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BACKGROUND: Vitamin D deficiency has been examined as a risk factor for severity and progression of kidney disease due to its immunomodulatory effects. There is paucity of data about its impact in IgA nephropathy (IgAN). METHODS: In a retrospective cohort study, 25 (OH) vitamin D assay was performed in bio-banked baseline serum samples collected during kidney biopsy of 105 adult patients with primary IgAN diagnosed between 2015 and 2019. A level of < 10 ng/mL was defined as Vitamin D deficiency. RESULTS: Mean age of patients was 34 ± 10.6 years, 69.5% were males. Mean baseline 25(OH) Vitamin D levels was 15.9 ± 11.9 ng/mL and 41(39%) patients had vitamin D deficiency. Serum albumin level was lower in vitamin D deficient patients compared to those who had higher vitamin D levels (3.7 ± 0.9 vs 4.1 ± 0.7 g/dl, p = 0.018)but there was no significant difference in baseline proteinuria and eGFR. Crescentic lesions were more frequent in vitamin D deficient group (19.5% vs 6.3%, p = 0.022). At median follow up of 21.5 months (6 - 56 months), there was no difference in remission (68.3% vs 65.6%, p = 0.777) and disease progression (12.5% vs 9.4%, p = 0.614) in those with and without Vitamin D deficiency respectively. On multivariate cox proportional hazard analysis, vitamin D deficiency was not a significant risk factor for renal survival (HR-1.79, 95% confidence interval:0.50-6.34, p = 0.368). CONCLUSION: There was no association between vitamin D deficiency and disease profile as well as renal outcome in Indian patients with IgAN.
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Glomerulonefritis por IGA , Deficiencia de Vitamina D , Adulto , Masculino , Humanos , Adulto Joven , Femenino , Glomerulonefritis por IGA/diagnóstico , Vitamina D , Estudios Retrospectivos , Progresión de la Enfermedad , Vitaminas , Gravedad del PacienteRESUMEN
Endometriosis is a common gynecological condition characterized by estrogen dependence, chronic pelvic pain, infertility, and diagnostic delay of between 5.4 and 12 years. Despite extensive study, no biomarker, either alone or in combination with other markers, has proven superior to laparoscopy for the diagnosis of endometriosis. Recent studies report that circulating levels of differentially expressed microRNA (miRNA) in women with endometriosis compared with controls are potential diagnostic tools. However, the lack of replication and absence of validated differential expression in novel study populations have led some to question the diagnostic value of miRNA. To elucidate potential reasons for the lack of replication of study results and explore future directions to enhance replicability of circulating miRNA results, we carried out an electronic search of the miRNA literature published between 2000 and 2020. Eighteen studies were identified in which 63 different miRNAs were differentially expressed in the circulation of women with endometriosis compared with controls. However, the differential expressions of only 14 miRNAs were duplicated in one or more studies. While individual miRNAs lacked diagnostic value, miRNA panels yielded sensitivity and specificity equal to or better than laparoscopy in five studies. Important differences in study design, sample processing, and analytical methods were identified rendering direct comparisons across studies problematic and could account for the lack of reproducibility of study results. We conclude that while the results of miRNA studies to date are encouraging, refinements to study design and analytical methods should enhance the reliability of circulating miRNA for the diagnosis of endometriosis.
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Endometriosis/metabolismo , MicroARNs/sangre , Biomarcadores/sangre , Endometriosis/sangre , Femenino , HumanosRESUMEN
BACKGROUND: Women with endometriosis are commonly treated by their sole provider. In this single-provider model of care, women frequently report long diagnostic delays, unresolved pelvic pain, multiple laparoscopic surgeries, sequential consultations with numerous providers, and an overall dissatisfaction with care. The emergence of multidisciplinary endometriosis centers aims to reduce diagnostic delays, improve pain management, and promote patient satisfaction; however, baseline data at the time of presentation to a multidisciplinary center are lacking. METHODS: A real-world, retrospective, single-site, cross-sectional study of women with surgically confirmed and/or clinically diagnosed endometriosis generated baseline data for a planned longitudinal assessment of multidisciplinary care of endometriosis. The primary objective was to determine the proportion of patients experiencing mild, moderate, or severe pain for dysmenorrhea, non-menstrual pelvic pain (NMPP), and dyspareunia at entry into a multidisciplinary endometriosis clinic. Also explored were relationships between pain scores and clinical endpoints obtained from electronic medical records. RESULTS: More than half (59%) of the study participants (n = 638) reported experiencing pelvic pain for ≥ 5 years. Pain intensity was highest for patients reporting dysmenorrhea, followed by NMPP, and dyspareunia. Significant correlations were observed between total pelvic pain and patient age (r = -0.22, p < 0.001, n = 506) and number of previous healthcare providers (r = 0.16, p = 0.006, n = 292); number of previous providers and duration of pain (r = 0.21, p = < 0.0001, n = 279); and duration of pain and years since diagnosis (r = 0.60, p < 0.001, n = 302). Mean pain scores differed significantly by age group for dysmenorrhea (p < 0.001), NMPP (p = 0.005), and total pelvic pain (p < 0.001), but not for dyspareunia (p = 0.06), with the highest mean pain scores reported among those < 30 years of age. CONCLUSION: These real-world data indicate that in the single-provider model of care, unresolved pelvic pain is common among women with endometriosis. Alternative care models, including a multidisciplinary approach, need to be evaluated for improvements in clinical outcomes. These data also highlight the importance of addressing NMPP, which may be particularly troublesome for patients.
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Dispareunia , Endometriosis , Adulto , Estudios Transversales , Dismenorrea/epidemiología , Dismenorrea/etiología , Dispareunia/epidemiología , Dispareunia/etiología , Endometriosis/complicaciones , Femenino , Humanos , Dolor Pélvico/etiología , Estudios RetrospectivosRESUMEN
BACKGROUND: Dyspareunia experienced by women diagnosed with endometriosis is associated with a decreased health-related quality of life (HRQoL). AIM: We evaluated the relationship of clinically meaningful improvements in dyspareunia with HRQoL changes among women with endometriosis. METHODS: This was a post hoc analysis of pooled data from the phase III ELARIS-I and ELARIS-II clinical trials. Women aged 18-49 years with moderate to severe endometriosis-associated pain were randomized to placebo, elagolix 150 mg once daily, or elagolix 200 mg twice daily. HRQoL was measured using the validated Endometriosis Health Profile-30 questionnaire (EHP-30), consisting of 5 core domains and a sexual intercourse modular domain. Dyspareunia was ranked 0-3 (none, mild, moderate, or severe) or not applicable using a daily eDiary and averaged monthly. A woman with a clinically meaningful dyspareunia response (dyspareunia responder) was defined as a woman with a reduction from the baseline in dyspareunia score greater than or equal to a predetermined cutoff while maintaining stable/decreased analgesic use. OUTCOMES: Dyspareunia response impact on EHP-30 scores was determined at 3 and 6 months using multivariate linear regression controlling for age, baseline EHP-30 scores, and dysmenorrhea and non-menstrual pelvic pain symptom severity. RESULTS: Analysis included 1,368 women with a mean age of 32.2 years. Dyspareunia responders had significant improvements vs non-responders in all adjusted mean EHP-30 domain scores at months 3 and 6 (control and powerlessness: -17.8 and -18.5; emotional well-being: -10.0 and -10.4; pain: -15.3 and -15.7; self-image: -11.4 and -12.8; social support: -14.3 and -14.0; and sexual intercourse: -18.1 and -19.7; all P < .0001). CLINICAL IMPLICATIONS: Dyspareunia improvements are associated with both personal and psychological benefits. STRENGTHS & LIMITATIONS: This study involved a large sample of women from a well-defined patient population to provide statistical power in evaluating the results. As such, the findings may not be generalizable in a real-world setting. Although the perception of dyspareunia and its severity and the associated effect on HRQoL was subjective, the use of a large patient sample was used to minimize potential issues with this limitation. CONCLUSION: Clinically meaningful responses in dyspareunia are associated with improvements across multiple HRQoL domains among women with endometriosis. Agarwal SK, Soliman AM, Pokrzywinski RM, et al. Clinically Meaningful Reduction in Dyspareunia Is Associated with Significant Improvements in Health-Related Quality of Life Among Women with Moderate to Severe Pain Associated with Endometriosis: A Pooled Analysis of Two Phase III Trials of Elagolix. J Sex Med 2020;17:2427-2433.
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Dispareunia , Endometriosis , Adolescente , Adulto , Dispareunia/tratamiento farmacológico , Dispareunia/etiología , Endometriosis/complicaciones , Endometriosis/tratamiento farmacológico , Femenino , Humanos , Hidrocarburos Fluorados , Persona de Mediana Edad , Pirimidinas , Calidad de Vida , Adulto JovenRESUMEN
AIM: Pattern of kidney diseases varies across geographies due to multiple factors. There is a paucity of information from South Asia due to the absence of nationwide/regional biopsy registries. This study aimed to delineate the spectrum of renal parenchymal diseases in our region. METHODS: Records of kidney biopsies done in our nephrology department between 2006 and 2016 were analysed. Clinico-pathological correlation was done from the available records. RESULTS: Of the 3275 biopsy evaluated, 61.9% were males, and mean age was 33.2 ± 14.2 years. 6.2% patients were elderly (age ≥ 60 years). Nephrotic syndrome (60.3%) was the commonest indication for biopsy. On histology, 73.0% patients had primary glomerulonephritis (GN), 15.5% secondary GN, 5.3% tubulo-interstitial and 3.7% vascular disease. Focal segmental glomerulosclerosis (FSGS) was the commonest primary GN accounting for 18.2% of all GNs, followed by minimal change disease (16.8%), membranous nephropathy (MN) (16.0%) and IgA nephropathy (10.4%). Lupus nephritis (10.6%) and amyloidosis (3.7%) were the commonest secondary GN. The commonest cause of nephrotic syndrome was minimal change disease (22.9%), acute nephritic syndrome was lupus nephritis (30.6%), rapidly progressive renal failure was pauci-immune crescentic GN (24.5%). IgA nephropathy was the commonest etiology of asymptomatic urinary abnormalities (26.3%) and gross haematuria (50%). About 60.9% patients of undetermined chronic kidney disease had glomerular diseases, and 13.6% had chronic tubulointerstitial nephritis. Lupus nephritis and acute cortical necrosis were significantly more common in females compared with males. CONCLUSION: This is one of the largest cohorts of kidney biopsies from India, and it delineates the unique features and differences in the pattern of kidney disease in our population.
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Glomerulonefritis Membranosa/patología , Glomeruloesclerosis Focal y Segmentaria/patología , Riñón/patología , Nefrosis Lipoidea/patología , Síndrome Nefrótico/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Femenino , Glomerulonefritis Membranosa/epidemiología , Glomeruloesclerosis Focal y Segmentaria/epidemiología , Humanos , India/epidemiología , Masculino , Persona de Mediana Edad , Nefrosis Lipoidea/epidemiología , Síndrome Nefrótico/epidemiología , Estudios Prospectivos , Estudios Retrospectivos , Factores de Tiempo , Adulto JovenRESUMEN
Endometriosis can have a profound impact on women's lives, including associated pain, infertility, decreased quality of life, and interference with daily life, relationships, and livelihood. The first step in alleviating these adverse sequelae is to diagnose the underlying condition. For many women, the journey to endometriosis diagnosis is long and fraught with barriers and misdiagnoses. Inherent challenges include a gold standard based on an invasive surgical procedure (laparoscopy) and diverse symptomatology, contributing to the well-established delay of 4-11 years from first symptom onset to surgical diagnosis. We believe that remedying the diagnostic delay requires increased patient education and timely referral to a women's healthcare provider and a shift in physician approach to the disorder. Endometriosis should be approached as a chronic, systemic, inflammatory, and heterogeneous disease that presents with symptoms of pelvic pain and/or infertility, rather than focusing primarily on surgical findings and pelvic lesions. Using this approach, symptoms, signs, and clinical findings of endometriosis are anticipated to become the main drivers of clinical diagnosis and earlier intervention. Combining these factors into a practical algorithm is expected to simplify endometriosis diagnosis and make the process accessible to more clinicians and patients, culminating in earlier effective management. The time has come to bridge disparities and to minimize delays in endometriosis diagnosis and treatment for the benefit of women worldwide.
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Dolor Crónico/fisiopatología , Dismenorrea/fisiopatología , Dispareunia/fisiopatología , Endometriosis/diagnóstico , Infertilidad Femenina/fisiopatología , Dolor Pélvico/fisiopatología , Dolor Crónico/etiología , Diagnóstico Tardío , Dismenorrea/etiología , Dispareunia/etiología , Endometriosis/complicaciones , Endometriosis/fisiopatología , Femenino , Humanos , Infertilidad Femenina/etiología , Laparoscopía , Dolor Pélvico/etiología , Sensibilidad y Especificidad , Tiempo de Tratamiento , UltrasonografíaRESUMEN
OBJECTIVES: To quantify patient preferences for endometriosis-associated pain treatments and risk tolerance in exchange for pain reduction and to explore whether preferences vary on the basis of patient characteristics. METHODS: US women with a self-reported physician diagnosis of endometriosis and moderate to severe dysmenorrhea and nonmenstrual pelvic pain (NMPP) completed an online discrete choice experiment survey. Each choice question had a pair of hypothetical treatments characterized by attributes with varying levels: improvements in severe dysmenorrhea, severe NMPP, and severe dyspareunia; mode of administration; and treatment-related risks of pregnancy-related problems, bone fracture later in life, and moderate to severe hot flashes. A random-parameters logit model was used to quantify preferences and the attributes' conditional relative importance. RESULTS: A total of 250 women (mean age 34 years) completed the survey. The conditional relative importance of attributes was 3.66 for risk of moderate to severe hot flashes among respondents with and 3.58 among respondents without experience with moderate to severe hot flashes; 1.70, 1.49, and 1.48 for improvements in dyspareunia, NMPP, and dysmenorrhea, respectively; 0.60 for risk of pregnancy-related problems; 0.53 for mode of administration; and 0.49 for bone fracture risk. Preference weights for bone fracture risk levels were not statistically significantly different. In exchange for a greater improvement in dysmenorrhea from severe to mild (vs moderate), respondents without a history of hot flashes accepted a greater increase in the risk of moderate to severe hot flashes (38%) than did respondents with this history (16%). CONCLUSIONS: Respondents placed the greatest weight on risk of hot flashes, followed by improvements in dyspareunia, NMPP, dysmenorrhea. Bone fracture risk did not drive preferences.
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Endometriosis/terapia , Manejo del Dolor/métodos , Prioridad del Paciente/psicología , Adulto , Dismenorrea/psicología , Dismenorrea/terapia , Endometriosis/psicología , Femenino , Humanos , Persona de Mediana Edad , Manejo del Dolor/psicología , Manejo del Dolor/normas , Dimensión del Dolor/métodos , Autoinforme , Encuestas y Cuestionarios , Estados UnidosRESUMEN
AIM: Few studies have assessed the impact of infections after renal transplantation (RTX) in low and middle income countries. This single centre study aimed to delineate the profile and impact of infections requiring hospitalization (IRH) occurring in the first year after RTX in India. METHOD: Patients who underwent RTX between July 2012 and June 2015 were followed up for 12 months after transplantation. RESULTS: 60.2% of the 387 patients studied had at least one IRH and total 492 infections were diagnosed. The most common were urinary tract (30.3%), gastrointestinal (17.1%) and pulmonary (11.2%) infections. Viral aetiology (33.3%) was most frequent, followed by bacterial (23.6%), parasitic (5.1%), tuberculosis (4.5%), and fungal infections (3.9%). 86.4% deaths were due to infections. One year patient and graft survival were inferior among recipients with IRH compared to those with no IRH: 91.8% vs. 98.1% (log rank = 0.010) and 90.1% vs. 97.4% (log rank = 0.006) respectively. Average monthly income per family member <5000 Rupees (75 USD), NODAT, and acute rejection were independent risk factors for IRH. CONCLUSION: The profile of IRH is unique involving opportunistic, community-acquired and endemic infections seen in this country. It is the predominant cause of mortality and graft loss in the first year after RTX. Poor economic status is an important determinant of IRH in our population.
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Infecciones Comunitarias Adquiridas/mortalidad , Países en Desarrollo , Enfermedades Endémicas , Rechazo de Injerto/mortalidad , Trasplante de Riñón/mortalidad , Infecciones Oportunistas/mortalidad , Adolescente , Adulto , Causas de Muerte , Infecciones Comunitarias Adquiridas/diagnóstico , Infecciones Comunitarias Adquiridas/inmunología , Femenino , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/inmunología , Supervivencia de Injerto , Humanos , Huésped Inmunocomprometido , Inmunosupresores/efectos adversos , India/epidemiología , Trasplante de Riñón/efectos adversos , Masculino , Persona de Mediana Edad , Infecciones Oportunistas/diagnóstico , Infecciones Oportunistas/inmunología , Readmisión del Paciente , Pobreza , Medición de Riesgo , Factores de Riesgo , Determinantes Sociales de la Salud , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
MicroRNA (miRNA), noncoding segments of RNA involved in post-transcriptional regulation of protein expression are differentially expressed in eutopic endometrium of women with and without endometriosis compared to endometriotic lesions. However, endometriotic lesion types are known to be biochemically distinct and therefore hypothesized that miRNAs are differentially expressed in endometriomas compared to peritoneal and deep-infiltrating lesions. Therefore, endometrial biopsies and ectopic implants from women (n = 38) undergoing laparoscopic surgery for chronic pelvic pain were collected. Samples of endometriomas, peritoneal or deep-infiltrating lesions were selected from our tissue bank for study participants who exclusively had only one lesion type noted on their surgical report. Quantitative real-time polymerase chain reaction for miR-9, miR-21, miR-424, miR-10a, miR-10b, and miR-204 was performed. miR-204 expression was significantly lower (P = 0.0016) in the eutopic endometrium of women with endometriosis compared to controls. Relative expression of miR-21, miR-424, and miR-10b differed significantly (P < 0.05) across endometriotic lesion types. Finally, all miRNAs isolated from endometriomas, peritoneal and deep-infiltrating lesions studied were differentially expressed compared to matched eutopic endometrium samples. We therefore conclude that miRNA expression in the eutopic endometrium from women with endometriosis differs from symptomatic controls. Moreover, miRNA expression pattern is dependent on the endometriotic lesion type studied. We suggest that identification of different miRNA expression patterns for endometriomas, peritoneal and deep-infiltrating lesions could contribute to individualized patient care for women with endometriosis.
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Endometriosis/metabolismo , Endometrio/metabolismo , MicroARNs/metabolismo , Enfermedades Peritoneales/metabolismo , Adulto , Endometriosis/genética , Endometriosis/cirugía , Endometrio/cirugía , Femenino , Regulación de la Expresión Génica , Humanos , MicroARNs/genética , Enfermedades Peritoneales/genética , Enfermedades Peritoneales/cirugíaRESUMEN
INTRODUCTION: Tuberculosis (TB) is an important cause of morbidity and mortality in renal transplant recipients. Immunosuppressive drugs are one of the most important risk factor for post-transplant tuberculosis (PTTB). A paucity of data exists about the impact of the type of calcineurin inhibitor on PTTB. METHODS: In this retrospective study, all adult patients on calcineurin inhibitor-based immunosuppression were included. Patients receiving TB chemoprophylaxis were excluded. Diabetes, duration of dialysis, hepatitis B and C, past treated TB, induction therapy, type of antimetabolite, acute rejection, new onset of diabetes after renal transplantation (RT) (NODAT) and cytomegalovirus (CMV) were analyzed in tacrolimus (Tac) and cyclosporine (CsA) groups. Primary outcome was incidence of TB and secondary outcomes were timeline of development of TB after RT and pattern of TB in the two groups. RESULTS: Of the 1664 patients included, 582 patients received CsA-based immunosuppression while 1082 received Tac-based immunosuppression. Duration of dialysis, positive tuberculin skin test, use of induction, mycophenolate mofetil use, CMV infection, and NODAT were significantly more, and hepatitis B infection, past treated TB, and acute rejection episodes were significantly less in the Tac group. At the end of follow-up, incidence of TB in the Tac group was significantly less than in the CsA group (6.1% vs 19.9%, P<.001). Mean time for development of TB after RT was similar in both the groups and nodal and disseminated TB were more common in the Tac group. CONCLUSION: In conclusion, our study shows that use of Tac as compared to CsA significantly decreases incidence of PTTB. Time of infection since transplant was similar in both the groups. However, nodal and disseminated TB were more common in the Tac group.
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Inhibidores de la Calcineurina/efectos adversos , Ciclosporina/efectos adversos , Terapia de Inmunosupresión/efectos adversos , Inmunosupresores/efectos adversos , Trasplante de Riñón/efectos adversos , Tacrolimus/efectos adversos , Tuberculosis/epidemiología , Adolescente , Adulto , Anciano , Antibióticos Antituberculosos/administración & dosificación , Antibióticos Antituberculosos/uso terapéutico , Inhibidores de la Calcineurina/uso terapéutico , Niño , Ciclosporina/administración & dosificación , Ciclosporina/uso terapéutico , Femenino , Estudios de Seguimiento , Rechazo de Injerto/prevención & control , Humanos , Terapia de Inmunosupresión/métodos , Inmunosupresores/administración & dosificación , Inmunosupresores/uso terapéutico , Incidencia , India/epidemiología , Masculino , Persona de Mediana Edad , Ácido Micofenólico/administración & dosificación , Ácido Micofenólico/uso terapéutico , Estudios Prospectivos , Estudios Retrospectivos , Tacrolimus/administración & dosificación , Tacrolimus/uso terapéutico , Tuberculosis/tratamiento farmacológico , Adulto JovenRESUMEN
STUDY QUESTION: Are brain-derived neurotrophic factor (BDNF) and its receptors, NTRK2, NGFR and SORT1, regulated by ovarian steroids in the uterus? SUMMARY ANSWER: BDNF and its low affinity receptor, nerve growth factor receptor (NGFR), are regulated by estradiol in the uterus. WHAT IS KNOWN ALREADY: Recent studies have revealed a central role for neurotrophins in placental development, endometrial stem cell neurogenesis, endometrial carcinoma and endometriosis. Complex signaling pathways involving BDNF and its receptors are regulated by ovarian hormones in the brain, however their expression and regulation in the uterus is poorly defined. STUDY DESIGN, SIZE, DURATION: This experimental animal study involved a total of 80 mice. PARTICIPANTS/MATERIALS, SETTING, METHODS: Female C57BL/6 mice (n = 50) were monitored daily for estrous cycle stage, and uterine horns were collected. A second group of mice (n = 30) were ovariectomized and given estradiol, progesterone, estradiol + progesterone, or saline for 4 days. Uterine expression of BDNF and its receptors were quantified by real-time PCR and western blot, and localized using immunohistochemistry. MAIN RESULTS AND THE ROLE OF CHANCE: During the estrous cycle, expression of BDNF, NTRK2 and SORT1 remained constant, while NGFR declined 11-fold from pro-estrus through to diestrus (P = 0.005). In ovariectomized mice, estradiol treatment increased uterine expression of mature BDNF greater than 6-fold (P = 0.013, 25 kDa; P = 0.003, 27 kDa), pro-BDNF 5-fold (P = 0.041, 37 kDa band; P = 0.046, 40 kDa band), and NGFR 5-fold (P < 0.001) when compared with other treatments. NTRK2 and SORT1 were unaffected by ovarian hormones. NGFR was primarily localized in epithelial cells in mice in diestrus or in ovariectomized mice treated with progesterone (P ≤ 0.001; P ≤ 0.001, respectively). In contrast, NGFR switched to a stromal localization in ovariectomized mice administered estradiol (P = 0.002). LIMITATIONS, REASONS FOR CAUTION: This study was performed in one only species. WIDER IMPLICATIONS OF THE FINDINGS: Results of this study demonstrate the uterine regulation of BDNF and NGFR by estradiol, and highlight the striking difference between hormone exposure during the estrous cycle and daily estradiol exposure after ovariectomy on neurotrophin expression in the uterus. The results also show the spatial regulation of NGFR in the uterus in response to ovarian hormones. Sustained estrogen exposure, as seen in estrogen-dependent disease, may alter the delicate neurotrophin balance and inappropriately activate potent BDNF-NTRK2 pathways which are capable of contributing to endometrial pathology. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the Canadian Institutes of Health Research (CIHR) (W.G.F.), a NSERC Discovery Grant (W.G.F.), and a Vanier Canada Graduate Scholarship-CIHR (J.M.W.). J.M.W. is a member of the CIHR sponsored Reproduction and Early Development in Health training program. The authors declare no conflicts of interest.
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Factor Neurotrófico Derivado del Encéfalo/metabolismo , Estrógenos/metabolismo , Regulación de la Expresión Génica , Ovario/metabolismo , Receptor trkB/metabolismo , Útero/metabolismo , Proteínas Adaptadoras del Transporte Vesicular/metabolismo , Animales , Estradiol/metabolismo , Estro , Femenino , Glicoproteínas de Membrana/metabolismo , Ratones , Ratones Endogámicos C57BL , Factores de Crecimiento Nervioso/metabolismo , Ovariectomía , Proteínas Tirosina Quinasas/metabolismo , Transducción de Señal , Células Madre/citología , Esteroides/metabolismoAsunto(s)
Políticas Editoriales , Nefrología , Diálisis Renal , Humanos , Publicaciones Periódicas como AsuntoRESUMEN
BACKGROUND & OBJECTIVES: Tuberculosis (TB) is a common infection in patients on haemodialysis. There is a definite role of treatment of latent TB (LTB) in these patients. However, diagnosis of LTB in these patients by tuberculin skin test (TST) is unreliable. There is suggestion that interferon gamma release assay (IGRA) will be more reliable test for diagnosis of LTB in this setting. Thus, we evaluated value of IGRA and TST for the diagnosis of LTB in patients on dialysis in an Indian setting. METHODS: Patients with end stage kidney disease on dialysis were included. Patients with active TB were excluded. Each patient was subjected to TST (induration of ≥10 mm was taken as positive) and QuantiFERON TB Gold In-Tube test (QFT-GIT) for diagnosis of LTB. RESULTS: A total of 185 patients were included; 129 (69.7%) were males and mean age was 36.7 ± 12.3 yr. Past history of TB was present in 18 (9.7%) patients. One hundred and thirty four (72.4%) patients had scar of BCG vaccination. QFT-GIT test was positive in 66 (36%), TST in 32 (17%) and both in 13 (7%) patients. Of the 66 patients positive with QFT-GIT, only 13 (19.6%) were positive for TST. Of the 32 patients positive with TST, only 13 (40.6%) were positive with QFT-GIT; 100 (54%) patients were negative for both the tests. Overall, 85 (45.9%) patients were positive for either of the two tests. Poor agreement was shown between the two methods. On logistic regression analysis, odds of QFT-GIT to be positive in patients with BCG vaccination was 1.23 and with history of TB 0.99, both being insignificant. odds of tuberculin skin test to be positive in patients with BCG vaccination was 1.04 and with history of TB 0.99, both again being insignificant. INTERPRETATION & CONCLUSIONS: Our findings showed that more number of patients (36%) on haemodialysis were positive for QuantiFERON Gold In-Tube test as compared to TST (17%). There was poor agreement between the two tests. No significant effect of BCG vaccination and history of TB in past was observed on both tests.
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Ensayos de Liberación de Interferón gamma , Interferón gamma/metabolismo , Tuberculosis Latente/diagnóstico , Diálisis Renal/efectos adversos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Vacuna BCG , Femenino , Humanos , India , Fallo Renal Crónico/patología , Tuberculosis Latente/patología , Masculino , Persona de Mediana Edad , Prueba de TuberculinaRESUMEN
In this prospective study, we measured serum levels of the soluble urokinase receptor (suPAR) in pediatric patients with nephrotic syndrome of various etiologies. Mean levels of suPAR were 3316 pg/ml in 99 patients with steroid-resistant focal segmental glomerulosclerosis and 3253 pg/ml in 117 patients with biopsy-proven minimal change disease, which were similar to that of 138 patients with steroid-sensitive nephrotic syndrome (3150 pg/ml) and 83 healthy controls (3021 pg/ml). Similar proportions of patients in each group had suPAR over 3000 pg/ml. Compared with controls, suPAR levels were significantly higher in patients with focal segmental glomerulosclerosis (FSGS) and estimated glomerular filtration rate (eGFR) under 30 ml/min per 1.73 m(2) (6365 pg/ml), congenital nephrotic syndrome (4398 pg/ml), and other proteinuric diseases with or without eGFR under 30 ml/min per 1.73 m(2) (5052 and 3875 pg/ml, respectively; both significant). There were no changes following therapy and during remission. Levels of suPAR significantly correlated in an inverse manner with eGFR (r=-0.36) and directly with C-reactive protein (r=0.20). The urinary suPAR-to-creatinine ratio significantly correlated with proteinuria (r=0.25) in 151 patients and controls. Using generalized estimating equations approach, serum suPAR significantly correlated with eGFR (coefficient=-13.75), age at sampling (2.72), and C-reactive protein (39.85). Thus, serum suPAR levels in nephrotic syndrome are similar to controls, and do not discriminate between FSGS, minimal change disease, or steroid-responsive illness.
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Glomeruloesclerosis Focal y Segmentaria/sangre , Síndrome Nefrótico/sangre , Receptores del Activador de Plasminógeno Tipo Uroquinasa/sangre , Proteína C-Reactiva/análisis , Niño , Preescolar , Femenino , Tasa de Filtración Glomerular , Glomeruloesclerosis Focal y Segmentaria/tratamiento farmacológico , Glomeruloesclerosis Focal y Segmentaria/fisiopatología , Humanos , Inmunosupresores/uso terapéutico , Lactante , Recién Nacido , Masculino , Síndrome Nefrótico/etiología , Síndrome Nefrótico/fisiopatología , Estudios Prospectivos , Proteinuria/orinaRESUMEN
Introduction: This retrospective database claims analysis describes the clinical characteristics and treatment patterns of commercially insured United States women with uterine fibroids (UF) and heavy menstrual bleeding (HMB). Methods: Women age 18-55 years with an incident UF diagnosis (index date) between 1/1/2012 and 12/31/2019 and ≥1 claim for HMB (UF-HMB), were identified from the Optum® Clinformatics® database. Outcomes included clinical characteristics, pharmacologic therapy use, and surgeries/procedures. Regression models were used to identify factors associated with time to post-diagnosis hormonal therapy and hysterectomy. Results: A total of 85,428 women had UF-HMB (mean [SD] age, 43.7 [6.4] years). The median follow-up was 3.2 years. After HMB, the most common symptoms were pelvic pressure/pain (27.6%) and backache (17.5%). Within 6 months of UF diagnosis, 40.2% of patients had received only pharmacologic therapy; 25.5% had received no treatment; 24.3% had a hysterectomy, and 10.0% had other procedures. By the end of follow-up, 50.0% had received a hysterectomy. Multiple factors were predictive of a higher likelihood of receiving hormonal therapy (geographic region, infertility, pre-index pregnancy) or hysterectomy (older age, prior hormonal treatment, specific bulk symptoms, White race). Conclusion: Within 6 months of UF diagnosis, fewer than one-half of women with UF-HMB had received hormonal therapy, one-quarter received no treatment, and one-quarter had received a hysterectomy or another gynecologic procedure. Patients who received a hysterectomy were more likely to be older, White, and to have bulk symptoms.
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Objective: This interview study sought to capture patients' experiences and perceptions of endometriosis symptoms and their impacts on daily life, as described by women in their own words. Using open-ended questions and a concept-elicitation approach, this study assessed the signs and symptoms of endometriosis and their impacts on different aspects of quality of life, including daily activities, functioning, and well-being. Materials and Methods: This interview study included US women with moderate-to-severe endometriosis-associated pain who completed one of two Phase 3, randomized, double-blind, placebo-controlled trials (SPIRIT 1 or SPIRIT 2; ClinicalTrials.gov identifiers: NCT03204318, NCT03204331). Interviews were conducted via a web/Internet-based video platform or telephone by trained interviewers, using open-ended questions in a concept-elicitation approach, and probes as needed to obtain additional feedback on the burden of endometriosis. Qualitative data from the interviews were analyzed, and emerging concepts were coded by independent coders. Concept saturation was evaluated to determine if all endometriosis-related symptoms and impacts had been described by the sample of women interviewed. Results: Forty women participated in this study. In total, 18 unique symptoms of endometriosis emerged from the interviews; pelvic pain (92.5%), dyspareunia (80.0%), and heavy bleeding (75.0%) were the most commonly reported endometriosis symptoms. A total of 33 unique impacts of endometriosis symptoms were identified across 11 concepts: physical impacts, impacts on activities of daily living, social impacts, sleep impacts, emotional impacts, appearance impacts, financial impacts, sex-related impacts, work/school-related impacts, fertility impacts, and cognitive impacts. Concept saturation was achieved for both symptoms and impacts of endometriosis. Conclusion: This interview study provides substantive qualitative data on the burden of endometriosis, from the perspective of affected women in the US. The findings demonstrate the debilitating effect of endometriosis symptoms, which limit and adversely impact women's daily lives.
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Shortage of organ donors is the most important obstacle standing in the way of lifesaving organ transplantation in a myriad of patients suffering from end-stage organ failure. It is vital that the transplant societies and associated appropriate authorities develop strategies to overcome the unmet needs for organ donation. The power of prominent social media (SoMe) platforms such as Facebook, Twitter, and Instagram, which reach millions of people, can increase awareness, provide education, and may ameliorate the pessimism toward organ donation among the general population. Additionally, public solicitation of organs may be helpful for waitlisted candidates for organ transplantation, who cannot find a suitable donor among near relations. However, the use of SoMe for organ donation has several ethical issues. This review attempts to highlight the advantages and limitations of using social media in the context of organ donation for transplantation. Some suggestions on the best utilization of social media platforms for organ donation while balancing ethical considerations have been highlighted here.
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Purpose: The diagnosis of endometriosis often takes several years, delaying appropriate care while patients suffer from pelvic pain, dysmenorrhea, and dyspareunia. Understanding whether residents in obstetrics and gynecology (OB/GYN) are being adequately exposed to and trained in the diagnosis and management of the disease is important for improving care. Methods: We conducted an online cross-sectional survey of OB/GYN residents to investigate their comfort level and familiarity with endometriosis diagnosis and management. Residency program directors and coordinators of 20 OB/GYN residency programs in California, USA were emailed to disseminate the 31-question, anonymous survey in January to February 2023. Responses were collected using Redcap and analysis was conducted using STATA. Results: 67 residents answered at least one non-demographic question and were included. A resident response rate was not calculated because we were unable to determine how many programs distributed the survey. 84% of residents felt they could recognise symptoms of endometriosis but over 30% of senior residents were not comfortable with sonographic diagnosis of endometrioma. Approximately one third of residents felt comfortable managing hypoestrogenic symptoms, osteoporotic risks, and add-back progestin for certain hormonal therapies. Academic-hospital based residents had significantly more exposure to attendings prescribing long-acting reversible contraception, GnRH antagonists, and GnRH agonists but there were no significant differences in trainee prescribing practices or comfort. More respondents would feel comfortable medically managing endometriosis (52%) than surgically managing the disease (26%) if they were in practice today, with only 39% of PGY3-4 residents feeling comfortable surgically managing endometriosis. Conclusion: There is considerable room for improvement in the education of residents in the diagnosis and medical and surgical management of endometriosis.
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From the context of organ donation, COVID-19 vaccine-induced thrombotic thrombocytopenia (VITT) is important as there is an ethical dilemma in utilizing versus discarding organs from potential donors succumbing to VITT. This consensus statement is an attempt by the National Organ and Tissue Transplant Organization (NOTTO) apex technical committees India to formulate the guidelines for deceased organ donation and transplantation in relation to VITT to help in appropriate decision making. VITT is a rare entity, but a meticulous approach should be taken by the Organ Procurement Organization's (OPO) team in screening such cases. All such cases must be strictly notified to the national authorities like NOTTO, as a resource for data collection and ensuring compliance withprotocols in the management of adverse events following immunization. Organs from any patient who developed thrombotic events up to 4 weeks after adenoviral vector-based vaccination should be linked to VITT and investigated appropriately. The viability of the organs must be thoroughly checked by the OPO, and the final decision in relation to organ use should be decided by the expert committee of the OPO team consisting of a virologist, a hematologist, and atreating team. Considering the organ shortage, in case of suspected/confirmed VITT, both clinicians and patients should consider the risk-benefit equationbased on available experience, and an appropriate written informed consent of potential recipients and family members should be obtained before transplantation of organs from suspected or proven VITT donors.