Long term outcomes of robotic-assisted abdominal wall reconstruction: a single surgeon experience.

INTRODUCTION: Robotic abdominal wall reconstruction (RAWR) is one of the most significant advances in the management of complex abdominal wall hernias. The objective of this study was to evaluate long term outcomes in a cohort of patients that underwent complex RAWR in a single center. METHODS: This was a longitudinal retrospective review of a cohort of 56 patients who underwent complex RAWR at least 24 months prior by a single surgeon at a tertiary care institution. All patients underwent bilateral retro-rectus release (rRRR) with or without robotic transversus abdominis release (rTAR). Data collected include demographics, hernia details, operative and technical details. The prospective analysis included a post-procedure visit of at least 24 months from the index procedure with a physical examination and quality of life survey using the Carolinas Comfort Scale (CCS). Patients with reported symptoms concerning for hernia recurrence underwent radiographic imaging. Descriptive statistics (mean ± standard deviation or median) were calculated for continuous variables. Chi-square or Fisher's exact test as deemed appropriate for categorical variables, and analysis of variance or the Kruskal-Wallis test for continuous data, were performed among the separate operative groups. A total score for the CCS was calculated and analyzed in accordance with the user guidelines. RESULTS: One-hundred and-forty patients met the inclusion criteria. Fifty-six patients consented to participate in the study. Mean age was 60.2 years. Mean BMI was 34.0. Ninety percent of patients had at least one comorbidity and 52% of patients were scored ASA 3 or higher. Fifty-nine percent were initial incisional hernias, 19.6% were recurrent incisional hernias and 8.9% were recurrent ventral hernias. The mean defect width was 9 cm for rTAR and 5 cm for rRRR. The mean implanted mesh size was 945.0 cm2 for rTAR and 362.5 cm2 for rRRR. The mean length of follow-up was 28.1 months. Fifty-seven percent of patients underwent post-op imaging at an average follow-up of 23.5 months. Recurrence rate was 3.6% for all groups. There were no recurrences in patients that underwent solely bilateral rRRR. Two patients (7.7%) that underwent rTAR procedures were found with recurrence. Average time to recurrence was 23 months. Quality of life survey demonstrated an overall CCS score of 6.63 ± 13.95 at 24 months with 12 (21.4%) patients reporting mesh sensation, 20 (35.7%) reporting pain, and 13 (23.2%) reporting movement limitation. CONCLUSION: Our study contributes to the paucity of literature describing long term outcomes of RAWR. Robotic techniques offer durable repairs with acceptable quality of life metrics.

Therapeutic strategies in the treatment of Menière's disease: the Italian experience.

PURPOSE: Ménière's disease (MD) is an inner ear disorder of unknown etiology, whose pathological substrate is the endolymphatic hydrops. Different treatments have been proposed; however, evidence of their effectiveness is lacking. The aim of this study was to evaluate by a questionnaire which medical and surgical treatments are used in Italy for the treatment of MD and to compare them with those proposed in other countries. METHODS: An electronic questionnaire of 40 questions was formulated and sent to Italian otolaryngologist (ENT) divided into two groups: Group 1 ("generalists" 60.8%) and Group 2 ("neurotologist- NO" 39.2%). RESULTS: One hundred and twenty five ENT replied. Treatment of the acute phase, apart from symptomatics, was based on diuretics that are prescribed by 83.5% of respondents, steroids, prescribed by 66.7%, and vasodilators, prescribed by 22%. In the intercritical phase, 87.2% of respondents recommended low-salt diet, 78.4% of respondents prescribed betahistine, and 52.8% diuretics. Statistical analysis did not show correlation neither with the declared specialization nor with the number of patients treated. In case of failure of medical treatment, IT gentamicin was suggested by 48.8% of the respondents and IT steroids by 40.8%. Statistical analysis showed that generalists prefer IT steroids and NO IT gentamicin (p 0.019). In case of failure of both medical treatment and IT treatment, vestibular neurectomy was indicated by 58.4% of the respondents, 6.4% indicated endolymphatic sac surgery, and 2.4% surgical labyrinthectomy. CONCLUSION: In Italy, the treatment of MD stand on a gradual approach that starts from the dietary-behavioral changes and a pharmacological therapy based on betahistine. In refractory cases, IT treatment initially with steroids and, therefore, with gentamicin allows the control in vertigo in the majority of cases. In case of failure of IT treatment, VNS is the surgery of choice.

Traumatic injuries to the pregnant patient: a critical literature review.

INTRODUCTION: Trauma during pregnancy is the leading non-obstetrical cause of maternal death and a significant public health burden. This study reviews the most common causes of trauma during pregnancy, morbidity, and mortality, and the impact upon perinatal outcomes associated with trauma, providing a management approach to pregnant trauma patients. MATERIALS AND METHODS: A systematic review of the current literature from January 2006 to July 2016 was performed. RESULTS: Fifty-one articles were identified, including a total of 95,949 patients. Motor vehicle crash was the most frequent cause of blunt trauma, followed by falls, assault both domestic and interpersonal violence, and penetrating injuries (gunshot and stab wounds). CONCLUSIONS: Trauma in pregnant women is associated with high rates of adverse maternal and neonatal outcomes. Knowledge of the mechanism of injury is important to identify the potential injuries and the complexity of the management of these patients. As in all traumatic events, prevention is of paramount importance.

Multiplex immunohistochemistry accurately defines the immune context of metastatic melanoma.

A prospective study explored the heterogeneous nature of metastatic melanoma using Multiplex immunohistochemistry (IHC) and flow cytometry (FACS). Multiplex IHC data quantitated immune subset number present intra-tumoral (IT) vs the tumor stroma, plus distance of immune subsets from the tumor margin (TM). In addition, mIHC showed a close association between the presence of IT CD8+ T cells and PDL1 expression in melanoma, which was more prevalent on macrophages than on melanoma cells. In contrast, FACS provided more detailed information regarding the T cell subset differentiation, their activation status and expression of immune checkpoint molecules. Interestingly, mIHC detected significantly higher Treg numbers than FACS and showed preferential CD4+ T cell distribution in the tumor stroma. Based on the mIHC and FACS data, we provide a model which defines metastatic melanoma immune context into four categories using the presence or absence of PDL1+ melanoma cells and/or macrophages, and their location within the tumor or on the periphery, combined with the presence or absence of IT CD8+ T cells. This model interprets melanoma immune context as a spectrum of tumor escape from immune control, and provides a snapshot upon which interpretation of checkpoint blockade inhibitor (CBI) therapy responses can be built.

The efficacy of platelet-rich plasma gel in MRSA-related surgical wound infection treatment: an experimental study in an animal model.

INTRODUCTION: The wound healing properties of platelet-rich plasma (PRP) gel have been documented in many studies. PRP gel has also become a promising agent for treating surgical site infections. In this study, we investigated the antibacterial activity and wound healing effectiveness of PRP in an animal model of Methicillin-resistant Staphylococcus aureus subsp. aureus (MRSA N315)-contaminated superficial soft tissue wounds. MATERIALS AND METHODS: Subcutaneous wounds in Wistar Albino male rats were created by making two cm midline incisions followed by inoculation of microorganisms. Study groups comprised of Sham (no treatment), PRP alone, MRSA alone, MRSA + PRP, MRSA + Vancomycin, and MRSA + Vancomycin + PRP groups. We inoculated 0.1 mL (3 × 108 CFU/mL) of MRSA in contaminated groups. After 8 days, all rats were killed, wounds were excised and subjected to histopathologic examination, and MRSA counts were determined. RESULTS: MRSA counts in MRSA, MRSA + PRP, MRSA + Vancomycin and MRSA + Vancomycin + PRP groups were 5.1 × 106 (SD ± 0.4) CFU/mL, 4.3 × 106 (SD ± 0.7) CFU/mL, 2.3 × 106 (SD ± 0.3) CFU/mL, 1.1 × 106 (SD ± 0.4) CFU/mL, respectively. The inflammation scores of MRSA + PRP, MRSA + Vancomycin, and MRSA + Vancomycin + PRP groups were significantly lower than the MRSA group. MRSA + Vancomycin + PRP group inflammation score was significantly lower than the MRSA + PRP group. DISCUSSION: All treatment groups were effective in wound healing and decreasing the MRSA counts. MRSA + PRP combined created identical inflammation scores to the PRP group. More in vivo studies are required to corroborate these findings.

Penetrating cardiac injuries: predictive model for outcomes based on 2016 patients from the National Trauma Data Bank.

BACKGROUND: Penetrating cardiac injuries are uncommon and lethal. The objectives of this study are to examine the national profile of cardiac injuries, identify independent predictors of outcome, generate, compare and validate previous predictive models for outcomes. We hypothesized that National Trauma Data Bank (NTDB) given its large number of patients, would validate these models. METHODS: The NTDB was queried for data on cardiac injuries, using survival as the main outcome measure. Statistical analysis was performed utilizing univariate and stepwise logistic regression. The stepwise logistic regression model was then compared with other predictive models of outcome. RESULTS: There were 2016 patients with penetrating cardiac injuries identified from 1,310,720 patients. Incidence: 0.16%. Mechanism of injury: GSWs-1264 (63%), SWs-716 (36%), Shotgun/impalement-19/16 (1%). Mean RTS 1.75, mean ISS 27 ± 23. Overall survival 675 (33%). 830 patients (41%) underwent ED thoracotomy, 47 survived (6%). Survival stratified by mechanism: GSWs 114/1264 (10%), SWs 564/717 (76%). Predictors of outcome for mortality-univariate analysis: vital signs, RTS, ISS, GCS: Field CPR, ED intubation, ED thoracotomy and aortic cross-clamping (p < 0.001). Stepwise logistic regression identified cardiac GSW's (p < 0.001; AOR 26.85; 95% CI 17.21-41.89), field CPR (p = 0.003; AOR 3.65; 95% CI 1.53-8.69), the absence of spontaneous ventilation (p = 0.008; AOR 1.08, 95% CI 1.02-1.14), the presence of an associated abdominal GSW (p = 0.009; AOR 2.58, 95% CI 1.26-5.26) need for ED airway (p = 0.0003 AOR 1386.30; 95% CI 126.0-15251.71) and aortic cross-clamping (p = 0.0003 AOR 0.18; 95% CI 0.11-0.28) as independent predictors for mortality. Overall predictive power of model-93%. CONCLUSION: Predictors of outcome were identified. Overall survival rates are lower than prospective studies report. Predictive model from NTDB generated larger number of strong independent predictors of outcomes, correlated and validated previous predictive models.

Predictors of outcome in 101 patients requiring emergent thoracotomy for penetrating pulmonary injuries.

BACKGROUND: Operative interventions are uncommonly required for penetrating pulmonary injuries. Similarly, because their incidence is low, few series appear sporadically in the literature. Objectives of this study are to identify predictors of outcome for patients requiring emergent thoracotomy for penetrating pulmonary injuries and evaluate the use of tissue sparing versus resective techniques for their management. STUDY DESIGN: This is a retrospective 169-month study of all patients with penetrating pulmonary injuries requiring thoracotomy. The main outcome measures are: physiologic parameters, AAST-OIS injury grade, surgical procedures and mortality. Statistical analysis includes univariate and stepwise logistic regression. RESULTS: 101 patients required thoracotomy for penetrating pulmonary injuries. Mechanism of injury includes: gunshot wounds (GSW)-73 (72%), stab wounds (SW)-28 (33%). Mean systolic BP 97 ± 47, mean HR 92 ± 47, and mean admission pH 7.22 ± 0.17. Mean RTS 6.25 ± 2.7, mean ISS 36 ± 22. The mean estimated blood loss (EBL) was 5277 ± 4955 mls. Predictors of outcome are: admission pH (p = 0.0014), admission base deficit (p < 0.0001), packed red blood cells (PRBCs) transfused (p = 0.023), whole blood transfused (p < 0.01). A total of 143 procedures were required in 101 patients: tissue sparing 114 (80%) versus resective procedures 29 (20%). Only pneumonectomy (p = 0.024) predicted outcome. Overall survival 64/101-64%. American Association for the Surgery of Trauma-Organ Injury Scale (AAST-OIS) injury grades I-III versus IV-VI predicts survival (p < 0.001). Stepwise logistic regression identified AAST-OIS injury grades IV-VI (p = 0.007; OR 6.38 [95% CI 1.64-24.78]), intraoperative dysrhythmias (p = 0.003; OR 17.38 [95% CI 2.59-116.49]) and associated cardiac injuries (p = 0.02; OR 8.74 [95% CI 1.37-55.79]) as independent predictors of outcome. CONCLUSIONS: Predictors of outcome for penetrating pulmonary injuries requiring thoracotomy are identified and must be taken into account in their operative management. Tissue sparing techniques-stapled pulmonary tractotomy is once again validated, and it remains effective as the mainstay for their management; however, only pneumonectomy predicts outcome. AAST-OIS injury grades IV-VI predict outcome with higher injury grades requiring resective procedures.

Isolated transverse process fractures: insignificant injury or marker of complex injury pattern?

INTRODUCTION: This study investigates the incidence of isolated transverse process fractures (ITPFx) amongst vertebral fractures in trauma patients, and specific-associated injury patterns present in patients with ITPFx. MATERIALS AND METHODS: A retrospective, 4-year review of our Level 1 Trauma Center registry was performed. Patients with blunt spinal column fractures were identified. Data collected included patient demographics, Injury Severity Score (ISS), type of imaging obtained, and concomitant injuries, including rib and pelvic fractures, liver, spleen, and kidney injury (SOI). RESULTS: Of the 10,186 patients admitted during the study period, 881 (8.6%) suffered blunt thoraco-abdominal trauma resulting in vertebral fractures; 214/881 (24%) had ITPFx. All patients (10,186) underwent dedicated spinal multi-detector CT (MDCT) imaging; 26/214 (12.1%) patients had MRI. In all 26 patients, the MRI confirmed the CT findings. 202/214 (94.4%) had associated injuries: rib and pelvic fractures, 45.5 and 20.2%, respectively, and splenic, liver and kidney injury with an incidence of 13.8, 10.9, and 9.4%, respectively. A higher incidence of rib fractures was associated with ITPFx at the T1-4 levels, whereas ITPFx at the level of L5 were associated with pelvic fractures and SOI. Multiple logistic regression analysis identified T1-4 and L5 fractures as predictors of rib fractures and pelvic fractures independent of ISS, with OR: 2.55 (95% CI: 1.12-5.82) and 6.81 (95% CI: 3.14-14.78), respectively. CONCLUSIONS: Based on the results of this study, we conclude that: (1) the use of MDCT imaging has increased the rate of identification of ITPFx; (2) dedicated spinal MDCT reconstruction and MRI may not be necessary to diagnose isolated thoracic and lumbar ITPFx; and (3) ITPFx of the thoracic spine and lower lumbar spine are markers of associated rib fractures and pelvic ring fractures, respectively, as well as of solid organ injuries.

Combat application tourniquet (CAT) eradicates popliteal pulses effectively by correcting the windlass turn degrees: a trial on 145 participants.

INTRODUCTION: We aimed to define an ideal range of windlass turn degrees for 100 % success rates within the study population. METHODS: CAT was applied at mid-thigh level. Data included age, lower extremity circumference (LEC), body mass index (BMI), and mean arterial pressure (MAP). Windlass turn degrees were measured in failed and successful participants. The failed participants' windlass mechanisms were twisted until the popliteal artery was occluded. Failure to success and additional turn degrees to secure the windlass mechanism of CAT was determined. Doppler ultrasound was used to examine the popliteal artery blood flow. RESULTS: 145 servicemen have participated in the study. Initially, 70 % successfully applied CAT. There was no statistically significant difference in BMI and MAP values between successful and failed participants. The mean LEC for failed and successful applications were 57.5 ± 4 and 56.8 ± 4, respectively. The required turn degrees for success ranged between 45° and 270°. After correction, the cumulative success rate of 93 and 100 % was reached at 990° and 1170° overall turn degrees. DISCUSSION: In order to adequately stop limb hemorrhage, soldiers should be taught their optimal turn degrees.

The impact of measurement of respiratory quotient by indirect calorimetry on the achievement of nitrogen balance in patients with severe traumatic brain injury.

BACKGROUND: This study evaluated the impact of IC on the optimization of nutritional support and the achievement of +NB in patients with TBI. MATERIALS AND METHODS: 27 patients (GCS ≤ 8), treated with a 5-day multimodality monitoring and goal-directed therapy protocol, received enteral nutrition on day 1 followed by IC on days 3 and 5 and assessment of NB on day 7. In the first cohort (n = 11), no adjustment in kcal was made. In the second cohort (n = 16), nutrition was targeted to an RQ of 0.83 by day 3. The first cohort was analyzed with respect to NB status; the second cohort was compared to patients with (-) and +NB of the first cohort. Data (mean ± SD) were analyzed with unpaired t test, and Chi square and Fisher exact tests. RESULTS: 4/11(36 %) patients in the first cohort had +NB. The predicted mortality by TRISS, substrate utilization, and RQ was significantly lower compared to the second cohort. The mortality predicted by the CrasH model did not differ between the two cohorts. A RQ of 0.74 was associated with the preferential use of fat and protein and -NB, whereas a RQ of 0.84 favored utilization of carbohydrates and +NB. All patients whose kcal intake was adjusted based on the RQ on day 3 reached a +NB by day 7. CONCLUSION: An increase in kcal ≥25 % in patients with a RQ < 0.83 on day 3 improves substrate utilization, decreases protein utilization and optimizes the achievement of +NB by day 7.

Contemporary wars and their contributions to vascular injury management.

INTRODUCTION: Man's inhumanity for man still knows no boundaries, as we continue as a species as a whole to engage in war. According to Kohn's Dictionary of Wars [1], of over 3,700 years of recorded history, there have been a total of 3,010 wars. One is hard pressed to actually find a period of time in which here has not been an active conflict in the globe. The world has experienced two world wars: WWI (1914-1918) and WWII (1939-1945). The total number of military casualties in WWI was over 37 million, while WWII so far, has been the deadliest military conflict in history with over 60 million people killed accounting for slightly over 2.5% of the world's population. MATERIAL AND METHODS: The purpose of this study is to review contemporary wars and their contributions to vascular injury management. It is precisely wartime contributions that have led to the more precise identification and management of these injuries resulting in countless lives and extremities saved. However, surgeons dealing with vascular injuries have faced a tough and arduous road. Their journey was initiated by surgical mavericks which undaunted, pressed on against all odds guided by William Stewart Halsted's classic statement in 1912: "One of the chief fascinations in surgery is the management of wounded vessels." CONCLUSION: Contemporary wars of the XX-XXI centuries gave birth, defined and advanced the field of vascular injury management.

Role 2 military hospitals: results of a new trauma care concept on 170 casualties.

INTRODUCTION: In recent military conflicts, military surgeons encounter more high-energy injuries associated with explosives. Advances in the field care and shorter evacuation time increased survival. However, casualties still incur severe injuries especially to the extremities. We present wound patterns, anatomical distribution and severity of injuries in a Role 2 hospital. MATERIALS AND METHODS: Two years data have been retrospectively reviewed. Only explosives and firearms injuries were included in the study. Patient profile, admission details, mechanism of injury, AIS anatomical locations, ISS, surgical and medical treatments have been analyzed. RESULTS: Data revealed 170 male casualties. IEDs and GSW accounted for 133 (78%) and 37 (22%) casualties, respectively. An average of 1.8 IED and 1.2 GSW anatomical locations were exposed to injuries. Regardless of the mechanism, injuries were most commonly located in the extremities. IEDs caused significantly higher soft tissue injuries. DISCUSSION: Explosives do not necessarily cause more severe injuries than firearms. However, fragments create multiple, complicated soft tissue injuries which constitute more than half of the injuries. Timely wound debridement and excision of contaminated tissue are crucial to manage extremity soft tissue injuries. CONCLUSION: Casualty care should be assessed within the context of the capabilities present at a hospital and the cause, type and severity of the wounds. The NATO description of Role 2 care only requires an integrated surgical team for damage control surgery with limited diagnostic and infrastructural capabilities.

An evaluation of combat application tourniquets on training military personnel: changes in application times and success rates in three successive phases.

INTRODUCTION: Haemorrhage from the injured extremity is a significant cause of preventable death in military settings. This study evaluated the effect of training on the efficacy of the combat application tourniquet (CAT) and to define standards for military personnel. METHOD: Participants from a training tank battalion were randomised. Data collected included age, body mass index, mean arterial pressure, hand dominance, femoral artery diameter and skin thickness. The study involved tourniquet application times (AT) and application success rates in basic, after-training and eyes-closed phases. Doppler ultrasound was used to identify the presence or absence of popliteal, radial and ulnar artery pulses. RESULTS: A total of 102 trainees participated. In the after-training phase, the left and right upper extremity ATs were 35 ± 13.1 s, and 34.8 ± 13.5 s and the right and left lower extremity ATs were 20.6 ± 6.0 s and 20.5 ± 5.5 s, respectively. The overall tourniquet success rates in three successive study phases were 69.6%, 82.4% and 91.2%, respectively. A negative significant relationship was found between extremity circumference and tourniquet success. DISCUSSION: The results show that the efficacy of CAT application increases with training. Further studies are required to investigate the reasons underlying application failures. This single group prospective randomised study involves level of evidence 4.

Popliteal vessel injuries: complex anatomy, difficult problems and surgical challenges.

The incidence of popliteal vessel injuries is low, even in busy urban trauma centers. As a result of this fact, few trauma centers and trauma surgeons have developed extensive experience in the management of these injuries. Popliteal vessel injuries in both civilian and military arenas incur significant morbidity. These injuries present a difficult challenge, and, although the overall incidence of these injuries remains low, the sequelae can be devastating. Successful outcomes for limb salvage and survival result from early recognition and rapid surgical intervention by a multidisciplinary approach with a great participation of different surgical specialties. From the historical perspective, anatomy, incidence and associated injuries, to the clinical presentation, diagnosis, management, and morbidity and mortality, the aim of this article is to review the various aspects of these complex injuries.

Three-dimensional endoanal ultrasonography of external anal sphincter defects in patients with faecal incontinence: correlation with symptoms and manometry.

AIM: Anal sphincter anatomy on two-dimensional endoanal -ultrasonography (EUS) does not always correlate with the clinical data. The purpose of this study was to determine whether three-dimensional (3D) measurements yield a better correlation. METHOD: The study group included consecutive patients who underwent 3D EUS for faecal incontinence over a 2-year period. The medical charts were reviewed for Cleveland Clinic Foundation Fecal Incontinence (CCF-FI) score and manometric pressures. Endoanal ultrasonographic images were reviewed for the presence of an external anal sphincter (EAS) defect and its extent, as determined by the radial angle, length in the sagittal plane and percentage volume deficit. Correlational analyses were performed between the clinical and imaging data. RESULTS: Sixty-one patients of median age 53 years (range 15-82) were evaluated. Thirty-two patients had either a complete (17) or partial (15) EAS defect, and 29 patients had an intact sphincter. The CCF-FI scores were similar in patients with and without an EAS defect (12.5 ± 5.6 and 11.4 ± 5.5, respectively). The intact-sphincter group had a significantly greater EAS length (3 ± 0.4 vs 2 ± 0.62 cm, P = 0.02) and higher mean maximal squeeze pressure (MMSP; 99.7 ± 52.6 vs 66.9 ± 52.9 mmHg, P = 0.009). There were no statistically significant correlations between MMSP, CCF-FI score and EAS status on 3D EUS. Mean percentage volume of the defect was similar in patients with complete and partial tears (14.5 ± 5.5 and 17.5 ± 7.2%, P = 0.25) and showed no correlation with physiological tests or symptom scores. CONCLUSION: Improvements in external anal sphincter imaging have not yielded a better association with the clinical findings. The lack of clinical differences between patients with different EAS tears may reflect their similar volumetric defects.

Penetrating carotid artery: uncommon complex and lethal injuries.

Carotid arterial injuries are the most difficult and certainly the most immediately life-threatening injuries found in penetrating neck trauma. Their propensity to bleed actively and potentially occludes the airway and makes surgical intervention very challenging. Their potential for causing fatal neurological outcomes demands that trauma surgeons exercise excellent judgment in the approach to their definitive management. The purpose of this article is to review the diagnosis and management of these injuries.

Subclavian vessel injuries: difficult anatomy and difficult territory.

INTRODUCTION: Thoracic and thoracic related vascular injuries represent complex challenges to the trauma surgeon. Subclavian vessel injuries, in particular, are uncommon and highly lethal. Regardless of the mechanism, such injuries can result in significant morbidity and mortality. MATERIALS AND METHODS: Systematic review of the literature, with emphasis on the diagnosis, treatment and outcomes of these injuries, incorporating the authors' experience. CONCLUSIONS: These injuries are associated with significant morbidity and mortality. Patients who survive transport are subject to potentially debilitating injury and possibly death. Management of these injuries varies, depending on hemodynamic stability, mechanism of injury, and associated injuries. Despite significant advancements, mortality due to subclavian vessel injury remains high.

A multiscale approach to sampling nascent peptide chains in the ribosomal exit tunnel.

We present a new multiscale method that combines all-atom molecular dynamics with coarse-grained sampling, towards the aim of bridging two levels of physiology: the atomic scale of protein side chains and small molecules, and the huge scale of macromolecular complexes like the ribosome. Our approach uses all-atom simulations of peptide (or other ligand) fragments to calculate local 3D spatial potentials of mean force (PMF). The individual fragment PMFs are then used as a potential for a coarse-grained chain representation of the entire molecule. Conformational space and sequence space are sampled efficiently using generalized ensemble Monte Carlo. Here, we apply this method to the study of nascent polypeptides inside the cavity of the ribosome exit tunnel. We show how the method can be used to explore the accessible conformational and sequence space of nascent polypeptide chains near the ribosome peptidyl transfer center (PTC), with the eventual aim of understanding the basis of specificity for co-translational regulation. The method has many potential applications to predicting binding specificity and design, and is sufficiently general to allow even greater separation of scales in future work.