Objective assessment of postural ergonomics in neurosurgery: integrating wearable technology in the operating room.

OBJECTIVE: Physical stress associated with the static posture of neurosurgeons over prolonged periods can result in fatigue and musculoskeletal disorders. Objective assessment of surgical ergonomics may contribute to postural awareness and prevent further complications. This pilot study examined the feasibility of using wearable technology as a biofeedback tool to address this gap. METHODS: Ten neurosurgeons, including 5 attendings (all faculty) and 5 trainees (1 fellow, 4 residents), were recruited and equipped with two wearable sensors attached to the back of their head and their upper back. The sensors collected the average time spent in extended (≤ -10°), neutral (> -10° and < 10°), and flexed (≥ 10°) static postures (undetected activity for more than 10 seconds) during spine and cranial procedures. Feasibility outcomes aimed for more than 70% of accurate data collection. Exploratory outcomes included the comparison of postural variability within and between participants adjusted to their demographics excluding nonrelated surgical activities, and postoperative self-assessment surveys. RESULTS: Sixteen (80%) of 20 possible recordings were successfully collected and analyzed from 11 procedures (8 spine, 3 cranial). Surgeons maintained a static posture during 52.7% of the active surgical time (mean 1.58 hrs). During spine procedures, all surgeons used an exoscope while standing, leading to a significantly longer time spent in a neutral static posture (p < 0.001, partial η2 = 0.14): attendings remained longer in a neutral static posture (36.4% ± 15.3%) than in the extended (9% ± 6.3%) and flexed (5.7% ± 3.4%) static postures; trainees also remained longer in a neutral static posture (30.2% ± 13.8%) than in the extended (11.1% ± 6.3%) and flexed (11.9% ± 6.6%) static postures. During cranial procedures, surgeons intermittently transitioned between standing/exoscope use and sitting/microscope use, with trainees spending a shorter time in a neutral static posture (16.3% vs 48.5%, p < 0.001) and a longer time in a flexed static posture (18.5% vs 2.7%, p < 0.001) compared with attendings. Additionally, longer cranial procedures correlated with surgeons spending a longer time (r = 0.94) in any static posture (extended, flexed, and neutral), with taller surgeons exhibiting longer periods in flexed and extended static postures (r = 0.86). Postoperative self-assessment revealed that attendings perceived spine procedures as more difficult than trainees (p = 0.029), while trainees found cranial procedures to be of greater difficulty than spine procedures (p = 0.012). Attendings felt more stressed (p = 0.048), less calmed (p = 0.024), less relaxed (p = 0.048), and experienced greater stiffness in their upper body (p = 0.048) and more shoulder pain (p = 0.024) during cranial versus spine procedures. CONCLUSIONS: Wearable technology is feasible to assess postural ergonomics and provide objective biofeedback to neurosurgeons during spine and cranial procedures. This study showed reproducibility for future comparative protocols focused on correcting posture and surgical ergonomic education.

Development of a Sensor Technology to Objectively Measure Dexterity for Cardiac Surgical Proficiency.

BACKGROUND: Technical skill is essential for good outcomes in cardiac surgery. However, no objective methods exist to measure dexterity while performing surgery. The purpose of this study was to validate sensor-based hand motion analysis (HMA) of technical dexterity while performing a graft anastomosis within a validated simulator. METHODS: Surgeons at various training levels performed an anastomosis while wearing flexible sensors (BioStamp nPoint, MC10 Inc) with integrated accelerometers and gyroscopes on each hand to quantify HMA kinematics. Groups were stratified as experts (n = 8) or novices (n = 18). The quality of the completed anastomosis was scored using the 10 Point Microsurgical Anastomosis Rating Scale (MARS10). HMA parameters were compared between groups and correlated with quality. Logistic regression was used to develop a predictive model from HMA parameters to distinguish experts from novices. RESULTS: Experts were faster (11 ± 6 minutes vs 21 ± 9 minutes; P = .012) and used fewer movements in both dominant (340 ± 166 moves vs 699 ± 284 moves; P = .003) and nondominant (359 ± 188 moves vs 567 ± 201 moves; P = .02) hands compared with novices. Experts' anastomoses were of higher quality compared with novices (9.0 ± 1.2 MARS10 vs 4.9 ± 3.2 MARS10; P = .002). Higher anastomosis quality correlated with 9 of 10 HMA parameters, including fewer and shorter movements of both hands (dominant, r = -0.65, r = -0.46; nondominant, r = -0.58, r = -0.39, respectively). CONCLUSIONS: Sensor-based HMA can distinguish technical dexterity differences between experts and novices, and correlates with quality. Objective quantification of hand dexterity may be a valuable adjunct to training and education in cardiac surgery training programs.

Optimizing Tissue Oxygenation in Reduction Mammoplasty: The Role of Continuous Diffusion of Oxygen: A Feasibility Pilot Randomized Controlled Trial.

INTRODUCTION: Bilateral reduction mammoplasty (BRM) aims to alleviate macromastia-related symptoms in women. This procedure involves a T-Junction suture at the medial inframammary fold that encompasses 12%-39% of wound breakdowns mainly due to reduced perfusion. Continuous diffusion of oxygen (CDO) may enhance breast tissue oxygenation to prevent such complication. We explored the feasibility of this therapy. METHODS: A 4-wk feasibility-pilot randomized controlled trial of women undergoing BRM was conducted. By internal randomization (left/right side), participants received standard of care (SOC) in one breast using topical skin adhesive, while their other breast received SOC + CDO at the T-junction covered by a silicon sheet (sCDO), or CDO directly to the T-Junction skin (dCDO). Feasibility outcomes included protocol delivery, outcome measurement, device-related adverse events, and device acceptability. Exploratory outcomes were T-Junction SatO2 and deoxyhemoglobin assessed with near-infrared spectroscopy and wound dehiscence. RESULTS: Sixteen participants (age = 33 ± 8 y; body mass index = 34.34 ± 5.85 kg/m2) were recruited, conforming n = 32 breasts (SOC, n = 16; dCDO, n = 10, sCDO, n = 6). At 4 wk, protocol delivery was 93.7%, outcome measuring 100%, and device-related adverse events 0%. Device acceptability showed an 85.4% strong agreement for attitude toward use, 78.2% perceived ease of use, and 77.7% perceived usefulness. Breasts undergoing sCDO showed higher SatO2 (P < 0.001), whereas lower deoxyhemoglobin (P < 0.001) compared to all other breast groups. However, wound dehiscence was not different between groups (P = 0.66). CONCLUSIONS: Self-applied CDO to the T-Junction is feasible, safe, and acceptable, in patients undergoing BRM. In a proper wound environment, CDO may enhance breast tissue oxygenation. However, it is unclear whether CDO leads to decreased wound dehiscence. This study showed reproducibility for larger randomized trials.

Electrical stimulation to regain lower extremity muscle perfusion and endurance in patients with post-acute sequelae of SARS CoV-2: A randomized controlled trial.

Muscle deconditioning and impaired vascular function in the lower extremities (LE) are among the long-term symptoms experienced by COVID-19 patients with a history of severe illness. These symptoms are part of the post-acute sequelae of Sars-CoV-2 (PASC) and currently lack evidence-based treatment. To investigate the efficacy of lower extremity electrical stimulation (E-Stim) in addressing PASC-related muscle deconditioning, we conducted a double-blinded randomized controlled trial. Eighteen (n = 18) patients with LE muscle deconditioning were randomly assigned to either the intervention (IG) or the control (CG) group, resulting in 36 LE being assessed. Both groups received daily 1 h E-Stim on both gastrocnemius muscles for 4 weeks, with the device functional in the IG and nonfunctional in the CG. Changes in plantar oxyhemoglobin (OxyHb) and gastrocnemius muscle endurance (GNMe) in response to 4 weeks of daily 1 h E-Stim were assessed. At each study visit, outcomes were measured at onset (t0 ), 60 min (t60 ), and 10 min after E-Stim therapy (t70 ) by recording ΔOxyHb with near-infrared spectroscopy. ΔGNMe was measured with surface electromyography at two time intervals: 0-5 min (Intv1 ) and: 55-60 min (Intv2 ). Baseline OxyHb decreased in both groups at t60 (IG: p = 0.046; CG: p = 0.026) and t70 (IG = p = 0.021; CG: p = 0.060) from t0 . At 4 weeks, the IG's OxyHb increased from t60 to t70 (p < 0.001), while the CG's decreased (p = 0.003). The IG had higher ΔOxyHb values than the CG at t70 (p = 0.004). Baseline GNMe did not increase in either group from Intv1 to Intv2 . At 4 weeks, the IG's GNMe increased (p = 0.031), whereas the CG did not change. There was a significant association between ΔOxyHb and ΔGNMe (r = 0.628, p = 0.003) at 4 weeks in the IG. In conclusion, E-Stim can improve muscle perfusion and muscle endurance in individuals with PASC experiencing LE muscle deconditioning.

Home-Based Electrical Stimulation to Accelerate Wound Healing-A Double-Blinded Randomized Control Trial.

BACKGROUND: Electrical stimulation (E-Stim) may offer a unique adjunctive treatment to heal complicated diabetic foot ulcers (DFU). Our primary goal is to examine the effectiveness of daily home-based E-Stim therapy to speed-up wound healing. METHODS: Patients with chronic DFUs and mild to severe peripheral arterial disease (PAD) were recruited and randomized to either control (CG) or intervention (IG) groups. The IG received 1-hour home-based E-Stim therapy on daily basis for 4 weeks (4W). E-Stim was delivered through electrical pads placed above the ankle joint using a bio-electric stimulation technology (BEST®) platform (Tennant Biomodulator® PRO). The CG was provided with an identical but non-functional device for the same period. The primary outcome included wound area reduction at 4W from baseline (BL). RESULTS: Thirty-eight patients were recruited and 5 were removed due to non-compliance or infection, leaving 33 participants (IG, n = 16; CG, n =17). At 4W, the IG showed a significant wound area reduction of 22% (BL: 7.4 ± 8.5 cm2 vs 4W: 5.8 ± 8.0 cm2, P = 0.002). Average of wound area was unchanged in the CG (P = 0.982). The self-report adherence to daily home-therapy was 93.9%. CONCLUSIONS: Daily home-based E-Stim provides early results on the feasibility, acceptability, and effectiveness of E-Stim as an adjunctive therapy to speed up wound healings in patients with chronic DFU and mild to severe PAD.

Frailty in People with Chronic Limb Threatening Ischemia and Diabetes-Related Foot Ulcers: A Systematic Review.

BACKGROUND: Frailty represents a state of multisystem impairment that may adversely impact people presenting with chronic limb-threatening ischemia (CLTI) and diabetes-related foot ulcers (DFUs). The aim of this systematic review was to explore the association between frailty and outcomes from CLTI and DFUs. METHODS: We performed a systematic literature search of electronic databases to find studies using a validated measure of frailty in individuals with CLTI and/or DFUs. The primary outcomes were the impact of frailty on the severity of initial clinical presentation and unfavorable follow-up outcomes including readmissions, major limb amputation, cardiovascular events, revascularization, and wound healing. RESULTS: Ten cohort studies were included. Two studies had a low risk of bias, 1 was unable to be assessed, 5 had moderate risk of bias, and 2 high risk of bias. The prevalence of frailty in people presenting with CLTI ranged from 27% to 88% and was 71% in people with DFUs. The presence of frailty in both people with CLTI and DFUs was associated with substantially increased severity at presentation (severity of ischemia and tissue loss) and poorer outcomes at follow-up (risk of readmission, limb amputation, and all-cause mortality). CONCLUSIONS: The presence of frailty in both people with CLTI and DFUs is likely associated with substantially higher complexity at presentation followed by a greater risk for readmission, amputation, and death during follow-up. Heterogeneity in the tools used to screen for frailty, poor definition of frailty, and unclear evaluation of exposure and outcomes limit further interpretation of findings.

Safety and efficacy of electrical stimulation for lower-extremity muscle weakness in intensive care unit 2019 Novel Coronavirus patients: A phase I double-blinded randomized controlled trial.

Background: Intensive care unit (ICU) prolonged immobilization may lead to lower-extremity muscle deconditioning among critically ill patients, particularly more accentuated in those with 2019 Novel Coronavirus (COVID-19) infection. Electrical stimulation (E-Stim) is known to improve musculoskeletal outcomes. This phase I double-blinded randomized controlled trial examined the safety and efficacy of lower-extremity E-Stim to prevent muscle deconditioning. Methods: Critically ill COVID-19 patients admitted to the ICU were randomly assigned to control (CG) or intervention (IG) groups. Both groups received daily E-Stim (1 h) for up to 14 days on both gastrocnemius muscles (GNMs). The device was functional in the IG and non-functional in the CG. Primary outcomes included ankle strength (Ankles) measured by an ankle-dynamometer, and GNM endurance (GNMe) in response to E-Stim assessed with surface electromyography (sEMG). Outcomes were measured at baseline, 3 and 9 days. Results: Thirty-two (IG = 16, CG = 16) lower extremities in 16 patients were independently assessed. The mean time between ICU admission and E-Stim therapy delivery was 1.8 ± 1.9 days (p = 0.29). At 3 days, the IG showed an improvement compared to the CG with medium effect sizes for Ankles (p = 0.06, Cohen's d = 0.77) and GNMe (p = 0.06, d = 0.69). At 9 days, the IG GNMe was significantly higher than the CG (p = 0.04, d = 0.97) with a 6.3% improvement from baseline (p = 0.029). E-Stim did not alter vital signs (i.e., heart/respiratory rate, blood saturation of oxygen), showed no adverse events (i.e., pain, skin damage, discomfort), nor interfere with ICU standard of care procedures (i.e., mechanical ventilation, prone rotation). Conclusion: This study supports the safety and efficacy of early E-Stim therapy to potentially prevent deterioration of lower-extremity muscle conditions in critically ill COVID-19 patients recently admitted to the ICU. If confirmed in a larger sample, E-Stim may be used as a practical adjunctive therapy. Clinical trial registration: [https://clinicaltrials.gov/], identifier [NCT04685213].

Guillotine Transmetatarsal Amputations With Staged Closure Promote Early Ambulation and Limb Salvage in Patients With Advanced Chronic Limb-Threatening Ischemia.

PURPOSE: Transmetatarsal amputation (TMA) with primary closure has long been an option for limb salvage in patients with advanced chronic limb-threatening ischemia (CLTI) with extensive tissue loss of the forefoot. However, TMA healing and closure techniques are challenging, specifically in high-risk patients. Guillotine transmetatarsal amputations (gTMA) with staged closure may provide an alternative treatment in this population. We report long-term outcomes of such technique. MATERIALS AND METHODS: A single-center retrospective cohort study of CLTI patients undergoing gTMA between 2017 and 2020 was performed. Limb salvage, wound healing, and survival rates were quantified using Kaplan-Meier (KM) analysis. Multivariate regression was used to identify the effect of patient characteristics on the outcomes. RESULTS: Forty-four gTMA procedures were reviewed. Median follow-up was 381 (interquartile range [IQR], 212-539.75) days. After gTMA, 87.8% (n=36) of the patients were able to ambulate after a median interval of 2 (IQR, 1-3) days. Eventual coverage was achieved in a personalized and staged approach by using a combination of skin substitutes (88.6%, n=39) ± split thickness skin grafts (STSG, 61.4%, n=27). KM estimates for limb salvage, wound healing, and survival were 84.1%, 54.5%, and 88.6% at 1 year and 81.8%, 63.8%, and 84.1% at 2 years. Wound healing was significantly associated with STSG application (p=0.002, OR=16.5, 95% CI 2.87-94.81). CONCLUSION: gTMA resulted in high limb salvage rates during long-term follow-up in CLTI patients. Adjunctive STSG placement may enhance wound healing at the gTMA site, thus leading to expedited wound closure. Surgeons may consider gTMA as an alternative to reduce limb loss in CLTI patients at high risk of major amputation. CLINICAL IMPACT: Currently, the clinical presentation of CLTI is becoming more complex to deal with due to the increasing comorbidities as the society becomes older. The data shown in this article means for clinicians that when facing diffused forefoot gangrene and extensive tissue loss, limb preservation could still be considered instead of major amputation. Guillotine transmetatarsal amputations in the setting of an aggressive multidisciplinary group, can be healed by the responsibly utilization of dermal substitutes and skin grafts leading to the preservation of the extremity, allowing mobility, avoiding of sarcopenia, and decreasing frailty. This will equate to maintenance of independent living and preservation of lifespan.

The Application of Digital Frailty Screening to Triage Nonhealing and Complex Wounds.

OBJECTIVE: We investigated the association between the complexity of diabetic foot ulcers (DFUs) and frailty. RESEARCH DESIGN AND METHODS: Individuals (n = 38) with Grade 2 Wagner DFU were classified into 3 groups based on the Society for Vascular Surgery risk-stratification for major limb amputation as Stage 1 at very low risk (n = 19), Stage 2 at low risk (n = 9), and Stage 3 to 4 at moderate-to-high risk (n = 10) of major limb amputation. Frailty status was objectively assessed using a validated digital frailty meter (FM). The FM works by quantifying weakness, slowness, rigidity, and exhaustion over a 20-second repetitive elbow flexion-extension exercise using a wrist-worn sensor. FM generates a frailty index (FI) ranging from 0 to 1; higher values indicate progressively greater severity of frailty. Skin perfusion pressure (SPP), albumin, and tissue oxygenation level (SatO2) were also measured. One-way analysis of variance (ANOVA) was used to identify group effect for wound complexity. Pearson's correlation coefficient was used to assess the associations with frailty and clinical endpoints. RESULTS: Frailty index was higher in Stage 3 and 4 as compared to Stage 1 (d = 1.4, P < .01) and Stage 2 (d = 1.2, P < .01). Among assessed frailty phenotypes, exhaustion was correlated with SPP (r = -0.63, P < .01) and albumin (r = -0.5, P < .01). CONCLUSION: Digital biomarkers of frailty may predict complexity of DFU and thus triage individuals who can be treated more simply in their primary clinic versus higher risk patients who require prompt referral to multidisciplinary, more complex care.

Continuous Diffusion of Oxygen Adjunct Therapy to Improve Scar Reduction After Cervicotomy - A Proof of Concept Randomized Controlled Trial.

BACKGROUND: Dressing materials are known to influence post-operative surgical wound healing and scar formation (SF). A particular dressing that could promote wound hydration is essential to ensure quick epithelialization and reduce SF. This study examined the effectiveness of a novel Continuous Diffusion of Oxygen (CDO) dressing to reduce scar length post cervicotomy. METHODS: A randomized controlled trial was performed in patients undergoing cervicotomy, either for thyroid or parathyroid disease. Patients were randomized to either control (CG) or intervention (IG) groups. The IG received a portable CDO system (TransCu O2, EO2 Concepts Inc., TX, USA), whereas the CG received a standard dressing for a 4-week period. The primary outcome was >10% of scar length reduction and %change in scar length. RESULTS: 21 patients were recruited (Age: 53 ± 16 years; 90% female; CG = 9, IG = 12). 5 patients were lost to follow-up. At 4 weeks, 88.8% of the IG significantly achieved >10% of scar reduction (versus CG = 28.5%, d = 0.48, P = 0.049), showing a 40.4% smaller scar (15.7% versus 11.2%, d = 0.13, P = 0.72) compared to the CG. However, the difference was not significant. A sub-sample of patients undergoing thyroidectomy showed a significant scar reduction using CDO (IG = 11.6% versus CG = 5.1%, d = 2.96, P = 0.009). CONCLUSIONS: This is the first study to assess scar reduction using CDO adjunct therapy after cervicotomy. Advanced CDO dressings may assist wound healing showing improved outcomes for scar visualization in patients undergoing thyroidectomy. A larger sample is required to validate this observation.

Effectiveness of Lower-Extremity Electrical Stimulation to Improve Skin Perfusion.

Background: Although numerous studies suggest the benefit of electrical stimulation (E-Stim) therapy to accelerate wound healing, the underlying mechanism of action is still debated. In this pilot study, we examined the potential effectiveness of lower-extremity E-Stim therapy to improve tissue perfusion in patients with diabetic foot ulcers. Methods: Thirty-eight patients with diabetic foot ulcers underwent 60 min of active E-Stim therapy on acupuncture points above the level of the ankle joint using a bioelectric stimulation technology platform. Perfusion changes in response to E-Stim were assessed by measuring skin perfusion pressure (SPP) at baseline and during 30 and 60 min of therapy; retention was assessed 10 min after therapy. Tissue oxygen saturation (SatO2) was measured using a noninvasive near-infrared camera. Results: Skin perfusion pressure increased in response to E-Stim therapy (P = .02), with maximum improvement observed at 60 min (11%; P = .007) compared with baseline; SPP reduced 10 min after therapy but remained higher than baseline (9%; P = .1). Magnitude of improvement at 60 min was negatively correlated with baseline SPP values (r = -0.45; P = .01), suggesting that those with lower perfusion could benefit more from E-Stim therapy. Similar trends were observed for SatO2, with statistically significant improvement for a subsample (n = 16) with moderate-to-severe peripheral artery disease. Conclusions: This study provides early results on the feasibility and effectiveness of E-Stim therapy to improve skin perfusion and SatO2. The magnitude of benefit is higher in those with poorer skin perfusion. Also, the effects of E-Stim could be washed out after stopping therapy, and regular daily application might be required for effective benefit in wound healing.

Utilization of Flexible-Wearable Sensors to Describe the Kinematics of Surgical Proficiency.

BACKGROUND: Traditional assessment (e.g., checklists, videotaping) for surgical proficiency may lead to subjectivity and does not predict performance in the clinical setting. Hand motion analysis is evolving as an objective tool for grading technical dexterity; however, most devices accompany with technical limitations or discomfort. We purpose the use of flexible wearable sensors to evaluate the kinematics of surgical proficiency. METHODS: Surgeons were recruited and performed a vascular anastomosis task in a single institution. A modified objective structured assessment of technical skills (mOSATS) was used for technical qualification. Flexible wearable sensors (BioStamp RCTM, mc10 Inc., Lexington, MA) were placed on the dorsum of the dominant hand (DH) and nondominant hand (nDH) to measure kinematic parameters: path length (Tpath), mean (Vmean) and peak (Vpeak) velocity, number of hand movements (Nmove), ratio of DH to nDH movements (rMov), and time of task (tTask) and further compared with the mOSATS score. RESULTS: Participants were categorized as experts (n = 12) and novices (n = 8) based on a cutoff mean mOSATS score. Significant differences for tTask (P = 0.02), rMov (P = 0.07), DH Tpath (P = 0.04), Vmean (P = 0.07), Vpeak (P = 0.04), and nDH Nmove (P = 0.02) were in favor of the experts. Overall, mOSATS had significant correlation with tTask (r = -0.69, P = 0.001), Nmove of DH (r = -0.44, P = 0.047) and nDH (r = -0.66, P = 0.001), and rMov (r = 0.52, P = 0.017). CONCLUSIONS: Hand motion analysis evaluated by flexible wearable sensors is feasible and informative. Experts utilize coordinated two-handed motion, whereas novices perform one-handed tasks in a hastily jerky manner. These tendencies create opportunity for improvement in surgical proficiency among trainees.

Association Between Wearable Device-Based Measures of Physical Frailty and Major Adverse Events Following Lower Extremity Revascularization.

Importance: Physical frailty is a key risk factor associated with higher rates of major adverse events (MAEs) after surgery. Assessing physical frailty is often challenging among patients with chronic limb-threatening ischemia (CLTI) who are often unable to perform gait-based assessments because of the presence of plantar wounds. Objective: To test a frailty meter (FM) that does not rely on gait to determine the risk of occurrence of MAEs after revascularization for patients with CLTI. Design, Setting, and Participants: This cohort study included 184 consecutively recruited patients with CLTI at 2 tertiary care centers. After 32 individuals were excluded, 152 participants were included in the study. Data collection was conducted between May 2018 and June 2019. Exposures: Physical frailty measurement within 1 week before limb revascularization and incidence of MAEs for as long as 1 month after surgery. Main Outcomes and Measures: The FM works by quantifying weakness, slowness, rigidity, and exhaustion during a 20-second repetitive elbow flexion-extension exercise using a wrist-worn sensor. The FM generates a frailty index (FI) ranging from 0 to 1; higher values indicate progressively greater severity of physical frailty. Results: Of 152 eligible participants (mean [SD] age, 67.0 [11.8] years; 59 [38.8%] women), 119 (78.2%) were unable to perform the gait test, while all could perform the FM test. Overall, 53 (34.9%), 58 (38.1%), and 41 (27.0%) were classified as robust (FI <0.20), prefrail (FI ≥0.20 to <0.35), or frail (FI ≥0.35), respectively. Within 30 days after surgery, 24 (15.7%) developed MAEs, either major adverse cardiovascular events (MACE; 8 [5.2%]) or major adverse limb events (MALE; 16 [10.5%]). Baseline demographic characteristics were not significantly different between frailty groups. In contrast, the FI was approximately 30% higher in the group that developed MAEs (mean [SD] score, 0.36 [0.14]) than those who were MAE free (mean [SD] score, 0.26 [0.13]; P = .001), with observed MAE rates of 4 patients (7.5%), 7 patients (12.1%), and 13 patients (31.7%) in the robust, prefrail and frail groups, respectively (P = .004). The FI distinguished individuals who developed MACE and MALE from those who were MAE free (MACE: mean [SD] FI score, 0.38 [0.16]; P = .03; MALE: mean [SD] FI score, 0.35 [0.13]; P = .004) after adjusting by body mass index. Conclusions and Relevance: In this cohort study, measuring physical frailty using a wrist-worn sensor during a short upper extremity test was a practical method for stratifying the risk of MAEs following revascularization for CLTI when the administration of gait-based tests is often challenging.

Endovascular Therapy in an "All-Comers" Risk Group for Chronic Limb-Threatening Ischemia Demonstrates Safety and Efficacy When Compared with the Established Performance Criteria Proposed by the Society for Vascular Surgery.

BACKGROUND: The aim of this study was to describe the applicability of the Society for Vascular Surgery (SVS) objective performance goals (OPGs) as a tool to evaluate results in the context of endovascular management of noncomplex and complex patients (i.e., end stage renal disease/history of prosthetic conduit) with chronic limb-threatening ischemia (CLTI). METHODS: Patients diagnosed with CLTI undergoing endovascular procedures from March 2016 to April 2017 were included, and medical records were examined. Patients were categorized as OPG risk (OPGR) and non-OPG risk (nOPGR) groups in accordance with the SVS performance criteria. We compared clinical events between the two groups and then further to the SVS OPGs. Thirty-day outcomes (safety) were major amputation (AMP), major adverse limb events (MALEs), and major adverse cardiovascular events (MACEs), and 1-year outcomes (efficacy) were limb salvage, MALE + 30-day perioperative death (MALE + POD), and survival. Mortality was demonstrated using Kaplan-Meier analysis. RESULTS: A total of 72 patients were included (OPGR = 58.3% vs. nOPGR = 41.7%). Mean follow-up was 20 months (range, 1-40 months). Retrograde pedal access was used in 65.2% of patients. The overall AMP rate was 2.7% (OPGR = 4.7%, nOPGR = 0%, P = 0.225, vs. SVS OPG<3%), MALE was 4.1% (OPGR = 7.1%, nOPGR = 0%, P = 0.135, vs. SVS OPG<8%), and MACE was 6.9% (OPGR = 2.3%, nOPGR = 13.3%, P = 0.071, vs. SVS OPG<8%). The limb salvage was 90.3% (OPGR = 88%, nOPGR = 93.3%, P = 0.46, vs. SVS OPG>84%), MALE + POD was 76.4% (OPGR = 78.6%, nOPGR = 73.4%, P = 0.606, vs. SVS OPG>71%), and survival was 77.7% (OPGR = 83.3%, nOPGR = 70%, P = 0.18, vs. SVS OPG>80%). CONCLUSIONS: The SVS OPGs set appropriate safety and efficacy standards as a bar for new technologies. In this series, endovascular therapy in all-comers exceeded the safety and efficacy endpoints proposed by the limited risk OPG panel.

A prospective analysis of symptom burden for patients with chronic myeloid leukemia in chronic phase treated with frontline second- and third-generation tyrosine kinase inhibitors.

BACKGROUND: Treatment with tyrosine kinase inhibitors (TKIs) for patients with chronic myeloid leukemia (CML) is effective but needs to continue for several years, possibly indefinitely. Although generally safe, TKI may have hitherto poorly recognized effects in the quality of life (QoL) of such patients. METHODS: We prospectively measured the symptom burden of patients with chronic phase CML enrolled on frontline TKI trials with dasatinib, nilotinib, or ponatinib. A total of 219 patients were enrolled and filled out the MD Anderson Symptom Inventory (MDASI)-CML questionnaire before the start of therapy and during follow-up at defined time points of 3, 6, 9, 12, 18, and 24 months. RESULTS: The median age was 50 years. Longitudinal analysis showed relatively stable symptom severity scores over time. Fatigue was the most common symptom in all three cohorts, both prior to the start of therapy and during therapy, including after achievement of deep molecular remission. Work was the most affected component of daily living. Overall patients tolerated therapy well with improvement of their symptoms from baseline, with few dose reductions related to toxicity or symptomatology. Although 31% of the patients who completed MDASI-CML achieved complete molecular remission by 24 months of treatment, nearly 90% experienced persistent mild symptoms. CONCLUSION: Side effects related to TKIs may impact the quality of life in patients with CML-CP. Further studies should investigate factors (comorbidities, concomitant medications, dose and schedule, etc) associated with these symptoms and interventions that may improve the patients' QoL, including treatment discontinuation when safely feasible.

Co-treatment with a C1B5 peptide of protein kinase Cγ and a low dose of gemcitabine strongly attenuated pancreatic cancer growth in mice through T cell activation.

Although gemcitabine is an effective chemotherapeutic for pancreatic cancer, severe side effects often accompany its use. Since we have discovered that locally administered C1B domain peptides effectively control tumor growth without any side effects, the efficacy of co-treatment with this peptide and a low dose of gemcitabine on the growth of pancreatic cancer was examined. Two- and three-dimensional cell culture studies clarified that a co-treatment with C1B5 peptide and gemcitabine significantly attenuated growth of PAN02 mouse and PANC-1 human pancreatic cancer cells in 2D and 3D cultures. Although treatment with the low dose of gemcitabine alone (76%) or the C1B5 peptide alone (39%) inhibited tumor growth moderately, a co-treatment with C1B5 peptide and a low dose of gemcitabine markedly inhibited the growth of PAN02 autografts in the mouse peritoneal cavity (94% inhibition) without any noticeable adverse effect. The number of peritoneal cavity-infiltrating neutrophils and granzyme B+ lymphocytes was significantly higher in the co-treatment group than in the control group. A significant increase of granzyme B mRNA expression was also detected in human T cells by the co-treatment. Taken together, the current study suggests that C1B5 peptide offers a remarkably effective combination treatment strategy to reduce side effects associated with gemcitabine, without losing its tumoricidal effect.