Comparative outcomes after treatment of peri-implant, periprosthetic, and interprosthetic femur fractures: which factors increase mortality risk?

Objectives: To compare mortality rates between patients treated surgically for periprosthetic fractures (PPF) after total hip arthroplasty (THA), total knee arthroplasty (TKA), peri-implant (PI), and interprosthetic (IP) fractures while identifying risk factors associated with mortality following PPF. Design: Retrospective. Setting: Single, Level II Trauma Center. Patients/Participants: A retrospective review was conducted of 129 consecutive patients treated surgically for fractures around a pre-existing prosthesis or implant from 2013 to 2020. Patients were separated into 4 comparison groups: THA, TKA, PI, and IP fractures. Intervention: Revision implant or arthroplasty, open reduction and internal fixation (ORIF), intramedullary nailing (IMN), percutaneous screws, or a combination of techniques. Main Outcome Measurements: Primary outcome measures include mortality rates of different types of PPF, PI, and IP fractures at 1-month, 3-month, 6-month, 1-year, and 2-year postoperative. We analyzed risk factors associated with mortality aimed to determine whether treatment type affects mortality. Results: One hundred twenty-nine patients were included for final analysis. Average follow-up was similar between all groups. The overall 1-year mortality rate was 1 month (5%), 3 months (12%), 6 months (13%), 1 year (15%), and 2 years (22%). There were no differences in mortality rates between each group at 30 days, 90 days, 6 months, 1 year, and 2 years (P-value = 0.86). A Kaplan-Meier survival curve demonstrated no difference in survivorship up to 2 years. Older than 65 years, history of hypothyroidism and dementia, and discharge to a skilled nursing facility (SNF) led to increased mortality. There was no survival benefit in treating patients with PPFs with either revision, ORIF, IMN, or a combination of techniques. Conclusion: The overall mortality rates observed were 1 month (5%), 3 months (12%), 6 months (13%), 1 year (15%), and 2 years (22%), and no differences were found between each group at all follow-up time points. Patients aged 65 and older with a history of hypothyroidism and/or dementia discharged to an SNF are at increased risk for mortality. From a mortality perspective, surgeons should not hesitate to choose the surgical treatment they feel most comfortable performing. Level of Evidence: Level III.

Identification of concomitant injuries associated with specific spine level fractures in polytrauma patients.

INTRODUCTION: Spine fractures are associated with high energy mechanisms and can lead to substantial morbidity and mortality in the trauma setting. Rapid identification and treatment of these fractures and their associated injuries are paramount in preventing adverse outcomes. The purpose of this study is to identify concomitant skeletal and non-skeletal injuries related to cervical, thoracic, and lumbar fractures. METHODS: A retrospective review of institutional American College of Surgeons (ACS) registry was conducted on 3,399 consecutive trauma patients identifying those with spine fractures from 1/2016-12/2019. Two-hundred ninety patients were included(8.5%) and separated into three groups based on fracture location: eighty-eight cervical(C)-spine, 129thoracic(T)-spine, and 143lumbar(L)-spine. Logistic regression analyses were performed to identify associated injuries, presenting injury severity score(ISS) and Glasgow coma scale(GCS), mechanism of injury, demographic data, substance use, and paralysis for each group. Cox hazard regression was utilized to identify factors associated with inpatient mortality. RESULTS: C-spine fractures were associated with head trauma(OR2.18,p = 0.003),intracranial bleeding (OR2.64,p = 0.001),facial(OR2.25,p = 0.02) and skull fractures(OR3.92,p = 0.001),and cervical cord injuries(OR4.78,p = 0.012). T-spine fractures were associated with rib fractures(OR2.31,p = 0.003). L-spine fractures were associated with rib(OR1.77, p = 0.04), pelvic(OR5.11,p<0.001), tibia/fibula (OR2.31,p = 0.05), and foot/ankle fractures(OR3.32,p = 0.04), thoracic(OR2.43,p = 0.008) and retroperitoneal cavity visceral injuries(OR27.3,p = 0.001). Falls≤6meters were also significantly associated with C-spine fractures(OR1.70,p = 0.04) while falls>6meters were associated with L-spine fractures(OR4.30,p = 0.001). Inpatient mortality risk increased in patients with C-spine fractures(HR4.41,p = 0.002), higher ISS(HR1.05, p<0.001), and lower GCS(HR0.85,p<0.001). Last, patients≥65-years-old were more likely to experience C-spine fractures(OR1.88,p = 0.03). CONCLUSION: Patients who experience fractures of the cervical, thoracic, or lumbar spine are at risk for additional fractures, visceral injury, and/or death. Awareness of the associations between spinal fractures and other injuries can increase diagnostic efficacy, improve patient care, and provide valuable prognostic information. These associations highlight the importance of effective and timely communication and multidisciplinary collaboration.

Esophagopharyngeal perforation and prevertebral abscess after anterior cervical discectomy and fusion: a case report.

Anterior cervical discectomy and fusion (ACDF) represents one of the most commonly performed spine surgeries. Dysphagia secondary to esophageal injury during retraction is one of the most common complications, and usually leads to self-limiting dysphagia. However, actual perforation and violation of the esophageal tissue is much rarer and can lead to delayed deep infections. Prevertebral abscess' are one of the most feared complications after ACDF, as they can lead to severe tissue swelling, osteomyelitis, hardware failure, and even death. Due to their rarity, a gold standard of workup and treatment is still unknown. A healthy 47-year-old female presents 9 months after a C4-C7 ACDF done at an outside institution with a large prevertebral abscess, osteomyelitis, hardware failure, and pseudoarthrosis secondary to esophagopharyngeal defect and prominent hardware. Overall, the patient underwent eight surgeries, and required an extended course of intravenous (IV) antibiotics, multiple diagnostic procedures, and complex soft tissue coverage using an anterolateral thigh free flap. Currently, the patient is doing well 6 months from her last procedure without any complications or plan for future surgery. This was an extremely rare case of a late occurring prevertebral abscess after ACDF. Dysphagia in the late postoperative setting should be evaluated carefully and thoroughly for any esophageal perforation and deep infection. As exemplified in this case, even partial thickness injuries to the esophageal-pharyngeal anatomy due to hardware irrigation can lead to catastrophic complications over time. Safe removal of all hardware anteriorly to avoid continued irritation of the esophagopharyngeal mucosa should be prioritized. If anterior hardware is necessary for stability, implants with the smallest footprint should be utilized. Early collaboration with ENT colleagues should be a priority and can provide crucial diagnostic and therapeutic interventions. Complex closure with a free flap was shown to be an effective way to provide successful definitive soft tissue coverage.

Comparing Intramedullary Nailing Versus Locked Plating in the Treatment of Native Distal Femur Fractures: Is One Superior to the Other?

INTRODUCTION: Distal femur fractures make up < 1% of all fractures and 3-6% of all femur fractures. In the literature, both intramedullary nailing (IMN) and locked plating (LP) have shown favorable results, but there is no consensus on a gold standard. The purpose of this systematic review is to compare outcomes of native distal femur fractures treated via IMN versus LP in an effort to determine if one is superior to the other. METHODS: Systematic review of MEDLINE, EMBASE, and Cochrane Library databases was conducted according to PRISMA guidelines. Only articles published within the last ten years were included. Evidence and study quality were evaluated with the MQOE and Oxford Criteria. RESULTS: Forty-six articles were included in the review. Fractures treated with IMN were found to have a 93.9% union rate, an average time to union of 19.2 weeks, an average arc of motion of 105.1 degrees, with an average of 14.4 degrees of malalignment. Fractures treated with LP were found to have a 90.2% union rate, an average time to union of 20.5 weeks, an average arc of motion of 104 degrees, with an average of 12.6 degrees of malalignment. CONCLUSION: Compiled data comparisons revealed no differences in union rate, malalignment, time to union, average arc of motion, or complication rates requiring a return to the operating room. Until higher level randomized data is available, either IMN or LP are acceptable methods of treatment for native distal femur fractures.

A Newborn With Skin Lesions, Thrombocytopenia, and Gastrointestinal Bleeding.

A term infant girl was admitted for evaluation of severe thrombocytopenia. She also had purpura-like skin lesions. A complete blood count showed a platelet count of 40×10/L (normal value: 150 to 400×10/L). She received random donor platelet transfusions and intravenous immunoglobulin therapy; however, thrombocytopenia persisted. She developed bloody stools on day 5 of life and hematemesis on day 9. Upper gastrointestinal endoscopy revealed multiple small, 2 to 5 mm, vascular lesions throughout the stomach body and proximal duodenum. Our multidisciplinary team will discuss an approach towards a term infant with thrombocytopenia and gastrointestinal bleeding, the diagnostic challenges, and patient management.

Equivalent union rates between intramedullary nail and locked plate fixation for distal femur periprosthetic fractures - a systematic review.

BACKGROUND: The incidence of periprosthetic fracture following total knee arthroplasty continues to rise as the number of knee arthroplasty procedures increases. Management of periprosthetic fractures can be complex, with locked compression plating (LCP) and intramedullary nailing (IMN) being the most commonly used treatment options. We performed a systematic review to report and compare the clinical and radiographic outcomes of patients treated with intramedullary nail fixation versus plate fixation for periprosthetic fractures of the distal femur. METHODS: Several databases were screened. Studies evaluating intramedullary nail fixation or locked plate fixation for distal femur periprosthetic fractures were included. Primary and secondary variables as mentioned below, when included, were analyzed and compared. RESULTS: One prospective comparative study, 9 retrospective comparative studies, and 28 retrospective case series with 1,188 patients were included in this review. No statistically significant differences were found between IMN and LCP when analyzing union rate or time to union. Plating demonstrated a statistically significant decrease in the overall complication rate and reoperation rate when compared with IMN (p<0.003). IMN demonstrated a slightly higher percentage of patients reaching full weight bearing status and a quicker time to full weight bearing (100% and 7.6 weeks) when compared to plating (94% and 15.8 weeks). A higher percentage of patients treated with IMN returned to preinjury activity when compared to those treated with plating (70.8% vs. 61.6%). CONCLUSIONS: Both intramedullary nail and locked plate fixation offer unique benefits in terms of clinical and radiographic outcomes for treatment of periprosthetic distal femur fractures after total knee arthroplasty. While the standard of care remains controversial, an increase in the recent literature has allowed for better clarification of the significant clinicoradiologic advantages and disadvantages of both popular treatment options.

The cost-effectiveness of antibiotic-loaded bone cement versus plain bone cement following total and partial knee and hip arthroplasty.

BACKGROUND: Postoperative infection is one of the most prevalent complications following total joint arthroplasty (TJA). As such procedures become more prevalent, it is imperative that we develop new prophylactic methods to prevent the need for revision procedures. In recent years, surgeons have opted to use antibiotic-loaded bone cement (ALBC) rather than plain bone cement (PBC) in primary hip and knee replacements due to its theoretical potential of lowering infection rates. However, the cost-effectiveness of this intervention remains in question.Questions/Purposes: To determine the rate of infection and cost-effectiveness of antibiotic-loaded bone cement as compared to plain bone cement in hip and knee arthroplasty. PATIENTS AND METHODS: We reviewed 4116 primary hip and knee arthroplasty cases performed between 2016 and 2018 at Morristown Medical Center in New Jersey. Data regarding demographics, complications, and any readmissions due to deep infection were collected retrospectively. During that time period there were a total of 4016 knee cases (423 ALBC, 3593 PBC) and 123 hip cases (63 ALBC, 60 PBC). The average cost for one bag of antibiotic-loaded bone cement and plain bone cement for hip and knee arthroplasty was $336.42 and $72.14, respectively. A statistical analysis was performed using Fisher's exact test; the National Healthcare Safety Network (NHSN) surgical site infection guidelines were used to distinguish between superficial and deep infections. RESULTS: Ten patients were readmitted due to deep infection, all of whom had undergone total knee arthroplasty. Of those cases, plain bone cement was used for the index procedure in seven instances and antibiotic-loaded cement was used in three. This resulted in an infection rate of 0.19% and 0.62%, respectively, p = 0.103. There was no statistically significant difference in infection rates between the two groups. A total of 778 bags of ALBC were used in 423 knee surgeries, and 98 bags of ALBC were used in 63 hip cases. The total cost for ALBC in TKA and THA procedures was $261,734.76 (778*336.42) and $32,969.16 (98*336.42), respectively. If PBC had been used during all index procedures, it would have resulted in a total savings of $231,509.28. CONCLUSIONS: Antibiotic-loaded cement did not significantly reduce the rate of infection for either knee or hip arthroplasty. Thus, the routine use of antibiotic-loaded cement in primary hip and knee arthroplasty may be an unnecessary financial burden to the healthcare system. A larger sample size and a randomized controlled trial would help confirm our findings and would provide further information on the cost-effectiveness of ALBC cement versus PBC.Significance/Clinical Relevance: In this review of cases performed from 2016 to 2018 there was no statistically significant difference between the rate of infection and the need for revision surgeries for patients treated with ALBC versus PBC. As hospital systems continue to transition towards a bundled payment model, it becomes imperative for providers to reduce any unnecessary costs in order to increase quality and efficiency. We estimate that our hospital system could save nearly $120,000/year by using plain bone cement instead of antibiotic-loaded cement.

Expression of phytoglobin affects nitric oxide metabolism and energy state of barley plants exposed to anoxia.

Class 1 plant hemoglobins (phytoglobins) are upregulated during low-oxygen stress and participate in metabolism and cell signaling via modulation of the levels of nitric oxide (NO). We studied the effects of overexpression and knockdown of the class 1 phytoglobin gene in barley (Hordeum vulgare L.) under low-oxygen stress. The overexpression of phytoglobin reduced the amount of NO released, while knockdown significantly stimulated NO emission. It has previously been shown that NO inhibits aconitase activity, so decreased aconitase activity in knockdown plants acts as a biomarker for high internal NO levels. The overexpression of phytoglobin corresponded to higher ATP/ADP ratios, pyrophosphate levels and aconitase activity under anoxia, while knockdown of phytoglobin resulted in the increased level of protein nitrosylation, elevation of alcohol dehydrogenase and nitrosoglutathione reductase activities. The overexpressing plants showed various signs of stunted growth under normoxia, but were the only type to germinate and survive under hypoxia. The results show that overexpression of phytoglobin protects plant cells via NO scavenging and improves their low-oxygen stress survival. However, it may not be useful for cereal crop improvement since it comes with a significant interference with normoxic NO signalling pathways.

An assessment of the biotechnological use of hemoglobin modulation in cereals.

Non-symbiotic hemoglobin (nsHb) genes are ubiquitous in plants, but their biological functions have mostly been studied in model plant species rather than in crops. nsHb influences cell signaling and metabolism by modulating the levels of nitric oxide (NO). Class 1 nsHb is upregulated under hypoxia and is involved in various biotic and abiotic stress responses. Ectopic overexpression of nsHb in Arabidopsis thaliana accelerates development, whilst targeted overexpression in seeds can increase seed yield. Such observations suggest that manipulating nsHb could be a valid biotechnological target. We studied the effects of overexpression of class 1 nsHb in the monocotyledonous crop plant barley (Hordeum vulgare cv. Golden Promise). nsHb was shown to be involved in NO metabolism in barley, as ectopic overexpression reduced the amount of NO released during hypoxia. Further, as in Arabidopsis, nsHb overexpression compromised basal resistance toward pathogens in barley. However, unlike Arabidopsis, nsHb ectopic overexpression delayed growth and development in barley, and seed specific overexpression reduced seed yield. Thus, nsHb overexpression in barley does not seem to be an efficient strategy for increasing yield in cereal crops. These findings highlight the necessity for using actual crop plants rather than laboratory model plants when assessing the effects of biotechnological approaches to crop improvement.

The role of nitric oxide and hemoglobin in plant development and morphogenesis.

Plant morphogenesis is regulated endogenously through phytohormones and other chemical signals, which may act either locally or distant from their place of synthesis. Nitric oxide (NO) is formed by a number of controlled processes in plant cells. It is a central signaling molecule with several effects on control of plant growth and development, such as shoot and root architecture. All plants are able to express non-symbiotic hemoglobins at low concentration. Their function is generally not related to oxygen transport or storage; instead they effectively oxidize NO to NO(3)(-) and thereby control the local cellular NO concentration. In this review, we analyze available data on the role of NO and plant hemoglobins in morphogenetic processes in plants. The comparison of the data suggests that hemoglobin gene expression in plants modulates development and morphogenesis of organs, such as roots and shoots, through the localized control of NO, and that hemoglobin gene expression should always be considered a modulating factor in processes controlled directly or indirectly by NO in plants.

Respiratory complex I deficiency results in low nitric oxide levels, induction of hemoglobin and upregulation of fermentation pathways.

The cytoplasmic male-sterile (CMS) mutant of Nicotiana sylvestris which lacks NAD7, one of the subunits of respiratory complex I (NADH: ubiquinone oxidoreductase, EC 1.6.5.3), is characterized by very low (~10 times lower as compared to the wild type plants) emissions of nitric oxide (NO) under hypoxic conditions. The level of the non-symbiotic class 1 hemoglobin, as shown by Western blotting, is increased compared to the wild type plants not only under hypoxia but this protein reveals its marked expression in the CMS mutant even under normoxic conditions. The activity of aconitase (EC 4.2.1.3) is low in the CMS mutant, especially in the mitochondrial compartment, which indicates the suppression of the tricarboxylic acid cycle. The CMS mutant exhibits the severalfold higher activities of alcohol dehydrogenase (EC 1.1.1.1) and lactate dehydrogenase (EC 1.1.1.27) under the normoxic conditions as compared to the wild type plants. It is concluded that the lack of functional complex I results in upregulation of the pathways of hypoxic metabolism which include both fermentation of pyruvate and scavenging of NO by the non-symbiotic hemoglobin.

Inhibition of aconitase by nitric oxide leads to induction of the alternative oxidase and to a shift of metabolism towards biosynthesis of amino acids.

Nitric oxide (NO) is a free radical molecule involved in signalling and in hypoxic metabolism. This work used the nitrate reductase double mutant of Arabidopsis thaliana (nia) and studied metabolic profiles, aconitase activity, and alternative oxidase (AOX) capacity and expression under normoxia and hypoxia (1% oxygen) in wild-type and nia plants. The roots of nia plants accumulated very little NO as compared to wild-type plants which exhibited ∼20-fold increase in NO emission under low oxygen conditions. These data suggest that nitrate reductase is involved in NO production either directly or by supplying nitrite to other sites of NO production (e.g. mitochondria). Various studies revealed that NO can induce AOX in mitochondria, but the mechanism has not been established yet. This study demonstrates that the NO produced in roots of wild-type plants inhibits aconitase which in turn leads to a marked increase in citrate levels. The accumulating citrate enhances AOX capacity, expression, and protein abundance. In contrast to wild-type plants, the nia double mutant failed to show AOX induction. The overall induction of AOX in wild-type roots correlated with accumulation of glycine, serine, leucine, lysine, and other amino acids. The findings show that NO inhibits aconitase under hypoxia which results in accumulation of citrate, the latter in turn inducing AOX and causing a shift of metabolism towards amino acid biosynthesis.

Anoxic nitric oxide cycling in plants: participating reactions and possible mechanisms.

At sufficiently low oxygen concentrations, hemeproteins are deoxygenated and become capable of reducing nitrite to nitric oxide (NO), in a reversal of the reaction in which NO is converted to nitrate or nitrite by oxygenated hemeproteins. The maximum rates of NO production depend on the oxygen avidity. The hemeproteins with the highest avidity, such as hexacoordinate hemoglobins, retain oxygen even under anoxic conditions resulting in their being extremely effective NO scavengers but essentially incapable of producing NO. Deoxyhemeprotein-related NO production can be observed in mitochondria (at the levels of cytochrome c oxidase, cytochrome c, complex III and possibly other sites), in plasma membrane, cytosol, endoplasmic reticulum and peroxisomes. In mitochondria, the use of nitrite as an alternative electron acceptor can contribute to a limited rate of ATP synthesis. Non-heme metal-containing proteins such as nitrate reductase and xanthine oxidase can also be involved in NO production. This will result in a strong anoxic redox flux of nitrogen through the hemoglobin-NO cycle involving nitrate reductase, nitrite: NO reductase, and NO dioxygenase. In normoxic conditions, NO is produced in very low quantities, mainly for signaling purposes and this nitrogen cycling is inoperative.