Vaccination in twin pregnancies: comparison between immunization before conception and during pregnancy.

To evaluate the development of neutralizing Anti-Spike Protein IgG (Anti-S-IgG) during twin pregnancies before conception vs. during pregnancy. In this prospective study, three blood samples were collected from pregnant women and subjected to anti-S-IgG immunodiagnostics. The patient's medical records, including vaccination and PCR test results, were collected from the hospital's electronic database. Age-matched non-pregnant women were used as a control group. We enrolled 83 women with twin pregnancies. 49 women were vaccinated before conception, 21 women were vaccinated during pregnancy, and 13 were not vaccinated. Of the 13 women who weren't vaccinated, three became positive during pregnancy, and all three were severely ill. By contrast, in women who were vaccinated during or before pregnancy, COVID-19 infection during pregnancy caused only mild symptoms. A ten-fold lower level of neutralizing Anti-S-IgG in the 3rd trimester was observed in healthy women who were vaccinated before conception and remained healthy until discharge from the hospital after delivery 1605 (IQR: 763-2410) compared to the healthy women who were vaccinated during pregnancy 152 AU/mL (IQR: 54-360). This difference was higher among women who were infected by COVID-19 (as verified by a positive PCR test). The third-trimester level of neutralizing Ant-S-IgG in the infected group was 4770 AU/mL (4760-6100) in infected women vaccinated before conception compared to those vaccinated during pregnancy who had 70 AU/mL (IQR: 20-170) (p < 0.001). In women vaccinated at 13-16 weeks gestation, neutralizing Anti-S-IgG at 20-22 weeks went up to 372 AU/mL (IQR: 120-1598) but rapidly dropped to 112 AU/mL (IQR: 54-357) at 28-30 weeks, (p < 0.001), a faster decline than in women vaccinated at a median 22 weeks before conception. Being infected by COVID-19 before conception was linked to having low Anti-S-IgG levels during pregnancy, whereas being infected by COVID-19 during pregnancy led to a very high response in the 3rd trimester. In twin pregnancies, significantly lower neutralizing Anti-S-IgG levels were observed in women vaccinated during pregnancy compared to those vaccinated before conception, whether infected or not infected by COVID-19. A full course of vaccination before conception is recommended.Trial registration. ClinicalTrials.gov Protocol Registration and Results System (PRS) Receipt Release Date: October 4, 2021. https://clinicaltrials.gov/ ID: NCT04595214.

Antiphospholipid antibodies in convalescent plasma of donors recovered from mild COVID-19 infection.

BACKGROUND AND OBJECTIVES: Passive immunization by the infusion of convalescent plasma (CP) obtained from patients who have recently recovered from COVID-19, thus having antibodies to severe acute respiratory syndrome coronavirus 2, is a potential strategy to reduce the severity of illness. A high prevalence of antiphospholipid antibodies (APLA) in patients with COVID-19 has been reported during the pandemic, raising a concern whether the use of CP could increase the risk of thrombosis in transfused patients. We aimed to evaluate the prevalence of APLA in COVID-19 CP (CCP) in order to assess the potential prothrombotic influence of transfused CCP to COVID-19 patients. MATERIALS AND METHODS: We studied the prevalence of APLA in 122 CCP samples collected from healthy donors who recovered from mild-COVID-19 at two time periods: September 2020-January 2021 (defined as 'early period' samples) and April-May 2021 (defined as 'late period' samples). Thirty-four healthy subjects unexposed to COVID-19 were used as controls. RESULTS: APLA were present in 7 of 122 (6%) CCP samples. One donor had anti-ß2-glycoprotein 1(anti-ß2GP1) IgG, one had anti-ß2GP1 IgM and five had lupus anticoagulant (LAC) using silica clotting time (SCT), all in 'late period' donors. In the control group, one subject had anti-ß2GP1 IgG, two had LAC using dilute Russell viper venom time (dRVVT) and four had LAC SCT (both LAC SCT and LAC dRVVT in one subject). CONCLUSION: The low prevalence of APLA in CCP donors reassures the safety of CCP administration to patients with severe COVID-19.

Usual nutritional scores have acceptable sensitivity and specificity for diagnosing malnutrition compared to GLIM criteria in hemodialysis patients.

Diagnosing malnutrition by the recently published Global Leadership Initiative on Malnutrition (GLIM) criteria requires using modern techniques for body composition measurements. We hypothesized that the prevalence of malnutrition identified by usual nutritional scores and according to GLIM criteria may be close to each other due to the number of components shared between them. Our aim was to compare the concurrent validity of four nutritional scores, malnutrition-inflammation score (MIS), objective score of nutrition on dialysis, geriatric nutritional index (GNRI), and nutritional risk index against the GLIM criteria for malnutrition in maintenance hemodialysis patients. This prospective observational study was performed on 318 maintenance hemodialysis outpatients (37% women) with a mean age of 68.7 ± 13.1 years and a median dialysis vintage of 21 months. According to the GLIM criteria, 45.9% of these patients were diagnosed with malnutrition. Nutritional scores, dietary intake and body composition parameters were measured. All nutritional scores showed a strong association with malnutrition in multivariable logistic regression models. In discriminating the nutritional risk, the ROC AUC was largest for GNRI (0.70, 95% CI: 0.65-0.75; P< .001). Nutritional risk index and MIS showed high specificity but lower sensitivity compared to GNRI and objective score of nutrition on dialysis. Compared to MIS, GNRI had better concurrent validity (higher sensitivity and acceptable specificity) but was inferior to MIS in terms of relation to certain etiologic and phenotypic components of the GLIM criteria (specifically, to dietary intake and decrease in dry weight). In summary, of the nutritional scores tested, GNRI is the most sensitive score in identifying malnutrition diagnosed by GLIM criteria, but MIS is more specific and better in predicting the individual components of the GLIM criteria.

Comorbidity burden may explain adiponectin's paradox as a marker of increased mortality risk in hemodialysis patients.

Despite experimental evidence of beneficial metabolic, antiatherosclerotic and antiinflammatory effects of the 30 kDa adipokine, adiponectin, maintenance hemodialysis (MHD) patients with high adiponectin blood levels have paradoxically high mortality rates. We aimed to examine the direction of the associations between adiponectin and all-cause and cardiovascular mortality as well as with markers of oxidative stress, inflammation and nutrition in MHD patients with varying degrees of comorbidities. A cohort of 261 MHD patients (mean age 68.6 ± 13.6 years, 38.7% women), grouped according to baseline comorbidity index (CI) and serum adiponectin levels, were followed prospectively for six years. High and low concentrations were established according to median CI and adiponectin levels and cross-classified. Across the four CI-adiponectin categories, the group with low comorbidities and high adiponectin exhibited the best outcomes. Conversely, the high comorbidity group with high adiponectin levels had the lowest survival rate in both all-cause mortality (log rankχ2 = 23.74, p < 0.001) and cardiovascular mortality (log rankχ2 = 34.16, p < 0.001). Further data adjustment for case-mix covariates including fat mass index did not substantially affect these results. In conclusion, the direction of adiponectin's prognostic associations in MHD patients is inverse in those with few comorbidities and direct in those with many comorbidities.

Obestatin levels in response to a meal and association with subsequent appetite sensations in maintenance hemodialysis patients.

BACKGROUND: Obestatin, a physiological opponent of acylated ghrelin, is linked to appetite suppression regulation in mice but its anorexigenic properties in humans are controversial. We aimed to investigate obestatin's potential role in dietary intake regulation by examining response to a meal in maintenance hemodialysis (MHD) patients. METHODS: In this prospective observational case series study, we investigated the response of obestatin to a fixed calorie meal (500 kcal) in 21 MHD patients (age 69.2 ± 13.1 years, 10 women, with a body mass index 27.2 ± 5.5 kg/m2). Parallel changes in serum obestatin and insulin levels and subjective scores of appetite (visual analogue scales for hunger, satiety, fullness and prospective food consumption) were recorded on fasting and 30, 60 and 120 min after the meal. RESULTS: In a linear mixed effects model controlling for baseline demographics and clinical parameters including serum insulin concentrations, postprandial levels of obestatin did not change significantly from baseline in response to the meal. The response was the same in MHD patients treated with high- or low-flux dialyzers. However, postprandial obestatin levels were associated with the rate of change in sensation of fullness (linear estimate: 11.60 (95% confidence interval 0.17 to 23.04, P < 0.05)). The remaining sensations of appetite did not correlate with postprandial obestatin levels in time. CONCLUSIONS: Obestatin levels do not change acutely with food administration in MHD patients, but associate with the changes in sensation of fullness. This supports the possible role of obestatin in the long-term regulation of appetite in MHD patients.

Serum Chromium Levels Are Higher in Peritoneal Dialysis than in Hemodialysis Patients.

Background:An elevation in serum chromium levels in individuals treated with renal replacement therapy has been previously described, but chromium levels have not been systematically studied in patients treated with different dialysis modalities. The aim of this study was to compare serum chromium levels in patients treated with chronic peritoneal dialysis (PD) and hemodialysis (HD).Methods:We studied 169 chronic dialysis patients in a single medical center, of which 148 were treated with HD and 21 with PD. Serum chromium levels were measured by atomic absorption spectrometry.Residual renal function was accessed using a timed urine collection for the measurement of urine output and calculation of glomerular filtration rate (GFR).Results:The median (interquartile range) serum chromium level was significantly higher in patients treated with PD than in patients treated with HD: 5.00 (3.24 - 6.15) vs 1.83 (1.29 - 2.45) mcg/L, p < 0.001. In a univariate analysis, serum chromium level was associated with PD modality: Exp (B) 7.46 (95% confidence interval [CI] 2.1 - 26.4), p = 0.002. The association of PD modality with serum chromium level was even more significant using a multivariate logistic regression model: odds ratio (OR) 11.87 (95% CI 2.85 - 49.52), p = 0.001 after adjustment for age, gender, diabetes, smoking, dialysis vintage, use of diuretics, and residual renal function.Conclusions:In patients treated with chronic dialysis, serum chromium levels are higher in patients treated with PD than in those treated with HD.

The effect of sitagliptin versus glibenclamide on arterial stiffness, blood pressure, lipids, and inflammation in type 2 diabetes mellitus patients.

AIM: This study evaluated the effect of sitagliptin versus glibenclamide on arterial stiffness, blood pressure, lipid profile, oxidative stress, and high-sensitivity C-reactive protein (hsCRP) in type 2 diabetes mellitus patients. SUBJECTS AND METHODS: Forty diabetes patients, inadequately controlled on metformin, were randomly assigned to either sitagliptin (100 mg/day) or glibenclamide (5 mg/day) for 3 months. Following a 1-month washout period, a crossover switch from glibenclamide to sitagliptin and vice versa was performed for an additional 3 months. Arterial stiffness, 24-h ambulatory blood pressure monitoring, lipids, hsCRP, glycated hemoglobin, fasting glucose, STAT-8-isoprostane (a measure of oxidative stress), body mass index (BMI), and waist circumference were measured at baseline and at 3 months with each of the study drugs. RESULTS: Thirty-four patients completed the study. Glibenclamide had a better glucose-lowering effect than sitagliptin, but this was associated with more hypoglycemic events. BMI increased following glibenclamide treatment, whereas sitagliptin proved weight-neutral. Mean BMI gain was +0.5±1.0 kg/m(2) for glibenclamide versus -0.01±0.9 kg/m(2) for sitagliptin (P<0.001). Triglyceride levels significantly dropped following sitagliptin, although they remained unaltered after glibenclamide treatment. Mean triglyceride decrease was -18.4±45 mg/mL after sitagliptin but -0.2±57 mg/dL following glibenclamide treatment (P=0.018). There was no change in low-density lipoprotein, high-density lipoprotein, arterial stiffness, blood pressure monitoring, hsCRP, or STAT-8-isoprostane with each of the study drugs. CONCLUSIONS: Sitagliptin, but not glibenclamide, demonstrated a significant beneficial effect on BMI and triglyceride levels. However, arterial stiffness, blood pressure, oxidative stress, and inflammatory status were not significantly affected by adding sitagliptin or glibenclamide to metformin-treated type 2 diabetes patients.

Effect of captopril treatment on recuperation from ischemia/reperfusion-induced acute renal injury.

BACKGROUND: Ischemia/reperfusion triggers acute kidney injury (AKI), mainly via aggravating hypoxia, oxidative stress, inflammation and renin-angiotensin system (RAS) activation. We investigated the role of angiotensin-converting enzyme (ACE) inhibition on the progression of AKI in a rat model of ischemia/reperfusion. METHODS: Ninety-nine Sprague-Dawley rats were subjected to 1 h ischemia/reperfusion and/or left unilateral nephrectomy, with concurrent intraperitoneal implantation of Alzet pump. Via this pump, they were continuously infused with captopril 0.5 mg/kg/day, captopril 2 mg/kg/day or saline. The rats were sacrificed following 24, 48 or 168 h. Blood samples, 24-h urine collections and kidneys were allocated, to evaluate renal function, angiotensin-II, nitric oxide (NO), apoptosis, hypoxia, oxidative stress and inflammation. RESULTS: Serum creatinine and cystatin-C significantly increased in ischemic rats, coinciding with histopathologic intrarenal damage, decreased NO, augmented angiotensin-II, interleukin (IL)-6, IL-10, transforming growth factor-beta. At the acute reperfusion stage, captopril prevented excessive angiotensin-II synthesis, ameliorated renal dysfunction, inhibited intrarenal inflammation and improved histopathologic findings. Most of the renoprotective effects of captopril were limited predominantly to acute reperfusion stage. Concurrently, captopril significantly decreased NO availability, exacerbated intrarenal hypoxia and augmented oxidative stress. CONCLUSIONS: At the acute stage of renal ischemia/reperfusion-induced AKI, ACE inhibition substantially contributed to the amelioration of acute injury by improving renal function, inhibiting systemic and intrarenal angiotensin-II, attenuating intrarenal inflammation and preserving renal tissue structure. Later on, at the post-reperfusion stage, most of the beneficial effects of captopril administration on the recuperating post-ischemic kidney were no longer evident. Concurrently, ACE inhibition exacerbated intrarenal hypoxia and accelerated oxidative stress, indicating that renal adaptation to some consequences of ischemia does require bioavailability of RAS components.

Hyperglycaemia emerging during general anaesthesia induces rat acute kidney injury via impaired microcirculation, augmented apoptosis and inhibited cell proliferation.

AIM: Major surgery under general anaesthesia frequently triggers acute kidney injury by yet unknown mechanisms. We investigated the role of anaesthesia-triggered systemic hyperglycaemia in impairment of renal functioning, renal tissue injury, intra-renal Angiotensin-II synthesis and endogenous insulin production in anaesthetized rats. METHODS: Eighty-eight Sprague-Dawley rats underwent general anaesthesia for 1 h by different anaesthetic compounds. Some of the animals were either injected with high glucose, or received insulin prior to anaesthesia. Blood pressure, renal functioning estimated by cystatin-C and urea, renal perfusion evaluated by laser Doppler technique, blood glucose and insulin were surveyed. Subsequently, rat kidneys were excised, to be used for immunohistochemical examinations or preparation of renal extracts for intra-renal Angiotensin-II measurements. RESULTS: Elevated blood sugar was observed 5 min following induction of anaesthesia, concurrently with deterioration of renal functioning, drop of systemic blood pressure and decreased renal blood flow. Blood insulin concentrations positively correlated with glucose levels. Intra-renal Angiotensin-II was significantly augmented. Immunohistochemical examinations demonstrated enhanced staining for pro-apoptotic proteins and negligible cell proliferation in tubular tissues. Renal damage resultant from anaesthesia-induced hyperglycaemia could be attenuated by insulin injections. Rats challenged with glucose prior to anaesthesia demonstrated cumulative hyperglycaemia, further increase in insulin secretion, drop of renal blood flow and increased apoptosis. The effects were specific, since they could not be mimicked by replacing glucose with mannose. CONCLUSION: Anaesthesia-induced hyperglycaemia affects intra-renal auto-regulation via decreased renal perfusion, thus triggering renal function deterioration and tubular injury. Increased intra-renal Angiotensin-II aggravates the damage. Tight hypoglycaemic control might prevent or, at least, attenuate anaesthesia-induced renal injury.