Following a Surgical Paradigm Shift Through the Adoption of Nerve Transfers Among Board-Eligible and Practicing Plastic Surgeons.

BACKGROUND: Nerve transfers represent a new paradigm in the treatment of nerve injuries. Their current level of adoption among surgeons is unknown. This study evaluates the incidence of nerve transfers on case logs of board-eligible plastic surgeons over the past 14 years and surveys practicing nerve surgeons regarding their use of this technique. METHODS: We queried the American Board of Plastic Surgery case log database for all nerve reconstruction Current Procedural Terminology codes from 2008 to 2021 and assessed trends and relationships between geographic region, examination year, and nerve transfer use. We surveyed nerve surgery professional societies to assess trends in practice, compared with a 2017 survey. RESULTS: A total of 1959 nerve reconstruction cases were logged by 738 candidates from 2008 to 2021. Twelve percent of cases included nerve transfers. The proportion of nerve transfer codes (Z = -11.57; P < .0001) and the proportion of candidates performing nerve transfers (Z = -9.21, P < .0001) increased over the study period. Nerve transfers were associated with geographic region (χ2 = 25.826, P = .0002), with most cases performed in the Midwest (26.4%). A higher proportion of practicing nerve surgeons reported performing nerve transfers in this survey than in our 2017 survey (χ2 = 16.7, P < .001). CONCLUSIONS: There has been an increase in nerve transfers logged in the past 14 years by board-eligible plastic surgeons, as well as increased use among currently practicing nerve surgeons. Although nerve transfer use is increasing among both plastic and orthopedic surgeons, a greater proportion of nerve reconstructions include nerve transfers in the plastic surgery cohort.

Calling on Sponsorship: Analysis of Speaker Gender Representation at Hand Society Meetings.

BACKGROUND: The paucity of leadership diversity in surgical specialties is well documented. Unequal opportunities for participation at scientific meetings may impact future promotions within academic infrastructures. This study evaluated gender representation of surgeon speakers at hand surgery meetings. METHODS: Data were retrieved from the 2010 and 2020 meetings of the American Association for Hand Surgery (AAHS) and American Society for Surgery of the Hand (ASSH). Programs were evaluated for invited and peer-reviewed speakers excluding keynote speakers and poster presentations. Gender was determined from publicly available sources. Bibliometric data (Hirsch index) for invited speakers were analyzed. RESULTS: In 2010 at the AAHS ( n = 142) and ASSH meetings ( n = 180), female surgeons represented 4% of the invited speakers and in 2020 increased to 15% at AAHS ( n = 193) and 19% at ASSH ( n = 439). From 2010 to 2020, female surgeon invited speakers had a 3.75-fold increase at AAHS and 4.75-fold increase at ASSH. Representation of female surgeon peer-reviewed presenters at these meetings was similar (2010 AAHS, 26%; and 2010 ASSH, 22%; 2020 AAHS, 23%; 2020 ASSH, 22%). The academic rank of women speakers was significantly lower ( P < 0.001) than for male speakers. At the assistant professor level, the mean Hirsch index was significantly lower ( P < 0.05) for female invited speakers. CONCLUSIONS: Although there was a significant improvement in gender diversity in invited speakers at the 2020 meetings compared with 2010, female surgeons remain underrepresented. Gender diversity is lacking at national hand surgery meetings, and continued effort and sponsorship of speaker diversity is imperative to curate an inclusive hand society experience.

Abductor Digiti Minimi and Anterior Interosseous to Ulnar Motor Nerve Transfer: The Super Turbocharge End-to-Side Transfer.

SUMMARY: Anterior interosseous nerve to ulnar motor nerve supercharged end-to-side (SETS) nerve transfer to restore intrinsic function is a recently adopted nerve transfer in severe ulnar neuropathy. Its success is predicated on the critical threshold number of axons innervating the intrinsic muscles. Given the relative expendability of the abductor digiti minimi (ADM) muscle and the critical function of the other intrinsic muscles, the authors modified their SETS transfer to redirect axons from the ADM to turbocharge the ulnar motor nerve to innervate the more critical intrinsic muscles. They refer to this procedure as a super turbocharged end-to-side (STETS) procedure. The ADM has been used previously as a muscle/tendon transfer for thumb opposition and more recently as a nerve transfer to reinnervate the thenar branch of the median nerve. Although current methods of assessment of reinnervation are likely unable to differentiate between contributions from the anterior interosseous nerve SETS versus ADM STETS transfer, this technique follows the fundamentals of modern nerve surgery, where directing the maximum number of nerve fibers in a timely fashion to the most critical target is paramount for the best functional recovery. The authors suggest that the STETS technique may optimize outcomes in ulnar neuropathy without additional patient morbidity.

Percutaneously introduced wireless intramuscular near-infrared spectroscopy device detects muscle oxygenation changes in porcine model of lower extremity compartment syndrome.

Serial examination and direct measurement of intracompartmental pressure (ICP) are suboptimal strategies for the detection of acute compartment syndrome (CS) because they are operator-dependent and yield information that only indirectly reflects intracompartmental muscle perfusion. As a result, instances of unnecessary fasciotomy and unrecognized CS are relatively common. Recently, near-infrared spectroscopy (NIRS)-based systems for compartment monitoring have generated interest as an adjunct tool. Under ideal conditions, NIRS directly measures the oxygenation of intracompartmental muscle (StO2 ), thereby obviating the challenges of interpreting equivocal clinical examination or ICP data. Despite these potential advantages, existing NIRS sensors are plagued by technical difficulties that limit clinical utility. Most of these limitations relate to their transcutaneous design that makes them susceptible to both interference from intervening skin/subcutaneous tissue, underlying hematoma, and instability of the skin-sensor interface. Here, we present a flexible, wireless, Bluetooth-enabled, percutaneously introducible intramuscular NIRS device that directly and continuously measures the StO2 of intracompartmental muscle. Proof of concept for this device is demonstrated in a swine lower extremity balloon compression model of acute CS, wherein we simultaneously track muscle oxygenation, ICP, and compartment perfusion pressure (PP). The observed StO2 decreased with increasing ICP and decreasing PP and then recovered following pressure reduction. The mean change in StO2 as the PP was decreased from baseline to 30 mmHg was -7.6%. The mean difference between baseline and nadir StO2 was -17.4%. Cross-correlations (absolute value) describing the correspondence between StO2 and ICP were >0.73. This novel intramuscular NIRS device identifies decreased muscle perfusion in the setting of evolving CS.

Patient-Reported Lower Extremity Outcomes Following Fibula or Medial Femoral Condyle Free Flaps for Upper Extremity Defects.

BACKGROUND: Free fibula flap (FFF) and medial femoral condyle (MFC) flap are commonly used for upper extremity osseous reconstruction, yet donor-site morbidity has never been systematically compared. METHODS: Patients who underwent an FFF or MFC for upper extremity extra-carpal osseous reconstruction at 3 academic hand centers were retrospectively identified. Only patients who underwent reconstruction for a defect in which either flap type is routinely used or has been described in the literature were deemed eligible. Patients who agreed to participate were asked to complete the Lower Extremity Functional Scale (LEFS) and Lower Limb Core Scale (LLCS). The reported population norm median score of LEFS is 77 points. The LLCS population norm mean score is 90.52 points. RESULTS: Twenty-one patients (10 MFC, 11 FFF) were enrolled. The median LEFS score for patients after MFC was 76 (interquartile range [IQR], 49-80) points and 75 (IQR, 56-79) points after FFF. The median LLCS score for patients after MFC was 96.4 (IQR, 87.9-100) points and 100 (IQR, 91-100) points after FFF. Median LEFS scores were slightly below the population norm, whereas median LLCS scores were above the norm for both FFF and MFC. All patients stated they would have the surgery again and that any dysfunction or pain in the leg was justified by the benefit in the arm. CONCLUSIONS: When considering whether to use an MFC or FFF for upper extremity reconstruction, both flap types appear to result in modest and comparable donor-site morbidity.

Intramuscular Microvascular Flow Sensing for Flap Monitoring in a Porcine Model of Arterial and Venous Occlusion.

BACKGROUND: Commercially available near infrared spectroscopy devices for continuous free flap tissue oxygenation (StO2) monitoring can only be used on flaps with a cutaneous component. Additionally, differences in skin quality and pigmentation may alter StO2 measurements. Here, we present a novel implantable heat convection probe that measures microvascular blood flow for peripheral monitoring of free flaps, and is not subject to the same issues that limit the clinical utility of near-infrared spectroscopy. METHODS: The intratissue microvascular flow-sensing device includes a resistive heater, 4 thermistors, a small battery, and a Bluetooth chip, which allows connection to a smart device. Convection of applied heat is measured and mathematically transformed into a measurement of blood flow velocity. This was tested alongside Vioptix T.Ox in a porcine rectus abdominis myocutaneous flap model of arterial and venous occlusion. After flap elevation, the thermal device was deployed intramuscularly, and the cutaneous T.Ox device was applied. Acland clamps were alternately applied to the flap artery and veins to achieve 15 minutes periods of flap ischemia and congestion with a 15 minutes intervening recovery period. In total, five devices were tested in three flaps in three separate pigs over 16 vaso-occlusive events. RESULTS: Flow measurements were responsive to both ischemia and congestion, and returned to baseline during recovery periods. Flow measurements corresponded closely with measured StO2. Cross-correlation at zero lag showed agreement between these two sensing modalities. Two novel devices tested simultaneously on the same flap showed only minor variations in flow measurements. CONCLUSION: This novel probe is capable of detecting changes in tissue microcirculatory blood flow. This device performed well in a swine model of flap ischemia and congestion, and shows promise as a potentially useful clinical tool. Future studies will investigate performance in fasciocutaneous flaps and characterize longevity of the device over a period of several days.

Pedicled Groin Flap for Reconstruction of Combined First Webspace and Dorsal Hand Contracture.

Background. The combination of first webspace and dorsal hand contracture is a challenging reconstructive problem. Complete soft tissue release results in a large wraparound defect that spans the radial side of the palm, first webspace, and the transverse dimension of the entire dorsal hand. In these situations local tissue is often compromised, and free flap reconstruction is commonly indicated. However, in cases where patients are unwilling or unable to undergo microsurgical reconstruction, regional tissue transfer provides an alternative reconstructive strategy. This case report describes a series of 3 patients with severe combined contractures of the first webspace and dorsal hand. Each patient was relatively contraindicated for local or free tissue transfer and was treated with 2-stage selective contracture release with progressive dorsal then volar defect creation and coverage using a pedicled groin flap. This operation requires thoughtful planning during soft tissue release to coordinate staged, dorsal then volar, defect creation with the progressive liberation of the groin flap at its distal and then proximal ends.

Wireless implantable optical probe for continuous monitoring of oxygen saturation in flaps and organ grafts.

Continuous, real-time monitoring of perfusion after microsurgical free tissue transfer or solid organ allotransplantation procedures can facilitate early diagnosis of and intervention for anastomotic thrombosis. Current technologies including Doppler systems, cutaneous O2-sensing probes, and fluorine magnetic resonance imaging methods are limited by their intermittent measurements, requirements for skilled personnel, indirect interfaces, and/or their tethered connections. This paper reports a wireless, miniaturized, minimally invasive near-infrared spectroscopic system designed for uninterrupted monitoring of local-tissue oxygenation. A bioresorbable barbed structure anchors the probe stably at implantation sites for a time period matched to the clinical need, with the ability for facile removal afterward. The probe connects to a skin-interfaced electronic module for wireless access to essential physiological parameters, including local tissue oxygenation, pulse oxygenation, and heart rate. In vitro tests and in vivo studies in porcine flap and kidney models demonstrate the ability of the system to continuously measure oxygenation with high accuracy and sensitivity.

Implantable, wireless, self-fixing thermal sensors for continuous measurements of microvascular blood flow in flaps and organ grafts.

Vascular pedicle thrombosis after free flap transfer or solid organ transplantation surgeries can lead to flap necrosis, organ loss requiring re-transplantation, or even death. Although implantable flow sensors can provide early warning of malperfusion and facilitate operative salvage, measurements performed with existing technologies often depend on extrinsic conditions such as mounting methods and environmental fluctuations. Furthermore, the mechanisms for fixing such probes to vascular or skeletal structures may disrupt the normal blood flow or cause unnecessary tissue damage. Requirements for wired connections to benchtop readout systems also increase costs, complicate clinical care and constrain movements of the patient. Here, we report a wireless, miniaturized flow sensing system that exploits sub-millimeter scale, multi-nodal thermal probes, with biodegradable barbs that secure the probes to the surrounding tissues in a manner that facilitates removal after a period of use. These smartphone-readable devices, together with experimentally validated analytical models of the thermal transport physics, enable reliable, accurate flow sensing in ways that are largely immune to variations in temperature and mechanical perturbations. In vivo demonstrations of this technology in porcine myocutaneous flap and kidney malperfusion models highlight the essential capabilities in microsurgical and transplantation-related biomedical application scenarios.

Intramuscular Near-Infrared Spectroscopy for Muscle Flap Monitoring in a Porcine Model.

BACKGROUND: Current near-infrared spectroscopy (NIRS)-based systems for continuous flap monitoring are limited to flaps which carry a cutaneous paddle. As such, this useful and reliable technology has not previously been applicable to muscle-only free flaps where other modalities with substantial limitations continue to be utilized. METHODS: We present the first NIRS probe which allows continuous monitoring of local tissue oxygen saturation (StO2) directly within the substance of muscle tissue. This probe is flexible, subcentimeter in scale, waterproof, biocompatible, and is fitted with resorbable barbs which facilitate temporary autostabilization followed by easy atraumatic removal. This novel device was compared with a ViOptix T.Ox monitor in a porcine rectus abdominus myocutaneous flap model of arterial and venous occlusions. During these experiments, the T.Ox device was affixed to the skin paddle, while the novel probe was within the muscle component of the same flap. RESULTS: The intramuscular NIRS device and skin-mounted ViOptix T.Ox devices produced very similar StO2 tracings throughout the vascular clamping events, with obvious and parallel changes occurring upon vascular clamping and release. The normalized cross-correlation at zero lag describing correspondence between the novel intramuscular NIRS and T.Ox devices was >0.99. CONCLUSION: This novel intramuscular NIRS probe offers continuous monitoring of oxygen saturation within muscle flaps. This experiment demonstrates the potential suitability of this intramuscular NIRS probe for the task of muscle-only free flap monitoring, where NIRS has not previously been applicable. Testing in the clinical environment is necessary to assess durability and reliability.

A Wireless Near-Infrared Spectroscopy Device for Flap Monitoring: Proof of Concept in a Porcine Musculocutaneous Flap Model.

BACKGROUND: Current near-infrared spectroscopy (NIRS)-based systems for continuous flap monitoring are highly sensitive for detecting malperfusion. However, the clinical utility and user experience are limited by the wired connection between the sensor and bedside console. This wire leads to instability of the flap-sensor interface and may cause false alarms. METHODS: We present a novel wearable wireless NIRS sensor for continuous fasciocutaneous free flap monitoring. This waterproof silicone-encapsulated Bluetooth-enabled device contains two light-emitting diodes and two photodetectors in addition to a battery sufficient for 5 days of uninterrupted function. This novel device was compared with a ViOptix T.Ox monitor in a porcine rectus abdominus myocutaneous flap model of arterial and venous occlusions. RESULTS: Devices were tested in four flaps using three animals. Both devices produced very similar tissue oxygen saturation (StO2) tracings throughout the vascular clamping events, with obvious and parallel changes occurring on arterial clamping, arterial release, venous clamping, and venous release. Small interdevice variations in absolute StO2 value readings and magnitude of change were observed. The normalized cross-correlation at zero lag describing correspondence between the novel NIRS and T.Ox devices was >0.99 in each trial. CONCLUSION: The wireless NIRS flap monitor is capable of detecting StO2 changes resultant from arterial vascular occlusive events. In this porcine flap model, the functionality of this novel sensor closely mirrored that of the T.Ox wired platform. This device is waterproof, highly adhesive, skin conforming, and has sufficient battery life to function for 5 days. Clinical testing is necessary to determine if this wireless functionality translates into fewer false-positive alarms and a better user experience.

Advanced Practice Nursing in Chile and the Role of the Registered Nurse: Integrating 2 Realities Through Continuous Education.

PURPOSE/AIMS: The aim of this study was to explore the perceptions that experienced and highly specialized nurses have of the clinical nurse specialist (CNS) role through description of the registered nurses' (RNs') experiences. DESIGN: This study used a qualitative descriptive design. METHODS: Interviews were conducted with 6 RNs (2 managers, 1 chief nursing officer, 2 educators, and 1 clinician) and 32 RNs who participated in 5 focus groups. Participants were purposively sampled from intensive care units and emergency departments from 4 public and private hospitals. The analysis of the narratives and field notes used thematic content analysis. RESULTS: Common aspects of the CNS competencies and the experienced RN were recognized. These included direct patient care, assessment, and mentoring, with important differences in management, research, and coaching competencies. CONCLUSION: The findings could facilitate the development of a master's program for the CNS in Chile. Formally recognizing the skills and clinical experiences of expert RNs may motivate nurses to pursue a master's degree that prepares them for advanced practice.

Severe Fireworks-Related Injuries: Demographic Characteristics, Injury Patterns, and Firework Types in 294 Consecutive Patients.

OBJECTIVES: The relationship between fireworks and patient characteristics is not known. Our objective was to examine how severe fireworks-related injuries in children and teens compare to adults. METHODS: We conducted a retrospective case series (2005-2015) study of patients who sustained consumer fireworks-related injuries requiring hospital admission and/or operation at a single level 1 trauma/burn center. The distribution of race, use behavior, injury type, body region injured, and firework type was examined by age groups, 1 to 10 years, 11 to 17 years, and 18 years or older. RESULTS: Data from 294 patients 1 to 61 years of age (mean, 24 years) were examined. The majority (91%) were male. The proportion of injuries from different firework types varied by age, with rockets causing the highest proportion in children aged 1 to 10 years, homemade fireworks in those aged 11 to 17 years, and shells/mortars in adults 18 years or older. Compared with adults, children aged 1 to 10 years were more frequently American Indian/Alaska Native, Hispanic, or Asian than White. Compared with adults, children aged 1 to 10 years and 11 to 17 years were more frequently bystanders than active users. Compared with adults, children aged 1 to 10 years and 11 to 17 years had a greater proportion of burn and face injuries. Children aged 1 to 10 years had a decreased proportion of hand injuries. Three patients, 2 adults and 1 child aged 11 to 17 years, died. CONCLUSIONS: Children, teens, and adults experience severe fireworks-related injuries differently, by demographic characteristics, injury patterns, and firework types. Tailored public health interventions could target safety messaging and injury prevention outreach efforts to reduce firework injuries among children and adolescents.

Identifying Common Peroneal Neuropathy before Foot Drop.

BACKGROUND: Common peroneal neuropathy shares the same pathophysiology as carpal tunnel syndrome. However, management is often delayed because of the traditional misconception of recognizing foot drop as the defining symptom for diagnosis. The authors believe recognizing common peroneal neuropathy before foot drop can relieve pain and help improve quality of life. METHODS: One hundred eighty-five patients who underwent surgical common peroneal neuropathy decompression between 2011 and 2017 were included. The mean follow-up time was 249 ± 28 days. Patients were classified into two stages of severity based on clinical presentation: pre-foot drop and overt foot drop. Demographics, presenting symptoms, clinical signs, electrodiagnostic studies and response to surgery were compared between these two groups. Multivariate regression analysis was used to identify variables that predicted outcome following surgery. RESULTS: Overt foot drop patients presented with significantly lower preoperative motor function (percentage of patients with Medical Research Council grade ≤ 1: overt foot drop, 90 percent; pre-foot drop, 0 percent; p < 0.001). Pre-foot drop patients presented with a significantly higher preoperative pain visual analogue scale score (pre-foot drop, 6.2 ± 0.2; overt foot drop, 4.6 ± 0.3; p < 0.001) and normal electrodiagnostic studies (pre-foot drop, 31.4 percent; overt foot drop, 0.1 percent). Postoperatively, both groups of patients showed significant improvement in quality-of-life score (pre-foot drop, 2.6 ± 0.3; overt foot drop, 2.7 ± 0.3). Patients with obesity or a traumatic cause for common peroneal neuropathy were less likely to have improvements in quality of life after surgical decompression. CONCLUSION: Increased recognition of common peroneal neuropathy can aid early management, relieve pain, and improve quality of life. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Nerve Entrapments.

There are more than 2 dozen nerve entrapment syndromes in the body. Generally, these occur at sites of fibroosseous or fibromuscular tunnels. Any insult that leads to an increase in the size of the nerve or a decrease in the volume of the tunnel will cause compression. Resultant nerve ischemia sets off a cascade of events that lead to predictable clinical signs and symptoms. Here, we review the most common nerve entrapment syndromes and highlight their assessment and management. Specific clinical scenarios that require a high suspicion for nerve entrapment are highlighted.

Selective effects of dorsal raphé nucleus glucocorticoid receptor deletion on depression-like behavior in female C57BL/6J mice.

We have shown differing effects of glucocorticoid receptor (GR) deletion from the dorsal raphé nucleus (DRN) and locus coeruleus (LC) on depression-relevant behavior in male mice, but DRN GR deletion has not been tested in female mice. Female floxed GR mice were given DRN injections of AAV2/9 pseudotype viral vectors transducing Cre recombinase to produce DRN GR gene deletion (Cre) and compared with mice receiving DRN injections of AAV2/9 transducing green fluorescent protein (GFP). Social interaction, a measure of depression-like withdrawal, was unaffected by DRN GR deletion, but forced swim immobility, a measure of despair-like passivity, was reduced in female Cre vs. GFP mice. Behavioral effects were not attributable to changes in basal corticosterone or LC GR deletion. Combined with our prior studies, the current findings suggest that DRN GR have sex-independent effects to promote forced swim immobility, but influence social interaction only in male mice. Differential effects of DRN GR deletion in female mice may provide insight into the greater incidence of depression and specific depression symptoms in women.

Glucocorticoid receptor deletion from locus coeruleus norepinephrine neurons promotes depression-like social withdrawal in female but not male mice.

Abnormal glucocorticoid levels can cause psychiatric symptoms ranging from depression to euphoria that have been implicated in mood disorders. My overarching hypothesis is that these opposing effects are mediated by glucocorticoid receptors (GR) in different brain regions. My laboratory has shown that GR in the serotonergic dorsal raphé nucleus (DRN) promote depression-like social and behavioral withdrawal in mice. We have also shown that GR in the DRN and noradrenergic locus coeruleus (LC) exhibit divergent regulation by antidepressants that have differential efficacy for depression subtypes with opposing abnormalities in glucocorticoids. The current study tested the hypothesis that LC GR would have effects opposite to those in the DRN by preventing rather than promoting social withdrawal. GR was deleted from LC NE neurons in female and male floxed GR mice by bilateral injections of lentivirus transducing Cre recombinase under control of a multimerized Phox 2a/2b response sequence (PRS) from the dopamine ß-hydroxylase promoter (PRS-Cre). Female but not male PRS-Cre mice exhibited lower social interaction compared to controls injected with lentivirus transducing green fluorescent protein (PRS-GFP). Differences in social interaction between PRS-GFP and PRS-Cre females were not associated with differences in exploratory behavior, plasma corticosterone, male-female differences in LC GR expression, or changes in LC mineralocorticoid receptor or tyrosine hydroxylase gene expression. These results indicate that LC NE GR have sex-dependent effects to prevent social withdrawal, supporting the concept that glucocorticoids exert opposing effects on depression symptoms via different brain targets, and potentially revealing novel drug targets to treat depression, particularly in women.

Multi-Institutional, Prospective Clinical Utility Study Evaluating the Impact of the 92-Gene Assay (CancerTYPE ID) on Final Diagnosis and Treatment Planning in Patients With Metastatic Cancer With an Unknown or Unclear Diagnosis.

PURPOSE: Metastatic cancers of unknown primary or with unclear diagnoses pose diagnostic and management challenges, often leading to poor outcomes. Studies of the 92-gene assay have demonstrated improved diagnostic accuracy compared with standard pathology techniques and improved survival in patients treated on the basis of assay results. The current study assessed the clinical impact of the 92-gene assay on diagnostic and treatment decisions for patients with unknown or uncertain diagnoses. METHODS: Patients in this prospective, multi-institutional, decision-impact study included those for whom the 92-gene assay was ordered as part of routine care. Participating physicians completed electronic case report forms that contained standardized, specialty-specific questionnaires. Data collection included patient and tumor characteristics and clinical history. The key study objective of clinical impact was calculated on the basis of changes in final diagnosis and treatment after testing. RESULTS: Data collection included 444 patients, 107 physicians (73 oncologists and 34 pathologists), and 28 sites. Molecular diagnoses from 22 different tumor types and subtypes across all cases were provided in 95.5% of patients with a reportable result (n = 397). Physicians reported that the 92-gene assay was used broadly for diagnostic dilemmas that ranged from single suspected tumor type (29%) to a differential diagnosis of two or more suspected tumor types (30%) or cancers of unknown primary (41%). Integration of 92-gene assay results led to a change in the recommended treatment in 47% of patients. CONCLUSION: Findings from this clinical utility study demonstrate that the 92-gene assay led to a change in treatment decisions in every other patient case. These data additionally define the role of this assay in clinical practice and strongly support the consideration of molecular tumor typing in the diagnosis and treatment planning of patients with metastatic cancer with unknown or uncertain diagnosis.