Publications by authors named "Shyam A Patel"

69 Publications

Understanding Health Economics in Spine Surgery.

JBJS Rev 2021 03 5;9(3). Epub 2021 Mar 5.

Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.

»: The United States has faced substantial increases in health-care expenditure, with specifically large increases in spine surgery costs.

»: Many different formulas are utilized to determine value in spine surgery, including cost- benefit analyses, cost-effectiveness analyses, and cost-utility analyses, with the overall determination of value being quality/cost.

»: Quality often is calculated indirectly using either process measures or outcome measures and represents the potential benefit of a given intervention, usually over a specific time period to yield quality-adjusted life years.

»: Costs are particularly difficult to calculate given the interhospital, regional, national, and global variability, as well as indirect costs of an intervention, and many different methods are utilized to estimate costs.

»: Spine surgeons should be familiar with the elements that compose cost-effectiveness and their potential shortcomings in order for providers and health-care policy makers to identify the highest-quality studies and interventions that provide the greatest benefit to patients.
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http://dx.doi.org/10.2106/JBJS.RVW.20.00124DOI Listing
March 2021

Mesenchymal Stem Cell-Secreted Extracellular Vesicles Instruct Stepwise Dedifferentiation of Breast Cancer Cells into Dormancy at the Bone Marrow Perivascular Region.

Cancer Res 2021 Mar 26;81(6):1567-1582. Epub 2021 Jan 26.

Rutgers School of Graduate Studies at New Jersey Medical School, Newark, New Jersey.

In the bone marrow (BM), breast cancer cells (BCC) can survive in dormancy for decades as cancer stem cells (CSC), resurging as tertiary metastasis. The endosteal region where BCCs exist as CSCs poses a challenge to target them, mostly due to the coexistence of endogenous hematopoietic stem cells. This study addresses the early period of dormancy when BCCs enter BM at the perivascular region to begin the transition into CSCs, which we propose as the final step in dormancy. A two-step process comprises the Wnt-β-catenin pathway mediating BCC dedifferentiation into CSCs at the BM perivascular niche. At this site, BCCs responded to two types of mesenchymal stem cell (MSC)-released extracellular vesicles (EV) that may include exosomes. Early released EVs began the transition into cycling quiescence, DNA repair, and reorganization into distinct BCC subsets. After contact with breast cancer, the content of EVs changed (primed) to complete dedifferentiation into a more homogeneous population with CSC properties. BCC progenitors (Oct4alo), which are distant from CSCs in a hierarchical stratification, were sensitive to MSC EVs. Despite CSC function, Oct4alo BCCs expressed multipotent pathways similar to CSCs. Oct4alo BCCs dedifferentiated and colocalized with MSCs (murine and human BM) . Overall, these findings elucidate a mechanism of early dormancy at the BM perivascular region and provide evidence of epigenome reorganization as a potential new therapy for breast cancer. SIGNIFICANCE: These findings describe how the initial process of dormancy and dedifferentiation of breast cancer cells at the bone marrow perivascular niche requires mesenchymal stem cell-derived exosomes, indicating a potential target for therapeutic intervention.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-2434DOI Listing
March 2021

Global Volunteering in Orthopaedics: Availability and Implementation Considerations.

J Am Acad Orthop Surg 2021 Feb;29(4):139-147

From the Department of Orthopaedic Surgery, Alpert Medical School, Brown University, Providence, RI.

The World Health Organization describes traumatic injuries as a "neglected epidemic" in developing countries, accounting for more deaths annually than HIV/AIDS, malaria, and tuberculosis combined. Low- and middle-income countries rely on volunteer assistance to address the growing surgical disease burden of traumatic injuries. Efforts to increase the availability of international electives for orthopaedic trainees can help with the short-term need for surgical personnel abroad and facilitate sustainability through capacity building, maximizing long-term benefits for all parties. The volunteer invariably benefits from this cross-cultural experience with many citing improved skills in communication, clinical diagnostics, appreciation of equality and diversity, and cost-consciousness. A consolidated discussion regarding barriers and implementation strategies can assist interested individuals and institutions plan for future volunteering endeavors.
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http://dx.doi.org/10.5435/JAAOS-D-20-00740DOI Listing
February 2021

Clonal IgH gene rearrangements identify Richter's transformation to diffuse large B cell lymphoma.

Ann Hematol 2020 Nov 7. Epub 2020 Nov 7.

Department of Medicine, Division of Hematology/Oncology, University of Massachusetts Medical School, UMass Memorial Medical Center, Worcester, MA, 01655, USA.

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http://dx.doi.org/10.1007/s00277-020-04334-6DOI Listing
November 2020

Patients Who Undergo Primary Lumbar Spine Fusion After Recent but Not Remote Total Hip Arthroplasty Are at Increased Risk for Complications, Revision Surgery, and Prolonged Opioid Use.

World Neurosurg 2020 Dec 3;144:e523-e532. Epub 2020 Sep 3.

Department of Orthopaedic Surgery, The Warren Alpert Medical School of Brown University/Rhode Island Hospital, Providence, Rhode Island, USA.

Objective: To evaluate the effect of a recent history of total hip arthroplasty (THA) on primary lumbar spine fusion (LSF) for concurrent hip and spine disease.

Methods: A total of 98,242 patient records from the PearlDiver Database were evaluated and divided into 3 cohorts: 1) patients with a history of LSF alone, 2) patients with a history of LSF for newly diagnosed lumbar disease after having a remote THA> 2 years previously, and 3) patients with a history of LSF after having recent THA <2 years before LSF who initially presented with concurrent hip and lumbar spine disease and underwent THA before LSF. Postoperative outcomes were assessed with multivariable logistic regression to determine the effect of THA on outcomes after LSF with respect to postoperative complications, LSF revision rates, and opioid use.

Results: Patients who had LSF after a recent THA had increased risk of deep venous thrombosis (adjusted odds ratio [aOR], 1.39; P = 0.0191), neurologic complications (aOR, 1.81; P = 0.0459), prolonged opioid use (aOR, 1.22; P = 0.0032), and revision LSF (12.8%; P = 0.0004 vs. 9.9%; OR, 1.41; P < 0.0001; hazard ratio, 1.69; P < 0.0001). Patients who underwent LSF after a remote history of THA had no significant difference in DVT (4.2% vs. 2.6%, aOR, 1.31; P = 0.2190), neurologic complications (1.0% vs. 0.5%, aOR, 2.02; P = 0.1220), revision surgery (9.6% vs. 9.9%, aOR, 1.06; P = 0.7197), or prolonged opioid use (36.5% vs. 24.4%, aOR, 1.17; P = 0.1120).

Conclusions: Patients who undergo LSF with a history of THA may be at increased risk of postoperative complications, revision LSF, and prolonged opioid use if their THA was performed for concurrent hip-spine disease in the recent past (<2 years).
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http://dx.doi.org/10.1016/j.wneu.2020.08.210DOI Listing
December 2020

Extramedullary Acute Myeloid Leukemia of the Renal Pelvis: Insights into a Visceral Niche.

Acta Haematol 2020 Aug 19:1-5. Epub 2020 Aug 19.

Department of Medicine - Hematology and Oncology, UMass Memorial Medical Center, University of Massachusetts Medical School, Worcester, Massachusetts, USA,

Acute myeloid leukemia (AML) is a stem cell malignancy that originates in the bone marrow and involves the peripheral blood. Extramedullary AML is rarer, but it is most commonly associated with the former French-American-British (FAB) subtypes M4 or M5 of AML. AML cells may also home to the central nervous system and other solid organs such as cortical bone and skin. Such target sites of metastasis depend on microenvironmental niche interactions, which have not been fully elucidated to date. Visceral organs usually do not represent a favorable niche for AML stem cell occupancy. Herein, we describe the case of an 80-year-old man with extramedullary AML involvement of the renal pelvis. Hypercalcemia and obstructive uropathy were presenting features. The visceral niche is a rare site of involvement of myeloid malignancy, and hypercalcemia may reflect a mechanism of extramedullary involvement. We propose a treatment paradigm for this uncommon subset of AML based on advanced age and complex karyotype.
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http://dx.doi.org/10.1159/000508526DOI Listing
August 2020

Venetoclax and hypomethylating agent therapy in high risk myelodysplastic syndromes: a retrospective evaluation of a real-world experience.

Leuk Lymphoma 2020 11 16;61(11):2700-2707. Epub 2020 Jun 16.

Department of Medicine, Division of Hematology, Cancer Institute, Stanford University, Stanford, CA, USA.

Treatment with hypomethylating agents (HMAs) azacitidine or decitabine is the current standard of care for high risk myelodysplastic syndromes (MDSs) but is associated with low rates of response. The limited number of treatment options for patients with high risk MDS highlights a need for new therapeutic options. Venetoclax is an inhibitor of the BCL-2 protein which, when combined with an HMA, has shown high response rates in unfit and previously untreated acute myeloid leukemia. We performed a retrospective study of high risk MDS patients receiving combination HMA plus venetoclax in order to determine their effectiveness in this context. We show that in our cohort, the combination results in high response rates but is associated with a high frequency of myelosuppression. These data highlight the efficacy of combination HMA plus venetoclax in high risk MDS, warranting further prospective evaluation in clinical trials.
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http://dx.doi.org/10.1080/10428194.2020.1775214DOI Listing
November 2020

Transpsoas Lumbar Interbody Fusion Without Psoas Stimulated Electromyography.

Clin Spine Surg 2021 Feb;34(1):E57-E63

Department of Orthopaedic Surgery, Rothman Orthopaedic Institute, Philadelphia, PA.

Study Design: This is a retrospective case review.

Objective: The objective of this study was to present an anatomic approach to transpsoas interbody fusion without psoas stimulated electromyography (sEMG) and to evaluate the rate of neurological and approach-related complications.

Background: The transpsoas approaches have become commonly utilized for lumbar interbody fusion and may have certain advantages compared with other methods of interbody stabilization. Traditionally, transpsoas approaches have been performed utilizing sEMG as it has been purported to reduce the risk of injury to the lumbar plexus; however, an anatomic approach to transpsoas surgery is also possible as cadaveric studies have demonstrated the anatomy of the psoas muscle and lumbar plexus.

Methods: Patients who underwent transpsoas interbody fusion using an anatomic approach without psoas sEMG between 2005 and 2018 were enrolled in this study. The preoperative and postoperative medical records for this cohort were carefully reviewed to identify any new or persistent radicular symptoms, neurological deficits or approach-related complications.

Results: A total of 133 patients (48 males, 85 females) underwent transpsoas interbody fusion at 222 levels in this cohort-which had a mean age of 63 (61, 65) years and body mass index of 28.8 (27.8, 29.9). New neurological complications were seen in 5 patients (3.8%) and 5 patients (3.8%) were found to have new postoperative radicular pain, up to 3 months postoperatively. The total number of perioperative, approach-related complications was 7 (5.3%) for the entire cohort.

Conclusion: An anatomic transpsoas approach to the interbody space without psoas sEMG demonstrated a rate of neurological and approach-related complications that was comparable or superior to the rate of complications reported using the traditional transpsoas approach with sEMG.
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http://dx.doi.org/10.1097/BSD.0000000000001021DOI Listing
February 2021

Complications of Thoracolumbar Adult Spinal Deformity Surgery.

JBJS Rev 2020 05;8(5):e0214

Rothman Orthopedics, Philadelphia, Pennsylvania.

Adult spinal deformity (ASD) is a challenging problem for spine surgeons given the high risk of complications, both medical and surgical. Surgeons should have a high index of suspicion for medical complications, including cardiac, pulmonary, thromboembolic, genitourinary and gastrointestinal, renal, cognitive and psychiatric, and skin conditions, in the perioperative period and have a low threshold for involving specialists. Surgical complications, including neurologic injuries, vascular injuries, proximal junctional kyphosis, durotomy, and pseudarthrosis and rod fracture, can be devastating for the patient and costly to the health-care system. Mortality rates have been reported to be between 1.0% and 3.5% following ASD surgery. With the increasing rate of ASD surgery, surgeons should properly counsel patients about these risks and have a high index of suspicion for complications in the perioperative period.
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http://dx.doi.org/10.2106/JBJS.RVW.19.00214DOI Listing
May 2020

Recognition and Management of Emergent Spinal Pathology Among First-Line Providers.

Orthopedics 2020 Jul 12;43(4):e244-e250. Epub 2020 Apr 12.

Spinal emergencies require prompt identification, management, and surgical referral (if needed) from first-line providers. Diagnostic delays from a failure to recognize emergency conditions can lead to adverse patient outcomes. The objective of this study was to understand the proficiency with which first-line providers can recognize and manage spinal conditions, particularly spinal emergencies. This was a cross-sectional analysis of 143 internal medicine, family medicine, emergency care, and neurology questionnaires collected at a single-site academic center. Participants were predominantly physicians (88.1%, n=126), with a smaller percentage of midlevel providers (11.9%, n=17). Only 35.0% (n=50) of respondents felt "very prepared" to handle spinal emergencies. Bivariate analyses revealed interdepartmental differences in clinical knowledge pertaining to the management of lumbar radiculopathy (P<.0001), epidural abscess (P=.0002), and cervical myelopathy (P<.0001). Following pairwise comparisons of interdepartmental differences, emergency medicine statistically outperformed internal medicine (P=.0007) and neurology (P<.0001) on initial management of lumbar radiculopathy, while also having markedly higher success in identifying and managing epidural abscess with respect to family medicine (P<.0001). The likelihood of appropriate initial treatment of cervical myelopathy was significantly higher for neurology than for emergency medicine (P<.0001). A minority of first-line providers reported being very prepared to handle spinal emergencies. Disparities exist between first-line provider specialties regarding clinical knowledge in managing and proficiently identifying emergent and nonemergent spinal conditions. Because appropriate handling of emergent spinal pathologies is essential to patient outcomes and optimal resource use, measures should be taken to further educate first-line providers regarding the spinal conditions they will be treating. [Orthopedics. 2020;43(4):e244-e250.].
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http://dx.doi.org/10.3928/01477447-20200404-07DOI Listing
July 2020

A User's Guide to Novel Therapies for Acute Myeloid Leukemia.

Clin Lymphoma Myeloma Leuk 2020 05 30;20(5):277-288. Epub 2020 Jan 30.

Division of Hematology/Oncology, Department of Medicine, University of Massachusetts Medical School, UMass Memorial Medical Center, Worcester, MA. Electronic address:

Few diseases have been marked by a 40-year period of stagnation with regard to therapeutic advances and United States Food and Drug Administration (FDA) approvals, as has been the case for acute myeloid leukemia (AML). Cytarabine and anthracyclines were introduced for the treatment of AML in the 1970s, and in the ensuing 4 decades, the pharmacologic pipeline has experienced a standstill. The absence of FDA approvals in AML is not a reflection of the lack of understanding of the disease biology. The field has seen major advances from the standpoint of stem cell biology and clonal evolution, and the field has also seen some therapeutic advances, but these therapeutic advances have arisen from optimization of the same traditional cytotoxic chemotherapeutics rather than the development of novel therapies. The year 2017 marked a turning point with regard to FDA approvals. This review summarizes the salient clinical trials that led to the approval of 8 novel agents in AML in the past 2 years. For these agents, the clinical activity is often defined by specific molecular aberrations or metabolic features of AML cells. We also emphasize the principles of management of AML in the current era of genomic medicine, with a focus on considerations for targeting mutation-specific vulnerabilities in select patients. This review also highlights unique challenges to the use of novel agents in 2020, including considerations of curative potential with regards to bridging to allogeneic stem cell transplant, tolerability, financial toxicities, and microenvironmental hurdles. Finally, we discuss prospects on future immunotherapeutic investigational agents in the pharmacologic pipeline.
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http://dx.doi.org/10.1016/j.clml.2020.01.011DOI Listing
May 2020

Increased Risk of Chronic Opioid Use and Revision After Anterior Cervical Diskectomy and Fusion in Patients with Prior Shoulder Arthroscopy.

World Neurosurg 2020 Mar 28;135:e202-e208. Epub 2019 Nov 28.

Department of Orthopaedics, Alpert Medical School of Brown University, Providence, Rhode Island, USA.

Objective: The purpose of this study was to compare differences in the outcomes of patients who undergo anterior cervical diskectomy and fusion (ACDF) with and without a history of shoulder arthroscopy.

Methods: The PearlDiver Patient Records Database (www.peardiverinc.com) from 2007 to 2017 was used to query patients by Current Procedural Terminology, isolating those who underwent ACDF with and without prior shoulder arthroscopy. Postoperative complications within 30 days of the index procedure, opioid use, and revision procedures were assessed for each cohort using ICD-9/10 and Current Procedural Terminology coding.

Results: A total of 39,969 ACDF patients were queried, of which 38,859 (97.2%) underwent ACDF alone and 1110 (2.8%) underwent ACDF with prior shoulder arthroscopy. ACDF revision rates were significantly greater in patients with prior shoulder arthroscopy compared with ACDF alone (5.8% vs. 3.6%, aOR = 1.64, P = 0.0002). Patients with prior shoulder arthroscopy were also significantly more likely to fill opioid prescriptions at 3 months (aOR 1.19, P = 0.02), 6 months (aOR 1.22, P = 0.01), and 12 months (aOR 1.18, P = 0.04).

Conclusions: Patients who undergo ACDF with a prior shoulder arthroscopy have significantly greater revision rates, respiratory complications, and prolonged opioid use compared with patients without prior shoulder arthroscopy. With efforts to limit narcotic use and the importance of maximizing patient satisfaction, this analysis improves on the surgeon's ability to set expectations and postoperative plans for patients undergoing ACDF who have a history of shoulder arthroscopy.
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http://dx.doi.org/10.1016/j.wneu.2019.11.116DOI Listing
March 2020

Altered mental status and hypercalcemia with a splenic mass.

J Trauma Acute Care Surg 2020 03;88(3):e114-e115

From the School of Medicine (S.K.), Stanford University; Department of Surgery (J.C., D.A.S.), Stanford Health Care, Stanford, California; and UMass Memorial Medical Center (S.A.P.), University of Massachusetts Medical School, Worcester, Massachusetts.

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http://dx.doi.org/10.1097/TA.0000000000002534DOI Listing
March 2020

Operative Versus Nonoperative Management of Displaced Midshaft Clavicle Fractures in Pediatric and Adolescent Patients: A Systematic Review and Meta-Analysis.

J Orthop Trauma 2019 Nov;33(11):e439-e446

Department of Orthopaedic Surgery, The Warren Alpert Medical School of Brown University, Providence, RI.

Objectives: The purpose of this study was to systematically review and quantitatively analyze outcomes in operative versus nonoperative management of displaced midshaft clavicle fractures in pediatric and adolescent patients.

Data Sources: Using the Preferred Reporting items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, systematic searches of PubMed and EMBASE were conducted to identify English-language studies reporting outcomes in displaced pediatric midshaft clavicle fractures from 1997 to 2018.

Study Selection: Studies that reported on outcomes of operative and/or nonoperative treatment of displaced midshaft clavicle fractures in patients younger than 19 years were included.

Data Extraction: Patient and treatment characteristics, union rates, time to union, time to return to activity, patient-reported outcome measures, and complications were extracted.

Data Synthesis: All extracted data were recorded and qualitatively compared. QuickDASH (Quick Disabilities of the Arm, Shoulder, and Hand) scores and Constant scores were pooled using random-effects modeling and compared among studies, which adequately reported data for hypothesis testing.

Conclusions: Three thousand eight hundred ten articles were identified, and 12 met inclusion criteria. These studies encompassed 497 patients with an average age of 14.1 years (8-18 years, range). Both operative and nonoperative management of displaced midshaft clavicle fractures in this population provide excellent rates of union and patient-reported outcome measures. Compared with nonoperative management, operative management yielded faster return to activity, superior Constant scores, and equal QuickDASH scores. Operative management had higher complication rates and complications that required secondary operative treatment (mostly related to implant prominence).

Level Of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
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http://dx.doi.org/10.1097/BOT.0000000000001580DOI Listing
November 2019

Opioid-limiting legislation associated with decreased 30-day opioid utilization following anterior cervical decompression and fusion.

Spine J 2020 01 2;20(1):69-77. Epub 2019 Sep 2.

Department of Orthopedic Surgery, Warren Alpert Medical School of Brown University, 2 Dudley St, Providence, RI, 02905, USA.

Background Context: Since 2016, 35 of 50 US states have passed opioid-limiting laws. The impact on postoperative opioid prescribing and secondary outcomes following anterior cervical discectomy and fusion (ACDF) remains unknown.

Purpose: To evaluate the effect of opioid-limiting regulations on postoperative opioid prescriptions, emergency department (ED) visits, unplanned readmissions, and reoperations following elective ACDF.

Study Design/setting: Retrospective review of prospectively-collected data.

Patient Sample: Two hundred and eleven patients (101 pre-law, 110 post-law) undergoing primary elective 1-3 level ACDF during specified pre-law (December 1st, 2015-June 30th, 2016) and post-law (June 1st, 2017-December 31st, 2017) study periods were evaluated.

Methods: Demographic, medical, surgical, clinical, and pharmacological data was collected from all patients. Total morphine milligram equivalents (MMEs) filled was compared at 30-day postoperative intervals, before and after stratification by preoperative opioid-tolerance. Thirty- and 90-day ED visit, readmission, and reoperation rates were calculated. Independent predictors of increased 30-day and chronic (>90 day) opioid utilization were evaluated.

Results: Demographic, medical, and surgical factors were similar pre-law versus post-law (all p>.05). Post-law, ACDF patients received fewer opioids in their first postoperative prescription (26.65 vs. 62.08 pills, p<.001; 202.23 vs. 549.18 MMEs, p<.001) and in their first 30 postoperative days (cumulative 30-day MMEs 444.14 vs. 877.87, p<.001). Furthermore, post-law reductions in cumulative 30-day MMEs were seen among both opioid-naïve (363.54 vs. 632.20 MMEs, p<.001) and opioid-tolerant (730.08 vs. 1,122.90 MMEs, p=.022) patient populations. Increased 30-day opioid utilization was associated with surgery in the pre-law period, preoperative opioid exposure, preoperative benzodiazepine exposure, and number of levels fused (all p<.05). Chronic (>90 day) opioid requirements were associated with preoperative opioid exposure (odds ratio 4.42, p<.001) but not with pre/post-law status (p>.05). Pre- and post-law patients were similar in terms of 30- or 90-day ED visits, unplanned readmissions, and reoperations (all p>.05).

Conclusions: Implementation of mandatory opioid prescribing limits effectively decreased 30-day postoperative opioid utilization following ACDF without a rebound increase in prescription refills, ED visits, unplanned hospital readmissions, or reoperations for pain.
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http://dx.doi.org/10.1016/j.spinee.2019.08.014DOI Listing
January 2020

Proximal junctional failure prevention in adult spinal deformity surgery utilizing interlaminar fixation constructs.

Orthop Rev (Pavia) 2019 May 23;11(2):8068. Epub 2019 May 23.

Division of Spine Surgery, Spinal Deformity Service, Department of Orthopedic Surgery, Alpert Medical School of Brown University, Providence RI, USA.

Proximal junctional kyphosis (PJK) is a common complication following fusion for Adult Spinal Deformity. PJK and proximal junctional failure (PJF) may lead to pain, neurological injury, reoperation, and increased healthcare costs. Efforts to prevent PJK and PJF have aimed to preserve or reconstruct the posterior spinal tension band and/or modifying instrumentation to allow for more gradual transitions in stiffness at the cranial end of long spinal constructs. We describe placement of an interlaminar fixation construct at the upper instrumented vertebra which may decrease PJK/PJF severity, and is placed with little additional operative time and minimal posterior soft tissue trauma.
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http://dx.doi.org/10.4081/or.2019.8068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6551454PMC
May 2019

Visual Obstruction of Flow Indicator Increases Inspiratory Volumes in Incentive Spirometry.

Respir Care 2019 May 22;64(5):590-594. Epub 2019 Jan 22.

Warren Alpert Medical School of Brown University, Providence, Rhode Island.

Background: Incentive spirometers were developed to facilitate sustained maximum inspiration. In addition to a slow-rising float that indicates volume displacement, the incentive spirometers includes a sensitive, rapid-fluttering flow indicator. Achieving the target inspiratory volume is believed to be the most important factor in successful incentive spirometers use. This investigation hypothesized that patients focus on the rapid fluttering of the flow indicator rather than volume float during incentive spirometers use. The effects of adjusting hand positioning to cover the flow indicator on inspiratory volumes were evaluated.

Methods: A randomized, prospective, counter-balanced crossover analysis of postoperative subjects was completed. In alternating assignment, the subjects were randomized to 1 of 2 study groups: (A) with the flow indicator covered first followed by the flow indicator standard exposed, and (B) with the flow indicator standard exposed first, followed by the flow indicator covered. The subjects were asked to perform 2 inhalations on their incentive spirometers in the first flow indicator condition: covered or the standard exposed. After a 2-min delay, the subjects were then asked to perform an additional 2 inhalations with the alternate flow indicator condition. The difference between mean inspiratory volumes under covered and standard exposed conditions was evaluated for all subjects, within and between groups.

Results: A total of 42 subjects were evaluated. For all the subjects, there was a mean increase of 255.4 mL of inspired volume when the flow indicator was covered (1,869.0 vs 1,613.7 mL, < .001). For the subjects in group B who had their flow indicators covered after standard exposure, mean inspiratory volumes increased by 285.7 mL (1,613.1 vs 1,898.8 mL, = .009). For subjects in group A who had their flow indicator covered before standard exposure, their mean inspiratory volumes increased by 225.0 mL (1,614.3 vs 1839.3 mL, = .007) when covered. There was no significant difference between the mean increases across patients in groups A and B (225.0 vs 285.7 mL, = .63).

Conclusions: Covering the flow indicator during incentive spirometers significantly increased achieved inspiratory volumes. Increased volumes were generated, irrespective of flow indicator covering order, which strongly suggested that the covering effect was greater than any learning or condition order carry-over effects. Because achieving target inspiratory volumes is considered the most important factor in successful incentive spirometers use, these findings may have immediate applications for improving incentive spirometers protocols, patient education, and device design implications.
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http://dx.doi.org/10.4187/respcare.06331DOI Listing
May 2019

Myelodysplastic Syndrome and Acute Myeloid Leukemia Risk Associated With Solid Tumor Chemotherapy.

Authors:
Shyam A Patel

JAMA Oncol 2019 03;5(3):303-304

Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California.

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http://dx.doi.org/10.1001/jamaoncol.2018.5617DOI Listing
March 2019

Patient Factors Associated with Successful Incentive Spirometry.

R I Med J (2013) 2018 Nov 1;101(9):14-18. Epub 2018 Nov 1.

Warren Alpert Medical School of Brown University, Providence, RI.

Background: Incentive spirometers (IS) are commonly prescribed after various surgical procedures with the intended effect of reducing postoperative pulmonary complications. Factors associated with correct use of IS by postoperative patients has not previously been studied.

Methods: A cross-sectional analysis of postoperative patients was completed to assess whether patients knew how to correctly inhale on their IS. For each patient, the following variables were collected: whether the device was within arm's reach of the patient, if the patient reported having used their IS, if they considered the IS to be helpful, and if they felt more confident using IS after a brief educational intervention was performed by study investigators.

Results: A total of 26.2% (11/42) of patients failed to use their IS correctly, and 38.1% (16/42) denied ever using the device in their postoperative care. Device location, perceived benefit, and previous use were identified as statistically significant determinants of successful use. Following a brief educational intervention by a physician, 73.8% (31/42) of patients were more confident in their ability to use IS during the remainder of their care.

Discussion: A substantial portion of postoperative patients failed to correctly utilize their IS. Device proximity to the patient, patient perspectives on potential benefits of IS, and previous use of the device may affect correct use. Patient education and optimization of device placement should be considered to increase compliance during IS implementation.
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November 2018

Spinal Emergencies in Primary Care Practice.

Am J Med 2019 03 3;132(3):300-306. Epub 2018 Oct 3.

Division of Spine Surgery, Department of Orthopaedic Surgery, Warren Alpert Medical School, Brown University, Providence, RI.

Atraumatic spinal emergencies often present a diagnostic and management dilemma for health care practitioners. Spinal epidural abscess, cauda equina syndrome, and spinal epidural hematoma are conditions that can insidiously present to outpatient medical offices, urgent care centers, and emergency departments. Unless a high level of clinical suspicion is maintained, these clinical entities may be initially misdiagnosed and mismanaged. Permanent neurologic sequela and even death can result if delays in appropriate treatment occur. A focused, critical review of 34 peer-reviewed articles was performed to identify current data about accurate diagnosis of spinal emergencies. This review highlights the key features of these 3 pathological entities with an emphasis on appropriate diagnostic strategy to intervene efficiently and minimize morbidity.
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http://dx.doi.org/10.1016/j.amjmed.2018.09.022DOI Listing
March 2019

Access to Orthopaedic Care.

JBJS Rev 2018 Sep;6(9):e7

The Rothman Institute at Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.

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http://dx.doi.org/10.2106/JBJS.RVW.17.00208DOI Listing
September 2018

Financial Impact of Incentive Spirometry.

Inquiry 2018 Jan-Dec;55:46958018794993

1 The Warren Alpert Medical School of Brown University, Providence, RI, USA.

Despite largely unproven clinical effectiveness, incentive spirometry (IS) is widely used in an effort to reduce postoperative pulmonary complications. The objective of the study is to evaluate the financial impact of implementing IS. The amount of time nurses and RTs spend each day doing IS-related activities was assessed utilizing an online survey distributed to the relevant national nursing and respiratory therapists (RT) societies along with questionnaire that was prospectively collected every day for 4 weeks at a single 10-bed cardiothoracic surgery step-down unit. Cost of RT time to teach IS use to patients and cost of nurse time spent reeducating and reminding patients to use IS were used to calculate IS implementation cost estimates per patient. Per-patient cost of IS implementation ranged from $65.30 to $240.96 for a mean 9-day step-down stay. For the 566 patients who stayed in the 10-bed step-down in 2016, the total estimated cost of implementing IS ranged from $36 959.80 to $136 383.36. Using national survey workload data, per-patient cost of IS implementation costed $107.36 (95% confidence interval [CI], $97.88-$116.98) for a hospital stay of 4.5 days. For the 9.7 million inpatient surgeries performed annually in the United States, the total annual cost of implementing postoperative IS is estimated to be $1.04 billion (95% CI, $949.4 million-$1.13 billion). The cost of implementing IS is substantial. Further efficacy studies are necessary to determine whether the cost is justifiable.
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http://dx.doi.org/10.1177/0046958018794993DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6122234PMC
February 2019

Tumor Molecular Testing Guides Anti-PD-1 Therapy and Provides Evidence for Pathogenicity of Mismatch Repair Variants.

Oncologist 2018 12 2;23(12):1395-1400. Epub 2018 Aug 2.

Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford Cancer Institute, Stanford, California, USA.

Lynch syndrome is characterized by germline abnormalities in mismatch repair (MMR) genes, leading to predisposition to multiple cancers [1]. A second hit to the unaffected allele is required for tumorigenesis. MMR proteins repair incorrectly paired nucleotides and prevent generation of insertions and deletions at microsatellites [2]. Aberrancies in these MMR proteins can be a result of germline mutations or somatic alterations. Defective MMR results in microsatellite instability (MSI) and a high mutational burden [3].The clinical implications of MSI are becoming readily apparent, as presence of MSI leads to the generation of neoantigens, stimulating tumor-associated lymphocytes [4], [5]. This has led to the use of programmed cell death protein 1 blockade for MMR-deficient tumors [6]. The U.S. Food and Drug Administration recently approved pembrolizumab for any advanced solid tumor demonstrating MSI and nivolumab for metastatic MSI colorectal cancer. However, the clinical significance of numerous MMR gene variants remains uncertain. The International Society for Gastrointestinal Hereditary Tumors classification system categorizes 2,360 MMR variants, which can be used to gauge pathogenicity [7]. There are many variants of uncertain significance (VUS; or class 3) for which clinicians are unable to provide recommendations. In this study, we employed the combination of germline testing and tumor mutational assessment to help discern the clinical relevance of VUS and guide immunotherapeutic decisions. KEY POINTS: A clinical dilemma arises when genomic testing yields variants of uncertain significance (VUS).Germline VUS were identified in two patients with gastrointestinal malignancies, but only one patient had a second-hit mutation in a mismatch repair gene leading to mismatch repair deficiency that conferred response to immunotherapy.The combination of germline testing along with tumor mutational assessment can help discern the clinical relevance of VUS and can help guide therapeutic decision-making toward individualized patient care.
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http://dx.doi.org/10.1634/theoncologist.2018-0108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6292542PMC
December 2018

Primary Atypical Lipomatous Tumor of the Orbit: A Case Report.

J Ophthalmic Vis Res 2018 Jan-Mar;13(1):78-80

Department of Radiology, John H. Stroger, Jr. Hospital of Cook County, Chicago, IL, USA.

Purpose: To describe a case of primary atypical orbital lipomatous tumor (ALT).

Case Report: A 35-year-old man presented with a two-month history of left eye proptosis and vertical diplopia. His visual acuity was 20/30 OD and 20/60 OS. External examination showed proptosis and downward displacement of the left eye with mild lid erythema. Extraocular movements were reduced in the left eye, with 10% and 70% motility in upgaze and abduction/adduction, respectively. Imaging showed a mass (22 × 16 × 46 mm) in the superior left orbit that infiltrated the orbital fat and the superior rectus muscle. A biopsy of the mass showed mature adipose tissue intermingled with fibrous zones of hyperchromatic stromal cells with nuclear atypia. Fluorescence hybridization analysis demonstrated positive amplification for MDM2/CEP12. The MDM2 to CEP12 ratio was 5:7. A diagnosis of ALT was confirmed. An orbital exenteration was recommended, which the patient declined.

Conclusion: Although rare, the differential for unilateral proptosis with or without diplopia should include orbital liposarcomas including the ALT subtype. Imaging, biopsy, staining, and/or FISH analysis for proto-oncogenes can assist with diagnosis and staging, while the standard treatment is exenteration.
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http://dx.doi.org/10.4103/jovr.jovr_208_15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5782463PMC
February 2018

Enasidenib-Induced Differentiation Syndrome in IDH2-Mutant Acute Myeloid Leukemia.

Authors:
Shyam A Patel

JAMA Oncol 2018 08;4(8):1110-1111

Department of Medicine, Divisions of Hematology and Oncology, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California.

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http://dx.doi.org/10.1001/jamaoncol.2017.4724DOI Listing
August 2018

An Unusual Case of Blepharochalasis.

J Ophthalmic Vis Res 2017 Jul-Sep;12(3):342-344

Department of Surgery, John H. Stroger, Jr. Hospital of Cook County Division of Ophthalmology, Chicago, IL, USA.

Purpose: To describe a rare case of blepharochalasis that progressed from unilateral to bilateral involvement at five years after disease onset.

Case Report: A previously healthy five-year-old white boy presented to our hospital for a screening visual examination. He was found to have a 2-mm right eyelid ptosis with crepe-like skin and subcutaneous telangiectatic vessels. His mother noted that since the age of three, the child has been having two to seven day-long episodes of right upper eyelid swelling and edema with tenderness. The episodes eventually progressed to involving the left eyelid as well. Oral steroid taper was found to effectively resolve these exacerbations, and a diagnosis of blepharochalasis was made.

Conclusion: Blepharochalasis should be in the differential diagnosis for young children presenting with unilateral or bilateral ptosis with periorbital skin abnormalities.
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http://dx.doi.org/10.4103/jovr.jovr_104_15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5525506PMC
August 2017

Harnessing antitumor immunity: Employment of tumor recall antigens to optimize the inflammatory response to cancer.

Oncol Lett 2017 Apr 13;13(4):2015-2020. Epub 2017 Feb 13.

Stanford Cancer Institute, Stanford University Medical Center, Stanford, CA 94305, USA.

The advent of immunotherapy for cancer has contributed to the era of personalized medicine for cancer. The various immunotherapy-based treatments that have been explored thus far include monoclonal antibody therapy, tumor vaccines, immune checkpoint blockade and adoptive T cell transfer, among others. The groundwork for all these immunotherapeutic modalities rests within the tumor microenvironment, specifically the immune factors that influence the tumor-drug interface. Prior to therapeutic design, the tumor microenvironmental interactions and the current barriers to successful treatment must first be understood. In the present review, it is proposed that cancer cell eradication within the tumor niche may be achieved by reprogramming of the immune microenvironment in favor of a pro-inflammatory antitumor profile at an early stage. This pro-inflammatory profile may, in turn, be influenced by tumor recall antigens, which function to stimulate the cell-mediated or humoral responses involved in antitumor immunity. These measures serve to counteract the immunotolerant state of the tumor microenvironment. Such measures are critical to therapeutic successes.
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http://dx.doi.org/10.3892/ol.2017.5721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5403274PMC
April 2017

Acute Myeloid Leukemia Relapse Presenting as Complete Monocular Vision Loss due to Optic Nerve Involvement.

Authors:
Shyam A Patel

Case Rep Hematol 2016 7;2016:3794284. Epub 2016 Sep 7.

Stanford Cancer Institute, Stanford University Medical Center, 875 Blake Wilbur Drive, Stanford, CA 94305, USA.

Acute myeloid leukemia (AML) involvement of the central nervous system is relatively rare, and detection of leptomeningeal disease typically occurs only after a patient presents with neurological symptoms. The case herein describes a 48-year-old man with relapsed/refractory AML of the mixed lineage leukemia rearrangement subtype, who presents with monocular vision loss due to leukemic eye infiltration. MRI revealed right optic nerve sheath enhancement and restricted diffusion concerning for nerve ischemia and infarct from hypercellularity. Cerebrospinal fluid (CSF) analysis showed a total WBC count of 81/mcl with 96% AML blasts. The onset and progression of visual loss were in concordance with rise in peripheral blood blast count. A low threshold for diagnosis of CSF involvement should be maintained in patients with hyperleukocytosis and high-risk cytogenetics so that prompt treatment with whole brain radiation and intrathecal chemotherapy can be delivered. This case suggests that the eye, as an immunoprivileged site, may serve as a sanctuary from which leukemic cells can resurge and contribute to relapsed disease in patients with high-risk cytogenetics.
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http://dx.doi.org/10.1155/2016/3794284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5030445PMC
September 2016

A case report of primary orbital non-Hodgkin's lymphoma causing complete vision loss.

GMS Ophthalmol Cases 2016 15;6:Doc06. Epub 2016 Apr 15.

John H. Stroger, Jr. Hospital of Cook County, Division of Pathology, Chicago, USA.

A 29-year-old male with acquired immunodeficiency syndrome presented with a week of left eye blurriness, which then progressed to complete vision loss. On exam, the left pupil was nonreactive to light, and fundoscopy showed significant optic nerve edema. CT and MRI of the left orbit showed a mass lesion compressing the posterior aspect of the sclera with diffuse thickening and contrast enhancement of the retrobulbar portion of the left optic nerve. The lesion demonstrated low T1 and intermediate T2 intensities and heterogeneous contrast enhancement and measured 17.4 mm x 15 mm x 10.6 mm. Anterior orbitotomy with exploration and biopsy were performed. Immunohistochemical studies confirmed diffuse large B-cell lymphoma and a workup showed no systemic involvement. Plans for treatment with chemotherapy and radiation were initiated. Even though rare, primary orbital NHL should be in the differential for relatively acute blindness without other symptoms, especially in patients with AIDS.
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http://dx.doi.org/10.3205/oc000043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5015789PMC
September 2016

Progressive Multifocal Leukoencephalopathy with Negative JC Virus PCR following Treatment of Follicular Lymphoma: Implications for Biologics in the Era of Targeted Cancer Therapy.

Case Rep Oncol Med 2015 15;2015:534529. Epub 2015 Dec 15.

Department of Medicine, Stanford University Medical Center, 300 Pasteur Drive, Stanford, CA 94305, USA.

Anticancer therapy predisposes patients to infections by the immunosuppression that results from treatment. Although 85% of patients with progressive multifocal leukoencephalopathy (PML) have concurrent HIV/AIDS, PML can also develop in patients after they receive chemotherapy for cancer. The case herein describes a 69-year-old man with history of follicular lymphoma who presented with progressive dysarthria and right-sided paralysis. He received rituximab one year prior to presentation. PET scan suggested no recurrence of lymphoma. Cerebrospinal fluid (CSF) analysis was negative and showed fewer than 500 copies/mL of JC virus. However, brain biopsy showed chromatin margination and viropathic change within oligodendrocytes, confirming PML. He was started on mirtazapine and mefloquine with some clinical improvement. To our knowledge, this is the first case of rituximab-associated PML in a patient with negative JC virus PCR from the CSF. Recognition of PML in the differential of oncology patients with CNS symptoms is an important consideration as we enter the era of targeted therapy and personalized cancer medicine involving biologics. Furthermore, screening of patients for presence of subclinical JC viremia prior to the use of biologics may be an important component of assessing patient candidacy for these agents.
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http://dx.doi.org/10.1155/2015/534529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4693014PMC
January 2016