Describing the Patient Journey of Women with Claims for Uterine Fibroids and Heavy Menstrual Bleeding Using a Commercial Database (2011-2020).

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.

NOTTO Guidelines for Vaccine Induced Thrombotic Thrombocytopenia in Organ Donation and Transplantation.

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.

Association of vitamin D status with disease severity and outcome in Indian patients with IgA nephropathy.

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.

Endometrial microbiota is more diverse in people with endometriosis than symptomatic controls.

Endometriosis is a chronic, estrogen-dependent gynecological condition affecting approximately 10% of reproductive age women. The most widely accepted theory of its etiology includes retrograde menstruation. Recent reports suggest the uterus is not sterile. Thus, the refluxed menstrual effluent may carry bacteria, and contribute to inflammation, the establishment and growth of endometriotic lesions. Here, we compared and contrasted uterine bacteria (endometrial microbiota) in people with surgically confirmed presence (N = 12) or absence of endometriosis (N = 9) using next-generation 16S rRNA gene sequencing. We obtained an average of > 9000 sequence reads per endometrial biopsy, and found the endometrial microbiota of people with endometriosis was more diverse (greater Shannon Diversity Index and proportion of 'Other' taxa) than symptomatic controls (with pelvic pain, surgically confirmed absence of endometriosis; diagnosed with other benign gynecological conditions). The relative abundance of bacterial taxa enriched in the endometrial microbiota of people with endometriosis belonged to the Actinobacteria phylum (Gram-positive), Oxalobacteraceae (Gram-negative) and Streptococcaceae (Gram-positive) families, and Tepidimonas (Gram-negative) genus, while those enriched in the symptomatic controls belonged to the Burkholderiaceae (Gram-negative) family, and Ralstonia (Gram-negative) genus. Taken together, results suggest the endometrial microbiota is perturbed in people with endometriosis.

Factors affecting stability of plasma brain-derived neurotrophic factor.

Circulating concentrations of brain-derived neurotrophic factor (BDNF) have been linked to cancer, neuropsychiatric, diabetes, and gynecological disorders. However, factors influencing plasma storage and subsequent BDNF quantification are incompletely understood. Therefore, the anticoagulant used in plasma separator tubes, storage-time, storage-temperature, and repeated freeze-thaw cycles on circulating BDNF concentrations was evaluated. Peripheral blood samples were collected from healthy women (n = 14) and men (n = 10) recruited prospectively from McMaster University (August 2014). Blood was collected from the cubital vein into plasma separator tubes containing five different anticoagulant systems [K2EDTA, Li-Hep, Li-Hep (gel), Na-Hep, Na-Hep (glass)], and placed on ice for transport to the lab for centrifugation. Plasma samples (n = 16) collected in K2EDTA tubes from women recruited to a previous study (April 2011 to December 2012) were used to determine the effect of multiple freeze-thaw cycles. Plasma BDNF was quantified using a commercially available ELISA kit. Plasma concentrations of BDNF were significantly affected by the type of plasma separator tube, storage-time, and number of freeze-thaw cycles. Storage temperature (- 20 vs. - 80 °C) did not significantly affect the quantity of BDNF measured as mean BDNF concentrations generally fell within our calculated acceptable change limit up to 6 months in the freezer. Our results suggest that for quantification of circulating BDNF blood collected in K2EDTA tubes and plasma stored up to 6 months at either - 20 or - 80 °C produces reproducible results that fall within an acceptable range. However, plasma samples stored beyond 6 months and repeated freeze-thaw cycles should be avoided.

Real-World Characterization of Women with Diagnosed Endometriosis Initiating Therapy with Elagolix Using a US Claims Database.

PURPOSE: Elagolix is an oral gonadotropin-releasing hormone antagonist approved in the United States for the management of moderate to severe pain associated with endometriosis. We performed a real-world evaluation of the demographic and clinical characteristics of women diagnosed with endometriosis who were initiating elagolix therapy in the United States. PATIENTS AND METHODS: This retrospective cohort database analysis included women 18-49 years of age with ≥1 pharmacy claim for elagolix between August 2018 and December 2019 from the Copyright © 2020 Truven Health Analytics LLC. All Rights Reserved. Women had continuous medical and pharmacy health plan enrollment during the baseline period (year immediately preceding the index date [date of earliest elagolix claim]) and had ≥1 medical claim with endometriosis (International Classification of Diseases [ICD]-9/10 code [617.x and N80.x]) on or before the index date. Baseline demographics, comorbidities, ICD code-based endometriosis anatomic site, endometriosis-related treatments, and pain symptoms were summarized descriptively. RESULTS: The study included 2083 patients with mean age at baseline of 33.2 ± 8.1 years. Comorbidities most commonly recorded were non-cancer, non-endometriosis pain (59.5%), including arthritis/joint pain (43.7%) and back/neck pain (31.7%), and mental disorder (40.7%), including anxiety (32.7%). The majority of endometriosis diagnosis codes recorded referred to unspecified location (52.3%) and pelvic peritoneum (23.0%); 61.0% of patients received a medical endometriosis-related treatment in the baseline period, with the most common treatments being contraceptives (various routes of administration, 40.2%) and progestins (31.7%). Additionally, 35.4% of the patients received an endometriosis-related surgery during baseline, with the most common being laparoscopy (33.2% of all patients). Opioids were used during the baseline period by 57.3% of the patients. For pain symptoms, 71.5%, 30.4%, and 19.3% of the patients had claims for pelvic pain, dysmenorrhea, and dyspareunia, respectively. CONCLUSION: Endometriosis therapies were used by a significant proportion of patients with endometriosis in the year immediately preceding elagolix initiation.

Spectrum of biopsy-proven renal disease in northern India: A single-centre study.

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.

Health Care Utilization and Costs Associated with Endometriosis Among Women with Medicaid Insurance.

BACKGROUND: Endometriosis is a painful chronic inflammatory disease caused by endometrial tissue implanting and growing outside the uterus, resulting in pelvic pain symptoms and subfertility. Treatment imposes a substantial economic burden on the patient and health care system. OBJECTIVE: To evaluate direct health care utilization and costs among women newly diagnosed with endometriosis compared with age-matched controls in a U.S. Medicaid population. METHODS: This retrospective cohort study used deidentified health care claims from the 2007-2015 MarketScan Multi-State Medicaid Database. Women (aged 18-49 years) newly diagnosed with endometriosis (ICD-9-CM 617.xx) during January 2008 through September 2014 were identified (date of first diagnosis = index date). Age-matched women without endometriosis (controls) were selected from the database and assigned index dates matching the distribution for endometriosis patients. Direct health care resource utilization (HCRU) and costs (medical and pharmacy) over the 12-month post-index period (2015 U.S. dollars) were computed by service category (hospitalization, emergency room visits, outpatient services, and prescriptions) and compared between study cohorts using the chi-square test for proportions and t-test for continuous variables. RESULTS: The final sample included 15,615 endometriosis patients and 86,829 matched controls. HCRU during the 12-month post-index follow-up period was significantly higher for endometriosis cases compared with controls in all measured categories. Hospital admissions occurred among 33.1% of cases and 7.2% of controls, and 65.8% of endometriosis patients were admitted for endometriosis-related surgery. Emergency room visits occurred in 71.5% of cases, and 42.2% of controls. Mean (SD) office visits were 10.4 (8.5) for endometriosis patients and 5.1 (6.9) for controls. Endometriosis patients had significantly more prescription claims than controls, 45.9 (42.0) versus 25.1 (39.1). Mean total direct health care costs were $13,670 ($29,843) for cases versus $5,779 ($23,614) for controls. All differences between cases and controls were significant at P < 0.001. CONCLUSIONS: Health care costs and resource utilization in all measured categories were higher among endometriosis cases than controls. The economic burden of endometriosis among patients with Medicaid insurance is substantial, underscoring the unmet medical need for earlier diagnosis and cost-effective treatments. DISCLOSURES: This study was funded by AbbVie and conducted by Truven Health Analytics, an IBM Company. AbbVie participated in developing the study design, data analysis and interpretation, manuscript writing and revisions, and approval for publication. Soliman and Vora are employees of AbbVie and may own AbbVie stock/stock options. Surrey has served in a consulting role on research to AbbVie and is on the speaker bureau for Ferring Laboratories. Bonafede and Nelson are employees of Truven Health Analytics, an IBM Company, which received compensation from AbbVie for the overall conduct of the study and preparation of the manuscript. Agarwal has served in a consulting role on research to AbbVie. Preliminary results of this study were previously presented in a podium session at the 2017 American Society for Reproductive Medicine Scientific Congress and Expo; October 28-November 1, 2017; San Antonio, TX.

Chronic Kidney Disease of Unknown Etiology: Hotspots in India and Other Asian Countries.

There has been increased reporting of chronic kidney disease of unknown etiology (CKDu) in certain agricultural communities in the world. In India, an increased prevalence of CKDu has been observed in the states of Andhra Pradesh, Odisha, Goa, and Maharashtra. Although no single causative factor has been proved, several have been proposed: water-borne agrochemicals, silica, chemical flavors in betel nuts, and pesticides. The renal biopsy findings have been similar to those seen in Sri Lanka and Mesoamerican nephropathy in that the predominant findings have been tubular atrophy and interstitial fibrosis with little or no involvement of the glomerular and vascular compartments. Because most of the affected communities belong to the lower socioeconomic group including farmers, a multipronged approach is required for addressing this CKDu epidemic with an emphasis on awareness, prevention, screening, surveillance, provision of renal replacement therapy, increased government spending on health care, and systematic research.

Impact of elagolix treatment on fatigue experienced by women with moderate to severe pain associated with endometriosis.

OBJECTIVE: To evaluate the efficacy of elagolix, an oral GnRH antagonist, for the reduction of fatigue in women with moderate or severe endometriosis-associated pain. DESIGN: Randomized, double-blind, multicenter, placebo-controlled phase III trial. SETTING: Clinics. PATIENT(S): A total of 860 women treated with elagolix or placebo. INTERVENTION(S): Women received either elagolix at 150 mg daily (QD) orally, elagolix at 200 mg twice daily (BID) orally, or placebo. MAIN OUTCOME MEASURE(S): Change from baseline to month 1, 3, and 6 visits, in Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form 6a questionnaire T-scores. RESULTS(S): At baseline, 54%-74% of women with moderate to severe pain associated with endometriosis reported having fatigue-related issues "quite a bit" or "very much," depending on the question asked. Fatigue extent was reduced to 29%-43% and 14%-29% for women treated with elagolix at 150 mg QD and 200 mg BID, respectively, at 6 months, compared with 35%-50% with placebo. The resultant decrease in fatigue T-scores was significant after elagolix treatment compared with placebo at 6 months, with changes of -2.21 and -5.90 with elagolix at 150 mg QD and 200 mg BID, respectively. Significant reduction in fatigue scores were observed among patients reporting clinically meaningful response "reduction" in dysmenorrhea, nonmenstrual pelvic pain, and dyspareunia (-7.31, -6.62, and -4.31, respectively) compared with nonresponders. CONCLUSION(S): In women with moderate to severe endometriosis related pain, elagolix significantly reduces fatigue levels.

Clinical diagnosis of endometriosis: a call to action.

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.

Long-Term Outcomes of Elagolix in Women With Endometriosis: Results From Two Extension Studies.

OBJECTIVE: To evaluate the efficacy and safety of elagolix, an oral, nonpeptide gonadotropin-releasing hormone antagonist, over 12 months in women with endometriosis-associated pain. METHODS: Elaris Endometriosis (EM)-III and -IV were extension studies that evaluated an additional 6 months of treatment after two 6-month, double-blind, placebo-controlled phase 3 trials (12 continuous treatment months) with two elagolix doses (150 mg once daily and 200 mg twice daily). Coprimary efficacy endpoints were the proportion of responders (clinically meaningful pain reduction and stable or decreased rescue analgesic use) based on average monthly dysmenorrhea and nonmenstrual pelvic pain scores. Safety assessments included adverse events, clinical laboratory tests, and endometrial and bone mineral density assessments. The power of Elaris EM-III and -IV was based on the comparison to placebo in Elaris EM-I and -II with an expected 25% dropout rate. RESULTS: Between December 28, 2012, and October 31, 2014 (Elaris EM-III), and between May 27, 2014, and January 6, 2016 (Elaris EM-IV), 569 participants were enrolled. After 12 months of treatment, Elaris EM-III responder rates for dysmenorrhea were 52.1% at 150 mg once daily (Elaris EM-IV 550.8%) and 78.2% at 200 mg twice daily (Elaris EMIV 575.9%). Elaris EM-III nonmenstrual pelvic pain responder rates were 67.5% at 150 mg once daily (Elaris EM-IV 566.4%) and 69.1% at 200 mg twice daily (Elaris EM-IV 567.2%)."After 12 months of treatment, Elaris EM-III dyspareunia responder rates were 45.2% at 150 mg once daily (Elaris EM-IV=45.9%) and 60.0% at 200 mg twice daily (Elaris EM-IV=58.1%). Hot flush was the most common adverse event. Decreases from baseline in bone mineral density and increases from baseline in lipids were observed after 12 months of treatment. There were no adverse endometrial findings. CONCLUSION: Long-term elagolix treatment provided sustained reductions in dysmenorrhea, nonmenstrual pelvic pain, and dyspareunia. The safety was consistent with reduced estrogen levels and no new safety concerns were associated with long-term elagolix use. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT01760954 and NCT02143713.

MicroRNA expression pattern differs depending on endometriosis lesion type.

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.

Soluble Major Histocompatibility Complex Class I related Chain A (sMICA) levels influence graft outcome following Renal Transplantation.

BACKGROUND: Since soluble isoforms of MICA play an important role in modulating the immune response, we evaluated a possible correlation between their levels and development of acute rejection following renal transplantation. METHODS: Serum samples collected at pre- and different time points post-transplant from 137 live related donor renal transplant recipients were evaluated retrospectively for sMICA levels and for the presence of MICA antibodies. Samples from 30 healthy volunteers were also tested as controls. RESULTS: Significantly higher levels of sMICA were observed in the pretransplant sera of allograft recipients as compared to healthy controls. Patients with acute cellular rejection experienced a significant fall in their levels at the time of diagnosis as compared to their pretransplant values and posttransplant follow up time points (p = .01, .003, .005 and .04 respectively at pre vs biopsy (Bx), POD7 vs Bx, POD 30 vs Bx, POD 90 vs Bx). However, no such difference was noted in patients undergoing antibody mediated rejection. Further the study did not reveal any correlation on the presence/absence of MICA antibodies with either an increase or decrease in sMICA levels. CONCLUSIONS: Estimating circulating levels of soluble MICA could provide useful information of prognostic importance in assessing graft outcome following renal transplantation.

Immunohistochemical Expression of Antitissue Transglutaminase 2 in Tissue Injuries: An Interpretation Beyond Celiac Disease.

Tissue transglutaminase 2 enzyme plays a diverse role in intracellular and extracellular functioning. Aberrant expression of anti-TG2 antibody has recently been proposed for extraintestinal identification of celiac disease (CeD), but its utility is questionable. To examine whether anti-TG2 immunohistochemical (IHC) staining can be of diagnostic value in identifying extraintestinal involvement in CeD, tissue blocks of patients with IgA nephropathies (IgAN), minimal change disease, membranous glomerulonephritis, membrano-proliferative glomerulonephritis, normal kidney, intestinal biopsies from CeD, tropical sprue, nonspecific duodenitis, and inflammatory bowel disease; liver biopsies from patients with chronic hepatitis B and C, acute liver failure (ALF), and CeD-associated liver diseases were retrieved and subjected to IHC staining for anti-tissue transglutaminase 2 enzyme. H-score was calculated by multiplying the area of positivity and stain intensity. Anti-TG2 stain H-scores were almost similar in IgAN and non-IgANs (H-score 6.31±3 vs. 7.03±2.7); however, H-scores in both of these groups were significantly higher than in normal renal parenchyma (1.6±1.5). Only 6.2% patients with IgAN with anti-TG2 immunostain positivity showed a positive anti-tTG antibody serology and villous abnormalities, suggestive of CeD. Intestinal biopsies from patients with CeD, tropical sprue, nonspecific duodenitis, and inflammatory bowel disease also showed high anti-TG2 H-scores, with no statistically significant differences. Liver biopsies from patients with both ALF, as well as chronic liver diseases showed high anti-TG2 H-scores; with highest stain expression in ALF. In conclusion, IHC expression of anti-TG2 stain correlates with both acute and chronic tissue injuries, irrespective of etiology and organ involvement. It is not a reliable marker for diagnosis of CeD.

Peripheral T-Cell Lymphoma: A Posttransplant Lymphoproliferative Disorder Presenting as a Jejunal Mass in a Renal Transplant Recipient.

Posttransplant lymphoproliferative disorders are a spectrum of lymphoproliferative disorders seen in recipients of solid-organ, bone marrow, and stem cell allografts. They include polyclonal early lesions mimicking infectious mononucleosis and monoclonal proliferations of B and T cells, indistinguishable from lymphomas occurring in immunocompetent individuals. Although most posttransplant lymphoproliferative disorders are B-cell neoplasms, T-cell posttransplant lymphoproliferative disorders are very rare. Among solid-organ transplants, renal allografts have low risk for development of posttransplant lymphoproliferative disorders. We describe the case of an adult male who developed a T-cell posttransplant lympho?roliferative disorder involving the small intestine after renal transplant, which was diagnosed as peripheral T-cell lymphoma, not otherwise specified.

Assessing brain-derived neurotrophic factor as a novel clinical marker of endometriosis.

OBJECTIVE: To evaluate novel clinical markers of endometriosis including the neurotrophins brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and neurotrophin 4/5 (NT4/5) and compare them to others previously reported in the literature including cancer antigen 125 (CA-125) and C-reactive protein (CRP). DESIGN: Prospective study. SETTING: University hospital. PATIENT(S): One hundred thirty-eight women were prospectively and consecutively recruited (April 2011-April 2015; cases: undergoing endometriosis surgery, n = 96; controls: benign gynecological surgery, n = 24 combined with healthy women, no history of pelvic pain, not undergoing surgery, n = 18). INTERVENTION(S): Collection of peripheral blood, gynecological and demographic information, eutopic biopsy in women undergoing laparoscopy. MAIN OUTCOME MEASURE(S): Circulating BDNF, NGF, NT4/5, CA-125, and CRP were quantified by ELISA. RESULT(S): Plasma concentrations of BDNF were significantly greater in women with endometriosis (1,091.9 pg/mL [640.4-1,683.1]; n = 68, untreated) than in controls (731.4 pg/mL [352.1-1,176.2]; n = 36), whereas circulating NGF, NT4/5, CA-125, and CRP were not different. When assessed for their ability to differentiate between women with revised Classification of the American Society of Reproductive Medicine stage 1 and 2 or stage 3 and 4 disease and controls, BDNF was the only putative marker able to identify stage 1 and 2 disease, with a sensitivity and specificity of 91.7% and 69.4%, respectively, using an arbitrary cutoff value of 1,000 pg/mL. We also demonstrated that circulating BDNF in women with endometriosis who were receiving ovarian suppression for disease was equivalent to that in the control group. This suggests that BDNF may also offer the opportunity to monitor patient response to treatment. CONCLUSION(S): Plasma BDNF is a potentially useful clinical marker of endometriosis that is superior to NGF, NT4/5, CA-125, and CRP.

C1q nephropathy and isolated CD59 deficiency manifesting as necrotizing crescentic glomerulonephritis: A rare association of two diseases.

C1q nephropathy is a recently described clinico-pathologic entity with a variable clinical presentation and pathology. Crescentic glomerulonephritis (GN) has been reported in only two patients in the available literature. CD59 deficiency, along with lack of CD55, is responsible for paroxysmal nocturnal hemoglobinuria (PNH). Few cases of isolated CD59 deficiency have been described with PNH-like features. A middle-aged adult male presented with rapidly progressive renal failure. Serological investigations were negative. A renal biopsy revealed necrotizing crescentic GN with rupture of Bowman's capsule. Immunofluorescence on the frozen sections showed dominant mesangial deposits of C1q along with IgM. Hematological work-up of the patient revealed isolated CD59 deficiency. Hence, a final diagnosis of C1q nephropathy and CD59 deficiency manifesting as crescentic GN and hemolytic anemia was made. The co-existence of two rare disorders, C1q nephropathy and CD59 deficiency, in a patient with necrotizing crescentic GN is described for the first time to the best of our knowledge. The pathogenetic link of these two entities with the clinical manifestation requires further study.

Estrogen induced changes in uterine brain-derived neurotrophic factor and its receptors.

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.

Application of the estrogen threshold hypothesis to the physiologic hypoestrogenemia of lactation.

OBJECTIVE: This study determined the impact of breastfeeding on hypoestrogenic symptoms among women in the postpartum period and correlated these findings with the Estrogen Threshold Hypothesis, which postulates that the hypoestrogenic symptoms experienced are related to circulating estrogen levels. STUDY DESIGN: Using a survey instrument that combined previously validated assessments of postpartum mood changes and menopausal symptoms, women were evaluated in the immediate postpartum period, prior to hospital discharge, and at 3 and 6 weeks postpartum. Each time period was analyzed independently, in a cross-sectional design, where women were categorized as "breastfeeding" or "bottle feeding." RESULTS: Of 236 women recruited, 171 (72.5%) intended to breastfeed, and 62 (26.3%) intended to bottle feed. At both the 3- and 6-week postpartum evaluations, a similar percentage of women in the breastfeeding and bottle-feeding groups reported hot flashes. However, breastfeeding women were more likely to report vaginal dryness than those who did not breastfeed: 20/150 (13.3%) versus 3/80 (3.8%) at 3 weeks, p<0.05; 25/143 (17.5%) versus 2/87 (2.3%) at 6 weeks, p<0.001. CONCLUSIONS: The Estrogen Threshold Hypothesis accurately predicts the findings of increased reported vaginal dryness but not hot flashes during lactation.