Sepsis-induced coagulopathy in preterm neonates with Gram-positive sepsis presents with hypercoagulation and reduced platelet activation compared with healthy preterm neonates.

Background: Neonatal sepsis is frequently accompanied by coagulopathy and thrombocytopenia attributed to the cross-link between inflammation and coagulation. However, sepsis-induced coagulopathy and platelet function in septic preterm neonates remain to be elucidated. In addition, there is no robust evidence for a causal relationship between thrombocytopenia and bleeding in preterm neonates with sepsis. Objective: This single-center prospective cohort study aimed to assess sepsis-induced coagulopathy and platelet function in preterm neonates during sepsis. Methods: We included 25 preterm neonates with Gram-positive sepsis born at gestational age 24 + 1 to 34 + 3 and studied in comparison to 30 healthy counterparts. Coagulation was assessed using conventional coagulation tests (CCTs) and rotational thromboelastometry (ROTEM). Platelet function was evaluated by flow cytometry. The study was conducted at 3-time points, at 1st, at 2nd to 3rd, and at 5th to 7th day of sepsis, respectively. Results: Compared with healthy controls, neonates with Gram-positive sepsis present in ROTEM a hypercoagulable state; a higher maximum clot firmness (MCF) and higher amplitudes of intrinsic rotational thromboelastometry (INTEM) (INTEM MCF: median, 71; P .004 and INTEM A10: median, 67; P .005, respectively), extrinsic rotational thromboelastometry (EXTEM) (EXTEM MCF: median, 70; P .02 and EXTEM A10: median, 67; P .02, respectively), and rotational thromboelastometry assay for fibrin formation (FIBTEM) (FIBTEM MCF: median, 25; P < .001 and FIBTEM A10: median, 23; P .002, respectively). Conversely, CCTs exhibited hypocoagulation. Thrombocytopenia in preterm neonates with Gram-positive sepsis is not associated with an increased bleeding risk. In Gram-positive sepsis, platelets display increased glycoprotein (GP) surface receptors' expression (GPIb: median, 2.8; P .03, GPIIb: median, 3.1; P .004, and GPIIIa: median, 3.9; P .008, respectively) and reduced activation (P-selectin: median, 1; P < .001). A higher expression of platelets GP and improved degranulation capacity were recorded in patients in higher gestational age groups of >32 weeks of gestation. Platelet GPIb expression is age-dependent in healthy neonates. Conclusion: Neonatal Gram-positive sepsis is characterized by a progressive hypercoagulation along with increased GP expression, reduced platelet activation, and thrombocytopenia without bleeding. Platelet GP expression and degranulation capacity are age-dependent among neonates with sepsis. Platelet GP expression is age-dependent among healthy counterparts.

Differences among Indian and European pemphigus patients based on demographics, clinical parameters and propensity for relapse: results of a prospective bicontinental cohort study.

Limited studies have explored pemphigus variations among different ethnic groups residing in their respective geographical locations. This bicontinental study aimed to compare clinical and immunological parameters in Indian and European pemphigus patients in complete remission, off therapy, or on minimal therapy. 105 patients (India, n= 75; Bulgaria, n=15; Greece, n=15) with pemphigus vulgaris (PV) or pemphigus foliaceous (PF) in complete remission on minimal therapy (n=64) or complete remission off therapy (n=41) were recruited. Demographic, clinical, and immunological parameters were compared. Indian patients were significantly younger, the maximal disease severity during the preceding active disease phase was significantly lower, and treatment duration until complete remission was significantly shorter, compared to European patients. European patients had significantly higher anti-Dsg3 serum levels and higher IgG positivity rate based on direct immunofluorescence microscopy at baseline. Furthermore, European patients revealed higher CD19, CD19+ CD27+ cell counts, compared with patients from India. Of note, none of the European patients (n=30) relapsed within the study period, in contrast to 29/75 (38.6%) Indian patients. Treatment strategies differed significantly between the two cohorts, with more frequent utilization of rituximab to achieve remission in the Indian cohort, while prednisolone was more widely used for maintaining remission in the European cohort. The observed heterogeneity of pemphigus among patients of different ethnicities in terms of demographics, clinical parameters, and propensity for relapse may be due to genetic background or different treatment strategies.

Effects of Different Drug Therapies and COVID-19 mRNA Vaccination on Semen Quality in a Man with Ankylosing Spondylitis: A Case Report.

Background and Objectives: Ankylosing spondylitis (AS) is a condition that affects 0.1% to 0.5% of the adult population. The aim of this case report was to investigate the possible effects of the drugs taken for treatment of AS as well as mRNA vaccination for COVID-19 on semen quality by performing a highly detailed analysis. Materials and Methods: Sperm characteristics were examined by light microscopy, DNA fragmentation (DFI) was analysed by flow cytometry and morphology was evaluated by transmission electron microscopy (TEM). Results: Semen analysis under therapy with (1) celecoxib and sulphasalazine showed: concentration 47 million/mL, 53% progressive motility, 7% normal morphology and 9.6% DFI, (2) Golimumab and before mRNA Vaccination showed: concentration 108 million/mL, 82% progressive motility, 1% normal morphology and 7.6% DFI, and (3) Golimumab and after 3 doses of mRNA Vaccination showed: concentration 142 million/mL, 85% progressive motility, 1% normal morphology and 6.8% DFI. TEM revealed head, neck and tail abnormalities, as well as the presence of cells with incomplete spermiogenesis white cells and phagocytes in the sample under therapy with celecoxib and sulphasalazine. Golimumab treatment lead to an increased incidence of elongated heads but in general reduced inflammation as no white cells were evident in TEM. Conclusion: The anti-inflamatory drugs celecoxib and sulphasalazine had no adverse effect on sperm quality as all parameters were within normal limits and the patient achieved under that treatment 2 pregnancies following natural conception that lead to the birth of a healthy boy and girl respectively. Anti-TNFa treatment with Golimumab exerted a negative effect on morphology but not on concentration, motility and DFI. After 3 doses of mRNA Vaccination, sperm concentration increased while motility, morphology and DFI remained similar to the values before vaccination suggesting no negative effect of the mRNA vaccine for COVID-19 on sperm quality.

l-selenomethionine supplementation in children and adolescents with autoimmune thyroiditis: A randomized double-blind placebo-controlled clinical trial.

WHAT IS KNOWN AND OBJECTIVE: Although a beneficial effect of selenium (Se) administration has been proposed in adults with autoimmune thyroiditis (AT), there is a paucity of similar data in children and adolescents. The purpose of the study was to investigate whether administration of a high dose of organic Se (200 µg daily as l-selenomethionine) has an effect on antithyroid antibody titres in children and adolescents with AT. METHODS: Seventy-one (71) children and adolescents, with a mean age of 11.3 ± 0.3 years (range 4.5-17.8), diagnosed with AT (antibodies against thyroid peroxidase [anti-TPO] and/or thyroglobulin [anti-Tg] ≥60 IU/mL, euthyroidism or treated hypothyroidism and goitre in thyroid gland ultrasonography) were randomized to receive 200 µg l-selenomethionine or placebo daily for 6 months. Blood samples were drawn for measurement of serum fT4, TSH, anti-TPO and anti-Tg levels, and thyroid gland ultrasonography was performed at the entry to the study and after 6 months of treatment. RESULTS AND DISCUSSION: At the end of the study, a statistically significantly higher reduction in anti-Tg levels was observed in the Se group compared to the placebo group (Δ: -70.9 ± 22.1 vs -6.7 ± 60.6 IU/mL, P = 0.021). Although anti-TPO levels were also decreased in the Se group, this change was not statistically different from that of the control group (Δ: -116.2 ± 68.4 vs +262.8 ± 255.5 IU/mL, P = 0.219). No significant difference in thyroid gland volume was observed between the two study groups (P > 0.05). WHAT IS NEW AND CONCLUSION: In this original study, organic Se supplementation appears to reduce anti-Tg levels in children and adolescents with AT.

The combination of ovarian volume and outline has better diagnostic accuracy than prostate-specific antigen (PSA) concentrations in women with polycystic ovarian syndrome (PCOs).

OBJECTIVES: The aim of this study was to determine the performance of prostate specific antigen (PSA) and ultrasound parameters, such as ovarian volume and outline, in the diagnosis of polycystic ovary syndrome (PCOS). STUDY DESIGN: This prospective, observational, case-controlled study included 43 women with PCOS, and 40 controls. Between day 3 and 5 of the menstrual cycle, fasting serum samples were collected and transvaginal ultrasound was performed. The diagnostic performance of each parameter [total PSA (tPSA), total-to-free PSA ratio (tPSA:fPSA), ovarian volume, ovarian outline] was estimated by means of receiver operating characteristic (ROC) analysis, along with area under the curve (AUC), threshold, sensitivity, specificity as well as positive (+) and negative (-) likelihood ratios (LRs). Multivariate logistical regression models, using ovarian volume and ovarian outline, were constructed. RESULTS: The tPSA and tPSA:fPSA ratio resulted in AUC of 0.74 and 0.70, respectively, with moderate specificity/sensitivity and insufficient LR+/- values. In the multivariate logistic regression model, the combination of ovarian volume and outline had a sensitivity of 97.7% and a specificity of 97.5% in the diagnosis of PCOS, with +LR and -LR values of 39.1 and 0.02, respectively. CONCLUSIONS: In women with PCOS, tPSA and tPSA:fPSA ratio have similar diagnostic performance. The use of a multivariate logistic regression model, incorporating ovarian volume and outline, offers very good diagnostic accuracy in distinguishing women with PCOS patients from controls.

Clinical significance of anti-desmoglein-1 and -3 circulating autoantibodies in Pemphigus Patients Measured by Area Index and Intensity Score.

Detection of anti-desmoglein-1 (anti-DSG-1) and anti-DSG-3 autoantibodies is widely used in the diagnosis of pemphigus. Two validated scoring systems, Pemphigus Disease Area Index (PDAI) and Autoimmune Bullous Skin Disorder Intensity Score (ABSIS), are used for the evaluation of clinical severity. The aim of this cross-sectional study was to interpret the titres of pemphigus autoantibodies in correlation with either total or location-dependent PDAI scores and ABSIS. A total of 35 pemphigus patients were selected and evaluated at 3 time points. Total PDAI and ABSIS seemed useful in pemphigus with cutaneous lesions or in the mucocutaneous form, while location-dependent PDAI and ABSIS scores were useful in the mucosal form. Anti-DSG-1 autoantibodies titres better showed the disease extent in pemphigus with cutaneous only or with mucocutaneous lesions. Anti-DSG-3 autoantibodies titres did not correlate to disease activity.

Association of autoantibodies to BP180 with disease activity in Greek patients with bullous pemphigoid.

39 bullous pemphigoid (BP) patients were studied to assess the clinical significance of anti-BP180 and anti-BP230 circulating autoantibodies of BP and correlate their titers with the clinical scores of the BP Disease Area Index (BPDAI) and the Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) as well as with the intensity of pruritus measured by the BPDAI pruritus component. All parameters were evaluated by the time of diagnosis (baseline), month 3, and month 6. Titers of anti-BP180 autoantibodies were strongly correlated with BPDAI (r = 0.557, P value < 0.0001) and ABSIS (r = 0.570, P value < 0.0001) values, as well as with BPDAI component for the intensity of pruritus (rho = 0.530, P value = 0.001) at baseline. At month 3, titers of anti-BP180 autoantibodies were strongly correlated with BPDAI (rho = 0.626, P value = 0.000) and ABSIS (rho = 0.625, P value = 0.000) values, as well as with the BPDAI component for the intensity of pruritus (rho = 0.625, P value = 0.000). At month 6, titers of anti-BP180 autoantibodies were strongly correlated with BPDAI (rho = 0.527, P value = 0.001) and ABSIS (rho = 0.526, P value = 0.001) values, as well as with the BPDAI component for the intensity of pruritus (rho = 0.525, P value = 0.001). There was no statistically significant correlation between titers of anti-BP230 autoantibodies and the BPDAI, ABSIS, and BPDAI component for the intensity of pruritus at the same time points.

The impact on ovarian reserve after laparoscopic ovarian cystectomy versus three-stage management in patients with endometriomas: a prospective randomized study.

OBJECTIVE: To investigate the effect of two different laparoscopic methods on ovarian reserve in patients with ovarian endometriomas. DESIGN: Prospective, randomized clinical trial. SETTING: Endoscopy unit of a university hospital. PATIENT(S): Twenty women with endometriomas. INTERVENTION(S): Patients were randomly selected to undergo either laparoscopic cystectomy for endometrioma (group 1) or the "three-step procedure" (group 2). Before and 6 months after laparoscopy all patients were evaluated, and 12 months postoperatively they underwent ultrasound scan examination. MAIN OUTCOME MEASURE(S): The primary end point was ovarian reserve damage based on the alterations of anti-Müllerian hormone (AMH). Secondary end points were the changes of antral follicle count and serum concentration of FSH, LH, E(2), and inhibin B. RESULT(S): Mean serum AMH was reduced significantly from 3.9-2.9 ng/mL in group 1 compared with the reduction from 4.5-3.99 ng/mL in group 2. CONCLUSION(S): Ovarian reserve determined by AMH is less diminished after the three-step procedure compared with cystectomy of endometriomas.

Does the presence of anti-CCP autoantibodies and their serum levels influence the severity and activity in rheumatoid arthritis patients?

This study aims to investigate the association of the presence and of the titer of autoantibodies against cyclic citrullinated peptides (aCCP), with clinical manifestations and disease activity in a cohort of patients with rheumatoid arthritis (RA). From January 2000 through December 2005, 135 patients were diagnosed with RA at the Rheumatology Unit of our hospital. Demographic, clinical, laboratory, and therapeutic parameters were evaluated in all patients at study entry and at every follow-up visit. Positivity in aCCP and also their levels were determined for all patients. At the end of the study, we reevaluated the above parameters, dividing patients into aCCP positive and aCCP negative. From 135 patients, 53.3% were aCCP positive. The majority of aCCP-positive patients were males (p<0.001), positive to rheumatoid factor (p<0.001) and current smokers (p<0.05). At diagnosis, aCCP-positive patients presented with higher tender joint counts (p<0.001) and swollen joint counts (p<0.001), and exhibited more active disease, expressed by higher disease activity scores for 28 joints (DAS-28) (p<0.001). At the end of the study, aCCP-positive patients also displayed more active disease, with higher DAS-28 (p<0.001), and more severe disease, as this was indicated by the higher radiological Larsen score (p<0.001). The serum levels of aCCP were not found to be associated with disease activity and severity. In early RA, the presence of aCCP is associated with increased disease activity and severity. This was found to be independent of circulating levels of aCCP.

Do serum and red blood cell folate levels indicate iron response in hemodialysis patients?

The relationship among iron status, ferritin, and folate levels, and the possible contribution of folate measurement in the prediction of iron response in hemodialysis patients, have not been assessed. In addition to serum ferritin and transferrin saturation (TSAT), serum and red blood cell (RBC) folate levels were evaluated as indices for intravenous iron therapy responsiveness in 60 hemodialysis patients. Patients were classified as iron responders or nonresponders depending on whether they exhibited a rise in hemoglobin above 1 g/dl after administration of 1 g of iron sucrose. An inverse relation between serum ferritin concentration and RBC folate levels was found in iron responders (n=26, r=-0.62, p<0.001) but not in nonresponders (n=34, r=0.07, p=nonsignificant). Only serum and RBC folate levels could predict iron response in patients with ferritin levels above 150 microg/l (n=25), with a sensitivity of 83.3% and a specificity of 94.7%. Our findings suggest that RBC folate concentration is inversely related with ferritin levels in iron-responsive but not in non-responsive hemodialysis patients. Serum and RBC folate concentration seems to predict response to iron administration better than serum ferritin or TSAT in patients with ferritin levels above 150 microg/l; therefore, in these patients, it might be used to guide iron management.

Increase in serum magnesium level in haemodialysis patients receiving sevelamer hydrochloride.

BACKGROUND: Clinical studies have shown that sevelamer hydrochloride improves lipid profiles and attenuates the progression of the cardiovascular calcifications in haemodialysis patients. It is known that both of these properties are associated with increased magnesium levels. The effect of sevelamer on serum magnesium level is not well documented. The aim of this study was to determine the effects of sevelamer treatment on serum magnesium in haemodialysis patients and to assess the association of magnesium levels with lipid profiles and intact parathyroid hormone (iPTH). METHODS: Phosphate binders were discontinued during a two week washout period. Forty-seven patients, whose serum phosphate was greater than 6.0 mg/dl at the end of washout, received sevelamer hydrochloride for eight weeks. The patients were then washed off sevelamer for another two weeks. RESULTS: Mean serum phosphorus concentration declined from 7.5 +/- 1.3 to 6.4 +/- 1.2 mg/dl (P < 0.001), mean serum magnesium levels increased from 2.75 +/- 0.35 to 2.90 +/- 0.41 mg/dl (P < 0.001) and median serum iPTH levels decreased from 297 to 213 pg/ml (P=0.001) during the eight weeks of sevelamer treatment. After the two week post-treatment washout phosphorus levels increased to 7.3 +/- 1.3 mg/dl (P < 0.001), magnesium levels were reduced to 2.77 +/- 0.39 mg/dl (P < 0.001) and iPTH levels increased to 240 pg/ml (P=0.012). No change was observed in serum calcium levels during the sevelamer treatment period and the subsequent washout period. The mean decline in total and low density lipoprotein (LDL) cholesterol during sevelamer treatment was 16.3 and 28.3 (P < 0.001), respectively. The mean increase in high density lipoprotein (HDL) cholesterol and in apolipoprotein A1 was 2.9 +/- 5.8 mg/dl (P=0.004) and 6.8 +/- 11.1 mg/dl (P=0.001), respectively. Multivariate analysis showed that the rise in serum magnesium concentration significantly correlated with reductions in iPTH levels (r=-0.40, P=0.016), but did not have any significant correlation with the changes in lipid profiles. CONCLUSIONS: Our findings indicate that patients on haemodialysis receiving sevelamer have a significant increase in serum magnesium concentrations. This increase in serum magnesium is associated with reduction in iPTH levels. The changes in lipid profiles of these patients however are not related to changes in serum magnesium levels.