Absence of E2f1 Negates Pro-osteogenic Impacts of p21 Absence.

Loss of p21 leads to increased bone formation post-injury; however, the mechanism(s) by which this occurs remains undetermined. E2f1 is downstream of p21 and as a transcription factor can act directly on gene expression; yet it is unknown if E2f1 plays a role in the osteogenic effects observed when p21 is differentially regulated. In this study we aimed to investigate the interplay between p21 and E2f1 and determine if the pro-regenerative osteogenic effects observed with the loss of p21 are E2f1 dependent. To accomplish this, we employed knockout p21 and E2f1 mice and additionally generated a p21/E2f1 double knockout. These mice underwent burr-hole injuries to their proximal tibiae and healing was assessed over 7 days via microCT imaging. We found that p21 and E2f1 play distinct roles in bone regeneration where the loss of p21 increased trabecular bone formation and loss of E2f1 increased cortical bone formation, yet loss of E2f1 led to poorer bone repair overall. Furthermore, when E2f1 was absent, either individually or simultaneously with p21, there was a dramatic decrease of the number of osteoblasts, osteoclasts, and chondrocytes at the site of injury compared to p21-/- and C57BL/6 mice. Together, these results suggest that E2f1 regulates the cell populations required for bone repair and has a distinct role in bone formation/repair compared to p21-/-E2f1-/-. These results highlight the possibility of cell cycle and/or p21/E2f1 being potential druggable targets that could be leveraged in clinical therapies to improve bone healing in pathologies such as osteoporosis.

Specialty Impact on Patient Outcomes: Paving a Way for an Integrated Approach to Spinal Disorders.

Spinal surgical procedures are steadily increasing globally due to broad indications of certain techniques encompassing a wide spectrum of conditions, including degenerative spine disorders, congenital anomalies, spinal metastases, and traumatic spinal fractures. The two specialties, neurosurgery (NS) and orthopedic surgery (OS), both possess the clinical adeptness to perform these procedures. With the advancing focus on comparative effectiveness research, it is vital to compare patient outcomes in spine surgeries performed by orthopedic surgeons and neurosurgeons, given their distinct approaches and training backgrounds to guide hospital programs and physicians to consider surgeon specialty when making informed decisions. Our review of the available literature revealed no significant difference in postoperative outcomes in terms of blood loss, neurological deficit, dural injury, intraoperative complications, and postoperative wound dehiscence in procedures performed by neurosurgeons and orthopedic surgeons. An increase in blood transfusion rates among patients operated by orthopedic surgeons and a longer operative time of procedures performed by neurosurgeons was a consistent finding among several studies. Other findings include a prolonged hospital stay, higher hospital readmission rates, and lower cost of procedures in patients operated on by orthopedic surgeons. A few studies revealed lower sepsis rates unplanned intubation rates and higher incidence of urinary tract infections (UTIs) and pneumonia postoperatively among patient cohorts operated by neurosurgeons. Certain limitations were identified in the studies including the use of large databases with incomplete information related to patient and surgeon demographics. Hence, it is imperative to account for these confounding variables in future studies to alleviate any biases. Nevertheless, it is essential to embrace a multidisciplinary approach integrating the surgical expertise of the two specialties and develop standardized management guidelines and techniques for spinal disorders to mitigate complications and enhance patient outcomes.

Age-Related Macular Degeneration: An Exponentially Emerging Imminent Threat of Visual Impairment and Irreversible Blindness.

Age-related macular degeneration (AMD) is a significant cause of blindness globally. With the exponential rise in the aging population, AMD is the third leading cause of visual impairment worldwide. Neovascular AMD (nAMD; Wet AMD) and geographical atrophy (GA, late-stage dry AMD) are the advanced AMD accountable for substantial cases of visual deterioration among the elderly. Our review of the literature depicted that notable risk factors include cigarette smoking, nutritional elements, cardiovascular disorders, and genetic markers, including genes regulating complement, lipid, and angiogenic pathways. Some studies have suggested a relative decline in the proportion of AMD cases in the last two decades attributable to novel diagnostic and therapeutic modalities. Accurate diagnosis is the result of a combination of clinical examination and imaging techniques, including retinal photography, angiography, and optical coherence tomography. The incorporation of dietary antioxidant supplements, explicitly lutein, slows the progression of the disease in advanced stages. The induction of vascular endothelial growth factor (VEGF) inhibitors in the treatment of neovascular AMD, often combined with other modalities, has shown an immensely favorable prognosis. Research to integrate gene therapy and regenerative techniques using stem cells is underway to further mitigate AMD-associated morbidity. It is imperative to establish screening and therapeutic guidelines for AMD to curtail the future social and financial burden and improve the diminishing quality of life among the elderly.

Carotid Artery Stenosis: A Look Into the Diagnostic and Management Strategies, and Related Complications.

Carotid stenosis (CS) is a buildup of atherosclerotic plaque within the artery leading to a wide range of symptoms, from mild symptoms, including blurred vision and confusion, to much more life-threatening presentations, including paralysis due to stroke. The presentation is insidious, with symptoms exhibiting predominantly at severe stenosis; hence the emphasis is placed on the importance of early diagnosis, treatment, and lifestyle modifications. CS is seen undergoing almost the same pathogenesis of any atherosclerotic plaque formation, from endothelial damage of the artery lumen to the formation of a fibrous cap with a foam cell, lipid-filled core. The findings of our review article were consistent with the recent literature, depicting that comorbid hypertension, diabetes, and chronic kidney disease (CKD), and lifestyle aspects, including smoking and diet, played the most salient role in plaque development. Among several imaging modalities, duplex ultrasound (DUS) imaging is the widely preferred method in clinical practice. Carotid endarterectomy (CEA) and carotid stenting are the primarily advocated procedures for symptomatic severe stenosis, with similar long-term outcomes. Although, earlier clinical trials showed promising results in mitigating the risk of stroke among asymptomatic severe CS with surgical intervention. However, recent advancements have shifted the focus to medical management alone due to comparable results among the asymptomatic population. Both surgical and medical regimens are beneficial in treating patients, but it is still an ongoing debate as to which is predominantly superior. The currently advancing trials and research will help elucidate definitive guidelines. However, the massive impact of lifestyle modifications advocates some degree of individualized multidisciplinary management strategies.

A marginal process of the zygomatic bone predicts a lateral exit of the zygomaticotemporal nerve: An anatomical study with application to surgery around the midface.

Previous studies have not verified the contents of accessory foramina of the zygomatic bone on dry skulls and thus could not conclude whether they carried accessory zygomaticofacial nerve branches or branches or the entire trunk of the zygomaticotemporal nerve (ZTN). Therefore, the aim of the current study is to present findings from cadaveric dissections to clarify this relationship. Fifty, fresh frozen, adult cadaveric sides underwent dissection of the ZTN. When identified, these nerves were quantified and their relationship to the zygomatic bone further documented by dissecting through the bone following the course of the nerve from a superficial to deep perspective. Additionally, 100 dry, adult, human skulls were analyzed looking for lateral foramina on the zygomatic bone. On three cadaveric sides (6%), the ZTN was found to pierce the zygomatic bone deeply and exit its superficial lateral surface. For dry skull specimens, a lateral zygomaticotemporal foramen (ZTF) was identified on nine sides (4.5%). For both groups, the presence of a strong marginal process of the zygomatic bone was strongly correlated to a ZTF exiting the lateral surface of the zygomatic bone. Although relatively uncommon, the ZTN can pierce the lateral aspect of the zygomatic bone and thus can be located superficial to the cheek. Such findings should be borne in mind during surgical or other invasive procedures in this area in order to minimize iatrogenic injury to the ZTN.

Prevalence of Petrooccipital Fissure Fusion: Osteological Study with Application to Approaches to the Skull Base and Imaging Interpretation.

INTRODUCTION: The petrooccipital fissure (POF) has relevance to skull base approaches, various tumors and craniosynostoses, and some cases of age-related hearing loss. However, the prevalence of fusion and classification of such is rarely found in the extant medical literature. METHODS: One-hundred and 10 dry human skulls (220 sides) were used for this study. The skulls were evaluated for fusion of the POF. Both the endocranial and exocranial aspects of the POF were analyzed. A classification scheme was developed to better describe the location of POF fusion. RESULTS: A fused POF was identified on 36 sides (16.4%) and commonly found bilaterally (11%). Of these, 30 sides (83.3%) were completely fused (type I) and 6 sides (2.7%) were partially fused (types II and III). For the partially fused fissures, the fused part was on all but 2 sides with the most anterior portion of the petrous part of the temporal bone and adjacent clivus (type II). For the 2 sides (both right sides), the fusion was more posteriorly located between the petrous part of the temporal bone and lateral clivus (type III). Fusion of the POF was more often found in specimens with a partially or fully ossified petroclival ligament. Completely fused POF was positively correlated to sides with an intrajugular bony septum. CONCLUSIONS: A POF fusion was relatively common and associated with an ossified petroclival ligament and intrajugular bony septation. Such a prevalence is important for clinicians and skull base surgeons interpreting imaging of the skull base.

Role of Surgery in Spinal Metastases.

Spinal metastases constitute two-third of all cases of bone metastases. Surgical intervention in these tumours has been recommended in highly selective cases, for confirming diagnosis, stabilizing the spine, and decompressing nerves or spinal cord for alleviation of pain and preservation of function.In this article,the authors have reviewed available evidence on role of surgery in spinal metastases and have presented results of selected papers on this vast topic.

Acute Myeloid Leukemia with Occult Systemic Mastocytosis or Atypical Mast Cells Post-induction.

Systemic mastocytosis (SM) is a state of disease that is related to the clonal, neoplastic proliferation of mast cells. Patients who present with SM-Acute Myeloid Leukemia (AML) often have the worst outcome. We present a case of an 18-year-old female who was diagnosed with AML (FLT3 (Fms like tyrosine kinase 3) and PML-RARA (promyelocytic leukemia-retinoic acid receptor alpha) translocation-negative) and after initial treatment with a standard induction regimen of cytarabine and daunorubicin (3+7 regimen), her bone marrow showed blast cells less than 5% and dense aggregates/sheets of atypical/immature mast cells with immunohistochemical stain CD117+ve and toluidine blue positive in mast cell aggregates. Mastocytosis is a clonal neoplastic proliferation of mast cells that accumulate in one or more organ system. Therefore, it is essential to diagnose systemic mastocytosis, particularly in patients of hematological neoplasms.