Real-World Use and Effectiveness Outcomes in Patients with Rheumatoid Arthritis Treated with Upadacitinib: An Analysis from the CorEvitas Registry.

INTRODUCTION: Data assessing longer-term real-world effectiveness and treatment patterns with upadacitinib (UPA), a Janus kinase inhibitor, in rheumatoid arthritis (RA) are lacking. We assessed improvement in clinical and patient-reported outcomes and treatment patterns for up to 12 months among adult patients with RA initiating UPA. METHODS: Data were collected from the CorEvitas® RA Registry (08/2019-04/2022). Eligible patients had moderate to severe RA (Clinical Disease Activity Index [CDAI] > 10) and follow-up visits at 6 or 12 months after UPA initiation. Outcomes were mean change from baseline, percentage achieving minimal clinically important differences (MCID) in clinical and patient-reported outcomes, and disease activity at follow-up. We evaluated clinical outcomes and therapy changes among patients with tumor necrosis factor inhibitor (TNFi) experience and among those receiving UPA as first-line therapy, as well as those receiving UPA as monotherapy versus as part of combination therapy. We further evaluated whether outcomes were similar among those that remained on therapy. RESULTS: Patients treated with UPA (6-month cohort, N = 469; 12-month cohort, N = 263) had statistically significant improvements (p < 0.001) in mean CDAI, tender/swollen joint counts, pain, and fatigue at follow-up. At 12 months, 46.0% achieved MCID in CDAI and 40.0% achieved low disease activity/remission. Overall, 43.0% discontinued UPA at 12 months; of those receiving combination treatment (N = 90) with conventional therapies and UPA, 42.2% (N = 38) discontinued conventional therapy. Findings were similar in the 6-month cohort and among subgroups. Changes from baseline and proportions of patients achieving MCID or clinical outcomes tended to be numerically lower among patients with TNFi experience and numerically higher among those receiving UPA as first-line therapy. CONCLUSIONS: UPA initiation was associated with improvements in clinical and patient-reported outcomes, with meaningful clinical improvements regardless of prior TNFi experience, line of therapy, or concomitant use of conventional therapies. Further research is needed to better understand sustained response of UPA over longer treatment periods.

Sagittal mechanical ratio: A novel technique to define sagittal alignment of the femur independent of distal anatomic landmarks.

BACKGROUND: Radiographic measurements to study sagittal alignment in the setting of knee are frequently difficult to evaluate due the presence of a prosthesis or implant that obscures traditional radiographic landmarks. In this paper we present a novel method of determining sagittal femoral alignment in the presence of obscuring implants. METHODS: 98 full-length femoral radiographs were reviewed and divided into two groups. In Group 1, the Distal Mechanical Point (DMP) was used to calculate the Distal Mechanical Ratio (DMR), defined as the ratio of the linear distance from the DMP to the anterior cortical axis divided by the distance from the anterior cortical axis to posterior condylar cortex. In group 2, the sagittal mechanical axis was measured using the true DMP (tDMP) and then separately measured using the DMR to find the calculated DMP (cDMP), and the angular variance between the calculated (cSMA) and true (tSMA) sagittal mechanical axis was calculated, as well as the linear distance between the tDMP and cDMP. Twenty additional patients with knee replacements were then selected and two observers used a cSMA to determine a femoral prosthesis flexion angle (FPFA), with intraobserver correlation calculated. RESULTS: The mean DMR was found to be 0.24, with high intraobserver correlation and normal distribution. Validation of the model demonstrated angular variance between tSMA and cSMA less than 1 degree and linear distance between tDMP and cDMP less than 1 mm. Calculation of cCMA in the presence of total knee arthroplasty revealed very strong intraobserver correlation of 0.89. CONCLUSION: The Distal Mechanical Ratio reliably predicted the true Sagittal Mechanical Axis within 1 degree and true Distal Mechanical Point within 1 mm, indicating that it may be a valuable tool for evaluating sagittal femoral alignment in cases where anatomic landmarks may be absent or obscured.

The articular surface technique for lumbar pedicle screw placement: a 3D feasibility study.

Background: Traditional pedicle screws (TPSs) and cortical based trajectory pedicle screws each apply stability with fusions of the lumbar spine and have shown good success. However, the technical considerations of each technique imply complications of loosening and failure that either technique is uniquely prone to having. The current study proposes a new pedicle screw technique through the articular surface of the vertebral superior facet. It is hypothesized that this path will allow utilization of a larger screw that rivals that of the TPS technique, while also maintaining the high-density bone encountered in the cortical based trajectory technique. Methods: Retrospective review of 50 consecutive trauma patients that underwent lumbar computed tomography (CT) scans at a Level 1 Trauma Center in the age range 18-45. These scans were uploaded to Brainlab software for ideal starting point and trajectory mapping of pedicle screws coursing through each superior facet and pedicle of vertebral levels L1-S1 without cortical breach. Satisfactory pedicle screw variables consisted of a medial angle <10 degrees, screw length at least 30 mm, screw width at least 5.0 mm, and starting point measurements such as distance to the inferior articular surface and distance to the lateral articular surface. Results: A total of 600 virtual pedicle screws were placed, in which 525 were satisfactory and measured with the above variables. The pedicle widths were shown to significantly widen with lower-level vertebra in the lumbar spine. Approximately 72% of unsuccessful pedicle screws were placed in levels L1 and L2 allowing wider pedicle screws to be placed more further down the vertebral column. Conclusions: The articular surface technique (AST) for pedicle screw placement is a viable alternative in lumbar spinal fusions that offers decreased soft tissue dissection. However, the technique is likely better suited for lower lumbar fusions in L3 to S1.

Effect of Visit Frequency of Pharmacist-Led Diabetes Medication Management Program.

BACKGROUND: Pharmacists have a positive effect on clinical outcomes in chronic disease state management, however, few studies have evaluated the effect that frequency of visits may have on diabetes biomarkers such as hemoglobin A1c and blood pressure readings. METHODS: Under the medication management program (MMP), patients with diabetes were seen monthly by pharmacists until early 2015, when time between visits was increased to every 3 months. A retrospective chart review was conducted to evaluate the primary outcome of the percent change in hemoglobin A1c and blood pressure after the change in visit frequency. RESULTS: In the 303 patients enrolled, no statistical difference existed between the pre and post average A1c (p-value = 0.10). The intermediate average A1c was statistically lower from the preintervention mean A1c (p-value = 0.001) but not from the postintervention mean A1c (p-value = 0.30). No statistical differences were seen between systolic blood pressure and diastolic blood pressure. CONCLUSION: Patients who have been seen by a clinical pharmacist more frequently (every month or every other month) for several years may be able to maintain their reduction in A1c with less-frequent visits (every 3 to 6 months).

Treatment of Chronic Kidney Disease-Related Metabolic Acidosis With Fruits and Vegetables Compared to NaHCO3 Yields More and Better Overall Health Outcomes and at Comparable Five-Year Cost.

OBJECTIVES: Current guidelines recommend treatment of metabolic acidosis in chronic kidney disease (CKD) with Na+-based alkali but base-producing fruits and vegetables (F + V) might yield more and better health outcomes, making the intervention cost-effective. DESIGN AND METHODS: In this post hoc analysis of a clinical trial we randomized 108 macroalbuminuric, nondiabetic CKD stage 3 participants with metabolic acidosis to receive F + V (n = 36) calculated to reduce dietary acid by half, oral NaHCO3 (HCO3-, n = 36) 0.3 mEq/kg body weight/day, or Usual Care (UC, n = 36) assessed annually for 5 years. We calculated a mean overall health score for the groups as follows: 1 for improved, 0 for no change, and -1 for worsened at 5 years for plasma total CO2, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, change in medication dose (reduction = 1, increased = -1, no change = 0), and 1 for met goal and 0 for not meeting goal for estimated glomerular filtration rate (>30 mL/min/1.73 m2) and systolic blood pressure (<130 mm Hg). We also assessed the number of participants with cardiovascular disease events (myocardial infarctions + strokes) and group medication and hospitalization costs. RESULTS: Net plasma total CO2 increase at 5 years was no different between HCO3- and F + V. Average health scores at 5 years differed among groups (P < .01) with F + V (7.4 [mean] ± 1.6 [standard deviation]) being descriptively larger than HCO3- and UC (2.9 ± 1.6 and 1.2 ± 1.6, respectively). The number of participants suffering cardiovascular disease events differed among groups (P = .009) with none (0) in F + V, 6 in UC, and 2 in HCO3-. Total 5-year household cost per beneficial health outcome differed among groups (P = .005) with UC being highest and that for HCO3- and F + V being comparable. CONCLUSIONS: Metabolic acidosis improved comparably with F + V or standard oral NaHCO3, but F + V yielded ancillary beneficial health outcomes, fewer participants with adverse cardiovascular events, and per-household cost that was comparable to NaHCO3.

Association of anticoagulation dose and survival in hospitalized COVID-19 patients: A retrospective propensity score-weighted analysis.

BACKGROUND: Hypercoagulability may contribute to COVID-19 pathogenicity. The role of anticoagulation (AC) at therapeutic (tAC) or prophylactic doses (pAC) is unclear. OBJECTIVES: We evaluated the impact on survival of different AC doses in COVID-19 patients. METHODS: Retrospective, multi-center cohort study of consecutive COVID-19 patients hospitalized between March 13 and May 5, 2020. RESULTS: A total of 3480 patients were included (mean age, 64.5 years [17.0]; 51.5% female; 52.1% black and 40.6% white). 18.5% (n = 642) required intensive care unit (ICU) stay. 60.9% received pAC (n = 2121), 28.7% received ≥3 days of tAC (n = 998), and 10.4% (n = 361) received no AC. Propensity score (PS) weighted Kaplan-Meier plot demonstrated different 25-day survival probability in the tAC and pAC groups (57.5% vs 50.7%). In a PS-weighted multivariate proportional hazards model, AC was associated with reduced risk of death at prophylactic (hazard ratio [HR] 0.35 [95% confidence interval {CI} 0.22-0.54]) and therapeutic doses (HR 0.14 [95% CI 0.05-0.23]) compared to no AC. Major bleeding occurred more frequently in tAC patients (81 [8.1%]) compared to no AC (20 [5.5%]) or pAC (46 [2.2%]) subjects. CONCLUSIONS: Higher doses of AC were associated with lower mortality in hospitalized COVID-19 patients. Prospective evaluation of efficacy and risk of AC in COVID-19 is warranted.

Impact of frailty and anticoagulation status on readmission and mortality rates following falls in patients over 80.

Falls are the leading cause of trauma-related mortality in geriatric patients. We hypothesized that frailty and anticoagulation status are risk factors for readmission and mortality following falls in patients >80 years. A retrospective review was performed on patients over 80 years old who presented to our level 1 trauma center for a fall and underwent a computed tomography of the head between January 2014 and January 2016. Frailty was assessed via the Rockwood Frailty Score. Clinical outcomes were death, readmission, recurrent falls, and delayed intracranial hemorrhage. Of 803 fall-related encounters, 173 patients over 80 years old were identified for inclusion. The 30-day readmission rate was 17.5% and was associated with an increased 6-month mortality (P = 0.01). One-year and 2-year mortality rates were 28% and 47%, respectively. Frailty was the strongest predictor of 6-month and overall mortality (P < 0.01). Anticoagulation status did not significantly influence these outcomes. The recurrent fall rate was 21%, and delayed intracranial hemorrhage did not occur in this study. Mortality of octogenarians after a fall is most influenced by patient frailty. Acknowledgment of frailty, risk of recurrent falls, and increased mortality should direct goals of care for geriatric trauma patients.

Fruit and Vegetable Treatment of Chronic Kidney Disease-Related Metabolic Acidosis Reduces Cardiovascular Risk Better than Sodium Bicarbonate.

BACKGROUND: Current guidelines recommend treatment of metabolic acidosis in chronic kidney disease (CKD) with sodium-based alkali. We tested the hypothesis that treatment with base-producing fruits and vegetables (F + V) better improves cardiovascular disease (CVD) risk indicators than oral sodium bicarbonate (NaHCO3). METHODS: We randomized 108 macroalbuminuric, matched, nondiabetic CKD patients with metabolic acidosis to F + V (n = 36) in amounts to reduce dietary acid by half, oral NaHCO3 (HCO3, n = 36) 0.3 mEq/kg bw/day, or to Usual Care (UC, n = 36) to assess the 5-year effect of these interventions on estimated glomerular filtration rate (eGFR) course as the primary analysis and on indicators of CVD risk as the secondary analysis. RESULTS: Five-year plasma total CO2 was higher in HCO3 and F + V than UC but was not different between HCO3 and F + V (difference p value < 0.01). Five-year net eGFR decrease was less in HCO3 (mean -12.3, 95% CI -12.9 to -11.7 mL/min/1.73 m2) and F + V (-10.0, 95% CI -10.6 to -9.4 mL/min/1.73 m2) than UC (-18.8, 95% CI -19.5 to -18.2 mL/min/1.73 m2; p value < 0.01) but was not different between HCO3 and F + V. Five-year systolic blood pressure was lower in F + V than UC and HCO3 (p value < 0.01). Despite similar baseline values, F + V had lower low-density lipoprotein, Lp(a), and higher serum vitamin K1 (low serum K1 is associated with coronary artery calcification) than HCO3 and UC at 5 years. CONCLUSION: Metabolic acidosis improvement and eGFR preservation were comparable in CKD patients treated with F + V or oral NaHCO3 but F + V better improved CVD risk indicators, making it a potentially better treatment option for reducing CVD risk.

Research priorities for maintaining biodiversity's contributions to people in Latin America.

Maintaining biodiversity is crucial for ensuring human well-being. The authors participated in a workshop held in Palenque, Mexico, in August 2018, that brought together 30 mostly early-career scientists working in different disciplines (natural, social and economic sciences) with the aim of identifying research priorities for studying the contributions of biodiversity to people and how these contributions might be impacted by environmental change. Five main groups of questions emerged: (1) Enhancing the quantity, quality, and availability of biodiversity data; (2) Integrating different knowledge systems; (3) Improved methods for integrating diverse data; (4) Fundamental questions in ecology and evolution; and (5) Multi-level governance across boundaries. We discuss the need for increased capacity building and investment in research programmes to address these challenges.

Efficacy of Liposomal Bupivacaine Compared with Multimodal Periarticular Injections for Postoperative Pain Control following Total Knee Arthroplasty.

Single-dose long-acting periarticular anesthetics have been shown to be an effective method of postoperative analgesia in total knee arthroplasty (TKA). This study retrospectively compares the efficacy of multimodal periarticular injection consisting of a combination of ropivacaine, duramorph, epinephrine, and toradol (HC) with liposomal bupivacaine (LB) periarticular injection in TKA. This study was a retrospective matched comparative chart review of two cohorts of patients who underwent TKA within a single health care system and cared for by one provider. We compared 22 patients who were treated with LB intraoperatively (LBG) with 41 matched controls who were treated with HC periarticular injection (HCG). These cases were retrospectively reviewed at 0 to 6, 6 to 12, 12 to 24, 24 to 48, and 48 to 72 hours. We reviewed pain scores and opioid use per the preceding time period, total opioid use, length of stay (LOS), and wound complications between the two groups. The two groups showed no statistical difference in total opioids used. In both the 6- to 12-hour and 12- to 24-hour intervals, the LBG required significantly more opioids than the HCG, with p-values of 0.0039 and 0.0061, respectively. Pain scores were not significantly different for any time period. We found no difference in LOS. The LBG tended to have lower doses of antiemetics than the HCG. No significant difference was found in postoperative pain scores and total opioid use between LB and multimodal periarticular intraoperative injections in TKA. Our data demonstrated decreased opioid consumption in the HC group compared with the LB group in both the 6- to 12-hour and 12- to 24-hour time intervals postoperatively. At our institution, LB costs US$314.99, whereas HC costs US$95.

Comparison of a standardized negative pressure wound therapy protocol after midline celiotomy to primary skin closure and traditional open wound vacuum-assisted closure management.

A negative pressure wound therapy (NPWT) protocol using Hydrofera Blue® bacteriostatic foam wicks and silver-impregnated foam overlay to close midline skin incisions after emergency celiotomy was compared to primary skin closure only and traditional open wound vacuum-assisted closure management as part of a quality improvement initiative. This single-institution retrospective cohort study assessed all consecutive emergency celiotomies from July 2013 to June 2014 excluding clean wounds. Included variables were demographics, wound classification, NPWT days, and surgical site occurrences (SSOs). Primary outcome was days of NPWT. Secondary outcomes included SSOs (surgical site infections, fascial dehiscence, return to operating room). Analysis used exact chi-square between categorical variables, Kruskal-Wallis for analysis of variance for ordinal and categorical variables, and Wilcoxon rank sum for total days of NPWT. One hundred fifty-eight patients underwent emergency celiotomy with primary skin closure (n = 51), open NPWT (n = 63), or the NPWT protocol (n = 44). There was no difference in American Society of Anesthesiologists Physical Status score, body mass index, wound classification, or SSO between the three groups. Total NPWT days were reduced in protocol versus open NPWT (median 3 vs 20.5 days, range 3-51 vs 3-405 days, P = 0.001). Primary skin closure and NPWT protocol had fewer patients discharged with NPWT than open NWPT (0% and 14% vs 63.5%, P < 0.0001, odds ratio = 10.7, 95% confidence interval 3.7-35.1). Primary skin closure and NPWT protocol decrease NPWT usage days and maintain low SSOs in emergency midline celiotomy incisions.

Rate of contralateral hip fracture after dynamic hip screw vs intramedullary nail for treatment of pertrochanteric hip fractures.

A retrospective, comparative study was performed reviewing the electronic medical records and digital radiographs of patients who underwent treatment for intertrochanteric and pertrochanteric hip fractures with either a hip screw and side plate (HSSP) or intramedullary nail. A total of 430 patients were treated with HSSP, and 725 were managed with a cephalomedullary nail (CMN). Of these, 103 sustained a contralateral hip fracture. Fixation technique was not associated with a significant difference in the rate of contralateral fracture. Among the patients with a contralateral fracture, the median time to contralateral fracture was 119.28 months following HSSP and 81.97 months following CMN. Bisphosphonate use was found to be a significant predictor of contralateral fracture for all patients, but when matching using propensity scores, its use was found to be insignificant. In conclusion, there was no difference in the rate of subsequent contralateral hip fracture when comparing HSSP with CMN. Additionally, the time to second surgery between the two treatment modalities was found to be statistically insignificant. It is unclear if bisphosphonate use increased the odds of having a contralateral fracture, regardless of the surgical intervention. The difference in the bisphosphonate effect using propensity score matching suggests that the results may be due to confounding variables and bias.

Dry Needling Versus Cortisone Injection in the Treatment of Greater Trochanteric Pain Syndrome: A Noninferiority Randomized Clinical Trial.

Study Design Prospective, randomized, partially blinded. Background Greater trochanteric pain syndrome (GTPS) is the current terminology for what was once called greater trochanteric or subgluteal bursitis. Cortisone (corticosteroid) injection into the lateral hip has traditionally been the accepted treatment for this condition; however, the effectiveness of injecting the bursa with steroids is increasingly being questioned. An equally effective treatment with fewer adverse side effects would be beneficial. Objective To investigate whether administration of dry needling (DN) is noninferior to cortisone injection in reducing lateral hip pain and improving function in patients with GTPS. Methods Forty-three participants (50 hips observed), all with GTPS, were randomly assigned to a group receiving cortisone injection or DN. Treatments were administered over 6 weeks, and clinical outcomes were collected at baseline and at 1, 3, and 6 weeks. The primary outcome measure was the numeric pain-rating scale (0-10). The secondary outcome measure was the Patient-Specific Functional Scale (0-10). Medication intake for pain was collected as a tertiary outcome. Results Baseline characteristics were similar between groups. A noninferiority test for a repeated-measures design for pain and averaged function scores at 6 weeks (with a noninferiority margin of 1.5 for both outcomes) indicated noninferiority of DN versus cortisone injection (both, P<.01). Medication usage (P = .74) was not different between groups at the same time point. No adverse side effects were reported. Conclusion Cortisone injections for GTPS did not provide greater pain relief or reduction in functional limitations than DN. Our data suggest that DN is a noninferior treatment alternative to cortisone injections in this patient population. Level of Evidence Therapy, level 1b. Registered December 2, 2015 at www.clinicaltrials.gov (NCT02639039). J Orthop Sports Phys Ther 2017;47(4):232-239. Epub 3 Mar 2017. doi:10.2519/jospt.2017.6994.

NSQIP-Based Quality Improvement Curriculum for Surgical Residents.

BACKGROUND: General surgery training has historically lacked a standardized approach to resident quality improvement (QI) education aside from traditional morbidity and mortality conference. In 2013, the ACGME formalized QI as a component of residency training. Our residency chose the NSQIP Quality In-Training Initiative (QITI) as the foundation for our QI training. We hypothesized that a focused curriculum based on outcomes would produce change in culture and improve the quality of patient care. STUDY DESIGN: Quality improvement curriculum design and implementation were retrospectively reviewed. Institutional NSQIP data pre-, during, and post-curriculum implementation were reviewed for improvement. RESULTS: A QITI project committee designed a 2-year curriculum, with 3 parts: didactics, focused on methods of data collection, QI processes, and techniques; review of current institutional performance, practice, and complication rates; and QI breakout groups tasked with creating "best practice" guidelines addressing common complications in our NSQIP semi-annual reports. Educational presentations were given to the surgical department addressing reduction of cardiac complications, pneumonia, surgical site infections (SSIs), and urinary tract infections (UTIs). Twenty-four residents completed both years of the QITI curriculum. National NSQIP decile ranks improved in known high outlier areas: cardiac complications, ninth to fourth decile; pneumonia, eighth to first decile; SSIs, tenth to second decile; and UTIs, eighth to third decile. Pneumonia and SSI rates demonstrated statistical improvement after curriculum implementation (p < 0.003). CONCLUSIONS: Implementing a QITI curriculum with a full resident complement is feasible and can positively affect surgical morbidity and nationally benchmarked performance. Resident QI education is essential to future success in delivering high quality surgical care.

Protocol-Driven Management of Suspected Common Duct Stones.

BACKGROUND: Common duct stones can be diagnosed by magnetic resonance cholangiopancreatography (MRCP), endoscopic ultrasound (EUS)/ERCP, and intraoperative cholangiogram (IOC). In 2015, our group adopted a standard approach of preoperative EUS/ERCP followed by laparoscopic cholecystectomy for patients with an admission bilirubin >4.0 mg/dL. For bilirubin <4.0 mg/dL, laparoscopic cholecystectomy with IOC was the initial procedure. Postoperative EUS/ERCP with endoscopic sphincterotomy was pursued for positive IOC. Exclusions included clinical suspicion of malignancy and surgically altered anatomy making endoscopic management impractical. STUDY DESIGN: A retrospective comparison of protocol and pre-protocol (baseline) patients was performed, looking at patient demographics, presence of pancreatitis, common duct stone risk factors, comorbidities, length of hospitalization, and postoperative morbidity. Statistical analysis was performed with t-test, chi-square, and Wilcoxon rank-sum test with significance at p < 0.05. RESULTS: There were 56 patients in each group, with a mean ± SD age of 50.5 ± 20.88 years and 49.3 ± 20.92 years, respectively (p = NS). There were no significant differences between baseline and protocol patients with respect to individual and cumulative preoperative comorbidities, pancreatitis, elevation of liver function tests, bilirubin, common duct size, and postoperative morbidity. There were fewer endoscopies (22 vs 35; p = 0.014), and shorter length of stay in protocol patients (2.8 days vs 3.8 days; p = 0.025). CONCLUSIONS: Protocol-driven management of patients with suspected common duct stones reduced the number of endoscopies and length of hospitalization, with no change in postoperative morbidity. This approach has the potential to decrease endoscopy-related morbidity and overall cost without affecting quality of care.

Effect of Obesity on Bone Healing After Foot and Ankle Long Bone Fractures.

As obesity has become more common, fractures in the obese population have become more frequent. Concern exists regarding alterations in bone health and healing in obese patients. A matched case-control study was performed at 1 institution to evaluate whether an association exists between nonunion and a high body mass index in metatarsal and ankle fractures. A total of 48 patients with nonunion were identified, and control patients matched 2 to 1 (n = 96) were selected. The control patients were matched for age, sex, and fracture type. No association was identified between nonunion and the continuous body mass index (p = .23) or morbid obesity, with a body mass index of ≥40 kg/m2 (p = .51). However, the results from both univariate and multivariate analysis suggested that patients with a current alcohol problem or a history of an alcohol problem might have a greater risk of nonunion. The odds ratio of a patient with a history of alcohol use experiencing nonunion was 2.7 (95% confidence interval 1.2 to 6.2). Further studies are warranted to confirm these findings.

High- versus low-dose leucovorin in the modified FOLFOX6 regimen for first-line treatment of metastatic colorectal cancer.

Background In response to the national leucovorin shortage in 2008, our institution adjusted the modified FOLFOX6 (leucovorin, fluorouracil, and oxaliplatin) protocol to utilize a lower dose of leucovorin (20 mg/m2). This adjustment was based on prospective studies suggesting that lower doses of leucovorin may be equally effective in other fluorouracil containing regimens. This retrospective study evaluates outcomes in metastatic colorectal cancer (mCRC) patients treated with low- (20 mg/m2) vs. high-dose (400 mg/m2) leucovorin in the FOLFOX6 regimen for mCRC. Methods This retrospective analysis included consecutive mCRC patients from 2004 to 2011 if they received at least one cycle of modified FOLFOX6 as first line therapy. Patients who received an initial leucovorin dose other than 20 mg/m2 or 400 mg/m2 on their first cycle were excluded. Patient characteristics included demographics, metastatic site at initial diagnosis, and treatment history including chemotherapy and surgery. Primary outcome was date of death or last contact. Cox proportional hazards regression analysis and Kaplan-Meier survival curves were utilized to evaluate the effect of leucovorin dose on overall survival. Log-rank tests were used to compare median survival times by dose group. Results Of the 93 mCRC patients who received first line modified FOLFOX6, leucovorin 400 mg/m2 was administered to 47 (51%) patients and 20 mg/m2 to 46 (49%) patients. There were no differences of baseline characteristics between the groups with exception of primary site of cancer ( p = 0.038). The overall survival time was 22.5 months (95% CI 16.6-29.6). The median survival time in the leucovorin 400 mg/m2 group was 23.1 months (95% CI 16.2-35.7) compared to leucovorin 20 mg/m2 which was 20.5 months (95% CI 14.2-34.2); p = 0.573. The median survival times in patients with one versus two or more sites with metastasis were statistically different (26.9 vs. 16.2 months, p = 0.009). Metastatic site removal or ablation showed differences in the median survival, 34.2 months (95% CI 20.8-50.9) vs. 16.6 months (95% CI 14.1-23.6) without metastatic disease removal ( p = 0.004). The odds of dying for patients with two metastatic sites was higher compared with the odds of those patients with one site, HR 1.8 (95% CI 1.08-3.0). Patients without metastatic site removal or ablation had higher odds of dying compared to those patients without this procedure, HR 0.47 (95% CI 0.27-0.81). Conclusion In this single center retrospective study, there was no difference in overall survival for mCRC patients treated with first line FOLFOX6 with low- vs. high-dose leucovorin.

Routine central lymph node dissection with total thyroidectomy for papillary thyroid cancer potentially minimizes level VI recurrence.

BACKGROUND: Treatment strategies for papillary thyroid cancer remain controversial due to the lack of large, randomized controlled trials. The purpose of this study was to review the benefit of routine bilateral central lymph node dissection (CLND) by analyzing local recurrence and complication rates from a single institution over a 15-year period. METHODS: A retrospective, institutional review board-approved review of the Baylor Scott & White Tumor Registry was performed on all patients who underwent operation for papillary thyroid cancer between 2000 and 2015. Patients were evaluated by age, sex, tumor size, operation performed, pathologic findings, adjuvant therapy, and date of recurrence. Primary outcomes were cancer recurrence, recurrent laryngeal nerve injury, and hypoparathyroidism. RESULTS: Total thyroidectomy with CLND was performed in 266 patients. Metastases to level VI lymph nodes were present in 106/266 (39.8%) patients. Average follow-up after thyroidectomy was 46 months (range 1-125 months). Papillary thyroid cancer recurred in 4 patients after thyroidectomy with CLND for primary tumors with mean size of 1.6 cm (range 1.0-2.0 cm). Two patients with T4 tumors had local recurrence in the paratracheal soft tissues, and 2 patients presented with recurrence in the lateral neck. Temporary nerve injuries occurred in 9/266 (3.4%) and permanent nerve injuries in 1/266 (0.4%) of CLND. Permanent hypoparathyroidism occurred in 4/266 (1.5%) patients. CONCLUSION: Total thyroidectomy with CLND can safely be performed routinely for treatment of papillary thyroid cancer in the hands of experienced endocrine surgeons. Dissection of level VI lymph nodes does not increase the risk of recurrent laryngeal nerve injury when performed routinely. Bilateral CLND with total thyroidectomy for papillary thyroid cancer potentially minimizes recurrence in the level VI compartment.