Intramedullary Nail Fixation for the Treatment of Symptomatic Fibular Nonunion: A Case Series.

Ankle fractures are a relatively common injury in the lower extremity. They can be treated with conservative management if they are nondisplaced and only involve the fibula. Nonunions at the fracture site, however, are a potential complicating factor during treatment. There is growing literature supporting the use of intramedullary fixation for fracture care. Not only does it have the advantages of using smaller incisions to preserve periosteum while providing improved biomechanical outcomes, but intramedullary reaming can help stimulate cells to promote bone healing. Few articles discuss the use and success of intramedullary reaming in revision surgery of the distal fibula. We present 3 cases of computed tomography-confirmed fibular nonunion following conservative fracture care, which underwent revision surgery with fibular nail fixation technique. These cases illustrate clinical and image findings as well as highlight the surgical technique used for each patient. At follow-up, all patients were asymptomatic and radiographs confirmed healing of the previous nonunion site. These cases are examples of successful revision for fibular fracture nonunion using intramedullary nail fixation.Level of Evidence: Level IV: Case series.

A Retrospective Analysis of Distal Fibula Fractures Treated With Intramedullary Fibular Nail Fixation.

There is growing literature supporting the use of intramedullary fixation for fracture care because of its smaller incisions, improved biomechanical outcomes, and faster time to weightbearing than traditional internal fixation methods. The aim of this study is to investigate the postoperative outcomes in ankle fractures treated with intramedullary nail fixation in the largest patient cohort to date. From 2015 to 2021, 151 patients were evaluated following surgical treatment of fibular fractures with intramedullary nail fixation. Patients were identified through a medical record database search for appropriate ankle fracture procedure codes. Patient information was reviewed for fracture type, adjunct procedures, time to weightbearing and postoperative complications. Radiographs were assessed for quality and time to radiographic union. The mean time to weightbearing was 4.8 weeks. Minor wound dehiscence was identified in 2 patients (1.3%). Superficial infection was present in 4 patients (2.6%) and a deep infection developed in 2 patients (1.3%). Two patients developed a nonunion (1.5%). There were no DVTs reported, although 1 patient developed a PE postoperatively. Radiographic quality of reduction and time to union is comparable to literature reported plate and screw construct outcomes. Reduction was classified as good in 86.1% of patients and radiographic union was appreciated in 98.5% of patients. This is the largest cohort study evaluating the outcomes of intramedullary nail fixation for ORIF of ankle fractures. These data reinforce that intramedullary nailing provides a minimally invasive approach with accurate anatomic reduction, excellent fracture union rates, low complication rates, and an early return to weightbearing.

Impaired fibrinolysis in severe Covid-19 infection is detectable in early stages of the disease.

BACKGROUND: A significant degree of mortality and morbidity in Covid-19 is due to thromboembolic disease. Coagulopathy has been well described in critically unwell patients on ICU. There is less clear evidence regarding these changes at the time of presentation to the Emergency Department and the progression of disease over time. OBJECTIVE: We sought to investigate whether coagulation markers can predict severity and how they change over the disease course. METHODS: Patients presenting to a single University Teaching Hospital were recruited and followed up if PCR was positive. Alongside routine blood testing, Rotational Thromboelastometry (ROTEM) was performed. Outcome data was recorded for all patients, and ROTEM values were compared across outcome groups. RESULTS: Extem and Intem Maximum Lysis were significantly reduced in those who died or required an ICU admission, indicating a reduced ability to break down clot mass in the most critically unwell patients. CONCLUSION: Comparisons between groups demonstrated that one distinguishing feature between those who require ICU admission or die of Covid-19 compared with those who survive a hospital stay to discharge was the extent to which fibrinolysis could occur. Mortality and morbidity in Covid-19 infection appears in part driven by an inability to break down clot mass.

Olaparib Combined with an ATR or Chk1 Inhibitor as a Treatment Strategy for Acquired Olaparib-Resistant BRCA1 Mutant Ovarian Cells.

OBJECTIVE: Despite the promise of PARP inhibitors (PARPi) for treating BRCA1/2 mutated ovarian cancer (OC), drug resistance invariably develops. We hypothesized rationale drug combinations, targeting key molecules in DNA repair pathways and the cell cycle may be synergistic and overcome acquired PARPi resistance. METHODS: Drug sensitivity to PARPi alone and in combination with inhibitors of key DNA repair and cell cycle proteins, including ATR (VE-821), Chk1 (MK-8776), Wee1 (MK-1775), RAD51 (RI-1) was assessed in PARPi-sensitive (UWB1) and -resistant (UWB1-R) gBRCA1 mutant OC cell lines using a cell proliferation assay. The Bliss synergy model was used to estimate the two-drug combination effect and pharmacologic synergy (Bliss score ≥ 0) or antagonistic (Bliss score ≥ 0) response of the PARPi in combination with the inhibitors. RESULTS: IC50 for olaparib alone was 1.6 ± 0.9 µM compared to 3.4 ± 0.6 µM (p = 0.05) for UWB1 and UWB1-R cells, respectively. UWB1-R demonstrated increased sensitivity to ATRi (p = 0.04) compared to UWB1. Olaparib (0.3-1.25 µM) and ATRi (0.8-2.5 µM) were synergistic with Bliss scores of 17.2 ± 0.2, 11.9 ± 0.6 for UWB1 and UWB1-R cells, respectively. Olaparib (0.3-1.25 µM) and Chk1i(0.05-1.25 µM) were synergistic with Bliss scores of 8.3 ± 1.6, 5.7 ± 2.9 for UWB1 and UWB1-R cells, respectively. CONCLUSIONS: Combining an ATRi or Chk1i with olaparib is synergistic in both PARPi-sensitive and -resistant BRCA1 mutated OC cell models, and are rationale combinations for further clinical development.

Preoperative Circulating Lymphocyte and Monocyte Counts Correlate with Patient Outcomes in Type I and Type II Endometrial Cancer.

Tumor-associated macrophages and tumor-infiltrating lymphocytes are associated with survival in solid malignancies. Given the physiological link to peripheral immune cell counts, we evaluated if peripheral immune cell counts were predictors of outcomes in endometrial cancer. A retrospective study was completed for endometrial cancer cases between 2000 and 2010. Kaplan-Meier, bivariate, and multivariable Cox proportion hazard analyses were performed examining the relations between survival and peripheral immune cell counts. Three hundred ten patients were identified. In bivariate analyses, high monocyte counts (> 0.7 × 109 cells/L) trended with decreased progression free survival (PFS) (p = 0.10) and poorer overall survival (OS) (p = 0.16). By contrast, high lymphocyte level (> 1.5 × 109 cells/L) was associated with improved PFS (p = 0.008) and OS (p = 0.006). These findings were consistent for type I and type II endometrial cancers. In a multivariable Cox model, high monocyte level was associated with a greater risk of disease recurrence (hazard ratio (HR) = 1.63, p < 0.035). Other significant predictors of recurrence were age, non-endometrioid histology, and the presence of lymph vascular space invasion (LVSI). In a multivariable Cox model, high lymphocyte count trended with a lower risk of death (HR = 0.66, p = 0.07). Age, surgical stage, non-endometrioid histology, and LVSI were also associated with death in this model. In this sample of endometrial cancer patients, we found that high preoperative lymphocyte counts were associated with improved overall improved survival. High monocyte counts were associated with poorer disease-free survival outcomes. Further studies that focused on understanding tumor-antagonizing and pro-tumoral effects of lymphocytes and monocytes, respectively, in endometrial cancer are recommended.

Disease-Specific Survival of Type I and Type II Epithelial Ovarian Cancers-Stage Challenges Categorical Assignments of Indolence & Aggressiveness.

Epithelial ovarian cancers (EOC) consist of several sub-types based on histology, clinical, molecular and epidemiological features that are termed "histo-types", which can be categorized into less aggressive Type I and more aggressive Type II malignancies. This investigation evaluated the disease-specific survival (DSS) of women with Type I and II EOC using histo-type, grade, and stage. A total of 200,658 EOC cases were identified in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) data. Kaplan-Meier survival analyses, one-factor ANOVA and Chi-square analyses were performed on 10-year DSS survivals. DSS strongly supported a 2-tiered classification (grade 1 vs. grade 2 & 3) for serous EOC. DSS of early stage serous EOC for grade 2 was significantly different from grade 3 indicating that a 2-tier classification for serous EOC applied only to late stage. DSS of Type I EOC was much better than Type II. However, DSS was 46-58% lower with late stage Type I than with early stage Type I indicating that Type I ovarian cancers should not be considered indolent. Early stage Type II EOC had much better DSS than late stage Type II stressing that stage has a large role in survival of both Type I and II EOC.

Uterine Corpus Malignancies in Appalachia Kentucky: Incidence, Survival, and Related Health Disparities.

OBJECTIVES: Uterine cancer is the nation's most common gynecologic malignancy, but it is understudied in the geographically and socioeconomically diverse state of Kentucky (KY). Our aim was to assess the frequency, distribution, and survival of uterine corpus malignancies in KY, and specifically the differences between Appalachia (AP) and non-Appalachia (NAP) KY. METHODS: This population-based cohort study used Surveillance, Epidemiology, and End Results data and the Kentucky Cancer Registry to study uterine corpus malignancy between January 1, 2000 and December 31, 2014. The analysis looked at the incidence between diagnoses in AP and NAP. The evaluation criteria included tumor histology (type I, type II, sarcoma, and mixed uterine malignancy), age, race, smoking status, stage at diagnosis, insurance status, and county of residence at diagnosis. RESULTS: The overall age-adjusted incidence rate and survival are similar for US and KY populations; however, histologic types and distribution differ. Compared with the United States, the incidence of corpus cancers in KY is higher for type I (P = 0.03), but lower for type II (P = 0.003), sarcoma (P = 0.006), and mixed (P < 0.001). AP KY has a higher incidence of type I (P < 0.0001) and mixed malignancy (P = 0.04), younger age at diagnosis (P < 0.0001), larger non-Hispanic white population (P < 0.0001), fewer smokers (P = 0.002), and more uninsured and Medicaid recipients (P < 0.0001) compared with NAP KY. The hazard ratio for death is similar in AP and NAP KY (0.896; 95% confidence interval 0.795-1.009). CONCLUSIONS: Type I and mixed uterine corpus cancers have a higher age-adjusted incidence and a younger age at diagnosis in AP compared with NAP KY.

Clinical Factors Associated with Longer Hospital Stay Following Ovarian Cancer Surgery.

Background: Ovarian cancer (OC) is the leading cause of death from gynecologic malignancy and is treated with a combination of cytoreductive surgery and platinum-based chemotherapy. Extended length of stay (LOS) after surgery can affect patient morbidity, overall costs, and hospital resource utilization. The primary objective of this study was to identify factors contributing to prolonged LOS for women undergoing surgery for ovarian cancer. Methods: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was queried to identify women from 2012-2016 who underwent hysterectomy for ovarian, fallopian tube and peritoneal cancer. The primary outcome was LOS >50th percentile. Preoperative and intraoperative variables were examined to determine which were associated with prolonged LOS. Results: From 2012-2016, 1771 women underwent elective abdominal surgery for OC and were entered in the ACS-NSQIP database. The mean and median LOS was 4.6 and 4.0 days (IQR 0-38), respectively. On multivariate analysis, factors associated with prolonged LOS included: American Society of Anesthesiologists (ASA) Classification III (aOR 1.71, 95% CI 1.38-2.13) or IV (aOR 1.88, 95% CI 1.44-2.46), presence of ascites (aOR 1.88, 95% CI 1.44-2.46), older age (aOR 1.23, 95% CI 1.13-1.35), platelet count >400,000/mm3 (aOR 1.74, 95% CI 1.29-2.35), preoperative blood transfusion (aOR 11.00, 95% CI 1.28-94.77), disseminated cancer (aOR 1.28, 95% CI 1.03-1.60), increased length of operation (121-180 min, aOR 1.47, 95% CI 1.13-1.91; >180 min, aOR 2.78, 95% CI 2.13-3.64), and postoperative blood transfusion within 72 h of incision (aOR 2.04, 95% CI 1.59-2.62) (p < 0.05 for all). Conclusions: Longer length of hospital stay following surgery for OC is associated with many patient, disease, and treatment-related factors. The extent of surgery, as evidenced by perioperative blood transfusion and length of surgical procedure, is a factor that can potentially be modified to shorten LOS, improve patient outcomes, and reduce hospital costs.

Adnexal tumors in menopausal women: surgery or surveillance?

Asymptomatic ovarian tumors in menopausal women do not always require surgical removal. Experts recommend an initial evaluation with transvaginal ultrasound to help characterize the tumor's malignant risk. Low-risk tumors can be monitored with ultrasound, whereas high-risk tumors should be referred to a gynecologic oncologist. Indeterminate tumors require secondary testing with the strategies outlined in this Practice Pearl.

Survival of Women With Type I and II Epithelial Ovarian Cancer Detected by Ultrasound Screening.

OBJECTIVE: To estimate the effect of ultrasound screening on stage at detection and long-term disease-specific survival of at-risk women with epithelial ovarian cancer. METHODS: Eligibility included all asymptomatic women 50 years of age or older and women 25 years of age or older with a documented family history of ovarian cancer. From 1987 to 2017, 46,101 women received annual ultrasound screening in a prospective cohort trial. Women with a persisting abnormal screen underwent tumor morphology indexing, serum biomarker analysis, and surgery. RESULTS: Seventy-one invasive epithelial ovarian cancers and 17 epithelial ovarian tumors of low malignant potential were detected. No women with a low malignant potential tumor experienced recurrent disease. Stage distribution for screen-detected invasive epithelial ovarian cancers was stage I-30 (42%), stage II-15 (21%), stage III-26 (37%), and stage IV-0 (0%). Follow-up varied from 9.2 months to 27 years (mean 7.9 years). Disease-specific survival at 5, 10, and 20 years for women with invasive epithelial ovarian cancer detected by screening was 86±4%, 68±7%, and 65±7%, respectively, vs 45±2%, 31±2%, and 19±3%, respectively, for unscreened women with clinically detected ovarian cancer from the same geographic area who were treated at the same institution by the same treatment protocols (P<.001). Twenty-seven percent of screen-detected malignancies were type I and 73% were type II. The disease-specific survival of women with type I and type II screen-detected tumors was significantly higher than that of women with clinically detected type I and type II tumors and was related directly to earlier stage at detection. CONCLUSION: Annual ultrasound screening of at-risk asymptomatic women was associated with lower stage at detection and increased 5-, 10-, and 20-year disease-specific survival of women with both type I and type II epithelial ovarian cancer. CLINICAL TRIAL REGISTRATION: OnCore Clinical Trials Management System, NCI-2013-01954.

Defective DNA repair in hereditary ovarian cancers: Implications for therapy.

PURPOSE: The role of mutated DNA repair pathways in hereditary ovarian cancer (OC) and the clinical basis for the use of poly(ADP-ribose) polymerase (PARP) enzyme inhibitors and an immune checkpoint inhibitor as novel targeted therapies in the treatment of certain OC subtypes are reviewed. SUMMARY: OC is the most lethal of all gynecologic malignancies and encompasses a highly diverse collection of cancers. Hereditary OCs are a unique subtype of OC encompassing up to 24% of all OCs, including cancers driven by germline mutations of the BRCA1 or BRCA2 genes, mutations associated with Fanconi anemia (FA), BRCAness germline mutations, and Lynch syndrome. With an increasing wealth of genomic data available in cancer research, a common thread of defective DNA repair pathways as a primary driver of hereditary OCs has emerged. OCs driven by BRCA1/2, FA-associated, and BRCAness germline mutations have a demonstrated sensitivity to PARP inhibitors due to underlying deficiencies in DNA homologous recombination; however, clinical responses are often partial and highly dependent on platinum sensitivity. Additionally, the immune checkpoint inhibitor pembrolizumab is indicated for certain metastatic solid tumors characterized by microsatellite instability, a distinguishing feature highly associated with DNA mismatch repair deficiency in Lynch syndrome-associated cancers, including some OCs. CONCLUSION: In hereditary OC syndromes, mutations in DNA repair pathways form the clinical basis for the use of PARP inhibitors and an immune checkpoint inhibitor as novel targeted therapies.

Fungal periapical abscess and the burn patient: A report of two cases of an unreported source for systemic infection.

Fungal infections in the intensive care unit are becoming a more common occurrence, especially in the care of the burn patient. Fungal infections in the critically burned patient, who by nature have a heightened inflammatory state and impaired immune response, have been found to carry a profound degree of morbidity and mortality. We present our experience in the care of severe thermal injuries; a series of patients with endodontic fungal infection which, as we found, pose a significant risk for the development of systemic infection and sepsis. Fungal periapical abscesses are a rare and, yet undescribed, potential source of systemic sepsis in the burn intensive care unit.

Helicopter transport of pediatric versus adult trauma patients.

OBJECTIVE: Conflicting reports exist regarding the appropriate utilization of helicopter transport for victims of trauma. It has been suggested that adult patients are more severely injured compared with pediatric patients when transported by helicopter. The purpose of this study was to determine whether injury severity and survival probability in pediatric trauma patients were similar to those for adults when helicopter transport was utilized at a suburban trauma center. METHODS: The authors conducted a retrospective review of all trauma patients transported by helicopter from the accident scene. Patients were identified from the Christiana Care Health System trauma registry from January 1995 to November 1999. Pediatric patients were defined as those aged 15 years and younger. Data collected were utilized to determine injury severity score (ISS), revised trauma score (RTS), and survival probability. RESULTS: Nine hundred sixty-nine patients were transported; 143 were pediatric. There was no statistical difference noted in ISS (14.21 adult, 12.76 pediatric; p = 0.1506) and RTS (7.23 adult, 7.31 pediatric; p = 0.1832). Mean length of stay was less for the pediatric group (7.5 days adult, 5.2 days pediatric; p = 0.008). Survival probabilities were likewise similar for the two groups, yet the difference met statistical significance (0.92 adult, 0.95 pediatric; p = 0.03). CONCLUSION: Pediatric patients transported from the accident scene by helicopter have similar ISSs and RTSs compared with adults. These data suggest that prehospital selection criteria for the two groups are similar.