Two sisters diagnosed with familial paraganglioma syndrome type 1 (FPGL1) and multiple endocrine neoplasia type 2A (MEN2A).

BACKGROUND: In clinical practice, genetic testing has become standard for many cancerous diseases. While a diagnosis of a single hereditary syndrome is not uncommon, the coexistence of two genetic diseases, even with partially common symptoms, remains unusual. Therefore, targeted next-generation sequencing (NGS), along with genetic consultation and imaging studies, is essential for every patient with confirmed paraganglioma. In this report, we present two sisters diagnosed with multiple endocrine neoplasia type 2 (MEN2A) and familial paraganglioma syndrome type 1 (FPGL1). CASE PRESENTATION: After presenting to the clinic with neck tumors persisting for several months, both patients underwent tumor removal procedures following imaging and laboratory studies. Pathological reports confirmed the diagnosis of paragangliomas. Subsequently, genetic testing, including NGS, revealed a mutation in the rearranged during transfection (RET) gene: the heterozygous change (c.2410G > A), (p.Val804Met), and a variant of the succinate dehydrogenase complex subunit D (SDHD) gene: (c.64 C > T), (p.Arg22Ter). Subsequently, thyroidectomy procedures were scheduled in both cases. CONCLUSION: To the best of our knowledge, this is the first report presenting these two mutations in two related patients, resulting in distinctive genetic syndromes with similar manifestations. This underscores that although infrequent, multiple hereditary disorders may co-occur in the same individual.

Translation and cross-cultural adaptation of the Get Active Questionnaire for Pregnancy (kwestionariusz "Badz Aktywna w Ciazy") to support physical activity among pregnant women in Poland.

INTRODUCTION: Physical activity during pregnancy is established to derive clinically meaningful improvements in pregnancy, childbirth, and postpartum health outcomes. Evidence-based pre-screening tools have been developed to support the implementation of physical activity programmes, and enhance communication between health care providers, exercise professionals and pregnant women. The Get Active Questionnaire for Pregnancy (GAQ-P) and the Health Care Provider Consultation Form for Prenatal Physical Activity (HCPCF) empower pregnant women to identify whether they require additional counselling from their obstetric health care provider in terms of physical activity. However, these tools are not available in Polish. This work details the process taken to translate the GAQ-P and HCPCF into Polish. MATERIAL AND METHODS: We followed the translation process outlined by the Translation and Cultural Adaptation International Society for Pharmacoeconomics and Outcomes Research (ISPOR) guidelines between August 2022 and August 2023. We formed an expert group that included representatives of the Polish Society of Sports Medicine, The Polish Society of Gynaecologists and Obstetricians, practitioners, and scientists in physical activity during pregnancy. We implemented 9 of the 10 steps recommended by ISOPR in the translation process. At the Cognitive Debriefing stage, we collected opinions on the Polish version of GAQ-P and HCPCF from 70 stakeholders on the clarity and cultural appropriateness of the translation. RESULTS AND CONCLUSIONS: Target users have positively evaluated the Polish version of GAQ-P and HCPCF. Thanks to the ISPOR methodology, we obtained a trustworthy, evidence-based screening tools, which can reduce the barriers for most women to be physically active during pregnancy.

Higher perfusion pressure and pump flow during cardiopulmonary bypass are beneficial for kidney function-a single-centre prospective study.

Background: Kidneys play an essential role in the circulatory system, regulating blood pressure and intravascular volume. They are also set on maintaining an adequate filtration pressure in the glomerulus. During the CPB, a decrease in systemic blood pressure and hemoglobin concentration may lead to renal ischemia and subsequent acute kidney injury. Methods: One hundred nine adult patients were prospectively enrolled in this study. The intervention in this study was increasing the flow of the CPB pump to reach the target MAP of > 90 mmHg during the procedure. The control group had a standard pump flow of 2.4 L/min/m2. Results: Standard pump flow of 2.4 L/min/m2 resulted in mean MAP < 90 mmHg during the CPB in most patients in the control group. Maintaining a higher MAP during CPB in this study population did not affect CSA-AKI incidence. However, it increased the intraoperative and postoperative diuresis and decreased renin release associated with CPB. Higher MAP during the CPB did not increase the incidence of cerebrovascular complications after the operation; patients in the highest MAP group had the lowest incidence of postoperative delirium, but the result did not obtain statistical significance. Conclusion: Maintaining MAP > 90 mmHg during the CPB positively impacts intraoperative and postoperative kidney function. It significantly reduces renal hypoperfusion during the procedure compared to MAP < 70 mmHg. MAP > 90 mmHg is safe for the central nervous system, and preliminary results suggest that it may have a beneficial impact on the incidence of postoperative delirium.

Alterations to Kidney Physiology during Cardiopulmonary Bypass-A Narrative Review of the Literature and Practical Remarks.

INTRODUCTION: According to different authors, cardiac surgery-associated acute kidney injury (CSA-AKI) incidence can be as high as 20-50%. This complication increases postoperative morbidity and mortality and impairs long-term kidney function in some patients. This review aims to summarize current knowledge regarding alterations to renal physiology during cardiopulmonary bypass (CPB) and to discuss possible nephroprotective strategies for cardiac surgeries. Relevant sections: Systemic and renal circulation, Vasoactive drugs, Fluid balance and Osmotic regulation and Inflammatory response. CONCLUSIONS: Considering the available scientific evidence, it is concluded that adequate kidney perfusion and fluid balance are the most critical factors determining postoperative kidney function. By adequate perfusion, one should understand perfusion with proper oxygen delivery and sufficient perfusion pressure. Maintaining the fluid balance is imperative for a normal kidney filtration process, which is essential for preserving the intra- and postoperative kidney function. FUTURE DIRECTIONS: The review of the available literature regarding kidney function during cardiac surgery revealed a need for a more holistic approach to this subject.

Screening for Preeclampsia and Fetal Growth Restriction in the First Trimester in Women without Chronic Hypertension.

BACKGROUND: Nowadays, it is possible to identify a group at increased risk of preeclampsia (PE) and fetal growth restriction (FGR) using the principles of the Fetal Medicine Foundation (FMF). It has been established for several years that acetylsalicylic acid (ASA) reduces the incidence of PE and FGR in high-risk populations. This study aimed to evaluate the implementation of ASA use after the first-trimester screening in a Polish population without chronic hypertension, as well as its impact on perinatal complications. MATERIAL AND METHODS: A total of 874 patients were enrolled in the study during the first-trimester ultrasound examination. The risk of PE and FGR was assessed according to the FMF guidelines, which include the maternal history, mean arterial pressure (MAP), uterine artery pulsatility index (UtPI), pregnancy-associated plasma protein A (PAPP-A) and placental growth factor (PLGF). Among patients with a risk higher than >1:100, ASA was administered at a dose of 150 mg. Perinatal outcomes were assessed among the different groups. RESULTS: When comparing women in the high-risk group with those in the low-risk group, a statistically significantly higher risk of pregnancy complications was observed in the high-risk group. These complications included pregnancy-induced hypertension (PIH) (OR 3.6 (1.9-7)), any PE (OR 7.8 (3-20)), late-onset PE (OR 8.5 (3.3-22.4)), FGR or small for gestational age (SGA) (OR 4.8 (2.5-9.2)), and gestational diabetes mellitus type 1 (GDM1) (OR 2.4 (1.4-4.2)). The pregnancies in the high-risk group were more likely to end with a cesarean section (OR 1.9 (1.2-3.1)), while the newborns had significantly lower weights (<10 pc (OR 2.9 (1.2-6.9)), <3 pc (OR 10.2 (2.5-41.7))). CONCLUSIONS: The first-trimester screening test for PE and FGR is a necessary and effective tool in identifying high-risk pregnancies. ASA prophylaxis among high-risk patients may have the most beneficial effect. Furthermore, this screening tool may significantly reduce the incidence of early-onset PE (eo-PE).

Evidence of Placental Aging in Late SGA, Fetal Growth Restriction and Stillbirth-A Systematic Review.

During pregnancy, the placenta undergoes a natural aging process, which is considered normal. However, it has been hypothesized that an abnormally accelerated and premature aging of the placenta may contribute to placenta-related health issues. Placental senescence has been linked to several obstetric complications, including abnormal fetal growth, preeclampsia, preterm birth, and stillbirth, with stillbirth being the most challenging. A systematic search was conducted on Pubmed, Embase, and Scopus databases. Twenty-two full-text articles were identified for the final synthesis. Of these, 15 presented original research and 7 presented narrative reviews. There is a paucity of evidence in the literature on the role of placental aging in late small for gestational age (SGA), fetal growth restriction (FGR), and stillbirth. For future research, guidelines for both planning and reporting research must be implemented. The inclusion criteria should include clear differentiation between early and late SGA and FGR. As for stillbirths, only those with no other known cause of stillbirth should be included in the studies. This means excluding stillbirths due to congenital defects, infections, placental abruption, and maternal conditions affecting feto-maternal hemodynamics.

Low-Dose Aspirin after ASPRE-More Questions Than Answers? Current International Approach after PE Screening in the First Trimester.

Preeclampsia (PE) is a multi-factorial disorder of pregnancy, and it continues to be one of the leading causes of fetal and maternal morbidity and mortality worldwide. Aspirin is universally recommended for high-risk women to reduce preeclampsia risk. The purpose of this review is to summarize the recommendations of various scientific societies on predicting preeclampsia and their indications for the inclusion of acetylsalicylic acid (ASA) prophylaxis. Fourteen guidelines were compared. The recommended dose, screening method, and gestational age at the start of the test vary depending on the recommendation. The societies are inclined to recommend using increasingly higher doses (>75 mg) of ASA, with many encouraging doses from 100 mg upward. Most societies indicate that the optimal time for implementing aspirin is prior to 16 weeks' gestation. Following the publication of the Aspirin for Evidence-Based Preeclampsia Prevention (ASPRE) trial results and other papers evaluating the Fetal Medicine Foundation (FMF) screening model, a large number of societies have changed their recommendations from those based on risk factors alone to the ones based on the risk assessment proposed by the FMF. This allows for the detection of a high-risk pregnancy population in whom aspirin will be remarkably effective in preventing preterm PE, thereby decreasing maternal and fetal morbidity.

Atypical Preeclampsia before 20 Weeks of Gestation-A Systematic Review.

This systematic review was conducted to gather evidence of preeclampsia occurring before the 20th week of gestation, additionally considering the role of PLGF and sFlt-1 in the development of the disease. In the three cases of preeclampsia before the 20th week of gestation presented in the authors' material, all pregnancies ended up with IUFD, and the SFlt-1/PLGF ratios were significantly elevated in all women. Eligible publications were identified with searches in the PubMed, Embase, Scopus, and Web of Science databases. No date or language restrictions were made. All original peer-reviewed scientific reports were included. A total of 30 publications were included in the final report, including case reports and case series. No other publication types regarding this issue were identified. In the literature, 34 cases of preeclampsia with onset occurring before the 20th week of gestation were identified, for a final total of 37 cases. Live births were reported in 5 cases (10.52%), and there were 9 intrauterine fetal demises (24.32%), and 23 terminations of pregnancy (62.16%). Preeclampsia before the 20th week of gestation is rare but can occur. We collected all available evidence regarding this phenomenon, with 37 cases reported worldwide. We call for large-scale cohort or register-based studies to establish revised definitions or develop new ones regarding the currently unrecognized very early onset preeclampsia.

Renal Microcirculation Injury as the Main Cause of Ischemic Acute Kidney Injury Development.

Acute kidney injury (AKI) can result from multiple factors. The main cause is reduced renal perfusion. Kidneys are susceptible to ischemia due to the anatomy of microcirculation that wraps around the renal tubules-peritubular capillary (PTC) network. Cortical and medullary superficial tubules have a large share in transport and require the supply of oxygen for ATP production, while it is the cortex that receives almost 100% of the blood flowing through the kidneys and the medulla only accounts for 5-10% of it. This difference makes the tubules present in the superficial layer of the medulla very susceptible to ischemia. Impaired blood flow causes damage to the endothelium, with an increase in its prothrombotic and pro-adhesive properties. This causes congestion in the microcirculation of the renal medulla. The next stage is the migration of pericytes with the disintegration of these vessels. The phenomenon of destruction of small vessels is called peritubular rarefaction, attributed as the main cause of further irreversible changes in the damaged kidney leading to the development of chronic kidney disease. In this article, we will present the characteristic structure of renal microcirculation, its regulation, and the mechanism of damage in acute ischemia, and we will try to find methods of prevention with particular emphasis on the inhibition of the renin-angiotensin-aldosterone system.

Malnutrition and Erythropoietin Resistance among Patients with End-Stage Kidney Disease: Where Is the Perpetrator of Disaster?

BACKGROUND: Hemodialyzed patients with poor erythropoietin response tend to have low volume of visceral adipose tissue and score high on malnutrition-inflammation score. This study investigates in-depth the role of leptin and chosen cytokines in the development of malnutrition-inflammation syndrome (MIS) and erythropoietin resistance. METHODS: Eighty-one hemodialyzed patients with erythropoietin-treated anemia were enrolled in the study. Their body composition was measured. Erythropoietin resistance index was calculated. Blood samples for leptin, IL-6, IL-18, TNF-alpha, and IL-1-alpha serum levels were drawn. RESULTS: Leptin showed negative correlation with erythropoietin resistance index (ERI), whilst IL-6 showed the opposite. IL-6 seemed to be linked more to HD parameters and vintage, while TNF-alpha and leptin were more dependent on body composition. IL-18 and IL-1-alpha did not affect nutritional parameters nor ERI. CONCLUSION: Modulation of adipokine- and cytokine-related signaling is a promising target in tempering malnutrition in hemodialyzed, and thus achieving better outcomes in anemia treatment. Large clinical studies that target the inflammatory response in hemodialysis, especially regarding IL-6, TNF-alpha, and leptin, would be of great worth.

The Utility of Novel Kidney Injury Biomarkers in Early Detection of CSA-AKI.

Cardiac surgery-associated acute kidney injury (CSA-AKI) is one of the most common complications of cardiac surgery procedures. In this study, the authors attempt to provide new data regarding the application of novel kidney injury biomarkers in the early diagnostics of CSA-AKI. 128 adult patients undergoing elective cardiac surgery procedures with the use of cardiopulmonary by-pass (CPB) were enrolled in this study. Novel kidney injury biomarkers were marked in the plasma and urine 6 h after weaning from the CPB. A significant difference in the postoperative biomarkers' concentration between the AKI and no-AKI group was found, regarding plasma IL-8, plasma TNF-α and urine NGAL, normalized for creatinine excretion (NGAL/Cr). These were also independent predictors of CSA-AKI. An independent risk factor for CSA-AKI proved to be preoperative CKD. Plasma IL-8 and TNF-α, as well as urine NGAL/Cr, are independent early indicators of CSA-AKI and pose a promising alternative for creatinine measurements. The cut-off points for these biomarkers proposed in this investigation should be confronted with more data and revised to achieve a suitable diagnostic value.

Birth Weight < 3rd Percentile Prediction Using Additional Biochemical Markers-The Uric Acid Level and Angiogenesis Markers (sFlt-1, PlGF)-An Exploratory Study.

(1) Aim: Ultrasound is the gold standard for assessing fetal growth disorders. The relationship between high sFlt-1/PlGF scores and LBW (low birth weight) was described. In this study, we attempted to assess whether uric acid could be used as a secondary marker in estimating the pregnancy risk associated with LBW. (2) Material and methods: 665 pregnant women with a suspected or confirmed form of placental insufficiency were enrolled. In each of the patients, sFlt-1 and PlGF and uric acid levels were determined. Patients were divided into two groups according to birth weight below and above the third percentile for the given gestational age with the criteria of the neonatal definition of FGR (fetal growth restriction). (3) Results: A significant negative correlation between neonatal birth weight and the uric acid level across the entire study group was observed. We found a significant negative correlation between neonatal birth weight and the uric acid level with birth weights < 3rd percentile. (4) Conclusions: There is a significant link between the uric acid concentration and LBW in the group with placental insufficiency. Uric acid can improve the prediction of LBW. An algorithm for LBW prognosis that makes use of biophysical (ultrasound) and biochemical (uric acid level, angiogenesis markers) parameters yields better results than using these parameters separately from each other.

Intrapatient Variability (IPV) and the Blood Concentration Normalized by the Dose (C/D Ratio) of Tacrolimus-Their Correlations and Effects on Long-Term Renal Allograft Function.

Tacrolimus, in combination with mycophenolate mofetil and glucocorticoids, is the basis of immunosuppressive therapy after renal transplantation. Tacrolimus intrapatient variability (IPV) and the blood concentration normalized by the dose (concentration/dose ratio, C/D ratio) both have an effect on the function of the transplanted kidney. In this study, we examined whether the metabolism rate affected IPV, whether the C/D ratio value was stable in the long-term follow-up, and whether it could be used for IPV measurements. In addition, our study population was examined for the effect of the C/D ratio and IPV on long-term renal function. The C/D ratio and IPV were examined in 170 patients at appointments held at 3, 6, 12 and 24 months after RTx. The average time post renal transplantation was 70 months. Renal function defined as creatinine concentration at the last appointment was examined. Results: the mean C/D ratio in the study group was 1.63. A negative correlation between the C/D ratio and creatinine concentration at the end of the follow-up was observed. Between the C/D ratio < and ≥1.63 groups, significant differences in creatinine concentration at the last appointment were found. No relationship was identified between the mean C/D ratio and IPV. The C/D ratio values increased significantly over a longer post-transplant period (12, 24, 60 and 120 m). We did not find a correlation between the mean IPV and the creatinine concentration from the last appointment. Our study group was divided into terciles according to IPV, while no renal graft function differences were found at the same appointment. Conclusion: the C/D ratio is useful for assessing the effects of the metabolism rate of tacrolimus on the long-term renal graft function. The C/D ratio does not affect the IPV value. IPV calculated from variability of the C/D ratio does not influence transplanted kidney function. The C/D changes over time.

Adverse Neonatal Outcome of Pregnancies Complicated by Preeclampsia.

Despite many available treatments, infants born to preeclamptic mothers continue to pose a serious clinical problem. The present study focuses on the evaluation of infants born to preeclamptic mothers for the occurrence of early-onset complications and attempts to link the clinical status of such infants to the angiogenesis markers in maternal blood (sFlt-1, PlGF). The study included 77 newborns and their mothers diagnosed with preeclampsia. The infants were assessed for their perinatal outcomes, with an emphasis on adverse neonatal outcomes such us infections, RDS, PDA, NEC, IVH, ROP, or BPD during the hospitalization period. The cutoff point was established using the ROC curve for the occurrence of any adverse neonatal outcome and it was 204 for the sFlt-1/PlGF and 32 birth week with AOC 0.644 and 0.91, respectively. The newborns born to mothers with high ratios had longer hospitalization times and, generally, were more frequently diagnosed with any of the aforementioned adverse neonatal outcomes. Also, the neonates born prior to or at 32 wkGA with higher sFlt-1/PlGF ratios were statistically significantly more common to be diagnosed with any of the adverse neonatal outcomes compared to those with lower ratio born prior to or at 32 wkGA. The sFlt-1/PlGF ratio can be a useful tool in predicting short-term adverse neonatal outcomes. Infants born after a full 33 weeks gestation developed almost no severe neonatal complications. Appropriate screening and preventive healthcare for preeclampsia can contribute significantly to reducing the incidence of neonatal complications.

The Most Promising Biomarkers of Allogeneic Kidney Transplant Rejection.

Clinical transplantology is a constantly evolving field of medicine. Kidney transplantation has become standard clinical practice, and it has a significant impact on reducing mortality and improving the quality of life of patients. Allogenic transplantation induces an immune response, which may lead to the rejection of the transplanted organ. The gold standard for evaluating rejection of the transplanted kidney by the recipient's organism is a biopsy of this organ. However, due to the high invasiveness of this procedure, alternative diagnostic methods are being sought. Therefore, the biomarkers may play an essential predictive role in transplant rejection. A review of the most promising biomarkers for early diagnosis and prognosis prediction of allogenic kidney transplant rejection summarizes novel data on neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), C-X-C motif chemokine 10 (CXCL-10), cystatin C (CysC), osteopontin (OPN), and clusterin (CLU) and analyses the dynamics of changes of the biomarkers mentioned above in kidney diseases and the mechanism of rejection of the transplanted kidney.

How Is Body Composition and Nutrition Status Associated with Erythropoietin Response in Hemodialyzed Patients? A Single-Center Prospective Cohort Study.

Background: Anemia is the most common finding in patients with end-stage kidney disease undergoing renal replacement therapy. A certain percentage of patients does not respond adequately to erythropoietin (EPO) treatment, not being able to reach desirable hemoglobin levels even when treated with large-dose EPO and intravenous/oral iron. In our study, we wanted to further investigate how nutritional status is associated with erythropoietin responsiveness. To quantify EPO response, we used the Erythropoietin Resistance Index (ERI), which is defined as the weekly weight-adjusted dose of EPO divided by the hemoglobin level. Patients and methods: Seventy-eight patients undergoing hemodialysis were included. All of them were measured by a SECA mBCA body composition analyzer and evaluated by Kalantar-Zadeh's MIS score. Routine biochemical tests were also taken into account. The Shapiro-Wilk test was used to study the distributions of quantitative variables, which were significantly different from normal (p < 0.05). We used nonparametric Mann-Whitney U-test to compare groups. Correlations were studied by means of Spearman's rank correlation coefficient. Bonferroni correction for multiple testing was performed. To find independent determinants of ERI, we additionally performed multivariate analysis using the General Linear Model (GLM). Results: In terms of body composition, factors that are associated with high ERI are low BMI, low fat mass, low visceral fat volume, high total body water percentage, low phase angle and low fat-free mass. In addition to body composition parameters, total MIS score and IL-6 serum levels correlated positively with ERI value. IL-6 was an independent determinant of ERI value, based on multivariate analysis. After correction for multiple analysis, BMI and eGFR both remained significant factors associated with EPO response. Conclusions: It seems crucial to prevent inflammatory malnutrition as a part of a holistic approach to anemia treatment in dialysis patients.

The role of uropathogenic Escherichia coli adhesive molecules in inflammatory response- comparative study on immunocompetent hosts and kidney recipients.

BACKGROUND: Urinary tract infections (UTI) represent one of the most common contagious diseases in humans. Uropathogenic Escherichia coli (UPEC) strains are recognized as the most frequent causative agent, and these express a range of virulence factors including the adhesins. Immune response to UPEC under immunosuppression has not been fully understood yet. Interleukin 1ß (IL1ß), 6 (IL6) and 17 (IL17) represent clinically relevant markers of inflammation. AIM: The study aimed to investigate the interplay between UPEC genotype and hosts' immune status in shaping local inflammatory response in the course of an UTI episode. The respective numbers of: 18 kidney recipients with UPEC UTI, 28 immunocompetent hosts with UPEC UTI and 29 healthy controls were involved. Urine IL1ß, IL6, and IL17/creatinine ratios in relation to fimH, csgA, papC, tosA, and flu genes presence in UPEC isolated from the urine samples were analyzed. Apart from traditional statistics, also machine learning algorithms were applied. RESULTS: The urine levels of IL1ß and IL 6 were similar in kidney recipients and the immunocompetent hosts. IL1ß levels were higher in both kidney recipients and immunocompetent hosts than in controls, while IL6 levels were higher only in immunocompetent hosts than in controls. In the machine learning classification model, high urine IL17 levels were significantly more prevalent in controls, while low IL17 levels in urines infected with Ag43-positive UPEC strains, regardless of the host's immune status. In the traditional statistical analysis, IL17 levels appeared significantly higher in urine samples from kidney recipients infected with Ag43-negative UPEC strains. CONCLUSIONS: In the UTI- affected patients, the combination of the immune status of an individual and Ag43 status of the UPEC strain determined urine IL17 level in the analyzed group. However, IL17 levels above median were overall more prevalent in controls.

Effectiveness of Different Algorithms and Cut-off Value in Preeclampsia First Trimester Screening.

Results: For the cut-off point >1 : 150, 86 women at an increased risk of eo-PE using algorithm 1 were identified. Of these 86 patients, 83 (96%) were identified using algorithm 2, 62 (72%) using algorithm 3, and 60 (69%) using algorithm 4. In addition, it was demonstrated that between 21% and 29% of women at a low risk of eo-PE could be given acetylsalicylic acid if a screening test was used that did not account for PlGF. Conclusions: In order to provide the highest level of health care to pregnant women, it is extremely important that full screening for eo-PE should be ensured. The cheapest algorithm based only on MAP and UtPI resulted in our patients being unnecessarily exposed to complications.