Pathologic Peri-Implant Proximal Femur Fracture: Takeaways from Our Experience.

Pathologic fractures of the distal femur secondary to bone metastases are not as common as those in the proximal femur, and they are rarely reported on in the literature. Even in the absence of current metastatic lesions in the femoral neck, traditional orthopaedic teaching has stressed the importance of protecting the entire femur, while recent studies have shown that it may not be necessary to stabilize the entire femur in the event of future metastases. Thus, there is no consensus regarding optimal surgical treatment, making the choice of fixation often based on the experience of the surgeon. In this paper, we reported on a patient who presented with a pathologic fracture of the distal femur who was stabilized with a retrograde intramedullary nail and then subsequently suffered a pathologic fracture of the proximal femur. To our knowledge, there have been no cases reported on a peri-implant pathologic fracture proximal to a retrograde intramedullary nail in the setting of metastatic bone disease. We would like to share our experience on how to surgically manage this and discuss the literature around management of distal femoral bone metastases.

A Systematic Review of the Efficacy and Safety of Tranexamic Acid in Facelift Surgery.

Tranexamic acid (TXA) has become widely utilized in different specialities including facelift surgery. The aim of this review was to robustly evaluate the quality of available evidence on the efficacy and safety of TXA use in facelift surgery. We searched the MEDLINE (National Institutes of Health, Bethesda, MD), Embase (Elsevier, Amsterdam, the Netherlands), CINAHL (EBSCO Information Services, Ipswich, MA), Cochrane Central Register of Controlled Trials (CENTRAL; Wiley, Hoboken, NJ), Google Scholar (Alphabet Inc. Mountain View, CA), Science Citation Index (Clarivate, London, UK), and Latin American and Caribbean Center on Health Sciences Information (LILACS; São Paulo, Brazil) databases for randomized controlled trials (RCTs) and observational studies. Primary outcomes were blood loss, postoperative hematoma, ecchymosis, and swelling, in addition to technical considerations and complications. We assessed review quality with the AMSTAR 2 tool, study quality with Grading of Recommendations, Assessment, Development, and Evaluations approach (GRADE) tool, and the risk of bias with Cochrane's RoB 2.0 tool for RCTs and ROBINS-I for nonrandomized studies. Of the 368 articles, a total of 3 studies including 150 patients met the inclusion criteria. The RCT reported a significant reduction in postoperative serosanguineous collections in the TXA group (P < .01), and in surgeon-rated postoperative ecchymosis and bruising. The prospective cohort study reported reduced drainage output in first 24 hours in the TXA group (P < .01). The retrospective cohort study reported lower intraoperative blood loss, mean postoperative day 1 drain output, percentage of drain removal on postoperative day 1, and number of days to drain removal in the TXA group (all P < .01). The quality of studies was moderate, and this review was the highest rated compared to previous reviews, as per the AMSTAR 2 tool. Based on limited literature, TXA improves clinical outcomes regardless of the route of administration. Topical TXA is an emerging route, expediting drain removal and reducing blood loss. Future Level I high-quality studies are required.

Frequency of visual involvement in a 10-year interdisciplinary cohort of patients with giant cell arteritis.

BACKGROUND: We present the largest study of the frequency and nature of visual complications in a cohort of 350 patients consecutively diagnosed with giant cell arteritis (GCA). METHODS: All individuals were assessed using structured forms and diagnosed using imaging or biopsy. A binary logistic regression model was used to analyse data for predicting visual loss. RESULTS: Visual symptoms occurred in 101 (28.9%) patients, with visual loss in one or both eyes in 48 (13.7%) patients. Four patients had binocular visual loss. Anterior ischaemic optic neuropathy (N=31), retinal artery obstruction (N=8) and occipital stroke (N=2) were the main causes of visual loss. Of the 47 individuals who had repeat visual acuity testing at 7 days, three individuals had improvement to 6/9 or better. After introducing the fast-track pathway, the frequency of visual loss decreased from 18.7% to 11.5%. Age at diagnosis (odds ratio (OR) 1.12) and headache (OR 0.22) were significant determinants of visual loss in a multivariate model. Jaw claudication trended to significance (OR 1.96, p=0.054). CONCLUSIONS: We recorded a visual loss frequency of 13.7% in the largest cohort of patients with GCA examined from a single centre. Although improvement in vision was rare, a dedicated fast-track pathway reduced visual loss. Headache could result in earlier diagnosis and protect against visual loss.

Novel Scoring Criteria for Preoperative Prediction of Neoadjuvant Chemotherapy Response in Osteosarcoma.

Background: The extent of tumor necrosis after neoadjuvant chemotherapy is an important predictive factor of survival in osteosarcoma. However, the response to chemotherapy is not known until after the definitive resection and limits the utility of this information for operative planning. Our study questions include: 1) Are there clinical and radiographic factors following neoadjuvant chemotherapy, but prior to the tumor resection, that may aid in predicting response to treatment? 2) Can we combine these criteria into a predictive composite score that can identify good and poor responders to chemotherapy? Methods: We identified consecutive patients diagnosed with osteosarcoma and managed with neoadjuvant chemotherapy prior to surgical resection. We assessed post-chemotherapy tumor ossification, tumor size and growth, and the presence of pain to devise a scoring criteria to predict the percent necrosis on the final histologic specimen. Bivariate analyses were done, and a receiver operating characteristic curve was constructed to determine predictive capacity. Results: Out of the 40 patients included in this study, 15 (38%) had a good response (≥ 90% necrosis) to treatment and ten patients (25%) had a poor response with ≤ 50% necrosis. Tumor size, growth and increase in ossification were significantly associated with a good response to treatment. For good responders, a composite score of 6 was seen to attain the highest sensitivity and specificity, 100% and 84%, respectively. Tumor size, no change in ossification, and post-chemotherapy pain were significantly associated with a poor response to treatment. For poor responders, a composite score of 7 was seen to have the highest sensitivity and specificity, 100% and 63%, respectively. Conclusion: Compared to the use of one single factor, our combined scoring criteria demonstrated a far improved accuracy in identifying good responders to neoadjuvant chemotherapy, where a score of 6 or less is predictive of a good response. However, the specificity of this scoring criteria to predict poor responders was low, indicating that this criterion may not be the most accurate method to identify poor responders. The utility of this score has implications regarding pre-operative counseling of the patient and operative planning.Level of Evidence: III.

Is local recurrence in bone and soft tissue sarcomas just a local recurrence or does it impact the overall survival, retrospective cohort from a sarcoma referral center.

BACKGROUND AND OBJECTIVES: Sarcoma local recurrence (LR) is often associated with metastasis, but it is unclear if LR can be a causal event leading to metastasis. We question if LR is best viewed as an independent oncologic event or as a worrisome harbinger threatening a patient's overall survival. METHODS: We identified patients with LR and/or metastasis from an ongoing cohort of 629 patients with primary sarcoma and performed a detailed review to assess the timing of metastasis resulting in the following groups: (1) Isolated LR, (2) LR before metastasis, (3) LR within 6 months of metastasis, (4) LR 6-12 months after metastasis, (5) LR >12 months after metastasis, and (6) metastasis at diagnosis. RESULTS: Overall, 43 patients met the inclusion criteria with an LR rate of 7%. Ten patients (2% of the entire cohort, 23% of LR) developed an LR before or within 6 months of metastasis. For patients without systemic disease preceding LR, 3 of 23 soft tissue sarcoma STS (13%) and 7 of 10 bone sarcoma (70%) subsequently developed metastasis (p < 0.01). CONCLUSION: LR with subsequent metastasis is a rare event. LR appears to be best viewed as a marker of tumor aggressiveness rather than the cause of metastasis and poor survival. LR in bone sarcoma patients should warn providers of a high risk of imminent metastasis.

What is the likelihood of nonpulmonary metastasis occurring in the absence of lung metastasis in bone and soft tissue sarcoma? A nested case-control from a sarcoma referral centre.

BACKGROUND AND OBJECTIVES: Nonpulmonary metastases (NPM) are rare, associated with a poorer prognosis, and maybe missed on conventional chest imaging for sarcoma surveillance. We determined (1) the proportion of NPM occurring in isolation or with synchronous or prior pulmonary metastases (PM), and (2) if initial NPM would have been recognized with a standard surveillance protocol. METHODS: Investigators identified patients who developed initial NPM without prior evidence of or concurrent PM from an ongoing cohort of bone and soft tissue sarcoma (STS) patients. Logistic regression at univariate level was done. RESULTS: There were 138/630 (22%) patients with metastasis and 66 (10%) had NPM: 50 (8%) patients had PM presenting first, while 16 (3%) had initial NPM. Malignant peripheral nerve sheath tumor, angiosarcoma, rhabdomyosarcoma, synovial sarcoma, and myxoid liposarcoma were six times more likely to develop initial NPM than other subtypes of STS with odds ratio = 6 (95% confidence interval: 1.93-18.65, p value < 0.01). Chest imaging and physical examination were sufficient to identify NPM in all except three bone sarcoma patients. CONCLUSIONS: Patients who develop initial NPM are rare and demonstrate a predilection towards some subtypes of extremity sarcoma. They develop oligometastatic disease, which may be amenable for surgical excision. All isolated or initial NPM in STS patients were discovered by physical examination and standard chest imaging.

Gestational intermittent hyperoxia rescues murine genetic congenital heart disease in part.

Cardiac development is a dynamic process, temporally and spatially. When disturbed, it leads to congenital cardiac anomalies that affect approximately 1% of live births. Genetic variants in several loci lead to anomalies, with the transcription factor NKX2-5 being one of the largest. However, there are also non-genetic factors that influence cardiac malformations. We examined the hypothesis that hyperoxia may be beneficial and can rescue genetic cardiac anomalies induced by an Nkx2-5 mutation. Intermittent mild hyperoxia (40% PO2) was applied for 10 h per day to normal wild-type female mice mated with heterozygous Nkx2-5 mutant males from gestational day 8.5 to birth. Hyperoxia therapy reduced excessive trabeculation in Nkx2-5 mutant mice compared to normoxic conditions (ratio of trabecular layer relative to compact layer area, normoxia 1.84 ± 0.07 vs. hyperoxia 1.51 ± 0.04) and frequency of muscular ventricular septal defects per heart (1.53 ± 0.32 vs. 0.68 ± 0.15); however, the incidence of membranous ventricular septal defects in Nkx2-5 mutant hearts was not changed. Nkx2-5 mutant embryonic hearts showed defective coronary vessel organization, which was improved by intermittent mild hyperoxia. The results of our study showed that mild gestational hyperoxia therapy rescued genetic cardiac malformation induced by Nkx2-5 mutation in part.

Association of LOXL1 gene common sequence variants in Jordanian patients with exfoliation syndrome and exfoliative glaucoma.

AIM: To investigate the association between single nucleotide polymorphisms (SNPs) in the LOXL1 gene with exfoliation syndrome/glaucoma (XFS/XFG) among Jordanians. METHODS: Sixty-one patients with XFS/XFG and 59 healthy control individuals were recruited in the study. Patients were diagnosed with XFS/XFG using standard clinical examination techniques. The exonic rs1048661 SNP and the intronic rs2165241 SNP in LOXL1 gene were genotyped using sequencing technique. Allele and genotype frequencies were compared between cases and controls using Chi-square analysis. RESULTS: The G allele of the rs1048661 SNP and the T allele of the rs2165241 SNP were common in the sample with frequencies of 86.4% and 81.4%, respectively. In addition, there were no significant differences in the genotypic and allelic distributions between patients and controls for rs1048661 SNP (P=0.770, OR=1.21, 95%CI: 0.56-2.60) and for rs2165241 SNP (P=0.605, OR=1.12, 95%CI: 0.59-2.09). In addition, no significant associations were found between haplotypes of the examined SNPs and XFS/XFG in the sample (P>0.05). CONCLUSION: Variations in LOXL1 gene may not be associated with XFS/XFG in the Jordanian population. More studies are required to confirm the current findings.

Mechanism Sharing Between Genetic and Gestational Hypoxia-Induced Cardiac Anomalies.

Background: Cardiac development is a dynamic process both temporally and spatially. These complex processes are often disturbed and lead to congenital cardiac anomalies that affect approximately 1% of live births. Disease-causing variants in several genetic loci lead to cardiac anomalies, with variants in transcription factor NKX2-5 gene being one of the largest variants known. Gestational hypoxia, such as seen in high-altitude pregnancy, has been known to affect cardiac development, yet the incidence and underlying mechanisms are largely unknown. Methods and Results: Normal wild-type female mice mated with heterozygous Nkx2-5 mutant males were housed under moderate hypoxia (14% O2) or normoxia (20.9% O2) conditions from 10.5 days of gestation. Wild-type mice exposed to hypoxia demonstrate excessive trabeculation, ventricular septal defects, irregular morphology of interventricular septum as well as atrial septal abnormalities, which overlap with those seen in heterozygous Nkx2-5 mutant mice. Genome-wide transcriptome done by RNA-seq of a 2-day hypoxic exposure on wild-type embryos revealed abnormal transcriptomes, in which approximately 60% share those from Nkx2-5 mutants without hypoxia. Gestational hypoxia reduced the expression of Nkx2-5 proteins in more than one-half along with a reduction in phosphorylation, suggesting that abnormal Nkx2-5 function is a common mechanism shared between genetic and gestational hypoxia-induced cardiac anomalies, at least at a specific developing stage. Conclusion: The results of our study provide insights into a common molecular mechanism underlying non-genetic and genetic cardiac anomalies.

A CASE OF FULL-THICKNESS MACULAR HOLE IN EYE WITH FOCAL CHOROIDAL EXCAVATION.

PURPOSE: To report an association between a Stage 4 full-thickness macular hole and focal choroidal excavation. METHODS: Case report. RESULTS: A 46-year-old male patient with high myopia was referred for macular hole surgery and found to have an associated focal choroidal excavation. The patient underwent uneventful combined procedure with closure of macular hole. CONCLUSION: Successful macular hole surgery can be achieved even in the presence of focal choroidal excavation.

Incidence of bullous pemphigoid and mortality of patients with bullous pemphigoid in Olmsted County, Minnesota, 1960 through 2009.

BACKGROUND: Bullous pemphigoid (BP) is an autoimmune blistering disease that is associated with increased mortality. OBJECTIVE: We sought to determine the incidence and mortality of patients with BP. METHODS: A total of 87 residents of Olmsted County, Minnesota, were identified who had their first lifetime diagnosis of BP from January 1960 through December 2009. Incidence and mortality were compared with age- and sex-matched control patients from the same geographic area. RESULTS: The adjusted incidence of BP was 2.4 per 100,000 person-years (95% confidence interval, 1.9-2.9). Incidence of BP increased significantly with age (P < .001) and over time (P = .034). Trend tests indicate increased diagnosis of localized disease (P = .006) may be a contributing factor. Survival observed in the incident BP cohort was significantly poorer than expected (P < .001). Survival was not different among patients with multisite versus localized disease (P = .90). LIMITATIONS: Retrospective study design and study population from a small geographic area are limitations. CONCLUSION: Incidence of BP in the United States is comparable with that found in Europe and Asia. The mortality of BP is lower in the United States than Europe, but higher than previous estimates.

Prevalence and determinants of diabetic retinopathy among persons ≥ 40 years of age with diabetes in Qatar: a community-based survey.

PURPOSE: We present the prevalence and determinants of diabetic retinopathy (DR) in persons 40 years and older with diabetes in Qatar. METHODS: This community-based survey was held in 2009 at 49 randomly selected clusters. Demographic details and history of diabetes mellitus (DM) and its management were collected by nurses. Ophthalmologists examined the retina by slit-lamp biomicroscopy using +90 D lens and/or indirect ophthalmoscopy. Digital photographs of retina were obtained. The best-corrected visual acuity of each eye was noted. Diabetic retinopathy was graded as mild, moderate, or severe nonproliferative DR, proliferative DR, or diabetic macular edema. RESULTS: We examined 540 (97.3%) participants with DM. Diabetes mellitus status of 487 persons could be confirmed from medical records. The age- and sex-adjusted prevalence of DR among the diabetic population 40 years and older was 23.5% (95% confidence interval [CI] 19.7-27.3), with 8192 cases of DR among patients with DM. Longer duration of diabetes (odds ratio 1.14 [95% CI 1.10-1.19]) and poor glycemic control (odds ratio 1.12 [95% CI 1.02-1.23]) were risk factors for DR. Awareness of regular eye checkup was found in 62% of participants. Only 20% of persons with sight-threatening DR had undergone laser treatment in at least 1 eye. Visual acuity in the better eye was 6/6 to 6/18 in 90% of persons with DR. CONCLUSIONS: Universal and periodic eye screening of patients with diabetes is recommended in Qatar. Health promotion for primary prevention and resource review are needed for early detection and management of sight-threatening DR.

Current concepts in intravitreal drug therapy for diabetic retinopathy.

Diabetic retinopathy (DR) is a major cause of preventable blindness in the developed countries. Despite the advances in understanding and management of DR, it remains a challenging condition to manage. The standard of care for patients with DR include strict metabolic control of hyperglycemia, blood pressure control, normalization of serum lipids, prompt retinal laser photocoagulation and vitrectomy. For patients who respond poorly and who progressively lose vision in spite of the standard of care, intravitreal administration of steroids or/and anti-vascular endothelial growth factor (anti-VEGF) drugs appear to be a promising second-line of therapy. This review discusses the current concepts and the role of these novel therapeutic approaches in the management of DR.