1. General Principles & Basic Science MCQs

DISCUSSION: Septic shock is associated with decreased systemic vascular resistance, decreased cardiac output, decreased pulmonary capillary wedge pressure, decreased central venous pressure, and decreased mixed venous oxygen saturation. Septic shock is different from hypovolemic shock in that the systemic vascular resistance is decreased, whereas it is increased in hypovolemic shock. Septic shock is a medical emergency caused by decreased tissue perfusion and oxygen delivery as a result of severe infection and sepsis, though the microbe may be systemic or localized to a particular site. It can cause multiple organ dysfunction syndrome (formerly known as multiple organ failure) and death. Its most common victims are children, immunocompromised individuals, and the elderly, as their immune systems cannot deal with the infection as effectively as those of healthy adults. The mortality rate from septic shock is reported to be 25%-50%.

Which of the following statistical tools is used to determine responsiveness?The only accurate statement is that, at 1 month, patients in group 3 are more likely to live longer than patients in group 1 and 2.The Kaplan-Meier curve is a statistical method used in survivorship analysis to estimate survival rates at different time points. The horizontal axis depicts the time points and the vertical axis depicts the probability of survival. At a given time point, greater survivorship is demonstrated by higher values on the vertical axis.Kocher et al. reviewed clinical epidemiology and biostatistics relevant in orthopaedicsurgery. They reported that survivorship data are typically analyzed with use of the Kaplan-Meier method. This analysis is used when the actual date of the end point is known. A survivorship curve can be plotted to illustrate the percentage of patients still alive after the intervention.Petrie et al. reviewed statistics, terminology and the principles involved in simple data analysis, and outlines areas of medical statistics that have gainedprominence in recent years in orthopaedic papers. The authors provide an insight into some of the more common errors that occur in published orthopaedic journals and which are frequently encountered at the review stage in papers submitted to the Journal of Bone and Joint Surgery.Figure A depicts a Kaplan-Meier curve for 3 groups of patients undergoing 3 different interventions.Incorrect Answers:When evaluating patient-reported outcomes in spine surgery, the Patient- Reported Outcomes Measurement Information System (PROMIS) has been found to have what differences compared to other assessment tools?Communication failures have been associated with increased treatment costs, increased complications, and delays in patient care.The leading cause of medical errors, wrong-site surgeries, diagnostic delays and loss to follow-up is attributed to communication errors. Studies have shown that this directly leads to increased complications, increased treatment costs, and delays in patient care. In the surgical setting, the performance of the pre-surgical time-out affords clarification of the treatment plan, confirmation of the procedure and site, and an opportunity for the team to address any concerns.Weller et al. reviewed barriers to effective teamwork in healthcare delivery. They found that effective communication across all team members, inclusive training, and the creation of democratic teams can reduce treatment delays and minimize complications. They concluded that all team members should have a shared understanding of the situation when involved in patients care.Lingard et al. performed a prospective study determining the feasibility of a preoperative 10-item checklist discussion including nurses, surgeons, and anesthesiologists. They reported that the discussion usually took place prior to bringing the patient to the OR and took on average 3.5 minuted. Overall, the guided discussion was very well received by participants and provided an opportunity to inform providers of the patient's information to address potential problems. The authors cited that variations in workflow patterns as a potential barrier to widescale implementation of the checklist discussion.Incorrect answers:The outcomes of three novel interventions are investigated and the preliminary results are depicted in Figure A. Which of the following statements is most accurate?Linezolid acts to inhibit protein synthesis by preventing the formation of the initiation complex between the 30S and 50S subunits of the ribosome.Linezolid is a type of oxazolidinone, a relatively newer class of antibiotics that are active against multidrug-resistant staphylococci, streptococci, and enterococci. Although many antimicrobial agents affect or disrupt protein synthesis in bacteria, linezolid is unique in that it disrupts protein synthesis at its origin rather than later in the cascade. It achieves this by binding to the50S subunit of the bacterial ribosome, preventing the formation of the initiation complex.Swaney et al. performed a study to investigate the mechanism of action of linezolid. They found that linezolid inhibits the formation of the initiation complex in bacterial translation systems by preventing the formation of the N- formylmethionyl-tRNA-ribosome-mRNA ternary complex.Thompson et al. performed a study on the efficacy of various antibiotics in treating periprosthetic joint infections (PJI). They administered oral linezolid with or without oral rifampin, intravenous vancomycin with oral rifampin, intravenous daptomycin or ceftaroline with or without oral rifampin, oral doxycycline, or sham treatment at human- exposure doses for 6 weeks in a mouse model of PJI. They found that oral-only linezolid-rifampin and all intravenous antibiotic-rifampin combinations resulted in no recoverable bacteria and minimized reactive bone changes. Additionally, although oral linezolid was found to be the most effective monotherapy, all oral and intravenous antibiotic monotherapies failed to clear infection or prevent reactive bone changes.They concluded that the oral-only linezolid-rifampin option might reduce venous access complications and health-care costs.Illustration A is a diagram depicting the mechanism of action of various antibiotics.Incorrect Answers:50S subunit of the bacterial ribosome, preventing protein chain elongation by inhibiting peptidyl transferase activity of the ribosome.elongation by blocking aminoacyl translocation.Failure of effective communication in the surgical setting has been associated with what?Unfractionated heparin works in the coagulation cascade by promoting the ability of antithrombin III to inhibit factors IIa, III, Xa.Heparin works by binding to and enhancing the ability of antithrombin III to inhibit factors IIa, III, Xa. It is metabolized by the liver. The risks associated with the use of unfractionated heparin include bleeding and heparin induced thrombocytopenia (HIT). The reversal agent is protamine sulfate.Agnelli et al. reviewed direct thrombin inhibitors for the prevention of VTE after major orthopaedic surgery. They reported widespread use, however, limitations in the use of unfractionated heparin and low-molecular-weight heparins. They highlighted that direct thrombin inhibitors (Ximelagatran) inactivate thrombin without requiring any plasma cofactor, inhibit both freeand fibrin-bound thrombin, and do not appreciably bind to plasma proteins. They concluded that the features of rapid absorption, conversion, bioavailability, low variability, dose-time, food independency, and the predictable anticoagulant activity make direct thrombin inhibitors an attractive antithrombotic agent especially for prolonged out-of hospital prophylaxis.Kwong et al. reviewed the efficacy and safety of fondaparinux, a selective factor Xa inhibitor and reported its efficacy and safety in 4 phase III clinical trials. They reported fondaparinux usage resulted in an overall 55% decrease in the risk of venous thromboembolism (VTE) relative to the low-molecular- weight heparin enoxaparin without increasing the incidence of clinically relevant bleeding, which was similarly low for both agents. They concludedthat the superior efficacy of fondaparinux relative to enoxaparin is the result of its unique mechanism of action, clinical pharmacology.McLynn et al. investigated the risk factors and chemoprophylaxis for VTE in elective spine surgery. They reported that independent risk factors for VTE included greater age, male gender, increasing body mass index, dependent functional status, lumbar spine surgery, longer operative time, perioperative blood transfusion, longer length of stay, and other postoperativecomplications. The majority of patients received unfractioned heparin and they observed this did not significantly influence the rate of VTE, but was associated with a significant increase in hematoma requiring a return to the operating room. They concluded that there is insufficient evidence to support the routine use of chemoprophylaxis in low-risk patients, and recommended full consideration of risks and benefits after elective spine surgery.Figure A depicts the coagulation cascade, with the factor circled in red (IIa) being the target of unfractionated heparin, through its effect on antithrombin III.Incorrect Answers:Which of the following antibiotics acts to inhibit protein synthesis by preventing the formation of the initiation complex between the 30S and 50S subunits of the ribosome?Acetaminophen inhibits prostaglandin E2 production through its effect on interleukin-1 beta. It exerts its effects on the central nervous system.Multimodal pain management has become an increasingly important consideration in total joint arthroplasty recovery, namely in regard to minimizing opioid requirements while optimizing pain control and patient satisfaction. Given the negative side effects and increasing scrutiny on narcotic use, modalities that help to decrease post-operative narcotic requirements have become a major focus and include nonsteroidal anti- inflammatories, selective COX-2 inhibitors, gabapentinoids, local anesthetic blocks, and acetaminophen. Acetaminophen acts directly the central nervous system, providing both pain relief and antipyretic effects. It does so by inhibiting prostaglandin E2 production through the blockade of interleukin-1 beta.Jinnah et al. performed a comparison of two multimodal pain regimens used for postoperative pain control in total joint arthroplasty patients. They hypothesized that using a multimodal pain protocol focusing on periarticular injections including liposomal bupivacaine would have improved results when compared with a parenteral opioid- based regimen. They found a decrease in length of stay and rate of discharge to skilled nursing facilities with the implementation of a novel multimodal protocol. They concluded that a multimodal approach inclusive of periarticular injection can lead to a reducedlength of stay.Politi et al. performed a prospective randomized trial comparing the use of intravenous versus oral acetaminophen in total joint arthroplasty. They found that IV acetaminophen did not provide a significant difference in pain relief except within the first 0-4 hours. They concluded that IV acetaminophen does not provide a significant benefit when compared to the oral form, which is also less expensive.Incorrect Answers:Which of the following agents results in blood anticoagulation by exerting inhibitory effects on the factor circled in the color red in Figure A?Based on the stress-strain curve in Figure A, ceramic has the highest modulus of elasticity.Young's modulus is a measure of the stiffness (ability to resist deformation) of a material in the elastic zone that is calculated by measuring the slope of the stress-strain curve in the elastic zone. A higher modulus of elasticity indicates a stiffer material. Relative values of Young's modulus include: (1) ceramic, (2) alloy, (3) stainless steel, (4) titanium, (5)cortical bone, (6) matrix polymers, (7) PMMA, (8) polyethylene, (9) cancellous bone, (10) tendon/ligaments, and (11) cartilage.Lang et al. published a review on the use of ceramics in total hip replacement. They report that properties of ceramic which make it particularly attractive for this application include its hardness, high compression strength, and excellent wettability. However, its low fracture toughness and linear elastic behavior make it prone to breakage under stress.Figure A is a stress-strain curve, the slope of which is used to determine Young's modulus.Incorrect Answers:Which of the following medications work by inhibiting prostaglandin E2 production through interleukin-1 beta?A power analysis determines the minimum number of patients needed in a study to show a clinically significant difference. It should be performed before starting the study.Power is the probability of finding a significant association if one truly exists. It is defined as 1 minus the probability of a type 2 error (beta) and is generally set to 80% meaning that we are willing to accept a 20% chance of a type 2 error. A power analysis will determine the minimum number of patients that shows a clinically significant difference. The minimum number of patients should be determined prior to initiating a study. Calculation of power after a study has been completed is controversial and discouraged.Vavken et al. performed a review on the management of confounding in controlled orthopaedic trials. They report that confounding occurs when the effect of exposure of an outcome is distorted by a confounding factor and will lead to spurious effect estimates in clinical studies. They performed a cross- sectional study of a sample of controlled trials reported in the orthopaedic literature in 2006. They conclude that only 30 studies reported that the had a power analysis performed.Kocher et al. performed a review of clinical epidemiology and biostatistics as a primer for orthopedic surgeons. They report that a power analysis should be performed prior to initiating the study. This will ensure the study is appropriately powered and decrease the effects of chance. They conclude that when a study determines no significant effect the power of the study should be reported.Incorrect Answers:Based on the stress-strain curve in Figure A, which of the following materials has the highest modulus of elasticity?The World Health Organization (WHO) defines osteopenia as a bone mineral density (BMD) that is between 1 and 2.5 standard deviations below young normal (T-score of - 1 to -2.5).The WHO defines osteopenia as decreased BMD without fracture risk. Osteopenia is defined as a T-score of 1 to 2.5 standard deviations below young normals (-1 to -2.5), while osteoporosis is defined as a T-score of more than

Iliotibial band syndrome (ITBS) is a common cause of lateral knee pain in runners. Potential etiologies for the pain include repetitive friction, compression, and bursal inflammation. An Ober test is used to assess iliotibial band tightness. With the patient lying on the unaffected side, the affected leg is abducted and extended. The test result is positive if the examiner is unable to adduct the leg from this position. An MRI scan can be helpful in making the diagnosis, but a negative MRI scan does not rule out ITBS. Studies have reported increased signal intensity on T2-weighted images deep to the iliotibial band adjacent to the lateral epicondyle, with thickening of the iliotibial band. Nonsurgical treatment is most appropriate initially and involves activity modification, ice, anti-inflammatory medications, and stretching. Corticosteroid injection to the iliotibial bursa is also an option to treat acute pain. After the initial inflammation improves, a strengthening program is started. Multiple surgical procedures have been described for recalcitrant cases, including iliotibial band excision, Z-lengthening, and iliotibial band bursectomy.

DISCUSSION: The vascular supply to the medial and lateral menisci originates predominantly from the medial and lateral genicular arteries. The popliteal artery splits into the superior genicular, which splits into medial and lateral branches supplying the patellar cartilage and the posterior cruciate ligament. The middle genicular artery also supplies the anterior cruciate ligament, posterior cruciate ligament, and collateral ligaments. The inferior genicular splits into medial and lateral branches and supplies the menisci and other knee ligaments. Despite propagation of incorrect terminology, there is no superior or lateral genicular artery.

DISCUSSION: Adult articular cartilage has less than 5% of the synthesis rate of type II collagen than that seen in developing teenagers. Both synthesis and degradation of type II collagen in normal adult articular cartilage is very low compared to children. In osteoarthrosis, both synthesis and degradation are increased, but the collagen does not properly incorporate into the matrix.

This patient has ischiofemoral impingement, in which there is abnormal contact between the lesser trochanter and the lateral border of the ischium. Patients typically present with posteriorly based hip pain and do not respond to intra-articular diagnostic injections. Examination can demonstrate pain with long strides, pain with palpation over the area, as well as reproduction of symptoms with the patient in the contralateral decubitus position and taking the affected hip into passive extension (ischiofemoral impingement test). MRI demonstrates a narrowed ischiofemoral space, as well as increased signal within the quadratus femoris muscle. The diagnosis can be confirmed with a diagnostic injection into this area. Treatment is typically nonsurgical, with surgical intervention consisting of resection of the lessertrochanter reserved for refractory cases.

DISCUSSION: Intradiskal pressure is lowest when the patient is in the supine position. Sitting is associated with higher intradiskal pressures than standing. Flexion also increases intradiskal pressure. The combination of flexion and sitting produces the highest intradiskal pressure. Nachemson and Morris found that intradiskal pressure increases as position changes from lying supine, lying prone, standing, leaning forward, sitting, and sitting leaning forward. Twisting or straining in positions of relatively high intradiskal pressure may predispose patients to herniation of the intervertebral disk. Patients with a herniated disk may also notice their pain worsens with activities that increase the disk pressure, including the positions mentioned, or activities that increase intra-abdominal pressure (coughing, sneezing, straining).

DISCUSSION: Surgical fixation of a scapular neck fracture is performed via the Judet approach, a posterior approach to the scapula/glenoid. The internervous plane is between the infraspinatus (suprascapular nerve) and the teres minor (axillary nerve). As outlined by Ball et al, the posterior branch of the axillary nerve has intimate association with the inferior aspects of the glenoid and shoulder joint capsule, which may place it at particular risk during a posterior approach to the shoulder.

The kidneys are responsible for monitoring and regulating calcium homeostasis as well as for controlling levels of phosphate, magnesium, and other minerals. Thekidneys act both as target organs for parathyroid hormone (PTH) and for excreting it. The proximal convoluted tubules of the kidneys are the site of production of 1,25-dihydroxycholecalciferol (the active form of vitamin D following hydroxylation of 25-hydroxycholecalciferol catalyzed by 1-hydroxylase), the foremost regulator of intestinal calcium absorption. This hormone also promotes osteoclastic resorption of bone and the feedback inhibition of PTH synthesis. Modest changes in the efficacy of renal excretion dramatically alter the body's ability to maintain mineral homeostasis. Phosphate reduces urine calcium excretion through several extrarenal mechanisms. An increase in phosphate will directly stimulate PTH secretion and can reduce ionized calcium, also enhancing PTH secretion. The increased PTH will enhance calcium resorption. Phosphate will complex with calcium in the intestine, decreasing the amount of calcium for absorption. It can also complex with calcium in the bone and soft tissues, decreasing the filtered load of calcium. Decreased phosphate will result in hypercalcuria. There appears to be a direct effect of phosphate to decreased calcium reabsorption in the distal nephron.

DISCUSSION: The axillary nerve is located approximately 7cm from the tip of the acromion. The axillary nerve comes off the brachial plexus (middle trunk, posterior division, posterior cord) carrying fibers from C5 and C6. The axillary nerve travels through the quadrangular space with the posterior circumflex humeral artery and vein to innervate the teres minor and deltoid muscles and supply sensation over the lateral shoulder. Based on the knowledge of the course of the axillary nerve, and potential complications regarding the vascular supply to the humeral head with the delto-pectoral approach, some authors are suggesting deltoid-splitting approach to the proximal humerus for reduction and fixation of proximal humeral fractures.

The CT scans reveal an occipital-cervical dissociation with subluxation of the occipitocervical joints bilaterally. Definitive management should consist of an occipital-cervical fusion with instrumentation. Immobilization in a Philadelphia collar is inadequate for this highly unstable injury, and halo immobilization, while affording adequate temporary immobilization, is not appropriate definitive management for this ligamentous injury. The patient does not have an injury at C4-C5 or C6-C7.

The WHO Safe Surgery guidelines checklist requires that antibiotic prophylaxis be given within 60 minutes prior to skin incision. This check is performed between nurse, anesthetist and surgeon.Preoperative checks are necessary for patient safety. On the WHO checklist, critical preoperative check points for the surgeon include: site marking, patient consent, allergies, blood loss, antibiotic prophylaxis, critical and non-routine steps, case duration, and whether preoperative imaging is readily visible.The WHO Surgical Safety Checklist (see below) has 3 checkpoints: before induction of anesthesia, before skin incision, and before leaving the operating room.Haynes et al. prospectively collected data on the outcomes of 3733 patients before, and 3955 patients after introduction of the Surgical Safety Checklist in 8 hospitals in 8 cities. They found an improvement in death rate (1.5% before, 0.8% after) and inpatient complication rate (11.0% before, 7.0% after). They concluded that implementation of the checklist led to reduction in death and complication rates.Illustration A shows the WHO Surgical Safety Checklist. Incorrect Answers:

DISCUSSION: Anatomic studies indicate that the safe areas for screws are superior and posterior. The external iliac artery is at risk with anteromedial placement, and the sciatic nerve may be compromised by posterior inferior screw placement.

DISCUSSION: The patient has bowlegs associated with very wide physes, particularly noted at the hips. The widening of the growth plates is a classic sign of rickets; however, the normal levels of calcium, phosphorus, and alkaline phosphatase rule out both nutritional and hypophosphatemic rickets. Patients with nutritional rickets or hypophosphatemic rickets have hypophosphatemia and increased alkaline phosphatase levels. Jansen metaphyseal dysostosis has very severe radiographic findings that are not found in this patient; however, these radiographic findings are classic for Schmid metaphyseal dysostosis.

DISCUSSION: Teres minor originates from the middle third of the dorsal surface of the lateral border of the scapula. It is supplied by the axillary nerve (C5).

The prevalence of a disease is a measure of the number of cases of a disease at or during a specific time point or time period. In this case, the researcher wants to know the prevalence of disease on a given day. Incidence measures new cases of a disease or event per unit of time. Correlation coefficient is a measure of how 2 things correlate with one another, while relative risk is a statistical outcome that is often used in case-control or cohort studies to provide a measure of the risk of a particular disease occurring when a certain exposure has already occurred.

DISCUSSION: Rickets causes widening of the hypertrophic layer of the physis because of the failure of mineralization and vascular invasion. The other zones of the physis may be altered in other disease conditions but remain relatively unchanged in rickets.

Scurvy results from vitamin C deficiency. Metabolically, vitamin C deficiency produces a decrease in chondroitin sulfate synthesis (enzymatic impairment of the conversion of glucose to galactosamine) and a deficiency in collagen synthesis by impaired hydroxylation of proline. The greatest problem in collagen synthesis is seen in the metaphysis. The metaphyseal bone becomes weakened and microfracture, hemorrhage, debris, and fibrous tissue accumulates. Collapse of the metaphysis and continued lateral growth produces the typical spurs associated with scurvy.

Warfarin, which is dosed daily, can take 72 to 96 hours to reach therapeutic levels. It has a plasma half-life of 36 to 42 hours. Low-molecular heparins have a plasma half-life of 4 to 5 hours, and fondaparinux has a half-life of 17 to 21 hours. Warfarin will not affect the International Normalized Ratio (INR) until 2 to 3 days after it is given. Patients on chronic warfarin therapy should have treatment stopped 3 to 5 days before elective surgery to allow the INR to normalize.

The neurovascular theory of Charcot arthropathy postulates that autonomic neuropathy results in a loss of sympathetic control, leading to localized hyperemia and arteriovenous shunting. This hyperemia causes increased osteoclastic activity, active bone resorption, and subsequent osteopenia, making the bones highly susceptible to fracture and collapse with normal weight-bearing.