Traumatic pelvic fracture with rupture of the ovarian vein - A case report.

INTRODUCTION AND IMPORTANCE: Traumatic pelvic fractures are complex injuries often associated with significant morbidity and mortality. Among the complications of pelvic trauma, rupture of the ovarian vein represents a rare yet potentially life-threatening event. Prompt recognition and appropriate management are essential to mitigate the risk of hemorrhage and associated complications. CASE PRESENTATION: We present a case of a 70-year-old woman who sustained a traumatic pelvic fracture following a skiing accident, resulting in rupture of the left ovarian vein. The patient came with the ambulance in the emergency room with lower abdominal tenderness, pelvic pain, but no signs of hemorrhagic shock. Imaging studies confirmed the diagnosis of a pelvic fracture with venous leakage of the left ovarian vein. CLINICAL DISCUSSION: This review synthesizes recent insights into the diagnosis, management, and complications associated with pelvic fractures, with an emphasis on optimizing patient outcomes through a multidisciplinary approach. The analysis incorporates findings from key studies, including those by Wong and Bucknill, Ma Y et al., and Tullington and Blecker, which advocate for the use of advanced diagnostic tools like CT scans and systematic evaluation processes. These studies underline the necessity of precise classification systems such as the Tile classification to guide treatment and predict outcomes. CONCLUSION: Management of traumatic pelvic fractures with associated vascular injuries requires a multidisciplinary approach involving trauma surgeons, interventional radiologists, and critical care specialists. Early recognition, accurate diagnosis, and timely intervention are paramount in optimizing outcomes and reducing the risk of mortality. This case underscores the importance of prompt intervention and highlights the challenges associated with traumatic pelvic fractures and rupture of the ovarian vein. Further research is warranted to enhance our understanding of optimal management strategies and improve outcomes for patients with these complex injuries.

The retinoid X receptor has a critical role in synthetic rexinoid-induced increase in cellular all-trans-retinoic acid.

Rexinoids are agonists of nuclear rexinoid X receptors (RXR) that heterodimerize with other nuclear receptors to regulate gene transcription. A number of selective RXR agonists have been developed for clinical use but their application has been hampered by the unwanted side effects associated with the use of rexinoids and a limited understanding of their mechanisms of action across different cell types. Our previous studies showed that treatment of organotypic human epidermis with the low toxicity UAB30 and UAB110 rexinoids resulted in increased steady-state levels of all-trans-retinoic acid (ATRA), the obligatory ligand of the RXR-RAR heterodimers. Here, we investigated the molecular mechanism underlying the increase in ATRA levels using a dominant negative RXRα that lacks the activation function 2 (AF-2) domain. The results demonstrated that overexpression of dnRXRα in human organotypic epidermis markedly reduced signaling by resident ATRA, suggesting the existence of endogenous RXR ligand, diminished the biological effects of UAB30 and UAB110 on epidermis morphology and gene expression, and nearly abolished the rexinoid-induced increase in ATRA levels. Global transcriptome analysis of dnRXRα-rafts in comparison to empty vector-transduced rafts showed that over 95% of the differentially expressed genes in rexinoid-treated rafts constitute direct or indirect ATRA-regulated genes. Thus, the biological effects of UAB30 and UAB110 are mediated through the AF-2 domain of RXRα with minimal side effects in human epidermis. As ATRA levels are known to be reduced in certain epithelial pathologies, treatment with UAB30 and UAB110 may represent a promising therapy for normalizing the endogenous ATRA concentration and signaling in epithelial tissues.

Long-term Results of the Treatment of Scapholunate Instability with Dynamic Extensor Carpi Radialis Brevis Tenodesis.

Scapholunate dissociation is the most common form of carpal instability. This retrospective case series aimed to assess long-term results obtained by treating scapholunate instability with dynamic tenodesis using the entire extensor carpi radialis brevis tendon, which is detached from the base of the third metacarpal, rerouted in the third extensor compartment, and fixed at the distal portion of the scaphoid to maintain reduced rotatory subluxation. Methods: Nine patients with scapholunate instability were treated. We reviewed eight patients with a mean follow-up of 12 years. One subgroup of four patients was affected by static scapholunate instability, and the other by dynamic scapholunate instability. Disability of the Arm, Shoulder, and Hand score, Patient Rated Wrist Evaluation score, modified Mayo score, and radiographs were used to determine functional and anatomical outcomes. Results: Excellent functional results did not correlate with radiological outcome in patients with static scapholunate instability. In this subgroup, scapholunate angle and gap and radiolunate angle improved in average but remained in the pathologic range. In only one of these patients, osteoarthritis was observed. In the subgroup of patients affected by dynamic instability, very good functional outcomes correlate with radiological results, except in one patient who developed arthritic changes. Conclusions: Dynamic tethering of the scaphoid with the extensor carpi radialis brevis tendon might be indicated in the treatment not only in patients affected by dynamic scapholunate instability but also in patients with static instability. Prospective studies with a larger number of patients are required to evaluate this method.

The impact of Covid-19 in proximal femur fractures. An observational study of the mortality rate.

BACKGROUND AND AIM: Fractures of the proximal femur in the elderly are probably the leading cause of death in the orthopedic patients. Furthermore, after the spread of the pandemic, the mortality rate in the elderly has certainly increased. The aim of our study is to evaluate whether the mortality following proximal femur fractures is affected by the concomitant pandemic. METHODS: We admitted to our study patients over 65 years old, who presented to our Emergency Room with a diagnosis of proximal femur fracture in the first quarter of the years 2019, the period before the development of the pandemic, of 2020 during the pandemic and of 2021 with the new wave of Covid-19. 2022 was not taken into consideration because the mortality data are not yet available and to have at least one year follow-up after surgery. All patients were divided by fracture's type and treatment; the time elapsed from trauma to surgery and from trauma to discharge was also evaluated. For each deceased patient, we considered the time elapsed from the operation to death and whether there was an episode of positivity to Covid-19 following the trauma and after discharge (all patients had a negative swab at the time of admission). CONCLUSIONS: Fractures of the proximal femur in the elderly patient are undoubtedly an important cause leading to the death. The spreading of the Covid-19 pandemic has allowed our department to reduce the gap between trauma and intervention time and from trauma to discharge which is undoubtedly a positive prognostic factor. However, the concurrence of a positivity from the virus does not seem to influence the mortality times following the fracture.

Next-generation retinoid X receptor agonists increase ATRA signaling in organotypic epithelium cultures and have distinct effects on receptor dynamics.

Retinoid X receptors (RXRs) are nuclear transcription factors that partner with other nuclear receptors to regulate numerous physiological processes. Although RXR represents a valid therapeutic target, only a few RXR-specific ligands (rexinoids) have been identified, in part due to the lack of clarity on how rexinoids selectively modulate RXR response. Previously, we showed that rexinoid UAB30 potentiates all-trans-retinoic acid (ATRA) signaling in human keratinocytes, in part by stimulating ATRA biosynthesis. Here, we examined the mechanism of action of next-generation rexinoids UAB110 and UAB111 that are more potent in vitro than UAB30 and the FDA-approved Targretin. Both UAB110 and UAB111 enhanced ATRA signaling in human organotypic epithelium at a 50-fold lower concentration than UAB30. This was consistent with the 2- to 5- fold greater increase in ATRA in organotypic epidermis treated with UAB110/111 versus UAB30. Furthermore, at 0.2 µM, UAB110/111 increased the expression of ATRA genes up to 16-fold stronger than Targretin. The less toxic and more potent UAB110 also induced more changes in differential gene expression than Targretin. Additionally, our hydrogen deuterium exchange mass spectrometry analysis showed that both ligands reduced the dynamics of the ligand-binding pocket but also induced unique dynamic responses that were indicative of higher affinity binding relative to UAB30, especially for Helix 3. UAB110 binding also showed increased dynamics towards the dimer interface through the Helix 8 and Helix 9 regions. These data suggest that UAB110 and UAB111 are potent activators of RXR-RAR signaling pathways but accomplish activation through different molecular responses to ligand binding.

The epigenetic state of IL-4-polarized macrophages enables inflammatory cistromic expansion and extended synergistic response to TLR ligands.

Prior exposure to microenvironmental signals could fundamentally change the response of macrophages to subsequent stimuli. It is believed that T helper-2 (Th2)-cell-type cytokine interleukin-4 (IL-4) and Toll-like receptor (TLR) ligand-activated transcriptional programs mutually antagonize each other, and no remarkable convergence has been identified between them. In contrast, here, we show that IL-4-polarized macrophages established a hyperinflammatory gene expression program upon lipopolysaccharide (LPS) exposure. This phenomenon, which we termed extended synergy, was supported by IL-4-directed epigenomic remodeling, LPS-activated NF-κB-p65 cistrome expansion, and increased enhancer activity. The EGR2 transcription factor contributed to the extended synergy in a macrophage-subtype-specific manner. Consequently, the previously alternatively polarized macrophages produced increased amounts of immune-modulatory factors both in vitro and in vivo in a murine Th2 cell-type airway inflammation model upon LPS exposure. Our findings establish that IL-4-induced epigenetic reprogramming is responsible for the development of inflammatory hyperresponsiveness to TLR activation and contributes to lung pathologies.

A growth factor-expressing macrophage subpopulation orchestrates regenerative inflammation via GDF-15.

Muscle regeneration is the result of the concerted action of multiple cell types driven by the temporarily controlled phenotype switches of infiltrating monocyte-derived macrophages. Pro-inflammatory macrophages transition into a phenotype that drives tissue repair through the production of effectors such as growth factors. This orchestrated sequence of regenerative inflammatory events, which we termed regeneration-promoting program (RPP), is essential for proper repair. However, it is not well understood how specialized repair-macrophage identity develops in the RPP at the transcriptional level and how induced macrophage-derived factors coordinate tissue repair. Gene expression kinetics-based clustering of blood circulating Ly6Chigh, infiltrating inflammatory Ly6Chigh, and reparative Ly6Clow macrophages, isolated from injured muscle, identified the TGF-ß superfamily member, GDF-15, as a component of the RPP. Myeloid GDF-15 is required for proper muscle regeneration following acute sterile injury, as revealed by gain- and loss-of-function studies. Mechanistically, GDF-15 acts both on proliferating myoblasts and on muscle-infiltrating myeloid cells. Epigenomic analyses of upstream regulators of Gdf15 expression identified that it is under the control of nuclear receptors RXR/PPARγ. Finally, immune single-cell RNA-seq profiling revealed that Gdf15 is coexpressed with other known muscle regeneration-associated growth factors, and their expression is limited to a unique subpopulation of repair-type macrophages (growth factor-expressing macrophages [GFEMs]).

Endoscopic Carpal Tunnel Release Without Invading the Tunnel: A New Transretinacular Technique.

Established endoscopic carpal tunnel release (ECTR) techniques carry a not entirely eludible risk of iatrogenic complications, mainly because of incomplete view of the cutting blade and intraoperative pressure increase inside the carpal tunnel (CT). We describe a novel single-portal ECTR method, conceived to reduce these risks, by optimizing visual control and avoiding dilatation of the CT. After incising the well exposed proximal third of the transverse carpal ligament (TCL), transection of the remainder is completed using a pediatric urethrotome. This small caliber instrument is moved in the plane of the TCL, without invading the tunnel, and provides detailed view of the TCL and any crossing anatomical structures at any given moment. We present the technique and the results of a retrospective case series of 33 patients with CT syndrome who underwent the procedure, after failing to respond to conservative treatment. Because of improved view and the avoidance of intraoperative pressure trauma to structures passing through the CT, the described approach may contribute to prevent iatrogenic complications and represent a valid improvement over conventional ECTR procedures.

The transcription factor EGR2 is the molecular linchpin connecting STAT6 activation to the late, stable epigenomic program of alternative macrophage polarization.

Macrophages polarize into functionally distinct subtypes while responding to microenvironmental cues. The identity of proximal transcription factors (TFs) downstream from the polarization signals are known, but their activity is typically transient, failing to explain the long-term, stable epigenomic programs developed. Here, we mapped the early and late epigenomic changes of interleukin-4 (IL-4)-induced alternative macrophage polarization. We identified the TF, early growth response 2 (EGR2), bridging the early transient and late stable gene expression program of polarization. EGR2 is a direct target of IL-4-activated STAT6, having broad action indispensable for 77% of the induced gene signature of alternative polarization, including its autoregulation and a robust, downstream TF cascade involving PPARG. Mechanistically, EGR2 binding results in chromatin opening and the recruitment of chromatin remodelers and RNA polymerase II. Egr2 induction is evolutionarily conserved during alternative polarization of mouse and human macrophages. In the context of tissue resident macrophages, Egr2 expression is most prominent in the lung of a variety of species. Thus, EGR2 is an example of an essential and evolutionarily conserved broad acting factor, linking transient polarization signals to stable epigenomic and transcriptional changes in macrophages.

Nascent Malunion of an Isolated Intraarticular Fracture of the Ulnar Head.

Background Isolated fractures of the ulnar head are rare. Only few cases have been reported in literature. Case Description We report a case of a 16-year-old student who was treated for an ulnar styloid fracture conservatively. An associated displaced intraarticular fracture of the ulnar head has been overlooked. He presented late in our clinic with a symptomatic nascent malunion of the ulnar head fracture. A corrective osteotomy by a palmar approach was performed. Fixation by screws was used with an excellent result at 7-year follow-up. Literature Review The rare cases of isolated ulnar head fractures reported in literature were treated by open reduction and internal fixation only in case of fracture dislocation. Clinical Relevance The authors highlight the fact that even a nascent malunion of an isolated intraarticular fracture of the ulnar head may be treated successfully by open reduction and internal fixation.