Abdelrahman, Amro M

Background: Neoadjuvant therapy (NAT) is used in borderline resectable/locally advanced (BR/LA) pancreatic ductal adenocarcinoma (PDAC). Anatomic imaging (CT/MRI) poorly predicts response, and biochemical (CA 19-9) markers are not useful (nonsecretors/nonelevated) in many patients. Pathologic response highly predicts survival post-NAT, but is only known postoperatively. Because metabolic imaging (FDG-PET) reveals primary tumor viability, this study aimed to evaluate our experience with preoperative FDG-PET in patients with BR/LA PDAC in predicting NAT response and survival. Methods: We reviewed all patients with resected BR/LA PDAC who underwent NAT with FDG-PET within 60 days of resection. Pre- and post-NAT metabolic (FDG-PET) and biochemical (CA 19-9) responses were dichotomized in addition to pathologic responses. We compared post-NAT metabolic and biochemical responses as preoperative predictors of pathologic responses and recurrence-free survival (RFS) and overall survival (OS). Results: We identified 202 eligible patients. Post-NAT, 58% of patients had optimization of CA 19-9 levels. Major metabolic and pathologic responses were present in 51% and 38% of patients, respectively. Median RFS and OS times were 21 and 48.7 months, respectively. Metabolic response was superior to biochemical response in predicting pathologic response (area under the curve, 0.86 vs 0.75; P <.001). Metabolic response was the only univariate preoperative predictor of OS (odds ratio, 0.25; 95% CI, 0.13–0.40), and was highly correlated ( P =.001) with pathologic response as opposed to biochemical response alone. After multivariate adjustment, metabolic response was the single largest independent preoperative predictor ( P <.001) for pathologic response (odds ratio, 43.2; 95% CI, 16.9–153.2), RFS (hazard ratio, 0.37; 95% CI, 0.2–0.6), and OS (hazard ratio, 0.21; 95% CI, 0.1–0.4). Conclusions: Among patients with post-NAT resected BR/LA PDAC, FDG-PET highly predicts pathologic response and survival, superior to biochemical responses alone. Given the poor ability of anatomic imaging or biochemical markers to assess NAT responses in these patients, FDG-PET is a preoperative metric of NAT efficacy, thereby allowing potential therapeutic alterations and surgical treatment decisions. We suggest that FDG-PET should be an adjunct and recommended modality during the NAT phase of care for these patients.

Abstract Background and aims Biliary tract cancers (BTCs) are uncommon, but highly lethal, gastrointestinal malignancies. Gemcitabine/cisplatin is a standard‐of‐care systemic therapy, but has a modest impact on survival and harbors toxicities, including myelosuppression, nephropathy, neuropathy, and ototoxicity. Whereas BTCs are characterized by aberrations activating the cyclinD1/cyclin‐dependent kinase (CDK)4/6/CDK inhibitor 2a/retinoblastoma pathway, clinical use of CDK4/6 inhibitors as monotherapy is limited by lack of validated biomarkers, diffident preclinical efficacy, and development of acquired drug resistance. Emerging studies have explored therapeutic strategies to enhance the antitumor efficacy of CDK4/6 inhibitors by the combination with chemotherapy regimens, but their mechanism of action remains elusive. Approach and results Here, we report in vitro and in vivo synergy in BTC models, showing enhanced efficacy, reduced toxicity, and better survival with a combination comprising gemcitabine/cisplatin and CDK4/6 inhibitors. Furthermore, we demonstrated that abemaciclib monotherapy had only modest efficacy attributable to autophagy‐induced resistance. Notably, triplet therapy was able to potentiate efficacy through elimination of the autophagic flux. Correspondingly, abemaciclib potentiated ribonucleotide reductase catalytic subunit M1 reduction, resulting in sensitization to gemcitabine. Conclusions As such, these data provide robust preclinical mechanistic evidence of synergy between gemcitabine/cisplatin and CDK4/6 inhibitors and delineate a path forward for translation of these findings to preliminary clinical studies in advanced BTC patients.

Abstract Objective The American College of Surgeons (ACS) encourages clinicians to provide training to laypeople on tourniquet application. It is unclear whether clinicians are confident in their abilities and equipped with adequate knowledge, skills, and resources. This study aimed to determine surgical trainee knowledge and attitudes regarding tourniquet application and compare the effectiveness of instructions. Methods Thirty surgical trainees performed a tourniquet application simulation using a Combat Application Tourniquet and one of the three instructions sets developed by ACS, Department of Homeland Security, and the tourniquet manufacturer. Participants reported tourniquet knowledge, attitudes, and confidence and discussed the instructions. One instruction set was updated and compared to the original set with 20 new trainees. Results Participants with ACS instructions passed the greatest number of steps (p &lt; 0.01) and completed the task significantly faster compared to those with manufacturer instructions (p &lt; 0.01). Participants (80%) reported favorable views toward tourniquets but 30–60% did not align with to ACS tourniquet guidelines. Focus group participants suggested revisions to the ACS instructions. Comparing the original and revised version of these instructions resulted in no significant improvements. Conclusions ACS instructions provide guidance; however, improvements to tourniquet instruction are needed for success in controlling exsanguinating hemorrhage.

With advancements in surgical techniques, patients have experienced improvements in health and recovery outcomes. However, about 87% of laparoscopic surgeons [1] and an increasing number of surveyed allied health professionals [2, 3] report musculoskeletal symptoms. Medical practitioners and human factors engineers have highlighted the “hostile” and “dangerous” operating room (OR) environment [1, 4, 5]. With increasing technology and surgical case complexity, physical demands for surgical team members will continue to increase due to circumstances such as technology restricting posture, taking up working space and more team members working around smaller surgical incisions [6]. There is widespread concern that these medical professionals’ work is unsustainable for safe and healthy patients and surgical team members. Surgical team members can benefit from posture improvement during surgery; however, direct postural feedback may be difficult during their work due to the high visual and auditory stimuli during surgery. The tactile modality has been recently explored as a method to provide additional information without interfering with cognitive resources dedicated to visual and auditory pathways [7]. Tactile devices have successfully been implemented in high-stress environments, e.g., military, healthcare, and rehabilitation with a resulting improvement in performance [8–11]. Vibrotactile feedback has been specifically implemented in the healthcare field for improved performance by 31–75% anesthesiologists during simulated tasks [10]. Additionally, it has contributed to improved postural control in rehabilitation patients[11]. Despite success in other application areas, the potential of tactile devices for improving healthcare workers’ safety and performance remains unexplored. This study is a part of a larger project to design a wearable device that provides realtime vibrotactile feedback for preventing fatigue and musculoskeletal disorders for healthcare workers in the workplace. This specific aim of this study is to measure distraction, frustration, and performance during a surgical simulation task performed with and without vibrotactile feedback. This is a test of initial feasibility of vibrotactile feedback for use in training proper ergonomics for surgical team members. The researchers hypothesize that there will be some distraction with the vibrotactile feedback wearable but no frustration or performance degradation during the basic simulation task.

The American College of Surgeons (ACS) and the Department of Homeland Security (DHS) encourage the use of tourniquets as part of the “Stop the Bleed” campaign. Both have provided instructions for layperson tourniquet application in order to save the life of a hemorrhaging trauma victim. This study sought to compare the impact of using ACS and DHS instructions with manufacturer-provided instructions for the completion of simulated tourniquet application steps. Thirty surgical trainees completed a simulated tourniquet application with one of the three instruction sets. Their completion time and success for each step were measured. Participants that received ACS instructions failed the fewest number of steps (p < 0.01) and completed the task faster (Mean (SD) = 70 (33) seconds) compared to those with the manufacturer-provided instructions (p < 0.01). Tourniquet instruction sets need to be refined in order to optimize the success rate of just-in-time guidance for tourniquet application.

Interruptions in the Emergency Department (ED) are moderately studied in regard to their impact on physicians’ workload. This study captured interruptions characteristics and measures of workload. Twenty-eight ED physicians were followed during their shifts; interruptions they faced were captured using a validated tablet PC-based tool. At the mid and end of their shift, providers completed a NASA-Task Load Index (TLX) questionnaire and a reaction time task. Descriptive statistics and ANOVA were used to identify relationships between physicians’ interruptions and workload. A total of 2355 interruptions were identified ( M =84.1, SD =14.5). The NASA-TLX results showed increase in physicians’ responses for all subscales from mid to end-shifts. Reaction time was higher at end-shift with mean difference of 33.75ms, 95% CI [20.35, 47.13], p < 0.001. At end-shift, there was a statistically significant positive correlation between reaction time and all NASA-TLX subscales. Interruption duration rather than frequency correlated positively with NASA-TLX scores. High/critical interruptions were the least frequent but had longer duration and greater impact on workload. This study provided a unique examination of interruptions over an entire provider shift and identified interruptions as potential causes of increased workload for ED physicians.

Medical care providers recognize nonadjustable examination tables in clinics as a barrier to comprehensively and safely providing routine healthcare for disabled, elderly and obese patients. The aim of this study was to understand how the availability of the adjustable examination table may affect the medical care provider’s perception of the quality of care provided to patients who need physical assistance. Fifty providers answered questionnaires to report their perceptions of two different examination tables’ usability. The first one is a mid-century industrial designed table and the other adjustable and ADA compliant, as used in a community health clinic. Before implementation of the new adjustable examination table, 34 medical care providers provided feedback on their experiences with nonadjustable examination tables. A second survey was administered approximately six months after implementation of the new adjustable examination tables to 16 medical care providers (with 2 indicating participation in the prior-to-implementation survey) for their feedback on experiences with the new adjustable examination tables. Providers reported significantly (p<0.05) more comfort in getting typical patients (27%), bariatric patients (50%), and geriatric patients (30%) into a sitting position when they used the adjustable examination table compared to the nonadjustable examination table. Providers considered the adjustable examination tables to have a more ideal width (60%) and length (64%) to accommodate a wider variety of patients than the nonadjustable examination tables. Providers also considered the adjustable table (33%) easier to use and preferable to the nonadjustable table. This research showed how the adjustable examination table improves healthcare provider experience to provide access to healthcare for patients with disabilities with better ergonomics and greater safety for both patients and providers.

Abstract Background Surgical performance, provider health, and patient safety can be compromised when workload demands exceed individual capability on the surgical team. The purpose of this study is to quantify and compare intraoperative workload among surgical team members. Methods Observations were conducted for an entire surgical day for 33 participating surgeons and their surgical team at one medical institution. Workload (mental, physical, case complexity, distractions, and case difficulty) was measured for each surgical team member using questions from validated questionnaires. Statistical analyses were performed with a mixed effects model. Results A total of 192 surgical team members participated in 78 operative cases, and 344 questionnaires were collected. Procedures with high surgeon mental and physical workload included endovascular and gastric surgeries, respectively. Ratings did not differ significantly among surgeons and residents, but scrub nurses physical demand ratings were 14–22 (out of 100) points lower than the surgeons, residents, and surgical assistants. Residents reported the highest mental workload, averaging 19–24 points higher than surgical assistants, scrub nurses, and circulating nurses. Mental and physical demands exceeded 50 points 28–45 % of the time for surgeons and residents. Workload did not differ between minimally invasive and open techniques. Conclusion The workload questionnaires are an effective tool for quantifying intraoperative workload across the surgical team to ensure mental and physical demands do not exceed thresholds where performance may decrease and injury risk increase. This tool has the potential to measure the safety of current procedures and drive design of workload interventions.

Surgical trainees undergo demanding training to achieve high surgical task proficiency. Abounding clinical and educational responsibilities mandate efficient and effective training. This research measured resident workload during laparoscopic skills training to identify excessive workload and how workload impacted task performance. Twenty-eight surgical trainees performed a standardized surgical training task and completed a workload questionnaire while observers measured physiological stress, posture risk assessment, and task performance. Participants self-reported mental demands, physical demands, temporal demands, performance, effort, and frustration. Effort (12±4) and frustration (12±5) were the highest subscales while physical demand (8±4) was the lowest. All participants were observed performing the task in at-risk postures, with 21% exhibiting risk levels requiring immediate intervention. Physical demand was associated with posture risk assessment scores (p<0.05). Mental demand was positively (R 2 =0.20, p<0.05) and frustration was negatively (R 2 =0.18, p<0.05) associated with skin conductance range. A point increase in physical demand was associated with a six second increase in performance time (β=6.0, p=0.01). These results support the fact that human factors and ergonomic tools can be used to relate surgical skills performance with workload, stress, and posture risks.

Laparoendoscopic single site surgery (LESS) can provide potential patient benefits beyond conventional laparoscopy (CL). However, LESS further exacerbates current ergonomic disadvantages of CL. LESS practices to compensate for the constraints include intracorporeal crossing of instruments (UL) for improved manipulation of instrumentation and extracorporeal crossing of hands (PL) for illusion mitigation. Preliminary results from this study involving 12 medical students (7 males) performing a simulated surgical task found statistical difference between CL, PL, and UL for physical demand (P<0.001), task complexity (P=0.002) and performance times (P<0.001) with no difference for mental demand (P=0.106). These initial findings show that the PL technique cannot currently compensate for the limitations of LESS to make UL more similar to CL. Further research is needed to determine if PL or another LESS compensatory practice can allow surgeons to more effectively perform procedures with a single port and therefore ensure patients reap its benefits.