Objective: Our study aimed to compare the posterior interposition technique against the posterolateral transosseous technique in the same cadaver specimens. Methods: Computer and cadaver models of 2 fixation techniques were developed. The computer model was constructed to analyze bone volume removed during implant placement and the bony surface area available for fusion. The cadaver model included quasi-static multidirectional bending flexibility and dynamic fatigue loading. Relative motions between the sacrum and ilium were measured intact, after joint destabilization, after fixation with direct-posterior and posterolateral techniques, and after 18,500 cycles of fatigue loading. Relative positions between each implant and the sacrum and ilium were measured after fixation and fatigue loading to ascertain the quality of the bone-implant interface. The 2 techniques were randomized to the left and right sacroiliac joints of the same cadavers. Results: The posterior interposition technique removed less bone volume and facilitated a larger surface area available for bony fusion. Posterior interposition significantly reduced the nutation/counternutation motion of the sacroiliac joint (42% ± 8%) and reduced it more than the posterolateral transosseous technique (14% ± 4%). Upon fatigue loading, the posterior interposition implant maintained the bone-implant interface across all specimens, while the posterolateral transosseous implant migrated or subsided in 20%–50% of specimens. Conclusion Posterior interposition fixation of the sacroiliac joint reduces joint motion. The amount of fixation from the posterior technique is superior and more durable than the amount of fixation achieved by the posterolateral technique.

Purpose: Pott’s puffy tumor (PPT), characterized by frontal bone osteomyelitis and subperiosteal abscess, typically arises as a complication of head trauma or frontal sinusitis and is associated with diverse triggers. Since 2001, PPT, previously considered rare in the pediatric population, has been increasingly reported, underscoring heightened recognition. By outlining specific protocols and guidelines, a clinical pathway (CP) facilitates rapid identification and treatment of PPT. Methods: We reviewed 11 cases of PPT in patients aged 0 to 18 years who were either hospitalized or discharged from 2 large hospitals in South Florida, United States, from January 31, 2016 through February 1, 2019. This multicenter retrospective case review was complemented by a comprehensive literature review. Additionally, the study team proposed a diagnostic CP tailored for the emergency department setting. Variables of interest included demographic data, clinical presentation, imaging studies, medical and surgical management details, laboratory/microbiological data, and clinical outcomes. Results: A total of 11 patients with PPT were identified, of whom 8 and 7 were boys and African Americans, respectively. The common symptoms were fever, headache, and frontal edema. All patients underwent antibiotic therapy for 6-8 weeks, as well as both computed tomography and magnetic resonance imaging. The imaging studies showed intracranial complications in the 10 patients such as epidural abscess, which were caused by Streptococcus pneumoniae, Streptococcus intermedius, Streptococcus pyogenes, Eikenella spp., and methicillin-sensitive Staphylococcus aureus. The 10 patients underwent endoscopic sinus surgeries, with 6 of them also doing craniotomies. No mortality or sequelae was reported. Conclusion This study contributes to the growing body of literature on PPT, shedding light on its evolving epidemiology, clinical manifestations, and management strategies while emphasizing the pivotal role of emergency physicians for optimal outcomes. The proposed CP aims to establish a standard of care that can be adopted across various pediatric emergency departments.

Purpose: In this systematic review and meta-analysis, we investigated assisted reproductive technology (ART) success in infertile men with clinical varicocele and abnormal semen parameters who underwent varicocele repair (VR) before the ART procedure as compared to those who did not. Materials and Methods: A comprehensive search of the Scopus, PubMed, Embase, and Cochrane Library databases was conducted using a specific query string to identify studies examining the impact of VR on ART outcomes, including fertilization rate, clinical pregnancy, pregnancy loss, and live-birth rate, until October 2023. Outcomes were analyzed based on the type of ART. Studies on VR in infertile men with non-obstructive azoospermia and those who underwent ART only due to female factor infertility were excluded from the study. Results: Out of 1,554 articles reviewed, only 9 met the inclusion criteria for the study. All the included articles were observational studies. The variability in study quality in the included literature resulted in a moderate overall risk of bias. Data analysis showed that for intrauterine insemination, there was no difference in the clinical pregnancy rate (odds ratio [OR] 1.01, 95% confidence interval [CI]: 0.42, 2.45; p=0.97). However, for intracytoplasmic sperm injection (ICSI), men with VR showed a significant improvement in fertilization rate (mean difference 10.9, 95% CI: 5.94, 15.89; p<0.01), clinical pregnancy rate (OR 1.38, 95% CI: 1.07, 1.78; p=0.01) and live-birth rate (OR 2.07, 95% CI: 1.45, 2.97; p<0.01), compared to men who did not undergo VR. Conclusions The findings of this systematic review and meta-analysis suggest that VR has a positive impact on pregnancy and live birth rates after ICSI. However, biases like small sample sizes and heterogeneous populations highlight the need for larger, well-designed prospective studies to validate these findings.

Purpose: Non-obstructive azoospermia (NOA) is a common, but complex problem, with multiple therapeutic options and a lack of clear guidelines. Hence, there is considerable controversy and marked variation in the management of NOA. This survey evaluates contemporary global practices related to medical and surgical management for patients with NOA. Materials and Methods: A 56-question online survey covering various aspects of the evaluation and management of NOA was sent to specialists around the globe. This paper analyzes the results of the second half of the survey dealing with the management of NOA. Results have been compared to current guidelines, and expert recommendations have been provided using a Delphi process. Results: Participants from 49 countries submitted 336 valid responses. Hormonal therapy for 3 to 6 months was suggested before surgical sperm retrieval (SSR) by 29.6% and 23.6% of participants for normogonadotropic hypogonadism and hypergonadotropic hypogonadism respectively. The SSR rate was reported as 50.0% by 26.0% to 50.0% of participants. Interestingly, 46.0% reported successful SSR in <10% of men with Klinefelter syndrome and 41.3% routinely recommended preimplantation genetic testing. Varicocele repair prior to SSR is recommended by 57.7%. Half of the respondents (57.4%) reported using ultrasound to identify the most vascularized areas in the testis for SSR. One-third proceed directly to microdissection testicular sperm extraction (mTESE) in every case of NOA while others use a staged approach. After a failed conventional TESE, 23.8% wait for 3 months, while 33.1% wait for 6 months before proceeding to mTESE. The cut-off of follicle-stimulating hormone for positive SSR was reported to be 12–19 IU/mL by 22.5% of participants and 20–40 IU/mL by 27.8%, while 31.8% reported no upper limit. Conclusions This is the largest survey to date on the real-world medical and surgical management of NOA by reproductive experts. It demonstrates a diverse practice pattern and highlights the need for evidence-based international consensus guidelines.

BACKGROUND: Priming strategies that improve the functionality of MSCs may be required to address issues limiting successful clinical translation of MSC therapies. For conditions requiring high trophic support such as brain and spinal cord injuries, priming MSCs to produce higher levels of trophic factors may be instrumental to facilitate translation of current MSC therapies. We developed and tested a novel molecular priming paradigm using docosahexaenoic acid (DHA) to prime adipose tissue-derived mesenchymal stromal cells (ASCs) to enhance the secretome neuroregulatory potential. METHODS: Comprehensive dose–response and time-course assays were carried to determine an optimal priming protocol. Secretome total protein measurements were taken in association with cell viability, density and morphometric assessments. Cell identity and differentiation capacity were studied by flow cytometry and lineage-specific markers. Cell growth was assessed by trypan-blue exclusion and senescence was probed over time using SA-b-gal, morphometry and gene expression. Secretomes were tested for their ability to support differentiation and neurite outgrowth of human neural progenitor cells (hNPCs). Neuroregulatory proteins in the secretome were identified using multiplex membrane arrays. RESULTS: Priming with 40 lM DHA for 72 h significantly enhanced the biosynthetic capacity of ASCs, producing a secretome with higher protein levels and increased metabolic viability. DHA priming enhanced ASCs adipogenic differentiation and adapted their responses to replicative senescence induction. Furthermore, priming increased concentrations of neurotrophic factors in the secretome promoting neurite outgrowth and modulating the differentiation of hNPCs. CONCLUSIONS These results provide proof-of-concept evidence that DHA priming is a viable strategy to improve the neuroregulatory profile of ASCs.

Background: Type 1 diabetes (T1D) results in autoreactive T cells chronically destroying pancreatic islets. This often results in irreplaceable loss of insulin-producing beta cells. To reverse course, a combinatorial strategy of employing glucose-responsive insulin restoration coupled with inhibiting autoreactive immune responses is required. Methods: Non-obese diabetic mice received a single intraperitoneal implantation of a novel biomaterial co-seeded with insulin-producing islets and T regulatory cells (Tregs). Controls included biomaterial seeded solely with islets, or biomaterial only groups. Mice were interrogated for changes in inflammation and diabetes progression via blood glucose monitoring, multiplex serum cytokine profiling, flow cytometry and immunohistochemistry assessments. Results: Islet and Tregs co-seeded biomaterial recipients had increased longevity, insulin secretion, and normoglycemia through 180 days post-implantation compared to controls. Serum profile revealed reduced TNFα, IFNγ, IL-1β and increased IL-10, insulin, C-Peptide, PP and PPY in recipients receiving co-seeded biomaterial. Evaluation of the resected co-seeded biomaterial revealed reduced infiltrating autoreactive CD8 + and CD4 + T cells concomitant with sustained presence of Foxp3 + Tregs; further analysis revealed that the few infiltrated resident effector CD4+ or CD8+ T cells were anergic, as measured by low levels of IFNγ and Granzyme-B upon stimulation when compared to controls. Interestingly, studies also revealed increased Tregs in the pancreas. However, there was no restoration of the pancreas beta cell compartment, suggesting normoglycemia and production of insulin levels were largely supported by the implanted co-seeded biomaterial. Conclusion These studies show the efficacy of a combinatorial approach seeding Tregs with pancreatic islets in a novel self-assembling organoid for reversing T1D.

The International Severe Asthma Registry (ISAR) was established in 2017 to advance the understanding of severe asthma and its management, thereby improving patient care worldwide. As the first global registry for adults with severe asthma, ISAR enabled individual registries to standardize and pool their data, creating a comprehensive, harmonized dataset with sufficient statistical power to address key research questions and knowledge gaps. Today, ISAR is the largest repository of real-world data on severe asthma, curating data on nearly 35,000 patients from 28 countries worldwide, and has become a leading contributor to severe asthma research. Research using ISAR data has provided valuable insights on the characteristics of severe asthma, its burdens and risk factors, real-world treatment effectiveness, and barriers to specialist care, which are collectively informing improved asthma management. Besides changing clinical thinking via research, ISAR aims to advance real-world practice through initiatives that improve registry data quality and severe asthma care. In 2024, ISAR refined essential research variables to enhance data quality and launched a web-based data acquisition and reporting system (QISAR), which integrates data collection with clinical consultations and enables longitudinal data tracking at patient, center, and population levels. Quality improvement priorities include collecting standardized data during consultations and tracking and optimizing patient journeys via QISAR and integrating primary/secondary care pathways to expedite specialist severe asthma management and facilitate clinical trial recruitment. ISAR envisions a future in which timely specialist referral and initiation of biologic therapy can obviate long-term systemic corticosteroid use and enable more patients to achieve remission.

The scientific understanding of adipose tissue has advanced tremendously during the past decade. Once thought to be an inert fat storage organ, we now know that adipose tissue serves important functions in energy balance and endocrinology, as well as playing a central role in the development of metabolic diseases. Adipose tissue lipid storage and lipolysis are tightly controlled by hormones, such as insulin, in response to the body’s energy needs. Adipose insulin sensitivity can be measured in vivo in humans using isotopic fatty acid tracers and the insulin clamp technique. These data allow investigators to calculate the plasma insulin concentration that results in a 50% suppression of lipolysis. In obesity, insulin’s action on adipose tissue lipolysis is clearly impaired, resulting in excess free fatty acids in circulation, which can lead to metabolic dysfunction. However, the cause of this impairment is unclear. The chronic, low-grade adipose tissue inflammation seen in obesity was thought to be the cause of adipose tissue insulin resistance. In this review, we discuss the structure of adipose tissue, how normal and abnormal adipose tissue metabolism contributes to metabolic diseases, and how inflammation might or might not play a role in adipose tissue insulin resistance.