Acoustic outcomes and voice-related quality of life in male-to-female transsexuals undergoing Wendler glottoplasty: a single-centre experience.

INTRODUCTION: Many transsexual women seek to feminise their voice through pitch elevation surgeries so that it becomes congruent with their gender identity. This study aims to determine the safety and effectiveness of Wendler glottoplasty (WG) in vocal feminisation through the assessment of acoustic and aerodynamic parameters of the voice, as well as voice-related quality of life (QoL) in male-to-female transsexuals. MATERIAL AND METHODS: We retrospectively reviewed the medical records of transsexual women who underwent WG for voice feminisation at our institution between 2016 and 2023. All acoustic and aerodynamic analyses, a voice self-assessment, and a videolaryngostroboscopic evaluation were performed in the immediate preoperative period and at the follow-up visit 6 weeks after the procedure. RESULTS: A total of 11 patients with a mean age of 32.73 years were included. After WG, there was a significant fundamental frequency and speaking fundamental frequency increase of 109.64 Hz and 83.48 Hz, respectively (p < 0.001), representing an average rise by 9.71 semitones and 8.36 semitones (STs), respectively. No significant differences were found between the mean pre- and postoperative values of fundamental frequencies, frequency range, upper limit of the frequency range of spoken voice, and maximum phonation time. Contrarily, the mean lower limit of frequency range rose by 75.56 Hz (p < 0.001), representing an average increase of 10.56 STs. None of the assessed spirometric parameters changed significantly after WG (p > 0.05). The mean overall Voice Handicap Index (VHI) and Voice-Related Quality of Life (V-RQOL) scores significantly improved after the surgery, decreasing by 24.54 points (p = 0.008) and 11.5 points (p = 0.001), respectively. A significant improvement was observed in the functional and emotional domains of VHI. Additionally, significantly fewer patients considered the overall quality of their voice to be "poor" after WG. CONCLUSIONS: WG constitutes an effective method of surgical voice feminisation in male-to-female transsexuals with concurrent improvement in their voice-related QoL. Furthermore, it remains a safe procedure without persistent complications and negative influence on the acoustic-aerodynamic measures of the voice.

PD-1 Receptor (+) T cells are associated with the efficacy of the combined treatment with regulatory t cells and rituximab in type 1 diabetes children via regulatory t cells suppressive activity amelioration.

An imbalance between exaggerated autoaggressive T cell responses, primarily CD8 + T cells, and impaired tolerogenic mechanisms underlie the development of type 1 diabetes mellitus. Disease-modifying strategies, particularly immunotherapy focusing on FoxP3 + T regulatory cells (Treg), and B cells facilitating antigen presentation for T cells, show promise. Selective depletion of B cells may be achieved with an anti-CD20 monoclonal antibody (mAb). In a 2-year-long flow cytometry follow-up, involving 32 peripheral blood T and B cell markers across three trial arms (Treg + rituximab N = 12, Treg + placebo N = 13, control N = 11), we observed significant changes. PD-1 receptor (+) CD4 + Treg, CD4 + effector T cells (Teffs), and CD8 + T cell percentages increased in the combined regimen group by the end of follow-up. Conversely, the control group exhibited a notable reduction in PD-1 receptor (+) CD4 + Teff percentages. Considering clinical endpoints, higher PD-1 receptor (+) expression on T cells correlated with positive responses, including a higher mixed meal tolerance test AUC, and reduced daily insulin dosage. PD-1 receptor (+) T cells emerged as a potential therapy outcome biomarker. In vitro validation confirmed that successful Teff suppression was associated with elevated PD-1 receptor (+) Treg levels. These findings support PD-1 receptor (+) T cells as a reliable indicator of treatment with combined immunotherapy consisting of Tregs and anti-CD20 mAb efficacy in type 1 diabetes mellitus.

Impact of Wendler glottoplasty on acoustic measures and quality of voice in transgender women: a systematic review and meta-analysis.

PURPOSE: Since new evidence regarding the impact of Wendler glottoplasty (WG) on the voice in transgender women became available in the literature in recent years, we aimed to perform an updated systematic review and meta-analysis to determine the actual safety and efficacy of WG in the process of vocal feminization. METHODS: PubMed, Embase, and Cochrane were searched for English-language articles published until July 4, 2023. Studies were found eligible if they evaluated the impact of WG on the acoustic-aerodynamic measures and quality of voice in transgender women. RESULTS: Twenty-three studies were identified. After exclusion of three studies due to incomplete data, 20 studies including 656 patients were included in the meta-analysis. After WG, there was a significant increase of fundamental frequency, speaking fundamental frequency, and lower limit of the frequency range (p < 0.001). Concurrently, a significant reduction of frequency range and maximum phonation time was observed (p < 0.001). No significant differences were found between the pre- and postoperative values regarding the Grade, Roughness, Breathiness, Asthenia, and Strain scale score (p = 0.339). The overall score in the Trans Woman Voice Questionnaire (TWVQ) significantly improved after WG (p < 0.001). CONCLUSIONS: WG is an effective voice feminization method in transgender women, associated with a high procedural success and low risk of postoperative complications. Significantly improved TWVQ score after surgery suggests its positive impact on the voice-related quality of life. Postoperative decrease of maximum phonation time and frequency range does not seem to significantly impact the effectiveness of voice production.

Does Massive Bowel Resection in Newborns Affect Further Immunity in Children?

BACKGROUND: The massive resection of the small intestine leading to short bowel syndrome (SBS) deprives an organism of many immunocompetent cells concentrated in gut-associated lymphoid tissue, the largest immune organ in humans. We have aimed to access the influence of bowel resection on adaptive immunity in children, based on peripheral lymphocyte subsets and serum immunoglobulins. METHODS: 15 children who underwent bowel resection in the first months of their life and required further home parenteral nutrition were enrolled into the study. Based on flow cytometry, the following subsets of lymphocytes were evaluated: T, B, NK, CD4+, C8+, and activated T cells. RESULTS: Statistically significant differences were found for the rates of lymphocytes B, T, CD8+, and NK cells. The absolute count of NK cells was lower in the SBS group than in the control group. Absolute counts of lymphocytes, lymphocytes B, T, CD4+, and percentages of lymphocytes CD4+, and activated T cells inversely correlated with age in SBS group. CONCLUSIONS: Children with SBS do not present with clinical signs of immunodeficiency as well as deficits in peripheral lymphocyte subsets and serum immunoglobulins. The tendency of the lymphocyte subpopulations to decrease over time points out the necessity for longer follow- up.

High maternal-fetal HLA eplet compatibility is associated with severe manifestation of preeclampsia.

Introduction: Preeclampsia is responsible for more than 70 000 and 500 000 maternal and fetal deaths, respectively each year. Incomplete remodelling of the spiral arteries in placenta is the most accepted theory of preeclampsia pathogenesis. However, the process is complexed with immunological background, as pregnancy resembles allograft transplantation. Fetus expresses human leukocyte antigens (HLA) inherited from both parents, thus is semiallogeneic to the maternal immune system. Therefore, induction of fetal tolerance is crucial for physiological outcome of pregnancy. Noteworthy, the immunogenicity of discordant HLA antigens is determined by functional epitopes called eplets, which are continuous and discontinuous short sequences of amino acids. This way various HLA molecules may express the same eplet and some HLA incompatibilities can be more immunogenic due to different eplet combination. Therefore, we hypothesized that maternal- fetal HLA incompatibility may be involved in the pathogenesis of gestational hypertension and its progression to preeclampsia. We also aimed to test if particular maternal-fetal eplet mismatches are more prone for induction of anti- fetal HLA antibodies in gestational hypertension and preeclampsia. Methods: High resolution next-generation sequencing of HLA-A, -B, -C, -DQB1 and -DRB1 antigens was performed in mothers and children from physiological pregnancies (12 pairs) and from pregnancies complicated with gestational hypertension (22 pairs) and preeclampsia (27 pairs). In the next step HLA eplet identification and analysis of HLA eplet incompatibilities was performed with in silico approach HLAMatchmaker algorithm. Simultaneously maternal sera were screened for anti-fetal HLA class I, class II and anti-MICA antibodies with Luminex, and data were analyzed with HLA-Fusion software. Results: We observed that high HLA-C, -B, and DQB1 maternal-fetal eplet compatibility was associated with severe preeclampsia (PE) manifestation. Both quantity and quality of HLA epletmismatches affected the severity of PE. Mismatches in HLA-B eplets: 65QIA+76ESN, 70IAO, 180E, HLA-C eplets: 193PL3, 267QE, and HLA-DRB1 eplet: 16Y were associated with a mild outcome of preeclampsia if the complication occurred. Conclusions: High HLA-C, HLA-DQB1 and HLA-B eplet compatibility between mother and child is associated with severe manifestation of preeclampsia. Both quantity and quality of maternal-fetal HLA eplet mismatches affects severity of preeclampsia.

Clinical Application of In Vitro Tests for COVID-19 Vaccine Delayed Hypersensitivity Diagnostics.

Drug hypersensitivity reactions can be classified as immediate or delayed. While diagnostic options for immediate reactions are well developed and standardized, delayed reactions (in many cases type IV according to Gell and Coombs) are a challenge for allergy work-up. In recent years, some in vitro markers have been proposed and used for delayed reactions, such as contact dermatitis. Primary strategy: Avoidance is difficult to achieve, especially for COVID-19 vaccinations, when immunity against infection is extremely important. The aim of our study was to evaluate the application of in vitro delayed hypersensitivity tests in COVID-19 vaccines. Seven patients with a positive history of severe delayed drug allergy were enrolled. Vein blood was collected to stimulate cells with the tested vaccines (Comirnaty, Janssen, Spikevax) and excipients with the assessment of CD40L, CD69, IL-2, IL-4, IL-6, IL-10, IFNgamma, TNFalfa, and intracellular markers: granulysin and INFgamma. In addition, basophile activation tests, patch tests, skin prick tests, and intradermal tests were performed with the tested vaccine. Finally, the decision was made to either administer a vaccine or resign. Two out of seven patients were considered positive for drug hypersensitivity in the in vitro test according to the high vaccine stimulation index measured with CD69 (6.91 and 12.18) and CD40L (5.38 and 15.91). All patch tests, BATs, and skin tests were negative. Serum interleukin measurements were inconclusive as the impact of the vaccine itself on the immunity system was high. Intracellular markers gave uncertain results due to the lack of stimulation on the positive control. CD69 and CD40L could be reliable in vitro markers for delayed hypersensitivity to COVID-19 vaccines. Patch tests, skin tests, BATs, and serum interleukins did not confirm their usefulness in our study.

Local T cell infiltrates are predominantly associated with corneal allograft rejection.

BACKGROUND: Corneal transplantations (CTXs) are a vision-saving procedure. Routinely, while CTXs' survival rates remain high, the risk of graft failure increases significantly for repeated CTXs. The reason is an alloimmunization following previous CTXs and development of memory T (Tm) and B (Bm) cells. METHODS: We characterized populations of cells present in explanted human corneas from patients receiving the first CTX and marked as a primary CTX (PCTX) or the second or more CTXs and marked as a repeated CTX (RCTX). Cells extracted from resected corneas and from peripheral blood mononuclear cells (PBMCs) were analyzed by the flow cytometry method using multiple surface and intracellular markers. RESULTS: Overall, the number of cells was similar in PCTX and RCTX patients. Extracted infiltrates from PCTXs and RCTXs contained similar numbers of T cell subsets, namely CD4+, CD8+, CD4+ Tm, CD8+ Tm, CD4+Foxp3+ T regulatory (Tregs), CD8+ Treg cells, while very few B cells (all p = NS). However, when compared to peripheral blood, PCTX and RCTX corneas contained significantly higher percentages of effector memory CD4+ and CD8+ T cells (both p < 0,05). In comparison to PCTX, RCTX group had the highest levels of Foxp3 in T CD4+ Tregs (p = 0,04) but decreased percentage of Helios-positive CD4+ Tregs. CONCLUSION: PCTXs and especially RCTXs are rejected mainly by local T cells. The accumulation of effector CD4+ and CD8+ T cells, as well as CD4+ and CD8+ Tm cells is associated with the final rejection. Furthermore, local CD4+ and CD8+ Tregs expressing Foxp3 and Helios are probably insufficient to impose the acceptance of CTX.

Study protocol of a prospective single-arm multicenter clinical study to assess the safety and performance of the aXess hemodialysis graft: The pivotal study.

BACKGROUND: Arteriovenous grafts (AVGs) are used for patients deemed unsuitable for the creation of an autogenous arteriovenous fistula (AVF) or unable to await maturation of the AVF before starting hemodialysis. However, AVGs are prone to infection and thrombosis resulting in low long-term patency rates. The novel aXess Hemodialysis Graft consists of porous polymeric biomaterial allowing the infiltration by cells and the growth of neotissue, while the graft itself is gradually absorbed, ultimately resulting in a fully functional natural blood vessel. The Pivotal Study will examine the long-term effectiveness and safety of the aXess Hemodialysis Graft. METHODS: The Pivotal Study is a prospective, single-arm, multicenter study that will be conducted in 110 subjects with end-stage renal disease who are not deemed suitable for the creation of an autogenous vascular access. The primary efficacy endpoint will be the primary patency rate at 6 months. The primary safety endpoint will be the freedom from device-related serious adverse events at 6 months. The secondary endpoints will include the procedural success rate, time to first cannulation, patency rates, the rate of access-related interventions to maintain patency, the freedom from device-related serious adverse events and the rate of access site infections. Patients will be followed for 60 months. An exploratory Health Economic and Outcomes Research sub-study will determine potential additional benefits of the aXess graft to patients, health care institutions, and reimbursement programs. DISCUSSION: The Pivotal study will examine the long-term performance and safety of the aXess Hemodialysis Graft and compare the outcome measures with historical data obtained with other graft types and autogenous AVFs. Potential advantages may include superior long-term patency rates and lower infection rates versus currently available AVGs and a shorter time to first cannulation compared to an autologous AVF. As such, the aXess Hemodialysis Graft may fulfill an unmet clinical need in the field of hemodialysis access.

T regulatory cells metabolism: The influence on functional properties and treatment potential.

CD4+CD25highFoxP3+ regulatory T cells (Tregs) constitute a small but substantial fraction of lymphocytes in the immune system. Tregs control inflammation associated with infections but also when it is improperly directed against its tissues or cells. The ability of Tregs to suppress (inhibit) the immune system is possible due to direct interactions with other cells but also in a paracrine fashion via the secretion of suppressive compounds. Today, attempts are made to use Tregs to treat autoimmune diseases, allergies, and rejection after bone marrow or organ transplantation. There is strong evidence that the metabolic program of Tregs is connected with the phenotype and function of these cells. A modulation towards a particular metabolic stage of Tregs may improve or weaken cells' stability and function. This may be an essential tool to drive the immune system keeping it activated during infections or suppressed when autoimmunity occurs.

In situ diffraction monitoring of nanocrystals structure evolving during catalytic reaction at their surface.

With decreasing size of crystals the number of their surface atoms becomes comparable to the number of bulk atoms and their powder diffraction pattern becomes sensitive to a changing surface structure. On the example of nanocrystalline gold supported on also nanocrystalline [Formula: see text] we show evolution of (a) the background pattern due to chemisorption phenomena, (b) peak positions due to adsorption on nonstoichiometric [Formula: see text] particles, (c) Au peaks intensity. The results of the measurements, complemented with mass spectrometry gas analysis, point to (1) a multiply twinned structure of gold, (2) high mobility of Au atoms enabling transport phenomena of Au atoms to the surface of ceria while varying the amount of Au in the crystalline form, and (3) reversible [Formula: see text] peaks position shifts on exposure to He-X-He where X is O2, H2, CO or CO oxidation reaction mixture, suggesting solely internal alternations of the [Formula: see text] crystal structure. We found no evidence of ceria lattice oxygen being consumed/supplied at any stage of the process. The work shows possibility of structurally interpreting different contributions to the multi-phase powder diffraction pattern during a complex physico-chemical process, including effects of physi-, chemisorption and surface evolution. It shows a way to structurally interpret heterogeneous catalytic reactions even if no bulk phase transition is involved.

Drug Retention and Safety of Secukinumab in a Real-World Cohort of Ankylosing Spondylitis and Psoriatic Arthritis Patients.

Real-life data that support effectiveness of secukinumab (SEC), an interleukin 17A inhibitor, in Poland are few. We aimed to evaluate SEC effectiveness based on drug retention and safety measures reported in electronic medical records (EMRs) of patients with psoriatic arthritis (PsA) and ankylosing spondylitis (AS) from two tertiary-care centers in the region of Lesser Poland. A total one-hundred eighty seven (127 PsA and 60 AS) first (n = 112), second (n = 59) and third-line SEC users were enrolled. The mean (SD) age of the sample was 45.7 (12.9), and 48% were male. All patients were classified with active and severe disease prior to initiation. Administrative delays for SEC users last a median 2 weeks. Median delay from symptom onset to diagnosis was 4 years (IQR 8), and differed by predominant disease subtype. The inefficacy rate was 10.7% and 18.6% for first and second-line users with median (IQR) drug maintenance estimated at 1.22 years (1.46) and 1.51 (1.38), respectively. First-year drug loss defined as drug switch due to inefficacy or adverse event was rare, with median estimates of 0.91 (95% CI; 0.85, 0.97) and 0.86 (95% CI; 0.77, 0.95) for first and second-line, respectively.

Assessment of life quality and health perception among recovered COVID-19 patients: multivariate analysis - own material and a review of previous reports on life quality assessment among convalescents.

BACKGROUND: The SARS-CoV-2 virus, causing acute respiratory disease, is responsible for the COVID-19 pandemic, which began in early 2020. In addition to symptoms typical of respiratory tract infections, the virus causes a number of non-specific, often long-lasting effects that hinder the daily functioning of individuals. The aim of the study was a subjective assessment of life quality and health perception among recovered COVID-19 patients. MATERIAL AND METHODS: The study included 337 subjects who had been infected with SARS-CoV-2 confirmed by a positive RT-PCR test. The study participants were of legal age. The convalescents completed a questionnaire that contained 26 questions about gender, height, body weight, blood type, general and specific symptoms, comorbidities, hospital stay and duration of specific symptoms, the severity of which was assessed on the Visual Analogue Scale (VAS). The subjects determined whether the COVID-19 infection influenced their health perception and life quality. RESULTS: According to 46% of the respondents, COVID-19 had an impact on their quality of life and health. The chance for patients to notice the negative effects of COVID-19 on their current health status and life quality increased with each subsequent symptom of the disease by 49%, with each day of its occurrence by 3%, and with each VAS point of the severity of all infection symptoms by 30%. CONCLUSIONS: The study shows that COVID-19 disease affects life quality and overall health perception after recovery. Significant impact of COVID-19 on the quality of life should be a signal to create mental support and rehabilitation programs for convalescents to minimize discomfort and shorten the duration of absenteeism from work. Med Pr. 2022;73(6):449-56.

Prospective Assessment of Risk Factors Influencing Facial Nerve Paresis in Patients after Surgery for Parotid Gland Tumors.

Background and objectives: Facial weakness is the most important complication of parotid gland tumor surgery. The aims of this study are as follows: (1) assessment of the prevalence of postparotidectomy facial nerve dysfunction; (2) clinical and electrophysiological assessment of the facial nerve function before parotidectomy and at 1 and 6 months postoperatively; (3) assessment of the association of postoperative facial palsy with selected risk factors; and (4) assessment of the correlation between the results of clinical and neurophysiological assessments of facial nerve function. Materials and Methods: This study comprised 50 patients (aged 24-75 years) who underwent parotidectomy at the Department of Otolaryngology and Laryngological Oncology in Zabrze, Poland between 2015 and 2017. The evaluation included neurological, clinical and electrophysiological assessments of the facial nerve prior to surgery and at 1 and 6 months postoperatively. Results: No facial palsy was found preoperatively or 6 months postoperatively. Facial nerve dysfunction was found in 74% of patients 1 month postoperatively. In most cases (54%), paresis was mild or moderate (House-Brackmann grades II and III). The results of electrophysiological tests before parotidectomy were either normal or showed some mild abnormalities. We found a statistically significant correlation between the clinical assessment of the facial nerve function (based on the House-Brackmann scale) one month postoperatively and the latency of the CMAP response from the orbicularis oculi and orbicularis oris muscles. In all three studies, a statistically significant correlation was found between the amplitude of the compound muscle action potential (CMAP) of the orbicularis oris muscle and the degree of facial nerve weakness. Conclusions: The factors that may influence the risk of postoperative facial nerve paralysis (prolonged surgical time and the size and location of the tumor other than in the superficial lobe only) may indirectly suggest that surgery-related difficulties and/or surgeon experience could be crucial to surgery safety.

Ageing-resembling phenotype of long-term allogeneic hematopoietic cells recipients compared to their donors.

BACKGROUND: Ageing is a complex phenomenon that leads to decreased proliferative activity, loss of function of the cells, and cellular senescence. Senescence of the immune system exacerbates individual's immune response, both humoral and cellular but increases the frequency of infections. We hypothesized that physiological ageing of adaptive immune system occurs in recipients of allogeneic hematopoietic cells transplant (allo-HCT) at faster rate when compared to their respective donors since the small number of donor cells undergo immense proliferative stress restoring recipients hematopoiesis. We compared molecular characterizations of ageing between recipients and donors of allo-HCT: telomeric length and immunophenotypic changes in main lymphocyte subsets - CD4+, CD8+, CD19+, CD56+. RESULTS: Median telomeric length (TL) of CD8+ lymphocytes was significantly longer in donors compared to recipients (on average 2,1 kb and 1,7 kb respectively, p = 0,02). Similar trends were observed for CD4+ and CD19+ although the results did not reach statistical significance. We have also found trends in the immunophenotype between recipients and donors in the subpopulations of CD4+ (naïve and effector memory), CD8+ Eomes+ and B-lymphocytes (B1 and B2). Lower infection risk recipients had also a significantly greater percentage of NK cells (22,3%) than high-risk patients (9,3%) p = 0,04. CONCLUSION: Our data do not support the initial hypothesis of accelerated aging in the long term all-HCT recipients with the exception of the recipients lymphocytes (mainly CD8+) which present some molecular features, characteristic for physiological ageing (telomeric shortening, immunophenotype) when compared to their respective donors. However, a history of lower infection numbers in HCT recipients seems to be associated with increased percentage of NK cells. The history of GVHD seems not to affect the rate of ageing. Therefore, it is safe to conclude that the observed subtle differences between recipients' and donors' cells result mainly from the proliferative stress in the early period after allo-HCT and the difference between hosts' and recipients' microenvironments.

Local and Systemic Immunity Are Impaired in End-Stage-Renal-Disease Patients Treated With Hemodialysis, Peritoneal Dialysis and Kidney Transplant Recipients Immunized With BNT162b2 Pfizer-BioNTech SARS-CoV-2 Vaccine.

Vaccination against COVID-19 in patients with end-stage renal disease (ESRD) on replacement therapy and kidney transplant recipients (KTRs) is particularly important due to the high mortality rate. Here, we tested the local and systemic immunity to the novel Pfizer BioNTech (BNT162b2) messenger RNA (mRNA) in ESRD, KTR patients, and healthy individuals (150 subjects). The ESRD group was divided into: hemodialysis (HD) and peritoneal dialysis (PD). We investigated the local and systemic immunity based on anti-N (nucleoprotein) and anti-S (spike1/2) Immunoglobulin A (IgA) and Immunoglobulin G (IgG) antibodies, respectively. Additionally, we performed an Interferon gamma (IFN-γ) release test Interferon-gamma release assay (IGRA) to monitor the cellular component of vaccine response. The control group had the highest level of anti-S IgG antibodies (153/2,080 binding antibody units (BAU)/ml) among all analyzed patients after the 1st and 2nd dose, respectively. The HD group (48/926 BAU/ml) had a diminished antibody level compared to PD (93/1,607 BAU/ml). Moreover, the seroconversion rate after the 1st dose was lower in HD than PD (56% vs. 86%). KTRs had extremely low seroconversion (33%). IgA-mediated immunity was the most effective in the control group, while other patients had diminished IgA production. We observed a lower percentage of vaccine responders based on the IFN-γ level in all research participants (100% vs. 85% in control, 100% vs. 80% in PD, 97% vs. 64% in HD). 63% of seropositive KTRs had a positive IGRA, while 28% of seronegative patients produced IFN-γ. Collectively, PD patients had the strongest response among ESRD patients. Two doses of the Pfizer vaccine are ineffective, especially in HD and KTRs. A closer investigation of ESRD and KTRs is required to set the COVID-19 vaccine clinical guidance. Clinical Trial Registration Number: www.ClinicalTrials.gov, identifier: NCT04 905 862.

KIR- Ligand Interactions in Hypertensive Disorders in Pregnancy.

Hypothesis: The activity of natural killer (NK) cells is considered an important factor for the tolerance of the fetus during pregnancy. The complications of pregnancy, such as hypertensive disorders (HDP), may be therefore associated with this immune compartment. Methods: The current study included 41 pregnant women diagnosed with HDPs (Gestational Hypertension; GH or Preeclampsia; PE) and 21 healthy women. All the patients were under continuous obstetric care during the pregnancy and labour. The number of mother-child mismatches within killer immunoglobulin-like receptors (KIRs), their ligands [MM], and missing KIR ligands [MSLs] was assessed. KIRs and their ligands were assessed with Next Generation Sequencing (NGS) and Polymerase Chain Reaction Sequence-Specific Oligonucleotide (PCR-SSO) typing. The subsets of NK cells were assessed with multicolor flow cytometry and correlated to the number of MSLs. Results: The number of MSLs was significantly higher in HDP patients when compared to healthy non-complicated pregnancy patients. Some MSLs, such as those with 2DS2 activating KIR, were present only in HDP patients. The percentage of CD56+CD16-CD94+ NK cells and CD56+CD16-CD279+ NK cells correlated with the number of MSLs with inhibiting KIRs only in healthy patients. In HDP patients, there was a correlation between the percentage of CD56-CD16+CD69+ NK cells and the number of MSLs with inhibiting and activating KIRs. As compared to the healthy group, the percentage of CD56+CD16-CD279+ NK cells and CD56-CD16+CD279+ NK cells were lower in HDP patients. HDP patients were also characterized by a higher percentage of CD56+CD16+perforin+ NK cells than their healthy counterparts. Conclusions: Patients with HDP were characterized by a higher number of MSLs within the KIRs receptors. It seemed that the number of MSLs in the healthy group was balanced by various receptors, such as CD94 or inhibitory CD279, expressed on NK cells. Conversely, in HDP patients the number of MSLs was associated with the activation detected as the increased level of CD69+ NK cells.

Endocrine Autoimmunity in Pregnancy.

Human gestation leads to a number of physiological alterations which peak at the development of placentta known for, among many other functions, being a transient but highly potent endocrine organ. Hormonal activity of placenta is marked by its ability to continuously produce and secrete high levels of progesterone. Progesterone guards the well-being of the fetoplacental unit throughout the gestation and one of the proposed mechanisms of this principle involves the development of local and systemic immune tolerance mainly due to impediment of CD4+ lymphocyte activation. However, though these alterations are present and well-established, autoimmunity is not entirely rare and a wide spectrum of diseases can continue, or develop de novo, throughout the gestation or even after the delivery. Up-to-date data supports the existence of a relationship between the clinical course of chosen autoimmune diseases and levels of circulating sex steroids. The most common autoimmune endocrinopathies in pregnant women are Hashimoto's disease, Graves' disease, and, more rarely, primary adrenal insufficiency in the form of Addison's disease. Gestation can influence the clinical course of these endocrinopathies in patients who were diagnosed before conception. Multiple particles, like TSH-receptor stimulating antibodies, thyroid hormones, glucocorticoids, and anti-thyroid medications, can cross the placental barrier and evoke biological action in fetal tissues. Thyroid pathology in the form of postpartum thyroiditis is particularly prevalent in patients with positive anti-thyroperoxidase and anti-thyroglobulin antibodies. Certain populations are more at risk of developing numerous gestational complications and require regular follow-up. In our paper, we would like to address physiological, physiopathological, and clinical aspects of endocrine autoimmunity throughout human gestation, as well as special circumstances to consider in pregnant women.

In-Depth Analysis of Anti-HLA Antibodies Using C1q Assay.

Alloantibodies are significant biomarkers of posttransplant kidney rejection. With solid-phase assays, the presence of alloantibodies and complement-binding capacities can be tested. It has been noted that complement-binding anti-HLA (C1q) correlates well with high titers of anti-HLA antibodies (single antigen bead, SAB), but we have recently shown that lower SAB titers may be associated with complement in the complement cytotoxicity test. If so, low titers of donor-specific antibodies could be stratified for complement binding and used for better donor-recipient matching. To study this, we tested 268 patients awaiting kidney transplantation for SAB and C1q and stratified them into positive (Allo+) and negative (Allo-) cohorts. Next, all assayed specificities of SAB were matched with the corresponding C1q in order to correlate mean fluorescence intensity levels. We found a strong correlation between SAB and C1q for all HLA loci apart from HLA-DP. Moreover, there was no strict cutoff for C1q prediction on SAB mean fluorescence intensity level. In addition, an unusual laboratory phenotype was found; that is, a positive C1q result without corresponding SAB specificity. We tested this phenomenon and found positive IgM SAB. CONCLUSIONS: Simultaneous C1q and SAB testing may serve as a tool for in-depth analysis of alloantibodies before transplantation.

Combined therapy with CD4+ CD25highCD127- T regulatory cells and anti-CD20 antibody in recent-onset type 1 diabetes is superior to monotherapy: Randomized phase I/II trial.

AIMS: Monotherapy with autologous expanded CD4+ CD25high CD127- T regulatory cells (Tregs) or rituximab has been documented to slow disease progression in patients with recent-onset type 1 diabetes mellitus (T1DM). Whether a combined therapy including both drugs would further benefit this patient population is unknown. MATERIALS AND METHODS: We conducted a three-arms clinical trial to explore the efficacy and safety of the combined treatment with Tregs and rituximab in paediatric patients with T1DM. The patients were allocated to three groups: Tregs only (n = 13), Tregs + rituximab (n = 12) and control (n = 11). The key primary efficacy analyses were C-peptide levels (mixed meal tolerance test) and the proportion of patients in remission at 12 and 24 months. RESULTS: At month 24, as compared with the control, both treatment groups remained superior in the area under the curve of C-peptide mixed meal tolerance test, whereas in the analysis of all visits only the combined therapy improved area under the curve at 12 and 24 months. The proportion of patients in remission was significantly higher in the combined group than in the control group at 3, 6, 9 and 21 months but not at 18 and 24 months. There was no significant difference between the Tregs only group and control group. Adverse events occurred in 80% patients, mostly in the combined group and Tregs only group. No adverse events led to the withdrawal of the intervention or death. All comparisons were performed with alpha level of 5%. CONCLUSIONS: Over 2 years, combined therapy with Tregs and rituximab was consistently superior to monotherapy in delaying T1DM progression in terms of C-peptide levels and the maintenance of remission.

Prospective Assessment of Intraoperative Facial Nerve Monitoring in Patients Undergoing Partial Parotidectomy.

The most significant complication of parotid gland tumor surgery is facial weakness. This study compares the occurrence of transient facial palsy in patients with parotid gland tumors who underwent surgery without monitoring to those who underwent surgery with monitoring. The study's aim was to investigate facial nerve function in patients undergoing parotidectomy as well as the effect of intraoperative facial nerve monitoring and the effect of certain risk factors on the surgery and onset of postoperative facial palsy. This prospective study included 100 patients who underwent parotidectomy. The study cohort was divided into two groups. Group I included 50 patients who underwent surgery without neuromonitoring and group II included 50 patients who underwent surgery with neuromonitoring. The neurological assessment was conducted using the House-Brackmann scale. Preoperatively and one month postoperatively, electroneuronography (ENoG) and blink reflex tests were done. The analyses showed a significant reduction of the compound muscle action potential (CMAP) amplitude of the orbicularis oculi and orbicularis oris muscles and prolonged R1 and R2 blink reflex latencies 1 month after surgery. On neurological and electrophysiological studies, the rate of postoperative transient facial nerve dysfunction was significantly different between the groups. Significantly more patients, operated with use of facial nerve monitoring, presented postoperatively normal nerve function (i.e., House-Brackmann grade I) compared to those who underwent surgery without monitoring (78% and 26%, respectively; p < 0.001). Monitoring had a statistically significant impact on the prevalence of facial nerve conduction disorders in patients who underwent surgery, according to the blink reflex and ENoG studies. The duration of the surgical procedure was not affected by monitoring in any way. The clinical evaluation of facial nerve function (House-Brackmann scale) and some ENoG results 1 month after surgery were found to have a significant correlation. To summarize, using monitoring considerably reduced the negative impact of local factors and the prevalence of transient facial nerve palsy.