Tubal Ligation Induces Quiescence in the Epithelia of the Fallopian Tube Fimbria

Tubal ligation keeps the fimbriated end of the fallopian tube intact while interrupting the conduit for sperm and egg between the uterus and ovary. Tubal ligation is associated with an approximately 20% decreased risk of high-grade serous ovarian cancers, which mounting evidence suggests arise from the distal fallopian tube epithelium. We postulated that biological changes at the epithelial cellular level of the distal fallopian tube may account for the surgical procedure's observed risk reduction. We compared the histology, presence of epithelial progenitors (basally located CD44-positive cells), and degree of epithelial proliferation (Ki67-positive cells) of distal fallopian tube from 10 patients with previous tubal ligation and 10 age-matched patients with uncut fallopian tubes. A significantly reduced population of proliferating epithelial progenitors (basally located CD44/Ki67 dual-positive cells) was detected in the tubal ligated specimens (P = .0002). To functionally assess the effect of tubal ligation, a murine model was utilized to compare the growth capacity of distal fallopian tube epithelial cells isolated from either ligated or sham-operated tubal epithelia. Murine fallopian tube epithelial cells isolated after tubal ligation showed a significantly reduced capacity to grow organoids in culture compared to sham-operated controls (P = .002). The findings of this study show that tubal ligation is associated with a reduced presence and decreased proliferation of progenitor cells in the distal fallopian tube epithelium. These compositional and functional changes suggest that tubal ligation induces quiescence of distal fallopian tube epithelial cells

Predictors of Hand Function Following Digit Replantation: Quantitative Review and Meta-Analysis

Background: Digit replantation affords the opportunity to restore hand function following amputation. To date, however, few studies have evaluated functional outcomes following replantation. Therefore, it was the objective of this study to perform a meta-analysis to better characterize the predictors of hand function. Methods: A literature search was performed using the PubMed database to identify studies that focused on digit amputation/replantation and functional outcomes. Studies were evaluated for patient- and injury-related factors and their respective effects on clinical outcomes of sensation, grip strength, and Disabilities of the Arm, Shoulder, and Hand (DASH) scores. Statistical analysis was conducted across the pooled data set to identify significant trends. Results: Twenty-eight studies representing 618 replanted digits were included in this study. We found the average grip strength was 78.7% (relative to contralateral), the average 2-point discrimination (2PD) was 7.8 mm, and the average DASH score was 12.81. After conducting statistical analysis, we found patients with more proximal injuries had lower grip strength scores (P < .05). We found 2PD scores were influenced by age, mechanism of injury, and amputation level (P < .05). Finally, we found DASH scores after replantation were predicted by mechanism of injury and level of amputation (P < .05). The following variables did not influence outcomes: gender, tobacco use, ischemia time, and digit number. Conclusions: Digit replant does not restore premorbid hand function but does result in adequate hand function. Expected functional outcomes following replant should be considered in the decision-making process. These data can help risk-stratify patients, guide postreplant expectations, and influence the decision for replantation

Surgical Treatment of Pediatric Dog-bite Wounds: A 5-year Retrospective Review

Introduction: Dog bites are a significant health concern in the pediatric population. Few studies published to date have stratified the injuries caused by dog bites based on surgical severity to elucidate the contributing risk factors.   Methods: We used an electronic hospital database to identify all patients ≤17 years of age treated for dog bites from 2013–2018. Data related to patient demographics, injury type, intervention, dog breed, and payer source were collected. We extracted socioeconomic data from the American Community Survey. Data related to dog breed was obtained from public records on dog licenses. We calculated descriptive statistics as well as relative risk of dog bite by breed. Results: Of 1,252 injuries identified in 967 pediatric patients, 17.1% required consultation with a surgical specialist for repair. Bites affecting the head/neck region were most common (61.7%) and most likely to require operating room intervention (P = 0.002). The relative risk of a patient being bitten in a low-income area was 2.24, compared with 0.46 in a high-income area. Among cases where the breed of dog responsible for the bite was known, the dog breed most commonly associated with severe bites was the pit bull (relative risk vs German shepherd 8.53, relative risk vs unknown, 3.28).  Conclusion: The majority of injuries did not require repair and were sufficiently handled by an emergency physician. Repair by a surgical specialist was required <20% of the time, usually for bites affecting the head/neck region. Disparities in the frequency and characteristics of dog bites across socioeconomic levels and dog breeds suggest that public education efforts may decrease the incidence of pediatric dog bites

Vascularized Fibular Epiphyseal Transfer for Pediatric Limb Salvage: Review of Applications and Outcomes

Summary:. Vascularized fibular epiphyseal transfer (VFET) offers a functional advantage in pediatric limb salvage due to the preservation of growth potential and an articular surface for remodeling. This review summarizes the available evidence on the clinical characteristics and outcomes of pediatric reconstruction applying VFET at different recipient sites and with varying techniques. VFET was used to reconstruct the proximal humerus, distal radius or ulna, proximal femur, distal fibula, calcaneus, and mandible. Although most often harvested on the anterior tibial artery, VFET has also been performed using the peroneal artery, the inferior lateral genicular artery, and a dual pedicle. Recipient site flap inset most often involved fixation with plates and/or screws as well as soft tissue reconstruction using a retained slip of biceps femoris tendon. Outcomes included limb growth, range of motion, and strength. The most common reported complications were bone flap fracture and peroneal nerve palsy. The anterior tibial artery was the most applied pedicle with reliable limb growth, but with the added risk of postoperative peroneal palsy. Bone flap fracture most often occurred at the proximal humerus and femur recipient sites. Plate fixation and the combined use of allograft had lower instances of bone flap fracture. This review highlights how the anticipated dynamic growth and remodeling this free flap offers in the long term must be weighed against its complexity and potential complications

A Designed Inhibitor of p53 Aggregation Rescues p53 Tumor Suppression in Ovarian Carcinomas.

Half of all human cancers lose p53 function by missense mutations, with an unknown fraction of these containing p53 in a self-aggregated amyloid-like state. Here we show that a cell-penetrating peptide, ReACp53, designed to inhibit p53 amyloid formation, rescues p53 function in cancer cell lines and in organoids derived from high-grade serous ovarian carcinomas (HGSOC), an aggressive cancer characterized by ubiquitous p53 mutations. Rescued p53 behaves similarly to its wild-type counterpart in regulating target genes, reducing cell proliferation and increasing cell death. Intraperitoneal administration decreases tumor proliferation and shrinks xenografts in vivo. Our data show the effectiveness of targeting a specific aggregation defect of p53 and its potential applicability to HGSOCs

A Designed Inhibitor of p53 Aggregation Rescues p53 Tumor Suppression in Ovarian Carcinomas

Half of all human cancers lose p53 function by missense mutations, with an unknown fraction of these containing p53 in a self-aggregated, amyloid-like state. Here we show that a cell-penetrating peptide, ReACp53, designed to inhibit p53 amyloid formation, rescues p53 function in cancer cell lines and in organoids derived from high-grade serous ovarian carcinomas (HGSOC), an aggressive cancer characterized by ubiquitous p53 mutations. Rescued p53 behaves similarly to its wild-type counterpart in regulating target genes, reducing cell proliferation and increasing cell death. Intraperitoneal administration decreases tumor proliferation and shrinks xenografts in vivo. Our data show the effectiveness of targeting a specific aggregation defect of p53 and its potential applicability to HGSOCs