P = 0.007, and P = 0.022, respectively). The level of Firmicutes was found to be significantly higher in mild forced expiratory volume in 1 s (FEV1) compared with moderate FEV1 (P = 0.032), whereas the level of the other bacteria species was comparable across FEV1 severity groups.ConclusionOur findings may encourage studies that target and modify gut microbiota to potentially achieve better outcomes in terms of respiratory function in CF.

DOP30 Long-term outcomes of Crohn’s perianal fistulas treatment: anti-TNF with surgical closure versus anti-TNF alone (PISA-II) - A patient preference RCT

Abstract Background The PISA-II trial showed that anti-TNF induction combined with surgical closure induces MRI healing more frequently than anti-TNF alone at 18 months follow-up (FU) and that this was associated with no recurrences at the time. The aim of this study was to compare long-term outcomes of both treatment arms. Methods In this FU study, data were collected from patients who participated in the PISA-II trial, a multicentre, international patient preference randomised controlled trial that compared anti-TNF induction combined with surgical closure to anti-TNF therapy alone as treatment for Crohn’s perianal fistulas. FU data were collected from the time of enrolment in the PISA-II trial until November 2021. Primary outcome was radiological healing at MRI and secondary outcomes included long-term clinical closure, recurrences, anti-TNF trough levels (suboptimal level was defined as infliximab &amp;lt;5.0ug/ml, adalimumab &amp;lt;5.9ug/ml), incontinence (improved, decreased or never had), and a decisional regret scale. Results Long-term FU data were collected from 88 out of 94 patients included in the PISA-II trial, 35/38 in the surgical closure arm and 53/56 in the anti-TNF treatment arm. Median FU was 5 years (IQR 4–7). During long-term FU radiological healing occurred in significantly more patients in the surgical closure arm (40% vs 17%; P=0.018). Long-term clinical closure occurred in 71% in the surgical closure arm and in 60% in the anti-TNF treatment arm (P=0.533). Recurrences occurred in 20% in the surgical closure arm and in 36% in the anti-TNF treatment arm (P=0.111). One patient with radiological healing developed a recurrence (4.3%) vs 12/57 (21.1%) patients with clinical closure. Trough levels were available in 32/53 patients treated with anti-TNF. Around the time of recurrence a suboptimal anti-TNF serum trough level occurred in 6/10. In the surgical closure arm, 6 patients had more and 6 patients had less incontinence problems after treatment, comparable to the 5 patient in the anti-TNF treatment arm with more and 8 with less incontinence problems. All patients in the surgical closure arm who completed the questionnaire (strongly) agreed that undergoing surgery was the right decision and 79% of the patients in the anti-TNF arm (strongly) agreed, 14% neither agreed nor disagreed and 7% disagreed that anti-TNF treatment was the right decision. Conclusion This study further supports the previous finding that anti-TNF induction combined with surgical closure should be considered in patients with Crohn’s perianal fistulas as long-term outcomes are favourable. Interestingly, surgical closure does not seem to be correlated to decreased continence, and all patients agreed that surgery was the right decision.

Serum vancomycin levels predict the short-term adverse outcomes of peritoneal dialysis-associated peritonitis.

The role of monitoring serum vancomycin levels during treatment of peritoneal dialysis (PD)-associated peritonitis is controversial. Substantial inter-individual variability may result in suboptimal serum levels despite similar dosing of vancomycin. The published predictors of suboptimal serum vancomycin levels remain limited. Data were retrospectively collected from 541 patients on continuous ambulatory peritoneal dialysis between 1 January 2018 and 31 December 312019. For gram-positive cocci and culture-negative peritonitis, we adopted a vancomycin administration and monitoring protocol. Short-term adverse outcomes of PD-associated peritonitis, including transfer to haemodialysis, death, persistent infection beyond planned therapy duration and relapse, were observed. The association between trough serum vancomycin levels and short-term adverse outcomes was evaluated. Intraperitoneal vancomycin was used in 61 gram-positive cocci or culture-negative peritonitis episodes in 56 patients. Fourteen episodes of short-term adverse outcomes occurred in 12 patients, whose average trough serum vancomycin levels on day 5 of treatment were significantly lower than those who didn't experience any adverse outcomes (8.4 ± 1.7 vs 12.5 ± 4.3 mg/L, p = 0.003). In gram-positive cocci or culture-negative peritonitis patients, those with higher day 5 trough serum vancomycin levels had a lower risk of short-term adverse outcomes (odds ratio: 0.6, 95% confidence interval: 0.4 to 0.9, p = 0.011). Receiver operating charecteristic curve (ROC) analyses showed that the day 5 trough serum vancomycin levels diagnostic threshold value for short-term adverse outcomes was 10.1 mg/L. After adjustments for gender, exchange volume and residual kidney function (RKF), baseline higher peritoneal transport was associated with a suboptimal (<10.1 mg/L) day 5 serum vancomycin level. Serum vancomycin levels are correlated with short-term adverse outcomes of PD-associated peritonitis, and higher peritoneal solute transport status is associated with suboptimal trough serum vancomycin levels on day 5.

Vitamin D and its association with symptom severity in knee osteoarthritis: a cross sectional study at a national referral hospital in Uganda

BackgroundVitamin D deficiency is highly prevalent among patients with osteoarthritis. It is associated with joint pain, stiffness and worse physical function. Whether vitamin D deficiency is associated with osteoarthritis is controversial. We investigated serum vitamin D levels and its association with symptom severity in patients with knee osteoarthritis.MethodsBetween January 2020 to March and May 2020, we conducted a cross sectional study at a national referral hospital in Uganda. Using the American College of Rheumatology clinical criteria, 107 consenting adults were diagnosed with knee osteoarthritis. A questionnaire captured patient demographics and clinical characteristics. Joint pain, stiffness and physical function severity were assessed and graded based on the Western Ontario and McMaster Universities Arthritis Index (WOMAC). We determined serum vitamin D levels by electrochemilumniscence immunoassay. The data were analysed and adjusted for age, sex, education, occupation, family history, body mass index (BMI) and calcium supplementation.ResultsOf the 107 patients, 92 (86%) patients were females, mean (SD) age was 58.1 (12.6) years. Nearly 65% of the patients had suboptimal serum vitamin D levels < 30 ng/ml. The median (Q1, Q3) WOMAC joint scores were as follows: pain 8.0 (5, 11), stiffness 1 (0, 2), physical function 29.0 (16, 41) and total WOMAC 39.0 (21, 54). Spearman correlations between serum vitamin D levels with symptom severity were as follows: joint pain (r = 0.18, p = 0.06), stiffness (r = 0.13, p = 0.17), physical function (r = 0.09, p = 0.36) and total WOMAC (r = 0.13, p = 0.19).ConclusionSerum vitamin D levels are not associated with joint pain, stiffness and physical function severity. Older age and higher BMI are associated with vitamin D deficiency in patients with knee osteoarthritis attending a national referral hospital rheumatology clinic in Uganda. Suboptimal vitamin D is an independent risk factor for total mortality in the general population. Clinical guidelines and further studies to determine age and BMI ranges required for vitamin D screening are needed in patients with osteoarthritis in Uganda. Patients are advised to keep a normal BMI.