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BACKGROUND: Recurrence of focal segmental glomerulosclerosis (FSGS) or steroid-resistant nephrotic syndrome (SRNS) after kidney transplant leads to significant morbidity and potentially earlier allograft loss. To date however, reported rates, risk factors and treatment outcomes have varied widely.
METHODS: We applied computational phenotypes to a multicenter aggregation of electronic health records data from 7 large pediatric health systems in the USA, to identify recurrence rates, risk factors, and treatment outcomes. We refined the data collection by chart review.
RESULTS: From > 7 million patients, we compared children with primary FSGS/SRNS who received a kidney transplant between 2009 and 2020 and who either developed recurrence (n = 67/165; 40.6%) or did not (n = 98/165). Serum albumin level at time of transplant was significantly lower and recipient HLA DR7 presence was significantly higher in the recurrence group. By 36 months post-transplant, complete remission occurred in 58.2% and partial remission in 17.9%. Through 6 years post-transplant, no remission after recurrence was associated with an increased risk of allograft loss over time (p < 0.0001), but any remission showed similar allograft survival and function decline to those with no recurrence. Since treatments were used in non-random fashion, using spline curves and multivariable non-linear analyses, complete + partial remission chance was significantly higher with greater plasmapheresis sessions, CTLA4-Ig doses or LDL-apheresis sessions. Only treatment with anti-CD20, CTLA4-Ig agents, or LDL-apheresis sessions were associated with complete remission. Excluding 25 patients with mutations did not significantly change our results.
CONCLUSIONS: Our contemporary high-risk cohort had higher favorable response rates than most prior reports, from combinations of agents.

Background: Patients with persistent or recurrent cervical cancer, following primary treatment with concurrent chemoradiation, represent a subgroup eligible for pelvic exenteration. In light of the substantial morbidity associated with open pelvic exenterations, minimally invasive surgical techniques have been introduced. This systematic review aims to analyze and discuss the current literature on robotic-assisted pelvic exenterations in cervical cancer. In addition, novel aspects of compartment-based magnetic resonance imaging (MRI) are highlighted. Methods: This systematic review followed the PRISMA guidelines, and a comprehensive literature search on robotic-assisted pelvic exenterations in cervical cancer was conducted to assess, as main objectives, early and late postoperative complications as well as oncological outcomes. Inclusion and exclusion criteria were applied to select eligible studies. Results: Among the reported cases of robotic-assisted pelvic exenterations in cervical cancer, 79.4% are anterior pelvic exenterations. Intraoperative complications are minimal and early/late major complications averaged between 30-35%, which is lower compared to open pelvic exenterations. Oncological outcomes are similar between robotic and open pelvic exenterations. Sensitivity for locoregional invasion increases up to 93% for compartment-based MRI in colorectal cancer. A refined delineation of the seven pelvic compartments for cervical cancer is proposed here. Conclusions: Robotic-assisted pelvic exenterations have demonstrated feasibility and safety, with reduced rates of major complications compared to open surgery, while maintaining surgical efficiency and oncological outcomes. Compartment-based MRI holds promise for standardizing the selection and categorization of pelvic exenteration procedures.

OBJECTIVE: Recurrent primary biliary cholangitis (rPBC) develops in approximately 30% of patients and negatively impacts graft and overall patient survival after liver transplantation (LT). There is a lack of data regarding the response rate to ursodeoxycholic acid (UDCA) in rPBC. We evaluated a large, international, multi-center cohort to assess the performance of PBC scores in predicting the risk of graft and overall survival after LT in patients with rPBC.
METHODS: A total of 332 patients with rPBC after LT were evaluated from 28 centers across Europe, North and South America. The median age at the time of rPBC was 58.0 years [IQR 53.2-62.6], and 298 patients (90%) were female. The biochemical response was measured with serum levels of alkaline phosphatase (ALP) and bilirubin, and Paris-2, GLOBE and UK-PBC scores at 1 year after UDCA initiation.
RESULTS: During a median follow-up of 8.7 years [IQR 4.3-12.9] after rPBC diagnosis, 52 patients (16%) had graft loss and 103 (31%) died. After 1 year of UDCA initiation the histological stage at rPBC (hazard ratio [HR] 3.97, 95% CI 1.36-11.55, p = 0.01), use of prednisone (HR 3.18, 95% CI 1.04-9.73, p = 0.04), ALP xULN (HR 1.59, 95% CI 1.26-2.01, p <0.001), Paris-2 criteria (HR 4.14, 95% CI 1.57-10.92, p = 0.004), GLOBE score (HR 2.82, 95% CI 1.71-4.66, p <0.001), and the UK-PBC score (HR 1.06, 95% CI 1.03-1.09, p <0.001) were associated with graft survival in the multivariate analysis. Similar results were observed for overall survival.
CONCLUSIONS: Patients with rPBC and disease activity, as indicated by standard PBC risk scores, have impaired outcomes, supporting efforts to treat recurrent disease in similar ways to pre-transplant PBC.
UNASSIGNED: One in three people who undergo liver transplantation for primary biliary cholangitis develop recurrent disease in their new liver. Patients with recurrent primary biliary cholangitis and incomplete response to ursodeoxycholic acid, according to conventional prognostic scores, have worse clinical outcomes, with higher risk of graft loss and mortality in similar ways to the disease before liver transplantation. Our results supportsupport efforts to treat recurrent disease in similar ways to pre-transplant primary biliary cholangitis.

Although many recent advancements have been made in women\'s health, perhaps one of the most neglected areas of research is the diagnosis and treatment of high-grade endometrial cancer (EnCa). The molecular classification of EnCa in concert with histology was a major step forward. The integration of profiling for mismatch repair deficiency and Human Epidermal Growth Factor 2 (HER2) overexpression, can further inform treatment options, especially for drug resistant recurrent disease. Recent early phase trials suggest that regardless of subtype, combination therapy with agents that have distinct mechanisms of action is a fruitful approach to the treatment of high-grade EnCa. Unfortunately, although the importance of diagnosis and treatment of high-grade EnCa is well recognized, it is understudied compared to other gynecologic and breast cancers. There remains a tremendous need to couple molecular profiling and biomarker development with promising treatment options to inform new treatment strategies with higher efficacy and safety for all who suffer from high-grade recurrent EnCa.

UNASSIGNED: The primary objective was to determine whether obliteration of the epitympanic area and mastoid cavity during canal wall up (CWU) cholesteatoma surgery reduces the rate of recurrent and residual cholesteatoma compared to not obliterating the same area. The secondary objective was to compare postoperative hearing outcomes between both techniques.
UNASSIGNED: A retrospective cohort study was conducted in a tertiary referral center. One-hundred-fourty-three ears were included of patients (≥18y) who underwent a CWU tympanomastoidectomy for cholesteatoma with or without bony obliteration between January 2015 and March 2020 in the University Medical Center Utrecht. The median follow-up was respectively 1.4 (IQR 1.1-2.2) vs. 2.0 years (IQR 1.2-3.1) (p = 0.013).
UNASSIGNED: All patients underwent CWU tympanomastoidectomy for cholesteatoma. For 73 ears bone dust, Bonalive® or a combination was used for obliteration of the mastoid and epitympanic area, the rest of the ears (n = 70) were not obliterated. In accordance with the Dutch protocol, included patients are planned to undergo an MRI scan with diffusion-weighted imaging (DWI) one, three and five years after surgery to detect recurrent or residual cholesteatoma.
UNASSIGNED: The primary outcome measure was recurrent and residual cholesteatoma as evaluated by MRI-DWI and/or micro-otoscopy and confirmed by micro-otoscopy and/or revision surgery. The secondary outcome measure was the postoperative hearing.
UNASSIGNED: In this cohort, the group treated with canal wall up tympanomastoidectomy with subsequent bony obliteration (73 ears, 51.0%) had significantly lower recurrent (4.1%) and residual (6.8%) cholesteatoma rates than the group without obliteration (70 ears, 25.7% and 20.0%, respectively; p < 0.001). There was no significant difference between both groups in postoperative bone conduction thresholds (mean difference 2.7 dB, p = 0.221) as well as the mean air-bone gap closure 6 weeks after surgery (2.3 dB in the non-obliteration and 1.5 dB in the obliteration group, p = 0.903).
UNASSIGNED: Based on our results, a canal wall up tympanomastoidectomy with bony obliteration is the treatment of choice, since the recurrent and residual disease rate is lower compared to the group without obliteration. The bony obliteration technique does not seem to affect the perceptive or conductive hearing results, as these are similar between both groups.

BACKGROUND: Recurrent disease after kidney transplant remains an important cause of allograft failure, accounting for 7-8% of graft loss and ranking as the fifth most common cause of allograft loss in the pediatric population. Although the pathophysiology of many recurrent diseases is incompletely understood, recent advances in basic science and therapeutics are improving outcomes and changing the course of several of these conditions.
METHODS: Review of the literature.
RESULTS: We discuss the diagnosis and management of recurrent disease.
CONCLUSIONS: We highlight new insights into the pathophysiology and treatment of post-transplant primary hyperoxaluria, focal segmental glomerulosclerosis, immune complex glomerulonephritis, C3 glomerulopathy, lupus nephritis, atypical hemolytic uremic syndrome, and IgA nephropathy.

Beyond the direct benefit that a transplanted organ provides to an individual recipient, the study of the transplant process has the potential to create a better understanding of the pathogenesis, etiology, progression and possible therapy for recurrence of disease after transplantation while at the same time providing insight into the original disease. Specific examples of this include: 1) recurrence of focal segmental glomerulosclerosis (FSGS) after kidney transplantation, 2) recurrent autoimmunity after pancreas transplantation, and 3) recurrence of disease after orthotopic liver transplantation (OLT) for cirrhosis related to progressive steatosis secondary to jejuno-ileal bypass (JIB) surgery. Our team has been studying these phenomena and their immunologic underpinnings, and we suggest that expanding the concept to other pathologic processes and/or transplanted organs that harbor the risk for recurrent disease may provide novel insight into the pathogenesis of a host of other disease processes that lead to organ failure.

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UNASSIGNED: Numerous studies concluded stress (acute, episodic acute, or chronic) increases the incidence of human alpha-herpes virus 1 (HSV-1) reactivation from latency in neurons. This review will summarize how stress stimulates viral gene expression, replication, and reactivation from latency.
UNASSIGNED: Stress (capital S) stress-mediated activation of the glucocorticoid receptor (GR) accelerates reactivation from latency, whereas a corticosteroid-specific antagonist impairs viral replication and reactivation from latency. GR and specific stress-induced cellular transcription factors also stimulate viral promoters that drive expression of key viral transcriptional regulators: infected cell protein 0 (ICP0), ICP4, ICP27 and viral tegument protein (VP16). Hence, GR is predicted to initially stimulate viral gene expression. GR-mediated immune-inhibitory functions are also predicted to enhance viral replication and viral spread.
UNASSIGNED: Identifying cellular factors and viral regulatory proteins that trigger reactivation from latency in neurons may provide new therapeutic strategies designed to reduce the incidence of reactivation from latency.