Integrated optical frequency division for microwave and mmWave generation.

The generation of ultra-low-noise microwave and mmWave in miniaturized, chip-based platforms can transform communication, radar and sensing systems1-3. Optical frequency division that leverages optical references and optical frequency combs has emerged as a powerful technique to generate microwaves with superior spectral purity than any other approaches4-7. Here we demonstrate a miniaturized optical frequency division system that can potentially transfer the approach to a complementary metal-oxide-semiconductor-compatible integrated photonic platform. Phase stability is provided by a large mode volume, planar-waveguide-based optical reference coil cavity8,9 and is divided down from optical to mmWave frequency by using soliton microcombs generated in a waveguide-coupled microresonator10-12. Besides achieving record-low phase noise for integrated photonic mmWave oscillators, these devices can be heterogeneously integrated with semiconductor lasers, amplifiers and photodiodes, holding the potential of large-volume, low-cost manufacturing for fundamental and mass-market applications13.

Photonic chip-based low-noise microwave oscillator.

Numerous modern technologies are reliant on the low-phase noise and exquisite timing stability of microwave signals. Substantial progress has been made in the field of microwave photonics, whereby low-noise microwave signals are generated by the down-conversion of ultrastable optical references using a frequency comb1-3. Such systems, however, are constructed with bulk or fibre optics and are difficult to further reduce in size and power consumption. In this work we address this challenge by leveraging advances in integrated photonics to demonstrate low-noise microwave generation via two-point optical frequency division4,5. Narrow-linewidth self-injection-locked integrated lasers6,7 are stabilized to a miniature Fabry-Pérot cavity8, and the frequency gap between the lasers is divided with an efficient dark soliton frequency comb9. The stabilized output of the microcomb is photodetected to produce a microwave signal at 20 GHz with phase noise of -96 dBc Hz-1 at 100 Hz offset frequency that decreases to -135 dBc Hz-1 at 10 kHz offset-values that are unprecedented for an integrated photonic system. All photonic components can be heterogeneously integrated on a single chip, providing a significant advance for the application of photonics to high-precision navigation, communication and timing systems.

Redo fundoplication vs. Roux-en-Y gastric bypass conversion for failed anti-reflux surgery: which is better?

INTRODUCTION: Different techniques have been proposed for reoperation after failed anti-reflux surgery. However, there is no consensus on which should be preferred. We aim to report and compare the outcomes of different revisional techniques for failed anti-reflux surgery. METHODS: We performed a retrospective analysis of patients who underwent redo fundoplication (RF) or Roux-en-Y gastric bypass (RYGB) conversion after a failed fundoplication at our institution between 2016 and 2021. The primary outcome was long-term presence of reflux or dysphagia following revisional surgery. Secondary outcomes included 30-day perioperative complications as well as long-term use of anti-reflux medication and radiographic recurrence of hiatal hernia (HH). RESULTS: A total of 165 (median age 63 years, 73.9% female) patients were included. RF was performed in 120 (73 Toupet and 47 Nissen), RYGB in 38, and 7 patients had fundoplication takedown alone. The RYGB group had a significantly higher BMI, and more prior revisional surgeries compared to the other groups. Median operative time and length of stay were longer for RYGB. Twenty (12.1%) patients experienced postoperative complications, with the highest incidence in the RYGB group. Reflux and dysphagia improved significantly for the whole cohort, with the greatest improvement noted with reflux in the RYGB group (89.5% with preoperative reflux vs. 10.5% with postoperative reflux, p = < .001). On multivariable regression we found that prior re-operative surgery was associated with persistent reflux and dysphagia, whereas RYGB conversion was protective against reflux. CONCLUSION: Conversion to RYGB may offer superior resolution of reflux than RF, especially for obese patients.

Mechanisms of Binding of Antimicrobial Peptide PGLa to DMPC/DMPG Membrane.

PGLa belongs to a class of antimicrobial peptides showing strong affinity to anionic bacterial membranes. Using all-atom explicit solvent replica exchange molecular dynamics with solute tempering, we studied binding of PGLa to a model anionic dimyristoylphosphatidylcholine/dimyristoylphosphatidylglycerol (DMPC/DMPG) bilayer. Due to a strong hydrophobic moment, PGLa upon binding adopts a helical structure and two distinct bound states separated by a significant free energy barrier. In these states, the C-terminus helix is either surface bound or inserted into the bilayer, whereas the N-terminus remains anchored in the bilayer. Analysis of the free energy landscape indicates that the transition between the two states involves a C-terminus helix rotation permitting the peptide to preserve the interactions between cationic Lys amino acids and anionic lipid phosphorus groups. We calculated the free energy of PGLa binding and showed that it is mostly governed by the balance between desolvation of PGLa positive charges and formation of electrostatic PGLa-lipid interactions. PGLa binding induces minor bilayer thinning but causes pronounced lipid redistribution resulting from an influx of DMPG lipids into the binding footprint and efflux of DMPC lipids. Our in silico results rationalize the S-state detected in NMR experiments.

Preoperative high respiratory quotient correlates with lower weight loss after bariatric surgery.

BACKGROUND: The respiratory coefficient (RQ), as determined by indirect calorimetry (IC), classifies diet as being carbohydrate rich (RQ = 0.7-0.8), fat rich (RQ = 0.9-1.0), or overfeeding (RQ > 1). We hypothesized that preoperative RQ may be associated with weight-loss outcomes after bariatric surgery. METHODS: From 2016 to 2018, 137 obese patients were enrolled in a Bariatric Registry and underwent dietary and behavioral counseling, followed by preoperative IC. Resting energy expenditure (REE) and RQ of all patients was measured. Patients were classified as over-feeders (OF; 42, 31%) with RQ > 1 or non-over-feeders (NOF; 95, 69%) with RQ < 1. At baseline, there was no difference between groups in gender [female: 105 (76.6%), male: 32 (23.4%)], body mass index (BMI; OF: 46.8 ± 7.8 vs. NOF: 44.8 ± 7.4 kg/m2, p = 0.40), or baseline REE (OF: 1897 ± 622 vs. NOF: 1874 ± 579, p = 0.74), although OF were younger [mean age (OF: 47.1 ± 13.0 years vs. NOF: 43.1 ± 13.4; p = 0.009). At 6-month follow-up 94 patients [53.28%; OF: 35 (83%) vs. NOF: 59 (62%), p = 0.016] were seen and 48 [35.03%; OF: 23 (55%) vs. NOF: 25 (59%), p = 0.001] at 12-month follow-up. On preoperative psychological assessment, OF had a significantly higher rate of childhood neglect (OF: 28 (47.46%) vs. NOF: 40 (28.99%); p = 0.01). RESULTS: At 1 year postoperatively, the OF had a significantly higher BMI (OF: 34.3 ± 6.5 vs. NOF: 29.3 ± 5.1 kg/m2, p = 0.009). Differences in weight were not significant at 6-month (OF: 36.0 ± 6.5 vs. NOF: 33.5 ± 5.9 kg/m2, p = 0.07). There was no difference between type of operation and RQ group (RYGB; OF: 55 (75%) vs. NOF: 18 (25%) and SG; OF: 40 (62%) vs. NOF: 24 (38%), p = 0.14), nor in BMI loss after operation. CONCLUSION: Evidence of overfeeding in the preoperative period prior to bariatric surgery is associated with higher resultant BMI at 1 year. Calculation of the RQ with IC has prognostic significance in bariatric surgery, and calculation of REE based on assumed normal RQ potentiates error. It is unclear if overfeeding is purely behavioral or secondary to potentially reversible metabolic etiology.

Chronic Wounds: Evaluation and Management.

Chronic wounds are those that do not progress through a normal, orderly, and timely sequence of repair. They are common and are often incorrectly treated. The morbidity and associated costs of chronic wounds highlight the need to implement wound prevention and treatment guidelines. Common lower extremity wounds include arterial, diabetic, pressure, and venous ulcers. Physical examination alone can often guide the diagnosis. All patients with a nonhealing lower extremity ulcer should have a vascular assessment, including documentation of wound location, size, depth, drainage, and tissue type; palpation of pedal pulses; and measurement of the ankle-brachial index. Atypical nonhealing wounds should be biopsied. The mainstay of treatment is the TIME principle: tissue debridement, infection control, moisture balance, and edges of the wound. After these general measures have been addressed, treatment is specific to the ulcer type. Patients with arterial ulcers should be immediately referred to a vascular surgeon for appropriate intervention. Treatment of venous ulcers involves compression and elevation of the lower extremities, plus exercise if tolerated. Diabetic foot ulcers are managed by offloading the foot and, if necessary, treating the underlying peripheral arterial disease. Pressure ulcers are managed by offloading the affected area.

Strategies for surgical remediation of the multi-fundoplication failure patient.

BACKGROUND: Outcomes are not well studied in patients undergoing remediation for multi-fundoplication failure, that is, two or more prior failed fundoplications. Re-operation must balance reflux control and restoration of the ability to eat with the challenge of reconstructing a distorted hiatus and GE junction. The purpose of this study is to present our experience with surgical remediation for multi-fundoplication failure. METHODS: Medical records were retrospectively reviewed of 91 patients who underwent third time or more esophagogastric operation for fundoplication failure at a single institution from 2007 to 2016. Dysphagia was present in 56% and heartburn in 51%. Median number of prior operations was 2 with range up to 6. Anatomic failure consisted of slipped wrap in 26 cases, wrap herniation in 23, hiatal stenosis in 24, hiatal mesh complication in 8, and wrap dehiscence in 10. Operative approaches generally followed an institutional algorithm and consisted of hiatal hernia repair with: re-do fundoplication in 55%, takedown of fundoplication alone in 24%, Roux-en-Y gastrojejunostomy in 14%, and GE junction resection in 7%. Laparoscopic approach was successful in 81%. RESULTS: Mean duration of operations was 217 min and median length of stay was 3 days. The complication rate was 13%, with 7% undergoing unplanned early re-operation. Patients were followed for mean 11 months, and recurrent hiatal hernia was detected in 13%. Late re-operation was performed in 6% for recurrent hiatal hernia. Recurrent reflux symptomatology resolved in 93%. Dysphagia resolved in 84%. There were no significant differences in outcomes with regard to number of prior operations, operative approach, BMI, or age. CONCLUSIONS: There is no single best approach to remediation in the multi-fundoplication failure patient. Re-do fundoplication is appropriate in over half of patients. Reoperation for multi-fundoplication failure can be performed via minimally invasive approach with excellent remediation of symptoms, low morbidity, and low recurrence rates.

Laparoscopic repair of giant paraesophageal hernia: are there factors associated with anatomic recurrence?

BACKGROUND: Repair of giant paraesophageal hernia (PEH) is associated with a favorably high rate of symptom improvement; however, rates of recurrence by objective measures remain high. Herein we analyze our experience with laparoscopic giant PEH repair to determine what factors if any can predict anatomic recurrence. METHODS: We prospectively collected data on PEH characteristics, variations in operative techniques, and surgeon factors for 595 patients undergoing laparoscopic PEH repair from 2008 to 2015. Upper GI study was performed at 6 months postoperatively and selectively thereafter-any supra-diaphragmatic stomach was considered hiatal hernia recurrence. Exclusion criteria included revisional operation (22.4%), size <5 cm (17.6%), inadequate follow-up (17.8%), and confounding concurrent operations (6.9%). Inclusion criteria were met by 202 patients (31% male, median age 71 years, and median BMI 28.7). RESULTS: At a median follow-up of 6 months (IQR 6-12), overall anatomic recurrence rate was 34.2%. Symptom recurrence rate was 9.9% and revisional operation was required in ten patients (4.9%). Neither patient demographics nor PEH characteristics (size, presence of Cameron erosions, esophagitis, or Barrett's) correlated with anatomic recurrence. Technical factors at operation (mobilized intra-abdominal length of esophagus, Collis gastroplasty, number of anterior/posterior stitches, use of crural buttress, use of pledgeted or mattress sutures, or gastrostomy) were also not correlated with recurrence. Regarding surgeon factors, annual volume of fewer than ten cases per year was associated with increased risk of anatomic failure (54 vs 33%, P = 0.02). Multivariate analysis identified surgeon experience (<10 cases per year) as an independent factor associated with early hiatal hernia recurrence (OR 3.7, 95% CI 1.34-10.9). CONCLUSIONS: Laparoscopic repair of giant PEH is associated with high anatomic recurrence rate but excellent symptom control. PEH characteristics and technical operative variables do not appear to significantly affect rates of recurrence. In contrast, surgeon volume does appear to contribute significantly to durability of repair.

Correction to: Endoscopic and surgical management of nonampullary duodenal neoplasms.

This article was updated to correct the author listing for Carlos Roberto Simons-Linares.

Endoscopic and surgical management of nonampullary duodenal neoplasms.

BACKGROUND: Sporadic nonampullary duodenal neoplasms (SNADN) can have malignant potential for which endoscopic and surgical resections are offered. We report combined gastroenterologic and surgical experience for treatment of SNADN, including endoscopic mucosal resection (EMR) and pancreas-preserving partial duodenectomy (PPPD). METHODS: We retrospectively reviewed 121 consecutive patients, who underwent 30 PPPDs and 91 EMRs for mucosal and submucosal SNADN. Decision to undergo EMR or surgical resection was based on expert endoscopist and surgeon discretion including multidisciplinary tumor board review. Main outcomes were recurrence rate of neoplasia and adverse events requiring hospital admission or prolonged care. EMRs were performed with submucosal lifting followed by snare resection. PPPD included total duodenectomy, supra-ampullary PPPD for neoplasms proximal to the ampulla, and infra-ampullary PPPD for lesions distal to the ampulla. Follow-up data were available for 65% of EMR and 73% of surgical patients. RESULTS: Surgically resected neoplasia was larger with more advanced neoplasia and submucosal lesions. En bloc resection was achieved in all surgical resections and in 53% of EMRs. Post-EMR, mucosal and submucosal neoplasia recurred in 32 and 0%, respectively, including five neoplasms (26%) after an initial negative esophagogastroduodenoscopy. All recurrences were treated endoscopically. Complications occurred in 14 endoscopically and eight surgically treated patients, none requiring surgical intervention. CONCLUSIONS: Post-EMR patients had higher recurrence of mucosal neoplasia, whereas submucosal neoplasms, mainly carcinoid, did not recur. Polyp size and positive resection margin were not associated with neoplasia recurrence. Patients with SNADN could benefit from a multidisciplinary approach to stratify the optimal treatment based on local expertise.

Revisional surgery after failed esophagogastric myotomy for achalasia: successful esophageal preservation.

BACKGROUND: Treatment failure with recurrent dysphagia after Heller myotomy occurs in fewer than 10 % of patients, most of whom will seek repeat surgical intervention. These reoperations are technically challenging, and as such, there exist only limited reports of reoperation with esophageal preservation. METHODS: We retrospectively reviewed the records of patients who sought operative intervention from March 1998 to December 2014 for obstructed swallowing after esophagogastric myotomy. All patients underwent a systematic approach, including complete hiatal dissection, takedown of prior fundoplication, and endoscopic assessment of myotomy. Patterns of failure were categorized as: fundoplication failure, inadequate myotomy, fibrosis, and mucosal stricture. RESULTS: A total of 58 patients underwent 65 elective reoperations. Four patients underwent esophagectomy as their initial reoperation, while three patients ultimately required esophagectomy. The remainder underwent reoperations with the goal of esophageal preservation. Of these 58, 46 were first-time reoperations; ten were second time; and two were third-time reoperations. Forty-one had prior operations via a trans-abdominal approach, 11 via thoracic approach, and 6 via combined approaches. All reoperations at our institution were performed laparoscopically (with two conversions to open). Inadequate myotomy was identified in 53 % of patients, fundoplication failure in 26 %, extensive fibrosis in 19 %, and mucosal stricture in 2 %. Intraoperative esophagogastric perforation occurred in 19 % of patients and was repaired. Our postoperative leak rate was 5 %. Esophageal preservation was possible in 55 of the 58 operations in which it was attempted. At median follow-up of 34 months, recurrent dysphagia after reoperation was seen in 63 % of those with a significant fibrosis versus 28 % with inadequate myotomy, 25 % with failed wrap, and 100 % with mucosal stricture (p = 0.10). CONCLUSIONS: Laparoscopic reoperation with esophageal preservation is successful in the majority of patients with recurrent dysphagia after Heller myotomy. The pattern of failure has implications for relief of dysphagia with reoperative intervention.

Prospective evaluation of 24-hour urine profiles following bariatric surgery in a modern comprehensive care bariatric clinic.

AIMS: To prospectively examine the effect of modern bariatric surgery on 24-hour urine parameters in a comprehensive care bariatric practice (CCBP). MATERIALS AND METHODS: 47 consecutive patients in our CCBP underwent serum and 24-hour urine analysis pre-operatively, and 30 returned at 12 months for repeat testing. Paired comparisons for serum metabolite and 24-hour urine measures were performed using a Wilcoxon signed-rank test for continuous variables and McNemar's test for categorical variables. Statistical tests were two-sided, with threshold of significance set at p = 0.05. RESULTS: All 30 patients with pre-operative and 12-month follow-up analysis were free of stone events. 20 (67%) had Roux-en-Y gastric bypass (RYGB), 6 (20%) had laparoscopic gastric banding (LGB), and 4 (13%)h ad laparoscopic sleeve gastrectomy (LSG). 24-hour urinary parameters were available for 27 patients. Median urine oxalate (mmol) was 0.29 pre-operatively and 0.21 at 12 months (p = 0.048). Median urine calcium (mg) was 143 pre-operatively and 180 at 12 months (p = 0.11). Median citrate excretion was 527 pre-operatively and 782 at 12 months (p = 0.22). Median serum creatinine was 0.7 pre-operatively and 0.8 at 12 months (p < 0.001). These trends were preserved with the exclusion of LGB and LSG patients. CONCLUSIONS: Modern bariatric surgery (RYGB, LGB, and LSG) as part of a CCBP can still demonstrate alterations of select urinary parameters (particularly oxalate and citrate) in select patients associated with an increased risk of urolithiasis at 1 year follow-up.

Binding and dimerization of PGLa peptides in anionic lipid bilayer studied by replica exchange molecular dynamics.

The 21-residue PGLa peptide is well known for antimicrobial activity attributed to its ability to compromize bacterial membranes. Using all-atom explicit solvent replica exchange molecular dynamics with solute tempering, we studied PGLa binding to a model anionic DMPC/DMPG bilayer at the high peptide:lipid ratio that promotes PGLa dimerization (a two peptides per leaflet system). As a reference we used our previous simulations at the low peptide:lipid ratio (a one peptide per leaflet system). We found that the increase in the peptide:lipid ratio suppresses PGLa helical propensity, tilts the bound peptide toward the bilayer hydrophobic core, and forces it deeper into the bilayer. Surprisingly, at the high peptide:lipid ratio PGLa binding induces weaker bilayer thinning, but deeper water permeation. We explain these effects by the cross-correlations between lipid shells surrounding PGLa that leads to a much diminished efflux of DMPC lipids from the peptide proximity at the high peptide:lipid ratio. Consistent with the experimental data the propensity for PGLa dimerization was found to be weak resulting in coexistence of monomers and dimers with distinctive properties. PGLa dimers assemble via apolar criss-cross interface and become partially expelled from the bilayer residing at the bilayer-water boundary. We rationalize their properties by the dimer tendency to preserve favorable electrostatic interactions between lysine and phosphate lipid groups as well as to avoid electrostatic repulsion between lysines in the low dielectric environment of the bilayer core. PGLa homedimer interface is predicted to be distinct from that involved in PGLa-magainin heterodimers.

Variability of NSQIP-assessed surgical quality based on age and disease process.

BACKGROUND: Recent national attention has focused on improving upon the surgical quality of hospitals across the United States. The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database includes expected morbidity probability for each surgical patient. We sought to investigate the accuracy of this probability across the spectrum of general surgical operations and assess the variability based on the age and disease process. MATERIALS AND METHODS: Using the 2008 ACS-NSQIP database, we identified 190,929 operations that would be in the scope of practice of a modern general surgeon; the four most common included breast resection (n = 22,175; 11.6%), colon resection (n = 21,363; 11.2%), cholecystectomy (n = 20,889; 10.9%), and inguinal hernia repair (n = 11,709; 6.1%). We calculated the surgical observed versus expected morbidity rates (O/E) of each operation type and compared them by decile of patient age. We then determined the effect of case mix and patient age on theoretical hospitals performing at the NSQIP average. RESULTS: There is substantial variability in O/E ratios when comparing these disease processes across deciles of age. For patients undergoing breast resections, 67.2% of morbidities were solely attributed to 30-d reoperations; colon resections had an O/E ratio greater than 1 for all age deciles except over 90 y old. For cholecystectomies and the majority of patients undergoing inguinal hernia repairs, there was a lower morbidity rate than expected. Case mix and patient age were found to independently affect assessment of hospital quality. CONCLUSIONS: It is conceivable that general surgery case mix and patient age could independently affect the quality assessment of a hospital. This variability may have implications for overall quality measures.

Cost analysis of open and laparoscopic pancreaticoduodenectomy: a single institution comparison.

INTRODUCTION: The laparoscopic approach to pancreaticoduodenectomy has been recently more frequently reported and is now being performed at multiple centers across the US. While laparoscopic pancreaticoduodenectomy (LPD) has been shown to be safe and feasible, comparing its cost in relation to open pancreaticoduodenectomy (OPD) has not been examined. The aim of this study is to examine the cost of LPD compared with OPD at a single institution over a 3-year time period. METHODS: An institutional database was analyzed to compare patients who underwent OPD and LPD (including Whipple resections and total pancreatectomy) between May 2009 and June 2012. A cost analysis was performed, which included the use the hospital billing database to assess surgical costs, hospital admission costs, and overall cost of the patient's care during the index admission. The operative costs were further analyzed with respect to OR time and surgical supplies. Standard statistical analysis was performed to assess for significance. RESULTS: In the study time period, 123 patients underwent pancreaticoduodenectomy, including 48 OPD (39%) and 75 LPD (61%). The groups were similar with respect to age, gender, ASA, vein resection, and indication for surgery. In the LPD group, the use of hand assist or conversion to OPD occurred in 3 (4%) and 10 (13%) patients, respectively. Additionally, 10% of the OPD group underwent total pancreatectomy (n = 5), compared to 21% of the LPD (n = 16). Mean operative time for OPD and LPD was 355 min (range 199-681) and 551 min (range 390-819) respectively (p < 0.0001). Median hospital stay for OPD and LPD was 8 days (range 5-63), and 7 days (range 4-68) respectively (p = 0.5). Morbidity rates were equal at 31% for the two groups. The LPD group was associated with significantly higher surgical cost due to both increased time and supply cost. However, mean hospital admission cost associated with OPD was greater in comparison to the LPD group, though not significant. The overall total cost of care was similar between the two groups. CONCLUSIONS: LPD is associated with equivalent overall cost compared with OPD. While operating time and supply costs were higher for LPD, this was balanced by decreased cost of the postoperative admission.

Technical and perioperative outcomes of minimally invasive esophagectomy in the prone position.

BACKGROUND: Minimally invasive esophagectomy (MIE) is performed through various approaches, including using video-assisted thoracoscopic surgery for mediastinal esophageal dissection. The prone technique allows for gravity-aided retraction of the lung. The aim of this study was to examine perioperative outcomes after prone MIE in relation to patient preoperative comorbidities. METHODS: A retrospective cohort study from our single tertiary-care center is presented. Between January 2007 and August 2010, a total of 42 patients underwent three-field prone MIE. The majority of patients were male (37 vs. 5 female), with an average age of 68 years (range = 37-87). The diagnoses for patients who underwent MIE were 35 adenocarcinoma, four Barrett's esophagus with high-grade dysplasia, two achalasia, and one squamous cell carcinoma. Neoadjuvant chemotherapy with or without radiotherapy was administered to 16 (38 %) patients. Preoperative comorbidities were quantified using the Modified Charlson Comorbidity Index; low risk was defined as a score of 0-2 (23 patients), moderate risk 3-4 (14 patients), and high risk 5 or higher (five patients). Postoperative complications were stratified using the Clavien Classification Scale; minor complications were grades 1 and 2 and major complications were grades 3-5. RESULTS: Median length of hospital stay was 8 days (range = 6-51) and median ICU stay was 2 days (range = 1-26). Average prone surgical time was 108 min (range = 67-198). Thirty-seven of 42 patients (88 %) were extubated on the day of operation. Postoperatively, all five high-risk patients had a complication, three of which were major. Eight of the 14 moderate-risk patients had a complication and three were major, and 17 of the 23 low-risk group had a complication with nine being major. There was a total of 15 major complications. Predominant complications were arrhythmias (15) and pneumonia (five), with four anastomotic leaks and two postoperative 30-day mortalities. CONCLUSIONS: This series supports using prone MIE. Despite a clinical pathway, including immediate extubation postoperatively, there is still a risk of pulmonary complications that appears to correlate with higher preoperative comorbidity scores.

Comparison of open with laparoscopic distal pancreatectomy: a single institution's transition over a 7-year period.

OBJECTIVES: Many studies have shown laparoscopic distal pancreatectomy (LDP) to have benefits over open distal pancreatectomy (ODP). This institution made a unique abrupt transition from an exclusively open approach to a preference for the laparoscopic technique. This study aimed to compare outcomes in patients undergoing LDP and ODP, respectively, over the period of transition. METHODS: A retrospective review of all patients undergoing LDP (n = 82) or ODP (n = 90) was performed. Surrogate oncologic markers for the subgroup of patients with malignant disease were also studied. RESULTS: The ODP and LDP groups were well matched with regard to demographics, comorbidities and tumour characteristics. Significant differences were noted in favour of the LDP group in which decreases were seen in estimated blood loss (<0.001), need for packed red blood cell transfusions (<0.001), length of hospital stay (<0.001) and intensive care unit stay (<0.001). No other significant differences in the occurrence of complications or oncologic outcomes were seen. Rates of Grade B and C fistulae were 10% and 6% in the ODP and LDP groups, respectively. Grade III-V complications occurred in 20% and 13% of the ODP and LDP groups, respectively. CONCLUSIONS: Laparoscopic distal pancreatectomy continues to compare favourably with ODP when well-matched patient series are reviewed. The results show a decreased need for blood transfusions and hospital resources in LDP. Additionally, there may be oncologic advantages associated with LDP compared with ODP in pancreatic malignancies.

Replica Exchange with Hybrid Tempering Efficiently Samples PGLa Peptide Binding to Anionic Bilayer.

We evaluated the utility of a variant of the replica exchange method, a replica exchange with hybrid tempering (REHT), for all-atom explicit water biomolecular simulations and compared it with a more traditional replica exchange with the solute tempering (REST) algorithm. As a test system, we selected a 21-mer antimicrobial peptide PGLa binding to an anionic DMPC/DMPG lipid bilayer. Application of REHT revealed the following binding mechanism. Due to the strong hydrophobic moment, the bound PGLa adopts an extensive helical structure. The binding free energy landscape identifies two major bound states, a metastable surface bound state and a dominant inserted state. In both states, positively charged PGLa amino acids maintain electrostatic interactions with anionic phosphate groups by rotating the PGLa helix around its axis. PGLa binding causes an influx of anionic DMPG and an efflux of zwitterionic DMPC lipids from the peptide proximity. PGLa thins the bilayer and disorders the adjacent fatty acid tails. Deep invasion of water wires into the bilayer hydrophobic core is detected in the inserted peptide state. The analysis of charge density distributions indicated that peptide positive charges are nearly compensated for by lipid negative charges and water dipole ordering, whereas ions play no role in peptide binding. Thus, electrostatic interactions are the key energetic factor in binding cationic PGLa to an anionic DMPC/DMPG bilayer. Comparison of REHT and REST shows that due to exclusion of lipids from tempered partition, REST lags behind REHT in peptide equilibration, particularly, with respect to peptide insertion and helix acquisition. As a result, REST struggles to provide accurate details of PGLa binding, although it still qualitatively maps the bimodal binding mechanism. Importantly, REHT not only equilibrates PGLa in the bilayer faster than REST, but also with less computational effort. We conclude that REHT is a preferable choice for studying interfacial biomolecular systems.

Can Risk-Based Thromboprophylaxis Practice Guidelines be Safely Used in Esophagectomy Cases? Experience of an Academic Health System.

BACKGROUND: Venous thromboembolism (VTE) occurs in 3-11% of esophagectomy patients and is associated with increased mortality and morbidity. The use of validated VTE risk assessment tools and compliance with recommended practice guidelines remains unclear. In this study, we seek to determine the use of Caprini guideline indicated VTE prophylaxis and its effect on VTE and bleeding complications following esophagectomy. METHODS: Esophagectomy cases were identified from the Mayo Clinic electronic health records. Caprini score and VTE prophylaxis regimen received were determined retrospectively. VTE prophylaxis was identified as appropriate or inappropriate based on the Caprini score and prophylaxis received preoperative, during hospitalization, and after hospital discharge. Study cohorts were compared by Pearson Chi-square test, Fisher's Exact test, Kruskal-Wallis test, and logistic regression models. Stata/MP 16.1 was used for analysis. Odds ratios and 95% confidence intervals were reported for logistic regression models. A p-value < 0.05 was considered significant. RESULTS: Four hundred and fifty-six esophagectomy cases were analyzed. The median Caprini score was thirteen. Appropriate prophylaxis resulted in a 6.9-fold reduction in inpatient VTE. All 30- and 90-day post-discharge VTEs occurred in those not receiving Caprini guideline-indicated VTE prophylaxis. Inpatient, 30- and 90-day post-discharge bleeding rates were 7.68%, 0.91%, and 2.11%, respectively; however, bleeding was not increased with receipt of appropriate prophylaxis. CONCLUSION: In this esophagectomy cohort, Caprini guideline indicated VTE prophylaxis resulted in reduced inpatient VTE events without increasing bleeding complications. Risk-based VTE prevention measures should be considered in this patient cohort known to be at heightened risk for postoperative VTE.

Proton Therapy With Concurrent Chemotherapy for Thoracic Esophageal Cancer: Toxicity, Disease Control, and Survival Outcomes.

Purpose: When treating esophageal cancer with radiation therapy, it is critical to limit the dose to surrounding structures, such as the lung and/or heart, as much as possible. Proton radiation therapy allows a reduced radiation dose to both the heart and lungs, potentially reducing the risk of cardiopulmonary toxicity. Here, we report disease control, survival, and toxicity outcomes among patients with esophageal cancer treated with proton radiation therapy and concurrent chemotherapy (chemoradiation therapy; CRT) with or without surgery. Materials and Methods: We enrolled 17 patients with thoracic esophageal carcinoma on a prospective registry between 2010 and 2021. Patients received proton therapy to a median dose of 50.4-GyRBE (range, 50.4-64.8) in 1.8-Gy fractions.Acute and late toxicities were graded per the Common Terminology Criteria for Adverse Events, version 4.0 (US National Cancer Institute, Bethesda, Maryland). In addition, disease control, patterns of failure, and survival outcomes were collected. Results: Nine patients received preoperative CRT, and 8 received definitive CRT. Overall, 88% of patients had adenocarcinoma, and 12% had squamous cell carcinoma. With a median follow-up of 2.1 years (range, 0.5-9.4), the 3-year local progression-free, disease-free, and overall survival rates were 85%, 66%, and 55%, respectively. Two patients (1 with adenocarcinoma and 1 with squamous cell carcinoma) recurred at the primary site after refusing surgery after a complete clinical response to CRT. The most common acute nonhematologic and hematologic toxicities, respectively, were grades 1 to 3 esophagitis and grades 1 to 4 leukopenia, both affecting 82% of patients. No acute cardiopulmonary toxicities were observed in the absence of surgical resection. Reagarding surgical complications, 3 postoperative cardiopulmonary complications occurred as follows: 1 grade 1 pleural effusion, 1 grade 3 pleural effusion, and 1 grade 2 anastomotic leak. Two severe late CRT toxicities occurred: 1 grade 5 tracheoesophageal fistula and 1 grade 3 esophageal stenosis requiring a feeding tube. Conclusion: Proton radiation therapy is a safe, effective treatment for esophageal cancer with increasing evidence supporting its role in reducing cardiopulmonary toxicity.