Citations

Abstract Purpose A protocol was developed to evaluate the value of an NK-1 receptor antagonist for preventing nausea and vomiting resulting from highly emetogenic chemotherapy when an olanzapine-based antiemetogenic regimen was used. Materials and Methods A221602, a prospective double-blind, placebo-controlled clinical trial, was developed to compare 2 ­olanzapine-containing antiemetic regimens, one with an NK-1 receptor antagonist (aprepitant or fosaprepitant) and one without. Trial patients had a malignant disease for which they received intravenous highly emetogenic chemotherapy (single day cisplatin ≥ 70 mg/m2 or doxorubicin plus cyclophosphamide on 1 day). Patients on both arms received commonly administered doses of a 5-HT3 receptor antagonist, dexamethasone, and olanzapine. Additionally, patients were randomized to receive an NK-1 receptor antagonist (fosaprepitant 150 mg IV or aprepitant 130 mg IV) or a corresponding placebo. The primary objective was to compare the proportion of patients with no nausea for 5 days following chemotherapy between the 2 study arms. This trial was designed to test for the noninferiority of deleting the NK-1 receptor antagonist, with noninferiority defined as a decrease in freedom from nausea by less than 10%. Results A total of 690 patients were entered on this trial, 50% on each arm. The proportion of patients without nausea for the complete 5-day study period was 7.4% lower (upper limit of the one-sided 95% confidence interval was 13.5%) in the arm without an NK-1 receptor antagonist compared with the arm with an NK-1 receptor antagonist. Conclusion This trial did not provide sufficient evidence to support that deletion of the NK-1 receptor antagonist was as good as keeping it, as a part of a 4-drug antiemetic regimen for highly emetogenic chemotherapy (ClinicalTrials.gov Identifier: NCT03578081).

Background: Multiple studies have compared outcomes among patients undergoing revision anterior cruciate ligament reconstruction (ACLR) with autograft versus allograft, but these data are inconsistently reported and long-term outcomes depending on graft type are yet to be determined. Purpose: To perform a systematic review of clinical outcomes after revision ACLR (rACLR) with autograft versus allograft. Study Design: Systematic review; Level of evidence, 4. Methods: A systematic review of the literature was performed by searching PubMed, the Cochrane Library, and Embase to identify studies that compared the outcomes of patients undergoing rACLR with autograft versus allograft. The search phrase used was autograft allograft revision anterior cruciate ligament reconstruction. Graft rerupture rates, return-to-sports rates, anteroposterior laxity, and patient-reported outcome scores (subjective International Knee Documentation Committee, Tegner, Lysholm, and Knee injury and Osteoarthritis Outcome Score) were evaluated. Results: Eleven studies met inclusion criteria, including 3011 patients undergoing rACLR with autograft (mean age, 28.9 years) and 1238 patients undergoing rACLR with allograft (mean age, 28.0 years). Mean follow-up was 57.3 months. The most common autograft and allograft types were bone–patellar tendon–bone grafts. Overall, 6.2% of patients undergoing rACLR experienced graft retear, including 4.7% in the autograft group and 10.2% in the allograft group ( P < .0001). Among studies that reported return-to-sports rates, 66.2% of patients with an autograft returned to sports as opposed to 45.3% of patients with an allograft ( P = .01). Two studies found significantly greater postoperative knee laxity in the allograft group as compared with the autograft group ( P < .05). Among all patient-reported outcomes, 1 study found 1 significant difference between groups: patients with an autograft had a significantly higher postoperative Lysholm score when compared with patients with an allograft. Conclusion: Patients undergoing revision ACLR with an autograft can be expected to experience lower rates of graft retear, higher rates of return to sports, and less postoperative anteroposterior knee laxity when compared with patients undergoing revision ACLR with an allograft.

Introduction Acute type A aortic dissection (ATAAD) is one of the most critical emergencies in cardiovascular surgery. Additional complications such as organ malperfusion can significantly decrease the chances of survival. Despite promptly performed surgical treatment, impaired organ perfusion may persist, thus close postoperative monitoring is recommended. But, is there a surgical consequence due to the existence of a preoperatively known malperfusion and is there a correlation between pre-, peri- and postoperative levels of serum lactate and proven malperfusion? Methods Between 2011 and 2018, 200 patients (66% male; median age: 62.5 years; interquartile range: +/−12.4 years) that received surgical treatment at our institution for an acute dissection DeBakey type I were enrolled in this study. The cohort was divided into two groups according to the preoperative existence of malperfusion and non-malperfusion. At least one kind of malperfusion occurred in 74 patients (Group A: 37%), while 126 patients (Group B: 63%) showed no evidence of malperfusion. Furthermore, lactate levels of both cohorts were differentiated into four periods: preoperative, intraoperative, 24 hours after surgery, and 2–4 days after surgery. Results The patients’ status differed significantly prior to surgery. Group A (malperfusion) showed an elevated requirement for mechanical resuscitation (A: 10.8%; B: 5.6%; p: 0.173), were significantly more often admitted in an intubated state (A: 14.9%; B: 2.4%; p: 0.001) and showed higher incidences of stroke (A: 18.9% ( n = 149); B: 3.2% ( n = 4); p: 0.001). Levels of serum lactate from the preoperative period until days 2–4 were significantly increased in the malperfusion cohort at all times. Conclusions Preexisting malperfusion due to ATAAD may significantly increase the chance of early mortality in patients with ATAAD. Serum lactate levels were a reliable marker for inadequate perfusion from admission until day 4 after surgery. Despite this, early intervention survival in this cohort remains limited.

AbstractBackgroundCompared to other sarcomas, myxoid liposarcoma (ML) is known to be radiosensitive, with improved oncologic outcomes. Although these tumors “shrink” following radiotherapy, there is a paucity of data examining the degree of radiosensitivity and oncologic outcome. The purpose of the study was to evaluate pre‐ and postradiotherapy tumor volume to determine if size reduction impacts outcome.MethodsWe reviewed 62 patients with ML undergoing surgical resection combined with preoperative radiotherapy, with pre‐ and postradiotherapy MRI. This included 34 (55%) males, with a mean age of 47 ± 14 years. All tumors were deep to the fascia, and 12 (19%) patients had tumors with a >5% round‐cell component.ResultsThe mean volume reduction was 54% ± 29%. Compared to patients with >25% volume reduction, patients with reduction ≤25% had worse 10‐year disease specific survival (86% vs. 37%, p < 0.01), in addition to an increased risk of metastatic disease (HR 4.63, p < 0.01) and death due to disease (HR 4.52, p < 0.01).ConclusionLack of volume reduction is a risk factor for metastatic disease and subsequent death due to disease in patients with extremity ML treated with combined preoperative radiotherapy and surgery. This data could be used to stratify patients for adjuvant therapies and follow‐up intervals.

AbstractBackgroundThe relationship between CINV duration and recurrence in subsequent cycles is largely unstudied. Our objective was to determine if patients experiencing CINV in their first cycle of chemotherapy (C1) would face increased risk of CINV in later cycles and whether the duration of the CINV would predict increased risk of recurrence.Patients and MethodsUsing data from a previously reported phase III trial, we assessed patients’ recurrence of breakthrough CINV after antiemetic prophylaxis for anthracycline+cyclophosphamide (AC) for breast cancer, comparing C1 short CINV vs. extended CINV as a secondary analysis. Complete response (CR) and CINV duration were primary and secondary endpoints, respectively. CR was considered prophylaxis success; lack of CR was considered treatment failure (TF).ResultsAmong 402 female patients, 99 (24.6%) had TF in C1 (TF1). The remaining 303 patients (CR1) had ≥93% CR rates in each subsequent cycle, while the 99 patients with TF1 had TF rates of 49.8% for cycles 2-4 (P &lt; .001). The 51 patients with extended TF (≥3 days) in C1 had recurrent TF in 73/105 later cycles (69.5%, P &lt; .001), while the 48 patients with short TF (1-2 days) in C1 had recurrent TF in 33/108 later cycles (30.6%). The relative risk of recurrence after C1 extended TF was 2.28 (CI 1.67-3.11; P &lt; .001) compared to short TF.ConclusionsProphylaxis success in C1 led to &gt;90% repeat success across cycles of AC-based chemotherapy. For patients with breakthrough CINV, extended duration strongly predicted recurrent CINV. The duration of CINV should be closely monitored, and augmenting antiemetic prophylaxis considered for future cycles when extended CINV occurs.

Case: This report describes a case of a posterior oblique ligament (POL) bony avulsion fracture associated with an anterior cruciate ligament (ACL) tear in a 16-year-old female gymnast. The avulsion fracture was discovered on repeat radiographs and magnetic resonance imaging after the patient developed increased pain after ACL reconstruction. After excising the bony avulsion and repairing the POL, she reported complete resolution of her preoperative pain. Conclusion: Bony avulsion fractures of the POL are rare and challenging to diagnose. Awareness of this injury and the subtle imaging findings will help clinicians appropriately diagnose and treat these lesions.

AbstractDespite being relatively uncommon in the general population, thumb amputations cause severe disability. More than 3,300 thumb amputations occurred in the United States. The thumb makes up around 40% of the function of the hand. Therefore, losing it would result in significant medical, hospital, and societal costs. Thumb reconstruction surgery's primary goal is to restore grip strength, including the range of motion, fine and tripod pinch, power grasp, strength, and sensibility, while secondary goals include restoring hand aesthetics. In cases of thumb replantation, like-for-like replacement is possible; however, when thumb replantation is not possible, great toe-to-hand transplantation is the best available reconstruction. When compared with other reconstructive options such as osteoplastic thumb reconstruction, pollicization, second toe transplantation, and the use of a thumb prosthesis, great toe transplantation provides superior function and aesthetics. For restoring pinch, sensitivity, strength, and aesthetics of the hand with well-tolerated donor site morbidity, toe to thumb transplantation is regarded as the gold standard.

12107 Background: Chemotherapy-induced nausea and vomiting (CINV), a major adverse effect of cancer treatment, can attenuate life quality. Multiple international antiemetic guidelines have recommended a 4-drug regimen (corticosteroid, 5-HT3 receptor antagonist, NK-1 receptor antagonist, and the antipsychotic medication olanzapine) for decreasing highly emetogenic CINV. This raised a question regarding whether antiemetic therapy regimens for highly emetogenic chemotherapy could be de-intensified, decreasing cost and side effects from anti-emetogenic agents. Methods: Study A221602 was developed to compare two olanzapine-containing antiemetic regimens, one with the use of an NK-1 receptor antagonist (aprepitant or fosaprepitant) and one without. Patients (pts) received intravenous highly emetogenic chemotherapy as either 1) cisplatin, given on one day, at a dose of ≥ 70 mg/m2, with or without other chemotherapy agent(s) or 2) doxorubicin (60 mg/m2) plus cyclophosphamide (600 mg/m2) on one day. Pts in both arms received 1) a 5-HT3 receptor antagonist (palonosetron 0.25 mg IV or ondansetron 8-16 mg IV or 16-24 mg PO,) on day one, 2) dexamethasone (12 mg PO, day one followed by 8 mg PO, days 2-4), and 3) olanzapine (10 mg/day PO, days 1 to 4). On Day 1, all agents were given prior to chemotherapy, with the exception that olanzapine could be taken prior to chemotherapy or at bedtime. Additionally, pts were randomized to receive an NK-1 receptor antagonist (fosaprepitant 150 mg IV or aprepitant 130 mg IV; 346 pts) or a matching placebo (344 pts). The primary objective was to compare the proportion of patients with no nausea for 5 days following receipt of their chemotherapy between the two study arms. Results: While there was no suggestion of outcome differences on day 1 between the two study arms, fewer pts (7.4%; upper limit of the 95% confidence interval was 13.5%) without NK-1 receptor antagonists were without nausea for the complete 5-day study period. Conclusions: Per the study design, created to exclude a 10% benefit for NK-1 receptor antagonists, the results did not provide sufficient evidence to reject the hypothesis that the 4-drug regimen was superior to the protocol 3-drug regimen (p=0.24). Support: UG1CA189823; Clinical trial information: NCT03578081.

Abstract Background With a growing prevalence of inflammatory bowel disease (IBD) in elderly patients, there is a clinical requirement to understand the impact of treatment in this population.1 Filgotinib (FIL) is an oral Janus kinase 1 preferential inhibitor. This post hoc analysis of data collected in the phase 2b/3 SELECTION programme evaluated the efficacy and safety of FIL in patients with ulcerative colitis (UC) stratified by age. Methods The SELECTION programme includes two Induction Studies, a Maintenance Study (NCT02914522) and a long-term extension (LTE) study (NCT02914535). Adults aged 18–75 years with moderately to severely active UC were randomized 2:2:1 to receive FIL 200 mg or 100 mg or placebo once daily for 11 weeks. Responders at week 10 were re-randomized 2:1 to continue assigned FIL treatment or placebo from week 11–58. In LTE, patients with disease worsening and those completing week 58 continued assigned treatment before receiving open-label FIL. We assessed the efficacy and safety of FIL at any dose in the overall cohort of SELECTION and LTE, stratified into five age groups: &lt;30, ≥30–&lt;40, ≥40–&lt;50, ≥50–&lt;60 and ≥60 years. Clinical remission was evaluated at week 10 and pMCS remission was assessed at week 10, 58 and LTE weeks 2, 4, 12 and 24. Exposure-adjusted incidence rates (EAIRs) were calculated for adverse events (AEs). A data cut-off of 28 February 2020 was used. Results Baseline disease activity and previous and concomitant treatments were comparable across age groups in each treatment arm. While there were fewer patients in the ≥60 years group, patient distribution was similar in all other age groups. FIL induced clinical (~16%) and pMCS (~36%) remission in similar proportions of patients across all age groups at week 10 (Figure 1). At week 58, pMCS remission was achieved in ~53% of FIL-treated patients across age groups (Figure 2). In LTE, the proportion of FIL-treated patients in pMCS remission generally increased with time and remained similar across all age groups (Figure 3). FIL-treated patients aged ≥60 years had higher EAIRs of any AE, infections, herpes zoster, malignancies, NMSC and MACE than younger patients (Table). One thromboembolic event occurred in a FIL-treated patient aged &lt;30 years. Three deaths related to cardiovascular disease occurred in FIL-treated patients aged ≥50 years. Conclusion These findings suggest FIL is efficacious in inducing and maintaining symptomatic remission and could have an acceptable safety profile in adults with UC of all ages, including ≥60 years old. Age-related increases in incidences of certain AEs might be expected in patients with IBD; however, the number of patients ≥60 years limits comparison of these data with reported rates. Reference 1Zammarchi et al. BMC Gastroenterol 2020;20;147