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PURPOSE: To assess the clinical outcome of patients with recurrent glioblastoma treated with salvage reirradiation. METHODS: Between 2005 and 2022, data from adult patients with glioblastoma treated with surgery and radio-chemotherapy Stupp regimen who developed a local in-field relapse and received stereotactic radiotherapy (SRT) were retrospectively reviewed. RESULTS: The study population included 44 patients with recurrent glioblastoma (median of 9.5 months after the first radiotherapy). Reirradiation alone was given to 47.7% of patients. The median maximum diameter of the recurrence was 13.5 mm. The most common SRT regimen (52.3%) was 35 Gy in 10 fractions. Acute toxicity was mild, with transient worsening of previous neurological symptoms in only 15% of patients. After a median follow-up of 15 months, 40% presented radiological response, but a remarkable number of early distant progressions were recorded (32.5%). The median time to progression was 4.8 months, being the dose, the scheme, the size of the recurrence or the strategy (exclusive RT vs. combined) unrelated factors. The median overall survival (OS) was 14.9 months. Karnofsky index < 70 and the size of the recurrence (maximum diameter < 25 mm) were significant factors associated with OS. Radiological changes after reirradiation were commonly seen (> 50% of patients) hindering the response assessment. CONCLUSIONS: Reirradiation is a feasible and safe therapeutic option to treat localized glioblastoma recurrences, able to control the disease for a few months in selected patients, especially those with good functional status and small lesions. Hypofractionated schemes provided a suitable toxicity profile. Radiological changes were common.
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Apesar de ser uma complicação recorrente em gestações, o abortamento pode gerar consequências bastante danosas à saúde física e mental da gestante, bem como de seu parceiro, especialmente em casos de abortamento recorrente. Este trabalho objetivou revisar as principais características epidemiológicas e fatores de risco descritos em relação ao abortamento recorrente. A respeito da metodologia, foi realizada uma revisão sistemática da bibliografia, tendo como foco os trabalhos que possuíssem os descritores "aborto", "recorrente" e "epidemiologia". Os artigos selecionados foram publicados entre os anos de 2016 e 2023, em português ou inglês. Em nossa pesquisa, observamos que a etiologia dos abortamentos é bastante diversa, incluindo fatores desconhecidos. É válido ressaltar que quanto maior o número de abortos espontâneos recorrentes antecedentes, maior parece ser a chance de nova perda de gestação. Não obstante, existem diferenças regionais determinantes para as etiologias e fatores de risco, sendo necessário compreender qual a causa do abortamento recorrente para que haja tratamento efetivo.
Despite being a recurrent complication in pregnancies, abortions can lead to harmful consequences for the physical and psychological health of the pregnant woman, as well as her partner's, especially in cases of recurrent miscarriage. This article aimed to review the main epidemiological characteristics and risk factors described in relation to recurrent miscarriage. About the methodology, it was developed a systematic review of pre-existing bibliography, focusing on papers that had the descriptors "abortion", "recurrent" and "epidemiology". The selected works were published between the years of 2016 and 2023, in Portuguese or English. In our research, we noticed that the etiology of miscarriages is quite diverse, including unknown factors. It is important to note that the higher the historical number of recurrent spontaneous miscarriages, the greater seems to be the chance of new pregnancy loss. However, there are regional differences that determine etiologies and risk factors. It is essential to understand what is causing the recurrent miscarriage in order to offer effective treatment.
A pesar de ser una complicación recurrente en los embarazos, el aborto puede tener consecuencias perjudiciales para la salud física y mental de la mujer embarazada, así como para su pareja, especialmente en casos de aborto recurrente. Este trabajo tuvo como objetivo revisar las principales características epidemiológicas y factores de riesgo descritos en relación con el aborto recurrente. En cuanto a la metodologia, se realizó una revisión sistemática de la bibliografía, centrándose en los trabajos que tenían los descriptores "aborto", "recurrente" y "epidemiología". Los artículos seleccionados se publicaron entre los años 2016 y 2023, en portugués o inglés. En nuestra investigación observamos que la etiología de los abortos es muy diversa, incluyendo factores desconocidos. Es válido destacar que a mayor número de abortos espontáneos recurrentes previos, parece aumentar la probabilidad de una nueva pérdida del embarazo. Sin embargo, existen diferencias regionales determinantes en las etiologías y factores de riesgo, siendo necesario comprender la causa del aborto recurrente para un tratamiento efectivo.
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BACKGROUND: Pharyngotonsillitis (PT) is an inflammatory and infectious condition affecting the tonsils in the oropharynx, predominantly caused by a variety of viral, fungal, and bacterial pathogens, including Streptococcus pyogenes. With the increasing challenge of antibiotic resistance, alternative therapeutic approaches are needed. METHODS: This study explores the effectiveness and safety of Photodynamic Therapy (PDT) as a therapeutic approach for managing acute PT. PDT involves the use of a photosensitizer, light, and molecular oxygen. We utilized a curcumin-based photosensitizer incorporated into a gum formulation, followed by exposure to blue LED irradiation (455 ± 30 nm, intensity of 200 mW for 6 min) with 1 to 2 PDT sessions depending on the clinical case. RESULTS: The treatment's impact was assessed through systematic monitoring of clinical progression post-treatment, encompassing clinical history, examination, and follow-up. In all three cases examined, PDT was observed to effectively eradicate the infection and prevent its recurrence during the period evaluated. CONCLUSION: Photodynamic Therapy, using a curcumin-based photosensitizer and blue LED light, appears to be a promising alternative to traditional antibiotics for the treatment of PT, demonstrating both efficacy in infection eradication and safety in application. Further studies are recommended to substantiate these findings and explore long-term outcomes.
Subject(s)
Curcumin , Pharyngitis , Photochemotherapy , Photosensitizing Agents , Tonsillitis , Photochemotherapy/methods , Humans , Photosensitizing Agents/therapeutic use , Curcumin/therapeutic use , Male , Female , Tonsillitis/drug therapy , Pharyngitis/drug therapy , Adult , Middle Aged , RecurrenceABSTRACT
The complement system, a vital component of innate immunity, consists of various proteins and pathways crucial for the recognition and elimination of pathogens. In addition, it plays a major role in the initiation of adaptive response through the opsonization of antigens, contributing to B-cell activation and memory maintenance. Deficiencies in complement proteins, particularly C3, can lead to severe and recurrent infections as well as immune complex disorders. Here, we present a case report of two siblings with total C3 deficiency resulting from compound heterozygous mutations in C3 (NM_000064.4): c.305dup; [p.Asn103GlnfsTer66] and c.1269 + 5G>T, previously unreported in C3-related diseases. Both, the index case and her sister, presented a history of recurrent infections since early childhood and one of them developed hemolytic uremic syndrome (HUS). Immunological evaluation revealed absent plasma C3 levels, decreased memory B cells, hypogammaglobulinemia, and impaired response to polysaccharide antigens. The siblings showed partial responses to antimicrobial prophylaxis and vaccination, requiring intravenous immunoglobulin replacement therapy, resulting in clinical improvement. Genetic analysis identified additional risk polymorphisms associated with atypical HUS. This case highlights the importance of comprehensive genetic and immunological evaluations in complement deficiencies, along with the potential role of immunoglobulin replacement therapy in managing associated antibody defects.
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INTRODUCTION: Macular holes are breaks in the retinal tissue at the center of the macula, affecting central vision. The standard treatment involves vitrectomy with membrane peeling and gas tamponade. However, for larger or chronic holes, alternative techniques like autologous retinal graft have emerged. This meta-analysis evaluates the efficacy and safety of retinal transplantation in managing large macular holes. METHODS: We conducted a systematic review and meta-analysis following PRISMA guidelines. The study was prospectively registered in PROSPERO (CRD42024504801). We searched PubMed, Web of Science, Cochrane, and Embase databases for observational studies including individuals with large macular holes with or without retinal detachments and retinal transplantation as the main therapy. We used a random-effects model to compute the mean difference with 95% confidence intervals and performed statistical analysis using R software. RESULTS: We conducted a comprehensive analysis of 19 studies involving 322 patients diagnosed with various types of macular holes (MHs). These included cohorts with refractory MH, high myopia associated with MH, primary MH, and MH with retinal detachment (RD). The findings were promising, revealing an overall closure rate of 94% of cases (95% CI 88-98, I2 = 20%). Moreover, there was a significant improvement in postoperative visual acuity across all subgroups, averaging 0.45 (95% CI 0.33-0.58 ; I2 = 72%; p < 0.01) overall. However, complications occurred with an overall incidence rate of 15% (95% CI 7-25; I2 = 59%). CONCLUSION: ART for large MH shows promising results, including significant improvements in visual acuity and a high rate of MH closure with low complication risks overall and for subgroups.
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More frequent among adults, phenocopies may be caused by somatic mutations or anti-cytokine autoantibodies, mimicking the phenotypes of primary immunodeficiencies. A fourteen-year-old girl was referred for a two-year history of weight loss and multiple recurrent abscesses, complicated recurrent pneumonia, pyelonephritis, osteomyelitis, and septic shock, without fever. She had started with nausea, hyporexia, and weight loss, then with abscesses in her hands, knee, ankle, and spleen. She also developed a rib fracture and left thoracic herpes zoster. The patient was cachectic, with normal vital signs, bilateral crackles on chest auscultation, tumefaction of the knee joint, and poorly healed wounds in hands and chest, oozing a yellowish fluid. Chest computed tomography revealed multiple bilateral bronchiectases. Laboratory workup reported chronic anemia, leukocytosis, neutrophilia, mild lymphopenia, thrombocytosis, pan-hypergammaglobulinemia, and elevated acute serum reactants. Lymphocyte subsets were low but present. Mycobacterium tuberculosis was detected via polymerase chain reaction in a bone biopsy specimen from ankle osteomyelitis. Whole-exome sequencing failed to identify a monogenic defect. Interleukin-12 was found markedly elevated in the serum of the patient. Phosphorylation of STAT4, induced by increasing doses of IL-12, was neutralized by patient serum, confirming the presence of anti-IL12 autoantibodies. IL-12 and IL-23 are crucial cytokines in the defense against intracellular microorganisms, the induction of interferon-gamma production by lymphocytes, and other inflammatory functions. Patients who develop neutralizing serum autoantibodies against IL12 manifest late in life with weight loss, multiple recurrent abscesses, poor wound healing, and fistulae. Treatment with anti-CD20 monoclonal antibodies was effective.
Subject(s)
Abscess , Autoantibodies , Humans , Female , Autoantibodies/immunology , Autoantibodies/blood , Adolescent , Abscess/immunology , Interleukin-12 Subunit p40/immunology , Recurrence , Osteomyelitis/immunologyABSTRACT
Cervical cancer constitutes a significant health burden for women worldwide despite being preventable by vaccination and screening. Advanced stages of the disease are associated with a poor prognosis, and treatment approaches have seen little change over several decades, resulting in an overall survival rate of no more than 17 months. Additionally, there are limited options for second-line treatment. The urgent need for innovative and effective therapies to improve the outlook for this group of patients, along with an enhanced understanding of the interactions between the disease and the host's immune system, has propelled immunotherapy into a rapidly advancing field with notable achievements. Among various immunotherapeutic approaches, immune checkpoint inhibitors emerge as the most advanced treatment option. Clinical trials assessing these inhibitors as single agents or in combination with chemotherapy show promising results. As immunotherapy begins to redefine standards of care for metastatic, recurrent, or persistent cervical cancer, this review addresses recent advances and current recommendations for its management in both first and second-line treatment. The goal is to provide insights into the evolving landscape of cervical cancer treatment, specifically focusing on immunotherapeutic interventions.
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Pancreaticopleural fistula is a rare complication of pancreatitis. We present a rare case of pancreaticopleural fistula in a 43-year-old alcoholic male. He presented with recurrent episodes of left pleural effusion that were managed with aspiration and chest tube placement. An MRI of the chest and upper abdomen revealed a pancreaticopleural fistula. The patient underwent distal pancreatectomy with splenectomy and Roux-en-Y pancreaticojejunostomy. The surgical approach was our first-line management due to the unavailability of octreotide and endoscopic retrograde cholangiopancreatography. His recovery was complicated by an empyema that was managed by tube thoracostomy and IV antibiotics. There was no issue detected at his 3-month follow-up clinic visit.
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OBJECTIVE: The purpose of this study was to determine the etiologies of recurrent miscarriage in our hospital and whether its diagnostic approach followed the recommendations of the American Society of Reproductive Medicine (ASRM) guidelines published in 2012 and the National Institute for Health and Care Excellence (NICE) guidelines published in 2011. METHODS: This was a retrospective study. The medical records of 158 patients diagnosed with recurrent miscarriage between 2013 and 2018 at Santander University Hospital were reviewed. The Institutional Review Board of HUS approved the study in May 2020. RESULTS: The most common etiologies identified were protein S deficiency, thrombophilia, and cervical insufficiency, with incidence rates of 25.9%, 10.7%, and 3.8%, respectively. Moreover, the most frequently requested diagnostic tests were for protein S, protein C, and anti-phospholipid IgG. Abnormal results for protein S were obtained in 49% of the patients, whereas lupus anticoagulant was abnormal in 12.8%, and Factor V Leiden gene mutations in 8.5% of the patients. Three substantial deviations from the recommended diagnostic approach for recurrent miscarriage by international guidelines were identified in our population: the lack of request for cytogenetic analysis of pregnancy tissue, request for cytogenetic analysis for the parents in only 0.6% of the study sample, and the request for imaging tests to assess uterine anatomy in only 6.3% of the studied population. Both the ASRM and NICE guidelines were only partially followed with a combined adherence rate of 66.5%. CONCLUSION: The diagnostic approach for recurrent miscarriage poses important clinical challenges when compared to the recommendations of international guidelines. Therefore, the development of a local recurrent miscarriage assessment protocol is proposed in our institution.
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Acute respiratory tract infections (RTIs) are one of the most common causes of pediatric consultations/hospitalizations and a major trigger for asthma exacerbations. Some consensus statements have recommended the use of immunostimulants to boost natural defenses against severe or repeated infections. One of the most common immunostimulants is OM-85; while several randomized clinical trials (RCTs) have evaluated its efficacy in preventing acute RTIs and wheezing/asthma exacerbations, results have been conflicting. Similarly, various systematic reviews with meta-analyses (SRMs) on OM-85 have used different strategies, populations, and outcomes; moreover, SRM conclusions are limited when the original studies are highly heterogeneous or have a low quality, hindering the generalizability of the findings. Here we summarize the evidence on the effect of OM-85 to prevent acute RTIs, wheezing/asthma episodes, or loss of asthma control in children, by including and critically evaluating all SRMs published to date. We searched for SRMs on OM-85 in three publication databases and found nine SRMs (seven for RTI, and two for wheezing/asthma). Among those, one had a high confidence evaluation of quality (AMSTAR-2 tool) and found a reduction in the total number of acute RTIs among the OM-85 group. Overall, no strong recommendations can be derived from the existing literature, mainly due to the high heterogeneity among included RCTs and SRMs. Further, large, high-quality RCTs are needed to confirm the true efficacy of OM-85 for the prevention of acute RTIs, asthma development, and asthma exacerbations.
Subject(s)
Asthma , Respiratory Sounds , Respiratory Tract Infections , Child , Child, Preschool , Humans , Adjuvants, Immunologic/therapeutic use , Bacterial Lysates , Cell Extracts/therapeutic use , Meta-Analysis as Topic , Randomized Controlled Trials as Topic , Respiratory Sounds/drug effects , Respiratory Tract Infections/prevention & control , Systematic Reviews as Topic , Treatment OutcomeABSTRACT
OBJECTIVE: Individuals with Down Syndrome (DS) exhibit a higher susceptibility to infections, suggesting potential immunological alterations within this population. Consequently, this study aims to assess the immune response profile in children with DS to identify potential immune dysfunctions associated with recurrent infections. METHODS: The authors conducted a retrospective analysis involving 49 DS patients, examining various epidemiological, clinical, cytogenetic, and laboratory variables. The study's sample comprised patients aged 2-20 years, with a predominance of males. These patients were categorized into two groups based on the presence or absence of recurrent infections, as indicated by the Jeffrey Modell Foundation alert signs. RESULTS: Immunoglobulin (Ig) A, G, and M levels were deemed normal, although individuals with DS experiencing recurrent infections exhibited significantly lower IgA levels. Additionally, CD3, CD4, CD8, and CD19 lymphocyte counts were found to be within normal ranges, with no significant differences between the two groups. While overall data indicated normal seroconversion levels of pneumococcal polysaccharide antibodies, a notable impairment in seroconversion was observed among DS patients with recurrent infections compared to those without such infections. CONCLUSION: The deficiency of anti-polysaccharide antibodies in individuals with DS may constitute an important immunological comorbidity. Therefore, it warrants further investigation, particularly among individuals with recurrent infections.
Subject(s)
Down Syndrome , Recurrence , Humans , Down Syndrome/immunology , Down Syndrome/complications , Male , Child , Female , Adolescent , Retrospective Studies , Child, Preschool , Young AdultABSTRACT
The recurrent laryngeal nerve is a bilateral branch of the vagus nerve that is mainly associated with the motor innervation of the intrinsic muscles of the larynx. Despite its bilateral distribution, the right and left recurrent laryngeal nerves display unequal length due to embryological processes related to the development of the aortic arches. This length asymmetry leads to theories about morphological compensations to provide symmetrical functions to the intrinsic muscles of the larynx. In this study we investigated the developmental and cross-sectional morphometrics of the recurrent laryngeal nerves in human fetuses. Fifteen stillbirth fetuses donated to anatomical and medical research were used for investigation. Fetuses had intrauterine age ranging from 30 to 40 weeks estimated by biometry methods. Specialized anatomical dissection of the visceral block of the neck was performed to prepare histological samples of the recurrent laryngeal nerves in its point of contact with the larynx, and morpho-quantitative techniques were applied to evaluate the epineurium and perineural space of the recurrent laryngeal nerves. No statistical difference in the cross-sectional morphology of the epineurium and perineural space between right and left recurrent laryngeal nerves intra-individually was confirmed, however, we found evidence that these structures are under greater development in the left recurrent laryngeal nerve during 30 to 40 weeks of intrauterine life. Our data suggest that the nerves are under morphological development that possibly set the stage for accommodation of larger diameter and myelinization of the left recurrent laryngeal nerve during post-natal life.
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El síndrome de Down, o trisomía 21, tiene una mortalidad mayor que la población general, debido principalmente a infecciones respiratorias. El objetivo de este trabajo es describir el compromiso inmunológico en una serie de casos de pacientes con síndrome de Down derivados a Inmunología por infecciones recurrentes o por hallazgo patológico de laboratorio, entre el 1 de junio de 2016 y el 31 de mayo de 2022. Se describe el compromiso de la inmunidad en 24 pacientes. Doce pacientes presentaron falla de respuesta a polisacáridos y recibieron quimioprofilaxis antibiótica y/o gammaglobulina sustitutiva. En 3 pacientes, se observó agammaglobulinemia con linfocitos B presentes y se indicó gammaglobulina sustitutiva. En 9 pacientes, se observó linfopenia T y en 1 paciente, compromiso inmune combinado.
Down syndrome, or trisomy 21, has a higher mortality than the general population, mainly due to respiratory tract infections. The objective of this study was to describe immune compromise in a series of cases of patients with Down syndrome referred to the Pediatric Immunology Section due to recurrent infections or pathological laboratory findings between 6/1/2016 and 5/31/2022. Here we describe immune compromise in 24 patients. Twelve patients failed to develop a polysaccharide response and received antibiotic chemoprophylaxis, or gamma globulin replacement therapy. Three patientsdeveloped agammaglobulinemia with presence of B cells and gamma globulin replacement therapy was indicated. Nine patients had T-cell lymphopenia and 1 patient, combined immune compromise.
Subject(s)
Humans , Infant , Child, Preschool , Child , Adolescent , Respiratory Tract Infections , Down Syndrome/complications , gamma-Globulins , Immunoglobulins, Intravenous/therapeutic use , Anti-Bacterial Agents/therapeutic useABSTRACT
In order to comprehend and enhance models that describes various brain regions it is important to study the dynamics of trained recurrent neural networks. Including Dale's law in such models usually presents several challenges. However, this is an important aspect that allows computational models to better capture the characteristics of the brain. Here we present a framework to train networks using such constraint. Then we have used it to train them in simple decision making tasks. We characterized the eigenvalue distributions of the recurrent weight matrices of such networks. Interestingly, we discovered that the non-dominant eigenvalues of the recurrent weight matrix are distributed in a circle with a radius less than 1 for those whose initial condition before training was random normal and in a ring for those whose initial condition was random orthogonal. In both cases, the radius does not depend on the fraction of excitatory and inhibitory units nor the size of the network. Diminution of the radius, compared to networks trained without the constraint, has implications on the activity and dynamics that we discussed here. Supplementary Information: The online version contains supplementary material available at 10.1007/s11571-023-09956-w.
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BACKGROUND: The aim of this study was to evaluate evolution of ultra-processed food intake and recurrent weight gain in patients who underwent Roux-en-Y gastric bypass. MATERIALS AND METHODS: This study is an observational longitudinal study that evaluated patients who underwent metabolic and bariatric surgery at four time points: before surgery and at 3, 12, and 60 months after surgery. Anthropometric and dietary intake data were collected through two 24-h dietary recalls. All foods consumed were classified according to degree of processing. Recurrent weight gain was considered the difference between current weight and nadir weight. RESULTS: The sample consisted of 58 patients with a mean age of 38.7 ± 8.9 years and 68% female. After 60 months, mean excess weight loss and recurrent weight gain were 73.6 ± 27.2% and 22.5 ± 17.4%. Calorie and macronutrient intake decreased significantly between the pre-surgery period, and 3 and 12 months post-surgery; however, there was no significant difference after 60 months. In relation to food groups or macronutrients, no difference was observed between the pre-surgery period and 60 months post-surgery. The contribution of unprocessed or minimally processed foods to calorie intake gradually decreased after 3 months post-surgery. CONCLUSION: The profile of dietary intake after 60 months of metabolic and bariatric surgery tends to approach that of the pre-surgery period. The contribution of unprocessed and minimally processed foods to calorie intake decreased after 60 months, while ultra-processed food contribution increased.
Subject(s)
Energy Intake , Gastric Bypass , Obesity, Morbid , Weight Gain , Humans , Female , Adult , Male , Longitudinal Studies , Obesity, Morbid/surgery , Gastric Bypass/statistics & numerical data , Weight Loss/physiology , Fast Foods/statistics & numerical data , Recurrence , Middle Aged , Food, ProcessedABSTRACT
We prospectively examined associations between mobility in neighborhood opportunity and early childhood recurrent wheezing/asthma. Downward mobility was associated with developing asthma, but not recurrent wheezing, though associations were attenuated after adjusting for family-level socioeconomic status. Elucidating how neighborhoods impact asthma may inform asthma equity initiatives in early childhood.
Subject(s)
Asthma , Recurrence , Respiratory Sounds , Humans , Asthma/epidemiology , Respiratory Sounds/etiology , Prospective Studies , Male , Female , Child, Preschool , Infant , Residence Characteristics , Socioeconomic FactorsABSTRACT
OBJECTIVE: Many pieces of literature have reported that inherited and acquired thrombophilia might be a risk factor for recurrent implantation failure (RIF), however, most studies have only focused on RIF patients and not their male partners. We studied the possible association of paternal thrombophilia with RIF risk. METHODS: Forty-two male partners aged 20-45 suffered from RIF compared with 42 males from couples with at least one successful pregnancy. All participants were investigated for thrombophilia markers. RESULTS: The prevalence of coagulation Factor V activity was significantly higher in the case group (42.9%) than in the control group (16.7%) (p=0.008) (OR=3.75; 95% CI, 1.38, 10.12). The prevalence of protein C and protein S deficiencies in RIF patients were 4.8% and 2.4%, respectively, and 0% in the controls. The prevalence of antithrombin III (ATIII) deficiency was significantly higher in the case group (19%) than in the control group (2.4%) (p=0.01). None of MTHFR C677T and MTHFR A1298C were statistically significant between the two groups. Combined thrombophilia was 45.2% in the men of the RIF group when compared with the control, 14.2% (p=0.001) (OR = 4.95; 95% CI, 1.75-13.86). CONCLUSIONS: Paternal thrombophilia may be related to recurrent implantation failure, so evaluation of this factor in RIF patients could be used to identify relevant risk groups and may help in the proper management of these cases to enhance the chance of implantation.
Subject(s)
Thrombophilia , Humans , Male , Thrombophilia/epidemiology , Adult , Case-Control Studies , Female , Middle Aged , Embryo Implantation , Young Adult , Pregnancy , Risk FactorsABSTRACT
BACKGROUND: This study aimed to identify prognostic factors for pregnancy outcomes and construct a prognostic model for pregnancy outcomes in women with Recurrent Spontaneous Abortions (RSA) treated with cyclosporin A. METHODS: A total of 154 RSA patients treated with cyclosporin A between October 2016 and October 2018 were retrospectively recruited. Multivariate logistic regression was applied to identify the prognostic factors for pregnancy success in RSA women treated with cyclosporin A. The Receiver Operating Characteristic (ROC) curve was applied to construct prognostic value, and the prognostic performance was assessed using area under the ROC. RESULTS: After adjusting potential confounding factors, the authors noted increased age (OR = 0.771; 95 % CI 0.693â0.858; p < 0.001) and positive antinuclear antibodies (OR = 0.204; 95 % CI 0.079â0.526; p = 0.001) were associated with a reduced incidence of pregnancy success, while positive anti-ß2 glycoprotein-I-antibody (OR = 21.941; 95 % CI 1.176â409.281; p = 0.039) was associated with an increased incidence of pregnancy success after treated with cyclosporin A. The AUC of combining these variables for predicting pregnancy failure was 0.809 (95 % CI 0.735â0.880). CONCLUSIONS: This study systematically identified the prognostic factors for pregnancy success in women treated with cyclosporin A, and the constructed prognostic model based on these factors with relatively higher prognostic value. Further large-scale prospective studies should be performed to validate the prognostic value of the constructed model.
Subject(s)
Abortion, Habitual , Cyclosporine , Immunosuppressive Agents , Pregnancy Outcome , Humans , Female , Pregnancy , Cyclosporine/therapeutic use , Adult , Retrospective Studies , Prognosis , Abortion, Habitual/drug therapy , Immunosuppressive Agents/therapeutic use , ROC Curve , Young AdultABSTRACT
Recurrent pregnancy loss (RPL) affects around 2% of women of reproductive age. Primary RPL is defined by ≥2 pregnancy losses and no normal birth delivery. In secondary RPL, the losses are after a normal pregnancy and delivery. Most cases have no clear aetiology, although primary cases are the most complex. Several gene single nucleotide polymorphisms (SNPs) have been associated with RPL. The frequency of some SNPs is increased in women suffering from RLP from Asian or Caucasian races; however, in admixed populations, the information on possible genetic links is scarce and contradictory. This study aimed to assess the frequency of two SNPs present in two different enzymes involved in medical conditions observed during pregnancy. It is a case-control study. Microsomal epoxy hydrolase (mEPH) is involved in detoxifying xenobiotics, is present in the ovaries, and is hormonally regulated. The endothelial nitric oxide synthase (NOS3) that forms nitric is involved in vascular tone. Two SNPs, rs1051740 (mEPH) and rs1799983 (NOS3), were assessed. The study included 50 controls and 63 primary RPL patients. The frequency of mutated alleles in both SNPs was significantly higher in patients (p < 0.05). Double-mutated homozygotes were encountered only in RPL patients (p < 0.05). Genetic polymorphisms rs1051740 and rs1799983 may be involved in primary RPL in the Venezuelan admix population. Genetic studies could provide crucial information on the aetiology of primary RPL.
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Training neural networks to perform different tasks is relevant across various disciplines. In particular, Recurrent Neural Networks (RNNs) are of great interest in Computational Neuroscience. Open-source frameworks dedicated to Machine Learning, such as Tensorflow and Keras have produced significant changes in the development of technologies that we currently use. This work contributes by comprehensively investigating and describing the application of RNNs for temporal processing through a study of a 3-bit Flip Flop memory implementation. We delve into the entire modeling process, encompassing equations, task parametrization, and software development. The obtained networks are meticulously analyzed to elucidate dynamics, aided by an array of visualization and analysis tools. Moreover, the provided code is versatile enough to facilitate the modeling of diverse tasks and systems. Furthermore, we present how memory states can be efficiently stored in the vertices of a cube in the dimensionally reduced space, supplementing previous results with a distinct approach.