Using the Flipped Classroom Model in Surgical Education: Efficacy and Trainee Perception.

OBJECTIVE: To describe the feasibility, efficacy, and learner perception of the flipped classroom model for teaching conferences within surgical training programs. DESIGN: For the flipped classroom conferences, video lectures were prepared by a faculty member, and sent to all attendees at least 2 days prior to lecture. The conference time was then spent going over cases and questions, rather than traditional lecture. We conducted a qualitative survey to assess learner's perceptions and pre-lecture quizzes to assess trainee preparedness. SETTING: The comparison of pre-conference quizzes between flipped classroom and traditional models was carried out at Brooke Army Medical Center (BAMC) in San Antonio, TX, a tertiary care facility with a general surgery residency program. The survey was conducted at BAMC and within the Complex General Surgical Oncology fellowship program at University of Texas MD Anderson Cancer Center, where a flipped classroom model was similarly employed. PARTICIPANTS: Surgical residents BAMC participated in pre-lecture quizzes. BAMC residents and MD Anderson fellows were invited to complete the online survey. RESULTS: Lecture videos did not increase mean preparation time (1.53 vs. 1.46 hours without vs. with video, p = 0.858), but did increase mean quiz scores from 67% to 80% (p = 0.031) with 32/35 learners utilizing videos. Videos increased the proportion of learners who self-reported preparing at all from 42% to 95% (p = 0.28), and preparing for at least one hour for conference from 23% to 49% (p = 0.014). Of survey respondents, 90% said videos were very helpful, 90% would use them weekly if available, and 90% prefer this format to traditional lecture. CONCLUSIONS: Utilization of a flipped classroom method was well received and preferred by surgical trainees, and it increased performance on pre-conference quizzes without increasing preparation time. Although creation of video lectures is work-intensive for lecturers, these results suggest it is more effective for learner preparation. These results could be generalizable to surgical residents nationwide as technology utilization increases in surgical education.

Robotic rectal cancer surgery: comparative study of the impact of obesity on early outcomes.

The aim of this study was to compare the outcomes of robotic total mesorectal excision (TME) in obese versus non-obese patients. A total of 533 patients, of whom 161 were obese (30·2 per cent) underwent robotic proctectomy during the study interval. Patient obesity was not associated with adverse short-term clinical outcomes after robotic rectal cancer surgery. Indicated in the obese perhaps?

Robotic lateral pelvic lymph node dissection after chemoradiation for rectal cancer: a Western perspective.

AIM: There are limited outcome data for lateral pelvic lymph node dissection (LPLND) following neoadjuvant chemoradiotherapy (nCRT), particularly in the West. Our aim was to evaluate the short-term perioperative and oncological outcomes of robotic LPLND at a single cancer centre. METHOD: A retrospective analysis of a prospective database of consecutive patients undergoing robotic LPLND for rectal cancer between November 2012 and February 2020 was performed. The main outcomes were short-term perioperative and oncological outcomes. Major morbidity was defined as Clavien-Dindo grade 3 or above. RESULTS: Forty patients underwent robotic LPLND during the study period. The mean age was 54 years (SD ± 15 years) and 13 (31.0%) were female. The median body mass index was 28.6 kg/m2 (IQR 25.5-32.6 kg/m2 ). Neoadjuvant CRT was performed in all patients. Resection of the primary rectal cancer and concurrent LPLND occurred in 36 (90.0%) patients, whilst the remaining 4 (10.0%) patients had subsequent LPLND after prior rectal resection. The median operating time was 420 min (IQR 313-540 min), estimated blood loss was 150 ml (IQR 55-200 ml) and length of hospital stay was 4 days (IQR 3-6 days). The major morbidity rate was 10.0% (n = 4). The median lymph node harvest from the LPLND was 6 (IQR 3-9) and 13 (32.5%) patients had one or more positive LPLNs. The median follow-up was 16 months (IQR 5-33 months), with 1 (2.5%) local central recurrence and 7 (17.5%) patients developing distant disease, resulting in 3 (7.5%) deaths. CONCLUSION: Robotic LPLND for rectal cancer can be performed in Western patients to completely resect extra-mesorectal LPLNs and is associated with acceptable perioperative morbidity.

Selective central vascular ligation (D3 lymphadenectomy) in patients undergoing minimally invasive complete mesocolic excision for colon cancer: optimizing the risk-benefit equation.

AIM: Complete mesocolic excision (CME) with central vascular ligation (CVL) has been advocated for right colon adenocarcinoma (RC), but the radicality of vascular dissection remains controversial. Our aim is to report outcomes of selective CVL (D3 lymphadenectomy) during minimally invasive CME for RC. METHOD: A prospective database identified patients who were treated for RC between 2009 and 2016. Minimally invasive CME was standard. The radicality of lymphadenectomy was defined as high ligation (HL) versus CVL based on operative reports and videos. Two blinded radiologists independently evaluated the pre- and postoperative CT scans for radiographically abnormal nodes. RESULTS: Of 197 patients who underwent CME, HL was performed in 56 (28%) and CVL in 141 (72%). There were no baseline differences in age, sex, body mass index, American Society of Anesthesiologists score or pathological staging, and there were no major intra-operative complications in either group (including no major vascular injuries). The median total number of nodes retrieved was 27 and 31 (P = 0.011) in HL and CVL groups, resepctively, with pathologically positive nodes identified in 33.9% and 39.8% (P = 0.704), respectively. Preoperative imaging identified abnormal cN3 nodes in 1.5% of patients; all of whom underwent CVL. No abnormal cN2 or cN3 nodes remained on postoperative imaging. The 60-day mortality was 0.5%, and major morbidity was 4%. One patient (0.5%) had an anastomotic recurrence after a median follow-up of 22 months. CONCLUSION: With imperfect preoperative clinical nodal staging, and in the absence of randomized data, the low morbidity and oncological outcomes observed support the approach of CME with HL as a minimum standard, with CVL (D3 lymphadenectomy) in selected cases.

Randomized clinical trial of accelerated enhanced recovery after minimally invasive colorectal cancer surgery (RecoverMI trial).

BACKGROUND: Minimally invasive surgery (MIS) and enhanced recovery protocols (ERPs) have improved postoperative recovery and shortened length of hospital stay (LOS). Telemedicine technology has potential to improve outcomes and patient experience further. This study was designed to determine whether the combination of MIS, ERP and a structured telemedicine programme (TeleRecovery) could shorten total 30-day LOS by 50 per cent. METHODS: This was a phase II prospective RCT at a large academic medical centre. Eligible patients aged 18-80 years undergoing minimally invasive colorectal resection using an ERP were randomized after surgery. The experimental arm (RecoverMI) included accelerated discharge on postoperative day (POD) 1 with or without evidence of bowel function and a televideoconference on POD 2. The control arm was standard postoperative care. The primary endpoint was total 30-day LOS (postoperative stay plus readmission/emergency department/observation days). Secondary endpoints included patient-reported outcomes measured by EQ-5D-5L™, Brief Pain Inventory (BPI) and a satisfaction questionnaire. RESULTS: Thirty patients were randomized after robotic (21 patients) or laparoscopic (9) colectomy, including 14 patients in the RecoverMI arm. Median 30-day total LOS was 28·3 (i.q.r. 23·7-43·6) h in the RecoverMI arm and 51·5 (43·8-67·0) h in the control arm (P = 0·041). There were no differences in severe adverse events or EQ-5D-5L™ score between the study arms. The BPI revealed low pain scores regardless of treatment arm. Satisfaction was high in both arms. CONCLUSION: In patients having surgery for colorectal neoplasms, the trimodal combination of MIS, ERP and TeleRecovery can reduce 30-day LOS while preserving patients' quality of life and satisfaction. Registration number: NCT02613728 ( https://clinicaltrials.gov).

ANTECEDENTES: La cirugía mínimamente invasiva (minimally invasive surgery, MIS) y los protocolos de recuperación intensificada (enhanced recovery protocols, ERP) han mejorado la recuperación postoperatoria y acortan la duración de la estancia (length of stay, LOS). La tecnología de la telemedicina tiene potencial para mejorar aún más los resultados y la experiencia del paciente. Este estudio se diseñó para determinar si la combinación de MIS, ERP y un programa estructurado de telemedicina (TeleRecovery) podría acortar la LOS total a los 30 días en un 50%. MÉTODOS: Se efectuó un ensayo controlado aleatorizado, prospectivo, de fase II en un gran centro médico académico. Los pacientes elegibles de 18-80 años de edad que se sometieron a resección colorrectal MIS mediante ERP se asignaron al azar después de la resección quirúrgica. El brazo experimental (RecoverMI) incluyó el alta acelerada en el día 1 del postoperatorio (postoperative day, POD) con o sin evidencia de recuperación del tránsito intestinal y una televideoconferencia en el día 2 POD. Los pacientes en el grupo control recibieron los cuidados postoperatorios habituales. El criterio de valoración principal fue la LOS total (estancia postoperatoria más reingreso/estancia en urgencias/días de observación) a los 30 días. Los criterios de valoración secundarios incluyeron los resultados referidos por los pacientes medidos por los cuestionarios EQ-5D-5L, el Cuestionario Breve del Dolor (Brief Pain Inventory, BPI) y un cuestionario de satisfacción. RESULTADOS: Treinta pacientes fueron aleatorizados después de una colectomía robótica (21) o laparoscópica (9), incluidos 14 pacientes en el grupo de RecoverMI. La mediana de la LOS total a los 30 días fue de 28,3 horas (rango intercuartílico, RIQ 23,7-43,6) en el grupo de RecoverMI y de 51,5 horas (RIQ 43,8-67,0) en el grupo control (P = 0,04). No hubo diferencias entre los grupos de estudio en los eventos adversos graves o en las puntuaciones del EQ-5D-5L. El BPI mostró puntuaciones bajas de dolor independientemente del grupo de tratamiento. La satisfacción fue alta en ambos grupos. CONCLUSIÓN: Entre los pacientes que se someten a cirugía por cáncer colorrectal, la combinación trimodal de MIS, ERP y TeleRecovery puede reducir la LOS a los 30 días, preservando la calidad de vida y la satisfacción del paciente.

Palladin contributes to invasive motility in human breast cancer cells.

Cancer metastasis involves multiple steps including detachment of the metastatic cells from neighboring cells, the acquisition of motility and invasion to other tissue. All of these steps require the reorganization of the actin cytoskeleton. In this study, we found that the protein palladin, a molecular scaffold with an important function in actin organization, is expressed at higher overall levels in tumors compared with benign breast tissue, and also expressed significantly higher in four invasive breast cancer cell lines when compared with four non-invasive cell lines. In addition, we found that palladin plays a key role in the formation of podosomes. Podosomes are actin-rich structures that function in adhesion and matrix degradation, and have been found in many invasive cell types. Our results show that phorbol ester treatment stimulated the formation of palladin-containing podosomes in invasive, but not in non-invasive cell lines. More importantly, palladin knockdown resulted in decreased podosome formation and a significant reduction in transwell migration and invasive motility. Palladin overexpression induced podosome formation in the non-invasive MCF7 cells, which are otherwise unable to form podosomes, suggesting that palladin plays a critical role in the assembly of podosomes. Overall, these results indicate that palladin overexpression contributes to the invasive behavior of metastatic cells.

In vitro processing of the proproteins GrdE of protein B of glycine reductase and PrdA of D-proline reductase from Clostridium sticklandii: formation of a pyruvoyl group from a cysteine residue.

GrdE and PrdA of Clostridium sticklandii are subunits of glycine reductase and D-proline reductase, respectively, that are processed post-translationally to form a catalytic active pyruvoyl group. The cleavage occurred on the N-terminal side of a cysteine residue, which is thus the precursor of a pyruvoyl moiety. Both proproteins could be over-expressed in Escherichia coli and conditions were developed for in vitro processing. GrdE could be expressed as full-size protein, whereas PrdA had to be truncated N-terminally to achieve successful over-expression. Both proproteins were cleaved at the in vivo observed cleavage site after addition of 200 mM NaBH4 in Tris buffer (pH 7.6) at room temperature as analysed by SDS/PAGE and MS. Cleavage of GrdE was observed with a half-time of approximately 30 min. Cys242, as the precursor of the pyruvoyl group in GrdE, was changed to alanine, serine, or threonine by site-directed mutagenesis. The Cys242-->Ser and Cys242-->Thr mutant proteins were also cleaved under similar conditions with extended half-times. However, the Cys242-->Ala mutant protein was not cleaved indicating a pivotal role of the thiol group of cysteine or hydroxyl group of serine and threonine during the processing of pyruvoyl group-dependent reductases.

Rapid and simultaneous activation of Stat3 and production of interleukin 6 in resuscitated hemorrhagic shock.

The inflammatory response of the liver to hemorrhagic shock includes the production of acute phase proteins and a variety of mediators, such as the cytokine interleukin (IL)-6. The transcription of acute phase protein genes in hepatocytes has been shown to be activated by Stat3, one of six distinct signal transducers and activators of transcription (STAT) proteins. IL-6 signals through activation of Stat3. In this study, we examined whether or not Stat3 was activated and IL-6 mRNA produced in the liver of rats subjected to hemorrhagic shock and whether or not both phases of shock, the ischemic and the resuscitation phases, were required. We report here that Stat3 activation and increased IL-6 expression required resuscitation and displayed identical kinetics following resuscitation, suggesting that liver production of IL-6 was responsible for liver Stat3 activation in hemorrhagic shock.

Alfentanil's analgesic, respiratory, and cardiovascular actions in relation to dose and plasma concentration in unanesthetized dogs.

Relationships between plasma concentrations of alfentanil and its analgesic, respiratory, and cardiovascular effects were determined in dogs. To avoid drug interaction, trained, unanesthetized, spontaneously breathing dogs were used. After a control period in the awake state, alfentanil was injected in increasing amounts (10, 20, 80, 160, and 320 micrograms/kg) at 5-min intervals to a total dose of 590 micrograms/kg administered over 20 min. The effects were observed on pain responses (heart rate and blood pressure changes and somatic reactions to tail clamping), respiration (respiratory rate, oxygen consumption [VO2], blood gas tensions) and circulation (heart rate and blood pressure). The plasma concentration-effect curves, derived by relating the changes in multiple variables from the awake state to the corresponding plasma concentrations (range 8-5079 ng/ml), plateaued at and around 200 ng/ml during the injection period but were displaced in parallel to two-fold higher concentrations during recovery, which resembles acute tolerance. At maximally effective analgesic concentrations, which precipitated profound cardiorespiratory slowing with conspicuous hypoxemia, the VO2 of 4.4 +/- 0.3 ml X kg-1 X min-1 corresponded with the calculated metabolic rate but increased to 6.3 +/- 1.6 ml X kg-1 during recovery. The analgesic action of alfentanil, which cannot be separated from its depressant cardiorespiratory effects and maximally effective analgesic concentrations (between 200 and 400 ng/ml), apparently does not jeopardize the adequacy of tissue oxygenation in dogs.