Publications by authors named "Ricardo Gonzalez"

279 Publications

A role for IL-33-activated ILC2s in eosinophilic vasculitis.

JCI Insight 2021 May 11. Epub 2021 May 11.

Department of Internal Medicine, Cochin Hospital, Paris, France.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare but serious disease with poorly understood mechanisms. Here we report that patients with EGPA have elevated levels of TSLP, IL-25, and sST2, well characterized cytokine "alarmins" that activate or modulate type 2 innate lymphoid cells (ILC2s). Patients with active EGPA have a concurrent reduction in circulating ILC2s, suggesting a role for ILC2s in the pathogenesis of this disease. To explore the mechanism of these findings in patients, we established a model of EGPA in which active vasculitis and pulmonary hemorrhage are induced by IL-33 administration in predisposed, hypereosinophilic mice. In this model, induction of pulmonary hemorrhage and vasculitis is dependent on ILC2s and signaling through IL4Ra. In the absence of IL4Ra or STAT6, IL-33-treated mice have less vascular leak and pulmonary edema, less endothelial activation, and reduced eotaxin production, cumulatively leading to a reduction of pathologic eosinophil migration into the lung parenchyma. These results offer a mouse model for use in future mechanistic studies of EGPA, and suggest that IL-33, ILC2s and IL4Ra signaling may be potential targets for further study and therapeutic targeting in patients with EGPA.
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http://dx.doi.org/10.1172/jci.insight.143366DOI Listing
May 2021

Female Sexual Function following Sling Surgery: A Prospective Parallel Cohort, Multi-Center Study of the Solyx™ Single Incision Sling System versus the Obtryx™ II Sling System (FDA-Mandated 522 Results at 36 Months).

J Urol 2021 May 6:101097JU0000000000001830. Epub 2021 May 6.

Department of Women's Health, Monash Medical Centre and Cabrini Hospital, Melbourne, Australia.

Purpose: Limited data exist regarding sexual function after single incision sling (SIS) surgery. We compared sexual function 36 months postoperatively between patients undergoing SIS and transobturator sling (TMUS) for treatment of stress urinary incontinence.

Materials And Methods: Assessment of sexual function was a planned secondary objective of this prospective, multi-center study that enrolled women to Solyx SIS or Obtryx II TMUS. The primary study aim was to compare efficacy and safety using non-inferiority design at 36 months Patient-reported outcomes of sexual function were assessed at baseline and 6, 12, 18, 24 and 36 months using Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12). Changes in sexual function were analyzed within and between groups. Outcomes for patients requiring surgical retreatment were determined.

Results: Baseline characteristics were balanced using propensity score stratification (N=141 SIS, N=140 TMUS). Groups were similar in age, body mass index and concomitant surgery performed. Average length of followup was 30 months. Baseline sexual activity was similar (123/141 SIS, 114/140 TMUS, p=0.18). Severity of urinary incontinence did not correlate with baseline sexual activity. Mean PISQ-12 scores increased significantly from baseline to 36 months for both groups, indicating better sexual function at each visit. There were no significant differences in PISQ-12 scores between groups except at 36 months, where the difference was small (-2.5, 95% CI [-4.7, 0.2]). Among patients undergoing surgical retreatment (9/281, 3%), improvement in sexual function was maintained. De novo dyspareunia was rare following both treatments (SIS 1/141, TMUS 0/140, p=1.00).

Conclusions: Patients have significant improvement in sexual function after SIS and TMUS. De novo sexual pain is low after sling surgery.
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http://dx.doi.org/10.1097/JU.0000000000001830DOI Listing
May 2021

Analysis of Differentiation Changes and Outcomes at Time of First Recurrence of Retroperitoneal Liposarcoma by Transatlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG).

Ann Surg Oncol 2021 Apr 27. Epub 2021 Apr 27.

Department of Surgery, Mayo Clinic, Jacksonville, FL, USA.

Background: Local recurrence following resection of retroperitoneal liposarcoma (RLPS) is common. Well-differentiated (WD) and dedifferentiated (DD) RLPS are distinct entities with differing outcomes. A few reports suggest that WDLPS can recur as DDLPS and that DDLPS can recur as WDLPS. This study evaluates whether this change in differentiation from the primary tumor to the first local recurrence impacts long-term outcomes.

Methods: Retrospective review from 22 sarcoma centers identified consecutive patients who underwent resection for a first locally recurrent RLPS from January 2002 to December 2011. Outcomes measured included overall survival, local recurrence, and distant metastasis.

Results: A total of 421 RPLS patients were identified. Of the 230 patients with primary DDLPS, 34 (15%) presented WDLPS upon recurrence (DD → WD); and of the 191 patients with primary WDLPS, 54 (28%) presented DDLPS upon recurrence (WD → DD). The 6-year overall survival probabilities (95% CI) for DD → DD, DD → WD, WD → WD, and WD → DD were 40% (32-48%), 73% (58-92%), 76% (68-85%), and 56% (43-73%) (p < 0.001), respectively. The 6-year second local recurrence incidence was 66% (59-73%), 63% (48-82%), 66% (57-76%), and 77% (66-90%), respectively. The 6-year distant metastasis incidence was 13% (9-19%), 3% (0.4-22%), 5% (2-11%), and 4% (1-16%), respectively. On multivariable analysis, DD → WD was associated with improved overall survival when compared with DD → DD (p < 0.001). Moreover, WD → DD was associated with a higher risk of LR (p = 0.025) CONCLUSION: A change in RLPS differentiation from primary tumor to first local recurrence appears to impact survival. These findings may be useful in counseling patients on their prognosis and subsequent management.
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http://dx.doi.org/10.1245/s10434-021-10024-yDOI Listing
April 2021

Management of Primary Retroperitoneal Sarcoma (RPS) in the Adult: An Updated Consensus Approach from the Transatlantic Australasian RPS Working Group.

Ann Surg Oncol 2021 Apr 14. Epub 2021 Apr 14.

Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Background: Retroperitoneal soft tissue sarcomas comprise a heterogeneous group of rare tumors of mesenchymal origin that include several well-defined histologic subtypes. In 2015, the Transatlantic Australasian RPS Working Group (TARPSWG) published consensus recommendations for the best management of primary retroperitoneal sarcoma (RPS). Since then, through international collaboration, new evidence and knowledge have been generated, creating the need for an updated consensus document.

Methods: The primary aim of this study was to critically evaluate the current evidence and develop an up-to-date consensus document on the approach to these difficult tumors. The resulting document applies to primary RPS that is non-visceral in origin, with exclusion criteria as previously described. The relevant literature was evaluated and an international group of experts consulted to formulate consensus statements regarding the best management of primary RPS. A level of evidence and grade of recommendation were attributed to each new/updated recommendation.

Results: Management of primary RPS was considered from diagnosis to follow-up. This rare and complex malignancy is best managed by an experienced multidisciplinary team in a specialized referral center. The best chance of cure is at the time of primary presentation, and an individualized management plan should be made based on the 29 consensus statements included in this article, which were agreed upon by all of the authors. Whenever possible, patients should be enrolled in prospective trials and studies.

Conclusions: Ongoing international collaboration is critical to expand upon current knowledge and further improve outcomes of patients with RPS. In addition, prospective data collection and participation in multi-institution trials are strongly encouraged.
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http://dx.doi.org/10.1245/s10434-021-09654-zDOI Listing
April 2021

SNAP23 is essential for platelet and mast cell development and required in connective tissue mast cells for anaphylaxis.

J Biol Chem 2021 Jan 8;296:100268. Epub 2021 Jan 8.

Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. Electronic address:

Degranulation, a fundamental effector response from mast cells (MCs) and platelets, is an example of regulated exocytosis. This process is mediated by SNARE proteins and their regulators. We have previously shown that several of these proteins are essential for exocytosis in MCs and platelets. Here, we assessed the role of the SNARE protein SNAP23 using conditional knockout mice, in which SNAP23 was selectively deleted from either the megakaryocyte/platelet or connective tissue MC lineages. We found that removal of SNAP23 in platelets results in severe defects in degranulation of all three platelet secretory granule types, i.e., alpha, dense, and lysosomal granules. The mutation also induces thrombocytopenia, abnormal platelet morphology and activation, and reduction in the number of alpha granules. Therefore, the degranulation defect might not be secondary to an intrinsic failure of the machinery mediating regulated exocytosis in platelets. When we removed SNAP23 expression in MCs, there was a complete developmental failure in vitro and in vivo. The developmental defects in platelets and MCs and the abnormal translocation of membrane proteins to the surface of platelets indicate that SNAP23 is also involved in constitutive exocytosis in these cells. The MC conditional deletant animals lacked connective tissue MCs, but their mucosal MCs were normal and expanded in response to an antigenic stimulus. We used this mouse to show that connective tissue MCs are required and mucosal MCs are not sufficient for an anaphylactic response.
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http://dx.doi.org/10.1016/j.jbc.2021.100268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948755PMC
January 2021

Immunological Risk Factors in Paediatric Kidney Transplantation.

Res Rep Urol 2021 23;13:87-95. Epub 2021 Feb 23.

Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.

Purpose: The aim of this study was to identify factors impacting recipient sensitization rates and paediatric renal transplant patient outcomes.

Patients And Methods: For this purpose, a retrospective analysis of 143 paediatric renal transplants was carried out. This included the evaluation of patient's and donor's demographic data, HLA mismatches, immunosuppressive therapy, rejection episodes, panel reactive antibody (PRA) and post-transplant lymphoproliferative disease (PTLD).

Results: The mean patient age at the point of transplant receival was 11.5 years with a mean follow up time of 9.33±5.05 years. It was noted that graft survival rates for donors over 59 years had the worst outcome. HLA match did not show statistically significant influence on graft outcome. Graft survival for more than one biopsy-proven rejection was also significantly shorter (p=0.008). PRA were found in 28% of the recipient's post-transplantation and showed association with lower graft survival rates (p<0.001). In the present study, 22.7% (5/22) of the patients with EBV infections presented a PTLD.

Conclusion: In conclusion, good graft survival with reduced sensitization for future transplantations and minimize the risk of PTLD, can be ensured through a balance between donor age, HLA match and condition of the recipient should be sought. Furthermore, paediatric patients should preferably receive organs from donors between the age of 10 and 59. EBV infection could be a relevant factor for developing PTLD.
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http://dx.doi.org/10.2147/RRU.S289853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914070PMC
February 2021

Skin-resident innate lymphoid cells converge on a pathogenic effector state.

Nature 2021 Apr 3;592(7852):128-132. Epub 2021 Feb 3.

Department of Medicine, Sandler Asthma Research Center, University of California San Francisco, San Francisco, CA, USA.

Tissue-resident innate lymphoid cells (ILCs) help sustain barrier function and respond to local signals. ILCs are traditionally classified as ILC1, ILC2 or ILC3 on the basis of their expression of specific transcription factors and cytokines. In the skin, disease-specific production of ILC3-associated cytokines interleukin (IL)-17 and IL-22 in response to IL-23 signalling contributes to dermal inflammation in psoriasis. However, it is not known whether this response is initiated by pre-committed ILCs or by cell-state transitions. Here we show that the induction of psoriasis in mice by IL-23 or imiquimod reconfigures a spectrum of skin ILCs, which converge on a pathogenic ILC3-like state. Tissue-resident ILCs were necessary and sufficient, in the absence of circulatory ILCs, to drive pathology. Single-cell RNA-sequencing (scRNA-seq) profiles of skin ILCs along a time course of psoriatic inflammation formed a dense transcriptional continuum-even at steady state-reflecting fluid ILC states, including a naive or quiescent-like state and an ILC2 effector state. Upon disease induction, the continuum shifted rapidly to span a mixed, ILC3-like subset also expressing cytokines characteristic of ILC2s, which we inferred as arising through multiple trajectories. We confirmed the transition potential of quiescent-like and ILC2 states using in vitro experiments, single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) and in vivo fate mapping. Our results highlight the range and flexibility of skin ILC responses, suggesting that immune activities primed in healthy tissues dynamically adapt to provocations and, left unchecked, drive pathological remodelling.
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http://dx.doi.org/10.1038/s41586-021-03188-wDOI Listing
April 2021

Effectiveness of convective water vapor energy therapy versus prostatic urethral lift for symptomatic benign prostatic hyperplasia: a systematic review and indirect comparison.

World J Urol 2021 Jan 30. Epub 2021 Jan 30.

Department of Urology, Houston Methodist Hospital, Houston, TX, 77030, USA.

Purpose: To synthesize the evidence from randomized controlled trials of prostatic urethral lift (PUL) and convective water vapor thermal energy therapy (WAVE) for minimally invasive treatment of men with benign prostatic hyperplasia.

Methods: A systematic search of databases was performed to identify trials comparing WAVE or PUL to either an active or sham surgery control in subjects with symptomatic benign prostatic obstruction. A controlled indirect treatment comparison based on the approach of Bucher was performed for outcomes including International Prostate Symptom Score and maximum urinary flow rate (Qmax). The durability of treatment response was assessed by life-table analysis of freedom from retreatment through 4 years.

Results: Two multicenter sham-controlled trials (Rezum II Study, NCT01912339: LIFT Study, NCT01294150) were identified. The trials employed a common sham procedure and were similar with respect to their designs and subjects' baseline characteristics. Comparisons on the treatment effect in excess of sham response found non-significant differences between WAVE and PUL for symptom score [mean difference (MD): - 1.7 points; 95% confidence interval (CI): - 4.8, 1.4] but Qmax improvements favored WAVE [MD: 3.4 ml/sec; CI: 1.2, 5.6]. The proportion free of retreatment through 4 years was 89.1% for WAVE versus 75.4% for PUL [log-rank P = 0.004].

Conclusions: PUL and WAVE provide similar subjective improvements but flow-rate improvement and durability of response seem greater for WAVE. The confirmation of these findings in a randomized trial is warranted.
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http://dx.doi.org/10.1007/s00345-021-03595-8DOI Listing
January 2021

Tumor interferon signaling and suppressive myeloid cells are associated with CAR T-cell failure in large B-cell lymphoma.

Blood 2021 May;137(19):2621-2633

Department of Blood and Marrow Transplant and Cellular Immunotherapy.

Axicabtagene ciloleucel (axi-cel) is a chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory large B-cell lymphoma (LBCL). This study evaluated whether immune dysregulation, present before CAR T-cell therapy, was associated with treatment failure. Tumor expression of interferon (IFN) signaling, high blood levels of monocytic myeloid-derived suppressor cells (M-MDSCs), and high blood interleukin-6 and ferritin levels were each associated with a lack of durable response. Similar to other cancers, we found that in LBCL tumors, IFN signaling is associated with the expression of multiple checkpoint ligands, including programmed cell death-ligand 1, and these were higher in patients who lacked durable responses to CAR-T therapy. Moreover, tumor IFN signaling and blood M-MDSCs associated with decreased axi-cel expansion. Finally, patients with high tumor burden had higher immune dysregulation with increased serum inflammatory markers and tumor IFN signaling. These data support that immune dysregulation in LBCL promotes axi-cel resistance via multiple mechanistic programs: insufficient axi-cel expansion associated with both circulating M-MDSC and tumor IFN signaling, which also gives rise to expression of immune checkpoint ligands.
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http://dx.doi.org/10.1182/blood.2020007445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120145PMC
May 2021

Expanded Tumor-infiltrating Lymphocytes From Soft Tissue Sarcoma Have Tumor-specific Function.

J Immunother 2021 Feb-Mar 01;44(2):63-70

Immunology.

Adoptive cell transfer (ACT) with tumor-infiltrating lymphocytes (TILs) can generate durable clinical responses in patients with metastatic melanoma and ongoing trials are evaluating efficacy in other advanced solid tumors. The aim of this study was to develop methods for the expansion of tumor-reactive TIL from resected soft tissue sarcoma to a degree required for the ACT. From 2015 to 2018, 70 patients were consented to an institutional review board-approved protocol, and fresh surgical specimens were taken directly from the operating room to the laboratory. Fragments of the tumor (1 mm3) or fresh tumor digest were placed in culture for a period of 4 weeks. Successfully propagated TIL from these cultures were collected and analyzed by flow cytometry. TIL were cocultured with autologous tumor and function was assessed by measurement of interferon-γ in the supernatant by enzyme-linked immunosorbent assay. Initial TIL cultures were further expanded using a rapid expansion protocol. Nearly all specimens generated an initial TIL culture (91% fragment method, 100% digest method). The phenotype of the TIL indicated a predominant CD3+ population after culture (43% fragment, 52% digest) and TIL were responsive to the autologous tumor (56% fragment, 40% digest). The cultured TIL expanded to a degree required for clinical use following rapid expansion protocol (median: 490-fold fragment, 403-fold digest). The data demonstrate the feasibility of TIL culture from fresh soft tissue sarcoma. The derived TIL have tumor-specific reactivity and can be expanded to clinically relevant numbers. An active ACT clinical trial using the methods described in this report is now approved for patients with metastatic soft tissue sarcoma.
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http://dx.doi.org/10.1097/CJI.0000000000000355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111686PMC
August 2019

Postoperative Morbidity After Resection of Recurrent Retroperitoneal Sarcoma: A Report from the Transatlantic Australasian RPS Working Group (TARPSWG).

Ann Surg Oncol 2021 May 2;28(5):2705-2714. Epub 2021 Jan 2.

Department of Surgery, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.

Background: This study aimed to evaluate perioperative morbidity after surgery for first locally recurrent (LR1) retroperitoneal sarcoma (RPS). Data concerning the safety of resecting recurrent RPS are lacking.

Methods: Data were collected on all patients undergoing resection of RPS-LR1 at 22 Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG) centers from 2002 to 2011. Uni- and multivariable logistic models were fitted to study the association between major (Clavien-Dindo grade ≥ 3) complications and patient/surgery characteristics as well as outcome. The resected organ score, a method of standardizing the number of organs resected, as previously described by the TARPSWG, was used.

Results: The 681 patients in this study had a median age of 59 years, and 51.8% were female. The most common histologic subtype was de-differentiated liposarcoma (43%), the median resected organ score was 1, and 83.3% of the patients achieved an R0 or R1 resection. Major complications occurred for 16% of the patients, and the 90-day mortality rate was 0.4%. In the multivariable analysis, a transfusion requirement was found to be a significant predictor of major complications (p < 0.001) and worse overall survival (OS) (p = 0.010). However, having a major complication was not associated with a worse OS or a higher incidence of local recurrence or distant metastasis.

Conclusions: A surgical approach to recurrent RPS is relatively safe and comparable with primary RPS in terms of complications and postoperative mortality when performed at specialized sarcoma centers. Because alternative effective therapies still are lacking, when indicated, resection of a recurrent RPS is a reasonable option. Every effort should be made to minimize the need for blood transfusions.
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http://dx.doi.org/10.1245/s10434-020-09445-yDOI Listing
May 2021

Variants in an Iberian Alzheimer Cohort Detected through an Optimized Sanger Sequencing Protocol.

Genes (Basel) 2020 Dec 22;12(1). Epub 2020 Dec 22.

IPATIMUP-Institute of Molecular Pathology and Immunology of the University of Porto, 4200-135 Porto, Portugal.

The primary genetic risk factor for late onset Alzheimer's disease (LOAD) is the allele of () gene. The three most common variants of are determined by single nucleotide polymorphisms (SNPs) rs429358 and rs7412. Our aim was to estimate allele and genotype frequencies of variants in an Iberian cohort, thus helping to understand differences in -related LOAD risk observed across populations. We analyzed saliva or buccal swab samples from 229 LOAD patients and 89 healthy elderly controls (≥68 years old) from Northern Portugal and Castile and León region, Spain. The genotyping was performed by Sanger sequencing, optimized to overcome GC content drawbacks. Results obtained in our Iberian LOAD and control cohorts are in line with previous large meta-analyses on frequencies in Caucasian populations; however, we found differences in allele frequencies between our Portuguese and Spanish subgroups of AD patients. Moreover, when comparing studies from Iberian and other Caucasian cohorts, differences in and frequencies and subsequent different -related LOAD risks must be clarified. These results show the importance of studying genetic variation at the gene in different populations (including analyses at a regional level) to increase our knowledge about its clinical significance.
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http://dx.doi.org/10.3390/genes12010004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822120PMC
December 2020

The iTind Temporarily Implanted Nitinol Device for the Treatment of Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia: A Multicenter, Randomized, Controlled Trial.

Urology 2020 Dec 26. Epub 2020 Dec 26.

Manhattan Medical Research, Manhattan, NY.

Objective: To report the results of a multicenter, randomized, controlled trial with a temporarily implanted nitinol device (iTind; Medi-Tate Ltd, Hadera, Israel) compared to sham for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia.

Materials And Methods: Men 50 years or older were randomized 2:1 between iTind and sham procedure arms. A self-expanding, temporary nitinol device was placed for 5-7 days and an 18F Foley catheter was inserted and removed for the iTind and sham group, respectively. Patients were assessed at baseline, 1.5, 3, and 12 months postoperatively using the IPSS, peak urinary flow rate, residual urine, quality of life, and the International Index of Erectile Function. Unblinding occurred at 3 months.

Results: A total of 175 men (mean age 61.1 ± 6.5) participated (118 iTind vs 57 sham). A total of 78.6% of patients in the iTind arm showed a reduction of ≥3 points in IPSS, vs 60% of patients in the control arm at 3 months. At 12 months, the iTind group reported a 9.25 decrease in IPSS (P< .0001), a 3.52ml/s increase in peak urinary flow rate (P < .0001) and a 1.9-point reduction in quality of life (P < .0001). Adverse events were typically mild and transient, most Clavien-Dindo grade I or II, in 38.1% of patients in the iTind arm and 17.5% in the control arm. No de novo ejaculatory or erectile dysfunction occurred.

Conclusion: Treatment with the second-generation iTind provided rapid and sustained improvement in lower urinary tract symptoms for the study period while preserving sexual function.
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http://dx.doi.org/10.1016/j.urology.2020.12.022DOI Listing
December 2020

NCCN Guidelines Insights: Soft Tissue Sarcoma, Version 1.2021.

J Natl Compr Canc Netw 2020 12 2;18(12):1604-1612. Epub 2020 Dec 2.

28UCSF Helen Diller Family Comprehensive Cancer Center; and.

The NCCN Guidelines for Soft Tissue Sarcoma provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with soft tissue sarcomas. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines, including the development of a separate and distinct guideline for gastrointestinal stromal tumors (GISTs); reconception of the management of desmoid tumors; inclusion of further recommendations for the diagnosis and management of extremity/body wall, head/neck sarcomas, and retroperitoneal sarcomas; modification and addition of systemic therapy regimens for sarcoma subtypes; and revision of the principles of radiation therapy for soft tissue sarcomas.
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http://dx.doi.org/10.6004/jnccn.2020.0058DOI Listing
December 2020

Editorial Comment.

J Urol 2021 02 1;205(2):537-538. Epub 2020 Dec 1.

Department of Urology, Texas A&M College of Medicine, Houston, Texas.

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http://dx.doi.org/10.1097/JU.0000000000001390.01DOI Listing
February 2021

Single-Cell Profiling Reveals Divergent, Globally Patterned Immune Responses in Murine Skin Inflammation.

iScience 2020 Oct 19;23(10):101582. Epub 2020 Sep 19.

Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA.

Inflammatory response heterogeneity has impeded high-resolution dissection of diverse immune cell populations during activation. We characterize mouse cutaneous immune cells by single-cell RNA sequencing, after inducing inflammation using imiquimod and oxazolone dermatitis models. We identify 13 CD45 subpopulations, which broadly represent most functionally characterized immune cell types. Oxazolone pervasively upregulates / expression across T cells and antigen-presenting cells (APCs). Oxazolone also induces / expression in newly infiltrating basophils, and and most prominently in APCs. In contrast, imiquimod broadly upregulates / and /. A comparative analysis of single-cell inflammatory transcriptional responses reveals that APC response to oxazolone is tightly restricted by cell identity, whereas imiquimod enforces shared programs on multiple APC populations in parallel. These global molecular patterns not only contrast immune responses on a systems level but also suggest that the mechanisms of new sources of inflammation can eventually be deduced by comparison to known signatures.
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http://dx.doi.org/10.1016/j.isci.2020.101582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648132PMC
October 2020

Intraoperative Localization Using an Implanted Radar Reflector Facilitates Resection of Non-Palpable Trunk and Extremity Sarcoma.

Ann Surg Oncol 2021 Jun 18;28(6):3366-3374. Epub 2020 Oct 18.

Sarcoma Department, H. Lee Moffitt Cancer Center, 12902 USF Magnolia Drive, Tampa, FL, 33612, USA.

Background: Resecting non-palpable soft tissue tumors presents a unique challenge, particularly with recurrent disease in which surrounding tissue has been surgically manipulated and often irradiated. SAVI SCOUT is a radar-based localization device that was developed for breast tumor localization and was recently FDA-approved for localization of soft tissue tumors. Application of this technology to soft tissue sarcoma has not been previously reported.

Methods: We assembled a single-institution retrospective case series of patients with trunk and extremity sarcomas resected by five sarcoma surgeons using SAVI SCOUT from December 2018 to May 2020. Reflectors were placed preoperatively using image-guidance, and the radar detector was used intraoperatively to localize the target lesion. Clinical variables were abstracted from the electronic medical record including treatment history, pathology, and early oncologic outcomes. Using a focused review, we compared margin status and recurrence rates with previously published cohorts.

Results: Ten SAVI SCOUT-localized sarcoma resections were performed. Eight were for locally recurrent disease, of which seven (83%) had prior radiation. The remaining lesions became non-palpable after neoadjuvant chemotherapy. SAVI SCOUT facilitated resection in all cases with a margin-negative resection rate (77%) comparable to prior cohorts. In this high-risk population with a median follow-up of 14 months, only one patient recurred locally 7.5 months after SAVI SCOUT-localized resection, requiring re-resection.

Conclusion: SAVI SCOUT technology facilitated resection of non-palpable recurrent sarcoma of the trunk and extremities in all ten cases attempted. In a high-risk patient population, the pattern of recurrence has been primarily distant with one instance of local tumor recurrence.
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http://dx.doi.org/10.1245/s10434-020-09229-4DOI Listing
June 2021

Sexual function in adult patients who have undergone augmentation surgery in childhood: what is really important?

Int J Impot Res 2021 Mar 10;33(2):170-177. Epub 2020 Oct 10.

Department of Pediatric Urology, Hospital of the Sisters of Charity, Linz, Austria.

Problems relating to the development of a healthy approach to sex and intimacy during puberty, after augmentation cystoplasty, are scarcely discussed in literature. Therefore, this may suggest that such issues are insufficiently addressed by pediatric urologists. We gathered four experts in the field as well as an experienced leader of a patient group and mother of a girl with spina bifida and asked questions relevant to the following areas of care: (a) diversion, urinary incontinence, and sexual life; (b) impact of a stoma on body image perception and self-esteem; (c) specific female concerns with regard to fertility and recurrent urinary infections; (d) specific male concerns on anejaculation and erectile dysfunction. Their answers are discussed in view of the available literature. All experts and the patient group representative agreed that most of these patients will experience: lack of self-confidence as the most frequent obstacle to starting a relationship and incontinence as a barrier to sexual activity. The cosmesis of the stoma and abdominal scars might influence self-esteem and therefore the sexual activity, however it appears to be a less common concern in males than females. Our results outline the importance and influence that the body image, self-esteem, and confidence present for the individual expectations of the patients related to sex life and sexual activity. Physicians should be encouraged to ask all postpubertal patients about their sexual concerns at every visit. Further studies and exchange of information between clinicians are needed to provide meaningful and analyzable patient-related outcome measures (PROMs).
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http://dx.doi.org/10.1038/s41443-020-00355-xDOI Listing
March 2021

Update: The Clinical Role of Vaginal Lasers for the Treatment of the Genitourinary Syndrome of Menopause.

Urology 2021 May 20;151:2-7. Epub 2020 Sep 20.

Houston Methodist Hospital, Department of Urology, Houston, TX. Electronic address:

Objective: To educate providers on the emergence of vaginal lasers for the treatment of the genitourinary syndrome of menopause (GSM) and discuss the peer-reviewed literature regarding their use.

Materials And Methods: A search of literature databases (PubMed and Medline) was performed for publications in February 2020. Keywords included genitourinary syndrome of menopause, urinary incontinence, overactive bladder, urgency, urinary tract infections, atrophy, laser, and vaginal. We reviewed the available published literature, identifying articles, guidance, and society statements on the use vaginal laser therapies.

Results: The literature regarding vaginal laser therapy in the treatment of the GSM is primarily limited to prospective case series with small numbers and short-term follow-up. Nevertheless, these studies have demonstrated reductions in genitourinary syndrome of menopause symptoms. High quality data describing the safety, benefits, and appropriate use of vaginal laser therapy is lacking.

Conclusion: Vaginal laser treatment for the GSM is of interest as it provides patients with a nonhormonal treatment option. Further research to better outline the indications, efficacy, safety, and applications of this technology is needed before supporting its universal use for the management of the GSM.
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http://dx.doi.org/10.1016/j.urology.2020.09.012DOI Listing
May 2021

Multisystem inflammatory syndrome in children (MIS-C): Report of the clinical and epidemiological characteristics of cases in Santiago de Chile during the SARS-CoV-2 pandemic.

Int J Infect Dis 2020 Nov 28;100:75-81. Epub 2020 Aug 28.

Department of Pediatrics, Hospital Roberto del Río, Faculty of Medicine, Universidad de Chile, Profesor Zañartu 1085, Independencia, Santiago, Chile; Virology Program, ICBM, Faculty of Medicine, Universidad de Chile, Independencia 1027 Pabellón J, Independencia, Santiago, Chile. Electronic address:

Objective: To describe the clinical and epidemiological characteristics of hospitalized children with multisystem inflammatory syndrome in children (MIS-C) in Santiago, Chile.

Methods: This was an observational study of children with MIS-C (May 1 to June 24, 2020), in three pediatric hospitals in Santiago. Demographic characteristics and epidemiological data, medical history, laboratory tests, cardiology evaluations, treatment, and clinical outcomes were analyzed.

Results: Twenty-seven patients were admitted (median age 6, range 0-14 years). Sixteen of the 27 (59%) required intensive care unit admission; there were no deaths. Seventy-four percent had no comorbidities, and the median number of days of symptoms before admission was 4 (range 2-9 days). Gastrointestinal symptoms were the most frequent, and inflammatory markers were increased at admission. A recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was detected in 82% of cases. The severe group showed significantly lower hemoglobin and albumin levels, decreased platelet counts, and higher d-dimer during disease evolution. Echocardiography showed abnormalities (myocardial, pericardial, or coronary) in 12 patients (46%) during their hospital stay. Anti-inflammatory treatment (immunoglobulin and/or corticosteroids) was prescribed in 24 patients. MIS-C appeared in clusters weeks after the peak of SARS-CoV-2 cases, especially in the most vulnerable areas of Santiago.

Conclusions: This study describes the first series (n = 27) of children with MIS-C in a Latin American country, showing favorable clinical outcomes. Education and alerts are required for clinical teams to establish an early diagnosis and prompt treatment.
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http://dx.doi.org/10.1016/j.ijid.2020.08.062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7452906PMC
November 2020

Patterns of recurrence and survival probability after second recurrence of retroperitoneal sarcoma: A study from TARPSWG.

Cancer 2020 11 14;126(22):4917-4925. Epub 2020 Aug 14.

Division of General Surgery, Mount Sinai Hospital, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada.

Background: In this series from the Transatlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG), the authors examined longitudinal outcomes of patients with a second recurrence of retroperitoneal sarcoma (RPS) after complete resection of a first local recurrence (LR).

Methods: Data from patients undergoing resection of a first LR from January 2002 to December 2011were collected from 22 sarcoma centers. The primary outcome was overall survival (OS) after second recurrence.

Results: Second recurrences occurred in 400 of 567 patients (70.5%) after an R0/R1 resection of a first locally recurrent RPS. Patterns of disease recurrence were LR in 323 patients (80.75%), distant metastases (DM) in 55 patients (13.75%), and both LR and DM in 22 patients (5.5%). The main subtype among the LR group was liposarcoma (77%), whereas DM mainly were leiomyosarcomas (43.6%). In patients with a second LR only, a total of 200 patients underwent re-resection (61.9%). The 5-year OS rate varied significantly based on the pattern of failure (P < .001): 45.6% for the LR group, 25.5% for the DM group, and 0% for the group with LR and DM. The only factors found to be associated with improved OS on multivariable analysis were both time between second surgery and the development of the second recurrence (32 months vs 8 months: hazard ratio, 0.44 [P < .001]) and surgery for second recurrence (yes vs no: hazard ratio, 3.25 [P < .001]). The 5-year OS rate for patients undergoing surgery for a second LR was 59% versus 18% in the patients not deemed suitable for surgical resection.

Conclusions: Survival rates after second recurrence of RPS varied based on patterns of disease recurrence and treatment. Durable disease-free survivors were identified after surgery for second LR in patients selected for this intervention.
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http://dx.doi.org/10.1002/cncr.33139DOI Listing
November 2020

Water vapor thermal therapy for lower urinary tract symptoms secondary to benign prostatic hyperplasia: Systematic review and meta-analysis.

Medicine (Baltimore) 2020 Jul;99(30):e21365

Boston Scientific, Marlborough, MA.

Background: Water vapor thermal therapy (WVTT) is a minimally invasive procedure for treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH). There are no known systematic reviews reporting the effectiveness and safety of this increasingly common BPH therapy.

Methods: We performed a systematic review and meta-analysis of studies utilizing WVTT for symptomatic BPH. The international prostate symptom score (IPSS), IPSS-quality of life (IPSS-QOL), BPH impact index (BPHII), and maximum flow rate (Qmax) were calculated as the weighted mean difference relative to baseline and reported in minimal clinically important difference (MCID) units. MCID thresholds were -3 for IPSS, -0.5 for IPSS-QOL, -0.5 for BPHII, and 2 mL/s for Qmax. The surgical retreatment rate was calculated using life-table methods.

Results: We identified 5 cohorts treated with WVTT from 4 studies (514 patients; 40% with median lobe obstruction) with 2 years median follow-up (range: 6 months to 4 years). The IPSS, IPSS-QOL, BPHII, and Qmax significantly improved at all intervals between 3 months and 4 years; this benefit ranged from 3.3 to 3.8 MCID units for IPSS, 3.9 to 4.6 MCID units for IPSS-QOL, 6.8 to 8.2 MCID units for BPHII, and 1.5 to 3.0 MCID units for Qmax. The surgical retreatment rate was 7.0% at 4 years of follow-up data. Most adverse events were nonserious and transient; dysuria, urinary retention, and urinary tract infection were most common. No cases of de novo erectile dysfunction occurred.

Conclusions: WVTT provided improvement in BPH symptoms that exceeded established MCID thresholds, preserved sexual function, and was associated with low surgical retreatment rates over 4 years.
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http://dx.doi.org/10.1097/MD.0000000000021365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387023PMC
July 2020

Chemotherapy improves distant control in localized high-grade soft tissue sarcoma of the extremity/trunk.

Clin Sarcoma Res 2020 9;10:11. Epub 2020 Jul 9.

Department of Sarcoma, Moffitt Cancer Center and Research Institute, Tampa, FL USA.

Background: Soft tissue sarcomas (STS) are rare and heterogeneous tumors making chemotherapy use controversial. Our goal was to identify a subset of patients with primary STS that benefit with the addition of chemotherapy.

Methods: A retrospective chart review included intermediate to high-grade localized primary STS of the extremity/trunk, and tumor size > 5 cm. The effect of chemotherapy was evaluated for local control (LC), distant control (DC), progression free survival (PFS), and overall survival (OS).

Results: In this cohort (n = 273), patients were treated with surgery (98%), radiation (81%), and chemotherapy (24.5%). With a median follow-up of 51 months, the entire cohort's 5-year LC, DC, PFS, and OS are 79.1%, 59.9%, 43.8%, and 68.7%, respectively. The addition of chemotherapy did not provide a DC benefit (p = 0.238) for the entire cohort. High-grade disease (n = 210) experienced a 5-year benefit in DC (68% vs. 54.4%, p = 0.04), which was more pronounced with MAI (Mesna, Adriamycin, Ifosfamide) based regimens (74.2%, p = 0.016), and a 5-year PFS (50.8% vs 45%, p = 0.025) and OS benefit (76.2% vs 70%, p = 0.067) vs. no chemotherapy. On multivariate analysis of the high-grade subset, chemotherapy independently predicted for a DC benefit (HR 0.48 95% CI 0.26-89, p = 0.019). The benefit of chemotherapy was more pronounced with MAI, showing a significant benefit in DC (HR 0.333 95% CI 0.145-0.767, p = 0.01) and PFS (HR 0.52 95% CI 0.28-0.99, p = 0.047).

Conclusion: In patients with localized STS > 5 cm, the high-grade subset had a distant control benefit with the addition of chemotherapy, leading to improved progression free survival. This is more pronounced with the use of MAI and should be considered in patients eligible for this regimen.
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http://dx.doi.org/10.1186/s13569-020-00132-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7350709PMC
July 2020

Tumor Microenvironment Composition and Severe Cytokine Release Syndrome (CRS) Influence Toxicity in Patients with Large B-Cell Lymphoma Treated with Axicabtagene Ciloleucel.

Clin Cancer Res 2020 09 15;26(18):4823-4831. Epub 2020 Jul 15.

Department of Blood and Marrow Transplantation and Cellular Immunotherapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.

Purpose: One of the challenges of adoptive T-cell therapy is the development of immune-mediated toxicities including cytokine release syndrome (CRS) and neurotoxicity (NT). We aimed to identify factors that place patients at high risk of severe toxicity or treatment-related death in a cohort of 75 patients with large B-cell lymphoma treated with a standard of care CD19 targeted CAR T-cell product (axicabtagene ciloleucel).

Experimental Design: Serum cytokine and catecholamine levels were measured prior to lymphodepleting chemotherapy, on the day of CAR T infusion and daily thereafter while patients remained hospitalized. Tumor biopsies were taken within 1 month prior to CAR T infusion for evaluation of gene expression.

Results: We identified an association between pretreatment levels of IL6 and life-threatening CRS and NT. Because the risk of toxicity was related to pretreatment factors, we hypothesized that the tumor microenvironment (TME) may influence CAR T-cell toxicity. In pretreatment patient tumor biopsies, gene expression of myeloid markers was associated with higher toxicity.

Conclusions: These results suggest that a proinflammatory state and an unfavorable TME preemptively put patients at risk for toxicity after CAR T-cell therapy. Tailoring toxicity management strategies to patient risk may reduce morbidity and mortality.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-1434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501265PMC
September 2020

The Clinical Significance of High Antimicrobial Resistance in Community-Acquired Urinary Tract Infections.

Can J Infect Dis Med Microbiol 2020 4;2020:2967260. Epub 2020 Jun 4.

Microbiology Department, Unidad de Patología Clínica, Guadalajara, Jal, Mexico.

Background: Urinary tract infections (UTIs) affect up to 150 million individuals annually worldwide, mainly due to () and . The emergence and spread of multidrug-resistant (MDR) bacteria are increasing, representing one of the biggest threats for human health. The objective of our study was to describe antimicrobial patterns of resistance and identify risk factors associated with MDR uropathogens.

Methods: We conducted a cross-sectional study in 296 patients with community-acquired UTI who underwent clinical and microbiologic analysis, and clinical associations to MDR uropathogens were investigated. . Microbiological analysis included (55%), ESBL- (26%), (6%), (5%), and others (8%). Higher frequencies of MDR bacteria were found among ESBL-, with resistance to ampicillin (100%), ceftriaxone (96%), gentamicin (57%), ciprofloxacin (89%), and TMP/SMX (53%). However, they were sensitive to fosfomycin (6.6%), nitrofurantoin (1.3%), and carbapenems (0%). Fosfomycin MIC90 for ESBL- was 5.78 g/mL. The only clinical variable with significant association to ESBL producers was the presence of comorbidities: hypertension and type 2 diabetes mellitus with an OR (95%CI) of 2.5(1.3 - 4.9)( < 0.01) and 2.8(1.2 - 6.7)( < 0.05), respectively.

Conclusions: In the majority of cases, resistance rates to commonly prescribed antimicrobials in UTIs were high, except for fosfomycin, nitrofurantoin, and carbapenems. To provide appropriate treatment, both the identification of risk factors and the uropathogen would be important. An active surveillance in UTIs in the community is required since the proportion of ESBL producers is increasing.
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http://dx.doi.org/10.1155/2020/2967260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293720PMC
June 2020

Arthroscopic Matrix-Encapsulated Autologous Chondrocyte Implantation: A Pilot Multicenter Investigation in Latin America.

Cartilage 2020 May 14:1947603520918630. Epub 2020 May 14.

Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Mexico City, DF, Mexico.

. To evaluate minimum biosecurity parameters (MBP) for arthroscopic matrix-encapsulated autologous chondrocyte implantation (AMECI) based on patients' clinical outcomes, magnetic resonance imaging (MRI) T2-mapping, Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score, and International Cartilage Repair Society (ICRS) second-look arthroscopic evaluation, laying the basis for a future multicenter study. . Pilot clinical study. We analyzed the logistics to perform AMECI to treat focal chondral lesions in different hospitals following strict biosecurity parameters related to tissue and construct transportation, chondrocyte isolation, and cell expansion. Patient progress was analyzed with patient-reported outcome measures, MRI T2-mapping, MOCART, and ICRS arthroscopic second-look evaluation. . Thirty-five lesions in 30 patients treated in 7 different hospitals were evaluated. Cell viability before implantation was >90%. Cell viability in construct remnants was 87% ± 11% at 24 hours, 75% ± 17.1% at 48 hours, and 60% ± 8% at 72 hours after implantation. Mean final follow-up was 37 months (12-72 months). Patients showed statistically significant improvement in all clinical scores and MOCART evaluations. MRI T2-mapping evaluation showed significant decrease in relaxation time from 61.2 ± 14.3 to 42.9 ± 7.2 ms ( < 0.05). Arthroscopic second-look evaluation showed grade II "near normal" tissue in 83% of patients. Two treatment failures were documented. . It was feasible to perform AMECI in 7 different institutions in a large metropolitan area following our biosecurity measures without any implant-related complication. Treated patients showed improvement in clinical, MRI T2-mapping, and MOCART scores, as well as a low failure rate and a favorable ICRS arthroscopic evaluation at a mid-term follow-up. . 2b.
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http://dx.doi.org/10.1177/1947603520918630DOI Listing
May 2020

The First Use of a ReX Synthon to Modulate Fe Spin Crossover via Supramolecular Halogen⋅⋅⋅Halogen Interactions.

Chemistry 2020 Sep 13;26(51):11835-11840. Epub 2020 Aug 13.

Institute of Inorganic Chemistry, Karlsruhe Institute of Technology, Engesserstrasse 15, 76131, Karlsruhe, Germany.

We have added the {Re X } (X=Br, Cl) synthon to a pocket-based ligand to provide supramolecular design using halogen⋅⋅⋅halogen interactions within an Fe system that has the potential to undergo spin crossover (SCO). By removing the solvent from the crystal lattice, we "switch on" halogen⋅⋅⋅halogen interactions between neighboring molecules, providing a supramolecular cooperative pathway for SCO. Furthermore, changes to the halogen-based interaction allow us to modify the temperature and nature of the SCO event.
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http://dx.doi.org/10.1002/chem.202001668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540276PMC
September 2020

Methodological Considerations for Using Fecal Glucocorticoid Metabolite Concentrations as an Indicator of Physiological Stress in the Brown Bear ().

Physiol Biochem Zool 2020 May/Jun;93(3):227-234

Reliable methods to measure stress-related glucocorticoid responses in free-ranging animals are important for wildlife management and conservation. Such methods are also paramount for our ability to improve our knowledge of the ecological consequences of physiological processes. The brown bear () is a large carnivore of ecological and cultural importance and is important for management. Here, we provide a physiological validation for an enzyme immunoassay (EIA) to quantify glucocorticoid metabolites in brown bear feces. We also provide an evaluation of the effects of sample exposure to ambient temperature on measured fecal glucocorticoid metabolite (fGCM) concentrations. We evaluated three EIA systems: a cortisol assay, an 11-oxoetiocholanolone assay, and an 11β-hydroxyetiocholanolone assay. Of these, the cortisol assay provided the best discrimination between peak fGCM concentrations detected 1-4 d after injections of synthetic adrenocorticotrophic hormone and preinjection baseline concentrations in four individual brown bears. The time of exposure to ambient temperature had substantial but variable effects on measured fGCM concentrations, including variation both between samples from the same individual and among samples from different bears. We propose that the validated EIA system for measuring fGCM concentrations in the brown bear could be a useful noninvasive method to monitor stress in this species. However, we highlight that this method requires that fecal samples be frozen immediately after defecation, which could be a limitation in many field situations.
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http://dx.doi.org/10.1086/708630DOI Listing
December 2020

Prospective study of a single-incision sling versus a transobturator sling in women with stress urinary incontinence: 3-year results.

Am J Obstet Gynecol 2020 10 14;223(4):545.e1-545.e11. Epub 2020 Mar 14.

Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX.

Background: Long-term safety and efficacy data on use of single-incision slings in stress urinary incontinence are limited.

Objective: To determine whether the single-incision sling Solyx (Boston Scientific, Marlborough, MA) is noninferior to the transobturator sling Obtryx II (Boston Scientific) in efficacy and safety for treatment of stress urinary incontinence. This 522 post-market surveillance study has been designed in response to a Food and Drug Administration request to evaluate improvement in stress urinary incontinence at 36 months following single-incision sling compared with baseline, as well as provide an assessment of mesh-related complications and subject-reported outcomes, relative to the transobturator sling control.

Study Design: This prospective, nonrandomized, parallel cohort, multicenter postapproval study enrolled subjects to receive single-incision sling or transobturator sling. Study sites were assigned to a cohort group based on documented competency with the cohort device. Patient follow-up was 36 months to compare efficacy and adverse events for noninferiority. Inclusion criteria included stress predominant urinary incontinence, a positive cough stress test, and post-void residual ≤150 cc. Participants were ineligible if they had undergone previous stress urinary incontinence surgery or had a previous mesh complication. Primary endpoint was treatment success defined by composite negative cough stress test and subjective improvement in stress urinary incontinence using Patient Global Impression of Improvement at 36 months. Secondary endpoints included adverse events and indications for retreatment. Noninferiority margins of 15% and 10% were prespecified for the primary efficacy and safety endpoints. Data analysis was performed using intent-to-treat and per-protocol methods. Due to the observational nature of the study, a propensity score methodology was applied to account for differences in patient and surgeon characteristics between treatment groups. The study design and variables to be included in the propensity score model were reviewed and approved by Food and Drug Administration reviewers before outcome analyses were performed.

Results: No evidence of imbalance in baseline characteristics was observed between groups after propensity score stratification in the 281 subjects. EBL (72.3±92 vs 73.1±63.9 mL, P=.786), time to spontaneous void (1.1±2 vs 0.8±2.8 days, P=.998), and time to discharge (0.7±0.7 vs 0.6±0.6 days, P=.524) were similar between groups. At 36 months, treatment success was 90.4% in the single-incision sling group and 88.9% in the transobturator sling group (P=.93). At 36 months, mesh-related complications were similar between groups (mesh exposure: 2.8% vs 5.0%, P=.38). Serious adverse events including pain during intercourse (0.7% vs 0%, P=1.00), pelvic pain (0.7% vs 0%, P=1.00), and urinary retention (2.8% vs 4.3%, P=.54) were similar between groups.

Conclusion: Single-incision sling was not inferior to transobturator sling for long-term treatment success of stress urinary incontinence. The rates of serious adverse events were acceptably low and similar between groups.
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http://dx.doi.org/10.1016/j.ajog.2020.03.008DOI Listing
October 2020

Tissue-specific pathways extrude activated ILC2s to disseminate type 2 immunity.

J Exp Med 2020 04;217(4)

Department of Medicine, University of California, San Francisco, San Francisco, CA.

Group 2 innate lymphoid cells (ILC2s) are tissue-resident cells prominent at barrier sites. Although precursors are found in blood, mature ILC2s can enter the circulation after small intestinal perturbation by migratory helminths and move to distant tissues to influence the local reparative response. Using fate-mapping and methods to bypass the lung or intestinal phases of Nippostrongylus brasiliensis infection, we show that blood ILC2s comprise heterogeneous populations derived from distinct tissues that are dependent on alarmins matched to the receptor profile of the specific tissue ILC2s. Activation of local ILC2s by tissue-specific alarmins induced their proliferation, lymph node migration, and blood dissemination, thus systemically distributing type 2 cytokines. These studies uncover a possible mechanism by which local innate responses transition to systemic type 2 responses by extrusion of activated sentinel ILC2s from tissue into the circulation.
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http://dx.doi.org/10.1084/jem.20191172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144525PMC
April 2020